Document ID: EPA-HQ-OPP-2009-0307-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-06-10T04:00Z

EPA Registration Division contact: Sidney Jackson 703-305-7610

Interregional Research Project Number 4 

PP 8E7505

 	EPA has received a pesticide petition (PP) 8E7505 from the
Interregional Research Project Number 4 (IR-4), IR-4 Project
Headquarters, Rutgers, The State University of New Jersey, 500 College
Road East, Suite 201 W, Princeton, NJ  08540, proposing, pursuant to
section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 346a(d), to amend 40 CFR part 180, by establishing a tolerance
for combined residues of the herbicide clethodim,
((E)-(+/-)-2-[1-[[(3-chloro-2-propenyl)oxy]imino]propyl]-5-[2-(ethylthio
)propyl]-3-hydroxy-2-cyclohexen-1-one) and its metabolites containing
the 5-(2-(ethylthio)propyl]cyclohexen-3-one and the
5-[2-(ethylthio)propyl]-5-hydroxycyclohexen-3-one moieties and their
sulfoxides and sulfones, expressed as clethodim, in or on the raw
agricultural commodity artichoke, gloge at 1.3 parts per million (ppm),
bushberry subgroup 13-07B at 3.0 ppm, caneberry subgroup 13-07A at 0.30
ppm and peach at 0.20 ppm.  EPA has determined that the petition
contains data or information regarding the elements set forth in section
408(d)(2) of the FFDCA; however, EPA has not fully evaluated the
sufficiency of the submitted data at this time or whether the data
support granting of the petition.  Additional data may be needed before
EPA rules on the petition.

A. Residue Chemistry                                       

. The metabolism of clethodim is adequately understood for the purpose
of granting the proposed tolerances.

.  Practical analytical methods for detecting and measuring levels of
clethodim have been developed and validated in/on all appropriate
agricultural commodities and respective processing fractions.  The limit
of quantification (LOQ) of clethodim in the methods is 0.2 ppm, which
will allow monitoring of food with residues at the levels proposed for
the tolerances.

.  Residue data has been submitted which adequately support the
requested tolerances. 

B. Toxicological Profile

A summary of the toxicological endpoints for clethodim used for human
risk assessment is discussed in Unit III.B of the Federal Register of
March 14, 2001 (66 FR 14829)(FRL-6770-8).  Chronic and short-term,
intermediate-term, and long-term aggregate risk assessments are
appropriate for clethodim and were performed by EPA.

C. Aggregate Exposure

.  A chronic dietary analyses was conducted to estimate exposure to
potential clethodim residues in/on the following crops and food items:
root and tuber vegetables, leaves of root and tuber vegetables, bulb
vegetables, leafy vegetables, brassica leafy vegetables, legume
vegetables (succulent and dry), fruiting vegetables, cucurbits
vegetables, berries, cranberry, strawberry, asparagus, peanuts, cotton,
sunflower, safflower, canola (rapeseed), flaxseed, hops, mint, sesame,
basil, alfalfa, clover, field corn, and incurred secondary residues in
meat, poultry, and milk.  All listed crops have approved tolerances,
except for leaves of root and tuber vegetables and berries, which is one
of the proposed uses. This risk analysis was conducted using the
Cumulative and Aggregate Risk Evaluation System (CARES, Version 2.2,
Built 7.8.4, February 13, 2006).   SEQ CHAPTER \h \r 1 The addition of
the proposed uses to the approved uses of clethodim is expected to make
a negligible incremental risk to the dietary risk assessment conducted
and therefore, the assessment has not been repeated to include these
minor uses.

This dietary analyses utilized field residue trial data distribution,
incurred secondary residues in meat, poultry, and milk (calculated based
on worse-case diets of cattle, poultry or swine), experimentally
determined processing factors (or default values when studies are not
available), 3-year average % crop treated, consumption data from
USDA’s Continuing Survey of Food Intakes by Individuals (CSFII) from
1994-1996, 1998 (USDA, 2000), and the USEPA guidance documents (USEPA,
1999 and USEPA, 2000).  These exposure and risk analyses are consistent
with the USEPA’s Tier III (for food) approach.  

