Fluopyram Human Health Risk Assessment DP No. D421926

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

DATE: December 22, 2015

SUBJECT: Fluopyram: Human Health Risk Assessment for Proposed New Uses on Crop 

Subgroup 1B, Subgroup 1C, Crop Group 2, Subgroup 3-07A, Subgroup 3-07B, 

Subgroup 4A, Subgroup 4B, Subgroup 5A, Subgroup 5B, Subgroup 6A, 

Subgroup 6B, Dried Beans, Soybean, Subgroup 8-10A, Subgroup 8-10B, 

Subgroup 9A, Subgroup 9B, Subgroup 10-10, Group 11-10, Subgroup 12-12A, 

Subgroup 12-12B, Subgroup 12-12C, Subgroup 13-07A, Subgroup 13-07B, 

Subgroup 13-07F, Subgroup 13-07G, Crop Group 15 (except corn and Rice), 

Crop Group 16, Subgroup 19A, Dill Seed, Subgroup 20A, Subgroup 20B, 

Subgroup 20C, Artichoke (Globe), Hops, and Sugarcane (Rotated). Amended 

Tolerance Requests for the Registered Uses due to Crop Group/Subgroup 

Expansion Requests. Proposed New Uses on Turf Grass, Ornamentals, and 

Christmas Trees, and as a Seed Treatment to Peanuts.

PC Code: 080302 DP Barcode: D421926

Decision No.: 492321 Registration Nos.: 432-RLGI; 432-RLGT; 432-RLGA; 432-

RLGL; 432-RLGU; 264-1078; 264-1084; 264-1085; 264-1090; 

264-1091

Petition No.: 4F8284 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical/Aggregate Case No.: NA

TXR No.: NA CAS No.: 658066-35-4

MRID No.: NA 40 CFR: §180.661

FROM: Barry O’Keefe, Senior Biologist/Risk Assessor

Meheret Negussie, Chemist

Whang Phang, Senior Toxicologist

Risk Assessment Branch III

Health Effects Division (7509P)

THROUGH: Christine Olinger, Chief

Risk Assessment Branch III

Health Effects Division (7509P)

TO: Tamue Gibson, Risk Manager

Shaja Joyner, Team Leader

Fungicide Herbicide Branch

Registration Division (7505P)
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The registrant, Bayer CropScience, is requesting new uses of fluopyram on artichoke (globe), 

Brassica (cole) leafy vegetables, Brassica (cole) leafy vegetables head and stem subgroup, bulb 

vegetables, canola, carrot, cereal grains (except rice), citrus, corn (including field, sweet, 

popcorn, and field corn grown for seed), cotton, cucurbit vegetables, fruiting vegetables, ginseng, 

grapes and other small vines fruits (except fuzzy kiwifruit), herbs and spices (except black 

pepper), hops, leafy vegetables, legume vegetables (including soybean), peanut, pome fruits, 

potato and other root, tuberous and corm vegetables, small berries (caneberries and bushberries), 

stone fruit, strawberry and other low growing berries, sugar beet, sunflower subgroup, tree nuts; 

use as a seed treatment to peanuts; turf grass (golf courses, sod farms, sports fields, residential, 

industrial, municipal, commercial, and other turf grass areas), ornamentals (in residential and 

commercial settings), and Christmas trees. 

The Registration Division (RD) of OPP has requested that the Health Effects Division (HED)

evaluate the hazard and exposure data and conduct dietary, aggregate, occupational and 

residential exposure assessments, as needed, to estimate the risk to human health that will result 

from the proposed uses of fluopyram. This memorandum serves as HED’s assessment of those 

exposures. 

The toxicology reevaluation was performed by Whang Phang, the drinking water assessment was 

conducted by Mohammed Ruhman (EPA Environmental Fate and Effects Division (EFED)), the 

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

Meheret Negussie, and the occupational and residential exposure assessment and aggregate 

human health risk assessment were conducted by Barry O’Keefe.
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TABLE OF CONTENTS

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

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

2.1 Data Deficiencies ............................................................................................................ 9

2.2 Tolerance Considerations.............................................................................................. 9

2.2.1 Enforcement Analytical Method ............................................................................... 9

2.2.2 International Harmonization................................................................................... 10

2.2.3 Recommended Tolerances....................................................................................... 10

2.2.4 Revisions to Petitioned-For Tolerances.................................................................. 16

2.3 Label Recommendations.............................................................................................. 17

3.0 Introduction...................................................................................................................... 18

3.1 Chemical Identity ......................................................................................................... 19

3.2 Physical/Chemical Characteristics ............................................................................. 19

3.3 Pesticide Use Pattern.................................................................................................... 19

3.4 Anticipated Exposure Pathways................................................................................. 38

3.5 Consideration of Environmental Justice.................................................................... 38

4.0 Hazard Characterization and Dose-Response Assessment.......................................... 38

4.1 Toxicological Effects .................................................................................................... 39

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) ............................... 40

4.2.1 Completeness of the Toxicology Database.............................................................. 40

4.2.2 Evidence of Neurotoxicity........................................................................................ 40

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 40

4.2.4 Residual Uncertainty in the Exposure Database ................................................... 40

4.3 Toxicity Endpoint and Point of Departure Selections.............................................. 41

4.3.1 Dose-Response Assessment...................................................................................... 41

4.3.2 Recommendation for Combining Routes of Exposures for Risk Assessment..... 41

4.3.3 Cancer Classification and Risk Assessment Recommendation............................ 42

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

Assessment............................................................................................................................... 42

5.1 Residues of Concern Summary and Rationale.......................................................... 44

5.2 Food Residue Profile .................................................................................................... 45

5.3 Water Residue Profile.................................................................................................. 45

5.4 Dietary Risk Assessment.............................................................................................. 46

5.4.1 Description of Residue Data Used in Dietary Assessment.................................... 46

5.4.2 Percent Crop Treated Used in Dietary Assessment .............................................. 46

5.4.3 Acute Dietary Risk Assessment............................................................................... 47

5.4.4 Chronic Dietary Risk Assessment........................................................................... 47

5.4.5 Cancer Dietary Risk Assessment............................................................................. 47

5.4.6 Summary Table......................................................................................................... 47

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 48

6.1 Residential Handler Exposure .................................................................................... 48

6.2 Residential Post-application Exposure....................................................................... 48

6.3 Residential Risk Estimates for Use in Aggregate Assessment.................................. 49

6.4 Residential Bystander Post-application Inhalation Exposure ................................. 50

6.5 Non-Occupational Spray Drift Exposure and Risk Estimates................................. 50
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7.0 Aggregate Exposure/Risk Characterization.................................................................. 51

7.1 Acute Aggregate Risk................................................................................................... 51

7.2 Short-Term Aggregate Risk........................................................................................ 51

7.3 Chronic Aggregate Risk .............................................................................................. 51

8.0 Cumulative Exposure/Risk Characterization ............................................................... 52

9.0 Occupational Exposure/Risk Characterization ............................................................ 52

9.1 Short-/Intermediate-Term Handler Risk................................................................... 52

9.2 Short-/Intermediate-Term Post-Application Risk .................................................... 53

9.2.2 Inhalation Post-application Risk............................................................................. 56

10.0 References......................................................................................................................... 58

Appendix A. Toxicology Profile................................................................................................ 60

A.1 Toxicology Data Requirements................................................................................... 60

A.2 Toxicity Profiles............................................................................................................ 61

Appendix B. Physical/Chemical Properties............................................................................. 72

Appendix C. Review of Human Research................................................................................ 73

Appendix D. Residential Handler and Post-application Exposure and Risk Estimates ..... 74

Appendix E. Occupational Handler and Post-application Exposure/Risk Summary Tables

....................................................................................................................................................... 76

Appendix F. International Residue Limit Status Sheet.......................................................... 84
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1.0 Executive Summary

Fluopyram, (N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-

(trifluoromethyl)benzamide) is a broad-spectrum systemic fungicide of the pyridinyl

ethylbenzamide group. It acts by inhibiting succinate dehydrogenase in the cell respiration of 

fungi. The mechanism of toxicity in mammals is not clearly defined.

Use Profile

The registrant, Bayer CropScience (BCS), is requesting numerous new uses on agricultural field 

crops and crop groups be added to the Luna®Privilege label (4.16 lb ai/gal) [EPA Reg. No. 264-

1078] that contains the sole active ingredient (ai) fluopyram. Additionally, BCS is requesting to 

add numerous agricultural field crops and crop groups to the following multi-active ingredient 

labels: 1) PropulseTM (1.67 lb ai/gal) [EPA Reg. No. 264-1084] which contains fluopyram and 

prothioconazole; 2) Luna®Tranquility (1.04 lb ai/gal) [EPA Reg. No. 264-1085] which contains 

fluopyram and pyrimethanil; 3) Luna

®

Sensation (2.1 lb ai/gal) [EPA Reg. No. 264-1090] which 

contains fluopyram and trifloxystrobin; and 4) Luna®Experience (1.67 lb ai/gal) [EPA Reg. No. 

264-1091] which contains fluopyram and tebuconazole. 

BCS has proposed to establish tolerances on the vast majority of crops. Furthermore, BCS has 

requested tolerance amendments as a result of expanding uses from representative commodities 

to crop groups/subgroups, addition of new uses, and tolerance re-assessment. The petitioner 

additionally submitted data from field trials conducted in Europe with a variety of crops, which 

included data from studies conducted in greenhouses to support greenhouse uses in North 

America. Most proposed applications are at a seasonal rate of 0.445 lb a.i./acre with various preharvest intervals (PHIs). 

BCS is proposing new use patterns: foliar; banded; soil/in-furrow; and chemigation/drip 

irrigation treatments. Additionally, for registered potato (foliar), cotton (seed and soil/in-furrow 

treatment) and soybean (seed treatment) new uses, a combination of seed/soil/in-furrow and 

foliar treatments are requested. 

Additionally, new rotational crop data for sugarcane have been submitted to support a 14-day

plantback interval (PBI) in Region 3. The database is adequate to support the proposals. 

In addition, BCS is requesting a new seed treatment use on peanut seeds to be added to the 

Luna®Privilege label (4.16 lb ai/gal) [EPA Reg. No. 264-1078].

BCS, is also requesting new non-food uses of fluopyram on several newly proposed labels, 

including turf grass (golf courses, sod farms, sports fields, residential, industrial, municipal, 

commercial, and other turf grass areas), ornamentals (in residential and commercial landscapes, 

interiorscapes, field grown and container ornamentals, in nurseries, and greenhouses, lathhouses, 

shadehouses, containers and other enclosed structures), fruit and nut trees (including citrus, 

grapes, pome fruits, stone fruits, and tree nuts), ornamental sunflower, and Christmas trees. The 

proposed labels are as follows: 1) Fluopyram 500 SC (4.16 lb ai/gal) [EPA File Symbol 432-

RLGI] which contains fluopyram; 2) FLU+TFS SC 500 (2.1 lb ai/gal) [EPA File Symbol 432-

RLGT] which contains fluopyram and trifloxystrobin; 3) FLU+TFS SC 32.5 (0.104 lb ai/gal) 
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[EPA File Symbol 432-RLGA] which contains fluopyram and trifloxystrobin; 4) FLU+TFS SC 

25 (0.104 lb ai/gal) [EPA File Symbol 432-RLGL] which contains fluopyram and 

trifloxystrobin; and 5) 13ESP715 3.3 SC (3.34 lb ai/gal) [EPA File Symbol 432-RLUG] which 

contains fluopyram. 

Most of the proposed labels require occupational handlers to wear the following personal 

protective equipment (PPE): long sleeved shirts, long pants, shoes, socks, and chemical resistant 

gloves. However, the FLU+TFS SC 32.5 and FLU+TFS SC 25 labels do not require the use of 

gloves. Additionally, the Luna®Privilege label requires water proof gloves for seed treatment 

activities and no gloves for baggers and bag sewers.

On all registered and proposed labels the restricted entry interval (REI) is 12 hours.

Fluopyram is currently registered on a variety of agricultural food crops, including apple, cherry 

(sweet and tart), cotton, dried beans, peanut, potato, strawberry, sugar beets, tree nuts, 

watermelon, viniferous variety grapes, and for seed treatment to cotton and soybean. There are 

no existing residential uses of fluopyram.

Exposure Profile

The proposed uses of fluopyram would result in exposures from both food and drinking water. 

There is a potential for short- and intermediate-term occupational dermal and inhalation exposure 

to fluopyram during handling tasks (mixing, loading, and application) and during postapplication activities. Long-term occupational exposure is not expected for the proposed use 

patterns associated with fluopyram. There is a potential for residential short-term dermal and 

inhalation exposure to fluopyram to adults during handling tasks. During residential postapplication activities there is a potential for short-term dermal exposure to adults, youths, and 

children and incidental oral exposure to children 1 to <2 years old.

Hazard Characterization

The liver was the target organ following fluopyram exposure across species and exposure 

durations. Treatment-related thyroid effects were also observed at dose levels causing adverse

liver perturbations in rats and mice. Decreased body weight was a common clinical finding 

throughout the toxicology database. Liver tumors were observed in female rats and thyroid 

tumors were observed in male mice in chronic feeding studies; however, a nongenotoxic mode of 

action was adequately demonstrated for the liver and thyroid tumors. Therefore, the Cancer 

Assessment Review Committee (CARC) classified fluopyram as “Not Likely to be Carcinogenic 

to Humans” at doses that do not induce cellular proliferation in the liver or thyroid glands. 

Fluopyram is not genotoxic or mutagenic.

HED recommends that the Food Quality Protection Act (FQPA) safety factor be reduced to 1x 

because there are no residual uncertainties with regard to pre- and postnatal susceptibility, the 

toxicology database is complete, and there is no evidence of neurotoxicity.

An acute dietary endpoint for the general population (including infants and children) was 

selected from the acute neurotoxicity study in rats based on decreased motor and locomotor 
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activity (no observed adverse effect level (NOAEL = 50 mg/kg). Because this effect was 

reversible within 48 hours and attributed to generalized systemic toxicity, fluopyram is not 

considered a neurotoxicant. The chronic dietary endpoint was based primarily on liver and 

thyroid effects in the chronic toxicity/carcinogenicity study in rats (NOAEL = 1.2 mg/kg/day). 

Short- and intermediate-term dermal endpoints were chosen from a dermal toxicity study in rats 

in which increased prothrombin time and altered cholesterol levels were seen at the limit dose 

(NOAEL = 300 mg/kg/day). Short- and intermediate-term inhalation and short-term incidental 

oral endpoints were selected from the multigeneration reproduction study in rats based on 

clinical chemistry and kidney effects in the parental generation (NOAEL = 14.5 mg/kg/day). 

Inhalation toxicity is assumed to be equivalent to oral toxicity. The level of concern (LOC) for 

all exposures is an MOE of 100>

Dietary Exposure (Food and Water)

The residue chemistry data and environmental fate data are adequate to assess human exposure. 

The assessments are based on reliable data and are not expected to underestimate exposure/risk.

Acute Dietary: The estimated acute dietary exposure to fluopyram from food and drinking water 

is below HED’s level of concern (<100%) for all population subgroups. The acute dietary

analysis is an unrefined conservative assessment that includes tolerance residue levels, the 

assumption of 100% crop treated, and processing factors (empirical and default). The acute 

estimated drinking water concentration (EDWC) was incorporated directly into the dietary

assessment (97.6 μg/L) and was calculated by PRZM-GW (Pesticide Root Zone Model- Ground 

Water) modeling. Combined dietary exposure from food and drinking water at the 95th

percentile of exposure utilized 19% of the acute population adjusted dose (aPAD) for the general 

US population, and 35% of the aPAD for children 1-2 years, the population subgroup with the 

highest estimated acute dietary exposure to fluopyram. 

Chronic Dietary: The estimated chronic dietary exposure to fluopyram from food and drinking 

water is below HED’s level of concern (<100%) for all population subgroups. The chronic 

dietary analysis is a refined assessment that includes average field trial residue levels, percent

crop treated, and processing factors (empirical and default). The chronic EDWC was 

incorporated directly into the dietary assessment (90.5 μg/L) and was calculated by PRZM-GW 

modeling. Chronic dietary exposure utilized 31% of the chronic population adjusted dose 

(cPAD) for the general US population, and 81% of the cPAD for the most highly exposed 

population subgroup (children 1-2 years). 

Residential Exposure

All residential handler risk estimates are not of concern to HED (all margins of exposure 

(MOEs) ≥100), with MOEs ranging from 8,900 to 190,000 for dermal exposures and 260,000 for 

inhalation exposures.

For treated lawns and turf, all residential post-application risk estimates are not of concern to 

HED (all MOEs ≥100), with dermal post-application MOEs for all life stages ranging from 1,000 

to 97,000 and incidental oral post-application MOEs for children 1 to <2 years old ranging from 

2,400 to 1,100,000. For treated gardens, ornamental trees and shrubs, and fruit trees, the dermal 
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post-application MOEs for all life stages range from 2,100 to 33,000 and are not of concern to 

HED (MOEs ≥100).

Aggregate Risk

There is potential for short-term, acute and chronic aggregate exposure to fluopyram. The 

aggregate acute and chronic risks are equivalent to the acute and chronic dietary risks and are not 

of concern. The short-term aggregate exposure results from dietary (which is considered 

background exposure) and residential (which is considered primary) exposure pathways. The 

short-term aggregate MOEs for small children and for adults are both 1,500, and are therefore

not of concern to HED (LOC <100).

Occupational Exposure/Risk

For occupational handlers for agricultural crops, turf, and Christmas trees, all short- and 

intermediate-term risk estimates resulted in margins of exposure (MOEs) ≥100, and therefore, do 

not exceed HED’s level of concern at any level of protection. For dermal exposures at baseline 

personal protective equipment (PPE), MOEs range from 410 to 1,500,000. For dermal exposures 

with gloves, MOEs range from 2,400 to 1,100,000. For inhalation exposures, MOEs range from 

7,400 to 5,400,000. For the seed treatment use on peanut seeds, risk estimates for dermal and 

inhalation short-term occupational handler exposures all resulted in MOEs ≥100, and therefore, 

do not exceed HED’s level of concern, with MOEs ranging from 1,400 to 9,200 for dermal 

exposures and from 1,700 to 17,000 for inhalation exposures.

Short- and intermediate-term dermal post-application exposures and risks to occupational 

workers were estimated using standard values established by HED, since no chemical-specific 

data were submitted. For all occupational post-application scenarios, the dermal MOEs, at day

zero following application, do not exceed HED’s level of concern (MOEs ≥100), with dermal 

MOEs ranging from 270 to 23,000. Additionally, several post-application worker scenarios 

involved with the mechanical harvesting of cotton were assessed. The dermal exposures to these 

harvesters of cotton resulted in risk estimate MOEs ranging from 3,100,000 to 17,000,000, which 

also do not exceed HED’s level of concern (MOEs ≥100).

Based on the Agency's current practices, a quantitative occupational post-application inhalation 

exposure assessment was not performed for fluopyram at this time. If new policies or procedures 

are put into place, the Agency may revisit the need for a quantitative occupational postapplication inhalation exposure assessment for fluopyram.

Restricted Entry Interval (REI): The 12-hour REI that appears on the proposed labels is

adequate to protect for worker exposure.

Review of Human Research

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

intentionally exposed to a pesticide or other chemical. These studies (Appendix C) have been 

determined to require a review of their ethical conduct, and one of these studies is also subject to 

review by the Human Studies Review Board. All of the listed studies have received the 

appropriate review.
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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).

2.0 HED Recommendations

Pending submission of a revised Section B (see Section 2.3, Label Recommendations), a revised 

Section F (see Section 2.2.3, Recommended Tolerances), and an analytical reference standard 

(see Section 2.1 under Submittal of Analytical Reference Standards), there are no issues that 

would preclude granting Section 3 registration for the requested uses of fluopyram and 

establishing/amending tolerances for fluopyram (both primary and inadvertent) on the requested 

crops.

2.1 Data Deficiencies

Pending submission of an analytical reference standard, there are no data gaps that need to be 

fulfilled for the requested actions. 

OCSPP 860.1650 Submittal of Analytical Reference Standards

An analytical reference standard for the AE C656948-benzamide metabolite must be submitted. 

