Imazethapyr; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food, 37392-37397 [05-12444]
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37392
Federal Register / Vol. 70, No. 124 / Wednesday, June 29, 2005 / Notices
2. Electronic access. You may access
this Federal Register document
electronically through the EPA Internet
under the ‘‘Federal Register’’ listings at
https://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 https://www.epa.gov/edocket/
to view public comments, to 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.
II. Background
This document announces EPA’s
intent to hold a public meeting or
Technical Briefing to present to
interested stakeholders the Agency’s
risk assessments for the soil fumigant
pesticides dazomet, metam sodium,
methyl bromide, and 1,3-D or Telone.
EPA is assessing risks and will develop
risk management decisions for five soil
fumigants, including dazomet, metam
sodium, and methyl bromide, plus
chloropicrin and a new active
ingredient, iodomethane. 1,3-D risks
will be discussed for comparative
purposes; however, the Agency’s risk
management decision for 1,3-D was
completed in September 1998. Risk
assessments for chloropicrin and
iodomethane will follow about a month
later due to recently submitted data
which are currently under review. The
Technical Briefing is part of EPA’s
process to involve the public in
developing pesticide registration and
reregistration eligibility decisions.
Through these programs, the Agency is
ensuring that all pesticides meet current
health and safety standards.
At the Technical Briefing, EPA will
describe the risk assessments and the
data, information and methodologies
used in developing them. Stakeholders
will have an opportunity to ask
clarifying questions. On the day of the
Technical Briefing, the soil fumigant
risk assessments and related documents
will be available in their respective
pesticide Dockets and EDOCKET on the
Agency’s web site. These docket ID
numbers will be as follows: Methyl
bromide (OPP–2005–0123), 1,3-D (OPP–
2005–0124), metam sodium (OPP–2005–
0125), and dazomet (OPP–2005–0128).
EPA will solicit public comment on the
risk assessments and related documents
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through Federal Register notices of
availability, which are scheduled to be
published on the day of the Technical
Briefing.
After considering public comments
received, EPA will revise the risk
assessments for dazomet, metam
sodium, methyl bromide, and 1,3-D (and
later for chloropicrin and iodomethane)
and develop any needed risk mitigation.
Stakeholders and the public will have
opportunities, including stakeholder
meetings during public comment
periods, to review the revised risk
assessments and provide ideas and
recommendations on risk mitigation
options.
EPA is evaluating the soil fumigants
to ensure that its risk assessment
approaches are consistent, and to ensure
that risk tradeoffs and economic
outcomes can be adequately predicted
in reaching risk management decisions.
Using this approach, the Agency expects
to address risks of concern while
maintaining key use benefits.
List of Subjects
Environmental protection, Pesticides
and pests.
Dated: June 23, 2005.
Debra Edwards,
Director, Special Review and Reregistration
Division, Office of Pesticide Programs.
[FR Doc. 05–12917 Filed 6–28–05; 8:45 am]
BILLING CODE 6560–50–S
ENVIRONMENTAL PROTECTION
AGENCY
[OPP–2005–0161; FRL–7718–5]
Imazethapyr; Notice of Filing a
Pesticide Petition to Establish a
Tolerance for a Certain Pesticide
Chemical in or on Food
Environmental Protection
Agency (EPA).
ACTION: Notice.
AGENCY:
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
identification (ID) number OPP–2005–
0161, must be received on or before July
29, 2005.
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.
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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.
FOR FURTHER INFORMATION CONTACT:
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by
this action if you an agricultural
producer, food manufacturer, or
pesticide manufacturer. Potentially
affected entities may include, but are
not limited to:
• Crop production (NAICS 111)
• Animal production (NAICS 112)
• Food manufacturing (NAICS 311)
• 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–2005–
0161. 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, 1801 S. Bell St., 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
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Federal Register / Vol. 70, No. 124 / Wednesday, June 29, 2005 / Notices
under the ‘‘Federal Register’’ listings at
https://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 https://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 in 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
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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 email 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 https://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–2005–0161. The
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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–
2005–0161. 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–2005–0161.
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, 1801 S. Bell St.,
Arlington, VA, Attention: Docket ID
Number OPP–2005–0161. 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
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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 theelements 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.
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Dated: June 10. 2005.
Betty Shackleford,
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 the petitioner 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.
BASF Corporation
PP 5F 6947
EPA has received a pesticide petition
(5F 6947) from BASF Corporation, 26
Davis Drive, P.O. Box 13528, Research
Triangle Park, North Carolina 27709–
3528 proposing, pursuant to section
408(d) of the Federal Food, Drug, and
Cosmetic Act (FFDCA), 21 U.S.C.
346a(d), to amend 40 CFR part 180 by
establishing a tolerance for residues of
imazethapyr,2–[4,5–dihydro–4–methyl–
4–(1–methylethyl)–5–oxo–1H-imidazol–
2–yl]–5–ethyl–3–pyridine-carboxylic
acid) as its free acid or its ammonium
salt (calculated as the acid), and its
metabolite 2–[4, 5–dihydro–4–methyl–
4–(1–methylethyl–5–oxo-1H-imidazol–
2–yl]–5–(1–hydroxyethyl)–3–
pyridinecarboxylic acid both free and
conjugated] in or on the raw agricultural
commodity rice grain at 0.3 parts per
million (ppm) and rice straw at 0.4 ppm.
