EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Tony Kish, PM Team 22, (703) 308-9443

Syngenta Crop Protection, LLC, PO Box 18300, Greensboro, NC 27419

Pesticide Petition: PP# 5F8368

EPA has received a pesticide petition (PP# 5F8368) from Syngenta Crop 

Protection, LLC, PO Box 18300, Greensboro, NC 27419 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 180.242 by establishing a tolerance for residues of Thiabendazole in 

or on the raw agricultural commodities Pea, field, hay at 0.15 parts per million (ppm); 

Pea, field, vines at 0.03 parts per million (ppm); Vegetable, foliage of legume, group 7, 

except pea, field, hay and vines at 0.01 parts per million (ppm); and Vegetable, legume, 

group 6 at 0.01 parts per million (ppm). Concurrently, Syngenta Crop Protection, LLC 

requests to amend the tolerances in 40 CFR 180.242 by removing tolerances in or on 

Bean, dry, seed at 0.1 ppm; and Soybean at 0.1 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

1. Plant metabolism. The qualitative nature of the residues in plants is adequately 

understood based on soybean, sugar beet, and wheat metabolism studies. The residues of 

concern in plants include thiabendazole and benzimidazole, free and conjugated.

2. Analytical method. Adequate analytical methodology is available for data 

collection enforcement of thiabendazole residues. The Pesticide Analytical Manual 

(PAM) Vol. II lists four spectrophotofluorometric methods (Methods I, A, B and C) for 

determining residues of thiabendazole per se in or on plant commodities, and one 

spectrophotofluorometric method (Method D) for determining residues of thiabendazole 

and 5-hydroxythiabendazole in milk.

3. Magnitude of residues. Syngenta Crop Protection, LLC has submitted complete 

residue data for Thiabendazole on beans and peas (as representative crops in support of 

Pea, field, hay; Pea, field, vines; Vegetable, foliage of legume, group 7, except pea, field, 

hay and vines; and Vegetable, legume, group 6).
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B. Toxicological Profile

1. Acute toxicity. Thiabendazole has very low acute toxicity via oral and dermal 

(Category IV). For acute inhalation, Thiabendazole is classified under Category III. 

Thiabendazole is minimally irritating to the eye (Category III) and not irritating to skin 

(Category IV). It is not a dermal sensitizer.

2. Genotoxicity. The available genetic toxicology studies on thiabendazole 

indicate that the compound is not mutagenic in bacteria or clastogenic in vitro in 

mammalian cells. Thiabendazole did not cause DNA strand breaks in cultured rat 

hepatocytes and was negative for structural chromosome aberrations in rats.

3. Reproductive and developmental toxicity. In the rat development study, the 

observed maternal and developmental LOAEL/NOAEL of 40/10 mg/kg/day was based 

on decrease in body weight and food consumption.

In the mouse prenatal development toxicity study, there were reductions in maternal body 

weight at mid (100 mg//kg/day) and high dose (299 mg/kg/day) treatment groups. There 

were accompanying reductions in feed consumption in the HDT group. The mouse 

maternal and developmental LOAEL/NOEAL were 100/25 mg/kg/day, respectively.

In a rabbit developmental study, decreased maternal body weight gains and decreased 

food consumption were seen at HDT (600 mg/kg/day). There was also decreased fetal 

body weight and increased resorptions at 600 mg/kg. The rabbit maternal and 

developmental LOAEL/NOAEL were 600/150 mg/kg, respectively.

In a 2-generation reproduction study in the rat, the parental systemic LOAEL was based 

on decreased body weight gain and food consumption seen at 30 mg/kg. The NOEAL 

was 10 mg/kg. The offspring LOAEL was based on decreased body weight gain in 

offspring during lactation seen at 30 mg/kg. The reproductive LOAEL was >90 mg/kg. 

The effects in the offspring were observed at higher dosages (90 mg/kg) than dosages (30 

mg/kg) causing parental toxicity. Therefore, there was no increased susceptibility.

4. Subchronic toxicity. In a 21 day dermal toxicity study in the rabbit, 

thiabendazole was administered dermally to rabbits. No systemic or dermal toxicities 

were noted at doses up to 1000 mg/kg/day. The systemic and dermal NOEL was 1000 

mg/kg.

In a subchronic toxicity study, thiabendazole was administered to rats in the diet. The 

NOEL of 10 mg/kg was based on reduced body weight gains and histopathological 

changes in the bone marrow, liver and thyroid.

