[Federal Register Volume 78, Number 54 (Wednesday, March 20, 2013)]
[Rules and Regulations]
[Pages 17123-17130]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-06191]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2010-0051; FRL-9381-1]


Amitraz; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of amitraz 
in or on honey and honeycomb. Arysta Lifescience America, Inc. 
requested the tolerance for honey under the Federal Food, Drug, and 
Cosmetic Act (FFDCA).

[[Page 17124]]


DATES: This regulation is effective March 20, 2013. Objections and 
requests for hearings must be received on or before May 20, 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-2010-0051 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: Stacey Groce, Registration Divison, 
Office of Pesticide Programs, Environmental Protection Agency, 1200 
Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone number: 
(703) 305-2505; 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.

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-2010-0051 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 20, 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-2010-0051 by one of 
the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/contacts.htm.

Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at http://www.epa.gov/dockets.

II. Summary of Petitioned-For Tolerance

    In the Federal Register of March 24, 2010 (75 FR 14154) (FRL-8815-
6), 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 
9F7673) by Veto-Pharma SA, c/o Arysta LifeScience America, 1450 
Broadway, 7th Floor, New York, NY 10018. The petition requested that 40 
CFR 180.287 be amended by establishing tolerances for residues of the 
insecticide, amitraz, (N'-[2,4-dimethylphenyl]-N-[[(2,4-
dimethylphenyl)imino]methyl]]-N-methylmethanimidamide) in or on honey 
at 1 part per million (ppm). That document referenced a summary of the 
petition prepared by Veto-Pharma, SA c/o Arysta, the registrant, which 
is available to the public in the docket, http://www.regulations.gov. 
There were no comments received in response to the notice of filing.
    Based upon review of data supporting the petition, EPA is 
establishing a lower tolerance for honey than was requested and is 
establishing a tolerance for honeycomb. The reasons for these changes 
are explained in detail 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 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 amitraz including exposure 
resulting from the tolerances established by this action. EPA's 
assessment of exposures and risks associated with amitraz 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

[[Page 17125]]

