EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Venus Eagle, PM 1; 703-308-8045

TEMPLATE:

Syngenta Crop Protection, LLC, P.O. Box 18300, Greensboro, NC 27419-8300

Petition number 3F8205

EPA has received a pesticide petition (petition number 3F8205) from Syngenta 

Crop Protection, LLC., P.O. Box 18300, Greensboro, NC 27419-8300 requesting, 

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 residues of

thiamethoxam {3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-

oxadiazin-4-imine} (CAS Reg. No. 153719-23-4) and its metabolite[N-(2-chloro-thiazol5-ylmethyl)-N’-methyl-N’-nitro-guanidine in or on alfalfa, seed at 1 parts per million 

(ppm); wheat, grain at 0.5 ppm; wheat, aspirated grain fraction at 2.5 ppm; wheat, bran at 

0.5 ppm; wheat, germ at 0.5 ppm; oat, grain at 0.9 ppm; rye, grain at 0.9 ppm; 

buckwheat, grain at 0.9 ppm; triticale, grain at 0.9ppm; vegetable, legume, subgroup 6A 

at 0.9 ppm; vegetable, legume, subgroup 6B at 0.5 ppm; vegetable, legume, subgroup 6C 

at 0.2 ppm; vegetable, foliage of legume, subgroup 7A at 4 ppm; rice, straw at 2 ppm; 

rice, grain at 6 ppm; sunflower, seed at 0.4 ppm; corn, field, grain at 0.03 ppm, soybean 

at 0.02 ppm; corn, pop, forage at 0.10 ppm; corn, pop, stover at 0.05 ppm; teosinte at 0.02 

ppm; wild rice at 0.02 ppm; millet, pearl, forage at 0.02 ppm; millet, pearl, stover at 0.02 

ppm; millet, proso, forage at 0.02 ppm; millet, proso, stover at 0.02 ppm; millet, proso, 

straw at 0.02 ppm; sorghum, forage at 0.02 ppm; sorghum, grain, stover at 0.02 ppm.

Additionally, Syngenta Crop Protection, LLC requests to amend 40 CFR part 

180.565 by increasing the existing tolerances in or on alfalfa, forage from 0.05 to 10 parts 

per million (ppm); alfalfa, hay from 0.12 to 8 ppm; barley, hay from 0.40 to 1.5 ppm; 

barley, straw from 0.40 to 3 ppm; barley, grain from 0.4 to 0.9 ppm; wheat, forage from 

0.50 to 3 ppm; wheat, hay from 0.02 to 8 ppm; wheat, straw from 0.02 to 6 ppm; corn, 

sweet forage from 0.10 to 5 ppm; corn, sweet, kernel plus cob with husks removed from 

0.02 to 0.03 ppm; corn, sweet, stover from 0.05 to 4 ppm; corn, field, forage from 0.10 to 

4 ppm; corn, field, stover from 0.05 to 4 ppm. 

Concurrently, Syngenta Crop Protection, LLC requests to amend the tolerances in 

40 CFR 180.565 by removing tolerances in or on vegetable, legume, group 6 at 0.02 

ppm; and grain, cereal, group 15, except barley at 0.02 ppm; sunflower at 0.02 ppm, upon 

approval of the tolerances listed above.

EPA has determined that the petition contains data or information regarding the 

elements set forth in section 408 (d) (2) of FDDCA; 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
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1. Plant metabolism. The primary metabolic pathways of thiamethoxam in plants 

(corn, rice, pears and cucumbers) were similar to those described for animals, with 

certain extensions of the pathway in plants. Parent compound and CGA-322704 were the 

major residues in all crops. The metabolism of thiamethoxam in plants and animals is 

understood for the purposes of the proposed tolerances. Parent thiamethoxam and the 

metabolite, CGA-322704, are the residues of concern for tolerance setting purposes.

