Dimethyl Esters of Glutaric Acid (i.e., Dimethyl Glutarate), Succinic Acid (i.e., Dimethyl Succinate), and Adipic Acid (i.e., Dimethyl Adipate); Exemption From the Requirement of a Tolerance, 582-588 [2013-31582]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 79, Number 3 (Monday, January 6, 2014)]
[Rules and Regulations]
[Pages 582-588]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-31582]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2012-0874; FRL-9904-57]


Dimethyl Esters of Glutaric Acid (i.e., Dimethyl Glutarate), 
Succinic Acid (i.e., Dimethyl Succinate), and Adipic Acid (i.e., 
Dimethyl Adipate); 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 dimethyl esters of glutaric acid (i.e., 
dimethyl glutarate), succinic acid (i.e., dimethyl succinate), and 
adipic acid (i.e., dimethyl adipate), herein referred to as DMEGSA, 
when used as inert ingredients (as solvents/co-solvents) in pesticide 
formulations applied to growing crops and raw agricultural commodities 
after harvest. SciReg, Inc., on behalf of Rhodia, Inc., 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 DMEGSA.

DATES: This regulation is effective January 6, 2014. Objections and 
requests for hearings must be received on or before March 7, 2014, 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-2012-0874, is available at https://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 https://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Lois Rossi, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone 
number: (703) 305-7090; email address: RDFRNotices@epa.gov

SUPPLEMENTARY INFORMATION:

[[Page 583]]

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 https://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl. To access the OCSPP test guidelines referenced in this document 
electronically, please go to https://www.epa.gov/ocspp and select ``Test 
Methods and Guidelines.''

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-2012-0874 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 
March 7, 2014. 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 Confidential Business Information (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-2012-0874, by one of 
the following methods:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be 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 https://www.epa.gov/dockets/contacts.htm.
    Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at https://www.epa.gov/dockets.

II. Petition for Exemption

    In the Federal Register of January, 16, 2013 (78 FR 3377) (FRL-
9375-4), EPA issued a document pursuant to FFDCA section 408, 21 U.S.C. 
346a, announcing the filing of a pesticide petition (IN-10520) by 
SciReg Inc. 12733 Director's Loop, Woodbridge, VA 22192, on behalf of 
Rhodia Inc., CN 7500, 8 Cedar Brook Drive, Cranbury NJ, 08512-7500. The 
petition requested that 40 CFR 180.910 be amended by establishing an 
exemption from the requirement of a tolerance for residues of dimethyl 
esters of glutaric acid (i.e., dimethyl glutarate, CAS Reg. No. 1119-
40-0), succinic acid (i.e., dimethyl succinate, CAS Reg. No. 106-65-0), 
and adipic acid (i.e., dimethyl adipate, CAS Reg. No. 627-93-0) when 
used as an inert ingredient as solvents/co-solvents in pesticide 
formulations applied to growing crops and raw agricultural commodities 
after harvest. That document referenced a summary of the petition 
prepared by on SciReg Inc., on behalf of Rhodia, Inc., the petitioner, 
which is available in the docket, https://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 
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

[[Page 584]]

