Syngenta Crop Protection, LLC

PP# 5F8441

EPA has received a pesticide petition PP# 5F8441 from Syngenta Crop Protection, LLC, 

P.O. Box 18300, 410 Swing Road, 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 180.685 by establishing a tolerance for residues of oxathiapiprolin in 

or on the following raw agricultural commodities:

Citrus fruit Crop Group 10-10 at 0.06 parts per million (ppm)

Citrus oil at 2.0 parts per million (ppm)

Citrus pulp at 0.09 parts per million (ppm)

Tuberous and Corm Vegetables, Subgroup 1C at 0.04 parts per million (ppm)

Potato, wet peel at 0.07 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 metabolism of oxathiapiprolin is adequately understood to 

support the proposed tolerances. Studies in grape, lettuce and potato when treated at the

label rates showed no significant metabolites. The metabolism of oxathiapiprolin in 

plants was similar regardless of the crop or the treatment regime. Oxathiapiprolin was the 

principle residue in most crop fractions at various sampling points up to crop maturity. 

The overall metabolism of oxathiapiprolin in rotated crops (cereals, root vegetables, leafy 

vegetables) was consistent with metabolism seen in the primary crops.

2. Analytical method. Adequate analytical methodology, high-pressure liquid 

chromatography with MS/MS detection, is available for enforcement purposes.

3. Magnitude of residues. Field trials to meet the United States requirements were carried 

out in orchards (citrus), field (potato). The trials covered a wide range of locations, 

climates and soil types and the data obtained reflect the commercial use of the 

oxathiapiprolin-containing products in the major US crop growing regions.

The results of these field trials substantiate oxathiapiprolin as the major residue at harvest 

in the crop commodities. Oxathiapiprolin is likewise the relevant residue in processed 

commodities.

B. Toxicological Profile

1. Acute toxicity. Based on EPA criteria, technical oxathiapiprolin is classified with an 

overall Toxicity Category IV (Tox Cat IV). This compound is considered a Tox Cat IV 
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based on no observed for acute oral, dermal or inhalation toxicity up to the OPPTS 

testing guidelines limit dose levels tested. Oxathiapiprolin is not an eye or skin irritant 

and it is not a dermal sensitizer. 

No evidence of neurotoxicity was observed in an acute neurotoxicity study conducted 

with oxathiapiprolin in rats. The no-observed-effect level (NOEL) and no-observedadverse-effect-level (NOAEL) in an acute neurotoxicity study where 2000 mg 

oxathiapiprolin/kg bw, which was the highest dose administered in the study.

2. Genotoxicty. Oxathiapiprolin was evaluated in a battery of in vitro and in vivo genetic 

toxicology studies. Negative results were obtained in all studies indicating that 

oxathiapiprolin does not cause genetic damage and therefore, does not pose a mutagenic 

hazard.

3. Reproductive and developmental toxicity. No effects on fertility were observed in oneand two- generation reproduction studies in rats. No effects on development were

observed in developmental toxicity studies in rats and rabbits. Slight delays in sexual 

maturation were observed in male rats in the multi-generation reproduction studies, with 

a NOAEL of 104 mg/kg bw/day. Decreases in offspring body weight were also observed

in the multi-generation reproduction studies at higher dose levels.

4. Subchronic toxicity. Short-term oral feeding studies with oxathiapiprolin were 

conducted in rats, mice and dogs with durations of up to 90 days. In addition, a 14 day 

oral gavage study (conducted as part of early discovery) and a 28-day dermal study were 

performed. No adverse effects were observed in any of these studies. In all cases, the 

NOAELs were greater than or equal to 1000 mg/kg bw/day. Non–adverse findings 

observed in these studies were limited to changes in organ weights, clinical chemistry 

parameters and liver cytochrome P450 isozymes.

Oxathiapiprolin showed no evidence of immunotoxicity in a 28-day feeding study in 

mice. Additionally, no indications of a potential for oxathiapiprolin to affect the immune 

system were noted in the subchronic/carcinogenicity studies with rats, mice or dogs. 

Based on this, oxathiapiprolin does not appear to pose an immunotoxic hazard.

Neurotoxicity endpoints were included in the subchronic (90-day feeding) study that 

tested up to 1096/1300 mg/kg bw/day in male/female rats. No evidence of neurotoxicity 

was observed in the 90-day dietary toxicity study in rats. There was also a lack of any 

treatment related clinical signs indicative of potential neurotoxicity observed in the 

repeated dose studies in mice or dogs.