The registrant is required to submit a reasonable amount of the analytical reference standard for 

the benzamide. The reference standard should be sent to the Analytical Chemistry Lab, which is 

located at Fort Meade, Maryland, to the attention of either 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

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

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

The German multiresidue method DFG Method S 19, a gas chromatography with mass selective 

detection (GC/MSD) method, is the method for the enforcement of tolerances for fluopyram 

residues in/on crop commodities. The method was previously validated using samples of orange 

(fruit), oil seed rape (seeds), wheat (grain), lettuce (head) and dry peas (seeds). For fluopyram in 

these commodities, the limit of quantitation (LOQ) was 0.01 ppm, and the calculated limit of 

detection (LOD) was 0.003 ppm. The method was subjected to independent laboratory

validation (ILV) using samples of cabbage (head), wheat (grain), orange (fruit), and oil seed rape 
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(seed) fortified with fluopyram at 0.01 ppm and 0.10 ppm. The average recoveries were within 

acceptable limits (70-120%), and relative standard deviations (RSDs) were <20%.

A high performance liquid chromatography method with tandem mass spectrometry detection 

(HPLC/MS/MS), Method 01079, has been accepted for the enforcement of tolerances for 

residues of fluopyram and its metabolite, AE C656948-benzamide, in livestock commodities. 

The LOQ is 0.01 ppm and the calculated LOD is 0.003 ppm for each analyte in each matrix. The 

method was adequately validated using cattle milk, fat, muscle, liver, and kidney, and hen whole 

egg fortified with fluopyram and AE C656948-benzamide, each at 0.01 and 0.10 ppm. The 

method was subjected to ILV using samples of milk, eggs, beef muscle, and beef liver fortified 

with fluopyram and AE C656948-benzamide, each at 0.01 and 0.10 ppm (D387587, L. Cheng, 

09/23/2011).

2.2.2 International Harmonization

The tolerance definitions are harmonized among the US, Canada, and Codex for all plant and 

livestock commodities. 

Harmonization with Codex is not possible because the recommended US tolerances are for crop 

groups/subgroups and are higher than the Codex maximum residue limits (MRLs) which are 

established mostly on the representative crops of the crop group/subgroup, except pome fruits, 

peach subgroup and tree nuts. The US tolerance on subgroup 13-07F can be increased to 2.0 to 

harmonize with Canada and Codex (grape) MRL. There are Codex maximum residue levels

MRLs established on berries (blackberry and raspberry 3 ppm), dry beans (0.07 ppm), broccoli 

and Brussels sprouts (0.3 ppm), head cabbage (0.15 ppm), cauliflower (0.09 ppm), carrot (0.4 

ppm), cherry (0.7 ppm), cucumber (0.5 ppm), dried grapes (currants, raisins and sultanas 5 ppm), 

grapes (2 ppm), lettuce (head and leaf 15 ppm), leek (0.15 ppm), onion bulb (0.07 ppm), peach 

subgroup (1 ppm), peanut (0.3 ppm), plums (0.5 ppm), pome fruits (0.5 ppm), potato (0.03 ppm), 

rapeseed (1 ppm), strawberry (0.4 ppm), sugar beet (0.04 ppm), tomato (0.4 ppm), and tree nuts 

(0.04 ppm). 

The established Canadian MRLs and the existing US tolerances are mostly similar. Canada and 

the US have received similar petitions and the MRLs are harmonized for almost all proposed 

crops, except soybean seed, crop subgroup 6C, crop subgroup 8-10A, crop subgroup 9B, crop 

group 15, herb subgroup 19A, and subgroup 20A (Refer to Appendix F). Mainly, the differences 

are due to different use patterns and policies.

The US and Codex/Canadian livestock MRLs are not harmonized due to different diets and 

different proposed/established uses.

2.2.3 Recommended Tolerances

HED has reviewed the available residue data and has determined the appropriate tolerance levels 

for residues of fluopyram to be established in/on the following commodities as indicated in Table 

2.2.3.1. The recommended tolerance expression is as stated in 40 CFR §180.661 (a), (b), and 

(d), and this expression agrees with the S. Knizner Memo of 05/27/2009.
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Table 2.2.3.1. Tolerance Summary for Fluopyram.

Commodity Proposed Tolerance 

(ppm)

Recommended/ 

Harmonized 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

ARTICHOKE, GLOBE 4.00 4.0 Artichoke, globe

Aspirated Grain Fractions 50.00 50 Grain, aspirated grain fractions

PEANUT 0.20 0.20 Peanut 

HOPS, Dried Cone 60.00 60 Hop, dried cones

SUGARCANE, cane 0.08 0.08 Sugarcane, cane

Tolerances need to be expressed 

in terms of indirect or 

inadvertent residues of 

fluopyram. Use limited to Region 

3.

VEGETABLES ROOT, 

Except Sugar Beets

0.30 0.30 Vegetable, root, except sugar 

beet, subgroup 1B

SUGARBEET, ROOTS 0.09 0.10 Sugarbeet, roots

VEGETABLES TUBEROUS 

and CORM 

0.10 0.10 Vegetable, tuberous and corm, 

subgroup 1C

POTATO, Wet Peel 0.30 0.30 Potato, wet peel

VEGETABLES, leaves of root 

and tuber

30.00 30 Vegetable, leaves of root and 

tuber, group 2

VEGETABLES, BULB, 

Onion, Bulb

0.30 0.40 Onion, bulb, subgroup 3-07A

VEGETABLES, BULB, 

Onion, green

15.00 15 Onion, green, subgroup 3-07B

VEGETABLES LEAFY, 

Lettuce, including radicchio

20 40 Leafy greens subgroup 4A 

VEGETABLES LEAFY, 

Spinach, including amaranth, 

chervil, chrysanthemum, corn 

salad, cress, dandelion, endive, 

orach and purslane1

40.0

VEGETABLES LEAFY, 

Celery, including Chinese 

celery and Swiss chard

20.0 20 Leaf petioles subgroup 4B

VEGETABLES, Head & Stem 

Brassica, 

4.00 4.0 Brassica, head and stem, 

subgroup 5A

VEGETABLES, Leafy 

Brassica Greens 

50.00 50 Brassica, leafy greens, subgroup 

5B

SOYBEAN, seed 0.30 0.30 Soybean, seed

VEGETABLES, Legume, 

Edible podded

4.00 4.0 Vegetable, legume, edible 

podded, subgroup 6A

VEGETABLES, Legume, 

succulent shelled peas and

beans

0.20 0.20 Pea and bean, succulent shelled, 

subgroup 6B
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Table 2.2.3.1. Tolerance Summary for Fluopyram.

Commodity Proposed Tolerance 

(ppm)

Recommended/ 

Harmonized 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

VEGETABLES, Legume, 

Dried bean, except soybeans 

and dried peas

0.70 0.15 Bean, dry

VEGETABLES, Fruiting, 

Tomato subgroup

1.0 1.0 Tomato subgroup 8-10A

VEGETABLES, Fruiting, 

Pepper/eggplant subgroup

3.0 4.0 Pepper/eggplant subgroup 8-

10B

VEGETABLES, Cucurbit, 

Melon subgroup

0.90 1.0 Melon subgroup 9A

To harmonize with Canada

VEGETABLES, Cucurbit, 

Cucumber/Squash subgroup

0.60 0.60 Squash/cucumber subgroup 9B

FRUIT, Citrus 0.90 1.0 Fruit, citrus, group 10-10

CITRUS Oil 8.0 8.0 Citrus, oil

FRUIT, Pome 0.80 0.80 Fruit, pome, group 11-10

FRUIT, Stone, Cherry 

subgroup

2.00 2.0 Cherry subgroup 12-12A

FRUIT, Stone, Peach subgroup 1.00 1.0 Peach subgroup 12-12B

FRUIT, Stone, Plum subgroup 0.50 0.50 Plum subgroup 12-12C

BERRIES AND SMALL 

FRUIT, Caneberry

5.00 5.0 Caneberry subgroup 13-07A

BERRIES AND SMALL 

FRUIT, Bushberry

7.00 7.0 Bushberry subgroup 13-07B

BERRIES AND SMALL 

FRUIT, Small fruit vine 

climbing, except fuzzy kiwi

1.50 2.0 Fruit, small vine climbing, 

except fuzzy kiwifruit, subgroup 

13-07F

To harmonize with 

Codex/Canada

RAISIN 4.00 3.0 Grape, raisin

BERRIES AND SMALL 

FRUIT, Low Growing Berry

2.00 2.0 Berry, low growing, except 

cranberry, subgroup 13-07G

NUT, Tree 0.04 0.05 Nut, tree, group 14-12

To harmonize with Canada

ALMOND, HULLS 10.00 10 Almond, hulls

GRAIN, Cereal, except rice 

and sorghum, GRAIN

0.90 4.0 Grain, cereal, group 15, except 

corn and rice 

0.02 Corn, field, grain
Fluopyram Human Health Risk Assessment DP No. D421926

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Table 2.2.3.1. Tolerance Summary for Fluopyram.

Commodity Proposed Tolerance 

(ppm)

Recommended/ 

Harmonized 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

0.02 Corn, pop, grain

0.01 Corn, sweet, kernel plus cob with 

husks removed 

Wheat, milled by-products 2.0 None Covered by the Crop group 15 

tolerance

GRAIN, Cereal, except rice, 

FORAGE, FODDER, HAY 

and STRAW,

20.00 20 Grain, cereal, forage, fodder and 

straw, group 16

HERBS AND SPICES and 

Spices, Herb Subgroup

70.00 40 Herb subgroup 19A

HERBS, Dried 40.00

Dill seed,

Including – Caraway seed, 

celery seed, coriael seed,

lovage seed, mustard seed and 

poppy seed1

70 70 Dill, seed; caraway seed; celery 

seed; coriander, seed; lovage 

seed; mustard seed; poppy seed

OILSEEDS, RAPESEED 

(CANOLA)

0.7 5.0 Rapeseed subgroup 20A

OILSEEDS, SUNFLOWER, 

SEED

0.70 0.70 Sunflower subgroup 20B

OILSEEDS, COTTONSEED 0.80 0.80 Cottonseed subgroup 20C

COTTON, Gin By-products 30.00 30 Cotton, gin byproducts

Tolerances proposed for residues of fluopyram and its metabolite 2-(trifluoromethyl)benzamide, expressed 

in parent equivalents:

CATTLE MEAT, BY 

PRODUCTS 40.00 7.5 Cattle, meat byproducts

CATTLE, FAT 4.00 0.70 Cattle, fat

CATTLE, MEAT 4.00 0.80 Cattle, meat

MILK, CATTLE 2.00 0.40 Milk

CHICKEN MEAT, 

BYPRODUCTS 0.40 0.16 Poultry, meat byproducts

CHICKEN, FAT 0.15 0.04 Poultry, fat

CHICKEN, MEAT 0.10 0.04 Poultry, meat

EGGS, CHICKEN 0.20 0.08 Egg

HOG, BY PRODUCTS 0.40 0.20 Hog, meat byproducts

HOG, FAT 0.04 0.20 Hog, fat

HOG, MEAT 0.04 0.02 Hog, meat 

Horse MEAT, BY 

PRODUCTS 40.00 7.5 Horse, meat byproducts

Horse, FAT 4.00 0.70 Horse, fat

Horse, MEAT 4.00 0.80 Horse, meat

Goat, BY PRODUCTS 40.00 7.5 Goat, meat byproducts
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Table 2.2.3.1. Tolerance Summary for Fluopyram.

Commodity Proposed Tolerance 

(ppm)

Recommended/ 

Harmonized 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Goat, FAT 4.00 0.70 Goat, fat

Goat, MEAT 4.00 0.80 Goat, meat

Sheep, BY PRODUCTS 40.00 7.5 Sheep, meat byproducts

Sheep, FAT 4.00 0.70 Sheep, fat

Sheep, MEAT 4.00 0.80 Sheep, meat

1As per HED SOP 2000.1 Crop Group/Subgroup Field Trial Data translation (9/12/2000

Table 2.2.3.2. Tolerance Summary for Fluopyram.

Commodity Established

Tolerance 

(ppm)

Proposed 

Tolerance

(ppm)

HEDRecommended 

Tolerance 

(ppm)

Comments 

(correct commodity definition)

40 CFR §180.661 (1)

Almond, hull

8.0 10 10

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Apple

0.30

Proposed 

as crop 

group

0.80

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Apple, wet pomace 0.60 None None Revoke covered under recommended 

tolerance as crop group 11.

Bean, dry

0.09

Proposed 

as crop 

subgroup 

(0.7)

0.15

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Beet, sugar, root

0.04 0.09 0.10

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Cotton, gin 

byproducts 0.70 30.0 30

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Cotton, undelinted 

seed 0.01

Proposed 

as crop 

group

0.80

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Cherry

0.60

Proposed 

as crop 

subgroup

2.0

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Grape, wine

2.0

Proposed 

as crop 

subgroup

2.0

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Nut, tree, group 14

0.05 0.04 0.05

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Peanut

0.09 0.20 0.20

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Pistachio 0.05 Proposed 0.05 Revoke existing tolerance upon 
Fluopyram Human Health Risk Assessment DP No. D421926

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Table 2.2.3.2. Tolerance Summary for Fluopyram.

Commodity Established

Tolerance 

(ppm)

Proposed 

Tolerance

(ppm)

HEDRecommended 

Tolerance 

(ppm)

Comments 

(correct commodity definition)

as crop 

group

establishing tolerances as indicated 

above.

Potato

0.02

Proposed 

as crop 

subgroup 

0.10

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Potato, processed 

potato waste 0.08 None None Revoke covered under recommended tolerance as crop subgroup 1C.

Soybean, seed

0.04 0.30 0.30

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Strawberry

1.5

Proposed 

as crop 

subgroup

2.0

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

Watermelon

1.0

Proposed 

as crop 

subgroup

1.0

Revoke existing tolerance upon 

establishing tolerances as indicated 

above.

40 CFR §180.661 (2)

Cattle, fat 0.05 4.0 0.70 For all (except hog meat), higher 

tolerances than established were

recommended. Revoke existing 

tolerances upon establishing tolerances as 

indicated.

Cattle, meat 0.05 4.0 0.80

Cattle, meat 

byproducts 0.40 40 7.5

Egg 0.06 0.20 0.08

Goat, fat 0.11 4.0 0.70

Goat, meat 0.15 4.0 0.80

Goat, meat 

byproducts 1.1 40 7.5

Hog, fat 0.02 0.04 0.20

Hog, meat 0.02 0.04 0.02

Hog, meat 

byproducts 0.03 40 0.20

Horse, fat 0.11 4.0 0.70

Horse, meat 0.15 4.0 0.80

Horse, meat 

byproducts 1.1 40 7.5

Milk 0.06 2.0 0.40

Poultry, fat 0.03 0.15 0.04

Poultry, meat 0.03 0.10 0.04

Poultry, meat 

byproducts 0.10 0.40 0.16

Sheep, fat 0.11 4.0 0.70

Sheep, meat 0.15 4.0 0.80

Sheep, meat 

byproducts 1.1 40 7.5

40 CFR §180.661 (d) Indirect or inadvertent residues

Canola, seed 1.8 Revoke Revoke existing tolerance upon 

establishing tolerances under 40 CFR

§180.661 (1)

Grain, cereal, 

except rice, group 

0.03
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Table 2.2.3.2. Tolerance Summary for Fluopyram.

Commodity Established

Tolerance 

(ppm)

Proposed 

Tolerance

(ppm)

HEDRecommended 

Tolerance 

(ppm)

Comments 

(correct commodity definition)

15

Grain, cereal, 

forage, fodder and 

straw, group 16

2.0

Soybean, forage 0.80

Soybean, hay 3.0

Tolerance that Need to be Proposed 40CFR§180.661 (c) Regional Registration Indirect or inadvertent 

residues

Sugarcane, cane None 0.08 0.08 Propose tolerance for Regional 

Registration (Region 3)

2.2.4 Revisions to Petitioned-For Tolerances

The petitioned for tolerances differ from the recommended tolerances for sugar beet roots, onion 

bulbs, leafy greens subgroup 4A, crop subgroup 6C, fruiting vegetables (8-10B), melon subgroup 

9A, citrus, subgroup 13-07F, raisin, tree nuts, crop group 15, herb subgroup 19A, dill seed, and 

subgroup 20A. 

For onion bulbs, citrus, tree nuts, crop group 15, rapeseed subgroup 20A, the Organization for 

Economic Cooperation and Development (OECD) statistical calculation procedures applied to 

the field trial residue data provided a different value than the proposed values.

For crop group 15 (sorghum) and rapeseed subgroup 20A (canola), the petitioner excluded a 

field trial as an outlier based on statistical tests. However, the trials could not be excluded by the 

Agency since there were no abnormal field conditions. In addition, for crop group 15, the 

minimum (sweet corn 0.01 ppm) and the maximum (wheat 0.72 ppm) residues differ by more 

than 5x. Therefore, the tolerance level (0.09 ppm) is not appropriate to establish a crop group 

tolerance. 

The proposed tolerance expressions on leafy vegetables and leafy petioles were not appropriate. 

The available data support a tolerance of 40 ppm for residues of fluopyram in/on crop subgroup 

4A and at 20 ppm on crop subgroup 4B. 

The petitioner has requested to establish tolerances on dill seed, including caraway seed, celery

seed, coriander seed, fennel seed, lovage seed, mustard seed and poppy seed. The request to 

translate from dill seed to these commodities is accepted since the exposures from these 

commodities are insignificant. However, separate tolerances, at 70 ppm, are needed for dill, 

seed; caraway seed; celery seed; coriander, seed; lovage seed; mustard seed; and poppy seed.

For harmonization purposes, tolerances for sugar beet roots, melon subgroup 9A, and subgroup 

13-07F were slightly increased and tolerances for tree nuts were slightly decreased. 

Separate tolerances were proposed for herbs and spices, subgroup 19A and dried herbs. Only 
Fluopyram Human Health Risk Assessment DP No. D421926

Page 17 of 87

one tolerance is possible for fresh and dried herbs; therefore, the higher value (40 ppm) is 

recommended.

The proposed grape, raisin tolerance of 4.0 ppm is not supported by the data. A tolerance of 3.0 

ppm needs to be proposed based on the HAFT (0.948 ppm) for grape and processing factor of 

2.4. 

The proposed tolerance for sugarcane, cane (0.08 ppm) must be revised to be specified in terms 

of indirect or inadvertent residues of fluopyram for regional registration. 

All proposed tolerances for livestock commodities are too high. The petitioner must propose 

tolerances as specified above in Table 2.2.3.1.

The proposed tolerances should be revised to reflect the correct commodity definitions as 

specified above in Table 2.2.3.1.

2.3 Label Recommendations

Some of the proposed products for fluopyram are intended for use by residential applicators on 

home lawns or residential areas, but require certain clothing and/or PPE to be worn. Thus, 

standard assumptions for residential/consumer applicator specific assessments, such as wearing 

shorts and a t-shirt without PPE like chemical-resistant gloves or respirators, would represent 

non-compliance with currently registered products. If products containing fluopyram are meant 

to be marketed towards and applied by residential handlers on residential turf, ornamentals, fruit 

trees, or gardens, HED recommends that the label requirements for clothing and/or PPE be 

reevaluated or separate consumer-specific labels be developed.

The proposed label for EPA Reg. No. 264-1078 must be revised as follows:

 to modify the proposed PHIs for dried bean seeds (crop subgroup 6C) and soybean seed 

to 14 days;

 to revise “Dried shelled pea and bean” to “Dried shelled bean” under legume vegetables 

(except soybeans) listing; 

 to modify “May be applied broadcast the day of harvest (field and greenhouse uses) with 

“May be applied broadcast the day of harvest (field uses).

 to add a separate entry for dill seed including (caraway seed, celery seed, coriander seed, 

fennel seed, lovage seed, mustard seed and poppy seed) with the same use pattern as 

proposed under the “Herbs and dill seed” listing with a 14-day PHI instead of a 3-day

PHI;

 to modify “legume vegetables (including soybeans)” with “legume vegetables (except 

cowpeas and dried peas); soybeans) throughout the use directions of LUNA PRIVILEGE 

(labeled uses, rotational crops etc)

 to modify the rotational crop restrictions to replace the statement “Sugarcane and alfalfa 

may be planted after 14 days” with “Alfalfa may be planted after 14 days and sugarcane 

may be planted after 14 days in Region 3” 

 to remove “Do not graze or feed soybean forage and hay to livestock after treating with 
Fluopyram Human Health Risk Assessment DP No. D421926

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Luna Privilege” from the use directions of cotton seed treatment; 

 to modify “herbs and spices (except black pepper)” to “herbs (fresh and dried); dill seed

including (caraway seed, celery seed, coriander seed, fennel seed, lovage seed, mustard 

seed and poppy seed)” from the use directions of peanut seed treatment plant back 

restrictions. 