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.
    Acute toxicity studies in various laboratory animals indicate that 
amitraz is moderately toxic via the dermal route, and it is slightly 
toxic via the oral and not acutely toxic via inhalation routes of 
exposure. Further, it is not a skin or eye irritant, nor is it a skin 
sensitizer.
    Multiple species display evidence of neurotoxicity following 
exposure to amitraz. Clinical signs of neurotoxicity were seen across 
species, sexes, and routes of administration. Based on available human 
and animal studies, human subjects were shown to be more sensitive than 
any other species tested, followed by the dog. In both the oral 
subchronic and chronic studies in dogs, signs of central nervous system 
depression were observed along with a decrease in pulse rate and 
hypothermia noted in the subchronic study. In both the oral subchronic 
and chronic studies and in the 21-day inhalation study in the rat, 
irritability, nervousness and/or excitability were observed. In the 
rabbit developmental toxicity study, clinical signs that were 
considered to be related to treatment included languor and polypnea. 
Sedation was also observed in rabbits in the repeated dose dermal 
study. In the single dose human metabolism study, neurotoxic effects 
such as dry mouth, drowsiness, decreased temperature, and bradycardia 
were seen within 90 to 160 minutes after ingestion and persisted for up 
to 12 hours at the lowest dose tested (0.25 mg/kg/day).
    No developmental toxicity was seen at the highest dose tested in 
two pre-natal developmental toxicity studies in rats. Two independent 
developmental toxicity studies were available in rabbits. Although 
technical deficiencies were encountered in the conduct of these 
studies, no developmental effects were seen either at the highest dose 
tested (in one study) or in the presence of maternal toxicity (second 
study). When taken together, these studies show that (1) amitraz does 
not cause developmental toxicity in this species and (2) rabbits are 
not more sensitive than rats since the doses tested in the rabbits were 
higher than the doses tested in the rat developmental study where no 
developmental toxicity was seen at any dose level. The database 
contains a 1-generation and a 3-generation reproduction study in rats. 
In the 1-generation study, no reproductive toxicity was seen at the 
highest dose tested and offspring toxicity was seen in the presence of 
parental/systemic toxicity. In the 3-generation reproduction study, no 
reproductive toxicity was seen at the highest dose tested, however, 
offspring toxicity was seen at a lower dose than the dose that caused 
parental/systemic toxicity.
    The CNS effects of amitraz do not appear to be cumulative, i.e., do 
not accumulate with increased duration. In the 90-day repeat dose dog 
study, the CNS effects appear early on (within 3 hours of dosing), 
rapidly end, and recur daily after dosing throughout the study. In the 
chronic (2-year) dog study, the CNS effects are seen following a single 
dose on the first 2 days of the study, with transient hypothermia 
detected in only one female throughout the rest of the study, 
indicative of some potential adaptation occurring at lower doses over 
longer periods of testing. The NOAEL and LOAEL for the 90-day and 
chronic dog studies are the same, also indicating that the CNS effects 
are not cumulative, but are a response to each daily dose that is 
likely reversible if exposure were to stop. Additionally, the single 
dose (acute) studies across several species show an onset of CNS 
effects within a few hours and recovery within a few hours to several 
days. The human metabolism study showed neurotoxic effects shortly 
after dosing, which disappeared within 12 hours. Although the 
metabolism study was limited to two subjects, both human subjects 
exposed experienced clear CNS effects that were consistent with the 
animal data. Because of the reversibility of the CNS effects, exposures 
of all durations can be regarded as a series of repeating one-day 
(acute) exposures.
    For other effects, such as body weight changes and the tumors in 
the mouse study, those effects are likely to be cumulative. However, 
those effects occur at higher dose levels than the CNS depression. The 
human endpoint (0.125 mg/kg/day) will be protective of other longer 
term systemic effects as it is a lower dose level than the dose levels 
where these other systemic effects such as body weight change occur.
    Although a mouse carcinogenicity study showed that amitraz was 
associated with common tumors (liver and lung) in the mouse, EPA has 
determined that quantification of risk using a non-linear approach 
(i.e., RfD) for amitraz will adequately account for all chronic 
toxicity, including carcinogenicity, that could result from exposure to 
amitraz and its metabolites. That conclusion is based on the following 
considerations: (1) No carcinogenic response was seen in an acceptable 
rat cancer study; (2) the tumors found in the mouse are commonly seen 
in the mouse and were only found at a dose that appears to have been 
excessive given the other adverse effects seen in the animals; (3) 
amitraz is not mutagenic; and (4) although there is limited positive 
mutagenicity data and equivocal evidence of cancer for a minor amitraz 
metabolite, that equivocal cancer evidence was present only at high 
doses and was not consistent with the tumors seen in the amitraz study.
    More detailed information on the studies received and the nature of 
the adverse effects caused by amitraz 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 the document entitled, ``Amitraz: Aggregate 
Human Health Risk Assessment for Section 3 New Use in Beehives,'' dated 
January 8, 2013, by going to http://www.regulations.gov. The referenced 
document is available in the docket established by this action, which 
is described under ADDRESSES. Locate and click on the hyperlink for 
docket ID number EPA-HQ-OPP-2010-0051. Double-click on the document to 
view the referenced information on pages 15-19 of 48.

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://

[[Page 17126]]

www.epa.gov/pesticides/factsheets/riskassess.htm.
    A summary of the toxicological endpoints for amitraz used for human 
risk assessment is shown in the table of this unit.

