[Federal Register Volume 81, Number 155 (Thursday, August 11, 2016)]
[Rules and Regulations]
[Pages 53012-53019]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-19117]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2011-0144; FRL-9944-48]


Aminocyclopyrachlor; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of 
aminocyclopyrachlor in or on milk and livestock commodities imported 
into the United States, which are identified and discussed later in 
this document. E.I. du Pont de Nemours and Company requested these 
tolerances under the

[[Page 53013]]

Federal Food, Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective August 11, 2016. Objections and 
requests for hearings must be received on or before October 11, 2016, 
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-2011-0144, 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), West William Jefferson Clinton 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: Susan Lewis, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; main telephone 
number: (703) 305-7090; 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 EPA's 
tolerance regulations at 40 CFR part 180 through the Government 
Printing Office's e-CFR site at http://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 http://www.epa.gov/test-guidelines-pesticides-and-toxic-substances.

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-2011-0144 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 
October 11, 2016. 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-2011-0144, 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 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.html.
    Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at http://www.epa.gov/dockets.

II. Summary of Petitioned-For Tolerance

    In the Federal Register of Tuesday, March 29, 2011 (76 FR 17376) 
(FRL-8867-4), EPA issued a document pursuant to FFDCA section 
408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide 
petition (PP 0F7817) by E.I. du Pont de Nemours and Company, 1007 
Market Street, Wilmington, DE 19898. The petition requested that 40 CFR 
part 180 be amended by establishing tolerances for residues of the 
herbicide aminocyclopyrachlor, 6-amino-5-chloro-2-cyclopropyl-4-
pyrimidinecarboxylic acid, and aminocyclopyrachlor methyl ester, methyl 
6-amino-5-chloro-2-cyclopropyl-4-pyrimidinecarboxylate, expressed as 
aminocyclopyrachlor, in or on grass, forage at 65 parts per million 
(ppm); grass, hay at 125 ppm; fat (of cattle, goat, horse, and sheep) 
at 0.07 ppm; meat (of cattle, goat, horse, and sheep) at 0.02 ppm; meat 
byproducts, excluding liver (of cattle, goat, horse, and sheep) at 0.4 
ppm; liver (of cattle, goat, horse, and sheep) at 0.06 ppm; and milk at 
0.035 ppm. That document referenced a summary of the petition prepared 
by E.I. du Pont de Nemours and Company, the registrant, which is 
available in the docket, http://www.regulations.gov. There were no 
comments received in response to the notice of filing.
    After issuance of the notice of filing, the registrant revised the 
petition by rescinding the proposed grass commodities and amending the 
purpose of establishing tolerances from domestic to import use (i.e. 
import tolerances).
    Based upon review of the data supporting the petition, EPA has 
lowered the proposed tolerances for milk, meat (of cattle, goat, horse, 
and sheep), and fat (of cattle, goat, horse, and sheep) and changed the 
proposed tolerances from liver and meat byproducts, except liver (of 
cattle, goat, horse, and sheep) to meat byproducts (of cattle, goat, 
horse, and sheep). The reasons for these changes are explained in Unit 
IV.C.

III. Aggregate Risk Assessment and Determination of Safety

    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish 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

[[Page 53014]]

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 . . .''
    Consistent with FFDCA section 408(b)(2)(D), and the factors 
specified in FFDCA section 408(b)(2)(D), 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 aminocyclopyrachlor including 
exposure resulting from the tolerances established by this action. 
EPA's assessment of exposures and risks associated with 
aminocyclopyrachlor follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
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.