2. Analytical method. Syngenta Crop Protection, LLC has submitted practical 

analytical methodology for detecting and measuring levels of thiamethoxam in or on raw 

agricultural commodities. This method is based on crop specific cleanup procedures and 

determination by liquid chromatography with either UV or MS detections. The limit of 

detection (LOC) for each analyte of this method is 1.25 ng injected for samples analyzed 

by UV and 0.25ng injected for samples analyzed by MS, and the limit quantification 

(LOQ) is 0.005 ppm for milk and juices, and 0.01 ppm for all other substrates.

3. Magnitude of residues. Tolerances currently exist for alfalfa, barley, wheat, 

legumes, rice and corn. Syngenta Crop Protection, LLC is proposing to amend those 

tolerances to facilitate foliar application. 

B. Toxicological Profile

1. Acute toxicity. The acute oral LD50 for thiamethoxam in the rat is 1563 mg/kg 

body weight. The acute dermal LD50 of thiamethoxam is >2000 mg/kg body weight. 

Thiamethoxam is non-toxic at atmospheric concentrations of 3.72 mg/l. Thiamethoxam 

is minimally irritating to the eye, non-irritating to skin and is not a dermal sensitizer.

In an acute neurotoxicity study in rats (OPPTS 870.6200a), the NOAEL was 100 

mg/kg/day with a NOAEL of 500 mg/kg/day based on drooped palpebral closure, 

decrease in rectal temperature and locomotor activity and increase in forelimb grip 

strength (males only). At higher dose levels, mortality, abnormal body tone, ptosis, 

impaired respiration, tremors, longer latency to first step in the open field, crouched over 

posture, gait impairment, hypo-arousal, decreased number of rears, uncoordinated 

landing during the righting reflex test, slight lacrimation (females only) and higher mean 

average input stimulus value in the auditory startle response test (males only).

2. Genotoxicty. In gene mutation studies with S. typhimurium and e. coli (OPPTS 

870.5100 and 870.5265), there was no evidence of gene mutation when tested up to 5000 

ug/plate and there was no evidence of cytotoxicity. 

In gene mutation study with chinese hamster V79 cells at HGPRT focus (OPPTS 

8705300), there was no evidence of gene mutation when tested up to the solubility limit. 

In a CHO cell cytogenetics study (OPPTS 870.5375), there was no evidence of 

chromosomal aberrations when tested up to cytotoxic or solubility limit concentrations.
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An in vivo mouse bonemarrow micronucleus study (OPPTS 870.5395) was negative 

when tested upto levels of toxicity in whole animals; however, no evidence of target cell 

cytoxicity was present. A UDS assay (OPPTS 870.5550) was negative when tested up to 

precipitating concentrations.

3. Reproductive and developmental toxicity. A prenatal development study in the rat 

(OPPTS 870.3700a) resulted in Maternal and Development NOAELs of 30 mg/kg/day 

and 200 mg/kg/day, respectively. The maternal LOAEL is 200 mg/kg/day based on 

decreased body weight, body weight gain and food consumption. The developmental 

LOAEL was 750 mg/kg/day based on decreased fetal body weight and an increased 

incidence of skeletal anomalies.

A prenatal development study in the rabbit (OPPTS 870.3700b) resulted in maternal and 

developmental LOAELs of 50 mg/kg/day. The maternal and developmental LOAEL is 

150 mg/kg/day. The maternal LOAEL is based on maternal deaths, hemorrhagic 

discharge, decreased body weight and food intake during the dosing period. The 

developmental LOAEL is based on decreased fetal body weights, increased incidence of 

post-implantation loss and a slight increase in the incidence of skeletal 

anomalies/variations.

In a reproduction and fertility effects study in rats (OPPTS 870.3800) the 

Parental/systemic NOAEL is 1.84 (males), 202.06 (females) mg/kg/day; the reproductive 

NOAEL is 0.61 (males), 202.06 (females) mg/kg/day and the offspring NOAEL is 61.25 

(males), 79.20 (females) mg/kg/day. The parental/systemic LOAEL is 61.25 (males), not 

determined (females) mg/kg/day based on increased incidence of hyaline change in renal 

tubules in F0 and F1 males. The reproductive LOAEL is 1.84 (males), not determined 

(females) mg/kg/day based on increased incidence and severity of tubular atrophy 

observed in testes of the F1 generation males. The offspring LOAEL is 158.32 (males), 

202.06 (females) mg/kg/day based on reduced body weight gain during lactation period 

in all litters.

