Document ID: EPA-HQ-OPP-2008-0658-0004
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-09-16T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

     OFFICE OF	

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

Date: 09/28/2007

MEMORANDUM

SUBJECT:	Clethodim: Human Health Risk Assessment for Proposed Use on
Field Corn. PC Code: 121011, Petition No.: PP#6F7117.  DP Number:
D333332.

		Regulatory Action: Registration Action New Section 3 Use

		Risk Assessment Type: Single Chemical Aggregate

FROM:	Christine L. Olinger, Risk Assessor

		Reregistration Branch 1

		Health Effects Division (7509P)

			AND

		Jerry Stokes, Chemist

Reregistration Branch 4

		Health Effects Division (7509P)

			AND

		Mark Dow, Ph.D., Biologist

		Debra Rate, Biologist

		Alternative Risk Integration Assessment (ARIA) Team

		Risk Integration Minor Use & Emergency Response Branch (RIMUERB)

		Registration Division (7505P)

THROUGH:	Michael S. Metzger, Chief

		Registration Action Branch 3

		Health Effects Division (7509P)

	AND

Paula Deschamp, Chief

		Registration Action Branch 3

		Health Effects Division (7509P)

TO:	Joanne Miller/James Stone

		Herbicide Branch 

		Registration Division (RD) (7505P) 

Valent U.S.A. Corporation has submitted an application to amend the
registration of the end-use product (EP) V-10137 1 EC Herbicide (EPA
Reg. No. 59639-132), an emulsifiable concentrate (EC) formulation of
clethodim containing 12.6% or 0.97 lb ai/gal, to include a new use on
field corn.

A summary of the findings and an assessment of human risk resulting from
the registered and proposed tolerances for clethodim are provided in
this document.  The risk assessment was provided by Christine Olinger
(RRB1), the residue chemistry data review by Jerry Stokes (RRB4) and
Debra Rate (ARIA), the dietary risk assessment by Debra Rate (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 _Toc178739302 \h  4 

