[Federal Register Volume 79, Number 31 (Friday, February 14, 2014)]
[Rules and Regulations]
[Pages 8825-8832]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-03260]



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Federal Register / Vol. 79, No. 31 / Friday, February 14, 2014 / 
Rules and Regulations

[[Page 8825]]



CONSUMER PRODUCT SAFETY COMMISSION

[CPSC Docket No. CPSC-2013-0010]

16 CFR Part 1500


Hazardous Substances and Articles; Administration and Enforcement 
Regulations: Final Rule; Revisions to Supplemental Definition of 
``Strong Sensitizer''

AGENCY: Consumer Product Safety Commission.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: The U.S. Consumer Product Safety Commission (CPSC or 
Commission) amends it regulations to revise the supplemental definition 
of ``strong sensitizer'' under the Federal Hazardous Substances Act 
(FHSA). The revised definition of ``strong sensitizer'' eliminates 
redundancy, removes certain subjective factors, incorporates new and 
anticipated technology, places the criteria for classification of 
strong sensitizers in the order of importance, defines criteria for 
``severity of reaction,'' and provides for the use of a weight-of-
evidence approach to determine whether a substance is a strong 
sensitizer.

DATES: The rule will become effective on March 17, 2014.

FOR FURTHER INFORMATION CONTACT: Carol Afflerbach, Compliance Officer, 
Office of Compliance and Field Operations, U.S. Consumer Product Safety 
Commission, 4330 East-West Highway, Bethesda, MD 20814; email: 
cafflerbach@cpsc.gov.

SUPPLEMENTARY INFORMATION: 

A. Background

    The FHSA, 15 U.S.C. 1261-1278, requires appropriate cautionary 
labeling on certain hazardous household products to alert consumers to 
the potential hazards that a product may present. Among the hazards 
addressed by the FHSA are products containing substances that are 
toxic, corrosive, an irritant, flammable or combustible, generate 
pressure through decomposition, heat or other means, or are strong 
sensitizers.
    Included within the FHSA's definition of ``hazardous substance'' is 
``any substance or mixture of substances'' that ``is a strong 
sensitizer,'' 15 U.S.C. 1261(f)1(iv). Section 2(k) of the FHSA, 15 
U.S.C. 1261(k), defines ``strong sensitizer'' as a substance which will 
cause on normal living tissue through an allergic or photodynamic 
process a hypersensitivity which becomes evident on reapplication of 
the same substance and which is designated as such by the Commission. 
Before designating any substance a strong sensitizer, the Commission, 
upon consideration of the frequency of occurrence and severity of the 
reaction, shall find that the substance has a significant potential for 
causing hypersensitivity.
    On August 12, 1961, the U.S. Food and Drug Administration (FDA) 
(which at that time administered the FHSA), issued regulations under 
the FHSA that supplemented the statutory definition of ``strong 
sensitizer'' by explaining that a `` `strong allergic sensitizer' is a 
substance that produces an allergenic sensitization in a substantial 
number of persons that come into contact with it'' and specifying that 
``[a]n allergic sensitization develops by means of an `antibody 
mechanism' in contradistinction to a primary irritant reaction which 
does not arise because of the participation of an `antibody mechanism.' 
'' 26 FR 7333, 7334. The regulation (the 1961 supplemental definition) 
listed five substances that the FDA had determined met the statutory 
definition for ``strong sensitizer'': (1) Paraphenylenediamine and 
products containing it; (2) powdered orris root and products containing 
it; (3) epoxy resins systems containing in any concentration 
ethylenediamine, diethylenetriamine, and diglycidyl ethers of molecular 
weight less than 200; (4) formaldehyde and products containing 1 
percent or more of formaldehyde; and (5) oil of bergamot and products 
containing 2 percent or more of oil of bergamot. Id. at 7335. Neither 
the FDA nor the CPSC has added any strong sensitizers to this list in 
the 1961 supplemental definition.
    In 1973, Congress transferred the responsibility for the 
administration of the FHSA to the Commission. On May 30, 1984, the 
Commission revoked the 1961supplemental definition because the 1961 
supplemental definition did not account for more recent scientific 
theories and was narrower than the statutory definition. 49 FR 22464.
    On August 14, 1986, the Commission issued a rule supplementing the 
statutory definition of ``strong sensitizer'' (1986 supplemental 
definition). 51 FR 29094. The 1986 supplemental definition clarified 
how the statutory definition should be interpreted and explained the 
factors the Commission would consider in determining whether a 
substance is a strong sensitizer. The 1986 supplemental definition 
stated that an ``allergic'' response is one that is directed by the 
immune system, such that a sensitization reaction could not be caused 
by an irritant or other nonallergenic qualities of the substance. The 
1986 supplemental definition also clarified that active sensitizers--
substances that produce a sensitivity reaction solely as the result of 
a person's first exposure to the substance as opposed to a reaction 
after reapplication of the same substance--are included in the class of 
substances that can be determined to be strong sensitizers. The 1986 
supplemental definition did not address strong sensitizers that cause 
hypersensitivity by a photodynamic process, principally because 
Commission staff was unaware of any household product subject to the 
FHSA that would cause significant exposure of consumers to a 
photodynamic chemical.
    In 2005, recognizing that the science on sensitization had changed 
since promulgation of the 1986 supplemental definition, the CPSC 
convened a panel of scientific experts from academia, industry, and the 
federal government to examine the available scientific and medical 
information concerning sensitizers, and if appropriate, propose 
revisions to the supplemental definition of ``strong sensitizer.'' 
Based on the panel's input, CPSC staff developed a draft technical 
report on proposed revisions to the supplemental definition. In 2007, 
the draft technical report underwent federal agency and external 
scientific peer review. In 2008,

