Avermectin B<INF>1</INF> and its delta-8,9-isomer; Pesticide
Tolerance
[Federal Register: September 7, 1999 (Volume 64, Number 172)]
[Rules and Regulations]
[Page 48548-48560]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr07se99-8]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300916; FRL-6380-7]
RIN 2070-AB78
Avermectin B<INF>1</INF> and its delta-8,9-isomer; Pesticide
Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a tolerance for combined residues
of the insecticide avermectin B<INF>1</INF> (a mixture of avermectins
containing greater than or equal to 80% avermectin B<INF>1a</INF> (5-O-
demethyl avermectin A<INF>1</INF>) and less than or equal to 20%
avermectin B<INF>1b</INF> (5-O-demethyl-25-de(1-methylpropyl)-25-(1-
methylethyl) avermectin A<INF>1</INF>)) and its delta-8,9-isomer in or
on grapes at 0.02 parts per million (ppm), peppers at 0.02 ppm, and
cotton gin byproducts at 0.15 ppm; makes permanent tolerances for
citrus, hops, potatoes, meat and meat by-products, milk, and cotton
seed which were previously time limited (expiring September 1, 1999);
and clarifies that permanent tolerances have previously been
established for almond hulls at 0.10 ppm and wet apple pomace at 0.10
ppm. Novartis Crop Protection, Inc. requested these tolerance actions
under the Federal Food, Drug, and Cosmetic Act, as amended by the Food
Quality Protection Act of 1996.
DATES: This regulation is effective September 7, 1999. Objections and
requests for hearings, identified by docket control number OPP-300916,
must be received by EPA on or before November 8, 1999.
ADDRESSES: Written objections and hearing requests may be submitted by
mail, in person, or by courier. Please follow the detailed instructions
for each method as provided in Unit VI. of the ``SUPPLEMENTARY
INFORMATION'' section. To ensure proper receipt by EPA, your objections
and hearing requests must identify docket control number OPP-300916 in
the subject line on the first page of your response.
FOR FURTHER INFORMATION CONTACT: By mail: Thomas C. Harris,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460;
telephone number: (703) 308-9423; and e-mail address:
harris.thomas@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be affected by this action if you are an agricultural
producer, food manufacturer, or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:
------------------------------------------------------------------------
Examples of Potentially
Categories NAICS Affected Entities
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Industry 111 Crop production
112 Animal production
311 Food manufacturing
32532 Pesticide manufacturing
------------------------------------------------------------------------
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 the table could also be
affected. The North American Industrial Classification System
[[Page 48549]]
(NAICS) codes have been provided to assist you and others in
determining whether or not this action might apply to certain entities.
If you have questions regarding the applicability of this action to a
particular entity, consult the person listed in the ``FOR FURTHER
INFORMATION CONTACT'' section.
B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?
1. Electronically.You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations'' and then look up the entry for this document under the
``Federal Register--Environmental Documents.'' You can also go directly
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
2. In person. The Agency has established an official record for
this action under docket control number OPP-300916. The official record
consists of the documents specifically referenced in this action, and
other information related to this action, including any information
claimed as Confidential Business Information (CBI). This official
record includes the documents that are physically located in the
docket, as well as the documents that are referenced in those
documents. The public version of the official record does not include
any information claimed as CBI. The public version of the official
record, which includes printed, paper versions of any electronic
comments submitted during an applicable comment period is available for
inspection in the Public Information and Records Integrity Branch
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.
II. Background and Statutory Findings
This regulation addresses three tolerance actions concerning
avermectin B<INF>1</INF> and its delta-8,9-isomer.
A. New Tolerances
In the Federal Register of August 11, 1997 (62 FR 42980) (FRL-5736-
1), EPA issued a notice pursuant to section 408 of the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as amended by the Food
Quality Protection Act of 1996 (FQPA) (Public Law 104-170) announcing
the filing of a pesticide petition (PP 7F4844) for tolerance by Merck
Research Laboratories, PO Box 450, Hillsborough Rd, Three Bridges, NJ.
The petition was later transferred to Novartis Crop Protection, Inc.,
PO Box 18300, Greensboro, NC 27419. There were no comments received in
response to the notice of filing.
The initial petition requested that 40 CFR 180.449 be amended by
establishing a tolerance for combined residues of the insecticide
avermectin B<INF>1</INF> (a mixture of avermectins containing greater
than or equal to 80% avermectin B<INF>1a</INF> (5-O-demethyl avermectin
A<INF>1</INF>) and less than or equal to 20% avermectin B<INF>1b</INF>
(5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin
A<INF>1</INF>)) and its delta-8,9-isomer, in or on grapes, raisins, and
other grape-derived food items at 0.02 ppm and chili peppers at 0.01
ppm. The petition was subsequently revised to express the tolerance as
simply peppers (combining the proposed chili peppers with the existing
0.01 ppm bell pepper tolerance) and raising the level to 0.02 ppm to
harmonize the tolerance with international residue limits. In addition,
the petition was also revised to express the proposed tolerance as
simply grapes at 0.02 ppm since residue data showed that separate,
higher tolerance levels were not needed for raisins and other grape-
derived food items as expressed in the original petition.
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) 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)
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 requirements of section 408 and a complete description of
the risk assessment process, see the final rule on Bifenthrin Pesticide
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).
B. Conversion of Certain Tolerances from Time-limited to Permanent
In the Federal Register of July 29, 1999 (64 FR 41112) (FRL-6095-
6), EPA issued a notice pursuant to section 408 of the FFDCA, 21 U.S.C.
346a as amended by the FQPA (Public Law 104-170) announcing the filing
of a pesticide petition (PP) by Novartis Crop Protection, Inc., PO Box
18300, Greensboro, NC 27419 to convert certain time limited tolerances
due to expire September 1, 1999 to permanent tolerances and to add a
new tolerance for a feed commodity. There were no comments received in
response to the notice of filing.
The petition referenced pesticide petitions PP 8F3592, 7F3500,
4E4419 and 5F4508. It requested that 40 CFR 180.449 be amended by
establishing permanent tolerances for combined residues of the
insecticide avermectin B<INF>1</INF> (a mixture of avermectins
containing greater than or equal to 80% avermectin B<INF>1a</INF> (5-O-
demethyl avermectin A<INF>1</INF>) and less than or equal to 20%
avermectin B<INF>1b</INF> (5-O-demethyl-25-de(1-methylpropyl)-25-(1-
methylethyl) avermectin A<INF>1</INF>)) and its delta-8,9-isomer, in or
on the agricultural commodities cattle, fat at 0.015 ppm; cattle, meat
byproducts at 0.02 ppm; cattle, meat at 0.02 ppm; citrus, dried pulp at
0.10 ppm; citrus, oil at 0.10 ppm; citrus, whole fruit at 0.02 ppm;
cotton seed at 0.005 ppm; cotton gin by-products at 0.15 ppm; hops,
dried at 0.20 ppm; milk at 0.005 ppm; and potatoes at 0.005 ppm.
With the exception of cotton gin by-products, these tolerances were
previously established as time-limited tolerances with an expiration
date of September 1, 1999 (see Federal Register of March 24, 1997 (62
FR 13833) (FRL-5597-7) to allow for resolution of the following three
issues:
1. The petitioner had to submit field residue trial data for cotton
gin byproducts and the EPA had to reevaluate dietary risk with respect
to secondary residues in meat and milk. These data were submitted; the
review is discussed later in this rule. As a result of this review, the
July 29, 1999 notice proposed the new tolerance for cotton gin
byproducts at 0.15 ppm.
2. The EPA needed to fully review the Monte Carlo analysis for
acute dietary risk submitted by the petitioner (especially the
anticipated residues and percent of crop treated data used). This
review was conducted as part of the tolerance assessment for grapes and
peppers.
[[Page 48550]]
3. The EPA needed to fully review the indoor residential risk
assessment submitted by the petitioner. This review was conducted as
part of the tolerance assessment for grapes and peppers. Since all
three issues have been satisfactorily addressed, the petitioner is
seeking to make the tolerances permanent.
C. Clarification: Certain Feed Tolerances Previously Established
In the Federal Register of April 10, 1996 (61 FR 15900) (FRL-5361-
9), EPA issued a final rule pursuant to section 409(e) of the FFDCA, 21
U.S.C. 348(b) announcing permanent tolerances under 40 CFR 186.300 for
combined residues of the insecticide avermectin B<INF>1</INF> (a
mixture of avermectins containing greater than or equal to 80%
avermectin B<INF>1a</INF> (5-O-demethyl avermectin A<INF>1</INF>) and
less than or equal to 20% avermectin B<INF>1b</INF> (5-O-demethyl-25-
de(1-methylpropyl)-25-(1-methylethyl) avermectin A<INF>1</INF>)) and
its delta-8,9-isomer, in or on the processed feed commodities apples,
wet pomace at 0.10 ppm and almonds, hulls at 0.10 ppm. This regulation
also established permanent tolerances under 40 CFR 180.449 on the raw
agricultural commodities almonds at 0.005 ppm; apples at 0.020 ppm; and
walnuts at 0.005 ppm.
