Document ID: EPA-HQ-OPP-2005-0535-0005
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-05-09T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF	

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: 03/07/2007. 

MEMORANDUM

SUBJECT:	Clethodim: Human Health Risk Assessment for Proposed Uses on
Herb Subgroup 19A, Leafy Greens Subgroup 4A, Sesame seed, Safflower
seed, Legume Vegetable Group 6, Hops, Asparagus, and Flax seed. PC Code:
121011, Petition Nos.: 4E6836, 5E6978, 4F6895, 5E6977, and 3E6555.  DP
Number: D323144.

		Regulatory Action: Registration Action New Section 3 Uses

		Risk Assessment Type: Single Chemical Aggregate

FROM:	Barry O’Keefe, Risk Assessor/Senior Biologist

		Registration Action Branch 3

		Health Effects Division (7509P)

			AND

		Linda Kutney, Chemist

		Mark Dow, Ph.D., Biologist

		Breann Hanson, Biologist

		Deborah Rate, Chemist

		Alternative Risk Integration Assessment (ARIA) Team

		Risk Integration Minor Use & Emergency Response Branch (RIMUERB)

		Registration Division (7505P)

THROUGH:	Paula Deschamp, Branch Chief

		Registration Action Branch 3

		Health Effects Division (7509P)

TO:	Barbara Madden, Team Leader

		Minor Use, Inerts and Emergency Response Branch (MUIERB) 

		Registration Division (RD) (7505P) 

The Interregional Research Project No. 4 (IR-4) submitted several
petitions for the establishment of permanent tolerances for the combined
residues of the herbicide clethodim. 

The petitioner, IR-4, on behalf of the state of Washington requested the
establishment of a tolerance for the combined residues of clethodim
[(E)-(±-2-[1-[[(3-chloro-2-propenyl)oxy]imino]propyl]-5-[2-(ethylthio)p
ropyl]-3-hydroxy-2-cyclohexen-1-one] and its metabolites containing the
2-cyclohexen-1-one moiety in or on hop, dried cones at 0.50 ppm
(5E6977).  

The petitioner, IR-4, on behalf of the states of Michigan, Washington,
Oklahoma, and Oregon requested the establishment of a tolerance for the
combined residues of clethodim and its metabolites containing the
2-cyclohexen-1-one moiety in or on asparagus at 2.0 ppm (5E6977).

The petitioner, IR-4, on behalf of the states of Arkansas, Florida,
Mississippi, New York, North Carolina, North Dakota, Oklahoma, Oregon,
South Dakota, Tennessee, Texas, and Washington and also Puerto Rico
requested the establishment of a tolerance for the combined residues of
clethodim and its metabolites containing the
5-(2-ethylthiopropyl)cyclohexen-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexen-3-one moieties and their
sulphoxides and sulphones, expressed as clethodim in or on the following
commodities: sesame, seed at 0.40 ppm; vegetable, legume, group 6 at 3.0
ppm; safflower, meal at 10.0 ppm; and safflower, seed at 5.0 ppm
(4F6895).

The petitioner, IR-4, on behalf of the states of Florida, Georgia, Texas
and California and also Puerto Rico requested the establishment of a
tolerance for the combined residues of clethodim and its metabolites
containing the 2-cyclohexen-1-one moiety in or on the leafy greens
subgroup 4A at 2.0 ppm and cilantro, leaves at 2.0 ppm (5E6978).  The
petitioner also requested the removal of established tolerances in or on
lettuce, leaf at 2.0 ppm and spinach at 2.0 ppm.

The petitioner, IR-4, on behalf of the states of California, Hawaii, and
Florida requested the establishment of a tolerance for the combined
residues of clethodim and its metabolites containing the
2-cyclohexen-1-one moiety in or on the herb subgroup 19A at 10.0 ppm
(4E6836).

The petitioner, IR-4, on behalf of the state of North Dakota requested
the establishment of a tolerance for the combined residues of clethodim
and its metabolites containing the 2-cyclohexen-1-one moiety in or on
flax seed at 0.5 ppm (3E6555).

A summary of the findings and an assessment of human risk resulting from
the registered and proposed tolerances for clethodim is provided in this
document.  The risk assessment was provided by Barry O’Keefe (RAB3),
the residue chemistry data review by Linda Kutney (RAB3) and Debra Rate
(ARIA), the dietary risk assessment by Breann Hanson (ARIA), the hazard
characterization by Steve Dapson (RAB3), and the
occupational/residential exposure assessment by Mark Dow (ARIA).

Table of Contents

  TOC \f  1.0	Executive Summary	  PAGEREF _Toc163010193 \h  4 

2.0	Ingredient Profile	  PAGEREF _Toc163010194 \h  9 

2.1	Summary of Registered/Proposed Uses	  PAGEREF _Toc163010195 \h  9 

3.0	Hazard Characterization/Assessment	  PAGEREF _Toc163010196 \h  12 

3.1	FQPA Considerations and Safety Factor for Infants and Children	 
PAGEREF _Toc163010197 \h  14 

3.2	Toxicity Endpoint Selection	  PAGEREF _Toc163010198 \h  14 

3.3	Endocrine disruption	  PAGEREF _Toc163010199 \h  16 

4.0	Dietary Exposure/Risk Characterization	  PAGEREF _Toc163010200 \h 
16 

4.1  Pesticide Metabolism and Environmental Degradation	  PAGEREF
_Toc163010201 \h  16 

4.1.1	Metabolism in Primary Crops	  PAGEREF _Toc163010202 \h  16 

4.1.2	Metabolism in Livestock	  PAGEREF _Toc163010203 \h  17 

4.1.3	Analytical Methodology	  PAGEREF _Toc163010204 \h  17 

4.1.4	Storage Stability Data	  PAGEREF _Toc163010205 \h  18 

4.1.5	Magnitude of the Residue in Plants	  PAGEREF _Toc163010206 \h  19 

4.1.6	Magnitude of the Residue in Processed Food/Feed	  PAGEREF
_Toc163010207 \h  25 

4.1.7	Magnitude of the Residue in Meat, Milk, Poultry, and Eggs	 
PAGEREF _Toc163010208 \h  27 

4.1.8	Confined and Field Accumulation in Rotational Crops	  PAGEREF
_Toc163010209 \h  32 

4.1.9	Drinking Water Residue Profile	  PAGEREF _Toc163010210 \h  32 

4.1.10	Proposed Tolerances	  PAGEREF _Toc163010211 \h  33 

4.2  Dietary Exposure and Risk	  PAGEREF _Toc163010212 \h  34 

4.2.1    Acute Dietary Exposure/Risk	  PAGEREF _Toc163010213 \h  34 

4.2.2    Chronic Dietary Exposure/Risk	  PAGEREF _Toc163010214 \h  35 

4.2.3    Cancer Dietary Risk	  PAGEREF _Toc163010215 \h  37 

5.0	Residential (Non-Occupational) Exposure/Risk Characterization	 
PAGEREF _Toc163010216 \h  38 

6.0	Aggregate Risk Assessments and Risk Characterization	  PAGEREF
_Toc163010217 \h  38 

7.0	Cumulative Risk Characterization/Assessment	  PAGEREF _Toc163010218
\h  38 

8.0	Occupational Exposure/Risk Pathway	  PAGEREF _Toc163010219 \h  39 

8.1	Short-/Intermediate-Term Handler Risk	  PAGEREF _Toc163010220 \h  39

8.2	Short-/Intermediate-Term Postapplication Risk	  PAGEREF
_Toc163010221 \h  42 

9.0	Data Needs and Label Requirements	  PAGEREF _Toc163010222 \h  44 

9.1	Residue Chemistry Data Needs and Label Requirements	  PAGEREF
_Toc163010223 \h  44 

9.2	Occupational Data Needs and Label Requirements	  PAGEREF
_Toc163010224 \h  45 

10.0	Tolerance Summary	  PAGEREF _Toc163010225 \h  45 

11.0	Subchronic and Chronic Toxicity Profile Table	  PAGEREF
_Toc163010226 \h  47 

 1.0	Executive Summary  TC \l1 "1.0	Executive Summary 

Clethodim (Select®) is a cyclohexenone post-emergence herbicide used
for control of a wide range of annual and perennial grass weeds in
numerous broad leaf crops.  Other chemicals with similar molecular
structure include sethoxydim, tralkoxydim and cycloxydim.  There are no
common degradates from these chemicals.  Also, EPA has not made a
determination regarding a common mechanism of toxicity for these
chemicals.  Therefore, this risk assessment is for clethodim only.

Clethodim products are currently registered for a variety of use sites
including agricultural crops, conifer trees (Christmas tree
farms/conifer nurseries), non-crop areas (railroads, highways, roads,
dividers, medians, pipelines, public utility lines, pumping stations,
transformer stations and substations, around airports, electric
utilities, commercial buildings, manufacturing plants, storage yards,
rail yards, fence lines, parkways, beneath greenhouse benches and around
golf courses), and greenhouse/ lathhouse/shadehouse ornamentals and
ornamental in outdoor settings such as nurseries, parks, roadside
plantings and landscapes.  There is no potential for residential
exposure from use of clethodim on these non-crop areas or ornamentals
settings

Permanent tolerances for residues of clethodim and its metabolites are
established (40 CFR §180.458) for various raw agricultural commodities
at levels ranging from 0.20 ppm to 20.0 ppm.  Permanent tolerances are
also established in/on the meat, meat byproducts, and fat of cattle,
goats, hogs, horses, poultry, and sheep at 0.2 ppm.

The Interregional Research Project No. 4 (IR-4) has submitted several
petitions for establishing tolerances for new uses of clethodim on hops,
asparagus, sesame, safflower, legume vegetable group 6, leafy greens
subgroup 4A, and herb subgroup 19A.  Additionally, for flax, IR-4 has
requested an increase in the application rate and a decrease in the
preharvest interval (PHI).  The Health Effects Division (HED) has
conducted an exposure assessment for these proposed additional and
changed uses.  HED has high confidence in the quality of the toxicology,
chemistry and exposure databases used to assess risk from clethodim. 

Hazard Assessment and Dose Response

Overall, the quality of the toxicology data base for clethodim is good
and the confidence in the hazard and dose-response assessments is high. 
Clethodim is of mild acute toxicity by oral, dermal, or inhalation
routes of exposure, but is a severe dermal irritant.  Clethodim is a
mild ocular irritant and is not a dermal sensitizer.  The toxicology
data base is complete and there are no data gaps. For more information
about the toxicology of clethodim, please see the 10/24/97 Hazard
Identification Assessment Review Committee (HIARC) Report.

Endpoints were identified for chronic dietary (chronic reference dose),
short-, intermediate- and long-term dermal and inhalation routes of
exposure, and corresponding risk assessments for these routes were
performed.  

An endpoint for acute dietary exposure was not identified since no
effects were observed in oral toxicity studies that could be
attributable to a single dose.  The chronic reference dose (RfD) of 0.01
mg/kg/day, is based on alterations in hematology and clinical chemistry
parameters and on increased absolute and relative liver weights observed
in a chronic dog study.  The chronic population-adjusted dose (cPAD) is
equal to the chronic RfD.

The endpoint chosen for short-term dermal and inhalation risk assessment
is based on a developmental toxicity study in rats in which maternal
effects (decreased body weight gain and clinical signs of toxicity) were
observed.  An oral NOAEL of 100 mg/kg/day was identified for short-term
dermal and inhalation risk assessment.  The endpoint chosen for
intermediate-term dermal and inhalation risk assessment is based on
increases in absolute and relative liver weights that were observed in a
subchronic oral toxicity study in dogs.  A NOAEL of 25 mg/kg/day was
identified for intermediate-term dermal and inhalation risk assessment

The HIARC determined that there is no evidence that clethodim is
neurotoxic.  The HIARC did not recommend that a developmental
neurotoxicity study be performed.  Mutagenicity studies for clethodim,
except for one positive in an in vitro mutagenicity chromosome
aberration study, were negative.  

Clethodim was negative for carcinogenicity in feeding studies in rats
and mice and was classified as "not likely" to be a human carcinogen. 
Dermal absorption is 30% based on a dermal absorption study in rats.

There is a complete toxicity database for clethodim and exposure data
are complete or are estimated based on data that reasonably account for
potential exposures.  There is no evidence of susceptibility following
in utero and/or postnatal exposure in the developmental toxicity studies
in rats or rabbits, and in the 2-generation rat reproduction study. 
There are no residual uncertainties concerning pre- and postnatal
toxicity and no neurotoxicity concerns.  The chronic dietary food
exposure assessment utilized tolerance level residues for most
commodities and incorporated average percent crop treated data for many
commodities.  Although partially refined, the assessments are
conservative and based on reliable data and will not underestimate
exposure/risk.  There is no potential for residential exposure.  Based
on these data and conclusions, the FQPA Safety Factor Committee
recommended that the FQPA safety factor be reduced to 1X for all
potential exposure scenarios to clethodim.  The dietary (food and
drinking water) exposure assessment will not underestimate the potential
exposure for infants, children, and/or women of childbearing age.  The
2002 FQPA policy supports this decision to reduce the safety factor.  We
have a complete database for toxicity and exposure, no evidence of
increased sensitivity, and no neurotoxicity concerns which support our
decision to reduce the FQPA factor to 1X.  The doses chosen are
adequately protective for infants and children.

Drinking Water Exposure Estimates

Surface and ground water contamination may occur from the sulfoxide and
sulfone degradates of clethodim, as well as from parent clethodim. 
However, the risk of water contamination is primarily associated with
clethodim sulfone and clethodim sulfoxide rather than parent clethodim
based on greater persistence and mobility for these degradates.  Parent
clethodim may move from the treated field to surface water or ground
water through run-off or leaching which occurs shortly after application
(e.g. rainfall).   Also, the sulphoxide and sulphone degradates may
migrate by runoff or leaching for longer periods of time since they are
more persistent.  All residues of clethodim (parent and degradates) are
very mobile in soil.  Tier 1 surface water concentrations for parent
clethodim and total toxic residues (parent + sulphoxide + sulphone) were
estimated using the FIRST (FQPA Index Reservoir Screening Tool) model. 
These drinking water estimates are based on a maximum application rate
of 0.5 lb ai/acre per year (2 applications).  The peak FIRST estimated
environmental concentration (EEC) for clethodim and it’s degradates,
sulphoxide and sulphone, in surface water is 38.9 ppb.  The chronic
FIRST EEC is 7.6 ppb.  Ground water sources were not included, as the
EECs for this water source are minimal in comparison to surface water.

Dietary Exposure Assessment

There was no appropriate endpoint for assessing acute dietary exposure;
therefore, no acute dietary risk assessment was performed.

A conservative chronic dietary exposure assessment was conducted for the
proposed and existing food uses and drinking water for clethodim.  This
partially refined chronic dietary exposure assessment was based on the
assumption of tolerance-level residues for most commodities with
existing and proposed tolerances and incorporated percent crop treated
information for the existing crops.  For all proposed crops 100% crop
treated (CT) was used.

The chronic dietary (food + drinking water) exposure to clethodim is
below HED’s level of concern for the general U.S. population and all
population subgroups.  The chronic dietary exposure utilized 29% cPAD
for the general U.S. population and 84% cPAD for children 1-2 years old,
the most highly exposed population subgroup. 

Aggregate Exposure Assessment

Based on the proposed Section 3 food crop uses, dietary aggregate
exposures (i.e. food plus drinking water) are anticipated.  There are no
residential use sites.  Consequently, only dietary (food plus drinking
water) exposures were aggregated for this assessment.  Estimates of
pesticide residues in drinking water (EECs) were incorporated directly
into the dietary exposure analysis to assess aggregate acute and chronic
risk.

Occupational Handler Exposure Assessment

Potential occupational exposure scenarios for handlers of clethodim
include mixing/loading liquids for groundboom and aerial applications,
and applying liquid formulations by groundboom and aerial application. 
Short- and intermediate-term dermal and inhalation exposure estimates
were calculated for these scenarios.  

No chemical specific data were available with which to assess potential
exposure to pesticide handlers.  Therefore, the estimates of exposure to
pesticide handlers are based upon surrogate study data available in the
PHED (v. 1.1, 1998).  

A MOE of 100 is adequate to protect occupational pesticide handlers from
short- or intermediate-term exposures to clethodim.  The proposed use
patterns do not exceed HED’s level of concern provided mixer/loaders
wear protective gloves as are required PPE on all labels considered
here.