2.0	Ingredient Profile	  PAGEREF _Toc178739303 \h  8 

2.1	Summary of Registered/Proposed Uses	  PAGEREF _Toc178739304 \h  8 

3.0	Hazard Characterization/Assessment	  PAGEREF _Toc178739305 \h  10 

3.1	FQPA Considerations and Safety Factor for Infants and Children	 
PAGEREF _Toc178739306 \h  12 

3.2	Toxicity Endpoint Selection	  PAGEREF _Toc178739307 \h  12 

3.3	Endocrine disruption	  PAGEREF _Toc178739308 \h  13 

4.0	Dietary Exposure/Risk Characterization	  PAGEREF _Toc178739309 \h 
14 

4.1  Pesticide Metabolism and Environmental Degradation	  PAGEREF
_Toc178739310 \h  14 

4.1.1	Metabolism in Primary Crops	  PAGEREF _Toc178739311 \h  14 

4.1.2	Metabolism in Livestock	  PAGEREF _Toc178739312 \h  14 

4.1.3	Analytical Methodology	  PAGEREF _Toc178739313 \h  15 

4.1.4	Storage Stability Data	  PAGEREF _Toc178739314 \h  16 

4.1.5	Magnitude of the Residue in Plants	  PAGEREF _Toc178739315 \h  16 

4.1.6	Magnitude of the Residue in Processed Food/Feed	  PAGEREF
_Toc178739316 \h  16 

4.1.7	Magnitude of the Residue in Meat, Milk, Poultry, and Eggs	 
PAGEREF _Toc178739317 \h  17 

4.1.8	Confined and Field Accumulation in Rotational Crops	  PAGEREF
_Toc178739318 \h  17 

4.1.9	Drinking Water Residue Profile	  PAGEREF _Toc178739319 \h  17 

4.1.10	Proposed Tolerances	  PAGEREF _Toc178739320 \h  18 

4.2  Dietary Exposure and Risk	  PAGEREF _Toc178739321 \h  18 

4.2.1  Acute Dietary Exposure/Risk	  PAGEREF _Toc178739322 \h  19 

4.2.2  Chronic Dietary Exposure/Risk	  PAGEREF _Toc178739323 \h  19 

4.2.3 Cancer Dietary Risk	  PAGEREF _Toc178739324 \h  21 

5.0	Residential (Non-Occupational) Exposure/Risk Characterization	 
PAGEREF _Toc178739325 \h  21 

6.0	Aggregate Risk Assessments and Risk Characterization	  PAGEREF
_Toc178739326 \h  21 

7.0	Cumulative Risk Characterization/Assessment	  PAGEREF _Toc178739327
\h  22 

8.0	Occupational Exposure/Risk Pathway	  PAGEREF _Toc178739328 \h  22 

8.1	Short-/Intermediate-Term Handler Risk	  PAGEREF _Toc178739329 \h  22

8.2	Short-/Intermediate-Term Postapplication Risk	  PAGEREF
_Toc178739330 \h  25 

9.0	Data Needs and Label Requirements	  PAGEREF _Toc178739331 \h  25 

9.1	Residue Chemistry Data Needs and Label Requirements	  PAGEREF
_Toc178739332 \h  25 

9.2	Occupational Data Needs and Label Requirements	  PAGEREF
_Toc178739333 \h  26 

Appendix A.  Toxicity Profile Tables	  PAGEREF _Toc178739334 \h  27 

Appendix B:  Review of Human Research	  PAGEREF _Toc178739335 \h  33 

 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
ornamentals 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.

Valent U.S.A. Corporation has submitted an application to amend the
registration of the end-use product (EP) V-10137 1 EC Herbicide (EPA
Reg. No. 59639-132), an emulsifiable concentrate (EC) formulation of
clethodim containing 12.6% or 0.97 lb ai/gal, to include a new use on
field corn.  The petitioner claims that V-10137 1 EC Herbicide is
ideally suited to control volunteer corn especially Roundup Ready® corn
that cannot be controlled with products containing glyphosate. The
proposed EP is to be used as a preplant burndown product for removing
Roundup Ready® corn in fields that are intended for replanting.  It is
proposed for a single preplant application using ground or aerial
equipment on field corn.  Only one application may be made per growing
season at a maximum seasonal rate of 0.05 lb ai/A.  The proposed
preharvest interval (PHI) is 90 days.

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 (no observable adverse affects level) 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

HED has determined that a developmental neurotoxoicty need not be
performed because there is no evidence in the available studies that
clethodim is neurotoxic.  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. 
There is a complete database for toxicity and exposure, no evidence of
increased sensitivity, and no neurotoxicity concerns which support the
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.  The
existing uses of clethodim have higher application rates than the
proposed new use on corn, so estimated drinking water concentrations
(EDWCs) are based on the existing uses.  Tier 1 surface water
concentrations for parent clethodim and total toxic residues (parent +
sulfoxide + sulfone) were estimated using the FIRST (FQPA Index
Reservoir Screening Tool) model and are based on a maximum application
rate of 0.5 lb ai/acre per year (2 applications).  The peak EDWC in
surface water is 38.9 ppb and the chronic EDWC is 7.6 ppb.  Ground water
sources were not included, as the estimates 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. 
Tolerance level residues for the existing uses as well as the proposed
new uses were used for all commodities except succulent beans.  An
average of the field trial data was used for succulent beans.  This
partially refined chronic dietary exposure assessment incorporated
percent crop treated information for most of the existing crops, and
assumed that all corn was treated. 

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 27% cPAD
for the general U.S. population and 73% 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 were incorporated directly into the
dietary exposure analysis to assess aggregate risk.  All of the
population subgroups evaluated are below the level of concern.

Occupational Handler Exposure Assessment

Potential occupational exposure scenarios for handlers of clethodim
include mixer/loaders using open-pour loading of liquid formulations in
support of aerial operations, mixer/loader/applicators using
low-pressure hand-wand sprayers, applicators using open-cab, ground-boom
sprayers, applicators using high-pressure "spray-guns" and aerial
applicators.  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 Margin of Exposure (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 the level of concern
provided mixer/loaders wear protective gloves that are required Personal
Protective Equipment (PPE) on the proposed label considered here.