Although that final rule listed tolerances for both raw
agricultural commodities and feed commodities, the 1996 edition of 40
CFR parts 150-189 (revised as of July 1, 1998), and subsequent
editions, listed only the tolerances for the raw agricultural
commodities and did not list the feed commodities established by this
regulation. With this current regulation the Agency is clarifying that
tolerances have been legally in effect since April 10, 1996 for the
processed feed commodities apples, wet pomace at 0.10 ppm and almonds,
hulls at 0.10 ppm. Due to amendments to the FFDCA by the FQPA, all
(i.e. raw, processed, and feed commodity) tolerances for avermectin
B<INF>1</INF> and its delta-8,9-isomer are now listed in the same
section of 40 CFR (180.449).
III. Aggregate Risk Assessment and Determination of Safety
Consistent with 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
avermectin B<INF>1</INF> and its delta-8,9-isomer and to make a
determination on aggregate exposure, consistent with section 408(b)(2),
for a tolerance for combined residues of the insecticide avermectin
B<INF>1</INF> (a mixture of avermectins containing greater than or
equal to 80% avermectin B<INF>1a</INF> (5-O-demethyl avermectin
A<INF>1</INF>) and less than or equal to 20% avermectin B<INF>1b</INF>
(5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin
A<INF>1</INF>)) and its delta-8,9-isomer on grapes at 0.02 ppm and
peppers at 0.02 ppm. EPA's assessment of the dietary exposures and
risks associated with establishing the tolerance 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. The nature of the toxic effects caused by avermectin
B<INF>1</INF> and its delta-8,9-isomer are discussed in this unit.
1. Acute toxicity/skin sensitization. The following summarizes the
acute toxicity of technical grade avermectin B<INF>1</INF>: the acute
oral LD<INF>50</INF> is 13.6 milligrams/kilogram (mg/kg) (toxicity
category I); the acute dermal LD<INF>50</INF> is 2,000 mg/kg (toxicity
category III); acute inhalation requirements were waived; primary eye
irritation results show the chemical to be very irritating exhibiting
corneal opacity, conjunctivitis, and iritis (toxicity category II);
primary skin irritation results show slight irritation (toxicity
category III); dermal sensitization results are negative.
2. Subchronic toxicity. In a 14-Week Oral Toxicity Study in Rats,
groups of 15 male and 15 female Charles River CD rats were gavaged with
0, 0.1, 0.2, or 0.4 mg/kg/day of C-076 (avermectin B<INF>1</INF>). The
rats had previously been exposed in utero to avermectin B<INF>1</INF>
at doses of 0, 0.01, 0.2, or 0.4 mg/kg/day. No toxic signs or deaths
were noted in any of the treatment groups. Body weight gain was
increased in the rats dosed at 0.4 mg/kg/day. There were no treatment-
related ophthalmologic changes, clinical pathology anomalies, gross or
histopathologic lesions, or changes in organ weights. The No Observable
Adverse Effect Level (NOAEL) is > 0.4 mg/kg/day, the highest dose
tested.
An 18-Week Oral Toxicity Study in Dogs resulted in a NOAEL of 0.25
mg/kg/day with the Lowest Observed Adverse Effect Level (LOAEL) being
0.5 mg/kg/day based on body tremors, one death, liver pathology, and
decreased body weight.
3. Chronic toxicity/ongogenicity/carcinogenicity. In a Combined
Chronic Toxicity/Oncogenicity Study in Rats, the oncogenic potential
was negative up to 2.0 mg/kg/day, the highest dose tested (HDT). The
high dose was increased to 2.5 mg/kg/day between weeks 10 and 13. The
high-dose is considered the Maximum Tolerated Dose (MTD). The systemic
NOAEL is 1.5 mg/kg/day (mid-dose). The LOAEL is 2.0 mg/kg/day based on
tremors in both sexes. A mid-dose female that had tremors was found to
have received a dose of about 2.5 mg/kg/day (based on actual food
consumption and body weight data). No pathological lesions could be
found to explain the tremors.
In a Carcinogenicity Study in Mice, oncogenic potential was
negative up to 8 mg/kg/day, the HDT. The high-dose (8 mg/kg/day) is
considered the MTD. The systemic NOAEL is 4 mg/kg/day. The LOAEL is 8
mg/kg/day based on increased incidence of dermatitis in males, an
increased incidence of extra-medullary splenic hematopoiesis in males,
increased mortality in males, and tremors and body weight decrease in
females.
In a 53-Week Oral Toxicity Study in Dogs, the NOAEL is 0.25 mg/kg/
day, and the LOAEL is 0.50 mg/kg/day based on a high incidence of
mydriasis (dilatation of the pupil of the eye) in males and females.
4. Developmental and reproductive toxicity. In a Developmental
Toxicity Study in Rats, groups of 25 female CRCD rats were mated, then
dosed by gavage with technical MK-0936 (avermectin B<INF>1</INF>) at 0
(vehicle control), 0.4, 0.8, or 1.6 mg/kg/day on gestation days 6
through 19. The lack of any maternal or developmental toxicity
demonstrates that the doses selected for this study were too low to
establish a LOAEL. The maternal and developmental NOAELs are > 1.6 mg/
kg/day (the HDT).
In a Developmental Toxicity Study in Rabbits, the maternal NOAEL is
1.0 mg/kg/day, and the maternal LOAEL is 2.0 mg/kg/day based on
decreased body weights, food consumption, and water consumption. The
developmental NOAEL is 1.0 mg/kg/day, and the Developmental LOAEL is
2.0 mg/kg/day based on cleft palate, clubbed foot, and delayed
ossification of sternebrae, metacarpals, and phalanges.
In a 2-generation Reproduction Study in Rats, the systemic and
reproductive NOAELs are <gr-thn-eq> 0.40 mg/kg/day. The developmental
NOAEL is 0.12 mg/kg/day, and the developmental LOAEL is 0.40 mg/kg/day
based on decreased pup body weight and viability during lactation, and
increased incidence of retinal rosettes in F2b weanlings.
In a Special Developmental Toxicity Study in CF-1 Mice, a genotypic
susceptibility to cleft palate was seen
[[Page 48551]]
following in utero exposure of avermectin B<INF>1</INF> delta 8-9
isomer (an isomeric photodegradation product found in plants). P-
glycoproteins are large proteins (150-180 kDa) found in the cell
membranes of animals ranging from sponges to humans. Groups of 12 P-
glycoprotein molecules span the lipid bilayer to form pores that
protect the cell by secreting toxic chemicals (such as the avermectins)
at the expense of ATP.
The CF-1 mouse strain is unique in that it contains a spontaneous
mutation in the P-glycoprotein gene resulting in heterogeneity in the
expression of the protein, a component of the blood-brain and blood-
placental barrier. Mice with a <plus-minus> or -/- genotype have
decreased expression of this protein. A decrease in expression of the
P-glycoprotein in both the gastrointestinal tract and brain increased
the sensitivity of CF-1 mice to avermectin toxicity by increasing its
absorption. Because the protein is also a component of the placental-
blood barrier, it was hypothesized that a deficiency of this protein in
the placenta may increase the sensitivity of the fetus to the
avermectins. In this exploratory developmental toxicity study, the role
of fetal P-glycoprotein genotype in the development of cleft palate in
CF-1 mice was investigated.
Heterozygous (<plus-minus>) male and female mice for P-glycoprotein
expression were mated. The dams were dosed by gavage with 1.5 mg/kg/day
of the test article on gestation days 6-15, inclusive. The pups had the
typical 1:2:1 Mendelian expression of P-glycoprotein deficiency (+/+,
<plus-minus>, and -/-, respectively).
There was a clear correlation between fetal P-glycoprotein genotype
and cleft palate incidence. Cleft palate was observed in 97% of fetuses
with the -/- genotype, 41% of fetuses with the <plus-minus> genotype,
and none of the fetuses with the +/+ genotype. It was postulated that
placental P-glycoprotein limited the potential of the test article to
induce cleft palate in the fetuses, presumably by regulating the amount
of test material allowed to cross the placental barrier into the
developing fetus.
The literature contains no mention of P-glycoprotein deficiency in
humans, and several scientists who are researching P-glycoprotein
confirmed this. Since there is no known human correlate for P-
glycoprotein deficiency, the CF-1 mouse should not be used for
assessing the risk of human exposure to avermectins. Although several
developmental toxicity studies were performed using CF-1 mice, they are
inappropriate for regulatory purposes.
5. Mutagenicity. The available studies clearly indicate that
avermectin B<INF>1</INF>, delta-8,9-isomer (a plant metabolite), and
the polar photolysis degradates are not mutagenic in microbial systems.
While avermectin B<INF>1</INF> has the potential to damage DNA, the
lack of an in vitro mutagenic or clastogenic effect correlates well
with the lack of an oncogenic effect in rat or mouse long-term feeding
studies and also with the absence of significant reproductive or
developmental toxicity attributable to a mutagenic mode of action
(i.e., decreased total implants or increased resorptions).
6. Metabolism. In a metabolism study in rats, two metabolites were
identified, 2,4-OH-ME-B<INF>1a</INF>, and 3''desmethyl avermectin
B<INF>1a</INF> (3''DM-B<INF>1a</INF>). No bioaccumulation was seen in
rat tissues.