The product labels for EPA Reg. Nos. 264-1084 and 264-1085 must be amended as follows:

 to specify that sugarcane may be rotated 30-days after application in Region 3.

 to modify “legume vegetables (including soybeans)” to “legume vegetables (except 

cowpeas and dried peas); soybeans) under rotational crops.

The product label for EPA Reg. No. 264-1091 should be amended as follows:

 to modify “legume vegetables (including soybeans)” to “legume vegetables (except 

cowpeas and dried peas); soybeans) under rotational crops;

 to specify that sugarcane may be rotated 120-days after application in Region 3.

 to delete the sentence “Do not allow livestock to graze treated area for 14 days and do not 

harvest for food or feed within 14 days of application” “Under barley; corn (sweet corn, 

field corn, field corn grown for seed, and popcorn); and wheat use directions. The PHI’s 

for these crops are not 14-days. 

The product label for EPA Reg. No. 264-1090 must be amended as follows: 

 to correct the listed crops in the Brassica leafy vegetable crop subgroups: (head and stem 

subgroup): “Chinese cabbage (bok choy)” should be removed; and in the leafy greens 

subgroup, “Chinese Cabbage” should be revised to “Chinese cabbage (bok choy)” 

 to add a separate entry for dill seed including (caraway seed, celery seed, coriander seed, 

fennel seed, lovage seed, mustard seed and poppy seed) with the same use pattern as 

proposed under the “Herbs and dill seed” listing with a 14-day PHI instead of a 3-day

PHI;

 to specify that sugarcane may be rotated 14-days after application in Region 3.

The product label for EPA Reg. No. 264-1167 must be amended as follows: 

 to modify “legume vegetables (including soybeans)” with “legume vegetables (except 

cowpeas and dried peas); soybeans) under rotational crop restrictions listing

 to modify the rotational crop restrictions to replace the statement “Sugarcane and alfalfa 

may be planted after 14 days” with “Alfalfa may be planted after 14 days and sugarcane 

may be planted after 14 days in Region 3” 

3.0 Introduction

Fluopyram (AE C656948) is a Group 7 fungicide with a broad spectrum of activity against 

numerous fungal diseases, including Ascomycetes, leaf spots, molds, scab, Alternaria, Septoria, 

Monilinia, Botrytis, Sclerotinia, and powdery mildews in a wide range of crops and plants. 

Fluopyram represents is a pyridylethylamide and its biochemical mode of action has been shown 

to rely on the inhibition of the enzyme succinate dehydrogenase (complex II) within the fungal 

mitochondrial respiratory chain, thus blocking electron transport. 
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3.1 Chemical Identity

Table 3.1. Fluopyram Nomenclature.

Chemical structure

Common name Fluopyram

Company experimental name AE C656948

IUPAC name N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridyl]ethyl]-α,α,α-trifluoro-o-toluamide

CAS name N-[2-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]ethyl]-2-

(trifluoromethyl)benzamide

CAS registry number 658066-35-4

End-use product (EP) 264-1167 Fluopyram ST; 264-1078 Luna® Privilege; 264-1084 Propulse; 264-

1085 Luna Tranquility; 264-1090 Luna Sensation; 264-1091 Luna Experience

Chemical structure of AE 

C656948-benzamide

metabolite (included in the 

tolerance expression for 

livestock commodities)

2-(Trifluoromethyl)-benzamide

3.2 Physical/Chemical Characteristics

Fluopyram is not a highly lipophilic molecule (log KOW = 3.3) and is not expected to pass the 

dermal barrier, pass through human milk, or bioaccumulate in significant quantity. Empirical 

dermal absorption data estimate that less than 2% is absorbed dermally in humans and 

metabolism data in rats demonstrate rapid absorption with ~98% elimination with 72 hours of 

administration. Fluopyram is persistent in soil (its half-life is 464 days) with very little abiotic 

degradation. Fluopyram, the major environmental residue and only compound modeled for 

drinking water exposure, is mobile, soluble, and stable in water. A summary of the physical and 

chemical properties of fluopyram are presented in Appendix B.

3.3 Pesticide Use Pattern

Fluopyram is currently registered on a variety of agricultural food crops, including apple, cherry 

(sweet and tart), cotton, dried beans, peanut, potato, strawberry, sugar beets, tree nuts, 

watermelon, viniferous variety grapes, and for seed treatment to cotton and soybean. There are 

currently no existing residential uses of fluopyram.

The registrant, Bayer CropScience, is requesting the addition of new uses of fluopyram on 

registered liquid formulation product labels, as follows: 

CF3

N

H

O

N

Cl CF3

CF3

NH2

O
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1) The Luna®Privilege label (4.16 lb ai/gal) [EPA Reg. No. 264-1078] contains only the 

active ingredient fluopyram. New uses are proposed on artichoke (globe), Brassica

(cole) leafy vegetables, bulb vegetables, canola, carrot, cereal grains (except rice), citrus, 

cotton, cucurbit vegetables, fruiting vegetables, ginseng, grapes and small vines fruits 

(except fuzzy kiwifruit), herbs and spices (except black pepper), hops, leafy vegetables, 

legume vegetables (including soybean), peanut, pome fruits, potato and other root, 

tuberous and corm vegetables, small berries (caneberries and bushberries), stone fruit, 

strawberry and other low growing berries (except cranberries), sugar beet, sunflower 

subgroup, and tree nuts. Additionally, the Luna Privilege label is also proposed for use as 

a seed treatment to peanuts.

2) The PropulseTM label (1.67 lb ai/gal) [EPA Reg. No. 264-1084] contains the active 

ingredients fluopyram and prothioconazole. New uses are proposed on barley, 

buckwheat, bushberry subgroup, canola, corn, crambe, cucurbit vegetables, field mustard, 

Indian rapeseed, low growing berries (except strawberries and cranberries), millet (pearl 

and proso), oats, rapeseed, rye, soybean, triticale, and wheat (spring, durum, and winter).

3) The Luna®Tranquility label (1.04 lb ai/gal) [EPA Reg. No. 264-1085] contains the 

active ingredients fluopyram and pyrimethanil. New uses are proposed on bulb 

vegetables, ginseng, lemons, pome fruit, tuberous and corm vegetables, small berries 

(caneberries and bushberries), stone fruit (except cherries), strawberries and other lowgrowing berries (except cranberries), and tomato.

4) The Luna®Sensation label (2.1 lb ai/gal) [EPA Reg. No. 264-1090] contains the active 

ingredients fluopyram and trifloxystrobin. New uses are proposed on artichoke (globe), 

Brassica (head and stem subgroup), Brassica (leafy greens subgroup), carrot, citrus, 

cucurbit vegetables, fruiting vegetables, ginseng, grapes and small vines fruits (except 

fuzzy kiwifruit), herbs and spices (except black pepper), hops, leafy vegetables (leafy

greens subgroup), leafy vegetables (leaf petioles subgroup), pome fruits, potato and other 

root, tuberous and corm vegetables, soybean, stone fruit, strawberry and other low 

growing berries (except cranberries), and wheat.

5) The Luna®Experience label (1.67 lb ai/gal) [EPA Reg. No. 264-1091] contains the 

active ingredients fluopyram and tebuconazole. New uses are proposed on barley, bean 

(fresh and dry, except succulent shelled), bulb vegetable, corn (sweet corn, field corn, 

field corn grown for seed, and popcorn), cotton, cucurbit vegetables, fruiting vegetables, 

grapes and small vines fruits (except fuzzy kiwifruit), hops, leafy Brassica greens, okra, 

pome fruits, soybean, stone fruit, sunflower, and wheat.

Bayer CropScience, is also requesting the registration of several new end-use products 

containing the following new non-food uses of fluopyram: turf grass (golf courses, sod farms, 

sports fields, residential, industrial, municipal, commercial, and other turf grass areas), 

ornamentals (in residential and commercial landscapes, interiorscapes, field grown and container 

ornamentals, in nurseries, and greenhouses, lathhouses, shadehouses, containers and other 

enclosed structures), and Christmas trees. These new end-use product labels also include 
Fluopyram Human Health Risk Assessment DP No. D421926

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proposed uses on citrus, grapes and small vine fruits, pome fruits, stone fruits, sunflower, and 

tree nuts. All of these uses can be used by occupational, as well as residential, handlers. The 

proposed end-use product labels are as follows: 1) Fluopyram 500 SC (4.16 lb ai/gal) [EPA File 

Symbol 432-RLGI] which contains the active ingredient fluopyram; 2) FLU+TFS SC 500 (2.1 lb 

ai/gal) [EPA File Symbol 432-RLGT] which contains the active ingredients fluopyram and 

trifloxystrobin; 3) FLU+TFS SC 32.5 (0.104 lb ai/gal) [EPA File Symbol 432-RLGA] which 

contains the active ingredients fluopyram and trifloxystrobin; 4) FLU+TFS SC 25 (0.104 lb 

ai/gal) [EPA File Symbol 432-RLGL] which contains the active ingredients fluopyram and 

trifloxystrobin; and 5) 13ESP715 3.3 SC (3.34 lb ai/gal) [EPA File Symbol 432-RLUG] which 

contains the active ingredient fluopyram. 

The proposed labels require occupational handlers to wear the following attire and PPE: long 

sleeved shirts, long pants, shoes, socks, and chemical resistant gloves. However, the FLU+TFS 

SC 32.5 and FLU+TFS SC 25 labels do not require the use of gloves. Additionally, for seed 

treatment of peanuts, the Luna®Privilege label requires water proof gloves for seed treatment 

activities and no gloves for baggers and bag sewers.

On all registered and proposed labels the proposed REI for new uses is 12 hours. 

The proposed uses and application rates are described in detail in Table 3.3.1.
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Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Agricultural Use Sites

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078] Artichoke (globe)

0.104 to 0.222

(3.2 to 6.84 fl oz/A)

NS 0.446 0

Retreatment interval of 7 

Luna Sensation to 10 days.

(2.1 lb ai/gal) [264-

1090]

0.0660 to 0.125

(4.0 to 7.6 fl oz/A)

Ground, aerial 

or chemigation

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

Brassica Leafy Vegetables Head and Stem Subgroup:

Broccoli, Chinese broccoli (Gai Lon), Brussels sprouts, 

Cabbage, Chinese cabbage (Napa), Chinese cabbage (Bok 

choy), Chinese mustard cabbage (Gai choy), Cauliflower, 

Cavalo broccolo, Kohlrabbi. Including all cultivars and/or 

hybrids of these.

0.0660 to 0.125

(4.0 to 7.6 fl oz/A) NS 0.446 0

Retreatment interval of 7 

to 10 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Brassica (cole) Leafy Vegetables: Broccoli, Broccoli raab 

(Rapini), Brussels sprouts, Cabbage, Cauliflower, Cavalo 

broccoli, Chinese broccoli (Gai Lon), Chinese cabbage (Bok 

choy), Chinese cabbage (Napa), Chinese mustard cabbage 

(Gai choy), Collards, Kale, Mizuna, Mustard greens, Mustard 

spinach, Rape greens, and Turnip greens. Including all 

cultivars and/or hybrids of these.

0.104 to 0.222

(3.2 to 6.84 fl oz/A) NS 0.446 0

Retreatment interval of 5 

to 10 days.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

Brassica Leafy Vegetables Leafy Greens Subgroup: 

Broccoli raab (Rapini), Chinese cabbage, Collards, Kale, 

Mizuna, Mustard greens, Mustard spinach, Rape greens, and 

Turnip greens. Including all cultivars and/or hybrids of these.

0.0660 to 0.125

(4.0 to 7.6 fl oz/A) NS 0.446 0

Retreatment interval of 7 

to 14 days.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Leafy Brassica Greens (Crop Subgroup 5B): Broccoli raab 

(rapini), Chinese cabbage (bok choy), Collards, Kale, 

Mizuma, Mustard greens, Mustard spinach, Rape greens, and 

Turnip greens,

0.0783 to 0.112

(6.0 to 8.6 fl oz/A) NS 0.446 7

Retreatment interval of 7 

to 14 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Bulb Vegetables: Chive fresh leaves, Chive fresh leaves 

(Chinese), Daylily bulb, Elegans hosta, Fritillaria (bulb and 

leaves), Garlic bulb, Garlib bulb (Great headed and Serpent), 

Kurrant, Leek, Leek (Lady’s and Wild), Lily bulb, Onion 

(Beltsville bunching, Bulb, Chinese bulb, Fresh, Green, 

Macrostem, Pearl, Potato bulb, Tree tops, and Welsh), Shallot 

(bulb and fresh leaves). Including all cultivars and/or hybrids 

of these.

0.13 to 0.222

(4.0 to 6.84 fl oz/A) NS 0.446 0

Retreatment interval of 5 

to 7 days.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Bulb Vegetables: Chive fresh leaves, Chive fresh leaves 

(Chinese), Daylily bulb, Elegans hosta, Fritillaria (bulb and 

leaves), Garlic bulb, Garlic bulb (Great headed and Serpent), 

Kurrant, Leek, Leek (Lady’s and Wild), Lily bulb, Onion 

0.104 to 0.167

(8.0 to 12.8 fl oz/A) NS 0.446 7

Retreatment interval of 10 

to 14 days.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 23 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

(Beltsville bunching, Bulb, Chinese bulb, Fresh, Green, 

Macrostem, Pearl, Potato bulb, Tree tops, and Welsh), Shallot 

(bulb and fresh leaves).

Luna Tranquility

(1.04 lb ai/gal) 

[264-1085]

Bulb Vegetables: Dry Bulb Onion, Eschalots, Green Onion, 

Garlic, Leeks, Japanese Bunching Onion, Scallions, Shallot, 

and Spring Onion.

0.130 to 0.219

(16.0 to 27.0 fl oz/A) NS 0.446 7

Retreatment interval of 7 

to 14 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Canola subgroup: Borage, Crambe, Cuphea, Echium, Flax 

seed, Gold of pleasure, Hare’ ear mustard, Lesquerella, 

Lunaria, Meadowfoam, Milkweed, Mustard seed, Oil radish, 

Poppy seed, Rapeseed, Sesame, and Sweet rocket. Including 

cultivars, varieties, and/or hybrids of these.

0.222

(6.84 fl oz/A) NS 0.446 14 Retreatment interval of 12 to 14 days.

Ground, aerial 

or chemigation

Propulse

(1.67 lb ai/gal) 

[264-1084]

Canola Rapeseed, Indian Rapeseed, Field Mustard, 

Crambe

0.177

(13.6 fl oz/A) NS 0.446 36 Retreatment interval of 14 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078] Carrot

0.156 to 0.222

(4.8 to 6.84 fl oz/A)

NS 0.446

0

Retreatment interval of 5 

to 7 days. Tops or greens 

from this crop may be 

utilized for food or feed.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

0.0660 to 0.125

(4.0 to 7.6 fl oz/A) 7

Retreatment interval of 14 

days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Cereal Grains (except Rice): Barley, Buckwheat, Corn 

(Sweet Corn, Field Corn, Field Corn Grown for Seed, and 

Popcorn), Millet, (Pearl and Proso), Oats, Rye, Sorghum, 

Sudan Grass, Teosinte, Triticale, and Wheat.

0.222

(6.84 fl oz/A) NS 0.446 14

Retreatment interval of 14 

days. Do not allow 

livestock to graze treated 

area for 14 days and do 

harvest for food or feed 

within 14 days of 

application.

Ground, aerial 

or chemigation

Propulse

(1.67 lb ai/gal) 

[264-1084]

Barley 0.177

(13.6 fl oz/A) NS 0.446 32 Retreatment interval of 14 days.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Barley 0.112

(8.6 fl oz/A) NS 0.446 30

Retreatment interval not 

specified. Do not allow 

livestock to graze treated 

area for 14 days and do 

not harvest for food or 

feed within 14 days of 

application.

Ground or 

aerial

Propulse

(1.67 lb ai/gal) 

[264-1084]

Buckwheat, Millet (Pearl and Proso), Oats, Rye 0.177

(13.6 fl oz/A) NS 0.446 30

Ground, aerial Propulse Wheat 0.177 NS 0.446 30 Retreatment interval of 14 
Fluopyram Human Health Risk Assessment DP No. D421926

Page 24 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

or chemigation (1.67 lb ai/gal) 

[264-1084]

(13.6 fl oz/A) days. 

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

Wheat 0.112

(6.84 fl oz/A) NS 0.446 35

Retreatment interval of 14 

to 21 days. If two 

applications or 0.224 lb 

ai/A/yr are applied, do not 

allow livestock to graze 

within the treated area and 

do not harvest the treated 

crop for forage or hay. If 

one application or 0.112 

lb ai/A/yr are applied, do 

not allow livestock to 

graze within the treated 

area within 30 days after 

application, and do not 

harvest the treated crop 

for forage within 30 days 

after application or for hay 

within 45 days after 

application.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Wheat 0.112

(8.6 fl oz/A) NS 0.446 30

Retreatment interval not 

specified. Do not allow 

livestock to graze treated 

area for 14 days and do 

not harvest for food or 

feed for 14 days of 

application.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Forage, Fodder or Straw from Cereal Grains: Barley, 

Buckwheat, Corn (Sweet Corn, Field Corn, Field Corn Grown 

for Seed, and Popcorn), Millet, (Pearl and Proso), Oats, Rye, 

Sorghum, Sudan Grass, Teosinte, Triticale, and Wheat.

0.222

(6.84 fl oz/A) NS 0.446 14

Retreatment interval of 14 

days. Do not allow 

livestock to graze treated 

area for 14 days and do 

harvest for food or feed 

within 14 days of 

application.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Citrus: Australian desert lime, Australian finger-lime, Brown 

River finger lime, Calamondin, Citron, Citrus hybrids, 

Grapefruit, Japanese summer grapefruit, Kumquat, Lemon, 

Lime, Mediterranean mandarin, Mount white lime, New 

Guinea wild lime, Orange (sour and sweet), Pummelo, 

Russell River lime, Satsuma mandarin, Sweet lime, 

Tachibana orange, Tahiti lime, Tangelo, Tangerine 

0.156 to 0.222

(4.8 to 6.84 fl oz/A) NS 0.446 7

Retreatment interval of 7 

to 21 days. Minimum 30 

day interval between soil 

applications.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 25 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

(Mandarin), Tangor, Trifoliate orange, Uniq fruit, White 

sapote (Casimiroa spp.) and cultivars, varieties, and/or 

hybrids of these.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

Citrus: Calamondin, Citrus Citron, Citrus hybrids (Citrus

spp., includes Chironja, Tangelo and Tangor), Grapefruit, 

Grapefruit, Kumquat, Lemon, Lime, Mandarin (Tangerine), 

Orange (Sweet and Sour), Pummelo, Tangelo, Satsuma 

Mandarin, White Sapote (Casimiroa spp.), and other cultivars 

and/or hybrids of these.

0.125

(7.6 fl oz/A) NS 0.446 7

Retreatment interval of 7 

to 21 days.

Fluopyram 500 SC

(4.16 lb ai/gal) 

[264-RLGI]

Citrus

0.156 to 0.221 lb ai/100 gal/A

4.8 to 6.8 fl oz/100 gal/A

NS

0.446 lb ai/A

13.7 fl oz/A

7

Retreatment interval of 7 

to 21 days. Retreatment 

interval for nematode 

control is 30 days.

