[Federal Register Volume 65, Number 68 (Friday, April 7, 2000)]
[Notices]
[Pages 18328-18332]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-8263]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-930; FRL-6499-4]
Notice of Filing a Pesticide Petition to Establish a Tolerance
for Certain Pesticide Chemicals in or on Food
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by docket control number PF-930, must be
received on or before May 8, 2000.
ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as
provided in Unit I.C. of the ``SUPPLEMENTARY INFORMATION.'' To ensure
proper receipt by EPA, it is imperative that you identify docket
control number PF-930 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, Ariel Rios Bldg., 1200 Pennsylvania
Ave., NW., Washington, DC 20460; telephone number: (703) 308-9423; e-
mail address: [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be 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
Categories NAICS Codes potentially
affected entities
------------------------------------------------------------------------
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 (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 under ``FOR FURTHER INFORMATION
CONTACT.''
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 PF-930. The official record
consists of the documents specifically referenced in this action, any
public comments received during an applicable comment period, 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 Highway, 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.
C. How and to Whom Do I Submit Comments?
You may submit comments through the mail, in person, or
electronically. To ensure proper receipt by EPA, it is imperative that
you identify docket control number PF-930 in the subject line on the
first page of your response.
1. By mail. Submit your comments to: Public Information and Records
Integrity Branch (PIRIB), Information Resources and Services Division
[[Page 18329]]
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC
20460.
2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
3.Electronically. You may submit your comments electronically by e-
mail to: ``[email protected],'' or you can submit a computer disk as
described above. Do not submit any information electronically that you
consider to be CBI. Avoid the use of special characters and any form of
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-930. Electronic comments may
also be filed online at many Federal Depository Libraries.
D. How Should I Handle CBI That I Want to Submit to the Agency?
Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI 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. In addition to one complete
version of the comment that includes any information claimed as CBI, a
copy of the comment that does not contain the information claimed as
CBI must be submitted for inclusion in the public version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person identified under ``FOR FURTHER INFORMATION
CONTACT.''
E. What Should I Consider as I Prepare My Comments for EPA?
You may find the following suggestions helpful for preparing your
comments:
1. Explain your views as clearly as possible.
2. Describe any assumptions that you used.
3. Provide copies of any technical information and/or data you used
that support your views.
4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
5. Provide specific examples to illustrate your concerns.
6. Make sure to submit your comments by the deadline in this
notice.
7. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
Register citation.
II. What Action is the Agency Taking?
EPA has received a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of certain
pesticide chemical in or on various food commodities under section 408
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that this petition contains data or information
regarding the elements set forth in section 408(d)(2); however, EPA has
not fully evaluated the sufficiency of the submitted data at this time
or whether the data supports granting of the petition. Additional data
may be needed before EPA rules on the petition.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: March 28, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the petitioner and represents the view of the
petitioner. EPA is publishing the petition summary verbatim without
editing it in any way. The petition summary announces the availability
of a description of the analytical methods available to EPA for the
detection and measurement of the pesticide chemical residues or an
explanation of why no such method is needed.
Novartis Crop Protection, Inc.
PP 9F5047
EPA has received a pesticide petition (PP 9F5047) from Novartis
Crop Protection, Inc., P.O. Box 18300, Greensboro, NC 27419 proposing,
pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act
(FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a
tolerance for residues of abamectin (avermectin B1) and or
its delta 8,9-isomer in or on the raw agricultural commodities plums at
0.01 parts per million (ppm), fruiting vegetables (except Cucurbits)
group at 0.02 ppm, and leafy vegetables (except Brassica) group at 0.10
ppm. EPA has determined that the petition contains data or information
regarding the elements set forth in section 408(d)(2) of the FFDCA;
however, EPA has not fully evaluated the sufficiency of the submitted
data at this time or whether the data support granting of the petition.