[[Page 8826]]

CPSC staff revised the draft technical report based on the input 
received from federal agency and external scientific peer reviewers. 
Subsequently, CPSC staff drafted a revision of the ``strong 
sensitizer'' supplemental definition, based on the peer reviewed 
technical report.
    The Commission approved publication of a notice of proposed 
rulemaking (NPR) to revise the supplemental definition of ``strong 
sensitizer'' (proposed definition or proposed rule). 78 FR 15660 (March 
12, 2013). The proposed definition of ``strong sensitizer'' eliminates 
redundancy, removes certain subjective factors, incorporates new and 
anticipated technology, ranks the criteria for classification of strong 
sensitizers in the order of importance, defines criteria for ``severity 
of reaction,'' and provides for the use of a weight-of-evidence 
approach to determine whether a substance is a strong sensitizer.
    In addition, the Commission approved publication of a notice of 
availability for a document prepared by CPSC staff titled, ``Strong 
Sensitizer Guidance.'' 78 FR 15710 (March 12, 2013). This guidance 
document was intended to clarify each component of the revised ``strong 
sensitizer'' definition and assist manufacturers in understanding how 
CPSC staff would assess whether a substance or product containing that 
substance should be considered a strong sensitizer and how the 
Commission would make such a determination.

B. Response to Comments on the Proposed Rule

    We received five comments on the NPR. The following individuals or 
entities submitted comments: a consulting toxicologist; the 
International Fragrance Association of North America; the People for 
the Ethical Treatment of Animals (PETA); the International Science 
Consortium and the Physicians Committee for Responsible Medicine; the 
American Chemistry Council; and the Diisocyanates Panel of the American 
Chemistry Council.
    Several commenters expressed general support for the proposed rule 
and made statements supporting specific aspects of the rule. For 
example, several commenters supported deleting the reference to 
sensitizers that occasionally induce an allergic response on first 
exposure so that substances that merely cause irritation upon initial 
exposure will not be considered strong sensitizers. Similarly, a 
commenter agreed with the proposal's emphasis that sensitization is an 
immunologically mediated, multi-stage process that occurs over a period 
of time. Several commenters raised issues that resulted in minor 
organizational and terminology changes to the proposed rule. All of the 
comments can be viewed at: www.regulations.gov, by searching under the 
docket number of the rulemaking, CPSC-2013-0010. Following is a summary 
of, and responses to, the comments.

Harmonization with International Criteria

    Comment: Two commenters recommended that the CPSC take action to 
align the agency's chemical classification regulations and practices 
with internationally harmonized criteria, encouraging the Commission to 
implement the Globally Harmonized System of Classification and Labeling 
of Chemicals (GHS). One of the commenters argued that harmonization of 
chemical classification and labeling will promote regulatory efficiency 
and facilitate trade without lowering the level of health and 
environmental protection afforded by current U.S. laws and regulations. 
One of the commenters recommended that the Commission use the GHS cut-
off value criteria for determining whether a substance is a sensitizer, 
unless there has been sensitization testing on the substance or product 
containing the substance.
    Response: The GHS is a system for standardizing and harmonizing the 
classification and labeling of chemicals, but the GHS is not a 
regulation or a standard. The intent of the GHS is to provide an 
internationally comprehensible system for communicating chemical 
hazards to all sectors (e.g., consumers, workers, emergency responders, 
and the public) along the entire life cycle of the chemical. The GHS 
establishes agreed-upon hazard classification and communication 
criteria with explanatory information on how to apply the system. 
Implementation of the GHS by the Commission would be broad-reaching, 
with potential impact beyond the FHSA, possibly involving the revision 
of existing CPSC statutes and regulations. The request that the 
Commission implement the GHS, therefore, goes well beyond the limited 
scope of this rulemaking proceeding.

Description of Strong Sensitizer Determination Process

    Comment: Two commenters requested a description of the 
administrative process that would be used to make a determination that 
a substance or product containing a substance is a strong sensitizer so 
that stakeholders will be aware of opportunities for participation in 
the process.
    Response: Under the FHSA, the Commission must first designate a 
substance a ``strong sensitizer'' for the substance to be considered a 
``strong sensitizer.'' (15 U.S.C 1261(k)). Such a designation would 
occur in a separate proceeding that is outside the scope of this 
action. The current action relates only to the regulatory definition of 
a ``strong sensitizer,'' not to the designation of a particular 
substance as a strong sensitizer.

