[Federal Register Volume 66, Number 165 (Friday, August 24, 2001)]
[Notices]
[Pages 44624-44629]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-21447]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-1038; FRL-6796-7]


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 control number PF-1038, must be 
received on or before September 24, 2001.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-1038 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: Hoyt Jamerson, Registration 
Support Branch, Registration Division (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: (703) 308-9368; e-mail address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    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 the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
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 Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'' ``Regulation and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-1038. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-1038 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [email protected], or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-1038. Electronic comments

[[Page 44625]]

may also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
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 version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified 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 
control 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 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 9, 2001.
James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represents the view of the 
petitioner. EPA is publishing the petition summary verbatim without 
editing it in any way. 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.
    EPA has received pesticide petitions [0E6202 and 1E6249] from the 
Interregional Research Project Number 4 (IR-4), 681 U.S. Highway #1 
South, North Brunswick, NJ 08902 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 tolerances for residues of the 
herbicide chemical clethodim, (E)-()-2-1-[(3-chloro-2-
propenyl)oxy]imino]propyl]-5-2(ethylthio) propyl]-3-hydroxy-2-
cyclohexen-1-one and its metabolites containing the 5-(2-ethylthio-
propyl) cyclohexene-3-one and 5-(2-ethylthiopropyl)-5-
hydroxycyclohexene-3-one moieties and their sulfoxides and sulfones, 
all expressed as clethodim] in or on the raw agricultural commodities: 
(1) pesticide petition (1E6249) proposes tolerances for green onions 
and leaf lettuce at 2.0 ppm, and head and stem Brassica (Crop subgroup 
5A) at 3.0 parts per million (ppm), (2) pesticide petition (0E6202) 
proposes tolerances for flax seed at 0.50 ppm, flax meal at 1.0 ppm, 
and mustard seed at 0.50 ppm.
    EPA has determined that the petition contain 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 
petitions. Additional data may be needed before EPA rules on the 
petitions.

Interregional Research Project Number 4 (IR-4)

PP 0E6202 and 1E6249

A. Background Information and Use Profile

    Clethodim is the active ingredient in SELECT 2 EC Herbicide (EPA 
Reg. No. 59639-3), SELECT Herbicide (also known as PRISM Herbicide, EPA 
Reg. No. 59639-78), and SELECT SUPER Herbicide (EPA Reg. No. 59639-102) 
post-emergence herbicides effective against a wide range of annual and 
perennial grasses. Clethodim Technical is registered by the EPA (EPA 
Reg. No. 59639-2) as a technical grade active ingredient for 
manufacturing use. SELECT 2 EC Herbicide is registered for use on 
alfalfa; cotton; dry beans; peanuts; onions, garlic, and shallots (all 
dry bulb); soybeans; sugar beets; tomatoes; and is an emulsifiable 
concentrate containing 2 pounds per gallon (26.4%) of active 
ingredient. SELECT Herbicide is registered for the same uses and is an 
emulsifiable concentrate containing 0.94 pounds per gallon (12.6%) of 
active ingredient. PRISM Herbicide is an alternate brand name for 
SELECT Herbicide. For optimum grass weed control, both SELECT 2EC and 
SELECT Herbicides require that adjuvant or crop oil concentrate be 
added to the spray solution. SELECT SUPER Herbicide is also an 
emulsifiable concentrate that includes the required adjuvant. SELECT 
SUPER Herbicide contains 1.0 pound per gallon (13.2%) of active 
ingredient and is registered on cotton, soybeans and sugar beets only. 
These products are applied to registered crops via broadcast foliar 
applications at rates up to 0.25 lb. Active ingredient/Acre (ai/A). For 
more difficult to control grass weeds, a second application within 
about 14 days is allowed. The maximum seasonal use rate is 0.5 lb. ai/
A.

