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ENVIRONMENTAL PROTECTION AGENCY
Environmental Protection Agency
CFR Citation: 40 CFR Part 180
OPP ID: [OPP-2003-0220; FRL-7316-6]
NOTICE: RULES
ACTION: Pesticides; tolerances in food, animal feeds, and raw agricultural commodities:
DOCUMENT ACTION: Final rule.
SUBJECT CATEGORY: AGENCY: Environmental Protection Agency (EPA).
DATES: This regulation is effective July 9, 2003. Objections and requests for hearings, identified by docket ID number OPP20030220, must be received on or before September 8, 2003.
DOCUMENT SUMMARY: This regulation establishes a tolerance for combined residues of emamectin and its metabolites in or on Brassica leafy vegetables (crop group 5); turnip greens; cotton, undelinted seed; cotton gin byproduct; leafy vegetables (except Brassica) (crop group 4); fruiting vegetables (crop group 8); and tomato paste. In addition, tolerances are established for indirect or inadvertent combined residues of emamectin and the associated 8,9Z isomers in or on milk and fat of cattle, goats, hogs, horses, and sheep; meat byproducts, except liver, of cattle, goats, hogs, horses , and sheep; liver of cattle, goats, hogs, horses, and sheep; and meat of cattle, goat, hogs, horses, and sheep. Syngenta Crop Protection, Inc. requested this tolerance under the Federal Food, Drug, and Cosmetic Act (FFDCA) , as amended by the Food Quality Protection Act of 1996 (FQPA).
SUMMARY: Emamectin,
SUPPLEMENTAL INFORMATION
I. General InformationA. 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: [sbull] Crop Production (NAICS 111, e.g.)
[sbull] Animal Production (NAICS 112, e.g.)
[sbull] Food Manufacturing (NAICS 311, e.g.)
[sbull] Pesticide Manufacturing (NAICS 32532, e.g.)
This listing is not intended to be exhaustive, but rather provides
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 Get Copies of this Document and Other Related Information?
1. Docket. EPA has established an official public docket for this
action under docket identification (ID) number OPP20030220. The
official public docket consists of the documents specifically
referenced in this action, any public comments received, and other
information related to this action. Although a part of the official
docket, the public docket does not include Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute. The official public docket is the collection of materials
that is available for public viewing at the Public Information and
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/. A frequently updated
electronic version of 40 CFR part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfr180_00.html , a
beta site currently under development. To access the OPPTS Harmonized
Guidelines referenced in this document, go directly to the guidelines
at http://www.epa.gov/opptsfrs/home/guidelin.htm.
An electronic version of the public docket is available through EPA's electronic public docket and comment system, EPA Dockets. You may use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public comments, access the index listing of the contents of the official public docket, and to access those documents in the public docket that are available electronically. Although not all docket materials may be available electronically, you may still access any of the publicly available docket materials through the docket facility identified in Unit I.B.1. Once in the system, select ``search,'' then key in the appropriate docket ID number.
II. Background and Statutory Findings
In the Federal Register of March 20, 2002 (67 FR 12990) (FRL6824 4), EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 346a, as amended by FQPA (Public Law 104170), announcing the filing of a pesticide petition (PP 7F4845) by Syngenta Crop Protection, Inc., P.O. Box 18300, Greensboro, NC 27419. That notice included a summary of the petition prepared by Syngenta Crop Protection, Inc., the registrant. There were no comments received in response to the notice of filing.
The original petition requested that 40 CFR 180.505 be amended by
establishing a tolerance for combined residues of the insecticide
emamectin benzoate, 4'epimethylamino4'deoxyavermectin B
deoxyavermectin B
Based on the EPA analysis of the residue chemistry and
toxicological databases, the petition was subsequently revised to
express the tolerance as the combined residues of emamectin, (a mixture of a minimum of 90% 4"epimethylamino4"deoxyavermectin
B
avermectin B
B
methyl)aminoavermectin (MFB
Section 408(b)(2)(A)(i) of the 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 the 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 the FFDCA requires EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to ``ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical
residue....''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the regulatory
[[Page 40793]]
requirements of section 408 of the FFDCA and a complete description of
the risk assessment process, see the final rule on Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL57547).
III. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D) of the 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, consistent with section
408(b)(2) of the FFDCA, for a tolerance for combined residues of
emamectin, (a mixture of a minimum of 90% 4"epimethylamino4"
deoxyavermectin B
avermectin B
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. The nature of the toxic effects caused by emamectin are
discussed in Table 1 of this unit as well as the noobservedadverse
effectlevel (NOAEL) and the lowestobservedadverseeffectlevel (LOAEL) from the toxicity studies reviewed.
Table 1.Subchronic, Chronic, and Other Toxicity
Guideline No. Study Type Results
870.3100 Subchronic Systemic Toxicity
FeedingRat MK NOAEL=2.5 mg/kg/day.
0243 Systemic Toxicity
LOAEL=5 mg/kg/day
based on tremors,
hindlimb splaying,
urogenital staining,
histological changes
in brain and spinal
cord, sciatic and
optic nerves and
skeletal muscles in
males, emaciation,
reduced body weight
and reduced food
consumption in both sexes.
870.3150 Subchronic Systemic Toxicity
FeedingDog MK NOAEL=0.25 mg/kg.
0243 Systemic Toxicity
LOAEL=0.50 mg/kg
based on microscopic
pathological signs
of neurotoxicity
consisting of
skeletal muscle
atrophy and white
matter multifocal
degeneration in the
brains of both sexes
and white matter
multifocal
degeneration in the
spinal cords of males.
870.3200 21Day Dermal No Study Available. ToxicityRat
870.3700 Developmental Maternal Toxicity
ToxicityRat MK NOAEL=2 mg/kg/day.
0243 Maternal Toxicity
LOAEL=4 mg/kg/day
based on a
significant trend
towards decreased
body weight gain
during the dosing
period.
Developmental
Toxicity NOAEL=4 mg/
kg/day.
Developmental
Toxicity LOAEL=8 mg/
kg/day based on
altered growth and
an increased
incidence of
supernumerary rib.
870.3700 Developmental Maternal Toxicity
ToxicityRabbit NOAEL=3 mg/kg/day.
MK0243 Maternal Toxicity
LOAEL=6 mg/kg/day
based on a
significant trend
towards decreased
body weight gain
during dosing period
and increased
clinical signs
(mydriasis and
decreased pupillary
reaction).
Developmental
Toxicity NOAEL=6 mg/
kg/day.
Developmental
Toxicity LOAEL=Not
Determined.
870.3800 Reproductive Systemic Toxicity
ToxicityRat MK NOAEL=0.6 mg/kg/day.
0244 Systemic Toxicity
LOAEL=1.8 mg/kg/day
based on decreased
body weight gain and
histopathological
changes (neuronal
degeneration in the
brain and spinal
cord) in both sexes
and generations.
Reproductive
Toxicity NOAEL=0.6
mg/kg/day.
Reproductive
Toxicity LOAEL=1.8
mg/kg/day based on
decreased fecundity
and fertility
indices and clinical
signs (tremors and
hind limb extension)
in offspring of both
generations. [[Page 40794]]
870.4100 ChronicFeeding Systemic Toxicity
Dog MK0244 NOAEL= 0.25 mg/kg/ day.
Systemic Toxicity
LOAEL=0.5 mg/kg/day
based on axonal
degeneration in the
pons, medulla and
peripheral nerves
(sciatic, sural, and
tibial) in both
sexes, clinical
signs of
neurotoxicity (whole
body tremors,
stiffness of the
hind legs), spinal
cord axonal
degeneration, and
muscle fiber
degeneration in
females.
870.4100 Chronic Feeding Systemic Toxicity
Rat MK0244 NOAEL=1.0 mg/kg/day.
Systemic Toxicity
LOAEL=2.5 mg/kg/day,
based on increased
incidence of
neuronal
degeneration in the
brain and spinal
cord, decreased
rearing, and an
increased incidence
of animals with low
arousal.
870.4200 Carcinogenicity Systemic Toxicity
Mouse (78week) NOAEL=2.5 mg/kg/day.
MK0244 Systemic Toxicity
LOAEL=5.0 mg/kg/day
for males and 7.5 mg/
kg/day for females
based on increased
mortality, decreased
weight gain,
neurological signs,
and increased
incidence of
severity of
infections. There
were no signs of
carcinogenicity in
this study.
870.4300 Chronic Toxicity/ Systemic Toxicity
Carcinogenicity NOAEL=1.0 mg/kg/day.
