The regulations in 9 CFR part 94 (referred to below as the regulations) govern the importation of certain animals and animal products into the United States in order to prevent the introduction of various animal diseases, including rinderpest and foot-and-mouth disease (FMD). Section 94.1 of the regulations lists regions of the world that are considered free of rinderpest and FMD. Section 94.11 lists regions of the world considered free of rinderpest and FMD but from which the importation of meat and other animal products into the United States is subject to additional restrictions because of those regions' proximity to or trading relationships with FMD-affected regions.

In an interim rule1 effective and published in theFederal Registeron October 25, 2010 (75 FR 65431-65432, Docket No. APHIS-2010-0077), we amended the regulations in paragraphs (a)(2) and (a)(3) of § 94.1 to remove Japan from the list of regions considered free of rinderpest and FMD and to add Japan to the list of regions considered free of rinderpest, respectively. We also amended the regulations in § 94.11 to remove Japan from the list of regions considered free of rinderpest and FMD but from which the importation of meat and other animal products of ruminants and swine into the United States is subject to additional restrictions. The interim rule also clarified that the importation into the United States of whole cuts of boneless beef, which had been allowed under the provisions in § 94.27 of the regulations, was being prohibited due to FMD. Those actions were necessary because, by July 4, 2010, Japan had reported FMD on a total of 292 premises in Miyazaki prefecture of that country to the World Organization for Animal Health (OIE).

The source of the virus has not been definitively identified. However, the Ministry of Agriculture, Forestry and Food in Japan suspects that it was introduced through people or personal goods from a nearby country contaminated with the FMD virus. Japan's official veterinary services addressed the FMD outbreak through a stamping-out policy that involved movement restrictions, culling, active surveillance, and ultimately vaccination. All vaccinated animals were subsequently culled. Intensive surveillance demonstrated that the virus did not spread outside Miyazaki prefecture. On February 4, 2011, the OIE reinstated Japan to its list of countries free of FMD without vaccination.

Although we removed Japan from the list of regions in the world considered free of rinderpest and FMD, and the list of regions considered free of rinderpest and FMD but from which the importation of meat and other animal products is subject to additional restrictions, we recognized that Japan immediately responded to the detection of the disease by imposing restrictions on the movement of susceptible animals and animal products, both within and from Japan, and initiating measures to eradicate the disease. We stated that, because of Japan's response to detection of the disease, we intended to reassess the situation in accordance with the standards of the OIE at a future date, and that as part of the reassessment process, we would consider all comments received during the comment period on the interim rule.

In this notice, we are announcing the availability for review and comment of a document titled “APHIS Evaluation of the Foot and Mouth Disease Status of Japan.” This evaluation examines the events that occurred during and after the outbreaks and assesses the risk of live animals and animal products fromJapan harboring the FMD virus. This risk analysis will serve as the basis for our determination whether to reinstate Japan to the list of regions free of FMD and rinderpest and the list of regions considered free of FMD and rinderpest but from which the importation of meat and other animal products of ruminants and swine into the United States is subject to additional restrictions. The risk analysis will also serve as the basis for our determination whether to allow the resumption of the importation of whole cuts of boneless beef from Japan. We are making the risk analysis available for public comment for 60 days.

The risk analysis may be viewed on the Regulations.gov Web site or in our reading room (seeADDRESSESabove for instructions for accessing Regulations.gov and information on the location and hours of the reading room). You may request paper copies of the risk analysis by calling or writing to the person listed underFOR FURTHER INFORMATION CONTACT. Please refer to the title of the analysis when requesting copies.

The National Aeronautics and Space Act (51 U.S.C. 20113) authorizes the Administrator of NASA to settle administrative claims of patent and copyright infringement by NASA. In addition to that authority to acquire license rights and interests in patents and copyrights through settlement of claims, the Administrator has authority to settle claims of patent and copyright infringement pursuant to 22 U.S.C. 2356, 35 U.S.C. 183 and 286, and 28 U.S.C. 1498(b).

In accordance with these authorities, NASA is issuing proposed regulations setting forth requirements for the filing of claims against NASA where a potential claimant believes NASA is infringing privately owned rights in patented inventions or copyrighted works. The proposed regulations are designed to inform potential claimants as to what information must be supplied in their communication to NASA regarding alleged infringement before NASA will consider a claim to have been filed. The regulations identify certain commonly received communications which are concerned with rights in patents and copyrights, but which will not be considered sufficient to constitute the formal filing of a claim.

The requirements for filing an administrative claim are important since the filing of a claim carries with it certain rights relating to the applicable statute of limitations for filing suit against the Government. In the case of patent infringement claims, Title 35 U.S.C. 286 provides that the six-year statute of limitations for filing suits for patent infringement may, in the case of claims against the Government, be tolled up to six years between the date of receipt of a written claim for compensation by the Government and the date of mailing by the Government of a notice that the claim has been denied. Copyright infringement claims can be tolled indefinitely under 28 U.S.C. 1498(b) between the date of receipt of a written claim for compensation by the Government and the date of mailing by the Government of a notice that the claim has been denied. The proposed regulations set forth guidelines as to what NASA considers necessary to file a claim for patent or copyright infringement.

Section 1245.202(a) provides that in order for a potential claimant's communication to NASA to formally instigate a claim, it must specifically allege infringement by NASA, request compensation, identify a patent or copyright alleged to be infringed, and indicate an act or item which the potential claimant believes infringes the claimant's patent or copyright. Section 1245.203(a) advises the potential claimant where to forward communications regarding the alleged infringement. Section 1245.202(b) of the regulation identifies information which, although not necessary in order for a communication to be considered sufficient to constitute the filing of a claim, is usually necessary to process a claim and, therefore, if presented initially with the claim, may serve to expedite the handling of the claim. The proposed regulations provide for written notification to the claimant upon completion of an investigation by NASA.

This rule does not contain an information collection requirement subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501et seq.).

Executive Orders 13563 and 12866 direct agencies to assess all costs and benefits of available regulatory alternatives and, if regulation is necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health and safety effects, distributive impacts, and equity). Executive Order 13563 emphasizes the importance of quantifying both costs and benefits, of reducing costs, of harmonizing rules,and of promoting flexibility. This rule has been designated a “significant regulatory action” although not economically significant, under section 3(f) of Executive Order 12866. Accordingly, the rule has been reviewed by the Office of Management and Budget.

It has been certified that this rule is not subject to the Regulatory Flexibility Act (5 U.S.C. 601) because it would not, if promulgated, have a significant economic impact on a substantial number of small entities. The rule sets forth policies and procedures for the filing and disposition of claims of infringement of privately owned rights in patented inventions or copyrighted works asserted against NASA. These policies and procedures would not have a significant economic impact on a substantial number of small entities as NASA typically has less than 10 of such claims asserted against it annually. Any small entities that believe they are being adversely affected by this rule are encouraged to submit comments; please see information under theDATESandADDRESSESheadings above for guidance.

Accordingly, Part 1245, Subpart 2, of Title 14 of the Code of Federal Regulations is proposed to be added to read as follows:

The Commission has received a submission from John L. Branum, Attorney at Law, on behalf of Bettsy Bumpas (“petitioner”), dated May 9, 2011, requesting that we initiate rulemaking to require torch fuel and lamp oil to bepackaged in containers that are not see-through. We are docketing this request as a petition under the Poison Prevention Packaging Act (“PPPA”). 15 U.S.C. 1471-1477.

The PPPA authorizes the Commission to issue requirements that certain household substances be sold in child-resistant containers. 15 U.S.C. 1471-1477. Child-resistant packaging requirements currently apply to torch fuel and lamp oil. (More specifically, the child-resistant packaging requirements apply to “kindling and/or illuminating preparations,” which includes “cigarette lighter fuel, charcoal lighter fuel, camping equipment fuel, torch fuel, and fuel for decorative and functional lanterns, which contain 10 percent or more by weight of petroleum distillates and have a viscosity of less than 100 Saybolt universal seconds at 100° Fahrenheit.” 16 CFR 1700.14(7)). The PPPA does not authorize the Commission to prescribe specific packaging designs for household substances. 15 U.S.C. 1472(d). However, in the case of a household substance for which special packaging,i.e.,child-resistant packaging, is required, the Commission may prohibit the packaging of such substance in packages which it determines are unnecessarily attractive to children. Id. Therefore, in order to issue a rule requiring that torch fuel and lamp oil not be sold in see-through containers, the Commission would need to determine that the packaging is “unnecessarily attractive” to children.

Petitioner asserts that certain petroleum distillates, including torch fuel and lamp oil, as currently packaged, resemble juice. Petitioner notes that because young children enjoy the taste of juice and are accustomed to drinking it regularly, packaging petroleum distillates in clear plastic bottles causes needless danger, as children may mistake it for juice.

Petitioner states that “the New Jersey Poison Information and Education System stated in June 2008 that four people were hospitalized, one was critically ill, and one killed due to torch oil being mistaken for apple juice.” Petitioner also states that “from 2002 through 2009 the Annual Report of the American Association of Poison Control Centers' National Data System has chronicled the exposure of many young children to lamp oils, which includes torch fuels.” Petitioner's son died after ingesting torch fuel from a clear plastic bottle.

While torch fuel and lamp oil are already subject to child-resistant packaging and labeling requirements under the Poison Prevention Packaging Act and the Federal Hazardous Substances Act, petitioner asserts that additional special packaging is necessary. Specifically, petitioner requests that the CPSC initiate rulemaking “that would require manufacturers of [torch fuel and lamp oils] to package the product in containers that make it impossible to see the product when in the container.” Petitioner notes that this could be accomplished “by packaging the fuel in a solid container or opaque plastic child-resistant container or a metal container.”

By this notice, we seek comments concerning this petition. Interested parties may obtain a copy of the petition by writing or calling the Office of the Secretary, U.S. Consumer Product Safety Commission, Room 820, 4330 East West Highway, Bethesda, MD 20814; telephone (301) 504-7923.

Copies of the petition are also available for inspection from 8:30 a.m. to 5 p.m., Monday through Friday, in the Commission's Public Reading Room, Room 419, 4330 East West Highway, Bethesda, MD, or from our Web site at:http://www.cpsc.gov.

The roundtable discussion will take place on Monday, August 1, 2011, commencing at 9 a.m. and ending at 4 p.m. Members of the public who wish to comment on the topics addressed at the discussion, may do so via:

• Paper submission to David Stawick, Secretary, Commodity Futures Trading Commission, Three Lafayette Centre, 1155 21st Street, NW., Washington, DC 20581, or Elizabeth M. Murphy, Secretary, Securities and Exchange Commission, 100 F Street, NE., Washington, DC 20549-1090; or

• Electronic submission via visitinghttp://comments.cftc.gov/PublicComments/ReleasesWithComments.aspxand submitting comments through the CFTC's Web site; and/or by e-mail torule-comments@sec.gov(all e-mails must reference the file number 4-636 in the subject field) or through the comment form available athttp://www.sec.gov/news/press/2011/2011-151.htm.

All submissions will be reviewed jointly by the Agencies. All comments must be in English or be accompanied by an English translation. Allsubmissions provided to either Agency in any electronic form or on paper will be published on the Web site of the respective Agency, without review and without removal of personally identifying information. Please submit only information that you wish to make publicly available.

The Dodd-Frank Act was enacted on July 21, 2010.2 Title VII of the legislation3 amends the Commodity Exchange Act4 and the Securities Exchange Act of 19345 to establish a comprehensive new regulatory framework for swaps and security-based swaps to reduce risk, increase transparency, and promote market integrity within the financial system. Among other things, Title VII: (1) Provides for the registration and comprehensive regulation of swap dealers, security-based swap dealers, major swap participants, and major security-based swap participants; (2) imposes clearing and trade executionrequirements on swaps and security-based swaps, subject to certain exceptions; (3) creates rigorous recordkeeping and real-time reporting regimes; and (4) enhances the Commissions' rulemaking and enforcement authorities with respect to certain registered entities and intermediaries subject to the Commissions' oversight.

Section 719(c)(1) of the Dodd-Frank Act requires the CFTC and SEC jointly to conduct a study on swap regulation and clearinghouse regulation in the United States, Asia, and Europe and to identify areas of regulation that are similar and other areas of regulation that could be harmonized.6 Pursuant to Section 719(c)(2) of the Dodd-Frank Act, the Commissions must submit a report to Congress within 18 months after the Dodd-Frank Act's enactment (i.e.,on or before Monday, January 23, 2012) that describes the results of the study and includes: (1) The identification of the major dealers, exchanges, clearinghouses, and regulators in each geographic area; (2) lists of the major swap contracts (including trading volumes, clearing volumes, and notional values) in each geographic area; and (3) a description of the methods for clearing swaps and the systems used for setting margin in each geographic area.7

In connection with the study and report required by Section 719(c) of the Dodd-Frank Act, the CFTC and SEC have determined to issue this request for information through public comment. Congress has directed the Commissions to conduct an independent joint study on specific topics and, in particular, to identify areas of regulation that could be harmonized.8 The Commissions have determined that this request for public comment will be an effective and transparent means of gathering information necessary for the study and report from interested parties. This public comment process will, as needed, be supplemented by other means of gathering the comprehensive range of information requested by Congress.9

The Commissions also are mindful of differences in regulatory development across jurisdictions. In the United States and under the Dodd-Frank Act, many of the required regulations with regard to swaps already have been proposed and made available for public comment.10 Other jurisdictions, however, are proceeding under different time frames. For example, the Japanese Diet amended the Financial Instruments and Exchange Act by adopting legislation on over-the-counter (OTC) derivatives on July 10, 2009, and on May 12, 2010. These amendments are expected to be implemented by November 2012. The European Commission (EC), in turn, proposed legislation on clearing and trade repositories on September 15, 2010.11 This proposed legislation calls for the European Securities and Markets Authority to propose technical standards by June 30, 2012.12

In order to strike a balance between meeting the statutory deadline for the study and report and providing timely information to Congress, the Commissions have determined to publish the request at this time and to provide for a 60-day comment period. Given the pace of developments in the regulation of OTC derivatives here in the United States and in other jurisdictions, the Commissions plan to conduct the study based upon information received and collected by the last day of the comment period.13 Comments should be submitted during the open comment period, but staff may consider comments filed after the deadline and may consult with interested and/or relevant parties after the comment period closes in order to obtain additional or clarifying information. The Commissions welcome public comment on all aspects of the study.14

The Commissions have developed the following requests for comment to gather information in support of the study mandated by Section 719(c) and request that commenters include a description, either in English or accompanied by an English translation, of the underlying source material used in composing each submitted response. Commenters may also provide any additional relevant information beyond that specifically requested. BecauseSection 719(c) requires the Commissions to prepare a report relating to the swap markets of the United States, Asia, and Europe, commenters are specifically asked to provide information about markets in those jurisdictions. Commenters also may provide any relevant information on other jurisdictions. If regulatory requirements in a jurisdiction are under consideration but not yet enacted or effective, commenters should make note of this in their answer and provide as much relevant information as possible on recent and anticipated developments.

While all commenters are welcome to respond to the items below in their entirety, in order to provide more focus, the requests for comment have been divided into three groups. The first group, items A-E, inquires about information to which foreign regulators may have the most efficient access. Item F, by contrast, inquires about information that may be available to a wider range of commenters, while item G inquires about information that exchanges and clearinghouses might be uniquely positioned to provide.

1. For each jurisdiction on which comment is being provided, please provide the name of the jurisdiction being commented upon.

2. Does the jurisdiction have a legal definition of the term “swap”, “security-based swap”, or other similar term or terms (hereinafter referred to as a “Swap” or “Swaps”)? If so, please provide such definition(s).15

3. Are Swaps included within the scope of any statute, regulation, or other legal requirement in the jurisdiction?

a. If not, is the jurisdiction planning to or considering whether to regulate, or to modify regulation of, Swaps?

b. Please further describe the present status of regulatory efforts and the anticipated timeline for such efforts.

4. What type of counterparty may enter into a Swap? Do any limitations apply?

5. Are certain types or classes of Swaps prohibited, or are certain entities prohibited from entering into certain types or classes of Swaps?

6. If Swaps are regulated:

a. Who determines which instruments, transactions, or agreements should be regulated as Swaps?

b. Which Swaps, if any, are required to be executed on an organized market, on an electronic execution facility, or on any other type of market?

c. Which Swaps, if any, are required to be cleared by a central counterparty and, for those required to be cleared, how are the trades of non-clearing participants cleared?16

d. Which Swap transactions, if any, are required to be reported to a data repository or other entity, the public, or regulatory authorities?

e. Is regulatory oversight of the Swap market conducted by one single regulatory authority or divided among different regulatory authorities? If the latter, please identify each relevant regulatory authority and describe its responsibilities and jurisdiction.

f. How does the regulatory framework regulate potential systemic risk created by Swaps? Does it, for example, create a new oversight body or designate certain entities as systemically important?

g. Does the regulatory authority, or regulatory authorities if more than one regulator has oversight responsibilities over the Swap market, have the ability to share information related to Swaps with domestic and foreign regulatory authorities?17

h. How are cross-border Swap transactions regulated? Does the Swap regulatory framework apply to persons located outside of the jurisdiction doing business with persons located within the jurisdiction, and, more generally, to cross-border Swap activities?

i. What enforcement authority exists over Swaps, and who may exercise such authority?

1. How does the regulatory framework address participants in the Swap market? What are the registration or licensing requirements for Swap-related dealers, market participants, intermediaries, or others (individually and collectively, “Participants”)?

2. Are any types of Participants in the Swap market excluded or exempted from Swap-related registration or licensing requirements?

3. What is the process for updating, withdrawing, or terminating Swap-related registration or an exemption from Swap-related registration?

4. What are the Swap-related prudential regulatory requirements (e.g.,capital, liquidity, margin, risk management, segregation, collateral)?

5. What are the requirements related to insolvency or bankruptcy in regard to Participants?

6. What are the Swap-related business conduct requirements (e.g.,interaction with counterparties, disclosure, supervision, reporting, recordkeeping, documentation, confirmation, valuation, conflicts of interest, avoidance of fraud and other abusive practices)?

7. Do Participants have the ability to share information with domestic and/or foreign regulatory authorities?

8. How are foreign Participants treated (e.g.,a special recognition category, an exclusion or an exemption from registration)?

1. Does the regulatory framework include requirements for organized markets, electronic execution facilities, and/or other types of markets for Swaps (hereinafter referred to as “Markets”)?

2. What are the registration or licensing requirements for such Markets?

3. Are any Markets excluded or exempted from such registration or licensing requirements?

4. What is the process for updating, withdrawing, or terminating such registration or exempting from such registration?

5. What are the ongoing regulatory responsibilities of such Markets (e.g.,access, surveillance, transparency, compliance, recordkeeping)?

6. Do Markets have the ability to share information with domestic and/or foreign regulatory authorities?

7. How are foreign Markets treated (e.g.,a special recognition category, an exclusion or an exemption from registration)?

1. Does the regulatory framework include requirements for central counterparties that provide clearing and settlement services for Swaps?

2. What are the registration or licensing requirements for such central counterparties?

3. Who is excluded or exempted from such registration or licensing requirements?

4. What is the process for updating, withdrawing, or terminating such registration or exempting from such registration?

5. What are the ongoing regulatory responsibilities of such central counterparties (e.g.,financial resources, risk management, safeguards against member or participant default, authority in the event of a default, recordkeeping)?18

6. Do such central counterparties have the ability to share information with domestic and/or foreign regulatory authorities?

7. How are foreign central counterparties treated (e.g.,a special recognition category, an exclusion or an exemption from registration)?

1. Does the regulatory framework include requirements for data repositories for Swaps?19

2. What are the registration or licensing requirements for such data repositories?

3. Who is excluded or exempted from such registration or licensing requirements?

4. What is the process for updating, withdrawing, or terminating such registration or exempting from such registration?

5. What are the ongoing regulatory responsibilities of such data repositories (e.g.,timing of reporting to the public, recordkeeping)?

6. Are such data repositories required to use a specified data standard when they provide data to regulatory authorities and, if so, what standard is required?

7. Do such data repositories have the ability to share information with domestic and/or foreign regulatory authorities?

8. How are foreign data repositories treated (e.g.,a special recognition category, an exclusion or an exemption from registration)?

9. What are the regulatory requirements in connection with data reporting for entities participating in the Swap market, such as counterparties or Participants (e.g.,maintaining records, reporting data to a repository, real-time reporting to the public, providing information to domestic and foreign regulatory authorities)?

1. Across jurisdictions, for any or all items listed above, which areas of regulation are similar and which areas are different?

2. In viewing the existing laws, institutions, and enforcement mechanisms of each respective jurisdiction as a whole, are such similarities and differences appropriate and desirable for regulatory purposes, or do certain aspects of a particular jurisdiction's Swap market warrant a different regulatory approach?

3. What are the potential costs and benefits (in terms of investor protection, market efficiency, competition, or other factors) that may arise from further consistency/harmonization of regulations across borders?

4. How should consistency in regulation across jurisdictions be measured and are there factors other than the harmonized text of a regulation that should be taken into consideration when assessing the degree to which cross-border regulatory harmonization has been implemented in practice?

5. Assuming that a theoretically “optimal” set of regulations for a particular jurisdiction might take into consideration elements unique to a specific market in ways that might make cross-border harmonization difficult, to what extent do the benefits of greater regulatory harmonization across borders outweigh the costs associated with having regulations that might be less tailored to a particular market's circumstances? In what areas do you believe the benefits of harmonization most outweigh any potential downsides?20 Are there any areas where you believe the likely benefits of “optimal” market-specific regulation outweigh the likely benefits of harmonization?

6. In the United States, what steps should or could be taken to better harmonize statutory requirements under the Dodd-Frank Act with statutory requirements implemented in other jurisdictions?

7. In the United States, what steps could be taken to harmonize CFTC or SEC regulations with regulations promulgated by authorities in other jurisdictions?

1. Please identify major organized markets and electronic execution facilities (and the Swaps-related regulator(s) for each) for the trading of Swaps.

a. For each market or facility, please provide a listing and description of the major contract classes and subclasses, such as credit default swaps (CDS),21 equity swaps, currency swaps, interest rate swaps (IRS),22 and commodity swaps;

b. For classes and subclasses of contracts identified in paragraph a above, please provide:

i. The trading volumes in 2009, 2010, and year-to-date; and

ii. The outstanding notional values at year-end 2008, 2009, 2010, and the most recent available.

2. Please identify major dealers participating in Swap markets (and the Swap-related regulator(s) for each).

3. Please identify major central counterparties (and the Swap-related regulator(s) for each) for the clearing of Swaps.

a. For each central counterparty, please provide a listing and description of the major classes and subclasses of cleared Swap contracts, such as CDS, equity swaps, currency swaps, IRS, and commodity swaps;

b. For classes and subclasses of contracts identified in paragraph a above, please provide:

i. The clearing volumes for 2009, 2010, and year-to-date; and

ii. The outstanding notional values at year-end 2008, 2009, 2010, and the most recent available;

c. For each central counterparty, please provide:

i. A description of the method used to clear Swaps;

ii. A description of the systems used to establish margin on individual Swaps and on Swap portfolios; and

iii. The name of each major clearing member of the central counterparty (and the Swap-related regulator(s) for each).

U.S. Federal regulations governing the protection of human subjects in research have been in existence for more than three decades. Twenty years have passed since the “Common Rule,” (codified at Subpart A of 45 CFR part 46) was adopted by 15 U.S. Federal departments and agencies in an effort to promote uniformity, understanding, and compliance with human subject protections.1

Existing regulations governing the protection of human subjects in Food and Drug Administration (FDA)-regulated research (21 CFR parts 50, 56, 312, and 812) are separate from the Common Rule but include similar requirements.

The history of contemporary human subjects protections began in 1947 with the Nuremberg Code, developed for the Nuremberg Military Tribunal as standards by which to judge the human experimentation conducted by the Nazis. The Code captures many of what are now taken to be the basic principles governing the ethical conduct of research involving human subjects.

Similar recommendations were made by the World Medical Association in its Declaration of Helsinki: Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects, first adopted in 1964 and subsequently revised many times.

Basic regulations governing the protection of human subjects in research supported or conducted by HHS (then the Department of Health, Education and Welfare) were first published in 1974. In the United States, a series of highly publicized abuses in research led to the enactment of the 1974 National Research Act (Pub. L. 93-348), which created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (National Commission). One of the charges to the National Commission was to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines to assure that such research is conducted in accordance with those principles. In 1979, the National Commission published “Ethical Principles and Guidelines for the Protection of Human Subjects of Research,” also known as the Belmont Report (http://www.hhs.gov/ohrp/policy/belmont.html) which identified three fundamental ethical principles for all human subjects research—respect for persons, beneficence, and justice.

Based on the Belmont Report and other work of the National Commission, HHS revised and expanded its regulations for the protection of human subjects in the late 1970s and early 1980s. The HHS regulations are codified at 45 CFR part 46, subparts A through E. The statutory authority for the HHS regulations derives from 5 U.S.C. 301; 42 U.S.C. 300v-1(b); and 42 U.S.C. 289.

In 1991, 14 other Federal departments and agencies joined HHS in adopting a uniform set of rules for the protection of human subjects, the “Common Rule,” identical to subpart A of 45 CFR part 46 of the HHS regulations.

The Common Rule requires that Federally funded investigators in most instances obtain and document the informed consent of research subjects, and describes requirements for institutional review board (IRB) membership, function, operations, research review, and recordkeeping. The regulations also delineate criteria for, and levels of, IRB review. Currently, except for human subjects research thatis determined to be exempt from the regulations, Federally funded research involving human subjects is reviewed by an IRB in one of two ways: (1) By a convened IRB, or (2) through an expedited review process.

Since the Common Rule was developed, the landscape of research activities has changed dramatically, accompanied by a marked increase in the volume of research. It is estimated that total spending on health-related research and development by the drug industry and the Federal government has tripled since 1990.2While traditional biomedical research conducted in academic medical centers continues to flourish, many studies are now also conducted at community hospitals, outpatient clinics, or physician-based practices. Clinical research is regularly conducted at multiple institutions across the U.S. and other countries. Recruitment firms, bioinformatics specialists, clinical trial coordinating centers, protocol developers, data analysts, contract research organizations (CROs), data and safety monitoring committees, community-based organizations, and other entities have joined investigators and sponsors as part of the clinical research enterprise.

Research has also increased, evolved, and diversified in other areas, such as national security, crime and crime prevention, economics, education, and the environment, using a wide array of methodologies in the social sciences and multidisciplinary studies. The application of technologies such as functional magnetic resonance imaging in neuroscience has led to substantial advances in the understanding of human physiology, cognition, and behavior. The advent of sophisticated computer software programs, the Internet, and mobile technology have created new areas of research activity, particularly within the social and behavioral sciences, exponentially increasing the amount of information available to researchers, while providing the means to access and analyze that information. In many areas of society, researchers are being called upon to provide evidence to more effectively guide social policy and practices.

The rapid growth and expansion of human subjects research has led to many questions about whether the current regulatory framework is adequate and appropriate for the protection of human subjects in the 21st century. Furthermore, decades of experience have revealed a great deal about the functioning—and limitations—of existing regulations, and prompted critical evaluations by the Institute of Medicine (IOM),3 4the U.S. Government Accountability Office,5 6 7and many scholars.8 9 10Federal consideration of such revisions to the regulatory schema, in addition to the issues that suggest a need for revision, is not without precedent. In its 2001 concluding report, the National Bioethics Advisory Commission (NBAC) made 30 recommendations that addressed areas including the scope and structure of the oversight system, the level of review applied to research, emphasizing the informed consent process, documentation and waiver of informed consent, protecting privacy and confidentiality, adverse event reporting, and review of cooperative or multi-site research studies.11NBAC's recommendations are one source for the revisions in the Common Rule currently being considered. Addressing these considerations now is timely and consistent with the President's Executive Order requiring Federal agencies to review existing significant regulations to determine whether they should be modified, streamlined, expanded, or repealed to make the agency's regulatory program more effective or less burdensome in achieving the regulatory objective.12

The concerns about the current Common Rule can roughly be categorized into seven areas. First, the system has been criticized as not adequately calibrating the review process to the risk of research. Critics have raised concerns that some IRBs spend considerable time reviewing minimal risk research, and that some IRBs have a tendency to overestimate the magnitude and probability of reasonably foreseeable risks.13Because significantly more research studies require convened IRB review, this greater IRB workload diverts time and resources from review of research that poses greater risks, theoretically resulting in inadequate attention to research that could seriously harm subjects.14

Questions have been raised about the appropriateness of the review process for social and behavioral research.15 16 17 18The nature of the possible risks to subjects is often significantly different in many social and behavioral research studies as compared to biomedical research, and critics contend that the difference is not adequately reflected in the current rules. While physical risks generally are the greatest concern in biomedical research, social and behavioral studies rarely pose physical risk but may pose psychological or informational risks. Some have argued that, particularly given the paucity of information suggesting significant risks to subjects in certain types of survey and interview-based research, the current system over-regulates such research.19 20 21Further, many critics see little evidence that most IRB review of social and behavioral research effectively does much to protect research subjects from psychological or informational risks.22Over-regulating social and behavioral research in general may serve to distract attention from attempts to identify those social and behavioral research studies that do pose threats to the welfare of subjects and thus do merit significant oversight.

Second, critics have commented about the inefficiencies of review by multiple IRBs for multi-site studies, which add bureaucratic complexity to the review process and delay initiation of research projects without evidence that multiple reviews provide additional protections to subjects.23There also has been a concern that the current multiple review system might actually be leading to weaker protections for subjects than if there were fewer reviews but greater responsibility on the part of the IRBs involved.

Third, questions have been raised about the extent and quality of the protections afforded by current informed consent requirements and practices. A variety of critics have highlighted problems with consent forms. In some research studies, consent forms have become lengthy and are often written in highly technical terms.24 25 26Many also claim that consent forms have evolved to protect institutions rather than to actually provide salient information to potential human subjects.27This is especially problematic if the forms fail to include information that is crucial for making a decision about participation, including appropriate information about financial relationships between researchers and study sponsors, or are written in a way that potential subjects are likely to fail to notice such information. At the same time, others raise concerns about the rigid application of written consent to all forms of research, especially research involving surveys, interviews, focus groups, or other similar methodologies.28In these types of research, it has been argued that written documentation of consent is unnecessary and that answering questions should be sufficient to indicate individual consent to participate.29

Fourth, increasing use of genetic information, existing (i.e., stored) biospecimens, medical records, and administrative claims data in research has changed the nature of the risks andbenefits of research participation. Risks related to these types of research are not physical but informational (e.g., resulting from the unauthorized release of information about subjects). The Privacy Rule promulgated under the Health Insurance Portability and Accountability Act of 1996 (HIPAA)30addresses some of these informational risks by imposing restrictions on how certain identifiable health information collected by health plans, healthcare clearinghouses, and certain healthcare providers (“covered entities”) may be used and disclosed, including for research. In addition, the HIPAA Security Rule requires that these entities implement certain administrative, physical, and technical safeguards to protect this information when in electronic form from unauthorized use or disclosure. However, the HIPAA Rules apply only to covered entities (and in certain respects to their business associates), and not all investigators are part of a covered entity (or business associates of a covered entity). Separate from the HIPAA Rules, the Privacy Act of 1974, as amended (5 U.S.C. 552a31) requires Federal agencies to protect personally identifiable information in their possession and control. However, it does not apply to non-Federal researchers.

Fifth, the monitoring and evaluation of the current system for protecting human subjects has been criticized.32There is concern that current regulations do not provide an ideal mechanism for the collection of information that would allow evaluation of the effectiveness of the research oversight system in protecting human subjects.