B. Residue Chemistry

    1. Plant and animal metabolism. The metabolism of 14C-
clethodim labeled in the ring structure and in the side chain has been 
studied in carrots, soybeans, and cotton as well as in lactating goats 
and laying hens. The major metabolic pathway in plants is initial 
sulfoxidation, forming clethodim sulfoxide, followed by further 
oxidation to form clethodim sulfone. These reactions are apparently 
followed by elimination of the chloroallyloxy side

[[Page 44626]]

chain to give the imine sulfoxide and sulfone, with further 
hydroxylation to form the 5-OH sulfoxide and 5-OH sulfone. Clethodim 
sulfoxide and clethodim sulfone conjugates were also detected as major 
or minor metabolites, depending on plant species and subfractions. Once 
the side chain is cleaved from clethodim, the chloroallyloxy moiety 
undergoes extensive metabolism to eliminate chlorine and incorporate 
three-carbon moieties into natural plant components.
    Ruminant and poultry metabolism studies demonstrated that transfer 
of administered 14C-clethodim residues to tissues was low. 
Total 14C-residues in goat milk, muscle and tissues 
accounted for less than 0.5% of the administered dose (24 ppm in diet 
for 3 days), and were less than 0.4 ppm in all cases. In poultry 
treated at 2.2 milligram/kilogram/day (mg/kg/day) for 5 days, total 
14C residues in eggs, muscle and most tissues were less than 
0.3 ppm, although higher in liver, kidney and the gastrointestinal 
tract (GI tract). Residues in eggs were less than 0.2 ppm.
    Comparing metabolites detected and quantified from plant and animal 
metabolism studies shows that there are no significant aglycones in 
plants which are not also present in the excreta or tissues of animals. 
Based on these metabolism studies, the residues of concern in crops and 
animal products are clethodim and its metabolites containing the 
cyclohexene moiety, and their sulfoxides and sulfones.
    2. Analytical method. Practical analytical methods for detecting 
and measuring levels of clethodim and its metabolites have been 
developed and validated in/on all appropriate agricultural commodities, 
respective processing fractions, milk, animal tissues, and 
environmental samples. The extraction methodology has been validated 
using aged radio chemical residue samples from 14C-
metabolism studies. The methods have been validated at independent 
laboratories, and EPA has successfully performed an analytical method 
trial. For most commodities, the primary enforcement method is EPA-RM-
26D-3, an high performance liquid chromotography (HPLC) method capable 
of distinguishing clethodim from the structurally related herbicide 
sethoxydim. However, for milk, natural interferences prevent adequate 
quantitation of clethodim moieties and the common-moiety method (RM-
26B-2) is the primary enforcement method with EPA-RM-26D-3 as the 
secondary method if needed to differentiate clethodim from sethoxydim.
    3. Magnitude of residues. A summary of field residue data 
supporting the proposed tolerances on green onion, leaf lettuce, head 
and stem brassica vegetables, flax and mustard seed is presented below.
    (a) Green Onion: In three (3) field trials, onions (green) were 
treated with two post-emergent applications of 0.24 to 0.34 lb. a.i./A 
and harvested 13 to 15 days after the application. The trials were 
performed in EPA regions 3, 6, and 10. Residues in onions (green) 
ranged from 0.20 ppm to 0.87 ppm total clethodim. These residue data 
support a tolerance for green onion of 2.0 ppm.
    (b) Leaf Lettuce: In six (6) field trials conducted in EPA regions 
2, 3, and 10, leaf lettuce was treated with two post-emergent 
applications of 0.23 to 0.32 lb. a.i./A each. Lettuce was harvested 13-
16 days after the last application. Clethodim residues ranged from 0.25 
to 1.10 ppm total clethodim. These residue data support a tolerance for 
leaf lettuce of 2.0 ppm.
    (c) Head and Stem Brassica: Proposed tolerances for Crop Subgroup 
4B are supported by field residue studies in broccoli and cabbage. In 
six (6) field trials, broccoli was treated with two post-emergent 
applications of 0.24 to 0.34 lb. a.i./A each, 13-14 days apart, and 
harvested 29-31 days after the last application. Residues in broccoli 
ranged from 0.1 ppm to 1.20 ppm total clethodim. In seven (7) field 
trials, cabbage was treated with two post-emergent applications of 0.25 
to 0.37 lb. a.i./A each, 14 days apart, and harvested 28-31 days after 
the last application. Residues in cabbage ranged from 0.24 ppm to 1.17 
ppm total clethodim. These data support a tolerance of 3.0 ppm in head 
and stem brassica.
    (d) Flax: In two (2) field trials, flax was treated with one post-
emergent application of 0.09 lb. a.i./A and harvested approximately 84 
to 108 days after the last application. These residue trials were 
performed in Canada in growing regions adjacent to the U.S. areas where 
flax is grown. These data were used to support a maximum residue level 
in Canada and are being cited in order to harmonize maximum residue 
levels between the U.S. and Canada and to remove the existing trade 
barrier. Clethodim residues ranged from 0.05 to 0.06 ppm total 
clethodim and support a tolerance for flax seed at 0.50 ppm.
    (e) Mustard Seed: Tolerances for mustard seed are supported by 
residue field trials on flax, summarized above, and a similar oilseed 
crop, canola. In 18 field trials, canola or rape was treated with one 
post-emergent application of 0.11 to 0.32 lb. a.i./A and harvested 
approximately 70 to 98 days after the application. Most of these trials 
were performed in Canada in growing regions adjacent to the U.S. areas 
where canola is grown. These data were used to support a maximum 
residue level in Canada and were cited in a previous petition (7F4873) 
to harmonize maximum residue levels for canola between the U.S. and 
Canada and to remove the existing trade barrier. Residues in canola 
seed samples ranged from  0.05 ppm to 0.54 ppm. The highest average 
field trial (HAFT) residue was 0.505 ppm. The averageresidue value for 
all trials, including samples less than the limit of detection at one-
half the limit, was 0.16 ppm (number of samples = 31, standard 
deviation, n-1 degrees of freedom = 0.14 ppm). Since the highest 
residues were the result of application rates (0.19 lb. a.i./A) higher 
than those proposed for the U.S. (0.08 lb. a.i./A), these data support 
tolerances of 0.50 ppm in mustard seed.
    Secondary Residues: The single feed item associated with these 
uses, flax meal, has potential anticipated clethodim residues well 
below other feed items with existing tolerances. Thus, clethodim 
residues in/on this proposed feed item does not effect the theoretical 
maximum dietary burden for the various livestock diets, and thus does 
not effect the magnitude of secondary residue tolerances. Therefore, no 
changes in existing secondary residue tolerances is being proposed.
    Rotational Crops: The results of a confined rotational crops 
accumulation study indicate that no rotational crop tolerances are 
required.

