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avermectin (Agri-Mek, Affirm) Pesticide Petition Filing 9/00


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[Federal Register: September 27, 2000 (Volume 65, Number 188)]
[Notices]
[Page 58080-58085]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr27se00-80]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-977; FRL-6746-4]


Notice of Filing Pesticide Petitions 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 pesticide
petitions 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-977, must be
received on or before October 27, 2000.

ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as

[[Page 58081]]

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-977 in the subject line on the first page of your
response.

FOR FURTHER INFORMATION CONTACT: By mail: For Pesticide Petition PP
(0E6118), contact Shaja R. Brothers, Registration Division (7505C),
Office of Pesticide Programs, Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703)
308-3194; e-mail address: brothers.shaja@epa.gov.
    For Pesticide Petition PP (0F6146), contact Thomas C. Harris,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460; telephone number: (703) 308-9423; 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
           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,'' ``Regulations and Proposed Rules,'' 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-977. 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-977 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
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, 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: opp-docket@epa.gov, 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-977. 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

[[Page 58082]]

name, date, and Federal Register citation.

II. What Action is the Agency Taking?

    EPA has received pesticide petitions as follows proposing the
establishment and/or amendment of regulations for residues of certain
pesticide chemicals 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 these petitions contain 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 support granting of the petitions. Additional data
may be needed before EPA rules on the petitions.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.

    Dated: September 15, 2000.
  James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioners summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. The petitions summaries 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.

Interregional Research Project Number 4

Novartis Crop Protection Inc.

0E6118 and 0F6146

    EPA has received a pesticide petition (0E6118) from Interregional
Research Project Number 4, 681 U.S. Highway #1 South, North Brunswick
NJ 08902-3390. EPA has also received a pesticide petition (PP 0F6146)
from Novartis Crop Protection Inc., Post Office Box 18300, Greensboro
NC 27419-8300. These petitions propose, pursuant to section 408(d) of
the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing
tolerances for residues of the insecticide, avermectin ( a mixture of
avermectins containing greater than or equal to 80% avermectin
B1a (5-O-demethyl avermectin A1) and less than or
equal to 20% avermectin B1b (5-O-demethyl-25-de(1-
methylethyl) avermectin A1)) and its delta 8,9-isomer in or
on the food commodities at the tolerance level as follows:
    1. PP 0E6118, which was submitted by IR-4, proposes the
establishment of a tolerance for celeriac (roots and tops) at 0.05
parts per million (ppm).
    2. PP 0F6146, which was submitted by Novartis Crop Protection Inc.,
proposes the establishment of tolerances for avocado at 0.02 ppm, grass
forage at 0.001 ppm, grass hay at 0.001 ppm, stone fruit crop group at
0.015 ppm, mint tops at 0.01 ppm, tree nut crop group and pistachios at
0.005 ppm, and the tuberous and corm vegetables crop subgroup at 0.005
ppm.

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.
    2. Analytical method. The analytical methods involves
homogenization, filtration, partition, and cleanup with analysis by
high performance liquid chromotography (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. Complete residue data for abamectin for
the petitioned tolerances has been submitted. The data support the
requested tolerances.

