EPA REGISTRATION DIVISION CO MPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contac t: 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 tolera nce for residues of thiamethoxam {3-[(2-chloro-5-thiaz olyl)methyl]tetrahydro-5-methyl- N -nitro-4 H -1,3,5- oxadiazin-4-imine} (CAS Reg. N o. 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); buckwheat, grain at 0.9 ppm; corn, fiel d, grain at 0.03 ppm; oat, grain at 0.9 ppm; rice, grain at 6 ppm; rice, straw at 2 ppm; rye, grain at 0.9 ppm; soybean at 0.02 ppm; sunflower, seed at 0.4 ppm; triticale, grain at 0.9 ppm; 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, s ubgroup 7A at 4 ppm; wh eat, aspirated grain fraction at 2.5 ppm; wheat, bran at 0.5 ppm; wheat, germ at 0.5 ppm; wheat, grain at 0.5

ppm. Additionally, Syngenta Crop Protection, LLC requests to amend 40 CFR part 180.565 by increasing the existing to lerances in or on alfalfa, forage from 0.05 to 10 ppm; alfalfa, hay from 0.12 to 8 ppm; barle y, grain from 0.4 to 0.9 ppm; barley, hay from 0.40 to 1.5 ppm; barley, straw from 0.40 to 3 ppm; corn, field, forage from 0.10 to 4 ppm; corn, field, stover from 0.05 to 4 ppm; corn, sweet, forage from 0.10 to 5 ppm; corn, sweet, kernel plus cob with husks remove d from 0.02 to 0.03 ppm; corn, sweet, stover from 0.05 to 4 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. Concurrently, Syngenta Crop Protection, LLC requests to amend the tolerances in 40 CFR 180.565 by removing tolerances in or on grain, cereal, group 15, except barley at 0.02 ppm; sunflower at 0.02 ppm; and vegeta ble, legume, group 6 at 0.02 ppm, upon approval of the tolerances listed above. EPA has determined that the petition cont ains 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

1. Plant metabolism . The primary metabolic pathways of thiamethoxam in plants (corn, rice, pears and cucumbers) were sim ilar to those described for animals, with2

certain extensions of the pathway in plan ts. Parent compound and CGA-322704 were the major residues in all crops. The metabolis m 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 measur ing levels of thiamethoxam in or on raw agricultural commodities. This method is ba sed on crop specific cleanup procedures and determination by liquid chromatography with ei ther UV or MS detections. The limit of detection (LOC) for each analyte of this me thod 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 Pr otection, LLC is proposing to amend those

tolerances to facilita te 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 c oncentrations of 3.72 mg/l. Thiamethoxam is minimally irritating to the eye, non-irritat ing 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 locomoto r activity and increase in forelimb grip strength (males only). At higher dose le vels, mortality, abnormal body tone, ptosis, impaired respiration, tremors, longer latency to first step in the open field, crouched over posture, gait impairment, hypo-arousal, decr eased number of rears, uncoordinated landing during the righting reflex test, slight lacrimation (females only) and higher mean average input stimulus value in the aud itory 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 hams ter V79 cells at HGPRT focus (OPPTS 8705300), there was no evidence of gene mutation wh en tested up to the solubility limit.

In a CHO cell cytogenetics study (OPP TS 870.5375), there was no evidence of chromosomal aberrations when tested up to cytotoxic or solubility limit concentrations.

An in vivo mouse bonemarrow micronuc leus study (OPPTS 870.5395) was negative when tested upto levels of t oxicity in whole animals; howev er, no evidence of target cell cytoxicity was present. A UDS assay (OPPT S 870.5550) was negative when tested up to3

precipitating concentrations.

3. Reproductive and developmental toxicity. A prenatal development study in the rat (OPPTS 870.3700a) resulted in Maternal a nd Development NOAELs of 30 mg/kg/day and 200 mg/kg/day, respectively. The mate rnal LOAEL is 200 mg/kg/day based on decreased body weight, body weight gain a nd food consumption. The developmental LOAEL was 750 mg/kg/day based on decrea sed fetal body weight and an increased

incidence of skeletal anomalies. A prenatal development study in the rabbi t (OPPTS 870.3700b) resulted in maternal and developmental LOAELs of 50 mg/kg/day. Th e maternal and developmental LOAEL is 150 mg/kg/day. The maternal LOAEL is ba sed on maternal deaths, hemorrhagic discharge, decreased body weight and food intake dur ing 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 eff ects study in rats (OPPTS 870.3800) the Parental/systemic NOAEL is 1.84 (males), 202.0 6 (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 pare ntal/systemic LOAEL is 61.25 (males), not determined (females) mg/kg/day based on incr eased incidence of hyaline change in renal tubules in F0 and F1 males. The reproducti ve LOAEL is 1.84 (males), not determined (females) mg/kg/day based on increased in cidence and severity of tubular atrophy observed in testes of the F1 generation ma les. The offspring LOAEL is 158.32 (males), 202.06 (females) mg/kg/day based on reduced body weight gain dur ing lactation period

in all litters.