Sixth, concerns have been expressed that the current regulatory system does not adequately protect all research subjects.33For instance, only some research studies funded by certain Federal agencies or those that involve the development of products subject to regulation by the FDA, are subject to the Common Rule or similar protections. As a result, there are many studies that are not subject to any such Federal oversight, even though they may involve substantial risks to the subjects.

Seventh, the multiple, differing regulatory requirements that can apply to a single research study have been criticized as complex, inconsistent, and lacking in clarity, which results in unwarranted variability across institutions and their IRBs in how the requirements are interpreted and implemented.34For example, Federal agencies that have adopted the Common Rule have issued guidance and developed norms of implementation that sometimes differ and may, in certain instances, even conflict with guidance from other Common Rule agencies. Similarly, the overlapping and sometimes, arguably, inconsistent requirements of the Common Rule and the HIPAA Privacy Rule have been criticized as being overly complex, causing confusion and frustration among investigators, IRBs, and others trying to comply with both sets of requirements.35

In response to these various criticisms, we propose changes to the following seven aspects of the current regulatory framework. The fundamental goal is to enhance the effectiveness of the research oversight system by improving the protections for human subjects while also reducing burdens, delays, and ambiguity for investigators and research subjects.

1. Refinement of the existing risk-based regulatory framework (Section II);

2. Utilization of a single IRB review of record for domestic sites of multi-site studies (Section III);

3. Improvement of consent forms and the consent process (Section IV);

4. Establishment of mandatory data security and information protection standards for all studies that involve identifiable or potentially identifiable data (Section V);

5. Establishment of an improved, more systematic approach for the collection and analysis of data on unanticipated problems and adverse events (Section VI);

6. Extension of Federal regulatory protections to all research, regardless of funding source, conducted at institutions in the U.S. that receive some Federal funding from a Common Rule agency for research with human subjects (Section VII); and

7. Improvement in the harmonization of regulations and related agency guidance (Section VIII).

We believe the proposals we are considering uphold and better reflect the ethical principles upon which the Common Rule is based. We recognize that this ANPRM is both lengthy and detailed. However this level of detail reflects the importance and types of changes that have been proposed by the Institute of Medicine (IOM), NBAC, and other commentators and are now being considered for adoption. Comment is now sought on these proposals and on the broader question of how to modernize, simplify, and enhance the current system. The intent is to revise the Common Rule36recognizing that other laws and regulations, such as the other subparts of the HHS human subjects protection regulations (Subparts B, C, and D, which deal with particular populations of vulnerable subjects, and Subpart E of 45 CFR part 46), FDA regulations, and the HIPAA Privacy Rule most likely will be affected and will need to be harmonized, as appropriate, with any proposed regulatory changes made to the Common Rule.

As we consider how the current regulations governing human subjects research should be revised, we will take into account the deliberations of the Presidential Commission for the Study of Bioethical Issues. We will also consider the public comments received on the request for information that the Commission issued on March 2, 2011, that sought public comment on the current Federal and international standards for protecting the health and well-being of participants in scientific studies supported by the Federal Government.37

Currently, the Common Rule provides for several tiers of independent review of research studies, as follows:

1. The highest level of review, applied to most studies involving more than minimal risk and to many studies involving no more than minimal risk, is review by a convened IRB.

2. The next level of review isexpeditedreview.38This generally involves review by a single IRB member. A study is eligible for expedited review if the research appears on a list published by the Secretary of HHS of categories of research eligible for such review, and the research is found by the reviewer(s) to involve no more than minimal risk.

3. Certain studies areexemptfrom IRB review.39The regulations specify six “exemption” categories; a study must fall within one or more of these six categories to be exempted from IRB review altogether. Although these studies are not subject to the Common Rule, and no review is actually required, guidance issued by the Office for Human Research Protection (OHRP) recommends that there be some type of review by someone other than the investigator to confirm that the study qualifies as exempt, and many institutions do indeed impose such a requirement.40

There has been criticism about this regulatory framework for reviewing research studies. Although it does attempt to match the level of review to the type of risks posed by a study, many argue that it does so in a less than ideal manner. For instance, many surveys that are unlikely to lead to any harm to subjects nonetheless undergo review by a convened IRB.41Further, argumentshave been made that some of the lines drawn between review categories are vague and difficult to apply.42Studies have shown that different levels of review are sometimes required by different IRBs for the same study.43 44

In response to these concerns, the IOM report on research protections recommended revising the current approach: “The degree of scrutiny, the extent of continuing oversight, and the safety monitoring procedures for research proposals should be calibrated to a study's degree of risk. Minimal risk studies should be handled diligently, but expeditiously, while studies involving high risk should receive the extra time and attention they require.”45The IOM surmised that this would reduce burdens that do not translate into meaningful protections of human subjects and would limit unnecessary drain on resources, enabling IRBs to give more attention to high risk studies and critical protection activities while improving the efficiency with which research projects are reviewed and overseen.

This ANPRM describes potential refinements to the current review framework intended to ensure that protections are commensurate with the level of risk of the research study. Five of the most significant changes being considered are summarized below, followed by a more detailed explanation of the proposals:

1. Establishing mandatory data security and information protection standards for identifiable information and rules protecting against the inappropriate re-identification of de-identified information that is collected or generated as part of a research study to minimize informational risks and thereby eliminate the need for IRBs to review informational risks of the research. For purposes of the Common Rule, we are considering adopting the HIPAA standards regarding what constitutes individually identifiable information, a limited data set, and de-identified information, in order to harmonize these definitions and concepts. Since this provision would cover studies currently considered “exempt” from the current regulations, a change in terminology would need to be considered (see Section B(3), below).

2. Revising the rules for continuing review. Continuing review would be eliminated for all minimal risk studies that undergo expedited review, unless the reviewer explicitly justifies why continuing review would enhance protection of research subjects. For studies initially reviewed by a convened IRB, continuing review would not be required, unless specifically mandated by the IRB, after the study reaches the stage where procedures are limited to either (i) analyzing data (even if it is identifiable), or (ii) accessing follow-up clinical data from procedures that subjects would undergo as part of standard care for their medical condition or disease (such as periodic CT scans to monitor whether the subjects' cancers have recurred or progressed).

3. Revising the regulations regarding expedited review to provide for mandatory regular updating of the list of categories of research that may be reviewed under this mechanism, creating a presumption that studies utilizing only research activities that appear on that list are indeed minimal risk, and providing for streamlined document submission requirements for review.

4. Revising the regulations regarding studies currently considered exempt to, among other things:

i. Require that researchers file with the IRB a brief form (approximately one page) to register their exempt studies, but generally allow the research to commence after the filing;

ii. Clarify that routine review by an IRB staff member or some other person of such minimal risk exempt studies is neither required nor even recommended;

iii. Expand the current category 2 exemption (45 CFR 46.101(b)(2)) to include all studies involving educational tests, surveys, interviews, and similar procedures so long as the subjects are competent adults, without any further qualifications (but subject to the data security and information protection standards discussed above);

iv. Add a new category for certain types of behavioral and social science research that goes beyond using only survey methodology, but nonetheless involves only specified minimal risk procedures, so long as the subjects are competent adults (but subject to the data security and information protection standards discussed above);

v. Expand the current category 4 exemption (regarding the collection or study of existing data, documents, records and biospecimens) (45 CFR 46.101(b)(4)) to include all secondary research use of identifiable data and biospecimens that have been collected for purposes other than the currently proposed research, provided that specified new consent requirements are satisfied. This expanded category 4 exemption would apply to the secondary use of identifiable data and biospecimens even if such data or biospecimens have not yet been collected at the time of the research proposal, and even if identifiers are retained by the researcher (instead of requiring at least expedited review, as is currently the case); and

vi. Require random retrospective audits of a sample of exempt studies to assess whether the exemptions were being appropriately applied.

5. Generally requiring written consent for research use of any biospecimens collected for clinical purposes after the effective date of the new rules (such as research with excess pathological specimens). Such consent could be obtained by use of a brief standard consent form agreeing to generally permit future research. This brief consent could be broad enough to cover all biospecimens to be collected related to a particular set of encounters with an institution (e.g.hospitalization) or even to any biospecimens to be collected at any time by that institution. These studies using biospecimens collected for clinical purposes would also fall under the expanded and revised exempt categories described in (4), above, and thus would not require IRB review or any routine administrative review but would be subject to the data security and information protection standards discussed above. This change would conform the rules for research use of clinically-collected biospecimens with the rules for biospecimens collected for research purposes. The general rule would be that a person needs to give consent, in writing, for research use of their biospecimens, though that consent need not be study-specific, and could cover open-ended future research.

Each of these five proposals and other proposed changes are discussed below. We seek comments and recommendations on the specific changes being considered.

Most research risks to the individual can be categorized into one of three types: physical, psychological, and informational risks. (Although there are other harms, such as legal, social, and economic harms, these can usually be viewed as variations on those core categories.) Physical risks are the most straightforward to understand—they are characterized by short term or long term damage to the body such as pain, bruising, infection, worsening current disease states, long-term symptoms, or even death. Psychological risks can include unintentional anxiety and stress including feelings of sadness or even depression, feelings of betrayal, and exacerbation of underlying psychiatric conditions such as post traumatic stress disorder. Psychological risks are notnecessarily restricted to psychiatric or social and behavioral research.

Informational risks derive from inappropriate use or disclosure of information, which could be harmful to the study subjects or groups. For instance, disclosure of illegal behavior, substance abuse, or chronic illness might jeopardize current or future employment, or cause emotional or social harm. In general, informational risks are correlated with the nature of the information and the degree of identifiability of the information. The majority of unauthorized disclosures of identifiable health information from investigators occur due to inadequate data security.46

Currently, IRBs evaluate all three categories of risk. IRB review or oversight of research posing informational risks may not be the best way to minimize the informational risks associated with data on human subjects. It is not clear that members have appropriate expertise regarding data protections. The current assumption that IRBs are responsible for reviewing and adequately addressing informational risks appears to lead to inconsistent protections and some cases in which there are inadequate protections for the information.47Furthermore, review of informational risk is an inefficient use of an IRB's time. Standardized data protections, rather than IRB review, may be a more effective way to minimize informational risks.

Accordingly, we are considering mandatory standards for data security and information protection whenever data are collected, generated, stored, or used. The level of protection required by these standards would be calibrated to the level of identifiability of the information, which would be based on the standards of identifiability under the HIPAA Privacy Rule. (These standards are discussed in detail in Section V.) With these standards in place to minimize the inappropriate use or disclosure of research information, the criteria for IRB approval of studies would be modified so that an IRB would no longer be responsible for assessing the adequacy of a study's procedures for protecting against informational risks. This change would not alter the IRB's role in assuring that the ethical principles of respect for persons, beneficence and justice are adequately fulfilled.

To improve the link between the type of review and the level of risk posed by research studies, we are considering the changes described below. Since there would be new mandatory standards for data security and information protection to address informational risks, only non-informational risks would be considered in determining the level of risk posed by research studies.

The requirement that research involving greater than minimal risk be reviewed by a convened IRB would not be changed from the current system. Other changes considered in this ANPRM, such as improvements in the ability of IRBs to require better consent forms, may enhance the effectiveness of such review.

With regard to continuing review of such studies, we are considering one change. Where the remaining activities in a study are limited to either (i) data analysis (even if identifiers are retained) or (ii) accessing follow-up clinical data from procedures that subjects would undergo as part of standard care for their medical problems (such as periodic CT scans to monitor whether the subjects' cancers have recurred or progressed), the default would be that no continuing review by an IRB would be required. The IRB would have the option to make a determination that overrides this default. Researchers would still have the current obligations to report various developments (such as unanticipated problems, or proposed changes to the study) to the IRB. This would be a change from the current rules, which require at least expedited IRB review of the activities described in (i) and (ii) directly above. By eliminating the requirement for continuing review of these activities, this change would allow for more effective use of IRBs' time by enabling the IRB to focus on reviewing information that is necessary to ensure protections of research subjects.

Under the Common Rule, a new research study can receive expedited review if the research activities to be conducted appear on the list of activities published by the Secretary of HHS that are eligible for such review (http://www.hhs.gov/ohrp/policy/expedited98.html), and is found by the reviewer(s) to involve no more than minimal risk. For research that will receive expedited review, three changes are being considered: (1) Revising the criteria that make research studies eligible for expedited review, (2) eliminating the requirement of routine annual continuing review of expedited studies, and (3) streamlining submission requirements.

Currently, a reviewer must determine that the study includes only research activities that appear in the list promulgated by the Secretary as eligible for expedited review, that the study as a whole involves no more than minimal risk, and that all of the criteria listed in 45 CFR 46.111 are met. We are considering changes in each of these three areas:

We are considering initially updating the current list of research activities, which was last updated in 1998. We also are considering mandating that a standing Federal panel periodically (such as every year or every two years) review and update the list, based on a systematic, empirical assessment of the levels of risk. This would provide greater clarity about what would be considered to constitute minimal risk, and create a process that allows for routinely reassessing and updating the list of research activities that would qualify as minimal risk.

As noted, currently a study can undergo expedited review if all of the activities involved appear on the list of eligible research activities and the study is found to be minimal risk. The current definition of minimal risk encompasses research activities where “the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”48Since the listed activities are ones with which there is a great deal of experience, and their risks are well known, it should be a rare instance in which a study that uses only the listed activities will, as a whole, pose more than minimal risk. Yet many studies which use only those activities—particularly those in the social and behavioral field—are frequently required to undergo review by a convened IRB.49We are accordingly considering providing a default presumption in the regulations that a study which includes only activities on the list is a minimal risk study and should receive expedited review. A reviewer would have the option of determining that the study should be reviewed by a convened IRB, when thatconclusion is supported by the specific circumstances of the study.

Given that a study is eligible for expedited review only if it involves minimal risk, and only if its activities are limited to those that appear on the published list, it is not clear that the study should be required to meet all of the criteria for IRB approval at 45 CFR 46.111. Currently, before an IRB may approve a research study, including research that is being reviewed under an expedited procedure, the IRB must find that the following criteria have been satisfied as required by 45 CFR 46.111:

1. Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

2. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

3. Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.

4. Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by § 46.116.

5. Informed consent will be appropriately documented, in accordance with, and to the extent required by § 46.117.

6. When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

7. When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

8. When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

Accordingly, we are considering whether all of those criteria should still be required for approval of studies that qualify for expedited review, and if not, which ones should not be required.

We believe that annual continuing review of research studies involving only activities that are already well-documented to generally involve no more than minimal risk may provide little if any added protection to subjects, and that it may be preferable for IRB resources to be devoted to research that poses greater than minimal risk.

Accordingly, we are considering changing the default to require no continuing review for studies that qualify for expedited review. Researchers would still be obligated to obtain IRB approval for changes to a study and to report to the IRB unanticipated problems and other similar items that are currently required to be reported.

For any specific study, the reviewer would have the authority to make a specific determination and provide a justification about why continuing review is appropriate for that minimal risk study, and to specify how frequently such review would be required.

Under the current Federal regulations, researchers typically must submit the same documents including a detailed protocol, informed consent documents, and any other supporting documents, regardless of whether the study will be reviewed by a convened IRB or be approved by the expedited review process. Although it is important to document why research qualifies for expedited review, it is unclear whether the time and effort expended in such preparation activities result in increased benefit in terms of protecting subjects.

Ideally, standard templates for protocols and consent forms and sample versions of those documents that are specifically designed for use in the most common types of studies would facilitate expedited review. Such forms would need to be carefully designed to eliminate those elements that are of relevance only in studies that pose greater than minimal risks and to substantially reduce the current burden of researchers involved in producing these documents and of the IRB members who review them.

Comments and recommendations are requested on any of the above proposals under consideration and on the following specific questions:

Question 1:Is the current definition of “minimal risk” in the regulations (45 CFR 46.102(i)—research activities where “the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests”)—appropriate? If not, how should it be changed?

Question 2:Would the proposals regarding continuing review for research that poses no more than minimal risk and qualifies for expedited review assure that subjects are adequately protected? What specific criteria should be used by IRBs in determining that a study that qualifies for expedited initial review should undergo continuing review?

Question 3:For research that poses greater than minimal risk, should annual continuing review be required if the remaining study activities only include those that could have been approved under expedited review or would fall under the revised exempt (Excused) category described in section 3, below (e.g.,a study in which a physical intervention occurred in the first year, all subjects have completed that intervention, and only annual written surveys are completed for the next five years)?

Question 4:Should the regulations be changed to indicate that IRBs should only consider “reasonably foreseeable risks or discomforts”?

Question 5:What criteria can or should be used to determine with specificity whether a study's psychological risks or other nonphysical, non-information risks, are greater than or less than minimal?

Question 6:Are there survey instruments or specific types of questions that should be classified as greater than minimal risk? How should the characteristics of the study population (e.g.mental health patients) be taken into consideration in the risk assessment?

Question 7:What research activities, if any, should be added to the publishedlist of activities that can be used in a study that qualifies for expedited review? Should any of the existing activities on that list be removed or revised? For instance, should the following be included as minimal risk research activities:

• Allergy skin testing.

• Skin punch biopsy (limited to two per protocol).

• Additional biopsy during a clinical test (e.g.,performing an extra colonic biopsy in the course of performing a routine colonoscopy).

• Glucose tolerance testing among adults.

Question 8:Should some threshold for radiological exams performed for research purposes, that is calibrated to this background level of exposure, be identified as involving no more than minimal risk?

Question 9:How frequently should a mandatory review and update of the list of research activities that can qualify for expedited review take place? Should the list be revised once a year, every two years, or less frequently?

Question 10:Which, if any, of the current criteria for IRB approval under 45 CFR 46.111 should not apply to a study that qualifies for expedited review?

Question 11:What are the advantages of requiring that expedited review be conducted by an IRB member? Would it be appropriate to instead allow such review to be done by an appropriately trained individual, such as the manager of the IRB office, who need not be a member of the IRB? If not, what are the disadvantages of relying on a non-IRB member to conduct expedited review? If so, what would qualify as being “appropriately trained”? Would the effort to make sure that such persons are appropriately trained outweigh the benefits from making this change?

Question 12:Are there other specific changes that could be made to reduce the burden imposed on researchers and their staffs in terms of meeting the requirements to submit documents to an IRB, without decreasing protections to subjects? Are there specific elements that can be appropriately eliminated from protocols or consent forms? Which other documents that are currently required to be submitted to IRBs can be shortened or perhaps appropriately eliminated? Conversely, are there specific additions to protocols or consent forms beyond those identified in this notice that would meaningfully add to the protection of subjects? What entity or organization should develop and disseminate such standardized document formats?

Question 13:Given the problems with the current system regarding wide variations in the substance of IRB reviews, would it be appropriate to require IRBs to submit periodic reports to OHRP in the instances in which they choose to override the defaults described in Sections B(1), B(2)(a)(ii), and B(2)(b) above? Should IRBs have to report instances in which they require continuing review or convened IRB review of a study which involves only activities identified as being on the list of those eligible for expedited review? If an IRB that chose to override these defaults was required to submit a report to OHRP, would this provide useful information about any lack of appropriate consistency among IRBs so that clarifying guidance could be provided as needed, or provide useful information to OHRP about the possible need to revise the expedited review list or the continuing review requirements?

We are considering revising the category of exempt research in ways that would both increase protections and broaden the types of studies covered. Specifically, although still not subject to IRB review, these studies would be subject to the new data security and information protection standards described in Section V, and in some cases, informed consent would be required as described in Section (c) below. Given that these studies would no longer be fully exempt from the regulations, they could more accurately be described as “Excused” from being required to undergo some form of IRB review (which terminology we will use hereafter in this ANPRM). (Note:FDA's statute requires IRB review and approval of any clinical device investigation. 21 U.S.C. 360j(g)(3)(A) and (B). Therefore, FDA-regulated studies involving specimens will not be eligible for the new Excused category and will remain subject to IRB oversight.) The new data security and information protection standards make it possible to increase the coverage of the Excused category, thereby reducing the burden on researchers conducting minimal risk studies, while actually increasing the protections for participants.

Some specific aspects of these changes are described here:

The existing six exemption categories would be retained as part of the new Excused category. The current criteria for defining those categories would be reviewed and revised appropriately so that they are clear enough that researchers could readily determine whether a study qualified to be in these categories. In addition, the following significant expansions of the current categories are being considered:

1. Limitations specified in the current exempt category 2 (research involving educational tests, surveys, focus groups, interviews, and similar procedures) would no longer be necessary when these studies are conducted with competent adults. The current exemption 2 under 45 CFR 46.101(b)(2) states: “Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (i) Information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (ii) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.” Specifically it is proposed that the language that appears after the word “unless” in provisions (i) and (ii) would be deleted. Thus, research conducted with competent adults, that involve educational tests, surveys, focus groups, interviews, and similar procedures would qualify for the new Excused category, regardless of the nature of the information being collected, and regardless of whether data is recorded in such a manner that subjects can be identified. It is proposed that the limitations on the current category 2 be eliminated since these studies would be conducted with competent adults and because these studies would now be subject to standard data security and information protection standards. The term “competent” as used here and throughout this ANPRM refers to adults who would be able to provide “legally effective informed consent,” as currently required by 45 CFR 46.116. This concept has been included in the Common Rule for decades, and is routinely implemented by researchers, generally with little difficulty. For example, researchers who currently conduct non-exempt surveys must make determinations regarding which subjects to include in their studies, and we are not aware of any evidence that suggests making such determinations has been a problem.

2. We are considering whether to include on the list of Excused studies certain types of social and behavioral research, conducted with competentadults, that would involve specified types of benign interventions beyond educational tests, surveys, focus groups, interviews, and similar procedures, that are commonly used in social and behavioral research, that are known to involve virtually no risk to subjects, and for which prior review does little to increase protections to subjects. These would be methodologies which are very familiar to people in everyday life and in which verbal or similar responses would be the research data being collected. For example, a researcher might ask subjects to watch a video, or read a paragraph or solve puzzles, and then ask them some questions to elicit word associations or time performance of activities. The specific methodologies might be spelled out in regulations, or they might be promulgated via a periodic mechanism to announce and update lists similar to the list that is published for activities that allow a study to be expedited.

3. Limitations specified in the current exempt category 4 (research involving the use of existing information or biospecimens) would be eliminated. The current exemption 4 under 45 CFR 46.101(b)(4) states: “Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.” Specifically, it is proposed that the category would be revised to clarify that the word “existing” means collected for purposes other than the proposed research and not that all of the data or biospecimens need exist at the time the study commenced. In addition, the limitation that the researcher cannot record and retain information that identifies the subjects would be eliminated. In other words, research that only involves the use of data or biospecimens collected for other purposes, even if the researcher intends to retain identifiers, would now come within the new Excused category, unless there are plans to provide individual results back to the subjects. Studies that include a plan to provide to subjects individual results from the analysis of their biospecimens or data would not qualify for this proposed Excused category.

As described below in Section (c), it is contemplated that certain relatively flexible consent requirements would be imposed on some of these studies. (See Table 1 at the end of Section V for a summary of this proposal.)

We are considering a mechanism to track Excused research, and to audit only a small but appropriate portion of such research, because it would still be subject to other regulatory protections, such as the proposed data security and information protection standards and certain consent requirements. In addition, such a mechanism to track and audit Excused research will also enable institutions to assure that the research does indeed meet the criteria for inclusion in the Excused category. (That is all that an audit would in most cases involve: a brief review of the registration form, similar to what many institutions currently do when they determine whether a study is exempt.) Key to this would be a requirement that researchers register their study with an institutional office by completing a brief form. This would make the institution aware of the research and identify the study's principal investigator. In addition the institution could choose to review some of the submissions at the time they are filed (and we contemplate that this would only be done in a relatively small percentage of the filings) and if deemed appropriate, require that the study be sent for expedited review or, in exceptionally rare cases, convened IRB review.

The proposed auditing requirement is intended to encourage institutions to use the regulatory flexibility proposed for the Excused category of research. Rather than maintaining many institutions' current practice of routinely requiring that research that meets the current exemption categories undergo some type of review before it is permitted to proceed, the proposed auditing requirement would provide institutions with information needed to assess their compliance with the new Excused category without unnecessarily subjecting all such research to either prospective review, or even routine review sometime after the study is begun.

We are contemplating that the consent practices for studies currently designated as exempt would remain in most respects unchanged for research falling within the new Excused category, even if some of those practices are clarified. For example, oral consent without written documentation would continue to be acceptable for many research studies involving educational tests, surveys, focus groups, interviews, and similar procedures.

However, we are considering the following revisions to the consent rules for the category of Excused research that involves the use ofpre-existing data or biospecimensas described in Section 3(a)(3) above.

First, written general consent (as described below) would be required for the research use of suchbiospecimens.This would be a change from the current rules which allow research without consent when a biospecimen is used for research under conditions where the researcher does not possess information that would allow them to identify the person whose biospecimen is being studied.

Second, with regard to the researchers' use ofpre-existing data(i.e.data that were previously collected for purposes other than the currently proposed research study):

a. If the data was originally collected fornon-researchpurposes, then, as is currently the rule, written consent would only be required if the researcher obtains information that identifies the subjects. There would accordingly be no change in the current ability of researchers to conduct such research using de-identified data or a limited data set, as such terms are used in the HIPAA Rules (see Section V), without obtaining consent.

b. If the data was originally collected forresearchpurposes, then consent would be required regardless of whether the researcher obtains identifiers. Note that this would be a change with regard to the current interpretation of the Common Rule in the case where the researcher does not obtain any identifiers. That is, the allowable current practice of telling the subjects, during the initial research consent, that the data they are providing will be used for one purpose, and then after stripping identifiers, allowing it to be used for a new purpose to which the subjects never consented, would not be allowed.

In most instances, the consent requirements described above would have been met at the time that the biospecimens or data were initially collected, when the subject would have signed a standard, brief general consent form allowing for broad, future research. This brief consent could be broad enough to cover all data and biospecimens to be collected related to a particular set of encounters with an institution (e.g.hospitalization) or to any data or biospecimens to be collected at anytime by the institution. Importantly, this standardized general consent form would permit the subject to say no to all future research. In addition, there are likely to be a handful of special categories of research withbiospecimens that, given the unique concerns they might raise for a significant segment of the public, would be dealt with by check-off boxes allowing subjects to separately say yes or no to that particular type of research (e.g.,perhaps creating a cell line, or reproductive research). Participation in a research study (such as a clinical trial) could not be conditioned on agreeing to allow future open-ended research using a biospecimen. With regard to the secondary research use ofpre-existing data,on those occasions when oral consent was acceptable under the regulations for the initial data collection, it is envisioned that subjects would have typically provided their oral consent for future research at the time of the initial data collection; a written consent form would not have to be signed in that circumstance. Table 1 at the end of Section V illustrates the consent requirements for pre-existing data in the context of the data security and information protection requirements which would also apply.

Third, these changes would only be applied prospectively, not retrospectively. In other words, they would only apply to biospecimens and data that are collected after the effective date of the new rules.

And fourth, there would be rules (to be determined) that would allow for waiver of consent under specified circumstances, though those conditions would not necessarily be the same as those for other types of research.

The proposal for changes described in sections (a) through (c) above would eliminate the current practice of not allowing researchers to begin conducting such minimal risk studies until a reviewer has determined the study does indeed meet the criteria for being exempt. Such delay is not currently required by the Common Rule, and appears to slow research without adding significant protection to subjects. Instead, under the plan being considered, researchers would file with their institution or IRB a brief registration form (about one page long) that provides essential information about the study, including, for example, information about who will be the principal investigator, and the purpose of the study. The researchers would then be authorized to begin conducting the study after the filing (unless the institution chose to review that filing and determined that the research did not qualify as Excused). It would be made clear that the regulations would not require, and in fact, would discourage, having each of these registration forms undergo a comprehensive administrative review prior to commencing the study or even afterward.

Comments and recommendations are requested on any of the above proposals under consideration and on the following specific questions:

Question 14:Are these expansions in the types of studies that would qualify for this Excused category appropriate? Would these changes be likely to discourage individuals from participating in research? Might these changes result in inappropriately reduced protections for research subjects, or diminished attention to the principles of respect for persons, beneficence, and justice?

Question 15:Beyond the expansions under consideration, are there other types of research studies that should qualify for the Excused category? Are there specific types of studies that are being considered for inclusion in these expansions, that should not be included because they should undergo prospective review for ethical or other reasons before a researcher is allowed to commence the research?

Question 16:Should research involving surveys and related methodologies qualify for the Excused category only if they do not involve topics that are emotionally charged, such as sexual or physical abuse? If so, what entity should be responsible for determining whether a topic is or is not emotionally charged?

Question 17:What specific social and behavioral research methodologies should fall within the Excused category? Under what circumstances, if any, should a study qualify for the Excused category if the study involves a form of deception (and if so, how should “deception” be defined)?

Question 18:Currently some IRBs make determinations regarding whether clinical results should be returned to study participants. How should such determinations be made if the study now fits in the Excused category? Can standard algorithms be developed for when test results should be provided to participants and when they should not (e.g.,if they can be clinically interpreted, they must be given to the participants?).

Question 19:Regarding the Excused category, should there be a brief waiting period (e.g.one week) before a researcher may commence research after submitting the one-page registration form, to allow institutions to look at the forms and determine if some studies should not be Excused?

Question 20:The term “Excused” may not be the ideal term to describe the studies that will come within the proposed revision of the current category of exempt studies, given that these studies will be subject to some protections that are actually greater than those that currently exist. Might a term such as “Registered” better emphasize that these studies will in fact be subject to a variety of requirements designed to protect participants? We welcome other suggestions for alternative labels that might be more appropriate.

Question 21:Is it appropriate to require institutions holding a Federalwide Assurance to conduct retrospective audits of a percentage of the Excused studies to make sure they qualify for inclusion in this category? Should the regulations specify a necessary minimum percentage of studies to be audited in order to satisfy the regulatory requirements? Should some other method besides a random selection be used to determine which Excused studies would be audited?

Question 22:Are retrospective audit mechanisms sufficient to provide adequate protections to subjects, as compared to having research undergo some type of review prior to a researcher receiving permission to begin a study? Might this new audit mechanism end up producing a greater burden than the current system? Do researchers possess the objectivity and expertise to make an initial assessment of whether their research qualifies for the Excused category? By allowing researchers to make their own determinations, without prospective independent review, will protections for some subjects be inappropriately weakened? If allowing researchers to make such determinations without independent review would generally be acceptable, are there nonetheless specific categories of studies included in the proposed expansion for which this change would inappropriately weaken protections for subjects? And will the use of a one-page registration form give institutions sufficient information to enable them to appropriately conduct the audits?

Question 23:Under what circumstances should it be permissible to waive consent for research involving the collection and study of existing data and biospecimens as described in Section 3(a)(3) above? Should the rules for waiving consent be different if the information or biospecimens were originally collected for research purposes or non-research purposes? Should a request to waive informed consent trigger a requirement for IRB review?

