[Federal Register: July 28, 2004 (Volume 69, Number 144)]
[Notices]
[Page 45037-45042]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28jy04-68]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2004-0188; FRL-7366-3]
Abamectin; Notice of Filing a Pesticide Petition to Establish a
Tolerance for a Certain Pesticide Chemical 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 a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by docket identification (ID) number OPP-
2004-0188, must be received on or before August 27, 2004.
ADDRESSES: Comments may be submitted electronically, by mail, or
through hand delivery/courier. Follow the detailed instructions as
provided in Unit I. of the SUPPLEMENTARY INFORMATION.
FOR FURTHER INFORMATION CONTACT: Thomas C. Harris, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; 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 potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Industry (NAICS code 111)
Crop production (NAICS code 112)
Animal production (NAICS code 311)
Food manufacturing (NAICS code 32532)
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
[[Page 45038]]
B. How Can I Get Copies of this Document and Other Related Information?
1. Docket. EPA has established an official public docket for this
action under docket ID number OPP-2004-0188. The official public docket
consists of the documents specifically referenced in this action, any
public comments received, and other information related to this action.
Although, a part of the official docket, the public docket does not
include Confidential Business Information (CBI) or other information
whose disclosure is restricted by statute. The official public docket
is the collection of materials that is available for public viewing at
the Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall 2, 1921 Jefferson Davis Hwy., Arlington, VA.
Note: Due to renumbering of buildings in area, the street address will
change to 1801 South Bell St., as of June 26, 2004. This docket
facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The docket telephone number is (703) 305-
5805.
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although not all docket materials may be
available electronically, you may still access any of the publicly
available docket materials through the docket facility identified in
Unit I.B.1. Once in the system, select ``search,'' then key in the
appropriate docket ID number.
Certain types of information will not be placed in the EPA
Dockets. Information claimed as CBI and other information whose
disclosure is restricted by statute, which is not included in the
official public docket, will not be available for public viewing in
EPA's electronic public docket. EPA's policy is that copyrighted
material will not be placed in EPA's electronic public docket but will
be available only in printed, paper form in the official public docket.
To the extent feasible, publicly available docket materials will be
made available in EPA's electronic public docket. When a document is
selected from the index list in EPA Dockets, the system will identify
whether the document is available for viewing in EPA's electronic
public docket. Although, not all docket materials may be available
electronically, you may still access any of the publicly available
docket materials through the docket facility identified in Unit I.B.1.
EPA intends to work towards providing electronic access to all of the
publicly available docket materials through EPA's electronic public
docket.
For public commenters, it is important to note that EPA's policy
is that public comments, whether submitted electronically or on paper,
will be made available for public viewing in EPA's electronic public
docket as EPA receives them and without change, unless the comment
contains copyrighted material, CBI, or other information whose
disclosure is restricted by statute. When EPA identifies a comment
containing copyrighted material, EPA will provide a reference to that
material in the version of the comment that is placed in EPA's
electronic public docket. The entire printed comment, including the
copyrighted material, will be available in the public docket.
Public comments submitted on computer disks that are mailed or
delivered to the docket will be transferred to EPA's electronic public
docket. Public comments that are mailed or delivered to the docket will
be scanned and placed in EPA's electronic public docket. Where
practical, physical objects will be photographed, and the photograph
will be placed in EPA's electronic public docket along with a brief
description written by the docket staff.
C. How and to Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through hand
delivery/courier. To ensure proper receipt by EPA, identify the
appropriate docket ID number in the subject line on the first page of
your comment. Please ensure that your comments are submitted within the
specified comment period. Comments received after the close of the
comment period will be marked ``late.'' EPA is not required to consider
these late comments. If you wish to submit CBI or information that is
otherwise protected by statute, please follow the instructions in Unit
I.D. Do not use EPA Dockets or e-mail to submit CBI or information
protected by statute.
