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

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

Petition Number 5E8401

EPA has received a pesticide petition 5E8401 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-thiazol-5-yl)methyl]-N’-

methyl-N’-nitro-guanidine calculated as the stoichiometric equivalent of thiamethoxam in 

or on the raw agricultural commodity banana at 0.04 parts per million (ppm). 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

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. One study (total of twelve crop-field trials) were 

successfully conducted in Central and South America to support the registration of 

Thiamethoxam on bananas after treatment with four or five root zone drench applications 

of a suspension concentrate (SC) formulation. 

The nominal use pattern was a soil/root zone drench application at 180 days prior 

to harvest at a rate of 4 L product/ha (144 g ai/ha abamectin + 288 g ai/ha thiamethoxam) 

followed by three (or four) successive soil/root zone drench applications at a rate of 2 L 
2

product/ha (72 g ai/ha abamectin + 144 g ai/ha thiamethoxam) on a 60-day retreatment 

interval (RTI). The initial application (4 L product/ha) was intended to control the soil 

insects and nematodes present in previously untreated plantations and each of these 

sequential applications were made at a lower rate in order to maintain the level of control. 

However, it was determined that the higher initial rate was not commercially feasible. 

Banana samples were harvested 0 days after the last application (DALA). At four 

trial sites, additional RAC samples were collected (3, 7, 10, and 14 DALA) to generate 

residue decline data.

Residues of abamectin, a mixture containing avermectin B1a (parent B1a + 8,9-Z 

B1a) and avermectin B1b, and residues of thiamethoxam plus its metabolite CGA322704 

were determined in or on banana whole fruit and banana pulp samples.

Total abamectin residue levels found in the whole banana fruit and banana pulp 

samples were below the LOQ level (<0.002 mg/kg). For the majority of the analyzed 

samples residues were Not Detectable (ND). Given that abamectin residues were not 

found in any samples in this study Syngenta does not intend to submit for an import 

tolerance for abamectin on banana.

Total Thiamethoxam (Thiamethoxam + CGA322704) residue levels found in the 

whole banana fruit were in the range between 0.0158 and 0.0285 mg/kg and in the 

banana pulp were in the range between 0.0158 and 0.0288 mg/kg

The results of this study support the registration of the product for banana 

according to the GAP and provides adequate data to allow for tolerances to established 

for Thiamethoxam in bananas imported into the United States and Canada.

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. 
3

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. 

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. Insert text.]

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.
4

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 

(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 
5

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 

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 4.02, Evaluation Copy) from Exponent; consumption data was 

from the USDA NHANES “What We Eat in America” survey, 2005-2010. These 

assessments included all current and pending uses as well as a proposed new banana 

import use. 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% 
6

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 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 0.345 

mg/kg-bw/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 1,900 (5.2% of the 

aRfD of 0.345 mg/kg-bw/day). The most exposed sub-population was children (1-2 

years old) with a MOE of 861 (11.4% of the aRfD of 0.345 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/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 

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 1,536 (6.5% 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 517 (19.3% 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.
7

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

thiamethoxam were determined using SCI-GROW (v2.3) and Modified Tier 1 Rice 

Model, which estimate pesticide concentration in groundwater and surface water (aquatic 

uses), respectively. The modeling was conducted to identify the highest EDWCs of 

parent thiamethoxam from all current and pending uses of thiamethoxam in addition to 

proposed importation of banana treated with thiamethoxam. For ground water, the 

currently registered Thiamethoxam Lawn and Landscape 0.22G use on turf (0.267 lb 

a.i./A/year) provided the highest EDWC of 4.14 ppb (acute and chronic). The Modified 

Tier 1 model estimated acute and chronic surface water drinking water concentrations of 

169.8 and 28.6 ppb, respectively. These surface water EDWCs resulted from the pending 

Endigo® ZCX use on dry-seeded rice (0.173 lb a.i./A) followed by 2 foliar applications 

(0.086 lb a.i./A/application). No percent cropped area adjustments were made to the 

surface water EDWCs.

Acute Exposure from Drinking Water. The acute surface water EDWC of 169.8 ppb 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 5,723 

(1.7% of the acute RfD of 0.345 mg/kg-bw/day). The most exposed sub-population was 

all infants with a MOE of 2,228 (4.5% of the acute RfD of 0.345 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 exposure value of 

28.6 ppb was used as a DEEM-FCIDTM input to determine chronic exposure from 

drinking water. The chronic surface water EDWC of 28.6 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 2,077 (4.8% of the chronic RfD of 0.012 mg/kg-bw/day). Chronic 

drinking water exposure to the most exposed sub-population (all infants) resulted in a 

MOE of 556 (18.0% 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 
8

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 

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 (oral, short-term) (incidental oral, all durations) from a 90-day oral tox 

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

(MOE = 1,316) for adults (19+ years) treating gardens and trees with a backpack sprayer. 

Post-application exposure risk for adult gardeners (19+ years) re-entering thiamethoxamtreated gardens and trees was acceptable (MOE = 850). Post-application exposure risk 

for youth gardeners (6-11 years) re-entering thiamethoxam-treated gardens and trees was 

acceptable (MOE = 1,200). Post-application exposure risk for adults (19+ years) reentering thiamethoxam-treated turf was acceptable (MOE = 582). Post-application 

exposure risk for youth golfers (6-11 years) re-entering thiamethoxam-treated golf 

courses was acceptable (MOE = 5,416). 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 = 277). 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 (shortterm MOE = 402). Since the MOEs for children (1-6 years), youths (6-11 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 Effect. 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 1,426 (6.9% of the aRfD of 0.345 mg/kg-bw/day) for the general U.S. 

population, which exceeds the Benchmark MOE of 100. For the short-term aggregate 
9

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 511 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 883 (11.3% 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 

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 634 (15.5% of the aRfD of 0.345 mg/kg-bw/day) for the most 

sensitive population subgroup, all infants, 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 251 for children (1-2 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 283 (35.4% of the cRfD of 0.012 

mg/kg-bw/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.