Question 24:The Common Rule has been criticized for inappropriately being applied to—and inhibiting research in— certain activities, including quality improvement, public health activities, and program evaluation studies.50 51 52Regarding quality improvement, for example, these activities are in many instances conducted by health care and other organizations under clear legal authority to change internal operating procedures to increase safety or otherwise improve performance, often without the consent of staff or clients, followed by monitoring or evaluation of the effects. It is far from clear that the Common Rule was intended to apply to such activities, nor that having it apply produces any meaningful benefits to the public. Indeed, its application to such activities, and requiring IRB review and compliance with informed consent requirements, might have a chilling effect on the ability to learn from, and conduct, important types of innovation. We seek comment on whether and, if so, how, the Common Rule should be changed to clarify whether or not oversight of quality improvement, program evaluation studies, or public health activities are covered. Are there specific types of these studies for which the existing rules (even after the changes proposed in this Notice) are inappropriate? If so, should this problem be addressed through modifications to the exemption (Excused) categories, or by changing the definition of “research” used in the Common Rule to exclude some of these studies, or a combination of both? And if the definition of research were to be changed, how should the activities to be excluded be defined (e.g.,“quality improvement” or “program evaluation”)? Are there some such activities that should not be excluded from being subject to the Common Rule because the protections provided by that rule are appropriate and no similar protections are provided by other regulations? With regard to quality improvement activities, might it be useful to adopt the distinction made by the HIPAA Privacy Rule (45 CFR 164.501(1)), which distinguishes between “health care operations” and “research” activities, defining “health care operations” to include “conducting quality assessment and improvement activities, including outcomes evaluation and development of clinical guidelines, provided that the obtaining of generalizable knowledge is not the primary purpose of any studies resulting from such activities”?

Question 25:Are there certain fields of study whose usual methods of inquiry were not intended to or should not be covered by the Common Rule (such as classics, history, languages, literature, and journalism) because they do not create generalizable knowledge and may be more appropriately covered by ethical codes that differ from the ethical principles embodied in the Common Rule? If so, what are those fields, and how should those methods of inquiry be identified? Should the Common Rule be revised to explicitly state that those activities are not subject to its requirements?

Question 26:The current exempt category 5 applies to certain research and demonstration projects that are designed to study or evaluate public benefit or service programs. Is the circumstance that a particular demonstration project generates “broad” knowledge incorrectly being used as a reason to prevent certain activities (including section 1115 waivers under Medicaid) from qualifying for exempt category 5? If so, how should this exemption (as part of the new category of Excused research) best be revised to assure that it will no longer be misinterpreted or misapplied? Would broadening the interpretation of the exemption result in inappropriately increased risks to participants in research? If so, how could such risks be mitigated? Also, is there a need to update or otherwise revise the “OPRR Guidance on 45 CFR 46.101(b)(5)”?

Question 27:The Common Rule currently states (45 CFR 46.111(a)(2)) that an IRB “should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among the research risks that fall within the purview of its responsibility.” Do IRBs correctly interpret this provision as meaning that while they should be evaluating risks to the individual subjects participating in a study, it is not part of their mandate to evaluate policy issues such as how groups of persons or institutions, for example, might object to conducting a study because the possible results of the study might be disagreeable to them?53If that is not how the provision is typically interpreted, is there a need to clarify its meaning?

Question 28:For research that requires IRB approval, the Common Rule does not currently require that the researcher always be allowed some form of appeal of a decision (e.g.,disapproval of a project). Some institutions have voluntarily chosen to provide appeal mechanisms in some instances, by, for example, allowing the researcher to present the project to a different IRB, or by having it reviewed by a special “appeal” IRB that is composed of members chosen from among the membership of the institution's other IRBs. Should the Common Rule include a requirement that every institution must provide an appropriate appeal mechanism? If so, what should be considered acceptable appeal mechanisms? Should such appeal mechanisms, or different ones, be available for appeals asserting that the investigation is not research, or that the research does not require IRB approval?

Question 29:As noted above, IRBs sometimes engage in activities beyond those that are required by the regulations. For example, an IRB might review some studies for the purpose of determining whether or not they qualify for exemption (the new Excused category), or might review studies involving the analysis of data that is publicly available. Would it be helpful, in furtherance of increased transparency, to require that each time an IRB takes such an action, it must specifically identify that activity as one that is not required by the regulations?

Currently, a substantial amount of research takes place by means of multi-site studies wherein a single research study is conducted at numerous institutions. Multi-site studies are particularly common in clinical trials, survey epidemiology, and education contexts. While the Common Rule does require that each institution engaged in a multi-site research study obtain IRB approval of the study, it does not require that a separate local IRB at each institution conduct such review. (Note:While the Common Rule does not require local IRB review by each institution engaged in a multi-site research study, the statute that pertains to FDA's regulation of device investigations requires sponsors to submit the protocol to the “local institutional review committee which has been established in accordance with regulations of the Secretary to supervise clinical testing of devices in the facilities where the proposed clinical testing is to be conducted.” The only statutory exception is if a local IRB does not exist or its review is determined to be “inadequate” (21 U.S.C. 360j(g)(3)(A)). Accordingly, the change proposed in this ANPRM regarding the use of one IRB of record for multi-site studies would not apply to FDA-regulated device studies.) However, in many cases, a local IRB for each institution does independently review the research protocol, informed consentdocuments and other materials, sometimes resulting in hundreds of reviews for one study. When any one of these IRBs requires changes to the research protocol that are adopted for the entire study, investigators must re-submit the revised protocol to all of the reviewing IRBs. This process can take many months and can significantly delay the initiation of research projects. Separately, there are reports showing that there can be widely differing outcomes regarding the level of review required from IRB to IRB, even for identical studies.54

The choice to have multi-site research reviewed by a central IRB, or by an IRB at another institution, is voluntary. In practice, most institutions have been reluctant to replace review by their local IRBs with review by a central IRB.55 56Participants in two meetings on alternative IRB models that OHRP co-sponsored in November 2005 and November 2006 indicated that one of the key factors influencing institutions' decisions about this issue is OHRP's current practice of enforcing compliance with the Common Rule through the institutions that were engaged in human subjects research, even in circumstances when the regulatory violation is directly related to the responsibilities of an external IRB.57

Many commentators58claim that multiple IRB reviews do not enhance the protection of human subjects and may, in fact, divert valuable resources from more detailed reviews of other studies. Relevant local contextual issues (e.g.,investigator competence, site suitability) pertinent to most clinical studies can be addressed through mechanisms other than local IRB review. For research where local perspectives might be distinctly important (e.g.,in relation to certain kinds of vulnerable populations targeted for recruitment) local IRB review could be limited to such consideration(s), but again, IRB review is not the only mechanism for addressing such issues. The evaluation of a study's social value, scientific validity, and risks and benefits, and the adequacy of the informed consent document and process generally do not require the unique perspective of a local IRB.

To respond to this concern, central IRBs have been developed. The National Cancer Institute created a central IRB for adult research studies in 2001 and a central pediatric oncology IRB in 2004. Similarly, the Department of Veterans Affairs has required review of certain multi-site protocols by a single national IRB since 2008. Also, certain groups of private institutions have joined together to develop their own central IRBs. These central IRBs reduce the workload for local IRBs and may minimize institutional conflicts of interest. Since 2006, FDA has endorsed the use of a centralized IRB review process in multi-site clinical trials of investigational new drugs and has issued guidance intended to assist sponsors, institutions, IRBs, and clinical investigators on its implementation.59

Public comment is requested on the feasibility, advantages, and disadvantages of mandating that all domestic sites in a multi-site study rely upon a single IRB as their IRB of record for that study. (This would apply regardless of whether the study underwent convened review or expedited review.) This proposal would only affect which IRB would be designated as the IRB of record for institutional compliance with the IRB review requirements of the Common Rule. It would not relieve any site of its other obligations under the regulations to protect human subjects. Nor would it prohibit institutions from choosing, for their own purposes, to conduct additional internal ethics reviews, though such reviews would no longer have any regulatory status in terms of compliance with the Common Rule (and could be discouraged). To address institutions' concerns about OHRP's practice of enforcing compliance with 45 CFR part 46 through the institutions that are engaged in human subjects research, appropriate accompanying changes would be made in enforcement procedures to hold external IRBs directly accountable for compliance with certain regulatory requirements (see,e.g.,the proposal on IRB accountability released by OHRP in 2009, athttp://www.hhs.gov/ohrp/newsroom/rfc/com030509.html)

This change is being considered only for domestic sites in multi-site studies. In most cases, independent local IRB reviews of international sites are appropriate because it might be difficult for an IRB in the U.S. to adequately evaluate local conditions in a foreign country that could play an important role in the ethical evaluation of the study.

Comments and recommendations are requested on the following:

Question 30:What are the advantages and disadvantages of mandating, as opposed to simply encouraging, one IRB of record for domestic multi-site research studies?

Question 31:How does local IRB review of research add to the protection of human subjects in multi-site research studies? How would mandating one IRB of record impair consideration of valuable local knowledge that enhances protection of human subjects? Should the public be concerned that a centralized IRB may not have adequate knowledge of an institution's specific perspective or the needs of their population, or that a centralized IRB may not share an institution's views or interpretations on certain ethical issues?

Question 32:To what extent are concerns about regulatory and legal liability contributing to institutions' decisions to rely on local IRB review for multi-site research? Would the changes we are considering adequately address these concerns?

Question 33:How significant are the inefficiencies created by local IRB review of multi-site studies?

Question 34:If there were only one IRB of record for multi-site studies, how should the IRB of record be selected? How could inappropriate forms of “IRB shopping”—intentionally selecting an IRB that is likely to approve the study without proper scrutiny—be prevented?

Currently, under the Common Rule and FDA regulations, investigators generally must obtain and document the subjects' informed consent to participate in research.60The regulations currently require that the consent forms include at least eight specific items of information. Various aspects of the consent forms have been heavily criticized, as has the amount of time IRBs devote to editing and revising consent forms.

In addition, consent forms may frequently fail to include some of the most important pieces of information that a person would need in order to make an “enlightened decision” (to quote the Nuremberg Code) to enroll in a research study.61Instead of presenting the information in a way that is most helpful to prospective subjects—such as explaining why someone might want to choose not to enroll—the forms often function as sales documents, instead of as genuine aids to good decision-making.62

While the regulations have changed in only relatively modest ways since 1974, the average length of consent forms has been increasing since then,63and the forms have become excessively long and legalistic, even for relatively routine and low risk research studies.64For example, it is not uncommon for the documents to stretch to 15 or even 30 pages in length. Moreover, studies have shown that the reading level of many of these documents is above the desired 8th grade level.65 66 67Length and high reading levels may inhibit people from reading the full document and from understanding relevant information.

Further, some have argued that the requirements for obtaining waivers of informed consent or waivers of documentation of informed consent are confusing and inflexible, which leads to inconsistent application.68These problems may not be inherent in the language of the Common Rule, but there may be some changes to the regulations or clarifications as to how to interpret and implement such regulations that could improve informed consent documents and process.

We are considering a number of modifications to the regulations to improve consent forms, including (1) prescribing appropriate content that must be included in consent forms, with greater specificity than is provided in the current regulations; (2) restricting content that would beinappropriateto include in consent forms; (3) limiting the acceptable length of various sections of a consent form; (4) prescribing how information should be presented in consent forms, such as information that should be included at the very beginning of the consent form, or types of information that should be included in appendices and not in the main body of the consent form; (5) reducing institutional “boilerplate” in consent forms (that is, standard language that does little to genuinely inform subjects, and often is intended to primarily protect institutions from lawsuits); and (6) making available standardized consent form templates, the use of which could satisfy applicable regulatory provisions.

Comments and recommendations are requested on the following:

Question 35:What factors contribute to the excessive length and complexity of informed consent forms, and how might they be addressed?

Question 36:What additional information, if any, should be required by the regulations to assure that consent forms appropriately describe to subjects, in concise and clear language, alternatives to participating in the research study and why it may or may not be in their best interests to participate? What modifications or deletions to the required elements would be appropriate?

Question 37:Would the contemplated modifications improve the quality of consent forms? If not, what changes would do so?

Question 38:Should the regulations require that, for certain types of studies, investigators assess how well potential research subjects comprehend the information provided to them before they are allowed to sign the consent form?

Question 39:If changes are made to the informed consent requirements of the Common Rule, would any conforming changes need to be made to the authorization requirements of the HIPAA Privacy Rule?

Question 40:Would informed consent be improved if the regulations included additional requirements regarding the consent process, and if so, what should be required? For example, should investigators be required to disclose in consent forms certain information about the financial relationships they have with study sponsors?

Currently the Common Rule permits an IRB to waive the requirements for obtaining informed consent under two sets of circumstances (45 CFR 46.116 (c) or (d)).69The most common set of circumstances requires that four specific criteria be satisfied (45 CFR 46.116(d)). Many commentators have argued that these conditions for waiver of consent are vague and applied haphazardly at different institutions.70 71In response to these concerns, the Secretary's Advisory Committee on Human Research Protections (SACHRP), through its Subcommittee on Subpart A, developed several recommendations regarding the interpretation of these waiver criteria.72

IRBs, under the Common Rule (45 CFR 46.117(c)), also may waive the requirement for the investigator to obtain a signed consent form for some or all subjects. The current criteria for such a waiver may not be flexible enough for dealing with a variety of circumstances, such as when Federally-sponsored research is conducted in an international setting where for cultural or historical reasons signing documents may be viewed as offensive and problematic. It is worth noting that for studies that only involve surveys, focus groups, and interviews with competent adults, there will usually be no need to apply the waiver of documentation criteria provided at 45 CFR 46.117(c). Such studies will generally qualify for the new Excused category, with only oral consent required.

Comments and recommendations are requested on the following:

Question 41:What changes to the regulations would clarify the current four criteria for waiver of informed consent and facilitate their consistent application?

Question 42:In circumstances where the regulations would permit oral consent, what information should investigators be required to provide to prospective subjects? Are all of the elements of informed consent included at 45 CFR 46.116 necessary to be conveyed, or are some elements unnecessary? If some elements should not be required for oral consent, which ones are unnecessary?

Question 43:Are there additional circumstances under which it should be permissible to waive the usual requirements for obtaining or documenting informed consent?

Question 44:Are there types of research involving surveys, focus groups, or other similar procedures in which oral consent without documentation should not be permitted? What principles or criteria distinguish these cases?

Critics of the existing rules have observed that the current requirements for informed consent for future research with pre-existing data and biospecimens are confusing and consume substantial amounts of researchers' and IRBs' time and resources. Under the Common Rule and the HIPAA Privacy Rule, if identifiers are removed, specimens and data that have been collected for purposes other than the proposed research can be used without any requirement for informed consent or a HIPAA authorization. When these identifiers have not been removed, under the Common Rule, investigators may be allowed in certain situations to obtain a general consent for future research with existing biospecimens and other information stored in databases. Conversely, the Department's current interpretation of the HIPAA Privacy Rule requires that authorizations for research be study-specific. Thus, the Privacy Rule currently has not been interpreted to permit general authorizations for future unspecified research uses of health information. Importantly, the HHS Office for Civil Rights (OCR) has recently sought and is currently reviewing public comment on the extent to which a single general authorization may cover a range of future research uses of an individual's health information (see 75 FR 40868, 40893 available athttp://www.hhs.gov/ocr/privacy/hipaa/understanding/coveredentities/nprmhitech.pdf).

Because biospecimens and data that have been collected for clinical use or purposes other than for the proposed research are often an important source of information and material for investigators, and the reuse of existing data and materials can be an efficientmechanism for conducting research without presenting additional physical or psychological risks to the individual, it seems prudent to consider changes to current regulations. As the IOM recently stated inBeyond the HIPAA Privacy Rule: Enhancing Privacy, Improving Health Through Research,it is important to “facilitate important health research by maximizing the usefulness of patient data associated with biospecimens banks and in research databases, thereby allowing novel hypotheses to be tested with existing data and materials as knowledge and technology improve.”73

Some critics, including potential and former research subjects, object to research performed on a person's biospecimens without consent. This was recently highlighted in the book,The Immortal Life of Henrietta Lacks. 74Conversely, investigators are concerned that the need for informed consent for every use of a biospecimen will greatly inhibit research.75 76 77They worry that obtaining individual consent for each separate research study will create unmanageable logistical demands, making valuable research impossible. They also worry that research will be skewed by individuals who refuse consent, undermining the scientific validity of the research. An accumulating body of data indicates that while most individuals want to be able to decide whether their biospecimens are available for research, they often do not desire to have control over which specific researchers use their samples, for which diseases, at which institutions.78 79 80

The potential changes to the consent rules that were described in detail in Section II(B)(3)(c) (in the discussion of revising the rules for exempt studies) are being considered to strengthen and align consent protections, simultaneously addressing the concerns of individuals, while ensuring the pursuit of important research.

Comments and recommendations are requested on any of the above proposals under consideration and on the following specific questions:

Question 45:Under what circumstances should future research use of data initially collected for non-research purposes require informed consent? Should consent requirements vary based on the likelihood of identifying a research subject? Are there other circumstances in which it should not be necessary to obtain additional consent for the research use of currently available data that were collected for a purpose other than the currently proposed research?

Question 46:Under what circumstances should unanticipated future analysis of data that were collected for a different research purpose be permitted without consent? Should consent requirements vary based on the likelihood of identifying a research subject?

Question 47:Should there be a change to the current practice of allowing research on biospecimens that have been collected outside of a research study (i.e.“left-over” tissue following surgery) without consent, as long as the subject's identity is never disclosed to the investigator?

Question 48:What, if any, are the circumstances in which it would be appropriate to waive the requirement to obtain consent for additional analysis of biospecimens?

Question 49:Is it desirable to implement the use of a standardized, general consent form to permit future research on biospecimens and data? Are there other options that should be considered, such as a public education campaign combined with a notification and opt-out process?

Question 50:What is the best method for providing individuals with a meaningful opportunity to choose not to consent to certain types of future research that might pose particular concerns for substantial numbers of research subjects beyond those presented by the usual research involving biospecimens? How should the consent categories that might be contained in the standardized consent form be defined (e.g.an option to say yes-or-no to future research in general, as well as a more specific option to say yes-or-no to certain specified types of research)? Should individuals have the option of identifying their own categories of research that they would either permit or disallow?

Question 51:If the requirement to obtain consent for all research uses of biospecimens is implemented, how should it be applied to biospecimens that are collected outside of the U.S. but are to be used in research supported by a Common Rule agency? Should there be different rules for that setting, and if so, what should they be? Should they be based on the relevant requirements in the countries where the biospecimens were collected?

Question 52:Should the new consent rules be applied only prospectively, that is, should previously existing biospecimens and data sets be “grandfathered” under the prior regulatory requirements? If so, what are the operational issues with doing so?

Question 53:In cases in which consent for future research use is not obtained at the time of collection, should there be a presumption that obtaining consent for the secondary analysis of existing biospecimens or identifiable data would be deemed impracticable, such that consent could be waived, when more than a specified threshold number of individuals are involved? (SACHRP provided the Secretary with recommendations on this issue.81) If so, what threshold number should constitute impracticability? Is the number of potential human subjects the only measure of impracticability?

Collection of identifiable data, as well as secondary analyses of such data, poses informational risks. The assurance that identifiable information will be safeguarded is important for an individual's willingness to participate in research. Further, we recognize that there is an increasing belief that what constitutes “identifiable” and “de-identified” data is fluid; rapidly evolving advances in technology coupled with the increasing volume of data readily available may soon allow identification of an individual from data that is currently considered de-identified. In this sense, much of what is currently considered de-identified is also potentially identifiable data.

While there are currently some regulatory approaches that can be used to safeguard and maintain the confidentiality of research participants' information, such protections are limited in scope. The HIPAA Privacy and Security Rules generally require safeguards for individually identifiable health information and place limits and conditions on the use and disclosure of such information. However, the Rules only apply to researchers if they are part of a HIPAA covered entity (e.g.,a covered health care provider or health plan) and, to a certain extent, to researchers that are business associates of a covered entity.

Separate from the HIPAA Rules, the Privacy Act of 1974, as amended (5 U.S.C. 552a82) binds Federal agencies to protect personally identifiable information in their possession and control. It prohibits the disclosure (without prior consent or notice) of records that are retrieved by personal identifiers. In addition, there are other Federal privacy provisions that may need to be considered, but all have a limited scope. For example, Title 5 of the E-Government Act,83entitled the “Confidential Information Protection and Statistical Efficiency Act of 2002,”(CIPSEA) provides additional protections for confidential statisticalinformation collected by the Federal government. However, neither the Privacy Act nor CIPSEA generally apply to grant-funded investigators who are neither Federal employees nor contractors. (An additional example is the Department of Justice's set of regulations for protecting information collected in certain research and other programs, at 28 CFR part 22.)

Furthermore, none of these statutes was written with an eye toward the advances that have come in genetic and information technologies that make complete de-identification of biospecimens impossible and re-identification of sensitive health data easier. Certificates of confidentiality may be issued upon request through the authority of HHS (section 301(d) of the Public Health Service Act (42 U.S.C. 241(d)) to any investigator conducting IRB-approved research that involves the collection of sensitive and identifiable information. However, certificates of confidentiality do notrequireinvestigators to refuse to disclose identifying information; rather, they convey the legalrightto refuse to disclose. Certificates of confidentiality also do not protect against unauthorized or accidental disclosures of identifiable private information due to inadequate data security procedures. The National Institute of Justice (NIJ) provides a different model for privacy protection: all NIJ-funded investigators collecting identifying information must apply for a privacy certificate and are required to keep identifiable data confidential (28 CFR part 22).

Consequently, other fundamental protections for research participants may be warranted beyond updating the requirements for independent review and informed consent currently provided by the Common Rule. As noted above (Section II(A)), a solution we are considering is to mandate data security and information protection standards that would apply to all research that collected, stored, analyzed or otherwise reused identifiable or potentially identifiable information. This would include research with biospecimens, survey data, and research using administrative records as well as secondary analysis of the data. However, we are considering applying these new protections only to prospective collections of data and biospecimens after the implementation of any changes to the Common Rule and not retrospectively to research involving existing data, including stored biospecimens and their subsequent analysis. Further, it is envisioned that these data security and information protection standards would be scaled appropriately to the level of identifiability of the data.

While the discussion below focuses on these data security and information protection standards, we also are interested in whether there are other changes that might be made to the Common Rule, such as appropriate limitations on researchers' disclosure of identifiable or potentially identifiable information, that would strengthen, and create more uniformity in, the promises of confidentiality that currently exist for human subjects.

Currently, the HIPAA Privacy Rule's standards for identifiable and de-identified information are not aligned with what is considered human subjects research under the Common Rule. Under the Common Rule research does not involve “human subjects” if the investigator does not obtain data about individuals through an interaction or intervention or obtain identifiable private information about individuals.84Under the regulatory definition of human subject, “private information” is described as “information about behavior that occurs in a context in which the individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).” Private information is not considered to be identifiable under the Common Rule if the identity of the subject is not or may not be “readily ascertained” by the investigator from the information. Under the HIPAA Privacy Rule, health information is de-identified and thus exempt from the Rule, if it neither identifies nor provides a reasonable basis to identify an individual.

The HIPAA Privacy Rule provides two ways to de-identify information: (1) A formal determination by a qualified expert that the risk is very small that an individual could be identified; or (2) the removal of all 18 specified identifiers of the individual and of the individual's relatives, household members, and employers, as long as the covered entity has no actual knowledge that the remaining information could be used to identify the individual (45 CFR 164.514(b)). Under these rules, some information that is not considered identifiable under the Common Rule may be considered identifiable for purposes of the HIPAA Privacy Rule, such as dates of service or zip codes. However, to accommodate investigators' need to have access to data elements such as these, the Privacy Rule also provides for alimited data setto be used for research purposes, which is data that has been stripped of direct identifiers but that may retain certain elements, such as dates of service and zip codes (45 CFR 164.514(e)(2)). Because a limited data set is not considered fully de-identified, the Privacy Rule requires that a covered entity enter into a data use agreement with the investigator to prohibit the re-identification of the information and to otherwise protect the information.

We are considering adopting the HIPAA standards for purposes of the Common Rule regarding what constitutes individually identifiable information, a limited data set, and de-identified information, in order to address inconsistencies regarding these definitions and concepts between the HIPAA Privacy Rule and the Common Rule. Furthermore, in light of emerging technologies and evolving informational risks, it might be advisable to evaluate the set of identifiers that must be removed for a data set to be considered “de-identified” under both human subjects regulations and the HIPAA Privacy Rule. Table 1 in Section II illustrates how the HIPAA Privacy Rule's standards of identifiability would apply to the Excused category of research involving pre-existing information or biospecimens.

Regardless of what information is removed, it is possible to extract DNA from a biospecimen itself and potentially link it to otherwise available data to identify individuals. Consequently, we are considering categorizing all research involving the primary collection of biospecimens as well as storage and secondary analysis of existing biospecimens as research involving identifiable information (see Table 1, at the end of this section).

Comments and recommendations are requested on the following:

Question 54:Will use of the HIPAA Privacy Rule's standards for identifiable and de-identified information, and limited data sets, facilitate the implementation of the data security and information protection provisions being considered? Are the HIPAA standards, which were designed for dealing with health information, appropriate for use in all types of research studies, including social and behavioral research? If the HIPAA standards are not appropriate for all studies, what standards would be more appropriate?

Question 55:What mechanism should be used to regularly evaluate and to recommend updates to what isconsidered de-identified information? Beyond the mere passage of time, should certain types of triggering events such as evolutions in technology or the development of new security risks also be used to demonstrate that it is appropriate to reevaluate what constitutes de-identified information?

Question 56:DNA extracted from de-identified biospecimens can be sequenced and analyzed in other ways, with the results sometimes being linked to other available data than may allow a researcher to identify the persons whose specimens were being studied. How should Federal regulations manage the risks associated with the possibility of identification of such biospecimens? Should a human biospecimen be considered identifiable in and of itself? What are the advantages and disadvantages of considering all future research with biospecimens to be research with identifiable information?

Question 57:Should some types of genomic data be considered identifiable and, if so, which types (e.g.,genome-wide SNP analyses or whole genome sequences)?

The goal of information protection is to prevent breach of confidentiality through unauthorized access, inappropriate disclosure, or re-identification at either the individual or in some cases the subgroup level. Information that contains direct identifiers of individuals poses a greater informational risk than does a limited data set, which in turn poses a greater informational risk than de-identified information.

As discussed in Section II(A), the majority of unauthorized disclosures of identifiable health information from investigators occur due to inadequate data security.85IRB review or oversight of research posing informational risks may not be the best way to minimize the informational risks associated with data on human subjects. Instead, informational risks may be best mitigated through compliance with stringent standards for data security and information protection that are effectively enforced through mechanisms such as periodic random audits.

We are considering three specific requirements that could strengthen the protections for research studies that pose informational risks. First, research involving the collection and use of identifiable data, as well as data in limited data set form, could be required to adhere to data security standards modeled on the HIPAA Security Rule.86In particular, for research involving individually identifiable information, all biospecimens, and limited data sets, data security standards could require the use of reasonable and appropriate encryption for data maintained or transmitted in electronic form and strong physical safeguards for information maintained in paper form, audit trails, and access controls that allow only authorized personnel to have access to the information. Further, investigators would be required to adhere to breach notification standards modeled on those applied to HIPAA covered entities for breaches of individually identifiable health information.87For research using limited data sets or de-identified information, investigators would be strictly prohibited from attempting to re-identify the subjects of the information. Requiring that investigators implement and adhere to these standard data security and information protection measures would lessen the need for investigators to enter into data use agreements to protect the limited data set, as is currently required under the HIPAA Privacy Rule. Because these mandatory protections would apply to all research studies, it should not be necessary for IRBs to review studies posing only informational risks or to consider informational risks in studies involving other risks to human subjects.

Second, data could be considered de-identified or in limited data set form even if investigators see the identifiers but do not record them in the permanent research file. To de-identify information or create limited data sets, many investigators have established complex procedures for having “trusted third parties” remove identifiers prior to passing on information to an investigator for a study. This adds another level of complexity and suggests that third parties are more trusted to protect information than investigators. If investigators adhere to the standards for data security and information protection there may be less need for these complex third party relationships.

Third, to strengthen the enforcement mechanisms under the Common Rule, we are considering providing for periodic random retrospective audits, and additional enforcement tools.

Comments and recommendations are requested on any of the above proposals under consideration and on the following specific questions:

Question 58:Should the new data security and information protection standards apply not just prospectively to data and biospecimens that are collected after the implementation of new rules, but instead to all data and biospecimens? Would the administrative burden of applying the rule to all data and biospecimens be substantially greater than applying it only prospectively to newly collected information and biospecimens? How should the new standards be enforced?

Question 59:Would study subjects be sufficiently protected from informational risks if investigators are required to adhere to a strict set of data security and information protection standards modeled on the HIPAA Rules? Are such standards appropriate not just for studies involving health information, but for all types of studies, including social and behavioral research? Or might a better system employ different standards for different types of research? (We note that the HIPAA Rules would allow subjects to authorize researchers to disclose the subjects' identities, in circumstances where investigators wish to publicly recognize their subjects in published reports, and the subjects appreciate that recognition.)

Question 60:Is there a need for additional standardized data security and information protection requirements that would apply to the phase of research that involves data gathering through an interaction or intervention with an individual (e.g.during the administration of a survey)?

Question 61:Are there additional data security and information protection standards that should be considered? Should such mandatory standards be modeled on those used by the Federal government (for instance, the National Institute of Standards and Technology recently issued a “Guide to Protecting the Confidentiality of Personally Identifiable Information.”)?

Question 62:If investigators are subject to data security and information protection requirements modeled on the HIPAA Rules, is it then acceptable for HIPAA covered entities to disclose limited data sets to investigators for research purposes without obtaining data use agreements?

Question 63:Given the concerns raised by some that even with the removal of the 18 HIPAA identifiers, re-identification of de-identified datasets is possible, should there be an absolute prohibition against re-identifying de-identified data?

Question 64:For research involving de-identified data, is the proposed prohibition against a researcher re-identifying such data a sufficient protection, or should there in some instances be requirements preventing the researcher from disclosing the de-identified data to, for example, thirdparties who might not be subject to these rules?

Question 65:Should registration with the institution be required for analysis of de-identified datasets, as was proposed in Section II(B)(3) for Excused research, so as to permit auditing for unauthorized re-identification?

Question 66:What entity or entities at an institution conducting research should be given the oversight authority to conduct the audits, and to make sure that these standards with regard to data security are being complied with? Should an institution have flexibility to determine which entity or entities will have this oversight responsibility for their institution?

Research agencies collect various types of safety data with the common goal of protecting human subjects. However, individual agency requirements for reporting such data vary. This has resulted in variations between agencies regarding their policies and requirements for the reporting of such data. For example, the Common Rule does not require investigators to report “adverse events”, but rather references “unanticipated problems involving risks to subjects or others.” The relationship of “unanticipated problems” to “adverse events” historically has been unclear. Furthermore, there are some agencies that do require the reporting of many “adverse events” beyond those that constitute “unanticipated problems.” Those reporting requirements often utilize variable definitions of what constitutes such an event and require these reports on different timeframes and on various templates utilizing inconsistent vocabularies describing the severity and nature of these events.

The adverse event data collected by each agency are stored and maintained in separate datasets. The lack of connectivity and interoperability inhibits the conduct of integrated analyses and comparative studies about the frequency and severity of adverse events. Similarly, current policy requirements and current data collection practices do not foster the collection of data about the numbers of participants in various areas of research—information that is needed for characterizing the magnitude and severity of any risks.

We are considering a number of changes to improve the current system for the real-time prompt collection of such data. These changes are intended to simplify and consolidate the reporting of information that isalready requiredto be promptly reported by an investigator, andnotto expand the information that has to be reported. These changes involve (1) Using a standardized, streamlined set of data elements that nonetheless are flexible enough to enable customized safety reporting and compliance with most Federal agency reporting requirements; (2) implementing a prototype of a Web-based, Federal-wide portal (already developed by NIH, FDA, and 4 other Federal agencies) that would build on these data elements and allow investigators to submit electronically certain pre- and post-market safety data and automatically have it delivered to appropriate agencies and oversight bodies; and (3) harmonizing safety reporting guidance across all Federal agencies, including harmonizing terminology and clarifying the scope and timing of such reports. In addition to these changes, the Federal government is also considering creating a central Web-based repository to house a great deal of the information collected through the portal.

