[Federal Register: February 26, 2003 (Volume 68, Number 38)]
[Notices]
[Page 8896-8900]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2003-0035; FRL-7293-9]
Butafenacil; 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 a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by docket ID number OPP-2003-0035, must be
received on or before March 28, 2003.
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: Jim Tompkins, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-5697; e-mail address: tompkins.jim@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:
[sbull] Crop production (NAICS 111)
[sbull] Animal production (NAICS 112)
[sbull] Food manufacturing (NAICS 311)
[sbull] Pesticide manufacturing (NAICS 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.
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-2003-0035. 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. 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
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.
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
[[Page 8897]]
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-2002-0035. 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-2003-0035. 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, DC 20460-0001, Attention: Docket ID number OPP-2003-0035.
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-2003-0035. 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 a pesticide petition 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 this petition contains 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 petition.
Additional data may be needed before EPA rules on the petition.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: February 12, 2003.
Debra Edwards,
Acting Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by FFDCA section 408(d)(3). The summary of the petition was
prepared by Syngenta Crop and represents the view of the petitioner.
The petition summary announces the availability of a description of the
analytical methods available to EPA for the detection and measurement
of the pesticide chemical residues, or an explanation of why no such
method is needed.
Syngenta Crop Protection, Inc.
PP 1F6309
EPA has received a pesticide petition (PP 1F6309) from Syngenta
Crop Protection, Inc., Greensboro, NC 27419 proposing, pursuant to
section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part
180, by establishing a tolerance for residues of butafenacil in or on
the raw agricultural commodity cotton, undelinted seed at 0.5 parts per
million (ppm) and cotton, gin byproducts at 13 ppm. EPA has determined
that the petition contains data or information regarding the elements
set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully
evaluated the sufficiency of the
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submitted data at this time or whether the data support granting of the
petition. Additional data may be needed before EPA rules on the
petition.
A. Residue Chemistry
1. Plant metabolism. The metabolic pathway of butafenacil in cotton
after defoliation applications is understood. The data support the
selection of the residue of concern for tolerance setting.
2. Analytical method. Syngenta Crop Protection, Inc. has submitted
practical analytical methodology for detecting and measuring levels of
butafenacil in or on raw agricultural commodities. This method is based
on crop-specific cleanup procedures and determination by liquid
chromatography with a liquid chromatography/mass spectroscopy (LC/MS)
detector. The limit of quantitation is 0.01 ppm for butafenacil for all
crops tested, including cotton. The limit of quantitation for
metabolites is also 0.01 ppm except for cotton gin trash where the
limit of quantitation is 0.05 ppm. The analytical method was validated
by determination of recoveries for fortified samples.
3. Magnitude of residues. A residue program was performed with
butafenacil on the full geography required to support use on cotton.
B. Toxicological Profile
1. Acute toxicity. Butafenacil technical and the 100 EC formulation
(0.83 lb active ingredient/gallon (ai/gal) have very low order of acute
toxicity by oral, dermal, and inhalation exposure routes. Butafenacil
technical is mildly irritating to the eye and non-irritating to the
skin. The 100 EC formulation is moderately irritating to the eye and
skin. Neither the technical nor the formulation are skin sensitizers.
The rat dermal LD50 is >5,000 milligram/kilogram (mg/kg).
The rat dermal LD50 is >4,000 mg/kg and the rat inhalation
LD50 is >5.1 milligrams per liter (mg/L) air. The end-use
formulation of butafenacil has a similar low acute toxicity profile.
2. Genotoxicity. Butafenacil has been tested for its potential to
induce gene mutation and chromosomal changes in five different test
systems. Butafenacil technical did not induce point mutations in
bacteria (ames assay in salmonella typhimurium or escherichia coli),
and was not genotoxic in an in vitro unscheduled DNA synthesis assay in
rat hepatocytes. Chromosome aberrations were not observed in an in
vitro test using Chinese hamster ovary cells and there were no
clastogenic or aneugenic effects on mouse bone marrow cell in vivo in a
mouse micronucleus test. There was a borderline positive response in
the gene mutation test in V79 cells in vitro at the highest
concentration in the presence of metabolic activation, which proved to
be cytotoxic. This effect was considered to be an isolated finding and
not to be of relevance when assessing the overall mutagenic potential
of butafenacil. To substantiate this finding, a corresponding in vivo
in-vitro DNA repair study on rat hepatocytes was performed. The results
of this test show no mutagenic potential of butafenacil. Consequently,
it can be concluded that butafenacil is not genotoxic.