In another subchronic toxicity study, thiabendazole was administered to rats by gavage at 

doses of 0, 25, 100, or 400 mg/kg/day for 14 weeks. The LOAEL for this study was 100 

mg/kg/day. The NOEL of 25 mg/kg was based on histopathological changes of the liver, 

thyroid, kidneys, and spleen.
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In a subchronic toxicity study in dogs, thiabendazole was administered orally in capsules 

to four beagle dogs at dose levels of 0, 35, 75, or 150 mg/kg/day for 14 weeks. The 

NOEL was 150 mg/kg based on the increase of gallbladder epithelial cytoplasmic 

vacuolation.

5. Chronic toxicity. In a chronic toxicity study, thiabendazole was administered 

orally in capsules to four beagle dogs at dose levels of 0, 10, 40, or 160 mg/kg/day for 52 

weeks. The LOAEL for this study was 40 mg/kg based on increased liver weight, splenic 

erythropoiesis and hemosiderosis in both sexes. The LOAEL was 10 mg/kg.

In a chronic toxicity and carcinogenicity study, thiabendazole was administered to rats in 

the diet at dose levels of 0, 10, 30, or 90 mg/kg/day for104 weeks. The systemic LOAEL 

was 30 mg/kg based on increase in incidence of benign thyroid follicular cell adenoma. 

The NOAEL was 10 mg/kg.

In a carcinogenicity study, thiabendazole was administered to 50 mice for 105 weeks. 

There was an increase in mortality in all dose groups. Body weight gains were 

significantly lower in high dose female and male. However, no treatment-related increase 

in tumor incidence above background level was observed.

6. Animal metabolism. The rat, goat and hen metabolism studies indicate that the 

qualitative nature of the residues in animals is adequately understood. The residue of 

concern in eggs, milk, and poultry and livestock tissue is thiabendazole and 5-hydroxythiabendazole (free and conjugated) and benzimidazole (free and conjugated).

In a rat metabolism study, radio-labeled thiabendazole was administered to rats by 

gavage. Thiabendazole was readily absorbed by male and female rats following oral 

dosing. Within 168 hours of dosing, over 89% of the dose was excreted in urine and 

feces. The majority of the administered dose was recovered in the urine identified as the 

glucuronide conjugate of 5-hydroxythiabendazole and the sulfate conjugate of 5-hydroxy 

thiabendazole. The data indicate that the renal excretion is the primary pathway for the 

elimination of thiabendazole from rats. At the low dose level, it was shown that 

thiabendazole oxidizes to form 5-hydroxythiabendazole, followed by conjugation to form 

glucuronide and sulfate conjugates of 5-hydroxythiabendazole.

7. Metabolite toxicology. The nature of residues in plants and animals is 

adequately understood. Residues of concern in plants include thiabendazole and its 

metabolite benzimidazole, free and conjugated. The residues of concern in animal 

commodities are thiabendazole and 5-hydroxy-thiabendazole (free and conjugated) and 

benzimidazole (free and conjugated). No additional toxicologically significant 

metabolites were detected in any of the plant or animal metabolism studies.

8. Endocrine disruption. Thiabendazole does not belong to a class of chemicals 

known or suspected of having adverse effects on the endocrine system. Developmental 

toxicity studies in rats and rabbits and a reproduction study in rats gave no indication that 
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thiabendazole might have any effects on endocrine function related to development and 

reproduction.

C. Aggregate Exposure

1. Dietary exposure. Tier III chronic aggregate risk assessments were completed 

for thiabendazole using the Dietary Exposure Evaluation Model software with the Food 

Commodity Intake Database (DEEM-FCIDTM, version 4.02). DEEM-FCID software 

incorporates food consumption data from the National Health and Nutrition Examination 

Survey)/“What We Eat in America” (NHANES/WWEIA) dietary survey conducted in 

2005-2010. These exposure assessments included all registered uses as well as proposed 

uses on succulent and dry beans and peas and the foliage of beans and peas (Crop Groups 

6A, 6B, 6C, and 7). USDA-PDP monitoring data were used for apple juice, apple sauce, 

apples, banana, cantaloupe, carrot, mango, mushrooms, orange juice, oranges, papaya, 

pears (baby food), potato, strawberry, and sweet potato in the refined probabilistic acute 

dietary assessments; field trial residue data were used for all remaining commodities. 

Existing or proposed tolerances were used in the unrefined chronic dietary assessments. 