support of this action. EPA has sufficient data to assess the hazards 
of and to make a determination on aggregate exposure for DMEGSA 
including exposure resulting from the exemption established by this 
action. EPA's assessment of exposures and risks associated with DMEGSA 
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 DMEGSA 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.
    Acute toxicity studies demonstrate low acute oral and dermal 
toxicity (Office of Chemical Safety and Pollution Prevention (OCSPP) 
870.1100 and 870.1200, respectively) with minimal eye irritation (OCSPP 
870.2400) and no dermal irritation (OCSPP 870.2500). Results from a 
dermal sensitization study were negative (OCSPP 870.2600).
    The repeat dose database contains oral, dermal, and inhalation 
studies. Due to their prevalence in commercial paint strippers, 
polishes, and lacquer thinners, the majority of the studies were 
conducted via inhalation, the most expected route of exposure from non-
pesticidal uses.
    Animals in a 14-day oral dietary study showed reduced weight gain 
and food consumption at 1,684 mg/kg/day (LOAEL) but showed no adverse 
effects at 842 mg/kg/day (NOAEL). Animals in a one month oral gavage 
study showed no adverse effects at the limit dose of 1,000 mg/kg/day. 
In addition, a 14-day dermal study was conducted and although mild skin 
irritation was noted in rats at doses equal to and greater than 100 mg/
kg/day, the effects were reversible and no systemic effects were 
observed at any dose tested up to the limit dose of 1,000 mg/kg/day.
    To support the safety finding as it relates to oral exposure, oral 
studies on the metabolites were also evaluated. Available repeat dose 
oral studies on the metabolites include a 13-week study on succinic 
acid, two 90-day studies on glutaric acid and a two year study on 
adipic acid. Succinic acid was shown to cause decreased body weight 
gain in rats at and above 2,500 mg/kg/day. Glutaric acid also caused a 
decrease in body weight gain in both rats and dogs at 1,000 and 750 mg/
kg/day, respectively. Similarly, adipic acid was seen to cause 
decreased body weight gain and food consumption in rats at 2,250 mg/kg/
day. The results of these studies indicate that the metabolites of 
DMEGSA are of low toxicity via the oral route of exposure.
    The majority of the repeat dose and reproductive/developmental 
studies conducted on dibasic esters (DBE, CAS Reg. No. 95481-62-2- a 
chemical mixture of approximately 55-75% dimethyl glutarate, 15-27% 
dimethyl succinate, and 10-25% dimethyl adipate) and/or the individual 
chemicals are via the inhalation route of exposure. The available 
database includes three 90-day inhalation studies in rats, one 
conducted with DMEGSA and two with DBE. In the first study rats were 
exposed to DMS and DMA at doses of 0 or 0.4 mg/L and DMG at doses of 0, 
0.01, 0.05, or 0.4 mg/L. Degeneration of the olfactory epithelium was 
observed for all chemicals at and above 0.05 mg/L with the severity of 
the local effect being dose dependent. Exposed animals also showed 
microscopic alterations in the liver (males) and lung (females). The 
hormonal changes observed in these studies with DMS, DMA, and DMG were: 
An increase in sperm counts (2/3 studies), a decrease in testosterone 
levels (1/3 studies), and a decrease in leutenizing hormone levels (1/3 
studies) in males and a decrease in estradiol levels in females (1/3 
studies). The significance of these findings is unclear because the 
decrease in male hormone levels should result in a decrease in sperm 