These innovations create the possibility of eliminating much of the existing multiplicity of different and confusing reporting mechanisms, and could foster greater uniformity and comparability among the safety information that gets reported. Consolidation of data reported using consistent vocabularies and terms would allow for more powerful and meaningful analyses of safety information across types of research studies than are possible at present.

Comments and recommendations are requested on any of the above proposalsunder consideration and on the following specific questions:

Question 67:Is the scope of events that must be reported under current policies, including the reporting of certain “unanticipated problems” as required under the Common Rule, generally adequate?

Question 68:With regard to data reported to the Federal government:

a. Should the number of research participants in Federally funded human subjects research be reported (either to funding agencies or to a central authority)? If so, how?

b. What additional data, not currently being collected, about participants in human subjects research should be systematically collected in order to provide an empirically-based assessment of the risks of particular areas of research or of human subjects research more globally?

c. To what types of research should such a requirement apply (e.g.,interventional studies only; all types of human subjects research, including behavioral and social science research)? In addition, are there other strategies and methods that should be implemented for gathering information on the effectiveness of the human subjects protection system?

Question 69:There are a variety of possible ways to support an empiric approach to optimizing human subjects protections. Toward that end, is it desirable to have all data on adverse events and unanticipated problems collected in a central database accessible by all pertinent Federal agencies?

Question 70:Clinical trials assessing the safety and efficacy of FDA-regulated medical products (i.e.,phase II through IV studies) are generally required to register and, following study completion, report summary results, including adverse events, in the publicly accessible database ClinicalTrials.gov. Is the access to information on individual studies provided by this resource sufficiently comprehensive and timely for the purposes of informing the public about the overall safety of all research with human participants?

Currently, an institution engaged in non-exempt human subjects research conducted or supported by any Federal department or agency that has adopted the Common Rule is required to hold an OHRP-approved Federalwide Assurance (FWA) or another assurance of compliance approved by the department or agency conducting or supporting the research. The FWA mandates the application of the Common Rule only to certain Federally funded research projects. Most institutions voluntarily extend the applicability of their FWAs to all the research conducted at their institutions, even research not conducted or supported by one of the Federal departments or agencies that have adopted the Common Rule. However, such extension is not required.

The IOM and NBAC, among many others, have called for legislation that would extend the Common Rule protections to all research with human subjects conducted in the U.S., regardless of funding source.

We are considering an alternative regulatory proposal to partially fulfill this goal: requiring domestic institutions that receive some Federal funding from a Common Rule agency for research with human subjects to extend the Common Rule protections to all research studies conducted at their institution.

Comments and recommendations are requested on the following:

Question 71:Should the applicability of the Common Rule be extended to all research that isnotFederally funded that is being conducted at a domestic institution that receives some Federal funding for research with human subjects from a Common Rule agency?

From the outset of the development of the Common Rule, the importance of consistency across the Federal government has been recognized. In May 1982, the Chairman of the Federal Coordinating Council for Science, Engineering, and Technology appointed an Ad Hoc Committee for the Protection of Human Research Subjects. In consultation with OSTP and the Office of Management and Budget, the Ad Hoc Committee agreed that uniformity is desirable among departments and agencies to eliminate unnecessary regulation and to promote increased understanding and ease of compliance by institutions that conduct Federally supported or regulated research involving human subjects. By 1991, 15 Federal departments and agencies had adopted the Common Rule.

However, each of the departments and agencies that have adopted the Common Rule may issue its own guidance regarding the protection of human subjects. Consequently, there are variations in the guidances issued.

In addition, other Federal laws and regulations have been enacted that relate to the protection of human subjects, most prominently, the research provisions of the HIPAA Privacy Rule. However, since the HIPAA regulations were developed mainly for the clinical context,88the rules are inconsistent with the Common Rule in certain areas. As noted above, one such inconsistency is the definition of identifiable data and another is the manner in which the two rules treat consent for future research.

Currently, there are multiple efforts to address such variation in guidance across the Federal government. The Common Rule departments and agencies have procedures for sharing proposed guidance before it is adopted. FDA and OHRP have been working closely on enhancing harmonization of guidance.

As the label of the Common Rule suggests, there seems to be a compelling case for consistency across Federal departments and agencies regarding guidance on the protections of human subjects. Nevertheless, there are arguments in favor of some departments or agencies imposing specific requirements, apart from the Common Rule, that are tailored to certain types of research. The various agencies that oversee the protection of human subjects range from regulatory agencies, to those agencies and departments that conduct research, to those that support and sponsor research. In addition, in some cases, statutory differences among the agencies have resulted in different regulatory requirements and agency guidances. Not only do the agencies have different relationships to the research, they oversee very different types and phases of research and thus there may be reasonable justifications for differences in guidance. Moreover, achieving consensus across the entire Federal government may be arduous, preventing timely issuance of guidance.

Comments and recommendations are requested on the following:

Question 72:To what extent do the differences in guidance on research protections from different agencies either strengthen or weaken protections for human subjects?

Question 73:To what extent do the existing differences in guidance on research protections from different agencies either facilitate or inhibit the conduct of research domestically and internationally? What are the most important such differences influencing the conduct of research?

Question 74:If all Common Rule agencies issued one set of guidance, would research be facilitated both domestically and internationally? Would a single set of guidance be able to adequately address human subjects protections in diverse populations andcontexts, and across the broad range of research contexts (including biomedical, national security, education and other types of social and behavioral research)?

When submitting responses to the specific questions asked in this notice, please cite the specific question by number.

In addition to the specific solicitation of comments throughout this ANPRM, general comment is invited on the current system of protections for human research subjects as implemented through the Common Rule, the HIPAA Privacy and Security Rules, and any other rules, regulations or guidance documents. In particular, comments are sought not only on ways to improve the efficiency of the current system, but about circumstances in which the protections provided by the current system might be inadequate and in need of supplementation or change in order to make sure that subjects are receiving appropriate protections.

We encourage you to participate in this rulemaking by submitting comments and related materials. All comments received will be posted without change tohttp://www.regulations.govand will include any personal information you have provided.

If you submit a comment, please include the docket number for this rulemaking (USCG-2011-0615), indicate the specific section of this document to which each comment applies, and provide a reason for each suggestion or recommendation. You may submit your comments and material online (viahttp://www.regulations.gov) or by fax, mail, or hand delivery, but please use only one of these means. If you submit a comment online viahttp://www.regulations.gov,it will be considered received by the Coast Guard when you successfully transmit the comment. If you fax, hand deliver, or mail your comment, it will be considered as having been received by the Coast Guard when it is received at the Docket Management Facility. We recommend that you include your name and a mailing address, an e-mail address, or a telephone number in the body of your document so that we can contact you if we have questions regarding your submission.

To submit your comment online, go tohttp://www.regulations.gov,click on the “submit a comment” box, which will then become highlighted in blue. In the “Document Type” drop down menu select “Proposed Rule” and insert “USCG-2011-0615” in the “Keyword” box. Click “Search” then click on the balloon shape in the “Actions” column. If you submit your comments by mail or hand delivery, submit them in an unbound format, no larger than 8½ by 11 inches, suitable for copying and electronic filing. If you submit comments by mail and would like to know that they reached the Facility, please enclose a stamped, self-addressed postcard or envelope. We will consider all comments and material received during the comment period and may change the rule based on your comments.

To view comments, as well as documents mentioned in this preamble as being available in the docket, go tohttp://www.regulations.gov,click on the “read comments” box, which will then become highlighted in blue. In the “Keyword” box insert “USCG-2011-0615” and click “Search.” Click the “Open Docket Folder” in the “Actions” column. You may also visit the Docket Management Facility in Room W12-140 on the ground floor of the Department of Transportation West Building, 1200 New Jersey Avenue, SE., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. We have an agreement with the Department of Transportation to use the Docket Management Facility.

Anyone can search the electronic form of comments received into any of our dockets by the name of the individual submitting the comment (or signing the comment, if submitted on behalf of an association, business, labor union,etc.). You may review a Privacy Act notice regarding our public dockets in the January 17, 2008, issue of theFederal Register(73 FR 3316).

We do not now plan to hold a public meeting. But you may submit a request for one on or before August 10, 2011 using one of the four methods specified underADDRESSES. Please explain why you believe a public meeting would be beneficial. If we determine that one would aid this rulemaking, we will hold one at a time and place announced by a later notice in theFederal Register.

The legal basis for the proposed rule is the Coast Guard's authority to establish regulated navigation areas andother limited access areas: 33 U.S.C. 1226, 1231; 46 U.S.C. Chapter 701, 3306, 3703; 50 U.S.C. 191, 195; 33 CFR 1.05-1, 6.04-1, 6.04-6, 160.5; Public Law 107-295, 116 Stat. 2064; Department of Homeland Security Delegation No. 0170.1.

The purpose of the proposed rule is to protect the public from the hazards associated with the launching of fireworks over navigable waters of the United States.

On November 19, 2011, a fireworks display is scheduled to take place during the Fourth Annual Chillounge Night St. Petersburg, an annual outdoor party, in St. Petersburg, Florida. The fireworks, which will be launched from Spa Beach Park, will explode over the waters of Tampa Bay. The fireworks display is scheduled to commence at 10 p.m. and conclude at approximately 10:05 p.m.

The proposed rule would establish a temporary safety zone that encompasses certain waters of Tampa Bay in the vicinity of Spa Beach in St. Petersburg, Florida. The safety zone would be enforced from 9:30 p.m. on November 19, 2011, 30 minutes prior to the scheduled commencement of the fireworks display at approximately 10 p.m., to ensure the safety zone is clear of persons and vessels. Enforcement of the safety zone would cease at 10:45 p.m. on November 19, 2011, 40 minutes after the scheduled conclusion of the fireworks display, to account for possible delays. Persons and vessels would be prohibited from entering, transiting through, anchoring in, or remaining within the safety zone unless authorized by the Captain of the Port St. Petersburg or a designated representative. Persons and vessels would be able to request authorization to enter, transit through, anchor in, or remain within the safety zone by contacting the Captain of the Port St. Petersburg by telephone at 727-824-7524, or a designated representative via VHF radio on channel 16, to request authorization. The Coast Guard would provide notice of the safety zone by Local Notice to Mariners, Broadcast Notice to Mariners, and on-scene designated representatives.

We developed this proposed rule after considering numerous statutes and executive orders related to rulemaking. Below we summarize our analyses based on 13 of these statutes or executive orders.

Executive Orders 12866 (“Regulatory Planning and Review”) and 13563 (“Improving Regulation and Regulatory Review”) direct agencies to assess the costs and benefits of available regulatory alternatives and, if regulation is necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health and safety effects, distributive impacts, and equity). Executive Order 13563 emphasizes the importance of quantifying both costs and benefits, of reducing costs, of harmonizing rules, and of promoting flexibility. This NPRM has not been designated a “significant regulatory action” under section 3(f) of Executive Order 12866. Accordingly, the NPRM has not been reviewed by the Office of Management and Budget. A draft regulatory assessment follows:

The economic impact of this proposed rule is not significant for the following reasons: (1) The safety zone would be enforced for less than two hours; (2) vessel traffic in the area would be minimal during the enforcement period; (3) although persons and vessels would not be able to enter, transit through, anchor in, or remain within the safety zone without authorization from the Captain of the Port St. Petersburg or a designated representative, they would be able to operate in the surrounding area during the enforcement period; (4) persons and vessels would still be able to enter, transit through, anchor in, or remain within the safety zone if authorized by the Captain of the Port St. Petersburg or a designated representative; and (5) the Coast Guard would provide advance notification of the safety zone to the local maritime community by Local Notice to Mariners and Broadcast Notice to Mariners.

Under the Regulatory Flexibility Act (5 U.S.C. 601-612), we have considered whether this proposed rule would have a significant economic impact on a substantial number of small entities. The term “small entities” comprises small businesses, not-for-profit organizations that are independently owned and operated and are not dominant in their fields, and governmental jurisdictions with populations of less than 50,000.

The Coast Guard certifies under 5 U.S.C. 605(b) that this proposed rule would not have a significant economic impact on a substantial number of small entities. This proposed rule may affect the following entities, some of which may be small entities: The owners or operators of vessels intending to enter, transit through, anchor in, or remain within that portion of Tampa Bay encompassed within the safety zone from 9:30 p.m. until 10:45 p.m. on November 19, 2011. For the reasons discussed in the Executive Order 12866 and Executive Order 13563 section above, this proposed rule would not have a significant economic impact on a substantial number of small entities.

If you think that your business, organization, or governmental jurisdiction qualifies as a small entity and that this proposed rule would have a significant economic impact on it, please submit a comment (seeADDRESSES) explaining why you think it qualifies and how and to what degree this proposed rule would economically affect it.

Under section 213(a) of the Small Business Regulatory Enforcement Fairness Act of 1996 (Pub. L. 104-121), we want to assist small entities in understanding this proposed rule so that they can better evaluate its effects on them and participate in the rulemaking. If the proposed rule would affect your small business, organization, or governmental jurisdiction and you have questions concerning its provisions or options for compliance, please contact Marine Science Technician First Class Jo A. Hoover, Sector St. Petersburg Prevention Department, Coast Guard; telephone 813-228-2191, e-mail Jo.A.Hoover@uscg.mil. The Coast Guard will not retaliate against small entities that question or complain about this proposed rule or any policy or action of the Coast Guard.

This proposed rule would call for no new collection of information under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

A rule has implications for federalism under Executive Order 13132, Federalism, if it has a substantial direct effect on State or local governments and would either preempt State law or impose a substantial direct cost of compliance on them. We have analyzed this proposed rule under that Order and have determined that it does not have implications for federalism.

The Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531-1538) requires Federal agencies to assess the effects of their discretionary regulatory actions. In particular, the Act addresses actionsthat may result in the expenditure by a State, local, or Tribal government, in the aggregate, or by the private sector of $100,000,000 or more in any one year. Though this proposed rule would not result in such an expenditure, we do discuss the effects of this proposed rule elsewhere in this preamble.

This proposed rule would not cause a taking of private property or otherwise have taking implications under Executive Order 12630, Governmental Actions and Interference with Constitutionally Protected Property Rights.

This proposed rule meets applicable standards in sections 3(a) and 3(b)(2) of Executive Order 12988, Civil Justice Reform, to minimize litigation, eliminate ambiguity, and reduce burden.

We have analyzed this proposed rule under Executive Order 13045, Protection of Children from Environmental Health Risks and Safety Risks. This proposed rule is not an economically significant rule and would not create an environmental risk to health or risk to safety that might disproportionately affect children.

This proposed rule does not have Tribal implications under Executive Order 13175, Consultation and Coordination with Indian Tribal Governments, because it would not have a substantial direct effect on one or more Indian Tribes, on the relationship between the Federal Government and Indian Tribes, or on the distribution of power and responsibilities between the Federal Government and Indian Tribes.

We have analyzed this proposed rule under Executive Order 13211, Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use. We have determined that it is not a “significant energy action” under that order because it is not a “significant regulatory action” under Executive Order 12866 and is not likely to have a significant adverse effect on the supply, distribution, or use of energy. The Administrator of the Office of Information and Regulatory Affairs has not designated it as a significant energy action. Therefore, it does not require a Statement of Energy Effects under Executive Order 13211.

The National Technology Transfer and Advancement Act (NTTAA) (15 U.S.C. 272 note) directs agencies to use voluntary consensus standards in their regulatory activities unless the agency provides Congress, through the Office of Management and Budget, with an explanation of why using these standards would be inconsistent with applicable law or otherwise impractical. Voluntary consensus standards are technical standards (e.g.,specifications of materials, performance, design, or operation; test methods; sampling procedures; and related management systems practices) that are developed or adopted by voluntary consensus standards bodies.

This proposed rule does not use technical standards. Therefore, we did not consider the use of voluntary consensus standards.

We have analyzed this proposed rule under Department of Homeland Security Management Directive 023-01 and Commandant Instruction M16475.lD, which guide the Coast Guard in complying with the National Environmental Policy Act of 1969 (NEPA) (42 U.S.C. 4321-4370f), and have made a preliminary determination that this action is one of a category of actions that do not individually or cumulatively have a significant effect on the human environment. A preliminary environmental analysis checklist supporting this determination is available in the docket where indicated underADDRESSES. This proposed rule involves establishing a temporary safety zone, as described in paragraph 34(g) of the Instruction, on the waters of Tampa Bay in St. Petersburg, Florida that will be enforced for less than two hours. We seek any comments or information that may lead to the discovery of a significant environmental impact from this proposed rule.

For the reasons discussed in the preamble, the Coast Guard proposes to amend 33 CFR part 165 as follows:

On May 31, 2011, the EPA Region 4 Acting Regional Administrator signed a proposed rulemaking to approve, on a limited basis, the State of Tennessee's Regional Haze State Implementation Plan. This action was published in theFederal Registeron June 9, 2011, (76 FR 33662) and provided a 30-day comment period. All written comments were due to EPA Region 4, as instructed in the proposed rule, on or before July 11, 2011. During the comment period, EPA received comments from two separate Commenters requesting that EPA extend the comment period suggesting a range of 30-60 days. The purpose of the Commenters' requests was to allow time to review the final CSAPR1 and assess the correlation between the CSAPR and the Regional Haze requirements and, specifically, any potential impacts on the Tennessee Regional Haze SIPrulemaking. EPA has considered these requests and has decided to reopen the comment period for an additional 15 days from the date of publication of today's rulemaking.

This reopening is for the limited purpose of public review and comment on the potential impacts of the final CSAPR on EPA's proposed rulemaking to approve Tennessee's Regional Haze SIP. EPA does not anticipate any impacts from the CSAPR on the proposed rulemaking on the Tennessee Regional Haze SIP. As noted in the CSAPR, EPA has not conducted any technical analysis to determine whether compliance with the CSAPR would satisfy Regional Haze Best Available Retrofit Technology (BART)-related requirements for electric generating units (EGUs). For that reason, EPA has neither made any determinations nor established any presumptions that compliance with the CSAPR satisfies BART-related requirements for EGUs. EPA intends to undertake a separate analysis to determine if compliance with the CSAPR would provide sufficient reductions to satisfy BART requirements for EGUs in accordance with Regional Haze Rule requirements for alternative BART compliance options as soon as practicable following official promulgation of the CSAPR.

This proposal addresses the following local rules: NSAQMD Rule 215, SMAQMD Rule 465, and SCAQMD Rules 1132 and 1162. In the Rules and Regulations section of thisFederal Register, we are approving these local rules in a direct final action without prior proposal because we believe these SIP revisions are not controversial. If we receive adverse comments, however, we will publish a timely withdrawal of the direct final rule and address the comments in subsequent action based on this proposed rule. Please note that if we receive adverse comment on an amendment, paragraph, or section of this rule and if that provision may be severed from the remainder of the rule, we may adopt as final those provisions of the rule that are not the subject of an adverse comment.

We do not plan to open a second comment period, so anyone interested in commenting should do so at this time. If we do not receive adverse comments, no further activity is planned. For further information, please see the direct final action.

You may be potentially affected by this action if you manufacture (defined by statute to include import) or process BPA (CASRN 80-05-7). BPA is listed on the Toxic Substances Control Act (TSCA) Chemical Substance Inventory (TSCA Inventory) under the name phenol, 4,4'-(1-methylethylidene)bis-. Potentially affected entities may include, but are not limited to:

• Chemical manufacturers (including importers) (NAICS codes 325, 32411),e.g.,chemical manufacturing and petroleum refineries of BPA.

• Plastics material and resin manufacturers (NAICS code 325211),e.g.,manufacturers and processors of BPA-based polycarbonate plastics and epoxy resins.

• Foundries (NAICS codes 331512, 331524, 331528),e.g.,steel investment foundries, aluminum foundries, and other non-ferrous foundries, except die-casting, using BPA in casting sands.

• Paint and coating manufacturers (NAICS code 325510),e.g.,manufacturers of epoxy-based paints and other coating products that may contain BPA.

• Paper recyclers (NAICS codes 322110, 322121, 3222),e.g.,pulp mills, paper (except newsprint) mills, and converted paper product manufacturers that may process waste thermal paper containing BPA.

• Materials recovery facilities (NAICS code 562920),e.g.,facilities separating and sorting recyclable materials that may handle thermal paper, polycarbonates, or food and beverage cans lined with BPA-based epoxy coatings.

• Custom compounders of purchased resins (NAICS code 325991),e.g.,facilities where resins are made from recycled polycarbonate plastics that may contain BPA.

This listing is not intended to be exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in this unit could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether this action might apply to certain entities. If you have any questions regarding the applicability of this action to a particular entity, consult the technical person listed underFOR FURTHER INFORMATION CONTACT.

1.Submitting CBI.Do not submit this information to EPA through regulations.gov or e-mail. Clearly mark the part or all of the information that you claim to be CBI. For CBI information in a disk orCD-ROM that you mail to EPA, mark the outside of the disk or CD-ROM as CBI and then identify electronically within the disk or CD-ROM the specific information that is claimed as CBI. In addition to one complete version of the comment that includes information claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public docket. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2.

2.Tips for preparing your comments.When submitting comments, remember to:

i. Identify the document by docket ID number and other identifying information (subject heading,Federal Registerdate and page number).

ii. Follow directions. The Agency may ask you to respond to specific questions or organize comments by referencing a Code of Federal Regulations (CFR) part or section number.

iii. Explain why you agree or disagree; suggest alternatives and substitute language for your requested changes.

iv. Describe any assumptions and provide any technical information and/or data that you used.

v. If you estimate potential costs or burdens, explain how you arrived at your estimate in sufficient detail to allow for it to be reproduced.

vi. Provide specific examples to illustrate your concerns and suggest alternatives.

vii. Explain your views as clearly as possible, avoiding the use of profanity or personal threats.

viii. Make sure to submit your comments by the comment period deadline identified.

As a follow-up to the BPA Action Plan released on March 29, 2010 (Ref. 1), EPA is issuing this ANPRM under TSCA section 4(a) (15 U.S.C. 2603(a)) to solicit public input on the necessity for and best approach to obtain environmental effects, exposure, and pathway information relevant to a determination that BPA either does or does not present an unreasonable risk of injury to the environment. In particular, EPA requests comment on:

1. Whether EPA should propose requiring specific toxicity testing to more fully characterize the effects of BPA on environmental organisms at low concentrations.

2. Whether EPA should propose requiring environmental testing consisting of sampling and monitoring, particularly in the vicinity of reported releases of BPA into the environment, and what design and protocol it should use for such sampling and monitoring, in order to identify potential sources and pathways of exposure and determine the extent to which environmental organisms may be exposed to BPA concentrations of concern as determined by existing data and by additional studies that are either already underway or would be conducted under a test rule.

3. EPA additionally requests comment and supporting information regarding which TSCA section 4(a)(1) finding authority would be most appropriate for the purpose of a BPA test rule proposal, as discussed in Unit II.C. Any proposal would ultimately be based on EPA's assessment of the relevant information available at the time of proposal.

In this ANPRM, EPA is considering requiring both toxicity testing for environmental organisms exposed to BPA and environmental testing consisting of sampling and monitoring in the vicinity of reported BPA releases to measure its environmental presence. The toxicity testing is being considered to resolve existing uncertainties concerning the potential for BPA to elicit adverse effects in ecologically relevant species, including endocrine-related impacts that could occur at low doses. The environmental testing is being considered to resolve existing uncertainties concerning potential sources of and pathways leading to environmental exposures and to determine whether or not the concentrations to which organisms currently may be exposed in the environment are at or above levels of concern for adverse effects, including endocrine-related effects.

On May 17, 1985, EPA published in theFederal Registera proposed rule (50 FR 20691) to require human health and environmental testing in response to the TSCA Interagency Testing Committee's (ITC) 14th report published in theFederal Registerissue of May 29, 1984 (49 FR 22389), which designated BPA for priority consideration for health and environmental effects. EPA proposed standard freshwater and marine acute fish and aquatic invertebrate toxicity tests, and freshwater aquatic plant toxicity tests. Test results were submitted in response to the proposal for freshwater and marine acute fish, acute aquatic invertebrate, and algal toxicity. EPA's final rule published in theFederal Registerissue of September 18, 1986 (51 FR 33047) (1986 Final Rule), terminated the test rule process for environmental effects testing for BPA. At the time, EPA determined that the test data were adequate and that chronic freshwater organism testing was not needed because the LC50values for the standard acute aquatic organism toxicity tests were greater than 1.0 parts per million (ppm) (1 milligram/Liter (mg/L)), and the ratios of 48-hour to 96-hour LC50values were not greater than 2. Since the 1986 Final Rule, however, several studies on BPA have raised concerns about its environmental effects at concentrations less than 1.0 ppm (1 mg/L).

As stated in the BPA Action Plan (Ref. 1), EPA does not intend to initiate regulatory action under TSCA at this time on the basis of human health. EPA remains committed to protecting human health, but notes that most human exposure, including exposure to children, comes through food packaging materials under the jurisdiction of the Food and Drug Administration (FDA) in HHS. FDA, together with the Centers for Disease Control and Prevention (CDC) and the National Institute of Environmental Health Sciences (NIEHS), is investing in important new health studies in both animals and humans to better determine and evaluate the potential health consequences of BPA exposures. EPA will continue to coordinate closely with FDA, CDC, and NIEHS on this activity. To the extent that FDA may identify health concerns from BPA in food contact materials, EPA will work with FDA to identify and assess potential substitutes. Levels of exposure that may be identified by the ongoing review as being of concern to human health, including children's health, will affect the extent to which EPA would take additional action to address potential risks to human health resulting from uses within TSCA jurisdiction.

1.What is currently known about the environmental hazard of BPA? The toxicity of BPA has been studied extensively, as indicated in the multiple studies cited in the BPA Action Plan (Ref. 1).1 There is general agreementamong multiple reviewers, including government regulatory agencies in the United States, Japan, the European Union (EU), and Canada, that BPA is a reproductive and developmental toxicant at doses in animal studies of≥50 mg/kilogram-body weight (kg-bw)/day (delayed puberty in male and female rats and male mice; discussed in Refs. 2-9);≥235 mg/kg-bw/day (reduced fetal or birth weight or growth early in life, effects on testis of male rats; Ref. 9); and≥500 mg/kg-bw/day (possible decreased fertility in mice, altered estrous cycling in female rats, and reduced survival of fetuses; Ref. 9). Systemic effects (reduction in body weight, changes in relative organ weights, and increases in liver toxicity; Refs. 2-8) were observed at doses above 5 mg/kg-bw/day (identified as a no observed adverse effect level (NOAEL); lowest observed adverse effect level (LOAEL) of 50 mg/kg-bw/day). There are reports of endocrine-related low-dose effects on puberty and neurological development (brain, behavior; Ref. 9) at doses in animal studies as low as 2 microgram (μg)/kg-bw/day. There is disagreement in the scientific community at large about whether effects seen at doses in animals less than 1 mg/kg/day are meaningful and relevant to humans. FDA, together with NIEHS and CDC, are engaging in additional research to better determine and evaluate the potential human health consequences of exposures to BPA, including exposures at low doses (Ref. 10). EPA is working with FDA, NIEHS, and CDC on this ongoing research, and is not considering any additional testing specifically in regard to human health issues at this time.

Many studies have been conducted to determine potential effects of BPA exposure on invertebrates, fish, amphibians, reptiles, birds, and wild mammals, and a review is provided by Crainet al.(Ref. 11). In general, studies have shown that BPA can affect growth, reproduction, and development in aquatic organisms. Evidence of sub-lethal effects mediated through either endocrine or non-endocrine related mechanisms in fish, amphibians, reptiles, and invertebrate aquatic organisms has been reported at potentially environmentally relevant exposure levels lower than those required for acute toxicity. There is a widespread variation in reported values for these sub-lethal effects, but many fall in the range of 1 µg/L to 1 mg/L (Ref. 6; also, see individual studies noted in Table 2 of Unit II.B.2.).

The ecological hazard for BPA has been evaluated in three different risk assessments performed by the EU, Canada, and Japan (Refs. 7, 6, and 8), as summarized in Table 1 of this unit. The different methodologies, endpoints, and study results used by each country to derive their ecological values highlight the significant uncertainty in the estimated hazard values. Japan concluded that “the current exposure levels of BPA will not pose unacceptable risks to the local populations of aquatic life, particularly fish” (Ref. 8). In contrast, the EU concluded that although the predicted exposure concentrations were significantly below its hazard values, there was a need for further information and/or testing on such organisms as freshwater snails (Ref. 7).

Canada used a study (Ref. 12) that reported reduced sperm quality and delayed ovulation in brown trout at a very low concentration in water (1.75 µg/L). Other effects such as the induction of intersex (or testes-ova in males and females), decreased spermatogenesis, induction of vitellogenin, delayed or ceased ovulation, or histological liver changes were also reported in other studies referenced in the EU and Japanese hazard evaluations. However, because there were no standardized test guidelines or risk assessment guidance for evaluating some of these endocrine-related effects at the time of these assessments, the EU and Japan set ecotoxicological hazard values based on conventional effects (mortality and reproductive effects) from standardized studies. In contrast, Canada concluded in its hazard characterization that:

Canada concluded that BPA concentrations in water have the potential to cause adverse effects on populations of pelagic organisms in Canada and concentrations in biota have the potential to cause adverse effects in populations of wildlife in Canada, but that there is a low risk of direct adverse effects to sediment organisms and to avian wildlife species in Canada. In the conclusion of its risk assessment, Canada stated that it is considered appropriate to apply a precautionary approach when characterizing risk, observing “it is concluded that bisphenol A is entering the environment in a quantity or concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity” (Ref. 6).

EPA considers that the uncertainty demonstrated by these divergent opinions concerning interpretation of the results of existing environmental toxicity studies, particularly studies addressing potential effects at low levels of exposure, may indicate further testing is necessary to resolve the question of whether or not BPA presents an unreasonable risk of injury to the environment on the basis of those effects. This is due to the combination of the existence of measured values, as discussed in Unit II.B.4. and as shown in that unit's Table 3, for BPA in U.S. surface waters at a mean-concentration range of up to 1.78 μg/L (parts per billion (ppb)) and a single-maximum concentration of 12 μg/L (ppb); in ground water at a mean-concentration range of up to 1.9 μg/L (ppb) and a maximum concentration of 2.55 μg/L (ppb); and in freshwater sediments at a median concentration of 0.6 μg/kg (ppb) dry weight and a maximum concentration of 140 μg/kg (ppb) (see Table 3 in Unit II.B.4.), and the existence of many hazard studies describing a variety of effects in aquatic organisms at some of these concentrations (see Table 2 in Unit II.B.2.), leaving little or no room for a reasonable or acceptable margin of exposure.

In order to assess the potential for BPA to harm the environment in the United States, EPA considers it important to address two basic areas of inquiry relevant to identifying the hazard and exposure components of a risk analysis:

a. What additional hazard information is needed to fully characterize the effects of BPA in environmental organisms at low doses and potentially environmentally relevant concentrations?

b. What levels of BPA are present in the environment, particularly in areas where environmental exposures are likely to be highest (e.g.,near BPA manufacturing facilities, polycarbonate and epoxy resin manufacturing and processing facilities, foundries, landfills, wastewater treatment plants (WWTPs), and other locations associated with uses and/or releases of BPA)?