Aminocyclopyrachlor

    Aminocyclopyrachlor (parent acid) has low acute toxicity by all 
routes of exposure (oral, dermal, inhalation), does not cause skin 
irritation or skin sensitization, but causes mild eye irritation. There 
are no target organs of toxicity for aminocyclopyrachlor. In the 
subchronic oral toxicity studies in rats, mild systemic toxicity 
effects of decreased body weights, body weight gains, food consumption, 
and food efficiency in both sexes were observed with repeated exposures 
at very high (limit) doses. There was no appreciable increase in the 
severity of these effects with time. The most sensitive species is the 
rat. Subchronic and chronic dietary studies in dogs and mice showed no 
adverse effects at all treatment doses including the limit dose. The 
subchronic dermal toxicity study in rat showed no evidence of toxicity 
at the limit dose. Subchronic inhalation toxicity studies are not 
available; however, based on the results of the acute inhalation 
studies showing low toxicity at twice the limit concentration, the 
likelihood of subchronic toxicity via inhalation route is expected to 
be low.
    In the prenatal developmental toxicity study, there were no adverse 
effects of aminocyclopyrachlor on prenatal development or maternal 
health in rats at all treatment doses including the limit dose. In the 
rabbit study, administration at the limit dose resulted in one 
treatment-related death and two abortions which were considered 
secondary effects to maternal weight losses which occurred over a 
period of 5 to 7 days. No developmental effects were observed in the 
offspring. There were no adverse effects of aminocyclopyrachlor on 
reproduction and fertility in rats at the limit dose. Toxicity in 
parental rats and offspring was limited to decreases in body weights at 
the limit dose.
    Aminocyclopyrachlor is classified as ``Not Likely to be 
Carcinogenic to Humans.'' This classification is based on no treatment-
related tumors seen in male or female rats or mice at doses that were 
adequate to assess carcinogenicity, and no evidence of mutagenicity 
from a full battery of in vitro and in vivo genotoxicity studies. There 
was no evidence of neurotoxicity or immunotoxicity observed in the 
rodent studies up to the limit dose.

Aminocyclopyrachlor-Methyl

    The toxicity database for aminocyclopyrachlor-methyl (ester) via 
the oral route of exposure is bridged with aminocyclopyrachlor (parent 
acid) based on evidence from metabolism studies, acute toxicity 
studies, and repeat-dose toxicity studies with common endpoints. The 
rat metabolism studies showed that aminocyclopyrachlor-methyl rapidly 
metabolizes (within 30 minutes) to aminocyclopyrachlor. A full suite of 
acute toxicity studies conducted with aminocyclopyrachlor and 
aminocyclopyrachlor-methyl resulted in the same toxicity category 
classifications. The subchronic oral toxicity study and the modified 
one-generation reproduction toxicity study in rats conducted with 
aminocyclopyrachlor-methyl showed effects of decreased body weights and 
body weight gains at the limit dose similar to those observed in the 
aminocyclopyrachlor studies. This one-generation reproduction study 
showed no evidence of reproductive, developmental, or neurotoxicity at 
the limit dose. There was no evidence of mutagenicity in the in vitro 
bacterial genotoxicity test conducted with aminocyclopyrachlor-methyl. 
The results of these studies show that aminocyclopyrachlor-methyl 
causes effects similar to aminocyclopyrachlor at the same dose levels. 
Therefore, studies conducted with aminocyclopyrachlor can be used to 
support aminocyclopyrachlor-methyl.

Cyclopropane Carboxylic Acid

    Cyclopropane carboxylic acid (CPCA), also known as IN-V0977, is an 
environmental photolytic degradate of aminocyclopyrachlor present only 
in surface water. CPCA has a different mode of toxic action than 
aminocyclopyrachlor and aminocyclopyrachlor-methyl. Based on extensive 
pre-clinical studies of the anxiolytic drug candidate panadiplon, which 
metabolizes to CPCA after oral administration, the target organ is the 
liver, causing impairment of mitochondrial function by inhibiting the 
beta oxidation of fatty acids, resulting in microvesicular steatosis 
(accumulation of small fat droplets in cells) that is often accompanied 
by liver necrosis and inflammation, decreased hepatic glycogen, and 
decreased blood glucose levels. These effects were observed with acute 
(1 to 3 days) and repeated (up to 14 days) exposures. The most 
sensitive species is the rabbit. Hepatic microvesicular steatosis in 
the rabbit follows a different dose-response than body-weight decreases 
observed with aminocyclopyrachlor and aminocyclopyrachlor-methyl in 
rats, with a 100-fold lower adverse-effect level.
    There are no chronic dietary toxicity studies available to assess 
the carcinogenic potential of CPCA. However, structural-activity 
relationship (SAR) analyses on CPCA and panadiplon indicated no 
structural alerts for genotoxicity or carcinogenicity. Also, there were 
no reports of tumorigenic responses to CPCA or panadiplon in the open 
scientific literature.
    Specific information on the studies received and the nature of the 
adverse effects caused by aminocyclopyrachlor, aminocyclopyrachlor-
methyl, and cyclopropane carboxylic acid, as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in document Aminocyclopyrachlor: Human Health Risk 
Assessment for Section 3, Food Use on Rangeland/Pastures/CRP Acres at 
pages 15-26 in docket ID number EPA-HQ-OPP-2011-0144.