EPA has determined that the petition
contains data or information regarding
the elements set forth in section
408(d)(2) of the FFDCA; however, EPA
has not fully evaluated the sufficiency
of the submitted data at this time or
whether the data supports granting of
the petition. Additional data may be
needed before EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. The qualitative
nature of the residues of imazethapyr in
rice is adequately understood. Based on
studies conducted on soybean, edible
and forage legumes and corn, parent
imazethapyr and common metabolites
CL 288511 and CL 182704 are the only
residues of concern for tolerance setting
purposes.
2. Analytical method. The analytical
method for rice commodities, grain and
straw is based on Capillary
Electrophoresis with limits of
quantitation (LOQ) of 0.05 ppm.
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Measurement of imazethapyr residues
in polished rice, hull and bran are
accomplished by Liquid
Chromatography/Atmospheric Pressure
Ionization-Electrospray (API/ES) Mass
Spectrometry (LC/MS). The validated
LOQ of the method is 0.025 ppm. A
CZE-methodology is available for the
determination of imazethapyr in
crayfish with limits of quantitation of 50
ppb. These independently validated
methods are appropriate for the
enforcement purposes of this petition.
3. Magnitude of residues. A total of
nineteen field trials were conducted
with imazethapyr and its metabolites on
rice in 1997 and 1998 at several
different use rates and timing intervals
to represent the use patterns which
would result in the highest residue. In
these trials, residues of parent
compound AC 263499 in grain and
straw were less than the limit of
quantitation (0.05 ppm). The hydroxy
metabolite, CL 288511 was detected in
grain samples at a maximum value of
0.085 ppm. All straw samples analyzed
for CL 288511 residues were less than
the limit of quantitation (0.05 ppm). The
glucose conjugate, CL 182704 was
detected at a maximum value of 0.11
ppm in grain. All straw samples
analyzed for CL 182704 residues were
less than the limit of quantitation (0.05
ppm). The raw agricultural commodity
(RAC) samples were also processed into
polished rice, hull and bran. Results
from these studies support the proposed
tolerances of 0.3 ppm for rice grain and
0.4 ppm for rice straw.
B. Toxicological Profile
1. Acute toxicity. Imazethapyr
technical is considered to be nontoxic
(Toxicity Category IV) to the rat by the
oral route of exposure. In an acute oral
toxicity study in rats, the LD50 value of
imazethapyr technical was greater than
5,000 mg/kg body weight for males and
females. The results from an acute
dermal toxicity study in rabbits indicate
that imazethapyr is slightly toxic
(Toxicity Category III) to rabbits by the
dermal route of exposure. The dermal
LD50 value of imazethapyr technical was
greater than 2,000 mg/kg bw for both
male and female rabbits. Imazethapyr
technical is considered to be non-toxic
(Toxicity Category IV) to the rat by the
respiratory route of exposure. The 4–
hour LC50 value was greater than 3.27
mg/l (analytical) and greater than 4.21
mg/l (gravimetric) for both males and
females. Imazethapyr technical was
shown to be non-irritating to rabbit skin
(Toxicity Category IV) and mildly
irritating to the rabbit eye (Toxicity
Category III). Based on the results of a
dermal sensitization study (Buehler),
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imazethapyr technical is not considered
a sensitizer in guinea pigs.
2. Genotoxicity. Imazethapyr
technical was tested in a battery of four
in vitro and one in vivo genotoxicity
assays measuring several different
endpoints of potential genotoxicity.
Collective results from these studies
indicate that imazethapyr does not pose
a mutagenic or genotoxic risk.
3.Reproductive and developmental
toxicity. The developmental toxicity
study in Sprague Dawley rats conducted
with imazethapyr technical showed no
evidence of developmental toxicity or
teratogenic effects in fetuses. Thus,
imazethapyr is neither a developmental
toxicant nor a teratogen in the rat. The
No-Observable-Effect-Level (NOEL) for
maternal toxicity was 375 mg/kg bw/
day, based on clinical signs of toxicity
in the dams (e.g. excessive salivation) at
1,125 mg/kg bw/day. Imazethapyr
technical did not exhibit developmental
toxicity or teratogenic effects at
maternal dosages up to and including
1,125 mg/kg bw/day, the highest dose
tested (HDT).
Results from a developmental toxicity
study in New Zealand White rabbits
with imazethapyr technical also
indicated no evidence of developmental
toxicity or teratogenicity. Thus,
imazethapyr technical is neither a
developmental toxicant nor a teratogen
in the rabbit. The NOEL for maternal
toxicity was 300 mg/kg bw/day, based
on decreased food consumption and
body weight gain, abortion, gastric
ulceration and death at 1,000 mg/kg bw/
day, the next HDT. The NOEL for
developmental toxicity and teratogenic
effects was determined to be <1,000 mg/
kg bw/day based on no developmental
toxicity or fetal malformations
associated with the administration of all
doses.
The results from the two-generation
reproduction toxicity study in rats with
imazethapyr technical support a NOEL
for reproductive toxicity of 10,000 ppm
(equivalent to 800 mg/kg bw/day). The
NOEL for non-reproductive parameters
(i.e. decreased weanling body weights)
is 5,000 ppm.
4. Subchronic toxicity. A short-term
(21–day) dermal toxicity study in
rabbits was conducted with imazethapyr
technical. No dermal irritation or
abnormal clinical signs were observed at
dose levels up to and including 1,000
mg/kg bw/day (HDT), supporting a
NOEL for dermal irritation and systemic
toxicity of 1,000 mg/kg bw/day.
In a subchronic (13–week) dietary
toxicity study in rats with imazethapyr
technical, no signs of systemic toxicity
were noted, supporting a NOEL of
10,000 ppm the highest concentration
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tested (equivalent to 820 mg/kg bw/
day).