C. Toxicological Profile

    A full battery of toxicology testing including studies of acute, 
sub-acute, and chronic toxicity; carcinogenicity; developmental and 
reproductive toxicity; mutagenicity; and rat metabolism is available 
for clethodim. The acute toxicity of clethodim is low by all routes. 
Clethodim is not a developmental or reproductive toxicant, and is not 
mutagenic or carcinogenic. EPA has established a reference dose (RfD) 
for clethodim of 0.01 mg/kg bwt/day, based on alterations in hematology 
and increased absolute and relative liver weights at 75 mg/kg/day 
observed in a chronic toxicity study in dogs with a no observed adverse 
effect level (NOAEL) of 1 mg/kg/day. An uncertainty factor of 100 is 
used in calculating the reference dose RfD to account for both inter- 
and intra-species variations. EPA has (not) identified toxicity 
endpoints of concern for acute exposures.

[[Page 44627]]

    1. Acute toxicity. Clethodim technical is slightly toxic to animals 
following acute oral (Toxicity Category III), dermal (Toxicity Category 
IV), or inhalation exposure (Toxicity Category IV). Clethodim is a 
moderate eye irritant (Category III), a skin irritant (Category II), 
and does not cause skin sensitization in the modified Buehler test in 
guinea pigs. In addition, an acute oral no-observed effect level 
(NOAEL) has been determined in rats to be 300 mg/kg.
    2. Genotoxicity. Clethodim does not present a genetic hazard. 
Clethodim technical did not induce gene mutation in microbial in vitro 
assays. A weak response in an in vitro assay for chromosome aberrations 
was not confirmed when clethodim was tested in an in vivo cytogenetics 
assay up to the maximally tolerated dose level, nor was the response 
observed in vitro using technical material of a higher purity. No 
evidence of unscheduled DNA synthesis was seen following in 
vitroexposure up to a dose level near the LD50 (1.5 g/kg). 
This evidence indicates that clethodim does not present a genetic 
hazard to intact animal systems.
    3. Reproductive and developmental toxicity. No reproductive 
toxicity was observed with clethodim technical at feeding levels up to 
2,500 ppm. Developmental toxicity was observed in 2 rodent species, but 
only at maternally toxic dose levels. Clethodim is therefore not 
considered a reproductive or developmental hazard. These studies 
indicate no unique toxicity to the developing fetus or young, growing 
animals.
    The developmental toxicity study conducted with clethodim technical 
in the rat resulted in a developmental and maternal NOAEL and lowest 
observed adverse effect level (LOAEL) of 100 and 350 mg/kg/day, 
respectively. The NOAEL and LOAEL for developmental toxicity were based 
on reductions in fetal body weight and increases in skeletal 
abnormalies.
    The developmental toxicity study conducted with clethodim technical 
in the rabbit resulted in a maternal toxicity NOAEL and LOAEL of 25 and 
100 mg/kg/day, respectively. Maternal toxicity was manifested as 
clinical signs of toxicity and reduced weight gain and food consumption 
duringtreatment. Developmental toxicity was not observed, and therefore 
the developmental toxicity NOAEL was 300 mg/kg/day, highest dose tested 
(HDT).
    The 2-generation reproduction study conducted with clethodim 
technical in the rat resulted in parental toxicity NOAEL and LOAEL of 
500 and 2,500 ppm, respectively, based on reductions in body weight in 
males, and decreased food consumption in both generations. The NOAEL 
for reproductive toxicity was 2,500 ppm, HDT.
    4. Subchronic toxicity. Subchronic oral toxicity studies conducted 
with clethodim technical in the rat and dog indicate a low level of 
toxicity. Effects observed at high dose levels consisted primarily of 
decreased body weights, increased liver size (increased weight and cell 
hypertrophy), and anemia (decreased erythrocyte counts, hemoglobin, or 
hematocrit) in rats and dogs. The NOAELs from these studies were 500 
ppm (ca. 25 mg/kg bw/day) in rats and 25 mg/kg bwt/day in dogs.
    A 21-day dermal toxicity study in rats with clethodim technical 
showed a LOAEL at 100 mg/kg bwt/day and a NOAEL at 1,000 mg/kg bwt/day, 
the highest dose tested.
