UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: February 20,2014 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Flutolanil - Preliminary Human Health Risk Assessment for Registration Review 

and Human Health Risk Assessment for Label Amendments for Brassica (Cole) 

Leafy Vegetables (Crop Group 5), Turnip Greens, Rice, and Turf and Addition of 

Banded Applications for Peanuts. 

PC Code: 128975 DP Barcodes: 0412198, 0413582, 0410729 

Decision Nos.: 478733 , 480092, 477208 Registration Nos.: 432-1223, 71711-28 

Petition Nos.: NA Regulatory Action: Registration Review and Section 3 

Registration 

Risk Assessment Type: Single Chemical/Aggregate 

TXRNo.: NA 

Case No.: 7010 

CAS No.: 66332-96-5 

MRID No.: NA 40 CFR: § 180.484 

FROM: Barry O'Keefe, Senior Biologist /3, 0 ~ Nancy Dodd, Chemist~ ~ 

Minerva Mercado, Toxicologi -- ......, 

Risk Assessment Branch III (RAB III) 

Health Effects Division (7509P) 

THROUGH: Christine Olinger, Branch Chief 

Risk Assessment Branch III (RAB III) 

Health Effects Division (7509P) 

Donna Davis, RARC Reviewer 

Pv Shah, RARC Reviewer 

TO: Erin Malone, Risk Manager 

Shaja Joyner, Product Manager 20 

Cynthia Giles-Parker, Branch Chief 

Fungicide Branch 

Registration Division (7505P) 

and 

Jill Bloom, Chemical Review Manager 

Tom Myers, Team Leader 

Kevin Costello, Branch Chief 

Risk Management and Implementation Branch II 

Pesticide Re-evaluation Division (7508P) 

Page 1 of 53 
This document provides the Health Effects Division (HED) preliminary human health exposure 

and risk assessment for the Registration Review of the fungicide flutolanil. Additionally, 

included in this assessment are a proposed increase in the maximum seasonal application rate to 

turf by Bayer CropScience that affects the estimated drinking water concentrations (EDWC) and 

proposed changes by Nichino America, Inc. as follows: 1) adding a banded application to the 

existing broadcast use for peanuts on the soluble concentrate (SC) label; 2) adding the Brassica 

(cole) leafy vegetables crop group and turnip greens to the SC label using residue data from the 

dry flowable (DF) formulation; and 3) slightly modifying the established SC use rate on rice. 

The toxicology reevaluation was performed by Minerva Mercado, the drinking water assessment 

was conducted by Jose Melendez (EPA Environmental Fate and Effects Division (EFED)), the 

review of the residue chemistry data and dietary exposure assessment were conducted by Nancy 

Dodd, and the human health risk assessment was conducted by Barry O'Keefe. 

Page 2 of 53 
Page 3 of 53

Table of Contents

1.0 Executive Summary ........................................................................................................... 5

2.0 HED Recommendations .................................................................................................... 7

2.1 Data Deficiencies ............................................................................................................ 7

2.2 Tolerance Considerations.............................................................................................. 8

2.2.1 Enforcement Analytical Method ............................................................................... 8

2.2.2 Recommended Tolerances......................................................................................... 8

2.2.3 International Harmonization..................................................................................... 9

3.0 Introduction...................................................................................................................... 10

3.1 Chemical Identity ......................................................................................................... 10

3.2 Physical/Chemical Characteristics ............................................................................. 10

3.3 Pesticide Use Pattern.................................................................................................... 10

3.4 Anticipated Exposure Pathways................................................................................. 13

3.5 Consideration of Environmental Justice.................................................................... 13

4.0 Hazard Characterization and Dose-Response Assessment.......................................... 14

4.1 Toxicology Studies Available for Analysis................................................................. 14

4.2 Absorption, Distribution, Metabolism and Excretion (ADME) .............................. 14

4.2.1 Dermal Absorption................................................................................................... 15

4.3 Summary of Toxicological Effects.............................................................................. 15

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 16

4.4.1 Completeness of the Toxicology Database.............................................................. 16

4.4.2 Evidence of Neurotoxicity ........................................................................................ 16

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 16

4.4.4 Residual Uncertainty in the Exposure Database ................................................... 16

4.5 Toxicity Endpoint and Point of Departure Selections .............................................. 17

4.5.1 Dose-Response Assessment...................................................................................... 17

4.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment ...... 17

4.5.3 Cancer Classification and Risk Assessment Recommendation............................ 18

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment............................................................................................................................... 18

4.6 Endocrine Disruption................................................................................................... 19

5.0 Dietary Exposure and Risk Assessment......................................................................... 20

5.1 Residues of Concern Summary and Rationale .......................................................... 20

5.2 Food Residue Profile .................................................................................................... 21

5.3 Water Residue Profile.................................................................................................. 22

5.4 Dietary Risk Assessment.............................................................................................. 23

5.4.1 Description of Residue Data Used in Dietary Assessment.................................... 23

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 23

5.4.3 Acute Dietary Risk Assessment............................................................................... 23

5.4.4 Chronic Dietary Risk Assessments ......................................................................... 23

5.4.5 Cancer Dietary Risk Assessments........................................................................... 23

5.4.6 Summary Table......................................................................................................... 24

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 24

7.0 Aggregate Exposure/Risk Characterization.................................................................. 24

8.0 Cumulative Exposure/Risk Characterization ............................................................... 25
Page 4 of 53

9.0 Occupational Exposure/Risk Characterization ............................................................ 25

10.0 References......................................................................................................................... 26

Appendix A. Toxicology Profile and Executive Summaries .................................................. 27

A.1 Toxicology Data Requirements................................................................................... 27

A.2 Toxicity Profiles............................................................................................................ 28

A.3 Hazard Identification and Endpoint Selection .......................................................... 31

A.4 Executive Summaries................................................................................................... 33

Appendix B. Nomenclature and Physicochemical Properties of Flutolanil.......................... 43

Appendix C. Incident Report.................................................................................................... 46

Appendix D. Food Residue Profile Details .............................................................................. 47

Appendix E. International Residue Limits Status Sheet........................................................ 52
Page 5 of 53

1.0 Executive Summary

Introduction

Flutolanil, N-[3-(1-methylethoxy)phenyl]-2-(trifluoromethyl)benzamide, is a systemic 

benzanilide fungicide with both preventative and curative actions against powdery scab, 

Spogospora subterranean, Rhizoctonia solani (the causal agent of limb/pod rot in peanuts), 

sheath blight in rice, black scurf in potato, wirestem in Brassica (Cole) leafy vegetables and 

turnip greens, and black scurf, Rhizoctonia solani, and crown rot in ginseng. Flutolanil is also 

effective in controlling white mold in peanuts and rust diseases in several crops. 

Use Profile

Flutolanil is currently registered for application to Brassica (Cole) leafy vegetables, peanuts, 

potatoes, rice, and turnip greens, and as a seed treatment for soybean and cotton. Tolerances 

have been established for these commodities as well as tolerances for inadvertent residues for 

wheat commodities as rotational crops and tolerances for ruminant commodities. Non-food uses 

of flutolanil include turf, and greenhouse, nursery, and potted ornamentals. 

Bayer CropScience has proposed an increase in the maximum seasonal application rate to turf 

from 9 fl oz to 17.1 fl oz. Additionally, Nichino America, Inc. has proposed the following: 1) 

adding a banded application to the existing broadcast use for peanuts on the soluble concentrate 

(SC) label; 2) adding the Brassica (cole) leafy vegetables crop group and turnip greens to the SC 

label using residue data from the DF formulation; and 3) slightly modifying the lowest 

established SC use rate on rice from 11.8 fl oz to 12 fl oz/A (0.35 to 0.36 lb ai/A).

Exposure Profile

The existing uses and the proposed changes to uses of flutolanil would result in exposures from

both food and drinking water. Non-occupational/residential exposures via dermal, inhalation, 

and incidental oral routes are expected. Non-occupational/residential exposures are expected to 

occur for short-term durations. Agricultural uses will result in occupational dermal and 

inhalation exposures from handler activities and dermal exposure from post-application 

activities. Occupational exposures are expected to occur for short- and intermediate-term 

durations.

Hazard Assessment 

The existing flutolanil toxicity/hazard database is adequate for hazard characterization and 

endpoint selection. The toxicology studies conducted on flutolanil demonstrate few biologically 

significant effects, mainly in the liver and gastrointestinal (GI) system. Liver effects were 

observed in several studies, but most of the changes were considered adaptive, especially in the 

rat. The dog was the most sensitive species for liver effects, showing clinical chemistry and liver 

weight changes together with glycogen deposition in the subchronic study. The chronic dog 

study saw effects suggestive of GI irritation, but no relevant liver effects were reported.

Evaluation of the available data for flutolanil did not reveal any evidence to indicate that it is 

neurotoxic or that it targets the immune system, fetal development, or reproduction. 
Page 6 of 53

There was no evidence for increased susceptibility of rat or rabbit fetuses to in utero exposure or 

rat pups to post-natal exposure to flutolanil. 

No adverse effects were observed in studies in which flutolanil was administered by the dermal 

route of exposure. The subchronic inhalation study has been waived based on a weight of 

evidence approach (TXR 0056560); i.e. low vapor pressure, low acute inhalation toxicity, and 

low subchronic and chronic toxicity. Further, there is no developmental or reproductive concern 

at dose levels that do not exceed the limit dose. For these reasons, it is concluded that 

appropriate points of departure (PODs) are not established for any dermal or inhalation exposure 

duration. For chronic dietary exposure, the POD was based on increased incidence of GI effects, 

decreased body weight and decreased food consumption observed in the chronic dog study. For 

incidental oral exposure, no hazard was identified from appropriate oral toxicity studies,

including developmental toxicity studies in rats and rabbits.

Based on the lack of evidence of carcinogenicity and the lack of evidence of mutagenicity, 

flutolanil is classified as “not likely to be carcinogenic to humans”.

Dietary Exposure

The residue chemistry data are adequate to assess human dietary exposure. The screening-level 

assessments will not underestimate exposure or risk. As no acute dietary endpoint was 

identified, an acute exposure analysis was not performed. Tolerance-level residues combined 

with 100% crop treated and default processing factors were used to determine the chronic dietary 

exposure and risk estimates. The chronic dietary exposure estimates for food and drinking water 

are below HED’s level of concern for the general U.S. population (11% of the chronic 

population adjusted dose (cPAD)). The most highly exposed population subgroup was all infants 

(<1 year old) at 29% of the cPAD. Estimated drinking water concentrations (EDWCs) were 

incorporated directly into the chronic dietary assessment. The maximum screening level EDWC 

for chronic exposure is 2530 ppb, found in ground water associated with the use on turf using the 

ground water Tier I/II model PRZM-GW.

Residential Exposure

There are existing non-occupational/residential uses associated with flutolanil. Registered 

products include several for use on turf grass and potted ornamentals which, if not specifically 

prohibited through label directions, could be used in a residential/public site. Although potential 

residential handler and post-application exposures exist, quantitative assessments were not 

conducted because no dermal, oral (incidental), or inhalation toxicological endpoints attributable 

to short- or intermediate-term exposures have been identified, and the current use patterns do not 

indicate long-term exposure (6 or more months of continuous exposure) potential. 

Aggregate Exposure

Aggregate risk assessments were performed for chronic aggregate exposure (food and drinking 

water) only; the resultant risk estimates are not of concern. Short-term aggregate risk 

assessments were not performed because toxicological endpoints from dermal, inhalation, and 

incidental oral exposures were not identified. Also, there is no intermediate-term residential 

exposure, so, intermediate-term aggregate risk assessments were not performed.. Additionally, 

the Agency does not expect residential exposure durations that would result in long term 
Page 7 of 53

exposures. A cancer aggregate risk assessment was also not performed because flutolanil has 

been classified as not likely to be carcinogenic to humans. 

Occupational Exposure

Workers may be exposed to flutolanil during mixing, loading, applying, and post-application 

activities. Based on the existing registered uses and the proposed application rates and use 

scenarios, short- and intermediate-term dermal and inhalation occupational exposures may occur. 

However, since short-and intermediate-term endpoints have not been established, an 

occupational exposure assessment was not conducted. Chronic occupational exposure is not 

expected; thus, chronic occupational exposure risk assessments also were not conducted.

Environmental Justice Considerations

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.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. Considerations made for the human 

health risk assessment are discussed in more detail below.

2.0 HED Recommendations

Provided the registrant submits the analytical standards as described in Section 2.1 and amends 

the proposed labels as described in Section 2.3, HED has no objection to the proposed 

amendments to the Brassica (cole) leafy vegetable, turnip greens, peanuts, and rice. These 

amendments are as follows: 1) add Brassica (cole) leafy vegetables and turnip greens to the 

Flutolanil 40 SC label; 2) add band application to peanuts to the Flutolanil 40 SC label; and 3) 

revise the lowest application rate on rice on the Flutolanil 40 SC label from 11.8 to 12.0 fl oz/A. 

Additionally, the proposal to increase the maximum seasonal application rate to turf from 9 fl oz 

to 17.1 fl oz is not a concern to HED; since this increase does not change any exposure and 

therefore a new assessment is not required. 

For registration review, data recommendations are discussed in Section 2.1. The tolerances for 

flutolanil will need to be updated in registration review as described in Section 2.2.

2.1 Data Deficiencies

Data recommended to be submitted under registration review and for any registration 

actions (i.e., the amendment to add the banded application on peanuts).

860.1650 Submittal of Analytical Reference Standards

Analytical reference standards for flutolanil, the common moiety 2-(trifluoromethyl)benzoic 

acid, M-2, M-3, M-4, and M-7 must be kept available at the EPA National Pesticide Standards 

Repository. The only flutolanil standards that are in stock are flutolanil and the common moiety 

2-(trifluoromethyl)benzoic acid (e-mail from Theresa Cole, Analytical Chemistry Branch, 

1/9/14). Analytical reference standards for M-2, M-3, M-4, and M-7 must be sent to the 

Repository.
Page 8 of 53

When new standards are submitted, they should be sent to the Analytical Chemistry Lab, which 

is located at Fort Meade, to the attention of either of Theresa Cole or Thuy Nguyen at the 

following address:

USEPA

National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

701 Mapes Road

Fort George G. Meade, MD 20755-5350

The full 9 digit zip code is mandatory or the mail will be returned to you.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate enforcement methods are available. A gas chromatography-mass spectrometry 

(GC/MS) enforcement method (AU/95R/04) is available which analyzes the flutolanil residues 

of concern in plants and livestock commodities for the tolerance expression and risk assessment. 

The method is available in MRID 44526201, entitled Validation of an Analytical Method for 

Residues of Flutolanil in Milk, Peanuts, and Rice. The method has undergone a successful 

independent validation with peanut nutmeat and hay, rice grain, milk, eggs, beef muscle, and 

beef fat. The AU/95R/04 analytical method determines all metabolites converted to the common 

moiety 2-trifluoromethyl benzoic acid (2-TFBA), including flutolanil, M-2, M-3, M-4, and M-7. 