In a subchronic (13–week) dietary
toxicity study in dogs with imazethapyr
technical, no signs of systemic toxicity
were noted, supporting a NOEL of
10,000 ppm (equivalent to 250 mg/kg
b.w./day), the highest concentration
tested.
5.Chronic toxicity. A one-year dietary
toxicity study was conducted with
imazethapyr technical in Beagle dogs at
dietary concentrations of 0, 1,000, 5,000
and 10,000 ppm. In this study, the
NOEL for systemic toxicity was 1,000
ppm (equivalent to 25 mg/kg bw/day),
based on slight anemia, i.e., decreased
red cell parameters observed at 5,000
and 10,000 ppm concentrations. No
treatment-related histopathological
lesions were observed at any dietary
concentration, including the highest
concentration tested (10,000 ppm).
In a two-year chronic dietary
oncogenicity and toxicity study in rats
conducted with imazethapyr technical,
the NOEL for oncogenicity and chronic
systemic toxicity was 10,000 ppm
(equivalent to 500 mg/kg bw/day), the
highest concentration tested. An 18–
month chronic dietary oncogenicity and
toxicity study in mice with imazethapyr
technical supports a NOEL for
oncogenicity of 10,000 ppm, the highest
concentration tested (equivalent to
1,500 mg/kg bw/day), and a NOEL for
chronic systemic toxicity of 5,000 ppm
(equivalent to 750 mg/kg bw/day), based
on decreased body weight gain in both
sexes).
The EPA has classified imazethapyr
as negative for carcinogenicity (evidence
of non-carcinogenicity for humans)
based on the absence of treatmentrelated tumors in acceptable
carcinogenicity studies in both rats and
mice.
6. Animal metabolism. The rat, goat
and hen metabolism studies indicate
that the qualitative nature of the
residues of imazethapyr in animals is
adequately understood.
In three rat metabolism studies
conducted with radiolabeled
imazethapyr technical the major route of
elimination of the herbicide was
through rapid excretion in urine and to
a much lesser extent in feces. In the first
study, almost 100% of the administered
material was recovered in excreta
within 96 hours (89–95% in urine, 6–
11% in feces). The major residue in
urine and feces was parent compound.
Approximately 2% of the dose was
metabolized and excreted as the ahydroxyethyl derivative of imazethapyr.
In the second study, the test material
was rapidly and completely eliminated
unchanged in the urine within 72 hours
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of dosing. After 24 hours, 92.1% of
radioactivity was excreted in the urine
with 4.67% in the feces. There was no
significant bioaccumulation of
radioactivity in the tissues from this rat
metabolism study (<0.01 ppm after 24
hours). In the third study, four groups
treated with radiolabeled imazethapyr
readily excreted <95% of the test
material in the urine and feces within
48 hours. A high percentage (97–99%)
of the test material was excreted in the
urine as unchanged parent, the
remainder as the a-hydroxyethyl
derivative of imazethapyr. For all three
studies, the major route of elimination
of the herbicide in rats was through
rapid excretion of unchanged parent
compound in urine. It is clear that
imazathapyr and its related residues do
not accumulate in tissues and organs.
In the goat metabolism study, parent
14C-imazethapyr was dosed to lactating
goats at 0.25 ppm and 1.25 ppm. Results
showed 14C-residues of <0.01 ppm in
milk and <0.05 ppm in leg muscle, loin
muscle, blood, fat, liver and kidney.
Laying hens dosed at 0.5 ppm and 2.5
ppm with 14C-imazethapyr showed 14Cresidues of <0.05 ppm in eggs and all
tissues (blood, muscle, skin/fat, liver
and kidney).
Additional animal metabolism studies
have been conducted with CL 288511
(main metabolite in treated crops fed to
livestock) in both laying hens and
lactating goats. These studies have been
repeated to support subsequent use
extensions on crops used as livestock
feed items which would theoretically
result in a higher dosing of imazethapyrderived residues to livestock (i.e., corn,
alfalfa). In these studies, lactating goats
dosed at 42 ppm of 14C-CL 288511
showed 14C-residues of <0.01 ppm in
milk, leg muscle, loin muscle and
omental fat. 14C-Residues in blood were
mostly <0.01 ppm but reached 0.01 ppm
on two of the treatment days. 14CResidue levels in the liver and kidney
were 0.02 and 0.09 ppm, respectively.
Laying hens dosed at 10.2 ppm of 14Cimazethapyr showed 14C-residues of
<0.01 ppm in eggs and all tissues (blood,
muscle, skin/fat, liver and kidney). 14Cimazethapyr or 14C-CL 288511 ingested
by either laying hens or lactating goats
was excreted within 48 hours of dosing.
These studies indicate that parent
imazethapyr and CL 288511-related
residues do not accumulate in milk or
edible tissues of the ruminant.
7. Metabolite toxicology. Metabolism
studies in soybean, peanut, corn and
alfalfa indicate that the only significant
metabolites are the a-hydroxyethyl
derivative of imazethapyr, CL 288511
and its glucose conjugate CL 182704.
The a-hydroxyethyl metabolite has also
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been identified in minor quantities in
the previously submitted rat metabolism
studies and in goat and hen metabolism
studies. No additional toxicologically
significant metabolites were detected in
any of the plant or animal metabolism
studies.
8. Endocrine disruption. Collective
organ weight data and histopathological
findings from the two-generation rat
reproductive study, as well as from the
subchronic and chronic toxicity studies
in three different animal species
demonstrate no apparent estrogenic
effects or treatment-related effects of
imazethapyr on the endocrine system.
