[Federal Register Volume 78, Number 59 (Wednesday, March 27, 2013)]
[Rules and Regulations]
[Pages 18519-18526]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-06916]



[[Page 18519]]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2012-0418; FRL-9379-1]


Abamectin; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation raises tolerances for residues of abamectin 
(also known as avermectin B1 a mixture of avermectins 
containing greater than or equal to 80% avermectin B1a (5-O-
demethyl avermectin A1) and less than or equal to 20% 
avermectin delta-8,9-isomer) in or on cotton and strawberries. Syngenta 
Crop Protection Inc. requested these tolerances under the Federal Food, 
Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective March 27, 2013. Objections and 
requests for hearings must be received on or before May 28, 2013, 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-2012-0418, 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: Jessica Rogala, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave. NW., Washington, DC 20460; telephone number: 
(703) 347-0263; 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 OPPTS 
harmonized test guidelines referenced in this document electronically, 
please go to http://www.epa.gov/oppts 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-2012-0418 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 
May 28, 2013. 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-2012-0418, 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.
     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. Summary of Petitioned-For Tolerance

    In the Federal Register of August 22, 2012 (77 FR 50661) (FRL-9358-
9), 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 
2F8009) by Syngenta Crop Protection LLC, P.O. Box 18300, Greensboro, NC 
27419-8300. The petition requested that 40 CFR 180.449 be amended by 
increasing the established tolerances for residues of the insecticide 
abamectin (also known as avermectin B1 a mixture of 
avermectins containing greater than or equal to 80% avermectin 
B1a (5-O-demethyl avermectin A1) and less than or 
equal to 20% avermectin B1b (5-O-demethyl-25-de(1-
methylpropyl)-25-(1-methylethyl) avermectin A1) and its 
delta-8,9-isomer) (referred to as ``abamectin'' in this document) in or 
on cotton, undelinted seed from 0.005 parts per million (ppm) to 0.015 
ppm; cotton, gin by-products from 0.15 ppm to 1.0 ppm and strawberry 
from 0.02 ppm to 0.06 ppm.
    That document referenced a summary of the petition prepared by 
Syngenta Crop Protection LLC., the registrant, which is available in 
the docket, http://www.regulations.gov. There were no comments received 
in response to the notice of filing.
    Based upon review of the data supporting the petition, EPA is 
establishing tolerance for cotton, undelinted seed and strawberry at 
levels that vary from levels requested. The reasons for these changes 
are explained in Unit IV.D.

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

[[Page 18520]]

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 * * 
* .''
    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 abamectin including exposure 
resulting from the tolerances established by this action. EPA's 
assessment of exposures and risks associated with abamectin 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. Abamectin has high to moderate acute toxicity by the oral 
route (depending on the vehicle), high acute toxicity by the inhalation 
route, and low acute toxicity by the dermal route. It is slightly 
irritating to the skin but is not an ocular irritant or a dermal 
sensitizer. The main target organ is the nervous system, and the 
reduced body weight effect is one of the most frequent findings. 
Neurotoxicity and developmental effects were detected in multiple 
studies and species of test animals. The dose/response curve is very 
steep in several studies, with severe effects (including death and 
morbid sacrifice) seen at dose levels as low as 0.4 milligrams/
kilogram/day (mg/kg/day) and 0.1 mg/kg/day in rats and mice, 
respectively, following repeated/chronic exposures. Increased 
susceptibility (qualitative and/or quantitative) was seen in prenatal 
developmental toxicity studies in mice and rabbits, and in 
developmental neurotoxicity studies in rats. Review of acceptable 
oncogenicity and mutagenicity studies provides no indication that 
abamectin is carcinogenic or mutagenic. Specific information on the 
studies received and the nature of the adverse effects caused by 
abamectin 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, 
Abamectin: Human Health Risk Assessment at 16, section 4.0 in docket ID 
number EPA-HQ-OPP-2012-0418.

