Proposed Registration Decision for the New Active 

Ingredient Oxathiapiprolin 

Date: 1/1 /t (' ---- -+~---------
SUMMARY 

This document announces that the Environmental Protection Agency (EPA) has completed its 

evaluation of the data/infonnation submitted to support the proposed new fungicide 

oxathiapiprolin (CAS# I 0033 18-67-9). The Agency has determined that it meets the regulatory 

and safety standards under the f ederal Insecticide. Fungicide and Rodenticide Act (FIFRA) and 

is proposing to register a wide variety of uses for this chemical. EPA has adeq uate information 

and data to support this proposal and no additional data arc needed for registration. 

Oxathiapiprolin is a fungicide for control of dov.rny mildew (caused by Pythium spp) and late 

bl ight (caused by Phytophthora spp.) diseases on food, ornamental crops and golf course turf. 

Five products are proposed to be unconditionally registered under Section 3(c)(S) of FIFRA. The 

E.l. DuPont De Nemours and Company proposes a technical and two end-use products named 

·'DuPont Zorvcc Technical", ··DuPont Zorvec Eni cade fungicide"', and "DuPont Zorvec 

Epicaltrin Fungicide"'. Syngenta Crop Protection. LLC proposes two end-use products: 

'·Oxathiapiprolin FHG OD'' and "Oxathiapiprolin FHG sc··, vvhich have additional uses for 

oxathiapiprolin. 

E. I. DuPont De Nemo urs and Company proposes the following outdoor food crops: Brassica, 

Head and Stem, Crop Subgroup SA; Bulb Onion Crop Subgroup 3-07A; Cucurbit Vegetables, 

Crop Group 9: Fruiting Vegetables, Crop Group 8-10; Grapes (import only): Green Onion. Crop 

Subgroup 3-078; Leafy Greens, Crop Subgroup 4A; Peas, edible-podded: Peas, succulent, 

shelled; Ginseng root; Tuberous and Corm Vegetables, Subgroup I C; and tobacco. The pro posed 

maximum application rates of oxathiapiprolin on crops ranges between 0.1245 lb. a.i./A/year for 

most foliar applications. and 0.5006 lb. a.i./Nycar for soil applications. The labels allow 2 to 5 

retreatments ( 12 drench treatments for ornamental plants) and rctreatment interva ls between 3 to 

14 days. The pre-harvest interval ranges from 0 to 14 days. 

Syngenta proposes the fo llowing non-food uses: a wide vari ety of ornamental plants grown in 

greenhouses. shade houses. lath houses. hoop houses. nurseries. commercial landscapes; and golf 

course turfto include greens, tees, and fairways. 

The proposed oxathiapiprolin label directions allow product applications to either food crop 

foliage or to the soil, but not a combined application. Product applications are proposed by 

ground and air sprays. chemigation, soil drench/spray. and drip irrigation. 

The proposed end-use product label directions are intended for use by professional applicators. 

There is a label restriction against use for home plantings. The proposed oxathiapiprolin labels 

were assessed and found to be appropriate for uses in greenhouses on ornamental plants, 

tomatoes, cucumbers, summer squash, bell peppers, and nonbell peppers. All other food uses on 

the labels will have a restriction statement against appli cations in a greenhouse because they 

were not requested and thus not assessed. 

The chemical was granted reduced risk status by the Agency's Reduced Risk Committee as part 

of the registrants" request for that determination of oxathiapiprolin data for all food and non-food 

uses. The toxicology database is considered complete. Due to the limited toxicity observed from 

the toxicological database, EPA determined that qualitative risk assessments were the 

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appropriate way to characterize this chemical. For human health, EPA conducted a qualitative 

risk assessment, in which toxicological endpoints and points of departure (POD) were not 

evident fo r oxathiapiprolin. Numeric tolerances are not needed but will be established only to 

support intemational hannonization purposes. 

Oxathiapiprolin is a broad-spectrum fungicide with preventati ve, residual, systemic. eradicative. 

and antisporulant properties for foliar and soil-bome fungal diseases. It provides a different mode 

of action than other fungicides and thus could minimize disease resistance. As proposed, it would 

be applied in a scheduled protective program and used in an application rotation program with 

products with a different mode of action. 

BACKGROUND 

EPA rece ived DuPont's three product applications and Syngenta's two product applications on 

12/3/20 13. The DuPont applications were also submitted for simultaneous review to the Pest 

Management Regulatory Agency (PMRA) of Canada and other countries. Syngenta 's non-food 

omamental plant applications were only submitted to EPA because registration for these uses is 

not being requested for use in Canada. 