     Table--Summary of Toxicological Doses and Endpoints for Amitraz for Use in Human Health Risk Assessment
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                                    Point of departure
        Exposure/scenario            and  uncertainty/    RfD, PAD, LOC for     Study and toxicological effects
                                      safety factors       risk assessment
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Acute dietary (General population  NOAEL = 0.125 mg/kg/  Acute RfD = 0.0125   A double-blind randomized
 including infants and children).   day.                  mg/kg/day.           crossover study in human
                                   UFH = 10x...........  aPAD = 0.00125 mg/    subjects. LOAEL = 0.25 mg/kg/day
                                   FQPA SF = UFDB = 10x   kg/day.              based on dry mouth, drowsiness,
                                                                               decreased temperature, decreased
                                                                               blood pressure and decreased
                                                                               heart rate.
Incidental oral short- and         NOAEL= 0.125 mg/kg/   Residential LOC for  A double-blind randomized
 intermediate term.                 day.                  MOE = 100.           crossover study in human
                                   UFH = 10x...........                        subjects. LOAEL = 0.25 mg/kg/day
                                   FQPA SF = UFDB = 10x                        based on dry mouth, drowsiness,
                                                                               decreased temperature, decreased
                                                                               blood pressure and decreased
                                                                               heart rate.
Dermal (All durations)...........  Oral NOAEL = 0.125    Residential LOC for  A double-blind randomized
                                    mg/kg/day.            MOE = 100.           crossover study in human
                                   Dermal Absorption                           subjects. LOAEL = 0.25 mg/kg/day
                                    Rate = 1.6%.                               based on dry mouth, drowsiness,
                                   UFH = 10x...........                        decreased temperature, decreased
                                   FQPA SF = UFDB = 10x                        blood pressure and decreased
                                                                               heart rate.
Inhalation (All durations).......  Oral NOAEL = 0.125    Residential LOC for  A double-blind randomized
                                    mg/kg/day.            MOE = 100.           crossover study in human
                                   UFH = 10x...........                        subjects. LOAEL = 0.25 mg/kg/day
                                   FQPA SF = UFDB = 10x                        based on dry mouth, drowsiness,
                                                                               decreased temperature, decreased
                                                                               blood pressure and decreased
                                                                               heart rate.
                                  ------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation)  EPA has determined that quantification of risk using a non-linear approach
                                    (i.e., RfD) will adequately account for all chronic toxicity, including
                                    carcinogenicity. Because of the reversibility of the CNS effects, exposures
                                    of all durations can be regarded as a series of repeating one-day (acute)
                                    exposures and there is no increase in hazard with increasing dosing
                                    duration. Therefore, the acute dietary endpoint is protective of the
                                    endpoints from repeat dosing studies, including cancer dietary exposures.
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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). RfD = reference dose. 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 amitraz, EPA considered exposure under the petitioned-for 
tolerances as well as all existing amitraz tolerances in 40 CFR 
180.287. EPA assessed dietary exposures from amitraz 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 amitraz. In estimating acute dietary exposure, EPA used food 
consumption information from the United States Department of 
Agriculture (USDA) 1994-1996 and 1998 Nationwide Continuing Surveys of 
Food Intake by Individuals (CSFII). As to residue levels in food, EPA 
conducted a partially refined acute dietary analysis using the Dietary 
Exposure Evaluation Model DEEM-FCID TM, Version 2.03 and 
assumed exposure through honey, imported cottonseed oil, meat and milk 
from dermal treatments of livestock. The residue values used for 
livestock products, except for milk, are based upon tolerance level 
residues. Milk residues were assessed using the high-end result from 
the original cattle dosing study. Percents of livestock treated were 
used. Residues in cottonseed oil were estimated using the tolerance 
level and percent crop imported. For honey, residue values from field 
trial data and 100% crop treated were used.
    ii. Chronic exposure. Based on data summarized in Unit lll.A., 
there is no increase in hazard from repeated exposures to amitraz; as 
such the acute dietary exposure assessment is protective of any chronic 
dietary exposures to amitraz because there is no increase in hazard 
with increasing dosing duration. Accordingly, a dietary exposure 
assessment for the purpose of assessing chronic dietary risk was not 
conducted.
    iii. Cancer. EPA determines whether quantitative cancer exposure 
and risk assessments are appropriate for a food-use pesticide based on 
the weight of the evidence from cancer studies and other relevant data. 
If quantitative cancer risk assessment is appropriate, cancer risk may 
be quantified using a linear or nonlinear approach. If sufficient 
information on the carcinogenic mode of action is available, a 
threshold or nonlinear approach is used and a cancer RfD is calculated 
based on an earlier noncancer key event. If carcinogenic mode of action 
data is not available, or if the mode of action data determines a 
mutagenic mode of action, a default linear cancer slope factor approach 
is utilized. Based on the data summarized in Unit III.A., the Agency 
has determined that quantification of risk using a nonlinear approach 
(i.e., RfD) would adequately account for all chronic toxicity, 
including carcinogenicity, that could result from exposure to amitraz. 
Therefore, the acute dietary assessment is protective of

