[Federal Register Volume 68, Number 156 (Wednesday, August 13, 2003)]
[Notices]
[Pages 48362-48366]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-20640]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2003-0266; FRL-7321-7]
Imazapyr; 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-2003-0266, must be
received on or before September 12, 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: [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
[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 identification (ID) number OPP-2003-0266. 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
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
[[Page 48363]]
brief description written by the docket staff.
C. How and To Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through hand
delivery/courier. To ensure proper receipt by EPA, identify the
appropriate docket ID number in the subject line on the first page of
your comment. Please ensure that your comments are submitted within the
specified comment period. Comments received after the close of the
comment period will be marked ``late.'' EPA is not required to consider
these late comments. If you wish to submit CBI or information that is
otherwise protected by statute, please follow the instructions in Unit
I.D. Do not use EPA Dockets or e-mail to submit CBI or information
protected by statute.
1. Electronically. If you submit an electronic comment as
prescribed in this unit, EPA recommends that you include your name,
mailing address, and an e-mail address or other contact information in
the body of your comment. Also include this contact information on the
outside of any disk or CD ROM you submit, and in any cover letter
accompanying the disk or CD ROM. This ensures that you can be
identified as the submitter of the comment and allows EPA to contact
you in case EPA cannot read your comment due to technical difficulties
or needs further information on the substance of your comment. EPA's
policy is that EPA will not edit your comment, and any identifying or
contact information provided in the body of a comment will be included
as part of the comment that is placed in the official public docket,
and made available in EPA's electronic public docket. If EPA cannot
read your comment due to technical difficulties and cannot contact you
for clarification, EPA may not be able to consider your comment.
i. EPA Dockets. Your use of EPA's electronic public docket to
submit comments to EPA electronically is EPA's preferred method for
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket, and follow the online instructions for submitting comments.
Once in the system, select ``search,'' and then key in docket ID number
OPP-2003-0266. The system is an ``anonymous access'' system, which
means EPA will not know your identity, e-mail address, or other contact
information unless you provide it in the body of your comment.
ii. E-mail. Comments may be sent by e-mail to [email protected],
Attention: Docket ID Number OPP-2003-0266. 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-2003-0266.
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-2003-0266. 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: August 7, 2003.
Debra Edwards,
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
[[Page 48364]]
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 0F6166
EPA has received a pesticide petition (PP 0F6166) from BASF, 26
Davis Drive, Research Triangle Park, NC 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 imazapyr [2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-
oxo-lH-imidazol-2-yl]-3-pyridinecarboxylic acid], applied as the
isopropylamine salt, in or on the raw agricultural commodity on grass
forage at 125 parts per million (ppm) and hay at 35 ppm, fish at 1 ppm,
shellfish at 0.1 ppm, milk at 0.01 ppm, and kidney at 0.5 ppm, meat by-
products other than kidney at 0.05 ppm, meat at 0.05 ppm, and fat at
0.05 ppm of cattle, sheep, goats, and horses. 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--i. Bermudagrass. Radiolabeled imazapyr was
applied at 1.5 lb acid equivalents/acre (ae)/A to field-grown
bermudagrass. Parent imazapyr accounted for the majority of the total
radioactive residue (TRR) in all harvested samples. No metabolites were
identified which require regulation.
ii. Ruminant. Goats were dosed with radiolabeled imazapyr at 17.7
ppm, 42.5 ppm, or 47 ppm dietary equivalents for 7 days. As assessed
for goats receiving the 17.7 or 42.5 ppm doses, TRR in fat, liver and
leg and loin muscle were non-detectable < 0.05 ppm. TRR in milk were a
maximum of 0.01, 0.02, and 0.02 ppm for the three goats, respectively,
while TRR in kidney were 0.08, 0.11, and 0.08 ppm, respectively. Of
these residues, parent imazapyr accounted for 50-66% of the TRR in milk
and 82-95% of the TRR in kidney. No metabolites were identified which
require regulation.
iii. Confined crop rotation. Radiolabeled imazapyr was applied to
soil at a rate of 0.79 lb ae/A. Root (carrot), lettuce (leafy
vegetables), and wheat (cereal grains), were planted at 330 through 540
days; shorter intervals were not required as rangeland and pastures are
not normally rotated to other crops. The TRR in all harvested samples
were <0.02 ppm and the major extractable component of these residues
was parent imazapyr. Therefore, there is no reasonable expectation of
inadvertent residues in rotational crops planted 12 months after
application.