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 http://www.epa.gov/pesticides/factsheets/riskassess.htm. A summary of the toxicological 
endpoints for abamectin used for human risk assessment is shown in the 
following Table.

   Table 1--Summary of Toxicological Doses and Endpoints for Abamectin for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                    Point of departure
        Exposure/scenario            and uncertainty/     RfD, PAD, LOC for     Study and toxicological effects
                                      safety factors       risk assessment
----------------------------------------------------------------------------------------------------------------
Acute dietary (General population  NOAEL = 0.5 mg/kg/    Acute RfD = .005 mg/ 12-week dose-range finding study
 including infants and children).   day.                  kg/day.              in dogs LOAEL = 1.0 mg/kg/day
                                   UFA = 10x...........                        based on Mydriasis seen 1-5 times
                                   UFH = 10x...........                        during the first week of
                                   FQPA SF = 1x........                        treatment. Acute neurotoxicity
                                                                               study in rats
                                                                              LOAEL= 1.5 mg/kg/day based on
                                                                               increased incidence of foot
                                                                               splay.
----------------------------------------------------------------------------------------------------------------
Chronic dietary (All populations)  NOAEL= 0.12 mg/kg/    cPAD = .0004 mg/kg/  Combined data from three
                                    day.                  day.                 reproduction studies and two
                                   UFA = 10x...........                        developmental neurotoxicity
                                   UFH = 10x...........                        studies (please see the
                                   FQPA SF = 3x........                        discussion on Chronic Dietary
                                                                               Endpoint)
                                                                              LOAEL = 0.2 mg/kg/day based on
                                                                               decreased pup body weight in pups
                                                                               at 0.2 mg/kg/day.
----------------------------------------------------------------------------------------------------------------
Incidental oral short-term and     NOAEL= 0.12 mg/kg/    LOC for MOE = 300..  Combined data from three
 Intermediate term (1 to 6          day.                                       reproduction studies and two
 months).                          UFA = 10x...........                        developmental neurotoxicity
                                   UFH = 10x...........                        studies (please see the
                                   FQPA SF = 3x........                        discussion on Chronic Dietary
                                                                               Endpoint)
                                                                              LOAEL = 0.2 mg/kg/day based on
                                                                               decreased pup body weight.
----------------------------------------------------------------------------------------------------------------

[[Page 18521]]

 
Dermal All Durations.............  Dermal study NOAEL =  LOC for MOE = 300..  Combined data from three
                                    0.12 mg/kg/day.                            reproduction studies and two
                                   UFA = 10x...........                        developmental neurotoxicity
                                   UFH = 10x...........                        studies (please see the
                                   FQPA SF = 3x........                        discussion on Chronic Dietary
                                                                               Endpoint)
                                                                              LOAEL = 0.2 mg/kg/day based on
                                                                               decreased pup body weight.
----------------------------------------------------------------------------------------------------------------
Inhalation short-term............  Inhalation study      LOC for MOE = 300..  Combined data from three
All durations....................   NOAEL = 0.12 mg/kg/                        reproduction studies and two
                                    day (inhalation                            developmental neurotoxicity
                                    absorption rate =                          studies (please see the
                                    100%).                                     discussion on Chronic Dietary
                                   UFA = 10x...........                        Endpoint)
                                   UFH = 10x...........                       LOAEL = 0.2 mg/kg/day based on
                                   FQPA SF = 3x........                        decreased pup body weight.
----------------------------------------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation)  Classification: Not likely to be carcinogenic to humans based on the absence
                                    of significant increase in tumor incidence in two adequate rodent
                                    carcinogenicity studies.
----------------------------------------------------------------------------------------------------------------
FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
  of concern. mg/kg/day = milligram/kilogram/day. MOE = margin of exposure. 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).