7. Neurotoxicity. There are no neurotoxicity or developmental
neurotoxicity studies of avermectin B<INF>1</INF>. However,
neurotoxicity was observed in other oral toxicity studies. A chronic
study in dogs resulted in mydriasis at 0.50 mg/kg/day. A chronic/
oncogenicity study in rats resulted in tremors in both sexes at the
LOAEL of 2.0 mg/kg/day. A chronic/carcinogenicity study in mice
resulted in tremors in females at the LOAEL of 8 mg/kg/day. In an 18-
week study in dogs signs, seen at 0.50 mg/kg/day included mydriasis,
whole body tremors, ataxia (lack of coordination), muscular tremors,
and ptyalism (excessive flow of saliva). In a 10-day developmental
toxicity study in CF-1 mice, hunched back and marked tremors were
observed after 6-7 days dosing at 0.3 mg/kg/day in the diet. In a
reproduction study in rats, spastic movements of the limbs and muscular
tremors of the entire body were seen in lactating pups, but not in the
dams, at 0.4 mg/kg/day. In a reproduction study in rats, whole body
tremors, ataxia, ptyalism, and ocular and/or nasal discharges were seen
in dams dosed at 2.0 mg/kg/day (no mention of neurotoxicity in the
pups). In two developmental toxicity studies in CF-1 mice, death was
preceded by tremors, then coma.
B. Toxicological Endpoints
1. Acute toxicity. An acute dietary Reference Dose (RfD) of 0.0025
mg/kg was based on data from a 1-year dog study. The NOAEL is 0.25 mg/
kg/day, and the LOAEL is 0.50 mg/kg/day based on mydriasis which was
observed after 1 week of dosing. An uncertainty factor of 100 was used
to account for interspecies extrapolation (10x) and intraspecies
variability (10x).
2. Short- and intermediate-term toxicity. Short- and intermediate-
term dermal and inhalation NOAELs are derived by route-to-route
extrapolation of the oral NOAEL of 0.25 mg/kg/day based on mydriasis
after 1 week of dosing in a 1-year dog study. Dermal absorption is
considered to be 1% based on a monkey study that found dermal
absorption to be less than 1% (rounded up to 1% for analysis purposes).
Oral and inhalation absorption are both assumed to be 100%.
3. Chronic toxicity. EPA has established the RfD for avermectin
B<INF>1</INF> and its delta-8,9-isomer at 0.0012 mg/kg/day. This
Reference Dose (RfD) is based on a 2-generation reproduction study in
rats. The developmental NOAEL is 0.12 mg/kg/day, and the developmental
LOAEL is 0.40 mg/kg/day based on decreased pup body weight and
viability during lactation, and increased incidence of retinal rosettes
in F2b weanlings. An uncertainty factor of 100 was used to account for
interspecies extrapolation (10x) and intraspecies variability(10x).
The long-term dermal NOAEL is a route-to-route extrapolation of the
oral NOAEL of 0.12 mg/kg/day based on decreased pup body weight and
viability during lactation, and increased incidence of retinal rosettes
in F2b weanlings in a 2-generation reproduction study in rats. Dermal
absorption is considered to be 1% based on a monkey study that found
dermal absorption to be less than 1% (rounded up to 1% for analysis
purposes).
The long-term inhalation NOAEL is a route-to-route extrapolation
from the oral NOAEL of 0.12 mg/kg/day based on decreased pup body
weight and viability during lactation, and increased incidence of
retinal rosettes in F2b weanlings in a 2-generation reproduction study
in rats. Oral and inhalation absorption are both assumed to be 100%.
4. Carcinogenicity. The Agency has classified avermectin
B<INF>1</INF> as a Cancer Group E chemical based on the absence of
significant tumor increases in two adequate rodent carcinogenicity
studies.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.449) for the combined residues of the insecticide avermectin
B<INF>1</INF> (a mixture of avermectins containing greater than or
equal to 80% avermectin B<INF>1a</INF> (5-O-demethyl avermectin
A<INF>1</INF>) and less than or equal to 20% avermectin B<INF>1b</INF>
(5-O-demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin
A<INF>1</INF>)) and its delta-8,9-isomer, in or on a variety of raw
agricultural commodities. Permanent tolerances include almonds (0.005
ppm); almonds, hulls (0.10 ppm); apples (0.020 ppm); apples, wet pomace
(0.10 ppm); celery
[[Page 48552]]
(0.05 ppm); cucurbits (0.005 ppm); head lettuce (0.05 ppm); pears (0.02
ppm) bell peppers (0.01 ppm) strawberry (0.02 ppm); fresh tomatoes
(0.01 ppm); walnuts (0.005 ppm). The following time limited tolerances
are due to expire September 1, 1999: cattle, fat (0.015 ppm); cattle,
meat (0.02 ppm); cattle, meat by products (0.02 ppm); citrus, dried
pulp (0.10 ppm); citrus, oil (0.10 ppm); citrus, whole fruit (0.02 ppm)
cotton seed (0.005 ppm); dried hops (0.2 ppm); milk (0.005 ppm);
potatoes (0.005 ppm). The following Section 18 time limited tolerances
will expire January 31, 2,000: basil (0.05 ppm); celeriac (0.05 ppm)
spinach (0.05 ppm). Finally, a section 18 time limited tolerance for
avocado (0.02 ppm) will expire September 20, 2,000. All of these
tolerances (i.e. both permanent and time-limited) were included in the
dietary risk analysis. Risk assessments were conducted by EPA to assess
dietary exposures from avermectin B<INF>1</INF> and its delta-8,9-
isomer as follows:
Section 408(b)(2)(E) 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), EPA will
issue a data call-in 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) states that the Agency may use data on the
actual percent of crop treated (PCT) for assessing chronic dietary risk
only if the Agency can make the following three findings: (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; (2) that the exposure estimate does not
underestimate exposure for any significant subpopulation group; and (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 percent of crop treated as required by
the section 408(b)(2)(F), EPA may require registrants to submit data on
PCT.
The Agency used the following information to conduct a dietary
exposure analysis. The maximum PCT is used for acute dietary exposure
estimates and represents the highest levels to which an individual
could be exposed. It is unlikely to underestimate an individual's acute
dietary exposure. The weighted average percent crop treated is used for
chronic dietary exposure and reasonably represents a person's dietary
exposure over a lifetime. It 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, so
that an individual is unlikely to be exposed to more than the average
percent crop treated over a lifetime. For each crop in the dietary
(food only) model the following percent crop treated values were used
for the acute and chronic analyses (respectively): almond 100%, 100%;
apple 6.1%, 1.9%; avocado 100%, 100%; basil 100%, 100%; cantaloupe 5%,
1.3%; celeriac 100%, 100%; celery 60%, 49%; citrus, other 43%, 32%;
cotton 4.8%, 3.2%; cucumber 100%, 31%; grapefruit, juice and peel
60.9%, 46%; grapefruit, peeled fruit 43%, 46%; grape 14%, 14%; hops
100%, 84%; lemon, juice and peel 34.4%, 17%; lemon, peeled fruit 43%,
17%; head lettuce 28%, 22%; lime, juice and peel 63.2%, 32%; lime,
peeled fruit 43%, 32%; melons 5%, 1.3%; orange, juice and peel 36.3%,
28%; orange, peeled fruit 43%, 28%; pear 75%, 56%; peppers 15%, 6.3%;
potato 5%, 0.3%; spinach 18%, 8.9%; squash 100%, 31%; strawberry 47%,
42%; tangelo 43%, 57%; tangerine, juice 74.3%, 53%; tangerine, fresh
43%, 53%; tomato 8%, 3.7%; walnut 100%, 100%; watermelon 5%, 1.3%. For
fresh, peeled citrus a weighted average (43%) was calculated pooling
all types of citrus; this value was used in the analysis of chronic
dietary exposure from citrus.
The Agency believes that the three conditions, discussed in section
408 (b)(2)(F) in this unit concerning the Agency's responsibilities in
assessing chronic dietary risk findings, have been met. With respect to
condition 1, EPA finds that the PCT information is reliable and has a
valid basis. The Agency has utilized statistical data from a number of
public and proprietary sources including USDA/National Agricultural
Statistics Service, Doane, Maritz, Kline, and National Center for Food
and Agricultural Policy. However, since the risk assessment includes
forecast estimates of usage of avermectin B<INF>1</INF> on the new
crops being added, the petitioner must seek permission from the Agency
to expand usage beyond these estimates (specifically, 14% crop treated
for grapes, 15% crop treated for peppers). Before the petitioner can
increase production of product for treatment of greater than 115,500
acres for grapes (14% of 825,000 total U.S. acres grown) or 17,850
acres for peppers (15% of 119,000 total U.S. acres grown), permission
from the Agency must be obtained. With respect to conditions 2 and 3,
the 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
information on the consumption of food bearing avermectin B<INF>1</INF>
and its delta-8,9-isomer in a particular area.
i. Acute exposure and risk. Acute dietary 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. The registrant has submitted an acute
dietary exposure assessment using probabilistic ``Monte Carlo''
modeling incorporating anticipated residue and percent of crop treated
refinements to calculate the Anticipated Residue Contribution (ARC).
EPA has examined the assumptions made in conducting the analysis for
the following crops: celery, strawberry, citrus, tomato, and pear,
apple, grape, and pepper. EPA found the analysis adequate with the
exception of the acute RfD; the analysis was not conducted with the
current acute population adjusted dose (PAD) of 0.00025 mg/kg/day.
Residue Data Files (RDF) and percent crop treated were used on all but
a few low consumption food items. Reduction factors for fractionation
and processing were utilized for citrus and pome fruit. Monitoring data
were not used for mixed/blended commodities.
EPA was able to further refine the acute dietary estimate from food
by using updated PCT data, resetting the processing factor for dried
potatoes to 1 which reflects the non-concentration of
[[Page 48553]]
avermectin B<INF>1</INF> in potato processed commodities, correcting
the residue files above to use one half the level of detection or one
half the level of quantification, where appropriate, and using the
average field trial residue level and previously established processing
factors for blended commodities. In addition, the analysis included
residues in pear juice for which no data has been previously required.