Occupational Postapplication Exposure Assessment

Workers performing postapplication activities such as scouting 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, do not exceed the 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 label provided for review lists an REI of 24 hours.  It is suggested
that RD confirms or corrects this label to reflect the proper REI of 48
hours.

Recommendations

  SEQ CHAPTER \h \r 1 Pending the receipt of the revised Section B and
label as described below, 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 corn, field,
forage at 0.2 ppm, corn, field, grain at 0.2 ppm, and corn, field,
stover at 0.2 ppm.   The Agency is requesting clarification on the
proposed use pattern described in Section B of the petition and the
proposed label, as it is somewhat inconsistent with the crop field trial
data submitted.  The product label includes a restriction prohibiting
the use of crop oil concentrate (COC) or methylated seed oil (MSO) on
field corn whereas the submitted field corn trials reflected the use of
1% crop oil concentrate in the spray mixtures.  HED does not have any
objections to the removal of this restriction if there are no
phytotoxicity issues.  In addition, the use directions state that
application should be sooner than 10 days before planting at the higher
rate and no sooner than 5 days before planting at the lower rate. 
However, the field trials in this submission state that applications
were made on the same day of planting or within 3 days of planting. 
Also the application rate was 2X the proposed label use rate.  The
registrant should clarify their intentions for use directions.  If these
differ from the Section B submitted in this petition, then a revised
Section B must be submitted.

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 label provided for review lists an REI of 24 hours.  It is suggested
that RD confirms or corrects this label to reflect the proper REI of 48
hours.

Environmental Justice Concerns  

Potential areas of environmental justice concerns, to the extent
possible, were considered in this human health risk assessment, in
accordance with U.S. Executive Order 12898, “Federal Actions to
Address Environmental Justice in Minority Populations,”
http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf
.

As a part of every pesticide risk assessment, OPP considers a large
variety of consumer subgroups according to well-established procedures. 
In line with OPP policy, HED estimates risks to population subgroups
from pesticide exposures that are based on patterns of that subgroup’s
food and water consumption, and activities in and around the home that
involve pesticide use in a residential setting.  Extensive data on food
consumption patterns are compiled by the USDA under the Continuing
Survey of Food Intake by Individuals (CSFII) and are used in pesticide
risk assessments for all registered food uses of a pesticide.  These
data are analyzed and categorized by subgroups based on age, season of
the year, ethnic group, and region of the country.  Additionally, OPP is
able to assess dietary exposure to smaller, specialized subgroups and
exposure assessments are performed when conditions or circumstances
warrant.

Review of Human Research  

This risk assessment relies in part on data from studies in which adult
human subjects were intentionally exposed to a pesticide or other
chemical.  These studies (listed in Appendix B) have been determined to
require a review of their ethical conduct, and have received that
review.

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 the
residue chemistry summary document (J. Stokes and D. Rate, D333329,
7/9/07).

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

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.  

Valent U.S.A. Corporation has submitted an application to amend the
registration of the end-use product V-10137 1 EC Herbicide (EPA Reg. No.
59639-132) to include a new use on field corn. The EP contains 12.6% ai
(equivalent to 0.97 lb ai/gal) and belongs to the emulsifiable
concentrate (EC) class of formulation.  It is intended to control
existing stand of Roundup ready field corn or volunteer Roundup ready
field corn prior to replanting field corn.  A summary of the proposed
use pattern on field corn is detailed in Table 3.

Table 3.  Summary of Proposed Use Directions of Clethodim on Field Corn.

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

(lb ai/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ai/A)	PHI

(days)	Use Directions and Limitations

Preplant

Ground (min. of 5 gallons/acre) or aerial (min. of 3 gallons/acre)	0.97
lb ai/gal EC

[59639-132]	0.03-0.05	1	0.05	90	At the higher rate (0.05 lb ai/A),
application may be made no sooner than 10 days before planting.  At the
lower rate (0.03 lb ai/A) application may be made no sooner that 5 days
before planting.  An adjuvant [non-ionic surfactant (NIS) at 0.25% v/v]
plus ammonium sulfate [(AMS) at 2.5-4 lb/A] should be added at
recommended rates.  Use of COC or MSO is prohibited.  