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to abamectin, EPA considered exposure under the petitioned-for 
tolerances as well as all existing abamectin tolerances in 40 CFR 
180.449. EPA assessed dietary exposures from abamectin 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. Such effects were identified 
for abamectin. In estimating acute dietary exposure, EPA used 2003-2008 
food consumption information from the U.S. Department of Agriculture 
(USDA) 2003-2008 National Health and Nutrition Examination Survey, What 
We Eat in America (NHANES/WWEIA). As to residue levels in food, a 
refined acute dietary (food and drinking water) exposure assessment was 
conducted. Tolerance level residues were used for bulb onions, chives, 
dry beans, and okra. Acute anticipated residues for the remaining 
commodities were derived from field trial data. Empirical and default 
processing factors were used. EPA also relied on available percent crop 
treated (PCT) information for registered uses of abamectin including 
strawberry and cotton. EPA relied on available data in estimating PCT) 
for existing uses of abamectin. Surface drinking water concentrations 
were estimated using the Tier II PRZM/EXAMS (Pesticide Root Zone Model/
Exposure Analysis Modeling System) computer model and a national 
default percent cropped area (PCA) value of 87%. The model predicts 
that the maximum concentration of total residues of abamectin in 
surface water (the 1-in-10-year peak exposure) is not likely to exceed 
2.3 ppb from the use of aerial/ground applications to dry beans in 
Michigan.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment EPA used 2003-2008 food consumption data from the USDA 2003-
2008 NHANES/WWEIA. As to residue levels in food, EPA a refined chronic 
dietary exposure assessment was conducted. Tolerance level residues 
were used for bulb onions, chives, dry beans, and and okra. Average 
residues from field trials were used for the remaining crops. Empirical 
and default processing factors were also used. EPA used available PCT 
information registered use of abamectin including strawberry and 
cotton. Drinking water was represented by a single point estimate of 
average abamectin residues (the 1-in-ten-year annual mean). The 
estimated surface water concentration of 1.3 parts per billion (ppb) 
was based on the application to dry beans in Michigan.
    iii. Cancer. Based on the data summarized in Unit III.A., EPA has 
concluded that abamectin does not pose a cancer risk to humans. 
Therefore, a quantitative dietary exposure assessment for the purpose 
of assessing cancer risk is unnecessary.
    iv. Anticipated residue and PCT information. Section 408(b)(2)(E) 
of FFDCA authorizes EPA to use available data and information on the 
anticipated residue levels of pesticide residues in food and the actual 
levels of pesticide residues that have been measured in food. If EPA 
relies on such information, EPA must require pursuant to FFDCA section 
408(f)(1) that data be provided 5 years after the tolerance is 
established, modified, or left in effect, demonstrating that the levels 
in food are not above the levels anticipated. For the present action, 
EPA will issue such data call-ins as are required by FFDCA section 
408(b)(2)(E) and authorized under FFDCA section 408(f)(1). Data will be 
required to be submitted no later than 5 years from the date of 
issuance of these tolerances.
    Section 408(b)(2)(F) of FFDCA states that the Agency may use data 
on the actual percent of food treated for assessing chronic dietary 
risk only if:
     Condition a: The data used are reliable and provide a 
valid basis to show what percentage of the food derived from such crop 
is likely to contain the pesticide residue.
     Condition b: The exposure estimate does not underestimate 
exposure for any significant subpopulation group.
     Condition c: Data are available on pesticide use and food 
consumption in a particular area, the exposure estimate does not 
understate exposure for the population in such area.
    In addition, the Agency must provide for periodic evaluation of any 
estimates