Additional data may be needed before EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. The metabolism of abamectin in plants is
adequately understood and the residues of concern include the parent
insecticide, abamectin or avermectin B1, which is a mixture
of a minimum of 80% avermectin B1a and a maximum of 20%
avermectin B1b and the delta 8,9-isomer of the
B1a and of the B1b components of the parent
insecticide. Animal metabolism also has been studied but is not
relevant to this petition, since the crops involved are not significant
animal feed items. Under photolytic conditions in the laboratory and in
the field, abamectin under goes isomerization around the 8,9-double
bond to produce small amounts of the delta-8,9 isomer. The photo-
oxidative half-life of the delta-8,9 isomer is 4.5 hours and that of
avermectin B1a is 6.5 hours.
2. Analytical method. The analytical method involves
homogenization, filtration, partition and cleanup with analysis by
HPLC-fluorescence detection. The methods are sufficiently sensitive to
detect residues at or above the tolerances proposed. All methods have
undergone independent laboratory validation as required by PR Notice
88-5.
3. Magnitude of residues. Abamectin was applied to leaf lettuce and
spinach in eleven trials in the following states: Colorado, California
(4) sites; Florida, Texas, Arizona leaf lettuce; South Carolina
spinach; New Jersey spinach; and New York leaf lettuce. Nine field
trials were conducted in the principal
[[Page 18330]]
plum growing areas of the United States including California (6),
Michigan (1), Oregon (1) and Washington (1). This data support the
proposed tolerances of 0.01 ppm for residues of abamectin on plums and
0.10 ppm on leafy vegetables (except Brassica) group. Tolerances and
residue data on tomatoes and peppers support the fruiting vegetable
(except Cucurbits) group tolerance.
B. Toxicological Profile
1. Acute toxicity. The data base includes the following studies: A
rat acute oral study with a LD50 of 4.4 to 11.8 milligrams/
kilograms (mg/kg) (males) and 10.9 to 14.9 mg/kg (females); an acute
oral toxicity in the CF-1 mouse with the delta 8,9-isomer has
LD50 greater than 80 mg/kg; a rabbit acute dermal study with
a LD50 greater than 2,000 mg/kg; a rat acute inhalation
study with a LC50 greater than 5.73 mg/L; a primary eye
irritation study in rabbits which showed irritation; a primary dermal
irritation study in rabbits which showed no irritation; a primary
dermal sensitization study in guinea pigs which showed no skin
sensitization potential; an acute oral toxicity study in monkeys with
no observed adverse effects level (NOAEL) of 1.0 mg/kg based upon
emesis at 2.0 mg/kg.
2. Genotoxicity. The ames assays conducted with and without
metabolic activation were both negative. The V-79 mammalian cell
mutagenesis assays conducted with and without metabolic activation did
not produce mutations. In an alkaline elution/rat hepatocyte assay,
abamectin was found to induce single strand DNA breaks without
significant toxicity in rat hepatocytes treated in vitro at doses
greater than 0.2 mM. This in vitro dose of 0.2 mM is biologically
unobtainable in vivo, due to the toxicity of the compound. However, at
these potentially lethal doses, in vivo treatment did not induce DNA
single strand breaks in hepatocytes. In the mouse bone marrow assay,
abamectin was not found to induce chromosomal damage. There are also
many studies and a great deal of clinical and follow-up experience with
regard to ivermectin, a closely similar human and animal drug.
3. Reproductive and developmental toxicity. A 2-generation study in
rats with a NOAEL of 0.12 mg/kg/day in pups based upon retinal folds,
decreased body weight, and mortality. The NOAELs for systemic and
reproductive toxicity were 0.4 mg/kg/day. In the 2-generation
reproduction study in rats with the delta 8,9-isomer, the NOAEL was 0.4
mg/kg/day and the NOAEL was greater than 0.4 mg/kg/day (HDT). An oral
teratology study in the CF-1 mouse with a maternal NOAEL of 0.05 mg/kg/
day based upon decreased body weights and tremors. The fetal NOAEL was
0.20 mg/kg/day based upon cleft palates. An oral teratology study with
the delta 8,9-isomer in CF-1 mice with a maternal NOAEL of 0.10 mg/kg/
day based upon decreased body weights. The fetal NOAEL was 0.06 mg/kg/
day based upon cleft palate. An oral teratology study in rabbits with a
maternal NOAEL of 1.0 mg/kg/day based upon decreased body weights and
tremors. The fetal NOAEL was 1.0 mg/kg/day based upon clubbed feet. An
oral teratology study in rats with a maternal and fetal NOAEL at 1.6
mg/kg/day, the highest dose tested (HDT). An oral teratology study with
the delta 8,9-isomer with a maternal NOAEL in CF-1 mice that expressed
P-glycoprotein greater than 1.5 mg/kg/day, the highest and only dose
tested. No cleft palates were observed in fetuses that expressed normal
levels of P-glycoprotein, but fetuses with low or no levels of P-
glycoprotein had increased incidence of cleft palates.