Occupational Postapplication Exposure Assessment

Workers performing postapplication activities such as scouting,
irrigating, harvesting, etc. may receive dermal exposure to clethodim
residues.  Dermal MOEs calculated on the day of application which
represent the highest day of exposure were above 100, and therefore don
not exceed HED’s level of concern.

As was indicated in the 21 February 2002 risk assessment, the interim
Worker Protection Standard (WPS) restricted entry interval for a
compound classified in Acute Toxicity Category I (primary dermal
irritation in this case) is 48 hours (see 40 CFR § 156.208 (c) (2). 
The labels provided for review list REIs of 24 hours.  It is suggested
that RD confirms or corrects these labels to reflect the proper REI of
48 hours.

Recommendations

Based on an effort to harmonize tolerances with Codex MRLs, the
tolerance requests for clethodim should be defined as the combined
residues of clethodim and its metabolites containing the
5-(2-ethylthiopropyl)cyclohexene-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones (PP# 4F4340, DP Num: 203378, J. Morales,
31/JAN/1995).  The following include recommendations and deficiencies
for the following petitions.

1.  PP#3E6555:  A revised Section F for the commodity flax, seed must be
submitted redefining clethodim as the combined residues of clethodim and
its metabolites containing the 5-(2-ethylthiopropyl)cyclohexene-3-one
and 5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones, and changing the proposed tolerance from 0.5
ppm to 0.6 ppm as recommended.  The label must be changed to match the
proposed use pattern of Section B.  Additionally, the established
tolerance for flax, meal at 1.0 ppm must be removed.

2.  PP#5E6977:  A revised Section F must be submitted to the Agency
redefining clethodim as the combined residues of clethodim and its
metabolites containing the 5-(2-ethylthiopropyl)cyclohexene-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones for hops, dried cones and asparagus, and
changing the proposed tolerance to 1.7 ppm for asparagus.  The label
must be changed to match the proposed use patterns of Section B.

3.  PP#4E6836:  A revised Section F must be submitted to the Agency
redefining clethodim as the combined residues of clethodim and its
metabolites containing the 5-(2-ethylthiopropyl)cyclohexene-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones for the herb subgroup 19A.  The separate
tolerance request for cilantro leaves must be removed from the Section
F, as cilantro leaves are a member of the herb subgroup 19A.  The
proposed tolerance of 10 ppm must be changed to match the tolerance
recommended by ARIA of 12.0 ppm.  The label must be changed to match the
proposed use pattern of Section B.

4.  PP#5E6978:  A revised Section F must be submitted to the Agency
redefining clethodim as the combined residues of clethodim and its
metabolites containing the 5-(2-ethylthiopropyl)cyclohexene-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones for leafy greens subgroup 4A.  The label must
be changed to match the proposed use pattern of Section B.

5.  PP#4F6895:  A revised Section F for sesame seed must be submitted to
the Agency requesting a tolerance of 0.35 ppm to concur with the
recommended tolerance.  The petitioner must change this same Section F
to correct the commodity definition to crop group 6, vegetable, legume
(except soybean) and change the proposed tolerance to 3.5 ppm.  The
label must be changed to match the proposed use patterns of Section B
with the exception of crop group 6, vegetable legume (except soybean),
for which the PHI must be changed to 30 days for the group to match the
longest PHI submitted for dry pea; therefore, a revised Section B must
also be submitted to the Agency.  The petitioner must submit a revised
label to bring the usage pattern for safflower to match that of the
proposed use pattern of Section B and sunflower, from which a direct
translation of supporting data was used.  This includes increasing the
PHI from 14 to 70 days.  

6.  The labels must be revised to include the restriction “Do not
plant any crop for 30 days after application unless clethodim is
registered for use on that crop.”

7.  The petitioner must resubmit reference standards for both DME and
DME-OH to update expired samples which were previously submitted (June
1993).

  SEQ CHAPTER \h \r 1 Pending the receipt of standards, and receipt of
the revised Section Fs, Section Bs, and labels, the Agency recommends
establishing permanent tolerances for the combined residues of clethodim
and its metabolites containing the
5-(2-ethylthiopropyl)cyclohexene-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones, expressed as clethodim, in/on leafy greens,
subgroup 4A at 2.0 ppm; flax, seed at 0.6 ppm; hop, dried cones at 0.5
ppm; asparagus at 1.7 ppm; the herb subgroup 19A at 12.0 ppm; sesame,
seed at 0.35 ppm; the vegetable, legume, Crop Group 6 (except soybean)
at 3.5 ppm; safflower, meal at 10.0 ppm; and safflower, seed at 5.0 ppm.
 The tolerances for the individual crops of bean, dry, seed at 2.5 ppm,
lettuce, leaf at 2.0 ppm, and spinach at 2.0 ppm must be removed.  The
established tolerance for flax, meal at 1.0 ppm must be removed.

As was indicated in the 21 February 2002 risk assessment, the interim
Worker Protection Standard (WPS) restricted entry interval (REI) for a
compound classified in Acute Toxicity Category I (primary dermal
irritation in this case) is 48 hours (see 40 CFR § 156.208 (c) (2). 
The labels provided for review list REIs of 24 hours.  It is suggested
that RD confirms or corrects these labels to reflect the proper REI of
48 hours.

2.0	Ingredient Profile  TC \l1 "2.0	Ingredient Profile 

Clethodim is a member of the cyclohexenone class of herbicides.  Product
chemistry data for clethodim were previously submitted and have been
reviewed.  No deficiencies and no toxicological concerns for any
clethodim impurities were cited.  Details about the product chemistry
and the physical/chemical properties of clethodim are available in
“CLETHODIM: Report of the Hazard Identification Assessment Review
Committee.” J. Rowland. HED Document No. 121011. 10/24/97.

2.1	Summary of Registered/Proposed Uses  TC \l2 "2.1	Summary of
Registered/Proposed Uses 

The use pattern summary is taken from the Sections B of the IR-4
submissions for the various crop use sites.  There are several products
containing clethodim which are suggested for use on one or more of the
proposed crop use sites.  They are as follows:

Prism® Herbicide (EPA Reg. No. 59639 - 78) is an 12.6 % liquid
formulation which contains 0.94 lb active ingredient (ai) per gallon. 
Prism® has a 24 hour restricted entry interval (REI).  Applicators and
other handlers are required to wear cover-alls over short pants and
short-sleeved shirt, chemical resistant footwear plus socks, protective
eyewear, and chemical resistant gloves (such as barrier laminate or
Viton) and a chemical resistant apron when mixing and loading.

Select® Herbicide (EPA Reg. No. 59639 - 78) which, according to the
labels provided to RD, is the same as Prism® Herbicide.  The
formulation is the same.  However, in addition to the Personal
Protective Equipment (PPE) mentioned on the Prism® label, the Select®
label also includes chemical-resistant headgear for overhead spraying.

Select® 2 EC Herbicide (EPA Reg. No. 59639 - 3) is an emulsifiable
concentrate liquid formulation which contains 26.4 % ai (2.0 lb
ai/gallon).  Occupational pesticide handlers using Select® 2 EC must
wear a long-sleeved shirt, long pants, shoes plus socks, protective
eyewear and chemical resistant gloves such as barrier laminate or Viton.
 The REI is 24 hours.

V-10139 1.6 EC Herbicide (EPA Reg. No. 59639 - 133) is a liquid
formulation which contains 20.4 % ai (1.6 lb ai/gal) emulsifiable
concentrate.  Applicators and other occupational handlers of V-10139
herbicide must wear a long-sleeved shirt, long pants, shoes plus socks,
protective eyewear and chemical resistant gloves such as barrier
laminate or Viton.  The REI is 24 hours.  

The directions for use on the various crop sites are as follows:

Asparagus - Make 2 broadcast applications of Prism® herbicide at the
rate of 0.25 lb ai/A.  The application interval is 14 days.  It is
recommended that a crop oil concentrate be used at a rate of 1.0 % v/v
in the finished spray.  The spray should be delivered in 10 - 40 gallons
of spray/A.  There is a 1 day preharvest interval (PHI).  A maximum of
0.5 lb ai/A/season may be applied.  

Flax – IR-4 suggests use of either Prism® or Select® 2 EC.  Two
applications are suggested, each at the rate of 0.25 lb ai/A for a
maximum 0.50 lb ai/A/season.  Applications should be made in 5 - 40
gallons/A.  The application interval is 14 days and the PHI is 20 days. 

HED notes that draft labeling (i.e., different documentation than the
IR-4 section B) for Select® 2 EC indicates different rates of
application, i.e., 0.0625 - 0.125 lb ai/A.  In addition, the draft
labeling also indicates a 60 day PHI.  A revised section G was received
from IR-4 correcting these mistakes on the Select® 2 EC label.

Herbs – IR-4 suggests use of Prism® at the rate of 0.25 lb ai/A for
two applications.  An application interval is not specified.  There is a
maximum of 0.5 lb ai/A/season.  The PHI is 21 days.  Sprays should be
made in sufficient water to ensure thorough coverage but in a minimum of
20 gallons of spray/A.  Use of a crop oil adjuvent is suggested at a
rate of 1.0 % v/v of finished spray.  Ground application is specified.  

Hops - Make 2 broadcast applications of Prism® herbicide to the hop
yard floor at the rate of 0.25 lb ai/A.  The application interval is 14
days.  It is recommended that a crop oil concentrate be used at a rate
of 1.0 % v/v in the finished spray.  The spray should be delivered in 10
- 40 gallons of spray/A.  There is a 21 day preharvest interval (PHI). 
A maximum of 0.5 lb ai/A/season may be applied.  

Leafy green vegetables - Make one or two post emergence applications of
Prism® herbicide at a rate of 0.25 lb ai/A.  Use of a crop oil
concentrate at a rate of 1.0 % v/v in the finish spray is suggested. 
Applications should be made in 20 gallons of spray/A by ground
equipment.  The PHI is 14 days.  

Legume vegetables - Prism® herbicide is suggested for use on the legume
vegetables at a rate of 0.25 lb ai/A.  Two broadcast foliar applications
are recommended for a maximum of 0.5 lb ai/A/season.  The application
interval is 14 days and the PHI is 21 days.  

Safflower - Make one application of Prism® herbicide not to exceed 0.25
lb ai/A prior to flowering but no later than 70 days prior to harvest
(i.e., the PHI is 70 days).  

Sesame - Make broadcast foliar applications of Prism® herbicide at the
rate of 0.25 lb ai/A.  The application interval is 14 days and the PHI
is 14 days.  A maximum of 0.5 lb ai/A/season may be applied.  

See Table 1. for a summary of the proposed uses.

Table 1. Use Pattern Summary for Proposed Uses of Clethodim

Crop/Site	Asparagus, Flax, Herb Crop Group, Hops, Leafy green
vegetables, Legume vegetables, Safflower, Sesame

Formulation	Prism® Herbicide (Reg. No. 59639 - 79), 87. 4 % liquid
contains 0.94 lb ai/gal.

Select® Herbicide (Reg. No.59639 - 78), see Prism®

Select 2 EC Herbicide (Reg. No. 59639 - 3), 26.4 % liquid contains 2.0
lb ai/gal.

V-10139 1.6 EC Herbicide, (Reg. No. 59639 - 133), 20.4 % liquid contains
1.6 lb ai/gal

Pest	annual and perennial species of grasses

Max. application rate	0.25 lb ai/A

Maximum/season	0.5 lb ai/A/season for all crops except Safflower

Number of applications	Safflower - 1 application/season

Leafy green vegetables - 1 or 2 applications/season

All other crop sites - 2 applications/season

Application Interval	14 days

No interval specified for herbs

safflower only 1 application

Preharvest  Interval	Asparagus - 1 day

Flax - 20 days

Herbs, Hops and Legume Vegetables - 21 days

Leafy green vegetables and Sesame - 14 days

Safflower - 70 days

Restricted Entry Interval	24 hours is listed on the labels but should be
confirmed, and as such, be changed to 48 hours

Manufacturer	Valent U.S.A. Corporation

3.0	Hazard Characterization/Assessment  TC \l1 "3.0	Hazard
Characterization/Assessment 

A detailed hazard characterization is available in the following
references:

1. CLETHODIM: Report of the Hazard Identification Assessment Review
Committee. J. Rowland. HED Document No. 121011. 10/24/97.

2. CLETHODIM - Report of the FQPA Safety Factor Committee. B. Tarplee.
HED Document No. 014309. 08/31/00.

The Hazard Identification Assessment Review Committee (HIARC) met on
October 16, 1997 to evaluate the toxicology database for clethodim. 
Endpoints were identified for chronic dietary (chronic reference dose),
short-, intermediate- and long-term dermal and inhalation routes of
exposure.  There were no effects observed in oral toxicity studies
including developmental toxicity studies in rats or rabbits that could
be attributable to a single dose (exposure).  Therefore, a dose and an
endpoint were not selected for acute dietary exposures.  Additionally,
incidental oral endpoints were not chosen because such residential
exposures are not expected to occur.

Overall, the quality of the toxicology database for clethodim is good
and the confidence in the hazard and dose-response assessments is high. 
Clethodim is of mild acute toxicity by oral, dermal, or inhalation
routes of exposure, but is a severe dermal irritant.  Clethodim is a
mild ocular irritant and is not a dermal sensitizer.  

In chronic studies, clethodim depresses body weights and increases liver
weights in association with histopathological changes, without
exhibiting carcinogenicity.  In a long term feeding study (MRID
41030112) in mice at high dietary doses (450 mg/kg/day) decreases in
survival and decreases in hematological parameters were observed. 
Additionally, at both upper doses (150 and 450 mg/kg/day) decreases in
liver weights with centrilobular hypertrophy, bile duct pigmentation and
hyperplasia were observed.  In a 21-day dermal toxicity study in rats
(MRID 41030109), clethodim produced signs of systemic toxicity at the
limit dose (1000 mg/kg/day) in the form of anogenital discharge,
depression in food efficiency and body weight gains, and increased liver
weights.  In rats at the high dose (279 mg/kg/day) in the 2-year feeding
study (MRID  41030121), clethodim produced depressed body weights and
body weight gains, decreased food consumption, and increased liver
weights with centrilobular hypertrophy.  In a long term feeding study in
dogs (dose levels 70 and 300 mg/kg/day), clethodim produced increased
liver weights with hepatocellular enlargement and increased liver
related enzymes, along with alterations in hematology and clinical
chemistry parameters. 

No effects were noted for offspring in a rat reproduction study (MRIDs
41030119 and 41030120).  Clethodim was negative for developmental
effects in rabbits (MRID 41030115), but produced reductions in fetal
weight and increases in skeletal anomalies in the rat developmental
study (MRIDs 41030114, 41030116) at maternally toxic doses that were
higher than doses in the rabbit study.  Developmental studies (in rats
and rabbits) and reproductive toxicity studies (in rats) showed no
increased fetal sensitivity compared to maternal animals. 

The HIARC determined that the toxicology database is complete and there
are no data gaps, and that there is no evidence that clethodim is
neurotoxic.  HIARC did not recommend that a developmental neurotoxicity
study be performed.  Mutagenicity studies for clethodim, except for one
positive in vitro mutagenicity chromosome aberration study (at the limit
dose), were negative.

Clethodim was negative for carcinogenicity in feeding studies in rats
and mice and was classified as "not likely" to be a human carcinogen. 
Based on the negative carcinogenicity bioassays and negative
mutagenicity studies, no concerns were expressed for clethodim's
potential as a carcinogen.  

In a rat metabolism study, clethodim was readily absorbed. It was
excreted mainly in the urine.  It was rapidly and extensively
metabolized with clethodim sulphoxide (63%) as the predominant
metabolite.  Less than 1% was eliminated as the unchanged parent
compound.  Dermal absorption is 30% based on a dermal absorption study
in rats (MRID 41030202).  

As mentioned above, an endpoint for acute dietary exposure was not
identified since no effects were observed in oral toxicity studies that
could be attributable to a single dose.  The chronic reference dose
(RfD) of 0.01 mg/kg/day is based on alterations in hematology and
clinical chemistry parameters and increases in absolute and relative
liver weights observed in a chronic dog study.  The chronic
population-adjusted dose (cPAD) is equal to the chronic RfD.