Since all other juices show reductions in avermectin B<INF>1</INF>
residues from the raw agricultural commodity, EPA will use the
reduction factor for apples in the analysis. Some of the resulting
high-end exposure estimates are listed below.
The resulting calculations are presented below as a percent of the
acute population adjusted dose (%PAD). The PAD is the reference dose
(acute or chronic) adjusted for (divided by) the FQPA safety factor.
EPA is generally concerned with acute exposures that exceed 100% of the
acute RfD/PAD. The risk estimate should be viewed as highly refined.
Additional refinement of the almond, basil, cotton seed, hops and
walnut residue estimates using RDF's and PCT would be unlikely to
reduce risk estimates significantly. In making a safety determination
for this tolerance, EPA is taking into account this refined acute
exposure assessment.
Table 1.-- Acute Dietary (Food Only) Risk for Selected Population Groups
------------------------------------------------------------------------
ARC (mg/ PAD
Subgroup kg) (%)
------------------------------------------------------------------------
U.S. Population....................................... 0.000088 4
All infants (< 1 yr.)................................. 0.000111 44
Nursing infants (< 1 yr.)............................. 0.000112 45
Non-nursing infants (< 1 yr.)......................... 0.000117 47
Children (1-6 yrs.)................................... 0.000176 70
Children (7-12 yrs.).................................. 0.00008 34
5
Females (13+ yrs. pregnant, non-nursing).............. 0.000054 22
Females (13+ yrs. nursing)............................ 0.000093 37
Females (13-19 yrs. non-pregnant, non-nursing)........ 0.000061 24
Females (13-50 yrs.).................................. 0.000070 28
Males (13-19 yrs.).................................... 0.000051 2
------------------------------------------------------------------------
ii. Chronic exposure and risk. In conducting this chronic dietary
(food only) risk assessment, EPA used anticipated residues and percent
crop-treated data for many crops. This chronic dietary (food only)
exposure should be viewed as a highly refined risk estimate; further
refinement using additional percent crop-treated values would not
result in a significantly lower dietary exposure estimate. Thus, in
making a safety determination for this tolerance, EPA is taking into
account this refined chronic exposure assessment. EPA is generally
concerned with exposures that exceed 100% of the chronic RfD/PAD. The
existing avermectin B<INF>1</INF> tolerances result in an ARC that is
equivalent to the following percentages of the RfD or PAD depending on
the subpopulation:
Table 2.--Chronic Dietary (Food Only) Risk for Selected Population
Groups
------------------------------------------------------------------------
ARCFOOD PAD
Subgroup (mg/kg) (%)
------------------------------------------------------------------------
U.S. Population....................................... 0.000008 < 1
U.S. Population - autumn season....................... 0.000008 7
Northeast region...................................... 0.000008 7
Western region........................................ 0.000009 7
Pacific region........................................ 0.000009 7
Non-hispanic other.................................... 0.000008 7
All infants (< 1 yr.)................................. 0.000016 14
Nursing infants (< 1 yr.)............................. 0.000009 7
Non-nursing infants (< 1 yr.)......................... 0.000020 17
Children (1-6 yrs.)................................... 0.000016 13
Children (7-12 yrs.).................................. 0.000010 8
Females (13+ yrs. nursing............................. 0.000008 6
Males (20+ years)..................................... 0.000007 <1
------------------------------------------------------------------------
The subgroups listed above are: (1) the U.S. population (48
states); (2) those for infants, children, females 13+, nursing; (3) the
other subgroups for which the percentage of the RfD/PAD occupied is
greater than that occupied by the subgroup U.S. population; and (4)
other subgroups of regulatory interest.
2. From drinking water. Avermectin B<INF>1</INF> is moderately
persistent and non-mobile. It is not expected to reach surface or
ground water in significant quantities. It is stable to hydrolysis at
pH 5, 7, and 9. It is also moderately persistent in aerobic soil
(topsoil) with half-lives of 37-131 days. The major pathways of
avermectin B<INF>1</INF> dissipation are binding to soil and sediment,
degradation in aerobic soil, and photolysis in water. In shallow, well-
mixed surface water with no suspended sediments, avermectin
B<INF>1</INF> degraded rapidly with a photodegradation half-life of 3
days. However, in most surface waters, suspended sediments and lack of
mixing would decrease the rate of photodegradation significantly. In
water, avermectin B<INF>1</INF> residues would be tightly bound to
sediment, reducing aqueous concentrations. There are no Maximum
Contaminant Levels (MCL) or Health Advisories (HA) established for
avermectin B<INF>1</INF> residues in drinking water.
To calculate exposure and risk from avermectin B<INF>1</INF> in
drinking water, the EPA analysis first used screening models to
calculate Estimated Environmental Concentrations (EECs) for groundwater
(screening concentration in ground water (SCI-GROW2)) and surface water
(generic expected environmental concentration (GENEEC)). A refined
model (Pesticide Root Zone Model-EXAMS (PRZM-EXAMS)) was then run on
surface water (refined models do not exist for ground water but given
the screening results it is unlikely that the EECs for ground water
would change significantly). The resulting EECs were then compared to
the Drinking Water Level of Concern (DWLOC) for various population
groups to determine acute and chronic risk.
The screening model SCI-GROW2 was used to calculate EECs for
avermectin B<INF>1</INF> in ground water from use in grapes, peppers,
and strawberries. Strawberries were analyzed since they represent the
highest avermectin B<INF>1</INF> use rate for any crop. These EECs were
0.0015, 0.0015, and .002 <greek-m>g/L for grapes, peppers, and
strawberries, respectively.
PRZM-EXAMS was used to perform a refined assessment of EECs for
avermectin B<INF>1</INF> in surface drinking water. Use sites modeled
were grapes grown with grassed middles in New York and strawberries
grown on black plastic mulch in Florida. Peppers were not modeled
because the application rate is lower than that for strawberries. Crop
specific consecutive PRZM-EXAMS simulations were conducted to evaluate
the cumulative probability distribution for peak, 4-day, 21-day, 60-
day, and 90-day EECs. PRZM-EXAMS EECs for avermectin B<INF>1</INF> were
0.18 and 0.88 <greek-m>g/L for peak values and 0.16 and 0.57
<greek-m>g/L for 90-day for grape and strawberries, respectively.
EPA decided to rely on the strawberry model to assess aggregate
risk since strawberries were considered a higher exposure scenario
(four applications per season allowed for strawberries vs. three
applications for peppers or two applications for grapes). However, EPA
noted that the certainty of the concentrations estimated for
strawberries is low, due to uncertainty on the amount of runoff from
plant beds covered in plastic mulch and uncertainty on the amount of
degradation of avermectin B<INF>1</INF> on black plastic compared to
soil. In order to refine the model in the future, the Agency will
require the registrant, as a condition of product registration, to
conduct additional tests on the effects of plastic mulch on surface
water pesticide concentrations.
[[Page 48554]]
A Drinking Water Level of Comparison (DWLOC) is a theoretical upper
limit of a pesticide's concentration in drinking water in light of
total aggregate exposure to that pesticide in food and through
residential uses. A DWLOC will vary depending on the toxic endpoint,
consumption, and body weight. Different populations will have different
DWLOCs. EPA uses DWLOCs internally in the risk assessment process as a
surrogate measure of potential exposure associated with pesticide
exposure through drinking water. In the absence of monitoring data for
pesticides, the DWLOC is used as a point of comparison against
conservative model estimates of potential pesticide concentration in
water. DWLOC values are not regulatory standards for drinking water.
Acute and chronic exposure and risk. No monitoring data of ground
water and surface water are available for avermectin B<INF>1</INF>. The
SCI-GROW2 modeling data for the grape and chili pepper uses resulted in
maximum concentrations in ground water of 0.0015 <greek-m>g/L for both
acute and chronic exposure. Refinements using PRZM-EXAMS indicate a
peak EEC in surface water at 0.88 <greek-m>g/L and a 90-day EEC at 0.57
<greek-m>g/L. The modeling data were compared to the results of the
following equations used to calculate acute and chronic DWLOC for
avermectin B<INF>1</INF> in ground and surface water. Additionally, as
a result of the retention of the FQPA Safety Factor, EPA considered the
PAD for females 13+, infants, and children to be 0.00025 and 0.00012
mg/kg/day for acute and chronic exposure, respectively. For all other
populations (e.g. U.S. population, Hispanics, adult males), exposures
will be compared to the acute and chronic PADs, 0.0025 and 0.0012 mg/
kg/day, respectively.
DWLOC's are calculated as follows: Acute = (acuteRfD/10) - (acute
food (mg/kg/day)) x (bodyweight) / consumption (L) x
10<SUP>-3</SUP> mg/<greek-m>g. Chronic = (RfD/10) - (chronic food (mg/
kg/day)) x (bodyweight)/consumption (L) x 10<SUP>-3</SUP> mg/
<greek-m>g. The 2 liters (L) of drinking water consumed/day by adults
and the 1 L per day consumed by children are default assumptions used
by the EPA. The Agency's default body weights for the U.S. population
and males is 70 kg and for females, 60 kg. EPA's default body weight
for children is 10 kg. There are no chronic residential exposures to
avermectin B<INF>1</INF>.