Rat Emamectin Systemic Toxicity
LOAEL=2.5/5.0 mg/kg/
day based on marked
neural degeneration
in the brain and
spinal cord of both
sexes, brain white
matter degeneration
in males, and on
decreased body
weight, body weight
gain, and food
efficiency in males.
There were no signs
of carcinogenicity
in this study.
Note: The initial
dose of the high
dose group was 5.0
mg/kg/day. Due to
unacceptable weight
loss and/or tremors
occurring at this
dose in another
concurrent study
(TT
657,831; L
695,638; L
930,905
(photometabolite
s of MK0244)
870.5300 Gene Mutation in Negative for the
Cultured V79 induction of forward
Chinese Hamster gene mutations in
Lung Cells MK Chinese hamster lung
0243 fibroblast cells up
to a severely
cytotoxic
nonactivated dose of
0.01mM or a severely
cytotoxic S9
activated dose of
0.04mM.
870.5385 Structural Negative for the
Chromosome induction of
Aberrationin chromosome
vivo mouse bone aberrations in the
marrowMK0244 bone marrow cells of
male CD1 mice.
870.5500 DNA DamageRat Negative for the
hepatocytes MK induction of single
0243 strand breaks (SBs)
in DNA of rat
hepatocytes.
870.6200 Acute Oral A Neurotoxicity NOAEL
Neurotoxicity was not established,
Rat MK0243 since toxic signs of
neurotoxicity as
well as histological
lesions in the
brain, spinal cord
and sciatic nerve
occurred at all
doses tested (27.4,
54.8 or 82.2 mg/kg)
870.6200 Subchronic Neurotoxicity
Neurotoxicity NOAEL=1.0 mg/kg/day.
Rat MK0243 LOAEL=5.0 mg/kg/day
(highest dose
tested) based on
mild tremors,
posture, rearing,
excessive
salivation, fur
appearance, gait,
strength, mobility
and righting reflex.
870.6200 2Week Dietary Neurotoxicity
NeurotoxicityCD NOAEL=2.0 mg/kg/day
1 Mice MK0243 (highest dose
tested). No
characteristic
neuronal lesions in
the brain, spinal
cord or sciatic
nerve in mice of
high dose group (2.0
mg/kg/day).
870.6200 15day Dietary Neurotoxicity
NeurotoxicityCF NOAEL=0.075 mg/kg/ 1 Mice MK244 day.
LOAEL=0.10 mg/kg/day
based on tremors
observed beginning
on day 3, decreases
in body weight and
food consumption as
well as degeneration
of the sciatic nerve.
[[Page 40795]]
870.6200 Dietary Neurotoxicity NOAEL
NeurotoxicityCF <0.1 mg/kg/day. One
1 Mice L660,599 of the lowdose
Supplementary males had tremors,
Study hunched posture and
piloerection on day 14.
870.6300 Developmental Maternal Toxicity
Neurotoxicity NOAEL=3.6/2.5 mg/kg/
Rat MK0244 day (highest dose
tested).
Developmental
Neurotoxicity
NOAEL=0.10 mg/kg/day
(lowest dose
tested). The LOAEL
is 0.60 mg/kg/day
based on the dose
related decrease in
open field motor
activity in females
at postnatal day 17.
870.7485 MetabolismRat Radiolabeled MAB
B. Toxicological Endpoints
The dose at which no adverse effects are observed (the NOAEL) from the toxicology study identified as appropriate for use in risk assessment is used to estimate the toxicological level of concern (LOC). However, the lowest dose at which adverse effects of concern are identified (the LOAEL) is sometimes used for risk assessment if no NOAEL was achieved in the toxicology study selected. An uncertainty factor (UF) is applied to reflect 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. An UF of 100 is routinely used, 10X to account for interspecies differences and 10X for intraspecies differences.
As explained below in Unit III.D.3, EPA determined that the special
FQPA SF be reduced to 1x. However, EPA also determined that an
additional 3x Modifying Uncertainty Factor (UF
neurotoxicity study) to acute and shortterm scenarios, to account for
the steepness of the doseresponse curve and the severity of effects at
the LOAEL (death and neuropathology). A 3x UF
For dietary risk assessment (other than cancer) the Agency uses the UF to calculate an acute or chronic reference dose (acute RfD or chronic RfD) where the RfD is equal to the NOAEL divided by the appropriate UF (RfD = NOAEL/UF). Where an additional safety factor (SF) is retained due to concerns unique to the FQPA, this additional factor is applied to the RfD by dividing the RfD by such additional factor. The acute or chronic population adjusted dose (aPAD or cPAD) is a modification of the RfD to accommodate this type of FQPA SF.