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

[[Page 53015]]

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 http://www.epa.gov/pesticides-science-and-assessing-pesticide-risks/assessing-human-health-risk-pesticides.
    Summaries of the toxicological endpoints for aminocyclopyrachlor 
and cyclopropane carboxylic acid used for human health risk assessment 
are shown in Tables 1 and 2 of this unit.

   Table 1--Summary of Toxicological Doses and Endpoints for Aminocyclopyrachlor for Use in Human Health Risk
                                                   Assessment
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                                    Point of departure
        Exposure/scenario            and  uncertainty/     RfD and PAD for      Study and toxicological effects
                                      safety factors       risk assessment
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Acute dietary (All populations)..           No hazard attributable to a single-exposure was identified.
rrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrr
Chronic dietary (All populations)  NOAEL= 279 mg/kg/day  Chronic RfD = 2.79   Combined Chronic Toxicity/
                                   UFA = 10x...........   mg/kg/day.           Carcinogenicity Rat Study.
                                   UFH = 10x...........  cPAD = 2.79 mg/kg/   LOAEL = 892 (males)/957 (females)
                                   FQPA SF = 1x........   day.                 mg/kg/day based on mild decreases
                                                                               in body weight/body weight gain.
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 Table 2--Summary of Toxicological Doses and Endpoints for Cyclopropane Carboxylic Acid for Use in Human Health
                                                 Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                    Point of departure
        Exposure/scenario            and uncertainty/      RfD and PAD for      Study and toxicological effects
                                      safety factors       risk assessment
----------------------------------------------------------------------------------------------------------------
Acute dietary (All populations)..  LOAEL= 2.55 mg/kg/    Acute RfD = 0.026    Panadiplon Subchronic Oral Rabbit
                                    day CPCA.             mg/kg/day.           Study
                                   UFA = 10x...........  aPAD = 0.0026 mg/kg/ LOAEL = 10 mg/kg/day panadiplon
                                   UFH = 10x...........   day.                 (calculated to 2.55 mg/kg/day
                                   FQPA SF (UFDB, UFL)                         CPCA) based on hepatic steatosis.
                                    = 10x.
Chronic dietary (All populations)  LOAEL= 2.55 mg/kg/    Chronic RfD =        Panadiplon Subchronic Oral Rabbit
                                    day CPCA.             0.0087 mg/kg/day.    Study
                                   UFA = 10x...........  cPAD = 0.00087 mg/   LOAEL = 10 mg/kg/day panadiplon
                                   UFH = 10x...........   kg/day.              (calculated to 2.55 mg/kg/day
                                   FQPA SF (UFDB, UFL,                         CPCA) based on hepatic steatosis.
                                    UFS) = 30x.
----------------------------------------------------------------------------------------------------------------
FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. mg/kg/day =
  milligram/kilogram/day. NOAEL = no-observed-adverse-effect-level. PAD = population adjusted dose (a = acute, c
  = chronic). RfD = reference dose. UF = uncertainty factor. UFA = extrapolation from animal to human
  (interspecies). UFDB = to account for the absence of data or other data deficiency. UFH = potential variation
  in sensitivity among members of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a
  NOAEL. UFS = use of a short-term study for long-term risk assessment.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to aminocyclopyrachlor, EPA considered exposure under the 
petitioned-for tolerances only, as there are no registered food/feed 
uses. CPCA is an environmental photodegradate of aminocyclopyrachlor 
present only in surface water; therefore, any dietary exposure would be 
from drinking water only and is not expected through food or feed. EPA 
assessed dietary exposures from aminocyclopyrachlor in food as follows:
    i. Acute exposure. Quantitative acute dietary exposure and risk 
assessments are performed for a food-use pesticide, if a toxicological 
study has indicated the possibility of an effect of concern occurring 
as a result of a 1-day or single exposure. No such effects were 
identified in the toxicological studies for aminocyclopyrachlor; 
therefore, a quantitative acute dietary exposure assessment was not 
conducted.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment for aminocyclopyrachlor, EPA used food consumption 
information from the United States Department of Agriculture (USDA) 
2003-2008 National Health and Nutrition Examination Survey, What We Eat 
in America (NHANES/WWEIA).
    iii. Cancer. Based on the data summarized in Unit III.A., EPA has 
concluded that aminocyclopyrachlor and CPCA do not pose cancer risks to 
humans. Therefore, dietary exposure assessment for the purpose of 
assessing cancer risk is unnecessary.
    iv. Anticipated residue and percent crop treated (PCT) information. 
EPA did not use anticipated residue and/or PCT information in the 
dietary assessment for aminocyclopyrachlor. Tolerance-level residues 
and 100 PCT were