5. Chronic toxicity. Based on the results of chronic feeding studies in rats and mice, 

oxathiapiprolin was not carcinogenic in either species. No indications of chronic toxicity 

were observed in either study. A one-year toxicity study was also conducted in dogs, with 

no toxicologically relevant findings. Possible test substance-related changes in organ 

weights and clinical chemistry parameters were observed.

6. Animal metabolism. [

14C]Oxathiapiprolin was investigated in rats after single low and
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high dose administration, and after multiple treatments at low doses. At the low does (10 

mg/kg bw) absorption was 31-49%, and declined to 5.4-7.7% at the high dose (200 

mg/kg bw). Peak plasma concentrations occurred at 0.25-9.5 hours. Plasma 14C residue 

concentrations showed steady-state kinetics in male and female rats after multiple low 

does administrations (10 gm/kg bw for 14 days)

Maximum tissue concentrations at Tmax occurred in the liver. Clearance was rapid for 

liver and other tissues by 168 hours after dosing. All tissues at 168 hours, including the 

carcass, collectively retained <0.05% of the dose. The pattern of distribution was similar 

between sexes and single and multiple dose administration. The low percentage and 

concentration values in tissues indicate very low potential for accumulation. 

Plasma terminal elimination half-lives ranged from 40-51 hours following single or 

multiple low-dose administration. Excretion in urine and feces was >95% complete by 48 

hours after single dosing. The pattern of excretion was similar after multiple dosing. 

Fecal excretion was the primary route of elimination (≥90%). Recovery in urine was 

much lower (≤2.5%). Essentially no excretion occurred by exhalation.

7. Metabolite toxicology. Oxathiapiprolin is considered to be the only molecule of 

toxicological relevance. Toxicology studies conducted with metabolites support this 

conclusion.

8. Endocrine disruption. No relevant effects were observed on any endocrine tissue in 

short- and long-term studies in rats, mice and dogs to suggest an adverse impact on 

estrogen or androgen pathways or on steroid biosynthesis. The reproduction studies in 

rats provided sufficient information to fully interpret the effects of oxathiapiprolin on 

reproduction. No observations in that study suggested an adverse effect on estrogen. 

Additionally, investigational studies were conducted that suggest no adverse effects on 

estrogen. The slight delay in maturation observed in male rats in the reproduction studies 

may be exacerbated by weight effects; however, the data suggest that other factors are 

involved. Investigational studies did not reveal any adverse effects on androgens by 

oxathiapiprolin in rats. 

C. Aggregate Exposure

1. Dietary exposure. Subsequent to the filing of a pesticide petition by E.I. du Pont de 

Nemours and Company, Wilmington, DE (DuPont), EPA established tolerances for 

residues of the fungicide oxathiapiprolin, 1-(4-{4-[(5RS)-5-(2,6-difluorophenyl)-4,5-

dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}-1-piperidyl)-2-[5-methyl-3-(trifluoromethyl)-

1H-pyrazol-1-yl] ethanone, in or on: Brassica, head and stem (Subgroup 5A); ginseng; 

grape; leafy greens (Subgroup 4A); onion, bulb (Subgroup 3-07A); onion, green 

(Subgroup 3-07B); pea, edible-podded; pea, succulent shelled; tomato, dried; vegetable, 

cucurbit (Group 9); vegetable, fruiting (Group 8-10); and vegetable, tuberous and corm 

(Subgroup 1C). With this Notice-of-Filing, Syngenta is requesting new tolerances for its 

proposed uses on potato and citrus (Crop Group 10-10). There is no expectation of 

residues of oxathiapiprolin in the meat, milk, or eggs of ruminants and/or poultry 

resulting from any current or proposed uses and no tolerances have been proposed for 
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those commodities at this time. 