The limits of quantitation (LOQs) are 0.05 ppm for whole milk and livestock tissues and 0.2 ppm 

for rice and peanut matrices. Radiovalidation was conducted on peanut vines, hulls, and 

nutmeats using a similar GC/MS common moiety method (AU/01/94). A confirmatory method 

is required because the method AU/95R/04 is a common moiety method. Nichino America 

submitted a liquid chromatography-mass spectrometry (LC/MS/MS) method (XAM-65), which 

is acceptable as a confirmatory method. Method XAM-65 separately determines residues of 

flutolanil and its major metabolite, M-4.

2.2.2 Recommended Tolerances

Tolerances for flutolanil are established in 40 CFR §180.484. Tolerances are established for 

residues of flutolanil, N-(3-(1-methylethoxy)phenyl)-2-(trifluoromethyl)benzamide, including its 

metabolites and degradates, in or on commodities. Compliance with the tolerance levels 

specified is to be determined by measuring only flutolanil and its metabolites converted to 2-

(trifluoromethyl)benzoic acid, calculated as flutolanil.

No tolerance revisions were proposed with the proposed amendments. The following tolerances 

should be modified as part of the registration review, except tolerances for peanut commodities 

which are modified due to the new request for the banded application to peanuts.

Tolerances are established [40 CFR §180. 484(a)] on rice straw and hulls. Tolerances on these 

commodities are no longer required (Table 1 Feedstuffs, June 2008) and should be removed. 
Page 9 of 53

Based on the OECD tolerance calculation procedures on peanut hay, including residues from 

both band and broadcast applications, the established tolerance of 15.0 ppm for peanut hay 

should be increased to 20.0 ppm. 

The tolerance of 0.1 ppm on turnip greens and the Brassica (cole) leafy vegetable group 5 should 

be increased to 0.20 ppm; this is a reconsideration of the previous conclusion, since detectable 

residues of parent were found in one field trial on mustard greens. 

Table 2.2.2. Tolerance Summary for Flutolanil.

Commodity Established 

Tolerance (ppm)

HED

Recommended 

Tolerance (ppm)

Comments

(correct commodity 

definition)

Peanut 0.5 0.5

Peanut, hay 15.0 20.0

Peanut, meal 1.0 1.0

Rice, bran 10.0 10.0

Rice, grain 7.0 7.0

Rice, hulls 25.0 Remove

Rice, straw 10.0 Remove

Turnip, greens 0.1 0.20

Vegetable, brassica, leafy, group 5 0.1 0.20

2.2.3 International Harmonization

An International Residue Limits (IRL) table is attached (Appendix E).

The US tolerance expression for plant and livestock commodities is flutolanil and its metabolites 

converted to 2-(trifluoromethyl) benzoic acid and calculated as flutolanil. The Codex tolerance 

expression is flutolanil for plants. For animal commodities, the Codex tolerance expression is 

flutolanil and its transformation products containing the 2-(trifluoromethyl) benzoic acid moiety. 

Thus, the US tolerance expression harmonizes with the Codex tolerance expression for livestock 

commodities but not for plants. 

There are no Codex, Canadian, or Mexican MRLs for peanuts, turnip greens, or the Brassica

(cole) leafy vegetables. Codex MRLs are established on rice grain, bran, and straw. Codex and 

US tolerance levels are the same for rice bran and rice straw. Codex and US tolerance levels for 

rice grain are different, i.e., 7.0 ppm in the US versus 2 for husked rice grain and 1 for polished 

rice grain in Codex. For livestock commodities, most Codex tolerance levels are the same as the 

US tolerance levels. However, the tolerances for the livestock liver and kidney are higher than 

the Codex MRLs and cannot be harmonized. 

2.3 Label Recommendations

HED’s recommendations are predicated on the recommended label changes. The rotational crop 

restrictions for the Flutolanil 40SC label (EPA Reg. No. 71711-28) should be amended to 

include Brassica (cole) leafy vegetables and turnip greens under the 0-day crop restriction 

interval.
Page 10 of 53

Since no tolerance is established for sugar beet, the 0-day rotational crop restriction for sugar 

beet on the Artisan Fungicide label (EPA Reg. No. 71711-17) should be removed.

3.0 Introduction

Flutolanil, N-[3-(1-methylethoxy)phenyl]-2-(trifluoromethyl)benzamide, is a systemic 

benzanilide fungicide with both preventative and curative actions. Its mode of action is 

inhibition of mitochondrial respiration by inhibition of the enzyme succinate dehydrogenase.

3.1 Chemical Identity

The chemical structure and nomenclature of flutolanil and its metabolites are presented in 

Appendix B, Table B.1.

3.2 Physical/Chemical Characteristics

Flutolanil has moderate water solubility of 6.53 mg/L @ 20-25o C. It has a log octanol/water 

partition coefficient (log Pow) of 3.74. Flutolanil is not very volatile, with a vapor pressure of 

4.87 x 10-8 mm Hg at 25

o C and a Henry’s Law Constant of 2.12 x 10-9

atm-m

3

/mol. 

The physicochemical properties of flutolanil are summarized in Appendix B, Table B.2.

3.3 Pesticide Use Pattern

Flutolanil is currently registered for application to Brassica (cole) leafy vegetables, peanuts, 

potatoes, rice, and turnip greens, and as a seed treatment for soybean and cotton. Tolerances 

have been established for these commodities as well as tolerances for inadvertent residues for 

wheat commodities as rotational crops and tolerances for ruminant commodities. Non-food uses 

of flutolanil include turf, and greenhouse, nursery, and potted ornamentals. 

Bayer CropScience has proposed an increase in the maximum seasonal application rate to turf 

from 9 fl oz to 17.1 fl oz. Additionally, Nichino America, Inc. has proposed the following: 1) 

adding a banded application to the existing broadcast use for peanuts on the SC label; 2) adding 

the Brassica (cole) leafy vegetables crop group and turnip greens to the SC label using residue 

data from the DF formulation; and 3) slightly modifying the lowest established SC use rate on 

rice from 11.8 fl oz to 12 fl oz/A (0.35 to 0.36 lb ai/A).

Brassica (Cole) Leafy Vegetable Crop Group 5 and Turnip Greens: Brassica (cole) leafy 

vegetable crop group 5 and turnip greens are registered by Gowan Company on the Moncut® 70-

DF label (EPA Reg. No. 10163-301) but not on the Nichino America Flutolanil 40SC Fungicide 

label (EPA Reg. No. 71711-28). The registered and proposed uses on Brassica (cole) leafy 

vegetables and turnip greens (as shown in Table 3.3 below) are for one ground application at 

planting or at transplanting as an in-furrow or directed spray at the base of transplants at the rate 

of 0.77 lb ai/A. The proposed pre-harvest interval (PHI) on the SC label is 45 days. No PHI is 

specified on the DF label, but the use is very early season on both labels.
Page 11 of 53

Peanuts: Peanuts are already registered on the Flutolanil 40SC Fungicide label (EPA Reg. No. 

71711-28) for broadcast use at a maximum of 64.0 fl oz per acre (1.9 lb ai/A) per crop cycle with 

a 40-day PHI. The proposed label amendment is to add band application at a maximum rate of 

64.0 fl oz per acre with a 90-day PHI as described in Table 3.3 below. The peanut use will be 

added to the Convoy Fungicide label. (Convoy Fungicide has the same registration number and 

is the same formulation as Flutolanil 40SC Fungicide.)

Rice: Rice is already registered on the Flutolanil 40SC Fungicide label (EPA Reg. No. 71711-

28). The proposal is to revise the application rates slightly (i.e., to revise the rates of 11.8-33.0 fl 

oz/A and 11.8 to 16.5 fl oz/A on the established label to 12.0 to 33.0 fl oz/A and 12.0 to 16.5 fl 

oz/A, respectively, on the proposed label). The rice use will be added to the Convoy Fungicide 

label. Convoy Fungicide has the same registration number and is the same formulation as 

Flutolanil 40SC Fungicide.

Table 3.3. Summary of Directions for Use of Flutolanil.

Applic. 

Timing, Type, 

and Equip.

Formulation

[EPA 

Reg. No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. 

Per 

Season

Max. 

Seasonal 

Applic. 

Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations**

Brassica (Cole) Leafy Vegetables (Crop Group 5) and Turnip Greens (Proposed)

(Broccoli; broccoli, Chinese (gai lon); broccoli raab (rapini); Brussels sprouts; cabbage; cabbage, Chinese (bok 

choy); cabbage, Chinese (napa); cabbage, Chinese mustard (gai choy); cauliflower; cavalo 11roccoli; collards; 

kale; kohlrabi; mizuna; mustard greens; mustard spinach; rape greens)

At planting or 

transplanting;

In-furrow or 

directed spray 

at the base of 

transplants;

Ground 

equipment

Flutolanil 

40SC 

[71711-

28]*

Convoy® 

Fungicide

[71711-

28]*

26.0 fl 

oz/A 

(0.77 lb 

ai/A)

1 

(implied)

26.0 fl oz/A 

(0.77 lb 

ai/A)

45 Apply to the row at 

planting, as an in-furrow or 

directed spray at the base of 

transplants.

If transplanted, apply in a 

narrow band directed at 

plant bases immediately 

after transplanting in 30-50 

gals/A.

Use a minimum of 3 gals. 

of spray volume per acre.

If applied as a soil drench at 

planting, observe a 45-day 

PHI.

Brassica (Cole) Leafy Vegetables (Crop Group 5) and Turnip Greens (Registered)

At planting or 

transplanting;

In-furrow or 

directed spray 

at the base of 

transplants;

Ground 

equipment

Moncut®

70-DF

[10163-

301]

1.1 lb/A 

(0.77 lb 

ai/A)

1 

(implied)

1.1 lb/A 

(0.77 lb 

ai/A)

Not 

Stated

Make one application to the 

row at planting, as an infurrow or directed spray at 

the base of transplants. 

Apply in a minimum of 3 

gallons of spray per acre.

Do not use oil as carrier or 

add other additives to the 

finished spray. Use is 

prohibited in some areas of 

Arkansas and NY state. 

Peanuts (Proposed)
Page 12 of 53

Table 3.3. Summary of Directions for Use of Flutolanil.

Applic. 

Timing, Type, 

and Equip.

Formulation

[EPA 

Reg. No.]

Applic. 

Rate 

(lb ai/A)

Max. No. 

Applic. 

Per 

Season

Max. 

Seasonal 

Applic. 

Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations**

Postemergence; 

Band 

application; 

Ground 

equipment

Flutolanil 

40SC 

[71711-

28]*

Convoy® 

Fungicide

[71711-

28]*

48.0-64.0 

fl oz/A 

(1.4-1.9 lb 

ai/A)

broadcast 

equivalent

not stated 64.0 fl oz/A

(1.9 lb ai/A)

90 For ground application, 

apply in a minimum of 20 

gals broadcast equivalent of 

water per acre. 

Apply in a band over the 

row within 40-60 days after 

planting but only after the 

entire crop has emerged.

Peanuts (Registered)

Postemergence; 

Broadcast 

application; 

Ground or 

aerial 

equipment

Flutolanil 

40SC 

[71711-

28]

20.0-32.0 

fl oz/A 

(0.59–

0.95 lb 

ai/A) or

10.0-16.0 

fl oz/A

(0.30-0.48 

lb ai/A)

64.0 fl oz/A

(1.9 lb ai/A)

40 Apply in a minimum of 10 

gal water per acre by 

ground or 5 gals water per 

acre by air.

Begin applications 

approximately 45-60 days 

after planting.

Make sequential 

applications at 21-30 day 

intervals at the higher rate 

or at 10-14 day intervals at 

the lower rate.

Rice (Proposed)

Postemergence; 

Broadcast; 

Ground or 

aerial 

equipment

Flutolanil 

40SC 

[71711-

28]*

Convoy® 

Fungicide

[71711-

28]*

12.0-33.0 

fl oz/A

(0.36-0.98 

lb ai/A)

1 33.0 fl oz/A

(0.98 lb 

ai/A)

30 Apply in a minimum of 10 

gal of water/A by ground or 

5 gal/A by air.

Apply 7-14 days after 

panicle differentiation.

If applied at the lower rate, 

follow with a second 

application 10-14 days after 

the first.

Do not apply within 30 days 

prior to harvest, or beyond 

75% heading development 

stage, whichever occurs 

first.

Flooded fields may be used 

by aquaculture of crayfish 

only following rice harvest.

12.0-16.5 

fl oz/A

(0.36-0.49 

lb ai/A)

2

Rice (Registered)

Postemergence; 

Broadcast; 

Ground or 

aerial 

equipment

Flutolanil 

40SC 

[71711-

28]*

11.8-33.0 

fl oz/A

(0.35-0.98 

lb ai/A)

1 33.0 fl oz/A

0.98 lb ai/A)

30 Apply in a minimum of 10 

gal of water/A by ground or 

5 gal/A by air.

Apply 7-14 days after 

panicle differentiation.

If applied at the lower rate, 
Page 13 of 53

11.8-16.5 

fl oz/A

(0.35-0.49 

lb ai/A)

2 follow with a second 

application 10-14 days after 

the first.

Do not apply within 30 days 

prior to harvest, or beyond 

75% heading development 

stage, whichever occurs 

first.

Flooded fields may be used 

by aquaculture of crayfish 

only following rice harvest.

*Formulations: Flutolanil 40SC Fungicide, also called Convoy® Fungicide, is a suspension concentrate which contains 3.8 lb 

ai/gal. Moncut® 70-DF is a dry flowable containing 70.0% ai.

** Rotational Crops: Rotational crop restrictions on the established 40SC label are not being changed. Plantback restrictions on 

the established SC label are 0 days for cotton, peanuts, potatoes, rice, and soybeans; 30 days for wheat; 150 days for leafy 

vegetables and small grain crops other than wheat; 240 days for corn and sorghum; and 365 days for all other crops. Rotational 

crop restrictions on the established 70-DF label are 0 days for cotton, peanuts, potatoes, rice, soybeans, and turnip greens, and 

Brassica (cole) leafy vegetables; 30 days for wheat; 150 days for leafy vegetables and small grain crops other than wheat; 240 

days for corn and sorghum; and 365 days for all other crops. The 70-DF is not for use on peanuts and rice in CA.

3.4 Anticipated Exposure Pathways

Humans may be exposed to flutolanil in food and drinking water, since flutolanil may be applied 

directly to growing crops and application may result in flutolanil reaching surface and ground 

water drinking water sources. In occupational settings, mixers, loaders, and applicators may be 

exposed while handling flutolanil. There is also a potential for post-application exposure for 

workers re-entering treated fields. Additionally, there is an existing residential uses on turf, so 

adults and children may be have post-application exposure to flutolanil.