Labeling Requirement for Strong Sensitizers

    Comment: One commenter requested that the Commission set forth the 
circumstances under which a substance or product containing a substance 
that has been designated a strong sensitizer would not require labeling 
under Section 2(p) of the FHSA (15 U.S.C. 1261(p).
    Response: A substance that is a strong sensitizer or a product 
containing a strong sensitizer would not require labeling, unless the 
substance met the FHSA definition of ``hazardous substance.'' A 
``hazardous substance'' is one that is a strong sensitizer (or has 
another of the specified ``hazardous substance'' characteristics) and 
``may cause substantial personal injury or substantial illness during 
or as a proximate result of any customary or reasonably foreseeable 
handling or use, including reasonably foreseeable ingestion by 
children.'' 15 U.S.C. 1261(f). Thus, manufacturers of products 
containing a strong sensitizer would have to determine whether the 
concentrations and availability of the substance in their products 
could cause substantial injury or illness as a result of reasonably 
foreseeable handling or use. Labeling under section 2(p) of the FHSA 
would only be required if the product containing a strong sensitizer 
would cause substantial injury or illness as a result of reasonably 
foreseeable handling or use.
    The Commission would also have the option of issuing a rule under 
Section 3(a) of the FHSA to designate a strong sensitizer as a 
hazardous substance to reduce uncertainty about which products would be 
considered a hazardous substance. Id. 15 U.S.C. 1262(a)(1). A hazardous 
substance that is not labeled properly with appropriate cautionary 
statements in accordance with section 2(p) of the FHSA is considered a 
``misbranded hazardous substance.'' Id. 15 U.S.C. 1261(p). Introducing, 
delivering for introduction, or receiving in interstate commerce a

[[Page 8827]]

misbranded hazardous substance is a prohibited act. Id. 15 U.S.C. 
1263(a) and (c).

Effect of Rule on Regulation of Products and Risk Management Actions

    Comment: One commenter asserted that replacing the 1986 
supplemental definition with the proposed definition could have far-
reaching effects on the regulation of products at a broader level and 
stated that classifying substances as strong sensitizers may prompt 
risk management actions by the CPSC or other regulatory bodies. The 
commenter encouraged the CPSC to see that classification determinations 
fully reflect a science- and risk-based approach that considers the 
degree of hazard and extent of exposure potential.
    Response: The Commission does not believe that replacing the 1986 
supplemental definition with the final rule definition will have ``far-
reaching effects.'' The rule does not designate any particular 
substance as a strong sensitizer, but the rule revises the regulatory 
definition of ``strong sensitizer.'' A separate proceeding involving a 
specific substance would be required before the agency could declare a 
substance to be a strong sensitizer. This rule simply provides guidance 
about the information and data that CPSC would consider and the 
relative importance of the information in making a strong sensitizer 
determination.
    Moreover, the determination that a substance is a strong sensitizer 
does not, by itself, require any action by a manufacturer. Under the 
FHSA, labeling or other regulatory action implicating risk management 
factors is required only when a substance meets the definition of 
``hazardous substance.'' (15 U.S.C. 1261(f)). A substance that the 
Commission designates as a strong sensitizer could be a ``hazardous 
substance'' under the FHSA, ``if such substance or mixture of 
substances may cause substantial personal injury or substantial illness 
during or as a proximate result of any customary or reasonably 
foreseeable handling or use, including reasonably foreseeable ingestion 
by children.'' Therefore, by definition, the FHSA considers exposure 
and requires a case-by-case hazard assessment. The final rule 
definition reflects both a science- and risk-based approach so that the 
decision for classification is not based solely on a product's 
ingredients.

Separate Treatment of Type I and Type IV Allergies in Sensitizer 
Definition

    Comment: One commenter recommended that Type I and Type IV 
allergies be addressed separately in the final rule definition because 
these types of allergies have different potential for causing illness, 
discomfort, and chronic morbidity; and consideration of different types 
of data would be necessary to evaluate the potential of substances that 
trigger these two different types of reactions to cause substantial 
illness.
    Response: A Type I allergy or immediate hypersensitivity is an 
allergic reaction provoked by reexposure to a specific type of allergen 
due to the production of specific antibodies. A Type IV allergy or 
delayed hypersensitivity is an allergic reaction that typically arises 
1 to 3 days after exposure to an allergen and is not an antibody-
mediated response. We agree that evaluating whether a substance is a 
strong sensitizer will depend on the substance and the allergic 
response the substance induces. However, we believe that the final rule 
definition would be significantly and unnecessarily more complex if 
these two types of allergies were separated into different categories.
    The criteria contained in the supplemental definition allow for 
flexibility in assessing all types of allergic reactions to 
sensitizers. In addition, the final rule definition includes the 
various potential routes of exposure for sensitizers, as well as 
anatomic sites of an allergic response. The outcome of exposure, 
whether a dermal or respiratory response, likely will require the 
analysis of different data for evaluation. Evaluating whether a 
substance is a strong sensitizer requires a case-by-case inquiry, based 
on high-quality relevant data. The Strong Sensitizer Guidance document 
explains the approach CPSC staff would take in evaluating the potential 
causal link between exposure to strong sensitizers and these two types 
of hypersensitivity. We believe that the final rule definition provides 
the flexibility for assessing these two types of allergic reactions to 
sensitizers without the need for specifically differentiating them.