4. Subchronic toxicity. A rat 8-week feeding study with a NOAEL of
1.4 mg/kg/day based upon tremors. A rat 14-week oral toxicity study
with a NOAEL of 0.4 mg/kg/day, the highest dose tested. A dog 12-week
feeding study with a NOAEL of 0.5 mg/kg/day based upon mydriasis. A dog
18-week oral study with a NOAEL of 0.25 mg/kg/day based upon mortality.
A CD-1 mouse 84-day feeding study with a NOAEL of 4 mg/kg/day based
upon decreased body weights.
5. Chronic toxicity. A rat 53-week oncogenicity feeding study,
negative for oncogenicity, with a NOAEL of 1.5 mg/kg/day based upon
tremors. A CD-1 mouse 94-week oncogenicity feeding study, negative for
oncogenicity, with a NOAEL of 4 mg/kg/day based upon decreased body
weights. A dog 53-week chronic feeding study, negative for
oncogenicity, with a NOAEL of 0.25 mg/kg/day based upon mydriasis.
6. Animal metabolism. Rats were given oral doses of 0.14 or 1.4 mg/
kg/day of abamectin or 1.4 mg/kg/day of the delta-8,9 isomer. Over 7
days, the percent excreted in urine were 0.3-1% of the administered
dose of abamectin and 0.4% of the dose of the isomer. The animals
eliminated 69-82% of the dose of abamectin and 94% of the dose of
isomer in feces. In rats, goats and cattle, unchanged parent compound
accounted for up to 50% of the total radioactive residues in tissues.
The 24-hydroxymethyl derivative of abamectin was found in rats, goats
and cattle treated with the compound and in rats treated with the
delta-8,9 isomer, and the 3',-O-demethyl derivative was
found in rats and cattle administered abamectin and in rats
administered the isomer.
7. Metabolite toxicology. There are no metabolites of concern based
on a differential metabolism between plants and animals. The potential
hazard of the 24-hydroxymethyl or the 3',-O-demethyl animal
metabolites was evaluated in through toxicology studies with abamectin,
photolytic break down product, the delta 8,9-isomer.
8. Endocrine disruption. There is no evidence that abamectin is an
endocrine disrupter. Evaluation of the rat multi-generational study
demonstrated no effect on the time to mating or on the mating and
fertility indices, suggesting no effects on the estrous cycle, on
mating behavior, or on male or female fertility at doses up to 0.4 mg/
kg/day, the highest dose tested. Furthermore, the range finding study
demonstrated no adverse effect on female fertility at doses up to 1.5
mg/kg/day, the highest dose tested. Similarly, chronic and subchronic
toxicity studies in mice, rats, and dogs did not demonstrate any
evidence of toxicity to the male or female reproductive tract, or to
the thyroid or pituitary based upon organ weights and gross and
histopathologic examination. In the developmental studies, the pattern
of toxicity observed does not seem suggestive of any endocrine effect.
Finally, experience with ivermectin in breeding animals, including
sperm evaluations in multiple species, shows no adverse effects
suggestive of endocrine disruption.