    5. Chronic toxicity. Clethodim technical has been tested in chronic 
studies with dogs, rats and mice. In chronic studies compound-related 
effects noted at high doses included decreased body weight, increased 
liver size (liver weight and hypertrophy), and anemia (decreased 
hemoglobin, hematocrit, and erythrocyte count). Bone marrow hyperplasia 
was observed in dogs at the highest dose tested. No treatment-related 
increases in incidence of neoplasms were observed in any study. Chronic 
NOAELs were 200 ppm for an 18-month feeding study in mice and 500 ppm 
for a 24-month study in rats. EPA has established a reference dose 
(RfD) for clethodim of 0.01 mg/kg bwt/day, based on the NOAEL in the 1-
year oral dog study and an uncertainty factor of 100. Effects cited by 
EPA include, alterations in hematology and increased absolute and 
relative liver weights at 75 mg/kg/day.
    Clethodim technical is not a carcinogen. Studies with clethodim 
have shown that repeated high dose exposures produced signs of 
toxicity, but did not produce cancer in test animals. No oncogenic 
response was observed in a rat 2-year chronic feeding/carcinogenicity 
study or in a 18-month study on mice. The carcinogenicity 
classification of clethodim is ``E'' no evidence of carcinogenicity for 
humans.
    A 1-year feeding study with clethodim technical in the dog resulted 
in a systemic NOAEL of 1 mg/kg/day in both sexes and an LOAEL of 75 mg/
kg/day based on increased absolute and relative liver weights, and 
alteration and clinical chemistry.
    An 18-month mouse carcinogenicity feeding study showed clethodim 
technical to be non-carcinogenic to mice under the conditions of the 
study. The systemic NOAEL was 200 ppm (8 mg/kg bwt/day), and the 
systemic LOAEL was 1,000 ppm (50 mg/kg bwt/day) based on treatment-
related effects on survival, red cell mass, absolute and relative liver 
weights, and microscopic findings in liver and lung.
    A 2-year chronic toxicity/carcinogenicity feeding study performed 
in the rat found clethodim technical to be noncarcinogenic to rats 
under the conditions of the study. The systemic NOAEL was 500 ppm 
(approximately 19 mg/kg bwt/day), and the systemic LOAEL was 2,500 ppm 
(approximately 100 mg/kg bwt/day) based on the observed body weight 
gain, the increases in liver weights, and the presence of centrilobular 
hepatic hypertrophy.
    6. Animal metabolism. The absorption, tissue distribution, 
metabolism and excretion of ring- and side chain-labeled 
14C- clethodim were studied in rats after single oral doses 
of 468 or 4.4 mg/kg/ bwt, and after a single oral dose of 4.8 mg/kg bwt 
14C-clethodim following 14 daily oral doses at 4.5 mg/kg bwt 
of unlabelled material. For all dose groups, most 14C-
clethodim (88-96%) of the administered radiolabel was excreted in the 
urine and feces within 2 days after radiolabeled test material dosing, 
and 92-98% of the administered dose was excreted within seven days. The 
low dose groups eliminated clethodim slightly faster than the high dose 
group, and repeated exposure to clethodim prior to radiolabel dosing 
did not affect the rate of elimination or distribution of recovered 
radiolabel. There were no apparent sex differences with respect to 
elimination or distribution of metabolites. Seven days after dosing, 
tissue residues were generally low, accounting for no more than 0.3% of 
the dosed 14C. Radiocarbon concentrations in fat were the 
higher than in other tissues analyzed. Recovery in tissues over time 
indicates that the potential for bioaccumulation is minimal. The 
primary excretory metabolites were identified as clethodim sulfoxide 
(48-63%), clethodim S-methyl sulfoxide (6-12%), clethodim imine 
sulfoxide (7-10%), and clethodim 5-hydroxy sulfoxide (3-5%). Minor 
metabolites included clethodim oxazole sulfoxide (2-3%), clethodim 
trione sulfoxide (1%), clethodim (1%), clethodim 5-hydroxy sulfone 
(0.3-1%), clethodim sulfone (0.1-1%), aromatic sulfone (0.2-0.7%), and 
S-methyl sulfone (0-0.4%).
    7. Metabolite toxicology. Metabolism studies of clethodim in rats, 
crop plants, goats and hens demonstrate that the parent is very rapidly 
metabolized and, in animals, eliminated. Because parent and metabolites 
are not retained in the