Acceptance of Data From Certain QSAR Models

    Comment: One commenter requested that the Commission revise the 
proposed definition to provide for the acceptance of data from 
Quantitative Structure-Activity Relationship (QSAR) models 
(mathematical models that relate a quantitative measure of chemical 
structure to biological activity) that the Organisation for Economic 
Co-operation and Development (OECD) has evaluated and approved for 
specific applicability domains.
    Response: The final rule definition specifically states that in 
determining whether a substance has a significant potential for causing 
hypersensitivity, chemical or functional properties of the substance of 
interest, in addition to QSAR data, can be considered. The panel of 
experts and external peer reviewers determined that QSAR data are not 
sufficient as stand-alone analyses for determining potency of a 
sensitizer but that QSAR analysis could be used in a weight-of-evidence 
approach.
    The OECD Council Act relating to the Mutual Acceptance of Data 
(MAD), which was agreed to by all OECD member countries, established 
that safety data developed in one member country will be accepted for 
use by the relevant registration authorities in assessing the chemical 
or product in another OECD country (i.e., the data do not have to be 
generated a second time for the purposes of safety assessment), under 
the assurance that the data were developed in compliance with the 
Principles of Good Laboratory Practice. Therefore, if a manufacturer 
submitted QSAR data to the Commission when the Commission was 
determining whether a substance is a strong sensitizer, the Commission 
would take the QSAR data into consideration. However, this QSAR data 
would not take precedence over high-quality human and animal data. The 
Commission believes that modifying the proposed definition in response 
to this comment is not warranted.

Ordering of Factors To Be Considered in Determining Whether a Substance 
Is a Strong Sensitizer

    Comment: One commenter suggested revising the order of the factors 
that would be taken into consideration to determine whether a substance 
is a ``strong'' sensitizer and including a reference in that paragraph 
to unranked data that appears elsewhere in the proposed definition. The 
commenter requests: (1) Shifting the order of factors as they appear in 
the paragraph listing the factors to be considered in determining 
whether a sensitizer is ``strong''--for example moving ``well-conducted 
animal studies'' to the end of the list; (2) moving two of the unranked 
factors listed in the proposed supplemental definition (quantitative 
structure-activity relationship information and bioavailability data) 
into the list of ranked factors as the third and fourth priority 
position; and (3) separating existing versus new in vitro and in vivo 
studies into different factor categories.

[[Page 8828]]

    Response: CPSC based the order of ranked data criteria in the 
proposed definition on extensive input from the international panel of 
scientific experts from academia, industry, and the federal government. 
We concurred with the panelists' suggestion to rank and list the 
qualifying factors in order of importance in the final rule definition, 
instead of ``any or all,'' which is how the factors appear in the 1986 
supplemental definition.
    The Commission believes that the ranked list of criteria for 
determining whether a substance or product containing a substance is a 
``strong'' sensitizer should remain as stated in the proposed 
definition but that the reference to unranked factors, such as 
quantitative structure-activity relationship information, in silico 
data and bioavailability data, should be moved to the end of the list 
of ranked factors so that the order is more logical. The list of 
criteria reflects Commission policy that human data take precedence 
over animal data and takes into consideration the value and relevance 
that the particular data would provide in making a determination of 
sensitizing strength, and therefore, the potential to cause 
hypersensitivity. The criteria list is consistent with the CPSC Animal 
Testing Policy, the FHSA Chronic Hazard Guidelines, and Commission 
policy that strongly encourage the use of scientifically validated 
alternatives to animal testing and the use of existing information, 
including expert opinion, prior human experience, and prior animal 
testing results.

Consistency of Order of Factors Listed Throughout the Rule

    Comment: One commenter pointed out that the factors to be 
considered in determining whether a substance has a ``significant 
potential for causing hypersensitivity'' were not listed in the same 
order when listed as factors to be considered in determining whether a 
substance is a ``strong'' sensitizer. The commenter requested that the 
Commission be consistent when listing the types of data in these two 
paragraphs.
    Response: We agree that the order of factors should be consistent 
in these paragraphs. Therefore, we have modified the proposed 
definition by: (1) moving ``chemical or functional properties of the 
substance'' to the end of the last sentence in the first paragraph of 
section (ii); and (2) in the same sentence reversing the positions of 
in vitro and in vivo.

Use of Existing Animal Testing Data

    Comment: One commenter recommended that we specify that existing 
animal testing data be submitted to the CPSC for consideration in 
making a strong sensitizer determination before additional animal 
testing data is generated.
    Response: As stated in the CPSC Animal Testing Policy, codified at 
16 CFR 1500.232, neither the FHSA, nor the regulations issued under the 
FHSA, require animal testing to determine whether a hazard exists. The 
Commission's regulations under the FHSA concerning toxicity and 
irritancy allow the use of animal tests to determine the presence of 
the hazard when human data or existing animal data are not available. 
However, the Commission's policy encourages manufacturers subject to 
the FHSA to use existing alternatives to animal testing wherever 
possible; supports limiting animal testing to a minimum number of 
animals; and advocates measures that eliminate or reduce the pain or 
discomfort to animals that can be associated with such tests. The 
Commission's animal testing policy encourages manufacturers of products 
subject to the FHSA to use existing alternatives to animal testing, 
whenever possible, such as: prior human experience (e.g., published 
case studies); in vitro or in silico test methods that have been 
approved by the Commission; literature resources containing the results 
of prior animal testing or limited human tests; and expert opinion. We 
believe that the animal testing policy codified at 16 CFR 1500.232, 
sufficiently communicates the preference for alternatives to animal 
testing, whenever possible, including the submission of relevant 
existing data resulting from prior animal testing.