1. Electronically. If you submit an electronic comment as
prescribed in this unit, EPA recommends that you include your name,
mailing address, and an e-mail address or other contact information in
the body of your comment. Also, include this contact information on the
outside of any disk or CD ROM you submit, and in any cover letter
accompanying the disk or CD ROM. This ensures that you can be
identified as the submitter of the comment and allows EPA to contact
you in case EPA cannot read your comment due to technical difficulties
or needs further information on the substance of your comment. EPA's
policy is that EPA will not edit your comment, and any identifying or
contact information provided in the body of a comment will be included
as part of the comment that is placed in the official public docket,
and made available in EPA's electronic public docket. If EPA cannot
read your comment due to technical difficulties and cannot contact you
for clarification, EPA may not be able to consider your comment.
i. EPA Dockets. Your use of EPA's electronic public docket to
submit comments to EPA electronically is EPA's preferred method for
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket/
, and follow the online instructions for submitting comments.
Once in the system, select ``search,'' and then key in docket ID number
OPP-2004-0188. The system is an ``anonymous access'' system, which
means EPA will not know your identity, e-mail address, or other contact
information unless you provide it in the body of your comment.
ii. E-mail. Comments may be sent by e-mail to opp-docket@epa.gov,
Attention: Docket ID number OPP-2004-0188. In contrast to EPA's
electronic public docket, EPA's e-mail system is not an ``anonymous
access'' system. If you send an e-mail comment directly to the docket
without going through EPA's electronic public docket, EPA's e-mail
system automatically captures your e-mail address. E-mail addresses
that are automatically captured by EPA's e-mail system are included as
part of the comment that is placed in the official public docket, and
made available in EPA's electronic public docket.
iii. Disk or CD ROM. You may submit comments on a disk or CD ROM
that you mail to the mailing address identified in Unit I.C.2. These
electronic submissions will be accepted in WordPerfect or ASCII file
format. Avoid the use of special characters and any form of encryption.
2. By mail. Send your comments to: Public Information and Records
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington,
[[Page 45039]]
DC 20460-0001, Attention: Docket ID number OPP-2004-0188.
3. By hand delivery or courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Office of Pesticide
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall
2, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket
ID number OPP-2004-0188. Note: Due to renumbering of buildings in area,
the street address will change to 1801 South Bell St., as of June 26,
2004. Such deliveries are only accepted during the docket's normal
hours of operation as identified in Unit I.B.1.
D. How Should I Submit CBI to the Agency?
Do not submit information that you consider to be CBI
electronically through EPA's electronic public docket or by e-mail. You
may claim information that you submit to EPA as CBI by marking any part
or all of that information as CBI (if you submit CBI on disk or CD ROM,
mark the outside of the disk or CD ROM as CBI and then identify
electronically within the disk or CD ROM the specific information that
is 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 docket and EPA's electronic public docket. If you submit
the copy that does not contain CBI on disk or CD ROM, mark the outside
of the disk or CD ROM clearly that it does not contain CBI. Information
not marked as CBI will be included in the public docket and EPA's
electronic public docket without prior notice. If you have any
questions about CBI or the procedures for claiming CBI, please consult
the person listed 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
ID 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 pesticide petitions as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical in or on various food commodities under section 408
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a.
EPA has determined that these pesticide petitions contain data or
information regarding the elements set forth in FFDCA 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
these pesticide petitions. Additional data may be needed before EPA
rules on the pesticide petitions.
List of Subjects
Environmental protection, Agricultural commodities, Feed
additives, Food additives, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: July 9, 2004.
Betty Shackleford,
Acting Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioners' summary of the pesticide petitions, PP 2H5642 and
PP 3E6557, is printed below as required by FFDCA section 408(d)(3). The
summary of the pesticide petitions was prepared by Whitmire Micro-Gen
Research Laboratories, Inc. and Interregional Research Project Number 4
and represents the view of the pesticide petitioners. The summary of
the pesticide petitions 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.
Whitmire Micro-Gen Research Laboratories, Inc.