B. Toxicological Profile

    1. Acute toxicity. The data base includes the following studies:
    i. A rat acute oral study with a lethal dose (LD)50 of
4.4 to 11.8 mg/kg (males) and 10.9 to 14.9 milligrams/kilograms (mg/kg)
(females).
    ii. An acute oral toxicity in the CF-1 mouse with the delta 8,9-
isomer has LD50 greater than 80 mg/kg.
    iii. A rabbit acute dermal study with a LD50 >2,000 mg/
kg.
    iv. A rat acute inhalation study with a LC50 >5.73 mg/L.
    v. A primary eye irritation study in rabbits which showed
irritation.
    vi. A primary dermal irritation study in rabbits which showed no
irritation.
    vii. A primary dermal sensitization study in guinea pigs which
showed no skin sensitization potential.
    viii. An acute oral toxicity study in monkeys with a no observed
adverse effect 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. In a 2-generation study
in rats the NOAEL was established at 0.12 mg/kg/day in pups based upon
retinal folds, decreased body weight (bwt), and mortality. The NOAELs
for systemic and reproductive toxicity were 0.4 mg/kg/day. In the 2-
generations reproduction study in rats with the delta 8,9-isomer, the
NOAEL was 0.4 mg/kg/day and the lowest observed adverse effect level
(LOAEL) was greater than 0.4 mg/kg/day highest dose tested (HDT).
    In an oral developmental toxicity study in the CF-1 mouse the
maternal NOAEL was 0.05 mg/kg/day based upon decreased bwts and
tremors. The fetal NOAEL was 0.20 mg/kg/day based upon cleft palates.
In an oral developmental toxicity study with the delta 8,9-isomer in
CF-1 mice the maternal NOAEL was 0.10 mg/kg/day based upon decreased
bwts. The fetal NOAEL was 0.06 mg/kg/day based upon cleft palate. In an
oral developmental toxicity study in rabbits the maternal NOAEL was 1.0
mg/kg/day based upon decreased bwts and tremors. The fetal NOAEL was
1.0 mg/kg/day based upon clubbed feet. In an oral developmental
toxicity study in rats the maternal and fetal NOAEL was 1.6 mg/kg/day,
the HDT. In an oral developmental toxicity study with the delta 8,9-
isomer the maternal NOAEL in CF-1 mice that expressed P-glycoprotein
was 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

[[Page 58083]]

no levels of P-glycoprotein had increased incidence of cleft palates.
    4. Subchronic toxicity. Subchronic toxicity studies included the
following:
    i. A rat 8-week feeding study with a NOAEL of 1.4 mg/kg/day based
upon tremors.
    ii. A rat 14-week oral toxicity study with a NOAEL of 0.4 mg/kg/
day, the HDT.
    iii. A dog 12-week feeding study with a NOAEL of 0.5 mg/kg/day
based upon mydriasis.
    iv. A dog 18-week oral study with a NOAEL of 0.25 mg/kg/day based
upon mortality.
    v. A. CD-1 mouse 84-day feeding study with a NOAEL of 4 mg/kg/day
based upon decreased bwts.
    5. Chronic toxicity. A rat 53-week carcinogencity feeding study was
negative for carcinogencity, with a NOAEL of 1.5 mg/kg/day based upon
tremors. A CD-1 mouse 94-week carcinogencity feeding study was negative
for carcinogencity, with a NOAEL of 4 mg/kg/day based upon decreased
bwts. A dog 53-week chronic feeding study was negative for
carcinogencity, 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 bwt/day of abamectin or 1.4 mg/kg bwt/day of the delta-8,9 isomer.
Over 7 days, the percentages 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 HDT. Furthermore, the range finding study demonstrated no
adverse effect on female fertility at doses up to 1.5 mg/kg/day, the
HDT. 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