FLU+TFS SC 500

(2.10 lb ai/gal) 

[264-RLGT]

0.125 lb ai/100 gal/A

7.6 fl oz/100 gal/A

0.446 lb ai/A

27.3 fl oz/A

FLU+TFS SC 25

(0.104 lb ai/gal) 

[264-RLGL]

0.125 lb ai/100 gal/A

154 fl oz/100 gal/A

0.445 lb ai/A

548 fl oz/A

13ESP715 3.3 SC

(3.34 lb ai/gal) 

[432-RLUG]

0.157 to 0.446 lb ai/100 gal/A

6.0 to 17.1 fl oz/100 gal/A

0.446 lb ai/A

17.1 fl oz/A

Ground, aerial 

or chemigation

Luna Tranquility

(1.04 lb ai/gal) 

[264-1085]

Lemon

0.219

(27.0 fl oz/A) NS 0.446 7

Retreatment interval not 

specified. The use of 

adjuvants is prohibited.

Ground, aerial 

or chemigation

Propulse

(1.67 lb ai/gal) 

[264-1084]

Corn (including Field Corn, Sweet Corn, Popcorn, and 

Field Corn grown for seed) 

0.177

(13.6 fl oz/A) NS 0.446 140

Retreatment interval of 7 

to 14 days. For field corn, 

field corn grown for seed, 

and popcorn, do not apply 

within 14 days of harvest 

for grain or fodder. For 

sweet corn, do not apply 

within 14 days of harvest 

for fodder. Sweet corn 

ears and forage may be 

harvested the same day of 

application.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Corn (Sweet Corn, Field Corn, Field Corn Grown for 

Seed, and Popcorn)

0.167

(12.8 fl oz/A) NS 0.446 See Limits

Retreatment interval of 14 

days. For field corn, field 

corn grown for seed, and 

popcorn, may be applied 

up to 21 days before 

harvest of forage, and 36 
Fluopyram Human Health Risk Assessment DP No. D421926

Page 26 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

days before the harvest of 

grain or fodder. For sweet 

corn, may be applied 

within 7 days before 

harvest of ears or forage, 

and 49 days before the 

harvest of fodder. Do not 

allow livestock to graze 

treated area for 14 days 

and do not harvest for 

food or feed within 14 

days of application.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Cotton Subgroup (20C): Includes cultivars, varieties and 

other hybrids of these.

0.156 to 0.222

(4.8 to 6.84 fl oz/A) NS 0.446 30 Retreatment interval not specified.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Cotton 0.222

(17.0 fl oz/A) NS 0.446 30 Retreatment interval of 7 to 14 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Cucurbit Vegetables: Chayote (fruit), Chinese waxgourd 

(Chinese preserving melon), Citron melon, Cucumber, 

Gherkin (edible, includes Hyotan, Cucuzza, Hechima, 

Chinese okra), Momordica spp. (includes Balsam apple, 

Balsam pear, Bitter melon, Chinese cucumber), Muskmelon 

(hybrids and/or cultivars of Cucumis melo including True 

cantaloupe, Cantaloupe, Casaba, Crenshaw melon, Golden 

Pershaw melon, Honeydew melon, Honey balls, Mango 

melon, Persian melon, Pineapple melon, Santa Claus melon, 

Snake melon), Pumpkin, Squash (includes Summer Squash 

types such as: Crookneck squash, Scallop squash, Straight 

neck squash, Vegetable marrow, Zucchini, and Winter squash 

types such as Acorn squash, Butternut squash, Calabaza, 

Hubbard squash, Spaghetti squash), and Watermelon 

(includes hybrids and/or varieties of Citrullus lanatus).

0.104 to 0.222

(3.2 to 6.84 fl oz/A) NS 0.446 0

Retreatment interval of 5 

to 14 days; except for soil 

applications with 

minimum 5 day interval 

between soil applications.

Ground or 

chemigation

Propulse

(1.67 lb ai/gal) 

[264-1084]

Cucurbit Vegetables: Chayote (fruit), Chinese waxgourd 

(Chinese preserving melon), Citron melon, Cucumber, 

Gherkin, Edible gourd (includes hyotan, cucuzza, hechima, 

Chinese okra), Momordica spp. (includes Balsam apple, 

Balsam pear, Bitter melon, Chinese cucumber), Muskmelon 

(includes cantaloupe), Pumpkin, Squash (summer and winter, 

includes Butternut squash, Calabaza, Hubbard squash, Acorn 

squash, Spaghetti squash), and Watermelon.

0.177

(13.6 fl oz/A) NS 0.446 7

Retreatment interval of 5 

to 10 days. Only 1 soil 

application allow; up to 

two foliar applications 

allowed.

Ground, aerial Luna Sensation Cucurbit Vegetables: Chayote (fruit), Chinese waxgourd 0.0660 to 0.125 4 0.446 0 Retreatment interval of 7 
Fluopyram Human Health Risk Assessment DP No. D421926

Page 27 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

or chemigation (2.1 lb ai/gal) [264-

1090]

(Chinese preserving melon), Citron melon, Cucumber, 

Gherkin (edible, includes Hyotan, Cucuzza, Hechima, 

Chinese okra), Momordica spp. (includes Balsam apple, 

Balsam pear, Bitter melon, Chinese cucumber), Muskmelon 

(hybrids and/or cultivars of Cucumis melo including True 

cantaloupe, Cantaloupe, Casaba, Crenshaw melon, Golden 

Pershaw melon, Honeydew melon, Honey balls, Mango 

melon, Persian melon, Pineapple melon, Santa Claus melon, 

Snake melon), Pumpkin, Squash (includes Summer Squash 

types such as: Crookneck squash, Scallop squash, Straight 

neck squash, Vegetable marrow, Zucchini, and Winter squash 

types such as Acorn squash, Butternut squash, Calabaza, 

Hubbard squash, Spaghetti squash), and Watermelon 

(includes hybrids and/or varieties of Citrullus lanatus).

(4.0 to 7.6 fl oz/A) to 14 days; except for soil 

applications with 

minimum 7 day interval 

between soil applications.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Cucurbit Vegetables: Chayote (fruit), Chinese waxgourd 

(Chinese preserving melon), Citron melon, Cucumber, 

Gherkin (edible, includes Hyotan, Cucuzza, Hechima, 

Chinese okra), Momordica spp. (includes Balsam apple, 

Balsam pear, Bitter melon, Chinese cucumber), Muskmelon 

(hybrids and/or cultivars of Cucumis melo including True 

cantaloupe, Cantaloupe, Casaba, Crenshaw melon, Golden 

Pershaw melon, Honeydew melon, Honey balls, Mango 

melon, Persian melon, Pineapple melon, Santa Claus melon, 

Snake melon), Pumpkin, Squash (includes Summer Squash 

types such as: Crookneck squash, Scallop squash, Straight 

neck squash, Vegetable marrow, Zucchini, and Winter squash 

types such as Acorn squash, Butternut squash, Calabaza, 

Hubbard squash, Spaghetti squash), and Watermelon 

(includes hybrids and/or varieties of Citrullus lanatus).

0.0783 to 0.222

(6.0 to 17.0 fl oz/A) NS 0.446 7

Retreatment interval of 10 

to 14 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Fruiting Vegetables: African eggplant, Bush Tomato, 

Cocona, Currant tomato, Eggplant, Garden huckleberry, Goji 

berry, Martynia, Naranjilla, Okra, Pea eggplant, Pepino, 

Pepper (Capsicum spp., including Bell, Chili, Cooking, 

Pimento and Sweet), Roselle, Scarlet eggplant, Sunberry, 

Tomatillo, Tomato, Tree tomato, and cultivars, varieties, 

and/or hybrids of these.

0.117 to 0.222

(3.60 to 6.84 fl oz/A) NS 0.446 0

Retreatment interval of 7 

days.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

Fruiting Vegetables: Eggplant, Groundcherry, Okra, 

Pepinos, Pepper (Capsicum spp., including Bell, Chili, 

Cooking, Pimento and Sweet), Tomatillo, and Tomato.

0.0825 to 0.125

(5.0 to 7.6 fl oz/A) 5 0.446 3

Retreatment interval of 7 

to 14 days.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Fruiting Vegetables: African eggplant, Bush Tomato, 

Cocona, Currant tomato, Eggplant, Garden huckleberry, Goji 

berry, Martynia, Naranjilla, Pea eggplant, Pepino, Non Bell 

0.0783 to 0.222

(6.0 to 17.0 fl oz/A) NS 0.446 7

Retreatment interval of 7 

to 14 days.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 28 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Pepper, Roselle, Scarlet eggplant, Sunberry, Tomatillo, 

Tomato, Tree tomato, and cultivars, varieties, and/or hybrids 

of these.

Ground, aerial 

or chemigation

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Okra

0.167

(12.8 fl oz/A) NS 0.446 3

Retreatment interval of 14 

days.

Ground, aerial 

or chemigation

Luna Tranquility

(1.04 lb ai/gal) 

[264-1085]

Tomato 0.0910

(11.2 fl oz/A NS 0.446 1

Retreatment interval of 7 

to 14 days. For 

greenhouse uses apply 

only in well-ventilated 

plastic tunnel houses or 

glass houses. Ventilate 

for at least 2 hours after 

application.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Ginseng

0.222

(6.84 fl oz/A) NS 0.446 7

Retreatment interval of 5 

to 7 days.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

0.125

(7.6 fl oz/A) NS 0.446 7

Retreatment interval of 14 

days.

Luna Tranquility

(1.04 lb ai/gal) 

[264-1085]

0.130 to 0.219

(16.0 to 27.0 fl oz/A) NS 0.446 30 Retreatment interval of 7 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Grapes and Small Vine Fruits (except fuzzy kiwifruit): 

Amur River grape, Gooseberry, Grape, Kiwifruit, Hardy, 

Maypop, Schisandra berry, and cultivars, varieties, and/or 

hybrids of these varieties.

0.104 to 0.222

(3.2 to 6.84 fl oz/A) NS 0.446 7

Retreatment interval of 12 

to 21 days.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

0.0660 to 0.125

(4.0 to 7.6 fl oz/A) 6 0.446 14 Retreatment interval of 12 to 21 days.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

0.0783 to 0.112

(6.0 to 8.6 fl oz/A) NS 0.446 14 Retreatment interval of 12 to 21 days.

Luna Tranquility

(1.04 lb ai/gal) 

[264-1085]

0.130 to 0.219

(16.0 to 27.0 fl oz/A) NS 0.446 7

Retreatment interval of 12 

to 14 days.

Ground, 

Drench or 

Chemigation

Fluopyram 500 SC

(4.16 lb ai/gal) 

[264-RLGI] Grapes and Small Vine Fruits

0.104 to 0.221 lb ai/100 gal/A

3.2 to 6.8 fl oz/100 gal/A NS 0.446 lb ai/A13.7 fl oz/A 7

Retreatment interval of 12 

to 21 days.

FLU+TFS SC 500

(2.10 lb ai/gal) 

[264-RLGT]

0.0656 to 0.125 lb ai/100 gal/A

4.0 to 7.6 fl oz/100 gal/A 6

0.446 lb ai/A

27.3 fl oz/A 14 Retreatment interval of 12 to 21 days.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 29 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

FLU+TFS SC 25

(0.104 lb ai/gal) 

[264-RLGL]

0.0821 to 0.125 lb ai/100 gal/A

101 to 154 fl oz/100 gal/A 6

0.445 lb ai/A

548 fl oz/A 14 Retreatment interval of 12 to 21 days.

13ESP715 3.3 SC

(3.34 lb ai/gal) 

[432-RLUG]

0.112 to 0.223 lb ai/100 gal/A

4.28 to 8.56 fl oz/100 gal/A NS 0.446 lb ai/A17.1 fl oz/A 7

Retreatment interval of 12 

to 21 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Herbs and Spices (except black pepper): Allspice, 

Angelica, Anise (anise seed), Anise (star), Annatto, (seed), 

Balm (lemon balm), Basil (fresh and dried), Borage, Bumet, 

Camomile, Caper buds, Caraway, Caraway (black), 

Cardamom, Cassia (bark and buds), Catnip, Celery seed, 

Chervil (dried), Chinese chive, Chive, Cinnamon, Clary, 

Clove (buds), Coriander (cilantro or Chinese parsley leaves), 

Coriander seed (cilantro seed), Costmary, Cilantro (leaf and 

seed), Cumin, Curry leaf, Dill (seed), Dillweed, Fennel 

[common and Florence (seed)], Fenugreek, Grains of 

paradise, Horehound, Hyssop, Juniper berry, Lavender, 

Lemongrass, Lovage (leaf and seed), Mace, Marigold, 

Mustard (seed), Nasturtium, Nutmeg, Parsley (dried), 

Pennyroyal, Poppy (seed), Rosemary, Rue, Saffron, Sage, 

Savory (summer and winter), Sweet bay (bay leaf), Tansy, 

Tarragon, Thyme, Vanilla, Wintergreen, Woodruff, and 

Wormwood.

0.13 to 0.222

(4.0 to 6.84 fl oz/A) NS 0.446 0

Retreatment interval of 7 

to 10 days.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

0.0660 to 0.125

(4.0 to 7.6 fl oz/A) NS 0.446 7

Retreatment interval of 7 

to 10 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Hops

0.104 to 0.222

(3.2 to 6.84 fl oz/A) NS 0.446 7

Retreatment interval of 14 

days.

NS

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

0.0495 to 0.125

(3.0 to 7.6 fl oz/A) 4 0.446 14

Retreatment interval of 14 

days. Do not replant areas 

within 30 days of the last 

application. Do not graze 

cover crops within the 

treated area. Do not 

harvest cover crops within 

the area treated for silage

and hay. Do not apply 

using aerial application. 

Do not apply using low 

volume applicators. Do 

not apply through any 

type of irrigation system. 

Do not apply on hops in 

California.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 30 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Ground, aerial 

or chemigation

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

0.104 to 0.222

(8.0 to 17.0 fl oz/A) NS 0.446 14 Retreatment interval of 14 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Leafy Vegetables (except Watercress): Amaranth (Leafy 

amaranth, Chinese spinach, Tampala), Arugula (Roquette), 

Cardoon, Celery, Celtuce, Chervil, Chinese celery, 

Chrysanthemum, (Edible-leaved and Garland), Cilantro, Corn 

salad, Cress (Garden), Cress (Upland, Yellow rocket, Winter 

cress), Dandelion, Dock (Sorrel), Endive (Escarole), Florence 

fennel (Sweet anise, Sweet fennel, Finocchio), Lettuce (Head 

and Leaf), Orach, Parsley, Purslane (Garden and Winter), 

Radicchio (Red Chicory), Rhubarb, Spinach [including New 

Zealand and vine (Malabar spinach, Indian spinach)], and 

Swiss chard.

0.104 to 0.222

(3.2 to 6.84 fl oz/A) NS 0.446

0

3

Retreatment interval of 7 

to 10 days. For lettuce 

greenhouse uses the PHI

is 3 days.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

Leafy Greens Vegetables (except Watercress): Amaranth 

(Leafy amaranth, Chinese spinach, Tampala), Arugula 

(Roquette), Chervil, Chrysanthemum, (Edible-leaved and 

Garland), Cilantro, Corn salad, Cress (Garden), Cress 

(Upland, Yellow rocket, Winter cress), Dandelion, Dock 

(Sorrel), Endive (Escarole), Lettuce (Head and Leaf), Orach, 

Parsley, Purslane (Garden and Winter), Radicchio (Red 

Chicory), Rhubarb, and Spinach [including New Zealand and 

vine (Malabar spinach, Indian spinach)]. 

0.125

(7.6 fl oz/A) NS 0.446 0

Retreatment interval of 14 

days.

Ground, aerial 

or chemigation

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

Leafy Petiole Vegetables: Cardon, Celery, Chinese celery, 

Florence fennel (including Sweet anise, Sweet fennel, 

Finocchio), Rhubarb, Swiss chard.

0.0660 to 0.0957

(4.0 to 5.8 fl oz/A) NS 0.446 7

Retreatment interval of 14 

days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Legume Vegetables (including Soybean): Edible Podded 

Legume Vegetables: Bean (Phaseolus spp.) (includes Runner 

Bean, Snap Bean, Wax Bean); Bean (Vigna spp.) (includes 

Asparagus Bean, Chinese Longbean, Moth Bean, Yardlong 

Bean); Jackbean; Pea (Pisum spp.) (includes Dwarf Pea, 

Edible-pod Pea, Snow Pea, Sugar Snap Pea); Pigeon Pea; 

Soybean (immature seed); Sword Bean. Succulent Shelled 

Pea and Bean: Bean (Phaseolus spp.) (includes Lima Bean 

(green); Broad Bean (succulent); Bean (Vigna spp.) ( except 

Cowpea, Southpea); Pea (Pisum spp.) (includes English Pea, 

Garden Pea, Green Pea); Pigeon Pea. Dried Shelled Pea and 

Bean. Dried Cultivars of Bean (Lupinus spp.) (includes Grain 

Lupin, Sweet Lupin, White Lupin, White Sweet Lupin); 

(Phaseolus spp.) (includes Field Bean, Kidney Bean, Lime 

Bean Dry), Navy Bean, Pinto Bean; Tepary Bean; Bean 

(Vigna spp.) (includes Adzuki Bean, Blackeyed Pea, Catjang, 

0.156 to 0.222

(4.8 to 6.84 fl oz/A) NS 0.446 0

Do not apply to cultivars 

that are to be grazed, cut 

for forage or hay, or used 

as livestock feed.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 31 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Moth Bean, Mung Bean, Rice Bean, Southern Pea, Urd Bean; 

except Cowpea & Crowder Pea); Broad Bean (Dry); 

Chickpea; Guar; Lablab Bean; and Lentil.

Ground, aerial 

or chemigation

Propulse

(1.67 lb ai/gal) 

[264-1084]

Dried Beans: Bean (Lupinus spp., includes Grain lupin, 

Sweet lupin, White lupin, and White sweet lupin), Bean 

(Phaseolus spp., includes Field bean, Kidney bean, Lima 

bean, Navy bean, Pinto bean, and Tepary bean), Bean (Vigna 

spp., includes Adzuki bean, Blackeyed pea, Catjang, Crowder 

pea, Moth bean, Mung bean, Rice bean, Southern pea, and 

Urd bean), Broad Bean (dry), Chickpea, Guar, Lablab Bean, 

and Lentil.

0.134 to 0.177

(10.3 to 13.6 fl oz/A) NS 0.446 14

Retreatment interval of 7 

to 14 days. Allow 7 days 

from the last application

until cutting or swathing 

the crop for harvest. Do 

not feed hay or threshings 

or allow livestock to graze 

in treated areas.

Ground, aerial 

or chemigation

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Beans (Fresh and Dry, except Succulent Shelled) 0.104 to 0.167

(8.0 to 12.8 fl oz/A) NS 0.446 14

Retreatment interval of 10 

to 14 days. Do not allow 

livestock to graze treated 

area for 14 days and do 

not harvest for food or 

feed within 14 days of 

application. 

Ground, aerial 

or chemigation

Propulse

(1.67 lb ai/gal) 

[264-1084]

Soybean

0.133

(10.2 fl oz/A) NS 0.446 21

Retreatment interval of 10 

to 14 days. Do not allow 

livestock to graze soybean 

and do not harvest 

soybean hay for food or 

feed.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

0.125

(7.6 fl oz/A) NS 0.446 21

Retreatment interval of 14 

days. Do not allow 

livestock to graze soybean 

and do not harvest 

soybean hay for food or 

feed.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

0.112

(8.6 fl oz/A) NS 0.446 21

Retreatment interval of 10 

to 14 days. Do not allow 

livestock to graze soybean 

and do not harvest 

soybean hay for food or 

feed. 

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Pome Fruits: Apple, Azarole, Crabapple, Loquat, Mayhaw, 

Medlar, Pear, Pear (Asian), Quince, Quince (Chinese and 

Japanese), Tejocote, and cultivars, varieties, and/or hybrids of 

these.

0.078 to 0.222

(2.4 to 6.84 fl oz/A) NS 0.446 7

Retreatment interval of 7 

to 14 days.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

0.0652 to 0.130

(5.0 to 10.0 fl oz/A) NS 0.446 75 Retreatment interval of 7 to 14 days.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 32 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Luna Sensation

(2.1 lb ai/gal) [264-

1090] Pome Fruits: Apple, Crabapple, Loquat, Mayhaw, Pear, 

Oriental Pear, Quince.