[[Page 17127]]

any cancer effects resulting from amitraz residues in food.
    iv. Anticipated residue and percent crop treated (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 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: Cotton 
seed oil, 2%; beef meat, 0.3%; beef meat dried, 0.3%; beef meat 
byproducts, 0.3%; beef fat, 0.3%; beef kidney, 0.3%; beef liver, 0.3%; 
pork meat, 1.2%, pork skin, 1.2%; pork meat byproducts, 1.2%; pork fat, 
1.2%; pork kidney, 1.2%; pork liver, 1.2%; milk fat, 0.3%; milk non-fat 
solids, 0.3%; milk water, 0.3%; milk sugar, 0.3%.
    In most cases, EPA uses available data from United States 
Department 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%.
    For this request, the EPA relied on available data in USDA NASS for 
cattle and swine to determine the percent of animal heads treated with 
amitraz. NASS does not report the total number of dairy cattle treated 
with a particular chemical because the applications vary significantly 
based on product formulation, method of application, and pest stress at 
particular locations. Rather, they report chemical usage on a rate per 
head per application and rate per head per year basis. To determine the 
number of cattle treated, EPA divided the total pounds of amitraz 
applied by the total rate per head per year, which NASS defines as the 
average number of pounds applied counting multiple applications. It was 
assumed that the average rate captures the variation in number of cows 
treated.
    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 amitraz may be applied in a particular area.
    2. Dietary exposure from drinking water. Drinking water was not 
included in the dietary assessment as it was determined that amitraz is 
not expected to enter water-bodies or drinking water through the 
current and proposed uses.
    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). Amitraz is currently 
registered for the following uses that could result in residential 
exposures: Pet uses from dog collars and spot-on treatments. EPA 
assessed residential exposure using the following assumptions: There is 
a potential for residential exposure to amitraz from existing pet uses 
(dog collars and spot-on treatments), either from applying (handling) 
the products or from post-application contact with the treated dog. A 
dermal exposure assessment was performed for adults applying the 
amitraz pet products. For post-application exposure to treated dogs, a 
dermal assessment was performed for adults and a dermal and oral (hand 
to mouth) assessment was performed for children 1-2 years of age. 
Handler and post-application inhalation exposure is expected to be 
negligible and was not quantitatively assessed. EPA did not assess 
intermediate-term or chronic residential exposures because amitraz is 
acutely toxic and does not increase in potency with repeated dosing. 
Residential exposures of all durations can be regarded as a series of 
repeating one-day exposures based on the current toxicity database for 
amitraz, which suggests that the central nervous system effects of 
amitraz are not cumulative, but are a response to each daily dose.
    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.'' EPA has not found amitraz 
to share a common mechanism of toxicity with any other substances, and 
amitraz does not appear to produce a toxic metabolite produced by other 
substances. For the purposes of this tolerance action, therefore, EPA 
has assumed that amitraz does not have a

[[Page 17128]]