[[Page 53016]]

assumed for all petitioned-for food commodities.
    2. Dietary exposure from drinking water. The Agency used screening 
level water exposure models in the dietary exposure analysis and risk 
assessment for aminocyclopyrachlor and CPCA in drinking water. These 
simulation models take into account data on the physical, chemical, and 
fate/transport characteristics. Further information regarding EPA 
drinking water models used in pesticide exposure assessment can be 
found at http://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/about-water-exposure-models-used-pesticide.
    The importation of milk and livestock commodities containing 
potential residues of aminocyclopyrachlor will not increase pesticide 
exposure in U.S. drinking water. Therefore, the drinking water 
estimates are based on pesticide exposure from the existing non-food/
non-feed uses of aminocyclopyrachlor.
    Based on the First Index Reservoir Screening Tool (FIRST) and 
Pesticide Root Zone Model Ground Water (PRZM-GW) models, the estimated 
drinking water concentrations (EDWCs) of aminocyclopyrachlor for 
chronic exposures for non-cancer assessments are estimated to be 18.3 
parts per billion (ppb) for surface water, and 78.0 ppb for ground 
water. The EDWCs of CPCA from surface water are estimated to be 1.7 ppb 
for acute exposure, and 1.2 ppb for chronic exposures for non-cancer 
assessments. Ground water EDWCs for CPCA were not calculated since CPCA 
is a photodegradate of aminocyclopyrachlor and is not anticipated to be 
present in ground water due to the absence of sunlight.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model. For chronic dietary risk 
assessment to aminocyclopyrachlor, the water concentration value of 
78.0 ppb was used to assess the contribution to drinking water. For 
acute dietary risk assessment to CPCA, the water concentration value of 
1.7 ppb was used to assess the contribution to drinking water. For 
chronic dietary risk assessment to CPCA, the water concentration value 
of 1.2 ppb was used to assess the contribution to drinking water.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in this document to refer to non-occupational, non-dietary 
exposure (e.g., for lawn and garden pest control, indoor pest control, 
termiticides, and flea and tick control on pets). Aminocyclopyrachlor 
is not currently registered for any specific use patterns that would 
result in residential exposure. In the risk assessment, EPA had 
assessed residential exposure based on previously-registered uses on 
lawn and turf, including golf courses; however, those residential use 
patterns are no longer registered, and therefore non-dietary 
residential exposure does not occur.
    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 aminocyclopyrachlor to share a common mechanism 
of toxicity with any other substances, and aminocyclopyrachlor does not 
appear to produce a toxic metabolite produced by other substances. For 
the purposes of this tolerance action, therefore, EPA has assumed that 
aminocyclopyrachlor 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 http://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides.