2. Analytical method. M 3023 is a reliable capillary
electrophoresis method with ultraviolet (CE/UV) detection for the
determination of imazapyr residues in grass forage and grass hay. M
3184 is a reliable CE/UV method for the determination of imazapyr
residues in meat, kidney, other meat byproducts, and fat of cattle,
sheep, goats, and horses. M 3075 is a reliable CE/UV method for the
determination of imazapyr residues in milk. M 3066 is a reliable CE/UV
method for the determination of imazapyr residues in fish and
shellfish.
3. Magnitude of residues--i. Grass. Imazapyr was applied at a
nominal rate of 0.75 lb ae/A to bluegrass, bermudagrass, tall fescue,
and bromegrass for a total of 14 field trials. Residues of imazapyr
were reached a maximum of 98 ppm in grass forage immediately after
treatment and 27 ppm upon drying to grass hay cut 7 days after
treatment. Therefore, tolerances of 125 ppm in/on grass forage and 35
ppm in/on grass hay are proposed.
ii. Ruminants. Lactating dairy cows were dosed orally each day for
28 or 29 consecutive days at feed equivalents of 0, 58, 157, 607, and
1,680 milligrams (mg) imazapyr per kilogram (kg) dry matter consumed.
The 58 mg/kg dose is equivalent to 1.4 times the anticipated dietary
burden for the worst-case cattle diet where 10% of the grass received
an imazapyr spot treatment, the proposed label use for range and
pasture grasses. At 58 mg/kg, imazapyr residues in milk were < 0.01
ppm; residues in muscle, fat, and liver were <0.05 ppm; and residues in
kidney averaged 0.25 ppm. Furthermore, imazapyr residues in milk were
shown not to be concentrated into milk fat. Therefore, the following
tolerances for imazapyr residues in cattle, sheep, goats, and horses
are proposed: Milk at 0.01 ppm; meat byproducts (except kidney) at 0.05
ppm; meat at 0.05 ppm; fat at 0.05 ppm; and kidney at 0.5 ppm.
iii. Fish and shellfish. Imazapyr was applied at 1.6 lb ae/A to two
ponds containing fish and aquatic invertebrates. Imazapyr residues were
observed from the organisms collected from the treated ponds at only
one site and only in the 3-hour-after-treatment samples. Average
residues from these samples were: Bluegill, 0.636 ppm; tilapia, 0.233
ppm; catfish, 0.068 ppm; crayfish, 0.059 ppm. In a separate study,
freshwater clams were exposed to a dose of imazapyr equivalent to 1.5
lb ae/A as applied to a 2.2-foot deep pond; residues of imazapyr in
these clams remained <0.05 ppm at all intervals evaluated (up to 28
days post-treatment). Given these results, tolerances for imazapyr are
proposed at 1 ppm for fish and 0.1 ppm for shellfish.
B. Toxicological Profile
1. Acute toxicity. Based on a battery of acute toxicity studies,
imazapyr has been placed in toxicity category I for eye irritation,
category IV for oral LD50 and primary dermal irritation, and
category III for dermal LD50 and inhalation LC50.
Imazapyr was a non-sensitizer when tested for dermal sensitization
(Buehler Method).
2. Genotoxicity. Studies on gene mutation and other genotoxic
effects, Ames Salmonella Assay, CHO/HGPRT Point Mutation Assay, in
vitro CHO cell chromosome aberration assay, dominant lethal assay, and
unscheduled DNA synthesis (UDS) in primary rat hepatocytes yielded
negative results.
3. Reproductive and developmental toxicity--i. For a rat
developmental toxicity study at doses of 0, 100, 300, or 1,000 mg/kg
body weight/day (b.w./day), the only clinical sign of toxicity was
salivation in gravid dams at 1,000 mg/kg b.w./day. The No-Observed-
Adverse-Effect Level (NOAEL) for maternal toxicity is 300 mg/kg b.w./
day. There were no developmental findings in this study up to the limit
dose of 1,000 mg/kg b.w./day, the highest dose tested (HDT).
ii. For a rabbit development toxicity study at doses of 0, 25, 100,
and 400 mg/kg b.w./day, the maternal and developmental NOAEL is 400 mg/
kg b.w./day HDT. Doses were based on pilot range-finder study, which
tested at 0, 250, 500, 1,000, and 2,000 mg/kg b.w./day. The only toxic
effect observed was increased salivation at 1,000 and 2,000 mg/kg b.w./
day.
iii. A 2-generation rat reproduction study at doses of 0, 1,000,
5,000, or 10,000 ppm yielded a NOAEL of 10,000 ppm highest
concentration tested (HCT) (800 mg/kg b.w./day for males, 980 mg/kg
b.w./day for females, as based on food consumption data).