The endpoint chosen for short-term dermal and inhalation risk assessment
is based on a developmental toxicity study in rats in which maternal
effects (decreased body weight gain and clinical signs of toxicity) were
observed.  An oral NOAEL of 100 mg/kg/day was identified for short-term
dermal and inhalation risk assessment.  The endpoint chosen for
intermediate-term dermal and inhalation risk assessment is based on
increases in absolute and relative liver weights that were observed in a
subchronic oral toxicity study in dogs.  A NOAEL of 25 mg/kg/day was
identified for intermediate-term dermal and inhalation risk assessment. 
 The endpoint chosen for long-term dermal and inhalation risk assessment
is the same as that selected for the chronic dietary exposure scenario,
i.e., from a chronic toxicity study in dogs in which alterations in
hematology and clinical chemistry patterns as well as increases in
absolute and relative liver weights were observed.  An oral NOAEL of 1
mg/kg/day was identified for long-term dermal and inhalation risk
assessment.

3.1	FQPA Considerations and Safety Factor for Infants and Children  TC
\l2 "3.1	FQPA Considerations and Safety Factor for Infants and Children 

There is a complete toxicity database for clethodim and exposure data
are complete or are estimated based on data that reasonably account for
potential exposures.  There is no evidence of susceptibility following
in utero and/or postnatal exposure in the developmental toxicity studies
in rats or rabbits, and in the 2-generation rat reproduction study. 
There are no residual uncertainties concerning pre- and postnatal
toxicity and no neurotoxicity concerns.  The chronic dietary food
exposure assessment utilized tolerance level residues for most
commodities and incorporated average percent crop treated data for many
commodities.  There is no potential for residential exposure.  Based on
these data and conclusions, the FQPA Safety Factor Committee recommended
that the FQPA safety factor be reduced to 1X for all potential exposure
scenarios to clethodim.  The dietary (food and drinking water) exposure
assessment will not underestimate the potential exposure for infants,
children, and/or women of childbearing age.  The 2002 FQPA policy
supports this decision to reduce the safety factor.  HED has a complete
database for toxicity and exposure, no evidence of increased
sensitivity, and no neurotoxicity concerns which support our decision to
reduce the FQPA factor to 1X.  The doses chosen as quantitative hazard
estimates are adequately protective for infants and children.

3.2	Toxicity Endpoint Selection  TC \l2 "3.2	Toxicity Endpoint Selection

Acute toxicity categories for clethodim are shown in Table 2.  Doses and
toxicological endpoints selected for various exposure scenarios are
summarized in Table 3.  The subchronic and chronic toxicity profile
table is shown in Appendix A.

Table 2	Acute Toxicity Profile - Clethodim 

Guideline No.	Study Type	MRID(s)	Results	Toxicity Category

870.1100	Acute oral [rat]	40974507

(1986)	LD50 = 

Males 1.63 g/kg Females 1.36 g/kg	III

870.1200	Acute dermal [rabbit]	40974510

(1986)	LD50 > 5.0 mg/kg	IV

870.1300	Acute inhalation [rat]	40974512

(1986)	LC50  3.9 mg/L	III

870.2400	Acute eye irritation [rabbit]	40974514

(1986)	mild ocular irritation	III

870.2500	Acute dermal irritation [rabbit]	40974516

(1986)	severe erythema observed at 72 hours	I 

870.2600	Skin sensitization [Guinea pig]	40974518

(1986)	Not a dermal sensitizer	N/A

Table 3. Toxicological Endpoints for Use in Risk Assessment 

Exposure

Scenario	

Dose Used in Risk Assessment, UF 	

FQPA SF* and Level of Concern (LOC) for Risk Assessment	

Study and Toxicological Effects

Acute Dietary

All Populations	

N/A	

N/A	

None Selected.  

There were no effects observed in oral toxicity studies including
developmental toxicity studies in rats and rabbits that could be
attributable to a single dose (exposure).  Therefore, a dose and
endpoint were not selected for this exposure scenario.

Chronic Dietary

All populations	

NOAEL= 1.0 mg/kg/day

UF = 100

Chronic RfD = 

0.01 mg/kg/day

	

FQPA  SF = 1

cPAD =chronic RfD

              FQPA SF

= 0.01 mg/kg/day	

Chronic Toxicity-Dog (1 year).  

Alterations in hematology and clinical chemistry parameters and
increased absolute and relative liver weights observed at the LOAEL of
75 mg/kg/day.

Short-Term Dermal (1 to 30 days)

	

Oral study Maternal NOAEL= 100 mg/kg/day

(dermal absorption rate = 30%)	

LOC for MOE = 100	

Developmental Toxicity-Rat.

LOAEL =  350 mg/kg/day based on decreased body weight gain and clinical
signs of toxicity (salivation). 

Intermediate-Term

Dermal (1 to 6 months)	

Oral study NOAEL= 

25 mg/kg/day

(dermal absorption rate = 30%)	

LOC for MOE = 100	

Subchronic Toxicity-Dog (90 days).

LOAEL = 75 mg/kg/day based on increased absolute and relative liver
weights with histopathology.

Long-Term Dermal (six months or more)	

Oral study NOAEL= 

1.0 mg/kg/day

(dermal absorption rate = 30%)	

LOC for MOE =100	

Chronic Toxicity-Dog (1 year).

LOAEL = 75 mg/kg/day based on alterations in hematology and clinical
chemistry parameters as well as increases in absolute and relative liver
weights.

Short-Term Inhalation (1 to 30 days)	

Oral study Maternal NOAEL= 100 mg/kg/day

(inhalation absorption rate = 100%)	

LOC for MOE =100	

Developmental-Rat

LOAEL = 350 mg/kg/day based on decreased body weight gain and clinical
signs of toxicity (salivation).

Intermediate-Term Inhalation (1 to 6 months)	

Oral study NOAEL = 25 mg/kg/day

(inhalation absorption rate = 100%)	

LOC for MOE = 100	

Subchronic Toxicity-Dog (90 days).

LOAEL = 75 mg/kg/day based on increased absolute and relative liver
weights with histopathology.

Long-Term Inhalation (six months or more)	

Oral study NOAEL= 

1.0 mg/kg/day

(inhalation absorption rate = 100%)	

LOC for MOE =100 	

Chronic Toxicity-Dog (1 year).

LOAEL = 75 mg/kg/day based on alterations in hematology and clinical
chemistry parameters as well as increases in absolute and relative liver
weights.

Cancer (oral, dermal, inhalation)	

N/A	

N/A	

Clethodim is classified as a "Not  Likely" carcinogen

UF = uncertainty factor, FQPA SF = Any additional safety factor retained
due to concerns unique to the FQPA, NOAEL = no observed adverse effect
level, LOAEL = lowest observed adverse effect level, PAD = population
adjusted dose (a = acute, c = chronic) RfD = reference dose, MOE =
margin of exposure, LOC = level of concern, NA = not applicable.  The
LOCs are based on standard uncertainty factors, i.e. interspecies
(animal to humans), 10x) and intra species (variation within a species,
10x).

3.3	Endocrine disruption  TC \l2 "3.3	Endocrine disruption 			

EPA is required under the FFDCA, as amended by FQPA, to develop a
screening program to determine whether certain substances (including all
pesticide active and other ingredients) "may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen,
or other such endocrine effects as the Administrator may designate." 
Following the recommendations of its Endocrine Disruptor Screening and
Testing Advisory Committee (EDSTAC), EPA determined that there was a
scientific basis for including, as part of the program, the androgen and
thyroid hormone systems, in addition to the estrogen hormone system. 
EPA also adopted EDSTAC’s recommendation that the Program include
evaluations of potential effects in wildlife.  For pesticide chemicals,
EPA will use FIFRA and, to the extent that effects in wildlife may help
determine whether a substance may have an effect in humans, FFDCA
authority to require the wildlife evaluations.  As the science develops
and resources allow, screening of additional hormone systems may be
added to the Endocrine Disruptor Screening Program (EDSP).

When the appropriate screening and/or testing protocols being considered
under the Agency’s EDSP have been developed, clethodim may be
subjected to additional screening and/or testing to better characterize
effects related to endocrine disruption.

4.0	Dietary Exposure/Risk Characterization  TC \l1 "4.0	Dietary
Exposure/Risk Characterization 

Reference: Clethodim.  Section 3 Registration for the Following Uses of
Clethodim on Flax, Seed; Hops, Dried Cones; Asparagus; Herb Subgroup
19A; Sesame, Seed; Legume Vegetable Group 6 (Except Soybean); Safflower,
Seed; Safflower, Meal; and Leafy Greens Subgroup 4A.  Summary of
Analytical Chemistry and Residue Data.  Petition Numbers: 3E6555,
5E6977, 4E6836, 4F6895, and 5E6978. DP Number 334913; D. Rate; 02/09/07.

4.1	Pesticide Metabolism and Environmental Degradation  TC \l2 "4.1 
Pesticide Metabolism and Environmental Degradation 

4.1.1	Metabolism in Primary Crops  TC \l3 "4.1.1	Metabolism in Primary
Crops 

PP#9F3743, MRID Nos. 41030137, 41030138, M. Nelson, 12/MAR/1990

Metabolism studies for clethodim in/on carrots, soybeans, and cotton
have been conducted and previously reviewed by HED.  The available
metabolism studies on soybean, cotton, and carrots included soybean
foliage, cotton foliage, and carrot leaves.  The metabolism in these
crops is similar.  HED previously concluded that additional metabolism
data may be required for future petitions on crops other than root crops
and oil seed crops.  However, metabolism data for soybean foliage,
cotton foliage, and carrot leaves can support the proposed uses for the
requested RACs in these petitions.  The residues of concern are
clethodim and its metabolites containing the 5-(2-ethylthiopropyl)
cyclohexene-3-one and 5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one
moieties and their sulphoxides and sulphones.  A revised Section F is
required in order to correct the residue definition on the submitted
Section F for hop, dried cones and asparagus i.e. petition # 5E6977.

4.1.2	Metabolism in Livestock  TC \l3 "4.1.2	Metabolism in Livestock 

PP#9F3743, MRID Nos. 41030137, 41030138, M. Nelson, 12/MAR/1990

Metabolism studies of [propyl-1-14C]-clethodim in a lactating goat and
laying hens have been previously reviewed.  The nature of the residue in
ruminants and poultry is adequately understood for the purposes of the
subject petitions.  HED previously concluded that the residues of
concern are clethodim and its metabolites containing the
2-cyclohexen-1-one moiety.  Of the submitted petitions, only safflower
(meal) is a livestock feed commodity.

4.1.3	Analytical Methodology  TC \l3 "4.1.3	Analytical Methodology 

Enforcement Method for Plants

PP#9F3743, DP Number 194694, F. Griffith, Jr., 28/SEP/1993

Adequate methodology is available for enforcement of the proposed
tolerances through the use of FDA Multiresidue Methods.  The analytical
method used to assay clethodim residues in/on the requested RACs was
RM-26B-3 (a modification of RM-26B-2) or RE 45601 (also adapted from
Valent method RM-26B), which was validated for the analyses of residues
of clethodim sulfoxide and its metabolite (5-hydroxy clethodim sulfone)
in/on green onions, leaf lettuce, and cabbage.  Briefly, samples were
extracted with methanol and then partitioned with dichloromethane. 
After evaporation, the samples were oxidized with hydrogen peroxide,
methylated with acidic methanol and then cleaned up on a silica gel 60
column and eluted with a hexane/acetone/methanol mixture.  Finally, the
samples were analyzed for combined clethodim residues (dimethylester
sulfone (DME) and 5-hydroxy dimethylester sulfone (DME-OH)) by gas
chromatography with flame photometric detection in the sulfur mode
(GC/FPD-S).  In the analytical results, DME and DME-OH were reported as
clethodim equivalents.  Only one crop, hops, dried cones, had residues
below the limit of quantitation (LOQ) (<0.50 ppm) for combined total
residues of clethodim (DME and DME-OH).  The concurrent recoveries of
clethodim (DME and DME-OH) for the submitted trials were generally
within the accepted range of 70-120%.  An exception was the concurrent
recovery of DME-OH in succulent pea at 62%.  There is no reason to
believe that the residues of clethodim were unstable, or that the
analytical method was not reliable under the conditions of these
studies.  The recoveries of clethodim residues in each matrix will not
have an impact on the recommendations of this action.

Analytical Methods - Livestock

Analytical Method RM-26B-3 (a modification of RM-26B-2) has been
successfully validated for use with livestock commodities and has been
submitted to the FDA for publication in PAM II.

Multiresidue Methodology

PP#9F3743, MRID Nos. 41030137, 41030138, M. Nelson, 12/MAR/1990

The petitioner has previously submitted data (1991; MRID No. 43166406,
and 1992; MRID No. 43166407) describing the testing of clethodim and its
metabolites through FDA Multiresidue Methods.  These data, which have
been forwarded to FDA for review indicate that adequate recoveries of
clethodim, clethodim sulphoxide, and 5-OH clethodim sulphone have been
obtained under FDA’s multiresidue protocols.

4.1.4	Storage Stability Data  TC \l3 "4.1.4	Storage Stability Data 

45858501-01.der, L.Kutney, 09/NOV/2006

46258101.der, L. Kutney, 08/NOV/2006

46258102.der, L. Kutney, 02/NOV/2006

46434603.der, L. Kutney, 30/OCT/2006

46434606.der, L. Kutney, 01/NOV/2006

46434608.der, L. Kutney, 07/NOV/2006

46434609.der, L. Kutney, 31/OCT/2006

46434607.der, L. Kutney, 01/NOV/2006

46434605-01.der, L. Kutney, 07/NOV/2006

46434602.der, L. Kutney, 01/NOV/2006

46434601.der, L. Kutney, 07/NOV/2006

The storage stability of clethodim in the requested RACs is summarized
in Table 4.  In each matrix, clethodim has been demonstrated to be
stable over the period of time the study samples were harvested and
analyzed.  There is no reason to believe that the residues of clethodim
were unstable under the conditions of these studies or that storage
stability will have any impact on the recommendations of this action.



TABLE 4.  Summary of Storage Conditions.

Matrix (RAC or Extract)	Storage Temp. ((C)	Actual Storage Duration

(days)	Storage Stability Recoveries (%)	Interval of Demonstrated

Storage Stability  (days)

	DME	DME-OH

	Vegetable, Leafy Greens Crop Subgroup 4A

 Lettuce (Head) (1997)	-25 to -15	748	Not

Conducted	98 - 112	732

Lettuce (Head) (2000)	-29 to -10	174	79-122	70-118	328

Flax Seed

Flax Seed	-21 ± 7	153	64 - 89	82 - 106	195 - 201

Herb Crop Subgroup 19A

Fresh basil leaves	-21 ± 7	406 (13.5 months))	75 – 88	93	385 (12.8
months)

Dry basil leaves	-21 ± 7	366 (12.2 months)	61 – 94	80 – 100	360 (12
months)

Fresh chive leaves	-21 ± 7	418	84	91	418

Dried chive leaves	-21 ± 7	369	76	86	374

Dried Hop Cones

Dried hop cones	< -21	319	78 - 86	81 - 86	336

Asparagus

Asparagus Spears	-21 ± 7	796 - 914	96	89	868 - 874

Sesame Seed

Sesame Seed	<0	692	74	76	674

Vegetable, Legume Crop Group 6 (except soybean)

Snap beans	<0	193	73	77	195-199

Dry Pea	-21 ± 7 	307	87-128	92-124	311

Lima bean	-21 ± 7	244	79-105	64-108	247-273

Succulent Pea	-21 ± 7	459	66 (80 adjusted)	58 (78 adjusted)	489

4.1.5	Magnitude of the Residue in Plants  TC \l3 "4.1.5	Magnitude of the
Residue in Plants 

45858501-01.der, L.Kutney, 09/NOV/2006

46258101.der, L. Kutney, 08/NOV/2006

46258102.der, L. Kutney, 02/NOV/2006

46434603.der, L. Kutney, 30/OCT/2006

46434606.der, L. Kutney, 01/NOV/2006

46434608.der, L. Kutney, 07/NOV/2006

46434609.der, L. Kutney, 31/OCT/2006

46434607.der, L. Kutney, 01/NOV/2006

46434605-01.der, L. Kutney, 07/NOV/2006

46434602.der, L. Kutney, 01/NOV/2006

46434601.der, L. Kutney, 07/NOV/2006

Field data were conducted at application rates on the proposed labels,
and with adequate geographic representation; therefore, the data reflect
the appropriate use patterns.  HED has confidence in these data to
support the proposed tolerances, and these data provide suitable inputs
for dietary risk analyses. Table 5 summarizes the residues of clethodim
on the RACs requested with these petitions from the submitted crop field
trials. 