[[Page 18522]]

used. To provide for the periodic evaluation of the estimate of PCT as 
required by FFDCA section 408(b)(2)(F), EPA may require registrants to 
submit data on PCT.
    The Agency estimated the PCT for existing uses as follows: The 
following maximum PCT estimates were used in the acute dietary risk 
assessment for the following crops that are currently registered for 
abamectin: Almonds: 75%; apples: 10%; apricots: 5%; avocados: 60%; 
cantaloupes: 30%; celery: 65%; cherries: 2.5%; cotton: 20%; cucumbers: 
10%; grapefruit: 80%; grapes: 25%; honeydew: 35%; lemons: 55%; lettuce: 
20%; oranges: 45%; peaches: 2.5%; pears: 80%; pecans: 2.5%; peppers: 
25%; potatoes: 2.5%; prunes: 10%; pumpkins: 10%; spinach: 45%; squash: 
10%; strawberries: 45%; tangerines: 65%; tomatoes: 20%; walnuts: 20%; 
and watermelons: 10%.
    The following average PCT estimates were used in the chronic 
dietary risk assessment for the following crops that are currently 
registered for abamectin: Almonds: 50%; apples: 5%; apricots: 5%; 
avocados: 40%; cantaloupes: 15%; celery: 40%; cherries: 1%; cotton: 5%; 
cucumbers: 5%; grapefruit: 60%; grapes: 10%; honeydew: 20%; lemons: 
35%; lettuce: 10%; oranges: 25%; peaches: 1%; pears: 70%; pecans: 1%; 
peppers: 10%; potatoes: 1%; prunes: 2.5%; pumpkins: 2.5%; spinach: 20%; 
squash: 5%; strawberries: 30%; tangerines: 60%; tomatoes: 10%; walnuts: 
10%; and watermelons: 5%.
    An emulsifiable concentrate (EC) formulation is currently 
registered for abamectin for use on cotton and strawberry. The 
petitioner has requested that the existing tolerance levels be 
increased to support the registration of cotton and strawberry for a 
suspension concentrate (SC) formulation. The residue field trials 
submitted indicate that the SC formulation result in higher pesticide 
residues than that of the EC formulation. However, the Agency does not 
expect that the registration of a different formulation will impact the 
PCT estimates.
    In most cases, EPA uses available data from USDA of Agriculture/
National Agricultural Statistics Service (USDA/NASS), proprietary 
market surveys, and the National Pesticide Use Database for the 
chemical/crop combination for the most recent 6-7 years. EPA uses an 
average PCT for chronic dietary risk analysis. The average PCT figure 
for each existing use is derived by combining available public and 
private market survey data for that use, averaging across all 
observations, and rounding to the nearest 5%, except for those 
situations in which the average PCT is less than one. In those cases, 
1% is used as the average PCT and 2.5% is used as the maximum PCT. EPA 
uses a maximum PCT for acute dietary risk analysis. The maximum PCT 
figure is the highest observed maximum value reported within the recent 
6 years of available public and private market survey data for the 
existing use and rounded up to the nearest multiple of 5%.
    The Agency believes that the three conditions discussed in Unit 
III.C.1.iv. have been met. With respect to Condition a, PCT estimates 
are derived from Federal and private market survey data, which are 
reliable and have a valid basis. The Agency is reasonably certain that 
the percentage of the food treated is not likely to be an 
underestimation. As to Conditions b and c, regional consumption 
information and consumption information for significant subpopulations 
is taken into account through EPA's computer-based model for evaluating 
the exposure of significant subpopulations including several regional 
groups. Use of this consumption information in EPA's risk assessment 
process ensures that EPA's exposure estimate does not understate 
exposure for any significant subpopulation group and allows the Agency 
to be reasonably certain that no regional population is exposed to 
residue levels higher than those estimated by the Agency. Other than 
the data available through national food consumption surveys, EPA does 
not have available reliable information on the regional consumption of 
food to which abamectin may be applied in a particular area.
    2. Dietary exposure from drinking water. The Agency used screening 
level water exposure models in the dietary exposure analysis and risk 
assessment for abamectin in drinking water. These simulation models 
take into account data on the physical, chemical, and fate/transport 
characteristics of abamectin. Further information regarding EPA 
drinking water models used in pesticide exposure assessment can be 
found at http://www.epa.gov/oppefed1/models/water/index.htm.
    Based on The Pesticide Root Zone Model/Exposure Analysis Modeling 
System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI-
GROW) models were used to estimate the drinking water concentrations 
(EDWCs) of abamectin. For acute exposures, the EDWCs are estimated to 
be 2.3 parts per billion (ppb) for surface water and 1.6 x 
10-3 ppb for ground water. The EDWCs of abamectin for 
chronic exposures are estimated to be 1.3 ppb for surface water and 1.6 
x 10-3 ppb for ground water.
    Modeled estimates of drinking water concentrations were directly 
entered into the dietary exposure model. For acute dietary risk 
assessment, the water concentration value of 2.3 ppb was used to assess 
the contribution to drinking water. For chronic dietary risk 
assessment, the water concentration of value 1.3 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).
    Abamectin is currently registered for the following uses that could 
result in residential exposures: Granular baits used to treat lawns and 
indoor bait products. EPA assessed residential exposure using the 
following assumptions: Adults were assessed for short-term residential 
handler exposure. Residential post-application exposure to adults and 
children is unlikely for all registered uses of abamectin. Further 
information regarding EPA standard assumptions and generic inputs for 
residential exposures may be found at http://www.epa.gov/pesticides/trac/science/trac6a05.pdf.
    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.''
    OPP's Guidance For Identifying Pesticide Chemicals and Other 
Substances that have a Common Mechanism of Toxicity (USEPA, 1999) 
describes the weight of the evidence approach for determining whether 
or not a group of pesticides share a common mechanism of toxicity. This 
guidance defines mechanism of toxicity as the major steps leading to a 
toxic effect following interaction of a pesticide with biological 
targets. All steps leading to an effect do not need to be specifically 
understood. Rather, it is the identification of the crucial events 
following chemical interaction that are required in order to describe a 
mechanism of toxicity. For example, a mechanism of toxicity may be 
described by knowing the following: A chemical binds to a given 
biological target in vitro, and causes the receptor-related molecular 
response; in vivo it also leads