4. Subchronic toxicity--i. A 90-day dietary study in rats at doses
of 0, 15,000, or 20,000 ppm resulted in a
[[Page 48365]]
NOAEL of 20,000 ppm HCT (approximately 1,695 mg/kg b.w./day for males,
1,785 mg/kg b.w./day for females, as based on food consumption data).
ii. A 21-day rabbit dermal toxicity study at doses of 0, 100, 200,
or 400 mg/kg b.w./day resulted with the NOAEL of 400 mg/kg b.w./day
HDT.
5. Chronic toxicity--i. A 1-year chronic toxicity study in dogs at
doses of 0, 1,000, 5,000, or 10,000 ppm yielded a NOAEL of 10,000 ppm
HCT (equivalent to 250 mg/kg b.w./day).
ii. A 2-year chronic toxicity/carcinogenicity study in rats at
doses of 0, 1,000, 5,000, or 10,000 ppm provided NOAELs for both
systemic toxicity and oncogenicity of 10,000 ppm HCT (approximately 500
mg/kg b.w./day for males, 640 mg/kg b.w./day for females, as based on
food consumption data).
iii. An 18-month oncogenicity study in mice at doses of 0, 1,000,
5,000, or 10,000 ppm provided NOAELs for both systemic toxicity and
oncogenicity of 10,000 ppm HCT (equivalent to 1,500 mg/kg b.w./day).
6. Animal metabolism. Results from a rat metabolism study indicated
that imazapyr was rapidly absorbed and excreted by 7 days post-dosing,
with the majority of the administered 14C-label (90%) eliminated in the
urine within 48 hours. Metabolite characterization studies showed that
essentially all the test material was excreted unchanged. Two minor
metabolites were detected in the urine or feces of treated rats;
however, their contribution combined was less than or equal to 0.5% of
the administered dose. An additional 12 unidentified metabolites were
isolated, but they contributed less than 3% of the total dose.
7. Metabolite toxicology. There were no metabolites identified in
plant or animal commodities which require regulation.
8. Endocrine disruption. There is sufficient data from the 2-
generation rat reproduction study as well as from the subchronic (90-
day) rat feeding study and chronic feeding studies in the dog (1-year),
rat (24-month), and mouse (18-month), to determine whether imazapyr has
potential estrogenic properties or causes other endocrine effects. The
collective data from these studies, indicate that imazapyr is not
associated with any treatment-related estrogenic or endocrine effects.
The 2-generation rat reproduction study, conducted at dietary
concentrations up to 10,000 ppm, showed no treatment-related effects on
reproductive performance (including estrous cycle data, mating indices,
pregnancy rates, fertility indices, gestational length, and gestation
indices) or on pup growth and development from parturition to adulthood
for both litter intervals. Histopathological examinations of the
testes, epididymides, prostate gland, and seminal vesicles, were
conducted for high-dose and control P1 and F1
adult males. Histopathological examinations of the mammary gland,
ovaries, uterus (corpus and cervix), and vagina, were conducted for
high-dose and control P1 and F1 adult females. In
addition, for F2b pups, histopathological examinations of
the adrenal glands, pancreatic islets, pituitary gland, thyroid gland,
parathyroid glands, testes, epididymides, prostate gland, seminal
vesicles, mammary gland, ovaries, uterus (corpus and cervix), and
vagina, were conducted. For all of these tissue examinations, no
treatment-related microscopic findings were observed in either males or
females. Further, no treatment-related macroscopic findings were
observed for either parental or pup generations.
Organ weight data and histopathological examinations from the
subchronic (90-day) rat feeding study and chronic feeding studies in
the dog (1-year), rat (24-month), and mouse (18-month), may also be
utilized to determine whether imazapyr has potential estrogenic
properties or causes other endocrine effects. Absolute and relative
weights of the adrenal glands (not measured in the dog study),
pituitary gland, thyroid/parathyroid gland, ovaries, and testes (with/
without epididymides) were recorded for animals at the interim (if
applicable) and terminal sacrifice periods in these studies. In
addition, detailed macroscopic and microscopic examinations of the
following organs were performed: Pituitary gland, thyroid gland,
parathyroid glands, pancreatic islets, adrenal glands, testes,
epididymides, prostate gland, seminal vesicles (not performed in the
dog study), mammary gland, ovaries, uterus (corpus and cervix), and
vagina. No information was found from the organ weight data or
macroscopic and microscopic examinations, from the subchronic (90-day)
rat feeding study and chronic feeding studies in the dog (1-year), rat
(24-month), and mouse (18-month), that suggests that imazapyr is
associated with any treatment-related estrogenic effects or effects on
the endocrine system.