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. As discussed in Unit III.A., 
there was no evidence of prenatal toxicity resulting from exposure to 
aminocyclopyrachlor. There was no evidence of increased susceptibility 
following in utero exposure in the rat and rabbit developmental 
toxicity studies. An increase in abortions in maternal rabbits was 
observed at the limit dose, but the abortions were considered secondary 
effects due to severe maternal body weight loss. There was also no 
evidence of increased susceptibility of offspring in the rat 
reproduction and fertility studies, with only body weight decreases 
observed in both maternal rats and offspring at the limit dose.
    For CPCA, there were no information available investigating 
developmental or offspring effects. However, there is indirect evidence 
in the open literature that the young may be more sensitive to the 
metabolic effects of CPCA, and this evidence does not allow this 
potential sensitivity to be ruled out. This evidence is provided by 
inherited conditions, specifically inborn errors of metabolism that 
results in compromised metabolism of fatty acids that is qualitatively 
similar to that of CPCA's effect of inhibition of beta oxidation of 
fatty acids. These inborn metabolism errors result in energy 
deficiencies during periods of fasting, and it is known that 
developing/young children are more sensitive to these effects than 
pregnant women or adults. The magnitude of this effect would be much 
more severe in the inherited case than for CPCA. This is because fatty 
acid oxidation is almost completely compromised in the inherited case 
and other cellular processes are also impacted, whereas only beta 
oxidation of fatty acids would be impacted for CPCA, and the magnitude 
of this impact is anticipated to be negligible for the estimated (low-
level) dietary exposures.
    3. Conclusion. For aminocyclopyrachlor, EPA has determined that 
reliable data show the safety of infants and children would be 
adequately protected if the FQPA SF were reduced to 1X.
    For the degradate cyclopropane carboxylic acid, the FQPA SF is 
retained at 10X for acute dietary exposures, to account for the 
extrapolation of data from a LOAEL to a NOAEL for hepatic steatosis/
necrosis in rabbits, and to account for any potential uncertainties 
regarding developmental toxicity effects based on the available data. 
This SF is considered protective because hepatic steatosis/necrosis and 
any developmental toxicity effects would be caused by the same cellular 
mechanism. Therefore, protecting for these liver effects would protect 
any potential developmental toxicity resulting from very low dietary 
exposures to CPCA.
    For chronic dietary exposures, the FQPA SF is increased from 10X to 
30X to account for the use of a short-term (acute) study to assess 
long-term (chronic) exposure. The additional 3X SF is considered 
protective since the

[[Page 53017]]