For nondietary risk assessments (other than cancer) the UF is used to determine the LOC. For example, when 100 is the appropriate UF (10X to account for interspecies differences and 10X for intraspecies differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and compared to the LOC.
The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q*
approach assumes that any amount of exposure will lead to some degree
of cancer risk. A Q* is calculated and used to estimate risk which
represents a probability of occurrence of additional cancer cases
(e.g., risk is expressed as1 x 106 or one in a million).
Under certain specific circumstances, MOE calculations will be used for
the carcinogenic risk assessment. In this nonlinear approach, a
``point of departure'' is identified below which carcinogenic effects
are not expected. The point of departure is typically a NOAEL based on
an endpoint related to cancer effects though it may be a different
value derived from the dose response curve. To estimate risk, a ratio of the point of
[[Page 40796]]
departure to exposure (MOE
Table 2.Summary of Toxicological Dose and Endpoints for emamectin for Use in Human Risk Assessment
Special FQPA SF* and
Exposure Scenario Dose Used in Risk Level of Concern for Study and Toxicological
Assessment, UF Risk Assessment Effects
Acute Dietary (All populations) NOAEL = 0.075 mg/kg/day Special FQPA SF = 1 15day mouse
UF = 300............... aPAD = acute RfD/ FQPA LOAEL = 0.1 mg/kg/day
Acute RfD = 0.00025 mg/ SF = 0.00025 mg/kg/day. based tremors on day 3
kg/day. of dosing.
Chronic Dietary (All populations) NOAEL= 0.075 mg/kg/day Special FQPA SF = 1 15day mouse
UF = 1,000............. cPAD = chronic RfD/FQPA LOAEL = 0.1 mg/kg/day
Chronic RfD = 0.000075 SF = 0.000075 mg/kg/ based on moribund
mg/kg/day. day. sacrifices, clinical
signs of
neurotoxicity,
decreases in body
weight and food
consumption and
histopathological
lesions in the sciatic
nerve.
ShortTerm Incidental Oral (130 Toxicological endpoints were not selected since there are no residential
days) uses at the present time and thus no potential exposure via this
scenario.
IntermediateTerm Incidental Oral (1 Toxicological endpoints were not selected since there are no residential
6 months) uses at the present time and thus no potential exposure via this
scenario
ShortTerm Dermal (1 to 30 days) Oral study NOAEL= 0.075 Occupational LOC for 15day mouse
mg/kg/day (dermal MOE = 300 LOAEL = 0.1 mg/kg/day
absorption rate = 1.8 Residential LOC for based on moribund
%) MOE: N/A. sacrifices, clinical
signs of
neurotoxicity,
decreases in body
weight and food
consumption and
histopathological
lesions in the sciatic
nerve.
IntermediateTerm Dermal (1 to 6 Oral study NOAEL= 0.075 Occupational LOC for 15day mouse
months) mg/kg/day (dermal MOE = 1,000 LOAEL = 0.1 mg/kg/day
absorption rate = 1.8 Residential LOC for based on moribund
%) MOE: N/A. sacrifices, clinical
signs of
neurotoxicity,
decreases in body
weight and food
consumption and
histopathological
lesions in the sciatic
nerve.
LongTerm Dermal (>6 months) Long term dermal exposure is not expected and there are no residential
uses at the present time. Therefore, quantification of risk is not
required.
ShortTerm Inhalation (1 to 30 days) Oral study NOAEL= 0.075 Occupational LOC for 15day mouse
mg/kg/day MOE = 300 LOAEL = 0.1 mg/kg/day
(inhalation absorption Residential LOC for based on moribund
rate = 100%). MOE: N/A. sacrifices, clinical
signs of
neurotoxicity,
decreases in body
weight and food
consumption and
histopathological
lesions in the sciatic
nerve.
IntermediateTerm Inhalation (1 to 6 Oral study NOAEL= 0.075 Occupational LOC for 15day mouse
months) mg/kg/day (inhalation MOE = 1,000 LOAEL = 0.1 mg/kg/day
absorption rate = Residential LOC for based on moribund
100%) MOE: N/A. sacrifices, clinical
signs of
neurotoxicity,
decreases in body
weight and food
consumption and
histopathological
lesions in the sciatic
nerve.