Risk assessments have been completed for proposed and existing uses of flutolanil. This risk 

assessment considers all of the aforementioned exposure pathways based on the existing 

flutolanil uses and the proposed changes to the flutolanil use pattern, but also considers existing 

uses of flutolanil, particularly in the dietary exposure assessment. 

3.5 Consideration of Environmental Justice

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.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. 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 U.S. Department of 

Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. 

Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and 

exposure assessments are performed when conditions or circumstances warrant. Whenever 
Page 14 of 53

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, 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.

4.0 Hazard Characterization and Dose-Response Assessment

The hazard characterization for flutolanil is discussed in detail in the original risk assessment 

(D268880, A. Lowit, 9/11/00). The conclusions from that assessment remain unchanged, with 

the exception that the chronic reference dose (RfD) which was revisited in a 2007 risk 

assessment (D334156, F. Fort 11/27/07).

4.1 Toxicology Studies Available for Analysis

The existing flutolanil database is adequate for hazard characterization and endpoint selection. 

Toxicology studies available for risk assessment are summarized in Appendix A.2 and include 

(1) subchronic oral toxicity studies in rats and dogs; (2) 21/28 day dermal toxicity study in rats; 

(3) developmental toxicity studies in rats and rabbits; (4) 2-generation reproduction study in rats; 

(5) chronic toxicity study in dogs; (6) carcinogenicity study in mice and combined 

chronic/carcinogenicity study in rats; (7) a battery of the required genotoxicity studies; (8) a 

metabolism studies in rats; (9) acute and subchronic neurotoxicity battery studies, and (10) 

immunotoxicity study in mice. The routes of administration for the toxicity studies are 

consistent with the potential exposure scenarios.

4.2 Absorption, Distribution, Metabolism and Excretion (ADME)

While absorption was not directly measured, urinary excretion data suggests that up to 45% of an 

oral dose of flutolanil may be absorbed. Absorption seems to increase with repeated dosing 

based on the radioactivity fraction eliminated in urine vs. feces; however, the increased urinary 

excretion may also be due to enzyme induction since an increased amount of water-soluble 

conjugates was detected in urine from rats dosed repeatedly. There was no appreciable 

concentration remaining in any tissue 7 days post dose, regardless of the dose level. According 

to the observed metabolites, flutolanil may be conjugated directly or hydroxylated at the 

isopropoxybenzene ring before conjugation. At the single low oral dose (20 mg/kg), excretion in 

urine and feces was equivalent (40% via each) route. Repeated low oral dosing resulted in 

increased urine (about 70%) with a corresponding decreased fecal excretion. At the single high 

dose (1000 mg/kg), most of the excretion was via the feces. The parent chemical accounted for 

the majority of the radioactivity eliminated in urine and feces. The major metabolite is N-(3'-

hydroxyphenyl)-2-(trifluoromethyl)benzamide, also known as de-isopropylflutolanil (3.5-36% in 

urine and 0.6-4.4% in feces). Males and females showed similar overall ADME profiles, except 

a higher percentage of the major metabolite was detected in urine of females with repeated 

dosing. Bioaccumulation was not demonstrated.
Page 15 of 53

4.2.1 Dermal Absorption

No dermal penetration study is available. However, no dermal or systemic toxicity was observed 

in rats in the 21/28 day dermal toxicity up to the limit dose (1000 mg/kg/day).

4.3 Summary of Toxicological Effects

Flutolanil is a systemic benzanilide fungicide with both preventative and curative actions against

a variety of plant diseases caused by fungi of the phylum Basidomycota, including Rhizoctnia 

solani and Sclerotium rolfsii (AKA Athelia rolfsii). Flutolanil strongly inhibits the succinate 

dehydrogenase complex (Complex II) in mitochondria of Basidomycota fungi but has minimal 

effect on mitochondria of other fungi and mammalian liver (Motoba et. al. 1988). The mode of 

action (MOE) of flutolanil in mammals has not been elucidated.

The toxicology studies conducted on flutolanil demonstrate few biologically significant effects, 

mainly in the liver and gastrointestinal (GI) system. Liver effects were observed in several

studies, but most of the changes were considered adaptive. Rat subchronic and chronic studies 

showed increases in liver weight but no supporting clinical chemistry and/or histopathology 

findings. The dog was the most sensitive species for liver effects, showing elevated alkaline 

phosphatase and cholesterol levels together with dose-related increases in absolute and relative 

liver weights and an increase in severity of glycogen deposition in the subchronic study. The 

chronic dog study saw an increase in emesis, salivation and soft stool as well as decreased body 

weight gains and food consumption that suggest GI irritation, but no relevant liver effects were 

reported.

Evaluation of the available data for flutolanil did not reveal any evidence to indicate that it is 

neurotoxic or that it targets the immune system. Guideline acute and subchronic neurotoxicity 

studies did not show any neurological effects at the limit dose (2000 mg/kg and 1024 mg/kg/day, 

respectively). A guideline immunotoxicity study showed no effect at the limit dose (1004.2 

mg/kg/day).

Flutolanil is not a developmental or reproductive toxicant. No maternal, reproductive, or 

developmental toxicity was observed at the limit dose (1000 mg/kg/day). There was no evidence 

for increased susceptibility of rat or rabbit fetuses to in utero exposure or rat pups to post-natal 

exposure to flutolanil. 

No adverse effects were observed in studies in which flutolanil was administered by the dermal 

route of exposure. The acute dermal LD50 is >2000 mg/kg (acute Toxicity Category III) and 

acute inhalation LD50 is between 0.51 and 2.04 mg/L (Toxicity Category III). The subchronic 

inhalation study has been waived based on a weight of evidence approach (TXR 0056560); i.e. 

low vapor pressure (4.87 x 10-8 mm Hg at 25oC), low acute inhalation toxicity (Toxicity category 

IV), and low subchronic toxicity with rat, rabbit and dog studies all showing no toxicity evident 

up to the limit dose, and low chronic toxicity, in which the principal adverse effects up to the 

limit dose are liver and body weight changes. Further, there is no developmental or reproductive 

concern at dose levels that do not exceed the limit dose. For these reasons, it is concluded that 

appropriate PODs are not available for any dermal or inhalation exposure length.
Page 16 of 53

Based on the lack of evidence of carcinogenicity and the lack of evidence of mutagenicity, 

flutolanil is classified as “not likely to be carcinogenic to humans”.

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

On October 25, 1999 the FQPA Safety Factor Committee recommended an FQPA safety factor 

of 1X (TXR 0013828). The risk assessment team reevaluated the flutolanil database and 

reaffirmed that the FQPA Safety Factor be reduced to 1X based on the reasons outlined below.

4.4.1 Completeness of the Toxicology Database

The flutolanil database is complete. Based on a weight of evidence approach, a subchronic 

inhalation study was waived (TXR 0056560). Guideline acute and subchronic neurotoxicity 

studies and the immunotoxicity study submitted by the registrant since the last risk assessment 

showed no relevant effects up to the limit dose (discussed in Section 4.3).

4.4.2 Evidence of Neurotoxicity

The flutolanil toxicology database revealed no evidence of neurological effects. Included in the 

evaluation were recently submitted acute and subchronic neurotoxicity studies tested up to the 

limit dose (2000 mg/kg acute, 1000 mg/kg subchronic), as well as all other repeated dose studies 

in the database, some conducted at limit doses (between 500 mg/kg/day and 1000 mg/kg/day).

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

The flutolanil toxicology database revealed no evidence of increased susceptibility in the 

developing or young animal. There was no increased sensitivity to fetuses as compared to 

maternal animals in the developmental rat and rabbit studies and no increased sensitivity to pups 

as compared to adults in a multi-generation reproduction study in rats.

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the flutolanil exposure database. An unrefined,

conservative chronic dietary exposure assessment for food and drinking water was conducted, 

assuming tolerance-level residues for all existing and proposed commodities and that 100% of 

registered and proposed crops treated. The drinking water assessment utilized water 

concentration values generated by models and associated modeling parameters which are 

designed to produce conservative, health protective, high-end estimates of water concentrations 

which are not likely to be exceeded. The dietary (food and drinking water) exposure assessment 

does not underestimate the potential exposure for infants, children, or women of child bearing 

age. Additionally, although residential dermal and incidental oral, post-application exposure 

may occur a quantitative assessment was not needed, since there was no hazard.
Page 17 of 53

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Detailed description of the toxicity studies used for selecting toxicity endpoints and PODs for the 

various exposure scenarios are presented in appendix Table A.2.2 and the Toxicology 

Disciplinary Chapter for Registration Support Document (M. Bonner 2000; D262989). A 2007 

reassessment of toxicological endpoints can be found in the Human Health RAD for Inadvertent 

or Indirect Tolerances for Use on Soybean, Wheat, Corn and Cotton (F. Fort 2007; D334156). 

The 2007 reassessment concurs with earlier endpoint selection except for the NOAEL used as 

chronic oral POD. Immunotoxicology, acute neurotoxicity screening battery, and subchronic 

neurotoxicity screening battery studies have been received since the last risk assessment. The 

new studies did not alter the endpoints or PODs listed in the last risk assessment. A review of 

the current toxicology literature revealed no additional information relevant to this risk 

assessment.

Given the lack of observable effects in most toxicology studies for flutolanil, an appropriate 

endpoint could be identified only for chronic dietary exposure scenarios (all populations). 

HED’s Hazard Identification Assessment Review Committee (HIARC 10/14/1999) selected the 

combined chronic/oncogenicity rat study NOAEL (87 mg/kg/day based on decreased body 

weight and increased liver weight) as the chronic dietary POD for flutolanil. However, a 2007 

reassessment of toxicological endpoints (F. Fort 11/27/2007; D334156, page 8) identified the 

chronic dog study NOAEL (50 mg/kg/day base on increased incidence of GI effects, decreased 

body weight and decreased food consumption) as a more appropriate chronic dietary POD. This 

is based on the conclusion that liver weight changes like those observed in the 

chronic/oncogenicity rat study are considered an adaptive response in the absence of supporting 

clinical chemistry or histopathological findings. Taking into consideration 3 new studies 

submitted since the last reassessment of toxicological endpoints (acute and subchronic 

neurotoxicity and immunotoxicity), which showed no effects up to the limit dose, the current 

flutolanil risk assessment team reaffirms the chronic dog study NOAEL (50 mg/kg/day) as the 

chronic dietary POD for all populations.

Based on the available toxicological data, no observed toxic effects could be attributed to a 

single, short- or intermediate-term oral exposure. Likewise, no observed toxic effects could be 

attributed to dermal exposures of any duration.

4.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment

Under FQPA, when there are potential residential exposures to the pesticide, aggregate risk 

assessment must consider exposures from three major sources: oral, dermal and inhalation 

exposures. These combined residential exposures must then be aggregated with dietary exposure 

(food and drinking water) to determine aggregate risk. In the case of flutolanil, no risk is 

expected from inhalation or dermal short- and intermediate term exposure scenarios since no 

hazard was identified from appropriate toxicology studies. Furthermore, the current use pattern 

does not indicate long-term dermal or inhalation exposure potential. Therefore, combining 
Page 18 of 53

routes of exposure is not necessary. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

Flutolanil is “not likely” to be a human carcinogen based on the lack of treatment-related tumors 

in the combined chronic/oncogenicity rat study (MRID 40342921) or in the carcinogenicity 

mouse study (MRID 41850803), and the lack of genotoxicity in an acceptable battery of 

mutagenicity studies.

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

The toxicological doses and endpoints selected for various exposure scenarios are summarized in 

Table 4.5.4.1.

Table 4.5.4.1 Summary of Toxicological Doses and Endpoints for Flutolanil for Use in Dietary, NonOccupational and Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/

FQPA Safety 

Factors

RfD, PAD, 

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including Infants 

and Children and 

Females 13-49 

years of age)

No hazard was identified from appropriate oral toxicity studies.

Chronic Dietary 

(All Populations)

NOAEL= 50 

mg/kg/day

UFA= 10X

UFH= 10X

FQPA SF= 1X

Chronic RfD = 

0.5

mg/kg/day

cPAD = 0.5 

mg/kg/day

2-year Chronic study in dogs. 

MRID 40342922

LOAEL = 250 mg/kg/day based on 

increased incidence of GI toxicity

(emesis, salivation, soft stool, decrease 

food consumption and decreased body 

weight)

Incidental Oral 

Short- (1-30 days) 

and IntermediateTerm (1-6 months)

No hazard was identified from appropriate oral toxicity studies.

Dermal and 

Inhalation Shortand IntermediateTerm

No hazard was identified from appropriate oral, dermal or inhalation toxicity studies 

including developmental toxicity studies in rats and rabbits.

Long-term 

inhalation The current use pattern does not indicate long-term inhalation exposure potential.

Cancer (oral, 

dermal, inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of 

significant tumor increases in two adequate rodent carcinogenicity studies. 

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 
Page 19 of 53

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level 

of concern. N/A = not applicable.

4.6 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its reregistration decision for flutolanil, EPA reviewed these data 

and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), flutolanil is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 20131and includes some pesticides 

scheduled for registration review and chemicals found in water. Neither of these lists should be 

construed as a list of known or likely endocrine disruptors.

Flutolanil is on List 1 for which EPA has received all the required Tier 1 assay data. The Agency 

is currently reviewing all of the assay data received for the appropriate List 1 chemicals and 

planning to make the conclusions of those reviews available in early 2015. For further 

information on the status of the EDSP, the policies and procedures, the lists of chemicals, future 

lists, the test guidelines and the Tier 1 screening battery, please visit our website.2

1

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

2

http://www.epa.gov/endo/
Page 20 of 53

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The residues of concern for the risk assessment and the tolerance expression are summarized in 

Table 5.1. 

Plants: The nature of the residue in plants is adequately understood based on acceptable 

metabolism studies on rice, cucumber leaves, and peanuts. When flutolanil is metabolized, the 

amide linkage between the two aromatic rings remains intact; metabolism occurs at the more 

highly activated aminophenyl ring. Flutolanil is metabolized via O-deisopropylation, 

hydroxylation, and methylation to yield N-(3'-hydroxyphenyl)-2-(trifluoromethyl)benzamide (M4), and N-(4'-hydroxy-3'-methoxy)phenyl-2-(trifluoromethyl)benzamide (M-7). Most of the 

metabolites are found bound or conjugated. The major identified components in plants were 

parent and metabolite M-4. The parent compound and metabolites containing the common 

moiety, 2-(trifluoromethyl)benzanilide, are the residues of concern which need to be included in 

the tolerance expression and dietary risk assessment. The enforcement method converts parent 

and metabolites containing the common moiety 2-(trifluoromethyl)benzanilide to 2-

(trifluoromethyl)benzoic acid.

Livestock: The nature of the residue in livestock is adequately understood based on acceptable 

metabolism studies in goats and poultry. As with plants, the amide linkage between the two

aromatic rings remains intact; metabolism occurs at the more highly activated aminophenyl ring. 