The proposed label specifies the following rotational crop restriction: 
“Do not plant rotational crops until 30 days after application unless
crop is listed on the label.”

Conclusions.  The use directions for field corn listed in V-10137 1 EC
Herbicide (EPA Reg. No. 59639-132) are adequate to allow evaluation of
the residue data relative to the proposed use.  HED, however, notes that
the product label includes a restriction prohibiting the use of COC or
MSO on field corn whereas the submitted field corn trials reflected the
use of 1% crop oil concentrate in the spray mixtures.  HED does not have
any objections to the removal of this restriction if there are no
phytotoxicity issues.  In addition, the use directions state that
application should be sooner than 10 days before planting at the higher
rate and no sooner than 5 days before planting at the lower rate. 
However, the field trials in this submission state that applications
were made on the same day of planting or within 3 days of planting. 
Also the application rate was 2X the proposed label use rate.  The
registrant should clarify their intentions for use directions.  If these
differ from the Section B submitted in this petition, then a revised
Section B must be submitted.

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 21/28-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 75 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.  The 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 sulfoxide (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 liver effects that were observed in a subchronic
oral toxicity study in dogs.  A NOAEL of 25 mg/kg/day was identified by
the HIARC in 1997 for intermediate-term dermal and inhalation risk
assessments.  Recently, there have been modifications to the policy for
selecting endpoints from studies where liver effects have been observed.
 The effects noted by the HIARC, increased liver weights, are now
considered to be adaptive responses, and should not be considered
adverse.  The point of departure (POD) originally selected by the HIARC,
25 mg/kg/day, will be used in this assessment, but future assessments
should use a POD of 75 mg/kg/day for intermediate-term dermal and
inhalation exposures.

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

Doses and toxicological endpoints selected for various exposure
scenarios are summarized in Table 3.1.  Acute toxicity categories for
clethodim as well as the subchronic and chronic toxicity profile table
may be found in Appendix A. 

Table 3.1. 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) 1.

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

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). 1

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

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

1 The POD used in the intermediate term assessments is based on the
original review of this study that selected liver weights as the effect
of concern.  Recent policy changes consider the liver weight changes as
an adaptive response and the revised evaluation of the study recommend
for modifying the NOAEL and LOAEL.  Although this assessment uses the
original POD selected, future assessments should used the revised
values.

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.  PP#6F7117.  Request For Amended Registration of
V-10137 1 EC Herbicide (EPA Reg. No. 59639-132) to Add New Use on Field
Corn and a Proposal to Establish Tolerances.  Summary of Analytical
Chemistry and Residue Data.  DP Number 333329; J. Stokes and D. Rate;
07/09/07.  Unless otherwise noted, information in this section is based
on this review.

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

A corn metabolism study was not submitted with this petition.  HED has
previously determined that the nature of the residue in plants is
adequately understood based on previously submitted metabolism studies
conducted on a root crop (carrots) and oilseeds (soybeans and cotton). 
For the purpose of this petition only, the available metabolism data for
soybean foliage, cotton foliage, and carrot leaves can support the
proposed use on the requested RACs (field corn forage and stover), and
the metabolism data for soybean seed and cottonseed can support the
proposed use on the field corn grain.  The residues of concern in crop
commodities are clethodim and its metabolites containing the
5-(2-ethylthiopropyl) cyclohexene-3-one and
5-(2-ethylthiopropyl)-5-hydroxycyclohexene-3-one moieties and their
sulfoxides and sulfones.  

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.  

4.1.3	Analytical Methodology  TC \l3 "4.1.3	Analytical Methodology 

Enforcement Method for Plants

PP#9F3743, M. Nelson, 5/4/90

  SEQ CHAPTER \h \r 1 Method RM-26B-2, which determines residues of
clethodim sulfoxide and its metabolite (5-OH clethodim sulfone) in crop
commodities, is available for tolerance enforcement and data collection.
 Method RM-26B-2 has undergone a successful petition method validation
in EPA Laboratories.  This method has been sent to FDA for publication
in the Pesticide Analytical Manual Volume II (PAM II).