The results indicate that the exposure to avermectin B<INF>1</INF>
in drinking water derived from ground water using SCI-GROW modeling
data are below the calculated DWLOC for all population subgroups of
concern from use of avermectin B<INF>1</INF> in grapes, peppers and
strawberries. Exposure to avermectin B<INF>1</INF> in drinking water
derived from surface water using the refined estimates from PRZM-EXAMS
and using the results for the crop with the highest use rate
(strawberries) the modeled exposure data are below the calculated DWLOC
for all population subgroups of concern except for the acute exposure
for children 1-6 yrs where the modeled exposure concentration slightly
exceeds the DWLOC (0.88 vs. 0.74 <greek-m>g/L).
Despite this slight exceedance, EPA believes that acute exposure to
avermectin from drinking water will not pose an unacceptable risk to
human health. Neither surface nor ground water models used by EPA were
designed specifically for estimating concentrations in drinking water.
There are significant uncertainties in both the toxicology used to
derive the DWLOC and the exposure estimate from the PRZM-EXAMS model.
EPA has compensated for these uncertainties by using reasonable high-
end assumptions. Given this approach, the Agency does not attach great
significance to such a small difference. However, EPA may do additional
analyses and, as a condition of product registration, the Agency will
require the registrant to submit (1) data on the effects of plastic
mulch on surface water pesticide concentrations and (2) data
characterizing the effectiveness of various types of drinking water
treatment on removing avermectin. These data are expected to confirm
that the actual concentration of avermectin in drinking water is less
than the level of concern for all sub-populations.
3. From non-dietary exposure. Avermectin B<INF>1</INF> and its
delta-8,9-isomer is currently registered for use on the following
residential non-food sites: residential lawns for fire ant control, and
residential indoor crack & crevice for cockroaches. Registered
residential uses may result in short-term to intermediate exposures.
However, based on current use patterns, chronic exposure (6 or more
months of continuous exposure) to avermectin B<INF>1</INF> is not
expected.
i. Short and intermediate exposure and risk--residential lawn
applications. For exposure of residential applicators, three scenarios
used were: (a) granular bait dispersed by hand, (b) belly grinder-
granular open pour-mixer/loader/applicator (MLAP) and (c) push type
granular MLAP. Short- and Intermediate-term total MOEs (dermal +
inhalation) are greater than 1,000 and therefore do not exceed EPA's
level of concern.
For postapplication exposure from treated lawns, EPA default
assumptions such as dermal transfer coefficient (Tc), exposure time
(ET), hand surface area (SA), ingestion frequency (FQ), residue
dissipation, and ingestion rates were used. These defaults were used to
estimate postapplication exposure to children and adults from treated
lawns. The application rate (AR) used for this assessment is based on
the label for Affirm Fire Ant Insecticide (0.011% avermectin
B<INF>1</INF>). The label recommends a broadcast application rate on
lawns of 1 lb of product/acre (1.1E-4 lb ai/acre). This is maximum rate
for all registered lawn uses. A margin of exposure (MOE) of 1,000 or
greater is required for the most sensitive subgroups. All lawn
postapplication MOEs exceeded this value and are therefore not of
concern. The dermal short- and intermediate-term MOEs for adults and
children are 83,000 and 86,000, respectively. The oral hand-to-mouth
short- and intermediate-term MOEs for children are 14,000 and 6,500,
respectively. The oral incidental ingestion short- and intermediate-
term MOEs for children are 610,000 and 290,000, respectively.
ii. Short and intermediate exposure and risk--residential indoor
crack and crevice uses. For residential applicators, exposure and risk
estimates for homeowners applying crack and crevice baits were
estimated using the EPA DRAFT Standard Operating Procedure (SOP) for
Residential Exposure Assessments (12/18/97).
The amount of active ingredient (ai) handled was based on the
assumption that one 30 gram package of Whitmire Avert Prescription Bait
Prescription Treatment 310 (0.05% ai) would be applied in a day. The
unit exposure from the EPA default wettable powder, open mixing and
loading scenarios was used as a surrogate for estimating dermal and
inhalation exposure to residential applicators. The short- and
intermediate-term MOEs for dermal and inhalation exposure are each 12
million, which does not exceed EPA's level of concern.
For estimating postapplication exposure and risk from indoor
treatment, two postapplication exposure studies were conducted with
crack and crevice products containing avermectin B<INF>1</INF>: (1)
Evaluation of Avert Prescription Treatment 310 Residual Study in Air,
Food and on Surfaces, dated November 8, 1990 and (2) Evaluation of
Indoor Exposure to a Crack and Crevice Application of Whitmire Avert
Crack and Crevice Prescription Treatment 310 and Prescription TC 93A
Bait, dated October 27, 1995. The 1990 study reported measured
avermectin B<INF>1</INF>
[[Page 48555]]
concentrations in wipe and air samples up to 7 days following the
application. The 1995 study reported non-detect values for all air and
surface residue (cotton cloth dosimeters) samples taken.
The EPA noted that neither study met 100% of the Pesticide
Assessment Guideline criteria. Among other shortcomings, the 1990 study
did not report the amount of avermectin B<INF>1</INF> applied. However,
subsequent documentation provided by the study director stated that the
application rate in the 1990 study was at least three times greater
than the normal label rate.
To be conservative, EPA decided that the values from the 1990 study
would be used for this risk assessment. EPA default assumptions for
dermal Tc, ET, SA, FQ, inhalation rates, and ingestion rates were used.
These defaults were used to estimate children's postapplication
exposure to the product Avert Prescription Treatment 310 (dry flowable
cockroach bait). According to Table A-1 of the SOP's for Residential
Exposure Assessments, the method used for estimating children's
postapplication exposure is believed to produce a central to high-end
estimate of exposure.
Based on the information available on the study, the air and
surface residue values taken from the 1990 study were divided by a
factor of 3 to account for the exaggerated application rate used in the
study. The avermectin B<INF>1</INF> residue value reported for
horizontal residues immediately after the application (4.2E-07 mg/
cm<SUP>2</SUP>) was divided by a factor of 3 (1.4E-6 mg/cm 2) and then
used to estimate children's dermal and hand-to-mouth exposure. A linear
regression analysis was performed on the reported air concentrations at
0 (immediately after), 1, 3 and 7 days after the application to
determine the average concentration for the first 21 hours following
the application. The analysis indicated an average concentration of
avermectin B<INF>1</INF> at 6.4E-04 mg/m<SUP>3</SUP> (4% dissipation,
adjusted R2 = 0.986 for log-transformed data). This value was divided
by a factor of 3 (2.1E-4 mg/m<SUP>3</SUP>) and then used to estimate
children's inhalation exposure.
The Short- and intermediate-term dermal MOE for children's
postapplication dermal is 78,000. The short- and intermediate-term oral
MOE for children's postapplication oral hand-to-mouth is 12,000. The
short- and intermediate-term inhalation MOE for children's
postapplication inhalation is 2,400.
The risk from children's post application exposure to crack and
crevice products containing avermectin B<INF>1</INF> does not exceed
EPA's level of concern. Avert Prescription Treatment 310 is a dust
formulation that is intended for the application to crack and crevices
only. Other formulations for similar crack and crevice products (i.e.,
gels, granulars, pressurized liquids, etc.) will have less migration
from the treated area and are expected to result in lower risk from
dermal, oral, and inhalation postapplication exposure.
4. Cumulative exposure to substances with common mechanism of
toxicity. Section 408(b)(2)(D)(v) 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 avermectin B<INF>1</INF> and its delta-8,9-isomer 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, avermectin B<INF>1</INF> and its delta-8,9-
isomer 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 avermectin B<INF>1</INF> and its delta-8,9-isomer
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. Aggregate Risks and Determination of Safety for U.S. Population
including Infants and Children
In examining aggregate exposures, FQPA directs EPA to consider
available information concerning exposures from the residue in food and
all other non-occupational exposures. The primary non-food sources of
exposure the Agency looks at include drinking water (whether from
ground or surface water), and exposure through pesticide use in
gardens, lawns or buildings (residential and other indoor and/or
outdoor uses). In evaluating food exposures, EPA takes into account
varying consumption patterns of major identifiable subgroups of
consumers, including infants and children.
1. Acute risk. Acute aggregate exposure takes into account acute
dietary food and water exposure. The registrant submitted an acute
dietary exposure analysis using probabilistic ``Monte Carlo'' modeling.
EPA has examined the assumptions made in conducting the analysis and
has recalculated the assessment using the submitted acute file, the
correct acute RfD, updated PCT data, correcting the residue files above
to use one half the Level of Detection (LOD) or one half the Level of
Quantitation (LOQ) where appropriate, and using the average field trial
residue level and previously established processing factors for blended
commodities. In addition, EPA's analysis included residues in pear
juice for which no data has been previously required. Since all other
juices show reductions in avermectin B<INF>1</INF> residues from the
raw agricultural commodity, EPA used the reduction factor for apples in
the analysis. The dietary (food only) acute %PAD range from 45% for
nursing infants < 1 year old to 70% for children 1-6 yrs. This risk
estimate should be viewed as highly refined since it used anticipated
residue values and percent crop-treated data in conjunction with Monte
Carlo analysis. The acute dietary exposure does not exceed EPA's level
of concern.
