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 27 419

- 8300

P etition number 3F8205

EPA has received a pesticide petition ( petition number 3F8205 ) from Syngenta Crop Protection, LLC., P.O. Box 18300, Greensboro, NC 27419

- 8300 request ing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmeti c Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of
t hiamethoxam {3

- [(2

- chloro

- 5

- thiazolyl)methyl]tetrahydro

- 5

- methyl

- N

- nitro

- 4 H

- 1,3,5

- oxadiazin

- 4

- imine} (CAS Reg. No. 153719

- 23

- 4) and its metabolite[ N

- (2

- chloro

- thiazol

5

- 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, gr ain 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; ri ce, 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 a lfalfa, 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, grai n 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 Chemistry2

1. Plant metabo lism

. 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 c rops. 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 chr omatography 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 mi lk 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 appl ication.

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 p alpebral 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 o pen 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 respon se 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 mut ation 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.3

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

a nd 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 skelet al 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 d ischarge, 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/variatio ns.
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 (fema les) 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 l itters.

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 (fema le) 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 r elative 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 ration4

(both sexes; decreased calcium levels and ovary weights and delayed maturat ion 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 rena l 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 suf ficient 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 (m ale), 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 se miniferous 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 cellu lar 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 base d 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, the5

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 ga ve 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 th e cytochrome P450 content, slight to moderate increases in the activity of several micro somal 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 under stood. 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, resid ues of the metabolite corrected for molecular weight are cons idered 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

. T here 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 re ference 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 thiamet hoxam using the Dietary Exposure Evaluation Model (DEEM

- FCID TM 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 ne w 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 chroni c assessments based upon economic, pest, and competitive pressures. Drinking water estimates were incorporated6

directly into the acute and chronic dietary exposure assessments using the highest estimated drinking water concentrations (EDWCs) for surface a nd 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/kg

bw/day based upon a developmental neurotoxicity study in rats with a no obser ved 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 v alues 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 percenti le, 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 B enchmark 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) ex posure 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/kg

bw/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 appli ed. 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 p ercent 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% o f 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 te rrestrial 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 . EDWCs7

of thiamethoxam from currently registered uses as well as pr oposed 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 currentl y 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 P ercent Cropped Area (PCA) factor). T he 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 s oftware as “water, direct and indirect, all sources” to model the acute drinking water exposures. Exposure contributions at the 95 th percentile of exposures were determined by taking the difference between the aggregate (food + drinking water) exposures a nd 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 i ndirect, 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 sub

p opulation (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 be lieves 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 us e 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, Opti gard 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 two8

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. Post

application exposure risk for adult gardener s (19+ years) re

- entering thiamethoxam

treated 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 thiameth oxam

- 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

- te rm 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. Cumula tive 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” concern ing 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 th at 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 aggrega ted 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
exp osure 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 o f the toxicity data supporting these petitions, Syngenta believes that there9

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 r esult 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 reside ntial 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) expo sure 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/kg

bw/day) for the most sensitive population subgroup, infants <1 year old, which exceeds the Benchmar k 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 fr om 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 M aximum 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, ma ize, 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.