4. Subchronic toxicity. A 90 day oral toxicity study in rats (OPPTS 870.3100) 

resulted in a NOAEL of 1.74 (males), 92.5 (females) mg/kg/day. The LOAEL is 17.4 

(male), 182.1 (female) mg/kg/day based on increased of hyaline change or renal tubules

epithelium (males), fatty change in adrenal gland of females, liver changes in females, all 

at the LOAEL.

A 90 day oral toxicity in mice (OPPTS 870.3100) resulted in a NOAEL of 1.41 (males), 

19.2 (females) mg/kg/day. The LOAEL was 14.3 (male), 231 (female) mg/kg/day based 

on increased incidence of hepatocellular hypertrophy. At higher dose levels: decrease in 

body weight and body weight gain, necrosis of individual hepatocytes, pigmentation of 

Kupffer cells, and lymphocytic infiltration of the liver in both sexes; slight hematologic 

effects and decreased absolute and relative kidney weights in males; and ovarian atrophy, 

decreased ovary and spleen weights and increased liver weights in females.

In an oral toxicity in dogs (OPPTS 870.3150), the NOAEL is 8.23 (males), 9.27 

(females) mg/kg/day. The LOAEL is 32.0 (male), 33.9 (female) mg/kg/day based on 

slightly prolonged prothrombin times and decreased plasma albumin and A/G ration 
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(both sexes; decreased calcium levels and ovary weights and delayed maturation in the 

ovaries (female); decreased cholesterol and phospholipid levels, testis weights, 

spermatogenesis, and spermatic giant cells in testes (male)

In a 28 day dermal study in rats (OPPTS 870.3200) the NOAEL was 250 (male), 60 

(female) mg/kg/day. The LOAEL was 1000 (male), 250 (female) mg/kg/day based on 

increased plasma glucose, triglyceride levels, and alkaline phosphatase activity and 

inflammatory cell infiltration in the liver and necrosis if single hepatocyts in females and

hyaline change in renal tubules and a very slight reduction in body weight in males. At 

higher dose levels in females, chronic tubular lesions in the kidneys and inflammatory 

cell infiltration in the adrenal cortex were observed. 

In a subchronic neurotoxicity screening study in rats (OPPTS 870.6200b) the NOAEL 

was 95.4 (males), 216.4 (female) mg/kg/day, both at the highest dose tested. The 

LOAEL was not determined. No treatment related observations at any dose level. 

LOAEL was not achieved. May not have been tested at sufficient high dose levels; 

however, a new study is not required because of the weight of evidence from other 

toxicity studies indicates no evidence of concern.

5. Chronic toxicity. In a chronic toxicity study in dogs (OPPTS 870.4100) the 

NOAEL was 4.05 (male), 4.49 (female) mg/kg/day. The LOAEL was 21.0 (male), 24.6 

(female) mg/kg/day based on increase in creatinine in both sexes, transient decrease in 

food consumption in females, and occasional increase in urea levels, decrease in ALT, 

and atrophy of seminiferous tubules in males.

In a mouse carcinogenicity study (OPPTS 870.4200) the NOAEL was 2.63 (male), 3.68 

(female) mg/kg/day. The LOAEL was 63.8 (male), 87.6 (female) mg/kg/day based on 

hepatocyte hypertrophy, single cell necrosis, inflammatory cell infiltration, pigment 

disposition, foci of cellular alteration, hyperplasia of Kupffer cells and increased mitotic 

activity, also an increase in the incidence of hepatocellular adenoma (both sexes). At 

higher doses, there was an increase in the incidence of hepatocellular adenocarcinoma 

(both sexes) and the number of animals with multiple tumors, evidence of 

carcinogenicity. 