3. Reproductive and developmental toxicity. In rat and rabbit
teratology studies there was no evidence of teratogenicity. Delayed
fetal development was apparent only at maternally toxic doses of
butafenacil technical in rabbits. In the rabbit study (with doses of 0,
10, 100, 1,000 mg/kg), 1,000 mg/kg/day caused a mean body weight loss
from days 12 to 16, decreased food consumption during the dosing period
and an increase in the incidence of post-implantation loss, almost
exclusively in the form of early resorptions. This increase in post-
implantation loss, which was restricted to the top dose, was considered
to be secondary to the maternal toxicity occurring at this dose level,
and not a direct effect by butafenacil. Slightly reduced fetal body
weights at 1,000 mg/kg/day were considered secondary to maternal
effects. The incidence and type of external, visceral and skeletal
findings were not affected by treatment. There was no indication of
developmental toxicity in rabbit offspring at 100 mg/kg/day. The no
observed adverse effect level (NOAEL) for both maternal and
developmental toxicity was established at 100 mg/kg/day in rabbits.
In the rat teratogenicity study 0, 10, 100, 1,000 mg/kg, there was
no observation of maternal toxicity. Body weight and food consumption
were comparable in all groups. Reproduction and fetal parameters were
not impaired. The incidence and type of external, visceral and skeletal
findings were comparable in all dose groups. No treatment-related
findings were noted. In conclusion, butafenacil was not teratogenic and
not toxic to the progeny. Maternal parameters were not affected. The
NOAEL for both maternal and developmental toxicity was >1,000 mg/kg/
day, the highest dose level tested.
In a rat multi-generation study, butafenacil technical was
administered in feed at concentrations of 0, 30, 300, or 1,000 ppm. The
dose in mg/kg/day spans a wide range over the duration of the study as
animals gain weight and go through gestation and lactation. The ranges
are 1.5-3.3, 15.5-31.9, and 50.9-101.6 for males and 1.7-6.3, 16.8-
65.4, and 49.8-215.8 mg/kg/day for females at the 30, 300, or 1,000 ppm
dietary levels, respectively. Butafenacil had no effect on reproductive
parameters for either the F0 or F1 generation of parent animals.
Parental body weight gain and food consumption were reduced at 300 and
1,000 ppm in both the F0 and F1 males and in F1 females. Increased
incidence of liver pathology was observed in males and females in the
F0 and F1 generations, including bile duct hyperplasia in both sexes at
300 and 1,000 ppm, hepatocellular hypertrophy in males at 1,000 ppm,
and foci of necrosis in both sexes at 1,000 ppm and males at 300 ppm.
Body weight gain was reduced during the lactation period at 300 and
1,000 ppm in offspring of the F0 generation and at 1,000 ppm in
offspring of the F1 generation.
In conclusion, the NOAEL for systemic toxicity in both sexes and
both generations of rats was 30 ppm (range = 1.5-3.3 mg/kg/day in males
and 1.7-6.3 mg/kg/day in females). The grand mean test item intake
(mean of all weekly means for both sexes, both generations, all time
points) at this dose level was 2.48 mg/kg/day. There were no effects on
the reproductive parameters and the NOAEL for reproductive toxicity was
>1,000 ppm. Offspring effects were observed only at dose levels that
also produced parental toxicity. There is no evidence that developing
offspring are more sensitive than adults to the effects of butafenacil.
4. Subchronic toxicity. In a 90-day subchronic neurotoxicity study
in rats, butafenacil was not neurotoxic when administered in the diet
for 13 weeks at concentrations resulting in average daily test
substance intakes of 0, 7.8, 23.5, or 74.4 mg/kg/day for males or at 0,
8.7, 26.0, or 78.9 mg/kg/day for females. There were no treatment-
related neurobehavioral or motor activity effects, no macroscopic
findings and no microscopic findings in central or peripheral nervous
tissue. All animals survived until scheduled sacrifice and there were
no treatment-related clinical observations. Histopathology of the liver
revealed effects in animals of both sexes from the top dose group. In
addition, one male at 23.5 mg/kg/day showed single cell necrosis of
hepatocytes. In conclusion, subchronic dietary administration of
butafenacil to rats did not produce neurotoxic effects at any dose
level. The NOAEL for liver toxicity was 7.8 mg/kg/day for males and
26.0 mg/kg/day for females.