Avermectin B<INF>1</INF> is a moderately persistent but non-mobile
compound in soil and water environments. The SCI-GROW modeling data for
avermectin B<INF>1</INF> for drinking water derived from ground water
sources resulting from use on grapes and peppers indicate levels less
than OPP's DWLOC for acute exposure. Using the refined PRZM-EXAMS
modeling data for drinking water derived from surface water sources
resulting from use on strawberries (the crop with the maximum use rate)
also indicates levels less than OPP's DWLOC for acute exposure in all
populations with the exception of children 1-6 years old where the peak
EEC of 0.88 <greek-m>g/L slightly exceed this subgroup's acute DWLOC
(0.74 <greek-m>g/L).
Despite this slight exceedance, EPA believes that acute exposure to
avermectin from drinking water will not pose an unacceptable risk to
human health. Neither surface nor ground water models used by EPA were
designed specifically for estimating concentrations in drinking water.
There are significant uncertainties in both the toxicology used to
derive the DWLOC and the exposure estimate from the PRZM-EXAMS model.
EPA has compensated for these uncertainties by using reasonable high-
end assumptions. Given this approach, the Agency does not attach great
significance to such a small difference. However, EPA may do additional
analyses and, as a condition of product registration, the Agency will
require the registrant to submit (1) data
[[Page 48556]]
on the effects of plastic mulch on surface water pesticide
concentrations and (2) data characterizing the effectiveness of various
types of drinking water treatment on removing avermectin. These data
are expected to confirm that the actual concentration of avermectin in
drinking water is less than the level of concern for all sub-
populations.
2. Chronic risk. Chronic aggregate exposure takes into account
chronic exposure via food, water, and residential uses. Since there is
no chronic residential exposure to avermectin B<INF>1</INF> only food
and water contributed to chronic risk.
Using the exposure assumptions described in this notice, EPA has
concluded that aggregate exposure to avermectin B<INF>1</INF> and its
delta-8,9-isomer from food will utilize < 1% of the PAD for the U.S.
population and will utilize from 6% to 17% of the PAD for infants and
children (depending on specific subgroup). The major identifiable
subgroup with the highest aggregate exposure is non-nursing infants
with 17% of the chronic PAD. EPA generally has no concern for exposures
below 100% of the RfD/PAD because the RfD/PAD represents the level at
or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health.
Avermectin B<INF>1</INF> is a moderately persistent, but non-mobile
compound in soil and water environments. The modeling data for
avermectin B<INF>1</INF> indicate chronic water residue levels less
than OPP's DWLOC's. EPA does not expect aggregate chronic exposure to
avermectin B<INF>1</INF> will pose an unacceptable risk to human
health.
3. Short- and intermediate-term risk. Short-term aggregate
exposure takes into account chronic dietary food and water (considered
to be a background exposure level) plus short-term residential uses
which include dermal, inhalation, and oral exposures. For children's
post-application exposure from crack and crevice uses, the worst case
exposure scenario, risks do not exceed EPA's level of concern. The
residential uses that were aggregated with chronic dietary food and
water are from lawn and crack and crevice uses and include: (1) Adult
dermal exposure from the highest adult residential applicator scenario
(3.4E-7 mg/kg/day from belly grinder granular open pour) and crack and
crevice applicator scenario (2.1E-8 mg/kg/day) with exposure from post-
application activities (3.0E-6 mg/kg/day), and inhalation from turf and
crack and crevice (3.9E-7 mg/kg/day). (2) Children's oral exposure from
turf and crack and crevice hand-to-mouth, with turf incidental
ingestion (3.8E-5 mg/kg/day), dermal exposure from turf and crack and
crevice (6.1E-6 mg/kg/day), and inhalation exposure from crack and
crevice (1.1E-4 mg/kg/day).
Using the exposures above, EPA calculated the short-term DWLOCs.
The DWLOC of 8.2 <greek-m>g/L for the U.S. population is greater than
the water EEC's. The DWLOC for infants/children (0.77 <greek-m>g/L) is
greater than the PRZM-EXAMS chronic value of 0.57 <greek-m>g/L. EPA
does not expect aggregate short-term exposure to avermectin
B<INF>1</INF> will pose an unacceptable risk to human health.
The worst case intermediate-term exposures to avermectin
B<INF>1</INF> for adults are the same as those described above for
short-term exposures. Using the exposures above, EPA calculated the
adult intermediate-term DWLOC of 8.2 <greek-m>g/L, which is greater
than the water EEC's. EPA does not expect aggregate intermediate-term
exposure to avermectin B<INF>1</INF> will pose an unacceptable risk to
adult human health.
The worst case intermediate-term exposures to avermectin
B<INF>1</INF> for infants and children are the same as those described
above. Since the short- and intermediate-term NOAELs are the same, the
DWLOC is also equal to the 0.77 <greek-m>g/L short-term value. Again,
given the 0.57 <greek-m>g/L PRZM-EXAMS value, EPA is not concerned with
the residues in drinking water. EPA does not expect aggregate
intermediate-term exposure to avermectin B<INF>1</INF> will pose an
unacceptable risk to human health.
4. Aggregate cancer risk for U.S. population. EPA classified
avermectin B<INF>1</INF> as a Cancer Group E chemical based on the
absence of significant tumor increases in two adequate rodent
carcinogenicity studies.
5. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the U.S. population, infants, or children from aggregate exposure to
avermectin B<INF>1</INF> and its delta-8,9-isomer residues.
E. Determination of Safety for Infants and Children
1. In general. In assessing the potential for additional
sensitivity of infants and children to residues of avermectin
B<INF>1</INF> and its delta-8,9-isomer, EPA considered data from
developmental toxicity studies in the rat and rabbit and a 2-generation
reproduction study in the rat. The developmental toxicity studies are
designed to evaluate adverse effects on the developing organism
resulting from maternal pesticide exposure gestation. Reproduction
studies provide information relating to effects from exposure to the
pesticide on the reproductive capability of mating animals and data on
systemic toxicity.
FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for pre- and postnatal toxicity and the
completeness of the database 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 margin of exposure (MOE) analysis or through using
uncertainty (safety) factors in calculating a dose level that poses no
appreciable risk to humans. EPA believes that reliable data support
using the standard uncertainty factor (usually 100 for combined inter-
and intra-species variability) and not the additional tenfold MOE/
uncertainty factor when EPA has a complete data base under existing
guidelines and when the severity of the effect in infants or children
or the potency or unusual toxic properties of a compound do not raise
concerns regarding the adequacy of the standard MOE/safety factor.
2. Developmental toxicity studies. Studies are discussed in Unit
III.A.4 of this preamble.
3. Reproductive toxicity study. Studies are discussed in Unit
III.A.4 of this preamble.
4. Pre- and postnatal sensitivity. There was evidence of increased
susceptibility to the offspring following pre- and postnatal exposure
to avermectin B<INF>1</INF> in the 2-generation reproduction study in
rats.
5. Conclusion. There is a complete toxicity database for
avermectin B<INF>1</INF> and its delta-8,9-isomer and exposure data is
complete or is estimated based on data that reasonably accounts for
potential exposures. The Agency is retaining the 10-fold safety factor
for increased susceptibility of infants and children for this pesticide
and is applying it to females 13+, infants, and children population
subgroups for acute, chronic, and residential exposure.
The 10x Safety Factor is being retained because:
(1) There was evidence of increased susceptibility to the offspring
following pre- and postnatal exposure to avermectin B<INF>1</INF> in
the two-generation reproduction study in rats.
(2) There is evidence of neurotoxicity manifested as clinical signs
of neurotoxicity in mice, rats, and dogs in developmental,
reproduction, chronic and/or carcinogenicity studies in mice, rats and/
or dogs.
[[Page 48557]]
(3) There is concern for Structure Activity Relationship:
ivermectin induced cleft palate in fetal rats, and cleft palate and
clubbed forefoot in fetal rabbits.
(4) EPA determined that a developmental neurotoxicity study in rats
is required for avermectin B<INF>1</INF>. This study could provide
additional information on potential increased susceptibility, effects
on the development of the fetal nervous system, as well as the
functional development of the young.
(5) There is concern for post-application exposure to infants and
children in treated areas, including incidental hand-to-mouth ingestion
of the pesticide.
IV. Other Considerations
A. Metabolism In Plants and Animals
Plant metabolism data have been previously submitted on cotton
seed, citrus, and celery. In addition, a report titled ``Comparative
Degradation of Avermectin B<INF>1a</INF> in Cotton Leaf, Citrus Fruit,
Celery, and In Vitro'' was submitted. The proposed use in this petition
on grapes and chili peppers specifies multiple applications up to a
maximum application rate on grapes of 32 fl oz/A/season (0.038 lb ai/A/
season) and on peppers of 48 oz/A/season (0.057 lb ai/A/season).
Previously, the metabolism components have been examined from radio-
labeled avermectin B<INF>1</INF> on celery (10 applications at 7 day
intervals for a total equivalent of 1.0 lb ai/A/season), radio-labeled
avermectin B<INF>1</INF> on cotton (3 applications at 50 to 89 day
intervals for a total equivalent of 0.60 lb/A/season), and exaggerated
application rates to citrus (30X, 2.25 lb ai/A). The available
metabolism data on cotton, celery, and citrus represent a wide enough
range of crop matrices, growth modes, and use rates. It is unlikely
that application of avermectin B<INF>1</INF> to grapes and chili
peppers will result in new degradation compounds that have not
previously been produced and subjected to toxicity testing. EPA
concludes that the metabolism data are sufficient (a) to support the
proposed use on grapes and chili peppers and (b) to support the
recommended tolerance on cotton gin byproducts. The residues of concern
in/on grapes, chili pepper, and cotton gin byproduct commodities are
the parent compound (avermectin B<INF>1a</INF> and B<INF>1b</INF>) and
its delta-8,9-isomer.