4. Subchronic toxicity. A 90 day oral toxicity st udy 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 incr eased 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 hypert rophy. At higher dose levels: decrease in body weight and body weight gain, necrosis of individual hepatocytes, pigmentation of Kupffer cells, and lymphocytic infiltration of th e liver in both sexes; slight hematologic

effects and decreased absolute and relative ki dney weights in males; and ovarian atrophy, decreased ovary and spleen weights and increased liver weights in females.

In an oral toxicity in dogs (OPPT S 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 (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)4

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 (m ale), 250 (female) mg/kg/day based on increased plasma glucose, triglyceride le vels, and alkaline ph osphatase activity and inflammatory cell infiltration in the liver and necrosis if si ngle hepatocyts in females and hyaline change in renal tubules and a very sl ight reduction in body wei ght in males. At higher dose levels in females, chronic tubula r lesions in the kidneys and inflammatory

cell infiltration in the adrenal cortex were observed. In a subchronic neurotoxicity screen ing study in rats (OPPTS 870.6200b) the NOAEL was 95.4 (males), 216.4 (female) mg/kg/day, bo th at the highest dose tested. The

LOAEL was not determined. No treatment re lated 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 creat inine in both sexes, transient decrease in food consumption in females, and occasional in crease in urea levels, decrease in ALT, and atrophy of seminifer ous 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 (m ale), 87.6 (female) mg/kg/day based on hepatocyte hypertrophy, single cell necrosis, inflammatory cell infiltration, pigment disposition, foci of cellular alteration, hyperp lasia 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 hepatoce llular adenocarcinoma (both sexes) and the number of animal s 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 L OAEL was 63.0 (male), 255 (female) mg/kg/day based on the increased incidence of lymphocy tic 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 (f emale) mg/kg/day based on proliferative activity of hepatocytes. At higher dose levels, increases in absolute and relative liver weights, speckled liver, hepa tocellular glycogenesis/fatty change, hepatocellular necrosis, apoptosis and pigmenta tion were observed.

In a 28 day feeding study to assess replic ative DNA synthesis in the male rat, the 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 treat ment related increase in the fraction of DNA5

synthesizing hepatocytes in S-phase. C GA-293343 did not stimulate hepatocyte cell proliferation in male rats.

In a special study to assess liv er 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 re lative 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 glutathi one 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 underst ood. The residues of concern ha ve 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 co nsidered 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-gene ration 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” surve y, 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 acu te assessments incorpor ated established or proposed tolerances (40CFR180.565) for th e 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 th e acute assessments. The Tier III chronic assessments incorporated fiel d trial residue valu es where thiamethoxam was applied at the maximum intended use rate and samples we re harvested at the minimum pre-harvest interval (PHI) to obtain the maximum expect ed residues. Estimated percent crop treated (%CT) values were incorpor ated into the Tier III chronic assessments based upon economic, pest, and competitive pressures. Drinking water estimates were incorporated directly into the acute an d chronic dietary exposure a ssessments using the highest estimated drinking water concentrations (EDWCs) for surface and ground water.6

i. Food. Acute Exposure. The thiamethoxam acute food risk assessments were performed for all population subgroups usi ng an acute reference dose of 0.35 mg/kgbw/day based upon a developmental neurotox icity 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-spe cies variations. No additi onal FQPA safety factor was applied. For the purpose of the acute aggreg ate risk assessments, the exposure values were expressed in terms of margin of e xposure (MOE), which was calculated by dividing the NOAEL by the exposure for each populati on subgroup. In addition, exposure was expressed as a percent of the acute referen ce 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 e xposed 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 th at no harm will result from dietary (food only) exposure to residues arising from a ll current, pending, and proposed uses of

thiamethoxam.