[[Page 18523]]

to the molecular response and causes a number of intervening biological 
and morphological steps that result in an adverse effect. In this 
context a common mechanism of toxicity pertains to two or more 
pesticide chemicals or other substances that cause a common toxic 
effect to human health by the same, or essentially the same, sequence 
of major biochemical events. Hence, the underlying basis of the 
toxicity is the same, or essentially the same, for each chemical. In 
the case of the macrocyclic lactone pesticides (e.g., abamectin, 
emamectin, and avermectin), there is a wealth of data on the 
insecticidal mechanism of action for avermectin: Its insecticidal 
actions are mediated by interaction with the glutamate-gated chloride 
channels and GABAA gated chloride channels. This is presumed 
to be the insecticidal mechanism of action of emamectin and abamectin 
as well. Insecticidal mechanism of action does not indicate a common 
mechanism of toxicity for human health. Further, mammals lack 
glutamate-gated chloride channels; the toxic actions of avermectin 
appear to be mediated via interaction with GABAA and 
possibly glycine gated chloride channels. There is evidence that 
avermectin B1a binds to GABAA receptors and 
activates Cl- flux into neurons (Abalis et al., 1986; Huang 
and Casida, 1997). However, there is a paucity of data regarding the 
resultant alterations in cellular excitability of mammalian neurons and 
neural networks (i.e., changes in cellular excitability and altered 
network function as documented with pyrethroids), as well as in vivo 
measurements of altered excitability associated with adverse outcomes. 
Thus, while the downstream steps leading to toxicity via disruption of 
GABAA receptor function for avermectin can be postulated, 
experimental data supporting these actions are lacking. In addition, 
specific data demonstrating GABAA receptor interaction in 
mammalian preparations are lacking for abamectin and emamectin. 
Moreover, the specificity of such interaction on the adverse outcome 
would need to be shown experimentally. GABAA receptors have 
multiple binding sites which have been proposed to relate to adverse 
outcomes. For example, Dawson et al (2000) showed for a group of 
avermectin-like compounds that rank order for anticonvulsant activity 
did not parallel the rank order for affinity at the 3H ivermectin site. 
The authors hypothesized that these findings may be related to 
differential affinity or efficacy at subtypes of the GABAA 
receptor. Other reports have indicated species differences in abamectin 
effects on GABAA receptor function in the mouse as compared 
to the rat (Soderlund et al., 1987).
    In conclusion, although GABAA receptor mediated 
neurotoxicity may be a common mechanism endpoint for the macrocyclic 
lactone pesticides, data demonstrating the interactions of emamectin 
and abamectin with mammalian GABAA receptors are not 
available, and data in mammalian preparations linking alterations in 
GABAA receptor function to disruptions in neuronal 
excitability in vitro and in vivo, and ultimately adverse outcome, are 
also currently lacking for this class of compounds. In the absence of 
such data, the key biological steps leading to the adverse outcome 
(i.e., the mammalian mechanism of action) cannot be established and by 
extension a common mechanism of toxicity cannot be established.
    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.