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/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 toxicology database is 
not complete to assess susceptibility following pre-and/or post natal 
exposure to amitraz. There was no evidence of increased susceptibility 
in rats since no developmental toxicity was seen at the highest dose 
tested in two independent pre-natal developmental toxicity studies in 
rats. Evidence for susceptibility in rabbits could not be ascertained 
due to technical deficiencies in the conduct of two independent 
developmental studies. However, the concern for the lack of 
susceptibility assessment is lessened because (1) in both studies, 
developmental effects occurred in the presence of maternal toxicity 
(one study) or at a dose higher than the dose that caused maternal 
toxicity (second study); (2) the doses tested in the rabbit studies 
were higher than the doses tested in developmental study in rats 
showing that rabbits are not more sensitive than rats. Two reproductive 
toxicity studies (1-generation and a 3-generation) are available; in 
the 1-generation study, no reproductive toxicity was seen at the 
highest dose tested and offspring toxicity was seen in the presence of 
parental/systemic toxicity. In the 3-generation reproduction study, no 
reproductive toxicity was seen at the highest dose tested, however, 
offspring toxicity was seen at a lower dose than the dose that caused 
parental/systemic toxicity. Both studies were deemed to be unacceptable 
due to technical deficiencies in the conduct of these studies. 
Neurotoxicity was seen in a variety of animal studies and in human 
subjects and the database does not contain specific neurotoxicity 
studies.
    3. Conclusion. The 10X FQPA Safety Factor (for the protection of 
infants and children) is retained in the form of a database uncertainty 
factor (UFDB), due to multiple toxicology data deficiencies 
for amitraz (i.e. reproduction, immunotoxicity, and DNT studies).
    i. The toxicity database for amitraz is incomplete, but adequate 
for purposes of risk assessment. An Extended One-Generation 
Reproductive Toxicity (EOGRT) study is required for amitraz to evaluate 
the reproductive, neurotoxic, and immunotoxic potential of amitraz.
    ii. Various mammalian species in multiple studies have demonstrated 
the signs of neurotoxicity for amitraz (i.e., sedation, hypothermia, 
drowsiness, etc). The DNT study will be a component of the EOGRT study, 
thus will specifically monitor the potential neurotoxicity of amitraz 
in targeted testing.
    iii. As mentioned in Unit III.D.2., the toxicology database is not 
complete to assess susceptibility following pre-and/or post natal 
exposure to amitraz.
    iv. There are no residual uncertainties identified in the amitraz 
exposure databases with regard to dietary or residential exposure and 
no outstanding exposure data gaps. The dietary assessments are based on 
conservative, health protective assumptions regarding exposure from 
food and are designed not to underestimate exposures. Residential 
exposures resulting from contact with dogs wearing amitraz pet collars 
is conservative. The residential risk estimates are based upon 
protective assumptions of application rate, duration of exposure, and 
contact with the treated animal. The fraction of application rate 
transferred, while non-chemical specific, represents the best data 
available to assess risk from exposures to the amitraz collar and will 
not underestimate risk. Drinking water was not included in the dietary 
assessment as it was determined that amitraz is not expected to enter 
water-bodies or drinking water through the current and proposed uses.
    A 10X FQPA safety factor is considered protective for the following 
reasons: (1) A clear NOAEL was used as the point of departure for risk 
assessment; (2) the NOAEL was from the most sensitive species; (3) the 
NOAEL is from an adequate study in humans that examined the most 
sensitive endpoint (neurotoxicity) seen in the animal data; (4) given 
the existing animal data, EPA expects that the most sensitive effect 
found in the EOGRT study will be a neurotoxic one; (5) EPA is applying 
a 10X intra-species safety factor to account for potential variability 
in the sensitivity in humans (including potentially greater sensitivity 
in infants and children than in the adults tested in the human study); 
and (6) in the 3-generation reproduction study, the only study showing 
the potential for increased susceptibility in offspring, offspring were 
less than 4X more sensitive than adult animals; retention of the 
additional default 10X safety factor for the protection of infants and 
children means that there will be a 100X factor to account primarily 
for potential sensitivity in the young even though the available 
(though incomplete) data show sensitivity in the young of no greater 
than 4X.

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. Using the exposure assumptions discussed in this 
unit for acute exposure, at the 99.9th percentile of exposure, the 
acute dietary exposure from food to amitraz will occupy 76% of the aPAD 
for children 1-2 years old, the population group receiving the greatest 
exposure.
    2. Chronic risk. Based on the data summarized in Unit lll.A., there 
is no increase in hazard with increasing dosing duration. In general, 
aggregate assessments combine average (chronic) dietary exposures with 
conservative residential exposures. However, in the case of amitraz, a 
chronic dietary assessment was not performed since the acute dietary 
assessment will result in higher estimated exposure levels and will 
therefore be protective of any chronic aggregate exposures.
    3. Short-term risk. Short-term aggregate exposure takes into 
account short-term residential exposure plus chronic exposure to food 
and water (considered to be a background exposure level). Amitraz is 
currently registered for uses that could result in short-term 
residential exposure. In general aggregate assessments combine average 
(chronic) dietary exposures with conservative residential exposures. 
However, in the case of amitraz, a