Interregional Research Project Number 4
PP 2H5642 and PP 3E6557
EPA has received a pesticide petition (PP 2H5642) from Whitmire
Micro-Gen Research Laboratories, Inc., 3568 Tree Court Industrial
Boulevard, St. Louis, MO 63122. EPA has also received a pesticide
petition (PP 3E6557) from Interregional Research Project Number 4, 681
U.S. Hwy. 1 South, North Brunswick, NJ 08902-3390. These
pesticide petitions propose, pursuant to FFDCA section 408(d), 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 as follows:
1. PP 2H5642, which was submitted by Whitmire Micro-Gen Research
Laboratories, Inc., proposed establishment of a tolerance for food
products in food handling establishments at 0.001 parts per million
(ppm).
2. PP 3E6557, which was submitted by Interregional Research Project
Number 4, proposed establishment of a tolerance for herb crop subgroup
19A (except chives) at 0.03 ppm.
EPA has determined that the pesticide petitions contain data or
information regarding the elements set forth in FFDCA 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
pesticide petitions. Additional data may be needed before EPA rules on
the pesticide petitions.
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 (also referred to as 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 96-1.
3. Magnitude of residues. Residue studies were submitted for food
handling establishments and for basil (the representative crop for herb
crop subgroup 19A (except chives)). Results from the studies
demonstrate that the highest residues found will not exceed the
proposed tolerances when abamectin is applied following the proposed
use directions.
[[Page 45040]]
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 milligram/kilogram (mg/kg) males and 10.9 to 14.9 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/
Liter.
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 millimeter (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 0.05mg/kg/day based upon decreased body weights 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 body weights.
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 body weights 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 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 body weights.
5. Chronic toxicity. A rat 53-week carcinogenicity feeding study
was negative for carcinogenicity, with a NOAEL of 1.5 mg/kg/day based
upon tremors. A CD-1 mouse 94-week carcinogenicity feeding study was
negative for carcinogenicity, with a NOAEL of 4 mg/kg/day based upon
decreased body weights. A dog 53-week chronic feeding study was
negative for carcinogenicity, 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 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. In support of the petition for
tolerance for abamectin in celeriac, the last EPA-approved tolerance,
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)
[[Page 45041]]
representing the percent of crop not treated. Non-detected residues of
avermectin B1a were entered into the software as
1/89/21/13/23/85/83/8 the limit of quantitation
(1/89/21/13/23/85/83/8 limit of quantitation (LOQ) and non-
detected residues of avermectin B1b were entered in as
1/89/21/13/23/81/163/8 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 99.9\th\ 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.
Food handling establishment studies indicate that residue of
abamectin in food is not expected from this use. While residues of
abamectin in herbs up to tolerance levels are likely, the exceedingly
small proportion of herbs in the diet limits exposure via this food
group. Thus the chronic dietary risk assessment will not be impacted by
these additional uses.
ii. Drinking water--a. 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. Whitmire Micro-Gen believes the estimates of
abamectin exposure in water derived from the PRAM/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 (December 2, 1997), 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, 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
DWLOCacute 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.
b. 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
calculatedchronic 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. Abamectin'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 abamectin using the EPA's draft Standard
Operating Procedures (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 abamectin 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-term 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) of FFDCA requires that, when considering
whether
[[Page 45042]]
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.'' EPA stated in the Federal Register (FR)
document published April 7, 1999, (64 FR 16843) (FRL-6070-6) that it
does not have, at this time, available data to determine whether
abamectin 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, Whitmire Micro-Gen 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. Use on herb crop subgroup 19A
(except chives) is not expected to have an impact on these
calculations. 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. Whitmire Micro-Gen
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 FQPA
(Public Law 104-170) 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 Whitmire
Micro-Gen 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. Whitmire Micro-Gen 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 Whitmire Micro-Gen 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 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 abamectin 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
Abamectin is a broad spectrum insecticide used throughout the
world to control pests of livestock, crops, ornamental plants and turf,
and household, commercial and industrial use areas. There is no codex
maximum residue limit MRLs for abamectin in or on food products in food
handling establishments or on herbs. Therefore, international
harmonization is not an issue at this time.
[FR Doc. 04-16852 Filed 7-27-04; 8:45 am]
BILLING CODE 6560-50-S