[Federal Register Volume 74, Number 151 (Friday, August 7, 2009)]
[Rules and Regulations]
[Pages 39545-39551]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-19006]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2008-0806; FRL-8427-7]
Avermectin B1 and its delta-8,9-isomer; Pesticide
Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for combined residues
of avermectin B1 and its delta-8,9-isomer in or on stone
fruit crop group 12, tree nut crop group 14, pistachio, tuberous and
corm vegetable crop subgroup 01C, goat fat, hog fat, horse fat, sheep
fat, cattle fat, and cattle meat byproducts. Existing tolerances for
cattle, fat and cattle, meat byproducts are revised. Existing
individual crop tolerances on almond, plum, potato, and walnut are
deleted and replaced by the establishment of new crop group tolerances.
Existing tolerances on almond, hulls and plum, prune, dried are
retained. This regulation also makes a technical correction to
correctly express the existing tolerances for mint (replace term
``mint'' with the more specific terms ``peppermint, tops'' and
``spearmint, tops''). Syngenta Crop Protection, Inc. and Y-TEX
Corporation requested these tolerances under the Federal Food, Drug,
and Cosmetic Act (FFDCA).
DATES: This regulation is effective August 7, 2009. Objections and
requests for hearings must be received on or before October 6, 2009,
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: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2008-0806. All documents in the
docket are listed in the docket index available at http://
www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.
FOR FURTHER INFORMATION CONTACT: Thomas C. Harris, Registration
Division (7505P), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 308-9423; e-mail 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.
Potentially affected entities may include, but are not limited to those
engaged in the following activities:
[[Page 39546]]
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in
determining whether this action might apply to certain entities. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing electronically available documents at
http://www.regulations.gov, you may access this Federal Register
document electronically through the EPA Internet under the ``Federal
Register'' listings at http://www.epa.gov/fedrgstr. You may also access
a frequently updated electronic version of EPA's tolerance regulations
at 40 CFR part 180 through the Government Printing Office's e-CFR cite
at http://www.gpoaccess.gov/ecfr. To access the OPPTS Harmonized
Guidelines referenced in this document, go directly to the guidelines
at http://www.epa.gov/opptsfrs/home/guidelin.htm.
C. Can I File an Objection or Hearing Request?
Under section 408(g) of FFDCA, 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-2008-0806 in the subject line on the first
page of your submission. All requests must be in writing, and must be
mailed or delivered to the Hearing Clerk as required by 40 CFR part 178
on or before October 6, 2009.
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 that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit this copy, identified by docket ID number
EPA-HQ-OPP-2008-0806, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket Facility's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Docket Facility telephone number is (703) 305-5805.
II. Petition for Tolerance
As listed below, EPA published notices pursuant to section
408(d)(3) of FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of
pesticide petitions in the Federal Register requesting that 40 CFR
180.449 be amended by establishing a tolerance for combined residues of
the insecticide/miticide 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, as listed below. Avermectin B1 is also
referred to as abamectin. Each notice included a summary of the
petition prepared by the registrant listed. There were no comments
received in response to these notices of filing.
September 27, 2000, 65 FR 58080, FRL-6746-4, PP 0F6146. This
petition was filed by Novartis Crop Protection, Inc. (now Syngenta Crop
Protection, Inc.), P.O. Box 18300, Greensboro, NC 27419-8300 for
tolerances of avermectin B1 and its delta-8,9-isomer in or
on grass forage at 0.001 ppm, grass hay at 0.001 ppm, stone fruit crop
group 12 at 0.015 ppm, tree nut crop group 14 at 0.005 ppm, pistachio
at 0.005 ppm, and the tuberous and corm vegetable crop subgroup 01C at
0.005 ppm. Tolerances for avocado and mint which were also requested in
that notice were established earlier (see February 16, 2005, 70 FR
7876).
