Fludioxonil Human-Health Risk Assessment DP# 389613

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

DATE: 21-MAY-2012

SUBJECT: Fludioxonil. Tolerance Petitions for Residues in/on Ginseng, Leafy Petioles 

Crop Subgroup 4B, Pineapple (post-harvest treatment), Tuberous and Corm 

Vegetable Subgroup 1C, Tropical Fruit (post-harvest treatment), Bulb Onion 

Subgroup 3-07A, Green Onion subgroup 3-07B, Caneberry Subgroup 13-07A, 

Bushberry Subgroup 13-07B, Small Fruit Vine Climbing Subgroup 13-07F 

(except fuzzy kiwifruit), Low-Growing Berry Subgroup 13-07G (except 

cranberry), Fruiting Vegetable Group 8-10 (except tomato), Citrus Fruit Group 

10-10, Pome Fruit Group 11-10, Leafy Vegetable (except Brassica) Subgroup 

4A, Dragon Fruit, and Tomato (post-harvest treatment). Human-Health Risk 

Assessment. 

PC Code: 071503 DP Barcode: D389613

Decision Nos.: 447549, 448805 Registration Nos.: 100-953, 100-1242, 100-969, 100-1308

Petition Nos.: 1E7853, 1E7870 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single 

chemical/Aggregate

Case No.: 7017

TXR No.: None CAS No.: 131341-86-1

MRID No.: None 40 CFR: §180.516

Reviewer: George F. Kramer, Ph.D., Senior Chemist

Anwar Y. Dunbar, Ph.D., Pharmacologist

Lata Venkateshwara Environmental Scientist

Risk Assessment Branch 1 (RAB1)

Health Effects Division (HED, 7509P)

Through: David E. Hrdy, Acting Branch Chief

RAB1/HED (7509P)

To: Barbara Madden/Laura Nollen, RM 05

Mary Waller/Lisa Jones, RM 21

Registration Division (RD, 7505P)

HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human 

health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard 

and exposure data and conduct dietary, occupational/residential, and aggregate exposure 

assessments, as needed, to estimate the risk to human health that will result from the registered 

and proposed new uses of fludioxonil (4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-

carbonitrile) on ginseng, leaf petioles, pineapple (post-harvest treatment), potato (post-harvest 

treatment), spinach, tropical fruit (post-harvest treatment), bulb onion, green onion, caneberry, 
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bushberry, small fruit vine climbing (except fuzzy kiwifruit), low-growing berry (except 

cranberry), fruiting vegetables, citrus fruit, pome fruit, leafy vegetables (except Brassica), 

dragon fruit, and tomato (post-harvest treatment).

The risk assessment, dietary-exposure assessment, and the residue chemistry data review were 

provided by George Kramer (RAB1); the hazard assessment by Anwar Dunbar (RAB1); the 

occupational/residential exposure assessment by Lata Venkateshwara (RAB1); and the drinking 

water assessment by Cheryl Sutton of the Environmental Fate and Effects Division (EFED).
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TABLE OF CONTENTS

1.0 EXECUTIVE SUMMARY ..................................................................................................... 4

2.0 HED Recommendations.......................................................................................................... 9

2.1 Data Deficiencies/Conditions of Registration.................................................................. 9

2.2 Tolerance Considerations................................................................................................ 10

3.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION............................... 13

3.1 Identification of Active Ingredient ................................................................................. 13

3.2 Physical and Chemical Properties.................................................................................. 14

4.0 HAZARD CHARACTERIZATION.................................................................................... 14

4.1 FQPA Considerations...................................................................................................... 16

4.2 Toxicity Endpoint and Point of Departure Selection.................................................... 16

5.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION .......................................... 18

5.1 Summary of Proposed Uses............................................................................................. 18

5.2 Dietary Exposure/Risk Pathway..................................................................................... 21

6.0 RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE/RISK 

CHARACTERIZATION ............................................................................................................. 28

6.1 Residential Handler Exposure/Risk............................................................................... 28

6.2 Residential Post-application Exposure and Risk .......................................................... 29

6.3 Combined Exposure......................................................................................................... 30

6.4 Other (Spray Drift, etc.).................................................................................................. 31

6.5 Residential Bystander Post-application Inhalation Exposure ..................................... 32

7.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION............... 32

7.1 Acute Aggregate Risk ...................................................................................................... 32

7.2 Short-Term Aggregate Risk............................................................................................ 32

7.3 Intermediate-Term Aggregate Risk ............................................................................... 33

7.4 Chronic Aggregate Risk .................................................................................................. 34

7.5 Cancer Aggregate Risk.................................................................................................... 34

8.0 CUMULATIVE RISK CHARACTERIZATION/ASSESSMENT ................................... 34

9.0 OCCUPATIONAL EXPOSURE/RISK PATHWAY......................................................... 35

9.1 Occupational Handler Risk............................................................................................. 35

9.2 Occupational Post-Application Risk .............................................................................. 39

Appendix A: Toxicity Profile ...................................................................................................... 39

Appendix B: International Residue Limits................................................................................ 43
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1.0 EXECUTIVE SUMMARY

Fludioxonil, 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile, is a phenylpyrrole fungicide registered for use on a variety of field and vegetable crops, fruit trees, berries, 

herbs, and grasses. It can be applied as a seed treatment, an at-planting soil application, and/or 

broadcast foliar application. Post-harvest uses are also allowed on selected fruit and root crops. 

A total of 26 end-use products (EPs) containing fludioxonil are currently registered to Syngenta 

Crop Protection for use on food/feed crops. These EPs contain 0.13 to 50% fludioxonil as the 

active ingredient (ai) and are formulated as wettable powders (WPs), water-dispersible granules 

(WDGs), flowable concentrates (FlCs), and dusts. Fludioxonil is also currently registered for 

use on residential turf and ornamentals. A human-health assessment scoping document in 

support of fludioxonil registration review has recently been completed (DP# 384857, W. 

Wassell et al., 6/13/2011).

Permanent tolerances have been established for residues of fludioxonil per se in/on a variety of 

plant commodities, ranging from 0.01 ppm on numerous commodities to 500 ppm on citrus oil 

[40 CFR §180.516(a)]. There are currently no tolerances for fludioxonil residues in livestock 

commodities.

Interregional Research Project No. 4 (IR-4) has submitted a petition (1E7853) for the use of 

fludioxonil on ginseng, pineapple (post-harvest treatment), tuberous and corm vegetable 

subgroup 1C, spinach, tropical fruit (post-harvest treatment), bulb onion, green onion, caneberry, 

bushberry, small fruit vine climbing (except fuzzy kiwifruit), low-growing berry (except 

cranberry), fruiting vegetables, citrus fruit, pome fruit, leafy vegetables (except Brassica), 

dragon fruit, and tomato (post-harvest treatment). In addition, Syngenta has submitted a petition 

(1E7870) for the use of fludioxonil on leafy petioles. 

No new data were submitted to support tolerances for residues in/on onion, bulb, subgroup 3-

07A; onion, green, subgroup 3-07B; low-growing berry 13-07G crop subgroup; caneberry

subgroup 13-07A; bushberry subgroup 13-07B; fruit, citrus, group 10; fruit, pome, group 11-10; 

or small fruit vine climbing subgroup 13-07F, except fuzzy kiwifruit. IR-4 has requested that 

existing tolerances be expanded to their respective crop groups or crop subgroups. Residue data 

for spinach, pepper, ginseng, and potato were reviewed with the Pest Management Regulatory

Agency (PMRA) of Canada as part of a joint review.

Toxicology/Hazard

Fludioxonil is of low acute toxicity; the full battery of acute tests indicated that technical grade 

fludioxonil is in Toxicity Category III or IV. It is not a dermal sensitizer. For subchronic and 

chronic toxicity, the primary effects in the mouse and rat were similar and included decreased 

body weight and food consumption associated with clinical pathological and histopathological 

effects in the liver and kidney. In the subchronic dog study, diarrhea was the most sensitive 

indicator of toxicity. In contrast, in the chronic toxicity study in dogs, decreased body-weight 

gain in females was the most sensitive indicator of toxicity. Liver toxicity was observed in both 

dog studies at higher doses. Fludioxonil was not developmentally toxic in rabbits. In a rat 

developmental toxicity study at the limit dose (1000 mg/kg/day), fludioxonil caused an increase 

in fetal incidence and litter incidence of dilated renal pelvis (in the presence of maternal 

toxicity). There was no quantitative or qualitative evidence of increased susceptibility to rats 

and rabbits following in utero exposure. There was no quantitative or qualitative evidence of 

increased susceptibility to rats following postnatal exposure.
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Fludioxonil is classified as a Group D Chemical; not classifiable as to human carcinogenic 

potential. Nonetheless, HED has determined that fludioxonil poses a negligible cancer risk. 

This conclusion was based on the fact that cancer studies show evidence of cancer in one sex of 

one species. There was no evidence of carcinogenicity in male rats, but there was a statistically

significant increase, both trend and pairwise, of combined hepatocellular tumors in female rats. 

The pairwise increase for combined tumors was significant at p=0.03, which is not a strong 

indication of a positive effect. Further, statistical significance was only found when liver 

adenomas were combined with liver carcinomas. Finally, the increase in these tumors was 

within, but at the high end, of the historical controls. There was no evidence of carcinogenicity

in mice when tested up to the limited dose 7,000 ppm. Fludioxonil was not mutagenic in the 

tests for gene mutations. However, based on the induction of polyploidy in the in vitro Chinese 

hamster ovary cell cytogenetic assay and the suggestive evidence of micronuclei induction in rat 

hepatocytes in vivo, additional mutagenicity testing was performed in three studies specifically 

designed to address the concerns regarding aneuploidy. The results of these assays were 

negative for aneuploidy activity.

In a 28-day dermal toxicity study in rats, the no-observed adverse-effect level (NOAEL), based 

on no significant adverse effects in either sex, was equal to or greater than 1000 mg/kg/day 

[highest-dose tested (HDT)]. 

In a rat metabolism study, tissue distribution showed that terminal residues were below the limit 

of detection (LOD) for most tissues except the liver, kidneys, blood, and lungs. The major route 

of excretion was the feces; with approximately 80% of the administered radioactivity at both the 

low and high doses in male and female rats excreted by this route. The remaining radioactivity

was excreted through the urine. Fludioxonil was well absorbed from the gastro-intestinal tract. 

In bile-duct-cannulated rats, approximately 70% of an administered radioactive dose was 

excreted via this route; supporting the bile as the origin of the fecal radioactivity. There were no 

apparent sex or dose related differences in the routes of excretion for fludioxonil. Examination 

of urine for metabolites of fludioxonil showed at least 20 metabolites; each one comprised a 

minor fraction of the administered dose (0.1 to 3.1%). There were no significant sex or dose 

differences in urinary metabolites. 

The fludioxonil risk assessment team evaluated the toxicology database, selected doses and 

endpoints for chronic dietary exposures, as well as occupational and residential exposure 

scenarios [short-, intermediate-, and long-term exposure (dermal and inhalation)], and addressed 

the sensitivity of infants and children from exposure to fludioxonil as required by the Food 

Quality Protection Act (FQPA) of 1996. Since the last risk assessment, a guideline 

immunotoxicity study has been submitted and is currently under review. HED’s Hazard and 

Science Policy Council (HASPOC) used a weight-of-evidence approach to require a 90-day

inhalation study and to not require the neurotoxicity screening battery studies (Memo, D. 

Smegal, 29-FEB-12, TXR# 0050679). Until this 90-day inhalation study is submitted and 

reviewed, a 10X database uncertainty factor (UFDB) will be used to account for uncertainty

stemming from the oral to inhalation route-to-route extrapolation. Toxicological points of 

departure (PODs) for dietary, occupational/residential exposure and risk assessment for 

fludioxonil are summarized in Tables 4.2.1 and 4.2.2, respectively. The potential enhanced 

sensitivity of infants and children from exposure to fludioxonil, as required by the FQPA of 

1996, was also addressed. The team concluded that the 10X Safety Factor (SF) should be 

reduced to 1X for oral exposures. 

Since the PODs are based on a common endpoint, oral and inhalation exposures can be 
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combined for aggregation of short- and intermediate-term risks. Since a POD was not identified 

for short- and intermediate-term dermal exposure risk assessments, assessment of dermal 

exposure and aggregation of dermal with inhalation and/or oral exposures is unnecessary. 

Dietary Exposure (Food Plus Water)

Acute and chronic dietary (food plus water) risk assessments were conducted using the Dietary

Exposure Evaluation Model (DEEM-FCIDTM, Version 2.03) which uses food consumption data 

from the U.S. Department of Agriculture’s (USDA’s) Continuing Surveys of Food Intakes by

Individuals (CSFII) from 1994-1996 and 1998. 

An unrefined acute dietary exposure and risk analysis was performed assuming tolerance-level 

residues, 100% crop-treated (CT), and DEEMTM (ver. 7.81) default processing factors. The 1-in10-year acute drinking water estimate (i.e., relevant to acute exposure) of 0.0838 ppm, provided 

by EFED, was directly incorporated into the acute assessment. This analysis was performed for 

females 13 to 49 years old, the only subgroup of interest for acute exposure. The acute dietary 

(food plus water) risk for females 13 to 49 years old utilizes 16% of acute population-adjusted 

dose (aPAD).

A partially refined chronic dietary exposure and risk assessment was performed assuming 

tolerance-level residues for most commodities [with the exception of celery, pineapple, potato, 

spinach, apple, grapefruit, lemon, lime, orange, pear, tomato, head lettuce, leaf lettuce, fresh 

parsley, Brassica leafy vegetables (crop group 5), grape, cherry, peach, and plum], 100% CT 

estimates, and DEEMTM (ver. 7.81) default processing factors [with the exception of citrus fruit 

juice (1X), apple juice (1X), grape juice (0.42X), raisin (1.65X), potato commodities (1X), and 

tomato commodities (1X), except dried tomato (14.3X)]. These processing factors are based on 

processing study data. Anticipated residue estimates (ARs) for celery, pineapple, potato, 

spinach, apple, grapefruit, lemon, lime, orange, pear, tomato, head lettuce, leaf lettuce, fresh 

parsley, Brassica leafy vegetables (crop group 5), grape, cherry, peach, and plum were 

generated from field trial and processing study data. The 1-in-10-year chronic drinking water 

estimate (i.e., relevant to chronic exposure) of 0.0385 ppm, provided by the EFED, was directly

incorporated into the chronic assessment. For the U.S. population the dietary risk (food plus 

water) utilizes 26% of the chronic PAD (cPAD). The chronic dietary risk estimate for the 

highest reported exposed population subgroup, children 1 to 2 years old, utilizes 68% of the 

cPAD. 

Fludioxonil is classified as a Group D chemical - not classifiable as to human carcinogenicity;

therefore, there is no need for a quantitative cancer risk assessment. 

Non-Occupational and Residential Exposure/Risks

The proposed uses will not result in residential exposures; however, fludioxonil is currently

registered for use in residential areas, including parks, golf courses, athletic fields, residential 

lawns, ornamentals, and greenhouses. The registered turf use has been reassessed in this 

document to reflect updates to HED’s Residential Standard Operating Procedures (SOPs), 2012. 

The currently registered label for turf is Medallion®Fungicide (EPA Reg. # 100-769). 

Medallion®Fungicide is a 50% WP in water-soluble packaging. The maximum single 

application rate is 0.50 oz per 1000 ft2 or 0.68 lbs ai/A. 

Residential handler and post-application exposure is expected from the use on residential turf. 
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Since HED did not select short- or intermediate-term dermal PODs, only residential adult 

handler inhalation exposure and incidental oral post-application exposure for children were 

assessed. All residential handler inhalation exposures were above the level of concern (LOC)

and are not of concern to HED. In addition, post-application risk estimates do not exceed 

HED’s LOC for any of the scenarios assessed. 