The petitioner has requested a tolerance for safflower, meal at 10 ppm
and safflower, seed at 5.0 ppm based on already established tolerances
on sunflower, meal and sunflower, seed.  Due to the similarity of the
two crops, the Agency is willing to give a direct translation of the
sunflower tolerances to the requests for tolerances in/or on safflower
commodities.  This translation of tolerance also includes the
translation of usage patterns.  The petitioner must submit a revised
label for the use of safflower to match that of sunflower.  If the
petitioner would like to have lower tolerances or different use
patterns, data supporting the lower tolerances and use patterns would
need to be submitted to the Agency.

Table 5.  Summary of Residues from the Crop Field Trials with Clethodim.

Crop Matrix	Total Applic. Rate

(lb ai/A)	PHI (days)	Residues (ppm)

	Mean	Std. Dev.	HAFT	Min.	Max.

Flax (proposed use = 0.50 lb ai/A total application rate, 12-15-day PHI)

Flax Seed	0.52	12-18	0.29	0.08	0.38	0.18	0.41

Herb Crop Subgroup 19A (proposed use = 0.50 lb ai/A total application
rate, 20-22 day PHI)

Basil, fresh	0.48	20-21	1.27	0.07	1.27	0.92	1.32

Basil, dried	0.48	20-21	---	---	---	6.32	6.32

Chives, fresh	0.48	20-22	0.81	0.72	1.90	0.24	2.16

Chives, dried	0.48	20	0.24	0	0.24	0.24	0.24

Hop, Dried Cones (proposed use = 0.50  lb ai/A total application rate,
20-21 day PHI)

Hops, Dried Cones	0.50	20-21	<0.50	0	<0.50	<0.50	<0.50

Asparagus (proposed use = 0.50  lb ai/A total application rate, 1 day
PHI)

Asparagus Spears	0.50	1	0.66	0.18	0.86	0.37	0.99

Sesame (proposed use = 0.50  lb ai/A total application rate, 13-15 day
PHI)

Sesame seed	0.50	13-15	0.23	0.032	0.23	0.19	0.28

Crop Subgroup 4A (proposed use = 0.50  lb ai/A total application rate,
13-15 day PHI)

Lettuce with wrapper leaves intact	0.50	13-15	<0.30	<0.11	<0.48	<0.22
<0.56

Lettuce with wrapper leaves removed	0.50	13-15	<0.27	<0.06	<0.34	<0.18
<0.34

Crop Group 6 (proposed use = 0.50  lb ai/A total application rate, 13-15
day PHI)

Snap beans	0.50	20-22	0.25	0.11	0.44	<0.18	0.46

Dry pea	0.50	29 – 31	0.60	0.36	1.16	<0.18	1.24

Lima bean	0.50	20 - 22	0.41	0.16	0.62	<0.18	0.65

Shelled pea	0.50	16-21	1.76	0.43	2.32	1.24	2.55

Edible-podded pea	0.50	20-22	1.30	0.46	1.74	<0.58	1.84

Flax, Seed

A tolerance currently exists for flax, seed and flax, meal.  The
petitioner previously submitted field trial data to support a tolerance
on flax, seed with an Agency recommended use pattern of one
post-emergent application at a rate of 0.08 lb ai/A with a 75 day PHI
(PP# 0E06202, DP Num: 271248, M. Xue, 14/JUN/2001).  However, no
processing data were submitted for flax.  In the absence of processing
data, data from canola was translated to flax to fulfill the data
requirements (PP# 0E006202, DP Num: 271248, M. Xue, 14/JUN/2001).  A
tolerance for flax, meal at 1.0 ppm was established for flax based on
this translated canola data.  To remove this tolerance or decrease this
tolerance on flax, meal, the petitioner needed to submit flax processing
studies.  To support the new use pattern of clethodim on flax, seed,  
SEQ CHAPTER \h \r 1 IR-4 has submitted field trial residue data for
clethodim on flax (PP# 3E6555).  Six field trials were conducted in the
2000 growing season in North Dakota (3 trials, EPA Regions 5 and 7) and
South Dakota (3 trials, EPA Region 5).  All field trial sites consisted
of one untreated control plot and one treated plot.  Two broadcast spray
applications of clethodim (Prism® 0.94 EC) were applied at ~ 0.25 lb
ai/A (~ 0.50 lb ai/A per season) with 13-14 days between applications,
and then harvested with a preharvest interval of 12-18 days.  Field
treated samples of flax seeds were stored up to 153 days.  

The field trials were acceptable and adequately supported.  However,
using the MRL calculator a tolerance of 0.6 ppm is recommended for the
commodity flax seed.  The calculated tolerance of 0.6 ppm is different
from the tolerance level (0.5 ppm) proposed by the petitioner.  A
revised Section F is required.

Herb Crop Subgroup 19A

To support the use of clethodim on the Herb Crop Subgroup 19A, crop
field trial studies were submitted for the representative crops, basil
and chives (PP# 4E6836).  The studies provide residues for both fresh
and dried samples of each RAC.  

Basil

  SEQ CHAPTER \h \r 1 IR-4 has submitted crop field trial data for
clethodim on basil (PP# 4E6836).  The submitted data were obtained from
field trials conducted in New York, New Jersey, and California (EPA
Regions 1, 2, and 10, respectively), one trial at each site.  All field
trial sites consisted of one untreated control plot and one treated plot
except for the California site (05759-CA*42), which had two control and
two treated plots for collection of fresh and dry basil.  At each trial
location, clethodim was foliarly applied as Prism® 0.94 EC, containing
12.6% clethodim.  This formulation was applied 2 times at the
application rate of ~ 0.25 lb ai/A (0.50 lb ai/A per season) with 13-15
days between applications.  

Chives

  SEQ CHAPTER \h \r 1 IR-4 has submitted crop field trial data for
clethodim on chives (PP# 4E6836).  The submitted data were obtained from
field trials conducted in New Jersey (1 trial) and California (3 trials)
(EPA Regions 2, and 10, respectively) during the 1997 growing season. 
All field trial sites consisted of one untreated (control) plot and one
treated plot except for the California site, 06246-CA*39, which had two
control and two treated plots for fresh and dry samples.  At each trial
location, clethodim was foliarly applied as Prism® 0.94 EC, containing
12.6% clethodim.  This formulation was applied two times at
approximately 0.25 lb ai/A (~0.50 lb ai/A per season) with 14-16 days
between applications.  

Since a tolerance for the Herb Crop Subgroup 19A is sought and not
individual tolerances, HED & ARIA recommend for a conservative tolerance
of 12.0 ppm to cover all categories (fresh and dried) of this crop
group.  This tolerance is based on the drying factor of 9 (e-mail
communication, B. Schneider, 10/JAN/2007) for basil multiplied by the
maximum residue reported in the fresh basil trials, rounded up to the
nearest whole number (9 X 1.27 = 11.43).  A revised Section F must be
submitted by the petitioner changing the requested tolerance of 10.0 ppm
to 12.0 ppm.

Hops

To support the use of clethodim on hops,   SEQ CHAPTER \h \r 1 IR-4 has
submitted field trial data for clethodim on hops (PP#5E6977).  Three
field trials were conducted in   SEQ CHAPTER \h \r 1 Idaho (1 trial, EPA
Region 11), Washington (1 trial, EPA Region 11) and Oregon (1 trial, EPA
Region 12) during the 2001 growing season.  All field trial sites
consisted of one untreated control plot and one treated plot.  Two
post-emergence spray applications of clethodim (Prism® 0.94 EC
herbicide) were made to both sides of the hop row on the yard floor at
0.25 lb ai/A (0.50 lb ai/A per season) with 7-14 days between
applications.  Hops were harvested at pre-harvest intervals (PHIs) of
20-21 days, dried within a day of harvest and stored frozen until
analysis for up to 319 days from collection to analysis. 

It was not necessary to use the MRL Calculator on this crop since all of
the residues were at or below the LOQ.  HED & ARIA recommend for a
tolerance of 0.5 ppm (LOQ) for hop, dried cones.

Asparagus

To support the use of clethodim on asparagus,   SEQ CHAPTER \h \r 1 IR-4
has submitted field trial data for clethodim on asparagus (PP#5E6977). 
Seven field trials were conducted in the 1997 season, from New Jersey (1
trial, EPA Region 2), Michigan (2 trials, EPA Region 5), Washington (1
trial, EPA Region 11) and California (3 trials, EPA Region 10).  All
field trial sites consisted of one untreated control plot and one
treated plot.  Two broadcast applications of clethodim were performed at
0.25 lb ai/A (0.50 lb ai/A per season), with 13-14 days between
applications.  Asparagus spears were harvested at pre-harvest intervals
of 1, 2 and 3 days and stored frozen until analysis. 

Using the supplied residue data and the MRL Calculator, a tolerance
level of 1.7 ppm is recommended for the commodity asparagus.  The MRL
calculations can be found in the appendix of the residue chemistry
summary document for each of the PHIs (1,2, or 3 days) tested in the
study.  The 2 day PHI gave the highest recommended tolerance at 1.7 ppm.
 HED & ARIA believe the most conservative risk estimate will be based on
using the highest tolerance recommendation, even though the requested
PHI is 1 day.  The petitioner must submit a revised Section F to the
Agency changing the proposed tolerance from 2.0 ppm to 1.7 ppm.

Sesame

To support the use of clethodim on sesame, IR-4 has submitted field
trial data for clethodim on sesame (PP#4F6895).  Four field trials were
conducted in Texas (EPA Region 6) during the 2000 growing season.  The
number and locations of field trials are in accordance with OPPTS
Guideline 860.1500.  Clethodim was applied twice foliarly at 0.25 lb
ai/A to sesame, at 15-day intervals, using the formulation Prism® 0.94
EC containing 12.6% clethodim.  The test substance was mixed with water
and a crop oil concentrate (1% v/v).  Sesame stalks were harvested 13-15
days following the last application.  

Using the supplied residue data and the MRL Calculator, a tolerance
level of 0.35 ppm is recommended for the commodity sesame, seed.  The
MRL calculations can be found in the appendix of the residue chemistry
summary document.  The petitioner must submit a revised Section F to
change the requested tolerance of 0.30 ppm to 0.35 ppm.  

Vegetable, Leafy Greens Crop Subgroup 4A

Tolerances for spinach and leaf lettuce were previously established at
2.0 ppm.

Lettuce, Head

IR-4 has submitted field trial data for clethodim on lettuce (head)
(PP#5E6978).  Three field trials were conducted in Florida, Ohio and New
York (EPA Regions 1, 3, and 5, respectively) during the 1997 growing
season.  Also, five California trials (EPA Region 10) and one Oregon
trial (EPA Region 12) were conducted during the 2000 growing season. 
The number and locations of field trials are in accordance with OPPTS
Guideline 860.1500.  At each trial location, Prism® 0.94 EC, a 12.6%
emulsifiable-concentrate (EC) formulation of clethodim, was foliarly
applied to lettuce twice at approximately 0.25 lb ai/A (0.50 lb ai/A per
season) with 13 to 15 days between applications.  The test substance was
mixed with water and a crop oil concentrate (1% v/v).  Lettuce with and
without wrapper leaves was harvested 13 to 15 days following the last
application.

Using the supplied residue data and the MRL Calculator, a tolerance
level of 0.80 ppm is recommended for the commodity head lettuce.  The
MRL calculations can be found in the appendix of the residue chemistry
summary document.  Based on the previously established tolerances on
members of the Crop Subgroup 4A, spinach and leaf lettuce, of 2.0 ppm
and the data submitted for lettuce, head (0.80 ppm), HED & ARIA
recommend that a tolerance of 2.0 ppm be established for the vegetable,
leafy greens Crop Subgroup 4A.

Crop Group 6 (Legume Vegetables)

To support the use of clethodim on Crop Group 6 (legume vegetables,
except soybean) RACs, crop field trial studies were submitted for the
representative crops: snap beans, dry pea, lima bean and succulent pea
(PP#4F6895).  A tolerance for dry beans has previously been established
at 2.5 ppm.

Snap Beans

IR-4 has submitted field trial data for clethodim on snap beans
(PP#4F6895).  Eight field trials were conducted in New York (EPA Region
1), North Carolina (EPA Region 2), Florida (EPA Region 3), Michigan (EPA
Region 5), Wisconsin (EPA Region 5), California (EPA Region 10),
Washington (EPA Region 11) and Ohio (EPA Region 5) during the 2001
growing season, one trial was conducted in each state.  The number and
locations of field trials are in accordance with OPPTS Guideline
860.1500 for crop group tolerances.  At each trial location, Prism®
0.94 EC, a 12.6% emulsifiable-concentrate formulation of clethodim, was
foliarly applied twice at approximately 0.25 lb ai/A (0.50 lb ai/A per
season).  At the New York, North Carolina and Ohio trials, three
applications were made, for a total of 0.75 lb ai/A.  The test substance
was mixed with water and a crop oil concentrate (1% v/v).  The
applications were made at 12-20 day intervals and mature snap beans were
collected 20-22 days following the final application.

Using the supplied residue data and the MRL Calculator, a tolerance
level of 0.90 ppm is recommended for the commodity snap beans.  The MRL
calculations can be found in the appendix of the residue chemistry
summary document.

Dry Pea

IR-4 has submitted field trial data for clethodim on dry pea
(PP#4F6895).  Six field trials were conducted, in Nebraska (EPA Region
7, two trials), South Dakota (EPA Region 7, one trial), and Washington
(EPA Region 11, three trials) during the 2001 growing season.  The
number and locations of field trials are in accordance with OPPTS
Guideline 860.1500.  At each trial location, Prism® 0.94 EC, a 12.6%
emulsifiable-concentrate formulation of clethodim, was foliarly applied
twice at 0.25 lb ai/A (0.50 lb ai/A per season).  The test substance was
mixed with water and a crop oil concentrate.  Clethodim was applied at
13-16 day intervals and mature pea plants were harvested 29-31 days
after the final application.  Pea plants were left in the field to dry
for one to two weeks and then collected.

Using the supplied residue data and the MRL Calculator, a tolerance
level of 2.5 ppm is recommended for the commodity dry peas.  The MRL
calculations can be found in the appendix of the residue chemistry
summary document.

Lima Bean

IR-4 has submitted field trial data for clethodim on lima beans
(PP#4F6895).  Eight field trials were conducted in New Jersey (EPA
Region 2, one trial), North Carolina (EPA Region 2, two trials),
Wisconsin (EPA Region 5, one trial), California (EPA Region 10, two
trials), Washington (EPA Region 11, one trial) and Georgia (EPA Region
2, one trial) during the 2001 growing season.  The number and locations
of field trials are in accordance with OPPTS Guideline 860.1500.  At
each trial location, Prism® 0.94 EC, a 12.6% emulsifiable-concentrate
(EC) formulation of clethodim was applied twice at approximately 0.25 lb
ai/A (0.50 lb ai/A per season).  At the North Carolina (01-NC04) trial,
a third application (for a total of approximately 0.75 lb ai/A) was
made.  The test substance was mixed with water and a crop oil
concentrate (1% v/v).  The foliar applications were made at 13-18 day
intervals and mature snap beans were collected 20-22 days following the
final application.

Using the supplied residue data and the MRL Calculator, a tolerance
level of 1.1 ppm is recommended for the commodity lima beans.  The MRL
calculations can be found in the appendix of the residue chemistry
summary document.

Succulent Pea

IR-4 has submitted field trial data for clethodim on succulent pea
(PP#4F6895).  Eight field trials (four succulent shelled pea and four
edible-podded pea) were conducted in Wisconsin (EPA Region 5, three
trials), Michigan (EPA Region 5, one trial), California (EPA Region 10,
one trial), Washington (EPA Region 11, one trial), Idaho (EPA Region 11,
one trial), and Oregon (EPA Region 12, three trials) in the 2002 growing
season.  The number and locations of field trials are not in strict
accordance with OPPTS Guideline 860.1500 as they pertain to crop group
tolerances.  At each trial location, Prism® 0.94 EC, a 12.6%
emulsifiable-concentrate (EC) formulation of clethodim was foliarly
applied twice at approximately 0.25 lb ai/A (0.50 lb ai/A per season)
with 12-14 days between applications.  The test substance was mixed with
water and a crop oil concentrate.  Mature pea plants were harvested
20-22 days following the final application with the exception of the
01-WA*04 trial, having a 16-day PHI.