0.0660 to 0.0957

(4.0 to 5.8 fl oz/A) 4 0.446 14 Retreatment interval of 7 to 14 days.

Luna Tranquility

(1.04 lb ai/gal) 

[264-1085]

0.0975 to 0.130

(12.0 to 16.0 fl oz/A) NS 0.446 72 Retreatment interval of 7 to 10 days.

Ground, 

Drench or 

Chemigation

Fluopyram 500 SC

(4.16 lb ai/gal)

[264-RLGI]

Pome Fruits

0.0780 to 0.221 lb ai/100 gal/A

2.4 to 6.8 fl oz/100 gal/A NS 0.446 lb ai/A13.7 fl oz/A 7

Retreatment interval of 7 

to 14 days.

FLU+TFS SC 500

(2.10 lb ai/gal) 

[264-RLGT]

0.0656 to 0.0952 lb ai/100 gal/A

4.0 to 5.8 fl oz/100 gal/A 4

0.345 lb ai/A

21.0 fl oz/A 14 Retreatment interval of 7 to 14 days.

FLU+TFS SC 25

(0.104 lb ai/gal) 

[264-RLGL]

0.0650 to 0.0951 lb ai/100 gal/A

80 to117 fl oz/100 gal/A 4

0.345 lb ai/A

425 fl oz/A 14 Retreatment interval of 7 to 14 days.

13ESP715 3.3 SC

(3.34 lb ai/gal) 

[432-RLUG]

0.0783 to 0.223 lb ai/100 gal/A

3.0 to 8.56 fl oz/100 gal/A NS 0.446 lb ai/A17.1 fl oz/A 7

Retreatment interval of 7 

to 14 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Potato and Other Root, Tuberous, and Corm Vegetables: 

Arracacha, Arrowroot, Artichoke (Chinese and Jerusalem), 

Beet (Garden), Burdock (Edible), Canna (Edible, Queensland 

arrowroot), Cassava (Bitter & Sweet), Celeriac (Celery root), 

Chayote (root), Chervil (Turnip-rooted), Chickory, Chufa, 

Dasheen (Taro), Ginger, Horseradish, Leren, Parsley (Turniprooted), Parsnip, Potato, Radish, Oriental radish (Daikon), 

Rutabaga, Salsify (Black), Salsify (Oyster plant), Salsify 

(Spanish), Skirret, Sweet potato, Tanier (Cocoyam), 

Turmeric, Turnip, Yam bean (Jicama, Manoic pea) and Yam 

(True).

0.13 to 0.222

(4.0 to 6.84 fl oz/A) NS 0.446 7

Retreatment interval of 5 

to 7 days. The grazing of 

livestock in treated areas 

within 7 days of 

application is prohibited.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

0.0825 to 0.0957

(5.0 to 5.8 fl oz/A) 4 0.446 7

Retreatment interval of 14 

days. 

Luna Tranquility

(1.04 lb ai/gal) 

[264-1085]

Potato and Other Root, Tuberous, and Corm Vegetables: 

Arracacha, Arrowroot, Artichoke (Chinese and Jerusalem), 

Canna (Edible), Cassava (Bitter & Sweet), Chayote (root), 

Chufa, Dasheen (Taro), Ginger, Leren, Potato, Sweet Potato, 

Tanier (Cocoyam), Turmeric, Yam bean, and Yam (True).

0.0650 to 0.0910

(8.0 to 11.2 fl oz/A) NS 0.446 7

Retreatment interval of 7 

to 14 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Small Berries (caneberries and bushberries): 

Blackberry Rubus spp. (including Andean blackberry, Artic 

blackberry, Bingleberry, Black blackberry, Boysenberry, 

Brombeere, California blackberry, Chesterberry, Cherokee 

blackberry, Cheyenne blackberry, Common blackberry, 

Coryberry, Darrowberry, Dewberry, Dirksen thornless berry, 

Evergreen blackberry, Himalayaberry, Hullberry, 

Lavacaberry, Loganberry, Lowberry, Lucretiaberry, 

0.156 to 0.222

(4.8 to 6.84 fl oz/A) NS 0.446 0

Retreatment interval of 7 

to 10 days.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 33 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Mammoth blackberry, Marionberry, Mora, Mures deronce, 

Nectarberry, Northern dewberry, Olallieberry, Oregon 

evergreen berry, Phenomenalberry, Rangeberry, Ravenberry, 

Rossberry, Shawnee blackberry, Southern dewberry, 

Tayberry, Youngberry, Zarzamora, and cultivars, varieties, 

and/or hybrids of these.

Raspberry Rubus spp. (Rubus occidentalis, Rubus strigosus, 

Rubus idaeus) (including Bababery, Black raspberry, 

Blackcap, Framboise, Frambueso, Himbeere, Keriberry, 

Mayberry, Purple raspberry, Red raspberry, Thimblberry, 

Tulameen, Wild raspberries, Yellow raspberry) and cultivars, 

varieties, and/or hybrids of these.

Bushberry (including Berry (Aronia), Blueberry (Highbush 

and Lowbush), Currant (Buffalo), Guava (Chilean), Currant 

(Black and Red), Barberry (European), Elderberry, 

Gooseberry, Cranberry (Highbush), Honeysuckle, 

Huckleberry, Jostaberry, Juneberry, Currant (Native), Salal, 

Sea buckthorn, and cultivars, varieties, and/or hybrids of 

these.

Ground, aerial 

or chemigation

Luna Tranquility

(1.04 lb ai/gal) 

[264-1085]

Small Berries (caneberries and bushberries): 

Blackberry Rubus spp. (including Andean blackberry, Artic 

blackberry, Bingleberry, Black Satin berry, Boysenberry, 

Brombeere, California blackberry, Chesterberry, Cherokee 

blackberry, Cheyenne blackberry, Common blackberry, 

Coryberry, Darrowberry, Dewberry, Dirksen thornless berry, 

Evergreen blackberry, Himalayaberry, Hullberry, 

Lavacaberry, Loganberry, Lowberry, Lucretiaberry, 

Mammoth blackberry, Marionberry, Mora, Mures deronce, 

Nectarberry, Northern dewberry, Olallieberry, Oregon 

evergreen berry, Phenomenalberry, Rangeberry, Ravenberry, 

Rossberry, Shawnee blackberry, Southern dewberry, 

Tayberry, Youngberry, Zarzamora, and cultivars, varieties, 

and/or hybrids of these.

Raspberry Rubus spp. (Rubus occidentalis, Rubus strigosus, 

Rubus idaeus) (including Bababery, Black raspberry, 

Blackcap, Framboise, Frambueso, Himbeere, Keriberry, 

Mayberry, Purple raspberry, Red raspberry, Thimblberry, 

Tulameen, Wild raspberries, Yellow raspberry) and cultivars, 

varieties, and/or hybrids of these.

Bushberry (including Berry (Aronia), Blueberry (Highbush 

and Lowbush), Currant (Buffalo), Guava (Chilean), Currant 

(Black and Red), Barberry (European), Elderberry, 

Gooseberry, Cranberry (Highbush), Honeysuckle, 

0.111 to 0.219

(13.6 to 27.0 fl oz/A) NS 0.446 0

Retreatment interval of 7 

to 14 days.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 34 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

Huckleberry, Jostaberry, Juneberry, Currant (Native), Salal, 

Sea buckthorn, and cultivars, varieties, and/or hybrids of 

these.

Ground or 

chemigation

Propulse

(1.67 lb ai/gal) 

[264-1084]

Bushberry subgroup: Aronia berry, Blueberry (Highbush 

and Lowbush), Chilean Guava, Currant (Black, Buffalo, and 

Red), Highbush Cranberry, Elderberry, European Barberry, 

Gooseberry, Edible Honeysuckle, Huckleberry, Jostaberry, 

Juneberry (Saskatoon berry), Ligonberry, Native Currant, 

Salal, Sea buckthorn, and cultivars, varieties, and/or hybrids 

of these.

0.177

(13.6 fl oz/A) NS 0.446 7

Retreatment interval of 7 

to 10 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Stone Fruit: Apricot, Apricot (Japanese), Capulin, Cherry 

(Black, Nanking, Canada, Sweet, Tart), Jujube (Chinese), 

Nectarine, Peach, Plum, Plum (American, Beach, Canada, 

Cherry, Chickasaw, Damson, Japanese, Klamath), Prune, 

Plumcot, Sloe, and cultivars, varieties, and/or hybrids of 

these.

0.13 to 0.222

(4.0 to 6.84 fl oz/A) NS 0.446 0

Retreatment interval of 5 

to 7 days.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

Stone Fruit: Apricot, Cherry (Sweet and Tart), Nectarine, 

Peach, Plum (including Chickasaw, Damson, Japanese), 

Plumcot, and Prune (Fresh and Dried).

0.0825 to 0.125

(5.0 to 7.6 fl oz/A) 4 0.446 1

Retreatment interval of 7 

to 14 days.

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Stone Fruit: Apricot, Cherry (Sweet, Tart), Nectarine, Peach, 

Plum (all varieties including Chickasaw, Damson, Japanese, 

and Stanley), Plumcot, and Prune (fresh and dried).

0.0783 to 0.130

(6.0 to 10.0 fl oz/A NS 0.446 0

Retreatment interval of 5 

to 7 days.

Luna Tranquility

(1.04 lb ai/gal) 

[264-1085]

Stone Fruit: Apricot, Nectarine, Peach, Plum (all varieties 

including Chickasaw, Damson, Japanese, and Stanley), 

Plumcot, and Prune (fresh and dried).

0.0975 to 0.219

(12.0 to 27.0 fl oz/A NS 0.446 2

Retreatment interval of 7 

to 14 days. Do not make 

more than two 

applications of a group 9 

fungicide within 30 days 

of harvest.

Ground, 

Drench or 

Chemigation

Fluopyram 500 SC

(4.16 lb ai/gal) 

[264-RLGI]

Stone Fruits

0.130 to 0.221 lb ai/100 gal/A

4.0 to 6.8 fl oz/100 gal/A NS 0.446 lb ai/A13.7 fl oz/A 0

Retreatment interval of 5 

to 7 days.

FLU+TFS SC 500

(2.10 lb ai/gal) 

[264-RLGT]

0.0820 to 0.125 lb ai/100 gal/A

5.0 to 7.6 fl oz/100 gal/A 4

0.251 lb ai/A

15.3 fl oz/A 1

Retreatment interval of 7 

to 14 days. 

FLU+TFS SC 25

(0.104 lb ai/gal) 

[264-RLGL]

0.0821 to 0.125 lb ai/100 gal/A

101 to 154 fl oz/100 gal/A 4

0.251 lb ai/A

309 fl oz/A 1

Retreatment interval of 7 

to 14 days.

13ESP715 3.3 SC

(3.34 lb ai/gal) 

[432-RLUG]

0.157 to 0.223 lb ai/100 gal/A

6.0 to 8.56 fl oz/100 gal/A NS 0.446 lb ai/A17.1 fl oz/ 0

Retreatment interval of 5 

to 7 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

Strawberry and Other Low-Growing Berries (except 

Cranberries): Bearberry, Bilberry, Blueberry (Low-bush), 

0.104 to 0.222

(3.2 to 6.84 fl oz/A) NS 0.446 0

Retreatment interval of 7 

days.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 35 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

[264-1078] Cloudberry, Ligonberry, Muntries, Partridgeberry, and 

Strawberry.

Ground or 

chemigation

Propulse

(1.67 lb ai/gal) 

[264-1084]

Low Growing Berry subgroup, except Strawberry and 

Cranberries: Bearberry, Bilberry, Cloudberry, Muntries, 

Partridgeberry, and cultivars, varieties, and/or hybrids of 

these.

0.134

(10.3 fl oz/A) NS 0.446 45 Retreatment interval of 7 to 10 days.

Ground, aerial 

or chemigation

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

Strawberry and Other Low-Growing Berries (except 

Cranberries): Bearberry, Bilberry, Blueberry (Low-bush), 

Cloudberry, Ligonberry, Muntries, Partridgeberry, and 

Strawberry.

0.0660 to 0.125

(4.0 to 7.6 fl oz/A) NS 0.446 0

Retreatment interval of 7 

to 14 days.

Luna Tranquility

(1.04 lb ai/gal) 

[264-1085]

Strawberry and Other Low-Growing Berries (except 

Cranberries): Bearberry, Bilberry, Blueberry (Low-bush), 

Cloudberry, Ligonberry, Muntries, Partridgeberry, and 

Strawberry.

0.130 to 0.219

(16.0 to 27.0 fl oz/A) NS 0.446 1

Retreatment interval of 7 

to 14 days.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Sugar beet

0.222

(6.84 fl oz/A) NS 0.446 7

Retreatment interval of 5 

to 7 days.

Propulse

(1.67 lb ai/gal) 

[264-1084]

0.177

(13.6 fl oz/A) NS 0.446 7

Retreatment interval of 14 

days.

Luna Sensation

(2.1 lb ai/gal) [264-

1090]

0.0924 to 0.125

(5.6 to 7.6 fl oz/A) NS 0.446 21

Retreatment interval of 10 

to 14 days. Tops or 

greens from this crop may 

be utilized for food or 

feed.

Ground, aerial 

or chemigation

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Sunflower Subgroup: Calendula, Castor oil plant, Chinese 

tallowtree, Euphorbia, Evening primrose, Jojoa, Niger seed, 

Rose hib, Safflower, Stokes aster, Sunflower, Tallowwood, 

Tea oil plant, Veronia, and cultivars, varieties and/or hybrids 

of these.

0.222

(6.84 fl oz/A) NS 0.446 14 Retreatment interval of 14 days.

Ground, aerial 

or chemigation

Luna Experience

(1.67 lb ai/gal) 

[264-1091]

Sunflower 0.117 to 0.167

(9.0 to 12.8 fl oz/A NS 0.446 50

Retreatment interval of 14 

Ground, days.

Drench or 

Chemigation

Fluopyram 500 SC

(4.16 lb ai/gal) 

[264-RLGI] Sunflower

0.221 lb ai/100 gal/A

6.8 fl oz/100 gal/A NS 0.446 lb ai/A13.7 fl oz/A 14

13ESP715 3.3 SC

(3.34 lb ai/gal) 

[432-RLUG]

0.223 lb ai/100 gal/A

8.56 fl oz/100 gal/A NS 0.446 lb ai/A17.1 fl oz/ 14

Ground or 

Chemigation

FLU+TFS SC 500

(2.10 lb ai/gal) 

[264-RLGT]

Tree Nuts 0.0820 to 0.125 lb ai/100 gal/A

5.0 to 7.6 fl oz/100 gal/A NS 0.251 lb ai/A15.3 fl oz/A 60 Retreatment interval of 7 to 21 days.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 36 of 87

Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

FLU+TFS SC 25

(0.104 lb ai/gal) 

[264-RLGL]

0.0821 to 0.125 lb ai/100 gal/A

101 to 154 fl oz/100 gal/A NS 0.251 lb ai/A309 fl oz/A 60

Seed Treatment

Seed treatment 

with 

commercial 

slurry mixture 

equipment 

only.

Luna Privilege

(4.16 lb ai/gal) 

[264-1078]

Peanut

0.049725 to 0.124475

lb ai/100 lb seed

(1.53 to 3.83 fl oz

per 100 lb of

peanut seeds)

1

0.446 (from all 

uses) NA

Do not use treated seed 

for food, feed, or oil 

purposes.

Non Agricultural Use Sites

Ground or 

Chemigation

Fluopyram 500 SC

(4.16 lb ai/gal) 

[264-RLGI]

Turf Grass: Golf Courses, Sod Farms, Sports Fields, 

Industrial, Municipal, Commercial, and other Turf Grass 

areas.

0.0013 to 0.0101 lb ai/1000 ft2

(0.04 to 0.31 fl oz/1000 ft2)

(0.0566 to 0.439 lb ai/A)

NS

0.3145 fl oz/1000 

ft2

13.7 fl oz/A

0.446 lb ai/A

NA Retreatment interval of 7 

to 28 days.

FLU+TFS SC 500

(2.10 lb ai/gal) 

[264-RLGT]

0.000820 to 0.00984 lb ai/1000 ft2

(0.05 to 0.6 fl oz/1000 ft2)

(0.0557 to 0.429 lb ai/A)

0.6267 fl oz/1000 

ft2

27.3 fl oz/A

0.446 lb ai/A

FLU+TFS SC 25

(0.104 lb ai/gal) 

[264-RLGL]

0.00121 to 0.0102 lb ai/1000 ft2

(1.5 to 12.6 fl oz/1000 ft2)

(0.0531 to 0.446 lb ai/A)

12.6 fl oz/1000 ft2

549 fl oz/A

0.446 lb ai/A

FLU+TFS SC 32.5

(0.104 lb ai/gal) 

[264-RLGA]

0.00121 to 0.0102 lb ai/1000 ft2

(1.5 to 12.6 fl oz/1000 ft2)

(0.0531 to 0.446 lb ai/A)

12.6 fl oz/1000 ft2

549 fl oz/A

0.446 lb ai/A

13ESP715 3.3 SC

(3.34 lb ai/gal) 

[432-RLUG]

0.0013 to 0.0102 lb ai/1000 ft2

(0.05 to 0.39 fl oz/1000 ft2)

(0.0566 to 0.444 lb ai/A)

0.393 fl oz/1000 ft2

17.1 fl oz/A

0.446 lb ai/A

Ground

Fluopyram 500 SC

(4.16 lb ai/gal) 

[264-RLGI]

Residential Turf Grass

0.0013 to 0.00912 lb ai/1000 ft2

(0.04 to 0.28 fl oz/1000 ft2)

(0.0566 to 0.396 lb ai/A)

NS

0.2847 fl oz/1000 

ft2

12.4 fl oz/A

0.403 lb ai/A

NA Retreatment interval of 7 

to 28 days.

FLU+TFS SC 500

(2.10 lb ai/gal) 

[264-RLGT]

0.000820 to 0.00919 lb ai/1000 ft2

(0.05 to 0.56 fl oz/1000 ft2)

(0.0557 to 0.400 lb ai/A)

0.5647 fl ozi/1000 

ft2

24.6 fl oz/A

0.404 lb ai/A

FLU+TFS SC 25

(0.104 lb ai/gal) 

[264-RLGL]

0.00121 to 0.00926 lb ai/1000 ft2

(1.5 to 11.4 fl oz/1000 ft2)

(0.0531 to 0.404 lb ai/A)

11.4 fl oz/1000 ft2

497 fl oz/A2

0.404 lb ai/A

FLU+TFS SC 32.5

(0.104 lb ai/gal) 

0.00121 to 0.00926 lb ai/1000 ft2

(1.5 to 11.4 fl oz/1000 ft2)

11.4 fl oz/1000 ft2

497 fl oz/A
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Table 3.3.1. Summary of Proposed Directions for Use of Fluopyram.

Application 

Timing, Type, 

and Equip.

Formulation

[EPA Reg. No.] Crops Application Rate (lb ai/A)

Max. 

No. 

Applic. 

per 

Season

Max. Seasonal 

Applic. Rate

(lb ai/A)

PHI

(days)

Use Directions and 

Limitations

[264-RLGA] (0.0531 to 0.404 lb ai/A) 0.404 lb ai/A

13ESP715 3.3 SC

(3.34 lb ai/gal) 

[432-RLUG]

0.0013 to 0.009285 lb ai/1000 ft2

(0.05 to 0.3558 fl oz/1000 ft2)

(0.0566 to 0.404 lb ai/A)

0.3558 fl oz/1000 

ft2

15.5 fl oz/A

0.404 lb ai/A

Ground, 

Drench or 

Chemigation

Fluopyram 500 SC

(4.16 lb ai/gal) 

[264-RLGI]

Ornamentals: in Residential and Commercial Landscapes, 

Interiorscapes, Field Grown and Container Ornamentals, in 

Nurseries, and Greenhouses, Lathhouses, Shadehouses, 

Containers and Other Enclosed Structures.

0.221 lb ai/100 gal/A

6.8 fl oz/100 gal/A

NS

13.7 fl oz/A

0.446 lb ai/A

NA

Retreatment interval of 7 

to 21 days.