C. Aggregate Exposure
1. Dietary exposure—i. Food. BASF
has determined that there are no toxic
effects attributable to a single dose of
imazethapyr. Therefore, a quantitative
acute dietary exposure and risk
assessment was not required.
Assessments were conducted to
evaluate the potential risk due to
chronic dietary exposure of the U.S.
population to residues of imazethapyr.
This herbicide and its metabolites (CL
288511, CL 182704) were expressed as
the parent compound (imazethapyr). A
dietary exposure analysis was
conducted for all current crops,
including the increased tolerance for
rice grain and straw, and secondary
residues in meat, meat byproducts, and
fat. The commodities include canola,
field corn, crop group 6, soybeans,
alfalfa, nongrass animal feed group,
peanuts, endive, crayfish, head lettuce,
and leaf lettuce.
The tier 1 chronic dietary exposure
estimates were based on the tolerance
values, 100 percent crop treated values,
default concentration/processing factors
and consumption data from the USDA
Continuing Survey of Food Intake by
Individuals (CSFII 1994 – 1996, 1998)
and the EPA Food Commodity
Ingredient Database (FCID) using
Exponent’s Dietary Exposure Evaluation
Module (DEEM-FCID) software.
Resulting exposure estimates were
compared against the imazethapyr
chronic Population Adjusted Dose
(cPAD) of 2.5 mg/kg bw/day.
Exposure estimates for the
imazethapyr chronic dietary
assessments were well below U.S. EPA’s
level of concern (See Table 1). The
estimated chronic dietary exposure was
<0.1% of the cPAD for all
subpopulations. Additional refinements
such as the use of anticipated residues
and predicted percent crop treated
would further reduce the estimated
chronic dietary exposure.
TABLE 1.—SUMMARY OF CHRONIC DIETARY EXPOSURE AND RISK FOR IMAZETHAPYR CONSIDERING ALL CURRENT CROPS
AND SECONDARY ANIMAL RESIDUES
Population Subgroups
Exposure Estimate (mg/kg bw/day)
%cPAD (cPAD = 2.5 mg/kg bw/day)
U.S. Population
0.000476
0.019
All Infants (<1 year old)
0.000693
0.028
Children (1-2 years old)
0.000945
0.038
Children (3-5 years old)
0.000959
0.038
Children (6-12 years old)
0.000701
0.028
Youth (13-19 years old)
0.000514
0.021
Females (13-49 years old)
0.000379
0.015
Adults (20-49 years old)
0.000424
0.017
Adults (50+ years old)
0.000304
0.012
ii. Drinking water. Because the
Agency does not have monitoring data,
drinking water concentration estimates
are made by reliance on simulation or
modeling taking into account data on
the physical characteristics of
imazethapyr. EPA determined that the
residue of concern in drinking water is
only imazethapyr. Surface water (rice
paddy model; peak and average 126 µg/
l) estimated drinking water
concentrations (EDWCs) for
imazethapyr were calculated. The
surface water EDWCs were generated
assuming two applications of
imazethapyr at 0.188 lbs ae/acre
(highest registered/proposed multiple
application rate). Based on several
prospective ground water studies the
upper bound ground water exposure
would not be expected to exceed 1 µg/
L. The estimated drinking water
concentrations (EDWC) for both surface
water and ground water are well below
the allowable level. Drinking water level
of comparison (DWLOC) calculations
and comparisons to surface water
estimations are given as follows in Table
2.
TABLE 2. — ESTIMATED CHRONIC DRINKING WATER VALUES FOR IMAZETHAPYR
U.S. Population1
DWLOCchronic
DWLOC chronic (µg/L)
87483
All Infants <1
year)
24993
Children (1-6
years)
Females (13-49
years)
Adults (20-49
years)
24991
74989
87485
126
126
126
E:\FR\FM\29JNN1.SGM
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EDWC’s
PRZM/EXAMS (BASF) Surface water
(µg/L)*
126
126
*acute value for surface water
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iii. Aggregate exposure (diet + water).
The estimated chronic aggregate
exposure of imazethapyr from potential
residues in food and water are
summarized in Table 3 as follows.
Imazethapyr is not registered for
residential use and therefore residential
exposure was not considered.
TABLE 3. — ESTIMATED CHRONIC AGGREGATE EXPOSURE FROM THE USE OF IMAZETHAPYR
Aggregate Exposure2
(mg/kg/day)
Chronic Food Exposure (mg/kg/day)
Chronic Drinking Water
Exposure1 (mg/kg/day)
U.S. Population
0.000476
0.003600
0.004076
0.16
Infants (< 1 year old)
0.000693
0.012600
0.013293
0.53
Children (1-6 years
old)
0.000937
0.012600
0.013537
0.54
Females (13-49
years old)
0.000379
0.004000
0.004379
0.18
Adults (20-49 years
old)
0.000424
0.003600
0.004024
0.16
Population Subgroup
1
2
Aggregate %cPAD
Aggregate Exposure = Food Exposure + Drinking Water Exposure
Drinking Water Exposure (mg/kg/day) = [Drinking Water Concentration (µg/L) * Water Consumed (L/day)/ Body weight (kg)]/1,000
The assessment results indicate the
aggregate exposure of imazethapyr from
potential residues in food and drinking
water will not exceed the U.S. EPA’s
level of concern (100% of PAD). The
percent chronic PAD was <1% for all
subpopulations. Additional refinements
such as the use of anticipated residues
and predicted percent crop treated
would further reduce the estimated
chronic dietary exposure and %cPAD.