The EPA stated in its June 25, 2015 human health safety technical review of the DuPont 

petition (DP Barcode D417279) that toxicological studies for oxathiapiprolin did not 

demonstrate any treatment related effects and did not subsequently establish any oral, 

dermal, or inhalation (acute, chronic, or short-term) endpoints for assessment of 

consumer exposures, and in keeping with the EPA’s current policy and practice with 

respect to oxathiapiprolin, Syngenta has not conducted any consumer risk assessments for 

its proposed uses on citrus fruit (crop group 10-10), tuberous and corm vegetables 

(subgroup 1C).

i. Food

Acute exposure. Due to the lack of toxicological endpoints and Points-of-Departure 

(PODs), a quantitative acute dietary risk assessment was not conducted. While dietary 

exposure to oxathiapiprolin may occur through food and drinking water, no risks of 

concern are anticipated due to the lack of toxicity at anticipated human exposure levels.

Chronic exposure. Due to the lack of toxicological endpoints and PODs, a quantitative 

chronic dietary risk assessment was not conducted. While dietary exposure to 

oxathiapiprolin may occur through food and drinking water, no risks of concern are 

anticipated due to the lack of toxicity at anticipated human exposure levels.

Cancer. A cancer dietary assessment was not conducted. Oxathiapiprolin is classified as 

"not likely to be carcinogenic to humans." No treatment-related increase in tumors was 

observed in carcinogenicity studies in rats and/or mice.

ii. Drinking water. Due to the lack of toxicological endpoints and PODs, a quantitative 

drinking water assessment was not conducted.

2. Non-dietary exposure

Residential Exposure. There is no residential handler exposure scenarios associated with 

the proposed use on turfgrass (i.e., golf courses and commercial landscapes). Residential 

exposures are also expected for adults and children conducting post-application activities 

on treated golf course (turf). However, since no toxicological endpoints of concern were 

identified for oxathiapiprolin and no PODs were selected, a quantitative residential risk 

assessment was not conducted. Although there is a proposed use on ornamental plants, 

the proposed use is only for nurseries and commercial greenhouses. HED notes that there 

are no direct homeowner applications of oxathiapiprolin to ornamentals; however, treated 

ornamentals could be purchased at a retail location for use in a residential setting. HED 

considers post-application exposure resulting from this scenario to be negligible. 

Furthermore, a quantitative residential post-application assessment for the use of 

oxathiapiprolin on commercial ornamentals was not performed because of the lack of 

potential exposure and the absence of toxicological endpoints or PODs.
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Occupational Exposure. Although there is potential for occupational handler and postapplication exposure, risk estimates for OXTP were not quantitatively assessed because 

no dermal or inhalation toxicological endpoints were identified or PODs selected. The 

PPE statement on proposed labels requires handlers to wear baseline clothing (i.e., longsleeved shirt, long pants, shoes plus socks), no chemical-resistant gloves and no 

respirator. No additional PPE recommendations are needed based on HED’s risk 

assessment. The PPE determination and REIs on proposed labels should be based on the 

acute toxicity of OXTP.

D. Cumulative Effects

Unlike other pesticides for which EPA has followed a cumulative risk approach based on 

a common mechanism of toxicity, E PA has not made a common mechanism of toxicity 

finding as to oxathiapiprolin and any other substances and oxathiapiprolin does not 

appear to produce a toxic metabolite produced by other substances. For the purposes of 

this tolerance action, therefore, EPA has not assumed that oxathiapiprolin has a common 

mechanism of toxicity with other substances. For information regarding EPA's efforts to 

determine which chemicals have a common mechanism of toxicity and to evaluate the 

cumulative effects of such chemicals, see the policy statements released by EPA's Office 

of Pesticide Programs concerning common mechanism determinations and procedures for 

cumulating effects from substances found to have a common mechanism on EPA' s 

website at: http://www.epa.gov/pesticides/cumulative.

E. Safety Determination

1. U.S. population. There is the potential for dietary (food and drinking water) and 

residential exposures associated with all current and proposed uses of oxathiapiprolin. 

However, due to the lack of toxicity at the human exposure levels anticipated for 

oxathiapiprolin based on the proposed use patterns, no quantitative dietary, residential, or 

aggregate exposure assessments are required and no risks of concern are anticipated.

2. Infants and children. There is the potential for dietary (food and drinking water) and 

residential exposures associated with all current and proposed uses of oxathiapiprolin. 

However, due to the lack of toxicity at the human exposure levels anticipated for 

oxathiapiprolin based on the proposed use patterns, no quantitative dietary, residential, or 

aggregate exposure assessments are required and no risks of concern are anticipated.

F. International Tolerances

Codex Alimentarious Commission has not yet established Maximum Residue Limits 

(CXLs) for oxathiapiprolin.