Based upon EPA review of the data supporting the petition, the
petition was subsequently amended to request permanent tolerances for
avermectin B1 and its delta-8,9-isomer at the revised levels
as follow: Stone fruit crop group 12 at 0.09 ppm, tree nut crop group
14 at 0.01 ppm, pistachios at 0.01 ppm, tuberous and corm vegetables
crop subgroup 01C at 0.01 ppm, goat fat at 0.01 ppm, hog fat at 0.01
ppm, horse fat at 0.01 ppm, and sheep fat at 0.01 ppm. The tolerance
requests for grass hay and grass forage were withdrawn pending
development of further data on grass hay. Existing individual crop
tolerances on almond, plum, potato, and walnut are deleted and replaced
by the establishment of new crop group tolerances. Existing tolerances
on almond, hulls and plum, prune, dried are retained. The proposed
tolerance levels were raised based on EPA's analysis of the residue
data, EPA's assessment of the limits of quantitation (LOQs) of the
analytical methods, current livestock feed items (OPPTS Guideline
860.100, Table 1 Feedstuffs, June 2008), and/or to coordinate with
Codex Maximum Residue Limits (MRLs) (see Unit IV.B.).
December 3, 2008, 73 FR 73648, FRL-8391-3, PP 8F7454. This petition
was filed by Y-TEX Corporation, 1825 Big Horn Avenue, P.O. Box 1450,
Cody, WY 82414, and proposes to amend the tolerances in 40 CFR 180.449
by increasing the tolerances of avermectin B1 and its delta-
8,9-isomer in or on cattle fat from 0.015 ppm to 0.03 ppm and cattle
meat byproducts from 0.02 ppm to 0.06 ppm. These tolerances support use
of avermectin in cattle ear tags.
This regulation also makes a technical amendment to correctly
express the existing tolerances for mint which were established in the
final rule published on February 16, 2005 (70 FR 7876) (FRL-7695-7).
That rule listed the tolerance as ``mint'' at 0.010 ppm. The correct
terminology is ``peppermint, tops'' at 0.010 ppm and ``spearmint,
tops'' at 0.010 ppm.
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
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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 section 408(b)(2)(D) of FFDCA, and the factors
specified in section 408(b)(2)(D) of FFDCA, 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 the petitioned-for
tolerances for combined residues of avermectin B1 and its
delta-8,9-isomer on stone fruit crop group 12 at 0.09 ppm, tree nut
crop group 14 at 0.01 ppm, pistachios at 0.01 ppm, tuberous and corm
vegetables crop subgroup 01C at 0.01 ppm, goat fat at 0.01 ppm, hog fat
at 0.01 ppm, horse fat at 0.01 ppm, sheep fat at 0.01 ppm, cattle fat
at 0.03 ppm, and cattle meat byproducts at 0.06 ppm. EPA's assessment
of exposures and risks associated with establishing tolerances 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.
Avermection B1 (also known as abamectin) has high to
moderate acute toxicity by the oral route, 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. In general, the results of available toxicity
studies with single or repeated dosing indicate that the main target
organ for avermection B1 is the nervous system, and that
decreased body weight is also one of the most frequent findings. There
was no observed estrogen, androgen, or thyroid mediated toxicity.
Neurotoxicity and developmental effects are 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 exposures. Increased susceptibility
(qualitative and/or quantitative) was seen in prenatal developmental
toxicity studies in mice and rabbits, and an increase in quantitative
and qualitative susceptibility was also seen in the rat reproductive
toxicity studies. Review of acceptable oncogenicity and mutagenicity
studies provide no indication that avermection B1 is
carcinogenic or mutagenic.
Specific information on the studies received and the nature of the
adverse effects caused by avermectin B1 and its delta-8,9-
isomer 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 the ``Abamectin,
Revised Human Health Risk Assessment for Proposed Uses on Pasture and
Rangeland Grass, Stone Fruit Crop Group 12, Tree Nut Crop Group 14,
Pistachio, Tuberous and Corm Vegetables Subgroup 01C, and Request for
Cattle Ear Tag Use,'' at page 18 in docket ID number EPA-HQ-OPP-2008-
0806.