    1. Dietary exposure--i. Food. An acute assessment was conducted for
avermectin B1a and B1b residues using the Dietary
Exposure Evaluation Model (DEEMTM) and food consumption
information from United State Department of Agriculture's (USDA)'s
1994-1996 continuing survey of food intake by individuals (CSFII).
Acute dietary exposure to the adult male subpopulation was compared to
an acute reference dose (RfD) of 0.0025 mg/kg/day based on a NOAEL of
0.25 mg/kg/day from a 1-year dog study and a 100X uncertainty factor
(UF). For all other populations (containing females, infants and
children) an acute population adjusted dose (PAD) of 0.00083 mg/kg/day
was used and reflects an appropriate 300X UF. This tier 3 probabilistic
analysis included the entire distribution of field trial residues and
percent of crop treated information was incorporated by adding zeroes
into the residue distribution file (RDF) representing the percent of
crop not treated. Non-detected residues of avermectin B1a
were entered into the software as 1/2 the limit of quantitation (1/2
(LOQ)) and non-detected residues of avermectin B1b were
entered in as 1/4 LOQ since the production ratio of B1a:
B1b is 80:20. The acute dietary exposure results for the
male (20 + years) population shows that 2.6% of the acute RfD was
utilized at the 99.9th percentile of exposure. For the
general U.S. population at the 99.9th percentile, exposure
was 13.2% of the acute PAD. The most sensitive subpopulation was non-
nursing infants (< 1-year old) with 39.3% of the acute PAD at the
99.9th percentile.
    For the male subpopulation, chronic exposure was compared to the
chronic RfD of 0.0012 mg/kg/day from a 2-generation reproduction study
in rats and a 100X UF. A 300X UF was utilized for populations
containing females (13 + years old) and infants and children and the
exposures were compared to a PAD of 0.0004 mg/kg/day. Residue values,
taken from field trials conducted at maximum application rates and
minimum pre-harvest intervals (PHI), were averaged and incorporated
into the assessment. Residue values were adjusted with percent of crop
treated information. For the male population (both 13-19 years and 20 +
years), exposure was 0.3% of the chronic RfD. The chronic exposure
results indicate that the U.S. population utilizes 1.3% of the chronic
PAD. The most sensitive subpopulation was non-nursing infants with 2.9%
of the chronic PAD. These results are conservative in that residue
values were generated from field trials with maximum application rates
and minimum post PHI. In addition, a significant reduction in residues
would be expected as abamectin-treated commodities travel through food
commerce, food preparation and storage.
    ii. Drinking water. Acute exposure The estimated maximum
concentration of abamectin in surface water is 0.88 parts per billion
(ppb) (Peak estimated environmental concentration ((EEC) value from
EPA's Pesticide Root Zone Model (PRZM)/EXAMS). This is an estimated
environmental concentration based on the use of abamectin on
strawberries (the maximum use rate on registered and proposed uses).
Use rates for crops on the current petition are all below the maximum
use rate for strawberries. Novartis believes the estimates of abamectin
exposure in water derived from the PRZM/EXAMS models are significantly
overstated. 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 abamectin on black plastic compared to soil.
Although there is a high degree of uncertainty to this analysis, this
is the best available estimate of concentrations of abamectin in
drinking water.
    Based on the EPA's ``Interim Guidance for Conducting Drinking Water
Exposure and Risk Assessments'' document (12/2/97), the acute drinking
water levels of comparison ((DWLOCacute)) were calculated
for abamectin. For the adult male subpopulation, the
DWLOCacute was determined based on an acute RfD of 0.0025
mg/kg/day based on a NOAEL of 0.25 mg/kg/day from a 1-year dog study
and a 100X UF. For all other populations (containing females,

[[Page 58084]]