Since there are no grape or chili pepper animal feed items of
regulatory concern, a discussion of animal metabolism is not germane to
petition PP 7F4844.
Animal metabolism data were not submitted in conjunction with
cotton petition (PP 7F3500). However, the metabolism of avermectin in
goat and rat has been reviewed. From these studies, it was determined
that the residues of concern in ruminants are avermectin B<INF>1a</INF>
and B<INF>1b</INF> and their delta-8,9-isomers. This conclusion was
based upon a feeding level of 1.0 mg/goat/day of <SUP>3</SUP>H-
avermectin. An additional metabolite (24-hydroxymethyl avermectin
B<INF>1a</INF>) was identified and is potentially of toxicological
significance, but was not included in the tolerance expression because
of its presence at low levels. However, EPA notes that if the livestock
dietary burden is increased and the tolerances for residues in meat and
milk need to be raised, then the 24-hydroxymethyl metabolite may need
to be included in the tolerance expression and appropriate enforcement
methods would need to be developed. Furthermore, an additional animal
metabolism study using <SUP>14</SUP>C-avermectin would be needed if the
expected ruminant dietary burden exceeded the dose level in the
previously submitted goat metabolism study. EPA concludes the available
ruminant metabolism study is adequate to support the proposed
tolerances for avermectin on cotton gin byproducts.
Cotton gin byproducts are not a poultry feed item. Therefore a
discussion of metabolism and secondary residues in poultry commodities
is not pertinent to petition PP 7F3500.
B. Analytical Enforcement Methodology
The registrant has used the analytical procedure designated Method
91-1 for data gathering purposes in these grape and chili pepper field
trials for avermectin B<INF>1</INF> and its delta-8,9-isomer.
Acceptable independent method validations (ILV) were submitted for both
commodities. The samples are extracted with acetonitrile/water/hexane,
cleaned up with an aminopropyl column, and derivatized with
trifluoroacetic anhydride. Quantitation of the residues of interest is
accomplished by high performance liquid chromatography (HPLC) with
fluorescence detector. The LOQ varies from .001 ppm for grapes to .004
ppm for chili peppers. Method 91-1 is adequate for data collection
purposes. Method 91-1 is somewhat similar to the registrant's method
for hops, Method M-036.2, which has been submitted for inclusion in
FDA's PAM II. Since they are similar, Method M-036.2 is adequate for
tolerance enforcement.
Residues of avermectin B<INF>1</INF> and 8,9-Z avermectin
B<INF>1</INF> in cotton gin byproducts were determined using a
modification of Method M-078. Samples are extracted with a methanol-
water mixture. The avermectins are partitioned into hexane and the
hexane extract is purified/concentrated on an NH2 SPE column. The
purified extract is derivatized with trifluoroacetic anhydride. The
derivatized avermectins are analyzed by reversed phase HPLC with
fluorescence detection. The avermectin B<INF>1a</INF> standard is used
to calculate the concentration of avermectin B<INF>1a</INF> + 8,9-Z
avermectin B<INF>1a</INF> and avermectin B<INF>1b</INF> + 8,9-Z
avermectin B<INF>1b</INF> in/on the sample. The modifications made to
Method M-078 included using a higher HPLC flow rate, preparing the
standard solutions at different concentrations, centrifuging the
samples with emulsions after shaking, and using equipment, apparatus,
and chemical manufacturers which were different from those specified in
the method. The limit of detection (LOD) is 0.001 ppm; the LOQ is 0.002
ppm. The method was validated by fortifying control gin trash samples
and analyzing them concurrently with the treated and control samples.
Method M-078 is very similar to the registrant's method for hops,
Method M-036.2, which has been submitted for inclusion in FDA's PAM II.
Since they are very similar and method recovery is good, Method M-078
is adequate for enforcement purposes.
Merck Method 32A is available for enforcing avermectin tolerances
in bovine tissues and milk. This method has been published in PAM II
(Method II).
Avermectin B<INF>1</INF> is not recovered using FDA multi-residue
protocol A described in PAM I.
C. Magnitude of Residues
The residue field trial data on grapes submitted with this petition
are adequate to support the proposed use. The highest residue found on
grapes at the 28-day pre-harvest interval (PHI) was 6.7 ppb (0.007
ppm). This supports the tolerance of 0.02 ppm proposed by the
registrant.
The residue field trial data on chili peppers submitted with this
petition are adequate to support the proposed use. The highest residue
found on chili peppers at the 7- day PHI was < 5 parts per billion
(ppb) (< 0.005 ppm). This supports the tolerance of 0.01 ppm on peppers
proposed by the registrant. However, the originally submitted Section F
lists chili peppers not peppers. In order to harmonize with
international residue limits discussed below, the Section F was revised
to express the tolerance as 0.02 ppm on peppers.
[[Page 48558]]
The grape processing study and existing storage stability database
are adequate to support the proposed tolerance on juice. The highest
residues found on commodities of regulatory concern were < 2 ppb (<
0.002 ppm) in juice. This supports the requested tolerance of 0.02 ppm
on grape juice. However, since the processing study shows that
avermectin B<INF>1</INF> does not concentrate in juice, a tolerance on
grape juice is not required.
Starting with raw grapes bearing residues of 10 ppb, the highest
avermectin B<INF>1</INF> residues found on raisins were 10.2 ppb (0.01
ppm). The results of the raisin storage stability study indicate that
the residues in raisins could have been as high as 20 ppb (2x
concentration factor, based on < 50% recoveries). Using this
concentration factor and the highest grape field trial value of 0.007
ppm, residues in raisins would be 0.014 ppm versus the grape tolerance
of 0.02 ppm. Therefore, even taking into account the poor recoveries
from the raisin storage stability study, a tolerance for raisins is not
necessary. Since tolerances are not needed for processed grape food
items, the Section F was revised to express the tolerance as grapes.
There are no chili pepper processed food items; therefore a
discussion of processed food items is not germane to this action.
Since there are no grape or pepper animal feed items of regulatory
interest, secondary avermectin B<INF>1</INF> residues in meat, milk,
poultry, and eggs will not be increased by the proposed tolerances for
these crops.
To support the tolerance on cotton gin byproducts, the petitioner
has submitted the results of eight field trials on cotton using the
maximum labeled rate. The existing storage stability database is
adequate to support the cotton gin byproduct analyses. The highest
residue level obtained was 0.101 ppm. The PHI was slightly longer than
that specified on the label, however. The label specifies a PHI of 20
days; the PHI used in the field trails was 25 days. EPA has concluded
that the data support the establishment of a tolerance of 0.15 ppm for
the residues of avermectin in/on cotton gin byproducts.
Since cotton gin byproducts are a feed item for some livestock an
analysis was performed to calculate the dietary burden in these
animals. Cotton gin byproducts are not a feed item for poultry or
swine; these commodities were not included in the analysis. Cotton gin
byproducts can comprise up to 20% of the diets of both beef and dairy
cattle. The following animal feed items are associated with commodities
with avermectin registrations: almond hulls, wet apple pomace, dried
citrus pulp, cotton seed, potato culls, and potato waste. Of these
commodities, cotton seed meal is the only highly nutritive one. The
others mainly provide fiber to the diet. Cotton seed meal will be
distributed to all parts of the country, but the others will not.
Therefore, it is reasonable to construct a dietary burden with cotton
seed meal and only one of the other ``esoteric'' feed items. Wet apple
pomace would contribute the highest residues to the diet, therefore a
dietary burden was constructed using cotton seed meal and apple pomace.
The feeding study was done at 3 different feeding levels: 0.010 ppm,
0.030 ppm, and 0.10 ppm. The dietary burden constructed with cotton
seed and apple pomace is essentially the same as the highest feeding
level: 0.10 ppm. The established tolerances are adequate to cover this
dietary burden. As the tolerances will not change, it is not necessary
to perform a dietary exposure analysis. EPA concludes that residues
present in animal commodities will not increase over current levels.
Therefore, it is not necessary to increase the established tolerances
for animal commodities. Furthermore, the establishment of a tolerance
for cotton gin byproducts does not affect risk to human health as
animal commodity tolerances will not be affected by the establishment
of this tolerance.
D. International Residue Limits
There are no Codex, Canadian, or Mexican Maximum Residue Limits
(MRL) for avermectin B<INF>1</INF> on grapes, grape processed
commodities. Therefore, international harmonization is not an issue for
the action on grapes.
There are no Canadian or Mexican MRLs for avermectin B<INF>1</INF>
on peppers. There is a Codex MRL for avermectin B<INF>1a</INF>,
B<INF>1b</INF>, (Z)-8,9-avermectin B<INF>1a</INF>, and (Z)-8,9-
avermectin B<INF>1b</INF> on sweet peppers at 0.02 ppm. The regulable
residues for the U.S. and Codex are identical. In order to harmonize
with this MRL, the Section F was revised to express the tolerance for
avermectin B<INF>1</INF> and its delta-8.9-isomer as 0.02 ppm on
peppers.
There are no Codex, Canadian, or Mexican MRLs for avermectin
B<INF>1</INF> on cotton gin by-products. Therefore, international
harmonization is not an issue for cotton gin by-products. A Codex MRL
has been established for cotton seed: 0.01 ppm. This MRL differs from
the proposed permanent tolerance for cotton seed: 0.005 ppm.