Consideration of in Vitro Studies in Making Strong Sensitizer 
Determinations

    Comment: One commenter asked why in vitro studies were added to the 
list of factors to consider in determining whether a substance is a 
strong sensitizer when such studies are not validated to determine 
potency. Another commenter requested that data from well-conducted in 
vitro assays be considered by the Commission in making this 
determination.
    Response: The 1986 supplemental definition and the final rule 
definition both list in vitro data as a factor to be considered in 
determining whether a substance is a strong sensitizer. We agree that 
currently, there are no validated in vitro assays for sensitizer 
potency determination. However, a large number of in vitro assays are 
in development, undergoing validation, or have completed validation for 
the determination of sensitization. The European Union Reference 
Laboratory for Alternatives to Animal Testing (EURL-ECVAM) completed 
validation of an in vitro assay and an in chemico assay this year. 
EURL-ECVAM recommended that neither assay could be used as a stand-
alone test; although EURL-ECVAM determined that the assays could be 
included in a weight-of-evidence approach or integrated testing 
strategy. Although the assays have some limitations, EURL-ECVAM 
concluded that with further work, these assays might be able to 
contribute to the assessment of sensitizer potency. As stated in the 
strong sensitizer guidance document, the CPSC would follow a weight-of-
evidence approach, using all available validated tools (including both 
positive and negative data), in determining whether a substance is a 
strong sensitizer.

Consideration of Reports of Consumer Incidents

    Comment: One commenter recommended including in the list of factors 
to be considered in determining whether a substance is a strong 
sensitizer, the CPSC's and manufacturers' records of incidents of 
consumer hypersensitivity to a substance or product containing a 
substance.
    Response: We agree that incident reports are an important 
consideration in determining a substance's ability to cause 
hypersensitivity. The final rule definition lists ``case histories'' as 
information that the Commission may consider in determining whether a 
substance has a significant potential for causing hypersensitivity. The 
term ``case histories'' includes reports of incidents of consumer 
hypersensitivity to a substance or product containing the substance 
that are received by manufacturers or the CPSC. Commission staff will 
consider revising the Strong Sensitizer Guidance document to provide 
additional clarification regarding the types and sources of incident 
reports that CPSC should consider when determining whether a substance 
is a strong sensitizer.

Description of ``Clinically Important Reaction''

    Comment: The proposed definition provides that in determining 
whether a substance is a strong sensitizer, the Commission must 
consider the severity of the reaction to the substance and only 
designate substances as strong

[[Page 8829]]

sensitizers that cause a ``clinically important reaction.'' The 
proposed definition includes a list of four potential reactions to 
strong sensitizer exposure that would be characterized as ``clinically 
important'' or manifestations of ``substantial illness.'' One of the 
clinically important reactions listed in the proposed definition is 
``substantial physical discomfort or distress.'' One commenter noted 
that ``discomfort and distress are actually perceptual (mental), 
although they may be caused by various agents (e.g., physical, chemical 
agent, biological).'' The commenter suggested replacing the phrase 
``substantial physical discomfort and distress'' with the phrase 
``physiological stress resulting in discomfort or distress.''
    Response: We agree that the phrase ``substantial physical 
discomfort or distress'' may not be clear, but we believe that 
``physiological stress resulting in discomfort or distress,'' as 
suggested by the commenter, may also be too vague. We have replaced 
``substantial physical discomfort or distress'' with ``substantial 
physiological effects, such as discomfort and distress,'' as a factor 
to be considered in determining whether a strong sensitizer produces 
``substantial illness.'' We believe that this phrase reflects better a 
scenario such as a systemic allergic contact dermatitis rash.

Meaning of ``Chronic Morbidity''

    Comment: One commenter asked whether the reference to ``chronic 
morbidity'' as a factor in determining whether a strong sensitizer 
produces ``substantial illness'' was associated with a specific length 
of time, such as 90 days.
    Response: The proposed definition includes a list of four potential 
reactions to strong sensitizer exposure that would be characterized as 
``clinically important'' or manifestations of ``substantial illness.'' 
One of the clinically important reactions listed in the proposed 
definition is ``chronic morbidity.'' The Commission does not view the 
use of the term ``chronic'' as referring to a specific length of time. 
Under the FHSA Chronic Hazard Guidelines (16 CFR 1500.135), which are 
broad guidelines containing a number of assumptions, methodologies, and 
procedures for determining chronic hazard and risk, the Commission does 
not set a length of time for ``chronic,'' but instead, the Commission 
leaves the determination open to expert judgment. We have replaced the 
phrase ``chronic morbidity'' with ``persistent morbidity'' in the final 
rule definition to clarify that a ``clinically important reaction'' is 
a substantial illness that occurs over an extended period of time.

Addition of ``Mortality'' to ``Substantial Illness'' Factors

    Comment: One commenter suggested that ``mortality'' be added to the 
list of factors to be considered in determining whether a strong 
sensitizer produces substantial illness.
    Response: Mortality (i.e., death) is not an illness but is a 
distinct endpoint that in rare cases could result from substantial 
uncontrolled anaphylaxis. We have revised the definition to include: 
``or in rare cases, mortality'' at the end of the section that lists 
the types of reactions to substances that may be considered 
``substantial illness.''

Removal of Oil of Bergamot From List of Strong Sensitizer Substances

    Comment: One commenter requested that oil of bergamot (and products 
containing 2 percent or more of oil of bergamot) be removed from the 
list of ``strong sensitizer'' substances.
    Response: Oil of bergamot is a phototoxin that FDA listed as a 
``strong sensitizer'' (the list appears in 16 CFR 1500.13). The current 
rulemaking proceeding only addresses revisions to the supplemental 
definition of ``strong sensitizer.'' To make any changes to the 
existing list of substances currently considered to be strong 
sensitizers, the Commission would need to conduct a separate 
proceeding.

