FILE NAME: Valent.doc (Aug 9 , 2011)

EPA Registration Division contact: Venus Eagle (703-308-8045)

[Insert Petition Number] amend 40 CFR 

Summary of Petition 

EPA has received a pesticide petition (Insert Petition Number) from 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 (a), by establishing 

tolerances 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:

Commodity

Proposed Tolerance

Parts per million

(For parent only unless indicated 

otherwise)

Strawberry 1.4 ppm 

Citrus Fruit Group ( 10-10) 0.5 ppm 

Citrus Pulp 1 ppm 

Pistachio 0.01 ppm 

Tea 50 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 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 on strawberry and the representative crops of citrus fruit crop grouping 

(grapefruit, lemon and orange) has been submitted which adequately support the 

requested tolerances. Pistachio petition will be supported by the existing tolerance for 

tree nuts (Crop Group 14) of 0.01 ppm. 

 

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 

and in the HED memorandum dated 8/13/2009 from Dr. Michael Doherty to Kable 

Davis/Venus Eagle “Clothianidin: Human Health Risk Assessment for Proposed Uses on 

Berries (Group 13-07H), Brassica Vegetables (Group 5), Cotton, Cucurbit Vegetables 

(Group 9), Fig, Fruiting Vegetables (Group 8), Leafy Green Vegetables (Group 4A), 

Peach, Pomegranate, Soybean, Tree Nuts (Group 14), and Tuberous and Corm 

Vegetables (Group 1C). PC Code: 044309” (DP Barcodes: D355373, D362354).

C. Aggregate Exposure and Risk Assessment

i. Dietary Exposure. Dietary exposure (food and water) 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 and its 

metabolite TMG plus residues of clothianidin resulting from the use of thiamethoxam. 

Residues were included from the use of clothianidin or thiamethoxam on all existing 

uses and newly proposed uses including rice, citrus fruits and strawberries. Residues 

from use of clothianidin on pistachio and tea were not included in the current 

assessment because the contribution to the overall aggregate exposure is considered 

negligible. These minor crop residues will be included in the aggregate exposure 

assessment at a later date.

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.

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 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.

ii. Non-Dietary Exposure – residential/recreational turf. Non-dietary exposure to 

clothianidin from residential or recreational (turf grass) application scenarios was 

assessed using conservative residential adult applicator and post-application 

assumptions using the CARES Residential Module. 

iii. Aggregate Assessment of Risks. The aggregate acute and chronic risk assessment 

includes food, water and residential exposures. Inclusion of chronic exposure scenarios 

for residential uses is a very conservative approach since the non-dietary turf related 

exposure does not represent chronic exposure risk based on the limited annual 

application rate. 

For acute risk assessment scenarios, the acute population adjusted dose (aPAD) of 0.25 

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 1. For the acute risk 

assessment, the maximum aggregate risk from food, water and residential uses is 6% of 

the aPAD in infants 0 years of age (0 to 1 years).

For chronic risk assessment scenarios, the chronic population adjusted dose (cPAD) 

used for the U.S. population and all subpopulations is 0.098 mg/kg/day based on a 2-

generation reproduction study NOAEL of 9.8 mg/kg/day and an FQPA safety factor of 1. 

For the chronic risk assessment, the maximum aggregate risk from food and water is 

3.2% of the cPAD in infants 0 years of age (0 to 1 years).

Based on these risk assessments, the margins of exposure (MOE) for all routes of

exposure and all population subgroups exceed 100 and therefore do not exceed EPA’s 

level of concern. 

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. 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. The 

available data indicate that there are no consistent specific target organs in mammals. 

Based on the completeness of the database and the observed effects, the FQPA Safety 

Factor has been reduced to 1X, leaving a 100X safety factor to account for withinspecies (10X) and across-species (10X) variability. Clothianidin has been classified as 

not likely to be carcinogenic to humans.

The results of the aggregate exposure risk assessment 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, including infants and 

children, 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, 

canola, stone fruits, grape, potato and pome fruits. Clothianidin is being evaluated by the 

JMPR and there are no Codex Maximum Residue Limits (MRL) established.