Method RM-26B-3 (a modification of RM-26B-2) was the analytical method
used to assay clethodim residues of concern in the submitted corn field
trials and processing study.  Briefly, residues of clethodim in corn
commodities were extracted with methanol (MeOH) and water, filtered, and
concentrated.  The residues were diluted with MeOH and water and cleaned
up by alkaline precipitation with the addition of calcium hydroxide. 
Residues in the resulting supernatant were filtered, acidified with
concentrated HCl, salinized, partitioned into dichloromethane (DCM), and
concentrated to remove the DCM.  Residues were diluted with 1% aqueous
barium hydroxide, oxidized with hydrogen peroxide solution under reflux,
cooled, and excess peroxide in the extracts was decomposed by adding
catalase and potassium pyrosulfite.  Residues were diluted with glacial
acetic acid, concentrated to dryness, redissolved in MeOH, and
derivatized in an acidified (HCl) MeOH solution under reflux (30
minutes) to dimethylester sulfone (DME) and 5-hydroxy dimethylester
sulfone (DME-OH).  Residues were cooled, neutralized with sodium
bicarbonate, partitioned into DCM, filtered, and concentrated to
dryness.  Residues were redissolved in acetone and (optionally) cleaned
up using a silica gel column.  Residues were analyzed by by gas
chromatography with flame photometric detection in the sulfur mode
(GC/FPD-S), and expressed as parent using molecular weight conversion
factors.  The adequacy of the method for data collection was verified by
fortifying untreated samples of field corn matrices with clethodim or
clethodim sulfoxide and 5-hydroxy clethodim sulfone at spike levels of
0.1-2.0 ppm.  Overall, method recoveries were within the acceptable
range of 70-120%.  The lowest level of concurrent method validation for
residues of DME and DME-OH (calculated as clethodim) were 0.1 ppm for
corn forage, grain, stover, and the processed commodities (flour, meal,
starch, and oil) and 0.2 ppm for grits

Analytical Methods - Livestock

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

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 

Samples collected from the field corn trials were stored frozen prior to
residue analysis for maximum intervals of 352 days (11.6 months) for
field corn forage, 298 days (9.8 months) for field corn grain, and 356
days (11.7 months) for field corn stover.  A concurrent storage
stability study was conducted in order to validate the storage
conditions and intervals of harvested RAC samples.  The storage
stability data showed that residues of clethodim and its metabolites are
reasonably stable under frozen storage for 425 days (14.0 months) in
field corn forage, 298 days (9.8 months) in field corn grain, and 535
days (17.6 months) in field corn stover.  Correction of the residue data
for storage degradation is not required.  No storage stability data are
required for the processed commodities of field corn because samples
were stored ~30 days prior to analysis.

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

The submitted residue data for field corn forage, grain, and stover are
adequate to fulfill data requirements.  The number and locations of
trials conducted are adequate and represent a 25 percent reduction in
the typical number of field trials due to the pesticidal use resulting
in no quantifiable residues.  The combined residues of clethodim and its
metabolites were less than the data-collection method limit of detection
(LOD) (<0.10 or <0.20 ppm) in/on all samples (n=34) of field corn
forage, grain, and stover which received one preplant application of the
test formulation at 0.092-0.097 lb ai/A (1.8-1.9x the maximum proposed
seasonal rate).  The proposed tolerances of 0.2 ppm each for field corn
forage, grain, and stover are adequate and reflect the combined limits
of quantitation (LOQs) of the common moiety enforcement method.  Residue
data and a tolerance for the aspirated grain fractions of field corn are
not required because residues are not expected in this commodity
following preplant application.

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

The submitted processing data for field corn grain are adequate to
fulfill data requirements.  Residues of clethodim, as DME and DME-OH,
reported as clethodim equivalents, were below the LOD (<0.05 ppm for
each analyte) in starch, refined oil, grits, meal, and flour.  The field
corn grain samples that were used for processing were treated at 0.471
lb ai/A (9.4x the maximum proposed seasonal rate) and also bore <0.05
ppm residues for each analyte.  The results suggest that tolerances for
the processed commodities of field corn grain are not required.