C. Revisions to the Strong Sensitizer Supplemental Definition

    As discussed in Section B, above, the comments received in response 
to the NPR generally supported the Commission's replacement of the 1986 
supplemental definition of ``strong sensitizer'' with the proposed 
definition. However, several commenters recommended additional changes 
that we have determined should be incorporated into the supplemental 
definition of strong sensitizer. Below, we discuss the differences 
between the 1986 supplemental definition and the proposed definition, 
along with the changes we have made to the proposed definition, based 
on comments and that have been incorporated into the final rule.

1. Definition of ``Sensitizer'' (Sec.  1500.3(c)(5)(i))

    The 1986 supplemental definition specified that a ``sensitizer'' 
will ``induce an immunologically-mediated (allergic) response, 
including allergic photosensitivity,'' that will become evident upon 
reexposure to the same substance, or occasionally, on first exposure, 
by virtue of active sensitization.
    The final rule reflects the traditional definition for 
``sensitization''; sensitization is a multi-stage immune-mediated 
process that occurs over a period of time. Replacing the phrase 
``immunologically-mediated (allergic) response'' with 
``immunologically-mediated hypersensitivity,'' captures those 
substances that sensitize through atypical mechanisms, rather than by 
inducing an obvious ``immunologically-mediated response.'' The final 
rule also eliminates the last sentence of the current definition based 
on concerns that the sentence could be misinterpreted to include 
substances that cause an irritant response only \1\ (the response that 
is noted after the first exposure to a substance is more frequently an 
irritant response and not an allergic response). Typically, allergic 
responses are the result of a two-step process: (1) induction 
(sensitization), which requires sufficient or cumulative exposure to 
induce an immune response with few or no symptoms; and (2) elicitation 
when an individual who has been sensitized demonstrates symptoms upon 
subsequent exposures. The final rule includes the phrase ``variable 
period of exposure'' to reflect the latency period that is a 
characteristic in the development of sensitization. This section of the 
final rule is the same as proposed.
---------------------------------------------------------------------------

    \1\ An ``irritant response'' is a nonimmune mediated response 
and one that results from direct injury to the tissue. An irritant 
is any agent that is capable of producing cell damage in any 
individual if applied for sufficient time and concentration.
---------------------------------------------------------------------------

2. Determination of Significant Potential for Causing Hypersensitivity 
(Sec.  500.3(c)(5)((ii))

    The statutory definition of ``strong sensitizer'' requires that, 
before designating a substance as a strong sensitizer, the Commission 
``upon consideration of the frequency of occurrence and severity of 
reaction, shall find that the substance has a significant potential for 
causing hypersensitivity.'' 15 U.S.C. 1261(k).
    As discussed in the NPR, the proposed definition added qualifiers 
for susceptibility profiles--genetics, age, gender, and atopic status-- 
to the information and data listed in the 1986 supplemental definition 
that may be considered in determining whether a substance has a 
significant potential for causing hypersensitivity. These 
characteristics are well-known modifiers in the development and 
exacerbation of allergic responses to chemical sensitizers. In response 
to a

[[Page 8830]]

comment, for the final rule, we have reordered the list as it appeared 
in the proposed definition so that the final definition presents the 
factors to be considered in determining whether a substance has a 
significant potential for causing hypersensitivity. This represents the 
same order as the factors to be considered in determining whether a 
substance is a ``strong'' sensitizer. This reordering results in 
``chemical or functional properties of the substance'' becoming the 
last category on the list, and the references to in vitro and in vivo 
experimental studies are reversed.
    As discussed in the NPR, the proposed definition also replaced the 
term ``normal'' with ``non-sensitized,'' which describes more 
accurately the general control population. This remains the same in the 
final rule.
    As discussed in the NPR, the proposed definition incorporated the 
factors to be considered in determining whether a substance is a 
``strong'' sensitizer into the subsection explaining ``significant 
potential for causing hypersensitivity.'' The 1986 supplemental 
definition of ``strong sensitizer'' contains a separate subsection that 
sets forth factors that should be considered in determining the 
strength of a sensitizer. (16 CFR 1500.3(c)(5)(ii)). This section of 
the 1986 supplemental definition includes several factors that are 
subjective rather than quantitative (i.e., physical discomfort, 
distress, hardship) and allows for risk assessment considerations in 
connection with an analysis that should only be a hazard 
characterization step.
    As discussed in the NPR, the proposed definition eliminated the 
``quantitative or qualitative risk assessment factor. '' We believe 
this terminology is confusing because the language places a risk 
assessment step within the hazard identification step of the process of 
determining whether a product containing a strong sensitizer is a 
hazardous substance that requires labeling. The NPR proposed definition 
remains the same in the final rule, except for the reordering of 
certain factors in response to a comment.
    As discussed in the NPR, the proposed definition makes clear that a 
weight-of-the-evidence approach is to be used in determining the 
strength of a sensitizer because of the imprecise nature of some of the 
current factors and the potential lack of information or data available 
to permit useful consideration of certain factors. Rather than allow an 
``any or all'' approach to the factors that would be considered by the 
Commission in determining whether a sensitizer is strong, the revision 
ranks data sources in order of importance following the FHSA preference 
for human data over animal data and takes into consideration the value 
and relevance that certain data would provide in evaluating the 
potential of a substance to cause hypersensitivity. For example, the 
proposed definition expressed a preference for general population 
epidemiological studies over occupational studies because the degree of 
sensitization in the workplace is likely to be greater than that of the 
general population, due to greater exposure (both in time and 
concentration) to the sensitizing agent. The ranking of data sources 
remains the same in the final rule.
    As discussed in the NPR, the proposed definition listed additional 
factors that the Commission can consider in determining a substance's 
sensitizing potential, for which validated methods currently do not 
exist but are in development, such as: Quantitative Structure-Activity 
Relationships (QSARs), and in silico \2\ data, along with the caveat 
that using these techniques would be in addition to consideration of 
human and animal data. We have revised the definition in the final rule 
to reposition these factors from the end of Section 1500.3(c)(5)(ii) to 
follow immediately the listing of ranked factors that are to be 
considered in determining whether a substance is a ``strong'' 
sensitizer.
---------------------------------------------------------------------------