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. The abamectin toxicity 
database is adequate to evaluate potential increased susceptibility of 
infants and children, and includes developmental toxicity studies in 
rat, mice, and rabbits; two 1-generation rat reproductive toxicity 
studies in rat; a 2-generation reproductive toxicity study in rat; and 
two developmental neurotoxicity studies in the rat. No developmental 
effects were seen in the rat developmental toxicity study. However, 
increased quantitative susceptibility was noted in the prenatal 
developmental toxicity studies in mice and rabbits, the rat 
reproductive toxicity studies, and the developmental neurotoxicity 
studies in rat.
    3. Conclusion. In previous abamectin risk assessments, the 10X FQPA 
safety factor was retained as a database uncertainty factor for the 
lack of a developmental neurotoxicity study. Two developmental 
neurotoxicity studies have now been submitted and reviewed and the 
findings in these studies were considered in the identification of 
toxicological points of departure and uncertainty/safety factors.
    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 acute dietary assessment and 3X for all assessments other 
than acute dietary. That decision is based on the following findings:
    i. The toxicity database for abamectin is complete except for 
immunotoxicity testing. Recent changes to 40 CFR part 158 imposed new 
data requirements for immunotoxicity testing (OPPTS Guideline 870.7800) 
for pesticide registration. However, the toxicity database for 
abamectin provides no indication of immunotoxicity and abamectin does 
not belong to a class of chemicals that would be expected to be 
immunotoxic. Therefore, EPA does not believe that conducting an 
immunotoxicity study will result in a NOAEL less than the NOAELs of 0.5 
mg/kg/day and 0.12 mg/kg/day already set for abamectin acute and 
repeated exposures, respectively, and an additional uncertainty factor 
is not needed to account for lack of an immunotoxicity study.
    ii. Signs of neurotoxicity ranging from decrease in foot splay 
reflex, mydriasis (i.e.,excessive dilation of the pupil), curvature of 
the spine, decreased fore- and hind-limb grip strength, tip-toe gate, 
tremors, ataxia, or spastic movements of the limbs were reported in 
various studies with different durations of abamectin exposure in rats, 
mice, and dogs. However, the results of two submitted rat developmental 
neurotoxicity studies did not show any evidence of neurotoxicity.
    iii. For all risk assessments involving repeated exposures to 
abamectin, EPA determined that a 3X safety factor would be appropriate, 
based on the severity of effects (decrease in pup body weight and 
mortality) and the steepness of the dose-response curve seen in the 
developmental neurotoxicity study and three reproductive toxicity 
studies in the rat. These studies have documented a very narrow dose 
range from NOAEL (0.12 mg/kg/day) to adverse effect (0.2 mg/kg/day) to 
severe adverse effect (0.4 mg/kg/day). Dose spacing is commonly

