[Federal Register Volume 77, Number 211 (Wednesday, October 31, 2012)]
[Rules and Regulations]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-26523]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Calcium Gluconate; Exemption From the Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of calcium gluconate when used as an inert
ingredient (sequestrant) in pesticide formulations applied to growing
crops. ISK Biosciences Corporation submitted a petition to EPA under
the Federal Food, Drug, and Cosmetic Act (FFDCA), requesting
establishment of an exemption from the requirement of a tolerance. This
regulation eliminates the need to establish a maximum permissible level
for residues of calcium gluconate.
DATES: This regulation is effective October 31, 2012. Objections and
requests for hearings must be received on or before December 31, 2012,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: The docket for this action, identified by docket
identification (ID) number EPA-HQ-OPP-2012-0131, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory
Public Docket (OPP Docket) in the Environmental Protection Agency
Docket Center (EPA/DC), EPA West Bldg., Rm. 3334, 1301 Constitution
Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open
from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal
holidays. The telephone number for the Public Reading Room is (202)
566-1744, and the telephone number for the OPP Docket is (703) 305-
5805. Please review the visitor instructions and additional information
about the docket available at http://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT: Roger Chesser, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone
number: (703) 347-8516; email address: email@example.com.
I. General Information
A. Does this action apply to me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
The following list of North American Industrial Classification System
(NAICS) codes is not intended to be exhaustive, but rather provides a
guide to help readers determine whether this document applies to them.
Potentially affected entities may include:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
B. How can I get electronic access to other related information?
You may access a frequently updated electronic version of 40 CFR
part 180 through the Government Printing Office's e-CFR site at http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
C. How can I file an objection or hearing request?
Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an
objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2012-0131 in the subject line on the first
page of your submission. All objections and requests for a hearing must
be in writing, and must be received by the Hearing Clerk on or before
December 31, 2012. Addresses for mail and hand delivery of objections
and hearing requests are provided in 40 CFR 178.25(b).
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing (excluding any CBI) for inclusion in the public docket.
Information not marked confidential pursuant to 40 CFR part 2 may be
disclosed publicly by EPA without prior notice. Submit the non-CBI copy
of your objection or hearing request, identified by docket ID number
EPA-HQ-OPP-2012-0131, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider to be Confidential Business
Information (CBI) or other information whose disclosure is restricted
Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC
Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at http://www.epa.gov/dockets/contacts.htm.
Additional instructions on commenting or visiting the docket, along
with more information about dockets generally, is available at http://www.epa.gov/dockets.
II. Petition for Exemption
In the Federal Register of May 2, 2012 (77 FR 25957) (FRL-9346-1),
EPA issued a notice pursuant to FFDCA section 408, 21 U.S.C. 346a,
announcing the filing of a pesticide petition (PP 1E7900) by ISK
Biosciences Corporation, 7470 Auburn Road, Suite A, Concord, OH 44077.
The petition requested that 40 CFR 180.920 be amended by establishing
an exemption from the requirement of a tolerance for residues of
calcium gluconate (CAS Reg. No. 299-28-5) when used as an inert
ingredient (sequestrant) in pesticide formulations applied to growing
crops. That notice referenced a summary of the petition prepared by ISK
Biosciences Corporation, the petitioner, which is available in the
docket, http://www.regulations.gov. There were no comments received in
response to the notice of filing.
III. Inert Ingredient Definition
Inert ingredients are all ingredients that are not active
ingredients as defined in 40 CFR 153.125 and include, but are not
limited to, the following types of ingredients (except when they have a
pesticidal efficacy of their own): Solvents such as alcohols and
hydrocarbons; surfactants such as polyoxyethylene polymers and fatty
acids; carriers such as clay and diatomaceous earth; thickeners such as
carrageenan and modified cellulose; wetting, spreading, and dispersing
agents; propellants in aerosol dispensers; microencapsulating agents;
and emulsifiers. The term ``inert'' is not intended to imply
nontoxicity; the ingredient may or may not be chemically active.