The specific metabolites identified as residues of concern are M-2 (N-[4'-hydroxy-3'-(1-

methylethoxy)phenyl]-2-(trifluoromethyl)benzamide), M-4, and M-7 in livestock tissues, and the 

glucuronide/sulfate conjugates of M-4 in milk. 

The parent compound and metabolites containing the common moiety, 2-

(trifluoromethyl)benzanilide, are the residues of concern which need to be included in the 

tolerance expression and dietary risk assessment. The enforcement method converts parent and 

metabolites containing the common moiety 2-(trifluoromethyl)benzanilide to 2-

(trifluoromethyl)benzoic acid.

Rotational Crops: The nature of the residue in rotational crop commodities is adequately 

understood based on an acceptable confined rotational crop study with lettuce, radish, and 

oat/sorghum conducted with [U14C-aminophenoxy]flutolanil. The major residue components 

were flutolanil and metabolites M-4 and M-5 (N-[3',4'-(dihydroxy)phenyl]-2-

(trifluoromethyl)benzamide). The residues of concern for the tolerance expression and dietary 

risk assessment for rotational crops are flutolanil and metabolites containing the common 

moiety, 2-(trifluoromethyl)benzanilide, which is converted by the enforcement method to 2-

(trifluoromethyl)benzoic acid.

Water: Parent is the major residue in water; no major (>10%) degradation products were 

identified in environmental fate studies. Only the parent needs to be included in the drinking 
Page 21 of 53

water exposure assessment for flutolanil (Metabolism Assessment Review Committee (MARC) 

determined on 12/16/1999; M. Xue, 1/6/00, no DP#). 

A summary of the metabolites and degradates of flutolanil for human health risk assessment is 

summarized in Table 5.1. 

Table 5.1. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance 

Expression.

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants

Primary Crop flutolanil and metabolites 

converted to 

2-(trifluoromethyl)benzoic 

acid

flutolanil and metabolites 

converted to 

2-(trifluoromethyl)benzoic 

acid Rotational Crop

Livestock

Ruminant flutolanil and metabolites 

converted to 

2-(trifluoromethyl)benzoic 

acid

flutolanil and metabolites 

converted to 

2-(trifluoromethyl)benzoic 

acid

Poultry

Drinking Water flutolanil (parent) Not Applicable

5.2 Food Residue Profile

Crop field trials: Flutolanil is a systemic fungicide. It forms a protective barrier on the plant, 

enters the plant, and moves upward in the xylem. Flutolanil is currently registered under 40 CFR 

§180.484(a) on cotton, peanuts, potatoes, rice, soybeans, turnip greens, the Brassica leafy 

vegetable group 5, and livestock commodities, including milk, eggs, and the meat, fat and meat 

byproducts of cattle, goats, hogs, horses, poultry, and sheep. Plant commodity tolerance levels 

range from 0.1 ppm in turnip greens and the Brassica leafy vegetable group 5 to 25 ppm in rice 

hulls. Livestock tolerance levels range from 0.05 ppm to 2.00 ppm. Flutolanil is also registered 

under 40 CFR §180.484(d) for indirect or inadvertent residues on wheat commodities at levels 

ranging from 0.05 ppm to 2.5 ppm. No Section 18 emergency exemptions or tolerances with 

regional registrations are established. Adequate field trials are available to support the 

established/recommended tolerances. Because of amendments (D413582, N. Dodd, 12/12/13), 

the Agency reconsidered a prior conclusion and now recommends increasing the 0.1 ppm 

established tolerances on turnip greens and the Brassica leafy vegetables crop group 5 to 0.20 

ppm, since detectable residues were found in one mustard green sample. The Agency also 

recommends increasing the 15.0 ppm established tolerance on peanut hay to 20.0 ppm, based on 

the Organization for Economic Cooperation and Development’s (OECD’s) tolerance calculation 

procedures, including residues from both band and broadcast applications. Also, the tolerances 

established on rice straw and hulls [40 CFR §180. 484(a)] are no longer required (Table 1 

Feedstuffs, June 2008) and should be removed.

Processing Studies: Of the registered crops, processed commodities are associated with cotton, 

peanut, potato, rice, soybean, and wheat. Adequate processing data are available as discussed in 

Appendix D.
Page 22 of 53

Storage Stability: Adequate storage stability data are available to support the field trials of the 

primary (treated) crops for existing uses and the rotational crop wheat as discussed and shown in 

Appendix D.

Meat, Milk, Poultry, and Eggs: Acceptable feeding studies with dairy cattle and poultry were 

previously reviewed. Tolerances are established for residues of flutolanil and its metabolites 

converted to 2-TFBA in ruminant (cattle, goat, horse, and sheep) commodities at 0.05 ppm for 

milk, 0.10 ppm for fat, 1.00 ppm for kidney, 2.00 ppm for liver, and 0.05 ppm for meat and meat 

byproducts, and in poultry commodities at 0.05 ppm for egg, fat, meat, and meat byproducts. 

Feeding studies are available on lactating cows and laying hens. Based on the feeding studies 

and the maximum reasonably balanced diets for livestock, the established livestock tolerances 

are adequate.

Rotational Crops: Rotational crop restrictions and inadvertent residue tolerances have been 

established on the Flutolanil 40SC label (EPA Reg. No. 71711-28) based on the available 

confined and field accumulation studies.

Since Brassica (cole) leafy vegetables and turnip greens are being registered on the 40SC label, 

the rotational crop restrictions for the Flutolanil 40SC label (EPA Reg. No. 71711-28) should be 

amended to include Brassica (cole) leafy vegetables and turnip greens under the 0-day rotational 

crop restriction interval.

Since no tolerance is established for sugar beet, the 0-day rotational crop restriction for sugar 

beet on the Artisan Fungicide label (EPA Reg. No. 71711-17) should be removed.

5.3 Water Residue Profile

There are no established Maximum Contaminant Levels for residues of flutolanil in drinking 

water. No health advisory levels for flutolanil in drinking water have been established. 

The drinking water residues used in the dietary assessment were provided by the Environmental 

Fate and Effects Division (EFED) and were incorporated directly into this dietary assessment. 

Water residues were incorporated in the DEEM Food Commodity Intake Database (FCID) into 

the food categories “water, direct, all sources” and “water, indirect, all sources.” 

The Tier I/II Estimated Drinking Water Concentrations (EDWCs) were calculated using the Tier 

I Rice Model v.1.0 (surface waters), the Tier II PRZM/EXAMS models (surface waters), the Tier 

I/II model PRZM-GW (in the Tier I mode), and the Tier I ground water model SCI-GROW for 

use in the human health risk assessment.

Results obtained from the models that yielded the highest EDWCs for flutolanil are summarized 

in Table 5.3. The maximum screening EDWC for chronic exposure is 2530 ppb, found in 

groundwater associated with the use on turf. Residues in surface water are lower. The 

maximum chronic EDWC in surface water is ≤531 ppb, which is associated with the use on rice.
Page 23 of 53

Table 5.3. Maximum EDWCs based on Ground Application of Flutolanil on Turf and Ground/Aerial 

Application on Rice.

Drinking 

Water Source Model Scenario/Use1 Acute (ppb) Chronic (ppb) Cancer/Chronic (ppb)

Surface water Tier 1 Rice 

Model Rice 531 <531

Ground water PRZM-GW WI Sand Turf 2730 2530

1 For rice, the application rate is 0.980 lb a.i./A/season; for turf, the application rate is 17.1 lb a.i./A/year.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

Tolerance level residues were used in the assessment. No acute dietary assessment was 

conducted. The EDWCs are residues in groundwater using the WI sand turf scenario. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

Percent crop treated refinements were not used for this assessment.

5.4.3 Acute Dietary Risk Assessment

No appropriate endpoint attributable to a single dose was identified. As no acute dietary 

endpoint was identified, an acute exposure analysis was not performed.

5.4.4 Chronic Dietary Risk Assessments

Tolerance-level residues combined with 100% crop treated and default processing factors were 

used to determine the chronic dietary exposure and risk estimates. As shown in Table 5.4.6, the 

chronic dietary exposure estimates for food and drinking water are below HED’s level of 

concern for the general U.S. population (11% of the chronic population adjusted dose (cPAD)). 

The most highly exposed population subgroup was all infants (<1 year old) at 29% of the cPAD. 

EDWCs were incorporated directly into the dietary assessment.

5.4.5 Cancer Dietary Risk Assessments

Flutolanil is classified as “not likely to be carcinogenic to humans,” so a quantitative cancer 

dietary assessment was not conducted.
Page 24 of 53

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary Food and Drinking Water Exposure and Risk for Flutolanil

Population Subgroup

Chronic Dietary

Dietary Exposure

(mg/kg/day) % cPAD*

General U.S. Population 0.055661 11

All Infants (< 1 year old)* 0.144721 29

Children 1-2 years old 0.084103 17

Children 3-5 years old 0.070104 14

Children 6-12 years old 0.049893 10

Youth 13-19 years old 0.040594 8.1

Adults 20-49 years old 0.055422 11

Adults 50-99 years old 0.053959 11

Females 13-49 years old 0.054666 11

* The values for the highest exposed population are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are existing non-occupational/residential uses associated with flutolanil. Registered 

products include several for use on turf grass and potted ornamentals which, if not specifically 

prohibited through label directions, could be used in a residential/public site. Additionally, spray 

drift, i.e. off-target movement of pesticides can occur via many types of pathways and it is 

governed by a variety of factors. Sprays that are released and do not deposit in the application 

area end up off-target and can lead to exposures to those it may directly contact. They can also 

deposit on surfaces where contact with residues can eventually lead to exposures (e.g. children 

playing on lawns where residues have deposited next to treated fields). Although potential 

residential handler and post-application exposures exist, and spray drift exposures could 

potentially exist, assessments were not conducted because no dermal, oral (incidental), or 

inhalation toxicological endpoints attributable to short- or intermediate-term exposures have 

been identified, and the current use patterns do not indicate long-term exposure (6 or more 

months of continuous exposure) potential. Also, because a turf use exists, a separate assessment 

from spray drift exposures is not needed.

7.0 Aggregate Exposure/Risk Characterization

In accordance with FQPA, HED must consider and aggregate (add) pesticide exposures and risks 

from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 
Page 25 of 53

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. 

For flutolanil, only potential chronic exposures from food and drinking water were aggregated. 

There were no observed effects attributable to a single dose and an acute dietary endpoint was 

not established. Short- and intermediate-term aggregate risk assessments were not performed 

because toxicological endpoints from dermal, inhalation, and incidental oral exposures were not 

identified. Additionally, the Agency does not expect residential exposure durations that would 

result in long-term exposures. A cancer aggregate risk assessment was also not performed 

because flutolanil is not carcinogenic. Because drinking water estimates have been combined 

with dietary exposures, the dietary assessment described earlier (see Section 5.4) serves as the 

aggregate exposure and risk assessment for flutolanil. Because aggregated food and drinking 

water exposures from this conservative assessment for the most highly exposed population 

subgroup (all infants <1 year old) only amount to 29% of the cPAD, exposure to flutolanil from 

all registered/proposed uses do not exceed HED’s level of concern.

8.0 Cumulative Exposure/Risk Characterization

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 flutolanil and any other substances and flutolanil 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 flutolanil 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/.

9.0 Occupational Exposure/Risk Characterization

Workers may be exposed to flutolanil during mixing, loading, applying, and post-application 

activities. Based on the proposed application rates and use scenarios, short- and intermediateterm occupational exposures may occur. However, since short-and intermediate-term toxicity 

endpoints have not been established, an occupational exposure assessment is not required. 

Chronic occupational exposure is not expected; thus, chronic occupational exposure risk 

assessments are also not required.

Restricted Entry Interval: For all activities and crops, the REI of 12 hours on existing labels is 

adequate to protect workers. In addition to systemic hazard, the WPS for Agricultural Pesticides 

sets a REI based on the acute toxicity of chemicals. Technical flutolanil is classified as toxicity 

category III for acute dermal toxicity and toxicity category IV for primary eye irritation and skin 

irritation. Under the WPS, active ingredients classified as acute toxicity categories III or IV for 

these routes are assigned a 12-hour REI. Therefore, the REI of 12-hours is adequate to protect 

agricultural workers from post-application exposures to flutolanil.
Page 26 of 53

10.0 References

Tier I/II Estimated Drinking Waters Concentrations of Flutolanil for the New Uses on Peanuts 

(Banded Applications), Brassica Leafy Vegetables (Crop Group 5) Plus Turnip Greens, Turf and 

Ornamentals for the Product Convoy® Fungicide, and for Increased Annual Rate on Turf for the 

Product ProStar® 70WP Fungicide. DP414000, J. Meléndez, 12/12/13.

Flutolanil Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk 

Assessment for the Section 3 Registration Actions on Brassica Leafy Vegetables (Crop Group 

5), Turnip Greens, Peanuts, and Rice, and for Registration Review. DP416620, N. Dodd, 

12/12/13.

Flutolanil. Petition for Amendments to Section 3 Uses of Flutolanil on Brassica (Cole) Leafy 

Vegetables (Crop Group 5), Turnip Greens, Peanuts, and Rice. Summary of Analytical 

Chemistry and Residue Data. DP413582, N. Dodd, 12/12/13.
Page 27 of 53

Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food use for flutolanil are in Table A.1. Use of the new 

guideline numbers does not imply that the new (1998) guideline protocols were used.

Table A.1. Toxicology Data Requirements.

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Primary Eye Irritation....................................................

870.2500 Primary Dermal Irritation ..............................................

870.2600 Dermal Sensitization......................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent) .........................................

870.3200 21-Day Dermal ..............................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

no

no

no

yes

yes

yes

-

waived 1

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (nonrodent).............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent) ..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse)....................................................

870.4300 Chronic/Oncogenicity....................................................

yes

yes

yes

yes

no

2

yes

2

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial.....................

870.5300 Mutagenicity—Gene Mutation - mammalian................

870.5xxx Mutagenicity—Structural Chromosomal Aberrations...

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotoxicity (hen)...............................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotoxicity Screening Battery (rat) .................

870.6200b 90-Day Neurotoxicity Screening Battery (rat)...............

870.6300 Develop. Neurotoxicity .................................................

no

no

yes

yes

no

-

-

yes

yes

-

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration ........................................................

870.7800 Immunotoxicity .............................................................

yes

no

yes

yes

-

yes

Special Studies for Ocular Effects no -

1 = Based on a weight of evidence approach a subchronic inhalation toxicity study is not required for the current 

uses (TXR 0056560).