FLU+TFS SC 500

(2.10 lb ai/gal) 

[264-RLGT]

0.0164 to 0.131 lb ai/100 gal/A

1.0 to 8.0 fl oz/100 gal/A

27.3 fl oz/A

0.446 lb ai/A

Retreatment interval of 7 

to 28 days.

FLU+TFS SC 25

(0.104 lb ai/gal) 

[264-RLGL]

0.0163 to 0.130 lb ai/100 gal/A

20 to 160 fl oz/100 gal/A

0.445 lb ai/A

548 fl oz/A

Retreatment interval of 7 

to 28 days.

13ESP715 3.3 SC

(3.34 lb ai/gal) 

[432-RLUG]

0.223 lb ai/100 gal/A

8.56 fl oz/100 gal/A

0.446 lb ai/A

17.1 fl oz/A

Retreatment interval of 7 

to 21 days.

Ground or 

Chemigation

Fluopyram 500 SC

(4.16 lb ai/gal) 

[264-RLGI]

Christmas Trees

0.221 lb ai/100 gal/A

6.8 fl oz/100 gal/A

NS

13.7 fl oz/A

0.446 lb ai/A

NA Retreatment interval of 7 

to 21 days.

FLU+TFS SC 500

(2.10 lb ai/gal) 

[264-RLGT]

0.220 lb ai/100 gal/A

13.4 fl oz/100 gal/A

27.1 fl oz/A

0.445 lb ai/A

FLU+TFS SC 25

(0.104 lb ai/gal) 

[264-RLGL]

0.220 lb ai/100 gal/A

271 fl oz/100 gal/A NS

13ESP715 3.3 SC

(3.34 lb ai/gal) 

[432-RLUG]

0.223 lb ai/100 gal/A

8.56 fl oz/100 gal/A

0.446 lb ai/A

17.1 fl oz/A
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3.4 Anticipated Exposure Pathways

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

applied directly to growing crops and application may result in fluopyram reaching surface and 

ground water sources of drinking water. In an occupational setting, applicators may be exposed 

by the dermal and inhalation routes while handling the pesticide prior to application, as well as 

during application. There is also a potential for post-application dermal and inhalation exposures

for workers re-entering treated fields. Additionally, there are proposed uses of fluopyram on turf 

and ornamentals; and therefore, exposure in residential or non-occupational settings is likely, and 

will result in short-term dermal and inhalation exposures for adult handlers and dermal (for 

adults and small children) and incidental oral (for small children) exposures from postapplication activities.

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 

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 last comprehensive risk assessment was completed in September, 2014 (D414231, B. 

O’Keefe, 09/22/2014). The toxicology database is complete and the hazard characterization is 

unchanged from the last assessment. This assessment includes summaries of prior hazard 

characterization.
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4.1 Toxicological Effects

Liver effects and decreased body weight were the most common and sensitive findings in the 

subchronic and chronic oral toxicity studies in rats, mice, and dogs. Liver effects were 

characterized by increased liver weight, hepatocellular hypertrophy, hepatocellular vacuolation, 

increased mitosis and hepatocellular necrosis. Increased liver tumors were also observed in 

female rats in the carcinogenicity study. Liver effects in rodents were seen at lower dose levels 

(as low as 6 mg/kg) than those in the dogs. Thyroid effects were found at dose levels similar to 

those that produced liver effects in rodents; effects consisted of follicular cell hypertrophy, 

increased thyroid weight and hyperplasia. Changes in thyroid hormone levels (T3 & T4) and 

increased thyroid stimulating hormone (TSH) were also seen in rats in a subchronic toxicity

study. In male mice, there was an increased incidence of thyroid adenomas. In the genotoxicity

battery, fluopyram was shown to have no genotoxic potential.

Fluopyram is not a developmental toxicant, nor did it adversely affect reproductive parameters. 

No evidence of qualitative or quantitative susceptibility was observed in these studies. 

In an acute neurotoxicity study, transient decreased motor activity was seen only on the day of 

treatment, but no other findings demonstrating neurotoxicity were found. In addition, no 

neurotoxicity was observed in the subchronic neurotoxicity study in the presence of other 

systemic adverse effects. Fluopyram did not produce treatment-related effects on the immune 

system.

With oral dosing, fluopyram was rapidly absorbed from the gastro-intestinal (GI) tract of male 

and female rats; the percentage absorbed was approximately 93% of the administered dose. The 

maximal plasma concentration was reached at 15 hours in males and 11 hours in females post 

dosing (5 mg/kg). The absorbed fluopyram was quickly distributed within the central 

compartments of the body (e.g. blood, liver, and kidney) and showed a distinctive preference 

towards the liver and to a smaller extent to the kidneys. The elimination results showed that 53-

65% of administered radioactivity was eliminated via feces and 32-41% was eliminated via the

urine. Less than 0.07-0.09% of the administered dose was expired. After 168 hours post dosing 

91-99% of the administered radioactivity was eliminated via urine and feces. Residue analysis 

showed that the highest radioactivity level was found in the liver (0.4 to 1.0% of the 

administered radioactivity). Fluopyram was extensively metabolized and more than 29 

metabolites were identified. Three major groups of metabolites were formed in the liver

(fluopyram-7-OH-GA, 8-OH-GA and enol-glucuronic acid). Bioaccumulation was not observed.

Fluopyram plant metabolites, fluopyram-pyridyl-carboxylic acid and fluopyram methylsulfoxide, demonstrated less acute toxic potential than the parent compound. Mutagenicity tests 

on these two metabolites were negative. 

A parallel approach was used to estimate the dermal absorption factor in human skin by using a 

proportional relationship: rat in vivo/rat in vitro = human in vivo/human in vitro. The dermal 

absorption values for human skin were calculated to be 0.2% for the neat formulation and 1.9% 

for the spray dilution.
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4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

The FQPA safety factor can be reduced to 1x because (1) the toxicology database is complete, 

(2) there is no evidence of neurotoxicity, (3) there is no evidence of increased susceptibility in 

the developing or young animals which were exposed during pre- or post-natal periods, and (4) 

there are no residual uncertainties in the exposure database.

4.2.1 Completeness of the Toxicology Database

The toxicology database for fluopyram is complete, and the available studies are adequate to 

characterize potential pre- and/or post-natal risks for infants and children, and includes 

acceptable developmental toxicity studies in the rat and rabbit, as well as acute and subchronic 

neurotoxicity studies. HED waived the required subchronic inhalation study based on a weight 

of evidence approach (TXR 0056523, 01/20/2013.)

4.2.2 Evidence of Neurotoxicity

The fluopyram toxicology database did not demonstrate evidence of neurotoxicity. Although 

transient decreases in motor and locomotor activities in the acute neurotoxicity study were seen 

on the day of treatment and limited use of hind-limbs and reduced motor activity was seen in the 

rat chronic/carcinogenicity study, there were no other associated neurobehavioral or 

histopathology changes found in other studies in the fluopyram toxicity database. The effects 

seen in the chronic/carcinogenicity study were in the presence of increased mortality and 

morbidity such as general pallor and emaciated appearance. Therefore, the reduced motor 

activity and limited use of hind-limbs seen in these two studies were judged to be the 

consequence of the systemic effects and not direct neurotoxicity.

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

The available developmental toxicity studies in rats and rabbits and the multi-generation 

reproduction in rats demonstrate no evidence of increased susceptibility in the developing or 

young animals which were exposed during pre- or post-natal periods.

4.2.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties in the exposure database. The acute dietary exposure 

assessment was performed using conservative exposure inputs, including tolerance level residues 

for all crops, whereas the chronic dietary assessment included average field trial residue levels 

for all crops. Both acute and chronic dietary assessments assumed 100% crop treated and 

incorporated empirical or default processing factors. The dietary exposure assessment also 

assumed that all drinking water will contain fluopyram at the highest EDWC levels modeled by 

EFED for ground or surface water. Therefore, it can be concluded that the dietary exposure 

analysis does not underestimate risk from acute and chronic dietary exposure to fluopyram. 

While there is the potential for handler and post-application residential exposure, the best data 

and approaches currently available were used in the fluopyram residential assessment. The 
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Agency used the current conservative approaches for residential assessment, many of which 

include recent upgrades to the SOPs. The Agency believes that the calculated risks represent 

conservative estimates of exposure because maximum application rates are used to define residue 

levels upon which the calculations are based. Therefore, residential exposures are unlikely to be 

under estimated.

4.3 Toxicity Endpoint and Point of Departure Selections

4.3.1 Dose-Response Assessment

For fluopyram, HED has selected the most sensitive and protective endpoints from the database 

to establish points of departure for the risk assessment (Table 4.5.4.1). For acute oral exposure, 

an acute neurotoxicity study in rats has been used to select the dose (50 mg/kg) and endpoint for 

establishing the aRfD (0.5 mg/kg/day) for the general population. The lowest observable 

adverse effect level (LOAEL) of 100 mg/kg is based on decreased motor and locomotor activity

in females, an effect attributable to general toxicity. For chronic dietary exposure, a combined 

chronic/carcinogenicity study in rats was used to select the dose (NOAEL=1.2 mg/kg/day) and 

endpoint for establishing the chronic reference dose (cRfD; 0.012 mg/kg/day). The toxicity

endpoint was based on follicular cell hypertrophy in the thyroid and increased liver weight with 

liver gross pathological and histopathological findings at 6.0 mg/kg/day. The point of departure 

derived from this study is protective of the adverse thyroid effects observed in the mouse 

carcinogenicity study seen at 105 mg/kg/day. A 2-generation reproduction study in rats was 

used to select the dose (NOAEL = 14.5 mg/kg/day) and endpoint for short-term incidental oral 

exposures. The LOAEL of 82.8 mg/kg/day was based on clinical chemistry changes, increased 

kidney weight in parents, and decreased body weight with secondary decreases in spleen and 

thymus weights in the offspring. This study was also chosen for short- and intermediate-term 

inhalation exposure scenarios, assuming inhalation and oral absorption equivalency (100%). A 

28-day dermal toxicity study was used to select the point of departure (NOAEL = 300 

mg/kg/day) and endpoint (↑ prothrombin time and altered cholesterol levels) for short-and 

intermediate term dermal exposure.

4.3.2 Recommendation for Combining Routes of Exposures for Risk Assessment

Since the inhalation point of departure is based on an oral study, oral exposures can be combined 

with inhalation exposures. Common toxicological effects were not observed at the LOAELs of 

studies selected for the assessment of short- and intermediate-term exposures by the dermal and 

inhalation routes; prothrombin time and altered cholesterol levels were the dermal endpoint 

whereas the inhalation endpoint was based on kidney, spleen and thymus effects accompanied by 

clinical chemistry and body weight changes. Therefore, it is not appropriate to combine these 

routes of exposure for risk assessment.
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4.3.3 Cancer Classification and Risk Assessment Recommendation

The CARC classified fluopyram as “Not Likely to be Carcinogenic to Humans” at doses that do 

not induce cellular proliferation in the liver or thyroid glands. This classification was based on 

convincing evidence that non-genotoxic modes of action for liver tumors in rats and thyroid 

tumors in mice have been established and that the carcinogenic effects have been demonstrated 

as a result of a mode of action dependent on activation of the CAR/PXR receptors (CARC 

Report, May 8, 2014).

The CARC has determined that quantification of risk is not required. There is sufficient data to 

ascertain the mode of action of fluopyram. The chronic Reference Dose (RfD) is derived using 

the NOAEL of 1.2 mg/kg/day as the “point of departure” which is below the dose of 11 

mg/kg/day that caused cell proliferation in the liver (i.e., a key event in tumor formation) and the 

subsequent liver tumors at a higher dose (89 mg/kg/day). Additionally, there is no concern for 

mutagenicity. 

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

Assessment

Table 4.3.4.1. Summary of Toxicological Doses and Endpoints for Fluopyram for Use in Dietary and NonOccupational 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)

NOAEL= 

50

mg/kg/day

UFA= 10X

UFH=10X

FQPA SF=1X

Acute RfD = 

0.50

mg/kg/day

aPAD = 0.50

mg/kg/day

Acute Neurotoxicity Study in Rats. 

The LOAEL of 100 mg/kg in females is 

based on decreased motor and locomotor 

activity in females. The LOAEL in males 

was 125 mg/kg/day. 

Acute Dietary

(Females 13-

49 years of 

age)

An endpoint attributable to a single dose exposure has not been identified for this subpopulation.

Chronic 

Dietary (All 

Populations)

NOAEL= 

1.2

mg/kg/day

UFA= 10X

UFH=10X

FQPA SF=1X

Chronic RfD 

= 0.012

mg/kg/day

cPAD = 0.012

mg/kg/day

Combined Chronic/Carcinogenicity in 

Rats

The LOAEL of 6.0 mg/kg/day is based on 

follicular cell hypertrophy in the thyroid, 

and increased liver weight with gross 

pathological and histopathological 

findings.

Incidental Oral 

Short-Term

(1-30 days)and 

IntermediateTerm (1-6 

months)

NOAEL= 

14.5

mg/kg/day

UFA= 10X

UFH=10X

FQPA SF=1X

Residential 

LOC for 

MOE = 100

Reproduction study in rats

The LOAEL of 82.8 mg/kg/day is based 

clinical chemistry changes and increased 

kidney weight in parents, and decreased 

body weight and body weight gain with 

decreases in spleen and thymus weights in 

offspring.
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Table 4.3.4.1. Summary of Toxicological Doses and Endpoints for Fluopyram for Use in Dietary and NonOccupational 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

Dermal ShortTerm (1-30 

days) and 

IntermediateTerm (1-6 

months)

NOAEL= 

300

mg/kg/day

UFA= 10X

UFH=10X

FQPA SF=1X

Residential 

LOC for 

MOE = 100

A 28-day dermal study in rats

The LOAEL of 1000 mg/kg/day is based 

on increased cholesterol (F), increased 

prothrombin time (M).

Inhalation 

Short- Term

(1-30 days)

and 

IntermediateTerm (1-6 

months)

NOAEL= 

14.5 

mg/kg/day

UFA= 10X

UFH=10X

FQPA SF=1X

Residential 

LOC for 

MOE = 100

Reproduction study in rats

The LOAEL of 82.8 mg/kg/day is based 

clinical chemistry changes and increased 

kidney weight in parents, and decreased 

body weight and body weight gain with 

decreases in spleen and thymus weights in 

offspring.

Cancer (oral, 

dermal, 

inhalation)

The CARC has classified fluopyram as “Not Likely to be Carcinogenic to Humans” at doses that 

do not induce cellular proliferation in the liver or thyroid glands and determined that 

quantification of cancer risk is not required.

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

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

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

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

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

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

of concern. 

Table 4.3.4.2 Summary of Toxicological Doses and Endpoints for Fluopyram for Use in Occupational Human 

Health Risk Assessments.

Exposure/ 

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal ShortTerm (1-30 

days) and 

IntermediateTerm (1-6 

months)

NOAEL= 

300

mg/kg/day

UFA= 10X

UFH=10X

Occupational 

LOC for MOE = 

100

A 28-day dermal study in rats

The LOAEL of 1000 mg/kg/day is based 

on increased cholesterol (F), increased 

prothrombin time (M).

Inhalation 

Short-Term (1-

30 days) and 

Intermediateterm (1-6 

months)

NOAEL= 

14.5 

mg/kg/day

UFA=10X

UFH=10X

Occupational

LOC for MOE = 

100

A 2-generation reproduction study in rats. 

The LOAEL of 82.8 mg/kg/day is based 

clinical chemistry changes and increased 

kidney weight in parents, and decreased 

body weight and body weight gain with 

decreases in spleen and thymus weights in 

offspring

Cancer (oral, 

dermal, 

inhalation)

The CARC has classified fluopyram as “Not Likely to be Carcinogenic to Humans” at doses that 

do not induce cellular proliferation in the liver or thyroid glands and has determined that 

quantification of cancer risk is not required.

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 
Fluopyram Human Health Risk Assessment DP No. D421926

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

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

sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of 

concern. N/A = not applicable.

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The nature of the residue in plants is adequately understood based on metabolism studies with 

grape, potato, bean, and red pepper (D387587, L. Cheng, 02/23/2011) and with wheat seed 

treatment (D420271, S. Funk, 05/20/2014). The nature of the residue in rotational crops is 

adequately understood based on confined rotational crop studies with rotated Swiss chard, turnip, 

and wheat. The metabolic pathway of fluopyram is similar in primary and rotational crops, and 

mainly involves hydroxylation of parent compound leading to AE C656948-7-hydroxy and AE 

C656948-8-hydroxy, conjugation of the hydroxylated parent compound, mainly with sugars, and 

cleavage of the molecule leading to AE C656948-benzamide, AE C656948-pyridyl-acetic acid 

(AE C656948-PAA), and AE C656948-pyridyl-carboxylic acid (AE C656948-PCA). HED has 

determined that the residue of concern in plant commodities (primary and rotational crop) for 

tolerance enforcement is fluopyram, and for risk assessment is fluopyram in all crops except in 

legumes and oilseed crops where AE C656948-benzamide is also included. 

The nature of the residue in livestock is adequately understood based on metabolism studies with 

goats and hens (D387587, L. Cheng, 02/23/2011). Metabolism of fluopyram in livestock mainly

involves hydroxylation of the parent compound to AE C656948-7-hydroxy and AE C656948-8-

hydroxy, elimination of water from compounds hydroxylated in the ethylene bridge leading to 

AE C656948-Z/E-olefines, cleavage of the molecule leading to AE C656948-benzamide and AE 

C656948-PAA, and conjugation of the hydroxylated parent compound, mainly with glucuronic 

acid. For tolerance enforcement, HED has determined that the residues of concern are fluopyram 

and AE C656948-benzamide. For risk assessment, the residues of concern in ruminants are 

fluopyram and its metabolites AE C656948-benzamide, AE C656948-E-olefine, AE C656948-Zolefine and AE C656948-7-hydroxy, and in hens are fluopyram and its metabolites AE C656948-

benzamide, AE C656948-E-olefine, and AE C656948-Z-olefine. 

A summary of metabolites and degradates to be included in the risk assessment and tolerance 

expressions is presented in Table 5.1.

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

Assessment and Tolerance Expressions.

Matrix Risk Assessment Tolerance Expression

Plants

Primary 

Crop

Fluopyram

(Fluopyram + benzamide for legumes and oil seed crops) Fluopyram

Rotational 

Crop

Fluopyram

(Fluopyram + benzamide for legumes and oil seed crops) Fluopyram

Livestock Ruminant Fluopyram + benzamide + 7-OH-fluopyram + olefins (E, 

Z) Fluopyram + benzamide
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Table 5.1. Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expressions.

Matrix Risk Assessment Tolerance Expression

Poultry Fluopyram + benzamide + olefins (E, Z) Fluopyram + benzamide

Drinking Water Fluopyram Not Applicable

5.2 Food Residue Profile

The crop field trials are adequate for tolerance assessment and for risk assessment. Residues 

were quantifiable in all cases except sweet corn. 

The previously reviewed cotton, peanut, and soybean processing study showed no concentration 

of fluopyram in oil and meal. The canola and sunflower processing studies showed that 

fluopyram did not concentrate in meal or refined oil. The benzamide metabolite did not 

concentrate in meal or oil. 

Fluopyram residues concentrate on apple wet pomace, corn bran, orange oil, potato wet peel, 

raisin, dried tomatoes, dried peaches, sugar beet (dried and refined sugar), wheat bran and wheat 

germ. 

Existing storage stability study data are adequate to support the intervals of frozen storage of all 

raw agricultural and processed commodities from the proposed uses. No corrections for 

degradation during storage are needed.

The livestock diets were revised using the recommended crop field trial data. Exposures 

increased from 0.38 ppm for beef cattle, 1.2 ppm for dairy cattle, 0.083 ppm for poultry, and 

0.082 ppm for swine to 3.58 ppm for beef cattle, 24.8 ppm for dairy cattle, 0.36 ppm for poultry, 

and 0.39 ppm for swine. 