Using the supplied residue data and the MRL Calculator, a tolerance
level of 3.5 ppm is recommended for the commodity succulent pea.  The
MRL calculations can be found in the appendix of the residue chemistry
summary document.

Conclusions:  An adequate number of crop field trials, representative
crops, and geographic locations, were submitted for this crop group. 
Based on the highest calculated individual tolerance of 3.5 ppm for the
RAC succulent pea, as recommended by the MRL calculator, HED &ARIA
recommends for a tolerance be established at 3.5 ppm for the vegetable,
legume crop group 6 (except soybean) (ChemSAC, 08/FEB/2006).   A revised
Section F must be submitted by the petitioner changing the requested
tolerance from 3.0 ppm to 3.5 ppm as recommended by HED & ARIA using MRL
spreadsheet calculations.

4.1.6	Magnitude of the Residue in Processed Food/Feed  TC \l3 "4.1.6
Magnitude of the Residue in Processed Food/Feed 

45858501-02.der, L. Kutney, 09/NOV/2006

46434605-02.der, L. Kutney, 07/NOV/2006

  SEQ CHAPTER \h \r 1 IR-4 has submitted field trial residue data for
clethodim on flax and sesame.  Six field trials were conducted for flax
in the 2000 growing season in North Dakota (3 trials, EPA Regions 5 and
7) and South Dakota (3 trialsEPA Region 5) and four field trials were
conducted for sesame in Texas (EPA Region 6) during the 2000 growing
season.  All field trial sites consisted of one untreated control plot
and one treated plot. 

Two broadcast spray applications of clethodim (Prism® 0.94 EC) were
applied at ~ 0.25 lb ai/A (~0.50 lb ai/A per season), a 1X rate, with
13-15 days between applications, and then harvested with a pre-harvest
interval of 12-18 days.  Field treated samples were stored up to 91 days
for flax meal, 181 days for flax oil, 50 days for sesame meal and 58
days for sesame oil.  

Two untreated (control) and two treated samples were taken from each
field trial to ensure a representative sample.  An additional two
samples were collected from the ND13 trial (one treated and one
untreated) for processing into flax seed oil and meal and samples
collected from the 00-TX48 trial were processed into sesame meal and
oil.

Total clethodim residues ranged from an average of 0.18-0.41 ppm on
treated flax seeds.  Total clethodim residues on flax meal and flax oil
averaged <0.18 ppm; therefore, the processing factor for flax meal and
oil are <0.8.  Total clethodim residues ranged from an average of
0.24-0.28 ppm on treated sesame seeds.  Total clethodim residues on
sesame meal and oil averaged 0.31 ppm and 0.37, respectively; therefore,
the processing factor for sesame meal and oil are 1.2 and 1.4,
respectively.

Processed flax meal and oil samples from flax seed containing clethodim
residues of 0.22 ppm were stored for up to 132 and 223 days,
respectively.  The maximum storage interval for field treated samples
was 50 days for sesame meal and 58 days for sesame oil.  Freezer storage
stability data were adequate.  Concurrent DME recoveries were 52-75% in
flax meal and 55-75% in flax oil, respectively.  Concurrent DME-OH
recoveries were 73% in meal and 67-80% in flax oil.  Concurrent
recoveries were 90-109% in sesame oil, and 84-93% in sesame oil. 
Residues of clethodim were determined to be adequately stable.  



TABLE 6  Residue Data From Flax and Sesame Seed, Meal and Oil Crop Field
Trials with Clethodim.

Trial ID

City, State

Year	Commodity	Region	Total Rate

(lbs ai/A)	PHI (days)	Clethodim

from

DME

(ppm)	Clethodim

from

DME-OH (ppm)	Total Clethodim (ppm)	Average

Clethodim (ppm)	

Processing

Factor

Flax

ND13

Fargo, ND 

 2000	Flax, seed

	5	0.516	14	<0.095, 0.15	<0.088, <0.088	<0.19, <0.24	<0.22	-

ND13

Fargo, ND 

 2000	Flax, meal

	5	0.516	14	<0.095	<0.088	<0.183	<0.18	<0.8

ND13

Fargo, ND 

 2000	Flax, oil

	5	0.516	14	<0.095	<0.088	<0.183	<0.18	<0.8

Sesame

00-TX48

(Mercedes, TX

2000)	Sesame, seed	6	0.50	15	0.15, 0.18	<0.088, 0.095	0.24, 0.28	0.26	1

00-TX48

(Mercedes, TX

2000)	Sesame, meal	6	0.50	15	0.22	0.088	0.31	0.31	1.2

00-TX48

(Mercedes, TX

2000)	Sesame, oil	6	0.50	15	0.20	0.17	0.37	0.37	1.4

Conclusions:  All the processing factors, except for sesame oil, are
less than or equal to 1.2X which is the level at which residues in
processed commodities may be of concern.  If HAFT X Processing Factor >
tolerance on sesame, seed, then a tolerance is required; otherwise the
RAC tolerance is sufficient.  The processing factors determined by these
studies will not raise the residues above the tolerances recommended by
HED & ARIA for these RACs.  Therefore, a separate tolerance is not
needed for sesame, oil.  The previously established tolerance based on
the translation of data from a canola processing study (PP# 0E006202, DP
Num: 271248, M. Xue, 14/JUN/2001) for flax, meal at 1.0 ppm must be
removed.

4.1.7	Magnitude of the Residue in Meat, Milk, Poultry, and Eggs  TC \l3
"4.1.7	Magnitude of the Residue in Meat, Milk, Poultry, and Eggs 

No feeding studies were submitted with this petition. Feeding studies
were previously submitted and reviewed (PP#9F3743, MRIDs 41030221 &
41030222, M. Nelson, 03/12/1990).  Permanent tolerances for livestock
and poultry have been established for the combined residues of
clethodim[(E)-(±)-2-[1-[[(3-chloro-2-propenyl)oxy]imino]propyl]-5-[2-(e
thylthio)propyl]-3-hydroxy-2-cyclohexen-1-one] and its metabolites
containing the 2-cyclohexen-1-one moiety (40 CFR §180.458).

Dairy Cattle 

The petitioner conducted a feeding study with lactating dairy cows (MRID
41030222). Fourteen Holstein cows were used for the study (randomly
divided into one control group of two cows and three test groups of four
cows each).  Following an acclimation period of 7 days, each cow in the
test groups was given an oral dose of a 5:95 mixture of
clethodim:clethodim sulphoxide contained in a gelatin capsule, once
daily for 28 consecutive days.  The dosing levels were 10 ppm, 30 ppm,
and 100 ppm equivalency in the diet for the three test groups based on
the highest daily food consumption, determined during the acclimation
period: 85 lbs/cow/day.  These dosing levels would be equivalent to
2.8x, 8.3x and 27.8x the dietary burden for beef cattle, and 2.6x, 7.9x
and 26.3x the dietary burden for dairy cattle based on a reasonable diet
composed of feed items likely to be fed to cattle, with and without
tolerances.

The results of residue analysis of bovine tissues and milk are
summarized in Table 7.

	Table 7. Clethodim Residues in Dairy Cows

Feeding Levels	

Chemicals	

Milk	

Liver	

Kidney	

Muscle	

Fat

10 ppm	

DME	

ND	

0.06	

0.05	

ND	

ND

	

DME-OH	

ND	

ND	

ND	

ND	

ND

	

S-MEDME	

ND	

ND	

ND	

ND	

ND

30 ppm	

DME	

0.03	

0.12	

0.17	

ND	

0.05

	

DME-OH	

ND	

ND	

ND	

ND	

ND

	

S-MEDME	

ND	

ND	

ND	

ND	

ND

100 ppm	

DME	

0.08	

0.45	

0.54	

0.07	

0.15

	

DME-OH	

ND	

ND	

ND	

ND	

ND

	

S-MEDME	

0.03	

0.09	

0.08	

ND	

ND

ND = Not Detected (<O.0125 ppm for milk and <0.05 ppm for tissues)

DME residues were found in liver and kidney at all feeding levels; in
milk and fat, at the 30 and 100 ppm feeding levels; and, in muscle, at
the l00 ppm level only.  S-MEDME was found in milk, liver, and kidney at
the 100 ppm level.  DME-OH was not found in milk or any tissue at any
feeding level.  Residues in milk plateaued on test days 1 or 2.

No detectable residues of DME, DME-OH, or S-MEDME were reported in any
control milk (<0.0125 ppm) or bovine tissue (<0.05 ppm) samples.  

Composite whole milk samples collected on test days 25, 26, and 27 from
the control group and the 100 ppm dose level group were processed to
obtain skim milk (nonfat solids), cream (fat solids), pasteurized milk,
and acid whey (lactose).  Analysis for total clethodim residues (DME +
DME-OH + S-MEDME) was performed on these processing fractions. Based on
the recommended tolerances in this submission and established
tolerances, the maximum theoretical residues in diets of beef and dairy
cattle were calculated and the current theoretical maximum dietary
burdens were determined (see Table 8).

TABLE 8. Theoretical dietary burden of clethodim from various feed
commodities for beef and dairy cattle

Feed Commodity	

Tolerance or Proposed Tolerance

(ppm)	

% Dry Matter	

Beef Cattle	

Dairy Cattle

	

% of Diet	

Burden (ppm)	

% of Diet	

Burden

(ppm)

Alfalfa, forage	

6.0	

35	

20	

3.4

Alfalfa, hay	

10.0	

89	

15	

1.7

Grass/nongrass/cereal grain, forage/silage/hay	0

25

	Beet, sugar, molasses	1.0	75	5	0.07	5	0.07

Potato, processed waste	0.5	20	30	0.75	10	0.25

Corn, field, grain/other grains/grain milled byproducts	0

40

30

	Cotton, undelinted seed	1.0	88

	10	0.11

Safflower/sunflower, meal	10.0	88	10	1.1

Total	

	

	

100	

3.6	

100	

3.8

HED Comments/Conclusions:

	

The established tolerances on meat and milk are adequate to cover the
proposed uses. According to a revision of Table 1 of OPPTS 860.1000
(referred to as “Table 1 Feedstuffs (October 2006)) and the
recommended and established tolerances for clethodim, the maximum
theoretical residues in the diets of beef cattle and dairy cattle were
calculated; the theoretical maximum dietary burdens were determined to
be 3.6 ppm for beef and 3.8 ppm for dairy cattle.  Based on the previous
feeding studies, the secondary residues in meat and milk will not exceed
the established tolerances.  This does not include foliage from legume
vegetables.  According to commercial practices, when legume vegetables
are harvested for dry seed the foliage would not be suitable for
livestock feed.  Therefore, the foliage of these legume vegetables is
not considered a feed item in the diets of the reference animals as
defined in the revision of Table 1 of OPPTS 860.1000.

Poultry

The petitioner conducted a feeding study with laying hens (MRID
41030221).  Young laying hens were randomly assigned (20 hens each) to
one of three test groups or the control group.  Following an acclimation
period of 35 days, each hen in the test groups received an oral dose of
a 5:95 mixture of clethodim:clethodim sulphoxide (purity, >98.5%)
contained in a gelatin capsule, once daily for 28 consecutive days.
Controls received gelatin capsules containing only the carrier (corn oil
and evaporated acetone).  Hens received poultry mash and water ad
libitum throughout the dosing period.

The dose levels for the three test groups were 10 ppm, 30 ppm, and l00
ppm equivalency in the diet based on the highest daily food consumption,
determined during the 35 day acclimation period: 151.3 grams/hen/day. 
These dosing levels would be equivalent to 3.3x, 10x and 33.3x the
theoretical maximum dietary burden for poultry based on a reasonable
diet.

The results of the residue analysis are summarized in Table 9.

TABLE 9. Clethodim Residues in Laying Hens

Feeding Levels	

Chemicals	

Eggs	

Fat	

Gizzard	

Liver	

Muscle

10 ppm	

DME a	

ND	

ND	

ND	

ND	

ND

	

DME-OH b	

ND	

ND	

ND	

ND	

ND

	

S-MEDME c	

ND	

ND	

ND	

ND	

ND

30 ppm	

DME	

0.05-0.09	

ND	

ND	

ND	

ND

	

DME-OH	

ND	

ND	

ND	

ND	

ND

	

S-MEDME	

ND	

ND	

ND	

ND	

ND

100 ppm	

DME	

0.14-0.24	

ND	

ND	

0.06	

ND

	

DME-OH	

ND	

ND	

ND	

ND	

ND

	

S-MEDME	

ND	

ND	

ND	

ND	

ND

a	Expressed  as clethodim (C)

b	Expressed  as 5-OH clethodim sulphoxide (5-0H-SO 2)

c	Expressed  as S-methyl clethodim sulphone (SMSO)

ND = no detectable residue (<0.05 ppm)

No detectable residues (0.05 ppm) of DME, DME-OH, or S-MEDME were found
in any control samples of eggs or poultry tissues. No residues were
detected (<0.05 ppm) in any of the fat, gizzard, or muscle samples, even
at the 100 ppm dose level.

Clethodim (DME) of 0.06 ppm was found in only one liver sample (day 29),
which was from the 100 ppm dose level.  No DME-OH and S-MEDME were
detected (<0.05 ppm) in any of the liver samples.

No detectable residues (<0.05 ppm) of DME, DME-OH, or S-MEDME were
reported in any control egg or poultry tissue samples.  No detectable
residues (<0.05 ppm) of clethodim were found in eggs from the 10 ppm
dose level.  Clethodim residues were found in eggs from both the 30 ppm
(0.05-0.09 ppm) and 100 ppm (0.14- 0.24 ppm) dose levels; these residues
declined to <0.05 ppm by day 29. No DME-OH and S-MEDME were detected
(<0.05 ppm) in any of the egg samples.

Based on the recommended tolerances in this submission and the
established tolerances, the maximum theoretical residues in poultry were
calculated and a reasonable theoretical dietary burden was determined
(see Table 10).

TABLE 10. Theoretical dietary burden of clethodim from various feed
commodities for poultry.

Feed Commodity	

Tolerance or Proposed Tolerance

(ppm)	

Poultry

% of Diet	

Burden

(ppm)

Corn, field, grain/other grains/grain milled byproducts	0	70

	

Safflower/sunflower, meal	

10.0	

10	

1.0

Soybean, seed	

10.0	

20	

2.0

Total	

	

100	

3.0

HED Comments/Conclusion:

The established tolerances on poultry and eggs are adequate to cover the
proposed uses.  According to a revision of Table 1 of OPPTS 860.1000
(referred to as “Table 1 Feedstuffs (October 2006)) and the
recommended and established tolerances for clethodim, the maximum
theoretical residues in a reasonable diet of poultry were calculated;
the theoretical maximum dietary burden was determined to be 3.0 ppm for
poultry.  Based on the previous poultry feeding studies, secondary
residues in poultry and eggs will not exceed the established tolerances.

Swine

The tolerances set for swine are based upon the cattle feeding study and
a reasonable diet.  Since legume foliage is not a swine feed item, and
the requested RACs are not fed to swine when using a reasonable diet,
secondary residues in swine will not exceed the established tolerances.

4.1.8	Confined and Field Rotational Accumulation in Rotational Crops 
TC \l3 "4.1.8	Confined and Field Accumulation in Rotational Crops 

A confined rotational crop study of [ring-4,6-14C]-clethodim with
carrots, lettuce, and wheat (MRID 41030211) was conducted.  The study
was reviewed by E. B. Conerly (EFGWB Science Chapter for Clethodim,
26/JUN/1990).  Results indicated that there is no need for field
rotational crop trials.  A 1- month plant back interval for crops
rotated with alfalfa was specified (DP Num: 236382, M. Collantes, et.
al, 10/FEB/1998).  The use directions submitted with the current
petitions do not specifically address rotational crops.  The directions
for use on fallow or non-producing agricultural land state “Do not
plant any crop for 30 days after application unless clethodim is
registered for use on that crop”.

4.1.9	Drinking Water Residue Profile TC \l3 "4.1.9	Drinking Water
Residue Profile 

Reference: Drinking water assessment for Clethodim on flax, leafy
greens, sesame, safflower, herbs, hops, asparagus, legumes. PC Code
121011, DP Number 313467, I. Abdel-Saheb, 11/30/06.

Surface and ground water contamination may occur from the sulphoxide and
sulphone degradates of clethodim, as well as from parent clethodim. 
However, the risk of water contamination is primarily associated with
clethodim sulphone and clethodim sulphoxide rather than parent clethodim
based on greater persistence and mobility for these degradates.