2.What additional hazard information is needed on the effects of BPA on environmental organisms?EPA performed a literature search to identify relevant scientific information to assess the acute and chronic toxicity of BPA to environmental organisms from 20072 to the present. A total of 468 articles were found (Ref. 13), of which 30 were found to be of some relevance (Ref. 14). Since thorough analyses of acute and chronic toxicity for “conventional endpoints” (which generally address immediate effects on survival or reproduction) had already been conducted for BPA by Canada, the EU, and Japan (Refs. 6-8), EPA performed a more detailed evaluation of the scientific literature for sub-lethal effects at lower concentrations (< 100 μg/L). These sub-lethal effects in both vertebrates and invertebrates could be mediated either through endocrine or non-endocrine-related mechanisms. There are many studies indicating such sub-lethal effects from BPA exposures at levels that, based on the information discussed in Unit II.B.4., appear to be potentially environmentally relevant concentrations because they may occur in the environment. Some of these studies are included in Table 2 of this unit.

There is debate in the scientific literature on how best to interpret these low-dose, sub-lethal effects of BPA and other chemicals on environmental organisms. EPA is concerned that these sub-lethal effects may be having a detrimental effect on populations of aquatic organisms over time based on the reported increased susceptibility of subsequent generations exposed to BPA in multi-generation invertebrate and fish studies. For example, in the intertidal copepod (Tigriopus japonicus), delayed development was reported in the first generation at 0.1 µg/L, but at a 10-fold lower concentration of 0.01 µg/L in the next generation (Ref. 15). In the freshwater midge (Chironomus riparius), the first generation did not have a significant delay in emergence time from the egg, but in the second generation emergence was delayed at 0.08 µg/L (Ref. 16). Egg hatchability decreased in fathead minnows (Pimephales promelas) at 640 µg/L in the first (F1) generation, then at 160 µg/L in the second (F2) generation (Ref. 17). Although the mechanisms of action leading to effects may be different for vertebrate and invertebrate organisms, this suggests the potential for increasing developmental and reproductive effects in populations of aquatic organisms that have repeated exposures to BPA for generations, even at very low concentrations.

Testing with BPA has been extensive at sub-lethal concentrations, but the studies with effects across multiple species generally have flaws associated with them, including lack of analytical monitoring, small sample size, inadequate replication, or use of inappropriate statistical analyses leading to incorrect conclusions of study results. Studies in ramshorn snails, for example, resulted in superfeminization (e.g.,the formation of additional female organs, enlarged accessory sex glands, gross malformations of the pallial oviduct, and a stimulation of egg and clutch production) at very low concentrations in one lab (Ref. 18), but those results were not found in studies by other researchers (Refs. 19-21).

In addition, in some studies, BPA demonstrated effects at very low concentrations, but no effects were observed at the higher test concentrations. For example, tadpoles exposed to 2.3, 23, and 230 µg/L of BPA (Ref. 22) before metamorphosis had an increased female to male ratio at 23 µg/L only. These types of anomalous responses have been reported across multiple species of fish and invertebrates for BPA and are characteristic of endocrine-activechemicals. They suggest inhibition of reproduction and development at low concentrations and overcompensation by the organism at higher concentrations in response to a toxicant (Ref. 23).

It is difficult to interpret this information in a regulatory context, because the scientific methods employed in individual academic settings to test a hypothesis are not necessarily geared toward meeting or establishing generally applicable guidelines for evaluating ecotoxicity and setting corresponding regulatory limits or controls. In terms of environmental toxicity, EPA considers the currently available research as evidence that BPA has the potential to interact with the estrogen hormone system. There is some evidence that BPA is also active via the thyroid hormone pathway in amphibians and fish (Refs. 24 and 25). More recent evidence indicates that BPA also acts as an androgen receptor antagonist in both mammals and fish (Ref. 26). There are currently efforts underway by EPA's Office of Science Coordination and Policy (OSCP) through the Endocrine Disruptor Screening Program (EDSP) and the Organization for Economic Cooperation and Development (OECD) Endocrine Disrupter Testing and Assessment Work Group (EDTAWG), among others, to determine the best approach to evaluate and assess such effects (Refs. 27-29).

EPA is inviting comment on the need to further determine the hazard of BPA to various ecological species. The purpose of further testing would be to produce high quality data that could be used for risk assessment purposes for any adverse reproductive or developmental effects in different species that might result from the interactions identified through the available research.

3.What are the issues for comment concerning toxicity testing? EPA invites comment on whether and what testing should be required to further describe the hazard of BPA to various ecological species to resolve the low dose effects issue. EPA particularly invites comment on the following, for which little or no clarifying hazard information appears to be currently available or for which much of the available data have been derived from studies of questionable quality or uncertain interpretation:

a. Effects of BPA on fish in long-term tests, including those that encompass multiple generations.

b. Effects of BPA on amphibians at sensitive life stages, specifically metamorphosis (thyroid effects) and sexual development/differentiation (hypothalamic-pituitary-gonadal axis effects).

c. Effects of BPA on birds over multiple generations.

d. Effects of BPA on aquatic invertebrate species.

EPA further invites comment on the availability of current test guidelines that could help address these issues. This may include, for example, considering the draft recommendations concerning aquatic life criteria for contaminants of emerging concern (Ref. 30). Additionally, EPA is inviting the public to describe and define where they believe there are data gaps concerning the environmental toxicity of BPA, especially at low concentrations, or whether and on what basis they believe the current data are sufficient to determine whether BPA does or does not present an unreasonable risk of injury to the environment.

4.What levels of BPA are present in the U.S. environment? BPA is present in the environment as a result of direct releases from manufacturing or processing facilities (Ref. 31). BPA also may be present in the environment as a result of fugitive emissions during processing and handling, release of unreacted monomer from products (Ref. 9), or possibly from degradation of products under certain conditions. In addition, although no environmental studies on thermal paper have been done in the United States, based on information from EPA's review of European and Japanese studies, the use of unconjugated BPA in thermal paper also may contribute to environmental releases of BPA from paper manufacturing and recycling plants and to the presence of BPA in the stream of recycled paper used in toilet paper, paper tableware, and other products, and may contribute to the presence of BPA in landfills because paper products are a major contributor to the U.S. solid waste stream (Refs. 7, 32-36).3

Significant research has been done to document widespread human population exposures to BPA in the United States using biomonitoring (Refs. 37-41). Although these studies and reports indicate that most people in the United States have measurable levels of BPA in their bodies, these data do not identify the relative source contributions to BPA exposure. Researchers generally accept that food contact uses of materials containing BPA, such as polycarbonate bottles or epoxy linings in food and beverage cans, are a likely major source of human exposure, but the relative contributions of food contact uses, potential TSCA uses, or other environmental sources cannot be extrapolated reliably from these existing data. For information about the multi-agency effort to evaluate the potential human health consequences of BPA exposures, see the discussion in Unit II.B.

According to the Toxics Release Inventory (TRI) Database, total release of BPA in the United States in 2007 was 1,132,062 pounds (lbs), with releases of 122,965 lbs to air, 6,246 lbs to water, 14,972 lbs released on-site to land, and 684,638 lbs transferred off-site to land. An additional 32,928 lbs were reported as off-site water transfer to Publicly Owned Treatment Works (POTWs), with another 2,759,705 lbs transferred to incineration (Ref. 31).

Some information is available for BPA concentrations in U.S. water and other environmental media (see Table 3 in Unit II.B.4., providing values from the U.S. studies cited in this discussion). Most environmental monitoring results show that the concentrations of BPA in surface water bodies are lower than 1 μg/L (ppb), mainly due to its partitioning and biodegradability properties (Ref. 42). BPA was detected at a median concentration of 0.14 μg/L (ppb) and a maximum concentration of 12 μg/L (ppb) in 41.2% of 85 samples collected from U.S. streams in 1999 and 2000 (Ref. 43). The maximum concentration of 12 μg/L (ppb) was much higher than any of the other samples reported in the study; the next highest concentration reported was 5.2 μg/L (ppb), and as indicated by the median concentration of 0.14 μg/L (ppb), BPA concentration in other U.S. waters was much lower. A recent review of reports of BPA in surface water found that BPA was reported in 26 studies in North America (2 in Canada and 24 in the United States) with detection in 80% (852 of 1,068) of surface water samples. The median concentration reported was 0.081 µg/L (ppb) and the 95th percentile concentration was 0.47 µg/L (ppb) (Ref. 44).

Two studies have addressed individual WWTPs in two different parts of the United States. In 2001 and 2002, BPA was not detected above the detection limit of 0.0001 μg/L (ppb) in Louisiana in effluent from a WWTP, in samples collected from surface waters in Louisiana, or in drinking water at various stages of treatment at plants in Louisiana (Ref. 45). A 2008 studysampled BPA in treated wastewater from the East Bay Municipal Utilities WWTP in Oakland, California, and in a variety of locations that discharge to this WWTP (Ref. 46). This study reported detecting (limit of detection = 0.25 µg/L (ppb)) BPA in two of three treated wastewater samples at 0.38 and 0.31 µg/L (ppb). It also reported detecting BPA in wastewater generated by a pharmaceutical manufacturer (0.295 µg/L (ppb)), an industrial laundry (21.5 µg/L (ppb)), and a paper products manufacturer (0.753 µg/L (ppb)).

While U.S. studies on wastewater are limited to only two State locations, a Canadian study published in 2000 reported BPA concentrations ranging from 49.9 to 0.031 µg/L (ppb) in sewage influent and effluent (generally < 1 µg/L (ppb) in the influent and < 0.3 µg/L (ppb) in the effluent) and from 36.7 to 0.104 µg/g (ppm) in raw and digested sewage sludge from multiple WWTPs in Canada (Ref. 47). The same authors reported that BPA contamination was detected in 100% of sewage samples from 31 WWTPs across Canada with concentrations ranging from 0.080 to 4.98 µg/L (ppb) (median 0.329 µg/L (ppb)) for the influent and from 0.010 to 1.08 µg/L (ppb)(median 0.136 µg/L (ppb)) for the effluent (Ref. 48). Based on comparison of influent and effluent levels, they estimated that BPA in the influent was removed by the sewage treatment process with a median reduction rate of 68%. BPA was detected in sludge samples at concentrations ranging from 0.033 to 36.7 µg/g (ppm), on a dry weight basis. The authors also reported a wide range of BPA in wastewater discharges from industrial facilities in the Toronto, Canada, area, with concentrations ranging from 0.23 to 149.2 µg/L (ppb). Higher BPA levels in wastewater were associated with facilities producing chemicals and chemical products and packaging and paper products, and with commercial dry cleaning establishments. BPA concentrations in pulp and paper mill sludge ranged from < 0.02 (below detection limit) to 3.33 µg/g (ppm), with a median value of 0.076 µg/g (ppm), on a dry weight basis (Ref. 48). EPA notes that U.S. wastewater treatment conditions and industrial and commercial discharges may differ from what was found in Canada, but considers this Canadian study to be informative.

Municipal wastewater treatment produces solid byproducts, commonly referred to as sewage sludge. After additional treatment to meet regulatory standards for pathogen, nutrient, and metal content, this treated sewage sludge, now classified as biosolids, may be disposed of by land application; biosolids may also be incinerated or disposed of in landfills. A U.S. study published in 2006 measured BPA in 9 treated biosolids products from WWTPs in 7 States and found that all contained between 1,090 and 14,400 μg/kg (ppb) (median 4,690 μg/kg (ppb)) (Ref. 49). A 2008 study reported BPA in treated biosolids from a municipal U.S. WWTP at 4,600 μg/kg (ppb) and reported 81 μg/kg (ppb) in soil that received the land-applied biosolids (Ref. 50). That study detected BPA at 81 μg/kg (ppb) in earthworms living in treated soil. The authors also reported detecting 147 μg/kg (ppb) in a nearby “control” soil that did not receive treatment with biosolids. That anomalous result was not explained.

In 2000, the U.S. Geological Survey (USGS) collected samples from 47 ambient ground water sites (not drinking water wells) in 18 States and analyzed them for 65 organic wastewater contaminants. BPA was detected in 29.8% of the sampled ground water sites, with a mean detected concentration of 1.78 μg/L (ppb) and a range of 1.06 to 2.55 μg/L (ppb). BPA was among the top 5 most frequently detected organic compounds in this study (Refs. 51 and 52).

In the summer of 2001, the USGS collected samples from 74 sources of raw, untreated, drinking water in 25 States and Puerto Rico, in areas that were known or suspected to have at least some human and/or animal wastewater sources in upstream or upgradient areas. These sources comprise 25 ground water and 49 surface water sources of drinking water serving populations ranging from one family to more than 8 million people. BPA was detected in 9.5% of these samples at a reporting level of 1 μg/L (ppb). The maximum concentration measured in these samples was 1.9 μg/L (ppb) (Refs. 51 and 53).

Landfill leachate from one U.S. study reported maximum BPA concentrations of 1.7 μg/L (ppb) in landfill leachate and 1.4 μg/L (ppb) in the receiving ground water plume at a landfill on Cape Cod, Massachusetts, that was known to be leaking (Ref. 54). Data for other landfill sites in the United States were not available, and this single point is not representative of the country. Landfill leachate from other countries contained more than 500 μg/L (ppb) of BPA (Ref. 42). Studies conducted at Japanese landfills resulted in maximum untreated leachate concentrations of 17,200 μg/L (ppb) and treated leachate concentrations of 5.1 μg/L (ppb) (Ref. 11).

Wilsonet al.(Ref. 55) reported that BPA concentrations in soil samples taken from outdoor play areas of homes and daycare centers ranged from 4-14 ppb dry weight, with means of 6-7 ppb dry weight. Kleckaet al.(Ref. 44) reported a median concentration of 0.6 ppb BPA in North American freshwater sediments, including non-detected samples; BPA concentrations in samples from the United States ranged from 1.4 to 140 ppb dry weight. Levels in U.S. marine sediments were reported to have a median of 3.5 ppb of BPA and to range from 1.5 to 5 ppb dry weight (Ref. 56).

Although there is disagreement in interpreting some of the effects observed in studies performed to date with BPA, as described in Unit II.B.1. and 2., a comparison of the range of the effect levels observed in many studies and the predicted no effect concentration (PNEC) values used in three international regulatory risk assessments (0.175 to 1.6 μg/L, Table 1 of Unit II.B.1.) with measured concentrations in some U.S. waters and sediments, which included values as high as 12 μg/L (ppb) (surface water), 2.55 μg/L (ppb) (ground water), and 140 ppb sediment (freshwater sediment) (Table 2 of Unit II.B.2.), indicate possible risk of injury to aquatic organisms. The single available measurement of BPA in leachate from one U.S. landfill site is not sufficient to represent or characterize the United States as a whole, and landfill leachate data from other countries suggest that BPA concentrations in leachate may be significantly higher than concentrations in surface water bodies. The direct exposure pathway from wastewater to environmental organisms, along with the widespread detection of BPA in WWTP sludges, further suggest that land application of WWTP sludges may be a significant environmental exposure pathway that needs to be better understood.4

Although most currently available environmental monitoring results show that the concentrations of BPA in U.S. water bodies are lower than 1 μg/L (ppb) (median concentration of 0.14 μg/L (ppb)), these environmental measurements represent isolated snapshots in time. Because these results come from a variety of studies designed for very different purposes and conditions (for example, laboratory analytical development contrasted with field monitoring), the data are not readily comparable and cannot be assembled into a nationally or regionally representative picture. Particularly in light of the corresponding uncertainties described in Unit II.B.1. and 2., concerning potential BPA hazards at low doses, the existing data do not allow EPA to determine how many areas may exceed potential concentrations of concern, how often or how long such concentrations may be exceeded, or the sources or pathways leading to BPA presence in the environment from manufacturing, processing, distribution in commerce, use, or disposal that may result in human and environmental exposures. EPA considers that these existing data would not be sufficient to determine whether or not an unreasonable risk to the environment exists. To help resolve these uncertainties, EPA is considering requiring that manufacturers and processors of BPA conduct environmental testing consisting of targeted sampling and monitoring of surface water, ground water, sediment, soil, landfill leachate, and drinking water on and adjacent to their properties, specifically in the vicinity of manufacturing facilities and such processing facilities as foundries, WWTPs, paper and plastics recycling facilities, and other sources of BPA releases as identified through TRI reporting and other information. These test data could also help guide development of effective risk management actions if it should be determined that activities involving BPA present an unreasonable risk of injury to aquatic or other environmental systems.

Fully understanding exposure pathways and in particular the magnitude, frequency, and duration of exposure could require a nationwide survey of the occurrence of the chemical in environmental media associated with production, processing, use, disposal, and recycling facilities. However, at this time, EPA is proposing that selected monitoring of a more limited scope be conducted to help identify the most likely locations of high exposure and the sources and pathways of exposure, to determine whether BPA may be present in those locations at concentrations that pose a risk of concern to aquatic or other systems. Monitoring of aquatic sites and sediments near releases (effluents and sludge) from manufacturing and processing sites (including on-site WWTPs) reporting high releases under TRI or associated with high releases identified from other information, as well as monitoring of sites that receive runoff from landfills, would be included.

EPA believes these targeted monitoring data may provide information relevant both to the characterization of environmental risk and to the potential focus of future risk management activities such as those under TSCA section 6, if the data indicate such activities are warranted. EPA also considers these data would further inform the issue of potential human exposure levels attributable to sources other than the direct foodcontact uses believed to be the principal source of human exposure, which are regulated by the FDA. As noted earlier in Unit II.B., EPA is working with FDA, NIEHS, and CDC on additional research to better determine and evaluate the potential human health consequences of exposures to BPA, including exposures at low doses. Levels of exposure that may be identified by FDA as being of concern to human health, including children's health, would affect the extent to which EPA would take additional action to address potential risks to human health resulting from uses within TSCA jurisdiction, but EPA is not considering any additional testing specifically in regard to human health issues at this time.5

In order to be useful to an investigation of potential environmental risks posed by BPA, environmental testing must be representative and of known quality. To accomplish this, data should be collected using approved or recognized sampling, preparation, and analytical techniques. Appropriate quality assurance and quality controls also should be incorporated in the protocols for collection and analyses.

A further complicating factor in the assessment of potential environmental risks posed by BPA is that organisms in the environment, rather than being exposed to a single chemical at a time, are likely to be exposed simultaneously to multiple chemicals. The presence of other endocrine-active chemicals, including other estrogenic chemicals, for example, could affect the potential for effects on environmental organisms. It may be useful, when monitoring for BPA, to identify the total estrogenicity of a sample along with the amount of BPA present.

Potential methodologies and protocols for use in monitoring programs may include ASTM D7574-09 Standard Test Method for Determination of Bisphenol A in Environmental Waters by Liquid Chromatography/Tandem Mass Spectrometry (Ref. 62); ASTM D5730-04 Standard Guide for Site Characterization for Environmental Purposes With Emphasis on Soil, Rock, the Vadose Zone and Ground Water (Ref. 63); EPA Method 8270D (SW-846), Semivolatile Organic Compounds by Gas Chromatography/Mass Spectrometry (GC/MS), Revision 4 (Ref. 64); and other methods cited and described in such publications as Barneset al.(2008) (Ref. 51) and Focazioet al.(2008) (Ref. 53).

5.What are the issues for comment concerning environmental testing consisting of sampling and monitoring? EPA particularly invites comment on:

a. The extent and type of environmental testing that may be sufficient to characterize the environmental presence of BPA.

b. The extent and type of environmental testing that may be sufficient to understand sources of and exposure from the high concentrations of BPA found in treated biosolids from WWTPs.

c. Whether environmental testing should be conducted now, or should be tiered to occur after the uncertainties associated with the hazards of BPA at low concentrations in the environment have been resolved.

d. The locations where such environmental testing should be undertaken, such as manufacturing, processing, recycling, foundry, and other use, treatment, and disposal sites identified with BPA releases reported under TRI or other information.

e. The media (e.g.,soil, sediment, sludge, WWTP influent and effluent, landfill leachate, drinking water, surface water, ground water) to be sampled at each such site.

f. Which parties should be required to conduct the testing and/or be potentially responsible for providing reimbursement to those who conduct specific tests.

g. The appropriate methods and protocols to use in such a environmental testing program.

h. Whether such an environmental testing program should include measurements for the total estrogenicity of samples collected as well as for the concentration of BPA, and what methods and protocols may be suitable for generating and interpreting such data.

i. Whether and what additional environmental testing activities may be necessary to understand and characterize non-food-contact uses, sources, and environmental pathways that may contribute to exposure to BPA. Though, as indicated in Unit II.B., the current focus of this ANPRM is on environmental effects, this information would inform the multi-agency effort to evaluate the potential human health consequences of BPA exposures.

j. Other information that may provide insight into sources and pathways of environmental and human exposure to BPA released into the environment. Though, as indicated in Unit II.B., the current focus of this ANPRM is on environmental effects, this information would inform the multi-agency effort to evaluate the potential human health consequences of BPA exposures.

k. The cost and economic feasibility of such environmental testing, for the different types of sites.

EPA is issuing this ANPRM on certain toxicity testing and on certain environmental testing consisting of sampling and monitoring for the chemical substance BPA under TSCA section 4(a) (15 U.S.C. 2603(a)).

Section 2(b)(1) of TSCA (15 U.S.C. 2601(b)) states that it is the policy of the United States that “adequate data should be developed with respect to the effect of chemical substances and mixtures on health and the environment and that the development of such data should be the responsibility of those who manufacture [which is defined by statue to include import] and those who process such chemical substances and mixtures[.]” To implement this policy, TSCA section 4(a)(1) provides that EPA shall require by rule that manufacturers or processors or both of chemical substances and mixtures conduct testing, if the Administrator finds in a final rule that:

If EPA in a final rule makes an appropriate finding under TSCA section 4(a)(1)(A) or (B) for a chemical substance or mixture, the Administrator shall require that testing be conducted on that chemical substance or mixture. The purpose of the testing would be to develop data with respect to the health and environmental effects for which there is an insufficiency of data and experience, and which are relevant to a determination that the manufacture, distribution in commerce, processing, use, or disposal of the substance or mixture, or any combination of such activities, does or does not present an unreasonable risk of injury to health or the environment. As indicated in Unit II.A.3., EPA requests comment and supporting information regarding which TSCA section 4(a)(1) finding authority would be most appropriate for the purpose of a BPA test rule proposal. Any proposal would ultimately be based on EPA's assessment of the relevant information available at the time of proposal.

Once the Administrator has made the relevant findings under TSCA section 4(a), EPA may require any health or environmental effects testing for which data are insufficient and which are necessary to develop the data. EPA need not limit the scope of testing required to the factual basis for the TSCA section 4(a)(1)(A)(i) or (B)(i) findings as long as EPA also finds that there are insufficient data and experience upon which the effects of the manufacture, distribution in commerce, processing, use, or disposal of such substance or mixture or of any combination of such activities on health or the environment can reasonably be determined or predicted, and that testing is necessary to develop such data. This approach is explained in more detail in EPA's TSCA section 4(a)(1)(B) Final Statement of Policy (B Policy) published in theFederal Registerissue of May 14, 1993 (58 FR 28736, 28738-28739).

Authority for requiring sampling and monitoring for a chemical substance or mixture can be found within TSCA section 4. Section 4(a) of TSCA authorizes EPA to require the development of data “which are relevant to a determination that the manufacture, distribution in commerce, processing, use, or disposal of such substance or mixture, or that any combination of such activities, does or does not present an unreasonable risk of injury to health and the environment.” The extent to which such activities may affect health or the environment is dependent in part upon the human and environmental exposures to the chemical substance occasioned by those activities. As an example, TSCA section 4(a)(2)(A) specifically addresses testing for persistence of a substance. Testing to identify where and in what concentrations a chemical substance or mixture may become present in the environment contributes to an understanding of human and environmental exposures resulting from those activities. As stated in Unit II.B., EPA does not intend to initiate regulatory action under TSCA at this time on the basis of human health.

Under Executive Order 12866, entitled “Regulatory Planning and Review” (58 FR 51735, October 4, 1993), this action was submitted to the Office of Management and Budget (OMB) for review. Any changes made to this document in response to OMB comments received by EPA during that review have been documented in the docket as required by the Executive Order.

Since this document does not impose or propose any requirements, and instead seeks comments and suggestions for the Agency to consider in possibly developing a subsequent proposed rule, the various other review requirements that apply when an agency imposes requirements do not apply to this action. Nevertheless, as part of your comments on this ANPRM, you may include any comments or information that you have regarding this action.

In particular, any comments or information that would help the Agency to assess the potential impact of a rule on small entities pursuant to the Regulatory Flexibility Act (RFA) (5 U.S.C. 601et seq.); to consider voluntary consensus standards pursuant to section 12(d) of the National Technology Transfer and Advancement Act of 1995 (NTTAA) (15 U.S.C. 272 note); to consider environmental health or safety effects on children pursuant to Executive Order 13045, entitled “Protection of Children from Environmental Health Risks and Safety Risks” (62 FR 19885, April 23, 1997); or to consider human health or environmental effects on minority or low-income populations pursuant to Executive Order 12898, entitled “Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations” (59 FR 7629, February 16, 1994).

The Agency will consider such comments during the development of any subsequent proposed rule as it takes appropriate steps to address any applicable requirements.

Background

Section 4(b)(3)(B) of the Endangered Species Act of 1973, as amended (Act) (16 U.S.C. 1531et seq.), requires that, for any petition to revise the Federal Lists of Endangered and Threatened Wildlife and Plants that contains substantial scientific or commercial information that listing the species may be warranted, we make a finding within 12 months of the date of receipt of the petition. In this finding, we will determine that the petitioned action is: (1) Not warranted, (2) warranted, or (3) warranted, but the immediate proposal of a regulation implementing the petitioned action is precluded by other pending proposals to determine whether species are endangered or threatened, and expeditious progress is being made to add or remove qualified species from the Federal Lists of Endangered and Threatened Wildlife and Plants. Section 4(b)(3)(C) of the Act requires that we treat a petition for which the requested action is found to be warranted but precluded as though resubmitted on the date of such finding, that is, requiring a subsequent finding to be made within 12 months. We must publish these 12-month findings in theFederal Register.

On August 30, 2006, we received a petition dated August 18, 2006, from three private citizens and three other parties (the Palouse Prairie Foundation, the Palouse Audubon Society, and Friends of the Clearwater) requesting that the giant Palouse earthworm (Driloleirus americanus) (GPE) be listed as an endangered or threatened species under the Act, and critical habitat be designated. The petition included supporting information regarding the species' taxonomy and ecology, distribution, present status, and causes of decline. On October 9, 2007, we published a 90-day finding stating that the August 30, 2006, petition did not provide substantial scientific or commercial information to indicate that listing the GPE may be warranted (72 FR 57273). On January 24, 2008, the petitioners filed a lawsuit in the U.S. District Court, Eastern District of Washington against the U.S. Department of the Interior and the Service challenging the “not substantial” decision (Palouse Prairie Foundation et al.v.Dirk Kempthorne, et al.,No. 2:08-cv-0032-FVS). On February 12, 2009, the District Court denied the Appellants' motion for summary judgment and granted summary judgment in favor of the Service, upholding the October 9, 2007, determination. The U.S. Court of Appeals for the Ninth Circuit affirmed the District Court ruling on June 14, 2010 (D.C. no. 2:08-cv-00032-FVS).

On July 1, 2009, we received a new petition dated June 30, 2009, from Friends of the Clearwater, Center for Biological Diversity, Palouse Audubon, Palouse Prairie Foundation, and Palouse Group of the Sierra Club (petitioners) requesting that the GPE be listed as an endangered or threatened species either in the entirety of its range, or in the Palouse bioregion as a significant portion of its range, and that critical habitat be designated under the Act. The petition clearly identified itself as such and included the requisite identification information for the petitioners, as required by 50 CFR 424.14(a). The petition included information on the GPE's taxonomy, species description, distribution, habitat, status, and potential threats. The petition was accompanied by a letter from Samuel W. James, who stated that he is “the only earthworm taxonomist operating in the U.S.A.” and has “extensive experience in biodiversity of earthworms” (2009in litt.), and included additional information about the GPE and potential threats to the species. In an August 5, 2009, letter to the petitioners, we acknowledged receipt of the petition and determined that issuing an emergency regulation temporarily listing the species under section 4(b)(7) of the Act was not warranted. We also stated that, due to funding constraints in fiscal year 2009, we would not be able to further address the petition at that time but that we would further evaluate the petition when funding became available in fiscal year 2010.

On July 20, 2010, the Service announced a 90-day finding on the 2009 petition to list the GPE as endangered or threatened under the Act, and to designate critical habitat (75 FR 42059). Based on our review, we found the petition presented substantial scientific or commercial information indicating that listing the GPE as endangered or threatened may be warranted. We initiated a review of the status of the species to determine whether listing the GPE was warranted, and requested scientific and commercial data, and other information, regarding the species. This notice constitutes the 12-month finding on the July 1, 2009, petition to list the GPE as endangered or threatened, as petitioned.

The GPE is one of about 100 native and at least 45 nonnative earthworms described in the United States (Hendrix and Bohlen 2002, p. 802). However, very little is known about the species. The GPE was first described by Smith in 1897, based on a collection near Pullman, Washington. At the time of this collection, Smith stated: “This species is very abundant in that region of the country and their burrows are sometimes seen extending to a depth of over 15 feet” (Smith 1897, pp. 202-203). His writing is based on second-hand information provided by R.W. Doane of Washington State Agricultural School (now Washington State University) in Pullman, Washington, which does not offer numerical or geographical context for his use of the terms “very abundant” or “that region of the country.” This burrow depth characterization has not been confirmed or contradicted by any subsequent field work.

Early descriptions indicate the GPE can be as long as 3 feet (ft) (0.9 meters (m); Smith 1897, p. 203). Reports in the popular literature of GPEs up to 3.3 ft (1 m) in length (Science Daily 2006, p. 1; Science Daily 2008, p. 1) have not been confirmed, and collections suggest that specimens are more moderate in size (approximately 6 to 8 inches (in) (15.2 to 20.3 centimeters (cm)) in length) (Smith 1937, p. 161; Science Daily 2006, p. 1; Science Daily 2008, p. 1).

The Service accepts the current taxonomic classification of the GPE (Subclass—Lumbricina; Superfamily—Megascolecoidea; Family—Megascolecidae; Genus—Driloleirus;Species—americanus) (Smith 1897, p. 203; Fender and McKey-Fender 1990, p. 372; Fender 1995, pp. 53-54). While the naming conventions of the GPE have changed over time (Megascolides americanusin 1897 (Smith 1897, p. 203) changed toDriloleirus americanusby 1990 (Fender and McKey-Fender 1990, p. 372), there is no information provided in the petition or in our files that would indicate scientific disagreement about its taxonomic classification as a species. Adult specimens in theDriloleirusgenus are generally distinctive, but identifying to the species level requires expert morphological analysis, including dissection or DNA evidence. Both methods take time, and there are few species experts. It is difficult to identify juvenile earthworm species, because they have no clitellum (a glandular section in the body wall, similar in shape to a saddle). The clitellum is akey morphological difference for determining many species, and juvenile earthworm coloration can also vary, depending on soil type. Newly hatched earthworms are even more difficult to identify, and until DNA analysis becomes a more available tool, earthworm identification requires the examination of sexually mature individuals. Depending on site conditions and growth, an earthworm would need to be 3 to 6 months of age before being recognizable as being in the genusDriloleirus(Johnson-Maynard 2011, pers. com.).