5. Chronic toxicity. Butafenacil technical was not oncogenic in
rats or
[[Page 8899]]
mice. A summary of results of chronic toxicity studies in rats, mice,
and dogs indicates that the primary target organ from chronic exposure
is liver, with effects on hematology parameters and body weight.
In a 12-month chronic oral toxicity study, dogs were fed capsules
containing butafenacil that resulted in daily test substance intakes of
0, 20, 100, 500, or 1,000 mg/kg/day. The administration of butafenacil
caused findings only at 500 and 1,000 mg/kg/day. These effects
consisted of loss in the body weight of male animals at 1,000 mg/kg/
day. Hematology parameters were slightly affected at 500 and 1,000 mg/
kg/day. Based on body weight loss at 1,000 mg/kg/day, the increase in
relative liver weight at 1,000 mg/kg/day and the hematological effects
at 500 and 1,000 mg/kg/day, the maximum tolerance dose (MTD) was
achieved at 1,000 mg/kg/day and the NOAEL for chronic toxicity in dogs
is 100 mg/kg/day.
In an 18-month oncogenicity study, mice were fed diets containing
butafenacil that resulted in average daily test substance intakes of 0,
0.12, 0.36, 1.18, 6.78 mg/kg/day. The treatment of mice with
butafenacil for 18 months revealed effects on hematology parameters in
males at 1.18 and 6.78 mg/kg/day, increased liver weights at 6.78 mg/
kg/day in both sexes and histopathological findings indicating that the
liver was the target organ of toxicity. The MTD was achieved at 6.78
mg/kg/day. Dose responsive non-neoplastic changes in the liver occurred
at 1.18 mg/kg/day in males and at 6.78 mg/kg/day in both sexes.
Butafenacil was not carcinogenic in this study. Based on the hematology
and liver effects, the NOAEL for chronic toxicity in mice was
established at 0.36 mg/kg/day in males and 1.20 mg/kg/day in females.
In a 2-year chronic toxicity and carcinogenicity study, rats were
fed diets containing butafenacil that resulted in average (sexes
combined) daily test substance intakes of 0, 0.42, 1.22, 4.10, or 12.2
mg/kg/day. Treatment had no effect on survival and there were no
treatment-related clinical signs. There were no effects on food
consumption and body weight. Hematology and clinical chemistry data
were comparable in all groups. Necropsy revealed no changes in organ
weights.
The treatment of rats with butafenacil for 24 months indicated the
liver as the target organ, with non-neoplastic histopathological
findings in the liver in both sexes at 4.10 and 12.2 mg/kg/day. Based
on the liver effects, the MTD was achieved at 12.2 mg/kg/day. No
increased incidence of tumor formation was noted, indicating that
butafenacil was not carcinogenic in this study. Based on the liver
effects at 4.10 and 12.2 mg/kg/day, the NOAEL was established at 1.14
mg/kg/day (1.14 mg/kg/day in males and 1.30 mg/kg/day in females).
6. Animal metabolism. The major initial metabolic processes in rat
involve the hydrolysis of the allyl ester to form the free carboxylic
acid compounds. Parent compound was of significant abundance only in
the feces from the high dose group. Subsequent metabolic routes involve
reduction, hydroxylation, and opening of the uracil ring. The phenyl
and uracil rings remain connected and all major metabolites have the
unchanged phenyl structure.
7. Metabolite toxicology. Toxicity studies, including acute oral,
mutagenicity, and 28-day feeding studies were conducted with major
metabolites found in environmental studies. An acute oral and a
mutagenicity test were conducted. The acute oral LD50 was at
least >2,000 mg/kg and all mutagenicity studies were negative. The 28-
day feeding study was conducted with major metabolites at 0, 300,
2,000, and 10,000 ppm. The target organ was confirmed as the liver for
all test materials. Based on the data from the studies and reasons
cited, none of these metabolites is considered to be of toxicological
concern.