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).

The proposed use on field corn is not likely to significantly increase
the dietary burdens for beef cattle, dairy cattle, and swine.  An
acceptable dairy cattle feeding study is available, and the results from
this study indicate that secondary residues in meat and milk will not
exceed the established tolerances.  The proposed use on field corn is
not likely to significantly increase the dietary burden for poultry.  An
acceptable poultry feeding study is available, and the results from this
study indicate that secondary residues in poultry eggs and meat 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,
6/26/90).  Results indicated that there is no need for field rotational
crop trials.  A 1- month plantback interval for crops rotated with
alfalfa was specified (DP# 236382, M. Collantes, et. al, 2/10/98).  The
general restrictions and limitations state do not plant rotational crops
until 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 

References:  Drinking water assessment for Clethodim on corn. PC Code
121011, DP Barcode: 333334, I. Abdel-Saheb, 5/25/07. 

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.

The proposed use application rates for corn are lower than the existing
uses of clethodim.  Therefore, the Environmental Fate and Effects
Division (EFED) has recommended using the estimated drinking water
concentrations (EDWC) from a previous assessment (I. Abdel-Saheb,
11/30/06).  The EDWCs used in this assessment may be found in the
following table. A more detailed description of the environmental fate
characteristics may be found in the aforementioned assessment.   

Table 4.1	Summary of Estimated Surface Water and Groundwater
Concentrations for the Combined Residues of Clethodim, Clethodim
Sulfoxide, and Clethodim Sulfone.

Scenario	Surface Water Conc., ppb a	Groundwater Conc., ppb b

Acute	38.9	1.39

Chronic (non-cancer)	7.6	1.39

a From the FIRST (FQPA Index Reservoir Screening Tool) Model

b From the SCI-GROW (Screening Concentration In GROund Water)model 

4.1.10	Proposed Tolerances TC \l3 "4.1.10	Proposed Tolerances 

Valent proposes that the residues of concern be defined as the parent,
clethodim and its metabolites containing the 5-[2-(ethylthio)propyl]
cyclohexen-3-one and the
5-[2-(ethylthio)propyl]-5-hydroxycyclohexen-3-one moieties and their
sulfoxides and sulfones, expressed as clethodim.  The proposed tolerance
expression is consistent with the clethodim tolerance expression listed
in [40 CFR 180.458(a)(3)] 

A summary of the recommended tolerances for raw agricultural commodities
associated with the current petition is listed in Table 4.2.  The
proposed tolerance in field corn forage, grain, and stover is 0.2 ppm,
the limit of quantitation of the residue analytical enforcement method. 
The Agency’s Guidance for Setting Pesticide Tolerances Based on Field
Trial Data was not used to determine tolerance levels for field corn
forage, grain, and stover since all treated samples bore residues below
the data-collection method LOD.

Table 4.2. 	Tolerance Summary for Clethodim.

Commodity	Established/Proposed Tolerance (ppm)	Recommended Tolerance
(ppm)	Comments; Correct Commodity Definition

Corn, Field, Forage	0.2	0.2	[Corn, field, forage]

Corn, Field, Grain	0.2	0.2	[Corn, field, grain]

Corn, Field, Stover	0.2	0.2	[Corn, field, stover]

There are no Codex, Canadian, or Mexican MRLs established for residues
of clethodim in/on the commodities discussed in the subject petition;
therefore, there are no questions with respect to Codex/U.S. tolerance
compatibility.  Codex MRLs are currently established on various crop and
livestock commodities in terms of the 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.  

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

Reference: Clethodim: Chronic Dietary (Food and Drinking Water) Exposure
Assessment for the Valent U.S.A. Corporation Petition Proposing
Tolerances for Residues of Clethodim on Field Corn (PP#6F7117); DP
Number 339714; D. Rate, 7/14/07.

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.

of 7.63 μg/L.