    \2\ QSARs are mathematical models that relate a quantitative 
measure of chemical structure to biological activity. In silico data 
is a computational approach using sophisticated computer models for 
the determination of a sensitizing potential. Both of these 
approaches are evolving methodologies that have not yet been 
validated, but are being pursued as testing options that would 
reduce the numbers of expensive laboratory and animal experiments 
being carried out.
---------------------------------------------------------------------------

    As discussed in the NPR, the proposed definition provided that for 
a substance to be considered a ``strong'' sensitizer, the substance 
must be found to produce a ``clinically important reaction,'' which is 
defined as a reaction with a significant impact on the quality of life. 
The Commission has revised the proposed definition in response to a 
comment to replace ``substantial physical effects'' with ``substantial 
physiological effects'' as a factor to be considered in determining 
whether a strong sensitizer produces ``substantial illness''; to 
replace ``chronic morbidity'' with ``persistent morbidity''; and to add 
``or in rare cases, mortality'' to the end of section 1500.3(c)(5)(ii). 
The change from ``physical'' to ``physiological'' is intended to 
describe more accurately and broadly the body's response to exposure to 
a substance that could rise to the level of a clinically important 
reaction. The change from ``chronic'' to ``persistent,'' also made in 
response to a comment, is intended to convey more clearly that a 
substantial illness may be one that endures for an extended period of 
time.
    As discussed in the NPR, the proposed definition also directed the 
Commission to consider the location of the hypersensitivity response, 
such as the face, hands, and feet, and the persistence of clinical 
manifestations in determining whether the substance produces a 
``clinically important reaction.'' This aspect of the NPR remains the 
same in the final rule.

3. Definition of Normal Living Tissue (Sec.  1500.3(c)(5)(iii))

    The statutory definition of ``strong sensitizer'' specifies that a 
strong sensitizer is a substance that will cause hypersensitivity on 
``normal living tissue.'' The 1986 supplemental definition identifies 
skin and other organ systems, such as the respiratory or 
gastrointestinal tract, as types of ``normal living tissue'' in which 
the allergic hypersensitivity reaction can occur. The proposed 
definition adds a specific reference to mucous membranes, such as 
ocular and oral systems, as additional types of normal living tissue 
upon which a substance can cause a hypersensitivity that warrants a 
determination that a substance is a ``strong sensitizer.'' This remains 
the same in the final rule.

D. Staff Guidance and Notice of Availability

    Commission staff developed a guidance document that is intended to 
clarify the ``strong sensitizer'' definition and assist manufacturers 
in understanding how CPSC staff would assess whether a substance and/or 
product containing that substance should be considered a ``strong 
sensitizer.'' A Notice of Availability was published in the Federal 
Register on March 12, 2013 (78 FR 15710), which provided a link to the 
location on the Commission's Web site where the staff guidance document 
can be found. Several commenters included questions and observations 
regarding the guidance document in their submissions addressing the 
proposed revision to the definition of ``strong sensitizer.'' 
Commission staff will review these comments, and where appropriate, 
will revise the guidance document.

E. Impact on Small Businesses

    The Commission certifies that this rule will not a have a 
significant impact on a substantial number of small entities

[[Page 8831]]

under section 605(b) of the Regulatory Flexibility Act (RFA), 5 U.S.C. 
605(b). For the NPR, the Commission's Directorate for Economic Analysis 
prepared an assessment of the impact of the proposed definition of 
``strong sensitizer.'' That assessment found that there would be little 
or no effect on small businesses and other entities because the 
amendment, which simply modifies the existing supplemental definition 
of ``strong sensitizer,'' will not result in compliance actions. 
Products will not need to be modified to comply with the revised 
supplemental definition, nor will the revised supplemental definition 
impose any additional testing or recordkeeping burdens. The obligation 
to label a product as a strong sensitizer and any costs associated with 
that obligation will not arise until the Commission has designated a 
particular substance contained in the product as a strong sensitizer, 
which would occur only in connection with a separate process. 
Thereafter, we would assess the potential small business impact of 
designating the particular substance as a strong sensitizer. Whether 
the final rule would impose any indirect burden on small businesses or 
other entities is unknown because the impact of the changes to the 
supplemental definition of strong sensitizer on future strong 
sensitizer designation proceedings is not known. The Commission did not 
receive any comments concerning the impact the rule would have on small 
businesses and is not aware of any information that would alter the 
assessment stated in the NPR.