C. Aggregate Exposure
Dietary exposure--i. Food. The acute dietary reference dose (RfD)
is 0.0025 mg/kg/day from a 1-year dog study. The NOAEL is 0.25 mg/kg/
day, and the lowest observed adverse effect level (LOAEL) is 0.50 mg/
kg/day based on mydriasis (pupil dilation) which was observed after 1-
week of dosing. An uncertainty factor of 100 to account for
interspecies extrapolation (10x) and intraspecies variability (10x) was
recommended. EPA has also retained the 10x safety factor for infants
and children resulting in an aRfD of 0.00025 mg/kg for appropriate
populations. EPA has determined that the studies conducted with the CF-
1 mouse are not relevant to human safety assessment. A Monte Carlo
acute dietary exposure analysis predicted the percent RfD used for the
general population is 39.9% at the 99.9%. Children 1-6 years constitute
the sub-population with the highest predicted exposure. The predicted
percent RfD utilization for
[[Page 18331]]
this subgroup is 69.5% for 99.9% of the individuals.
EPA has established the RfD for abamectin at 0.0012 mg/kg/day from
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 to account for interspecies extrapolation (10x) and intraspecies
variability (10x) was recommended. EPA has also retained the 10x safety
factor for infants and children resulting in an RfD of 0.00012 mg/kg/
day for appropriate population dietary exposure analysis for abamectin
in the most exposed population (non-nursing infants 1-year old) shows
the percent RfD utilization to be only 20.0%. For the average U.S.
population (48 contiguous states), dietary exposure for abamectin shows
a minimal utilization of 9.4% of the RfD.
ii. Drinking water. EPA modeling data (Generic Expected
Environmental Concentration/Screening Concentration In Ground Water
(GENEEC/SCIGROW)) indicated the worst case estimated environmental
concentrations (EEC) of 0.485 ug/L avermectin for acute and 0.239 ug/L
for chronic exposure, both in surface water from the same use of
abamectin on strawberries (the maximum use rate on the label). Refined
modeling data pesticide root zone model exposure analysis modeling
system (PRZM EXAM) indicate a worst case EEC of 0.88 ug/L for acute and
0.57 ug/L for chronic, both calculated for an abamectin use on
strawberries grown on black plastic mulch. EPA noted and Novartis
agrees that the certainty of the concentrations estimated for
strawberries is low, due to uncertainty on the amount of run off from
plant beds covered in plastic mulch and uncertainty on the amount of
degradation of abamectin on black plastic compared to soil.
Novartis believes the estimates of abamectin exposure in water
derived from the PRZM-EXAMS model are overstated for several reasons.
The PRZM-EXAMS model was designed to estimate exposure from ecological
risk assessments and thus use a scenario of a body of water
approximating the size of a 1 hectare (2.5 acres) pond. This tends to
overstate drinking water exposure levels for the following reasons.
a. Surface water source drinking water generally comes from bodies
of water that is substantially larger than a 1 hectare (2.5 acres)
pond.
b. The modeled scenario also assumes that essentially the whole
basin receives an application of the pesticide. Yet in virtually all
cases, basins large enough to support a drinking water facility will
contain a substantial fraction of the area which does not receive
pesticide.
c. There is often at least some flow in a river or turnover in a
reservoir or lake of water persistence to the pesticide near the
drinking water facility is usually over estimated.
d. Even assuming a reservoir is directly adjacent to an
agricultural field, the agricultural field may not be used to grow a
crop on which the pesticide in question is registered for use.
e. The PRZM-EXAMS modeled scenario does not take into account
reductions in residue loading due to applications of less than the
maximum application rate or no treatment of the crop at all (percent
crop treated data).
Although there is a high degree of uncertainty to this analysis,
this is the best available estimate of concentrations of abamectin in
drinking water. Although the peak EEC of 0.88 ug/L slightly exceeds the
acute DWLOC, 0.76 ug/L, considering the uncertain nature of the
modeling estimate, Novartis does not expect aggregate acute exposure to
avermectin will pose an unacceptable risk to human health.
2. Non-dietary exposure. Avermectin's registered residential use
include indoor crack/crevice and outdoor application to lawns. For lawn
use, EPA conducted a risk assessment for adult applicators and post
application exposure to avermectin using EPA's Draft SOP's for
residential exposure assessments. The highest predicted exposure oral
hand to mouth for children, resulted in a calculated margin of exposure
14,000. For children's post application exposure to avermectin from
indoor crack/crevice products, valid exposure studies demonstrate there
is no exposure and therefore no risk for indoor residential scenarios.