Tolerance level residues for the existing uses as well as the proposed
new uses were used for all commodities except succulent beans.  An
average of the field trial data was used for succulent beans.  Percent
crop treated (%CT) values were used for some commodities and were
obtained from a Screening-Level Usage Analysis (SLUA) (A. Grube,
11/21/2006), and may be found in Table 4.3.   DEEM default processing
factors were used for sesame oil, dried meat, dried onions, peanut
butter, and tomato processed commodities.  Processing studies have not
shown concentration of residues in corn processed commodities, so the
processed commodities were assumed to have the same residues as the raw
commodity.

Table 4.3.  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 is 27% of the
cPAD for the U.S. population.  The chronic dietary exposure for the
highest reported exposed population subgroup, children 1-2 years old, is
73% of the cPAD.

The results of the chronic dietary exposure analysis are reported in the
Table 4.4 below. 

Table 4.4.  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	0.002737	27

All Infants (< 1 year old)	0.007157	72

Children 1-2 years old	0.007270	73

Children 3-5 years old	0.005667	57

Children 6-12 years old	0.003647	37

Youth 13-19 years old	0.002347	24

Adults 20-49 years old	0.002144	21

Adults 50+ years old	0.002211	22

Females 13-49 years old	0.002056	21

* % 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 for more commodities, 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 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” human carcinogen. 
Therefore, clethodim is not expected to pose a cancer risk for humans. 

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

There are no new proposed or existing uses of clethodim that will result
in residential exposures. Therefore, a residential exposure risk
assessment was not conducted. 

 

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  
HYPERLINK "http://www.epa.gov/pesticides/cumulative/" 
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 Field Corn. PC Code: 121011, DP Number
339716, M. Dow, 5/31/07.

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

For the proposed new uses, the most highly exposed occupational
pesticide handlers are expected to be mixer/loaders using open-pour
loading of liquid formulations in support of aerial operations,
mixer/loader/applicators using low-pressure hand-wand sprayers,
applicators using open-cab, ground-boom sprayers, applicators using
high-pressure "spray-guns", aerial applicators, and flaggers of aerial
applications.  It is anticipated that most ground applications will be
applied by the grower.  Although treatment blocks may be quite large, it
is unlikely that pesticide handlers would be exposed continuously for 30
days or more (short-term duration exposures).  Short-term exposures are
much more likely to occur, but that the IT assessment was conducted
because is possible for handlers to have intermediate-term exposure.

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 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” and the use of protective gloves or other PPE
as might be necessary.   The proposed label directs applicators and
other handlers to wear long-sleeved shirt, long pants, shoes plus socks,
chemical resistant gloves and protective eyewear. 

Since the short-term and the intermediate-term dermal and inhalation
NOAELs were identified from the same oral 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).  A 30% dermal absorption factor was used when
calculating dermal exposure and 100% absorption was used when estimating
exposure via the inhalation route.  Further information on the toxicity
may be found in Section 3.2 of this document.  A MOE of 100 is adequate
to protect occupational pesticide handlers from short- or
intermediate-term exposures to clethodim.  

A summary of the estimated risks may be found in Table 8.1.  The
proposed use patterns do not exceed HED’s level of concern provided
mixer/loaders wear protective gloves as is currently included on the
proposed label for corn.



Table 8.1.  Estimated Risks for Short- and Intermediate-Term
Occupational Exposures from the Proposed New Use of Clethodim on Corn.

Exposure Scenario	Application Rate

(lb a.i./acre)1	Units Treated Daily 2	Inhalation Unit Exposure (mg
a.i./lb)3	Dermal Unit Exposure (mg a.i./lb)3	Combined Dermal +
Inhalation Exposure

	Mitigation Level	Short-Term MOE 4	Intermediate-Term MOE 4

Mixer/Loader – Liquid – Open Pour	0.045 lb 	1200 A	0.0012 HC	2.9 HC
Single Layer, No Gloves	150	37

0.023 HC	Single Layer, Gloves	16,000	4,000

Applicator – Ground-boom – Open Cab	0.045 lb 	200 A	0.00074 HC	0.014
HC	Single Layer, No Gloves	160,000	39,000

Applicator – Fixed Wing – Aerial	0.045 lb 	1200 A	0.000068 MC	0.005
MC	Single Layer, No Gloves	80,000	20,000