F. Environmental Considerations

    Generally, CPSC rules are considered to ``have little or no 
potential for affecting the human environment,'' and environmental 
assessments and environmental impact statements are not usually 
prepared for these rules (see 16 CFR 1021.5(c)(1)). The Commission does 
not expect the rule to have any adverse impact on the environment under 
this categorical exclusion.

G. Executive Orders

    According to Executive Order 12988 (February 5, 1996), agencies 
must state in clear language the preemptive effect, if any, of new 
regulations. Section 18 of the FHSA addresses the preemptive effect of 
certain rules issued under the FHSA. 15 U.S.C. 1261n. Because this 
rulemaking would revise a regulatory definition, rather than issue a 
labeling or banning requirement, section 18 of the FHSA does not 
provide for the rule to have preemptive effect.

H. Paperwork Reduction Act

    This rule would not impose any information collection requirements. 
Accordingly, this rule is not subject to the Paperwork Reduction Act, 
44 U.S.C. 3501-3520.

I. Effective Date

    The Administrative Procedure Act generally requires that a 
substantive rule be published not less than 30 days before its 
effective date, unless the agency finds, for good cause shown, that a 
lesser time period is required. 5 U.S.C. 553(d)(3). The final rule will 
take effect March 17, 2014.

List of Subjects in 16 CFR Part 1500

    Consumer protection, Hazardous substances, Imports, Infants and 
children, Labeling, Law enforcement, Reporting and recordkeeping 
requirements, and Toys.

    Accordingly, 16 CFR part 1500 is amended as follows:

PART 1500--[AMENDED]

0
1. The authority citation for part 1500 continues to read as follows:

    Authority: 15 U.S.C. 1261-1278.


0
2. Revise paragraph (c)(5) of Sec.  1500.3 to read as follows:


Sec.  1500.3  Definitions

* * * * *
    (c) * * *
    (5) The definition of strong sensitizer in section 2(k) of the 
Federal Hazardous Substances Act (restated in paragraph (b)(9) of this 
section) is supplemented by the following definitions:
    (i) Sensitizer. A sensitizer is a substance that is capable of 
inducing a state of immunologically mediated hypersensitivity 
(including allergic photosensitivity) following a variable period of 
exposure to that substance. Hypersensitivity to a substance will become 
evident by an allergic reaction elicited upon reexposure to the same 
substance.
    (ii) Significant potential for causing hypersensitivity. (A) Before 
designating any substance a ``strong sensitizer,'' the Commission shall 
find that the substance has significant potential for causing 
hypersensitivity. Significant potential for causing hypersensitivity is 
a relative determination that must be made separately for each 
substance. The determination may be based on documented medical 
evidence of hypersensitivity reactions upon subsequent exposure to the 
same substance obtained from epidemiological surveys or case histories; 
controlled in vivo or in vitro experimental studies; susceptibility 
profiles (e.g., genetics, age, gender, atopic status) in non-sensitized 
or allergic subjects; and chemical or functional properties of the 
substance.
    (B) In determining whether a substance is a ``strong'' sensitizer, 
the Commission shall consider the available data for a number of 
factors, following a weight-of-evidence approach. The following factors 
(if available), ranked in descending order of importance, should be 
considered: well-conducted clinical and diagnostic studies, 
epidemiological studies, with a preference for general population 
studies over occupational studies, well-conducted animal studies, well-
conducted in vitro test studies, cross-reactivity data, and case 
histories.
    (C) Additional consideration may be given to Quantitative 
Structure-Activity Relationships (QSARs), in silico data, specific 
human sensitization threshold values, other data on potency and 
sensitizer bioavailability, if data are available and the methods 
validated. Bioavailability is the dose of the allergen available to 
interact with a tissue. Bioavailability is a reflection of how well the 
skin or another organ can absorb the allergen and the actual 
penetrating ability of the allergen, including factors such as size and 
composition of the chemical.
    (D) Criteria for a ``well-conducted'' study would include: 
validated outcomes, relevant dosing, route of administration, and use 
of appropriate controls. Studies should be carried out according to 
national and/or international test guidelines and according to good 
laboratory practice (GLP), compliance with good clinical practice 
(GCP), and good epidemiological practice (GEP).
    (E) Before the Commission designates any substance as a ``strong'' 
sensitizer, frequency of occurrence and range of severity of reactions 
in exposed subpopulations having average or high susceptibility will be 
considered. The minimal severity of a reaction for the purpose of 
designating a material as a ``strong sensitizer'' is a clinically 
important reaction. A clinically important reaction would be considered 
one with a significant impact on quality of life. Consideration should 
be given to the location of the hypersensitivity response, such as the 
face, hands, and feet as well as persistence of clinical 
manifestations. For example, strong sensitizers may produce substantial 
illness, including any or all of the following: substantial 
physiological effects, such as discomfort and distress, substantial 
hardship, functional or structural impairment, persistent morbidity, or 
in rare cases, mortality.

[[Page 8832]]

    (iii) Normal living tissue. The allergic hypersensitivity reaction 
occurs in normal living tissues, including the skin, mucous membranes 
(e.g., ocular, oral), and other organ systems, such as the respiratory 
tract and gastrointestinal tract, either singularly or in combination, 
following sensitization by contact, ingestion, or inhalation.
* * * * *

    Dated: February 11, 2014.
Todd A. Stevenson,
Secretary, U.S. Consumer Product Safety Commission.
[FR Doc. 2014-03260 Filed 2-13-14; 8:45 am]
BILLING CODE 6355-01-P