Overall, considering a ‘‘worst-case’’
scenario, we can conclude with
reasonable certainty that no harm will
occur from chronic aggregate exposure
of imazethapyr residues from the
current crops, including the higher
proposed tolerance values.
2. Non-dietary exposure . Imazethapyr
products are not currently registered for
requested to be registered for residential
use; therefore the estimate of residential
exposure is not relevant to this tolerance
petition.
D. Cumulative Effects
Imazethapyr is a member of the
imidazolinone class of herbicides. Other
compounds of this class are registered
for use in the United States However,
the herbicidal activity of the
imidazolinones is due to the inhibition
of acetohydroxyacid synthase (AHAS),
an enzyme only found in plants. AHAS
is part of the biosynthetic pathway
leading to the formation of branched
chain amino acids. Animals lack AHAS
and this biosynthetic pathway. This lack
of AHAS contributes to the low toxicity
of the imidazolinone compounds in
animals. We are aware of no information
to indicate or suggest that imazethapyr
has any toxic effects on mammals that
would be cumulative with those of any
other chemical. Therefore, for the
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purposes of this tolerance petition no
assumption has been made with regard
to cumulative exposure with other
compounds having a common mode of
action.
E. Safety Determination
1. U.S. population. Using the
conservative exposure assumptions
described above and based on the
completeness and the reliability of the
toxicity data, BASF has estimated the
aggregate exposure to imazethapyr will
utilize less than 1% of the cPAD for the
U.S. population and all subpopulations,
respectively.
2. Infants and children. All
subpopulations based on age were
considered. Infants and children
remained below 1% of the aggregate
cPAD for food and water. BASF,
considering a worst-case situation,
concludes with reasonable certainty that
no harm will result to infants or
children from aggregate exposure to
imazethapyr residues.
No additional FQPA safety factor(s)
are considered to be appropriate for
imazethapyr. There is a complete
toxicity database for imazethapyr and
the exposure data are complete or are
estimated based on data that reasonably
accounts for potential exposures. Based
on the toxicology data and conclusions,
a FQPA safety factor of 1X appears to be
appropriate for imazethapyr.
F. International Tolerances
There are no Codex maximum residue
levels established or proposed for
residues of imazethapyr on rice.
[FR Doc. 05–12444 Filed 6–28–05; 8:45 am]
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ENVIRONMENTAL PROTECTION
AGENCY
[OPP–2005–0033; FRL–7718–8]
Paraquat Dichloride; Notice of Filing a
Pesticide Petition to Establish a
Tolerance for a Certain Pesticide
Chemical in or on Food
Environmental Potection
Agency (EPA).
ACTION: Notice.
AGENCY:
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
identification (ID) number OPP–2005–
0033, must be received on or before July
29, 2005.
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.
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:
FOR FURTHER INFORMATION CONTACT:
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
E:\FR\FM\29JNN1.SGM
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]]>Agencies
[Federal Register Volume 70, Number 124 (Wednesday, June 29, 2005)]
[Notices]
[Pages 37392-37397]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-12444]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
[OPP-2005-0161; FRL-7718-5]
Imazethapyr; 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.
-----------------------------------------------------------------------
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 identification (ID) number OPP-
2005-0161, must be received on or before July 29, 2005.
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 potentially affected by this action if you an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS 111)
Animal production (NAICS 112)
Food manufacturing (NAICS 311)
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-2005-0161. 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, 1801 S. Bell St., 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
[[Page 37393]]
under the ``Federal Register'' listings at https://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 https://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 in 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 https://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-2005-0161. 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-2005-0161. 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-2005-0161.
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, 1801 S. Bell St., Arlington, VA, Attention: Docket ID
Number OPP-2005-0161. 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
[[Page 37394]]
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 theelements 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: June 10. 2005.
Betty Shackleford,
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 the petitioner 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.
BASF Corporation
PP 5F 6947
EPA has received a pesticide petition (5F 6947) from BASF
Corporation, 26 Davis Drive, P.O. Box 13528, Research Triangle Park,
North Carolina 27709-3528 proposing, pursuant to section 408(d) of the
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to
amend 40 CFR part 180 by establishing a tolerance for residues of
imazethapyr,2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-
imidazol-2-yl]-5-ethyl-3-pyridine-carboxylic acid) as its free acid or
its ammonium salt (calculated as the acid), and its metabolite 2-[4, 5-
dihydro-4-methyl-4-(1-methylethyl-5-oxo-1H-imidazol-2-yl]-5-(1-
hydroxyethyl)-3-pyridinecarboxylic acid both free and conjugated] in or
on the raw agricultural commodity rice grain at 0.3 parts per million
(ppm) and rice straw at 0.4 ppm. EPA has determined that the petition
contains data or information regarding the elements set forth in
section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated
the sufficiency of the submitted data at this time or whether the data
supports granting of the petition. Additional data may be needed before
EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. The qualitative nature of the residues of
imazethapyr in rice is adequately understood. Based on studies
conducted on soybean, edible and forage legumes and corn, parent
imazethapyr and common metabolites CL 288511 and CL 182704 are the only
residues of concern for tolerance setting purposes.
2. Analytical method. The analytical method for rice commodities,
grain and straw is based on Capillary Electrophoresis with limits of
quantitation (LOQ) of 0.05 ppm. Measurement of imazethapyr residues in
polished rice, hull and bran are accomplished by Liquid Chromatography/
Atmospheric Pressure Ionization-Electrospray (API/ES) Mass Spectrometry
(LC/MS). The validated LOQ of the method is 0.025 ppm. A CZE-
methodology is available for the determination of imazethapyr in
crayfish with limits of quantitation of 50 ppb. These independently
validated methods are appropriate for the enforcement purposes of this
petition.