Generally, EPA has exempted inert ingredients from the requirement of a
tolerance based on the low toxicity of the individual inert
IV. Aggregate Risk Assessment and Determination of Safety
Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an
exemption from the requirement for a tolerance (the legal limit for a
pesticide chemical residue in or on a food) only if EPA determines that
the tolerance is ``safe.'' Section 408(b)(2)(A)(ii) of FFDCA defines
``safe'' to mean that ``there is a reasonable certainty that no harm
will result from aggregate exposure to the pesticide chemical residue,
including all anticipated dietary exposures and all other exposures for
which there is reliable information.'' This includes exposure through
drinking water and in residential settings, but does not include
occupational exposure. Section 408(b)(2)(C) of FFDCA requires EPA to
give special consideration to exposure of infants and children to the
pesticide chemical residue in establishing a tolerance and to ``ensure
that there is a reasonable certainty that no harm will result to
infants and children from aggregate exposure to the pesticide chemical
residue * * *.''
EPA establishes exemptions from the requirement of a tolerance only
in those cases where it can be clearly demonstrated that the risks from
aggregate exposure to pesticide chemical residues under reasonably
foreseeable circumstances will pose no appreciable risks to human
health. In order to determine the risks from aggregate exposure to
pesticide inert ingredients, the Agency considers the toxicity of the
inert in conjunction with possible exposure to residues of the inert
ingredient through food, drinking water, and through other exposures
that occur as a result of pesticide use in residential settings. If EPA
is able to determine that a finite tolerance is not necessary to ensure
that there is a reasonable certainty that no harm will result from
aggregate exposure to the inert ingredient, an exemption from the
requirement of a tolerance may be established.
Consistent with FFDCA section 408(c)(2)(A), and the factors
specified in FFDCA section 408(c)(2)(B), EPA has reviewed the available
scientific data and other relevant information in support of this
action. EPA has sufficient data to assess the hazards of and to make a
determination on aggregate exposure for calcium gluconate including
exposure resulting from the exemption established by this action. EPA's
assessment of exposures and risks associated with calcium gluconate
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered their
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. Specific information on the studies received and the nature
of the adverse effects caused by calcium gluconate as well as the no-
observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-
effect-level (LOAEL) from the toxicity studies are discussed in this
Calcium gluconate has been evaluated by the Joint Food and
Agriculture Organization/World Health Organization (FAO/WHO) Expert
Committee on Food Additives (JECFA) which determined that calcium
gluconate was of very low toxicity and allocated an acceptable daily
intake (ADI) of ``not specified''. The JECFA evaluation of calcium
gluconate was part of a group--gluconic acid and its inorganic salts,
that were assessed together based on the fact that the calcium,
magnesium, potassium, and sodium salts of gluconic acid are freely
ionizable and that it was appropriate to allocate ADIs on the basis of
data on their corresponding anion (gluconic acid) as calcium gluconate
dissociates under normal physiologic conditions into gluconic acid. ADI
``not specified'' is used to refer to a food substance of very low
toxicity, which, on the basis of available data (chemical, biochemical,
toxicological, and other) and the total dietary intake of the substance
arising from its use at the levels necessary to achieve the desired
effect and from its acceptable background levels in food, does not, in
the opinion of the Committee, represent a hazard to health. For that
reason, and for reasons stated in individual evaluations, the
establishment of an ADI expressed in numerical form is not necessary.
Calcium gluconate was added to the CODEX General Standard for Food
Additives (GSFA) in 1999.
Toxicological studies considered by JECFA in their evaluation of
gluconic acid and its inorganic salts included acute oral toxicity
studies in the rat, mouse, rabbit and hamster with LD50
values ranging from >2,000 milligrams/kilogram (mg/kg) to 7,850 mg/kg.