duration of the acute study was 14 days with the dose administered as a 
bolus (via gavage). Because the exposure in this study was repeated and 
a bolus dose was used that would overestimate dietary exposure, the 
severity of the liver effects are not expected to vary substantially 
with time.
    Those decisions are based on the following findings:
    i. The toxicity database for aminocyclopyrachlor is adequate for 
assessing the sensitivity of infants and children under FQPA and for 
selecting endpoints for risk assessment.
    The database for CPCA is also adequate, as there is a substantial 
amount of toxicological information available in the open literature 
that identifies the target organ of toxicity, the mechanism of 
toxicity, and the most sensitive species. The FQPA SFs account for any 
residual uncertainties in the toxicity database for CPCA.
    ii. There is no indication that aminocyclopyrachlor is a neurotoxic 
chemical and there is no need for a developmental neurotoxicity study 
or additional UFs to account for neurotoxicity. Based on the mechanism 
of toxicity for CPCA that has been identified in the open scientific 
literature, the nervous system is not expected to be more sensitive 
than the liver. Although there are no studies available that directly 
investigate the effects of CPCA on the nervous system, there is 
indirect evidence that the endpoint on which the Agency is regulating 
CPCA (hepatic steatosis/necrosis) is protective of the nervous system. 
First, the molecular mechanism underlying hepatic steatosis has been 
identified as inhibition of the metabolic pathway of beta oxidation of 
fatty acids in the mitochondria. This is a major, energy producing 
pathway in liver but not in the brain. Since the ketone bodies 
generated by this process in the liver are metabolized by the brain for 
energy, any brain effects from inhibition of this pathway would be 
secondary to liver effects. Second, CPCA is a metabolite of panadiplon, 
a drug that was developed to target the nervous system as an 
anxiolytic. Panadiplon failed in preclinical development not as a 
result of neurotoxicity, but as a result of liver toxicity that was 
caused by CPCA. This further supports that adverse effects on the liver 
is more sensitive than the brain. Since the endpoint chosen for risk 
assessment is protective for liver effects, it is therefore also 
protective for any primary or secondary neurotoxicity that may result 
from CPCA exposure.
    iii. There is no evidence that aminocyclopyrachlor results in 
increased susceptibility in in utero rats or rabbits in the prenatal 
developmental studies or in young rats in the 2-generation reproduction 
study. In the rabbit prenatal developmental study, an increase in 
abortions was observed at the limit dose, which were considered 
secondary effects to severe decreases in maternal body weight.
    As discussed in Unit III.D.2., there is no information available 
that directly investigates the developmental effects of CPCA. However, 
based on the known information, the magnitude of the potential impact 
of CPCA exposure on the inhibition of beta oxidation of fatty acids is 
anticipated to be negligible for the estimated dietary exposure, and 
less than the non-CPCA-related effects resulting from inborn metabolic 
errors which compromises the metabolism of fatty acids and other 
cellular processes.
    iv. There are no residual uncertainties identified in the exposure 
databases. The dietary food exposure assessments were performed based 
on 100 PCT and tolerance-level residues. EPA made conservative 
(protective) assumptions in the ground and surface water modeling used 
to assess exposure to aminocyclopyrachlor and CPCA in drinking water. 
These assessments will not underestimate the exposure and risks posed 
by aminocyclopyrachlor and CPCA.

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. For aminocyclopyrachlor, no adverse effect resulting 
from a single oral exposure was identified and no acute dietary 
endpoint was selected. Therefore, aminocyclopyrachlor is not expected 
to pose an acute risk.
    For CPCA, using the exposure assumptions discussed in this unit for 
acute exposure, the acute dietary exposure from drinking water only 
will occupy 11% of the aPAD for all infants less than 1 year old, the 
population group receiving the greatest exposure.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure will 
utilize <1% of the cPAD for aminocyclopyrachlor (from food and water) 
and 7.4% of the cPAD for CPCA (from water only) for all infants less 
than 1 year old, the population group receiving the greatest exposure. 
Based on the explanation in Unit III.C.3. regarding residential use 
patterns, chronic residential exposure to residues of 
aminocyclopyrachlor and CPCA is not expected.
    3. Short- and Intermediate-term risks. Short- and intermediate-term 
aggregate exposures take into account short- and intermediate-term 
residential exposures plus chronic exposure to food and water 
(considered to be a background exposure level).
    Short- and intermediate-term adverse effects were identified; 
however, aminocyclopyrachlor is no longer registered for any use 
patterns that would result in residential exposure. Short- and 
intermediate-term risks are assessed based on short-term/intermediate-
term residential exposure plus chronic dietary exposure. Because there 
is no residential exposure and chronic dietary exposure has already 
been assessed under the appropriately protective cPAD (which is at 
least as protective as the POD used to assess short-/intermediate-term 
risk), no further assessment of short- and intermediate-term risks are 
necessary, and EPA relies on the chronic dietary risk assessments for 
evaluating short- and intermediate-term risks for aminocyclopyrachlor 
and CPCA.
    4. Aggregate cancer risk for U.S. population. Based on the lack of 
evidence of carcinogenicity in two adequate rodent carcinogenicity 
studies, aminocyclopyrachlor is not expected to pose a cancer risk to 
humans. As discussed in Unit III.A., CPCA is also not expected to pose 
a cancer risk to humans.
    5. 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 aminocyclopyrachlor and CPCA residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology ([DuPont-27162, Revision No. 1; 
high-performance liquid chromatography with tandem mass spectrometry 
detection (HPLC/MS/MS)) is available to enforce the tolerance 
expression.

