[Federal Register Volume 69, Number 144 (Wednesday, July 28, 2004)]
[Notices]
[Pages 45037-45042]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-16852]


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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: 
[email protected].

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 [email protected], 
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