EPA and PMRA combined their resources and conducted a global j oint review of oxathiapiprolin 

food uses with participation from Australia, Mexico and Japan, and regulatory observers from 

South Korea, China, and the Philippines. Each country conducted primary or secondary review 

for the 4 11 studies submitted. Human health and ecological risk assessments were develo ped by 

EPA and PMRA individuall y. 

DuPont petitioned EPA under the Federal Food, Drug and Cosmetic Act (FFDCA) to establish 

tolerances for the food crops listed above. At this time, there are no established Codex maximum 

residue limits (MRLs) for oxathiapiprolin. 

EVALUATION OF RISK TO HUMAN HEALTH AND THE 

ENVIRONMENT 

In evaluating a pesticide registration application, the EPA assesses a ,..,ide variety of pesticide 

specifi c infonnatio n inc luding where and how the pesticide would be used. environmental fate 

(i.e .. what happens to the pesticide once irs applied). and toxicity studies (i.e .. effects on humans 

and other non-ta rget organisms) to determine the likelihood of adverse effects (i.e .. risk) from 

exposures associated with the proposed use of the product. Risk assessments are developed to 

evaluate the environmental fate of the compound as well as how it might affect a wide range of 

non-target organisms including humans and terrestrial and aquatic wildlife (plants and animals). 

On the basis of these assessments. EPA evaluates and approves language for each pesticide label 

to ensure the directions for use and sarety measures are appropriate to mitigate any risks of 

concern. In this way. the pesti cide 's label helps to communicate essential limitations and 

mitigations that are necessary for public safety. It is a FIFRA violation to use a pesticide in a 

way that is inconsistent with the label. 

Assessment of Risk to Human Health 

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The toxicology database for oxathiapiprolin is considered complete for the purpose of risk 

assessment. 

In the oral and dermal guideline toxicity studies, including subchronic. chronic, neurotoxicity, 

and immunotoxicity studies, no treatment related effects were seen at doses up to the limit dose. 

No treatment related effects were observed in maternal or fetal animals in rat or rabbit 

developmental toxicity studies. Treatment related effects were observed in offspring animals in 

rat reproduction studies. However, these effects were only observed at doses above the limit 

dose. Such high doses are not relevant for human health risk because human exposure at this 

level is not anticipated in conjunction with the use directions on the proposed product labels. 

There was no evidence of carcinogenicity in cancer studies with rats or mice. Oxathiapiprolin is 

classified as '·not likely to be carcinogenic to humans.'' There is no mutagenic concern for 

oxathiapiprolin. including its metabolites. An inhalation toxicity study was not submitted. 

However, in consideration of all other available data and through a weight of evidence (WOE) 

approach. EPA concluded that the inhalation study is not required for oxathiapiprolin. Based on 

the lack of toxicity for oxathiapiprolin across the database. the inhalation toxicity study has 

therefore been waived. 

Due to the lack of toxicity observed in the oxathiapiprolin database, toxicological endpoints and 

POD were not evident in the data for oxathiapiprolin. Therefore, the normal quantitative risk 

assessment approach which uses endpoints is not needed and a qualitative human health risk 

assessment has been conducted to evaluate the proposed uses. This includes assessment of 

dietary, residential. and occupational (handler and post-application) risk estimates. 

In acute toxicity studies, exposure to oxathiapiprolin resulted in the lowest toxicity category via 

the oral. dermal. and inhalation routes of exposure (Toxicity Category IV). Oxathiapiprolin is 

not a dermal or eye irritant, or a skin sensitizer. Oxathiapiprolin is not a dermal or eye irritant, or 

a skin sensitizer. Based on the acute toxicity categories of the technical active ingredient the ReEntry Interval (REI) would be 12 hours based on the Worker Protection Standard. However, 

DuPont proposed a 4 hour REI which is the lowest REI allowed on any label. DuPont requested 

the 4 hour REI based on satisfying the criteria in PR Notice 95-3 which are: (I) the acute 

toxicity categories are III and IV for acute dermal, inhalation, primary skin irritation, and 

primary eye irritation; (2) it is not a dermal sensitizer; (3) it is not a cholinesterase inhibitor: 4) 

there are no known reproductive. developmental, carcinogenic, or neurotoxic effects; and 5) 

there is no adverse incident information (illness or injury reports) related to post-application 

exposures. As stated below in the " Proposed Regulatory Decision. the Agency has evaluated the 

proposed REI reduction and dete1mined that the active ingredient meets the toxicity criteria for 

reducing the REI to 4 hours. The Personal Protective Equipment (PPE) statements on the 

proposed labels require handlers to wear baseline clothing (i.e., long sleeved shirt, long pants. 

shoes plus socks). 

The residue chemistry database is considered to be complete. including adequate ana lytical 

methods; metabolism in target crops, rotational crops. and livestock; storage stability; residues 

from field trials: and residues in processed commodities. All residue study results are supported 

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by adequate storage stability data. The field trial studi es were conducted using the proposed 

anal ytical enforcement method. 