Chronic Exposure. The thiamethoxam chronic dietary food risk assessments were performed for all population subgroups usi ng a chronic reference dose of 0.012 mg/kgbw/day based upon a two generation reproduc tion study in rats with a no observed adverse effect level (NOAEL) of 1.2 mg/kg/da y and an uncertainty factor of 100X to account for intra- and inter-spe cies variations. No additi onal 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 calcu lated 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-popula tion was children (1-2 years old) with a MOE of 537 (18.6% of the cR fD of 0.012 mg/kg-bw/day). Since the Benchmark MOE

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

above the Benchmark MOE or below 100% of th e 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, pendi ng, and proposed uses of thiamethoxam.

Cancer: A quantitative risk assessment us ing 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 concentra tion in surface water for terres trial uses; and the modified

Tier I Rice Model and Provisional Cra nberry Model which estimates pesticide concentration in tail water from rice paddies and cranberry bogs, respectively. EDWCs 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 ppb7

for acute and 63.3 ppb for chronic based on the currently registered use on turf. The highest surface water EDWCs resulted from th e currently registered seed treatment use on dry-seeded rice. The modi fied Tier I Rice model provided an acute EDWC of 161 ppb and a chronic EDWC of 13.8 ppb (adjus ted for a 0.95 Percent Cropped Area (PCA) factor). The surface water acute EDWC a nd 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 exposur es. Exposure contributions at the 95 th

percentile of exposures were determined by taking the diffe rence 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 Rf D 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 surfac e water EDWC of 63.3 ppb was input directly into the DEEM-FCIDTM soft ware as “water, direct and indirect, all sources” to model the chronic drinking wa ter exposures. Chr onic 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 wa ter exposure to the most exposed subpopulation (infants, <1 year ol d) 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 th at no harm will result from chronic drinking water exposure to residues arising fro m the current uses for thiamethoxam.]

2. Non-dietary exposure

. Residential exposure risk assessm ents 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 e xposure assessments are required for these products. Homeowner application of Meri dian 0.33G, Thiamethoxam 0.22G, Meridian 25WG, Thiamethoxam 0.40/Lambda-cyha lothrin 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 generation oral reproduction st udy 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, shor t-term) (incidental oral, all durations) from a 90-day oral8

tox study in dogs. Residential handler expos ure risk from thiamethoxam was acceptable (MOE = 732) for adults (19+ years) treating ga rdens and trees with a belly grinder. Postapplication exposure risk for adult garden ers (19+ years) re-entering thiamethoxamtreated gardens and trees was acceptable (MOE = 194). Post-application exposure risk for youth gardeners (13-19 years) re-enteri ng thiamethoxam-treated gardens and trees was acceptable (MOE = 284). Post-applicati on exposure risk for youth golfers (6-12 years) re-entering thiamethoxam-treated gol f 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-enteri ng thiamethoxam-treated residential turf grass (short-term MOE = 640). Post-application de rmal 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 (shor t-term MOE = 640). Since the MOEs for children (1-6 years), youths (6-12 years), youths (13-19 year s), and adults (19+ years)

were above the Benchmark MOE of 100, resi dential exposure risk s 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 part icular pesticide’s residues and “other substances that have a common mechanism of toxicity”. Unlike ot her pesticides for which EPA has followed a cumulative risk approach based on a co mmon mechanism of toxicity, EPA has not made a common mechanism of toxicity fi nding 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 analys is (food plus water) showed that exposure from all current, pending, a nd 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 corres ponding food, water and resident ial MOEs were aggregated using the inverse MOE approach. The shor t-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 propos ed 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 supporti ng these petitions, Syngent a believes that there 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, wate r, and all other types of non-occupational9

exposures.

2. Infants and children. The acu te dietary exposure analysis (food plus water) showed that exposure from all current, pending, a nd 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, wh ich exceeds the Benchmark MOE of 100. For the short-term aggregate exposure an alysis the correspon ding food, water and residential MOEs were aggreg ated using the inverse MOE approach. The short-term aggregate (food, drinking water, and resident ial) 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 expos ure from all current, pending, and proposed

uses of thiamethoxam would result in a MO E of 213 (47% of th e 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 comp leteness 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 a ll other types of non-occupational exposures.

F. International Tolerances

In 2011 the Codex Alimentarius Commi ssion established Maximum Residue Limits (MRLs) for thiamethoxam in various agricultural commodities including artichokes, bananas, barley, berries, Bra ssica vegetables (head), cacao beans, celery, citrus, coffee, fruiting vegetables, cucurbits, leafy vegetables, legumes, maize, oilseeds, papayas, pecans, peppers (chili, dried), pin eapples, pome fruits, popcorn, pulses, root and tuber vegetables, stone fruits, sweet corn, te a (green, black; fermented and dried), wheat, and various meat, milk, and egg commodities.