infants, and children), the DWLOCacute was determined based
on a population adjusted dose PAD of 0.00083 mg/kg/day and reflects an
appropriate 300X UF. The acute dietary exposure results for the male
(20 + years) population shows an exposure estimate of 0.000066 mg/kg
bwt/day at the 99.9th percentile of exposure, thus a
DWLOCacute of 85 for this subpopulation. For the general
U.S. population at the 99.9th percentile, an exposure
estimate of 0.000110 mg/kg bwt/day was determined, thus a DWLOC acute
of 25. The most exposed subpopulation was non-nursing infants (<1 year
old) with an exposure estimate of 0.000327 mg/kg bwt/day at the
99.9th percentile, thus a DWLOCacute of 3 for
this subpopulation. Based on this analysis, abamectin EECs do not
exceed the calculated acute DWLOCs. Based on a maximum EEC of 0.88 ppb,
acute exposure through the consumption of drinking water is below 19%
of the acute population adjusted dose for all subpopulations.
    Chronic exposure. The estimated maximum concentrations of abamectin
in surface and ground water are 0.37 ppb (Mean of annual values from
PRZM/EXAMS) and 0.002 ppb screening concentration in ground water (SCI-
GROW), respectively. These are EECs based on the use of abamectin on
strawberries (the maximum use rate on registered and proposed uses).
Use rates for crops on the current petition are all below the maximum
use rate for strawberries. The chronic drinking water levels of
comparison (DWLOCchronic) were calculated for abamectin. For
the adult male subpopulation, the DWLOCchronic was
determined based on the chronic RfD of 0.0012 mg/kg/day from a 2-
generation reproduction study in rats and a 100X uncertainty factor. A
300X UF was utilized for populations containing females (13 + years
old) and infants and children and the DWLOCchronic was
determined based on a population-adjusted dose PAD of 0.0004 mg/kg/day.
The chronic dietary exposure results for the male (13-19 yrs and 20 +
years) population shows an exposure estimate of 0.000004 mg/kg bwt/day,
thus a DWLOCchronic of 42 for this subpopulation. For the
general U.S. population, an exposure estimate of 0.000005 mg/kg bwt/day
was determined, thus a DWLOCchronic of 14. The most exposed
subpopulation was non-nursing infants (<1 year old) with an exposure
estimate of 0.000012 mg/kg bwt/day, thus a DWLOCchronic of
2.3 for this subpopulation. Based on this analysis, abamectin EECs do
not exceed the calculated chronic DWLOCs. Based on a maximum EEC of
0.37 ppb, chronic exposure through the consumption of drinking water is
below 16% of the chronic population adjusted dose for all
subpopulations.
    2. Non-dietary exposure. Avermectin's registered residential uses
include indoor crack/crevice and outdoor application to lawns. For lawn
uses, EPA conducted a risk assessment for adult applicators and post-
application exposure to avermectin using the EPA's draft SOPs for
residential exposure assessments. The highest predicted exposure, oral
hand to mouth for children, resulted in a calculated margin of exposure
(MOE) of 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 the registered uses do
not exceed EPA's level of concern.
    i. Chronic exposure and risk. Chronic exposures for the residential
uses are not expected.
    ii. Short- and intermediate-term exposure and risk. 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 consider
``available information'' concerning the cumulative effects of a
particular pesticide residue and ``other substances that have a common
mechanism of toxicity.'' The EPA stated in the Federal Register (FR)
document published April 7, 1999, (Volume 64 Page 16843) (FRL-6070-6)
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 dietary exposure is below
100% of the RfD and the predicted acute exposure is below 100% of the
acute RfD for all subpopulations. Chronic exposure through the
consumption of drinking water has been estimated to be well below any
level of concern. Acute exposure to residues of abamectin in drinking
water has been estimated to be above the drinking water level of
comparison DWLOC for children (1-6 years old) but the certainty of this
calculation is low due to the uncertainty on the amount of runoff from
strawberry plant beds covered in plastic mulch and the uncertainty on
the amount of degradation of abamectin on black plastic as compared to
soil. Novartis concludes that there is a reasonable certainty that no
harm will result from aggregate exposure to abamectin residues.
    2. Infants and children. The food quality protection act (Public
Law 104-170) (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 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 much 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 (FDA) to 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 HDT and in juvenile
rhesus monkeys after repeated administration of 1.0 mg/kg/day HDT. The
comparative data on

[[Page 58085]]

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 2 times the LD50 in the
adult rat and more than 20 times the LD50 in the neonatal
rat. The absence of a 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

    There are no abamectin Codex maximum residue levels for avocados,
celeriac, grass forage, grass hay, stone fruit, mint, tree nut crop
group, pistachios and tuberous and corm vegetables crop subgroup.
[FR Doc. 00-24575 Filed 9-26-00; 8:45 am]
BILLING CODE 6560-50-S
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