[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