[[Page 17129]]

chronic dietary assessment was not performed since the acute dietary 
assessment will result in higher estimated exposure levels and will 
therefore be protective of any chronic exposures. As a screening level 
aggregate assessment, residential post-application exposures from the 
small to medium dog collar uses (the residential scenario resulting in 
the highest estimated exposures) were combined with acute dietary 
exposures at the 95th percentile of exposure. While aggregation using 
an average background exposure would more appropriately reflect 
expected exposures, in the absence of a chronic dietary assessment, use 
of acute exposures at the 95th percentile of exposure provides a high-
end aggregate risk screen.
    For children 1-2 years old, the most highly exposed children's 
subgroup, and for adults, using the exposure assumptions described in 
this unit for short-term exposures, EPA has concluded that the combined 
short-term food and residential exposures result in aggregate MOEs of 
120 and 450, respectively. For amitraz, MOEs of 100 or greater are not 
of concern.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account intermediate-term residential exposure plus chronic 
exposure to food and water (considered to be a background exposure 
level). An intermediate-term aggregate risk assessment was not 
conducted because amitraz is acutely toxic and its potency does not 
increase with repeated dosing. Therefore, the acute and short-term 
aggregate assessments are protective of intermediate-term aggregate 
risks anticipated from amitraz exposure.
    5. Aggregate cancer risk for U.S. population. For the reasons 
discussed in Unit lll.A., (cancer effects are non-linear and appear at 
higher doses than acute effects), and Unit lll.E.2., (chronic exposures 
are lower than acute exposures), the acute aggregate assessment is 
protective of potential cancer risk.
    6. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population or to infants and children from aggregate 
exposure to amitraz residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    There are two adequate methods, Methods I (designed for animal 
tissues and milk) and II (designed for plant commodities) available to 
enforce the proposed tolerances for honey and honeycomb. Both are GLC 
methods with electron capture detection (ECD), and involve conversion 
of residues of amitraz and its metabolites containing the 2,4-
dimethylaniline moiety to 2,4-DMA using acid and base hydrolysis, 
respectively. The methods 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. There are currently no established Codex MRLs for residues 
of amitraz in/or on honey or honeycomb.

C. Revisions to Petitioned-For Tolerances

    The petitioner requested a tolerance of 1.0 ppm for amitraz in 
honey. Based on field trial data (for honey and honeycomb) and using 
the Organization for the Economical Cooperation and Development (OECD) 
calculation procedure, the Agency determined that a tolerance of 0.2 
ppm for amitraz in honey would be adequate to cover residues from 
amitraz use in beehives and would harmonize with the European Union 
(EU) maximum residue level (MRL) for total amitraz in honey.
    The registrant did not request a tolerance for honeycomb in its 
petition to the Agency. However, based on the honeycomb field trial 
samples and use of the OECD calculation procedure, EPA has determined 
that a tolerance of 9 ppm is appropriate for honeycomb.
    Finally, 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 amitraz 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 the 
insecticide amitraz, (N'-[2,4-dimethylphenyl]-N-[[(2,4-
dimethylphenyl)imino]methyl]]-N-methylmethanimidamide), including its 
metabolites and degredates in or on honey at 0.2 ppm and honeycomb at 9 
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

[[Page 17130]]

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 7, 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. Section 180.287 is amended by revising paragraph (a) introductory 
text and by adding, alphabetically, the following commodities to the 
table in paragraph (a) to read as follows:


Sec.  180.287  Amitraz; tolerances for residues.

    (a) General. Tolerances are established for residues of the 
insecticide amitraz (N'-[2,4-dimethylphenyl]-N-[[(2,4-
dimethylphenyl)imino]methyl]]-N-methylmethanimidamide), including its 
metabolites and degradates, in or on the commodities in the following 
table. Compliance with the tolerance levels specified is to be 
determined by measuring amitraz residues convertible to 2,4-
dimethylaniline, expressed as the stoichiometric equivalent of amitraz, 
in or on the following raw agricultural commodities:

------------------------------------------------------------------------
                 Commodity                        Parts per million
------------------------------------------------------------------------
 
                                * * * * *
Honey......................................  0.2 ppm.
Honeycomb..................................  9 ppm.
 
                                * * * * *
------------------------------------------------------------------------

* * * * *
[FR Doc. 2013-06191 Filed 3-19-13; 8:45 am]
BILLING CODE 6560-50-P