2 = A chronic/oncogenicity study is available for the rat, thus separate chronic and oncogenicity studies are not 

necessary.
Page 28 of 53

A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile – Flutolanil Technical1

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral mouse 40342905 LD50 > 10,000 mg/kg IV

870.1200 Acute dermal rat 40342906 LD50 > 5,000 mg/kg III

870.1300 Acute inhalation rat 40342910 LC50 males between 0.51 

mg/L and 2.04 mg/L

LC50 females ≥ 2.04 mg/L

III

870.2400 Acute eye irritation rabbit 40342912 Minimal irritation IV

870.2500 Acute dermal irritation rabbit 40342915 Not a dermal irritant IV

870.2600 Skin sensitization guinea pig 40342917 Not a dermal sensitizer N/A

1 All studies were conducted on technical grade flutolanil, 98% purity.

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Flutolanil Technical.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 90-Day oral toxicity 

(rat)

40342919 (1986) 

Acceptable-Guideline 

0, 500, 4000, 20000 

ppm (M: 0, 37, 299, 

1512 mg/kg/d; F: 0, 

44, 339, 1743 

mg/kg/d) 

NOAEL = 1512 mg/kg/day (HDT) 

LOAEL not established based on changes in 

absolute and relative liver weights considered

adaptive due to absence of supportive clinical 

chemistry and histopathology findings.

870.3150 90-Day oral toxicity 

(dog)

40342920 (1986)

Acceptable-Guideline 

0, 80, 400, 2000 

mg/kg/d 

NOAEL = 80 mg/kg/day,

LOAEL = 400 mg/kg/day based on increases in

liver weight and severity of hepatic glycogen 

deposition in both males and females; elevated 

alkaline phosphatase and cholesterol levels 

observed at the next highest dose. 

870.3200 21/28-Day dermal 

toxicity (rat)

41841205 (1991)

Acceptable-Guideline

0, 1000 mg/kg/d

Systemic NOAEL = 1000 mg/kg/day

LOAEL not established based on changes in 

adrenal gland weight (males only) and pulmonary 

findings considered incidental because they were 

not observed in any other studies.

Dermal irritation NOAEL= 1000 mg/kg/day 

(limit dose)

LOAEL not established based on the absence of 

treatment-related dermal effects at the application 

site. 
Page 29 of 53

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Flutolanil Technical.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700a Prenatal 

developmental in rat

41850804 (1987)

Acceptable-Guideline

0, 40, 200, 1000 

mg/kg/d

Maternal NOAEL = 1000 mg/kg/day

LOAEL not established based on the absence of 

maternal effects at any dose.

Developmental NOAEL = 1000 mg/kg/day

LOAEL not established based on the absence of 

developmental effects at any dose.

870.3700b Prenatal 

developmental in 

rabbit

40342924 (1987)

Acceptable-Guideline

0, 40, 200, 1000 

mg/kg/d 

Maternal NOAEL = 1000 mg/kg/day

LOAEL not established based on the absence of 

maternal effects at any dose.

Developmental NOAEL = 1000 mg/kg/day

LOAEL not established based on the absence of 

developmental effects at any dose.

870.3800 Reproduction and 

fertility effects –

2 generation (rat)

41850805 (1992)

Acceptable-Guideline 

0, 200, 2000, 20000 

ppm (M: 0, 16, 159,

1625 mg/kg/d; F: 0,

19, 190, 1936 

mg/kg/d)

Parental/Systemic NOAEL = 1625 mg/kg/day

LOAEL not established based on the absence of 

parental effects at any dose.

Reproductive NOAEL = 1625 mg/kg/day

LOAEL not established based on the absence of 

reproductive effects at any dose.

Offspring NOAEL = 1625 mg/kg/day

LOAEL not established based on the absence of 

effects in the offspring at any dose.

870.4100a Chronic toxicity

(rodents)

Combined chronic / carcinogenicity study available (see below)

870.4100b Chronic toxicity (dog) 40342922 (1982)

Acceptable-Guideline

0, 50, 250, 1250 

mg/kg/d

NOAEL = 50 mg/kg/day

LOAEL = 250 mg/kg/day based on increased 

incidence emesis, salivation, soft stool, decreased 

body weight gains and decreased food 

consumption.

870.4300a Chronic / 

Carcinogenicity

(rat)

40342921 (1982)

Acceptable-Guideline

0, 40, 200, 2000, 

10000 ppm (M: 0, 2, 

9, 87, 460 mg/kg/d;

F: 0, 2, 10, 103, 536 

mg/kg/d)

NOAEL = 460 mg/kg/day

LOAEL = not established based on changes in 

liver weights considered adaptive due to absence 

of supportive clinical chemistry and 

histopathology findings.

No evidence of carcinogenicity

870.4200 Carcinogenicity

(mouse)

41850803 (1990)

Acceptable-Guideline

0, 300, 1500, 7000, 

30000 ppm (M: 0, 32,

162, 735, 3333 

mg/kg/d; F: 0, 34, 

168, 839, 3676 

mg/kg/d)

NOAEL = 3333 (M) and 3676 (F) mg/kg/day

LOAEL = not established based on changes in 

liver weights (F only) and fatty vacuolation 

considered adaptive due to absence of supportive 

clinical chemistry.

No evidence of carcinogenicity
Page 30 of 53

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Flutolanil Technical.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.5100 Bacterial Reverse 

Mutation Test 

40342926 (1981)

Acceptable-Guideline

0, 10, 50, 100, 500, 

1000, 5000, 10000, 

25000 ug/plate.

Negative with and without metabolic activation

(S9) in Salmonella strains TA98, TA10, TA1535, 

TA1537, and TA1538 and in E. Coli WP2 uvrA 

strain.

870.5300 In vitro Mouse 

Lymphoma Cells Gene 

Mutations at TK+/-

Locus Test

41841207 (1989)

Acceptable-Guideline

0, 6, 15, 30, 60, 80, 

100 ug/mL

Negative with and without metabolic activation

(S9).

870.5375 In vitro Chinese 

Hamster Lung Cell

Chromosome 

Aberration Test

40342925 (1986)

Acceptable-Guideline

0, 37, 75, 150 

uM/plate

Positive in the presence of S9 metabolic 

activation (S9).

870. 5375 In vitro Human 

Lymphocytes

Chromosome 

Aberration Test 

42606628 (1990) 

Acceptable-Guideline

0, 120, 250, 500, 

1000 ug/mL

Negative with and without metabolic activation 

(S9).

870.5395 Mouse Erythrocyte 

Micronucleus Assay

40342927 (1983)

Acceptable-Guideline

0, 6400, 8000, 10000 

mg/kg either in a 

single dose or 10 

gm/kg/day over 4 

days.

Negative in the bone marrow of M and F

BDF1mice.

870.5550 Unscheduled DNA 

Synthesis Assays in 

Cultured Primary Rat 

Hepatocytes

41841206 (1989)

Acceptable-Guideline

0, 2.67, 27, 53, 80 

ug/mL

Negative in the induction of unscheduled DNA 

synthesis. 

870.6200a Acute neurotoxicity 

screening battery

48796402 (2012)

Acceptable-Guideline

Single dose of 0, 125, 

500, or 2000 mg/kg 

NOAEL = 2000 mg/kg/day

LOAEL = not established based on the lack of 

treatment-related adverse effects up to 14 days 

after dosing and after pathological examination of 

tissues.
Page 31 of 53

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile of Flutolanil Technical.

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.6200b Subchronic 

neurotoxicity 

screening battery

48798501 (2012)

Acceptable-Guideline

Feed Concentration 

adjusted based on 

body weight and 

estimated food 

consumption to 

achieve 0, 62.6, 250, 

and 1000 mg/kg (M: 

0, 62.8, 250.5, and 

977.8 mg/kg/day; F: 

0, 66.2, 255.8, and 

1024.0 mg/kg/day)

NOAEL = 1024.0 mg/kg/day

LOAEL = not established based on the lack of 

treatment-related adverse effects during weeks -1, 

2, 4, 8, and 13 of dosing and after pathological 

examination of tissues.

870.7485 Metabolism and 

pharmacokinetics (rat)

42606602 (1992)

Acceptable-Guideline

Single dose: 20 and 

1000 mg/kg 

Repeated dose: 20 

mg/kg for 14 days

No appreciable tissue levels of flutolanil at study 

termination (168 hours post-dose).

Single dose: at 20 mg/kg 42-45% of dose

excreted in urine, 41% in feces; at 1000 mg/kg 7-

10% of dose excreted in urine, 67-78% in feces.

Repeated dose: at 20 mg/kg 70-71% of dose 

excreted in urine, 29-32% in feces. 

No appreciable tissue levels 7 days post-dose.

Urinary metabolite: N-(3'-hydroxyphenyl)-2-

(trifluoromethyl) benzamide (aka M-4)

Fecal metabolite: Mainly parent chemical with 

limited conversion to M-4.

870.7800 Immunotoxicity (rat) 48647001 (2011)

Acceptable-Guideline

0, 750, 3000 or 

12,000 ppm (M: 0.0, 

61.13, 253.9, 1004.2 

mg/kg/day; F: 0.0, 

74.6, 253.3, 1026.0 

mg/kg/day)

NOAEL = 1004.2 mg/kg/day 

LOAEL not established based on the absence of 

systemic or immune system effects at any dose.

HDT = Highest Dose Tested; F = females; M = males

A.3 Hazard Identification and Endpoint Selection

This section reflects the 2000 Toxicology Chapter (D262989) and a 2007 reassessment of 

toxicological endpoints (F. Fort, 11/27/2007; D334156, page 8).

A.3.1 Acute Reference Dose (aRfD) - Females age 13-49 and General Population

Study Selected: None

Dose and Endpoint for Risk Assessment: No aRfD selected. LOAEL not established based on 
Page 32 of 53

acute oral LD50 > 10,000 mg/kg (Toxicity Category IV) and no treatment-related effects in 

developmental studies up to the limit dose (1000 mg/kg/day) for technical grade flutolanil.

Comments about Study/Endpoint/Uncertainty Factors: Toxic effects observed in oral 

toxicity studies could not be attributed to a single dose. Additionally, based on the assumption 

that developmental toxicity could occur in a single exposure, it is common practice in the 

Agency to use developmental toxicity studies in selecting endpoints for acute dietary risk 

assessment. However no treatment-related maternal or developmental effects were observed. 

A.3.2 Chronic Reference Dose (cRfD)

Study Selected: Chronic Toxicity – Dog

MRID No.: 40342922

Executive Summary: See Appendix A.4, Guideline § 870.4100b

Dose and Endpoint for Risk Assessment: cRfD = 0.5 mg/kg/day; cPAD = 0.5 mg/kg/day. 

NOAEL = 50 mg/kg/day based on increased incidence of clinical sighs (emesis, salivation and 

soft stool), decreased body weight gains and decreased food consumption seen at LOAEL = 250 

mg/kg/day.

Comments about Study/Endpoint/Uncertainty Factors: This study was selected because it 

provided the most sensitive endpoint among all available chronic (i.e. 2-year exposure) feed 

studies. Uncertainty Factors accounts for both interspecies extrapolation (UFA=10X) and 

intraspecies variability (UFH=10X). Since the toxicity database for flutolanil is complete, 

additional UFD is not required. An FQPA Safety Factor of 1X was applied because there is no 

evidence that flutolanil results in increased susceptibility of rat or rabbit fetuses or juvenile rats.

A.3.3 Incidental Oral Exposure (Short- and Intermediate-Term)

Study Selected: None

Dose and Endpoint for Risk Assessment: No appropriate endpoint was identified in the 

database for these durations and route of exposure.

Comments about Study/Endpoint/Uncertainty Factors: Toxic effects observed in oral 

toxicity studies could not be attributed to short or intermediate term exposures. 

A.3.4 Dermal Exposure (Short-, Intermediate- and Long-Term) 

Study Selected: None

Dose and Endpoint for Risk Assessment: No appropriate endpoint was identified in the 

database for these durations and route of exposure.
Page 33 of 53

Comments about Study/Endpoint/Uncertainty Factors: In a 21-day repeated dose dermal 

toxicity study in rats (MRID No. 41841205), no systemic or dermal toxicity was observed at 

1000 mg/kg/day, the highest dose tested (limit dose). The likelihood of toxic effects resulting 

from repeated dermal exposure to flutolanil is quite low.

A.3.5 Inhalation Exposure (Short-, Intermediate- and Long-Term) 

Study Selected: None

Dose and Endpoint for Risk Assessment: No appropriate endpoint was identified in the 

database for short- or intermediate- term inhalation exposure. The current use pattern does not 

indicate long-term inhalation exposure potential.

Comments about Study/Endpoint/Uncertainty Factors: On 2/20/2013 HASPOC concluded, 

based on a WOE approach, that a subchronic inhalation toxicity study is not required for 

flutolanil. This approach included all of the available hazard and exposure information for 

flutolanil, such as: 1) the low vapor pressure of flutolanil (4.87 x 10-8 mm Hg @ 25°C); 2) the 

low acute inhalation toxicity of flutolanil (Toxicity Category IV); and 3) the low subchronic 

toxicity of flutolanil, with rat, rabbit and dog studies all showing no toxicity evident up to the 

Limit dose; and low chronic toxicity, in which the principal adverse effects up to the Limit Dose 

are liver and body weight changes and 5) if an oral PODs would have been used, MOEs for 

residential handlers would have been greater than the Agency’s level of concern.

A.4 Executive Summaries 

This section contains the most recent executive summary or conclusion for each study. In some 

cases, they incorporate recent changes as explained in Supplementary Data Evaluation Records. 

The document source is indicated in parenthesis by the study title.

A.4.1 Subchronic Toxicity

870.3100 90-Day Oral Toxicity – Rat (P. Chin 3/25/2008, TXR 0053361)

In a subchronic oral toxicity study (MRID 40342919), flutolanil [97.5% a.i.; Lot No. 543251 

(36)] was administered in the diet to groups of 10 male and 10 female CD (Sprague-Dawley 

derived) rats at concentrations of 0, 500, 4000, and 20000 ppm for 90 days. The dietary 

concentrations were equivalent to 0, 37, 299, and 1512 mg/kg/day, respectively, for males and 0, 

44, 339, and 1743 mg/kg/day, respectively, for females.

No treatment-related changes in ophthalmoscopic, hematological, clinical chemistry, gross 

pathology, or histopathology parameters were observed in either sex. At 1512 mg/kg/day 

(HDT), the absolute liver weights in females were increased (19%) over control and the relative 

liver weights in males and females were increased (14-20%) over control. At 299 mg/kg/day, 

the absolute and relative liver weights in females were increased (8-11%) over control. The 

increase in liver weights was considered to be an adaptive response to flutolanil treatment 

because these effects were not supported by clinical chemistry or histopathology findings.
Page 34 of 53

The NOAEL was 1512 mg/kg/day (HDT) and the LOAEL was not established. 

This study is classified acceptable/guideline and satisfies the guideline requirement (OPPTS 

870.3100a; OECD 408) for a subchronic oral toxicity study in the rat. 