Aggregate Exposure/Risks

Acute Aggregate Exposure

Acute aggregate risk estimates do not exceed the LOC. Since the acute aggregate risk 

assessment includes only food and water, and the acute dietary analysis included both, no 

further calculations are necessary. Since the acute dietary risk does not exceed the LOC, the 

acute aggregate risk does not exceed the LOC.

Short-term Aggregate Exposure (Food + Water + Residential)

Due to the application of fludioxonil on residential turf, there is potential for short-term handler 

and post-application exposure. Since no dermal POD was selected, the short-term aggregate 

assessment for children includes exposure from food, water, and post-application non-dietary

oral exposures (resulting from contact with treated lawns). For adults, short-term aggregate 

combines dietary (food + water) exposure with inhalation exposure (resulting from residential 

handlers treating lawns). The short-term aggregate exposures and risks do not exceed the LOC. 

Intermediate-term Aggregate Exposure (Food + Water + Residential)

Due to the application of fludioxonil on residential turf, there is potential for intermediate-term 

post-application exposure. Since no dermal POD was selected and post-application inhalation 

exposure is expected to be minimal, the only intermediate-term residential exposure is 

incidental oral post-application exposure for children on treated lawns (resulting from the 

currently registered use). The intermediate-term aggregate assessment for children includes 

exposure from food, water, and post-application non-dietary oral exposures resulting from 

contact with treated lawns. The intermediate-term aggregate exposure and risk does not exceed 

the LOC. 

Chronic Aggregate Exposure

Chronic aggregate risk estimates do not exceed the LOC. Since no chronic residential exposure 

is expected to result from the residential uses of fludioxonil, the chronic aggregate risk 

assessment includes only food and water. As the chronic dietary analysis included both food 

and water, further estimates of risk are not necessary. 

Occupational Exposure/Risks

It is anticipated that there will be occupational hander and post-application exposure from the 

proposed uses on agricultural crops. It is the policy of HED to use the best available data to 

assess handler exposure. Sources of generic handler data, used as surrogate data in the absence 

of chemical-specific data, include the Pesticide Handlers Exposure Database Version 1.1 

(PHED 1.1), the Agricultural Handler Exposure Task Force (AHETF) database, the Outdoor 

Residential Exposure Task Force (ORETF) database, or other registrant-submitted occupational 

exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data 

protection provisions of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The 

standard values recommended for use in predicting handler exposure that are used in this 

assessment, known as “unit exposures,” are outlined in the “Occupational Pesticide Handler 
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Unit Exposure Surrogate Reference Table” (http://www.epa.gov/opp00001/science/handlerexposure-table.pdf), which, along with additional information on HED policy on use of 

surrogate data, including descriptions of the various sources, can be found at 

http://www.epa.gov/pesticides/science/handler-exposure-data.html.

Occupational handlers are anticipated to have short- and intermediate-term dermal and inhalation 

exposures. However, since no short- or intermediate-term dermal PODs were selected, only 

inhalation exposures are assessed in this document. HED has determined that risks are of 

concern for short-term exposures (i.e., MOEs <1000) for mixing/loading WPs for aerial and 

chemigation applications, and require a PF5 respirator with 80% protection factor to reach 

acceptable MOEs. HED has also determined that for intermediate-term exposures, the personalprotective equipment (PPE) required to reach acceptable MOEs (i.e., MOEs >1000) for 

mixing/loading WPs for aerial and chemigation applications includes engineering controls. 

Furthermore, for mixing/loading WPs for groundboom applications and for mixing/loading dry

flowables (DFs) for aerial and groundboom applications, a PF5 respirator with 80% protection 

factor is required for intermediate-term exposures to reach MOEs >1000.

Environmental Justice Consideration

Potential areas of environmental-justice concerns, to the extent possible, were considered in this 

human-health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations” 

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf).

As a part of every pesticide risk assessment in accordance with well-established procedures, 

OPP considers a large variety of consumer subgroups. In line with OPP policy, HED estimates 

risks to population subgroups from pesticide exposures that are based on patterns of that 

subgroup’s food and water consumption, and activities in and around the home that involve 

pesticide use in a residential setting. Extensive data on food consumption patterns are compiled 

by the USDA under CSFII; and are used in pesticide risk assessments for all registered food 

uses. These data are analyzed and categorized by subgroups based on age, season of the year, 

ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to 

smaller, specialized subgroups; and exposure assessments are performed when conditions or 

circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of 

pesticide products and associated risks for adult applicators and for young children, youths, and

adults entering or playing on treated areas post-application are evaluated. Further 

considerations are currently in development as OPP has committed resources and expertise to 

the development of specialized software and models that consider exposure to bystanders and 

farm workers as well as lifestyle and traditional dietary patterns among specific subgroups.

Review of Human Research

This risk assessment relies in part on data from studies in which adult human subjects were 

intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many

such studies, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as PHED and the Agricultural Reentry Task Force (ARTF) database. 

EPA has reviewed all the studies in these multi-pesticide generic exposure databases, and based 

on available evidence has found them to have been neither fundamentally unethical nor 

significantly deficient relative to standards of ethical research conduct prevailing when they were 

conducted. There is no regulatory barrier to continued reliance on these studies, and all 
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applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 

CFR Part 26) have been satisfied.

2.0 HED Recommendations

Provided revised Sections B and F are submitted, HED concludes that the toxicological, residue 

chemistry and occupational/residential databases support a conditional Section 3 registration and 

establishment of the tolerances listed in Section 2.2. 

2.1 Data Deficiencies/Conditions of Registration

Prior to Registration: 

Residue Chemistry

860.1200 Directions for Use

 Adjuvants were not used in all of the submitted residue field trials. Since adjuvants were 

not used in the ginseng, fruiting vegetables, bulb onion subgrcoup 3-07A, green onion 

subgroup 3-07B, caneberry subgroup 13-07A, bushberry subgroup 13-07B, small fruit 

vine climbing subgroup 13-07F (except fuzzy kiwifruit), low-growing berry subgroup 

13-07G (except cranberry), and fruiting vegetable group 8-10 residue field trials, the 

label should prohibit adjuvant use on these crops.

860.1650 Submittal of Analytical Reference Standards

 An analytical reference standard for fludioxonil is currently available at the EPA 

National Pesticide Standards Repository (personal communication with Theresa Cole, 

8/15/11) with an expiration date of 5/30/13. However, a reference standard of 

CGA192155 (2,2-difluoro-l,3-benzodioxole-4-carboxylic acid) should be sent to the 

Repository, which is located at Fort Meade, to the attention of Theresa Cole at the 

following address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

(Note that the mail will be returned if the extended zip code is not used.)

860.1550 Proposed Tolerances

 A summary of the recommended tolerance levels along with recommendations for 

commodity definitions are presented in Section 2.2. The petitioner is required to submit 

a revised Section F to reflect the recommendations in Section 2.2.
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Occupational Exposure

860.1200 Directions for Use

 The occupational risk assessment indicates that risks are of concern for short-term 

exposures for mixing/loading WPs for aerial and chemigation applications, and require a 

PF5 respirator with 80% protection factor to reach acceptable MOEs. HED has also 

determined that for intermediate-term exposures, the PPE required to reach acceptable 

MOEs for mixing/loading WPs for aerial and chemigation applications includes 

engineering controls. Furthermore, for mixing/loading WPs for groundboom 

applications and for mixing/loading DFs for aerial and groundboom applications, a PF5 

respirator with 80% protection factor is required for intermediate-term exposures to 

reach MOEs >1000. RD should ensure that the proper PPE is listed on the label. 

As a Condition of Registration: 

Toxicology

 A 90-day inhalation study (870.3465).

2.2 Tolerance Considerations

Enforcement Analytical Method: Adequate high-performance liquid chromatography/ultraviolet 

light detector (HPLC/UV) methods (Syngenta Methods AG-597 and AG-597B) are available for 

enforcing tolerances for residues of fludioxonil in/on plant commodities. In the current field trials 

and processing studies, residues of fludioxonil were determined using a liquid chromatography and 

tandem mass-spectrometry detection (LC-MS/MS) method, which is a modified version of Method 

AG-597B. The LC-MS/MS method was adequately validated in conjunction with the analysis of 

field trial and processing study samples. The validated limit of quantitation (LOQ) for fludioxonil 

was 0.01 or 0.02 ppm in each matrix, and the LOD was 0.003 or 0.006 ppm. LC-MS/MS 

Analytical Method GRM025.03A (as modified in MRID# 48526508) is suitable as an enforcement 

method for livestock commodities as defined in SOP No. ACB-019 (9/15/08). This is a commonmoiety method in which fludioxonil and its metabolites of regulatory concern are converted to 

CGA192155 (2,2-difluoro-1,3-benzodioxole-4-carboxylic acid).

International Harmonization: There are currently no established Codex, Canadian, or Mexican 

maximum residue limits (MRLs) for fludioxonil in/on tropical fruits. The following U.S., 

Canadian, and Codex tolerances/MRLs for residues of fludioxonil are harmonized: bushberries, 

grapes, citrus fruits, and pome fruits. Additionally, the U.S. and Canadian tolerances/MRLs for 

tuberous and corm vegetables subgroup 1C, spinach, fruiting vegetables except tomato, and 

ginseng are being harmonized as part of this joint review. 

The U.S., Canadian, and Codex tolerances/MRLs for residues of fludioxonil in/on bulb onions, 

caneberries, grapes (small vine climbing fruit, subgroup 13-07F), strawberries (low-growing 

berry subgroup 13-07G), tomatoes, and leafy vegetables cannot be harmonized as the Canadian, 

and Codex MRLs differ. For leafy vegetables except Brassica subgroup 4A, the U.S. and 

Canada are harmonized at 30 ppm, but a Codex MRL is established for head lettuce at 10 ppm. 

For the bulb onion subgroup 3-07A, small vine climbing fruit subgroup 13-07F, and lowgrowing berry subgroup 13-07G, HED recommends that the U.S. tolerances be increased in 

order to harmonize with Codex; bulb onion subgroup 3-07A from 0.20 to 0.50 ppm, small vine 
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climbing fruit subgroup 13-07F from 1.0 to 2.0 ppm and low-growing berry subgroup 13-07G

from 2.0 to 3.0 ppm. 

The tolerances/MRLs cannot be harmonized for green onions, tomatoes, leafy vegetables except 

Brassica subgroup 4A, and leafy petioles as the U.S. residue data/use patterns necessitate a 

higher value. 

For livestock commodities, the U.S. and Codex residue definitions are harmonized; however, the 

Canadian residue definition is not harmonized. The numerical values for the U.S. and Canadian 

livestock tolerances/MRLs are harmonized (see Appendix B). 

Recommended Tolerances: Table 2.2.1 is a summary of the proposed and HED-recommended 

tolerance for residues of fludioxonil. In accordance with the most recent guidance concerning 

tolerance expressions, HED recommends that the tolerance expression for 180.516 (a) be changed 

as indicated below. A revised Section F specifying the new tolerance expression and the HEDrecommended tolerances should be submitted. 

40 CFR §180.516 (a) General. (1) should be as follows: Tolerances are established for 

residues of the fungicide fludioxonil, including its metabolites and degradates, in or on the 

commodities in the table below. Compliance with the tolerance levels specified below is to be 

determined by measuring only fludioxonil, 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1-H-pyrrole3-carbonitrile).

40 CFR §180.516 (a) General. (2) should be as follows: Tolerances are established for 

residues of the fungicide fludioxonil, including its metabolites and degradates, in or on the 

commodities in the table below. Compliance with the tolerance levels specified below is to be 

determined by measuring only the sum of fludioxonil, 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1-

H-pyrrole-3-carbonitrile), and its metabolites converted to 2,2-difluoro-l,3-benzodioxole-4-

carboxylic acid, calculated as the stoichiometric equivalent of fludioxonil.

Table 2.2.1. Tolerance Summary for Fludioxonil. 

Commodity

Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Correct Commodity 

Definition/Comments

To be established under 40 CFR §180.516 (a) General. (1) 

Guava 5 5.0

Feijoa 5 5.0

Jaboticaba 5 5.0

Wax jambu 5 5.0

Starfruit 5 5.0

Passionfruit 5 5.0

Acerola 5 5.0

Avocado 5 5.0

Black sapote 5 5.0

Mamey sapote 5 5.0

Canistel 5 5.0

Mango 5 5.0

Papaya 5 5.0

Sapodilla 5 5.0

Star apple 5 5.0

Lychee 20 20

Longan 20 20

Spanish lime 20 20
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Table 2.2.1. Tolerance Summary for Fludioxonil. 

Commodity

Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Correct Commodity 

Definition/Comments

Rambutan 20 20

Pulasan 20 20

Sugar apple 20 20

Atemoya 20 20

Custard apple 20 20

Cherimoya 20 20

Ilama 20 20

Soursop 20 20

Biriba 20 20

Ginseng 3.0 4.0

Onion, bulb subgroup 3-07A 0.2 0.50 Increased in order to harmonize 

with Codex MRL.

Onion, green subgroup 3-

07B 7.0 7.0

Caneberry subgroup 13-07A 5.0 5.0

Bushberry subgroup 13-07B 2.0 2.0

Small fruit vine climbing 

subgroup 13-07F, except 

fuzzy kiwifruit

1.0 2.0

Fruit, small, vine climbing, 

subgroup 13-07F, except fuzzy 

kiwifruit. Increased in order to 

harmonize with Codex MRL.

Low growing berry subgroup 

13-07G, except cranberry 2.0 3.0 Increased in order to harmonize with Codex MRL.

Vegetable, fruiting group 8-

10, except tomato 0.7 0.50

Tomato 3.0 5.0

Fruit, citrus, group 10-10 10 10

Fruit, pome, group 11-10 5 5.0

Vegetable, leafy, except 

brassica, subgroup 04A 30 30 Vegetable, leafy, except Brassica, subgroup 4A

Vegetable, tuberous and 

corm, subgroup 1C 6.0 6.0

Pineapple 8.0 20

Dragon-fruit 1.0 1.0 Dragon fruit

Leafy petioles crop subgroup 

4B 14 15

To be established under 40 CFR §180.516 (a) General. (2)

Milk - 0.01

Cattle, meat byproducts - 0.05

Cattle, meat - 0.01

Cattle, fat - 0.05

Goat, meat byproducts - 0.05

Goat, meat - 0.01

Goat, fat - 0.05

Horse, meat byproducts - 0.05

Horse, meat - 0.01

Horse, fat - 0.05

Sheep, meat byproducts - 0.05

Sheep, meat - 0.01

Sheep, fat - 0.05

Remove from 40 CFR §180.516 (a):

Onion, bulb 0.20 These tolerances should be removed 

from 40 CFR §180.516 because 

tolerances are being established for 

crop groups that contain these raw

Onion, green 7.0

Caneberry subgroup 13A 5.0

Bushberry subgroup 13B 2.0
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Table 2.2.1. Tolerance Summary for Fludioxonil. 

Commodity

Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Correct Commodity 

Definition/Comments

Juneberry 2.0 agricultural commodities (RACs) or 

a higher tolerance is required based 

on the proposed use pattern. 

Lingonberry 2.0

Salal 2.0

Grape 1.0

Strawberry 2.0

Vegetable, fruiting group 8 0.01

Tomatillo 0.50

Fruit, citrus, group 10 10

Fruit, pome, group 11 5.0

Leafy greens subgroup 4A, 

except spinach 30

Vegetable, tuberous and 

corn, except potato, 

subgroup 1D

3.5

Revisions to Petition-For Tolerances: Based on the proposed uses and the submitted data, HED 

concluded that crop group tolerances were appropriate. The HED recommended tolerances are 

based on the submitted field trial data and the Organization for Economic Co-operation and 

Development (OECD) tolerance calculation procedures. For the bulb onion subgroup 3-07A, 

small vine climbing fruit subgroup 13-07F, and low-growing berry subgroup 13-07G, HED 

recommends that the U.S. tolerances be increased in order to harmonize with the established 

Codex MRLs.