8. Endocrine disruption. Butafenacil does not belong to a class of
chemicals known or suspected of having adverse effects on the endocrine
system. There is no evidence that butafenacil has any effect on
endocrine function in development or reproductive studies. Furthermore,
histological investigation of endocrine organs in chronic dog, mouse,
and rat studies did not indicate that the endocrine system is targeted
by butafenacil.
9. Neurotoxicity. In an acute neurotoxicity study in rats,
butafenacil was administered orally by gavage at 0 or 2,000 mg/kg. All
animals survived and body weight development and food consumption were
not affected by treatment. There were no toxicologically relevant
clinical signs nor changes in observations and functional tests
conducted as part of the functional observational battery. No
treatment-related effects on any of the different motor activity
parameters were seen. Macroscopical and microscopical examination of
the multiple areas of the central and peripheral nervous system, the
eyes, optic nerves, and skeletal muscle of the male and female, control
and treated animals did not reveal any treatment-related neuropathic
changes. In conclusion, butafenacil was devoid of any acute
neurotoxicity when administered to rats at a single oral dose of 2,000
mg/kg. The NOAEL was greater than 2,000 mg/kg body weight.
C. Aggregate Exposure
1. Dietary exposure. Dietary exposure from butafenacil potentially
exists through both food commodities and drinking water. Each exposure
pathway is addressed below.
i. Food. Chronic and acute dietary exposure evaluations for
butafenacil were performed using average field trial residues and
assuming 100% crop treated. Cotton is the only raw agricultural
commodity included in the assessment. All dietary exposure evaluations
were made using the Dietary Exposure Evaluation Model (DEEM) and the
USDA's Continuing Survey of Food Intake By Individuals (1994-96).
Chronic exposure was compared to a chronic NOAEL of 100.0 mg/kg body
weight/day (bwt/day) from a 1-year dog study. The acute NOAEL is 100
mg/kg in a rabbit teratology study based on maternal body weight loss
and increased post-implantation loss. A 100X-uncertainty factor was
assumed for both chronic and acute values. Both chronic and acute
exposures were expressed as a percent of a reference dose of 1.0 mg/kg/
day.
Secondary residues in animal commodities were calculated by
constructing diets for beef and dairy cattle, poultry and swine in
order to calculate anticipated residues in meat, fat, milk and pork.
The beef cattle diet was used to calculate meat, fat and organ meats.
The dairy cattle diet was used to estimate residues in milk. The swine
diet was used for secondary residues in pork commodities and the
poultry diet was used for residues in poultry commodities. Each diet
was calculated using averaged field trial residues. Beef (cattle and
dairy), and swine transfer factors were derived from a lactating goat
14C-metabolism study.
The results were favorable in both acute and chronic assessment
scenarios. Acute and chronic exposure values were negligible (less than
0.01% of the acute and chronic reference dose of 1 mg/kg bwt/day.
The major contributors to chronic exposure (children 1-6 years old)
were milk, accounting for 48% of the total exposure, cottonseed oil
accounting for 28%, and meat (beef) products accounting for 25% of the
total. In the U.S. population, the percentage contribution to the
chronic exposure from meat (beef) products and milk were each 34% and
cottonseed oil
[[Page 8900]]
accounted for 31% of the total. Major sources of acute exposures for
the U.S. population and children 1-6 years old included cottonseed oil
and meat (beef) commodities. The %RfD for all populations was less than
0.01% of the reference dose (RfD) of 1.0 mg/kg bwt/day.
ii. Drinking water--a. Acute drinking water exposure. The estimated
tier 1 maximum concentrations of butafenacil in surface water and
ground water are 1.98 ppb and 0.000038 ppb, respectively. The acute RfD
for butafenacil is 1.0 mg/kg bwt/day. From the acute dietary exposure
analysis, acute food exposure from the uses of butafenacil were
neglegible for all populations. Using this information, acute drinking
water levels of comparison (DWLOC) were calculated for butafenacil. The
lowest DWLOC was 10,000 ppb. Based on this analysis, butafenacil
estimated environmental concentrations (EECs) do not exceed the
calculated acute DWLOCs.