870.3150 90-Day Oral Toxicity – Dog (M. Mercado-Feliciano 8/20/2013, TXR

0056766)

In a 90-day oral toxicity study (MRID 40342920) technical grade flutolanil (Lot No. 543251(36); 

purity: 97.5%) was administered to 4 beagle dogs sex/dose in capsules at dose levels of 0, 80, 

400, or 2000 mg/kg bw/day for 95-98 days. At study termination, all animals were sacrificed 

and subjected to gross pathological examination and histological examination of selected tissues.

There were no unscheduled deaths or significant clinical observations at any dose level. Levels 

of alkaline phosphatase in blood were elevated in high dose males (123%, p<0.01) and females 

(83%, p<0.05) at study end, and in high dose males (92%, p<0.01) at 1.5 months of dosing. 

Absolute and relative (to bw) liver weights were increased in high dose males (29% and 26%, 

respectively; p<0.01). Absolute liver weight was increased (32%, p< 0.05) in high dose females. 

While glycogen deposition in the liver was observed in the same number of animals in each dose 

group, severity increased with dose: from minimal-to-mild in control and low dose groups, to 

mild in the mid dose group and mild-to-moderate in the high dose group; the same trend was 

observed in males and females. These results suggest adaptive changes in the liver. Since no 

adverse treatment-related effects were seen in this study, a LOAEL could not be 

established. The observed NOAEL in male and female dog was 2000 mg/kg bw/day.

This 90-day oral toxicity study in the dog is acceptable (guideline) and satisfies the guideline 

requirement for a 90-day oral toxicity study (OPPTS 870.3150; OECD 409) in non-rodent 

species. 

870.3200 21/28-Day Dermal Toxicity – Rat (M. Mercado-Feliciano 8/20/2013, 

TXR 0056766)

In a 21-day dermal toxicity study (MRID 41841205), flutolanil (97.6% a.i., lot # 543251) was 

applied to the shaved skin of 5 Sprague-Dawley derived CD® rats /sex/dose at dose levels of 0, 

or 1000 mg/kg bw/day, 6 hours/day for 5 days/week during a 21-day period. At study 

termination, all animals were sacrificed and subjected to gross pathological examination, clinical 

chemistry, hematology and histological examination of selected tissues.

There were no compound related effects on mortality, clinical signs, body weight, food 

consumption, hematology, clinical chemistry, or gross and histologic pathology. Mean absolute 

and relative adrenal weights were decreased in males (19%, p≤0.01, and 20%, p≤0.05, 

respectively). Alveolar emphysema and perivascular lymphocytes were observed in the lungs of 

two treated males and one treated female; however these effects may be due to the ether 

anesthesia and not treatment-related. Since no adverse treatment-related effects were seen in 

this study, a LOAEL could not be established. The observed NOAEL in male and female 
Page 35 of 53

rats was 1000 mg/kg bw/day.

This 21-day dermal toxicity study in the rat is acceptable (guideline) and satisfies the guideline 

requirement for a 21/28-day dermal toxicity study (OPPTS 870.3200; OECD 410) in rat.

A.4.2 Prenatal Developmental Toxicity

870.3700a Prenatal Developmental Toxicity Study – Rat (M. Mercado-Feliciano 

8/20/2013, TXR 0056766)

In a developmental toxicity study (MRID 41850804) flutolanil (97.5%% a.i., lot # 543251) was 

administered to 22 female Sprague-Dawley, CD®] rats/dose by gavage] at dose levels of 0, 40, 

200, or 1000 mg/kg bw/day from days 6 through 15 of gestation. 

There were no treatment-related effects on survival, clinical signs, body weight, food 

consumption, or cesarean parameters. Post-implantation loss increased from 6.5% in the control 

to 8.1% (+25%) at 1000 mg/kg/day; however it was within the historical control range (1.7-

12.7%). Since no adverse treatment-related effects were seen in this study, a maternal LOAEL 

could not be established. The observed maternal NOAEL is 1000 mg/kg bw/day. 

There were no treatment-related effects in developmental parameters. The incidence of 

incomplete ossification was increased compared to controls on a per fetus basis, but not on a 

litter basis; therefore it was not considered to be compound related. Since no adverse 

treatment-related effects were seen in this study, the developmental LOAEL could not be 

established. The developmental NOAEL is 1000 mg/kg bw/day.

The developmental toxicity study in the rat is classified acceptable (guideline) and satisfies the 

guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in the 

rat. 

870.3700b Prenatal Developmental Toxicity Study – Rabbit (M. MercadoFeliciano 8/20/2013, TXR 0056766)

In a developmental toxicity study (MRID 40342924) Flutolanil (97.5% a.i., lot No. 543251(36)) 

was administered to 16 females New Zealand white rabbits /dose in by gavage at dose levels of 

0, 40, 200, or 1000 mg/kg bw/day from days 6 through 18 of gestation. 

There were no treatment-related effects on survival, clinical signs, body weight, food 

consumption, or cesarean parameters. The number of resorptions was increased in the mid and 

high doses (1 resorption in a total of 14 control dams, 0 for 15 dams at 40 mg/kg/day, 4 for 13 

dams at 200 mg/kg/day, 7 for 13 dams at 1000 mg/kg/day). However, control and treated group 

had similar number of live fetuses per dam (7.4, 6.6, 7.8 and 7.3 for the 0, 40, 200 and 1000 

mg/kg/day groups, respectively), and there was no altered growth (as evidenced by pup weight 

and skeletal ossification), and no treatment-related effects on anomalies and no treatment-related 

malformations. Consequently, the increase in resorptions is not considered biologically 

significant. Since no adverse treatment-related effects were seen in this study, a maternal 
Page 36 of 53

LOAEL could not be established. The observed maternal NOAEL is 1000 mg/kg bw/day.

Since no adverse there no treatment-related effects in developmental parameters were seen in 

this study, a developmental LOAEL could not be established. The developmental NOAEL is 

1000 mg/kg bw/day. 

The developmental toxicity study in the rabbit is classified acceptable (guideline) and satisfies 

the guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in 

rabbits. 

A.4.3 Reproductive Toxicity

870.3800 Reproduction and Fertility Effects – Rat (M. Mercado-Feliciano 8/20/2013, 

TXR 0056766)

In a 2-generation reproduction study (MRID 41850805) Flutolanil (98% a.i., lot # 543251 and 

90706) was administered to 30 Sprague-Dawley Crl:CD® rats /sex/dose in diet at dose levels of 

0, 200, 2000, or 20,000 ppm (equivalent to 0, 16, 161, 1636 mg/kg bw/day for males and 0, 19, 

188, 1917 mg/kg bw/day for females). On lactation Day 4, litters were culled to 4 pups/sex 

when possible. Pups were weaned on Day 21 of lactation. 

No compound-related mortality, clinical signs, or effects on body weight, gross or 

histopathology were observed for either sex or generation. At 20,000 ppm, mean relative liver 

weights were increased in F0 generation males (8%) and females (16%) and F1 generation 

females (9%) compared to controls. These results suggest adaptive changes in the liver. Since 

no adverse treatment-related effects were seen in this study, a parental systemic LOAEL 

could not be established. The parental systemic NOAEL is 20,000 ppm (1636 mg/kg 

bw/day in males, 1917 mg/kg bw/day in females).

No compound-related reproductive effects were observed at any dosage level. F0 live birth index 

at both 2000 and 20,000 ppm was significantly lower (97%) than control (100%); however this 

was not considered compound-related because (1) the control group had unusually high pup 

viability, and (2) the F1 live birth index for all dosed groups was comparable to control, despite 

longer exposure to the compound. Since no adverse treatment-related effects were seen in 

this study, an offspring LOAEL could not be established. The offspring NOAEL is 20,000 

ppm (1917 mg/kg bw/day). 

This study is acceptable (guideline) and satisfies the guideline requirement for a 2-generation 

reproductive study (OPPTS 870.3800); OECD 416 in rats

A.4.4 Chronic Toxicity

870.4300 Combined Chronic Toxicity/Carcinogenicity Feeding – Rat (P. Chin 

3/25/2008, TXR 0053361)

In a combined chronic toxicity/carcinogenicity feeding (MRID No. 40342921), flutolanil (97.5-
Page 37 of 53

99.8% a.i.; lot # 2, 6, 7, 9, 11 and 14) was administered in the diet to groups of 50 male and 50 

female SD [Crj:CD (SD) SPF] rats at concentrations of 0, 40, 200, 2000, and 10000 ppm for 2 

years. The dietary concentrations were equivalent to 0, 2, 9, 87, and 460 mg/kg/day, 

respectively, for males and 0, 2, 10, 103, and 536 mg/kg/day, respectively, for females. 

No treatment-related changes in ophthalmoscopic, hematological, clinical chemistry, urinalysis, 

gross pathology, or histopathology parameters were observed in either sex. In 460 mg/kg/day 

male rats only, body weight gain relative to the control was decreased up to 10% during the first 

13 weeks. Following the initial 13 weeks, the body weight gain differences between the high 

dose and control were less apparent. At 460 mg/kg/day, the relative liver weights in males were 

increased (12-14%) over control at 3 and 24 months. In females, absolute liver weights were 

increased (15-18%) over control at 3, 12, and 24 months and relative liver weights were 

increased (10-11%) over control at 3 and 12 months. However, the increase in liver weights in 

male and female rats at 460 mg/kg/day was considered to be an adaptive response to flutolanil 

because these effects were not supported by clinical chemistry or histopathology findings. There 

was not a treatment-related increase in tumor incidence in any treated groups when compared to 

controls. Dosing was considered adequate to assess the chronic toxicity and the carcinogenic 

potential of the test substance based on findings from the 90-day study (MRID 40342919). In 

the 90-day study, the NOAEL was 1512 mg/kg/day (HDT) and the LOAEL was not established. 

At 1512 mg/kg/day, the liver weights were increased over control, however, the increase in liver 

weights was considered to be an adaptive response to flutolanil treatment because these effects 

were not supported by clinical chemistry or histopathology findings.

The NOAEL in this chronic toxicity/carcinogenicity study in the rat was 460 mg/kg/day (HDT) 

and the LOAEL was not established.

This chronic toxicity/carcinogenicity study in the rat is classified acceptable/guideline and 

satisfies the guideline requirement for a chronic toxicity/carcinogenicity study in the rat [OPPTS 

870.4300); OECD 453].

870.4100b Chronic Toxicity – Dog (P. Chin 3/25/2008, TXR 0053361)

In a chronic oral toxicity study (MRID 40342922), flutolanil (97.5-99.8% a.i., Lot No. 2, 6, 8, 9, 

11, 12, 14, 15, and 16) was administered orally, by gelatin capsule, to 6 male and 6 female 

beagle dogs/group at dose levels of 0, 50, 250, and 1250 mg/kg/day for 2-years. All dogs 

survived until study termination. No treatment-related changes in ophthalmoscopic, 

hematological, clinical chemistry, organ weights, gross pathology, or histopathology parameters 

were observed in either sex. 

Following 65 weeks of exposure, there was a dose-related increase in the incidence of clinical 

signs (emesis, salivation, and soft stool) in both sexes at 250 and 1250 mg/kg/day, which 

continued until study termination. In addition, at 1250 mg/kg/day, decreased body weight gains 

(from the 82nd week in males and from the 81st week in females) and decreased food 

consumption (from the 79th week in males and from the 74th week in females) were observed. 

The LOAEL was 250 mg/kg/day based on increased incidence of clinical toxic signs (emesis, 

salivation, and soft stool). The NOAEL was 50 mg/kg/day.
Page 38 of 53

This chronic study in dogs is classified acceptable/guideline and it satisfies the guideline 

requirement (870.4100b) for a chronic oral toxicity study in a nonrodent. NOTE: This 

abbreviated DER provides a revised Executive Summary to upgrade the original DER. 

A.4.5 Carcinogenicity

870.4200b Carcinogenicity (Feeding) – Mouse (M. Mercado-Feliciano 8/20/2013, TXR

0056766)

In a carcinogenicity study (MRID 41850803) Flutolanil (97.6% a.i., lot # 543251 was 

administered to 52 CD-1 (ICR)BR mice /sex/dose in diet at dose levels of 0, 300, 1500, or 7000, 

or 30,000 ppm (equivalent to 0, 32, 162, 735, 3333 mg/kg bw/day males and 0, 34, 168, 839, 

3676 mg/kg bw/day females) for 79 weeks. 

Survival, clinical signs, body weights, food consumption and hematology parameters were 

similar in treated groups and controls, except for a non-dose-responsive increase in percent 

survival in all female treatment groups compared with controls. Mean relative (to bw) liver 

weight was increased (33%, p<0.0l) in high-dose females (but not in males) when compared to 

controls. There were no other treatment-related changes in organ weights or gross pathology. 

There were no treatment-related neoplastic lesions. There were positive dose-related trends

(p<0.05) in periacinar fatty vacuolation in males and centriacinar fatty vacuolation in females.

These results suggest adaptive changes in the liver. Since no adverse treatment-related effects 

were seen in this study, a LOAEL could not be established. The observed NOAELs were

3333 mg/kg/day in males and 3676 mg/kg/day in females.

At the doses tested, there was no treatment related increase in tumor incidence when compared to 

controls. Dosing was considered adequate based on the observed adaptive changes in the liver.

This carcinogenicity study in mice is acceptable (guideline) and satisfies guideline requirement

for a carcinogenicity study [OPPTS 870.4200; OECD 451] in mice.

A.4.6 Mutagenicity

Gene Mutation

870.5100, Salmonella and E. coli

reverse mutation assays

MRID 40342926

Acceptable 

Negative up to 25 mg/plate both in the presence and absence of metabolic 

activation. (S.C. Dapson 6/16/1988, TXR 006673)

870.5195, Mutation Assay at TK+/-

Locus in Mouse Lymphoma Cells

MRID 41841207

Acceptable

Negative up to 100 μg/ml (>50% cytotoxicity) in the presence and absence of 

metabolic activation. (S.C. Dapson 5/7/1993, TXR 010239)
Page 39 of 53

Cytogenetics

870.5375, Chromosomal Aberration 

Assay in Cultured Mammalian Cells

MRID 40342925

Acceptable

Test was positive at 150 μM (48.5 μg/ml) only in the presence of metabolic

activation; this dose also produced about 50% reduction in colony formation.