LongTerm Inhalation (>6 months) Not required; long term occupational exposure is not expected and there
are no residential uses at the present time. Therefore, quantification
of risk is not required.
*The reference to the special FQPA SF refers to any additional SF retained due to concerns unique to the FQPA. C. Exposure Assessment
1. Dietary exposure from food and feed uses. Tolerances have been established (40 CFR 180.505) for the combined residues of emamectin and its metabolites, in or on a variety of raw agricultural commodities and livestock. Tolerances range from 0.002 to 0.05. Risk assessments were conducted by EPA to assess dietary exposures from emamectin in food as follows:
i. Acute exposure. Acute dietary risk assessments are performed for
a fooduse pesticide if a toxicological study has indicated the
possibility of an effect of concern occurring as a result of a one day or single exposure. The Dietary Exposure Evaluation Model
(DEEM[reg]) analysis evaluated the individual food
consumption as reported by respondents in the USDA 19941996 and 1998
nationwide Continuing Surveys of Food Intake by Individuals (CSFII) and
accumulated exposure to the chemical for each commodity. The following
assumptions were made for the acute exposure assessments: A highly
refined, Tier 3, acute dietary exposure assessment was conducted for
the general U.S. population and various population subgroups. This was
a probabilistic assessment using anticipated residue estimates from the [[Page 40797]]
current and previously submitted field trial data as well as EPA
percent crop treated (PCT) estimates for a number of commodities. PCT
estimates used were 1% for cotton commodities; 52% for head lettuce;
2.5% for the subgroup 4A (leafy greens); 20% for the subgroup 4B (leaf
petioles), the group 5 (Brassica leafy vegetables), and peppers; and
11% for tomatoes and its processing commodities. Anticipated residues
were used for group 5 (Brassica leafy vegetables), group 4 (leafy
vegetables (except Brassica)), and group 8 (fruiting vegetables). The
calculation of anticipated residues for tomatoes (a representative
commodity in group 8) used the following approach: For residues of
MAB
The acute dietary exposure estimates are below EPA's level of concern (< 100% aPAD) at the 99.9th exposure percentile for the general U.S. population (29% of the aPAD) and all other population subgroups. The most highly exposed population subgroup is children 35 years old, at 58% of the aPAD. The acute assessment was highly refined, however, inclusion of additional PCT data and modified concentration/ processing factors could aid in further refining the acute dietary assessment.
ii. Chronic exposure. In conducting this chronic dietary risk assessment the (DEEM[reg]) analysis evaluated the individual food consumption as reported by respondents in the USDA 19941996 and 1998 nationwide CSFII and accumulated exposure to the chemical for each commodity. The following assumptions were made for the chronic exposure assessments: For chronic exposure and risk assessment, an estimate of the residue level in each food or foodform (e.g., orange or orange juice) on the food commodity residue list is multiplied by the average daily consumption estimate for that food/food form. The resulting residue consumption estimate for each food/foodform is summed with the residue consumption estimates for all other food/foodforms on the commodity residue list to arrive at the total average estimated exposure. Exposure is expressed in mg/kg body weight/day and as a percent of the cPAD. This procedure is performed for each population subgroup. A somewhat refined Tier 2 chronic dietary exposure assessment was conducted for the general U.S. population and various population subgroups. The assumptions of the assessment were tolerance level residues for all commodities except milk (for which anticipated residue estimates were used), and PCT estimates for a number of commodities. PCT estimates used were 0.4% for cotton commodities; 26% for head lettuce; 1.5% for the subgroup 4A (leafy greens); 10% for the subgroup 4B (leaf petioles), the group 5 (Brassica leafy vegetables), and peppers; and 6% for tomatoes and its processing commodities. Anticipated residue levels of 0.0003 ppm for milk and skim milk, and 0.0009 ppm for cream were used. The recommended tolerance level residues were used for all other crops and meat products. Additionally, default DEEM[reg] (version 7.76) concentration factors were used when necessary.