counts, yet the opposite effect was observed. The single study showing 
changes in estradiol was not observed in the other two studies. 
Furthermore, there were no functional parameters such as estrous cycle 
and sperm motility or morphology affected. In addition, a reproductive 
study was conducted with DBE and there were no effects on fertility, 
viability of pups at birth, and the ability of the mothers to lactate.
    Two other 90-day rat studies (OCSPP 870.3465), tested DBE and 
again, degeneration of the olfactory epithelium was noted at all doses 
tested (0.02-1.0 mg/L). In both studies decreases in liver weight were 
observed but no histopathological findings were evident. Similarly, 
when rats were exposed to 1 mg/L DBE slight increases in relative heart 
and testes weights in males and a slight decrease in absolute spleen 
weight in females were observed. These slight organ weight changes were 
not accompanied by any histopathological changes and are therefore, 
considered of minimal biological significance. No other significant 
effects were observed.
    Repeat dose inhalation studies have demonstrated the chemicals 
potential to affect the olfactory mucosa in the nasal passage of rats. 
These local effects are believed to be related to the hydrolysis of 
DMEGSA by carboxylesterases located in the nasal/olfactory epithelium 
to the dicarboxylic acid metabolites. These effects on the olfactory 
epithelium are expected to be of much lower impact in humans due to 
major anatomical and physiological differences between rats and humans. 
See Unit VI.B for further discussion.
    Depressed pup weights were observed in a one-generation 
reproduction inhalation toxicity study with DBE at 1.0 mg/L but were 
only seen in the presence of maternal toxicity. Two developmental 
inhalation toxicity studies (OCSPP 870.3700) were conducted, one 
testing DBE on rats and with DMG on rabbits. In both studies no 
developmental effects were observed at doses up to and including 1.0 
mg/L. Similarly, no adverse developmental effects were observed in oral 
studies on the metabolites glutaric acid (rat and rabbit) and adipic 
acid (rat and mice) at doses up to and including 1,300 mg/kg/day.
    An Ames test conducted with DBE was negative; however, a chromosome 
aberration study conducted with DBE was positive at high concentrations 
in the presence of S9 metabolic activation (negative without S9 
activation) in lymphocytes from female donors. This result is not 
consistent with what is known about the hydrolysis products of the 
methyl esters. Methanol is not clastogenic or genotoxic. Glutaric acid, 
succinic acid, and adipic acid are all endogenous and not considered to 
be clastogenic or genotoxic; a chromosome aberration study conducted 
with adipic acid was negative. As such, it is possible that, in the 
presence of S9 metabolic activation, the esters were hydrolyzed and the 
acids released, affecting the pH, making it more acidic. This is known 
to cause false positive effects in cytogenicity assays. Therefore, an 
in vivo genotoxicity assay on somatic cells was performed. A bone 
marrow micronucleus assay was performed in mice following a single 
inhalatory nose-only exposure to DBE for six hours. There were no 
statistically significant differences in the proportion of 
micronucleated polychromatic erythrocytes between mice of all groups 
including controls at any sampling time up to 72 hours following 
exposure up to a very high concentration of 19 mg/L, illustrating the 
absence of clastogenicity