B. Toxicological Endpoints
For hazards that have a threshold below which there is no
appreciable risk, a toxicological point of departure (POD) is
identified as the basis for derivation of reference values for risk
assessment. The POD may be defined as the highest dose at which no
adverse effects are observed (the NOAEL) in the toxicology study
identified as appropriate for use in risk assessment. However, if a
NOAEL cannot be determined, the lowest dose at which adverse effects of
concern are identified (the LOAEL) or a Benchmark Dose (BMD) approach
is sometimes used for risk assessment. Uncertainty/safety factors (UFs)
are used in conjunction with the POD to take into account uncertainties
inherent in the extrapolation from laboratory animal data to humans and
in the variations in sensitivity among members of the human population
as well as other unknowns. Safety is assessed for acute and chronic
dietary risks by comparing aggregate food and water exposure to the
pesticide to the acute population adjusted dose (aPAD) and chronic
population adjusted dose (cPAD). The aPAD and cPAD are calculated by
dividing the POD by all applicable UFs. Aggregate short-, intermediate-
, and chronic-term risks are evaluated by comparing food, water, and
residential exposure to the POD to ensure that the margin of exposure
(MOE) called for by the product of all applicable UFs is not exceeded.
This latter value is referred to as the Level of Concern (LOC).
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
greater than that 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 avermectin
B1 and its delta-8,9-isomer used for human risk assessment
can be found at http://www.regulations.gov in the document ``Abamectin,
Revised Human Health Risk Assessment for Proposed Uses on Pasture and
Rangeland Grass, Stone Fruit Crop Group 12, Tree Nut Crop Group 14,
Pistachio, Tuberous and Corm Vegetables Subgroup 01C, and Request for
Cattle Ear Tag Use,'' at page 25 in docket ID number EPA-HQ-OPP-2008-
0806.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to avermectin B1 and its delta-8,9-isomer, EPA
considered exposure under the petitioned-for tolerances as well as all
existing avermectin B1 and its delta-8,9-isomer tolerances
in (40 CFR 180.449). EPA assessed dietary exposures from avermectin
B1 and its delta-8,9-isomer 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.
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 used a
probabilistic distribution of anticipated residues derived from field
trial data for all commodities. Default processing factors and maximum
surveyed percent crop treated (PCT) were used as available. See Unit
C.1.iv. below for full listing of PCTs.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the food consumption data from the USDA 1994-1996
and 1998 CSFII. As to residue levels in food, EPA
[[Page 39548]]
used point estimates of anticipated residues derived from field trial
data for all commodities. Default processing factors and average
surveyed percent crop treated (PCT) were used as available. Also,
residues of avermectin B1 and its delta-8,9-isomer in foods
exposed in a food-handling establishment were assumed to be 0.0002 ppm
which is one-half the Limit of Detection (LOD). See Unit C.1.iv. below
for full listing of PCTs.
iii. Cancer. Based on the absence of a significant increase in
tumor incidence in two rodent studies, EPA classified avermectin
B1 as ``not likely to be carcinogenic to humans'' and, thus,
an exposure assessment for evaluating cancer risk is unnecessary.
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 used PCT information as follows (average and maximum,
respectively):
------------------------------------------------------------------------
Percent Crop Treated
(PCT)
Commodity ---------------------
Average Maximum
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Almond 50 75
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Apple 5 10
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Avocado 40 60
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Cantaloupe 15 30
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Celery 40 65
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Cottonseed oil 5 5
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Cucumber 5 10
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Grape 5 15
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Grape, raisin 5 15
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Grapefruit 60 80
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Honeydew 15 30
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Hop 85 100
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Lemon 30 50
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Lettuce 10 15
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Orange 20 40
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Pear 65 80
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Pepper 25 100
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Potato 1 2.5
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Pumpkin 2.5 5
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Spinach 20 45
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Squash 5 10
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Strawberry 35 45
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Tangerine 40 45
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Tomato 15 100
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Walnut 5 20
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Watermelon 5 10
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EPA assumed 100 PCT (both average and maximum) for other crops not
listed above, and for all livestock commodities. Maximum PCT was used
for analysis of acute exposure while average PCT was used for analysis
of chronic exposure.