Assessment of Risks to the Environment 

Envi ronmental Fate 

Oxathiapiprolin is characterized by a relatively low water solubility with low potential for 

volatili zation from dry/wet and water surfaces. The octanol/water partition coefficient suggests 

that the chemical has the potential to bio-concentrate in aq uatic organisms such as fish. 

Oxathiapiprolin is not expected to be affected by hydrol ysis, aqueous photolysis, and photolysis 

in soil and anaerobic soil metabolism. The chemical is expected to be relatively persistent in the 

soil and water sediment systems. In these soil and water sediment systems, bio-transformation/biodegradation are the major processes that are expected to affect the fate of oxathiapiprolin. 

Ecological Effects 

Because of its low solubility. oxathiapi prolin did not demonstrate acute or chronic effects of 

concern to freshwater and estuarine/marine fish. Chronic Risk Quotients (RQ) to freshwater 

sediment-dwelling invertebrates were estimated to be 2.72 which slightly exceeded the Level of 

Concern (LOC) of 1.0 when calculated from sediment-based toxicity endpoints. However. the 

chronic LOC was not exceeded for any proposed use when the RQs were estimated using pore 

water and water column based toxicity endpoints. To further characterize these findings, it is noted 

that separate spiked-water and spiked-sediment system toxicity studies yielded sediment and pore 

water-based toxicity endpoints. The endpoints from the spiked sediment system arc approximately 

an order of magnitude less than those determined from the spiked water system. 

Although no study is available to characteri ze the toxicity to sediment dwelling estuarine/marine 

invertebrates, the current suite of data for freshwater invertebrates indicate that estuarine/marine 

organisms are not disproportionately more sensitive than freshwater organisms. Longer term 

freshwater sediment and freshwater water column toxicity studies (28 day), as opposed to the 

guideline subchronic I 0-day toxicity studies were submitted for freshwater invertebrates. Because 

the data indicate an expected similar level of risk to estuarine/marine sediment dwe lling organisms, 

no further studies characterizing the toxicity to freshwater or estuarine/marine sediment dwelling 

invertebrates are needed as they are determined to have little overall added value to the current 

risk picture. 

There were no LOC exceedances oflisted and non-listed species of aquatic plants for the proposed 

uses of oxathiapiprolin. No acute and chronic avian and mammal LOCs are exceeded, thus, risk 

to birds (and their surrogates) and mammals are not expected. Despite the environmental fate data 

indicating that oxathiapiprolin has the potential to bio-concentrate in aquatic organisms such as 

fish, there was no acute or chronic risk above the LOC indicated for birds and mammals consuming 

oxathiapiprolin-containing aquatic taxa. This is due primarily to oxathiapiprolin's low acute and 

chronic toxicity to birds and mammals. 

No risks above the LOC to terrestrial plants are expected. The highest application rates tested on 

plants. which was more than twice the highest proposed application rate for all uses of 

oxathiapiprolin, did not elicit a toxicity endpoint at or above the 25% trigger level. The no-adverse 

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effect concentration (NOAEC) also exceeded the maximum application rate, reinforcing the 

conclusion of no risk expected for both listed and non-listed species of terrestrial plants. 

The results of the Tier l risk assessment to adult honeybees via direct contact and oral exposure 

resulting from foliar and soil applications, respecti vely. indicate all RQs fall below the terrestria l 

invertebrate acute LOC of 0.4. A Tier II semi-field bee study was conducted which examines 

effects from the larvae stage through pupation. to adults in an outdoor flight cage where bees are 

exposed to oxathiapiprolin-treated blooming plants. This study indicates that while there were 

reductions in survival at Days 12 and 13 after application. as well as reductions in flight intensity 

on the day of application. the bees recovered from these e ffects during the course of the 25 day 

study. This is indicated when the entire study interval was considered, all response variables 

related to colony health. survivaL and foraging behavior were similar to controls. Based on the 

results of the Tier I honey bee assessment which indicated no LOC exceedances (i. e. acute contact 

and oral risk to adult honey bees). and Tier lJ semi-field study which indicated honey bee colonies 

showed recovery in multiple response variables, the proposed uses of oxathiapiprolin are not 

expected to significantly impact honey bees at the colony level. Therefore, at this time, no 

additional bee studies are requested. 

The ecological risk assessment determined that for the following proposed uses. brassica 

vegetables, bulb vegetables, leafy vegetables, peas, tobacco and turf, there were no acute or chronic 

LOC exceedances of any taxa assessed and that a .. no effect finding .. can be made for listed species. 