Distribution of native earthworm species in the Pacific Northwest is limited by several factors. Pleistocene glaciation covered nearly the whole of Canada and the northern edge of the United States, eliminating earthworms from the area covered with ice (Fender 1995, p. 54). Since the retreat of the glaciers, earthworms in the Lumbricidae family have been able to colonize the ice-free areas in a few centuries, although earthworm distribution in the Megascolecidae family (to which the GPE belongs) stops near the terminal moraines (ridges of rock, gravel and soil across valleys at the end glaciers or ice fields) of the ice sheet. This may be because the megascolecids prefer fine-textured soils, which are largely absent at the edge of Pleistocene glaciation (Fender 1995, p. 55). Other barriers, including mountain ranges and arid areas (Baileyet al.2002, p. 26), have slowed recolonization of the Columbia Basin.

At the time of the original description, in 1897, this taxon was known only from the area around Pullman, Washington (Smith 1937, p. 157). The GPE was originally considered to be an endemic species (a species native to a particular region), that uses grassland sites with deep soil and native vegetation of the Palouse bioregion (Wells 1983, p. 213; James 1995, p. 1; Niwaet al.2001, p. 34). The Palouse bioregion is an area of rolling hills and deep soil in southeastern Washington and adjacent northwestern Idaho. More recently, this species has also been found in Douglas-fir forests in the Palouse region (Johnson-Maynard, September 21, 2010,in litt.p. 1; November 30, 2010,in litt.p. 1), and on the eastern slope of the North Cascades Mountains (Cascades) west of Ellensburg, Washington (Fender and McKey-Fender 1990, p. 358). In 2010, the GPE was also documented in dry pine forest habitat near Leavenworth, Washington (Johnson-Maynard 2010, p. 3,in litt.). This broader distribution, which is now known to include Latah County (Idaho), Whitman County (Washington), Kittitas County (Washington), and Chelan County (Washington), provides evidence that the species may not be endemic to Palouse grasslands.

Confirmed GPE locations, and other potential GPE locations (DNA is currently being analyzed for these specimens), are identified in Table 1. Two of the potential GPE collections are of particular interest: one in shrub/grassland habitat near Chelan, Washington, and one in second-growth forest habitat east of Moscow, Idaho (Johnson-Maynard 2010, pp. 1-2; November 30, 2010,in litt.p. 2). The DNA or morphology results for these specimens are not yet available to enable identification to the species level, but if these specimens are confirmed to be GPE, the currently known distribution and habitat types documented for the species will be expanded. One commenter provided a list of possible GPE locations in the Palouse region (Hall 2010,in litt.pp. 2-3), but acknowledged that the sites were not confirmed. Although these anecdotal locality reports may be helpful in identifying areas for future GPE surveys, they are not relevant to this finding.

Table 1 identifies confirmed GPE and potential GPE locations (at this time just identified toDriloleirusgenus; DNA analysis is pending), and information on survey methods for each collection where available. While negative survey data are important to understand the distribution of any species, the Service found little information on surveys with negative results in the Palouse, and no information on negative surveys outside of the Palouse. The available information on negative survey results is presented in Table 1.

Earthworms are not randomly distributed in the soil (Guild 1952, as referenced in Edwards and Lofty 1977, p. 127), and some are difficult to detect. Factors that influence this non-random distribution could include: (1) Physical and chemical characteristics of the soil; (2) food availability; (3) the reproductive potential and dispersal capabilities of the species; or (4) interactions between these factors (Murchie 1958, as referenced in Edwards and Lofty 1977, p. 127). Earthworms also occur in patchy distributions, which make it difficult to determine population demographics (Whalen 2004, pp. 143, 148, Umicker 2009, p. 187). Edwards and Bohlen (1996, p. 90) stated that assessments of size, distribution, and structure of earthworm populations are difficult because numbers change with season, demography, and vertical distribution in the substrate.

In his letter submitted with the petition, James (2009in litt.p. 2) states that a reasonable and sufficient effort has been made to find the GPE in a variety of habitats within its presumed range, and that these efforts have failed except in very rare instances in natural or little-disturbed vegetation. James also stated that the Washington State University team surveyed many locations (most importantly in agricultural lands), looking for large burrows that may indicate the presence of large earthworms, but only foundLumbricus terrestris(the common night crawler), an invasive species (James 2009,in litt.pp. 2-3). However, recently collected and confirmed specimens that have been documented in forested habitats and on the eastern slope of the Cascade Mountains in Washington (Table 1) indicate that survey efforts for the GPE to date have not been adequate to establish its distribution or the diversity of habitat types in which it occurs. Therefore, we believe the petitioners' assumptions regarding the presumed distribution of the GPE are likely erroneous.

Fauci and Bezdicek's study (2002, pp. 258-259) compared nonnative lumbricid earthworm distribution in the Palouse region of eastern Washington and northern Idaho. In the spring of 1999, they surveyed 46 sites in the Palouse, including sites in agricultural fields with a history of conservation tillage, areas next to waterways, and perennial vegetation areas along road rights-of-way or on old homesteads. Survey methods included digging six spades of soil in a 10-square-meter area, then hand-sorting and examining the soil. Additional samples were taken if immature worms were found to ensure adults for identification. Although the results for the GPE were negative, the Fauci and Bezdicek survey was not designed to specifically find this species. In addition, survey protocols have not yet been developed for the GPE; therefore, it is uncertain the protocol used in this study would have found GPE, if present. If reports that the GPE lives in burrows more than 15 feet deep are correct, the spade sampling method used by Fauci and Bezdicek would appear to be inadequate to confirm the species' absence.

Other negative earthworm surveys in the Palouse area were also not specifically designed to find the GPE. Umikeret al.(2009, pp. 184-185, 187) compared soil characteristics, cropping practices, and earthworm densities in 24 agricultural fields in the Palouse, but did not identify the earthworms to species level in that study (p. 187). However, adultDriloleirusearthworms are distinctive enough that they likely would have been documented, had they been collected. JuvenileDriloleirusearthworms, on the other hand, are not distinctive (Johnson-Maynard 2011, pers. com.), and hence could have been missed in this survey. Johnson-Maynardet al.(2007, p. 338) compared earthworm dynamics and soil properties in conventionally tilled and no-till agricultural fields on one research farm in the Palouse, and found only the nonnative southern worm (Aporrectodea trapezoids) (p. 340). Smetaket al.(2007, p. 161) investigated earthworm population density in urban settings in Moscow, Idaho; no native earthworm species were collected (p. 166). Nevertheless, while the negative survey data are interesting, in that the GPE has not been detected in agricultural fields or urban areas to date, coupled with information in Table 1, these data demonstrate how geographically limited the known survey efforts have been.

It is apparent that additional GPE surveys are needed to determine the range, habitat preference, and life history of this species, particularly in light of the recent confirmation of the species near Leavenworth, Washington, in forested habitat. James (2000, p. 5) acknowledges there have been a limited number of earthworms collected in the Columbia basin, which includes the eastern slope of the Cascade Mountains and the Palouse area, and only a small portion of potential habitat has been surveyed. In addition to limited survey efforts, this species is difficult to detect. Fender (September 14, 2010,in litt.p. 1) noted thatDriloleirusspecies can at times be found near the surface during suitable survey conditions, but if conditions are dry they may be undetectable. Johnson-Maynard (September 21, 2010,in litt.p. 2) noted that one Palouse site had negative survey results for native earthworms in 2005, but later sampling in 2010 detected one adult GPE at the same site. The Xerces Society stated that due to the difficulty in detecting the Oregon giant earthworm (Driloleirus macelfreshi) (a similar species in the same genus), abundance estimates have not been made, and the species' status and threats cannot be determined until an effective survey protocol is developed and tested (Xerces Society 2009, p. 3).

Due to the difficulty in surveying for the GPE, the Idaho Department of Fish and Game, the Service, and others have contributed resources to the University of Idaho to develop appropriate survey protocols to address the scientific challenges associated with GPE surveys (Groen 2010,in litt.p. 2; Johnson-Maynard 2010,in litt.p. 2; Science Daily 2008, p. 2). Staff at the University of Idaho, including Johnson-Maynard and others, are currently working to develop and refine sampling methods and strategies, including a soil electroshocking technique that appears to be promising.

In summary, the level of survey effort for the GPE has been low, the species is difficult to detect, and effective survey methods are still being developed. There is a lack of survey data, and large geographic and taxonomic gaps in our knowledge (Fleckenstein 2011,in litt.p. 1). Researchers have only recently begun to look more broadly for the species including localities along the eastern slope of the Cascades. However, the GPE has now been documented in dry forest habitats, which provides further evidence that the complete range and distribution of the species is presently unknown, but are likely broader than the area identified by the petitioners.

Habitat requirements for the GPE are not well understood. The original descriptions by Smith (1897, 1937) do not present any descriptive information about the habitat where the specimens were initially collected. The GPE was originally thought to be a Palouse-region grassland species, and several specimens have been found in Palouse grassland remnants (Table 1; Sánchez-de León and Johnson-Maynard 2009, p. 1393; Science Daily 2008, p. 1; Johnson-Maynard September 21, 2010,in litt.pp. 1-2; Johnson-Maynard, November 30, 2010,in litt.p. 2-3; Jensen 2010,in litt.p. 6). Wellset al.(1983, p. 213) stated that Fender collected specimens under hawthorn thickets; Johnson-Maynard (September 21, 2010,in litt.p. 1) described the vegetation type at Johnson and Johnson's Moscow Mountain site as Douglas-fir forest.

There is limited specific information on the habitat type associated with the GPE collected near Ellensburg, Washington. Fender and McKey-Fender (1990) described the location as “in the hills west of Ellensburg,” and they described the GPE range at this locality as extending into “treeless areas” (pp. 358, 366). The GPE was not collected in recent surveys conducted in agricultural and urban locations in Latah County, Idaho (Johnson-Maynardet al.2007, p. 340, Smetaket al.2007, p. 166; Umikeret al.2009, p. 187), and Whitman County, Washington (Fauci and Bezdicek, 2002 p. 257). Vegetation and soil characteristics of confirmed and potential GPE sites are described above in Table 1, where that information was available. Sánchez-de León and Johnson-Maynard (2009, p. 1394; Petition, p. 5) observed that remaining prairie remnants in the Palouse are often steep or rocky, or contain shallow soil, and, therefore, may be less suitable for earthworms (Sánchez-de León and Johnson-Maynard 2009, pp. 1394, 1398; Petition, p. 5). However, Johnson-Maynard (2010, pp. 2-3) noted that soils at the Paradise Ridge site near Latah, Idaho, had a high gravel content, suggesting that the GPE may be able to exist in soil types that would not be expected to be preferred habitat for most earthworms. She further noted that pastDriloleirussamples provided by a landowner near Leavenworth, Washington, were obtained from a compacted area covered with gravel. Johnson-Maynard (2010, pp. 3-4) described the confirmed GPE collection site near Leavenworth, Washington, as Ponderosa pine forest with an understory ofBalsamorhiza sagittata(arrowleaf balsamroot) and annual grasses. Although the GPE has also been documented in forests on the eastern slope of the Cascades and in Douglas-fir forests in the Palouse, significant uncertainties exist as to whether the species occurs in specific types or ages of forests, occurs in previously logged forests, or may be habitat-limited because of elevation or other site characteristics.

Earthworms are generally divided into three life-history strategies based on their habitat use: epigeic, endogeic, or anecic (Bouche 1977, as referenced in James 2000, p. 2; Edwards and Bohlen 1996, pp. 113-115). Epigeic worms live near the ground's surface and consume organic litter on and near the surface. Endogeic worms (which the petitioners currently believe the GPE to be (James 2009,in litt.p. 3)): (1) Live in the upper layers of mineral soil, (2) consume organic material in the mineral soil or at the soil-litter interface, and (3) are often pale in appearance (Edwards and Bohlen 1996, p. 114). Anecic worms, which the petitioners initially believed the GPE to be (James 2009,in litt.p. 3), and we believe the GPE to be based onthe prevailing evidence, live in deep, semi-permanent burrows and move to the surface to feed on fresh plant litter. Anecic earthworms are the largest and longest lived of the three earthworm types (James 2000, p. 2; 1995, p. 6), and transport fresh plant material from the soil surface to subterranean levels. Deep-burrowing anecic earthworms usually produce castings on the surface near exits to their burrows (Edwards and Bohlen 1996, p. 198). GPE castings were observed at the Leavenworth, Washington, study area (Johnson-Maynard 2010, p. 2).

James (2009,in litt.p. 3) concluded that, based on the lack of pigmentation and information indicating that the species is not associated with surface castings, the GPE “is probably an endogeic, meaning living entirely in the soil, on soil resources consisting of organic matter in varying stages of decomposition.” He also states that deep burrow depths would be useful in avoiding dry soil conditions common in late summer within the range of the species (September 3, 2010, in litt. p. 1). Fender (September 14, 2010,in litt.p. 1) thinks deep soils would be helpful to survival and sees no reason to doubt the earlier descriptions of burrowing depths.

Characterizing earthworm life histories within one of three life-history strategies may not be entirely instructive, because some species may exhibit a combination of characteristics (Bouche 1977, as referenced in Edwards and Bohlen 1996, p. 113). However, understanding an earthworm species' life history is important for evaluating potential threats, the pathways that expose them to threats, and how they might respond.

As stated earlier, James (2009,in litt.,p. 3) initially speculated that the GPE was an anecic species, but now believes the species is probably an endogeic earthworm. He indicated that this conclusion is based on seeing a GPE specimen and learning more about the genus; if the GPE lacks pigmentation in the head and does not defecate at the surface (i.e.,leave castings), it is highly unlikely to have an anecic life-history strategy. We have no information indicating whether James has conducted field surveys for this particular earthworm species; however, his current opinion appears to be inconsistent with the existing literature, descriptions of GPE burrowing depths described in the literature, and field observations of castings by researchers at the Leavenworth, Washington, GPE location (Smith 1897, pp. 202-203; Fender and McKey-Fender 1990, p. 364; James 2000, p. 5; Johnson-Maynard 2010, p. 2).

In our 2010 90-day finding (75 FR 42059), we solicited scientific information on the GPE's endogeic or anecic life-history strategy to inform our status review. Johnson-Maynard (in litt.2010, p. 2) stated that the GPE is likely anecic, based on her surveys at locations near Leavenworth, WA. In those studies, the GPE was associated with pores leading down into unconsolidated parent material, and surface castings were observed, which are indicative of a deep-burrowing species. Johnson-Maynard has conducted or been involved with a number of field surveys where GPE specimens were collected (see Table 1 above). Therefore, based on the best available scientific information, field observations, and the existing literature, we believe the prevailing evidence indicates the GPE is an anecic earthworm species, although we acknowledge that there are still significant uncertainties regarding its biological requirements.

In summary, the current understanding regarding the life cycles of even quite common earthworms is inadequate and requires more study (Edwards and Lofty 1977, p. 68), and there are many species about which little is known (Edwards and Bohlen 1996, p. 46). Accordingly, there are significant scientific uncertainties regarding the biology, distribution, habitat, and population trends of the GPE. The GPE's distribution has been documented to include areas within the Palouse bioregion, and areas within the eastern slope of the Cascade Mountains in Washington. We do not know whether there are other occupied sites between or outside of these locations, as few surveys have been conducted, the species is difficult to survey for, and survey methods are still being developed.

Documented habitat types used by the GPE in the Palouse bioregion include native grasslands and Douglas-fir forest. In addition, the GPE location near Leavenworth, Washington, is described as dry Ponderosa pine forest. There is very little specific information on habitat type at the GPE location west of Ellensburg, Washington. TheDriloleirusearthworm species recently collected near Chelan, Washington, and east of Moscow, Idaho, are being identified (see Table 1 above). If these specimens are confirmed to be the GPE through DNA or other analysis, the species' range and diversity of habitat types used would be expanded.

Section 4 of the Act (16 U.S.C. 1533) and implementing regulations (50 CFR part 424) set forth procedures for adding species to, removing species from, or reclassifying species on the Federal Lists of Endangered and Threatened Wildlife and Plants. Under section 4(a)(1) of the Act, a species may be determined to be endangered or threatened based on any of the following five factors:

(A) The present or threatened destruction, modification, or curtailment of its habitat or range;

(B) Overutilization for commercial, recreational, scientific, or educational purposes;

(C) Disease or predation;

(D) The inadequacy of existing regulatory mechanisms; or

(E) Other natural or manmade factors affecting its continued existence.

In making this finding, information pertaining to the GPE in relation to the five factors provided in section 4(a)(1) of the Act is discussed below. In addition, in making this 12-month finding on the petition we considered and evaluated the best available scientific and commercial information.

Given the paucity of information on GPE, surrogates may be useful. The petitioners claim that it is appropriate to use other earthworms as surrogates to determine effects to the GPE, provided they are biologically and ecologically similar (Sappingtonet al.2001, p. 2869; Caroet al.2005, p. 1821; Petition, p. 10). In some instances, the use of surrogate species (such as other earthworms) may be helpful in evaluating potential effects to the GPE, provided the appropriate scientific controls and precautions are taken. Caroet al.(2005, p. 1821) states “for substitute species to be appropriate, they should share the same key ecological or behavioral traits that make the target species sensitive to environmental disturbance and the relationship between populations' vital rates and disturbance levels should match that of the target; these conditions are unlikely to pertain in most circumstances and the use of substitute species to predict endangered populations' responses to disturbance is questionable.” The Oregon giant earthworm (Driloleirus macelfreshi) is in the same genus, and is believed to construct permanent, deep, subsurface burrows (a characteristic that indicates an anecic life-history strategy), and could potentially be an appropriate surrogate. However, the status and threats of this species cannot be determined until an effective survey protocol is developed and tested (Foltz 2009, pp. 2-3). Therefore, using it as a surrogate would provide little to no additional insight into potential threats to GPE. No other relevant surrogatespecies have been suggested or investigated.

Historical information regarding potential habitat loss is presented in the following discussion, for context. However, the focus for purposes of our analysis and response to the petition is on current and future habitat conditions, and whether the activities responsible for those conditions present a threat to the GPE such that listing under the Act is warranted.

As described in the 2010 90-day finding (75 FR 42061), the petitioners claim that the GPE is threatened by habitat conversion, loss, and fragmentation from agriculture and urban sprawl in the Palouse region (Petition, pp. 1, 7). The petitioners cite Sánchez-de León and Johnson-Maynard (2009, pp. 1393-1394, 1398), who state that combined effects of land-use change, habitat fragmentation, and competitive interactions have caused native earthworm declines. James (2009, p. 1) stated that indigenous earthworms are sensitive to habitat disturbance, and that to find indigenous earthworms one must work in undisturbed or mildly disturbed vegetation. Undisturbed vegetation is rare in the Palouse bioregion, as the native grassland habitat has been reduced to less than 1 percent of its pre-agricultural extent (Petition, p. 8; James 2009, p. 1; Nosset al.1995, p. 74).

Estimates of native habitat conversion in the Palouse bioregion vary, but several studies indicate the conversion has been high: 99.9 percent of Palouse prairie habitats have been converted to agriculture (Noss 1995, p. 74); 94 percent of the grasslands and 97 percent of the wetlands in the Palouse bioregion have been converted to crop, hay, or pasture (Blacket al.1998, pp. 9-10); 21 percent of previously forested lands have been converted to agriculture or urban uses (Gilmore 2004, p. 3); and less than 1 percent of the original bunchgrass prairie habitat remains (Donovanet al.2009, p. 1). However, comments on the 90-day finding noted that habitat loss in the Palouse due to agriculture happened historically and is not currently occurring. Much of the prairie was converted to farms by 1910, and much of the urban growth around the Pullman area occurred on farmland, not remaining prairie fragments (McGregor 2010,in litt.,p. 2; McGregor 1982, p. 109). However, habitat conversion in the Palouse may still occur, as neither Latah County, Idaho, nor Whitman County, Washington, have ordinances to prevent native habitat conversion (Latah County Board of Commissioners 2010, pp. 1-27; Whitman County 2010, pp. 1-76).

The petition identified several locations in the Palouse area that contain prairie remnants (Petition, p. 5). A study of four prairie remnants and adjacent Conservation Reserve Program (CRP) fields was carried out by Sánchez-de León and Johnson-Maynard (2009, pp. 1393, 1395; Petition, p. 4). In that study, the researchers collected one GPE, and commented that many remaining prairie remnants are not suitable for tillage because they are often steep or rocky, or contain shallow soil (2009, p. 6; Petition, p. 5). They also hypothesized that prairie remnants may not be the preferred habitat for the GPE due to shallow rocky soil. They described the GPE collection site at Paradise Ridge near Latah, Idaho, as having a high gravel content (Johnson-Maynard 2010, pp. 2-3). They acknowledged that sampling challenges could bias survey information on the GPE, and cautioned that hand-sampling methods may underestimate abundance of anecic species (Sánchez-de León and Johnson-Maynard 2009, p. 1399).

There is no baseline (i.e.,pre-agriculture) density and distribution information on the GPE, and there are significant challenges associated with surveying for this species. These challenges, coupled with the fact that earthworms have patchy distributions (Guild 1952, as referenced in Edwards and Lofty 1977, p. 127; Murchie 1958, as referenced in Edwards and Lofty 1977, p. 127; Whalen 2004, pp. 143, 148; Umicker 2009, p. 187), preclude our ability to correlate land use impacts with GPE abundance, based on the best available information. The GPE has been documented in both the Palouse bioregion and on the eastern slope of the Cascade Mountains, near Ellensburg and Leavenworth, in central Washington (see Table 1 above). There is little descriptive information about the habitat associated with the GPE that was collected near Ellensburg; it isn't clear whether the location is grassland or a different habitat type, and the specific location is uncertain. James (2009in litt.,p. 2) speculated the Ellensburg site collection is a relict of a distribution that must have been more or less continuous at one time, but due to climate change and increased aridity has now become fragmented. Fender and McKey-Fender (1990) described the locality as being “in the hills west of Ellensburg,” and noted that the range of the GPE extends into “treeless areas” (pp. 358, 366). A report by Adolfson Associates (2005, p. 1) was presented as evidence of urban sprawl being a threat to GPE habitat. However, this report was limited to areas within the City of Ellensburg, Washington boundary, and is not particularly instructive in terms of correlating future urban development with loss of GPE habitat because pre-development density or distribution or both in that area are unknown. The petitioners also claim the grasslands around Ellensburg have been extensively modified by agriculture, similar to the Palouse bioregion (Adolfson Associates 2005, p. 2; Petition, p. 8; James 2009,in litt.,p. 2). However, the best available information is insufficient to determine or infer how or whether the GPE has been impacted by habitat loss and fragmentation in this area, because we have no baseline information with which to correlate land use modification with GPE abundance.

The best available scientific information is also inconclusive as to whether the GPE occurs in a certain forest type or age, or whether the species occurs in a broad variety of habitats. The GPE site near Moscow, Idaho, is in Douglas-fir forest habitat, and the Leavenworth, Washington, site is in dry ponderosa pine forest. Quigleyet al.(1996, p. 54) stated that in the Columbia Basin, the total area in forest has remained relatively constant during the last two centuries, and broad indicators of sustainability indicate that Basin forest acreage and inventory volumes are relatively constant. If the GPE is a forested habitat generalist, it could be stable in forested locations; however, if it requires a forest of a specific type or age it may or may not be impacted by habitat loss, depending on the type of development activity involved. In either case, the available scientific evidence does not address that uncertainty.

In summary, the GPE's current and historical population size, distribution, and range of habitat types used are unknown. Based on recent collections, the GPE's range outside of the Palouse region has been expanded and now includes portions of the eastern slope of the Cascade Mountains. The GPE has also been documented in both grassland and forested habitats in the Palouse. However, survey efforts have been limited, and sampling protocols are still being developed to improve researchers' ability to detect the species during field investigations. While habitat conversion may occur and there may be local impacts, the GPE range is much wider than previously known and includes more diverse habitats than previouslyknown. Because we cannot identify the full extent of the GPE's range or the varieties of habitat types it may use, we are unable to correlate habitat conversion with GPE abundance. Therefore, for the reasons stated above, the best available scientific information does not indicate current or future habitat loss or fragmentation represents a threat to the species.

The petitioners present several claims in their petition, each of which has been evaluated and addressed below. They claim that earthworms or their grassland habitats are influenced by soil disturbance, tillage, traffic, food sources, chemical and pesticide residues, and soil microclimate (Jenningset al.1990, p. 75; Edwards and Bohlen 1996, pp. 283-289; Edwardset al.1995, pp. 200-201; USDA-NRCS 2001, p. 2; Petition, p. 10). Moisture, temperature, and food availability influence earthworm populations in general, and earthworms need the organic matter found in the topsoil that agriculture removes (James 2000, pp. 1-2; Petition, p. 11). Bare soil can increase the effects of flooding, drought, or other weather conditions due to the lack of vegetation that buffers soil from extreme moisture, dryness, and temperature fluctuations. These conditions can temporarily or permanently make soils unusable by earthworms (James 2000, pp. 1-2; Petition, p. 11). James (2009,in litt.,p. 1) stated that earthworms are highly sensitive to habitat disturbance, such as forest clear cutting or conversion of any habitat to agriculture, and the native earthworms are generally destroyed by any type of drastic and sudden habitat modification. One commenter stated there may have been long periods of bare soil historically in the Palouse region, but seeding and fertilizing technology improvements now enable farmers to prepare seedbeds with minimal disturbance (McGregor 2010,in litt.,p. 2). James also stated, “when seeking the indigenous earthworms, it is almost always a complete waste of time to work in anything but undisturbed or mildly disturbed stands of vegetation” (James 2009,in litt.,p. 1). GPE have been found in forested locations, but it is unknown whether these are previously disturbed habitats.

We acknowledge that soil disturbance has occurred and may still be occurring in GPE habitat. However, we currently have no information linking soil disturbance with GPE presence or absence. Survey efforts for GPE have been limited, and sampling protocols remain to be developed. Until we have a better understanding of the species' distribution and habitat information, we are unable to determine with reasonable confidence whether the GPE uses disturbed or undisturbed habitats, or both. Therefore, the best available scientific information does not indicate soil disturbance is a threat to the GPE.

The petitioners claim that soil compaction from farm machinery or other activities can affect earthworms by making burrowing and feeding more difficult (James 2000, p. 9), by decreasing soil pore size and thereby decreasing nutrient retention and changing the soil food web (Niwaet al.2001, pp. 7, 13), or by favoring nonnative earthworms that prefer course soils rather than the fine soils apparently preferred by the GPE (Fender and McKey-Fender 1990, p. 364; Petition, p. 11). Johnson-Maynard (September 21, 2010,in litt.,pp. 2-3) noted that the effects of soil compaction on earthworm density can vary based on the species' ecological strategy (i.e.,anecic versus endogeic); larger species, such as anecic earthworms, have been found to be less sensitive to soil compaction than smaller species (Cluzeauet al.1992, p. 1661) and may be more abundant in compacted areas compared to non-compacted areas (Cuendet 1992, p. 1467). Fender (1995, p. 57) has often found other Argilophilini worms (a tribe of native Pacific Northwest earthworms that includes the GPE) in compacted trails; Capowiezet al.(2009, p. 214) notes that our current knowledge of the sensitivity of earthworms to compaction is limited. In addition, the assumption that compaction would favor exotic species over native species due to their preference for finer-textures soils is invalid; while compaction does impact total porosity and pore size distribution, it does not alter soil texture (Johnson-Maynard, September 21, 2010,in litt.,p. 3). Johnson-Maynard states that generalizations such as those presented by the authors of the 2009 petition, suggesting that compaction favors nonnative species, should be interpreted with caution (Johnson-Maynard, September 21, 2010,in litt.,p. 3). In addition, survey efforts for the GPE have been limited, and sampling protocols remain to be developed. Until we have a better understanding of the species' distribution and habitat information, we are unable to determine with reasonable confidence whether soil compaction is occurring in GPE habitat, and if it is, whether it is resulting in a negative response in the species. Therefore, the best available scientific information does not indicate soil compaction is a threat to the species.

The pH scale describes how acidic or basic a substance is, and ranges from 0 to 14, with 7 being neutral, below 7 being acidic, and greater than 7 being basic. The petitioners cite soil chemistry effects, notably a reduction in soil pH from nitrogenous fertilizer application, as having deleterious effects on earthworms (Maet al.1990, p. 76), and state that generally earthworms do not thrive in soils with a pH below 5 (Petition, p. 11; Edwards and Lofty 1977, p. 234). However, the best available scientific information related to the responses of earthworms to pH appears to both support and contradict the petitioners' claim with regard to the GPE. Soil pH is a factor that often greatly affects earthworm populations, both in numbers of individuals and numbers of species. According to the Natural Resources Conservation Service (USDA-NRCS 2001, p. 5), earthworms do not thrive in soils with a pH below 5 (USDA-NRCS 2001, p. 2; Edwards and Lofty 1977, p. 234; Edwards and Bohlen 1996, p. 276). However, one Australian study of tillage effects to one native anecic earthworm species (Spencefiella hamiltoni) described the surface soil in the study area as highly acidic (pH = 4.1), with the pH increasing (or acidity decreasing) with depth (pH = 5.0 at 0.8 meters) (Chan 2004, p. 90). Some earthworm species are intolerant of acid soil conditions, some are tolerant, and others can tolerate wide ranges of soil pH (Edwards and Bohlen 1996, p. 142). Because soil pH is related to other soil factors, such as clay content, or cation exchange capacity (the ability to hold plant nutrients), it is often difficult to establish a direct cause-and-effect relationship between soil pH and the size of earthworm populations (Edwards and Bohlen 1996, p. 144).

Fender (1995, p. 56) stated that Argilophilini worms appear to have higher tolerance than lumbricids (nonnative earthworms, such as the night crawler) for low pH (below 5, acidic) soils; high clay; and resinous, low-nitrogen, plant litter. Sánchez-de León and Johnson-Maynard (2009, pp. 1397, 1399) found a significant negative interaction between soil pH and mean earthworm density and mean earthworm fresh weight. The nonnative southern earthworm (Aporectodea trapezoids) was more abundant in CRP sites with lower pH values (pH 5.9 to 6.2) than prairie soils (pH 6.3 to 6.6) in a study of four paired CRP and prairie remnant sites. Their data did not support their hypothesis that nativeearthworms would be dominant in prairie remnants and exotic earthworms dominant in CRP set-aside lands (Sánchez-de León and Johnson-Maynard 2009, pp. 1398). In that study, one GPE was collected during sampling at the Smoot Hill prairie remnant study site. In the study, the prairie remnants' mean soil pH at depth was pH 6.3 (20-30 cm), pH 6.5 (10-20 cm), and pH 6.6 (0-10 cm), while in the CRP study sites the mean soil pH at depth was pH 6.2 (20-30 cm), pH 6.0 (10-20 cm), and pH 5.9 (0-10 cm) (Sánchez-de León and Johnson-Maynard 2009, p. 1397). The researchers stated they were unsure whether lower pH (more acid) in CRP sites correlated with some other non-measured soil parameter, such as previous fertilizer applications and resultant increased organic matter. They hypothesized the negative relationship between earthworm density and soil pH could be a reflection of a past land use rather than a direct effect of soil pH on earthworms (Sánchez-de León and Johnson-Maynard 2009, p. 1399). Other studies in the Palouse region demonstrated the mean soil pH in direct-seeded agricultural fields was pH 5.35, and in conventional tillage fields pH 5.61 (Umikeret al.2009, p. 184). One commenter (McGregor 2010,in litt.,p. 4) stated less than 0.5 to 1 percent of the soils sampled in the Palouse have pH levels below 5.