3. Magnitude of residues. A total of nineteen field trials were
conducted with imazethapyr and its metabolites on rice in 1997 and 1998
at several different use rates and timing intervals to represent the
use patterns which would result in the highest residue. In these
trials, residues of parent compound AC 263499 in grain and straw were
less than the limit of quantitation (0.05 ppm). The hydroxy metabolite,
CL 288511 was detected in grain samples at a maximum value of 0.085
ppm. All straw samples analyzed for CL 288511 residues were less than
the limit of quantitation (0.05 ppm). The glucose conjugate, CL 182704
was detected at a maximum value of 0.11 ppm in grain. All straw samples
analyzed for CL 182704 residues were less than the limit of
quantitation (0.05 ppm). The raw agricultural commodity (RAC) samples
were also processed into polished rice, hull and bran. Results from
these studies support the proposed tolerances of 0.3 ppm for rice grain
and 0.4 ppm for rice straw.
B. Toxicological Profile
1. Acute toxicity. Imazethapyr technical is considered to be
nontoxic (Toxicity Category IV) to the rat by the oral route of
exposure. In an acute oral toxicity study in rats, the LD50
value of imazethapyr technical was greater than 5,000 mg/kg body weight
for males and females. The results from an acute dermal toxicity study
in rabbits indicate that imazethapyr is slightly toxic (Toxicity
Category III) to rabbits by the dermal route of exposure. The dermal
LD50 value of imazethapyr technical was greater than 2,000
mg/kg bw for both male and female rabbits. Imazethapyr technical is
considered to be non-toxic (Toxicity Category IV) to the rat by the
respiratory route of exposure. The 4-hour LC50 value was
greater than 3.27 mg/l (analytical) and greater than 4.21 mg/l
(gravimetric) for both males and females. Imazethapyr technical was
shown to be non-irritating to rabbit skin (Toxicity Category IV) and
mildly irritating to the rabbit eye (Toxicity Category III). Based on
the results of a dermal sensitization study (Buehler),
[[Page 37395]]
imazethapyr technical is not considered a sensitizer in guinea pigs.
2. Genotoxicity. Imazethapyr technical was tested in a battery of
four in vitro and one in vivo genotoxicity assays measuring several
different endpoints of potential genotoxicity. Collective results from
these studies indicate that imazethapyr does not pose a mutagenic or
genotoxic risk.
3.Reproductive and developmental toxicity. The developmental
toxicity study in Sprague Dawley rats conducted with imazethapyr
technical showed no evidence of developmental toxicity or teratogenic
effects in fetuses. Thus, imazethapyr is neither a developmental
toxicant nor a teratogen in the rat. The No-Observable-Effect-Level
(NOEL) for maternal toxicity was 375 mg/kg bw/day, based on clinical
signs of toxicity in the dams (e.g. excessive salivation) at 1,125 mg/
kg bw/day. Imazethapyr technical did not exhibit developmental toxicity
or teratogenic effects at maternal dosages up to and including 1,125
mg/kg bw/day, the highest dose tested (HDT).
Results from a developmental toxicity study in New Zealand White
rabbits with imazethapyr technical also indicated no evidence of
developmental toxicity or teratogenicity. Thus, imazethapyr technical
is neither a developmental toxicant nor a teratogen in the rabbit. The
NOEL for maternal toxicity was 300 mg/kg bw/day, based on decreased
food consumption and body weight gain, abortion, gastric ulceration and
death at 1,000 mg/kg bw/day, the next HDT. The NOEL for developmental
toxicity and teratogenic effects was determined to be <1,000 mg/kg bw/
day based on no developmental toxicity or fetal malformations
associated with the administration of all doses.
The results from the two-generation reproduction toxicity study in
rats with imazethapyr technical support a NOEL for reproductive
toxicity of 10,000 ppm (equivalent to 800 mg/kg bw/day). The NOEL for
non-reproductive parameters (i.e. decreased weanling body weights) is
5,000 ppm.
4. Subchronic toxicity. A short-term (21-day) dermal toxicity study
in rabbits was conducted with imazethapyr technical. No dermal
irritation or abnormal clinical signs were observed at dose levels up
to and including 1,000 mg/kg bw/day (HDT), supporting a NOEL for dermal
irritation and systemic toxicity of 1,000 mg/kg bw/day.
In a subchronic (13-week) dietary toxicity study in rats with
imazethapyr technical, no signs of systemic toxicity were noted,
supporting a NOEL of 10,000 ppm the highest concentration tested
(equivalent to 820 mg/kg bw/day).
In a subchronic (13-week) dietary toxicity study in dogs with
imazethapyr technical, no signs of systemic toxicity were noted,
supporting a NOEL of 10,000 ppm (equivalent to 250 mg/kg b.w./day), the
highest concentration tested.
5.Chronic toxicity. A one-year dietary toxicity study was conducted
with imazethapyr technical in Beagle dogs at dietary concentrations of
0, 1,000, 5,000 and 10,000 ppm. In this study, the NOEL for systemic
toxicity was 1,000 ppm (equivalent to 25 mg/kg bw/day), based on slight
anemia, i.e., decreased red cell parameters observed at 5,000 and
10,000 ppm concentrations. No treatment-related histopathological
lesions were observed at any dietary concentration, including the
highest concentration tested (10,000 ppm).