The only significant routes of dissipation of clethodim are microbial
degradation in soil and movement by leaching or runoff.  Parent
clethodim is moderately persistent to hydrolysis at pH 5 with half-lives
of 26-42 days and stable at pH 7 and 9 with half-lives greater than 300
days.  Even though acceptable water and soil photolysis studies show
half-lives of 1.5 to 9.3 days, this may not be an important route of
dissipation because of suspended sediment and shading.  Photolysis is
only an important route of dissipation in shallow, well-mixed surface
water with no shading.  The half-lives in aerobic soil are 2-3 days for
parent clethodim, and 30-38 days for total toxic residues (parent +
sulphoxide + sulphone).  The sulphoxide and sulphone metabolites are
more persistent than parent clethodim and are formed in significant
quantities in soil.  All residues of clethodim (parent and metabolites)
are very mobile in soil with five out of six soil desorption
coefficients (Kd) less than one.  The field dissipation studies show
that parent clethodim was only found at levels at or near the
quantitation limit of 0.02 ppm, which is consistent with the rapid
degradation in soil.  Clethodim sulphoxide had an apparent half-life of
2.5 to 3.7 days, indicating that movement from the treated field may
have been an important route of dissipation.

The drinking water estimates below are based on a maximum application
rate of 0.5 lb ai/acre per year (2 applications). 

Surface water

Parent clethodim may move from the treated field to surface water or
ground water through run-off or leaching which occurs shortly after
application (e.g. rainfall).   Also, the sulphoxide and sulphone
degradates may migrate by runoff or leaching for longer periods of time
since they are more persistent.  All residues of clethodim (parent and
degradates) are very mobile in soil.  Tier 1 surface water
concentrations for parent clethodim and total toxic residues (parent +
sulphoxide + sulphone) were estimated using the FIRST (FQPA Index
Reservoir Screening Tool) model. 

The peak FIRST estimated environmental concentration (EEC) for clethodim
and its degradates, sulphoxide and sulphone, in surface water is 38.9
ppb.  The chronic FIRST EEC is 7.6 ppb. 

Ground water

Parent clethodim is mobile, but has a short metabolic half-life in soil
under aerobic conditions.  Therefore, parent compound should not be a
ground water concern in most environments.  While it is expected that
parent clethodim can be transformed to sulphoxide or sulphone products
quickly by soil metabolism (t½ = 1 - 3 days), it may be more persistent
since it is leached below the more biologically active top soil.  In
such instances (i.e., leaching rainfall shortly after application)
parent clethodim concentrations may be higher than estimated.  In the
event that parent clethodim did reach ground water, the available routes
of disappearance would be dilution, some metabolism to persistent
degradates, and slow hydrolysis with the rate depending on the pH of the
ground water.  Estimates are provided for both parent clethodim and
total toxic clethodim (parent + sulphoxide+sulphone).

For drinking water derived from ground water, the SCI-GROW model
estimates a total toxic clethodim concentration of 1.39 ug/L for the
proposed IR-4 uses.  The SCI-GROW value should be used for acute,
chronic, and cancer risk assessment on each of their respective crops.

Ground water sources were not included in the dietary assessment, as the
EECs for this water source are minimal in comparison to surface water.

4.1.10	Proposed Tolerances TC \l3 "4.1.10	Proposed Tolerances 

The tolerance expression for clethodim in/on plants (40 CFR 180.458(a)
(3) is the combined residues of clethodim and metabolites containing the
5-2-ethylthiopropyl)cyclohexene-3-one and
5-(2-(ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones.



Table 11.  Tolerance Summary for Clethodim

Commodity	Established/Proposed Tolerance (ppm)	Recommended Tolerance
(ppm)	Comments (correct commodity definition)

Leafy greens subgroup 4A	2.0	                     2.0

	Flax, seed	0.5	                     0.6

	Hop, dried cones	0.50	                     0.5

	Asparagus	2.0	                     1.7

	Herb subgroup 19A	10	                    12.0

	Sesame, seed	0.40	                     0.35

	Vegetable, legume, group	3.0	                     3.5	Corrected
commodity definition 

Vegetable, legume, group 6, except soybean.

Safflower, meal	10.0	                    10.0

	Safflower, seed	5.0	                     5.0

	

Based on the newly submitted field trial data, harmonization with
current Codex MRLs set on beans (dry), beans, except broad bean and soya
bean (dry), and field pea (dry) is not appropriate (ChemSAC, minutes of
08/FEB/2006).  The Codex MRLs of these commodities should be increased
to accommodate these new data.  Harmonization with Canada on the
tolerance levels for flax seed, beans, chickpeas, lentils, and peas
(dry) and Mexico on bean (kidney) is also not possible based on the MRL
Calculations of the newly submitted data.  

4.2	Dietary Exposure and Risk TC \l2 "4.2  Dietary Exposure and Risk 

Reference: Clethodim Amended Chronic Dietary (Food and Drinking Water)
Exposure Assessment for the Interregional Research Project No. 4 (IR-4)
Petition Proposing Tolerances for Residues of Clethodim on Herb Subgroup
19A (PP#4E6836), Leafy Greens Subgroup 4A (PP#5E6978), Sesame, Legume
Vegetable Group 6 (except Soybean) and Safflower (PP#4F6895), Hops and
Asparagus (PP#5E6977) and Flax (PP#3E6555).  PC Code: 121011; Decision
Number: 353916; DP Number 333069; B. Hanson; 03/07/07.

Dietary risk assessment incorporates both exposure and toxicity of a
given pesticide.  The risk is expressed as a percentage of a maximum
acceptable dose (i.e., the dose which HED has concluded will result in
no unreasonable adverse health effects).  This dose is referred to as
the population adjusted dose (PAD).  HED is concerned when estimated
dietary risk exceeds 100% of the PAD.  

4.2.1	Acute Dietary Exposure/Risk  TC \l3 "4.2.1  Acute Dietary
Exposure/Risk 

There was no appropriate endpoint for assessing acute dietary exposure;
therefore, no acute dietary risk assessment was performed.

4.2.2	Chronic Dietary Exposure/Risk  TC \l3 "4.2.2  Chronic Dietary
Exposure/Risk 

Chronic dietary (food plus drinking water) exposure analyses were
performed to support the registration of the proposed new uses of
clethodim.  The analyses were conducted using the Dietary Exposure
Evaluation Model (DEEM-FCIDTM, version 2.03), which used food
consumption data from the U.S. Department of Agriculture’s Continuing
Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. 
The 1994-96, 98 data are based on the reported consumption of more than
20,000 individuals over two non-consecutive survey days.  Foods “as
consumed” (e.g., apple pie) are linked to EPA-defined food commodities
(e.g. apples, peeled fruit - cooked; fresh or N/S; baked; or wheat flour
- cooked; fresh or N/S, baked) using publicly available recipe
translation files developed jointly by USDA/ARS and EPA.  For chronic
exposure assessment, consumption data are averaged for the entire U.S.
population and within population subgroups.  Based on analysis of the
1994-96, 98 CSFII consumption data, which took into account dietary
patterns and survey respondents, HED concluded that it is most
appropriate to report risk for the following population subgroups: the
general U.S. population, all infants (<1 year old), children 1-2,
children 3-5, children 6-12, youth 13-19, adults 20-49, females 13-49,
and adults 50+ years old.

For chronic dietary exposure assessment, an estimate of the residue
level in each food or food-form (e.g., orange or orange juice) on the
food commodity residue list is multiplied by the average daily
consumption estimate for that food/food form to produce a residue intake
estimate.  The resulting residue intake estimate for each food/food form
is summed with the residue intake estimates for all other food/food
forms on the commodity residue list to arrive at the total average
estimated exposure.  Exposure is expressed in mg/kg body weight/day and
as a percent of the cPAD.  This procedure is performed for each
population subgroup.

The drinking water residues used in the dietary risk assessment were
provided by the Environmental Fate and Effects Division (EFED) and
summarized in the following memoranda: “Drinking Water Assessment for
Clethodim on Flax, Leafy Greens, Sesame, Safflower, Herbs, Hops,
Asparagus, Legumes,” (I. Abdel-Saheb,  DP Number 313467, 30/11/2006)
and incorporated directly into this dietary assessment.  Water residues
were incorporated in the DEEM-FCID into the food categories “water,
direct, all sources” and “water, indirect, all sources.” 

EFED recommended that total toxic EEC’s generated by the FIRST model
be used instead of EEC’s for parent clethodim.  The chronic (annual
mean) value for clethodim in surface water used as drinking water is
7.63 ug/L.

Residue Data Used for the Chronic Assessment:

The chronic dietary exposure analysis was performed for the general U.S.
population and all population subgroups using tolerance level residues
and total residues of concern (plants; parent and metabolites).

This partially refined chronic dietary exposure assessment was based on
the assumption of tolerance-level residues for most commodities with
existing and proposed tolerances and incorporated percent crop treated
information for the existing crops.  For all proposed crops 100% CT was
used.  A Screening-Level Usage Analysis (SLUA) was provided by the
Biological and Economic Analysis Division (BEAD) for %CT information of
current uses of clethodim; see Table 12 (A. Grube, 11/21/2006).  This
information supersedes all previous %CT data.  Recommended tolerances
were provided by ARIA, see Table 11 (D. Rate, DP Number: 334913,
02/09/2007).  The higher soybean tolerance of 10 ppm was used instead of
the proposed Crop Group 6 tolerance of 3.0 ppm.  The expired tomato,
paste and puree tolerances have been replaced with the crop group 8
tolerance of 1.0 ppm.  DEEM default processing factors are again being
used to refine the residue estimates of appropriate commodities except
for potato, dry (granules/flakes).  According to a processed food/feed
study which was reviewed by HED (M. Xue, DP Numbers: 240302, 254018,
09/07/2000) and never incorporated into subsequent dietary risk
assessments, the 2.0 ppm tolerance on potato granules/flakes is adequate
and covers the HAFT residues of 0.78 ppm from field trials and a residue
concentration factor of 2.5x (0.78 x 2.5 = 1.95).

Table 12.  Percent Crop Treated Information Used in Chronic Dietary
Exposure Analysis

Commodity	Percent of Crop Treated

(Weighted Average)

Beets	<1

Broccoli	10

Cabbage	<1

Cantaloupes	<1

Carrots	10

Celery	5

Cotton	<1

Cucumbers	<1

Dry Beans	5

Lettuce	<1

Onions	10

Peanuts	5

Potatoes	5

Pumpkins	5

Soybeans	5

Squash	5

Strawberries	<1

Sugar Beets	45

Sunflowers	20

Sweet Potatoes	<1

Tomatoes	<1

Watermelons	5

Results of the Chronic Dietary Exposure Analysis

The chronic dietary exposure for food and surface water utilized 29% of
the cPAD for the U.S. population.  The chronic dietary exposure for the
highest reported exposed population subgroup, children 1-2 years old,
utilized 84% of the cPAD.

The results of the chronic dietary exposure analysis are reported in the
Summary Table (Table 13, below).  

Table 13.  Summary of Dietary (Food and Drinking Water) Exposure Risk
for Clethodim

Population Subgroup	Chronic Dietary

	Dietary Exposure

(mg/kg/day)	% cPAD*

General U.S. Population	0.002938	29

All Infants (< 1 year old)	0.008072	81

Children 1-2 years old	    0.008370**	    84**

Children 3-5 years old	0.005994	60

Children 6-12 years old	0.003688	37

Youth 13-19 years old	0.002174	22

Adults 20-49 years old	0.002274	23

Adults 50+ years old	0.002575	26

Females 13-49 years old	0.002173	22

* % PADs are reported to 2 significant figures.

* *The values for the highest exposed population for each type of risk
assessment are bolded.

These analyses are conservative dietary exposure assessments.  Further
refinement to the analyses could be made through the use of anticipated
residues, incorporation of additional percentages of crops treated with
clethodim, and/or monitoring data that better reflect residues at the
time of consumption.  Since risk estimates are below HED’s level of
concern, a more highly refined analysis is not needed at this time.

4.2.3	Cancer Dietary Risk  TC \l3 "4.2.3 Cancer Dietary Risk 

Clethodim has been classified as a “Not Likely” carcinogen. 
Therefore, a dietary cancer risk assessment is not required.



5.0	Residential (Non-Occupational) Exposure/Risk Characterization  TC
\l1 "5.0	Residential (Non-Occupational) Exposure/Risk Characterization 

The risk assessment team has reviewed the most recent HED risk
assessment for clethodim (DP Number 278451, Memo M. Rust, 21 FEB 2002)
with regards to statements relative to residential use.  The team
re-evaluated the product labels cited in the risk assessment as well as
the newly proposed labels and determined that no residential exposure
will result from the use of clethodim in non-crop areas or ornamentals
in commercial greenhouse/lathhouse or outdoor settings.

6.0	Aggregate Risk Assessments and Risk Characterization  TC \l1 "6.0
Aggregate Risk Assessments and Risk Characterization 

In accordance with the FQPA, HED must consider and aggregate (add)
pesticide exposures and risks from three major sources: food, drinking
water, and residential exposures.  In an aggregate assessment, exposures
from relevant sources are added together and compared to quantitative
estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can
be aggregated.  When aggregating exposures and risks from various
sources, HED considers both the route and duration of exposure.

Based on the proposed Section 3 food crop uses, dietary aggregate
exposures (i.e. food plus drinking water) are anticipated.  There are no
residential uses.  Consequently, only dietary (food plus drinking water)
exposures were aggregated for this assessment.  Estimates of pesticide
residues in drinking water (EDWCs) were incorporated directly into the
dietary exposure analysis to assess aggregate acute and chronic risk. 
Refer to section 4.2 for these risk estimates.  

7.0	Cumulative Risk Characterization/Assessment  TC \l1 "7.0	Cumulative
Risk Characterization/Assessment 

Unlike other pesticides for which EPA has followed a cumulative risk
approach based on a common mechanism of toxicity, EPA has not made a
common mechanism of toxicity finding as to clethodim and any other
substances and clethodim does not appear to produce a toxic metabolite
produced by other substances. For the purposes of this tolerance action,
therefore, EPA has not assumed that clethodim has a common mechanism of
toxicity with other substances. For information regarding EPA’s
efforts to determine which chemicals have a common mechanism of toxicity
and to evaluate the cumulative effects of such chemicals, see the policy
statements released by EPA’s Office of Pesticide Programs concerning
common mechanism determinations and procedures for cumulating effects
from substances found to have a common mechanism on EPA’s website at
http://www.epa.gov/pesticides/cumulative/.



8.0	Occupational Exposure/Risk Pathway  TC \l1 "8.0	Occupational
Exposure/Risk Pathway 

Reference: CLETHODIM - Human Non-Dietary Exposure/Risk Assessment for
the Proposed Use of Clethodim on:  Asparagus, Flax, Herbs (Crop Subgroup
19 A), Hops, Leafy Green Vegetables (Crop Subgroup 4A), Legume
Vegetables (Crop Group 6) Safflower, and Sesame. PC Code: 121011, DP
Number 332900, M. Dow, 11/01/06.

8.1	Short-/Intermediate-Term Handler Risk  TC \l2 "8.1
Short-/Intermediate-Term Handler Risk 

Based upon the proposed use patterns, the most likely method of
application will be by groundboom spray machinery.  For hops, the
directions indicate application to the hop yard floor i.e., the ground. 
When they are suggested, the spray volumes per acre seem to preclude
aerial application as a practical method.  However, there is no apparent
prohibition to aerial application.  And, while it is doubtful that
aerial application would be used to any appreciable extent, it is
considered in the exposure assessment herein.

For the proposed new uses, the most highly exposed occupational
pesticide handlers will be mixer/loaders using open-pour loading of
liquid formulations in support of aerial operations, applicators using
open-cab, ground-boom sprayers and aerial applicators.

Since the treatment blocks (i.e., areas treated) are relatively small
for the proposed new crop uses (as compared to typical field crops such
as cotton, corn, soybeans or wheat), HED believes pesticide handlers
will be exposed to short-term duration (1-30 days) exposures, but not to
intermediate-term (1-6 months) duration exposures.  Although multiple
applications are possible, they are separated by 14 day re-treatment
intervals.  It is unlikely that pesticide handlers would be exposed
continuously for 30 days or more.  Estimates of intermediate-term
exposures are, however, presented.