Conversion factors for the thiabendazole metabolite benzimidazole were taken from 

EPA’s March 10, 2014 dietary exposure assessments (DP D416470). Maximum 

reasonably balanced diets were used with livestock transfer factors to predict residues in 

meat and milk commodities; poultry and egg commodities were not included in these 

assessments per current EPA practice. DEEMTM (version 7.87) default processing factors 

were used for all commodities. Percent crop treated (%CT) values were taken from 

EPA’s March 10, 2014 dietary exposure assessments for thiabendazole (DP D416470). 

Drinking water estimates were selected using the higher of the estimated drinking water 

concentrations (EDWCs) for surface and ground water.

i. Food. Acute Risk. The acute dietary risk assessment was performed for all 

population subgroups with an acute reference dose of 0.05 mg/kg-bw/day based upon an 

acute neurotoxicity study in rats with a NOAEL of 50 mg/kg-bw/day and a combined 

uncertainly factor of 1000X; the 1000-fold safety factor includes intra- (10X) and 

interspecies (10X) variations. An additional 10X uncertainly factor was applied due to 

lack of a developmental thyroid study. 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 reference dose (%RfD). Acute 

dietary exposure to the U.S. population resulted in a MOE of 3,621 (27.6% of the aRfD 

of 0.05 mg/kg-bw/day). Acute exposure to the most exposed subpopulation (children 1 to 

2 years old) resulted in a MOE of 1,391 (71.9% of the aRfD of 0.05 mg/kg-bw/day). 

Since the Benchmark MOE for this assessment is 1000 and since EPA generally has no 

concern for exposures above the Benchmark MOE or below 100% of the reference dose, 

Syngenta believes that there is a reasonable certainty that no harm will result from acute 

dietary (food only) exposure to residues arising from all current and proposed uses of 

thiabendazole.

Chronic Risk. The chronic dietary risk assessment was performed for all population 
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subgroups with a chronic reference dose of 0.033 mg/kg-bw/day based on a 2 year 

chronic/carcinogenicity study in rats with a NOAEL of 10 mg/kg-bw/day and an 

uncertainly factor of 300X. The 30-fold safety factor includes intra- (3X) and interspecies 

(10X) variations; an additional 10X uncertainly factor was applied due to lack of a 

comparative thyroid study. 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 reference dose (%RfD). Chronic dietary exposure to the 

U.S. population resulted in a MOE of 22,570 (1.3% of the cRfD of 0.033 mg/kg-bw/day). 

Chronic exposure to the most exposed sub-population (children 1 to 2 years old) resulted 

in a MOE of 5,561 (5.4% of the cRfD of 0.033 mg/kg-bw/day). Since the Benchmark 

MOE for this assessment is 300 and since EPA generally has no concern for exposures 

above the Benchmark MOE or below 100% of the reference dose, Syngenta believes that 

there is a reasonable certainty that no harm will result from chronic dietary (food only) 

exposure to residues arising from all current and proposed uses of thiabendazole.

Cancer Risk. Thiabendazole has been classified as, “Likely to be carcinogenic at doses 

high enough to cause a disturbance of the thyroid hormonal balance but not likely to be 

carcinogenic at doses lower that those which could cause a disturbance of this hormonal 

balance. Quantification of cancer risk is not required.”

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

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

estimate pesticide concentration in groundwater and Tier I model FIRST which estimates 

pesticide concentration in surface water. EDWCs of thiabendazole from currently 

registered uses plus the proposed seed treatment uses on succulent and dry beans and 

peas and the foliage of beans and peas (Crop Groups 6A, 6B, 6C, and 7) were 

determined. For groundwater, the PRZM-GW model provided acute EDWC of 0.536 ppb 

and SCI-GROW model provided chronic EDWC of 0.061 ppb based on the current seed 

treatment use on wheat. For surface water, FIRST provided acute and chronic EDWCs of 

3.128 ppb and 0.384 ppb, respectively, based on the current seed treatment use on wheat 

(Percent Cropped Area (PCA) of 1 was used). The surface water acute and chronic 

EDWCs were used for risk assessment purposes.

Acute Exposure from Drinking Water. The acute surface water EDWC of 3.128 ppb was 

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

to model the acute drinking water exposures. Acute drinking water exposure to the U.S. 

population resulted in a MOE of 568,182 (0.2% of the aRfD of 0.05 mg/kg-bw/day). 