3.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION

3.1 Identification of Active Ingredient

Table 3.1. Fludioxonil Nomenclature.

Compound

Common name Fludioxonil

Company experimental name CGA-173506

IUPAC name 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile

CAS name 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile

CAS registry number 131341-86-1

End-use product (EP) Switch®62.5WG Fungicide (25% WDG; EPA Reg. No. 100-953)

Scholar®230SC Fungicide (20.5% SC; EPA Reg. No. 100-1242)

Scholar®50 WP Fungicide (50% WP; EPA Reg. No. 100-969)

Cannonball® WP (50% WP; EPA Reg. No. 100-1360)

Graduate A+TM (20.6% SC; EPA Reg. No. 100-1308)

Compound

Company experimental name CGA192155

O

O

F

F

N

H

CN
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Table 3.1. Fludioxonil Nomenclature.

IUPAC name 2,2-difluoro-benzo[l,3]dioxole-4-carboxylic acid

CAS name 2,2-difluoro-1,3-benzodioxole-4-carboxylic acid

CAS registry number 126120-85-2

3.2 Physical and Chemical Properties

Table 3.2. Physicochemical Properties of Fludioxonil.

Parameter Value Reference

Melting point 199.8 °C DP# 348539, D. Rate, 

09/10/08 pH 8-9 @ 25 °C (1% aqueous dispersion)

Density 1.54 g/cm3typical at 23 °C

Water solubility (25 C) 1.8 mg/L

Solvent solubility (g/L at 20 C) Ethanol 44,000

Acetone 190,000

Toluene 2,700

n-Octanol 20,000

n-Hexane 7.8

Vapor pressure at 25 C 2.9 x 10-9 mm Hg

Dissociation constant (pKa) pKa1 <0

pKa2 ~14.1

Octanol/water partition coefficient, Log(KOW) 4.12 @ 25 °C

UV/visible absorption spectrum 12,384 L/mol x cm @ 266 nm (neutral solution)

12,327 L/mol x cm @ 265 nm (acidic solution)

11,790 L/mol x cm @ 271 nm (basic solution)

4.0 HAZARD CHARACTERIZATION

NOTE: In 2008, the Alternative Risk Integration and Assessment (ARIA) Team of RD

completed a Section 3 risk assessment for the application of fludioxonil to avocado, carrot, 

cucurbit, lemon, parsley, radish, sweet potato, tomato, and Brassica vegetables (Memo, 

7/10/2008, B. Hanson, et al.; D342827). A complete discussion of the hazard assessment can 

be found in this previous risk assessment. Since the last risk assessment, a guideline 

immunotoxicity study has been submitted and is currently under review. HED’s HASPOC used 

a weight-of-evidence approach to require a 90-day inhalation study and to not require the 

neurotoxicity screening battery studies (Memo, D. Smegal, 29-FEB-12, TXR# 0050679). For 

the inhalation study, this approach considered all of the available hazard and exposure 

information for fludioxonil, including: (1) the use of an oral POD that results in MOEs as low 

as 70 for risk via the inhalation route resulting from occupational exposure; (2) the 

physical/chemical properties of fludioxonil; (3) the toxicological profile of fludioxonil; and (4) 

signs of respiratory toxicity (dyspnea) in the acute inhalation toxicity study. Until this 90-day

inhalation study is submitted and reviewed, a 10X UFDB will be used to account for uncertainty

stemming from the oral to inhalation route-to-route extrapolation. For the neurotoxicity

screening battery, the decision included the following considerations: 1) lack of evidence for 

clinical signs of neurotoxicity, changes in brain weight or neuropathology in the available 

toxicology studies for fludioxonil except for some convulsions in mice following handling at 

high doses that were considered to be agonal in nature; 2) target organs of toxicity are the liver, 

kidney, and to a less degree, the hematopoietic system; 3) no data are available for other 

structurally similar chemicals (i.e., phenyl-pyrrole fungicides) that showed concern for 

neurotoxicity; 4) rats, the species of choice for conducting the neurotoxicity battery, are not the 
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most sensitive species; and 5) considering the potential impact of the neurotoxicity studies 

providing a POD lower than those used in the overall risk assessment.

Fludioxonil is of low acute toxicity, since technical grade fludioxonil is in Toxicity Category III 

or IV for the full battery of acute tests and is not a dermal sensitizer. For subchronic and 

chronic toxicity, the primary effects in the mouse and rat were similar and included decreased 

body weight and food consumption associated with clinical pathological and histopathological 

effects in the liver and kidney. In the subchronic dog study, diarrhea was the most sensitive 

indicator of toxicity. In contrast, decreased weight gain in females was the most sensitive 

indicator of toxicity in the chronic toxicity study in dogs. Liver toxicity was observed in both 

dog studies at higher doses. Fludioxonil was not developmentally toxic in rabbits. In a rat 

developmental toxicity study, fludioxonil caused an increase in fetal incidence and litter 

incidence of dilated renal pelvis at the limit dose (1000 mg/kg/day). Maternal toxicity occurred 

at the same dose and manifested as a reduction in corrected body-weight gain. There was no 

quantitative or qualitative evidence of increased susceptibility following in utero exposure to 

rats and rabbits or following pre-/postnatal exposure to rats. There was no evidence of 

immunotoxicity when tested up to including the limit dose.

There was no evidence of carcinogenicity in male or female CD-1 mice and male SpragueDawley rats following dietary administration at doses that were adequate for assessing the 

carcinogenic potential of fludioxonil. In female Sprague-Dawley rats, there was a statistically 

significant increase in tumor incidence only when hepatocellular adenomas and carcinomas 

were combined (not for individual tumor types). The pairwise increase for combined tumors 

was significant at p=0.03, which is not a strong indication of a positive effect. Further, 

statistical significance was only found when liver adenomas were combined with liver 

carcinomas. Finally, the increase in these tumors was within, but at the high end, of the 

historical controls. Based on these findings and in accordance with the Agency's 1986 

“Guidelines for Carcinogen Risk Assessment,” fludioxonil was classified as a Group D 

carcinogen; therefore, there is no need for a quantitative cancer risk assessment. The cancer 

classification of fludioxonil was not re-assessed since no new information on carcinogenicity of 

the compound was required. The classification is based on the guidance used when this 

assessment was completed (1996) and should continue to be considered scientifically sound. 

Fludioxonil was not mutagenic in the tests for gene mutations. However, based on the induction 

of polyploidy in the in vitro Chinese hamster ovary cell cytogenetic assay and the suggestive 

evidence of micronuclei induction in rat hepatocytes in vivo, additional mutagenicity testing was 

performed in three studies specifically designed to address the concerns regarding aneuploidy. 

The results of these assays were negative for aneuploidy activity.

In a 28-day dermal toxicity study in rats, the NOAEL was equal to or greater than 1000 

mg/kg/day (HDT) based on no significant adverse effects in either sex. 

In a rat metabolism study, tissue distribution showed that terminal residues were below the LOD 

for most tissues except the liver, kidneys, blood, and lungs. The major route of excretion was 

the feces, with approximately 80% of the administered radioactivity excreted by this route in 

male and female rats at both the low and high dose. The remaining radioactivity was excreted 

through the urine. Fludioxonil was well absorbed from the gastro-intestinal tract. In bile ductcannulated rats, approximately 70% of an administered radioactive dose was excreted via this 

route, supporting the bile as the origin of the fecal radioactivity. There were no apparent sex- or 

dose-related differences in the routes of excretion for fludioxonil. Examination of urine for 
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metabolites of fludioxonil showed at least 20 metabolites, each comprising a minor fraction of 

the administered dose (0.1 to 3.1%). There were no significant differences in urinary

metabolites with sex or dose. 

4.1 FQPA Considerations

Based on the weight-of-evidence considerations for both hazard and exposure, the Agency has 

determined that the overall assessment does not underestimate risk for the current uses and, 

therefore, a UFDB in the form of the FQPA SF is reduced to 1X for oral exposures. This 

recommendation is based on the following considerations:

 The toxicology database is adequate for FQPA assessment. 

 There was no evidence of increased susceptibility following in utero exposure to rats 

and rabbits or following pre-/post-natal exposure to rats. In rats, developmental effects

occurred in the presence of maternal effects. In rabbits, no developmental toxicity was 

seen up to the highest dose tested which demonstrated maternal toxicity. In the twogeneration rat reproduction study, offspring toxicity was seen at the dose that produced 

parental toxicity. There are no residual uncertainties of pre- and/or post-natal toxicity. 

 The only potential indicator of neurotoxicity for fludioxonil was some convulsions in 

mice following handling at high doses that were considered to be agonal in nature. 

 A developmental neurotoxicity study is not required.

 There are no residual uncertainties in the exposure database. The dietary and residential 

exposure analyses are conservative in nature. The dietary exposure assessment assumes 

100% crop treated and uses tolerance-level residues or made use of average residues 

derived from crop field trial studies (maximum application rate and minimum preharvest interval). 

 The residential exposure assessment uses chemical-specific turf-transferable residue data 

and the 2012 Residential SOPs and is considered health-protective.

 Although an inhalation study is required for fludioxonil, the oral PODs used for 

assessing inhalation risk are based on the most sensitive endpoints established in the 

most sensitive species. Furthermore, an additional 10X uncertainty factor (UFDB) will 

be used to further protect for the uncertainty from this oral to inhalation route-to-route 

extrapolation. Based on these oral PODs, all residential handler inhalation exposures 

were well above the LOC and are not of concern to HED. Therefore, the risk estimate is 

conservative and will not underestimate risk via the inhalation route.

4.2 Toxicity Endpoint and Point of Departure Selection

Table 4.2.1. Summary of Toxicological Doses and Endpoints for Fludioxonil for Use in Dietary and NonOccupational Human-Health Risk Assessments.

Exposure/

Scenario POD

Uncertainty/

FQPA SFs

RfD, PAD, 

LOC for Risk 

Assessment Study and Toxicological Effects 

Acute Dietary 

(General 

Population, 

including 

Infants and 

Children)

There were no appropriate toxicological effects attributable to a single exposure (dose) observed 

in available oral toxicity studies, including maternal toxicity in the developmental toxicity studies. 

Therefore, a dose and endpoint were not identified for this risk assessment.
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Table 4.2.1. Summary of Toxicological Doses and Endpoints for Fludioxonil for Use in Dietary and NonOccupational Human-Health Risk Assessments.

Exposure/

Scenario POD

Uncertainty/

FQPA SFs

RfD, PAD, 

LOC for Risk 

Assessment Study and Toxicological Effects 

Acute Dietary

(Females 13-

49 years of 

age)

NOAEL = 100 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Acute RfD = 

1 mg/kg/day

aPAD = 1 

mg/kg/day

Prenatal developmental toxicity in rats.

LOAEL = 1000 mg/kg/day based on the 

increased incidence of fetuses and litters 

with dilated renal pelvis and dilated ureter 

in rat developmental study.

Chronic 

Dietary (All 

Populations)

NOAEL = 3.3 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Chronic RfD 

= 0.033

mg/kg/day

cPAD = 0.033 

mg/kg/day

Chronic toxicity in dogs.

LOAEL = 35.5 mg/kg/day based on 

decreased weight gain in female dogs 

during weeks 1-52 of one-year dog 

feeding study.

Incidental Oral 

Short-Term (1-

30 days)

NOAEL = 10 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential 

LOC for MOE 

= 100

Rabbit developmental study.

LOAEL = 100 mg/kg/day based on 

decreased weight gain during dosing 

period.

Incidental Oral 

IntermediateTerm (1-6 

months)

NOAEL = 3.3 

mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential 

LOC for MOE 

= 100

Chronic toxicity in dogs.

LOAEL = 35.5 mg/kg/day based on 

decreased weight gain in female dogs 

during weeks 1-52 of one-year dog 

feeding study.

Dermal Short-

(1-30 days) 

and 

IntermediateTerm (1-6 

months)

No hazard identified and therefore quantification is not required. There are no developmental 

concerns via the dermal route and no systemic toxicity was seen following dermal exposure.

Inhalation 

Short- Term

(1-30 days)

Oral NOAEL 

= 10 

mg/kg/day

(inhalation 

absorption = 

100%)a

UFA = 10X

UFH = 10X

FQPA SF = 1X

UFDB = 10X

Residential 

LOC for MOE 

= 1000

Rabbit developmental study.

LOAEL = 100 mg/kg/day based on 

decreased weight gain during dosing 

period.

Inhalation 

IntermediateTerm (1-6 

months)

Oral NOAEL 

= 3.3 

mg/kg/day

(inhalation 

absorption = 

100%)a

UFA = 10X

UFH = 10X

FQPA SF = 1X

UFDB = 10X

Residential 

LOC for MOE 

= 1000

Chronic toxicity in dogs.

LOAEL = 35.5 mg/kg/day based on 

decreased weight gain in female dogs 

during weeks 1-52 of one-year dog 

feeding study.

Cancer (oral, 

dermal, 

inhalation)

Classification: Group D chemical - not classifiable as to human carcinogenicity. 

Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data 

and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant 

human exposures. NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. 

UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). UFDB = to account for the absence of key date 

(i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population-adjusted dose (a = acute, c = 

chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 

a

 Inhalation absorption default value of 100% is used with oral toxicity endpoint for route-to-route extrapolation.
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Table 4.2.2. Summary of Toxicological Doses and Endpoints for Fludioxonil for Use in Occupational HumanHealth Risk Assessments.

Exposure/

Scenario POD UFs

LOC for Risk 

Assessment Study and Toxicological Effects

Dermal Short-

(1-30 days) and 

IntermediateTerm (1-6 

months)

No hazard identified and therefore quantification is not required. There are no developmental 

concerns via the dermal route and no systemic toxicity was seen following dermal exposure.

Inhalation 

Short-Term (1-

30 days)

Oral NOAEL 

= 10 

mg/kg/day

(inhalation 

absorption = 

100%)a

UFA =10X

UFH = 10X

UFDB = 10X

Occupational LOC 

for MOE = 1000

Rabbit developmental study

LOAEL = 100 mg/kg/day based on 

Decreased weight gain during dosing 

period.

Inhalation 

Intermediateterm (1-6 

months)

Oral NOAEL 

= 3.3 

mg/kg/day

(inhalation 

absorption = 

100%)a

UFA =10X

UFH = 10X

UFDB = 10X

Occupational LOC 

for MOE = 1000

Chronic toxicity in dogs

LOAEL = 35.5 mg/kg/day based on 

decreased weight gain in female dogs 

during weeks 1-52 of one-year dog feeding 

study.

Cancer (oral, 

dermal, 

inhalation)

Classification: Group D chemical - not classifiable as to human carcinogenicity. 

Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data and 

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). UFDB = to account for the absence of key date 

(i.e., lack of a critical study). MOE = margin of exposure. LOC = level of concern. 

a

 Inhalation absorption default value of 100% is used with oral toxicity endpoint for route-to-route extrapolation.

5.0 EXPOSURE ASSESSMENT AND CHARACTERIZATION

5.1 Summary of Proposed Uses

There are currently 26 EPs containing fludioxonil that are registered to Syngenta Crop Protection 

in the U.S. for use on food/feed crops. These EPs contain 0.13 to 50% fludioxonil and are 

formulated as WPs, WDGs, FlCs, and dusts. One of the formulations registered for foliar 

application on a variety of fruit, nut, vegetable, and herb crops is a 62.5% WDG, a multipleactive-ingredient (MAI) formulation that contains 25% fludioxonil and 37.5% cyprodinil. This 

formulation is registered in the U.S. under the trade name Switch®62.5 WG (EPA Reg. No. 100-

953). Other formulations include Cannonball® WP (EPA Reg. No. 100-1360), Scholar®(EPA 

Reg. No. 100-969), Graduate A+TM (EPA Reg. No. 100-1308), and Scholar®SC (EPA Reg. No. 