For all other proposed uses that include cucurbit vegetables, fruiting vegetables, ginseng, tuberous 

vegetables. and ornamentals, there was at least one scenario assessed for which there was an 

exceedance of LOC (RQs range from 1.01 to 2.72) and the taxa of concern were freshwater 

sediment dwelling invertebrates exposed to oxathiapiprolin on a chronic basis. It is noted that for 

the tuberous vegetable use scenarios that were assessed, the highest RQ estimated was 1.0 I, 

negligibly above the chronic LOC of I. For the fruiting vegetables use scenarios. the highest RQ 

estimated was 2.72, marginally above the chronic LOC of 1. 

BENEFITS 

Oxathiapiprolin was granted reduced risk status for all the proposed food and non-food uses. It is 

a broad-spectrum fungicide with preventative, residual, systemic, eradicati ve, and antisporulant 

properties for foli ar and soil-borne fungal diseases. Oxathiapiprolin appears to exhibit a unique 

mode of action. Its unique mode of action suggests that it may play a role in resistance 

management. It can be used as part of an integrated disease control program with fungicides of 

other modes of action that can be part of a resistance management strategy for the proposed 

crops. Resistance management recommendations on the agricultural labels include the limitation 

of no more than two sequential applications and use of effective chemical alternati ves in rotation 

programs. Utilization of integrated pest management programs is also encouraged on the 

proposed labe ling. It is intended for use as a fungicide for protection of crops against diff1cult to 

control diseases caused by Oomycetes group of fungi (i.e. downy mildew and late blight). The 

maximum yearly application rate is 0.5 lbs./ A, which could result in a reduction of the pesticide 

loading in the environment compared to certain registered alternatives. Benefits might also be 

recognized for oxathiapiprolin treatments on registered crops with minor pesticide uses (such as 

ginseng and yams). The use of oxathiapiprolin could offer benefits as a tool in integrated 

fungicide program to facilitate the season-long control of specific fungal pest and extending 

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lifespan of many currently registered fungicides. From a worker safety standpoint, and based on 

the toxicity of the pesticide, agricultural products will have a 4 hour REI. which is the shortest 

period for any agricultura l pesticides. 

ALTERNATIVES 

According to infonnation provided by the registrants, usc of oxathiapiprolin could be expected 

to be an alternative. based on the pest control claims in several currentl y registered pesticides, 

which include: Chlorothalonil; Mancozeb; Zoxamide; Mandipropamid; Difenoconazole; 

Dimethomorph; Cyazofamid; Fluazinam; Fluopicolide; and Cymoxanil. 

PUBLIC COMMENTS 

The Notice of Receipt for this new chemical was published in the Federal Register on 4118/20 14 

with a small, non-substantive conection published 6111 /2014. The Notice of Filing was 

published 5/23/2014. The docket is EPA-I-IQ-OPP-2014-0114. Only one comment was received 

to date and will be addressed in the tolerance rule. 

PROPOSED REGULATORY DECISION 

EPA reviewed 4 11 studies and other informatio n submitted to support proposed uses for the new 

fungicide called Oxathiapiprolin. Because no toxicological endpoints were evident after 

reviewing the complete database, a qualitative (no endpoints) human health risk assessment was 

conducted instead of a quantitative (endpoints) risk assessment. The qua li tative assessment 

revealed no human health risks which exceed Agency concerns. Because it is being assessed as 

part of a global joint review, and is intended to be registered in additio nal countries, the Agency 

is setting tolerances for harmonization purposes. 

Oxathiapiprolin received a reduced risk classification and meets the low toxicity criteria 

published in the Federal Register on May 3, 1995, stated in Pesticide Registration Notice 95-3, 

and provided in EPA Label Review Manual (revised May 20 14). 

A quantitative ecological risk assessment was conducted and found no acute and chronic LOC 

exceedances for all taxa assessed with the exception of marginal chronic risk to freshwater 

sediment-dwelling invertebrates for certain proposed uses. In addition to the reduced risk 

classification received for this pesticide. EPA believes that the benefit of adding a novel mode of 

action compared to available fungicides can help producers develop pesticide resistance 

management programs for foliar and soil-borne fungal diseases; refer to the Benefits section for 

additio nal information. 

Therefore, the Agency has determined that registration of the five proposed products meets the 

FIFRA standard and the marginal risk found (ie. sediment dwelling invertebrates) associated 

with certain proposed uses is outweighed by the benefits ofthe use of these products. No 

additional data are being required for registration. Therefore. EPA is proposing the unconditional 

registration for the five proposed oxathiapiprolin products under Section 3(c)(5) of FIFRA. 

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The human health and environmental risk assessments supporting this decision as well as the 

draft labeling can be found in the regulatory docket (Document lD: EPA-HQ-OPP-2014-011 4). 

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