Acute drinking water exposure to the most exposed sub-population (children 1-2 years 

old) resulted in a MOE of 253,807 (0.4% of the aRfD of 0.05 mg/kg-bw/day). Since the 

Benchmark MOE for this assessment was 1000 and since EPA generally has no concern 

for exposures above the benchmark or below 100% of the reference dose, Syngenta 

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

water exposure to residues arising from all current and proposed uses of thiabendazole.

Chronic Exposure from Drinking Water. The chronic surface water EDWC of 0.384 ppb 
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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 >1,000,000 (<0.1% of the cRfD of 0.033 

mg/kg-bw/day). Chronic drinking water exposure to the most exposed sub-population (all 

infants, <1 year old) resulted in a MOE of 348,683 (0.1% of the cRfD of 0.033 mg/kgbw/day). Since the Benchmark MOE for this assessment was 300 and since EPA 

generally has no concern for exposures above the benchmark or below 100% of the 

reference dose, Syngenta believes that there is a reasonable certainty that no harm will 

result from chronic drinking water exposure to residues arising from all current and 

proposed uses of thiabendazole.

2. Non-dietary exposure. There are currently no registered uses for thiabendazole 

registered by Syngenta that would result in residential handler (mixer/loader/applicator) 

or post-application exposure. Also, there are currently no registered agricultural uses that 

would result in off-site drift. Risk assessments for thiabendazole as a paint additive were 

not assessed as these uses are no longer owned by Syngenta and use rates can no longer 

be verified.

D. Cumulative Effects

Cumulative Exposure to Substances with a Common Mechanism of Toxicity. 

Section 408(b)(2)(D)(v) 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 thiabendazole and any other substances 

and thiabendazole does not appear to produce a toxic metabolite produced by other 

substances. Therefore, for the purposes of this tolerance action, EPA has not yet assumed 

that thiabendazole has a common mechanism of toxicity with other substances.

E. Safety Determination

1. U.S. population. Using the conservative assumptions described above, and 

based on the completeness and reliability of the toxicity data, the acute aggregate (food 

plus water) exposure calculation for current and proposed uses of thiabendazole resulted 

in a MOE of 3,598 (27.8% of the aRfD of 0.05 mg/kg-bw/day) for the U.S. population. 

The chronic aggregate (food plus water) exposure calculation for current and proposed 

uses of thiabendazole resulted in a MOE of 22,519 (1.3% of the cRfD of 0.033 mg/kgbw/day) for the U.S. population. Since the acute aggregate MOE of 3,598 exceeds the 

acute aggregate Benchmark MOE of 1000, Syngenta believes that there is a reasonable 

certainty that no harm will occur to the U.S. population from acute and chronic aggregate 

exposures arising from all current and proposed uses of thiabendazole.

2. Infants and children. Using the conservative assumptions described in the 

exposure section above, and based on the completeness and reliability of the toxicity 
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data, the acute aggregate (food plus water) exposure calculation for current and proposed 

uses of thiabendazole resulted in a MOE of 1,384 (72.2% of the aRfD of 0.05 mg/kgbw/day) for children 1-2 years old (the most sensitive population subgroup). The chronic 

aggregate (food plus water) exposure calculation for current and proposed uses of 

thiabendazole resulted in a MOE of 5,529 (5.4% of the cRfD of 0.033 mg/kg-bw/day) for 

children 1-2 years old (the most sensitive population subgroup). Since the acute 

aggregate MOE of 1,384 exceeds the acute aggregate Benchmark MOE of 1000, 

Syngenta believes that there is a reasonable certainty that no harm will occur to infants or 

children from acute and chronic aggregate exposures arising from all current and 

proposed uses of thiabendazole.

F. International Tolerances

The Codex Alimentarius Commission has established maximum residue limits 

(MRLs) for thiabendazole in or on commodities including avocado, banana, cattle 

kidney, cattle liver, cattle meat, cattle milk, citrus fruits, eggs, mango, mushrooms, 

papaya, pome fruits, potato, poultry meat, and witloof chicory (sprouts). Codex MRLs for 

thiabendazole are currently expressed in terms of the parent for plant commodities and in 

terms of the sum of parent and 5-hydroxythiabendazole and its sulfate conjugate for 

animal commodities. The tolerance expressions for U.S. tolerances include residues of 

benzimidazole; as such, the U.S. tolerance definition is not compatible with Codex MRLs 

for plant commodities.