[[Page 53018]]

    The method may be requested from: Chief, Analytical Chemistry 
Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 
20755-5350; telephone number: (410) 305-2905; email address: 
[email protected].

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). Codex is a joint United Nations 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 any MRLs for aminocyclopyrachlor.

C. Revisions to Petitioned-For Tolerances

    Based on the available residue chemistry data and EPA policy on 
livestock tolerances, the proposed tolerances for liver (0.06 ppm) and 
meat byproducts except liver (0.40 ppm) of cattle, goat, horse, and 
sheep are replaced by establishing tolerances for meat byproducts of 
cattle, goat, horse, and sheep at 0.30 ppm. Also, based on the residue 
data, EPA is lowering the proposed tolerances for fat of cattle, horse, 
goat, and sheep from 0.07 ppm to 0.05 ppm. Lastly, EPA is also lowering 
the proposed tolerances for milk from 0.035 ppm to 0.01 ppm, and meat 
of cattle, goat, horse, and sheep from 0.02 ppm to 0.01 ppm to 
harmonize with established Canadian MRLs.

V. Conclusion

    Therefore, tolerances are established for residues of the herbicide 
aminocyclopyrachlor, 6-amino-5-chloro-2-cyclopropyl-4-
pyrimidinecarboxylic acid, including its metabolites and degradates, in 
or on cattle, fat at 0.05 ppm; cattle, meat at 0.01 ppm; cattle, meat 
byproducts at 0.30 ppm; goat, fat at 0.05 ppm; goat, meat at 0.01 ppm; 
goat, meat byproducts at 0.30 ppm; horse, fat at 0.05 ppm; horse, meat 
at 0.01 ppm; horse, meat byproducts at 0.30 ppm; milk at 0.01 ppm; 
sheep, fat at 0.05 ppm; sheep, meat at 0.01 ppm; and sheep, meat 
byproducts at 0.30 ppm.

VI. Statutory and Executive Order Reviews

    This action establishes tolerances 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 action has been 
exempted from review under Executive Order 12866, this action 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 action 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 action 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 
action. In addition, this action does not impose any enforceable duty 
or contain any unfunded mandate as described under Title II of the 
Unfunded Mandates Reform Act (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 
(NTTAA) (15 U.S.C. 272 note).

VII. 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: July 28, 2016.
Jack E. Housenger,
Director, 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. Add Sec.  180.689 to subpart C to read as follows:


Sec.  180.689  Aminocyclopyrachlor; tolerances for residues.

    (a) General. Tolerances are established for residues of the 
herbicide aminocyclopyrachlor, including its metabolites and 
degradates, in or on the commodities in the table below. Compliance 
with the tolerance levels specified below is to be determined by 
measuring only the sum of aminocyclopyrachlor, 6-amino-5-chloro-2-
cyclopropyl-4-pyrimidinecarboxylic acid, and aminocyclopyrachlor methyl 
ester, methyl 6-amino-5-chloro-2-cyclopropyl-4-pyrimidinecarboxylate, 
calculated as the stoichiometric equivalent of aminocyclopyrachlor.

------------------------------------------------------------------------
                                                            Parts per
                       Commodity                             million
------------------------------------------------------------------------
Cattle, fat \1\.......................................              0.05
Cattle, meat \1\......................................              0.01
Cattle, meat byproducts \1\...........................              0.30
Goat, fat \1\.........................................              0.05
Goat, meat \1\........................................              0.01

[[Page 53019]]

 
Goat, meat byproducts \1\.............................              0.30
Horse, fat \1\........................................              0.05
Horse, meat \1\.......................................              0.01
Horse, meat byproducts \1\............................              0.30
Milk \1\..............................................              0.01
Sheep, fat \1\........................................              0.05
Sheep, meat \1\.......................................              0.01
Sheep, meat byproducts \1\............................              0.30
------------------------------------------------------------------------
\1\ There are no U.S. registrations as of August 11, 2016.

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]

[FR Doc. 2016-19117 Filed 8-10-16; 8:45 am]
 BILLING CODE 6560-50-P