In most cases, EPA uses available data from the U.S. 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 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 <1. 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 avermectin B1 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 avermectin B1 and its major soil degradate (a
mixture of an 8-alpha-hydroxy and a ring opened aldehyde derivative) in
drinking water. These simulation models take into account data on the
physical, chemical, and fate/transport characteristics of avermectin
B1 and its major soil degradate (a mixture of an 8-alpha-
hydroxy and a ring opened aldehyde derivative). 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) for surface water and Screening Concentration in
[[Page 39549]]
Ground Water (SCI-GROW) models for ground water, the estimated drinking
water concentrations (EDWCs) of avermectin B1 and its major
soil degradate (a mixture of an 8-alpha-hydroxy and a ring opened
aldehyde derivative) for acute exposures are estimated to be 0.464
parts per billion (ppb) for surface water and 0.00184 ppb for ground
water; and for chronic exposures for non-cancer assessments are
estimated to be 0.211 ppb for surface water and 0.00184 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 0.464 ppb was used to
assess the contribution to drinking water. For chronic dietary risk
assessment, the water concentration of value 0.211 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).
Avermectin B1 is currently registered for the following
uses that could result in residential exposures: Residential lawn
application for fire ant control, and residential indoor crack and
crevice application for cockroaches and ants. EPA assessed residential
exposure as follows. Exposure and risk estimates for homeowners
applying crack and crevice baits were estimated using the Standard
Operating Procedure (SOP) for Residential Exposure Assessments. The
unit exposure from the wettable powder, open mixing and loading
scenario listed in the SOP for Residential Exposure Assessments was
used as a surrogate for estimating dermal and inhalation exposure for
an activity that involves the use of a small syringe-type duster to
make bait placements along the baseboards and into cracks and crevices.
The method used for estimating residential applicator exposure is
believed to produce a high-end estimate of exposure.
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 avermectin B1 to share a common
mechanism of toxicity with any other substances, and avermectin
B1 does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action, therefore,
EPA has assumed that avermectin B1 does not have a common
mechanism of toxicity with other substances. For information regarding
EPA's efforts to determine which chemicals have a common mechanism of
toxicity and to evaluate the cumulative effects of such chemicals, see
EPA's website 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. Increased susceptibility was
seen in prenatal developmental toxicity studies in mice and rabbits
following in utero exposure to avermectin B1. There was also
an increase in susceptibility in the rat reproductive toxicity study
and the rat developmental neurotoxicity study.
3. Conclusion. EPA has retained an additional FQPA SF for chronic/
long-term and short/intermediate-term assessments due to the steepness
of the dose-response curve and severity of effects (death) at the
LOAEL. For all risk assessments involving repeat exposures, the
selected toxicity endpoint is based on the decrease in pup body weight
seen in the developmental neurotoxicity study and three reproduction
studies in the rat. Although the study identified a NOAEL for the
effects observed in the pups, the data clearly indicate that the
decrease in pup body weight seen at 0.2 mg/kg/day rapidly progresses to
death at the next higher tested dose level (0.4 mg/kg/day) in both
reproduction and developmental neurotoxicity studies. The combined data
from several reproduction toxicity and developmental neurotoxicity
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 greater than the 2x between NOAEL
and LOAEL here, 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 such a severe effect.
Nonetheless, EPA has determined that reliable data show the safety
of infants and children would be adequately protected if the 10X FQPA
safety (SF) were reduced to 3X for chronic/long term and short/
intermediate-term assessments and reduced to 1X for acute assessments.
This conclusion is based on the following findings:
i. 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 with the
steepness of the dose response curve and the severe effects seen here.
ii. This adjusted point of departure (0.04 mg/kg/day) would also
address the concerns for the increased susceptibility seen at higher
doses in the two-generation reproduction study in rats (LOAEL = 0.4 mg/
kg/day), prenatal developmental study in CD-1 mice (LOAEL = 0.75 mg/kg/
day), the prenatal developmental toxicity study in rabbits (LOAEL = 2
mg/kg/day), and the one-generation reproduction study (LOAEL = 0.2 mg/
kg/day).
iii. The toxicity database for avermectin B1 is
complete, except for immunotoxicity studies. EPA began requiring
functional immunotoxicity testing of all food and non-food use
pesticides on December 26, 2007. To address the issue of an
immunotoxicity data gap and the associated database uncertainty factor,
the Agency examined the entire database of avermectin B1 and
determined that an additional uncertainty factor is not needed to
account for potential immunotoxicity. Avermectin B1 has not
been found to induce effects associated with immunotoxicity and
avermectin B1 does not belong to a class of chemicals that
would be expected to be immunotoxic. Therefore, based on the above
considerations, EPA does not believe that conducting a special
Harmonized Guideline series 870.7800 immunotoxicity study will result
in a NOAEL less than the NOAELs of 0.5 and 0.12 mg/kg/day already set
for avermectin B1 acute and repeated
[[Page 39550]]
exposures, respectively. An additional uncertainty factor
(UFDB) for database uncertainties associated with
immunotoxicity does not need to be applied at this time.