5.3 Water Residue Profile

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

(D427985M, A. Ruhman, 10/26/2015). The residue of concern in drinking water for this single 

chemical risk assessment is fluopyram, (Residues of Concern Knowledge-base Subcommittee 

[ROCKS], D367115, 07/16/2009). The EFED estimated surface water and ground water 

residues for fluopyram using the surface water concentration calculator (SWCC) and PRZM-GW

model, respectively. The EDWCs includes all new uses and currently registered uses. The 

drinking water models and their descriptions are available at the EPA internet site: 

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

For surface water EDWCs, the peak value is 50.6 ppb and the chronic (non-cancer) value is 17.3

ppb.
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For ground water, the highest acute ground water EDWC is 97.6 ppb of parent fluopyram and the 

chronic value is 90.5 ppb of parent fluopyram. Ground water EDWCs are used in the dietary

assessment, since they were higher than those for surface water. For the human health risk 

assessment, the highest relevant EDWCs are recommended. 

Table 5.3. Estimated Surface and Ground Water Concentrations for Fluopyram.

Scenario Surface Water Conc., ppb Ground Water Conc., ppb

Acute 50.6 97.6a

Chronic (non-cancer) 17.3 90.5a

Chronic (cancer) 11.0 NA

a Bold values were used in the dietary assessment.

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

The acute dietary analysis is an unrefined conservative assessment that included tolerance 

residue levels, the assumption of 100% crop treated, and processing factors (empirical and 

default). The EDWC was incorporated directly into the acute dietary assessment (ground water 

EDWC of 97.6 ug/L) and was calculated by PRZM-GW modeling.

The chronic dietary analysis is a refined assessment that included average residue levels, % crop 

treated, and processing factors (empirical and default). The EDWC from PRZM-GW modeling 

was incorporated directly into the chronic dietary assessment (ground water EDWC of 90.5 

μg/L).

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute dietary exposure analysis assumed that 100% of the proposed crops were treated with 

fluopyram.

The Biological and Economic Analysis Division (BEAD) has provided updated percent crop 

treated data for new uses (PCTn) for fluopyram (DP# 427397, 09/22/2015), which includes both 

average and maximum PCT values. In addition, the previous PCTn (2010 and 2011) were 

considered acceptable (DP# 370371 (2010); DP# 381225 (2011); DP# 387227 (2011).

The following average percent crop treated estimates were used in the chronic dietary risk 

assessment for the following crops that are currently registered/proposed for fluopyram: 

potatoes 64%; sugar beets 48%; celery 60%; head lettuce 67%; leaf lettuce 62%; spinach 43%

(BEAD recommends using USDA/NASS spinach PCT values as a proxy for Brassica leafy

vegetables and leafy vegetables); broccoli 24%; snap beans 44%; dry beans/peas 7%; soybeans 

17%; fresh tomatoes 64%; processed tomatoes 57%; cantaloupes 22%; cucumbers 41%; 

pumpkins 45%; squash 47%; watermelons 54%; oranges 39%; apples 40%; pears 43%; peaches 

56%; grape wine 79% (used for grape, wine and sherry); strawberries 75%; almonds 33%; corn 
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field 9%; corn, sweet 50%; wheat 17% (from spring wheat at 17% and winter wheat at 6%); 

peanuts 67%; blueberries 54%; and blackberries 55%. 

5.4.3 Acute Dietary Risk Assessment

Estimated acute dietary exposure to fluopyram from food and drinking water for all population 

subgroups is below 100% of the acute Population Adjusted Dose (aPAD). Combined dietary

exposure from food and drinking water at the 95th percentile of exposure is estimated to be

0.096117 mg/kg/day for the overall U.S. population, equivalent to19% of the aPAD. The 

population subgroup with the highest estimated acute dietary exposure to fluopyram is children 

1-2 years old, with an estimated exposure at the 95th percentile of 0.175170 mg/kg/day, 

equivalent to 35% of the aPAD. HED is concerned when estimated dietary risk exceeds 100% of 

the aPAD (see Table 5.4.6).

5.4.4 Chronic Dietary Risk Assessment

Estimated chronic dietary exposure from food and drinking for all population subgroups is below 

100% of the chronic Population Adjusted Dose (cPAD). Combined dietary exposure from food 

and drinking water is estimated to be 0.003703 mg/kg/day for the general U.S. population, 

equivalent to 31% of the cPAD. The population subgroup with the highest estimated chronic 

dietary exposure to fluopyram is children 1 to 2 years old, with an estimated exposure of 

0.009733 mg/kg/day, equivalent to 81% of the cPAD. HED is concerned when estimated dietary

risk exceeds 100% of the cPAD (see Table 5.4.6). 

5.4.5 Cancer Dietary Risk Assessment

The CARC classified fluopyram as “Not Likely to be Carcinogenic to Humans”. Therefore, a 

cancer dietary exposure analysis is not required.

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food & Drinking Water) Exposure and Risk for Fluopyram

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure(mg/kg/day) % cPAD

General U.S. Population 0.096117 19 0.003703 31

All Infants (< 1 year old) 0.137520 28 0.007331 61

Children 1-2 years old 0.175170 35 0.009733 81

Children 3-5 years old 0.160828 32 0.006787 56

Children 6-12 years old 0.092779 19 0.004079 34

Youth 13-19 years old 0.073266 15 0.002617 22
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Table 5.4.6. Summary of Dietary (Food & Drinking Water) Exposure and Risk for Fluopyram

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure(mg/kg/day) % cPAD

Adults 20-49 years old 0.088800 18 0.003324 28

Adults 50+ years old 0.091387 18 0.003315 28

Females 13-49 years old 0.092231 18 0.003256 27

1The population subgroup with the highest estimated acute and chronic dietary (food + drinking water) exposure and risk is indicated by bold 

text.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

Based on the proposed product labels, several products are intended for use by homeowners, or 

by occupational handlers in residential settings. Therefore, non-occupational/residential risk 

assessments have been completed.

6.1 Residential Handler Exposure

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

residential handler scenarios of mixing, loading, and applying liquid formulations to gardens, 

ornamentals, fruit trees, and turf by manually pressurized handwand, hose-end sprayers, 

backpack, or sprinkler cans. Short-term dermal and inhalation exposures were assessed for 

residential handlers. All residential handler risk estimates are not of concern to HED (all MOEs 

≥100), with MOEs ranging from 8,900 to 190,000 for dermal exposures and 260,000 to 130,000 

for inhalation exposures. Summaries of the short-term risk estimates for residential handlers are 

included in Appendix D, Table D.1.

6.2 Residential Post-application Exposure

There is the potential for post-application exposure to fluopyram for individuals exposed as a 

result of being in an environment that has been previously treated with fluopyram. The 

quantitative exposure/risk assessment for residential post-application exposures includes the 

following scenarios: 

 Adults and children (1 to < 2 years old) dermal exposure to treated turf during high 

contact lawn activities,

 Children (1 to < 2 years old) incidental oral exposure as a result of contacting treated turf,

 Adults and youths (11 to <16 yr old) dermal exposure to treated turf during mowing and 

golfing activities,

 Children (6 to < 11 years old) dermal exposure to treated turf during golfing activities, 

and

 Adults and children (6 to < 11 years old) dermal exposure to treated gardens.
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Exposures are expected to be short-term in duration. Short-term dermal and incidental oral 

exposure and risk estimates have been assessed. The exposure assessment for dermal exposure 

to treated gardens is protective of exposure to treated ornamental and fruit trees. 

Turf Transferable Residue (TTR) data for Fluopyram

Because turf transferable residue data were not available for fluopyram, turf residues were 

estimated using default assumptions. A TTR study is not required for fluopyram at this time. 

Refer to Section 9.2.1 of this document for a detailed rationale.

Dislodgeable Foliar Residue (DFR) data for Fluopyram

Because dislodgeable foliar residue data were not available for fluopyram, foliar residues were 

estimated using default assumptions. A DFR study is not required for fluopyram at this time. 

Refer to Section 9.2.1 of this document for a detailed rationale.

Combining Exposure and Risk Estimates

HED combines risk values resulting from separate routes of exposure when it is likely they can

occur simultaneously based on the use pattern and the behavior associated with the exposed 

population, and if the hazard associated with the points of departure is similar across routes. 

Since dermal and incidental oral exposure routes do not share a common toxicological endpoint 

for fluopyram, risk estimates have not been combined for those routes. 

Summaries of the short-term risk estimates for residential post-application exposures are 

included in Appendix D, Tables D.2 through D.4.

Tables D.2 and D.3 summarize the residential post-application exposure and risk estimates for 

exposures to treated lawns and turf. The proposed liquid formulations do not lead to postapplication risk estimates of concern. Residential dermal post-application MOEs for all life 

stages range from 1,000 to 97,000. Residential incidental oral post-application MOEs for 

children 1 to <2 years old range from 2,400 to 1,100,000.

Table D.4 summarizes the residential post-application exposure and risk estimates for exposures 

to treated gardens, ornamental trees and shrubs, and fruit trees. The proposed liquid 

formulations do not lead to post-application risk estimates of concern (all MOEs ≥100). 

Residential dermal post-application MOEs for all life stages range from 2,100 to 33,000.

6.3 Residential Risk Estimates for Use in Aggregate Assessment

The most conservative residential handler or post-application risk estimates should be used in the 

aggregate risk assessment. The residential exposures that are recommended for use in the 

aggregate assessment for fluopyram are as follows:

 The recommended residential exposure for use in the adult aggregate assessment reflects 

dermal post-application exposure to treated lawns from high contact activities.

 The recommended residential exposure for use in the children (11 to <16 years old) 

aggregate assessment reflects dermal post-application exposure from golfing.

 The recommended residential exposure for use in the children (6 to <11 years old) 
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aggregate assessment reflected dermal post-application exposure to treated gardens.

 The recommended residential exposure for use in the children (1 to <2 years old) 

aggregate assessment reflects dermal post-application exposure to treated lawns from 

high contact activities.

The residential risk estimates from these exposures are presented in Table 6.3.1. 

Table 6.3.1. Recommendations for the Residential Exposures for the Fluopyram Aggregate Assessment.

Lifestage Dose 

(mg/kg/day)4 MOE5

Adults [inhalation handler exposure from treating lawns by hose-end sprayer] 0.000056 260,000

Child (1 to <2 years old) [incidental oral hand-to-mouth post-application exposure to treated lawns] 0.00615 2,400

6.4 Residential Bystander Post-application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby pesticide applications. The agency sought expert advice and input on issues 

related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2009-0687-

0037). The agency has evaluated the SAP report and has developed a Volatilization Screening 

Tool and a subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the Agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for fluopyram.

In addition to this screen, the Agency has developed a preliminary bystander volatilization 

inhalation exposure assessment for fluopyram utilizing the currently available inhalation toxicity

and air monitoring data. 

6.5 Non-Occupational Spray Drift Exposure and Risk Estimates

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom and 

airblast) employed for fluopyram. The agency has been working with the Spray Drift Task Force 

(a task force composed of various registrants which was developed as a result of a Data Call-In 

issued by EPA), EPA Regional Offices and State Lead Agencies for pesticide regulation and 

other parties to develop the best spray drift management practices (see the agency’s Spray Drift 

website at http://www2.epa.gov/reducing-pesticide-drift for more information). The agency has 

also developed a policy on how to appropriately consider spray drift as a potential source of 

exposure in risk assessments for pesticides. The potential for spray drift will be quantitatively

evaluated for each pesticide during the Registration Review process which ensures that all uses 

for that pesticide will be considered concurrently. The approach is outlined in the revised (2012) 

Standard Operating Procedures For Residential Risk Assessment (SOPs) - Residential Exposure 
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Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift. This 

document outlines the quantification of indirect non-occupational exposure to drift. 

7.0 Aggregate Exposure/Risk Characterization

In accordance with the 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 

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. There is potential acute and chronic exposure via the diet (food and 

drinking water). Additionally, there are proposed residential uses so short-term residential 

exposures are likely to occur; and therefore, short-term aggregate risks were assessed. 

7.1 Acute Aggregate Risk

The aggregate acute risk estimates include exposure to residues of fluopyram in food and 

drinking water, and does not include dermal, inhalation, or incidental oral exposure. As 

demonstrated under section 5.4.3, acute aggregate risks are not of concern. 

7.2 Short-Term Aggregate Risk

There is potential short-term exposure to fluopyram via dietary (which is considered background 

exposure) and residential (which is considered primary) exposure pathways. For children 6 to 

<11 years old and youths 11 to <16 years old, these pathways lead to exposure via oral 

(background) as well as dermal (primary) routes. For adults, these pathways lead to exposure via 

oral (background) as well as dermal and inhalation (primary) routes. The most conservative 

scenarios were chosen for each. For a description of the residential exposure scenarios 

considered in the aggregate assessment, see Section 6.3. 

The short-term aggregate MOEs for small children and for adults are both 1,500, and are 

therefore not of concern to HED (see Table 7.2.1). 

Table 7.2.1. Short-Term Aggregate Risk Calculations 

Lifestage Residential Exposure Scenario NOAEL

mg/kg/day

LOC1 Max 

Exposure2

Residential 

Exposure

mg/kg/day

Average 

Dietary 

Exposure

mg/kg/day

Total 

Exposure 

mg/kg/day

Aggregate 

MOE2

Child 1 to <2 yr Incidental oral hand-to-mouth post-application 

exposure to treated lawns 14.5 100 0.145 0.000056 0.009733 0.009789 1,500

Adult Inhalation handler exposure from treating 

lawns by hose-end sprayer 14.5 100 0.145 0.00615 0.003324 0.009474 1,500

1 The Level of Concern MOE is 100.

2 Maximum Exposure (mg/kg/day) = NOAEL/LOC MOE

3 Aggregate MOE = [NOAEL ÷ (Average Dietary Exposure + Residential Exposure)]

7.3 Chronic Aggregate Risk

Chronic exposure from the residential pathway is not anticipated based on the current fluopyram 

use pattern. The chronic aggregate risk (food and drinking water) is below HED’s LOC (i.e., 
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<100% cPAD for the general U.S. population and all population subgroups). See Section 5.4.4 

for details.

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 fluopyram and any other substances and fluopyram 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 fluopyram 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

This document presents an assessment of the proposed uses of fluopyram on numerous 

agricultural field crops, turf grass, ornamentals, and Christmas trees, and seed treatment to 

peanuts. Refer to Table 3.3.1 for a detailed description of the proposed uses. Based on 

application rates and label information, only short- and intermediate-term exposures are expected 

for occupational handlers and post-application workers. Long-term exposure is not expected for 

the proposed use patterns.

9.1 Short-/Intermediate-Term Handler Risk

Based on the anticipated use patterns and proposed labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

The quantitative dermal and inhalation exposure/risk assessment developed for occupational 

handlers is based on the following scenarios: 

1) Mixing/loading liquids for aerial and chemigation application,

2) Mixing/loading liquids for groundboom application,

3) Mixing/loading liquids for airblast application, 

4) Applying sprays via aerial equipment, 

5) Applying sprays via groundboom equipment, 

6) Applying sprays via airblast equipment, 

7) Flagging for aerial sprays, 

8) Mixing, loading, and applying liquids with manually pressurized handwand, 

9) Mixing, loading, and applying liquids with mechanically-pressurized handgun, and

10) Mixing, loading, and applying liquids with a backpack.

The proposed labels require occupational handlers to wear the following attire and PPE: long 

sleeved shirts, long pants, shoes, socks, and chemical resistant gloves. However, the FLU+TFS

SC 32.5 and FLU+TFS SC 25 labels do not require the use of gloves. 
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For all exposure scenarios the risk estimates do not exceed HED’s LOC (i.e., MOEs ≥100) at 

baseline (i.e., long sleeved shirt, long pants, shoes plus socks, without gloves or a respirator). 

The MOEs ranged from 410 to 1,500,000 for dermal exposure at baseline, 2,400 to 1,100,000 for 

dermal exposure with the addition of gloves, and 7,400 to 30,000,000 for inhalation exposure. 

Refer to Appendix E, Table E.1, for the summary of occupational handler risk estimates.

The proposed seed treatment of peanuts is on the Luna®Privilege label (4.16 lb ai/gal) [EPA 

Reg. No. 264-1078], which requires water proof gloves for seed treatment activities and no 

gloves for baggers and bag sewers.

For seed treatment use on peanut seeds, the quantitative exposure/risk assessment developed for 

occupational handlers is based on the following scenarios: 1) Mixing/loading liquids for 

commercial seed treatment; 2) Bagging treated seed; 3) Sewing bags; 4) Multiple activities; and 

5) Planting treated seed. Risk estimates for dermal and inhalation short-term occupational 

handler exposures all resulted in MOEs ≥100, and therefore, do not exceed HED’s level of 

concern, with MOEs ranging from 1,400 to 9,200 for dermal exposures and from 1,700 to 17,000 

for inhalation exposures. Refer to Appendix E, Table E.2. 

9.2 Short-/Intermediate-Term Post-Application Risk

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

9.2.1 Dermal Post-application Risk

The post-application dermal exposure and risk estimates associated with agricultural crops, 

Christmas trees, and nursery ornamentals are summarized in Appendix E, Table E.4. For each 

crop or crop group the post-application activities with the highest transfer coefficient and highest 

exposure contact are presented. Short- and intermediate-term dermal post-application exposures 

and risks to occupational workers were estimated using standard values established by HED 

since no chemical-specific data were submitted. The transfer coefficients (TC) used for all postapplication activities were the TCs established by the Science Advisory Council for Exposure 

Policy Number 3.1 (http://www.epa.gov/pesticides/science/exposac_policy3.pdf). This policy

reflects adoption of all Agricultural Re-Entry Task Force (ARTF) data. Use of the data in this 

policy requires compensation to the ARTF under FIFRA. The transfer coefficients (TCs) used in 

this assessment were taken from the Agency’s revised Agricultural Transfer Coefficient SOP. 

Many of the TCs in this SOP are based on work of the ARTF. The occupational post-application 

MOEs for all crops and crop groups and scenarios do not exceed HED’s level of concern (MOEs 

≥100) on day 0 (i.e., 12 hours following application) with dermal MOEs ranging from 250 to 
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23,000. All other scenarios involving lesser contact activities would have higher MOEs and are 

also not of concern.

For use on cotton, HED has also assessed the post-application dermal exposure and risk 

estimates for workers involved in harvesting cotton bolls. Although most of cotton harvesting is 

done mechanically, there are still some activities, with the potential for exposure, that are 

associated with the harvesting of cotton. The anticipated post-application activities and dermal 

transfer coefficients for these activities are presented in Appendix E, Table E.5. The 

recommended transfer coefficients are derived from EPA’s Science Advisory Council for 

Exposure (ExpoSAC) Policy 3 (http://www.epa.gov/pesticides/science/exposac-policy3-

march2013.pdf). No chemical specific data are available for the amount of residue available on 

the cotton bolls; i.e., dislodgeable boll residue (DBR) data. Such data are available from a study

with the active ingredient tribufos; i.e., MRID 42701601. Note to RD: These data may be 

proprietary, and subject to the data protection provisions of FIFRA, and therefore, may 

trigger a data compensation issue between registrants. Since the proposed fluopyram labels 

include a 30 day pre-harvest interval, the best fit residue data used from MRID 42701601 was 

chosen from 30 days after harvest and then adjusted for the difference in application rates. All of 

the cotton harvesting activities resulted in MOEs ranging from 3,100,000 to 17,000,000, which 

do not exceed the LOC, and are therefore not of concern; see Appendix F, Table F.6.

For use on turf, the exposure/risk assessment for the proposed uses results in a post-application 

occupational MOE of 9,000, which is above the dermal LOC (MOE ≥100); and therefore is not 

of concern; see Appendix E, Table E.7.

Dislodgeable Foliar Residues:

There were no chemical-specific dislodgeable foliar residue data to assess post-application risks 

to workers while performing tasks related to crops treated with fluopyram. For agricultural 

crops, occupational post-application exposures and risks were assessed using HED’s default 

assumptions that 25% of the initial application is available for transfer on day 0 (i.e., 12 hours 

after application) and that the residue dissipates at a rate of 10% per day. 