In summary, studies investigating relationships between earthworms and soil pH indicate that earthworm response can vary with species, location, life-history strategy, or other attributes. The best available scientific information on this relationship for the GPE is limited (e.g.,to our knowledge, only the Smoot Hill study has investigated the potential soil pH relationship). There is significant uncertainty regarding the correlation between soil pH and GPE occurrence or persistence, and insufficient data to identify pH cause-and-effect relationships that might be limiting for the persistence of this species. However, in the Palouse region, soil pH levels do not appear to be so acidic (below pH 5) that they negatively affect earthworms generally. Also, the GPE may be more tolerant to acidity than some species of earthworms. In addition, the range of the GPE is wider than previously known, and includes pine forests on the eastern slope of the Cascades, although the full extent and type of forested habitats occupied by the GPE are not yet known. Detailed soil characteristics are not known for the GPE location near Leavenworth, Washington. Accordingly, the best available information does not indicate that changes in soil chemistry represent a threat to the GPE.

The petition states that tillage removes the original topsoil, which may reduce earthworm burrow densities, soil aeration, soil infiltration rates, and the amount of organic matter available to the GPE for forage (Petition, pp. 10-11). Literature cited by the petitioners stated the original topsoil has been lost from 10 percent of Palouse cropland, and 60 percent of cropland has lost 25 to 75 percent of its topsoil (Veseth 1986b, p. 2). The petition did not present detailed information on agriculture activities in the Ellensburg area, although the Adolphson Associates report (2005, pp. 14-22) presented with the petition includes maps and photographs depicting areas converted to agriculture within the Ellensburg, Washington, city boundaries.

The potential threats to the GPE from tillage and cultivation are reduced food sources and burrow compaction, but would likely vary depending on its life-history strategy. Annual crops put a small fraction of their production into root mass (James 2009,in litt., pp. 3-4), whereas perennial prairie grasses put approximately 50 percent of their annual production into roots, which provide resources for soil invertebrates (including endogeic earthworms). Endogeic earthworms, which the petitioners assert the GPE to be (James 2009,in litt., pp. 3-4), would probably be more susceptible to agricultural activities that reduce soil organic matter, based on their need for organic matter as a food source. However, anecic earthworms use surface litter as a food source, and the best available scientific information supports the GPE being an anecic earthworm species. In either case, surveys to date in the Palouse have not documented the GPE in either agricultural fields or CRP lands (Fauci and Bezdicek, 2002, p. 254; Sánchez-de León and Johnson-Maynard 2009, p. 1393; Johnson-Maynardet al.2007, p. 340). Therefore, we have no information indicating that the GPE would be exposed to reduced soil organic matter or reduced surface litter caused by ongoing cultivation in the Palouse region.

One Australian study demonstrated that 3 years of tillage reduced earthworm burrow density by nearly 90 percent (Chan 2004, p. 89; Petition, p. 10), which reduced the maximum infiltration rate of the soil and significantly increased the likelihood of runoff and erosion. Chan's study (2004, p. 90) compared tillage effects to soil infiltration by monitoring burrow density for the North Auckland worm (Spenceriella hamiltoni), an anecic member of the Megascolecidae (in the same family as the GPE), under three conditions: no-till (crops drilled directly into ground with a special slit drill), conventional one-pass, and conventional two-pass tilled agriculture (Chan 2004, p. 94). The effect of tillage on earthworm abundance is usually negative because tilling causes physical damage and burial of residues, although tillage could also increase the abundance of some earthworm species due to increases in food supply by incorporation of residues into the soil (Chan 2004, p. 90). In this study, tillage was found to decrease burrow density and water infiltration into the soil (Chan 2004, pp. 89, 94). The author concluded that under cropping, preservation of earthworm burrows can be achieved by adopting conservation tillage techniques (Chan 2004, p. 96). Conservation tillage techniques generally involve establishing crops in a previous crop's residues, which conserves water and minimizes soil disturbance and erosion.

Johnson-Maynard (September 21, 2010,in litt., p. 2) discusses studies in which tillage effects on earthworm density were found to be dependent on the ecological grouping of earthworms in an area (i.e., anecic or endogeic). Chan (2001, pp. 179, 185-187) found in a 3-year study that tillage had a strong negative impact on anecic species due to a combination of direct damage, burial of residue (food source), and destruction of earthworm burrows, while endogeic species were positively affected in the short term due to their smaller size (less physical damage) and increased availability of organic matter. In the Palouse bioregion, tillage removes the original topsoil, which may reduce earthworm burrow densities, soil aeration, soil infiltration rates, and the amount of organic matter available to the giant Palouse earthworm for forage (Veseth 1986b, p. 2; Petition, pp. 10-11). Edwards and Bohlen (1996, p. 215) stated that earthworm populations were much larger in soil that was manipulated using no-till methods. No-till agriculture accounted for 14,563 acres (5,893 hectares), or roughly 5 percent of the total surveyed acreage in the Palouse in 1989, up from the previous 5-year average (1984-1988) of 3 percent (Hall 1999, p. 15).

The GPE has been documented in the Palouse in remnant native grassland and in Douglas-fir forests, and in ponderosa pine forest at the Leavenworth site near Chelan, Washington. The GPE distribution is wider than previously known, but its total distribution remains uncertain because the species is verydifficult to detect, survey protocols are still being developed, and the level of survey efforts within and outside of the Palouse area has been very low. While there may have been historical impacts to the GPE from agriculture in the Palouse, the magnitude of threats from those activities is difficult to determine because we have no baseline population or distribution information with which to make a comparison, other than the anecdotal statement in Smith (1897, pp. 202-203). In addition, to date the GPE has not been found in agriculture fields in the Palouse, and we have no information that indicates the GPE is or will be exposed to tillage and agriculture. Accordingly, the best available information does not indicate that tilling and agriculture represent a threat to the GPE.

James stated that grazing degrades earthworm habitats, potentially to the point of causing extirpation, and that soil compaction from livestock grazing can affect earthworms by making burrowing and feeding more difficult (James 2000, pp. 9-10). The petition also claims that livestock grazing changes the quality and accessibility of detrital material, decreasing organic matter available to earthworms through conversion of herbage to partly digested clumps of organic matter (James 2000, p. 9; Petition, p. 14).

The petitioners describe livestock grazing as a pervasive land use in the range of the GPE. James (2000, p. 9) stated: (1) Livestock grazing can cause soil compaction, thereby making burrowing and feeding more difficult for earthworms; (2) effects are variable by earthworm species or habitat type (or both); (3) large earthworm species are less heavily impacted by grazing; and (4) “without further knowledge about native earthworms and the presence or absence of earthworms in lands subject to grazing in the Columbia River basin assessment area, it is of little use to speculate further.” Cluzeauet al.(1992, pp. 1661, 1663) demonstrated intensive trampling by cattle can reduce earthworm densities, particularly for smaller species and those living near the surface. No specific information was provided by the petitioners regarding the extent of livestock grazing impacts in the Palouse or Ellensburg areas. However, several individuals (Field 2010,in litt., p. 2; Jensen 2010,in litt., p. 6) commented that grazing can benefit some earthworms through increasing organic matter and plant species diversity (Dorseyet al.1998, p. 2; Taylor and Neary 2008, p. 2). We cannot assess the distribution of the GPE in relation to grazing activities or grazing intensity because the species' range is unknown, but is wider than previously documented, there have been very few surveys, and the habitats used by the species are more variable than previously known. However, the best available information indicates grazing can sometimes benefit earthworms and larger species like the GPE may be less impacted by grazing than smaller species. Accordingly, based on the best available information, grazing has not been demonstrated to be a threat to the species.

Earthworms have been shown to be sensitive to some pesticides (Edwards and Bohlen 1996, pp. 283-285), and the toxicity varies depending on the type of pesticide used. Generally, carbamates (organic compounds derived from carbamic acid and frequently used in insecticides) are the most toxic (Edwards and Bohlen 1996, pp. 283-285). In addition, although chemicals may not result in direct toxicity, they may have indirect effects such as reduction in organic matter, which is a food source for earthworms. Contaminant exposure and toxicity depends on a wide range of chemical, physical, and biological factors, and the rate of application. Specific knowledge of the fate and transport of the chemical within the environment, physicochemical attributes of the exposure media, and biological characteristics of the organism are required to determine if a species may be impacted by environmental contaminants. Although pesticide application is widespread within the Palouse, information on GPE distribution, biology, and life history is limited. There is significant uncertainty with regard to determining the potential impact pesticides might present to this species, and what application rate(s) would be required for those impacts to rise to a level of being a threat to the species. Exposure could also vary, depending on the GPE's life-history strategy. Anecic species (which we believe the GPE to be based on the best available scientific information) may have less exposure than other forms. For example, the black-headed worm (Aporrectodea longa), an anecic species, was determined to be less susceptible to pesticides because of its ability to burrow deep into the soil. This species also undergoes an obligatory diapause in the summer months, which may limit pesticide exposure (Wheatley and Hardman 1968, as referenced in Edwards and Bohlen 1996, p. 280; Gerard 1967, as referenced in Edwards and Bohlen 1996, p. 280). It is unknown whether the GPE undergoes a diapause. In addition, in a midwestern United States study on agriculture and earthworms, Simonsonet al.(2010, p. 147) found the most commonly applied pesticides and increased crop diversity did not have a significant effect on either the endogeic or anecic earthworm groups.

From 1992 through 1995, pesticides were assessed as part of the National Water-Quality Assessment (NAWQA) Program, and at least one pesticide was detected within 97 percent of surface water samples collected within the Palouse bioregion. No pesticides were found in groundwater (the only source of drinking water in the area) at concentrations that exceeded drinking water standards or guidelines (Roberts and Wagner 1996, p. 15). Although some data are available for pesticide presence in surface and groundwater, there is little information on pesticide presence or concentrations in soils within documented GPE habitat. Many currently used pesticides are water soluble and are much less persistent in soils than the organochlorine pesticides used in the past.

Approximately 700,000 pounds of commonly used pesticides are applied in the Palouse bioregion annually (Roberts and Wagner 1996, p. 2), and agricultural interests in the Palouse region apply many herbicides to control invasive and noxious plants (Hallet al.1999, p. 12, Table 3.08; Kellogget al.2000, p. 2). Wagneret al.(1995, pp. 21-22) identified several pesticides used in an area within the Palouse bioregion, several of which were detected in water samples, including Triazine (Atrazine) (pp. 15-16, Table 4), although several comments (e.g., McGregorin litt., p. 4) stated that Triazine family herbicides are not used commercially for agriculture in the Palouse. The petition claims no-till farming uses herbicides rather than tilling for weed control, resulting in higher herbicide use in no-till fields than in tilled fields (Veseth 1986a, p. 1; Petition, p. 12); however, no-till farming was estimated in 1989 to be used on only 5 percent of the fields in the Palouse region (Hall 1999, p. 15). Several individuals from the Palouse bioregion commented that no-till farming uses glyphosate herbicides (Jensen 2010,in litt., p. 5; McGregor 2010,in litt., p. 2; Mick 2010,in litt., p. 2), which studies show have no toxicity for earthworms when properly applied (Edwards and Bohlen 1996, p. 304). Individuals also commented that agricultural users apply fertilizers and pesticides sparingly and with precision because of the costs involved (Barstow2010in litt.,p. 2; Jensen 2010in litt., p. 5).

There is limited information available on pesticide use outside of the Palouse bioregion in the vicinity of documented GPE locations. One study detected such chemicals in irrigation canal monitoring sites in the Yakima watershed (Johnson 2007, p. 1). However, the monitoring sites used for the Johnson (2007) study appear to be lower in the watershed than the Ellensburg GPE location (Fender and McKey-Fender 1990, pp. 358, 366). Although groundwater and surface water pesticide monitoring studies provide an indication of pesticide use in the general area, the data are not informative on whether pesticides are present in GPE-documented habitats. We are also unaware of any pesticide monitoring studies in the vicinity of the GPE location near Leavenworth, Washington.

In summary, agricultural lands have been the primary focus areas for pesticide and herbicide monitoring studies; however, the GPE has not been documented to date in these types of areas. Although we have some information on pesticide applications in the Palouse area, and some generalized information regarding pesticide toxicity to earthworms, the available information is inadequate to determine how and whether those pesticides impact soils or habitats occupied by the GPE. We have some limited pesticide application information for the Ellensburg, Washington, vicinity, although the data are not particularly enlightening with regard to proximity to the GPE location, and we have no pesticide information related to the GPE location documented near Leavenworth, Washington. However, information on another anecic species (Wheatley and Hardman 1968, as referenced in Edwards and Bohlen 1996, p. 280; Gerard 1967, as referenced in Edwards and Bohlen 1996, p. 280) indicates deep-burrowing anecic species are less susceptible to pesticides. In addition, the prevailing information indicates the GPE is an anecic species, and anecic species have less exposure to pesticides than other earthworm life-history forms. We do not have information on GPE pesticide exposure in areas outside of the Palouse region, and the exposure will vary with the distribution, habitat types, and pesticide uses in those areas. The GPE has a wider range and occurs in more diverse habitats than previously known, and we have little information on pesticide applications occurring in those areas. Accordingly, the best available scientific information does not indicate the application of pesticides or herbicides is a threat to the GPE.

The petitioners claim that urban sprawl and rural development negatively impact GPE habitat in the Palouse and Ellensburg areas. The Ellensburg, Washington; Pullman, Washington; and Moscow, Idaho human populations increased by approximately 76, 88, and 73 percent, respectively since 1980 (Petition, p. 12;http://www.census.gov, figure 4). The petition states that urban development compacts soil, removes topsoil, and favors nonnative, invasive earthworms (Petition, pp. 12-13), and road construction affects remaining prairie remnants (Petition, p. 13). If urban or rural development were to occur on remnant prairie habitats in the Palouse, there may potentially be an impact to the GPE. However, the Palouse prairie is not the only habitat type used by the GPE, as the species has also been located in Douglas-fir forest in the Palouse and in ponderosa pine forest near Leavenworth, Washington (see Table 1 above).

The petitioners (Petition p. 13) expressed concern about a potential rerouting of U.S. 95 through a large prairie remnant in the Palouse bioregion south of Moscow, Idaho. The planning for this project is ongoing (Idaho Department of Transportation (IDOT) 2011a, p. 1). There were three action alternatives under consideration (IDOT 2011c, p. 1), one of which (the eastern alternative) would impact Paradise Ridge, an area where the GPE has been documented. However, the IDOT forwarded only alternatives that would have no direct impact on rare plant communities (including remnant prairie habitat) for further analysis (IDOT 2011b, p. 21, 25), and as a result, the Paradise Ridge GPE site will not be affected by the IDOT project. Urban and rural development in prairie remnants is still possible, given that Latah County, Idaho, and Whitman County, Washington, do not prohibit this type of development (Latah County Board of Commissioners 2010; Whitman County 2010); however, there are significant scientific uncertainties regarding the full extent of habitat types used by the GPE, as well as the species' distribution, range, and population trends. In summary, the best available scientific information does not indicate that urbanization and rural development are threats to the GPE.

The impact of forest management actions on soils varies, and uneven-aged management (i.e., selective harvest) can result in machinery-induced soil compaction over a larger area than even-aged management (i.e., clearcut harvest) (Harveyet al.1994, p. 44). However, while selective timber harvest practices may result in soil disturbance or compaction from heavy equipment, there will be less loss of surface or soil organic matter than when clearcut timber harvest methods are used (James 2000, p. 10). Forest management operations can alter the cycling of above-ground organic materials and their incorporation into soil (Harveyet al.1994, p. 11), which may result in not only impacts to soil nutrients, but also changes to soil characteristics such as water-holding capacity, aeration, drainage, and cation exchange.

The GPE has been documented in Douglas-fir forest at Moscow Mountain in the Palouse, and recently confirmed in dry ponderosa pine forest near Leavenworth, Washington (see Table 1 above), although information regarding details on the forest stand at the GPE locations, and the extent of habitats the GPE occupies in forested environments, is incomplete. Forest types have changed in the Columbia Basin since historical times, although the numbers of forested acres are not substantially different (Quigleyet al.1996, p. 54). The potential impacts to the GPE from forest management activities would likely depend on whether the species requires certain forest types or ages, and if so, the specific nature of the management prescription being applied in those areas. There are uncertainties with regard to whether the GPE is restricted to certain types of forests, certain ages of forest, or certain elevations or other site characteristics, or whether surface vegetation is relevant to the species. If the GPE occurs in multiple types and ages of forest, the availability of a particular forested habitat type may not be a limiting factor, and forest management may have little impact.

James stated in 1995, that he can “confidently state that nothing is known of the impact of any management practice on any Columbia River Basin native earthworm species” (James 1995, p. 12). However, in 2000, James stated that logging: (1) Degrades earthworm habitat, potentially to the point of causing extirpation and changes in plant communities, and (2) may degrade habitat through changing soil type, soil temperature, moisture regime, or food resources (James 2000, p. 10). In his 2000 study, James also related the primary effect of tree removal on endogeic earthworms to soil climate and the availability of surface and soil organic matter sufficient to support earthworms until second-growth plants become established. James also statedthat epigeic species would be expected to suffer most from the loss of tree cover because the preferred microhabitat would be less hospitable and ultimately less abundant, with the loss of annual leaf input, and indicated that disturbance caused from heavy equipment use may be the most deleterious to earthworms (Shaefer and others 1990, in James 2000, p. 10). However, James did not discuss how these types of activities would affect an earthworm species with a deep-burrowing, anecic, life-history strategy (James 2000, p. 10), such as the GPE. The Service recognizes that forest management activities can affect soils, temperatures, and vegetation, and the impacts would vary with types of forest management, types of forest, and habitat needs of the GPE. However, we were unable to determine how much forested habitat the GPE occupies or where it occurs in forested habitat (other than the above confirmed localities). Additional surveys will be needed to determine the extent of forested habitat occupied by the species. In addition, we have no information to indicate how GPE would respond to different types of forest management activities. Therefore, the best available information does not indicate that forest management activities represent a threat to the GPE.

The GPE is known to occur in both grassland habitats and forested habitats in the Palouse. Native grassland habitats in the Palouse have declined to very low levels; information on changes to forested habitats in the Palouse is less well understood. The species' range outside of the Palouse region is substantially greater than was previously known, and includes portions of the eastern slope of the Cascade Mountains. Survey efforts have been limited, it is difficult to survey for the species, and effective survey methods remain to be developed. In addition, there are significant scientific uncertainties regarding the GPE's distribution, habitat diversity, biology, and population trends, which need to be resolved to be able to conduct a credible scientific assessment of potential threats to the species. The best available information is inconclusive with regard to whether soil pH is a limiting factor, or whether there are certain types of management activities that affect soil pH in a manner that presents a threat to the GPE. The literature suggests that compacting soils may result in impacts to earthworms, depending on their life-history strategy. However, there is no information with which to determine with reasonable confidence whether soil compaction is occurring in GPE habitat, and if so, whether it would result in a negative response in the species.

While there may have been historical impacts to the GPE from agricultural conversion in the Palouse, most agriculture conversion activities were completed by 1910 (McGregor, 1982, p. 109). The extent to which agricultural activities currently present a threat to the GPE is undeterminable, given the limited information available on the species' life history, its range, and the diversity of habitat types where it occurs. However, the species has not been collected in agricultural areas to date. The extent of the GPE's range and habitat types used beyond the Palouse is also unknown. While there may potentially be impacts from grazing activities, we have an incomplete understanding of the species' occupied habitat, whether grazing occurs therein, the magnitude and intensity of grazing activities in those areas, and the GPE's exposure to grazing impacts. We have some information on pesticides used in the Palouse area, and we have generalized information on pesticide toxicity to earthworms. However, we are unable to correlate that information to soils or habitats used by the GPE in the Palouse or elsewhere, and whether the GPE is exposed to those chemicals. The limited information on pesticide applications in the Ellensburg, Washington, vicinity is not instructive with regard to whether or not those activities might threaten the GPE, and there is no information related to pesticide application in the Leavenworth, Washington, GPE locality. Because of our limited knowledge of the species' range and occupied habitat, we cannot credibly evaluate the threat of urban or rural development to the species. We recognize that forest management activities can affect soils, temperatures, and vegetation, but there is no information correlating these activities to a possible negative response by the GPE. In summary, there is very little information available, and the best available scientific information does not indicate the present or threatened destruction, modification, or curtailment of the GPE's habitat or range from any of the above activities constitutes a threat to the species such that listing under the Act is warranted.

The petition did not identify overutilization for commercial, recreational, scientific, or educational purposes as a potential threat to the GPE. Unlike butterflies, for example, earthworms are not likely targets for collection by hobbyists. Recent records of the GPE are based on the few individuals that were killed during or after their collection (fewer than 10). While we anticipate some additional GPE mortality due to scientific collection as we learn more about the species, we have no reason to believe the loss of a few individuals for scientific purposes would present a threat to the continued existence of the species. Therefore, we conclude that overutilization for commercial, recreational, scientific, or educational purposes is not a threat to the species such that listing under the Act is warranted.

The petition did not identify any threats to the GPE related to disease or predation. Hendrix and Bohlen (2002, p. 802) stated that imported nonnative earthworms may be vectors for plant or animal pathogens or viruses, but the authors do not correlate this potential threat to the GPE. Although James (1995, p. 11) stated that predation on earthworms can be accentuated by tilling the soil and exposing earthworms to bird predators, the correlation to the GPE is uncertain as the GPE is believed to be an anecic species and therefore may be less likely to be exposed by tilling. Also, surveys to date have not found the GPE in agricultural fields, although we acknowledge the extent of those surveys has been limited. However, the species would not be exposed to increased predation caused by ongoing tillage if it does not occupy agricultural areas. In summary, we do not have any evidence indicating that disease or predation is a threat to the GPE such that listing under the Act is warranted.

In our 2010 90-day finding (75 FR 42064; July 20, 2010), we determined the existing regulatory mechanisms may be inadequate to address potential threats to the GPE. The petitioners claim Federal, State, or local regulations do not specifically protect the GPE or its habitat. The Washington Department of Fish and Wildlife identifies the GPE as a species of concern (WDFW 2009, p. 1), although this status does not provide regulatory protection for the species. The petition states the Palouse Subbasin Management Plan (Gilmore 2004) includes objectives to protect and restore native grassland habitat within the Palouse subbasin, and increase wildlife habitat value on agricultural land, but is voluntary in nature anddoes not provide regulatory mechanisms that protect the GPE or its habitat. Habitat conversion in the Palouse may still occur, as neither Latah County, Idaho, nor Whitman County, Washington, have ordinances or regulations to prevent native habitat conversion (Latah County Board of Commissioners 2010, pp. 1-27; Whitman County 2010, pp. 1-76). However, we do not have evidence that habitat loss is a threat (see Factor A discussion). The petition also acknowledges the existence of the U.S. Forest Service, Bureau of Land Management, U.S. Fish and Wildlife Service, Environmental Protection Agency, and National Oceanic and Atmospheric Administration (NOAA) Fisheries Memorandum of Understanding (MOU, USDA Forest Serviceet al.2003), in which the agencies agreed to voluntarily utilize the scientific findings of the Interior Columbia Basin Strategy (CBS) to guide project implementation and to revise resource management plans. The petitioners state the MOU and CBS do not address the GPE or provide regulatory mechanisms for its protection (Petition, p. 15), and claim existing regulations are ineffective in reducing the importation of nonnative earthworm species, which present a threat to the GPE. However, the best available information does not indicate that exotic earthworms represent a threat to the GPE (see Factor E discussion).

The U.S. Environmental Protection Agency (EPA) Office of Pesticide Programs evaluates which ingredients and which pesticide products can be used (registered) in the United States. The EPA evaluates the potential effects of pesticides on human health and the environment, conducts risk assessments, and works with companies to develop label instructions that ensure safety (see the National Pesticide Information Center athttp://www.npic.orst.edu/reg.htm). One study found the use of pesticides at recommended rates had no detectable negative effects on earthworms in anecic or endogeic species (Simonsenet al.,2010, cited in Johnson-Maynard, 2010,in litt.,p. 2). Therefore, the best available information indicates that the species is not threatened by the inadequacy of pesticide management.

Surveys for the GPE have been limited, and there are significant uncertainties regarding the species' distribution and life history, as well as the diversity of habitat types where it may be found. This type of information is essential to credibly assess whether or not existing regulatory mechanisms are adequate to address potential threats to the species. While we acknowledge the regulations and plans described above do not provide specific protections for the GPE, we have no information to indicate this lack of specific protections is resulting in threats to the species. Therefore, we find that the available information does not support a conclusion that the inadequacy of existing regulatory mechanisms is a threat to the GPE.

The petitioners claim that the GPE is threatened by invasive, nonnative earthworms (Petition, p. 1). In a 3-year study of earthworms in the Palouse region of eastern Washington and Idaho, Sánchez-de León and Johnson-Maynard (2009, p. 1393) found a dominance of invasive, nonnative earthworms in both native and nonnative grasslands. Nonnative earthworms can invade new habitats, change the ecological soil functions, and displace native species (Hendrix and Bohlen 2002, p. 805; Petition, p. 16). Earthworm populations are dominated by nonnative earthworms in agricultural sites and native prairie remnants in the Palouse region (Fauci and Bezdicek 2002, p. 257; Sánchez-de León and Johnson-Maynard 2009, pp. 1396, 1399-1400; Petition, p. 16). Habitat conversion favors invasion of nonnative earthworm species that are better adapted to a disturbed or degraded environment (Petition, p. 16; James 1995, p. 5). James (1995, p. 5) stated that many exotic species occur in the Columbia Basin, possibly altering previously worm-free soils and nutrient cycling pathways, competing with native species, and generally modifying any processes linked to soil physical or chemical properties. He also stated that invasive earthworm species present a potential threat to the GPE, and described the loss of a deep-dwelling Illinois earthworm species as an example of this threat, although the particular study was not cited (James 2009,in litt.,p. 2). Based on the limited information that was provided, we were unable to locate the study. James stated that although invasive earthworms do not always reduce or eliminate populations of indigenous worms, the invasion cannot help, and some species may be highly competitive with, a deeper-dwelling species like the GPE, while others may not (James 2009,in litt.,p. 2). There are substantial weaknesses in extrapolating data from an Illinois earthworm species to the GPE, because we have no information that would indicate the responses would be similar. While the Service concludes that the GPE is anecic based on the best available information, there is some expert disagreement on the GPE's life-history strategy. However, it is unclear whether this matters in relation to invasion by nonnative earthworms, and James (2009in litt.p. 2) did not present a scientific basis for using an Illinois species as a surrogate for the GPE.

We agree that a correlation of decline and extirpation of some native earthworm species with the arrival of introduced earthworm species is well documented (Hendrix and Bohlen 2002, pp. 805-806; Sánchez-de León and Johnson-Maynard 2009, pp. 1393-1394), although the cause may not always be direct. The causes of the declines of native species of earthworms are not documented, but theories center on ecosystem disturbance (Hendrix and Bohlen 2002, pp. 805-806) and competitive exclusion (James 2000, p. 8; Hendrix and Bohlen 2002, pp. 805-806). In addition, James (2009,in litt.,p. 2) noted that invasive earthworms do not always reduce or eliminate populations of indigenous earthworms. Depending on ecological requirements, some species may be highly competitive with a deeper-dwelling species like the GPE, and some not competitive, or there may be a combination of effects coupled with habitat modification. Co-occurrence of native and nonnative earthworm species is common both in disturbed and undisturbed ecosystems; however, it is not known if this is a transient or permanent state (Hendrix 2006, p. 1203). Ecosystem disturbance sufficient to degrade or destroy habitat for native species may be caused by the arrival of introduced worm species, or the arrival of introduced species may follow habitat degradation caused by other factors (Hendrix and Bohlen 2002, pp. 805-806). Nonnative earthworm invasions may depend on the degree of disturbance, competition with natives, and adaptability to site conditions (Hendrix and Bohlen 2002, p. 1203; Sánchez-de León and Johnson-Maynard 2009, p. 1394).

In a 2003-2005 research effort in the Palouse region of southeastern Washington and northern Idaho, Sánchez-de León and Johnson-Maynard (2009, pp. 1394-1395) compared four paired study sites representing native prairie remnants and CRP set-aside lands. The study objective was to characterize and compare native and nonnative earthworm populations in two important grassland ecosystems within the Palouse region. Their results found that one invasive earthworm species, the southern worm (Aporrectodea trapezoides) comprised90 percent of the total earthworm density in their study areas (Sánchez-de León and Johnson-Maynard 2009, p. 1396). One GPE was collected at one of the four prairie remnant study sites. The authors suggested that because native earthworms are found in fragmented native habitats along with exotic earthworms, the GPE may be able to coexist with exotic species in Palouse prairie remnants. They indicated that further study would be required to determine whether the GPE is a resilient species based on its deep-burrowing behavior, or whether the results of their study demonstrate a species replacement process (Sánchez-de León and Johnson-Maynard 2009, pp. 1398).

The rarity of native earthworms in their native prairie remnant study areas lends support to the researchers' theory that native earthworms are being replaced by nonnative earthworms, even in visibly intact remnants of fragmented habitats (Sánchez-de León and Johnson-Maynard 2009, pp. 1398-1399). The researchers suggestedApporectodea trapezoidesmay compete with the GPE for food in upper layers of soil (Sánchez-de León and Johnson-Maynard 2009, pp. 1398-1399), but could not exclude the possibility that the GPE did not historically occur in high densities within these prairie remnants because of their steep slope or high rock content, the very factors that prevented these areas from being plowed and preserved them as remnant prairie (Sánchez-de León and Johnson-Maynard 2009, p. 1398). They acknowledged that these findings are inconsistent with other studies showing that native earthworms predominate in undisturbed or minimally disturbed grasslands (James 1991, pp. 2101-2109; Callahamet al.2003, pp. 1079-1093; Winsomeet al.2006, pp. 38-53;inSánchez-de León and Johnson-Maynard 2009, pp. 1397-1398).

The researchers suggested that a combination of extensive habitat fragmentation in the Palouse region, low habitat quality of remaining prairie remnants, and possible competitive interactions with nonnative earthworms could have decimated GPE populations at their study sites (Sánchez-de León and Johnson-Maynard 2009, p. 1398). They acknowledged that no information is available on GPE pre-agricultural density or distribution, but the description of the species as being abundant by Smith (1897) contrasts with the rarity of finding the earthworm today. They stated that this suggests a significant reduction in population size (Sánchez-de León and Johnson-Maynard 2009, pp. 1394, 1399), but acknowledge their sampling methodology could have influenced the results. The hand-sorting sampling method is regarded as the best method to estimate abundance of most earthworm species, but is also known to underestimate the abundance of deep-burrowing species. The researchers recommend the use of a combination of methods for future studies, including non-destructive alternatives such as electrical methods or extraction methods with chemicals of low toxicity that are more suited for deep-burrowing earthworm species (Sánchez-de León and Johnson-Maynard 2009, p. 1399).

The GPE's range is more extensive than previously known, survey efforts for this species have been limited, and effective survey protocols remain to be developed. We acknowledge conflicting opinions by earthworm researchers regarding the GPE's life-history strategy, which could influence how it interacts with exotic earthworms. However, we believe the prevailing evidence points to the GPE being a deep-burrowing anecic species, based on observations in the field by scientists who appear to be most familiar with this particular species, and the report by Smith (1897, pp. 202-203) describing burrows extending to a depth of over 15 feet in new road cuts. Endogeic worms (which the petitioners believe the GPE to be) live in the upper layers of mineral soil, whereas anecic earthworms live in deep, semi-permanent burrows. The researchers Sánchez-de León and Johnson-Maynard also acknowledge that the hand-sorting sampling method (which has apparently been applied in most earthworm surveys) underestimates the abundance of deep-burrowing species. In addition, the limited evidence available does not lead to a reasoned scientific conclusion regarding competitive interactions between exotic earthworms and the GPE. In summary, we do not have evidence to support a conclusion that competition with exotic earthworms is a threat to the GPE.