Gluconic acid and its inorganic salts have been tested in in vitro
assays (bacterial reverse mutation assays) which demonstrated that
gluconic acid was not mutagenic with or without metabolic activation.
In various subchronic, chronic, reproductive and developmental
studies evaluated using gluconic acid and its inorganic salts by JECFA,
no observable adverse effects were noted at or above limit dose levels
(i.e., > 1,000 mg/kg/day). (JECFA 1999).
B. Toxicological Points of Departure/Levels of Concern
As discussed above, there was no hazard identified in repeat dose
toxicity and reproductive/developmental studies with gluconic acid and
its inorganic salts at the limit dose of 1,000 mg/kg/day to either
parental animals or their offspring. Thus, due to its low potential
hazard and lack of a hazard endpoint, the Agency has determined that a
quantitative risk assessment using safety factors applied to a point of
departure protective of an identified hazard endpoint is not
appropriate for calcium gluconate.
Calcium gluconate was not mutagenic in an in vitro chromosome
aberration test, bacterial gene mutation test. In addition, the
available in vitro and in vivo mutagenicity data with glucuronic acid
and its inorganic salts were negative. Based on the available
information from the mutation studies, it is not anticipated to be
C. Exposure Assessment
No hazard endpoint of concern for calcium gluconate was identified
for the acute and chronic dietary assessment (food and drinking water),
or for the short, intermediate, and long term residential assessments
(via all exposure routes); therefore, acute and chronic dietary and
short-, intermediate-, and long-term residential exposure assessments
were not performed.
D. Cumulative Effects From Substances With a Common Mechanism of
Section 408(b)(2)(D)(v) of FFDCA requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
consider ``available information'' concerning the cumulative effects of
a particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.''
While the toxicity of calcium gluconate is expected to be similar
to the other inorganic salts of gluconic acid as well as gluconic acid
itself, there are no toxicological endpoints of concern identified for
any of these substances. Therefore a cumulative risk assessment was not
For information regarding EPA's efforts to determine which
chemicals have a common mechanism of toxicity and to evaluate the
cumulative effects of such chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.
E. Safety Factor for Infants and Children
Section 408(b)(2)(C) of FFDCA provides that EPA shall apply an
additional tenfold (10X) margin of safety for infants and children in
the case of threshold effects to account for prenatal and postnatal
toxicity and the completeness of the database on toxicity and exposure
unless EPA determines based on reliable data that a different margin of
safety will be safe for infants and children. This additional margin of
safety is commonly referred to as the Food Quality Protection Act
Safety Factor (FQPA SF). In applying this provision, EPA either retains
the default value of 10X, or uses a different additional safety factor
when reliable data available to EPA support the choice of a different
The toxicity database for calcium gluconate identified no hazard
endpoint of concern for calcium gluconate and there is no residual
uncertainty regarding prenatal and/or postnatal toxicity. No acute or
subchronic neurotoxicity studies are available, but there were no
clinical signs of neurotoxicity or any systemic toxicity observed in
the available database at doses up to 1,000 mg/kg/day. No developmental
or reproductive effects were seen in the available studies at doses up
to and including 1,000 mg/kg/day.
Based on this information, there is no concern, at this time, for
increased sensitivity to infants and children to calcium gluconate when
used as an inert ingredient in pesticide formulations applied to
growing crops and a safety factor analysis has not been used to assess
risk. For the same reason, EPA has determined that an additional safety
factor is not needed to protect the safety of infants and children.