In a combined carcinogenicity study in rats (OPPTS 870.4300) the NOAEL was 21.0 

(male), 50.3 (female) mg/kg/day. The LOAEL was 63.0 (male), 255 (female) mg/kg/day 

based on the increased incidence of lymphocytic infiltration of the renal pelvis and

chronic nephropathy in males in decreased body weight gain, slight increase in the 

severity of hemosiderosis of the spleen, foci of cellular alteration in liver and chronic 

tubular lesions in kidney in females. No evidence of carcinogenicity. 

In a hepatic cell proliferation study in mice, the NOAEL was 16 (male), 20 (female) 

mg/kg/day. The LOAEL was 72 (male), 87 (female) mg/kg/day based on proliferative 

activity of hepatocytes. At higher dose levels, increases in absolute and relative liver 

weights, speckled liver, hepatocellular glycogenesis/fatty change, hepatocellular necrosis, 

apoptosis and pigmentation were observed.

In a 28 day feeding study to assess replicative DNA synthesis in the male rat, the 
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NOAEL was 711 mg/kg/day. The LOAEL was not established. Immunohistochemical 

staining of the liver sections from control and high dose animals for proliferating cell 

nuclear antigen gave no indication for a treatment related increase in the fraction of DNA 

synthesizing hepatocytes in S-phase. CGA-293343 did not stimulate hepatocyte cell 

proliferation in male rats.

In a special study to assess liver biochemistry in the mouse, the NOAEL was 17 (male), 

20 (female) mg/kg/day. The LOAEL was 74 (male), 92 (female) mg/kg/day based on 

marginal to slight increases in absolute and relative liver weights, a slight increase in the 

microsomal protein content of the livers, moderate increases in the cytochrome P450 

content, slight to moderate increases in the activity of several microsomal enzymes, slight 

to moderate induction of cytstolic glutathione S-transfer activity. Treatment did not 

affect peroxisomal fatty acid β-oxidation.

6. Animal metabolism. The metabolism of thiamethoxam in rats and livestock 

animals is adequately understood. The residues of concern have been determined to be 

parent thiamethoxam and its metabolite [N-(2-chloro-thiazol-5-ylmethyl)-N’-methyl-N’-

nitro-guanidine] expressed as thiamethoxam.

7. Metabolite toxicology. For most risk assessment purposes, residues of the 

metabolite corrected for molecular weight are considered to be toxicologically equivalent 

to parent thiamethoxam. However, EPA has determined that the metabolite should not be 

included in the cancer risk assessment.

8. Endocrine disruption. There are no specific studies requested by the Endocrine 

Disruptor Screening Program (EDSP) at this time because endocrine effects have been 

well characterized in an acceptable 2-generation reproduction study with a clear NOAEL 

and LOAEL, and the chronic reference dose (cRfD) selected for thiamethoxam risk 

assessments is considered protective of the observed endocrine effects.

C. Aggregate Exposure

1. Dietary exposure. Tier I acute and Tier III chronic aggregate risk assessments 

were performed for thiamethoxam using the Dietary Exposure Evaluation Model 

(DEEM-FCIDTM Version 3.16) from Exponent; consumption data was from the USDA 

NHANES “What We Eat in America” survey, 2003-2008. These assessments included 

all current and pending uses as well as proposed new uses on alfalfa, barley, legumes, 

rice, sunflower and sweet corn. The Tier I acute assessments incorporated established or 

proposed tolerances (40CFR180.565) for the combined residues of thiamethoxam 

(CGA293343) and its metabolite (CGA322704) in or on a variety of raw agricultural 

commodities including meat and milk; percent of crop treated values were conservatively 

estimated to be 100% for all uses in the acute assessments. The Tier III chronic 

assessments incorporated field trial residue values where thiamethoxam was applied at 

the maximum intended use rate and samples were harvested at the minimum pre-harvest 

interval (PHI) to obtain the maximum expected residues. Estimated percent crop treated 

(%CT) values were incorporated into the Tier III chronic assessments based upon 

economic, pest, and competitive pressures. Drinking water estimates were incorporated 
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directly into the acute and chronic dietary exposure assessments using the highest 

estimated drinking water concentrations (EDWCs) for surface and ground water. 