Higher doses were cytotoxic. (S.C. Dapson 6/16/1988, TXR 006673)

870.5395, Mouse Erythrocyte 

Micronucleus Test in Vivo

MRID 40342927

Acceptable

The test was negative up to 10 g/kg. (S.C. Dapson 6/16/1988, TXR 006673)

870.5375, Chromosomal Aberration in 

Cultured Human Lymphocytes

MRID 42606628

Acceptable

The test was negative up to 1 mg/mL (S.C. Dapson 8/6/1993, TXR 010470)

870.5550, Unscheduled DNA Synthesis 

in Primary Male Rats Hepatocytes

MRID 41841206

Acceptable

The test was negative up to 80 μg/mL. Precipitation occurred at 

concentrations ≥ 80 g/mL. (S.C. Dapson 5/7/1993, TXR 010239)

A.4.7 Neurotoxicity

870.6200 Acute Neurotoxicity Screening Battery (M.S. Ottley 3/26/2013, TXR

0056619)

In an acute neurotoxicity study (MRID 48796402), four groups of 20 HsdHan:WIST rats 

(10/sex/group; 8 weeks of age) were administered a single dose of 0, 125, 500, or 2000 mg/kg 

bw (mg/kg) of Flutolanil Technical [98.7% (Batch No. 9AE0011P) in 1% methylcellulose] by 

gavage dose and observed for 14 days. Neurobehavioral assessment [functional observational 

battery (FOB) and motor activity (MA) testing] were performed on 10 rats/sex/group on days 1, 

7, and 14. At study termination, 5 rats/sex/group were euthanized and perfused in situ for 

neuropathological examination. The remaining animals were sacrificed and selected tissues were 

taken for microscopic examination. 

There were no mortalities or toxicologically significant clinical observations at any dose level. 

There were no treatment-related or statistically significant differences in body weight or body 

weight gain in males or females observed at any dose level. There were no treatment-related, 

toxicologically significant, or statistically significant findings in any of the neurological 

endpoints examined in the study. Macroscopic and microscopic examination of tissues showed 

no treatment-related findings.

No treatment-related adverse effects were seen in this study and the NOAEL in male and female 

HsdHan:WIST rats was 2000 mg/kg bw/day. The LOAEL was not established. 

This neurotoxicity study is classified as acceptable/guideline and satisfies the guideline 

requirement for an acute neurotoxicity study in rats (870.6200; OECD 424). 
Page 40 of 53

870.6200 Subchronic Neurotoxicity Screening Battery (M.S. Ottley 3/26/2013, TXR

0056619)

In an subchronic neurotoxicity study (MRID 48798501), four groups of 20 HsdHan:WIST rats 

(10/sex/group; 6 weeks of age) were administered Flutolanil Technical [98.7% (Batch No. 

9AE0011P) in the diet in concentrations designed to deliver doses of 0, 62.6, 250, or 1000 mg/kg 

bw (mg/kg) for 13 weeks. Achieved doses were 0, 62.8, 250.5, and 977.8 mg/kg/day for males, 

and 0, 66.2, 255.8, and 1024.0 mg/kg/day for females. Neurobehavioral assessment [functional 

observational battery (FOB) and motor activity (MA) testing] was performed on 10 

rats/sex/group during weeks -1, 2, 4, 8, and 13. At study termination, 5 rats/sex/group were 

euthanized and perfused in situ for neuropathological examination. The remaining animals were 

sacrificed and selected tissues were preserved. Only tissues prepared for neuropathological 

examination from the control and high-dose groups were evaluated microscopically. 

There were no mortalities or toxicologically significant clinical observations at any dose level. 

There were no treatment-related or statistically significant differences in food consumption, body 

weight or body weight gain in males or females observed at any dose level. There were no 

treatment-related, toxicologically significant, or statistically significant findings in any of the 

neurological endpoints examined in the study. Macroscopic and microscopic examination of 

tissues showed no treatment-related findings.

No treatment-related adverse were seen in this study and the NOAEL was 977.8 mg/kg/day for 

males and 1024.0 mg/kg/day for females. The LOAEL was not established.

This neurotoxicity study is classified as acceptable/guideline and satisfies the guideline 

requirement for a subchronic neurotoxicity study in rats (870.6200; OECD 424). 

A.4.8 Metabolism

870.7485 Metabolism – Rat (T.F. McMahon 4/18/1995, TXR 0011495; T.F. 

McMahon 10/23/1995, TXR0011701; M. Mercado-Feliciano 8/20/2013, TXR 0056766)

Disposition and metabolism of 14C-Flutolanil was investigated (MRID 42606602) in male and 

female rats at a low oral dose of 20 mg/kg, repeated low oral doses of 20 mg/kg x 14 days, and a 

single high dose of 1000 mg/kg. Absorption of Flutolanil was incomplete at the single low and 

high oral doses, but appeared to be increased after repeated low oral dosing. There were no 

appreciable tissue levels of Flutolanil at study termination. At the single low oral dose, excretion 

in urine and feces was equivalent, with approximately 40% of an administered dose excreted via 

each route in male and female rats. Repeated low oral dosing resulted in an increased percentage 

in urine (about 70%) with a corresponding decrease in fecal excretion. At the single high dose, 

the majority of radioactivity (66- 78%) was excreted via the feces, with less than 10% found in 

urine. Identification of urinary and fecal metabolites by TLC showed the presence of one major 

metabolite in urine, M-4 (structure not identified) in all dose groups. In feces, radioactivity was 

excreted mainly as parent chemical, with limited conversion to M-4. This study was originally 

classified as core-supplementary data since it did not satisfy the guideline requirements (40 CFR 
Page 41 of 53

158.340, 85-1) for a metabolism study in rats. The registrant has adequately addressed the 

remaining deficiency with regard to the original metabolism study. Based on the review of these 

submitted data, the original study is now upgraded to acceptable (guideline). 

A.4.9 Immunotoxicity

870.7800 Immunotoxicity (Y.G. Yang 6/26/2012, TXR 0056378)

In a 28-day dietary immunotoxicity study (MRID 48647001), Flutolanil TGAI, (98.7% a.i., Lot 

No. 9AE0011P) was administered in the diet to Crl:CD® (SD) rats (10/sex/group) at dietary 

concentrations of 0, 750, 3000 or 12,000 ppm (0.0, 61.13, 253.9, or 1004.2 mg/kg/day for males 

and 0.0, 74.6, 253.3, or 1026.0 mg/kg/day for females, respectively) for 28 days. Animals in the 

positive control group (5/sex) received intraperitoneal injections of cyclophosphamide (25 

mg/kg) at a dose volume of 10 mL/kg (2.5 mg/mL) for four consecutive days prior to scheduled 

sacrifice. Animals in all study groups were immunized with sheep red blood cells (SRBC) by 

intravenous injection (0.5 mL/animal, 4 x 108 SRBC/mL) four days prior to the scheduled 

sacrifice. On Day 29, all animals were fasted overnight and anesthetized with sodium 

pentobarbital, exsanguinated, and necropsied. Spleens were harvested for evaluation of T-cell 

dependent antibody response (TDAR) with an antibody forming cells (AFC) assay. Other 

parameters evaluated were: clinical observations, mortality, body weight, body weight gain, and 

food consumption, select organ weights (i.e. brain, spleen and thymus), and macropathology 

investigations.

There were no test substance-related effects on mortality, clinical observations, mean body 

weight, body weight gain, food consumption, terminal body weight, and brain, spleen or thymus 

weights in any group.

For systemic toxicity, the NOAEL is 12,000 ppm (1004.2 mg/kg/day in males and 1026.0 

mg/kg/day in females); the LOAEL was not determined.

Evaluation of immune function using an antibody forming cell (AFC) assay indicated that 

Flutolanil had no significant effect on anti-SRBC antibody response (AFC/106 cells and

AFC/spleen). A high inter-individual variability was noted in all the treatment groups as well as 

in the control group. Evaluation of individual animal data of this study did not show any trend or 

distribution that would demonstrate significant suppression of anti-SRBC AFC response. 

Positive control animals had statistically significant decreases in immune function parameters 

(AFC/spleen, AFC/106 splenocytes, and absolute splenocyte cellularity); decreases in mean 

absolute spleen and thymus weights also noted when compared to vehicle control group. The 

positive control group confirmed the ability of the test system to detect immunosuppressive 

effects and confirmed the sensitivity of the study design.

The Natural Killer (NK) cells activity was not evaluated in this study. The toxicology database 

for Flutolanil does not reveal any evidence of treatment-related effects on the immune system. 

The overall weight of evidence suggests that this chemical does not directly target the immune 

system. Under HED guidance, a NK cell activity assay is not required at this time.
Page 42 of 53

Under conditions of this study, the immunotoxicity NOAEL is 12,000 ppm (1004.2 mg/kg/day in 

males and 1026.0 mg/kg/day in females). The LOAEL was not determined.

This 28-day dietary immunotoxicity study in the rat is acceptable/guideline and satisfies

guideline requirement for an immunotoxicity study (OPPTS 870.7800).
Page 43 of 53

Appendix B. Nomenclature and Physicochemical Properties of Flutolanil.

Table B.1. Chemical Names and Structures of Flutolanil and Metabolites. 

Common name;

Company code

Chemical name Chemical structure

Flutolanil; M1 N-[3'-(1-

methylethoxy)phenyl]-2-

(trifluoromethyl)benzamide

M-2 N-[4'-hydroxy-3'-(1-

methylethoxy)phenyl]-2-

(trifluoromethyl)benzamide

M-3 N-[3'-(2-hydroxy-1-

methylethoxy)phenyl]-2-

(trifluoromethyl)benzamide

M-4 N-(3'-hydroxyphenyl)-2-

(trifluoromethyl)benzamide

N

H

O

CH3

CH3

O

CF3

N

H

O

CH3

CH3

O

CF3

OH

N

H

O

CH3

O

CF3

OH

N

H

OH

O

CF3
Page 44 of 53

Table B.1. Chemical Names and Structures of Flutolanil and Metabolites. 

Common name;

Company code

Chemical name Chemical structure

M-5 N-[3',4'-(dihydroxy)phenyl]-2-

(trifluoromethyl)benzamide

M-6 N-(3'-methoxy)phenyl -2-

(trifluoromethyl)benzamide

M-7 N-(4'-hydroxy-3'-

methoxy)phenyl -2-

(trifluoromethyl)benzamide

M-11 2-[[3-[2-

(trifluoromethyl)benzoyl]-

amino]phenoxy]propanoic acid

2-TFBA: 2-(trifluoromethyl)benzoic 

acid

N

H

OH

O

CF3

OH

N

H

O

O

CF3

CH3

N

H

O

O

CF3

CH3

OH

N

H

O

CH3

O

CF3

O

HO

O

CF3

OH
Page 45 of 53

Table B.2. Physicochemical Properties of Flutolanil.

Parameter Value Reference

Molecular weight (g/mole) 323.3 DP#s 190584 and 190586, 

3/24/94, J. Garbus; MRID 

42606601

Melting range 100.4-103.8 °C

pH 5.69

Density (g/cm3) 1.325 @ 20-25 °C

Water solubility 6.53 mg/L at 20 °C

Solvent solubility(g/L) at 20 °C 

Acetone 1440

Methanol 232 

n-Hexane 0.9 

Toluene 57

Ethyl acetate 675

Vapor pressure 4.87 x 10-8 mm Hg at 25 °C

Dissociation constant, pKa Not applicable

Octanol/water partition 

coefficient, Log(KOW)

log POW = 3.74

Soil half-life (aerobic soil 

metabolism)

256.65 days (mean)
Page 46 of 53

Appendix C. Incident Report

(e-mail dated 7/30/13 from Shanna Recore)

TEB has been asked to review the incidents in IDS and NIOSH SENSOR-Pesticides for the 

flutolanil preliminary risk assessment due August 2013. Flutolanil incidents were previously 

analyzed 2008 (Updated Review of Flutolanil Incident Reports, M. Hawkins and J Cordova, 

07/24/2008). There was one incident identified in the Main Incident Data System from 2000 to 

July 24, 2008. This incident update is being provided via e-mail for following reasons: 1) the 

previous incident analysis was prepared in the last 5 years; 2) the incidents did not warrant 

further analysis; and 3) the current incident analysis is consistent with the previous analysis.

Updated incident analyses of the Main and Aggregate Incident Data System (IDS) from January 

1, 2008 to May 8, 2013, and the National Institute of Occupational Safety and Health Sentinel 

Event Notification System for Occupational Risks (NIOSH SENSOR) from 1998 to 2008 are 

consistent with the previous analysis. The results are as follows:

 From January 1, 2007, to May 8, 2013, there was one incident reported to Main IDS 

that involved flutolanil that was part of a lawsuit and will not be considered in this 

update. There were three incidents identified Aggregate IDS that involve flutolanil.

These incidents were classified as minor severity.

 From 1998 to 2009, one incident was identified in SENSOR involving flutolanil.

This case involved multiple active ingredients. The case occurred in New York in 

2006, was moderate in severity and included the following details in the report:

“Former farmhand was loading bins for "cutting potatoes" (process of 

separating good potatoes from bad). This is done in an enclosed area. When 

the door to this area is opened, the wind blows in. This stirs up the air flow 

and causes product to blow back on him. RUP was used by an unsupervised, 

uncertified applicator. He had no barrier on his hands to protect himself from 

coming into contact with product. Other recommended PPE also not worn.”

The medical record states that the “symptoms started in early spring after 

products are used repeatedly 5 days/week. Symptoms got progressively worse 

over the next 7 months. He is repeatedly seen through ED or PCP with 

complaints of chest pain, sore throat, nausea”

Based on the continued low frequency and severity of incident cases reported for flutolanil, there 

does not appear to be a concern at this time that would warrant further investigation. The 

Agency will continue to monitor the incident information and if a concern is triggered, additional 

analysis will be conducted.
Page 47 of 53

Appendix D. Food Residue Profile Details

Processing studies: Of the registered crops, processed commodities are associated with cotton, 

peanut, potato, rice, soybean, and wheat. Adequate processing data are available as discussed 

below.

Cotton: For the seed treatment use (D364462, S. Funk, 1/25/10), a cotton processing study was 

not required because of low residues in the cotton seed. 

Peanut: The processed commodities for peanut are meal and refined oil. Flutolanil concentrates 

2.2x in meal but does not concentrate (0.29x) in refined oil (D190879, G. F. Kramer, Ph.D., 

1/12/94 and D207486, G.F. Kramer, Ph.D., 11/3/94).

Potato: The processed commodities for potato are granules/flakes, chips and wet peel. There is 

no concentration in granules/flakes and chips but residues concentrate 1.7x in wet peel 

(D226667, M. Xue, 2/1/00).

Rice: The processed commodities for rice are polished rice and bran. Residues concentrate 3.5x 

in rice hulls and 1.4x in rice bran, but do not concentrate in polished rice (D201704, J. Garbus, 

Ph.D., 5/9/94 and D226667, M. Xue, 2/1/00).

Soybean: The processed commodities for soybean are meal, hulls, and refined oil. An adequate 

processing study (D335050, F. Fort, 11/26/07) indicated that residues do not concentrate in 

soybean hulls, meal, and oil.

Wheat: The processed commodities for wheat are bran, flour, germ, middlings, and shorts. An 

adequate processing study was submitted (D335050, F. Fort, 11/26/07) that indicated that 

residues do not concentrate in wheat flour, germ, middlings, and shorts, but do concentrate in 

bran. Residues from the submitted rotational crop field trials were <0.05 ppm in wheat grain but 

averaged 0.16 ppm in bran. HED concluded in the risk assessment (D335050 F. Fort, 11/26/07) 

that a tolerance of 0.20 ppm is appropriate for indirect or inadvertent residues in wheat bran.