C. Aggregate Exposure
1. Dietary exposure--i. Food--a. Acute dietary exposure. An acute
dietary risk assessment is not required because no acute toxicological
endpoints were identified by the EPA for imazapyr.
b. Chronic dietary exposure. Novigen Sciences, Inc. conducted a
Tier 1 assessment of potential chronic dietary exposure from the
proposed uses of imazapyr for weed control in pasture/range grasses and
for aquatic weed control. These uses may result in dietary residues in
shellfish, freshwater finfish, milk, and tissues of cattle, sheep,
goats, and horses. This assessment also included the current tolerances
on field corn commodities. For this Tier 1 analysis, tolerance values
were used for fish at 1.0 ppm; shellfish at 0.1 ppm; kidney of cattle,
sheep, goats, and horses at 0.5 ppm; other meat byproducts of cattle,
sheep, goats, and horses at 0.05 ppm; meat of cattle, sheep, goats, and
horses 0.05 ppm; fat of cattle, sheep, goats, and horses at 0.05 ppm;
and milk at 0.01 ppm. Tolerance level residues were assumed, including
those for field corn grain (0.05 ppm). Chronic dietary exposure
analyses for the overall U.S. population and 25 population subgroups,
including infants and children, were compared to the chronic Reference
Dose (RfD) of 2.5 mg/kg b.w./day. Results of the chronic dietary
analyses for all population subgroups examined were less than 0.1% of
the chronic RfD. Exposure estimates for children 1 to 6 years of age,
the most highly exposed population group, were only 0.000575 mg/kg
b.w./day or less than 0.1% of the RfD. Therefore, the results of the
chronic dietary assessment demonstrate a reasonable expectation of no
harm from the proposed and existing uses of imazapyr.
ii. Drinking water. According to label restrictions, ARSENAL
herbicide will not be applied directly to water within
1/89/21/13/23/85/83/8 mile upstream of an active potable water
intake in flowing water (i.e., river, stream, etc.) or within
1/89/21/13/23/85/83/8 mile of an active potable water intake
in a standing body of water such as lake, pond or reservoir. However,
for purposes of demonstrating the large margin of exposure to imazapyr
residues in drinking water, no label restrictions will be presumed.
Rather, a level of 0.200 ppm in the water will be used, as based upon
data from Missouri and Florida sites at 1-hour after treatment (maximum
levels of imazapyr were approximately 0.197 ppm and 0.092 ppm,
respectively). If 0.200 ppm is chosen as the maximum potential residues
in the aquatic dissipation studies, then the standard (chronic)
exposure analyses would be:
Adult male (200 [mu]g/L x 10-3 mg/[mu]g X 2 L/day) / 70
kg = 0.0057 mg/kg/day
Adult female (200 [mu]g/L x 10-3 mg/[mu]g X 2 L/day) /
60 kg = 0.0067 mg/kg/day
[[Page 48366]]
Children (200 [mu]g/L x 10-3 mg/[mu]g X 1 L/day) / 10 kg
= 0.02 mg/kg/day
The degree of risk can be characterized by the magnitude of the
margin of exposure (MOE), which is the ratio of the NOAEL from the
animal toxicity study used to set the RfD to an estimated human
exposure value (MOE = NOAEL/Human Exposure). Based on the NOAEL of 250
mg/kg b.w./day from the chronic dog study and children's exposure value
(worst case) of 0.02 mg/kg b.w./day, a very high, favorable MOE of
12,500 times is derived. Thus, there is a reasonable expectation of no
harm from the proposed and existing uses of imazapyr.
2. Non-dietary exposure. There is no available information
quantifying non-dietary exposure to imazapyr. However, based on
physical and chemical characteristics of the compound, the use
patterns, and available information concerning its environmental fate,
non-dietary exposure is expected to be negligible.
Previous registrations for imazapyr included non-crop sites.
Labeled use sites for one group of imazapyr products include railroad,
utility, pipeline, and highway rights-of-way, utility plant sites,
petroleum tank farms, pumping installations, fence rows, storage areas,
non-irrigation ditchbanks, under asphalt, under pond liners, wildlife
management areas, forestry site preparation, and other non-crop areas.