i. Food. Acute Exposure. The thiamethoxam acute food risk assessments were 

performed for all population subgroups using an acute reference dose of 0.35 mg/kgbw/day based upon a developmental neurotoxicity study in rats with a no observed 

adverse effect level (NOAEL) of 34.5 mg/kg/day and an uncertainty factor of 100X to 

account for intra- and inter-species variations. No additional FQPA safety factor was 

applied. For the purpose of the acute aggregate risk assessments, the exposure values 

were expressed in terms of margin of exposure (MOE), which was calculated by dividing 

the NOAEL by the exposure for each population subgroup. In addition, exposure was 

expressed as a percent of the acute reference dose (%aRfD). At the 95th percentile, acute 

(food only) exposure to the U.S. population resulted in a MOE of 1,893 (5.2% of the 

aRfD of 0.35 mg/kg-bw/day). The most exposed sub-population was children (1-2 years 

old) with a MOE of 839 (11.7% of the aRfD of 0.35 mg/kg-bw/day). Since the 

Benchmark MOE for this assessment was 100 and since the EPA generally has no 

concern for exposures above the Benchmark MOE or below 100% of the aRfD, Syngenta 

believes that there is a reasonable certainty that no harm will result from dietary (food 

only) exposure to residues arising from all current, pending, and proposed uses of 

thiamethoxam. 

Chronic Exposure. The thiamethoxam chronic dietary food risk assessments were 

performed for all population subgroups using a chronic reference dose of 0.012 mg/kgbw/day based upon a two generation reproduction study in rats with a no observed 

adverse effect level (NOAEL) of 1.2 mg/kg/day and an uncertainty factor of 100X to 

account for intra- and inter-species variations. No additional FQPA safety factor was 

applied. For the purpose of aggregate risk assessment, the exposure values were 

expressed in terms of margin of exposure (MOE), which was calculated by dividing the 

NOAEL by the exposure for each population subgroup. In addition, exposure was 

expressed as a percent of the chronic reference dose (%cRfD). Chronic (food only) 

exposure to the U.S. population resulted in a MOE of 1,602 (6.2% of the cRfD of 0.012 

mg/kg-bw/day). The most exposed sub-population was children (1-2 years old) with a 

MOE of 537 (18.6% of the cRfD of 0.012 mg/kg-bw/day). Since the Benchmark MOE 

for this assessment was 100 and since the EPA generally has no concern for exposures 

above the Benchmark MOE or below 100% of the cRfD, Syngenta believes that there is a 

reasonable certainty that no harm will result from dietary (food only) exposure to 

residues arising from all current, pending, and proposed uses of thiamethoxam.

Cancer: A quantitative risk assessment using a cancer endpoint was not performed.

ii. Drinking water. The Estimated Drinking Water Concentrations (EDWCs) of 

thiamethoxam were determined using Tier l models, SCI-GROW and PRZM-GW which 

estimate pesticide concentration in ground water, Tier II model PRZM/EXAMS which 

estimates pesticide concentration in surface water for terrestrial uses; and the modified 

Tier I Rice Model and Provisional Cranberry Model which estimates pesticide 

concentration in tail water from rice paddies and cranberry bogs, respectively. EDWCs 
7

of thiamethoxam from currently registered uses as well as proposed foliar uses on alfalfa, 

rice, legumes (beans and peas), corn, small cereal grains, and sunflower were determined. 

The highest ground water EDWCs resulting from PRZM-GW modeling were 81.1 ppb 

for acute and 63.3 ppb for chronic based on the currently registered use on turf. The 

highest surface water EDWCs resulted from the currently registered seed treatment use 

on dry-seeded rice. The modified Tier I Rice model provided an acute EDWC of 161 

ppb and a chronic EDWC of 13.8 ppb (adjusted for a 0.95 Percent Cropped Area (PCA) 

factor). The surface water acute EDWC and the ground water chronic EDWC were used 

for risk assessment purposes.