Storage Stability: Adequate storage stability data are available to support the field trials of the 

primary (treated) crops for existing uses and the rotational crop wheat as discussed below and 

shown in Table D.1.

Brassica (cole) leafy vegetables and turnip greens: Adequate storage stability data are available 

for flutolanil and its metabolite M-4 in/on cabbage, mustard greens, and broccoli. The data 

indicate that residues of flutolanil and its metabolite M-4 are stable in frozen storage up to 297 

days in cabbage, 519 days in mustard greens, and 569 days in broccoli.

Cotton: Storage stability data were not required for cotton because of the short storage duration 

(D364462, S. Funk, 1/25/10).
Page 48 of 53

Peanuts: Adequate storage stability data are available for flutolanil and its metabolite M-4 in/on 

peanut commodities. The data indicate that residues of flutolanil and its metabolite M-4 are 

stable in frozen storage for up to 3 years in/on peanut nutmeat, oil, hulls.

Potato: Potato samples were stored for 3.5 years (D268880, A. Lowit, 9/11/00). MRID 

45756604 indicated that flutolanil and M-4 are stable in potatoes after 54 months (4.5 years) and 

67 months (5.6 years) frozen storage at -10 to -20°C.

Rice: Adequate storage stability data were previously submitted for flutolanil and its metabolite 

M-4 in/on rice commodities. The data indicate that residues of flutolanil and its metabolite M-4 

are stable in frozen storage (-20 °C) for up to ~31 months in/on rice grain and straw.

Soybean: Storage stability data were not required for soybean because of the short storage 

duration (D364462, S. Funk, 1/25/10).

Wheat: Flutolanil (parent) has been shown to be stable in wheat grain stored frozen (-20oC) for 

207 days (MRID 42606611). Matrices of the rotational crop wheat in the field rotational crop 

study (MRID 43175803) were stored frozen (-20oC) for the following intervals: grain for 334-

369 days; forage for 496-675 days; straw for 352-443 days; and hay for 418 days.

Table D.1. Summary of Storage Conditions and Durations of Samples from Crop Field Trials. 

Matrix [MRID] Storage Temperature

(°C)

Actual Storage Duration

(days)

Interval of Demonstrated 

Storage Stability 

Broccoli [47832603] -4 to -22oC 357 to 564 569 days

Cabbage [47832601] -29 to -10oC 48 to 293 297 days

Mustard greens [47832602] -4 to -22oC 299 to 511 519 days

Peanuts [42742004] frozen 904 – nutmeat

916 - hay

3 years in/on nutmeat, oil, 

and hulls

Peanuts [43175801] frozen 407 – nutmeat and hay

Potato [439714-20, -21, -22] frozen 3.5 years 54 months (4.5 years) and 

67 months (5.6 years)

(MRID 45756604)

Rice [48092301] -20 ± 5°C 32-84 days1

(1.1-2.8 months)

931 days (~31 months or 

2.5 yrs) in/on rice grain and 

straw (MRID 44526202)

Rice [44529502] frozen 1200 days (3.3 years) 931 days (2.5 years)

Wheat [43175803] -20°C 334-369 grain

496-675 forage

353-443 straw

418 hay

207 days in/on wheat grain 

(MRID 42606611);

931 days in/on rice grain & 

straw (MRID 44526202);

519 days in/on mustard 

greens

Meat, Milk, Poultry, and Eggs

Acceptable feeding studies with dairy cattle and poultry were previously reviewed. No 

detectable residues of flutolanil and its metabolites M-2, M-4, or M-7 were found in the whole 

milk, cream, skim milk, muscle, and fat of dairy cows sacrificed after dosing for 28 days at 29.4 
Page 49 of 53

(2.9x), 85.0 (8.5x), and 286 ppm (29x) in the feed. Detectable residues were found in liver at 

0.05, 0.06, and 0.21 ppm at the 29.4, 85.0, and 286 ppm feeding levels and in kidney at 0.06, 

0.15, and 0.82 ppm at the 29.4, 85.0, and 286 ppm feeding levels. 

A feeding study on laying hens is available in which hens were dosed with flutolanil for 28 days

at levels of 1.29 (0.80x), 3.87 (2.4x), and 12.9 ppm (8.0x) in the diet. Eggs were collected 

throughout the feeding study. Samples of tissue (liver, breast muscle, thigh muscle, fat, skin) 

and egg (white, yolk) were analyzed by GC/MS for flutolanil (M-1), and its major metabolites, 

M-2, M-4, and M-7. Except for one residue of 0.12 ppm in liver at the highest feeding level, no 

detectable residues of parent or any metabolite were found. 

Adequate storage stability data are available on livestock matrices stored frozen (-20oC) (MRID 

43175811 and 43175812) to support the livestock feeding studies as reported in Table D.2 

below.

Table D.2. Summary of Storage Conditions and Durations of Samples from Livestock Feeding Studies.

Livestock Matrix [MRID] Storage Temperature

(°C)

Actual Storage Duration Interval of Demonstrated 

Storage Stability1

Beef fat [43175808] frozen 119 days 92 days (avg. 51% 

Chicken fat [42606612] recovery in beef fat)frozen ~5 months

Beef kidney [43175808] frozen 119 days 127 days in beef muscle

Beef liver [43175808] frozen 112 days 122 days in chicken liver

Beef muscle [43175808] frozen 111 days

Chicken liver [42606612] frozen ~5 months

Chicken muscle [42606612] frozen ~5 months

Eggs [42606612] frozen ~5 months 125 days

Milk [43175808] frozen 114 days 115 days

1 MRIDs 43175811 and 43175812

Livestock dietary burdens are calculated in Table D.3 below.

Table D.3. Calculation of Dietary Burdens of Flutolanil Residues to Livestock.

Feedstuff Type1 % Dry 

Matter2 % Diet2 Recommended Tolerance (ppm)

Dietary Contribution 

(ppm)3

Beef Cattle

Cotton, cotton gin 

byproducts

R 90 5/0 0.20 0.00

Cotton, meal PC 89 5 0.20 0.00

Cotton, hulls R 90 5/0 0.20 0.011

Soybean forage R 35 15/25 8.00 3.42

Rice, grain CC 88 20 7.00 1.59

Soybean, meal PC 92 15/5 0.20 0.011

TOTAL BURDEN -- -- 55 -- 5.03

Dairy Cattle

Cotton, undelinted seed PC 88 10 0.20 0.023

Cotton, meal PC 89 10/0 0.20 0.00
Page 50 of 53

Table D.3. Calculation of Dietary Burdens of Flutolanil Residues to Livestock.

Feedstuff Type1 % Dry 

Matter2 % Diet2 Recommended Tolerance (ppm)

Dietary Contribution 

(ppm)3

Soybean forage R 35 25 8.00 5.71

Soybean hay R 30 5 2.5 0.42

Peanut hay R 85 15 12.89 (HAFT) 2.27

Rice, grain CC 88 20 7.00 1.59

Soybean, meal PC 92 15/0 0.20 0.00

TOTAL BURDEN -- -- 75 -- 10.01

Poultry

Cotton, meal PC 89 20/5 0.20 0.011

Rice, grain CC 88 20 7.00 1.40

Peanut, meal PC 85 20 1.00 0.20

TOTAL BURDEN -- -- 45 -- 1.61

Swine

Cotton, meal PC 89 15/0 0.20 0.00

Rice, grain CC 88 20 7.00 1.40

Wheat, milled byproducts CC 88 50 0.20 0.10

Peanut, meal PC 85 15 1.00 0.15

Soybean, meal PC 92 5/0 0.20 0.00

TOTAL BURDEN -- -- 85 -- 1.65

1 R: Roughage; CC: Carbohydrate concentrate; PC: Protein concentrate.

2 OPPTS 860.1000 Table 1 Feedstuffs (06/30/2008). First entry is maximum for the particular commodity; second 

entry is assigned per the total for maximum reasonably based diet.

3 Contribution = ([tolerance /% DM] X % diet) for beef and dairy cattle; contribution = ([tolerance] X % diet) for 

poultry and swine. 

Conclusions. Tolerances are established for residues of flutolanil and its metabolites converted 

to 2-TFBA in ruminant (cattle, goat, horse, and sheep) commodities at 0.05 ppm for milk, 0.10 

ppm for fat, 1.00 ppm for kidney, 2.00 ppm for liver, and 0.05 ppm for meat and meat 

byproducts, and in poultry commodities at 0.05 ppm for egg, fat, meat, and meat byproducts. 

Feeding studies are available on lactating cows and laying hens. Based on the feeding studies 

and the maximum reasonably balanced diets for livestock, the established livestock tolerances 

are adequate.

Rotational crops:

In the confined rotational crop study the total radioactive residues (TRR) were 0.01-0.04 ppm in 

all raw agricultural commodities (RACs) of mature crops at the 366 DAT (days after treatment) 

plantback interval. Residue levels were highest at the 30 DAT interval and declined by 90% or 

more by the 366 DAT interval. 

Field rotational crop studies were previously reviewed for winter wheat, corn, soybeans, and 

cotton planted 2, 3, or 4 months (wheat) or 8-10 months (corn, cotton, and soybean) following 

the harvest of flutolanil-treated peanuts. In addition, field rotational crop studies were submitted 

and reviewed for soybean and grain sorghum following the harvest of flutolanil-treated rice. 
Page 51 of 53

More recently, Nichino America, Inc. submitted the results of a field rotational crop study on 

corn and cotton. For this latter study, samples of corn and cotton matrices were stored frozen for 

7.5-8 years from harvest to analysis. HED concluded that the field rotational study on corn and 

cotton is unacceptable because no storage stability data are available which demonstrate that 

residues of flutolanil and M-4 are stable in corn forage, fodder and grain and cotton seed stored 

frozen for up to 8 years and because the analytical method did not determine the residue of 

concern.

A field rotational crop study was also reported on soybeans and wheat concurrently with the 

above study on corn and cotton. Crops were planted 29-36 days following application of the 

70% WDG formulation at 2.0 lb ai/A (1x the maximum registered seasonal rate for any crop) to 

bare soil. Detectable flutolanil-derived residues were found in all crop samples of soybean and 

wheat except wheat grain, where residues were <0.05 ppm.

Tolerances for indirect or inadvertent residues are established for wheat commodities in 40 CFR 

180.484 (a).

Rotational crop restrictions are included on the established Flutolanil 40SC label (EPA Reg. No. 

71711-28). Plantback restrictions on the established 40SC label are 0 days for cotton, peanuts, 

potatoes, rice, and soybeans; 30 days for wheat; 150 days for leafy vegetables and small grain 

crops other than wheat; 240 days for corn and sorghum; and 365 days for all other crops.

Rotational crop restrictions on the established Moncut® 70-DF label (EPA Reg. No. 10163-301) 

are 0 days for cotton, peanuts, potatoes, rice, soybeans, turnip greens, and Brassica (cole) leafy 

vegetables; 30 days for wheat; 150 days for leafy vegetables and small grain crops other than 

wheat; 240 days for corn and sorghum; and 365 days for all other crops. 

Conclusions. Rotational crop restrictions and inadvertent residue tolerances have been 

established on the Flutolanil 40SC label (EPA Reg. No. 71711-28) based on the available 

confined and field accumulation studies.

Since Brassica (cole) leafy vegetables and turnip greens are being registered on the 40SC label, 

the rotational crop restrictions for the Flutolanil 40SC label (EPA Reg. No. 71711-28) should be 

amended to include Brassica (cole) leafy vegetables and turnip greens under the 0-day rotational 

crop restriction interval.

Since no tolerance is established for sugar beet, the 0-day rotational crop restriction for sugar 

beet on the Artisan Fungicide label (EPA Reg. No. 71711-17) should be removed.
Page 52 of 53

Appendix E. International Residue Limits Status Sheet

Table E.1. Summary of US and International Tolerances and Maximum Residue Limits

US Canada Mexico1 Codex2

Residue Definition:

40 CFR180.484 (a)

flutolanil, N -(3-(1-

methylethoxy)phenyl)-2-

(trifluoromethyl)benzamide, and its 

metabolites converted to 2-

(trifluoromethyl)benzoic acid and 

calculated as flutolanil.

None For plant commodities, flutolanil.

For animal commodities, flutolanil 

and transformation products 

containing the 2-trifluoromethylbenzoic acid moiety, expressed as 

flutolanil.

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

Commodity US Canada Mexico1 Codex2

Cattle, fat 0.10 None

Cattle, kidney 1.00 0.1

Cattle, liver 2.00 0.2

Cattle, meat byproducts 0.05

Cattle, meat 0.05 0.05 (*)

Cotton, gin byproducts 0.20

Cotton, undelinted seed 0.20

Egg 0.05 0.05 (*)

Goat, fat 0.10

Goat, kidney 1.00 0.1

Goat, liver 2.00 0.2

Goat, meat byproducts 0.05

Goat, meat 0.05 0.05 (*)

Hog, fat 0.10

Hog, kidney 1.00 0.1

Hog, liver 2.00 0.2

Hog, meat byproducts 0.05

Hog, meat 0.05 0.05 (*)

Horse, fat 0.10

Horse, kidney 1.00

Horse, liver 2.00

Horse, meat byproducts 0.05

Horse, meat 0.05 0.05 (*)

Milk 0.05 0.05 (*)

Peanut 0.5

Peanut, hay 20.0

Peanut, meal 1.0

Potato 0.20

Potato, wet peel 0.30

Poultry, fat 0.05

Poultry, meat 0.05 0.05 (*)

Poultry, meat byproducts 0.05 0.05 (*)

Rice, bran 10.0 10 (unprocessed)

Rice, grain 7.0 2 husked

1 polished

Rice, hulls 25.0
Page 53 of 53

Table E.1. Summary of US and International Tolerances and Maximum Residue Limits

US Canada Mexico1 Codex2

Rice, straw 10.0 10

Sheep, fat 0.10

Sheep, kidney 1.00 0.1

Sheep, liver 2.00 0.2

Sheep, meat 0.05 0.05 (*)

Sheep, meat byproducts 0.05

Soybean, forage 8.0

Soybean, hay 2.5

Soybean, seed 0.20

Turnip, greens 0.20

Vegetable, brassica, group 5 0.20

Residue Definition:

40CFR180.484 (d)

indirect or inadvertent residues of 

the fungicide flutolanil, N -(3-(1-

methylethoxy)phenyl)-2-

(trifluoromethyl)benzamide, and 

its metabolites converted to 2-

(trifluoromethyl)benzoic acid and 

calculated as flutolanil

None None

Wheat, bran 0.20

Wheat, forage 2.5

Wheat, grain 0.05

Wheat, hay 1.2

Wheat, straw 0.20

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2

* = absent at the limit of quantitation.