[[Page 585]]

of the test substance in vivo. In addition, a rat micronucleus study 
conducted with DMG was negative.
    No neuropathological changes or effects on the functional 
observation battery parameters were reported in any of the studies. The 
agency does not believe DMEGSA will be neurotoxic. Chronic/
carcinogenicity studies could not be identified for DMEGSA. A DEREK 
evaluation for DMG and DMS was conducted and did not show any special 
alerts. In addition, carcinogenicity studies were conducted with adipic 
acid and monosodium succinate in rats and no carcinogenic effects were 
observed. Therefore, the agency does not expect DMEGSA to be 
carcinogenic in humans.

B. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA 
identifies toxicological points of departure (POD) and levels of 
concern to use in evaluating the risk posed by human exposure to the 
pesticide. For hazards that have a threshold below which there is no 
appreciable risk, the toxicological POD is used as the basis for 
derivation of reference values for risk assessment. PODs are developed 
based on a careful analysis of the doses in each toxicological study to 
determine the dose at which no adverse effects are observed (the NOAEL) 
and the lowest dose at which adverse effects of concern are identified 
(the LOAEL). Uncertainty/safety factors are used in conjunction with 
the POD to calculate a safe exposure level--generally referred to as a 
population-adjusted dose (PAD) or a reference dose (RfD)--and a safe 
margin of exposure (MOE). For non-threshold risks, the Agency assumes 
that any amount of exposure will lead to some degree of risk. Thus, the 
Agency estimates risk in terms of the probability of an occurrence of 
the adverse effect expected in a lifetime. For more information on the 
general principles EPA uses in risk characterization and a complete 
description of the risk assessment process, see https://www.epa.gov/pesticides/factsheets/riskassess.htm.
    Various inhalation studies with DMEGSA show local effects (likely a 
result of irritation at the point of contact in the nasal region) as 
well as some changes in hormone levels that, although consistently 
observed, are not considered to be toxicologically significant. The 
effects on the olfactory epithelium are expected to be of much lower 
impact in humans due to major physiological differences between rats 
and humans (e.g., rats have a larger surface of nasal epithelium and 
different air flow and breathing pattern (e.g., rats are obligate nose 
breathers) and greater carboxylesterase activity in nasal/olfactory 
epithelium than do humans) so the local exposure will be significantly 
lower in humans. In vitro experiments with human nasal tissue 
homogenates suggest that DBE metabolism in human nasal tissue is 100 to 
1000 times less active than rat nasal tissue. Therefore, humans are 
expected to be much less sensitive. In the absence of other systemic 
toxicity along with the expected decrease in sensitivity of humans to 
olfactory responses, EPA concluded that these effects were not 
sufficiently adverse to be used as an endpoint for risk assessment.
    As noted in Unit VI. A. above, exposed animals in repeat dose 
inhalation studies showed microscopic organ changes and hormonal 
changes in studies with DMS, DMA, and DMG. The significance of these 
findings is unclear because for example, the decrease in male hormone 
levels should result in a decrease in sperm counts, yet the opposite 
effect was observed. The single study showing changes in estradiol was 
not observed in the other two studies. Furthermore, there were no 
functional parameters such as estrous cycle and sperm motility or 
morphology affected. In addition, a reproductive study was conducted 
with DBE and there were no effects on fertility, viability of pups at 
birth, and the ability of the mothers to lactate. For these reasons the 
point of departure for the risk assessment for chronic oral routes of 
exposure was from the 14-day oral toxicity study in rats. The NOAEL was 
842 mg/kg/day and the LOAEL was 1684 mg/kg/day based on reduced weight 
gain and food consumption. A 1000 fold uncertainty factor was used for 
the chronic exposure (10X interspecies extrapolation, 10X for 
intraspecies variability and 10X FQPA safety factor)).
    The dermal study did not result in an endpoint of concern. Adverse 
local olfactory effects were observed in inhalation toxicity studies; 
however, due to anatomical and physiological difference between study 
animals and humans, the effects are likely to be less severe in humans 
and subsequently of minimal toxicological concern. No systemic endpoint 
of concern was identified in the available inhalation toxicity studies; 
therefore, quantification of inhalation risk is not necessary.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to DMEGSA, EPA considered exposure under the proposed 
exemption from the requirement of a tolerance. EPA assessed dietary 
exposures from DMEGSA in food as follows:
    Because no acute endpoint of concern was identified, a quantitative 
acute dietary exposure assessment is unnecessary. In conducting the 
chronic dietary exposure assessment using the Dietary Exposure 
Evaluation Model DEEM-FCIDTM, Version 3.16, EPA used food consumption 
information from the U.S. Department of Agriculture's National Health 
and Nutrition Examination Survey, What we eat in America, (NHANES/
WWEIA). This dietary survey was conducted from 2003 to 2008. The Inert 
Dietary Exposure Evaluation Model (I-DEEM) is a highly conservative 
model with the assumption that the residue level of the inert 
ingredient would be no higher than the highest tolerance for a given 
commodity. Implicit in this assumption is that there would be similar 
rates of degradation between the active and inert ingredient (if any) 
and that the concentration of inert ingredient in the scenarios leading 
to these highest of tolerances would be no higher than the 
concentration of the active ingredient. The model assumes 100 percent 
crop treated (PCT) for all crops and that every food eaten by a person 
each day has tolerance-level residues. A complete description of the 
general approach taken to assess inert ingredient risks in the absence 
of residue data is contained in the memorandum entitled ``Alkyl Amines 
Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and 
Drinking Water) Dietary Exposure and Risk Assessments for the Inerts.'' 
(D361707, S. Piper, 2/25/09) and can be found at https://www.regulations.gov in docket ID number EPA-HQ-OPP-2008-0738.
    2. Dietary exposure from drinking water. For the purpose of the 
screening level dietary risk assessment to support this request for an 
exemption from the requirement of a tolerance for DMEGSA, a 
conservative drinking water concentration value of 100 ppb based on 
screening level modeling was used to assess the contribution to 
drinking water for the chronic dietary risk assessments for parent 
compound. These values were directly entered into the dietary exposure 
model.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in this document to refer to non-occupational, non-dietary 
exposure (e.g., textiles (clothing and diapers), carpets, swimming 
pools, and hard surface disinfection on walls, floors, tables).