[[Page 44628]]

body, the potential for acute toxicity from in situ formed metabolites 
is low. The potential for chronic toxicity is adequately tested by 
chronic exposure to the parent at the MTD and consequent chronic 
exposure to the internally formed metabolites. Two metabolites of 
clethodim, clethodim imine sulfone and clethodim 5-hydroxy sulfone, 
have been tested in toxicity screening studies to evaluate the 
potential impact of these metabolites on the toxicity of clethodim. In 
general, these metabolites were found to be less toxic than Clethodim 
Technical for acute and oral toxicity studies; reproduction and 
teratology screening studies; and several mutagenicity studies.
    8. Dermal Penetration. The dermal penetration of SELECT 2 EC 
Herbicide, the end-use product, was tested on unabraded, shaved skin of 
rats. Single doses of approximately 0.05, 0.5, and 5.0 mg of 
radiolabeled 14C-clethodim) SELECT 2 EC Herbicide, were 
applied topically to 10 cm2 sites on the dorsal trunk. Clethodim was 
found to be slowly absorbed through the skin in a time-dependent 
manner. The percent of dose absorbed increased with length of exposure 
and decreased with increasing dose. Ten-hour absorption rates ranged 
from 7.5% to 30.0%. Most of the absorbed material was found in the 
urine and carcass, and most of the unabsorbed material was found in the 
skin scrubbings indicating that material was still on the skin surface.
    9. Endocrine disruption. No special studies to investigate the 
potential for estrogenic or other endocrine effects of clethodim have 
been performed. However, as summarized above, a large and detailed 
toxicology data base exists for the compound including studies 
acceptable to the Agency in all required categories. These studies 
include acute, sub-chronic, chronic, developmental, and reproductive 
toxicology studies including detailed histology and histopathology of 
numerous tissues, including endocrine organs, following repeated or 
long term exposure. These studies are considered capable of revealing 
endocrine effects, and the results of all of these studies show no 
evidence of any endocrine-mediated effects and no pathology of the 
endocrine organs. Consequently, it is concluded that clethodim does not 
possess estrogenic or endocrine disrupting properties.