iv. With respect to acute dietary exposure, the endpoint selected
for risk assessment is based on mydriasis observed in dogs. The
additional 3x factor applied to chronic and other exposure scenarios is
not applicable to acute exposure because steepness of the dose and
severity of effects were not seen in the studies where mydriasis
occurred. In addition, reduced body weight is not considered a single
dose effect and would not be appropriate as a toxicity endpoint for
acute exposure scenarios.
v. There are no residual concerns with respect to the exposure
databases. The chronic and acute dietary food exposure assessment
utilizes reliable data on anticipated residues and percent crop treated
as well as default processing factors. The dietary drinking water
assessment utilized modeling results which included conservative
assumptions for the parent and all degradates of concern. Conservative
assumptions were used in the water models. Therefore, the water
exposure assessment will not underestimate the potential risks for
infants and children. Likewise, the use of maximum application rates
and central-to-high end inputs results in calculated residential
exposures that should not underestimate the risks to infants and
children from these requested uses.
E. Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic pesticide exposures are
safe by comparing aggregate exposure estimates to the acute population
adjusted dose (aPAD) and chronic population adjusted dose (cPAD). The
aPAD and cPAD represent the highest safe exposures, taking into account
all appropriate SFs. EPA calculates the aPAD and cPAD by dividing the
POD by all applicable UFs. For linear cancer risks, EPA calculates the
probability of additional cancer cases 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 POD to ensure that the MOE called for by the product of
all applicable UFs is not exceeded.
1. Acute risk. The acute aggregate risk assessment takes into
account exposure from dietary (food and water) consumption. Using the
exposure assumptions discussed in this unit for acute exposure, the
acute dietary exposure from food and water to avermectin B1
and its delta-8,9-isomer will occupy 27% of the aPAD for children 1 to
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
avermectin B1 and its delta-8,9-isomer from food and water
will utilize 47% of the cPAD for children 1 to 2 years old, the
population group receiving the greatest exposure. Based on the
explanation in Unit III.C.3., regarding residential use patterns,
chronic residential exposure to residues of avermectin B1
and its delta-8,9-isomer is not expected.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account short-term residential exposure
plus chronic exposure to food and water (considered to be a background
exposure level). High-end estimates of residential exposure were used,
while average values were used for food and drinking water exposure.
Avermectin B1 is currently registered for uses that could
result in short- and intermediate-term residential exposure and the
Agency has determined that it is appropriate to aggregate chronic
exposure through food and water with short- and intermediate-term
residential exposures to avermectin B1 and its delta-8,9-
isomer. Using the exposure assumptions described in this unit for
short-term exposures, EPA has concluded the combined short- and
intermediate-term food, water, and residential exposures result in
aggregate MOEs of 500 for children 1 to 2 years old, the population
group receiving the greatest exposure.
4. Aggregate cancer risk for U.S. population. Based on the absence
of a significant increase in tumor incidence in two rodent studies, EPA
classified avermectin B1 as ``not likely to be carcinogenic
to humans'' and it is, therefore, not expected to pose a cancer risk.
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 avermectin B1 and its delta-8,9-isomer residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methods for avermectin B1 in plant
and livestock commodities are available in PAM II. The methods have
been validated for citrus and processed fractions (Method I), ginned
cottonseed (Method IA), and bovine tissues and milk (Method II). These
methods determine residues in plant and livestock commodities at limits
of quantitation of 0.02 ppm for meat and meat byproducts and <=0.01 ppm
for other plant/livestock commodities. The limits of detection of the
methods for plant and livestock commodities is 0.001 ppm for each
analyte, equivalent to 0.002 ppm for two analyte peaks (i.e.,
avermectin B1a and its delta-8,9-isomer in one peak and
avermectin B1b and its delta-8,9-isomer in the other peak).