Acute Exposure from Drinking Water. The acute surface water EDWC of 161ppb was 

input directly into the DEEM-FCIDTM software as “water, direct and indirect, all sources” 

to model the acute drinking water exposures. Exposure contributions at the 95th

percentile of exposures were determined by taking the difference between the aggregate 

(food + drinking water) exposures and the food (alone) exposures for each population 

subgroup. Acute drinking water exposure U.S. population resulted in a MOE of 6210 

(1.6% of the acute RfD of 0.35 mg/kg-bw/day). The most exposed sub-population was 

all infants (<1 year old) with a MOE of 2864 (3.5% of the acute RfD of 0.35 mg/kg/day). 

Since the benchmark MOE for this assessment was 100 and since EPA generally has no 

concern for exposures below 100% of the acute RfD, Syngenta believes that there is a 

reasonable certainty that no harm will result from acute drinking water exposure to 

residues arising from the current uses for thiamethoxam.

Chronic Exposure from Drinking Water. The chronic surface water EDWC of 63.3 ppb 

was input directly into the DEEM-FCIDTM software as “water, direct and indirect, all 

sources” to model the chronic drinking water exposures. Chronic drinking water 

exposure to the U.S. population resulted in a MOE of 905 (11% of the chronic RfD of 

0.012 mg/kg-bw/day). Chronic drinking water exposure to the most exposed subpopulation (infants, <1 year old) resulted in a MOE of 351 (28.5% of the chronic RfD of 

0.012 mg/kg-bw/day). Since the Benchmark MOE for this assessment was 100 and since 

EPA generally has no concern for exposures below 100% of the chronic RfD, Syngenta 

believes that there is a reasonable certainty that no harm will result from chronic drinking 

water exposure to residues arising from the current uses for thiamethoxam.]

2. Non-dietary exposure. Residential exposure risk assessments were performed for use 

of thiamethoxam formulated as Meridian 0.33G, Thiamethoxam 0.22G, Meridian 25WG, 

Thiamethoxam 0.40/Lambda-cyhalothrin 0.16 ME Concentrate, Thiamethoxam 

0.01/Lambda-cyhalothrin 0.004 ME RTU, Optigard ZT, Optigard Flex, Tandem, or 

Derby. Optigard ZT, Optigard Flex, Tandem, and Derby are labeled for professional use 

only; therefore no residential handler exposure assessments are required for these 

products. Homeowner application of Meridian 0.33G, Thiamethoxam 0.22G, Meridian 

25WG, Thiamethoxam 0.40/Lambda-cyhalothrin 0.16 ME Concentrate, or 

Thiamethoxam 0.01/Lambda-cyhalothrin 0.004 ME RTU is allowed; therefore residential 

handler exposure assessments are required. The following endpoints were used: a 1.2 

mg/kg/day NOAEL for adults (dermal and inhalation, all durations) from a two 
8

generation oral reproduction study in rats; a 60 mg/kg/day NOAEL for children 1-6 years 

(dermal, short-term) from a 28-day dermal study in rats; a 8.23 mg/kg/day NOAEL for 

children 1-6 years (dermal, short-term) (incidental oral, all durations) from a 90-day oral 

tox study in dogs. Residential handler exposure risk from thiamethoxam was acceptable 

(MOE = 732) for adults (19+ years) treating gardens and trees with a belly grinder. Postapplication exposure risk for adult gardeners (19+ years) re-entering thiamethoxamtreated gardens and trees was acceptable (MOE = 194). Post-application exposure risk 

for youth gardeners (13-19 years) re-entering thiamethoxam-treated gardens and trees 

was acceptable (MOE = 284). Post-application exposure risk for youth golfers (6-12 

years) re-entering thiamethoxam-treated golf courses was acceptable (MOE = 5,427). 