Short-and intermediate-term risk for registered uses do not exceed
EPA's level of concern. Chronic exposure and risk for the residential
use is not expected. Short-and intermediate-term exposure and risk for
the registered uses do not exceed EPA's level of concern.
D. Cumulative Effects
Section 408(b)(2)(D)(v) requires that, when considering whether to
establish, modify, or revoke a tolerance, the Agency considers
``available information'' concerning the cumulative effects of a
particular pesticide residue and ``other substances that have a common
mechanism of toxicity.'' EPA stated in the FR notice published on April
7, 1999, that it does not have at this time available data to determine
whether avermectin has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment.
E. Safety Determination
1. U.S. population. Using the exposure assumptions described above
and based on the completeness and reliability of the toxicity data
base, Novartis has calculated aggregate exposure levels for this
chemical. The calculations show that chronic exposure is below 100% of
the RfD and the predicted acute exposure is below 100% of the acute RfD
for all subpopulations. Novartis concludes that there is a reasonable
certainty that no harm will result from aggregate exposure to abamectin
residues.
2. Infants and children. The FQPA authorizes the employment of an
additional safety factor of up to 10x to guard against the possibility
of prenatal or postnatal toxicity, or to account for an incomplete data
base on toxicity or exposure. EPA has chosen to retain the FQPA 10x
safety factor for abamectin based on several reasons including evidence
of neurotoxicity, susceptibility of neonatal rat pups, similarity to
ivermectin, lack of a developmental neurotoxicity study, and concern
for exposure to infants and children. It is the opinion of Novartis
that a 3x safety factor is more appropriate for abamectin at this time.
EPA has evaluated abamectin repeatedly since its introduction in 1985
and has found repeatedly that the level of dietary exposure is
sufficiently low to provide ample margins of safety to guard against
any potential adverse effects of abamectin. In addition, valid exposure
studies demonstrate there is no exposure via indoor applications of
abamectin products. Novartis states that the data base for abamectin is
complete and that the developmental neurotoxicity study is a new and
not yet initially required study. Additionally, there is more
information regarding human risk potential than is the case with most
pesticides, because of the widespread animal drug and human drug uses
of ivermectin, the closely related analog of abamectin.
It is the opinion of Novartis that the use of a full 10x safety
factor to address risks to infants and children is not necessary. The
established chronic endpoint for abamectin in the neonatal rat is
overly conservative. Similar endpoints for ivermectin are not used by
the Food and Drug Administration to
[[Page 18332]]
support the allowable daily intake for ivermectin residues in food from
treated animals. No evidence of toxicity was observed in neonatal
rhesus monkeys after 14 days of repeated administration of 0.1 mg/kg/
day highest dose tested in juvenile rhesus monkeys after repeated
administration of 1.0 mg/kg/day, highest dose tested. The comparative
data on abamectin and ivermectin in primates also clearly demonstrate
the dose response for exposure to either compound is much less steep
than that seen in the neonatal rat. Single doses as high as 24 mg/kg of
either abamectin or ivermectin in rhesus monkeys did not result in
mortality; however, this dose was more than two times the
LD50 in the adult rat and more than 20 times the
LD50 in the neonatal rat. The absence of steep dose response
curve in primates provides a further margin of safety regarding the
probability of toxicity occurring in infants or children exposed to
avermectin compounds. The significant human clinical experience and
widespread animal drug uses of ivermectin without systemically toxic,
developmental, or postnatal effects supports the safety of abamectin to
infants and children.
F. International Tolerances
Codex has established an abamectin Maximum Residue Level of 0.02
ppm for peppers. The fruiting vegetable tolerance of 0.02 ppm for
abamectin is harmonized with Codex.
[FR Doc. 00-8263 Filed 4-6-00; 8:45 am]
BILLING CODE 6560-50-F