Mixer/Loader/Applicator – Low Pressure Hand Wand	0.045 lb	40 gal/day
at 5 gal/A	0.03 MC	100 LC	Single Layer, No Gloves	650	160

0.43 LC	Single Layer, Gloves	120,000	31,000

Mixer/Loader/Applicator – High Pressure Spray Gun	0.045 lb	1000
gal/day at 5 gal/A	0.12 HC	3.0 LC	Single Layer, No Gloves	760	190

2.5 LC	Single Layer, Gloves	870	220

Flagger	0.045 lb	350 A	0.00035 HC	0.011 HC	Single Layer, No Gloves
120,000	30,000

1.  Applic. Rate from Section B of the submission

2.  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; 

3.  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:  Single layer work clothing
(long pants, long-sleeved shirt, shoes plus socks).  Units = mg
a.i./pound of active ingredient handled.  Data Confidence: LC = Low
Confidence, MC = Medium Confidence, HC = High Confidence.

4.  Combined Margin of Exposure (MOE) = NOAEL /(ADDdermal +
ADDinhalation); ADD =  Average Daily Dose = Unit Exposure * Application
Rate * Units Treated * Absorption Factor  (30% dermal absorption & 100%
inhalation absorption) ( Body Weight (70 kg); NOAEL = No Observable
Adverse Effect Level of 100 mg a.i./kg bw/day for short-term dermal and
inhalation exposures, and 25 mg a.i./kg bw/day for intermediate-term
dermal and inhalation exposures.

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

It is possible for agricultural workers to have post-application
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 post-application
agricultural activities that may occur and which may result in
post-application exposures to pesticide residues.  

For the proposed new use on field corn, scouting is the most likely
early season activity.  Due to the low vapor pressure of clethodim, the
only exposure pathway of concern is dermal contact with treated foliage.
  The following information was used in the post-application assessment:

Transfer coefficient of (TC) of 400 cm²/hr (HED ExpoSAC Standard
Operating Procedure (SOP) No. 3.1)

Lacking compound specific dislodgeable foliar residue (DFR) data, OPP
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). 

Application Rate of 0.045 lb ai/A

8 hour work day

30% Dermal Absorption

The estimated short-term post-application margin of exposure for
scouting corn treated with clethodim is 72,000, which exceeds 100, and
therefore, is not of concern.  

Restricted Entry Interval (REI)

As was indicated in previous risk assessments, 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 label
provided for review lists an REI of 24 hours.  It is suggested that RD
confirms or corrects this label 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 

The use directions for field corn listed in V-10137 1 EC Herbicide (EPA
Reg. No. 59639-132) are adequate to allow evaluation of the residue data
relative to the proposed use.  HED, however, notes that the product
label includes a restriction prohibiting the use of COC or MSO on field
corn whereas the submitted field corn trials reflected the use 1% crop
oil concentrate in the spray mixtures.  HED does not have any objections
to the removal of this restriction if there are no phytotoxicity issues.
 In addition, the use directions state that application should be sooner
than 10 days before planting at the higher rate and no sooner than 5
days before planting at the lower rate.  However, the field trials in
this submission state that applications were made on the same day of
planting or within 3 days of planting.  Also the application rate was 2X
the proposed label use rate.  The registrant should clarify their
intentions for use directions.  If these differ from the Section B
submitted in this petition, then a revised Section B must be submitted.

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 label provided for review lists an REI of 24 hours.  It is suggested
that RD confirms or corrects this label to reflect the proper REI.

  TC \l1 " Appendix A.  Toxicity Profile Tables 

Appendix A.  Toxicity Profile Tables

Table A.1	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 A.2. 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.

Note that the NOAEL/LOAEL selected above represents the values selected
in the revised Data Evaluation Record (DER).  The original DER selected
NOAELs and LOAELs based only on increased liver weights, which is now
considered an adaptive response and is not considered an adverse effect.

870.3200

	21/28-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

	21/28-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 =  50 mg/kg/day

Systemic Toxicity LOAEL = 100 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 2000 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 body 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.

Appendix B:  Review of Human Research TC \l1 " Appendix B:  Review of
Human Research 

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Agricultural Chemicals Association, released February, 1995."

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