Post-application dermal plus non-dietary oral hand-to-mouth exposure risk was 

acceptable for children (1-6 years) re-entering thiamethoxam-treated residential turf grass 

(short-term MOE = 640). Post-application dermal plus non-dietary oral hand-to-mouth 

exposure risk was acceptable for children (1-6 years) re-entering thiamethoxam-treated 

indoor hard or carpeted surfaces areas (short-term MOE = 640). Since the MOEs for 

children (1-6 years), youths (6-12 years), youths (13-19 years), and adults (19+ years) 

were above the Benchmark MOE of 100, residential exposure risks for thiamethoxam do 

not exceed the EPA’s Level of Concern.

D. Cumulative Effects

Cumulative Exposure to Substances with a Common Mechanism of Toxicity. 

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, 

modify, or revoke a tolerance, the Agency consider “available information” concerning 

the cumulative effects of a particular pesticide’s residues and “other substances that have 

a common mechanism of toxicity”. 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 thiamethoxam and any other 

substances and thiamethoxam does not appear to produce a toxic metabolite produced by 

other substances. For the purposes of this tolerance action, the EPA has not assumed that 

thiamethoxam has a common mechanism of toxicity with other substances.

E. Safety Determination

1. U.S. population. The acute dietary exposure analysis (food plus water) showed 

that exposure from all current, pending, and proposed uses of thiamethoxam would result 

in a MOE of 1,451 (6.8% of the aRfD of 0.35 mg/kg-bw/day) for the general U.S. 

population, which exceeds the Benchmark MOE of 100. For the short-term aggregate 

exposure analysis the corresponding food, water and residential MOEs were aggregated 

using the inverse MOE approach. The short-term aggregate (food, drinking water, and 

residential) MOE was 185 for adults (20-49 years old), which exceeds the Benchmark 

MOE of 100. The chronic dietary exposure analysis (food plus water) showed that 

exposure from all current, pending, and proposed uses of thiamethoxam resulted in a 

MOE of 578 (17.2% of the cRfD of 0.012 mg/kg-bw/day) for the general U.S. 

population, which also exceeds the Benchmark MOE of 100. Based on the completeness 

and reliability of the toxicity data supporting these petitions, Syngenta believes that there 
9

is a reasonable certainty that no harm will result from aggregate exposure to residues 

arising from all current, pending, and proposed uses of thiamethoxam, including 

anticipated dietary exposure from food, water, and all other types of non-occupational 

exposures.

2. Infants and children. The acute dietary exposure analysis (food plus water) showed 

that exposure from all current, pending, and proposed uses of thiamethoxam would result 

in a MOE of 691 (14.3% of the aRfD of 0.35 mg/kg-bw/day) for the most sensitive 

population subgroup, infants <1 year old, which exceeds the Benchmark MOE of 100. 

For the short-term aggregate exposure analysis the corresponding food, water and 

residential MOEs were aggregated using the inverse MOE approach. The short-term 

aggregate (food, drinking water, and residential) MOE was 505 for children (1-6 years), 

which exceeds the Benchmark MOE of 100. The chronic aggregate dietary (food plus 

water) exposure analysis showed that exposure from all current, pending, and proposed 

uses of thiamethoxam would result in a MOE of 213 (47% of the cRfD of 0.012 mg/kgbw/day) for the most sensitive population subgroup, infants <1 year old, which exceeds 

the Benchmark MOE of 100. Based on the completeness and reliability of the toxicity 

data supporting these petitions, Syngenta believes that there is a reasonable certainty that 

no harm will result to infants and children from aggregate exposure to residues arising 

from all current, pending, and proposed uses of thiamethoxam, including anticipated 

dietary exposure from food, water, and all other types of non-occupational exposures.

F. International Tolerances

In 2011 the Codex Alimentarius Commission established Maximum Residue 

Limits (MRLs) for thiamethoxam in various agricultural commodities including 

artichokes, bananas, barley, berries, Brassica vegetables (head), cacao beans, celery, 

citrus, coffee, fruiting vegetables, cucurbits, leafy vegetables, legumes, maize, oilseeds, 

papayas, pecans, peppers (chili, dried), pineapples, pome fruits, popcorn, pulses, root and 

tuber vegetables, stone fruits, sweet corn, tea (green, black; fermented and dried), wheat, 

and various meat, milk, and egg commodities.