100-1242). Information pertaining to the proposed end-use products is listed in Table 5.1.1. A 

summary of the proposed use patterns is detailed in Table 5.1.2. 
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Table 5.1.1. Summary of Proposed End-Use Products.

Trade Name

Reg. 

No.

ai (% 

fludioxonil in

formulation)

Formulation 

Type Target Crops

Target 

Pests Label Date

Switch®

62.5WG

100-

953 25 WG A variety of fruit, nut, vegetable, and herb crops

Soil, 

crown, and 

foliar 

diseases.

Draft labels 

submitted 

3/28/11

Cannonball®

WP

100-

1360 50 WP Onions, berries, ginseng

Scholar® 100-

969 50 WP Postharvest fruit, 

potatoes, tomatoes Postharvest 

fungal 

diseases

Scholar®SC 100-

1242 20.4 SC

Graduate A+TM 100-

1308 20.6 SC Citrus

Table 5.1.2. Summary of Directions for Use of Fludioxonil.

Applic. Timing, 

Type, and Equip.

Formulation

[EPA Reg. No.] App. Rate

Max. No. 

App. per 

Season

Max. Seasonal 

App. Rate

PHI

(days)

Use Directions and 

Limitations

Leafy Vegetables (except Brassica)

Broadcast foliar 

application, 

ground 

equipment only

25% WDG1

[100-953]

0.225

(lb ai/acre) 4

0.9

(lb ai/acre) 0

7- to 10-day retreatment 

interval (RTI)

Fruiting Vegetables

Broadcast foliar 

application, 

ground 

equipment only

25% WDG1

[100-953]

0.225

(lb ai/acre) 4

0.9

(lb ai/acre) 0

14- to 21-day RTI

Do not apply to small 

tomatoes in greenhouse

Ginseng

Drip irrigation 

or ground 

drenching

50% WP

[100-1360]

0.25

(lb ai/acre) 4

1.0

(lb ai/acre) 14

Applications are to be 

made in ≥3 gal/acre using 

ground or aerial 

equipment. 

Pineapple

Postharvest

high-volume 

(dilute)

20.4% SC

[100-1242]

0.24 lb 

ai/50 gal

1

0.24 lb ai/50 gal

Mix in water or wax/water 

50% WP emulsion.

[100-969]

0.25 lb 

ai/50 gal 0.25 lb ai/50 gal

Postharvest

peduncle spray 

(dilute)

20.4% SC

[100-1242]

0.24 lb 

ai/50 gal

1

0.24 lb ai/50 gal Mix in water or wax/water 

emulsion.

Use T-jet application 

system

50% WP

[100-969]

0.25 lb 

ai/50 gal 0.25 lb ai/50 gal

Potato

Postharvest

in-line aqueous 

spray

20.4% SC

[100-1242]

0.009 lb 

ai/ton 

tubers

1

0.009 lb ai/ton 

tubers

Must tank mix with 

difenoconazole or 

azoxystrobin.

Use T-jet application 

system.

50% WP

[100-969]

0.009 lb 

ai/ton 

tubers

0.009 lb ai/ton 

tubers
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Table 5.1.2. Summary of Directions for Use of Fludioxonil.

Applic. Timing, 

Type, and Equip.

Formulation

[EPA Reg. No.] App. Rate

Max. No. 

App. per 

Season

Max. Seasonal 

App. Rate

PHI

(days)

Use Directions and 

Limitations

Tomato

Postharvest

in-line 

drip/drench

20.4% SC

[100-1242]

0.48 lb 

ai/100 gal

1

0.48 lb ai/100 

gal

Mix in water or wax/water 

emulsion.

Must tank mix with 

propiconazole.

50% WP

[100-969]

0.5 lb 

ai/100 gal 0.5 lb ai/100 gal

Postharvest

high-volume 

(dilute)

20.4% SC

100-1242

0.25 lb 

ai/50,000 

lbs fruit

1

0.25 lb 

ai/50,000 lbs 

fruit

Mix in water or wax/water 

emulsion.

Use T-jet application 

system. 

Must tank mix with 

propiconazole.

Not for processing 

tomatoes.

50% WP

[100-969]

0.24 lb 

ai/50,000 

lbs fruit

0.24 lb 

ai/50,000 lbs 

fruit

Tropical Fruit 

Postharvest

in-line 

drip/drench

20.4% SC

[100-1242]

0.48 lb 

ai/100 gal

1

0.48 lb ai/100 

gal Mix in water or wax/water 

emulsion.

Dip for ~30 seconds. 50% WP

[100-969]

0.5 lb 

ai/100 gal 0.5 lb ai/100 gal

Citrus Fruit

Postharvest

in-line 

drip/drench

20.4% SC

[100-1242]

1.0 lb 

ai/100 gal

2

2.0 lb ai/100 gal

Mix in water or wax/water 

emulsion. 

Dip for 30 seconds 

minimum.

50% WP

[100-969]

1.0 lb 

ai/100 gal 2.0 lb ai/100 gal

20.6% SC

[100-1308]

1.0 lb 

ai/100 gal 2.0 lb ai/100 gal

Postharvest

in-line aqueous 

fruit coating 

spray 

application

20.4% SC

100-1242

1.0 lb 

ai/250,000 

lbs fruit

2

2.0 lb 

ai/250,000 lbs 

fruit

Mix in water or wax/water 

emulsion.

Use T-jet application 

system. 

50% WP

[100-969]

1.0 lb 

ai/250,000 

lbs fruit

2.0 lb 

ai/250,000 lbs 

fruit

20.6% SC

[100-1308]

1.0 lb 

ai/250,000 

lbs fruit

2.0 lb 

ai/250,000 lbs 

fruit

1

Switch®62.5 WG is an MAI formulation containing 25% fludioxonil and 37.5% cyprodinil.

2 A minimum plant-back interval (PBI) is 30 days for crops not listed on the label.

Conclusions: The proposed use directions are sufficient to allow for evaluation of the available 

residue data. Provided that the use directions for ginseng, fruiting vegetables, bulb onion 

subgroup 3-07A, green onion subgroup 3-07B, caneberry subgroup 13-07A, bushberry subgroup 

13-07B, small fruit vine climbing subgroup 13-07F (except fuzzy kiwifruit), low-growing berry

subgroup 13-07G (except cranberry), and fruiting vegetable group 8-10 are revised to prohibit 

the use of adjuvants, the available field trial data support the use directions for the proposed uses.
Fludioxonil Human-Health Risk Assessment DP# 389613

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5.2 Dietary Exposure/Risk Pathway

The residue chemistry assessment was completed by HED (Memo, G. Kramer, 05/21/2012; DP# 

389980). The drinking water assessment was completed by EFED (Memo, C. Sutton, 

10/27/2011; DP# 389616). The dietary-exposure assessment was completed by HED (Memo, G. 

Kramer, 05/21/2012; DP# 389981).

5.2.1 Residue Profile

Background

A human-health assessment scoping document in support of fludioxonil registration review has 

recently been completed (DP# 384857, W. Wassell et al., 6/13/2011). In that document, it was 

noted that permanent tolerances have been established for residues of fludioxonil per se in/on a 

variety of plant commodities, ranging from 0.01 ppm on numerous commodities to 500 ppm on 

citrus oil [40 CFR §180.516(a)]. There are currently no tolerances for fludioxonil residues in 

livestock commodities.

IR-4 has submitted a petition (1E7853) for the use of fludioxonil on ginseng, pineapple (postharvest treatment), tuberous and corm vegetable subgroup 1C, spinach, tropical fruit (postharvest treatment), bulb onion, green onion, caneberry, bushberry, small fruit vine climbing 

(except fuzzy kiwifruit), low-growing berry (except cranberry), fruiting vegetables, citrus fruit, 

pome fruit, leafy vegetables (except Brassica), dragon fruit, and tomato (post-harvest treatment). 

In addition, Syngenta has submitted a petition (1E7870) for the use of fludioxonil on leafy

petioles. The petitioners request that the following tolerances be established as a result of the 

proposed uses for the residues of fludioxonil in/on:

PP# 1E7853

Guava 5 ppm

Feijoa 5 ppm

Jaboticaba 5 ppm

Wax jambu 5 ppm

Starfruit 5 ppm

Passionfruit 5 ppm

Acerola 5 ppm

Avocado 5 ppm

Black sapote 5 ppm

Mamey sapote 5 ppm

Canistel 5 ppm

Mango 5 ppm

Papaya 5 ppm

Sapodilla 5 ppm

Star apple 5 ppm

Lychee 20 ppm

Longan 20 ppm

Spanish lime 20 ppm

Rambutan 20 ppm

Pulasan 20 ppm

Sugar apple 20 ppm

Atemoya 20 ppm

Custard apple 20 ppm

Cherimoya 20 ppm

Ilama 20 ppm

Soursop 20 ppm
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Biriba 20 ppm

Ginseng 3.0 ppm

Onion, bulb subgroup 3-07A 0.2 ppm

Onion, green subgroup 3-07B 7.0 ppm

Caneberry subgroup 13-07A 5.0 ppm

Bushberry subgroup 13-07B 2.0 ppm

Small fruit vine climbing subgroup 13-07F, except fuzzy kiwifruit 1.0 ppm

Low growing berry subgroup 13-07G, except cranberry 2.0 ppm

Vegetable, fruiting group 8-10, except tomato 0.7 ppm

Tomato 3.0 ppm

Fruit, citrus, group 10-10 10 ppm

Fruit, pome, group 11-10 5 ppm

Vegetable, leafy, except brassica, subgroup 4A 30 ppm

Vegetable, tuberous and corm, subgroup 1C 6.0 ppm

Pineapple 8.0 ppm

Dragon-fruit 1.0 ppm

PP# 1E7870

Leafy petioles crop subgroup 4B 14 ppm

Nature of the Residue in Plants 

The nature of the fludioxonil residues in plants is adequately understood based on adequate 

metabolism studies on peaches, grapes, onions, and head lettuce. Based on the results from these 

studies, HED has determined that the residue of concern in plants following foliar applications, 

for tolerance enforcement and risk assessment purposes, is fludioxonil per se.

Nature of the Residue in Livestock 

The nature of the residues in livestock is also understood based on the adequate goat and hen 

metabolism studies. For purposes of tolerance enforcement and risk assessment, the residues of 

concern in ruminants are fludioxonil and Metabolite B-1, and the residues of concern in poultry

are fludioxonil, CGA-344623, and Metabolite I-1.

Residue Analytical Methods

Adequate HPLC/UV methods (Syngenta Methods AG-597 and AG-597B) are available for 

enforcing tolerances of fludioxonil in plant commodities. In the current field trials and 

processing studies, residues of fludioxonil were determined using a LC-MS/MS method, which 

is a modified version of Method AG-597B. The LC-MS/MS method was adequately validated in 

conjunction with the analysis of field trial and processing study samples. The validated LOQ for 

fludioxonil was 0.01 or 0.02 ppm in each matrix, and the LOD was 0.003 or 0.006 ppm. 

LC-MS/MS Analytical Method GRM025.03A (as modified in MRID# 48526508) is suitable as 

an enforcement method for livestock commodities as defined in SOP No. ACB-019 (9/15/08). 

This is a common-moiety method in which fludioxonil and its metabolites of regulatory concern 

are converted to CGA192155 (2,2-difluoro-1,3-benzodioxole-4-carboxylic acid).

Magnitude of the Residue in Livestock

Based on the available goat and poultry metabolism data and the previously calculated dietary

exposures of livestock to fludioxonil residues, HED had concluded that quantifiable residues of 

fludioxonil were unlikely to occur in livestock commodities. As processed potato waste is a 

significant feedstuff for livestock (ruminants only), the dietary burden of fludioxonil was 

recalculated for this petition using the Agency’s most recent guidance on constructing reasonably 

balanced livestock diets (Memo, 6/30/08). Based upon this diet and the results of a newly 

submitted ruminant feeding study, tolerances for total fludioxonil residues should be established 
Fludioxonil Human-Health Risk Assessment DP# 389613

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Page 23 of 45

at 0.05 ppm for residues in fat and meat byproducts of cattle, goats, horses, and sheep and at 0.01 

ppm for milk and for the meat of cattle, goats, horses, and sheep.

Magnitude of the Residue in Plants

No new data were submitted to support tolerances on onion, bulb, subgroup 3-07A; onion, green, 

subgroup 3-07B; low-growing berry 13-07G crop subgroup; caneberry subgroup 13-07A; 

bushberry subgroup 13-07B; fruit, citrus, group 10-10; fruit, pome, group 11-10; or small fruit 

vine climbing subgroup 13-07F, except fuzzy kiwifruit. IR-4 has requested that existing 

tolerances be expanded to their respective crop groups or crop subgroups.

The submitted field trial residue data for ginseng, celery as a representative crop of the leaf 

petioles crop subgroup 4B, bell and non-bell peppers as a representative crop of the fruiting 

vegetable group 8-10 (except tomato), pineapple, potatoes as a representative crop of the 

tuberous and corm vegetable subgroup 1C, spinach as a representative commodity of leafy

vegetable (except Brassica) subgroup 4A, and tomatoes are adequate. The field trial data reflect 

the proposed use pattern, an adequate number of trials were conducted in the appropriate 

geographic regions, and samples were analyzed for the residue of concern using validated datacollection methods (storage intervals were also validated). Using the OECD tolerance 

calculation procedures for the residue data sets indicate that the requested tolerance levels are not 

appropriate for several commodities. A revised Section F is requested.

Magnitude of the Residue in Processed Fractions

The submitted pineapple and potato processing studies are also adequate. Separate tolerances are 

not required for any of the processed fractions.

Magnitude of the Residue in Rotational Crops

Adequate confined and limited field rotational crop trials are available and support the labelspecified 30-day PBI for crops without uses on the fludioxonil label. The available data indicate 

that tolerances are not currently required for rotational crops.

Tolerance Summary

There are currently no established Codex, Canadian, or Mexican MRLs for fludioxonil in/on 

tropical fruits. The following U.S., Canadian, and Codex tolerances/MRLs for residues of 

fludioxonil are harmonized: bushberries, grapes, citrus fruits, and pome fruits. Additionally, the 

U.S. and Canadian tolerances/MRLs for potatoes, spinach, fruiting vegetables except tomato, and 

ginseng are being harmonized as part of this joint review.

The U.S., Canadian, and Codex tolerances/MRLs for residues of fludioxonil in/on bulb onions, 

caneberries, grapes (small vine climbing fruit, subgroup 13-07F), strawberries (low-growing 

berry subgroup 13-07G), tomatoes, and leafy vegetables cannot be harmonized as the Canadian, 

and Codex MRLs differ. For leafy vegetables except Brassica subgroup 4A, the U.S. and 

Canada are harmonized at 30 ppm, but a Codex MRL is established for head lettuce at 10 ppm. 

For the bulb onion subgroup 3-07A, small vine climbing fruit subgroup 13-07F, and lowgrowing berry subgroup 13-07G, HED recommends that the U.S. tolerances be increased in 

order to harmonize with Codex; bulb onion subgroup 3-07A from 0.20 to 0.50 ppm, small vine 

climbing fruit subgroup 13-07F from 1.0 to 2.0 ppm and low-growing berry subgroup 13-07G

from 2.0 to 3.0 ppm. 
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The tolerances/MRLs cannot be harmonized for green onions, tomatoes, leafy vegetables except 

Brassica subgroup 4A, and leafy petioles as the U.S. residue data/use patterns necessitate a 

higher value. 

For livestock commodities, the U.S. and Codex residue definitions are harmonized; however, the 

Canadian residue definition is not harmonized. The numerical values for the U.S. and Canadian 

livestock tolerances/MRLs are harmonized. 