In a two-year chronic dietary oncogenicity and toxicity study in
rats conducted with imazethapyr technical, the NOEL for oncogenicity
and chronic systemic toxicity was 10,000 ppm (equivalent to 500 mg/kg
bw/day), the highest concentration tested. An 18-month chronic dietary
oncogenicity and toxicity study in mice with imazethapyr technical
supports a NOEL for oncogenicity of 10,000 ppm, the highest
concentration tested (equivalent to 1,500 mg/kg bw/day), and a NOEL for
chronic systemic toxicity of 5,000 ppm (equivalent to 750 mg/kg bw/
day), based on decreased body weight gain in both sexes).
The EPA has classified imazethapyr as negative for carcinogenicity
(evidence of non-carcinogenicity for humans) based on the absence of
treatment-related tumors in acceptable carcinogenicity studies in both
rats and mice.
6. Animal metabolism. The rat, goat and hen metabolism studies
indicate that the qualitative nature of the residues of imazethapyr in
animals is adequately understood.
In three rat metabolism studies conducted with radiolabeled
imazethapyr technical the major route of elimination of the herbicide
was through rapid excretion in urine and to a much lesser extent in
feces. In the first study, almost 100% of the administered material was
recovered in excreta within 96 hours (89-95% in urine, 6-11% in feces).
The major residue in urine and feces was parent compound. Approximately
2% of the dose was metabolized and excreted as the [alpha]-hydroxyethyl
derivative of imazethapyr. In the second study, the test material was
rapidly and completely eliminated unchanged in the urine within 72
hours of dosing. After 24 hours, 92.1% of radioactivity was excreted in
the urine with 4.67% in the feces. There was no significant
bioaccumulation of radioactivity in the tissues from this rat
metabolism study (<0.01 ppm after 24 hours). In the third study, four
groups treated with radiolabeled imazethapyr readily excreted <95% of
the test material in the urine and feces within 48 hours. A high
percentage (97-99%) of the test material was excreted in the urine as
unchanged parent, the remainder as the [alpha]-hydroxyethyl derivative
of imazethapyr. For all three studies, the major route of elimination
of the herbicide in rats was through rapid excretion of unchanged
parent compound in urine. It is clear that imazathapyr and its related
residues do not accumulate in tissues and organs.
In the goat metabolism study, parent 14C-imazethapyr was
dosed to lactating goats at 0.25 ppm and 1.25 ppm. Results showed
14C-residues of <0.01 ppm in milk and <0.05 ppm in leg
muscle, loin muscle, blood, fat, liver and kidney. Laying hens dosed at
0.5 ppm and 2.5 ppm with 14C-imazethapyr showed
14C-residues of <0.05 ppm in eggs and all tissues (blood,
muscle, skin/fat, liver and kidney).
Additional animal metabolism studies have been conducted with CL
288511 (main metabolite in treated crops fed to livestock) in both
laying hens and lactating goats. These studies have been repeated to
support subsequent use extensions on crops used as livestock feed items
which would theoretically result in a higher dosing of imazethapyr-
derived residues to livestock ( i.e., corn, alfalfa). In these studies,
lactating goats dosed at 42 ppm of 14C-CL 288511 showed
14C-residues of <0.01 ppm in milk, leg muscle, loin muscle
and omental fat. 14C-Residues in blood were mostly <0.01 ppm
but reached 0.01 ppm on two of the treatment days. 14C-
Residue levels in the liver and kidney were 0.02 and 0.09 ppm,
respectively. Laying hens dosed at 10.2 ppm of 14C-
imazethapyr showed 14C-residues of <0.01 ppm in eggs and all
tissues (blood, muscle, skin/fat, liver and kidney). 14C-
imazethapyr or 14C-CL 288511 ingested by either laying hens
or lactating goats was excreted within 48 hours of dosing. These
studies indicate that parent imazethapyr and CL 288511-related residues
do not accumulate in milk or edible tissues of the ruminant.
7. Metabolite toxicology. Metabolism studies in soybean, peanut,
corn and alfalfa indicate that the only significant metabolites are the
[alpha]-hydroxyethyl derivative of imazethapyr, CL 288511 and its
glucose conjugate CL 182704. The [alpha]-hydroxyethyl metabolite has
also
[[Page 37396]]
been identified in minor quantities in the previously submitted rat
metabolism studies and in goat and hen metabolism studies. No
additional toxicologically significant metabolites were detected in any
of the plant or animal metabolism studies.
8. Endocrine disruption. Collective organ weight data and
histopathological findings from the two-generation rat reproductive
study, as well as from the subchronic and chronic toxicity studies in
three different animal species demonstrate no apparent estrogenic
effects or treatment-related effects of imazethapyr on the endocrine
system.
C. Aggregate Exposure
1. Dietary exposure--i. Food. BASF has determined that there are no
toxic effects attributable to a single dose of imazethapyr. Therefore,
a quantitative acute dietary exposure and risk assessment was not
required.
Assessments were conducted to evaluate the potential risk due to
chronic dietary exposure of the U.S. population to residues of
imazethapyr. This herbicide and its metabolites (CL 288511, CL 182704)
were expressed as the parent compound (imazethapyr). A dietary exposure
analysis was conducted for all current crops, including the increased
tolerance for rice grain and straw, and secondary residues in meat,
meat byproducts, and fat. The commodities include canola, field corn,
crop group 6, soybeans, alfalfa, nongrass animal feed group, peanuts,
endive, crayfish, head lettuce, and leaf lettuce.
The tier 1 chronic dietary exposure estimates were based on the
tolerance values, 100 percent crop treated values, default
concentration/processing factors and consumption data from the USDA
Continuing Survey of Food Intake by Individuals (CSFII 1994 - 1996,
1998) and the EPA Food Commodity Ingredient Database (FCID) using
Exponent's Dietary Exposure Evaluation Module (DEEM-FCID) software.