C. Aggregate Exposure

    1. Dietary exposure. EPA has established a RfD for clethodim of 
0.01 mg/kg bwt/day, based on the NOAEL in the 1-year oral dog study and 
an uncertainty factor of 100. Effects cited by EPA include, alterations 
in hematology and increased absolute and relative liver weights at 75 
mg/kg/day. Toxic endpoints of concern have not been identified for 
acute or short-term exposures by any route, or chronic endpoints of 
concern by any route other than oral. Therefore, only aggregate chronic 
dietary risk analyses are required.
    i. Food. Chronic dietary exposure to clethodim residues was 
calculated for established and pending uses of clethodim for the U.S. 
population and 26 population subgroups using anticipated residues 
(average residues from field residue studies) and accounting for the 
percent of the crop treated.
    ii. Drinking water. Since clethodim is applied outdoors 
postemergence to growing agricultural crops, the potential exists for 
clethodim and/or its metabolites to reach ground or surface water that 
may be used for drinking water. To model very conservative estimates of 
the potential concentrations of clethodim and its sulfoxide metabolite 
in drinking water, the Agency used screening concentration in ground 
water (SCI-GROW), and generic expected environmental concentration 
(GENEEC) for surface water. The sum of the parent and metabolite 
estimated concentrations in surface water greatly exceeded those in 
groundwater. Dividing the GENEEC derived 56-day average concentration 
by three gives 10 micrograms per liter (ppb) as the Agency's worse case 
estimate for drinking water contamination [Federal Register 63(67): 
1701-8 (April 8, 1998). Using standard assumptions about body weight 
and water consumption, the chronic exposure from this drinking water 
would be 0.00029 and 0.001 mg/kg bwt/day for adults and children, 
respectively; 10% of the RfD for children. Based on this worse case 
analysis, the contribution of water to the chronic dietary risk exceeds 
food, but is still acceptable.
    2. Non-dietary exposure. Clethodim is currently registered for use 
as a broadcast application on winter dormant perennial turf to control 
annual grasses. It is conceivable that this outdoor uses could result 
in acute or short- and/or intermediate- term residential exposure. 
Under current EPA criteria, the registered and proposed uses of 
clethodim would not constitute a chronic residential exposure scenario. 
Because toxic endpoints of concern have not been identified for short- 
or intermediate-term exposure, these risk analyses are not necessary.

D. Cumulative Effects

    Section 408(b)(2)(D)(v) requires that the Agency must consider 
``available information'' concerning the cumulative effects of a 
particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.'' Available information in this context 
include not only toxicity, chemistry, and exposure data, but also 
scientific policies and methodologies for understanding common 
mechanisms of toxicity and conducting cumulative risk assessments. For 
most pesticides, although the Agency has some information in its files 
that may turn out to be helpful in eventually determining whether a 
pesticide shares a common mechanism of toxicity with any other 
substances, EPA does not at this time have the methodologies to resolve 
the complex scientific issues concerning common mechanism of toxicity 
in a meaningful way.
    There are other pesticidal compounds that are structurally related 
to clethodim including sethoxydim, cycloxydim, and tralkoxydim. 
Analytical methods convert some of these herbicides and their 
metabolites to common moieties. Plant and animal metabolism data 
demonstrates that no common metabolites are formed. In consideration of 
potential cumulative effects of clethodim and other substances that may 
have a common mechanism of toxicity, there are currently no available 
data or other reliable information indicating that any toxic effects 
produced by clethodim would be cumulative with those of other chemical 
compounds. Thus, only the potential risks of clethodim have been 
considered in this assessment of aggregate exposure and effects.
    Valent will submit information for EPA to consider concerning 
potential cumulative effects of clethodim consistent with the schedule 
established by EPA at 62 Federal Register 42020 (August 4, 1997) and 
other subsequent EPA publications pursuant to the Food Quality 
Protection Act (FQPA).