[[Page 586]]

    The majority of the current pesticidal uses (e.g., use in paints 
and wood products) of DMEGSA are for industrial and commercial 
settings; however, DMEGSA are approved for use in textiles, as paper 
coatings, and in and around homes and landscapes. There are no approved 
antimicrobial uses of DMEGSA. Neither the dermal nor inhalation studies 
resulted in an endpoint of concern; therefore, there was no need to 
quantify dermal or inhalation exposure. Since there is potential for 
use of this chemical in and around homes, residential exposure was 
evaluated using agency approved models to estimate high end post-
application oral exposures to children from treated lawns. The 
residential and aggregate level of concern (LOC) is for margins of 
exposure (MOE) that are less than 1000 and is based on 10X interspecies 
extrapolation, 10X for intraspecies variability, and 10X FQPA safety 
factor.
    4. 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.''
    EPA has not found DMEGSA to share a common mechanism of toxicity 
with any other substances, and DMEGSA does not appear to produce a 
toxic metabolite produced by other substances. For the purposes of this 
tolerance action, therefore, EPA has assumed that DMEGSA does not have 
a common mechanism of toxicity with other substances. 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 https://www.epa.gov/pesticides/cumulative.

D. Safety Factor for Infants and Children

    1. In general. 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 FQPA Safety 
Factor (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.
    2. Prenatal and postnatal sensitivity. No evidence of increased 
susceptibility was seen in the available developmental and reproductive 
toxicity studies for DMEGSA and its metabolites. Depressed pup weights 
were observed in a one-generation reproduction inhalation toxicity 
study with DBE at 1.0 mg/L but were only seen in the presence of 
maternal toxicity. Two developmental inhalation toxicity studies were 
conducted, one testing DBE on rats and with DMG on rabbits. In both 
studies no developmental effects were observed at doses up to and 
including 1.0 mg/L; while maternal toxicity was observed at doses of 
0.3 mg/L and above. Similarly, no adverse developmental effects were 
observed in oral studies on the metabolites glutaric acid (rat and 
rabbit) and adipic acid (rat and mice) at doses up to and including 
1,300 mg/kg/day.
    3. Conclusion. EPA concludes that the FQPA safety factor of 10X for 
DMEGSA should be retained because of the need to extrapolate from a 
subchronic study for a chronic risk assessment. In making this 
determination, EPA considered the following factors:
    i. The toxicity database for DMEGSA and their metabolites includes 
several subchronic and chronic studies, several developmental and 
reproductive toxicity studies, and mutagenicity studies. No chronic 
studies are available on DBEs; however, chronic toxicity studies on 
metabolites are available to characterize long term toxicity potential 
of DBEs.
    ii. Increased incidence of delayed renal papillary development and 
decreased pup weights were observed in reproductive/developmental 
inhalation toxicity studies at 1000 mg/m\3\; however, these effects 
were only observed in the presence of depressed maternal body weight. 
In addition, there were no systemic effects seen in oral studies at 
doses up to and including the limit dose of 1000 mg/kg/day indicating 
no evidence of increased susceptibility.
    iii. There is no indication that DMEGSA are neurotoxic chemicals. 
Although no neurotoxicity studies are available in the database, no 
clinical signs of neurotoxicity were observed in the available 
subchronic and chronic studies. Therefore, there is no need for a 
developmental neurotoxicity study or additional UFs to account for 
neurotoxicity.
    vi. The dietary food exposure assessment utilizes proposed 
tolerance level or higher residues and 100% CT information for all 
commodities. By using these screening-level assessments, chronic 
exposures/risks will not be underestimated.

Based on the absence of reproductive and developmental toxicity for 
DMEGSA in inhalation studies at maternally toxic doses, the high 
developmental NOAEL for glutaric acid, and the lack of neurotoxicity, 
there is no concern for increased sensitivity to infants and children 
to DMEGSA when used as an inert ingredients in pesticide formulations. 
However, due to the lack of a chronic oral toxicity study the 10X FQPA 
safety factor has been retained to protect infants and children.