Particularly for ground applications, private (i.e., grower) applicators
may perform all functions, that is, mix, load and apply the material. 
The HED ExpoSAC SOP Number 12 (29 March 2000) directs that although the
same individual may perform all those tasks, they shall be assessed
separately.  The available exposure data for combined
mixer/loader/applicator scenarios are limited in comparison to the
monitoring of these two activities separately.  These exposure scenarios
are outlined in the Pesticide Handler Exposure Database (PHED) Surrogate
Exposure Guide (August 1998).  HED has adopted a methodology to present
the exposure and risk estimates separately for the job functions in some
scenarios and to present them as combined in other cases.  Most exposure
scenarios for hand-held equipment (such as hand wands, backpack
sprayers, and push-type granular spreaders) are assessed as a combined
job function.  With these types of hand held operations, all handling
activities are assumed to be conducted by the same individual.  The
available monitoring data support this and HED presents them in this
way.  Conversely, for equipment types such as fixed-wing aircraft,
groundboom tractors, or air-blast sprayers, the applicator exposures are
assessed and presented separately from those of the mixers and loaders. 
By separating the two job functions, HED determines the most appropriate
levels of personal protective equipment (PPE) for each aspect of the job
without requiring an applicator to wear unnecessary PPE that might be
required for a mixer/loader (e.g., chemical resistant gloves may only be
necessary during the pouring of a liquid formulation).

No chemical specific data were available with which to assess potential
exposure to pesticide handlers.  The estimates of exposure to pesticide
handlers are based upon surrogate study data available in the PHED (v.
1.1, 1998).  For pesticide handlers, it is HED’s standard practice to
present estimates of dermal exposure for “baseline”, that is, for
workers wearing a single layer of work clothing consisting of a long
sleeved shirt, long pants, shoes plus socks and no protective gloves as
well as for “baseline” plus the use of protective gloves or other
PPE as might be necessary.  PPE for the various products was discussed
earlier.  

The HIARC identified short-term dermal and inhalation exposure duration
(1-30 days) toxicological endpoints from a developmental study in the
rat.   The toxic effects were maternal effects i.e., decreased body
weight gain and clinical signs of toxicity were observed.  The NOAEL for
both routes of exposure is 100 mg ai/kg bw/day.  The HIARC identified a
30% dermal absorption factor for use in calculating dermal exposure. 
HED assumes 100% absorption via the inhalation route of exposure.  A 70
kg bw (body weight) is used for all exposure calculations.

Since the short-term dermal and inhalation NOAELs were identified from
the same study and are associated with the same toxic effects, the
dermal and inhalation exposures are summed then divided into the NOAEL
to obtain the short-term duration Margin of Exposure (MOE).  See Table
14 for a summary of short-term exposures and risks to occupational
pesticide handlers.

The HIARC also identified toxicological endpoints with which to assess
intermediate-term duration exposures (1-6 months).  The
intermediate-term dermal and inhalation NOAELs are 25 mg ai/kg bw/day
and were identified from a chronic toxicity study in the dog.  The
effects seen were alterations in hematology and clinical chemistry as
well as increases in absolute and relative liver weights.  Since the
intermediate-term dermal and inhalation NOAELs were identified from the
same study and are associated with the same toxic effects, the dermal
and inhalation exposures are summed then divided into the NOAEL to
derive the intermediate-term MOE.  See Table 15 for a summary of
intermediate-term exposures and risks to occupational pesticide
handlers.

Clethodim is classified as "not likely" to be carcinogenic to humans.  
Therefore, a cancer risk assessment is not necessary.

A MOE of 100 is adequate to protect occupational pesticide handlers from
short- or intermediate-term exposures to clethodim.  The proposed use
patterns do not exceed HED’s level of concern provided mixer/loaders
wear protective gloves as is required on all labels considered here.

Table 14. Estimated Short-Term Handler Exposure & Risk from Proposed
Uses of Clethodim

Unit Exposure1

mg a.i./lb handled	

Applic. Rate2	

Units Treated3

Per Day	

Average Daily

Dose4

mg a.i./kg bw/day	

NOAEL5

mg a.i./kg bw/day	

MOE6

Short-Term

Mixer/Loader - Liquid - Open-pour

Dermal:

SLNoGlove  2.9 HC

SLWGloves  0.023 HC

Inhal              0.0012 HC	

0.25 lb ai/A	

350 A/day	

SLNoGlove 1.088

SLWGlove 0.0086

Inhal           0.0015	

100	SLNoGlove

92

SLWGlove

9900

Applicator - Groundboom - Open Cab

Dermal:

SLNoGlove   0.014 HC

SLWGloves   0.014 MC

Inhal              0.00074 HC	

0.25 lb ai/A	

200 A/day	

SLNoGlove 0.003

SLWGlove  0.003

Inhal          0.00053	

100	SLNoGlove

28,329

SLWGlove

28,329

Applicator - Fixed-wing - Aerial (Pilots not required to wear gloves)

Dermal:

SLNoGlove  0.0050 MC

Inhal           0.000068 MC 	

0.25 lb ai/A	

350 A/day	

SLNoGlove 0.0019

Inhal        0.000085	

100	

SLNoGlove

50,378

1.  Unit Exposures are taken from “PHED SURROGATE EXPOSURE GUIDE”,
Estimates of Worker Exposure from The Pesticide Handler Exposure
Database Version 1.1, August 1998.   Dermal:  SLNoGlove = Single layer
work clothing (long pants, long-sleeved shirt, shoes plus socks) No
gloves;  SLWGloves = single layer work clothing WITH  the use of
protective gloves; Inhal. = Inhalation.  Units = mg a.i./pound of active
ingredient handled.  Data Confidence: LC = Low Confidence, MC = Medium
Confidence, HC = High Confidence.

2.  Applic. Rate = Taken from Sections B of the IR-4 submissions.

3.  Units Treated are taken from “Standard Values for Daily Acres
Treated in Agriculture”; SOP No. 9.1.  ExpoSAC; Revised 5 July 2000; 

4.  Average Daily Dose (ADD) = Unit Exposure * Applic. Rate * Units
Treated * absorption factor (30% dermal absorption) ( Body Weight (70
kg).  

5.  NOAEL = No Observable Adverse Effect Level 100 mg a.i./kg bw/day for
short-term  dermal and inhalation exposure.

6.  MOE = Margin of Exposure = NOAEL  ( ADD.  

Table 15. Estimated Intermediate-Term Handler Exposure & Risk from
Proposed Uses of Clethodim

Unit Exposure1

mg a.i./lb handled	

Applic. Rate2	

Units Treated3

Per Day	

Average Daily

Dose4

mg a.i./kg bw/day	

NOAEL5

mg a.i./kg bw/day	

MOE6

Intermediate-Term

Mixer/Loader – Liquid - Open-pour

Dermal:

SLNoGlove  2.9 HC

SLWGloves  0.023 HC

Inhal              0.0012 HC	

0.25 lb ai/A	

350 A/day	

SLNoGlove 1.088

SLWGlove 0.0086

Inhal           0.0015	

25	SLNoGlove

23

SLWGlove

2,475

Applicator - Groundboom - Open Cab

Dermal:

SLNoGlove   0.014 HC

SLWGloves   0.014 MC

Inhal              0.00074 HC	

0.25 lb ai/A	

200 A/day	

SLNoGlove 0.003

SLWGlove  0.003

Inhal          0.00053	

25	SLNoGlove

7,082

SLWGlove

7,082

Applicator - Fixed-wing - Aerial (Pilots not required to wear gloves)

Dermal:

SLNoGlove  0.0050 MC

Inhal           0.000068 MC 	

0.25 lb ai/A	

350 A/day	

SLNoGlove 0.0019

Inhal        0.000085	

25	

SLNoGlove

12,594

1.  Unit Exposures are taken from “PHED SURROGATE EXPOSURE GUIDE”,
Estimates of Worker Exposure from The Pesticide Handler Exposure
Database Version 1.1, August 1998.   Dermal:  SLNOGlove = Single layer
work clothing (long pants, long-sleeved shirt, shoes plus socks) No
gloves;  SLWGloves = single layer work clothing WITH  the use of
protective gloves;   Inhal. = Inhalation.  Units = mg a.i./pound of
active ingredient handled.  Data Confidence: LC = Low Confidence, MC =
Medium Confidence, HC = High Confidence.

2.  Applic. Rate = Taken from.

3.  Units Treated are taken from “Standard Values for Daily Acres
Treated in Agriculture”; SOP No. 9.1.   Science Advisory Council for
Exposure; Revised 5 July 2000; 

4.  Average Daily Dose (ADD) = Unit Exposure * Applic. Rate * Units
Treated * absorption factor  (30 % dermal absorption) ( Body Weight (70
kg) 

5.  NOAEL = No Observable Adverse Effect Level 25 mg a.i./kg bw/day for
intermediate-term  dermal and inhalation exposure

6.  MOE = Margin of Exposure = NOAEL ( ADD.

8.2	Short-/Intermediate-Term Postapplication Risk  TC \l2 "8.2
Short-/Intermediate-Term Postapplication Risk 

It is possible for agricultural workers to have postapplication
exposures to pesticide residues during the course of typical
agricultural activities.  HED, in conjunction with the Agricultural
Re-entry Task Force (ARTF), has identified a number of postapplication
agricultural activities that may occur and which may result in
postapplication exposures to pesticide residues.  HED has also
identified Transfer Coefficients (TC) (cm²/hr) relative to the various
activities which express the amount of foliar contact over time, during
each of the activities identified.  For the proposed new crop use sites,
the highest TC is 1,500 cm²/hr which results from "scouting" (i.e.,
crop advisors) in flax, leafy green vegetables, legume vegetables and
safflower.  One might typically expect high exposures in late season
hops; however the directions for application to hops indicates
application to the hop yard floor.  Under those conditions, scouting in
hops has a TC of 100 cm2/hr.  Therefore, as a “screening” level
assessment, HED herein uses a TC of 1,500 cm²/hr.

The TCs used in this assessment are from an interim TC Standard
Operating Procedure (SOP) developed by HED’s ExpoSAC using proprietary
data from the ARTF database (SOP # 3.1).  It is the intention of HED’s
ExpoSAC that this SOP will be periodically updated to incorporate
additional information about agricultural practices in crops and new
data on transfer coefficients.  Much of this information will originate
from exposure studies currently being conducted by the ARTF, from
further analysis of studies already submitted to the Agency, and from
studies in the published scientific literature.

Lacking compound specific dislodgeable foliar residue (DFR) data, HED
assumes 20 % of the application rate is available as DFR on day zero
after application.  This is adapted from the ExpoSAC SOP No. 003 (7 May
1998 - Revised 7 August 2000).

The following convention may be used to estimate postapplication
exposure.  

Average Daily Dose (ADD) (mg a.i./kg bw/day) = DFR µg/cm2 * TC cm2/hr *
hr/day * 0.001 mg/µg * 1/70 kg bw 

 and where:

Surrogate Dislodgeable Foliar Residue (DFR) = application rate * 20%
available as dislodgeable residue * (1-D)t * 4.54 x 108 µg/lb * 2.47 x
10-8 A/cm2 .  

0.25 lb a.i./A * 0.20 * (1-0)0 * 4.54 x 108 µg/lb *  2.47 x10-8 A/cm²
= 0.56 µg/cm2 , therefore,

0.56 µg/cm2 * 1,500 cm2/hr * 8 hr/day * 0.001 mg/µg * 0.30 (% dermal
absorption) ( 70 kg bw = 0.029 mg/kg bw/day.

MOE = NOAEL ( ADD then 100.0 mg/kg bw/day ( 0.029 mg/kg bw/day = 3,448.

A MOE of 100 is adequate to protect agricultural workers from
post-application exposures.  Since the estimated MOEs are > 100, the
proposed uses do not exceed HED’s level of concern.

	RESTRICTED ENTRY INTERVAL (REI)

As was indicated in the 21 February 2002 risk assessment, the interim
Worker Protection Standard (WPS) restricted entry interval for a
compound classified in Acute Toxicity Category I (primary dermal
irritation in this case) is 48 hours (see 40 CFR § 156.208 (c) (2). 
The labels provided for review list REIs of 24 hours.  It is suggested
that RD confirms or corrects these labels to reflect the proper REI of
48 hours.

9.0	Data Needs and Label Recommendations  TC \l1 "9.0	Data Needs and
Label Requirements 

9.1	Residue Chemistry Data Needs and Label Requirements  TC \l2 "9.1
Residue Chemistry Data Needs and Label Requirements 

Based on an effort to harmonize tolerances with Codex and MRL, the
tolerance requests for clethodim should be defined as the combined
residues of clethodim and its metabolites containing the
5-(2-ethylthiopropyl)cyclohexene-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones (PP# 4F4340, DP Num: 203378, J. Morales,
31/JAN/1995).  The following include recommendations and deficiencies
for the following petitions.

1.  PP#3E6555:  A revised Section F for the commodity flax, seed must be
submitted redefining clethodim as the combined residues of clethodim and
its metabolites containing the 5-(2-ethylthiopropyl)cyclohexene-3-one
and 5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones, and changing the proposed tolerance from 0.5
ppm to 0.6 ppm as recommended.  The label must be changed to match the
proposed use pattern of Section B.  Additionally, the established
tolerance for flax, meal at 1.0 ppm must be removed.

2.  PP#5E6977:  A revised Section F must be submitted to the Agency
redefining clethodim as the combined residues of clethodim and its
metabolites containing the 5-(2-ethylthiopropyl)cyclohexene-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones for hops, dried cones and asparagus, and
changing the proposed tolerance to 1.7 ppm for asparagus.  The label
must be changed to match the proposed use patterns of Section B.

3.  PP#4E6836:  A revised Section F must be submitted to the Agency
redefining clethodim as the combined residues of clethodim and its
metabolites containing the 5-(2-ethylthiopropyl)cyclohexene-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones for the herb subgroup 19A.  The separate
tolerance request for cilantro leaves must be removed from the Section
F, as cilantro leaves are a member of the herb subgroup 19A.  The
proposed tolerance of 10 ppm must be changed to match the tolerance
recommended by ARIA of 12.0 ppm.  The label must be changed to match the
proposed use pattern of Section B.

4.  PP#5E6978:  A revised Section F must be submitted to the Agency
redefining clethodim as the combined residues of clethodim and its
metabolites containing the 5-(2-ethylthiopropyl)cyclohexene-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones for leafy greens subgroup 4A.  The label must
be changed to match the proposed use pattern of Section B.

5.  PP#4F6895:  A revised Section F for sesame seed must be submitted to
the Agency requesting a tolerance of 0.35 ppm to concur with the
recommended tolerance.  The petitioner must change this same Section F
to correct the commodity definition to crop group 6, vegetable legume
(except soybean) and change the proposed tolerance to 3.5 ppm.  The
label must be changed to match the proposed use patterns of Section B
with the exception of crop group 6, vegetable legume (except soybean),
for which the PHI must be changed to 30 days for the group to match the
longest PHI submitted for dry pea; therefore, a revised Section B must
also be submitted to the Agency.  The petitioner must submit a revised
label to bring the usage pattern for safflower to match that of the
proposed use pattern of Section B and sunflower, from which a direct
translation of supporting data was used.  This includes increasing the
PHI from 14 to 70 days.

6.  The labels must be revised to include the restriction “Do not
plant any crop for 30 days after application unless clethodim is
registered for use on that crop.”

7.  The petitioner must resubmit reference standards for both DME and
DME-OH to update expired samples which were previously submitted (June
1993).

9.2	Occupational Data Needs and Label Requirements  TC \l2 "9.2
Occupational Data Needs and Label Requirements 

As was indicated in the 21 February 2002 risk assessment, the interim
Worker Protection Standard (WPS) restricted entry interval (REI) for a
compound classified in Acute Toxicity Category I (primary dermal
irritation in this case) is 48 hours (see 40 CFR § 156.208 (c) (2). 
The labels provided for review list REIs of 24 hours.  It is suggested
that RD confirms or corrects these labels to reflect the proper REI.

10.0	Tolerance Summary  TC \l1 "10.0	Tolerance Summary 

The tolerance expression for clethodim in/on plants (40 CFR 180.458(a)
(3) is the combined residues of clethodim and metabolites containing the
5-(2-(ethylthiopropyl) cyclohexene-3-one and
5-(2-(ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphoxides and sulphones.

Table 16.  Summary of Proposed Tolerances for Clethodim

Commodity	Established/Proposed Tolerance (ppm)	Recommended Tolerance
(ppm)	Comments (correct commodity definition)

Leafy greens subgroup 4A	2.0	                     2.0

	Flax, seed	0.5	                     0.6

	Hop, dried cones	0.50	                     0.5

	Asparagus	2.0	                     1.7

	Herb subgroup 19A	10	                    12.0

	Sesame, seed	0.40	                     0.35

	Vegetable, legume, group	3.0	                     3.5	Corrected
commodity definition. 