b. Chronic drinking water exposure. The estimated maximum
concentrations of butafenacil in surface water and ground water are
0.033 ppb Day 56 EEC/3 from Generic Expected Environmental
Concentration (GENEEC) and 0.000025 parts per billion (ppb) (SCI-GROW,
maximum at 0.16 lb active ingredient/acre/year, respectively. The
chronic RfD for butafenacil is 1.0 mg/kg bwt/day. From the chronic
dietary exposure analysis, an exposure to butafenacil is negligible for
all populations. Based on EPA's ``Interim Guidance for Conducting
Drinking Water Exposure and Risk Assessments'' document (December 2,
1997), chronic drinking water levels of comparison were calculated for
butafenacil. The lowest DWLOC was 10,000 ppb. Based on this analysis,
butafenacil EECs do not exceed the calculated chronic DWLOCs.
2. Non-dietary exposure. There are no residential uses and
therefore, no need for non-dietary exposure assessment for this use.
D. Cumulative Effects
The potential for cumulative effects of butafenacil and other
substances that have a common mechanism of toxicity has been
considered. Butafenacil is a member of the class of herbicides
designated as uracil-derivatives. There is no reliable information to
indicate that toxic effects produced by butafenacil would be cumulative
with those of any other chemical including another pesticide.
Therefore, Syngenta believes it is appropriate to consider only the
potential risks of butafenacil in an aggregate risk assessment.
E. Safety Determination
1. U.S. population. Using the acute and chronic exposure
assumptions and the proposed RfDs described above, the aggregate
exposure, including drinking water to butafenacil to the U.S.
population (48 contiguous states, all seasons) was calculated to be
less than 0.01% of the RfD of 1.0 mg/kg bwt/day. Therefore, Syngenta
concludes that there is reasonable certainty that no harm will result
from the aggregate acute or chronic exposure to butafenacil residues.
2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of butafenacil, data
from developmental toxicity studies in the rat and rabbit and a multi-
generation reproduction study in the rat have been considered. In the
rat and rabbit teratology studies there was no evidence of
teratogenicity. Delayed fetal development was apparent only at
maternally toxic doses of butafenacil technical in rabbits. In the
rabbit study 1,000 mg/kg/day caused effects indicative of maternal
toxicity. There was no indication of developmental toxicity in rabbit
offspring at 100 mg/kg/day. The NOAEL for both maternal and
developmental toxicity was established at 100 mg/kg/day in rabbits.
In the rat teratogenicity study there was no observation of
maternal toxicity. Body weight and food consumption were comparable in
all groups. Reproduction and fetal parameters were not impaired.
Butafenacil was not teratogenic and not toxic to the progeny. Maternal
parameters were not affected. The NOAEL for both maternal and
developmental toxicity was =1,000 mg/kg/day, the highest
dose level tested.
In a rat multi-generation study the NOAEL for systemic toxicity in
both sexes and both generations of rats was 2.48 mg/kg/day. There were
no effects on the reproductive parameters and the NOAEL for
reproductive toxicity was =1,000 ppm. Offspring effects were
observed only at dose levels that also produced parental toxicity.
There is no evidence that developing offsprings are more sensitive than
adults to the effects of butafenacil.
FFDCA section 408 provides that EPA may apply an additional safety
factor for infants and children in the case of threshold effects to
account for prenatal and postnatal toxicity and the completeness of the
data base. Based on the current toxicological requirements, the data
base for butafenacil relative to prenatal and postnatal effects for
children is complete. Further, for butafenacil, the developmental
studies showed no increased sensitivity in fetuses as compared to
maternal animals following in-utero exposures in rats and rabbits, and
no increased sensitivity in pups as compared to the adults in the
multi-generation reproductive toxicity study. Therefore, it is
concluded, that an additional uncertainty factor is not warranted to
protect the health of infants and children and that a RfD of 1.0 mg/kg
bwt/day is appropriated for assessing aggregate risk to infants and
children from butafenacil.
F. International Tolerances
There are no codex established for residues of butafenacil on
cotton, undelinted seed or cotton, gin byproducts.
[FR Doc. 03-4386 Filed 2-25-03; 8:45 am]
BILLING CODE 6560-50-S