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic dietary pesticide 
exposures are safe by comparing aggregate exposure estimates to the 
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA 
calculates the lifetime probability of acquiring cancer given the 
estimated aggregate exposure. Short-, intermediate-, and chronic-term 
risks are evaluated by comparing the estimated aggregate food, water, 
and residential exposure to the appropriate PODs to ensure that an 
adequate MOE exists.
    1. Acute risk. An acute aggregate risk assessment takes into 
account acute exposure estimates from dietary consumption of food and 
drinking water. No adverse effect resulting from a single oral exposure 
was identified and no acute dietary endpoint was selected. Therefore, 
DMEGSA is not expected to pose an acute risk.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
DMEGSA from food and water will utilize 83.9% of the cPAD for children 
1-2 years old, the population group receiving the greatest exposure. 
There are no current or proposed residential uses for DMEGSA at this 
time. Based on the explanation in this unit, regarding residential use 
patterns, chronic residential exposure to residues of DMEGSA is not 
expected.
    3. Short-term risk. Short-term aggregate exposure takes into 
account short-term residential exposure plus chronic exposure to food 
and water (considered to be a background exposure level). A short-term 
adverse effect was identified; however, DMEGSA is not currently used as 
an inert ingredient in pesticide products that are registered for any 
use patterns that would result in short-term residential exposure. They 
may, however, be used in the future as an

[[Page 587]]

inert ingredient in pesticide products that are registered for uses 
that could result in short-term residential exposure, and the Agency 
has determined that it is appropriate to aggregate chronic exposure 
through food and water with short-term residential exposures to DMEGSA.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water, 
and residential oral exposures result in aggregate MOEs for children of 
1450 for hand-to-mouth exposure to treated lawns. Because EPA's level 
of concern for DMEGSA is a MOE of 1000 or below, these MOEs are not of 
concern.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account intermediate-term residential exposure plus chronic 
exposure to food and water (considered to be a background exposure 
level).
    An intermediate-term adverse effect was identified; however, DMEGSA 
is not currently used as an inert ingredient in pesticide products that 
are registered for any use patterns that would result in intermediate-
term residential exposure. They may, however, be used in the future 
pesticide products that are registered for uses that could result in 
intermediate-term residential exposure, and the Agency has determined 
that it is appropriate to aggregate chronic exposure through food and 
water with intermediate-term residential oral exposures to DMEGSA.
    Using the exposure assumptions described in this unit for 
intermediate-term exposures, EPA has concluded that the combined 
intermediate-term food, water, and residential exposures result in 
aggregate MOEs for children of 1500 for hand-to-mouth exposure to 
treated lawns. Because EPA's level of concern for DMEGSA is a MOE of 
1000 or below, these MOEs are not of concern.
    5. Aggregate cancer risk for U.S. population. Based on the lack of 
evidence of carcinogenicity in available studies of the metabolites of 
the subject chemicals and a DEREK assessment of DMEGSA which revealed 
no alerts, DMEGSA is not expected to pose a cancer risk to humans.
    6. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population or to infants and children from aggregate 
exposure to DMEGSA residues.

V. Other Considerations

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.

VI. Conclusions

    Therefore, an exemption from the requirement of a tolerance is 
established under 40 CFR 180. 910 for dimethyl glutarate (CAS Reg. No. 
1119-40-0), dimethyl succinate (CAS Reg. No. 106-65-0), and dimethyl 
adipate (CAS Reg. No. 627-93-0) when used as inert ingredients 
(solvent/co-solvent) in pesticide formulations applied to growing crops 
and raw agricultural commodities after harvest.

VII. Statutory and Executive Order Reviews

    This final rule establishes 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 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 
recordkeeping requirements.

    Dated: December 23, 2013.
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.  180.910, alphabetically add the following inert 
ingredient(s) to the table to read as follows:

[[Page 588]]

Sec.  180.910  Inert ingredients used pre- and post-harvest; exemptions 
from the requirement of tolerance.

* * * * *

------------------------------------------------------------------------
       Inert ingredients              Limits                Uses
------------------------------------------------------------------------
 
                              * * * * * * *
Dimethyl adipate (CAS no. 627-  None.............  Solvent/co-solvent
 93-0).
 
                              * * * * * * *
Dimethyl glutarate (CAS no.     None.............  Solvent/co-solvent
 1119-40-0).
 
                              * * * * * * *
Dimethyl succinate (CAS no.     None.............  Solvent/co-solvent
 106-65-0).
 
                              * * * * * * *
------------------------------------------------------------------------

[FR Doc. 2013-31582 Filed 1-3-14; 8:45 am]
BILLING CODE 6560-50-P