The chronic dietary exposure estimates are below HED's level of concern (<100% cPAD) for the general U.S. population (19% of the cPAD) and all population subgroups. The most highly exposed population subgroup is children 12 years old, at 34% of the cPAD. The chronic assessment was somewhat refined; inclusion of ARs, additional PCT information, and modified concentration/processing factors would further refine the chronic dietary assessment.
iii. Cancer. Emamectin is classified as a ``not likely'' human carcinogen based on the lack of evidence of carcinogenicity in male and female rats or male and female mice at doses that were judged to be adequate to assess the carcinogenic potential of the chemical.
iv. Anticipated residue and percent crop treated (PCT) information. Section 408(b)(2)(E) of the 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 chemicals that have been measured in food. If EPA relies on such information, EPA must require 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. Following the initial data submission, EPA is authorized to require similar data on a time frame it deems appropriate. As required by section 408(b)(2)(E) of the FFDCA, EPA will issue a data callin for information relating to anticipated residues to be submitted no later than 5 years from the date of issuance of this tolerance.
Section 408(b)(2)(F) of the FFDCA states that the Agency may use data on the actual percent of food treated for assessing chronic dietary risk only if the Agency can make the following findings: Condition 1, that 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 such pesticide residue; Condition 2, that the exposure estimate does not underestimate exposure for any significant subpopulation group; and Condition 3, if 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 section 408(b)(2)(F) of the FFDCA, EPA may require registrants to submit data on PCT.
The Agency used PCT information as detailed above under Unit III.C.1.i and III.C.1.ii Different PCTs and anticipated residues were used for the acute versus the chronic dietary risk from food and feed uses as explained in these units.
The Agency believes that the three conditions listed in Unit
III.C.1.iv have been met. With respect to Condition 1, PCT estimates
for existing registrations are derived from Federal and private market
survey data, which are reliable and have a valid basis. EPA uses a
weighted average PCT for chronic dietary exposure estimates. This
weighted average PCT figure is derived by averaging Statelevel data
for a period of up to 10 years, and weighting for the more robust and
recent data. A weighted average of the PCT reasonably represents a
person's dietary exposure over a lifetime, and is unlikely to
underestimate exposure to an individual because of the fact that
pesticide use patterns (both regionally and nationally) tend to change
continuously over time, such that an individual is unlikely to be
exposed to more than the average PCT over a lifetime. For acute dietary
exposure estimates, EPA uses an estimated maximum PCT. The exposure
estimates resulting from this approach reasonably represent the highest
levels to which an individual could be exposed, and are unlikely to
underestimate an individual's acute dietary exposure. For new uses, PCT [[Page 40798]]
estimates are based on the use of existing alternative insecticides
against insects that emmamectin will control. The Agency is reasonably
certain that the percentage of the food treated is not likely to be an
underestimation. As to Conditions 2 and 3, regional consumption
information and consumption information for significant subpopulations
is taken into account through EPA's computerbased 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 information on the regional consumption of food to which emamectin may be applied in a particular area.
2. Dietary exposure from drinking water. The Agency lacks sufficient monitoring exposure data to complete a comprehensive dietary exposure analysis and risk assessment for emamectin in drinking water. Because the Agency does not have comprehensive monitoring data, drinking water concentration estimates are made by reliance on simulation or modeling taking into account data on the physical characteristics of emamectin.
The Agency uses the First Index Reservoir Screening Tool (FIRST) or the Pesticide Root Zone/Exposure Analysis Modeling System (PRZM/EXAMS), to produce estimates of pesticide concentrations in an index reservoir. The screening concentration in ground water (SCIGROW) model is used to predict pesticide concentrations in shallow groundwater. For a screeninglevel assessment for surface water EPA will use FIRST (a tier 1 model) before using PRZM/EXAMS (a tier 2 model). The FIRST model is a subset of the PRZM/EXAMS model that uses a specific highend runoff scenario for pesticides. While both FIRST and PRZM/EXAMS incorporate an index reservoir environment, the PRZM/EXAMS model includes a percent crop area factor as an adjustment to account for the maximum percent crop coverage within a watershed or drainage basin.
None of these models include consideration of the impact processing (mixing, dilution, or treatment) of raw water for distribution as drinking water would likely have on the removal of pesticides from the source water. The primary use of these models by the Agency at this stage is to provide a coarse screen for sorting out pesticides for which it is highly unlikely that drinking water concentrations would ever exceed human health levels of concern.