Imazapyr products for the above uses are clearly not intended for use
in residential or recreational areas that have a high potential of
exposure for the general population. The labels state that these
imazapyr products are not for use on lawns, walks, driveways, tennis
courts or similar areas.
Other imazapyr products are labeled as plant growth regulators for
applications to limited care-low maintenance areas, such as roadsides,
airports, fairgrounds, and golf course roughs, and to limited wear
areas such as industrial, institutional, and cemetery grounds. These
low rate uses entail minimal exposure potential for the general
population. The product labeling does not allow use on turf that is
being grown for sale or other commercial use, such as sod. There are
imazapyr products marketed for residential use. These total vegetation
control products are used for spot treatments or bare ground
applications. These products are to be applied only where no plant
growth is desired and are not to be used on lawns. Therefore, even for
the limited residential uses, the potential for exposure is minimal.
For the aquatic use, a recreational swimmer risk assessment is not
required because no acute toxicological endpoints for oral, dermal, and
inhalation routes of exposure were identified by EPA for imazapyr.
Moreover, the dermal NOAEL for the 21-day rabbit toxicity study is the
HDT (400 mg/kg b.w./day), indicating that imazapyr is non-toxic
following repeated dermal exposure.
3. Operator exposure. Specifically, for potential short- and
intermediate-term occupational exposure, professional contractors
(representing worst-case for the proposed uses) would be mixing/
loading/applying the end-use product for less than 90 days per year
(and less than 30 consecutive days per year). Importantly, in its risk
characterization of imazapyr for use in/on corn (1997), EPA found no
toxicological endpoints indicating potential for adverse effects that
were identified for short-term (1-7 days) and intermediate-term (7 days
to several months) occupational exposure. In the 21-day dermal toxicity
study, the NOAEL was determined to be 400 mg/kg b.w./day HDT. This was
further supported by oral NOAELs of 250 mg/kg b.w./day HDT in the
chronic dog study and 500 mg/kg b.w./day HDT (males) or 640 mg/kg b.w./
day HDT (females) in the chronic rat study. Therefore, short- and
intermediate-term risk assessments are not required.
D. Cumulative Effects
Imazapyr belongs to the imidazolinone class of compounds. Other
compounds in this class are registered herbicides. 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 imazapyr has any toxic effects on mammals that
would be cumulative with those of any other chemical.
E. Safety Determination
1. U.S. population. Based on the chronic RfD of 2.50 mg/kg b.w./
day, the proposed application will utilize less than 0.1% of this
value. Exposure estimates for the general U.S. population were only
0.000227 mg/kg b.w./day. Exposure estimates for children 1 to 6 years
of age, the most highly exposed population group, were only 0.000575
mg/kg b.w./day or less than 0.1% of the RfD. EPA generally has no
concern for exposure below 100% of the RfD which represents the level
at or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health. The complete and reliable
toxicity data, indicating low potential mammalian toxicity, and the
conservative chronic exposure assumptions support the conclusion that
there is a ``reasonable certainty of no harm'' from aggregate exposure
to imazapyr residues.
2. Infants and children. No developmental, reproductive or
fetotoxic effects were noted at the highest doses of imazapyr tested.
The only maternal effect in the rat teratology study was increased
salivation in the highest dose group. The NOAEL used to calculate the
RfD for the general U.S. population is 250 mg/kg b.w./day derived from
the 1-year chronic toxicity study in dogs. That NOAEL is lower than the
developmental NOAELs for the teratology studies in rabbits and rats
(1.6 and 4 times, respectively), as well as lower than the NOAEL for
the 2-generation reproduction study in male and female rats (3.2 - 3.9
times).
EPA has found the data base relative to prenatal and postnatal
effects for children to be complete, valid and reliable. There were no
effects observed in the offspring in the developmental studies in rats
and rabbits. In the reproduction study, the lack of any pup effects
observed at 10,000 ppm (the highest dose tested) in their growth and
development from parturition through adulthood, suggests that there is
no additional sensitivity for infants and children. Therefore, an
additional safety (uncertainty) factor is not warranted and the RfD of
2.50 mg/kg b.w./day, which utilizes a 100-fold safety factor, is
appropriate to assure a reasonable certainty of no harm to infants and
children.
Therefore, the registrant believes that the results of the
toxicology and metabolism studies support both the safety of imazapyr
to humans based on the intended use as a herbicide for aquatic and
grass uses and the granting of the requested tolerances.
F. International Tolerances
There are no Codex tolerances established for imazapyr.
[FR Doc. 03-20640 Filed 8-12-03; 8:45 am]
BILLING CODE 6560-50-S