5.2.2 Drinking Water Residue Profile

Estimated drinking water concentrations (EDWCs) were generated using EFED’s standard suite 

of models (DP#389616, C. Sutton, 10/27/2011). The Pesticide Root Zone Model (PRZM, 

v3.12.2, May 2005) and Exposure Analysis Modeling System (EXAMS, v2.98.4.6, April 2005) 

are simulation models used to generate EDWCs of fludioxonil residues that may occur in surface 

water used as drinking water. The PRZM model simulates pesticide movement and 

transformation on and across the agricultural field resulting from crop applications. Percentcropped areas (PCA) that account for the maximum area within a watershed that may be planted 

with the modeled crop are applied to concentrations predicted by PRZM/EXAMS. The models 

and their descriptions are available at the EPA internet site: 

http://www.epa.gov/oppefed1/models/water/. 

Screening Concentration in Ground Water (SCI-GROW v2.3, Jul. 29, 2003) is a regression 

model used as a screening tool to estimate pesticide concentrations found in groundwater used as 

drinking water. The output of SCI-GROW represents the concentrations of fludioxonil that 

might be expected in shallow unconfined aquifers under sandy soils, which is representative of 

the groundwater most vulnerable to pesticide contamination and likely to serve as a drinking 

water source. 

The maximum proposed application rate among all new proposed uses (for onion subgroups 3-

07A and 3-07B) is 0.25 lbs ai/A/application, applied four times per year with a 7-day application 

interval, for a maximum total annual application rate of 1.0 lb ai/A/yr. Because the maximum 

proposed application rate among all of the uses considered for this assessment is less than the 

rates previously assessed by EFED for ornamentals, the EDWCs based on use on ornamentals 

are recommended for use in the human-health dietary assessment. However, based on 

information provided in Syngenta’s 9/9/2011 submission “Fludioxonil Registration Review 

Public Comments Response to Initial 60-Day Comment Period, Case Number: 7017, Docket 

Number: EPA-HQ-OPP-2010-1067,” EFED concurs that the use of the container-grown 

ornamentals application rate is not appropriate for estimating EDWCs. As noted by the 

registrant, the strong adsorption of the pesticide to the potting media used for container-grown 

ornamentals, as well as the use of containers, results in attenuation of pesticide movement from 

the containers to the underlying soil in the field, thereby reducing potential runoff of the 

pesticide. Thus, EFED now recommends that the values from the Tier I DWA of 6/22/2009 

(D364264) be used in HED’s dietary exposure and risk assessment. The values in the Tier I 

DWA are based on the use of fludioxonil on field-grown ornamentals at one application of 2 lb 

ai/A/yr. The resulting acute and chronic EDWCs in surface water were 83.8 ppb (1-in-10-year 

acute estimate) and 38.5 ppb (1-in-10-year chronic estimate), respectively. The EDWC for 

groundwater (for both acute and chronic analysis) is 0.2 ppb. Since the surface water 

concentrations were the highest, the acute and chronic dietary runs were conducted assuming 

surface water residues of 0.0838 ppm and 0.0385 ppm, respectively, for all water sources (direct 

and indirect). 
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Table 5.2.2. Tier II EDWCs Resulting From Applications of Fludioxonil on Ornamentals (Total Rate 

of 4 lb ai/A/yr).

Drinking water source 

(model) Use

1-in-10-year acute 

(μg/L)

1-in-10-year chronic 

(μg/L)

Surface water 

(PRZM/EXAMS)

Container-grown 

ornamental 83.8 38.5

Groundwater (SCIGROW) Container-grown 

ornamental 0.2 0.2

5.2.3 Dietary Exposure and Risk

Fludioxonil acute and chronic dietary exposure assessments were conducted using the DEEMFCIDTM model, Version 2.03, which incorporates consumption data from USDA’s CSFII, 1994-

1996 and 1998. The 1994-96, 98 data are based on the reported consumption of more than 

20,000 individuals over two non-consecutive survey days. Foods “as consumed” (e.g., apple pie) 

are linked to EPA-defined food commodities (e.g., apples, peeled fruit - cooked; fresh or N/S; 

baked; or wheat flour - cooked; fresh or N/S, baked) using publicly available recipe translation 

files developed jointly by USDA/ARS and EPA. For chronic exposure assessment, consumption 

data are averaged for the entire U.S. population and within population subgroups, but for acute 

exposure assessment are retained as individual consumption events. Based on analysis of the 

1994-96, 98 CSFII consumption data, which took into account dietary patterns and survey

respondents, HED concluded that it is most appropriate to report risk for the following 

population subgroups: the general U.S. population, all infants (<1 year old), children 1-2, 

children 3-5, children 6-12, youth 13-19, adults 20-49, females 13-49, and adults 50+ years old.

For chronic dietary exposure assessment, an estimate of the residue level in each food or foodform (e.g., orange or orange juice) on the food commodity residue list is multiplied by the 

average daily consumption estimate for that food/food form to produce a residue intake estimate. 

The resulting residue intake estimate for each food/food form is summed with the residue intake 

estimates for all other food/food forms on the commodity residue list to arrive at the total 

average estimated exposure. Exposure is expressed in mg/kg body weight/day and as a percent 

of the cPAD. This procedure is performed for each population subgroup.

For acute exposure assessments, individual one-day food consumption data are used on an 

individual-by-individual basis. The reported consumption amounts of each food item can be 

multiplied by a residue point estimate and summed to obtain a total daily pesticide exposure for a 

deterministic exposure assessment, or “matched” in multiple random pairings with residue values 

and then summed in a probabilistic assessment. The resulting distribution of exposures is 

expressed as a percentage of the aPAD on both a user (i.e., only those who reported eating 

relevant commodities/food forms) and a per-capita (i.e., those who reported eating the relevant 

commodities as well as those who did not) basis. In accordance with HED policy, per capita 

exposure and risk are reported for all tiers of analysis. However, for Tiers 1 and 2, any 

significant differences in user vs. per capita exposure and risk are specifically identified and 

noted in the risk assessment.

5.2.3.1 Acute Dietary Exposure/Risk

An unrefined acute dietary exposure and risk analysis was performed assuming tolerance-level 

residues, 100% CT, and DEEMTM (ver. 7.81) default processing factors. The 1-in-10-year acute 

drinking water estimate (i.e., relevant to acute exposure) of 0.0838 ppm, previously provided by 
Fludioxonil Human-Health Risk Assessment DP# 389613

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Page 26 of 45

EFED, was directly incorporated into the acute assessment. This analysis was performed for the 

population subgroup females 13 to 49 years old, which is the only subgroup of interest for acute 

exposure. The acute dietary (food plus water) risk utilizes 16% of a PAD for females 13 to 49 

years old.

There were no appropriate toxicological effects attributable to a single exposure (dose) for the 

general population or any other population subgroups; therefore, these population subgroups 

were not included in this assessment. 

5.2.3.2 Chronic Dietary Exposure/Risk

A partially refined chronic dietary exposure and risk assessment was performed assuming 

tolerance-level residues for most commodities [with the exception of celery, pineapple, potato, 

spinach, apple, grapefruit, lemon, lime, orange, pear, tomato, head lettuce, leaf lettuce, fresh 

parsley, Brassica leafy vegetables (crop group 5), grape, cherry, peach and plum], 100% CT 

estimates, and DEEMTM (ver. 7.81) default processing factors [with the exception of citrus fruit 

juice (1X), apple juice (1X), grape juice (0.42X), raisin (1.65X), potato commodities (1X), and 

tomato commodities (1X), except dried tomato (14.3X)]. These processing factors are based 

upon processing study data. ARs for celery, pineapple, potato, spinach, apple, grapefruit, 

lemon, lime, orange, pear, tomato, head lettuce, leaf lettuce, fresh parsley, Brassica leafy

vegetables (crop group 5), grape, cherry, peach, and plum were generated from field trial and 

processing study data for the chronic analysis. The 1-in-10-year chronic drinking water 

estimate (i.e., relevant to chronic exposure) of 0.0385 ppm, provided by the EFED, was directly

incorporated into the chronic assessment. For the U.S. population the dietary risk (food plus 

water) utilizes 26% of the cPAD. The chronic dietary risk estimate for the highest reported 

exposed population subgroup, children 1 to 2 years old, is 68% of the cPAD.

The results of the acute and chronic dietary exposure analyses are reported in the Summary

Table (Table 5.2.3.2, below). 

Table 5.2.3.2. Summary of Dietary Exposure (Food Plus Water) and Risk Assessment for Fludioxonil.

Population Subgroup

Acute Dietary (95th Percentile) Chronic Dietary

Dietary 

Exposure 

(mg/kg/day) % aPAD*

Dietary Exposure

(mg/kg/day) % cPAD*

General U.S. Population

N/A

0.008711 26

All Infants (<1 year old) 0.018891 57

Children 1-2 years old 0.022497 68

Children 3-5 years old 0.017817 54

Children 6-12 years old 0.011011 33

Youth 13-19 years old 0.006547 20

Adults 20-49 years old 0.006943 21

Adults 50+ years old 0.007778 24

Females 13-49 years old 0.163378 16 0.007073 21

* % PADs are reported to 2 significant figures. The values for the highest exposed population for each type of risk

assessment are bolded.

5.2.3.3 Cancer Dietary Risk

Fludioxonil is classified as a Group D chemical - not classifiable as to human carcinogenicity;

therefore, a cancer dietary exposure and risk assessment was not performed for fludioxonil.
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5.2.4 Anticipated Residue and Percent Crop Treated (%CT) Information

The acute and chronic dietary assessments for fludioxonil assumed 100% CT. The chronic 

assessment was based on the assumption of tolerance-level residues for most commodities with 

existing and recommended tolerances. ARs for apple, grapefruit, lemon, lime, orange, pear, head 

lettuce (with wrapper), leaf lettuce, fresh parsley, Brassica leafy vegetables (crop group 5), 

grape, cherry, peach, and plum were previously generated from field trials (D. Rate, DP#379936, 

07/14/2010). ARs for tomato, celery, pineapple, potato, and spinach were also generated from 

field trial data for this assessment; see Table 5.2.4, below. For Brassica leafy vegetables (crop 

group 5), the field trial data were translated from the representative commodities in the crop 

groups to the non-representative commodities according to HED SOP 2000.1: “Guidance for 

Translation of Field Trial Data from Representative Commodities in the Crop Group Regulation 

to Other Commodities in Each Crop Group/Subgroup.” ARs were determined for apple, 

grapefruit, lemon, and lime juices (J. Sullivan and M. Papathakis, 02/27/2004) using average 

residues from field trials and processing studies. As a result, processing factors were set to 1X 

for these juices. The value for orange juice was set to 0.0 ppm as fungicide-treated fruit are not 

processed and Pesticide Data Program (PDP) monitoring data reported no detectable residues in 

orange juice (16th Annual Summary, data from calendar year 2006). The submitted grape 

processing study indicated that fludioxonil residues do not concentrate in juice or appreciably in 

raisin. The processing factors were set to 0.42X for grape juice and 1.65X for raisin. The 

submitted tomato, pineapple, and potato processing study indicated that fludioxonil residues do 

not appreciably concentrate in processed commodities made from treated tomato, pineapple, and 

potato samples; therefore, separate tolerances are not required for tomato, pineapple, and potato 

processed commodities. Processing factors were set to 1X for these processed commodities 

(pineapple juice; tomato paste, juice, and puree; and potato chips, flakes, and flour). DEEMTM

(ver. 7.81) default processing factors were used for all other processed commodities for which 

they are available.

Table 5.2.4. AR Values Used for the Chronic Assessment.

Commodity AR (ppm)2

Apple, whole

 juice

1.1

0.1

Grapefruit, whole

 juice

2.6

0.74

Lemon, whole

 juice

1.7

0.02

Lime, whole

 juice

1.7

0.02

Orange1, whole

 juice

1.5

0.0

Pear, whole 1.6

Tomato 0.89

Lettuce, head (with wrapper leaves) 2.09

Lettuce, leaf 10.77

Parsley, fresh 1.23

Brassica leafy vegetables (crop 

group 5)

 Cabbage

 Mustard greens

 Broccoli

0.34

1.03

0.13

Grape 0.33

Cherry 0.82

Peach 0.40
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Table 5.2.4. AR Values Used for the Chronic Assessment.

Commodity AR (ppm)2

Plum 0.51

Celery 4.9

Pineapple 5.64

Potato 1.82

Spinach 7.1

 

1 Also represents tangerine.

 

2 ARs calculated for the current memo were taken from field trial data associated with the following

 MRID Nos.: 48478501, 48437302, 48437101, 48437305, and 48438204.

6.0 RESIDENTIAL (NON-OCCUPATIONAL) EXPOSURE/RISK 

CHARACTERIZATION

The proposed uses will not result in residential exposures; however, fludioxonil is currently

registered for use in residential areas, including parks, golf courses, athletic fields, residential 

lawns, ornamentals, and greenhouses. 

HED previously assessed the use of fludioxonil in residential use scenarios to control certain 

diseases of turfgrass and certain foliar, stem and root diseases in ornamentals in residential 

landscapes and greenhouses (Memo, 11/10/09, W. Wassell, et al., D362493; 05/06/02, T. 

Swackhammer, D282570; and 9/30/08, M. Dow, D356221). A Human-Health Assessment 

Scoping Document in Support of the Registration Review (W. Wassell, D384857) was 

completed in 2011. As noted in the recent scoping document, in addition to the conventional 

uses of fludioxonil is residential areas, there are also antimicrobial uses. The antimicrobial uses 

in residential areas will be further reviewed and assessed during Registration Review. The 

residential turf uses of fludioxonil are expected to result in the highest potential exposure of all 

registered residential uses of fludioxonil and, therefore, were reassessed in this risk assessment. 

The registered turf use has been reassessed in this document to reflect updates to HED’s 

Residential SOPs, 2012 and the revised UFDB for inhalation risks (Memo, L Venkateshwara, 

D389982). The currently registered label for turf is Medallion®Fungicide EPA Reg. # 100-769. 

Medallion®Fungicide is a 50% WP in water-soluble packaging. The maximum single 

application rate is 0.50 oz per 1000 ft2 or 0.68 lbs ai/A. For a complete review of the calculations 

associated with the residential turf uses of fludioxonil, see the aforementioned L. Venkateshwara 

memo. 

6.1 Residential Handler Exposure/Risk

The residential handler exposure assessment estimates only inhalation exposures for individuals 

using fludioxonil on residential turfgrass as there are no dermal endpoints for fludioxonil. The 

following are key differences between residential and occupational handler assessments include 

the following: 

 Residential handler exposure scenarios are considered to be short-term only, due to the 

infrequent use patterns associated with homeowner products.

 A tiered approach for personal protection using increasing levels of PPE is not used in 

residential handler risk assessments. Homeowner handler assessments are based on the 

assumption that individuals are wearing shorts, short-sleeved shirts, socks, and shoes.
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 Homeowner handlers are expected to complete all tasks associated with the use of a 

pesticide product including mixing/loading if needed as well as the application.

The quantitative exposure/risk assessment developed for residential handlers is based on the 

following scenarios: 

(1) Mixing/loading/applying WP in water-soluble packaging with manually pressurized 

handwand,

(2) Mixing/loading/applying WP in water-soluble packaging with backpack sprayer, 

(3) Mixing/loading/applying WP in water-soluble packaging with hose end sprayer, and 

(4) Mixing/loading/applying WP in water-soluble packaging with a sprinkler can.

Unit exposure values and estimates for area treated were taken from the HED’s 2012 SOPs for 

Residential Pesticide Exposure Assessment for Lawns/Turf. 

Short-term risks for residential handlers are presented in Table 6.1.1. Intermediate-term 

exposures are not likely because of the intermittent nature of applications by homeowners. 