E. Safety Determination

    An acute dietary endpoint was not identified. Thus, the risk from 
acute aggregate dietary exposure to clethodim is considered to be 
negligible. Aggregate chronic dietary exposure to various sub-
populations of children and adults demonstrate acceptable risk. 
Aggregate chronic exposures to clethodim for all population subgroups 
occupy considerably less than 100% of the RfD. It should be noted that 
the bulk of the calculated aggregate chronic exposures consist of very 
conservatively estimated

[[Page 44629]]

concentrations of clethodim and its sulfoxide metabolite in drinking 
water. Because there are no identified short- or intermediate-term 
dermal toxic endpoints of concern, these risk analyses are not 
necessary.
    It can be concluded that there is a reasonable certainty that no 
harm will result to individuals in the U.S. population or in any sub-
group of the U.S. population, including infants and children, from 
aggregate chronic exposures to clethodim residues resulting from 
approved and pending uses.
    1. U.S. population. Using the dietary exposure assessment 
procedures described above for clethodim, calculated chronic dietary 
exposure -- taking into account percent of crop treated and using 
anticipated residues -- from existing and proposed uses of clethodim is 
minimal. The estimated chronic dietary exposure from food for the 
overall U.S. population and many non-child/infant subgroups is 0.000174 
to 0.000204 mg/kg bwt/day, 1.7 to 2.0% of the RfD. Addition of the 
small but worse case potential chronic exposure from drinking water 
(calculated above) increases exposure by 0.0003 mg/kg bwt/day and the 
maximum occupancy of the RfD from 2.0 per cent to 5.0%. Generally, the 
Agency has no cause for concern if total residue contribution is less 
than 100% of the RfD. It can be concluded that there is a reasonable 
certainty that no harm will result to the overall U.S. Population and 
many non-child/infant subgroups from aggregate, chronic exposure to 
clethodim residues.
    2. Infants and children. Safety Factor for Infants and Children: In 
assessing the potential for additional sensitivity of infants and 
children to residues of clethodim, FFDCA section 408 provides that EPA 
shall apply an additional margin of safety, up to ten-fold, for added 
protection for infants and children in the case of threshold effects 
unless EPA determines that a different margin of safety will be safe 
for infants and children.
    The toxicological data base for evaluating pre- and post-natal 
toxicity for clethodim is complete with respect to current data 
requirements. There are no special pre- or post-natal toxicity concerns 
for infants and children, based on the results of the rat and rabbit 
developmental toxicity studies or the 3-generation reproductive 
toxicity study in rats. Reliable data support use of the standard 100-
fold uncertainty factor and an additional uncertainty factor is not 
needed for clethodim to be further protective of infants and children.
    Chronic Exposure and Risk -- Infant and child sub-populations: 
Using the conservative exposure assumptions described above 
(anticipated residues and percent of crop treated), the percentage of 
the RfD that will be utilized by dietary (food only) exposure to 
residues of clethodim ranges from 0.7% for nursing infants (1 year 
old), up to 4.8 % for children (1-6 years). Adding the worse case 
potential incremental exposure to infants and children from clethodim 
in drinking water (0.001 mg/kg bwt/day) greatly increases the 
aggregate, chronic dietary exposure and the occupancy of the RfD by 
10.0 % to 14.8 % for Children (1-6 years). EPA generally has no concern 
for exposures below 100% of the RfD because the RfD represents the 
level at or below which daily aggregate dietary exposure over a 
lifetime will not pose appreciable risks to human health. It can be 
concluded that there is a reasonable certainty that no harm will result 
to infants and children from aggregate, chronic exposure to clethodim 
residues.

F. International Tolerances

    Although some have been proposed, there are no Canadian, Mexican, 
or Codex tolerances or maximum residue limits established for 
clethodim. There are no conflicts between this proposed action and 
international residue limits.
[FR Doc. 01-21447 Filed 8-23-01; 8:45 am]
BILLING CODE 6560-50-S