[[Page 18524]]

greater than 2X between NOAEL and LOAEL, and the 3X difference between 
the NOAEL and the dose that induced mortality in the pups in the 
developmental neurotoxicity study provides little margin of safety for 
the severity of the effects seen. Retaining an additional 3X FQPA 
safety factor effectively provides a 10X margin between the dose which 
causes death (0.4 mg/kg/day) and the NOAEL adjusted by the additional 
safety factor (0.12 mg/kg/day/3X = 0.04 mg/kg/day). A dose spacing of 
10X between a NOAEL and LOAEL is as broad, if not broader, than the 
dose spacing generally used in animal testing and thus removes the 
residual concern of the steepness of the dose-response curve and the 
severe effects noted. Additionally, this adjusted point of departure 
(0.04 mg/kg/day) would address the concerns for the increased 
susceptibility seen at higher doses in the 2-generation reproduction 
study in rats (LOAEL = 0.4 mg/kg/day), prenatal developmental study in 
mice (LOAEL = 0.75 mg/kg/day), the prenatal developmental toxicity 
study in rabbits (LOAEL = 2 mg/kg/day), and the 1-generation rat 
reproduction study (LOAEL = 0.2 mg/kg/day).
    With respect to acute dietary exposure, the endpoint selected for 
risk assessment is based on mydriasis observed in dogs. EPA determined 
that the additional 3X factor applied to chronic and other exposure 
scenarios is not applicable to acute exposure for the following 
reasons:
    a. The concerns noted for steepness of the dose-response curve and 
the severity of effects were not seen in the studies where mydriasis 
occurred.
    b. The reduced body weights noted in studies following repeated 
exposure to abamectin are not a single dose effect.
    c. The increased susceptibility seen in the prenatal developmental 
toxicity studies, reproductive toxicity studies, and the developmental 
neurotoxicity studies were seen at a dose lower (LOAEL 0.2 mg/kg/day) 
than the dose (LOAEL 1.0 mg/kg/day) that caused mydriasis. Therefore, 
EPA has determined that it would be appropriate if the FQPA SF were 
reduced to 1X for the acute dietary assessment.
    iv. There are no residual uncertainties identified in the exposure 
databases. The acute and chronic dietary exposure assessments were 
refined and utilized tolerance level or anticipated residues, default 
or empirical processing factors, and PCT estimates. EPA made 
conservative (protective) assumptions in the ground and surface water 
modeling used to assess exposure to abamectin in drinking water. These 
assessments will not underestimate the exposure and risks posed by 
abamectin. Residential post-application exposure to adults and children 
is unlikely for all registered uses of abamectin

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 percent adjusted dose (PAD) and chronic percent adjusted dose 
(cPAD). For linear cancer risks, EPA calculates the lifetime 
probability of acquiring cancer given the estimated aggregate exposure. 
Short-term, intermediate-term, 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. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food and water 
to abamectin will occupy 24% of the aPAD for children 1-2 years 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 to 
abamectin from food and water will utilize 53% of the cPAD for children 
1-2 years old the population group receiving the greatest exposure.
    3. Short-term and intermediate-term risk. Short-term and 
intermediate-term aggregate exposure takes into account short- and 
intermediate-term residential exposure plus chronic exposure to food 
and water (considered to be a background exposure level). Abamectin is 
currently registered for uses that could result in short- and/or 
intermediate-term residential exposure, and the Agency has determined 
that it is appropriate to aggregate chronic exposure through food and 
water with short- and/or intermediate-term residential exposures to 
abamectin .
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water, 
and residential exposures result in an aggregate MOE of 1800 for the 
general population Residential post-application exposure to adults and 
children is unlikely for all registered uses of abamectin. Because 
EPA's level of concern for abamectin is an MOE of 300 or below, this 
MOE is not of concern.
    4. Aggregate cancer risk for U.S. population. Based on the lack of 
evidence of carcinogenicity in two adequate rodent carcinogenicity 
studies, abamectin is 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 abamectin residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodologies are available in Pesticide 
Analytical Manual II (PAM II) for citrus and processed fractions 
(Method I), ginned cottonseed (Method IA), and bovine tissues and milk 
(Method II). Additionally, Method M-073 and M-936-95-2 have been 
validated by the Agency and submitted for inclusion in PAM II as 
enforcement methods. These five methods are adequate for enforcement of 
the tolerances on plants and livestock. Method M-073 and M 936-95-2 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). The Codex Alimentarius 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 a MRL for abamectin.