Resulting exposure estimates were compared against the imazethapyr
chronic Population Adjusted Dose (cPAD) of 2.5 mg/kg bw/day.
Exposure estimates for the imazethapyr chronic dietary assessments
were well below U.S. EPA's level of concern (See Table 1). The
estimated chronic dietary exposure was <0.1% of the cPAD for all
subpopulations. Additional refinements such as the use of anticipated
residues and predicted percent crop treated would further reduce the
estimated chronic dietary exposure.
Table 1.--Summary of Chronic Dietary Exposure and Risk for Imazethapyr Considering All Current Crops and Secondary Animal Residues
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Population Subgroups Exposure Estimate (mg/kg bw/day) %cPAD (cPAD = 2.5 mg/kg bw/day)
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U.S. Population 0.000476 0.019
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ii. Drinking water. Because the Agency does not have monitoring
data, drinking water concentration estimates are made by reliance on
simulation or modeling taking into account data on the physical
characteristics of imazethapyr. EPA determined that the residue of
concern in drinking water is only imazethapyr. Surface water (rice
paddy model; peak and average 126 [mu]g/l) estimated drinking water
concentrations (EDWCs) for imazethapyr were calculated. The surface
water EDWCs were generated assuming two applications of imazethapyr at
0.188 lbs ae/acre (highest registered/proposed multiple application
rate). Based on several prospective ground water studies the upper
bound ground water exposure would not be expected to exceed 1 [mu]g/L.
The estimated drinking water concentrations (EDWC) for both surface
water and ground water are well below the allowable level. Drinking
water level of comparison (DWLOC) calculations and comparisons to
surface water estimations are given as follows in Table 2.
Table 2. -- Estimated Chronic Drinking Water Values for Imazethapyr
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DWLOCchronic U.S. Population\1\ All Infants <1 year) Children (1-6 years) Females (13-49 years) Adults (20-49 years)
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DWLOC chronic ([mu]g/L) 87483 24993 24991 74989 87485
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*acute value for surface water
[[Page 37397]]
iii. Aggregate exposure (diet + water). The estimated chronic
aggregate exposure of imazethapyr from potential residues in food and
water are summarized in Table 3 as follows. Imazethapyr is not
registered for residential use and therefore residential exposure was
not considered.
Table 3. -- Estimated Chronic Aggregate Exposure From the Use of Imazethapyr
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Chronic Drinking Water Aggregate Exposure2 (mg/
Population Subgroup Chronic Food Exposure (mg/kg/day) Exposure1 (mg/kg/day) kg/day) Aggregate %cPAD
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U.S. Population 0.000476 0.003600 0.004076 0.16
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\1\ Aggregate Exposure = Food Exposure + Drinking Water Exposure
\2\ Drinking Water Exposure (mg/kg/day) = [Drinking Water Concentration ([mu]g/L) * Water Consumed (L/day)/ Body weight (kg)]/1,000
The assessment results indicate the aggregate exposure of
imazethapyr from potential residues in food and drinking water will not
exceed the U.S. EPA's level of concern (100% of PAD). The percent
chronic PAD was <1% for all subpopulations. Additional refinements such
as the use of anticipated residues and predicted percent crop treated
would further reduce the estimated chronic dietary exposure and %cPAD.
Overall, considering a ``worst-case'' scenario, we can conclude with
reasonable certainty that no harm will occur from chronic aggregate
exposure of imazethapyr residues from the current crops, including the
higher proposed tolerance values.
2. Non-dietary exposure . Imazethapyr products are not currently
registered for requested to be registered for residential use;
therefore the estimate of residential exposure is not relevant to this
tolerance petition.
D. Cumulative Effects
Imazethapyr is a member of the imidazolinone class of herbicides.
Other compounds of this class are registered for use in the United
States However, the herbicidal activity of the imidazolinones is due to
the inhibition of acetohydroxyacid synthase (AHAS), an enzyme only
found in plants. AHAS is part of the biosynthetic pathway leading to
the formation of branched chain amino acids. Animals lack AHAS and this
biosynthetic pathway. This lack of AHAS contributes to the low toxicity
of the imidazolinone compounds in animals. We are aware of no
information to indicate or suggest that imazethapyr has any toxic
effects on mammals that would be cumulative with those of any other
chemical. Therefore, for the purposes of this tolerance petition no
assumption has been made with regard to cumulative exposure with other
compounds having a common mode of action.
E. Safety Determination
1. U.S. population. Using the conservative exposure assumptions
described above and based on the completeness and the reliability of
the toxicity data, BASF has estimated the aggregate exposure to
imazethapyr will utilize less than 1% of the cPAD for the U.S.
population and all subpopulations, respectively.
2. Infants and children. All subpopulations based on age were
considered. Infants and children remained below 1% of the aggregate
cPAD for food and water. BASF, considering a worst-case situation,
concludes with reasonable certainty that no harm will result to infants
or children from aggregate exposure to imazethapyr residues.
No additional FQPA safety factor(s) are considered to be
appropriate for imazethapyr. There is a complete toxicity database for
imazethapyr and the exposure data are complete or are estimated based
on data that reasonably accounts for potential exposures. Based on the
toxicology data and conclusions, a FQPA safety factor of 1X appears to
be appropriate for imazethapyr.
F. International Tolerances
There are no Codex maximum residue levels established or proposed
for residues of imazethapyr on rice.
[FR Doc. 05-12444 Filed 6-28-05; 8:45 am]
BILLING CODE 6560-50-S