The plant methods used for data collection adequately measure the
residues of concern. The methods have been validated at 0.001, 0.002,
or 0.005 ppm (depending on the commodity and the method) for each of
two analyte peaks (avermectin B1a and its delta-8,9-isomer
in one peak and avermectin B1b and its delta-8,9-isomer in
the other peak), which means that the LOQs of the data collection
methods would be 0.002, 0.004 or 0.01 ppm.
The 1990 Pestrak database indicates that avermectin B1
and its metabolites are not recovered or not likely to be recovered by
FDA multiresidue methods. Therefore, the multiresidue methods can not
be used to determine residues for dietary exposure assessment and can
not be used as the primary enforcement method.
B. International Residue Limits
The Codex tolerance expressions for plants are consistent with the
U.S. tolerance expression.
C. Response to Comments
No comments were received to the Notices of Filing.
D. Revisions to Petitioned-For Tolerances
The correct commodity definitions are obtained from the ``Food and
Feed Commodity Vocabulary'', which can be found at http://www.epa.gov/
pesticides/foodfeed. Some proposed tolerance levels were raised based
on EPA's analysis of the residue data, EPA's assessment of the limits
of quantitation of the analytical methods, current livestock feed items
(OPPTS Guideline 860.100, Table 1 Feedstuffs, June 2008), and/or to
coordinate with Codex Maximum Residue Limits (MRLs).
V. Conclusion
Therefore, tolerances are established for combined residues of
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-
[[Page 39551]]
methylpropyl)-25-(1-methylethyl) avermectin A1)), and its
delta-8,9-isomer in/on cattle, fat at 0.03 ppm; cattle, meat byproducts
at 0.06 ppm; fruit, stone, group 12 at 0.09 ppm; goat, fat at 0.01 ppm;
hog, fat at 0.01 ppm; horse, fat at 0.01 ppm; nut, tree, group 14 at
0.01 ppm; pistachio at 0.01 ppm; sheep, fat at 0.01 ppm; and vegetable,
tuberous and corm subgroup 01C at 0.01 ppm.
Existing tolerances for cattle, fat and cattle, meat byproducts are
revised. Existing individual crop tolerances on almond, plum, potato,
and walnut are deleted and replaced by the establishment of new crop
group tolerances. Existing tolerances on almond, hulls and plum, prune,
dried are retained. The expression for existing mint tolerances is
corrected by deleting the term mint and replacing with peppermint, tops
at 0.010 ppm and spearmint, tops at 0.010 ppm.
VI. Statutory and Executive Order Reviews
This final rule establishes tolerances under section 408(d) of
FFDCA 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 section 408(d) of FFDCA, 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 section 408(n)(4) of FFDCA. 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) (Public Law 104-4).
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), Public Law 104-113, section 12(d) (15 U.S.C. 272
note).
VII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. 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 this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: July 28, 2009.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.
0
Therefore, 40 CFR chapter I is amended as follows:
PART 180--AMENDED
0
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. In Sec. 180.449, the table to paragraph (a) is amended by revising
the entries for cattle, fat and cattle, meat byproducts; by removing
the entries for almond, plum, mint, potato and walnut; and by adding
alphabetically, the remaining entries in the table to read as follows:
180.449 Avermectin B1 and its delta-8,9-isomer; tolerances
for residues.
(a) * * *
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
* * * * *
Cattle, fat.................................................. 0.03
Cattle, meat byproducts...................................... 0.06
* * * * *
Fruit, stone, group 12....................................... 0.09
Goat, fat.................................................... 0.01
* * * * *
Hog, fat..................................................... 0.01
* * * * *
Horse, fat................................................... 0.01
* * * * *
Nut, tree, group 14.......................................... 0.01
* * * * *
Peppermint, tops............................................. 0.010
Pistachio.................................................... 0.01
* * * * *
Sheep, fat................................................... 0.01
* * * * *
Spearmint, tops.............................................. 0.010
Vegetable, tuberous and corm, subgroup 01C................... 0.01
------------------------------------------------------------------------
* * * * *
FR Doc. E9-19006 Filed 8-6-09; 8:45 am
BILLING CODE 6560-50-S