[Federal Register Volume 77, Number 211 (Wednesday, October 31, 2012)]
[Rules and Regulations]
[Pages 65824-65827]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-26523]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2012-0131; FRL-9362-4]


Calcium Gluconate; Exemption From the Requirement of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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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 protected].

SUPPLEMENTARY INFORMATION:

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 
by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
20460-0001.
     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.

[[Page 65825]]

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 
ingredients.

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 
follows.

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 
unit.
    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 
carcinogenic.

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.

[[Page 65826]]

D. Cumulative Effects From Substances With a Common Mechanism of 
Toxicity

    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 
performed.
    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 
factor.
    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/
kg/day.
    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.

VI. Conclusions

    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

[[Page 65827]]

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 
recordkeeping requirements.

    Dated: October 15, 2012.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority:  21 U.S.C. 321(q), 346a and 371.

0
2. In Sec.  180.920, the table is amended by adding alphabetically the 
following entry immediately before the entry for ``Camphor (CAS Reg. 
No. 76-22-2).''


Sec.  180.920  Inert ingredients used pre-harvest; exemptions from the 
requirement of a tolerance.

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------------------------------------------------------------------------
          Inert ingredients             Limits            Uses
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                                * * * * *
Calcium gluconate (CAS Reg. No. 299-   .......  Sequestrant.
 28-5).
 
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[FR Doc. 2012-26523 Filed 10-30-12; 8:45 am]
BILLING CODE 6560-50-P