Short-term inhalation risk estimates to residential handlers do not exceed HED’s LOC for all 

scenarios. Although an inhalation study is required for fludioxonil, the oral PODs used for 

assessing inhalation risk are based on the most sensitive endpoints established in the most 

sensitive species. Furthermore, an additional 10X UFDB will be used to further protect for the 

uncertainty from this oral to inhalation route-to-route extrapolation. Based on these oral PODs, 

all residential handler inhalation exposures were well above the LOC and are not of concern to 

HED. Therefore, the risk estimate is conservative and will not underestimate risk via the 

inhalation route.

Table 6.1.1. Residential Handler Exposure and Risk Estimates for Fludioxonil Applications to 

Turfgrass.

Exposure Scenario

Application 

Rate (lb 

ai/A)a

Area Treated

Daily (acres)b

Baseline Unit 

Exposuresb(mg/lb ai)

Baseline Dosed

(mg/kg/day) Baseline MOEe

InhalationcInhalationcInhalationc

Mixer/Loader/Applicator

Mixing/Loading/Applying 

WP in Water-soluble 

Packaging with Manuallypressurized Handwand 

0.68 0.023 0.018 3.5E-06 2,800,000

Mixing/Loading/Applying 

WP in Water-soluble 

Packaging with Backpack 

Sprayer 

0.68 0.023 0.018 3.5E-06 2,800,000

Mixing/Loading/Applying 

WP in Water-soluble 

Packaging with Hose-end 

Sprayer

0.68 0.5 0.034 1.5E-04 69,000

Mixing/Loading/Applying 

WP in Water-soluble 

Packaging with Sprinkler 

Can

0.68 0.023 0.034 6.7E-06 1,500,000

a. Application rates based on label for fludioxonil (Medallion®Fungicide, EPA Reg.# 100-769).

b. Based on HED’s SOPs for Residential Pesticide Exposure Assessment; Lawns/Turf (February, 2012).

c. Baseline Inhalation: no respirator. 

d. Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/A) x acres treated * absorption factor (inhalation = 100%) / body 

weight (80 kg).

e. MOE = NOAEL (10 mg/kg/day) / daily dose (mg/kg/day). Level of concern = 1000.

6.2 Residential Post-application Exposure and Risk

Fludioxonil can be used in many areas that can be frequented by the general population including 
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residential areas (e.g., home lawns). As a result, individuals can be exposed by entering these 

areas if they have been previously treated. 

6.2.1 Post-application Inhalation

Based on the Agency’s current practices, a quantitative post-application inhalation exposure 

assessment was not performed for fludioxonil at this time. However, volatilization of pesticides 

may be a potential source of post-application inhalation exposure to individuals nearby to 

pesticide applications. The Agency sought expert advice and input on issues related to 

volatilization of pesticides from its FIFRA Scientific Advisory Panel (SAP) in December 2009. 

The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, developing policies and 

procedures, to identifying the need for and, subsequently, the way to incorporate post-application 

inhalation exposure into the Agency's risk assessments. If new policies or procedures are put 

into place, the Agency may revisit the need for a quantitative post-application inhalation 

exposure assessment for fludioxonil.

6.2.2 Post-application Dermal and Incidental Oral

Dermal post-application exposure/risk has not been assessed because there is no dermal POD. 

Short- and intermediate-term incidental oral exposure and risk estimates have been assessed 

here. Intermediate-term exposures may be possible as the Medallion® label specifies that the 

product may be applied at 14-day application intervals, with an annual maximum rate of 2 lbs 

ai/A/yr, which equates to about three applications at the maximum per application rate. 

Fludioxonil has exhibited half-lives ranging from 95 to 440 days in thatch sod based on fielddissipation studies (05/06/02, T. Swackhammer, D282570). Therefore, this assessment included 

a residential post-application assessment for toddler incidental ingestion exposures related to 

residential lawn applications.

 Physical activities on turf: children 1 < 2 years old (incidental oral).

The lifestage (i.e., children 1 < 2 years old) selected for this post-application scenario is based on 

an analysis provided as an Appendix in the 2012 Residential SOPs. This lifestage is not the only

lifestage that could be potentially exposed for these post-application scenarios; however, the 

assessment of this lifestage is health protective for the exposures and risks for any other 

potentially exposed lifestages. Table 6.2.2.1 presents the post-application incidental oral MOE 

values calculated for children 1 < 2 years old after applications of fludioxonil to turf. Postapplication risk estimates do not exceed HED’s LOC for any of the scenarios assessed. 

Table 6.2.2.1. Short-Term Residential Post-application Exposure and Risk Estimates for Fludioxonil.

Lifestage Post-application Exposure Scenario Dose (mg/kg/day)

Short-term 

MOEs

Intermediateterm MOEs

Child 1 < 2 year old Turf -

sprays

Hand-to-Mouth 0.0101 990 330

Object-to-Mouth 0.00031 32,000 11,000

Incidental Soil Ingestion 2.2E-05 450,000 150,000

6.3 Combined Exposure

HED combines risk estimates resulting from separate post-application exposure scenarios when 

it is likely they can occur simultaneously based on the use pattern and the behavior associated 
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with the exposed population and when the toxicological effects are similar. For fludioxonil, 

there is no dermal POD; therefore, the only route of exposure is incidental oral for children. 

The incidental oral scenarios (i.e., hand-to-mouth, object-to-mouth, and soil ingestion) should be 

considered inter-related and it is likely that they occur interspersed amongst each other across 

time. Combining all three of these scenarios would be overly conservative because of the 

conservative nature of each individual assessment. Therefore, only the hand-to-mouth scenario 

was chosen as a health protective estimate of children’s exposure to pesticides used on turf.

Table 6.3.1. Short- and Intermediate-Term Residential Exposures for the Fludioxonil Combined Residential Turf Risk 

Estimates.

Population

Handler Exposure 

(mg/kg/day)1

Residential 

Handler Total 

Exposure 

(mg/kg/day)3

Residential 

Handler 

Total MOE

Post-application 

Exposure (mg/kg/day)2 Residential Postapplication Total 

Exposure (mg/kg/day)3

Residential 

Postapplication 

Inhalation Dermal Inhal. Oral Total MOE

Short-Term

Adult Male 1.5E-04 1.5E-04 69,000 NA N/A N/A NA NA

Child 1 < 2 

years old N/A NA N/A 0.0101 0.0101 990

Intermediate-Term

Child 1 < 2 

years old N/A N/A N/A 0.0101 0.0090 370

1

 Handler exposure represents high-end inhalation handler exposure, where the exposure duration is appropriate to assess.

2

 Post-application exposure represents high-end incidental oral exposure for the relevant exposure duration.

3

 For adults, residential total exposure combines the highest inhalation exposures, where applicable. For young children, total 

residential exposure combines high-end post application incidental oral AND dermal exposure, where applicable.

6.4 Other (Spray Drift, etc.)

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from the ground application method employed for fludioxonil. The 

Agency has been working with the Spray Drift Task Force, EPA Regional Offices, and State 

Lead Agencies for pesticide regulation and other parties to develop the best spray-driftmanagement practices (see the Agency’s Spray Drift website for more information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical-by-chemical basis, the 

Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT®computer model 

to its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic 

methods. After the policy is in place, the Agency may impose further refinements in spray-driftmanagement practices to reduce off-target drift with specific products with significant risks 

associated with drift.

Although a quantitative residential post-application inhalation exposure assessment was not 

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation 

exposure assessment was performed for flaggers. This exposure scenario is representative of a 

worse case inhalation (drift) exposure and may be considered protective of most outdoor 

agricultural and commercial post-application inhalation exposure scenarios. 
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6.5 Residential Bystander Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative residential bystander post-application 

inhalation exposure assessment was not performed for fludioxonil this time primarily because it 

is applied at a low use rate. However, volatilization of pesticides may be a potential source of 

post-application inhalation exposure to individuals nearby to pesticide applications. The Agency 

sought expert advice and input on issues related to volatilization of pesticides from its FIFRA 

SAP in December 2009. The Agency received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures, 

to identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for fludioxonil.

7.0 AGGREGATE RISK ASSESSMENTS AND RISK CHARACTERIZATION

In accordance with the FQPA, HED must consider and aggregate pesticide exposures and risks 

from non-occupational sources, including food, drinking water, and residential pathways. In an

aggregate assessment, exposures from relevant sources are added together and compared to 

quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be 

aggregated. When aggregating exposures and risks from various sources, HED considers both 

the route and duration of exposure.

7.1 Acute Aggregate Risk

Based on the exposure pathways, the acute aggregate risk assessment should include exposure 

from food and water only. Since the acute dietary analysis included both food and water 

exposures, no further estimates of risk are necessary. The acute dietary risk does not exceed the 

LOC; therefore, the acute aggregate risk does not exceed the LOC.

7.2 Short-Term Aggregate Risk

In aggregating short-term risk, HED considers background chronic dietary exposure (food + 

water) and short-term, residential exposures. Fludioxonil is registered for use in residential 

areas; therefore, there is the potential for residential handler and post-application exposure. 

Because the registered use on turf represents the higher potential exposure of all registered 

residential uses, potential exposures resulting from the turf use are included in the short-term 

aggregate assessment. Aggregating residential turf exposure with potential dietary exposures 

provided a conservative assessment that is protective of all potential aggregate exposures to 

fludioxonil. Since no dermal POD was selected and post-application inhalation exposure is 

expected to be minimal, the only short-term residential exposures are (1) incidental oral postapplication exposures for children on treated lawns (resulting from the currently registered use) 

and (2) inhalation exposure for residential handlers (resulting from the currently registered use). 

The short-term aggregate assessment for children includes exposure from food, water, and postapplication non-dietary oral exposures using an MOE approach. Table 7.2.1 summarizes the 

short-term aggregate exposure estimates to fludioxonil residues for children (1-2 years old). For 

adults, short-term aggregate combines dietary (food + water) exposure with inhalation exposure 

resulting from residential handlers treating lawns. For the adult assessment, because the short-
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term oral and inhalation risks are estimated using the same oral POD, these routes of exposure 

can be combined. However, because the LOCs for oral and inhalation routes of exposure are not 

the same (an MOE of <100 defines the LOC for incidental oral risk while inhalation risk is 

defined by an MOE of <1000) an aggregate risk index (ARI) was required to estimate aggregate 

risk for adults. EPA identifies as a LOC ARIs that fail to reach or exceed the level of one. ARIs 

below one result in a risk estimate of concern. Table 7.2.2 summarizes the short-term aggregate 

exposure estimates to fludioxonil residues for adults.

Table 7.2.1. Short-Term Aggregate Risk (Food, Drinking Water, and Residential Exposure).

Population

Short-Term Scenario

NOAEL

mg/kg/day

LOC

MOE1

Average

Food + Water

Exposure

mg/kg/day

Inhalation 

Residential 

Exposure2

mg/kg/day

Oral 

Residential 

Exposure3

mg/kg/day

Aggregate MOE

(food, water

& residential)4

Children (1-

2 years old) 10 100 0.022497 -

0.0101 310

1 The LOC MOE is 100, based on inter- and intra-species SFs totaling 100.

2

Inhalation exposure from Table 6.3.1.

3 Oral residential exposure = [incidental oral exposure]. From Table 6.3.1.

4 Aggregate MOE = [NOAEL ÷ (avg. food + water exposure + residential exposure)].

Table 7.2.2. Short-Term Aggregate Risk (Food, Drinking Water, and Residential Exposure).

Population

Level of 

Concern ARI1

ARI (Food + 

Water)2

Residential ARIs3

Total 

Aggregate 

ARI4

Handlers Post 

Application 

Dermal 

Exposure

Dermal

Exposure

Inhalation 

Exposure

General U.S. 

Population

1 11 - 69 - 9.5

Adults 50+ 

years old

1 13 - 69 - 11

1

 ARI (Aggregate Risk Index) = MOECalculated / MOEAcceptable.

2

 ARIFood + Water = (10 mg/kg/day/0.008711 mg/kg/day) / 100 = 11 (general U.S. population); and (10 mg/kg/day/0.007778 mg/kg/day) / 100 = 13 

(adults 50+ years old).

3

 ARIDermal =MOE / 100 and, ARIInhalation = MOE / 1000.

4

 ARITotal Aggregate = 1/[(1/ARIFood + water) + (1/ARIResidential Handler Deraml ) + (1/ARIResidential Handler Inhalation) + (1/ARIPost Application Dermal)].

All short-term aggregate risk estimates result a MOE >100 or an ARI >1. Short-term aggregate 

exposure to fludioxonil, as a result of all registered and proposed uses, is thus below HED's 

LOC.

7.3 Intermediate-Term Aggregate Risk

In aggregating intermediate-term risk, HED considers background chronic dietary exposure 

(food + water) and intermediate-term, residential exposures. Fludioxonil is registered for use in 

residential areas; therefore, there is the potential for intermediate-term residential exposure. 

Because the registered use on turf represents the higher potential exposure of all registered 

residential uses, potential exposures resulting from the turf use are included in the intermediateterm aggregate assessment. Aggregating residential turf exposure with potential dietary

exposures provided a conservative assessment that is protective of all potential aggregate 

exposures to fludioxonil. Since no dermal POD was selected and post-application inhalation 

exposure is expected to be minimal, the only intermediate-term residential exposure is incidental 

oral post-application exposures for children on treated lawns (resulting from the currently 

registered use). The intermediate-term aggregate assessment for children includes exposure from 

food, water, and post-application non-dietary oral exposures resulting from contact with treated 
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lawns. Table 7.3 summarizes the intermediate-term aggregate exposure estimates to fludioxonil 

residues.

Table 7.3. Intermediate-Term Aggregate Risk (Food, Drinking Water, and Residential Exposure).

Population

Short-Term Scenario

NOAEL

mg/kg/day

LOC

MOE1

Average

Food + Water

Exposure

mg/kg/day

Inhalation 

Residential 

Exposure2

mg/kg/day

Oral 

Residential 

Exposure3

mg/kg/day

Aggregate MOE

(food, water

& residential)4

Children (1-

2 years) 3.3 100 0.022497 -

0.0090 105

1 The LOC MOE is 100, based on inter- and intra-species SFs totaling 100.

2

Inhalation exposure from Table 6.3.1.

3 Oral residential exposure = [incidental oral exposure]. From Table 6.3.1.

4 Aggregate MOE = [NOAEL ÷ (avg. food + water exposure + residential exposure)].

All intermediate-term aggregate risk estimates result in MOEs greater than 100. Intermediateterm aggregate exposure to fludioxonil, as a result of all registered and proposed uses, is below 

HED's LOC.

7.4 Chronic Aggregate Risk

Since chronic residential exposure is not expected to result from the residential uses of 

fludioxonil, the chronic aggregate risk assessment includes exposures from food and water only. 

As the chronic dietary analysis that was performed included both food and water, no further 

calculations are necessary. Since the chronic dietary risk does not exceed the LOC, the chronic 

aggregate risk does not exceed the LOC.

7.5 Cancer Aggregate Risk

Fludioxonil is classified as a Group D chemical - not classifiable as to human carcinogenicity; 

therefore, there is no need for a quantitative cancer risk assessment.

8.0 CUMULATIVE RISK CHARACTERIZATION/ASSESSMENT

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 fludioxonil and any other substances, and fludioxonil 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 fludioxonil 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/.
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9.0 OCCUPATIONAL EXPOSURE/RISK PATHWAY

The potential uses are on agricultural crops; therefore, there is potential for occupational handler 

and post-application exposure. For a complete review of the calculations associated with the 

occupational uses of fludioxonil, see the co-pending HED memo (L. Venkateshwara, D389982).