For Drinking water, a Tier I modeling for estimating drinking water
concentration, conducted by EFED (Draft HED Memorandum to D. Kenny, J.
Miller, PM Team 23, dated 2/10/1998) was utilized.  These modeled water
concentrations were used in combination of water consumption data
(CSFII). These analyses for drinking water exposure are consistent with
USEPA’s Tier I approach.

.  a. Acute exposure - No acute endpoint has been identified for
clethodim. Therefore, no assessment of acute exposure from food is
required.

b. Chronic exposure - The chronic dietary exposure estimate of clethodim
residues in food was calculated to be, at most, 11.6% of the chronic
Population Adjusted Dose (c-PAD) with a MOE of 880. The population
subgroup with the highest exposure was children 1-2 years old. 

 The c-PAD was defined as the NOAEL from a 1-year chronic dog study and
includes an uncertainty factor of 100 to account for intra- and
inter-species variation  (NOAEL = 1 mg/kg bw/day, c-PAD = 0.01
mg/kg/day).

.   The chronic dietary exposure estimate of clethodim residues in
drinking water was calculated to be, at most, 20.6% of the chronic
Population Adjusted Dose (c-PAD) with a MOE of 630.  The population
subgroup with the highest exposure was infants 0 years old.  

.  Clethodim is proposed only for agricultural uses and no homeowner or
turf uses. Thus, no non-dietary risk assessment is needed. 

D. Cumulative Effects  

Section 408(b)(2)(D)(v) requires that the Agency must consider
"available information" concerning the cumulative effects of a
particular pesticide's residues and "other substances that have a common
mechanism of toxicity." Available information in this context includes
toxicity, chemistry, and exposure data, but also scientific policies and
methodologies for understanding common mechanisms of toxicity and
conducting cumulative risk assessments. Although the Agency has some
information in its files that may turn out to be helpful in eventually
determining whether a pesticide shares a common mechanism of toxicity
with any other substances, EPA does not at this time have the
methodologies to resolve the complex scientific issues concerning common
mechanism of toxicity in a meaningful way for most registered
pesticides.

E. Safety Determination  

i. Acute Risk.  No acute endpoint has been identified for clethodim.
Therefore, no assessment of acute exposure from food is required.

ii. Chronic Risk.  The potential chronic exposure from food to the U.S.
Population and various non-child/infant population subgroups will
utilize at most 2.7% of the c-PAD.  Addition of dietary exposure from
drinking water increases this exposure to 8.7% of the c-PAD.  The Agency
has no cause for concern if total chronic residue contribution is less
than 100% of the c-PAD, because the PAD represents the level at or below
which daily aggregate exposure over a lifetime will not pose appreciable
risk to human health.  Therefore, it can be concluded that there is a
reasonable certainty that no harm will result to the non-child/infant
U.S. population from aggregate, chronic exposure to clethodim residues.

.  i. Safety Factor for Infants and Children. EPA has determined that
the special 10x SF to protect infants and children should be removed
[Federal Register of July 17, 2002 (67 FR 46897) (FRL-7185-7)].  The
FQPA factor has been removed because there is no indication of
quantitative or qualitative increased susceptibility of rats or rabbits
to in utero and/or postnatal exposure; a developmental neurotoxicity
study is not required; and the dietary (food and drinking water) and
non-dietary (residential) exposure assessments will not underestimate
the potential exposures for infants and children.

ii. Acute Risk. No acute endpoint has been identified for clethodim.
Therefore, no assessment of acute exposure from food is required.

iii. Chronic Risk.  The potential chronic exposure from food to children
1-2 years old (the most highly exposed child/infant subgroup) will
utilize at most 11.6% of the c-PAD.  Addition of dietary exposure from
drinking water increases this exposure to 21.3% of the c-PAD. The
potential chronic exposure from food and water to infants “0” years
old is 24.8% of the c-PAD. Therefore, it can be concluded that there is
a reasonable certainty that no harm will result to infants and children
from aggregate, chronic exposure to clethodim residues.

F. International Tolerances

The following Codex Maximum Residue Limits (MRL) have been established
for clethodim:

Commodity	Codex MRL (ppm)

Bean, dry	2.0

Onion, dry bulb	0.5

Peanut	5.0

Potato	0.5

Sugar beet, roots	0.1

Sunflower, seed	0.5

Tomato	1.0

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