Since the models used are considered to be screening tools in the risk assessment process, the Agency does not use estimated
environmental concentrations (EECs) from these models to quantify
drinking water exposure and risk as a %RfD or %PAD. Instead, drinking
water levels of comparison (DWLOCs) are calculated and used as a point of comparison against the model estimates of a pesticide's
concentration in water. DWLOCs are theoretical upper limits on a
pesticide's concentration in drinking water in light of total aggregate
exposure to a pesticide in food, and from residential uses. Since
DWLOCs address total aggregate exposure to emamectin they are further discussed in the aggregate risk Unit III.E.
Refined (Tier II) surface water concentrations were developed for emamectin and its metabolites with the PRZM/EXAMS model, using an index reservoir scenario for the aerial and ground applications of emamectin on cotton. The model assumes that emamectin is applied at the maximum label rate (0.015 lb active ingredient/acre with a maximum of 0.09 lb active ingredient/acre/season for the dispersable granule; and 0.016 lb active ingredient/acre with a maximum of 0.064 lb active ingredient/ acre/season for the emulsifiable concentrate). The results indicate that emamectin and its metabolites have a very low potential to reach surface waters as dissolved species. However, emamectin does have the potential to reach surface water bodies through erosion of soil particles to which the compound is sorbed. One percent of the application rate is assumed to drift from the application site during ground application. For the additional proposed aerial application, 5% of the application rate is assumed to drift from the application site to water bodies.
Surface water and ground water EECs are based on the PRZM/EXAMS and SCIGROW models respectively. The EECs of emamectin for acute exposure are estimated to be 0.298 parts per billion (ppb) for surface water from aerial application and 0.293 ppb for surface water from ground application. The EEC for chronic exposure is estimated to be 0.080 ppb for surface water. Ground water EECs are based on the Tier I SCIGROW model. The EEC of emamectin for both acute and chronic exposure is estimated to be 0.006 ppb for ground water.
3. From nondietary exposure. The term ``residential exposure'' is used in this preamble to refer to nonoccupational, nondietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets). Emamectin is not registered for use on any sites that would result in residential exposure.
4. Cumulative exposure to substances with a common mechanism of toxicity. Section 408(b)(2)(D)(v) of the 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 does not have, at this time, available data to determine whether emamectin has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, emamectin does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that emamectin has 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 the final rule for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997). D. Safety Factor for Infants and Children
1. In general. Section 408 of the FFDCA provides that EPA shall apply an additional tenfold 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 data base on toxicity and exposure unless EPA determines that a different margin of safety will be safe for infants and children. Margins of safety are incorporated into EPA risk assessments either directly through use of a MOE analysis or through using uncertainty (safety) factors in calculating a dose level that poses no appreciable risk to humans.
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2. Prenatal and postnatal sensitivity. EPA concludedthat there is low concern, and no residual uncertainty, for pre and/or postnatal toxicity resulting from exposure to emamectin, based on the following:
i. There is no quantitative or qualitative evidence of increased
susceptibility of rat and rabbit fetuses to in utero exposure in
developmental studies. There is no quantitative evidence of increased
susceptibility of rat offspring in the two generation reproduction
study, however, an increase in qualitative susceptibility was
determined. EPA determined that the concern is low because: (a) There was a clear NOAEL for offspring toxicity.
(b) Effects unique to offspring (decreased fertility in
F
(c) The decreased fertility seen in F
ii. There is evidence of increased qualitative and quantitative susceptibility in the rat developmental neurotoxicity study, but EPA determined that the concern is low because: Although multiple offsping effects (including decreased pup body weight, head and body tremors, hind limb extension and splay, changes in motor activity and auditory startle) were seen at the highest dose, and no maternal effects were seen at any dose, there was a clear NOAEL for offspring toxicity at the low dose, and the offspring LOAEL (at the mid dose) is based on a single effect seen on only one day (decreased motor activity on PND 17) and no other offspring toxicity was seen at the LOAEL.
3. Conclusion. EPA concluded that the toxicology database was
complete for FQPA purposes and that there are no residual uncertainties
for pre/postnatal toxicity. Based on the quality of the data, EPA
determined that the special FQPA SF should be reduced to 1x. However,
as explained in Unit III.3.B. of this preamble, EPA determined that an
additional 3x or 10x modifying uncertainty factor should be used for shortterm or intermediateterm exposure, respectively. The
recommendation for the 1x FQPA SF is based on the follow
FOR FURTHER INFORMATION CONTACT Thomas C. Harris, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, [[Page 40792]]
DC 204600001; telephone number: (703) 3089423; email address:
harris.thomas@epa.gov.
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