9.1 Occupational Handler Risk

Occupational handlers may experience short- and intermediate-term dermal exposure to 

fludioxonil while performing tasks involving applications to agricultural crops. The quantitative 

exposure/risk assessment developed for occupational handlers is based on the following 

scenarios:

Mixer/Loader:

1. open mixing/loading WP for aerial application; 

2. open mixing/loading WP for groundboom application;

3. open mixing/loading WP for chemigation application;

4. open mixing/loading DF for aerial application;

5. open mixing/loading DF for groundboom application;

6. open mixing/loading DF for airblast application;

7. open mixing/loading WP for dip application;

8. open mixing/loading DF for dip application;

Applicator:

9. application of sprays via aerial application;

10. application of sprays via groundboom applications; 

11. application of sprays via airblast application;

Flagger:

12. flagging for aerial application;

Mixer/Loader/Applicator:

13. mixing/loading/applying WP with backpack sprayer;

14. mixing/loading/applying DF/WDG with a backpack sprayer;

15. mixing/loading/applying WP with mechanically-pressurized handgun sprayer;

16. mixing/loading/applying DF/WDG with mechanically-pressurized handgun sprayer;

17. mixing/loading/applying WP with manually-pressurized handgun;

18. mixing/loading/applying DF/WDG with manually-pressurized handwand;

Post-harvest Handler Scenarios:

19. open mixing/loading liquids for post-harvest commodity treatment; and

20. open mixing/loading WP for post-harvest commodity treatment.

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic handler data, used as surrogate data in the absence of chemical-specific data, include 

PHED 1.1, the AHETF database, the ORETF database, or other registrant-submitted 

occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and 

subject to the data protection provisions of FIFRA. The standard values recommended for use in 

predicting handler exposure that are used in this assessment, known as “unit exposures,” are 

outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” 
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(http://www.epa.gov/opp00001/science/handler-exposure-table.pdf), which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at http://www.epa.gov/pesticides/science/handler-exposuredata.html.

For pesticide handlers, it is HED standard practice to present estimates of exposure for 

“baseline” (i.e., workers wearing a single layer of work clothing consisting of a long-sleeved 

shirt, long pants, shoes plus socks and no protective gloves and no respirator), as well as for 

“baseline” and the use of protective gloves or other PPE as might be necessary (e.g., respirator). 

The five proposed labels involved in this assessment directs applicators and other handlers to 

wear long-sleeved shirt, long pants, shoes plus socks, and chemical-resistant gloves. 

Handler exposure is expected to be short- or intermediate-term based on information provided on 

proposed labels. Long-term exposures are not expected; therefore, a long-term assessment was 

not conducted. The average adult body weight of 80 kg was used for estimating the inhalation 

dose. Since the short- and intermediate-term inhalation PODs are based on an oral study and no 

inhalation absorption data are available, toxicity by the inhalation route is considered equivalent 

to the estimated toxicity by the oral route of exposure.

Table 9.1.1 presents the estimated risks for workers based on the short and intermediate-term 

inhalation exposures with baseline attire, or with additional PPE. HED has determined that risks 

are of concern for short-term exposures (i.e., MOEs <1000) for mixing/loading WPs for aerial 

and chemigation applications, and require a PF5 respirator with 80% protection factor to reach 

acceptable MOEs. HED has also determined for intermediate-term exposures, the PPE required 

to reach acceptable MOEs (i.e., MOEs >1000) for mixing/loading WPs for aerial and 

chemigation applications includes engineering controls. Furthermore, for mixing/loading WPs

for groundboom applications and mixing/loading DFs for aerial and groundboom applications, a 

PF5 respirator with 80% protection factor is required for the intermediate-term exposures to 

reach MOEs >1000. 

Table 9.1.1. Fludioxonil Occupational Inhalation Exposures and Risks.

Exposure Scenario

App Rate 

(lb ai/acre, 

unless 

otherwise 

noted)a

Source of Maximum 

Ratef

Area 

Treated 

Daily (acres, 

unless 

otherwise 

noted)b

Inhalation 

Unit 

Exposures

(mg/lb ai)e

Inhalation 

Doses 

(mg/kg/day)c

Short-term 

Inhalation 

MOEsd

Intermediate

-term 

Inhalation 

MOEsd

Mixer/Loader

Mixing/Loading WPs for 

Aerial Applications 0.25

Cannonball® (100-1360) 

on strawberries (foliar 

applied)

350

0.0434 0.054 210 70

PF5: 

0.00868 0.0095 1100 350

PF10:

0.00438 0.0047 2100 700

Engineering 

Control:

0.00024

0.00026 38000 13000

Mixing/Loading WPs for 

Groundboom 0.55

Cannonball® (100-1360) 

on onions, garlic

(soil directed)

80

0.0434 0.024 420 140

PF5: 

0.00868 0.0047 2100 700

PF10:

0.00438 0.0024 4200 1400
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Table 9.1.1. Fludioxonil Occupational Inhalation Exposures and Risks.

Exposure Scenario

App Rate 

(lb ai/acre, 

unless 

otherwise 

noted)a

Source of Maximum 

Ratef

Area 

Treated 

Daily (acres, 

unless 

otherwise 

noted)b

Inhalation 

Unit 

Exposures

(mg/lb ai)e

Inhalation 

Doses 

(mg/kg/day)c

Short-term 

Inhalation 

MOEsd

Intermediate

-term 

Inhalation 

MOEsd

Mixing/Loading WPs for 

Chemigation 0.25

Cannonball® (100-1360) 

on ginseng

(soil directed)

350

0.0434 0.054 210 70

PF5: 

0.00868 0.0095 1100 350

PF10:

0.00438 0.0047 2100 700

Engineering 

Control:

0.00024

0.00026 38000 13000

Mixing/Loading WPs for Dip 

Applications 0.00125

Cannonball® (100-1360) 

on strawberries (dip/crown 

treatments)

100 0.0434 0.000068 150000 49000

1000 0.0434 0.00068 15000 4900

Mixing/Loading DFs for 

Aerial Applications 0.22

Switch® (100-953) on 

berries, bushberries, 

caneberries, grapes, 

strawberries, tropical fruit)

350

0.00896 0.0087 1200 380

PF5:

0.001792 0.0017 5800 1900

Mixing/Loading DFs for 

Groundboom 0.55

Switch® (100-953) on 

berries, bushberries, 

caneberries, leafy 

vegetables, onions, garlic, 

strawberries, tomato, 

peppers, eggplant and 

other fruiting vegetables

80

0.00896 0.005 2000 670

PF5:

0.001792 0.00099 10000 3300

Mixing/Loading DFs for 

Airblast 0.22 Switch® (100-953) on grapes, tropical fruit 40 0.00896 0.00099 10000 3300

Mixing/loading DFs for Dip 

Applications

0.00125 lb 

ai/gal

Switch® (100-953) on 

strawberries (dip/crown 

treatments) 

100 0.00896 0.000014 710000 230000

1000 0.00896 0.00014 71000 23000

Applicator

Applying Sprays via 

Groundboom Equipment 0.55 Cannonball® (100-1360) and Switch® (100-953) 80 0.00034 0.00019 53000 18000

Applying Sprays via Aerial 

Equipment 0.25

Cannonball® (100-1360) 

on strawberries (foliar 

applied)

350

Engineering 

Control:

0.000068

0.000075 130000 44000

Applying Sprays via Airblast 

Equipment 0.22 Switch® (100-953) on grapes, tropical fruit 40 0.00471 0.00052 19000 66000

Flagger

Flagging for Aerial Sprays 

Applications 0.25

Cannonball® (100-1360) 

on strawberries (foliar 

applied

350 0.00035 0.00039 26000 8600

Mixer/Loader/Applicator

Applying WP with backpack 

sprayer 

0.000625 lb 

ai/gal

Cannonball® (100-1360) 

on bushberries 

(greenhouse use)

40 gallons Baseline: 

0.140 0.000044 230000 75000

Applying WP with 

mechanically-pressurized 

handgun sprayer 

0.000625 lb 

ai/gal

Cannonball® (100-1360) 

on bushberries 

(greenhouse use)

1000 gallons Baseline: 

0.120 0.00094 11000 3500

Applying WP with manuallypressurized handwand0.000625 lb 

ai/gal

Cannonball® (100-1360) 

on bushberries

(greenhouse use)

40 gallons Baseline: 

0.030 0.0000094 1100000 350000

Applying DF/WDG with a 

backpack sprayer 0.22

Switch® (100-953 on 

tomato, peppers, eggplant 

and other fruiting 

vegetables

(greenhouse use)

5 Baseline: 

0.140 0.0019 5200 1700
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Table 9.1.1. Fludioxonil Occupational Inhalation Exposures and Risks.

Exposure Scenario

App Rate 

(lb ai/acre, 

unless 

otherwise 

noted)a

Source of Maximum 

Ratef

Area 

Treated 

Daily (acres, 

unless 

otherwise 

noted)b

Inhalation 

Unit 

Exposures

(mg/lb ai)e

Inhalation 

Doses 

(mg/kg/day)c

Short-term 

Inhalation 

MOEsd

Intermediate

-term 

Inhalation 

MOEsd

Applying DF/WDG with 

mechanically-pressurized 

handgun sprayer 

0.22

Switch® (100-953) on 

tomato, peppers, eggplant 

and other fruiting 

vegetables

(greenhouse use)

5 Baseline: 

0.120 0.0017 6000 2000

Applying DF/WDG with 

manually-pressurized 

handwand 

0.22

Switch® (100-953) on 

tomato, peppers, eggplant 

and other fruiting 

vegetables

(greenhouse use)

5

Baseline: 

0.030 0.00042 24000 8000

a. Application rate = maximum application rate from labels.

b. Amount handled per day values are HED estimates of acres treated per day based on ExpoSAC SOP #9 “Standard Values for Daily 

Acres Treated in Agriculture,” industry sources, and HED estimates.

c. Inhalation Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/A or lb ai/gallon) x amount handled or area 

treated/day (acres/day or gallons/day) x absorption factor (100%) / body weight (80 kg adult).

d. Inhalation MOE = NOAEL (10 mg/kg/day for short-term exposure and 3.3 mg/kg/day for intermediate-term exposure) / inhalation 

daily dose (mg/kg/day). LOC = 1000.

e. Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” September 26, 2011. Baseline inhalation: no 

respirator. PF5: respirator that reduces exposure by 80%. Engineering control: enclosed cockpit for aerial applicators.

f. Maximum rates are from labels: Cannonball® WP (EPA Reg. # 100-1360) is a 50 % WP and Switch®62.5 WG (EPA Reg. # 100-953) 

is a combination product which contains 37.5 %, by weight, cyprodinil ai and 25.0 %, by weight, fludioxonil ai. It is formulated as a 

WDG. 

Table 9.1.2. Occupational Handler Short- and Intermediate-Term Inhalation Exposure and Risk Estimates for the 

Post-Harvest Use of Fludioxonil.

Crop

Solution 

Concentration1

(lb ai/gal soln)

Amount Treated 

per Day2(1 

gal/lbs of crop)

Amount Processed 

per Day3(lbs 

boxes/hr)

Inhalation 

UE4

(μg/lb ai)

ST & IT Inhalation 

Daily Dose5 (mg 

ai/kg/day) ST MOE6IT MOE7

Open Mixing/Loading WP: Scholar® 50% WP (100-969)

Citrus 0.01 0.000125 180,000

43.4

0.001116 9,000 3,000

Pineapple 0.005 0.000125 180,000 0.000558 18,000 5,900

Pome Fruit 0.0025 0.000125 180,000 0.000279 36,000 12,000

Potato 0.01875 0.000125 180,000 0.0020925 4,800 1,600

Tomato 0.005 0.000125 180,000 0.000558 18,000 5,900

Tropical Fruit 0.005 0.000125 180,000 0.000558 18,000 5,900

Open Mixing/Loading Liquids: Graduate A+TM 20.6 % or 1.99 lbs ai per gallon (EPA Reg. # 100-1308) 

Citrus 0.00995 0.000125 180,000

0.219

5.58E-06 1,800,000 590,000

Pineapple 0.0048 0.000125 180,000 2.70E-06 3,700,000 1,200,000

Pome Fruit 0.0024 0.000125 180,000 1.35E-06 7,400,000 2,400,000

Potato 0.018 0.000125 180,000 1.01E-05 990,000 330,000

Tomato 0.0048 0.000125 180,000 2.70E-06 3,700,000 1,200,000

Tropical Fruit 0.0048 0.000125 180,000 2.70E-06 3,700,000 1,200,000

1. Solution concentration – (a) for WP product: application rate (oz product/gal water) x 1 lb/16 oz x % ai; (b) for liquid product: 

application rate (fl oz product/gal water) x lb ai/gal x 1 gal/128 fl oz.

2. Amount treated per day – assumption from ExpoSAC draft policy on post harvest use (D. Jaquith, 11/2005); 1 gallon treats 8,000 lbs fruit.

3. Amount processed per day - lbs boxes per hour. Assumed that a packing facility could potentially pack 2,000 boxes per hour, each weighing 90 

lbs (2,000 boxes/hr x 90 lbs each = 180,000 lbs boxes/hr). 

4. Based on “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” September 26, 2011. Baseline = no respirator.

5. Daily dose = [amount processed (lb boxes/hr) x amount treated daily (gal/lb) x soln. concentration (lb ai/gal soln.) x unit exposure x 8 (hr/day) 

x absorption factor (1.0)]/body weight (80 kg).

6. Short-term MOE = NOAEL (10 mg/kg/day)/daily dose (mg ai/kg/day).

7. Intermediate-term MOE = NOAEL (3.3 mg/kg/day)/daily dose (mg ai/kg/day).
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9.2 Occupational Post-Application Risk

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for fludioxonil at this time primarily because it has a low vapor 

pressure (2.9 x 10-9 mm Hg @ 25°C) and it is applied at low application rates. However, 

volatilization of pesticides may be a potential source of post-application inhalation exposure to 

individuals nearby pesticide applications. The Agency sought expert advice and input on issues 

related to volatilization of pesticides from its FIFRA SAP in December 2009. The Agency

received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). Although a quantitative 

occupational post-application inhalation exposure assessment was not performed, an inhalation 

exposure assessment was performed for occupational handlers. This assessment resulted in risks 

that did not exceed HED’s LOC at baseline inhalation PPE. Handler exposure resulting from 

application of pesticides outdoors is likely to result in higher exposure than post-application 

exposure. Therefore, it is expected that these handler inhalation exposure estimates would be 

protective of most occupational post-application inhalation exposure scenarios. The Agency is 

in the process of evaluating the SAP report as well as available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, 

develop policies and procedures, to identify the need for and, subsequently, the way to 

incorporate occupational post-application inhalation exposure into the Agency's risk 

assessments. If new policies or procedures are put into place, the Agency may revisit the need 

for a quantitative occupational post-application inhalation exposure assessment for fludioxonil. 

HED assumes that inhalation exposures are minimal following outdoor applications of an ai with 

low vapor pressure; therefore, post-application inhalation exposures and risks were not 

quantitatively assessed. 

There is potential for dermal post-application exposure; however, since no short-term dermal 

POD was selected, no post-application dermal exposures and risks are assessed.

Attachment A: Toxicology Profile Tables.

Appendix B: International Residue Limits for Fludioxonil.

cc: G. Kramer (RAB1), L. Venkateshwara (RAB1), A. Dunbar (RAB1)

RDI: Branch (2/2/12)

G.F. Kramer:S10957:PY-S:(703)305-5079:7509P:RAB1
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Appendix A: Toxicity Profile

Acute Toxicity Profile.

Table A1. Acute Toxicity of Technical Grade Fludioxonil.

Guideline 

No. Study Type MRID No. Results

Toxicity 

Category

870.1100 Acute Oral 43124105 LD50 > 5000 mg/kg IV

870.1200 Acute Dermal 43124106 LD50 > 2000 mg/kg III

870.1300 Acute Inhalation 43080019 LC50 = 2.636 m/L IV

870.2400 Primary Eye Irritation 43124107 slight irritant III

870.2500 Primary Skin Irritation 43124108 non-irritating IV

870.2600 Dermal Sensitization 43080024 not a sensitizer -

Toxicity Profile of Fludioxonil.

Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses Results

870.3100a

90-Day oral toxicity in 

rats

43080026 (1990)

Acceptable/guideline

0, 10, 100, 1000, 

7000, 20,000 ppm

M: 0.8, 6.6, 64, 428, 

1283 mg/kg/day

F: 1.0, 7.1, 70, 462, 

1288 mg/kg/day

NOAEL = 64 mg/kg/day (M) and 70 mg/kg/day (F).

LOAEL = 428 mg/kg/day (M) and 462 mg/kg/day (F) based on 

decreased weight gain (both sexes), chronic nephropathy (M), and 

centrilobular hepatocyte hypertrophy (F).

870.3100b

90-Day oral toxicity in 

mice

43080027 (1990)

Acceptable/guideline

0, 10, 100, 1000, 

3000, 7000 ppm

M: 1.3, 13.9, 144, 

445, 1052 mg/kg/day

F: 1.9, 16.8, 178, 559, 

1307 mg/kg/day

NOAEL = 445 mg/kg day (M) and 559 mg/kg/day (F).

LOAEL = 1052 mg/kg/day (M) and 1307 mg/kg/day (F) based on 

decreased body weight gain (F), increased alkaline phosphatase 

(M), increased relative liver weight, increased incidence of 

nephropathy and centrilobular hypertrophy (both sexes).

870.3100c

90-Day oral toxicity in 

dogs

43080029 (1990)

Acceptable/guideline

0, 200, 2000, 

15,000/10,000 ppm

M & F: 5, 50, 

375/250 mg/kg/day

NOAEL = 5 mg/kg/day (both sexes).

LOAEL = 50 mg/kg/day based on an increased incidence of 

diarrhea (both sexes).

870.3200

21/28-Day dermal 

toxicity in rats

43080030 (1990)

Acceptable/guideline

M & F: 0, 40, 200, or 

1000 mg/kg/day

NOAEL 1000 mg/kg/day for both sexes.

870.3250

90-Day dermal 

toxicity in rats

NA NA

870.3465

90-Day inhalation 

toxicity in rats

NA NA

870.3700a

Prenatal 

developmental toxicity 

in rats

43080034 (1988) 

Acceptable/guideline

F: 0, 10, 100, or 1000 

mg/kg/day

Maternal NOAEL = 100 mg/kg/day.

LOAEL = 1000 mg/kg/day based on reduction in corrected weight 

gain.

Developmental NOAEL = 100 mg/kg/day.

LOAEL = 1000 mg/kg/day based on increase in the fetal incidence 

and litter incidence of dilated renal pelvis and dilated ureter.
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Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses Results

870.3700b

Prenatal 

developmental toxicity 

in rabbits

43080035 (1989) 

Acceptable/guideline

F: 0, 10, 100, or 300 

mg/kg/day

Maternal NOAEL = 10 mg/kg/day.

LOAEL = 100 mg /kg/day based on decreased body weight gain 

and decreased food efficiency.

Developmental NOAEL 300 mg/kg/day.

870.3800

Reproduction and 

fertility effects in rats

43080036 (1992)

Acceptable/guideline

0, 30, 300, or 3,000 

ppm

F0F1 M: 2.19, 22.13, 

221.61 mg/kg/day

F0F1 F: 2.45, 24.24, 

249.67 mg/kg/day 

Parental/Systemic NOAEL = 22.13 mg/kg/day (M) and 24.24 

mg/kg/day (F).

LOAEL = 221.61 mg/kg/day (M) and 249.67 mg/kg/day (F) based 

on increased clinical signs, decreased body weights, decreased 

weight gain, and decreased food consumption in both sexes

Reproductive/Offspring NOAEL = 22.13 mg/kg/day (M) and 24.24 

mg/kg/day (F).

LOAEL = 221.61 mg/kg/day (M) and 249.67 mg/kg/day (F) based 

on reduced pup weights during lactation.

870.4100b

Chronic toxicity in 

dogs

43080031 (1992)

Acceptable/guideline

0, 100, 1000, or 8,000 

ppm

M: 0, 3.1, 33.1, or 

297.8 mg/kg/day 

F: 0, 3.3, 35.5, or 

330.7 mg/kg/day

NOAEL = 3.3 mg/kg/day (F) and 33.1 mg/kg/day (M).

LOAEL = 35.5 mg/kg/day (F) and 297.8 mg/kg/day (M) based 

upon decreased weight gain (F) and decreased body weight, 

reduction in hematological parameters (platelets), increase in 

cholesterol and alkaline phosphatase, and increased relative liver 

weight (M).

870.4300

Combined Chronic 

Toxicity/

Carcinogenicity in rats

43080037 (1993)

Acceptable/guideline

0,10, 30, 100, 1,000, 

or 3,000 ppm 

M: 0.37, 1.1, 3.7, 37, 

or 113 mg/kg/day

F: 0.44, 1.3, 4.4, 44, 

or 141 mg/kg/day

NOAEL = 37 mg/kg/day (M) and 44 mg/kg/day (F).

LOAEL = 113 mg/kg/day (M) and 141 mg/kg/day (F) based on 

decreased mean body weight gain, slight anemia (F), and increased 

incidence and severity of liver lesions (degeneration) in both sexes. 

There was no evidence of carcinogenicity in male rats, but there 

was a statistically significant increase, both trend and pairwise, of 

combined hepatocellular tumors in female rats. Classified as a 

Group D chemical by HED Cancer Peer Review Committee.

870.4200a

Carcinogenicity in 

Mice

43080032 (1993)

0, 10, 100, 1,000 or 

3,000 ppm

M: 1.1, 11.3, 112, or 

360 mg/kg/day

F: 1.4, 13.5, 133, or 

417 mg/kg/day

NOAEL = 11.3 mg/kg/day (M) and 133 mg/kg/day (F).

LOAEL = 112 mg/kg/day (M) and 417 mg/kg/day (F) based on the 

increased incidence of mice convulsing when handled (M), 

increased absolute liver weight, and grossly enlarged livers (F). 

Statistically significant trend for malignant lymphomas in females.

870.4200b

Carcinogenicity in 

mice

43080033 (1993)

Acceptable/guideline

0, 3, 30, 5000, or 

7,000 ppm

M: 0.33, 3.3, 590, or 

851 mg/kg/day

F: 0.41, 4.1, 715, or 

1,008 mg/kg/day

NOAEL = 590 mg/kg/day (M) and 715 mg/kg/day (F).

LOAEL = 851 mg/kg/day (M) and 1008 mg/kg/day (F) based on 

reduced survival (F), decreased body weights (M), bile duct 

hyperplasia (M), and severe nephropathy (both sexes). 

No evidence of carcinogenicity.

870.5100

Gene mutation in 

bacteria

43080038 (1989)

Acceptable/guideline

Strains TA 98, 100, 1535, 1537 of S. typhimurium, and strain 

WP2uvrA of E. coli were negative for mutagenic activity when 

tested from 20 to 5000 μg/plate in absence and presence of 

metabolic activation.

870.5300

Gene mutation in 

mammalian cells in 

culture

43152501 (1989)

Acceptable/guideline

Chinese hamster V79 ovary cells were tested from 0.50 to 60 

μg/mL. Negative up to limit of solubility and cytotoxicity.

870.5375

in vitro Chromosome 

aberration 

43080040 (1989)

Acceptable/guideline

Chinese hamster ovary cells were tested with and without 

metabolic activation from 1.37 to 700 μg/mL. Positive for nondisjunction of chromosomes both in the presence and absence of 

activation.
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Guideline No./ Study 

Type

MRID No. (year)/ 

Classification /Doses Results

870.5385

Bone marrow

chromosome 

aberrations assay 

43080042 (1993)

Acceptable/guideline 

Chinese hamsters were orally dosed at levels from 1250 to 5000 

mg/kg. There was no significant increase in the frequency of 

chromosome aberrations in bone marrow at any dose tested.

870.5395

In vivo Mouse 

micronucleus assay

43080041 (1990)

Acceptable/guideline

Both sexes of NMRI mice were dosed up to 5000 mg/kg/day. 

There were no significant increases in the number or percentage of 

micronucleated polychromatic erythrocytes.

870.5395

In vivo Rat hepatocyte 

micronucleus assay

43080043 (1991)

Acceptable/guideline

Male rats were orally dosed 1250, 2500, and 5000 mg/kg and 

hepatocytes were harvested. Micronucleated hepatocytes were 

found in Phase II at the low and mid dose levels but not at the high 

dose level and not in Phase I. Positive for mutagenicity in 

hepatocytes exposed in vivo.

870.5550

in vitro unscheduled 

DNA synthesis assay

43080039 (1989)

Acceptable/guideline 

There was no evidence of unscheduled DNA synthesis in rat 

hepatocytes at doses from 4.1 to 5000 μg/mL.

870.5450 

Dominant lethal assay 

in mice

43080044 (1992)

Acceptable/guideline 

Male mice singly dosed at 0, 1250, 2500, or 5000 mg/kg/day and 

mated for 8 consecutive weeks had no evidence of a dominant 

lethal mutation.

870.7485

Metabolism in rats

43560504, 43560505, 

43429513 (1990)

Acceptable/

guideline

14C-Fludioxonil given by gavage and bile-duct cannulation to 

groups of male and female rats. Absorption was estimated to be 

between 67-91%. Terminal tissue distribution showed that 

terminal residues were below the limit of detection for most tissues 

except the liver, kidneys, blood, and lungs, which showed low 

levels. The major route of excretion was the feces, with 

approximately 80% of the administered radioactivity excreted by 

this route in male and female rats at both the low and high dose. 

The remaining radioactivity was excreted through urine. In bile 

duct-cannulated rats, approximately 70% of an administered 

radioactive dose was excreted via this route, supporting the bile as 

the origin of the fecal radioactivity. There were no apparent sex- or 

dose-related differences in the routes of excretion for fludioxonil. 

Examination of urine for metabolites of fludioxonil showed at least 

20 metabolites, each comprising a minor fraction of the 

administered dose (0.1-3.1%). 

870.7600

Dermal penetration NA NA

870.7800

Immunotoxicity

48478502 (2011) 

Classification pending 

formal review

0, 1000, 2000, 5000 

ppm (equivalent to 0, 

253.8, 454, 1230 

mg/kg/day [F])

Preliminary NOAEL = 1230 mg/kg/day.

Preliminary LOAEL = not established.

No evidence of immunotoxicity.
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Appendix B: International Residue Limits 

Fludioxonil (118203; Date of Request: 08/29/2011)

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.516:

Plant: fludioxonil, 4-(2,2-difluoro1,3-benzodioxol-4-yl)-1-H-pyrrole3-carbonitrile)

Livestock: fludioxonil, including its 

metabolites and degradates, in or on 

the commodities in the table below. 

Compliance with the tolerance 

levels specified below is to be 

determined by measuring only the 

sum of fludioxonil, 4-(2,2-difluoro1,3-benzodioxol-4-yl)-1-H-pyrrole3-carbonitrile), and its metabolites 

converted to 2,2-difluoro-l,3-

benzodioxole-4-carboxylic acid, 

calculated as the stoichiometric 

equivalent of fludioxonil

4-(2,2-difluoro-1,3-benzodioxol4-yl)-1H-pyrrole-3-carbonitrilePlant : 

fludioxonil.

Livestock : 

fludioxonil and 

metabolites 

determined as 

2,2-difluoro-1,3-

benzodioxole-4-

carboxylic acid 

and calculated as 

fludioxonil.

The residue is 

fat-soluble.

Commodity1 Tolerance (ppm)/Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex3

Guava 5.0

Feijoa 5.0

Jaboticaba 5.0

Wax jambu 5.0

Starfruit 5.0

Passionfruit 5.0

Acerola 5.0

Avocado 5.0

Black sapote 5.0

Mamey sapote 5.0

Canistel 5.0

Mango 5.0

Papaya 5.0

Sapodilla 5.0

Star apple 5.0

Lychee 20

Longan 20

Spanish lime 20

Rambutan 20

Pulasan 20

Sugar apple 20

Atemoya 20

Custard apple 20

Cherimoya 20

Ilama 20

Soursop 20

Biriba 20
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Ginseng 4.0

Onion, bulb subgroup 3-07A 0.50

0.02 Chinese onions, 

garlic, great headed 

garlic, potato onions, 

shallots

0.2 dry bulb onions

0.5 onion, bulb

Onion, green subgroup 3-07B 7.0

0.02 Chinese, chives, 

chive leaves, leeks, 

green onions, Welsh 

onion tops

Caneberry subgroup 13-07A 5.0

4.2 blackberries, 

loganberries, 

raspberries 

5 blackberries, 

raspberries, red, 

black, 

dewberries 

(including 

boysenberry and 

loganberry) 

Bushberry subgroup 13-07B 2.0

2.0 blueberries, 

currant, elderberries, 

gooseberries, 

huckleberries, salal 

berries, saskatoon 

berries (juneberries)

2 blueberries 

Fruit, small, vine climbing, 

subgroup 13-07F, except fuzzy 

kiwifruit

2.0

1 gooseberries 

1 grape

20 kiwifruit

2 grapes

15 kiwifruit Po

Low growing berry subgroup 13-

07G, except cranberry 3.0

2 blueberries, 

lingonberries, 

strawberries

2 blueberries

3 strawberry

Vegetable, fruiting group 8-10, 

except tomato 0.50

**0.01 bell peppers, 

eggplants, ground 

cherries, non-bell 

peppers, pepinos, 

pepper hybrids

0.3 eggplant

1 peppers, sweet 

(including 

pimento or 

pimiento) 

Tomato 5.0 0.01 tomatoes, 

tomatillos

0.5 

Fruit, citrus, group 10-10 10

10 calamondin, citrus 

citron, citrus hybrids, 

grapefruits, 

kumquats, lemons, 

limes, oranges, 

pummelos, 

tangerines, Satsuma 

mandarins

500 citrus oil

7 citrus fruits 

10 citrus fruits 

Po (proposed)

Fruit, pome, group 11-10 5.0

5.0 apples, 

crabapples, loquats, 

mayhaws, pears, 

quinces

5 pome fruits Po

0.7 pear 

20 apple 

pomace, dry
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Vegetable, leafy, except Brassica, 

subgroup 4A 30

30 amaranth, arugula, 

corn salad, dandelion 

leaves, dock, edible 

leaved 

chrysanthemum, 

endives, fresh chervil 

leaves, fresh parsley 

leaves, garden cress, 

garden purslane, 

garland 

chrysanthemum, head 

lettuce, leaf lettuce, 

orach leaves, 

radicchio, upland 

cress, winter purslane

**0.01 New Zealand 

spinach, spinach, 

vine spinach

10 lettuce, head

Vegetable, tuberous and corm, 

subgroup 1C 6.0 **0.02 potato 0.02 potato

Pineapple 20

Dragon fruit 1.0

Leafy petioles crop subgroup 04B 15

0.01 cardoon, celery, 

celtuce, Chinese 

celery, fresh Florence 

fennel leaves and 

stalks, rhubarb, Swiss 

chard 

Milk 0.01 0.01 0.01 milks

Cattle, Goat, Horse, Sheep: meat 

byproducts 0.05

0.05 kidney and liver 

of cattle, goats, 

horses, sheeps

0.05 edible offal 

(mammalian) (*)

Cattle, Goat, Horse, Sheep: fat 0.05 0.05 fat of cattle, 

goats, horses, sheeps

Cattle, Goat, Horse, Sheep: meat 0.01

0.01 meat of cattle, 

goats, horses, sheeps

0.01 (*) meat 

from mammals 

other than 

marine 

mammals)

Completed: M. Negussie; 09/01/2011

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.

** = Levels to be harmonized as part of this joint review.