F. Aggregate Risks and Determination of Safety
Given the lack of concern for hazard posed by calcium gluconate,
EPA concludes that there are no dietary or aggregate dietary/non-
dietary risks of concern as a result of exposure to calcium gluconate
in food and water, or from residential exposure. Residues of concern
are not anticipated for dietary exposure (food and drinking water) or
for residential exposure from the use of calcium gluconate as an inert
ingredient in pesticide products. As discussed in this unit, EPA
expects aggregate exposure to calcium gluconate to pose no appreciable
dietary risk given that the data show a lack of any systemic toxicity
or adverse developmental/reproductive effects at doses up to 1,000 mg/
Taking into consideration all available information on calcium
gluconate, EPA has determined that there is a reasonable certainty that
no harm to any population subgroup, including infants and children,
will result from aggregate exposure to calcium gluconate under
reasonable foreseeable circumstances. Therefore, the establishment of
an exemption from tolerance under 40 CFR 180.920 for residues of
calcium gluconate (CAS Reg. No. 299-28-5) when used as an inert
ingredient in pesticide formulations applied to growing crops, is safe
under FFDCA section 408.
V. Other Considerations
A. Analytical Enforcement Methodology
An analytical method is not required for enforcement purposes since
the Agency is establishing an exemption from the requirement of a
tolerance without any numerical limitation.
B. International Residue Limits
In making its tolerance decisions, EPA seeks to harmonize U.S.
tolerances with international standards whenever possible, consistent
with U.S. food safety standards and agricultural practices. EPA
considers the international maximum residue limits (MRLs) established
by the Codex Alimentarius Commission (Codex), as required by FFDCA
section 408(b)(4). The Codex Alimentarius is a joint United Nation Food
and Agriculture Organization/World Health Organization food standards
program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level. The CODEX has not
established a MRL for calcium gluconate.
Therefore, an exemption from the requirement of a tolerance is
established under 40 CFR 180.920 for calcium gluconate (CAS Reg. No.
299-28-5) when used as an inert ingredient (sequestrant) in pesticide
formulations applied to growing crops.
VII. Statutory and Executive Order Reviews
This final rule establishes an exemption from the requirement of a
tolerance under FFDCA section 408(d) in response to a petition
submitted to the Agency. The Office of Management and Budget (OMB) has
exempted these types of actions from review under Executive Order
12866, entitled ``Regulatory Planning and Review'' (58 FR 51735,
October 4, 1993). Because this final rule has been exempted from review
under Executive Order 12866, this final rule is not subject to
Executive Order 13211, entitled ``Actions Concerning Regulations That
Significantly Affect Energy Supply, Distribution, or Use'' (66 FR
28355, May 22, 2001) or Executive Order 13045, entitled ``Protection of
Children from Environmental Health Risks and Safety Risks'' (62 FR
19885, April 23, 1997). This final rule does not contain any
information collections subject to OMB approval under the Paperwork
Reduction Act (PRA) (44 U.S.C. 3501 et seq.), nor does it require any
special considerations under Executive Order 12898, entitled ``Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations'' (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under FFDCA section 408(d), such as the tolerance
exemption in this final rule, do not require the issuance of a proposed
rule, the requirements of the Regulatory Flexibility Act (RFA) (5
U.S.C. 601 et seq.), do not apply.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4). As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled ``Federalism'' (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
``Consultation and Coordination with Indian Tribal Governments'' (65 FR
67249, November 9, 2000) do not apply to this final rule. In addition,
this final rule does not impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (2 U.S.C. 1501 et seq.).
This action does not involve any technical standards that would
require Agency consideration of 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).
VIII. Congressional Review Act
Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.),
EPA will submit a report containing this rule and other required
information to the U.S. Senate, the U.S. House of Representatives, and
the Comptroller General of the United States prior to publication of
the rule in the Federal Register. This action is not a ``major rule''
as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
Dated: October 15, 2012.
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. In Sec. 180.920, the table is amended by adding alphabetically the
following entry immediately before the entry for ``Camphor (CAS Reg.
Sec. 180.920 Inert ingredients used pre-harvest; exemptions from the
requirement of a tolerance.
* * * * *
Inert ingredients Limits Uses
* * * * *
Calcium gluconate (CAS Reg. No. 299- ....... Sequestrant.
* * * * *
* * * * *
[FR Doc. 2012-26523 Filed 10-30-12; 8:45 am]
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