Vegetable, legume, group 6, except soybean

Safflower, meal	10.0	                    10.0

	Safflower, seed	5.0	                     5.0

	

A tolerance was previously established for flax meal at 1.0 ppm.  No
processing studies were previously submitted for flax.  The tolerance on
flax meal was based on data translated from canola.  Data from the newly
submitted flax processing study indicates that the tolerance for flax,
meal at 1.0 ppm must be removed.  The processing factor for flax meal
was <0.8.  Therefore, the HAFT X Processing Factor is less than the
tolerance on flax, seed, and therefore a separate tolerance is not
required for flax, meal.

Based on the newly submitted field trial data, harmonization with
current Codex MRLs set on beans (dry), beans, except broad bean and soya
bean, field pea is not appropriate (ChemSAC, minutes of 08/FEB/2006). 
The Codex Status of these commodities should be increased to accommodate
this new data.  Harmonization with Canada on the tolerance for flax
seed, beans, chickpeas, lentils, and peas (dry) and Mexico on bean
(kidney) is also not possible based on the MRL Calculations of the newly
submitted data.  

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name:

((E)-(()-2-[1-[[(3-chloro-2-propenyl)oxy]imino]propyl]-5-[2-(ethylthio)p
ropyl]-3-hydroxy-2-cyclohexen-1-one	

Common Name: Clethodim

	

X Proposed tolerance

( Reevaluated tolerance

( Other	

Date: 01/03/2007

Codex Status (Maximum Residue Limits)	

U. S. Tolerances

( No Codex proposal step 6 or above

( No Codex proposal step 6 or above for the crops requested	

Petition Number: 4E6836

DP Num: 334913

Other Identifier:

Residue definition (step 8/CXL): Sum of clethodim and its metabolites
containing 5-(2-ethylthiopropyl) cyclohexene-3-one and
5-(2-ethylthiopropyl)- 5-hydroxycyclohexene- 3-one moieties and their
sulphoxides and sulphones, expressed as clethodim

	

Reviewer/Branch: Debra Rate/RIMUERB

	

Residue definition: combined residues of
((E)-(()-2-[1-[[(3-chloro-2-propenyl)oxy]imino]propyl]-5-[2-(ethylthio)p
ropyl]-3-hydroxy-2-cyclohexen-1-one and its metabolites containing the
5-(2-ethylthiopropyl)cyclohexene-3-one and
5-(2-(ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulphones and sulphoxides 

Crop (s)	

MRL (mg/kg)	

Crop(s) 	

Tolerance (ppm)

Beans (dry)	

2	

Herb Subgroup 19A	

12.0

Beans, except broad bean and soya bean	

0.5 (*)	

Hop, dried cones	

0.50

Field peas (dry)	

2	

Asparagus	

1.7

Soya bean (dry)	

10	

Sesame, seed	

0.35

Vegetable, legume, group (Crop Group 6)	

3.5

Safflower, meal	

10

Safflower, seed	

5.0

Leafy Greens, Subgroup 4A	2.0

Flax, seed	0.60

Limits for Canada	

Limits for Mexico

(  No Limits

(No Limits for the crops requested	

(No Limits

( No Limits for the crops requested

Residue definition:  (E,E)-(±)-2-[1-[[-3-chloro-

2-propenyl)oxy]imino]propyl]-5-[2-(ethylthio)

propyl]-3-hydroxy-2-cyclohexen-1-one,

including metabolites containing the 2-

cyclohex-1-enone moiety	

Residue definition:  clethodim

Crop(s)	

MRL (ppm)	

Crop(s)	

MRL (ppm)

Soybeans	10	Bean (kidney bean)	2

Beans	0.5	Soya bean	10

Chickpeas	0.5

Lentils	0.5

Peas (dry)	0.5

Flaxseed	0.3

S. Funk, 01/03/07

11.0	Appendix A. Subchronic and Chronic Toxicity Profile Table  TC \l1
"11.0	Subchronic and Chronic Toxicity Profile Table 

Appendix A. 	Subchronic, Chronic and Other Toxicity Profile

Guideline No. 	Study Type	MRID No. (year)/ Classification /Doses	Results

870.3100

	5-Week oral toxicity (rat)	41030110 (1986)

Acceptable/Nonguideline

0, 5, 200, 1000, 4000,  8000 ppm

equivalent to 0, 0.256, 12.5, 65.6, 261, 515 mg/kg/day in males and 0,
0.288, 13.9, 70.6, 291, 554 mg/kg/day in females	Systemic Toxicity NOAEL
= 12.5/13.9 mg/kg/day (M/F)

Systemic Toxicity LOAEL = 65.6/70.6 mg/kg/day (M/F) based on hematologic
effects, increased liver weights with supportive pathology.

870.3100

	4-Week oral toxicity (mouse)	41030103 (1986)

Acceptable-Nonguideline

0, 100, 250, 625, 1500, 4000 ppm

Calculated by standard conversion factors to 0, 22.5, 37.5, 93.8, 225.0,
600.0 mg/kg/day	Systemic Toxicity NOAEL => 93.8 mg/kg/day

Systemic Toxicity LOAEL > 93.8 mg/kg/day 

870.3100

	90-Day oral toxicity (rat) with 6 week recovery groups	41030107 (1986)

Acceptable/Guideline

0, 50, 500, 2500, 5000 ppm

0, 2.3/2.8, 25/30, 134/159, 279/341 mg/kg/day (M/F)	Systemic Toxicity
NOAEL = 25/30 mg/kg/day (M/F)

Systemic Toxicity LOAEL = 134/159 mg/kg/day (M/F) based on decreased
body weights attributable to decreased food consumption, decreased body
weight gains, and increased liver weights with a histological correlate
of centrilobular hepatic hypertrophy.

870.3150

	90-Day oral toxicity (dog)	41030106 (1987)

Acceptable/Guideline

0, 1, 25, 75, 125 mg/kg/day	Systemic Toxicity NOAEL = 75 mg/kg/day

Systemic Toxicity LOAEL = 125 mg/kg/day based on increased absolute
liver weights with histological correlates of cytoplasmic vesiculation
and vacuolation of the central lobular hepatocytes in male and female
dogs.

870.3200

	28-Day dermal toxicity (rat)	41030109 (1987)

Unacceptable (upgradable)/Guideline 

0, 1%, 10%, 100% (w/w) in 0.7% CMC & 1% Tween 80

0, 10, 100, 1000 mg/kg/day

	Systemic Toxicity NOAEL = 100 mg/kg/day

Systemic Toxicity LOAEL = 1000 mg/kg/day based on anogenital discharge
and anogenital staining on males and females, decreased food efficiency
and body weight gain for males, and increased absolute and relative
liver weight in females. 

Dermal Toxicity NOAEL = not established.

Dermal Toxicity LOAEL = 10 mg/kg/day based on skin irritation.

870.3200

Select 2.0	28-Day dermal toxicity (rat)

	41030201 (1987)

Acceptable/Guideline 

0, 10, 50, 100/200 mg/kg/day

(high dose reduced to 100 after 4 applications due to severe irritation)
Systemic Toxicity NOAEL =  100 mg/kg/day

Systemic Toxicity LOAEL = 50 mg/kg/day based on increased reticulocyte
count.

Dermal Toxicity NOAEL = not established

Dermal Toxicity LOAEL = 10 mg/kg/day based on observed dermal
irritation.

870.3700a

	Prenatal developmental in (rat)	41030114 (1986) pilot

41030116 (1987)

Acceptable/Guideline

0, 10, 100, 350, 700 mg/kg/day	

Maternal Systemic Toxicity NOAEL = 100 mg/kg/day

Maternal Systemic Toxicity LOAEL = 350 mg/kg/day based on clinical signs
of toxicity and reduced body weight gains.

Developmental Toxicity NOAEL = 100 mg/kg/day

Developmental Toxicity LOAEL= 350 mg/kg/day based on reduced fetal body
weights and reduced ossification of the lower vertebrae.

870.3700b

	Prenatal developmental in (rabbit)	41030113 (1986) pilot

41030115 (1987)

Acceptable/Guideline

0, 25, 100, 300 mg/kg/day	Maternal Systemic Toxicity NOAEL = 25
mg/kg/day

Maternal Systemic Toxicity LOAEL = 100 mg/kg/day based on clinical signs
of toxicity, reduced body weight gains, and reduced food consumption.

Developmental Toxicity NOAEL > 300 mg/kg/day 

Developmental Toxicity LOAEL: >300 mg/kg/day

870.3800

	Reproduction and fertility effects

(rat)	41030119 (1986) pilot

41030120 (1987)

Acceptable/Guideline

0, 5, 20, 500, 2500 ppm

0, 0-1/0-1, 1-2/1-3, 28-60/36-61, 141-295/180-282 mg/kg/day (M/F)	

Parental Systemic Toxicity NOAEL = 51 mg/kg/day.

Parental Systemic LOAEL = 263 mg/kg/day based on reduced body weight,
particularly in males, and reduced food consumption during both
generations. 

Reproductive Toxicity NOAEL => 263 mg/kg/day. 

Reproductive Toxicity LOAEL: > 263 mg/kg/day.

Offspring/Developmental Toxicity NOAEL => 263 mg/kg/day.

Offspring/Developmental Toxicity LOAEL > 263 mg/kg/day.

870.4100a

	Chronic toxicity

(rats)	See combined chronic toxicity/carcinogenicity

	870.4100b

	Chronic toxicity (dog)	41030111 (1988)

Acceptable/Guideline

0, 1, 75, 300 mg/kg/day in capsules	

Systemic Toxicity NOAEL = 75/1 mg/kg/day (M/F)

Systemic Toxicity LOAEL = 300/75 mg/kg/day (M/F) based on clinical
pathology in females (increased platelet count and ALT activity and
decreased glucose levels) and males (decreased RBC, I-IGB, HCT and
glucose levels; and increased platelet and leukocyte counts, cholesterol
and triglyceride levels and ALT and ALP activities).

870.4200

	Carcinogenicity

(mouse)

78 weeks	41030112 (1988)

Acceptable/Guideline

0, 20, 200, 1000, 2000/3000 ppm (high dose received 200 ppm for first 15
weeks then increased to 3000 ppm)

Calculated by standard conversion factors to 0, 1, 10, 50, 150 mg/kg/day
Systemic Toxicity NOAEL = 10 mg/kg/day

Systemic Toxicity LOAEL = 50 mg/kg/day based on treatment-related
effects on survival, red cell mass, liver weights, and microscopic
findings in the lung and liver.

No evidence of carcinogenicity. 

870.4300

	Combined Chronic Toxicity/

Carcinogenicity

(rat)	41030121 (1988)

Acceptable/Guideline

0, 5, 20, 500, 2500 ppm

0, 0.18, 0.64, 19, 100 mg/kg/day	Systemic Toxicity NOAEL = 19 mg/kg/day
in females.

Systemic Toxicity LOAEL = 100 mg/kg/day in females based on decreased
mean body weights.

Systemic Toxicity NOAEL => 100 mg/kg/day in males.

Systemic Toxicity LOAEL > 100 mg/kg/day in males.

No evidence of carcinogenicity.

870.5100 	Gene Mutation

	41030122 (1986)

Acceptable	Negative. There was no evidence of induced mutant colonies
over background in strains TA98, TA100, TA1535 and TA1537 with and
without S9 activation.-

870.5100	Gene Mutation

	41030123 (1986)

Acceptable	Negative.  There was no evidence of treatment-related induced
mutant colonies over background in strains TA98, TA100, TA1535, TA1537,
or WP2 with or without S9 activation.

870.5375

	CHO Assay	41030128 (1986)

Acceptable	Positive There was evidence of a dose-related increase in
structural chromosomal aberrations over background in the absence of
metabolic activation at concentrations near the limits of solubility and
cytotoxicity.

870.5375	CHO Assay	41030129 (1986)

Acceptable

	Negative.  There was no evidence of a dose-related increase in
structural chromosomal aberrations over background in the presence or
absence of metabolic activation at any concentration tested up to the
limit of solubility.

870.5395

	Micronucleus Assay	41030125 (1987)

Acceptable	Negative.  There is no evidence that Clethodim induced
chromosomal aberrations in bone marrow cells of rats over background
levels.

870.5550

 	Unscheduled DNA Synthesis	41030124 (1986)

Acceptable	Negative.  There was no evidence that unscheduled DNA
synthesis, as determined by radioactive tracer procedures [nuclear
silver grain counts] was induced.

870.7485

	Metabolism and pharmacokinetics

(rat)	41030132 (1988)

Single oral dose 4.5 or 450 mg

Repeated dose 4.5 or 450 mg for 14 days

Acceptable	Clethodim is readily absorbed and eliminated (87-92%, urine;
9-17%, feces; <1% expired air) after 7 days.  Gastrointestinal
absorption estimated at 89-96%.  No evidence of bioconcentration. 
Extensively metabolized with < 1% eliminated as unchanged parent
compound.  Predominant metabolite is clethodim sulphoxide (48-68%) after
48 hours.

870.7600

Select 2.0 EC (25.85% Clethodim)	Dermal penetration

(rat)	41030202 (1987)

0.05, 0.5, 5.0 mg/rat

Acceptable	Based on the results of this study, the dermal absorption
value for SELECT 2EC after 10-hours of exposure, the typical worker
exposure time, was 28.4%.

870.3100

Clethodim Imine Sulfone	5-Week oral toxicity (rat)	41030104 (1988)

Acceptable/Nonguideline

0, 80.8, 871, 7820 ppm (nominal doses)

Equivalent to 0, 6.7/7.8, 70.9/83.7, 604.0/723.0 mg/kg/day (M/F)
Systemic Toxicity NOAEL = 70.9/83.7 mg/kg/day (M/F)

Systemic Toxicity LOAEL = 604/723 mg/kg/day (M/F) based on increased
serum cholesterol and increased liver weights. 

	870.3100

Clethodim

High Purity w/process neutrals	5-Week oral toxicity (rat)	41030108
(1987)

Acceptable/Nonguideline

0, 1200 (process neutrals), 6800 (high purity clethodim) ppm

4.9/5.8, 148/175 mg/kg/day (M/F)	This study was not to establish a NOAEL
or LOAEL.  

The high purity clethodim produced lower boy weight gain, mild anemia
and mild liver hypertrophy at 148/175 mg/kg/day (M/F).

870.3700a

Clethodim

Metabolite 5-hydroxy sulfone	Prenatal developmental in (rat)	41030118
(1988)

Acceptable/Nonguideline

0, 10, 100, 700 mg/kg/day	Maternal Systemic Toxicity NOAEL => 700
mg/kg/day

Maternal Systemic Toxicity LOAEL > 700 mg/kg/day

Developmental Toxicity NOAEL => 700 mg/kg/day

Developmental Toxicity LOAEL > 700 mg/kg/day

870.3700a

Clethodim

Imine Sulfone

	Prenatal developmental in (rat)	41030117 (1988)

Acceptable/Nonguideline

0, 10, 100, 700 mg/kg/day	Maternal Systemic Toxicity NOAEL = 10
mg/kg/day

Maternal Systemic Toxicity LOAEL = 100 mg/kg/day based on reduced body
weight gains and food consumption.

Developmental Toxicity NOAEL = 100 mg/kg/day

Developmental Toxicity LOAEL = 700 mg/kg/day based on reduced fetal body
weights, reduced sternal ossification, and an increased incidence of a
cervical rib.

870.5100 

5-Hydroxy-clethodim sulfone	Gene Mutation

	41030126 (1987)

Acceptable	Negative.  There was no evidence of significant induced
mutant colonies over background in strains TA98, TA100, TA1535 and
TA1537 and WP2 uvrA with and without S9 activation. 

870.5100 

Clethodim-imine- sulfone	Gene Mutation

	41030127 (1988)

Acceptable	Negative.  There was no evidence of significant induced
mutant colonies over background in strains TA98, TA100, TA1535 and
TA1537 and WP2 uvrA with and without S9 activation. 

870.5375

Clethodim-imine- sulfone	CHO Assay	41030130 (1988)

Acceptable	Negative.  There was no evidence of a dose-related increase
in structural chromosomal aberrations over background in the presence or
absence of metabolic activation at any concentration tested up to the
limit of solubility.

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