E. Rotational Crop Restrictions
Review of the results of the confined rotational crop study
indicated that avermectin B<INF>1</INF> residues accumulated in some
rotational crops at levels up to 10 - 12 ppb. However, the
radioactivity was due to polar degradates that were of little
toxicological concern as compared to the parent compound avermectin
B<INF>1</INF> and/or the delta-8,9-isomer. Therefore, the requirements
for field rotational crop studies have been waived.
V. Conclusion
Therefore, the tolerance is established for combined residues of
the insecticide avermectin B<INF>1</INF> (a mixture of avermectins
containing greater than or equal to 80% avermectin B<INF>1a</INF> (5-O-
demethyl avermectin A<INF>1</INF>) and less than or equal to 20%
avermectin B<INF>1b</INF> (5-O-demethyl-25-de(1-methylpropyl)-25-(1-
methylethyl) avermectin A<INF>1</INF>)) and its delta-8,9-isomer in
grapes at 0.02 ppm, peppers at 0.02 ppm, and cotton gin byproducts at
0.15 ppm. Furthermore, the following tolerances which were previously
time-limited (expiring September 1, 1999) are now made permanent:
cattle, fat at 0.015 ppm; cattle, meat byproducts at 0.02 ppm; cattle,
meat at 0.02 ppm; citrus, dried pulp at 0.10 ppm; citrus, oil at 0.10
ppm; citrus, whole fruit at 0.02 ppm; cotton seed at 0.005 ppm; hops,
dried at 0.20 ppm; milk at 0.005 ppm; and potatoes at 0.005 ppm.
VI. Objections and Hearing Requests
Under section 408(g) of the FFDCA, as amended by the FQPA, any
person may file an objection to any aspect of this regulation and may
also request a hearing on those objections. The EPA procedural
regulations which govern the submission of objections and requests for
hearings appear in 40 CFR part 178. Although the procedures in those
regulations require some modification to reflect the amendments made to
the FFDCA by the FQPA of 1996, EPA will continue to use those
procedures, with appropriate adjustments, until the necessary
modifications can be made. The new section 408(g) provides essentially
the same process for persons to ``object'' to a regulation for an
exemption from the requirement of a tolerance issued by EPA under new
section 408(d), as was provided in the old FFDCA sections 408 and 409.
However, the period for filing objections is now 60 days, rather than
30 days.
A. What Do I Need to Do to File an Objection or Request a Hearing?
You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in this unit
and in 40 CFR part 178. To ensure proper receipt by EPA, you must
identify docket control number OPP-300916 in the subject line
[[Page 48559]]
on the first page of your submission. All requests must be in writing,
and must be mailed or delivered to the Hearing Clerk on or before
November 8, 1999.
1. Filing the request. Your objection must specify the specific
provisions in the regulation that you object to, and the grounds for
the objections (40 CFR 178.25). If a hearing is requested, the
objections must include a statement of the factual issues(s) on which a
hearing is requested, the requestor's contentions on such issues, and a
summary of any evidence relied upon by the objector (40 CFR 178.27).
Information submitted in connection with an objection or hearing
request may be claimed confidential by marking any part or all of that
information as CBI. Information so marked will not be disclosed except
in accordance with procedures set forth in 40 CFR part 2. A copy of the
information that does not contain CBI must be submitted for inclusion
in the public record. Information not marked confidential may be
disclosed publicly by EPA without prior notice.
Mail your written request to: Office of the Hearing Clerk (1900),
Environmental Protection Agency, 401 M St. SW. Washington, DC 20460.
You may also deliver your request to the Office of the Hearing Clerk in
Room M3708, Waterside Mall, 401 M St. SW. Washington, DC 20460. The
Office of the Hearing Clerk is open from 8 a.m. to 4 p.m. Monday
through Friday, excluding legal holidays. The telephone number for the
Office of the Hearing Clerk is (202) 260-4865.
2. Tolerance fee payment. If you file an objection or request a
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must
mail the fee to: EPA Headquarters Accounting Operations Branch, Office
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please
identify the fee submission be labeling it ``Tolerance Petition Fees.''
EPA is authorized to waive any fee requirement ''when in the
judgement of the Administrator such a waiver or refund is equitable and
not contrary to the purpose of this subsection.'' (cite). For
additional information regarding the waiver of these fees, you may
contact James Tompkins by phone at (703) 305-5697, by e-mail at
tompkins.jim@epa.gov, or by mailing a request for information to Mr.
Tompkins at Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St. SW., Washington,
DC 20460.
If you would like to request a waiver of the tolerance objection
fees, you must mail your request for such a waiver to: James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St. SW.
Washington, DC 20460.
3. Copies for the Docket. In addition to filing an objection or
hearing request with the Hearing Clerk as described in Unit VI.A. of
this preamble, you should also send a copy of your request to the PIRB
for its inclusion in the official record that is described in Unit
I.B.2. of this preamble. Mail your copies, identified by docket number
OPP-300916, to: Public Information and Records Integrity Branch,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St. SW.
Washington, DC 20460. In person or by courier, bring a copy to the
location of the PRIB described in Unit I.B.2. of this preamble. You may
also send an electronic copy of your request via e-mail to: opp-
docket@epa.gov. Please use an ASCII file format and avoid the use of
special characters and any form of encryption. Copies of electronic
objections and hearing requests will also be accepted on disks in
WordPerfect 5.1/6.1 file format or ASCII file format. Do not include
any CBI in your electronic copy. You may also submit an electronic copy
of your request at many Federal Depository Libraries.
B. When Will the Agency Grant a Request for a Hearing?
A request for a hearing will be granted if the Administrator
determines that the material submitted shows the following: There is a
genuine and substantial issue of fact; there is a reasonable
possibility that available evidence identified by the requestor would,
if established resolve one or more of such issues in favor of the
requestor, taking into account uncontested claims or facts to the
contrary; and resolution of the factual issues(s) in the manner sought
by the requestor would be adequate to justify the action requested (40
CFR 178.32).
VII. Regulatory Assessment Requirements
This final rule establishes tolerances under section 408(d) of the
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). 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., or 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). Nor
does it require prior consultation with State, local, and tribal
government officials as specified by Executive Order 12875, entitled
Enhancing the Intergovernmental Partnership (58 FR 58093, October 28,
1993) and Executive Order 13084, entitled Consultation and Coordination
with Indian Tribal Governments (63 FR 27655, May 19,1998), or special
consideration of environmental justice related issues under Executive
Order 12898, entitled Federal Actions to Address Environmental Justice
in Minority Populations and Low-Income Populations (59 FR 7629,
February 16, 1994), or require OMB review in accordance with Executive
Order 13045, entitled Protection of Children from Environmental Health
Risks and Safety Risks (62 FR 19885, April 23, 1997). The Agency has
determined that this action will not have a substantial direct effect
on States, on the relationship between the national government and the
States, or on the distribution of power and responsibilities among the
various levels of government, as specified in Executive Order 12612,
entitled Federalism (52 FR 41685, October 30, 1987). This action
directly regulates growers, food processors, food handlers and food
retailers, not States. This action does not alter the relationships or
distribution of power and responsibilities established by Congress in
the preemption provisions of the Federal Food, Drug, and Cosmetic Act,
21 U.S.C. section 346a(b)(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). In addition, since
tolerances and exemptions that are established on the basis of a
petition under FFDCA section 408(d), such as the tolerances 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.
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq. as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a
[[Page 48560]]
copy of the rule, 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 rule in the Federal Register. This 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: August 31, 1999.
Richard P. Keigwin, Jr.,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 321(q), (346a), and 371.
2. Section 180.449 is amended by revising paragraph (a) to read as
follows:
Sec. 180.449 Avermectin B<INF>1</INF> and its delta-8,9-isomer;
tolerances for residues.
(a) General. Tolerances are established for the combined residues
of the insecticide avermectin B<INF>1</INF> (a mixture of avermectins
containing greater than or equal to 80% avermectin B<INF>1a</INF> (5-O-
demethyl avermectin A<INF>1</INF>) and less than or equal to 20%
avermectin B<INF>1b</INF> (5-O-demethyl-25-de(1-methylpropyl)-25-(1-
methylethyl) avermectin A<INF>1</INF>)) and its delta-8,9-isomer in or
on the following commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Almonds.................................................... 0.005
Almond, hulls.............................................. 0.10
Apples..................................................... 0.020
Apples, pomace (wet)....................................... 0.10
Cattle, fat................................................ 0.015
Cattle, mbyp............................................... 0.02
Cattle, meat............................................... 0.02
Celery..................................................... 0.05
Citrus, dried pulp......................................... 0.10
Citrus, oil................................................ 0.10
Citrus whole fruit......................................... 0.02
Cotton gin by-products..................................... 0.15
Cotton seed................................................ 0.005
Cucurbits (cucumbers, mellons, and squashes)............... 0.005
Grapes..................................................... 0.02
Hops, dried................................................ 0.20
Lettuce, head.............................................. 0.05
Milk....................................................... 0.005
Pears...................................................... 0.02
Peppers.................................................... 0.02
Potatoes................................................... 0.005
Strawberry................................................. 0.02
Tomatoes, fresh............................................ 0.01
Walnuts.................................................... 0.005
------------------------------------------------------------------------
* * * * *
[FR Doc. 99-23194 Filed 9-3-99; 8:45 am]
BILLING CODE 6560-50-F
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