D. Revisions to Petitioned-For Tolerances

    Based upon review of the data supporting the petition, EPA revised 
the proposed tolerance for cotton, undelinted seed from 0.015 ppm to 
0.02 ppm and strawberry from 0.06 to 0.05 ppm. The established 
tolerances are based on residue data using the EC

[[Page 18525]]

formulation. Residues from crop field trials using the suspension 
concentrate (SC) formulation of abamectin plus adjuvant are higher than 
the established tolerances on cotton and strawberry, which are based on 
the EC formulation; therefore, higher tolerances are needed for use of 
the SC formulation on cotton and strawberry. EPA revised the tolerance 
level based on analysis of the residue field trial data using the 
Agency's Tolerance Spreadsheet in accordance with the Agency's Guidance 
for Setting Pesticide Tolerances Based on Field Trial Data. 
Additionally, The Agency has revised the tolerance expression to 
clarify:
    1. That, as provided in FFDCA section 408(a)(3), the tolerance 
covers metabolites and degradates of abamectin not specifically 
mentioned; and
    2. That compliance with the specified tolerance levels is to be 
determined by measuring only the specific compounds mentioned in the 
tolerance expression.

V. Conclusion

    Therefore, tolerances are established for residues of abamectin 
(avermectin B1 a mixture of avermectins containing greater 
than or equal to 80% avermectin B1a (5-O-demethyl avermectin 
A1) and less than or equal to 20% avermectin B1b 
(5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin 
A1]) and its delta-8,9-isomer) in or on undelinted cotton 
seed at 0.02 ppm, cotton gin byproducts at 1.0 ppm, and strawberry at 
0.05 ppm.

VI. Statutory and Executive Order Reviews

    This final rule 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 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).

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: March 18, 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 180.449 is amended in paragraph (a) by:
0
i. Revising the introductory text.
0
ii. Revising in the table, the tolerance levels for Cotton, gin 
byproducts; Cotton, undelinted seed; and Strawberry to read as follows.


Sec.  180.449  Avermectin B1 and its delta-8,9-isomer; tolerances for 
residues.

    (a) General. Tolerances are established for residues of abamectin, 
including its metabolites and degradates, in or on the commodities in 
the following table. Compliance with the tolerance levels specified in 
the following table is to be determined by measuring only avermectin B1 
a mixture of avermectins containing greater than or equal to 80% 
avermectin B1 a (5-O-demethyl avermectin A1) and less than or equal to 
20% avermectin B1b (5-O-demethyl-25-de(1-methylpropyl)-25-(1-
methylethyl) avermectin A1) and its delta-8,9-isomer in or on the 
following commodities:

------------------------------------------------------------------------
                   Commodity                        Parts per  million
------------------------------------------------------------------------
 
                              * * * * * * *
------------------------------------------------------------------------
Cotton, gin byproducts.........................                      1.0
Cotton, undelinted seed........................                     0.02
 

[[Page 18526]]

 
                              * * * * * * *
------------------------------------------------------------------------
Strawberry.....................................                     0.05
------------------------------------------------------------------------
 
                              * * * * * * *
------------------------------------------------------------------------

[FR Doc. 2013-06916 Filed 3-26-13; 8:45 am]
BILLING CODE 6560-50-P