The petitioners describe the existence of introduced annual grasses and noxious weeds in the Palouse region, includingPoa pratensis(Kentucky bluegrass), crops,Bromus tectorum(cheatgrass), andCentaurea solstitialis(yellowstar-thistle) (Gilmore 2004, pp. 1-87), and state that it is likely these species do not provide the same quality and quantity of earthworm forage as native vegetation (Petition, p. 17). However, they did not provide any evidence to support this statement. There may be differences in nutritive value between weeds and native plants, and there may be differences in phenology (e.g.,nonnative plants emerging at a different time than native plants), but it is unknown if this is important to the GPE. Invasive weed control in the Palouse is difficult (Jensen, 2010,in litt.,p. 3; Nyamai 2009, pp. 6-7, 21-22). Native plant communities in the Palouse are susceptible to invasion by nonnative plants (Gilmore 2004, pp. 1-26; James 2000, p. 8); domination of deep-soil sites by Kentucky bluegrass is common, and in shallow soils cheatgrass and yellowstar-thistle weeds compete with native grasslands. McGregor (1982, pp. 124-125) commented that nonnative weeds, including cheatgrass, have been present in the Palouse region since the 1890s. The Draft Palouse Subbasin Management Plan (Gilmore 2004, pp. 1-86) states that exotic weed invasions are possibly the greatest threat facing the grasslands and shrublands of the arid and semiarid West today, and species-rich ecosystems are being converted to monotonous weedlands as aggressive weeds replace native plants and degrade habitat for wildlife.

There are significant scientific uncertainties regarding the distribution and life history of the GPE, and the range of habitat types it occupies is unknown. Although there have been some studies relevant to nonnative plant invasion and conversion of native habitats and ecosystems, we are unaware of any scientific studies or other data that would allow an extrapolation of these observations to the GPE. Accordingly, we have no information to indicate that the introduction of nonnative plants represents a threat to the species.

The petitioners noted that, because Fender and McKey-Fender (1990, p. 366) describe annual precipitation as a parameter of GPE habitat, it is likely that changing weather patterns caused by global warming will impact this species' habitat and distribution (Petition, p. 17). This citation in fact defines the lower limit of precipitation tolerated by argilophilini worm species to be about 15 in (38 cm) annually, which the authors characterize as being “about the edge of moist forests in our area, although the range ofDriloleirus americanusextends into treeless areas.” Although the petition expresses a concern about future climate change and its effects on the GPE, it did not present information or data in this regard.

The Service evaluated information available in our files and queried other available information related to this potential threat. Lawler and Mathias(2007, pp. 19-20) investigated possible climate change impacts to vascular plants, stating that plants may mature earlier, creating potential mismatches between pollinators and plants, parasites and hosts, and herbivores and food sources; increased summer temperatures and decreased summer precipitation may lead to changes in distribution of some plant species; sagebrush steppe and grasslands may contract, while dry forests and woodlands expand; and plant distribution changes will depend in part on plant water-use efficiencies. According to the United Nations Framework Convention on Climate Change (2010, p. 1), plant growth may benefit from fewer freezes and chills, but some crops may be damaged by higher temperatures, particularly if combined with water shortages. Certain weeds may expand their range into higher-latitude habitats. Higher levels of carbon dioxide should stimulate photosynthesis in certain plants, in principle. This is particularly true for C3 plants (named for their carbon fixation pathway) because increased carbon dioxide tends to suppress their photo-respiration. C3 plants make up the majority of species globally, especially in cooler and wetter habitats, and include most crop species, such as wheat, rice, barley, cassava, and potato.

It is difficult to predict how or if future changes in growth or distribution of vegetation resulting from climate change will affect local conditions for weeds, native vegetation, or both, or to predict how such changes would affect earthworms. Earthworm mortality can result from extreme temperatures, and the upper lethal temperature for different earthworm species is lower than for other invertebrates ((Edwards and Bohlen 1996, p. 146) (e.g.,28 °C (82 °F) forLumbricus terrestris;37 to 37.75 °C (98.6 to 100 °F) forPheretima californica(Schread 1952, as referenced in Edwards and Lofty 1977, pp. 156-157)). Earthworms tolerate higher temperatures by migrating, or burrowing deeper, but must still be able to feed on the surface or the top layers of the soil.

The petition did not present any specific information, and we are unaware of any studies, that would facilitate an evaluation of the extent to which the GPE may be affected by: (1) Increased air temperatures or soil changes; (2) earlier seasonality of plant production; or (3) changes in plant distribution. Climate change models used in the Intergovernmental Panel on Climate Change Fourth Assessment Report project increased air annual temperatures in the Pacific Northwest of, on average, 1.1 °C (2.0 °F) by the 2020s, 1.8 °C (3.2 °F) by the 2040s, and 2.9 °C (5.3 °F) by the 2080s, compared to 1970 and 1999 (averaged across all climate models); however, increased air temperature does not necessarily correlate with increased surface or soil temperatures. Projected changes in annual precipitation averaged over all models are small (+1 to +2 percent), but some models project an enhanced seasonal precipitation cycle with changes toward wetter autumns and winters, and drier summers (Littellet al.,2009, p. 1). In the Pullman, Washington, area, baseline annual precipitation is estimated at 21.1 in (53.6 cm); models projecting to 2080 do not project annual precipitation below 15 in (38.1 cm) under any scenarios (Climate Impacts Group 2009, pp. 197-198). Fifteen inches (38.1 cm) of annual precipitation has been suggested as the lower limit of precipitation tolerated by argilophilini worm species, such as the GPE (Fender and McKey-Fender 1990, p. 366).

The impact of climate change on selected but economically significant crops in eastern Washington was predicted to be generally mild in the short term (i.e.,the next two decades), but increasingly detrimental with time (potential yield losses reaching 25 percent for some crops by the end of the century). The projected elevated carbon dioxide (CO2) was expected to provide significant mitigation of climate change and its effects, and in fact result in important yield gains for some crops (Littellet al.2009, p. 212), and it is likely that some native or nonnative plants would be similarly increased, potentially increasing the forage base for GPE.

Existing climate change projections are inadequate to allow a prediction regarding whether or how future climate change will impact the GPE or its habitat. This is further complicated by the significant uncertainties that exist regarding the species' distribution, biology, and habitat needs. However, given that the prevailing evidence indicates the species is anecic based on the results of survey efforts and the description of deep burrows associated with the species (Smith 1897, pp. 202-203), it is reasonable to conclude the species' deep-burrowing behavior will limit its exposure and increase its adaptability to increased soil temperatures. It is unclear how or whether drier summers would impact the GPE, or whether vegetation changes would impact the GPE. Therefore, based on the best available information, we conclude that climate change does not constitute a threat to the species.

Although the decline and extirpation of some native earthworm species with the arrival of introduced earthworm species has been well documented, survey efforts for this species have been limited and effective survey protocols remain to be developed. In addition, there are conflicting opinions by earthworm researchers regarding the GPE's life history strategy, which could influence how it interacts with exotic earthworm species. Native plant communities in the Palouse bioregion are susceptible to invasion by nonnative plants, although we are unaware of any studies that correlate nonnative plant invasion and conversion of GPE habitat. The petition stated that future climate change could affect the GPE, although no supporting information or data was presented. Our examination of this concern has determined that existing climate change projections are inadequate to predict how future climate change may impact the GPE, which is further complicated because of the significant uncertainties regarding the species' distribution, life history, and the range of habitat types it occupies. In summary, there is no scientific evidence to support a conclusion that the GPE is threatened by competitive interactions with exotic earthworms, the conversion of habitat by nonnative plants, or future climate change.

A summary of our conclusions for each of the five factors is found in Table 2. More specific information for each threat considered under the five factors is available in theSummary of Information Pertaining to the Five Factorssection above.

As required by the Act, we considered the five factors in assessing whether the GPE is endangered or threatened throughout all or a significant portion of its range. We examined the best scientific and commercial information available regarding the past, present, and future threats faced by the GPE. We reviewed the petition, information available in our files, and other available published and unpublished information, and we consulted with the most qualified GPE experts and queried universities, State agencies, conservation districts, and other entities. In considering what factors might constitute threats, we must look beyond the mere exposure of the species to the factor to determine whether the species responds to the factor in a way that causes actual impacts to the species. If there is exposure to a factor, but no response, or only a positive response, that factor is not a threat. If there is exposure and the species responds negatively, the factor may be a threat and we then attempt to determine how significant a threat it is. If the threat is significant, it may drive or contribute to the risk of extinction of the species such that the species warrants listing as endangered or threatened as those terms are defined by the Act. This does not necessarily require empirical proof of a threat. Thecombination of exposure and some corroborating evidence of how the species is likely impacted could suffice. The mere identification of factors that could impact a species negatively is not sufficient to compel a finding that listing is appropriate; we require evidence that these factors are operative threats that act on the species to the point that the species meets the definition of endangered or threatened under the Act.

The analysis of threats (the five factors) to determine if the status of GPE meets the definition of endangered or threatened was particularly challenging, because the range of the species appears to be greater than it was originally thought to be. In addition to the Palouse area prairie, the species has been documented in dry forest habitat on the east slope of the Cascades. Survey effort for this species has been low, especially outside of the Palouse grasslands, and appropriate survey methods remain to be developed. In addition, the life history of the GPE is not completely understood. There is still some scientific debate regarding whether the GPE is an anecic or endogeic species, although the most recent field observations and prevailing scientific evidence indicates it is a deep-burrowing anecic species (Johnson-Maynard 2010, p. 2), which would result in a different exposure to threats than if it were an endogeic species. There is no scientific basis to conclude that any of the activities identified as threats by the petitioners are, in fact, threats to the GPE.

Based on our review of the best available scientific and commercial information pertaining to the five factors, we find that the threats are not of sufficient imminence, intensity, or magnitude to indicate that the GPE is in danger of extinction (endangered), or likely to become endangered within the foreseeable future (threatened), throughout all of its range. Therefore, we find that the GPE does not meet the definition of an endangered or threatened species throughout its range.

After assessing whether the species is endangered or threatened throughout its range, we next consider whether a distinct vertebrate population segment (DPS) or whether any significant portion of the GPE range meets the definition of endangered or is likely to become endangered in the foreseeable future (threatened), in accordance with the Service's Policy Regarding the Recognition of Distinct Vertebrate Population Segments under the Endangered Species Act (61 FR 4722, February 7, 1996). Because the GPE is not a vertebrate species, the Distinct Vertebrate Population Segment policy is not applicable to this finding.

Having determined that the GPE does not meet the definition of an endangered or threatened species, we must next consider whether there are any significant portions of the range where the GPE is in danger of extinction or is likely to become endangered in the foreseeable future. Because of significant uncertainties regarding the range of the GPE, the limited survey efforts, and the paucity of information regarding its life history, there is nothing to suggest that threats are disproportionately acting on any portion of the species' range, such that the species is at risk of extinction now or in the foreseeable future. Therefore, we find that listing the GPE as an endangered or threatened species is not warranted throughout all or a significant portion of its range. The designation of critical habitat for this species as requested by the petitioner is not appropriate, based on our determination that the species does not warrant listing under the Act.

The Service continues to be interested in the status of this unique species. We request that you submit any new information concerning the status of, or threats to, the GPE to our Washington Fish and Wildlife Office (seeADDRESSES) whenever it becomes available. New information will help us monitor the GPE and encourage its conservation.

A complete list of references cited is available on the Internet athttp://www.regulations.govand upon request from the Washington Fish and Wildlife Office (seeADDRESSES).

The primary authors of this notice are the staff members of the Washington Fish and Wildlife Office.

The authority for this section is section 4 of the Endangered Species Act of 1973, as amended (16 U.S.C. 1531et seq.).

I. Why do we conduct a 5-year review?

Under the Act (16 U.S.C. 1531et seq.), we maintain Lists of Endangered and Threatened Wildlife and Plants (which we collectively refer to as the List) in the Code of Federal Regulations (CFR) at 50 CFR 17.11 (for animals) and 17.12 (for plants). Section 4(c)(2)(A) of the Act requires us to review each listed species' status at least once every 5 years. Then, under section 4(c)(2)(B), we determine whether to remove any species from the List (delist), toreclassify it from endangered to threatened, or to reclassify it from threatened to endangered. Any change in Federal classification requires a separate rulemaking process.

In classifying, we use the following definitions, from 50 CFR 424.02:

(A)Speciesincludes any species or subspecies of fish, wildlife, or plant, and any distinct population segment of any species of vertebrate, that interbreeds when mature;

(B)Endangered speciesmeans any species that is in danger of extinction throughout all or a significant portion of its range; and

(C)Threatened speciesmeans any species that is likely to become an endangered species within the foreseeable future throughout all or a significant portion of its range.

We must support delisting by the best scientific and commercial data available, and only consider delisting if data substantiate that the species is neither endangered nor threatened for one or more of the following reasons (50 CFR 424.11(d)):

(A) The species is considered extinct;

(B) The species is considered to be recovered; or

(C) The original data available when the species was listed, or the interpretation of data, were in error.

Our regulations at 50 CFR 424.21 require that we publish a notice in theFederal Registerannouncing the species we are reviewing.

This notice announces our active 5-year status reviews of the species.

We consider all new information available at the time we conduct a 5-year status review. We consider the best scientific and commercial data that have become available since our current listing determination, or most recent status review that is accessible from our Web sitehttp://www.fws.gov/midwest/Endangered/recovery/5yr_rev/completed5yrs.html,such as:

(A) Species biology, including but not limited to population trends, distribution, abundance, demographics, and genetics;

(B) Habitat conditions, including but not limited to amount, distribution, and suitability;

(C) Conservation measures that have been implemented that benefit the species;

(D) Threat status and trends (see five factors under heading “How Do We Determine Whether a Species Is Endangered or Threatened?”); and

(E) Other new information, data, or corrections, including but not limited to taxonomic or nomenclatural changes, identification of erroneous information contained in the List, and improved analytical methods.

For the copperbelly water snake, we specifically request information that pertains only to the northern distinct population segment (DPS). The copperbelly watersnake was listed as a DPS of a vertebrate taxon. The listed DPS occurs in Michigan, Ohio, and Indiana north of 40 degrees north latitude (approximately Indianapolis, Indiana). A DPS is defined in the February 7, 1996, Policy Regarding the Recognition of Distinct Vertebrate Population Segments (61 FR 4722). Three elements are considered to list a population under the Act as a DPS: (1) The discreteness of the population segment in relation to the remainder of the species to which it belongs; (2) The significance of the population segment to the species to which it belongs; and (3) The population segment's conservation status in relation to the Act's standards for listing (i.e.,is the population segment endangered or threatened?). Distinct population segments of vertebrate species, as well as subspecies of all listed species, may be proposed for separate reclassification or for removal from the List. As required by the DPS policy, we will assess the validity of the current DPS designation during the 5-year review. The southern population (i.e.,in Illinois, Kentucky, and Indiana south of 40 degrees north latitude) is not listed as a threatened species at this time and is not part of this 5-year review.

Section 4(a)(1) of the Act requires that we determine whether a species is endangered or threatened based on one or more of the five following factors:

(A) The present or threatened destruction, modification, or curtailment of its habitat or range;

(B) Overutilization for commercial, recreational, scientific, or educational purposes;

(C) Disease or predation;

(D) The inadequacy of existing regulatory mechanisms; or

(E) Other natural or manmade factors affecting its continued existence.

Under section 4(b)(1) of the Act, we must base our assessment of these factors solely on the best scientific and commercial data available.

For each species under review, if we find new information that indicates a change in classification may be warranted, we may propose a new rule that could do one of the following:

(A) Reclassify the species from threatened to endangered (uplist);

(B) Reclassify the species from endangered to threatened (downlist); or

(C) Remove the species from the List (delist).

If we determine that a change in classification is not warranted, then the species remains on the List under its current status.

To ensure that a 5-year review is complete and based on the best available scientific and commercial information, we request new information from all sources. See “What Information Do We Consider in Our Review?” for specific criteria. If you submit information, support it with documentation such as maps, bibliographic references, methods used to gather and analyze the data, and/or copies of any pertinent publications, reports, or letters by knowledgeable sources.

Submit your comments and materials to the appropriate U.S. Fish and Wildlife Service office listed under “VIII. Contacts.”

Submit all electronic information in Text or Rich Text format toFW3MidwestRegion_5YearReview@fws.gov.Please send information for each species in a separate e-mail. Provide your name and return address in the body of your message, and include the following identifier in your e-mail subject line: Information on 5-year review for [NAME OF SPECIES].

Before including your address, phone number, e-mail address, or other personal identifying information in your comment, you should be aware that your entire comment—including your personal identifying information—may be made publicly available at any time. While you can ask us in your comment to withhold your personal identifying information from public review, we cannot guarantee that we will be able to do so. Comments and materials received will be available for public inspection, by appointment, during normal business hours at the offices where the comments are submitted.

Send your comments and information on the following species, as well as requests for information, to the corresponding contacts. You may view information we receive in response to this notice, as well as other documentation in our files, at the following locations by appointment, during normal business hours.

We publish this notice under the authority of the Endangered Species Act of 1973, as amended (16 U.S.C. 1531et seq.).

Background

Section 4(b)(3)(B) of the Act (16 U.S.C. 1531et seq.) requires that, for any petition to revise the Federal Lists of Threatened and Endangered Wildlife and Plants that contains substantial scientific or commercial information that listing a species may be warranted, we make a finding within 12 months of the date of receipt of the petition. In this finding, we determine whether the petitioned action is: (a) Not warranted, (b) warranted, or (c) warranted, but immediate proposal of a regulation implementing the petitioned action is precluded by other pending proposals to determine whether species are endangered or threatened, and expeditious progress is being made to add or remove qualified species from the Federal Lists of Endangered and Threatened Wildlife and Plants. Section 4(b)(3)(C) of the Act requires that we treat a petition for which the requested action is found to be warranted but precluded as though resubmitted on the date of such finding, that is, requiring a subsequent finding to be made within 12 months. We must publish these 12-month findings in theFederal Register.

Federal action for the frigid ambersnail began on July 30, 2007, after we received a petition dated July 24, 2007, from Forest Guardians (now WildEarth Guardians) requesting that the Service: (1) Consider all full species in our mountain-prairie region ranked as G1 or G1G2 by the organization NatureServe, except those that are currently listed, proposed for listing, or candidates for listing; and (2) list each species as either endangered or threatened (Forest Guardians 2007, pp. 1-37). We acknowledged the receipt of the petition in a letter to the Forest Guardians, dated August 24, 2007 (Slack 2007, p. 1). In that letter we stated, based on preliminary review, that we found no compelling evidence to support an emergency listing for any of the species covered by the petition.

On March 19, 2008, WildEarth Guardians filed a complaint (1:08-CV-472-CKK) indicating that the Service had failed to make 90-day petition findings under section 4 of the Act for the 206 mountain-prairie species, including the frigid ambersnail. On February 5, 2009, we published a 90-day finding (74 FR 6122) for 165 of the 206 mountain-prairie species, which did not include the frigid ambersnail. On March 13, 2009, the Service and WildEarth Guardians filed a stipulated settlement in the District of Columbia Court, agreeing that the Service would submit to theFederal Registera finding as to whether WildEarth Guardians' petition presented substantial information indicating that the petitioned action may be warranted for 38 mountain-prairie region species by August 9, 2009 (WildEarth Guardiansv.Salazar2009, case 1:08-CV-472-CKK). On August 18, 2009, we published a 90-day finding (74 FR 41649) for 38 mountain-prairie region species, and initiated status reviews on 29 of those species, including the frigid ambersnail.

On January 8, 2010, WildEarth Guardians filed a complaint indicating that the Service had failed to complete a 12-month finding on the frigid ambersnail, and on January 20, 2010, they filed an amended complaint. On June 29, 2010, this complaint was consolidated in the District of Columbia District Court along with 11 other individual cases filed by WildEarth Guardians, all related to multiple-species petitions. This litigation is currently unresolved.

This notice constitutes the 12-month finding on the July 24, 2007, petition to list the frigid ambersnail as endangered.

The frigid ambersnail is a prehistoric snail known from the Pleistocene period, which spanned from 1.8 million to approximately 10,000 years ago. The species has an extensive fossil record. Based on that fossil record, its historical range included eight states: Iowa, Illinois, Indiana, Louisiana, Mississippi, Missouri, Ohio, and New York (Frest 1991, p. 17). Individuals, that at the time were thought to be living specimens of frigid ambersnails, were subsequently found in the Black Hills of South Dakota and south of Green Bay in Wisconsin (Frest and Johannes 2002, pp. 73-74). Current, putative populations are only now known from Iowa, the Black Hills National Forest of South Dakota and, possibly, Wisconsin. Currently, taxonomy regarding these extant populations is unclear as to whether these are frigid ambersnails (as described from the prehistoric fossils) or members of a different, likely more common, taxon.

Catinella gelidawas initially described as a widespread prehistoric fossil. The genusCatinellabelongs to phylum Mollusca, class Gastropoda, order Stylommatophora (terrestrial snails and slugs), and family Succineidae. Baker (1927, pp. 118-119) first described the fossil shell of the frigid ambersnail as a subspecies ofSuccinea grosvenorii(Baker 1927). Baker (1927) describes the fossil species as having a small (less than 10 mm (0.4 inches), elongated shell. The whorls (a single turn in the spiral of the shell) are convex and separated by deep sutures—the last whorl is small, flat-sided, and slightly convex. The spire (the part of the shell that consists of all of the whorls, except the body whorl) is long and acute with a rounded aperture (main opening of the shell) that is about half as long as the shell. The columella (central column inside the shell) is straight, gently curving to the parietal wall (margin of the aperture and part of the wall of the body whorl that is closest to the columella), and does not form a distinct angle. The slight callus (thickened calcareous deposit which may be present on the parietal wall of the aperture of the adult shell) is spread over the parietal wall. The sculpture (ornamentation on the outer surface of the shell) is fine with vertical striae (thin, narrow grooves).

Thirty-six years after Baker (1927) first described the species, the fossil form was reclassified as distinct fromSuccinea grosvenoriand retained as a separate species namedCatinella gelidaby Leslie Hubricht (Hubricht 1963, pp. 137-138). As Hubricht (1963, p.137) stated: “This species [Succinea grosvenori gelida], is certainly not related toSuccinea grosvenorias now understood. Some shells resemble a slenderCatinella vermeta(Say), and others resemble shells ofCatinella wandae(Webb) from Grand Teton National Park, Teton County, Wyoming, and it is possible that the namegelidahas been applied to more than one species. In view of the impossibility of demonstrating the relationship to either of the above species by anatomical studies,Catinella gelidais here retained as a separate species.” As Hubricht states, identification of the fossil form used fossil shell characterics only.

In 1985, Terrence Frest (1985, p. 4) described what was thought to be the first live specimen of the frigid ambersnail from the carbonate cliffs of Iowa. The basis for his identification was geologic location and shellmorphology. Prior to this, the species was thought to only occur in fossil form. What were thought to be additional relic populations were then identified in the Black Hills of South Dakota and south of Green Bay in Wisconsin (Frest and Johannes 2002, pp. 73-74).

Frest's (1991, p. 16) described the physical appearance of individuals in those relic populations by expanding on Baker's (1927, pp. 118-119) description of the fossil form of frigid ambersnail. However, Frest's (1991, p. 16) description still provides information on the shell only, stating that “Live specimens are slightly smaller on average than fossil (e.g.,average length 7.0 rather than 7.0-8.0 mm), but otherwise identical. In life the color is a peculiar light yellow-green; the body is dark grey to nearly black. The sculpture on both fossil and recent specimens is rather stronger than in most Succineidae.”

A number of researchers (e.g.,Patterson 1971, p. 133; Grimm 1996, p. 1; Coles and Walsh 1999, p. 32; Pigatiet al.2010, p. 5) have suggested that for accurate identification of species of living land snails within the Succineidae family, supporting anatomical information is critical in addition to morphological information. Patterson (1971, p. 133) stated the following in his taxonomic studies of the land snail's family Succineidae, “The taxonomic placement of most species of the Succineidae is still based largely on shell characters, which, because of little diversity and considerable convergence, give only fragmentary or unreliable aid in systematic analyses. Currently, features of the male and female reproductive tract, the radula and jaw, and to some extent, patterns of pigmentation, are being used to characterize some genera and species. However, to date, only a very few species have been studied with regard to such morphological characters, which leaves the systematics of the Succineidae in an inadequate and confused state.”

Grimm (1996, p. 1) and Coles and Walsh (1999, p. 32) also considered the use of additional anatomical features, such as genitalic structure, to be crucial for the accurate identification of extantCatinellaspecies. Pigatiet al.(2010, p. 5) recently described the need for additional morphological characteristics to distinguish among species for the Succineidae family and the genusCatinella:“In the fossil record, species-levelidentification of fossil shells is possible for most small terrestrial gastropods and, therefore, the results of our investigation of modern gastropods can be applied directly to the fossil record. An exception is the Succineidae family, which is composed of three genera (Catinella, Oxyloma,andSuccinea) that are difficult to differentiate in modern faunas. Their simple shells exhibit few diagnostic characteristics and, therefore, species-level identification is based on soft-body reproductive organ morphology, which is rarely preserved in the fossil record.”

In 2002, Frest and Johannes acknowledged the difficulty of using a fossil form as the originally described specimen of frigid ambersnail to identify living individuals. However, they continued to support the species classification, stating that, “as it happens, shell characters ofC. gelidaare sufficiently distinctive as to make it unlikely to be confused with other described North American succineids. Preliminary dissections of specimens from the Iowa-Minnesota colonies confirm placement of those specimens inCatinella.The body color is unlike any other described species. The few live South Dakota specimens seen appear identical in morphology to those from Iowa” (Frest and Johannes 2002, p. 70). Although Frest and Johannes (2002, p. 7) have stated that fossil shell morphological characteristics alone were adequate to classify a living specimen, current researchers (such as Anderson (2005) and Nekola (2009, 2010) (see below)) do not support this assertion.

Anderson (2005) examinedCatinella-like shells in Wind Cave National Park, South Dakota. In her analysis, she identified theCatinellaspecimens to genus level only, noting the conflicting opinion on the use of shell characteristics for identification to species level (Anderson 2005, p. 189). She cites Burch (1962) and Hoagland and Davis (1987) as cautioning against using such characteristics alone in identifying species in this taxonomic family.

Jeffrey Nekola is a professor with the University of New Mexico and is considered an expert in land snails, has authored numerous publications on the topic, and has field experience with fauna of the carbonate cliffs of Iowa and the surrounding area. Nekola indicated several issues with the classification of the living frigid ambersnail in response to our publication of a 90-day finding (74 FR 41649) and initiation of status review on a petition to list the frigid ambersnail (Catinella gelida) as endangered. Nekola (2010, pers. comm.) stated that there is not a published account of a dissection of the frigid ambersnail. Nekola has examined living snail soft body parts from ambersnails (from Nekola 1998 and 2003) that met the description of the fossil frigid ambersnail (as described by Frest 1991). He (Nekola pers. comm. 2010) subsequently analyzed this material and found the soft body parts to be similar to those found in the slope ambersnail (C. wandae). In addition, Nekola (2009, p. 103) questions the validity of using soft body parts for the taxonomic identification of species in this genus. He notes that the structure of the genitalia in this group of snails is highly variable and that, looking at genitalia, individuals may resemble different species as they pass through various stages of development from embryo to adult (Nekola 2009, p. 103). This is supported by Coles (2010, pers. comm.), who stated that based on his own work, the relative size and development of the maleCatinellagenital appendix can vary with age.

Because of the difficulty in defining characteristic soft parts, Nekola now believes that the only positive way to distinguish species inCatinella's group is to look at genetic data within and between populations, at the species and genus levels (Nekola 2009, p. 103). Ostlie (2009, p. 51) supports obtaining additional information, such as analysis of DNA, to confirm identification of the species.

Based on the best available current scientific information, the validity of the frigid ambersnail as an extant species has reasonably been questioned. The frigid ambersnail (Catinella gelida) is not recognized as a valid extant species or subspecies by the Integrated Taxonomic Information System (ITIS 2011) or the Council of Systematic Malacologists and the American Malacological Union (Turgeonet al.1998, p. 143). Uncertainties regarding taxonomic classification remain not only for the genusCatinella,but also for members of the snail family Succineidae. In recent analyses, species designation for members of this family has been determined to be too questionable to differentiate the species using shell appearance and location alone (Burch 1962, p. 67; Hoagland and Davis 1987, pp. 518-519; Anderson 2005, p. 189; Nekola 2003b, p. 8; Barthel and Nekola 2000, p. 24). Furthermore, using soft body parts to identify species in this snail family also appears questionable, especially as the characteristics of those body parts change as the individuals mature (Nekola 2009, p. 103; Coles 2010, pers. comm.).

In summary, the taxonomic identity of the extant snails that have been referred to as the “frigid ambersnail” has been substantially questioned in recent years. While some individual researcherscontinue to recognize currently living individuals of ambersnail asCatinella gelida,this entity is not widely recognized as an extant species or subspecies by the scientific community at this time. The type of additional information that may permit a formal description may include a more thorough description of an extant type specimen, an evaluation of various lines of evidence (morphological, ecological, biogeographical, genetic) relevant to its taxonomic status, resolution of any discrepancies in taxonomic nomenclature, or a combination of these (e.g.,Weaver 2006, pp. 49-65), and that the taxon be accepted as valid by widely recognized sources (e.g.,Turgeonet al.1998, entire; ITIS 2010).

Therefore, we find based on the best information available, thatCatinella gelidais not a modern living (extant) species.Catinella gelidawas described from a fossil, and the most current information now indicates that the currently living specimens that were classified as frigid ambersnail were likely misclassified, and are likely notCatinella gelida.The taxonomy of these living ambersnails is uncertain.Catinella gelidaitself, as described from the fossil specimen, likely exists only in fossil form, and the currently living individuals likely belong to a different taxon. Therefore, we find that the currently living specimens, that were previously thought to be frigid ambersnail, are not valid taxonomically. Although additional study could affect the taxonomic conclusion of this finding, the taxonomic identity of the modern living (extant) frigid ambersnail has not been confirmed as of this date by current species experts.

We have carefully assessed the best scientific and commercial information available regarding the taxonomic status of the frigid ambersnail (Catinella gelida). We reviewed the petition, available published and unpublished scientific and commercial information, and information submitted to us during the information collection period on our status review following our 90-day finding. We also consulted with recognized experts. The frigid ambersnail is not recognized as an extant species or subspecies by the scientific community, and the taxonomic status of extant specimens is currently uncertain. The named petitioned entity,Catinella gelida,is extinct and only exists in fossil form. Modern, existing populations, that were originally described asC. gelida,are notC. gelida,and their taxonomic identity remains uncertain. Consequently, the Service does not at this time consider the petitioned entity, the frigid ambersnail, to be a listable entity under section 3(16) of the Act (16 U.S.C. 1532(16)). The Service encourages additional scientific investigations that will resolve the significant uncertainties concerning the taxonomy of frigid ambersnail. Because we have concluded the frigid ambersnail is not a listable entity, we will not further evaluate this ambersnail under section 4(a)(1) of the Act. On the basis of this review, we find that listing the frigid ambersnail as endangered or threatened is not warranted because the frigid ambersnail does not meet the definition of a “species” under the Act.

A complete list of all references cited herein is available on the Internet athttp://www.regulations.govand upon request from the Field Supervisor at the Rock Island Ecological Services Office (seeADDRESSESsection).

The primary authors of this document are the staff members of the Rock Island Ecological Services Field Office, Moline, Illinois (seeADDRESSESsection).