FILE NAME:  IR4_Clothianidin.doc (Sept 19, 2008)

EPA Registration Division contact: Laura Nollen (703) 305-7390

Interregional Research Project Number 4 (IR-4) 

Petition Number (PP 8E7460)

Summary of Petition

EPA has received a pesticide petition (8E7460) from   SEQ CHAPTER \h \r
1  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  08450, 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 180.586 by establishing a tolerance
for residues of the insecticide chemical clothianidin,
(E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine, in or
on the following agricultural commodities: Berry, low growing, subgroup
13-07H, except strawberry at 0.01 parts per million (ppm); Peach at 0.70
ppm; and Vegetables, Tuberous and Corm, Subgroup 1C at 0.05 ppm.
Additionally it is proposing to delete the existing tolerance for potato
at 0.05 ppm since it will be superseded by the proposed tolerance on
subgroup 1C. EPA has determined that the petition contains data or
information regarding the elements set forth in section 408(d)(2) of the
FFDCA; however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of the
petition.  Additional data may be needed before EPA rules on the
petition.

A. Residue Chemistry                                       

1. Plant metabolism. The metabolism of clothianidin is adequately
understood for the purpose of granting the proposed tolerances.

2.  Analytical method.  Adequate enforcement methodology (liquid
chromatography/mass spectroscopy/mass spectroscopy, LC/MS/MS analysis)
is available to enforce the tolerance expression.  

3. Magnitude of residues.  Residue data has been submitted which
adequately support the requested tolerances based on representative
crops.

B. Toxicological Profile

A complete, valid and reliable database of mammalian and genetic
toxicology studies has been submitted to EPA that supports the proposed
tolerances for clothianidin. The nature of the toxic effects caused by
clothianidin, as well as the no observed adverse effect level (NOAEL)
and the lowest observed adverse effect level (LOAEL) from the toxicity
studies reviewed, are discussed in the Federal Register of May 30, 2003
(68 FR 32390) (FRL-7306-8). 
[http://www.epa.gov/EPA-PEST/2003/May/Day-30/p13564.htm

 C. Aggregate Exposure and Risk Assessment

 i. Dietary Exposure – food.  Dietary exposure (food) assessments were
conducted to evaluate the potential risk due to acute and chronic
dietary exposure of the U.S. population and various subgroups to
combined residues of clothianidin in/on the following new crops as
specified in the current petition: bushberries, sub crop group 13-07H;
peach; and root and tuber sub crop group 1C.  In addition, crops with
existing clothianidin tolerances (40 CFR 180.586), including those with
clothianidin residues resulting from treatment with the active
ingredient thiamethoxam, were included in the assessment.  Clothianidin
and thiamethoxam are also both registered for use on turf grass.

The Cumulative and Aggregate Risk Evaluation System (CARES) Version 3.0b
was used to conduct these assessments using a combination (when
available) of actual or generated residue data, experimentally obtained
processing factors, and an estimation of percent crop treated.  Default
factors or tolerance level residues were used when experimentally
determined data were not available.   

ii. Dietary Exposure – water. Dietary exposure from drinking water was
estimated using a Tier II PRZM/EXAMS assessment to determine the EDWCs
in the Standard Index Reservoir associated with clothianidin proposed
and existing uses.  A 30-year daily concentration time series data set
generated from the scenario with the maximum (worst case) EDWS estimates
was then imported into CARES Water module in order to calculate acute
and chronic drinking water and aggregate risks.

iii. Non-Dietary Exposure – residential/recreational turf. 
Non-dietary exposure to clothianidin from residential or recreational
(turf grass) application scenarios was assessed using the CARES
Residential module.  The risk assessment was conducted using residential
adult applicator and post-application assumptions.  

iv. Aggregate Assessment of Risks.  The aggregate acute risk assessment
includes food, water and residential exposures.  Because chronic
exposure scenarios are not expected from residential uses of
clothianidin, the chronic exposure risk assessment only includes food
and water exposures.  

For acute risk assessment scenarios, the acute population adjusted dose
(aPAD) of 0.025 mg/kg was used to assess risks from acute dietary
exposure to the general population and to various sub-populations.  The
aPAD is based on the NOAEL of 25 mg/kg/day from an acute neurotoxicity
study (general population) or a developmental toxicity study (females
13-49 years of age) with an FQPA safety factor of 10.   

For chronic risk assessment scenarios, the chronic population adjusted
dose (cPAD) used for the U.S. population and all subpopulations is
0.0098 mg/kg/day based on a 2-generation reproduction study NOAEL of 9.8
mg/kg/day and an FQPA safety factor of 10.

Based on these risk assessments, the margins of exposure (MOE) for all
routes of exposure and all population subgroups exceed 1000 and
therefore do not exceed EPA’s level of concern.  

D44. 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. Clothianidin is a member of the
neonicotinoid class of pesticides and is a metabolite of thiamethoxam.
Structural similarities or common effects do not constitute a common
mechanism of toxicity and there is currently no evidence that
neonicotinoids share a common mechanism of toxicity.  For purposes of
this petition, clothianidin residues from use of clothianidin and
thiamethoxam have been considered.  

E. Safety Determination.  The toxicological database for clothianidin is
complete, with the exception of a developmental immunotoxicity study. 
EPA has determined there is insufficient data to justify the selection
of an additional safety factor for the protection of infants and
children lower than the default value of 10X for both single and
repeated doses.  Therefore, a data base uncertainty factor (UFDB), has
been applied to both single and repeated dose exposure scenarios (i.e.,
acute and chronic RfDs, short- and intermediate-term incidental oral
exposures, resulting from residential uses of clothiandin) to account
for the lack of the developmental immunotoxicity study with
clothianidin.  

The results of the aggregate exposure risk assessment (taking into
account the full 1000X margin of safety) indicate the MOE’s do not
exceed EPA’s level of concern.  There is therefore a reasonable
certainty that no harm will result to the general population or to any
population subgroup resulting from aggregate exposure to residues of
clothianidin.  

F. International Tolerances.  Canadian maximum residue limits (MRL) have
been established for residues of clothianidin at 0.01 milligram/kilogram
(mg/kg) in milk, corn and canola. Clothianidin has not been evaluated by
the JMPR and there are no Codex Maximum Residue Limits (MRL)
established. 