In accordance with 40 CFR §158, DFR data are required for all occupational (e.g., crop, nursery, 

greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own 

farms, retail tree farms) uses that could result in post-application exposure to foliage. In the 

absence of chemical-specific DFR data, EPA uses default values. The 2012 Standard Operating 

Procedures for Residential Pesticide Exposure Assessment includes an analysis of a number of 

DFR studies, which resulted in the selection of a revised default values for the fraction of the 

application rate available for transfer after a foliar application (FAR). These values are based on 

an analysis of 19 DFR studies. Since that time, the Agricultural Re-entry Task Force has 

submitted information (MRID 49299201) that corrects an application rate error made in the 

original submission of “ARF039 – Determination of Dermal and Inhalation Exposure to Reentry

Workers During Chrysanthemum Pinching in a Greenhouse” (EPA MRID 45344501). As a 

result, the range of FAR values was revised from 2% - 89% to 2% - 47%. In the data, a large 

range of transferability is observed and this variability can potentially be attributable to many 

factors such as active ingredient; formulation; field conditions in the studies; weather conditions 

(e.g., humidity); or many other difficult to quantify factors. Although witnessed across multiple 
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chemicals, this range in FAR values is not expected when considering DFR data for a single 

chemical. At this time, the ARTF submission did not alter the selection of 25% as the 

reasonable, high-end default value. Because DFR data are not available for fluopyram, EPA is 

using the default value of 25%. Although there may be a small degree of uncertainty in the use 

of the default DFR value for fluopyram (i.e., there is a small chance that the FAR value may

exceed the applicable default value), it is likely that the health-protective aspects of EPA’s 

occupational post-application assessment methodology will more than compensate for this 

potential uncertainty. For example, when assessing residential and occupational postapplication exposure to gardens and ornamentals, EPA assumes the following: exposures occur 

to zero-day (i.e., day of application ) residues every day of the assessed exposure duration (i.e., 

EPA assumes that no dissipation or degradation occurs, it doesn’t rain, etc); individuals perform 

the same post-application activities performed in the transfer coefficient study day after day (e.g., 

weeding, harvesting, pruning, etc.); and individuals engage in these post-application activities for 

a high-end amount of time every day (represented by data reflecting time spent gardening based 

on survey data).

Given the conservatisms discussed above and the potential compounding nature of these 

conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that 

exposure is not being underestimated. 

Since the highest estimated residential and occupational post-application exposures using default 

DFR values for fluopyram are minimal in comparison to the level of concern (i.e., the calculated 

MOE is greater than 2 times higher than the level of concern, residential MOE = 2,100 and 

occupational MOE = 250 compared to the LOC of 100); EPA is not imposing the 40 CFR §158 

DFR data requirement at this time. In this instance, it is unlikely that chemical-specific DFR 

data would be needed to further refine exposure assessments or would add appreciably to our 

overall understanding of the availability of dislodgeable foliar pesticide residues for fluopyram. 

Turf Transferrable Residues

A turf transferrable residue study has not been submitted for fluopyram. Therefore, HED’s 

standard operating procedures and assumptions were used to determine an estimate of day zero 

fluopyram residues on treated turf. 

In accordance with 40 CFR §158, TTR data are required for all occupational (e.g., sod farms, 

golf courses, parks, and recreational areas) or residential turf uses that could result in postapplication exposure to turf. In the absence of chemical-specific TTR data, EPA uses default 

values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment includes an analysis of all TTR data, available at the time, which resulted in the 

selection of revised liquid and granular default values for the fraction of the application rate 

available for transfer after a turf application (FAR). These values are based on an analysis of 59 

TTR studies performed with the Modified California Roller Method (36 studies using liquids, 11 

studies using wettable powders/water dispersible granules, and 12 studies using granules). The 

liquid results (N=131) indicate a range of FAR values from 0.0005% to 6.1% and the granular 

results (N=37) indicate a range of 0.00064% to 0.69%. In both the liquid and granular data, a 

large range of transferability is observed and this variability can potentially be attributable to 

many factors such as active ingredient; formulation; field conditions in the studies; weather 
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conditions (e.g., humidity); or many other difficult to quantify factors. Although witnessed 

across multiple chemicals, this range in FAR values is not expected when considering TTR data 

for a single chemical. HED selected 1% and 0.2% as high-end default values for liquid and 

granular products, respectively. Because TTR data are not available for fluopyram, EPA is using 

the default value of 1%. Although there may be a small degree of uncertainty in the use of the 

default TTR value for fluopyram (i.e., there is a small chance that the FAR value may exceed the 

applicable default value), it is likely that the health-protective aspects of EPA’s residential and 

occupational post-application turf assessment methodology will more than compensate for this 

potential uncertainty (i.e., the methodology is likely to overestimate exposure by a factor greater 

than the factor than the highest measured FAR values exceed the defaults). For example, when 

assessing residential post-application turf exposure, EPA assumes the following: exposures 

occur to zero-day (i.e., day of application ) residues every day of the assessed exposure duration 

(i.e., EPA assumes that no dissipation or degradation occurs, it doesn’t rain, the grass is not 

mowed, etc.); individuals perform the same post-application activities performed in the turf 

transfer coefficient study day after day (e.g., tumbling, playing on turf with toys, etc.); and 

individuals engage in these post-application activities for a high-end amount of time every day

that is represented by data reflecting time children spend outdoors and not specifically engaged 

in activities on turf, when in actuality children do not spend all of their outdoor time on turf and 

high-end levels of activity will not occur every day.

Given the conservatisms discussed above and the potential compounding nature of these 

conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that 

exposure is not being underestimated.

Since the estimated residential turf post-application exposure from high contact activities on 

lawns and the occupational post-application activities on golf course turf using default TTR 

values for fluopyram are minimal in comparison to the level of concern (i.e., the calculated 

MOEs are greater than 10 times higher than the level of concern, residential MOE = 1,000 and 

occupational MOE = 9,000, compared to the LOC of 100); EPA is not imposing the 40 CFR 

§158 TTR data requirement at this time. In this instance, it is unlikely that chemical-specific 

TTR data would be needed to further refine exposure assessments or would add appreciably to 

our general understanding of the availability of turf transferable pesticide residues.

Restricted Entry Interval: Since post-application risks were not a concern on day 0 (12 hours 

following application), the REI is based on the acute toxicity of fluopyram technical material. 

Fluopyram is classified as Toxicity Category III by the acute oral and dermal routes of exposure

and Toxicity Category IV for acute inhalation, eye irritation potential and skin irritation 

potential. Under the WPS for Agricultural Pesticides, active ingredients classified as acute 

toxicity categories III or IV for these routes are assigned a 12-hour REI. Therefore, the 12-hour 

REI that appears on the proposed labels is adequate.

9.2.2 Inhalation Post-application Risk

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 
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pesticides. The agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency has 

evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent 

Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agency will utilize this analysis to determine 

if data (i.e., flux studies, route-specific inhalation toxicological studies) or further analysis is 

required for fluopyram].

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

occupational post-application inhalation exposure into the agency's risk assessments.

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

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.”
Fluopyram Human Health Risk Assessment DP No. D421926

Page 58 of 87

10.0 References

O’ Keefe, B., 12/18/2015, D426622. Fluopyram: Occupational and Residential Exposure 

Assessment for New Uses on artichoke (globe), Brassica (cole) leafy vegetables, Brassica (cole) 

leafy vegetables head and stem subgroup, bulb vegetables, canola, carrot, cereal grains (except 

rice), citrus, corn (including field, sweet, popcorn, and field corn grown for seed)cotton, cucurbit 

vegetables, fruiting vegetables, ginseng, grapes and small vines fruits (except fuzzy kiwifruit), 

herbs and spices (except black pepper), hops, leafy vegetables, legume vegetables (including 

soybean), peanut, pome fruits, potato and other root, tuberous and corm vegetables, small berries 

(caneberries and bushberries), stone fruit, strawberry and other low growing berries, sugar beet, 

sunflower subgroup, tree nuts; use as a seed treatment to peanuts; turf grass (golf courses, sod 

farms, sports fields, residential, industrial, municipal, commercial, and other turf grass areas), 

ornamentals (in residential and commercial settings), and Christmas trees.

Cheng, L., 09/23/2011, D387587 and D389081. Fluopyram. Application for Section 3 

Registration for Use on Apple, Banana (Import only), Dried Beans, Cherry, Grape (Wine 

Production only), Peanut, Pistachio, Potato, Sugar Beet, Strawberry, Tree Nuts Crop Group 14, 

Watermelon, and Rotational Crops Alfalfa, Canola, Cotton, Cereal Grains Crop (Except Rice) 

Group 15, and Forage, Fodder, and Straw of Cereal Grains Crop (Except Rice) Group 16. 

Summary of Analytical Chemistry and Residue Data.

Negussie, M., 11/10/2015, D426620. Fluopyram. Tolerances and Registration for Use on Crop 

Subgroup 1B, Subgroup 1C, Crop Group 2, Subgroup 3-07A, Subgroup 3-07B, Subgroup 4A, 

Subgroup 4B, Subgroup 5A, Subgroup 5B, Subgroup 6A, Subgroup 6B, Dry Bean, Subgroup 8-

10A, Subgroup 8-10B, Subgroup 9A, Subgroup 9B, Subgroup 10-10, Group 11-10, Subgroup 

12-12A, Subgroup 12-12B, Subgroup 12-12C, Subgroup 13-07A, Subgroup 13-07B, Subgroup 

13-07F, Subgroup 13-07G, Crop Group 15 (except corn and rice), Crop Group 16, Subgroup 

19A, Dill Seed, Subgroup 20A, Subgroup 20B, Subgroup 20C, Artichoke (Globe), Hops, 

Soybean, and Sugarcane (Rotated). Amended Tolerance Requests for the Registered Uses due to 

Crop Group/Subgroup Expansion Requests, Additional Use Patterns, and Tolerance ReAssessments. Summary of Analytical Chemistry and Residue Data.

Negussie, M., 11/10/2015, D426621. Fluopyram: Acute and Chronic Aggregate Dietary 

Exposure and Risk Assessments for Section 3 Registration for New Uses on Crop Subgroup 1B, 

Subgroup 1C, Crop Group 2, Subgroup 3-07A, Subgroup 3-07B, Subgroup 4A, Subgroup 4B,

Subgroup 5A, Subgroup 5B, Subgroup 6A, Subgroup 6B, Dry Bean, Subgroup 8-10A, Subgroup 

8-10B, Subgroup 9A, Subgroup 9B, Subgroup 10-10, Group 11-10, Subgroup 12-12A, Subgroup 

12-12B, Subgroup 12-12C, Subgroup 13-07A, Subgroup 13-07B, Subgroup 13-07F, Subgroup 

13-07G, Crop Group 15 (except corn and rice), Crop Group 16, Subgroup 19A, Dill Seed, 

Subgroup 20A, Subgroup 20B, Subgroup 20C, Artichoke (Globe), Hops, Soybean, and 

Sugarcane (Rotated). Amended Tolerance Requests for the Registered Uses due to Crop 

Group/Subgroup Expansion Requests, Additional Use Patterns, and Tolerance Re-Assessments. 

Summary of Analytical Chemistry and Residue Data.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 59 of 87

Ruhman, M. A., 10/26/2015: Refinement of the Estimated Drinking Water Concentrations of 

Fluopyram New Uses on Artichoke, Vegetables (Brassica, bulb, cucurbits, fruiting, leafy, 

legumes and root/tuberous/corm), Carrot, Cereal grains, Citrus, Cotton, Ginseng, Grapes, Small 

vines fruits, grasses (forage/feed/seed), Herbs, Hops, Soybean, Oil seed group, Ornamentals, 

Peanut, Pome fruits, Potato, Small berries, Stone fruit, Strawberry and other low-growing 

berries, Sugarbeet, Tree nuts and Turf for Use in Human Health Risk Assessment.

Ruhman, M. A., 04/01/2015: Estimated Drinking Water Concentrations of Fluopyram New Uses 

on Artichoke, Vegetables (Brassica, bulb, cucurbits, fruiting, leafy, legumes and 

root/tuberous/corm), Carrot, Cereal grains, Citrus, Cotton, Ginseng, Grapes, Small vines fruits, 

grasses (forage/feed/seed), Herbs, Hops, Soybean, Oil seed group, Ornamentals, Peanut, Pome 

fruits, Potato, Small berries, Stone fruit, Strawberry and other low-growing berries, Sugarbeet, 

Tree nuts and Turf for Use in Human Health Risk Assessment.

Scollon, E., 7/16/2009, D367115. Fluopyram. Report of the Residues of Concern 

Knowledgebase Subcommittee (ROCKS).

Rowland, J., 05/08/2014, TXR0056961. Fluopyram: Report of the Cancer Assessment Review 

Committee.

Rury, K., 01/30/2013, TXR 0056523. Fluopyram: Summary of Hazard and Science Policy

Council (HASPOC) Meeting of November 29, 2012: Recommendations on the Waiver Request 

for the Subchronic Inhalation Study Data Requirement.
Fluopyram Human Health Risk Assessment DP No. D421926

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Appendix A. Toxicology Profile

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.500) for food use for fluopyram 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

yes

no

yes

yes

yes

yes

-

Waiveda

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

-

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

yes

yes

yes

yes

yes

a

: (HASPOC, 1/30/2013; TXR 0056523) : 
Fluopyram Human Health Risk Assessment DP No. D421926

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A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile for Fluopyram.

Guideline 

No. Study Type MRID Results Toxicity Category

870.1100 Acute oral - rat 47372430 No mortalities observed at 2000 

mg/kg

III

870.1200 Acute dermal -rat 47372432 LD50 > 2000 mg/kg III

870.1300 Acute inhalation - rat 47372435

47372434

LC50 at 4 hours > 5112 mg/m3

LC50 > 5.1 mg/L

IV

870.2400 Acute eye irritation - rabbit 47723701 Non-irritating IV

870.2500 Acute dermal irritation - rabbit 47372436 Non-irritating IV

870.2600 Skin sensitization - mouse 47372440 Non-sensitizing Not Applicable

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

Non-guideline 28-day dietary rat 

study (exploratory)

47372516; (2004)

Acceptable

50, 400, 3200 ppm

(4., 31, & 254 mg/kg/day ♂

4.6, 36, & 263 mg/kg/day 

♀)

NOAEL = 31 mg/kg/day

LOAEL = 254 mg/kg/day based on  platelet count and 

prothrombin time (M),  cholesterol and triglycerides 

(M/F),  aspartate aminotransferase and alkaline 

phosphatase

 liver weight with hepatocellular hypertrophy (M/F)

 thyroid weight with follicular cell hypertrophy (M)

Non-guideline 28-day rat study 

(dietary) 

(preliminary)

AE C657188 (PCA), 

a soil metabolite of 

AE C638206

47372521; (2003)

Acceptable

20; 200; 2,000, & 20,000 

ppm

(1.5; 15; 149; & 1,574 

mg/kg/day for ♂

1.6; 16; 162; & 1,581 

mg/kg/day for ♀)

NOAEL=1574 mg/kg (HDT) no compound related 

effects were seen.

870.3100 90-day dietary rat 

study 

47372441; (2005)

Acceptable/guideline

0, 50, 200, 1000, 3200 ppm

♂: 3, 13, 61, & 204 

mg/kg/day 

♀: 4, 15, 70, & 230 

mg/kg/day 

NOAEL = 13 mg/kg/day

LOAEL = 61 mg/kg/day based on ↓ body weight & 

food consumption, hematology parameters affected. ↑ 

cholesterol conc & -glutamyltransferase activity. 

Slight ↑ in TSH, T3 & T4. 

↑ liver, thyroid gland & kidney weights.

Liver: centrilobular hypertrophy & periportal to 

midzonal hepatocellular macrovacuolation. Thyroid 

gland: follicular cell hypertrophy. 
Fluopyram Human Health Risk Assessment DP No. D421926

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

Non-guideline 28-day dietary study 

in the mouse 

(preliminary)

47372517; (2004)

Acceptable 

150; 1,000; 5,000 ppm

♂: 25, 162, & 747 mg/kg/day

♀: 31, 162, & 954 mg/kg/day

NOAEL = 25 mg/kg/day

LOAEL = 162 mg/kg/day based on ↓ body weight gain 

(M), ↑ ALT (M), 

↑ liver weights, 27-49% (M/F) associated with: 

centrilobular hypertrophy, single cell and focal 

necrosis, hepatocellular eosinophilia and bile duct/oval 

cell hyperplasia (M/F). 

Adrenal gland: hypertrophy of zona fasciculata (F).

870.3100 90-day dietary study 

in the mouse

47372442; (2005)

Acceptable/guideline

30, 150, 1000 ppm

♂: 5, 27, & 188 mg/kg/day; 

♀: 7, 32, & 216 mg/kg/day

NOAEL = 27 mg/kg/day

LOAEL = 188 mg/kg/day based on ↑ ALT & ↓ 

albumin conc. (M/F), ↓ cholesterol conc & ↑ alkaline 

phosphatase (M), ↑ liver weights, 34-45% (M/F), ↑ 

adrenal gland weights, 87-92% (M)

Liver: centrilobular hypertrophy and

focal necrosis (M/F)

Adrenal gland: ↓ ceroid pigment (M), ↑ cortical 

vacuolation (F).

Non-guideline 28-day oral toxicity

study in dogs 

(gavage)

47372515; (2004)

Acceptable

30, 150, & 750 mg/kg/day

NOAEL = 150 mg/kg/day

LOAEL = 750 mg/kg/day based on ↓ erythrocyte 

count, hemoglobin, hematocrit (M), ↑ alkaline 

phosphatase (M/F), ↓ albumin conc. (M/F), ↑ -

glutamyltransferase activity and triglyceride 

concentration (F).

↑ liver weights associated with hepatocellular 

hypertrophy (M/F).

870.3150 90-day dietary 

toxicity study in the 

dog

47372443; (2006)

Acceptable/guideline

800; 5,000, & 20,000/10,000 

ppm (at day 15, the high dose 

group dietary concentration 

was reduced due to lack of 

palatability)

♂: 29, 171, & 332 mg/kg/day

♀: 33, 184, & 337 mg/kg/day

NOAEL = 29 mg/kg/day

LOAEL = 171 mg/kg/day based on liver effects 

characterized by ↑ alkaline phosphatase, -

glutamyltransferase activity, ALT & AST; ↓ albumin 

conc and bilirubin; ↑ liver weights associated with 

hepatocellular hypertrophy, intracytoplasmic 

eosinophilic droplets and single cell necrosis. Both 

sexes were affected.

870.3200 28-day dermal 

toxicity study in the 

rat

47372444; (2007)

Acceptable/guideline

100; 300; & 1,000 mg/kg/day

NOAEL = 300 m/kg/day

LOAEL = 1,000 mg/kg/day based on ↑ cholesterol (F), 

↑ prothrombin time (M).

870.3700 Developmental 

toxicity in the rat

47372445; (2008, Report)

(Study conducted in 2006)

Acceptable/guideline

Maternal NOAEL = 30 mg/kg/day

Maternal LOAEL = 150 mg/kg/day based on decreased 

body weight gains and food consumption, higher liver 

weights and diffused centrilobular hepatocellular 

hypertrophy.

Developmental NOAEL= 150 mg/kg/day

Developmental LOAEL = 450 mg/kg/day based 

Decreased fetal body weight (5%), increased incidence 

of two minor variations at both the visceral and skeletal 

evaluation.
Fluopyram Human Health Risk Assessment DP No. D421926

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

870.3700 Developmental 

toxicity study in the 

rabbit

47372446; (2006)

Acceptable/guideline

10, 25, & 75 mg/kg bw/day 

(gavage, GD 6-28)

Maternal NOAEL = 25 mg/kg/day

Maternal LOAEL = 75 mg/kg/day based on reduced 

body weight gain and food consumption.

Developmental NOAEL = 25 mg/kg/day

Developmental LOAEL = 75 mg/kg/day based on 

decreased fetal body weight (-11%).

Non-guideline Dose range-finding 

reproduction study 

in the rat

47372448; (2008) (Report)

Acceptable

30; 150; 750; & 1,500 ppm

♂: 2,10, 50, & 102 

mg/kg/day 

♀: 2, 12, 58, & 118 

mg/kg/day.

Parental NOAEL = 10 mg/kg/day 

Parental LOAEL = 50 mg/kg/day based on increased 

liver and kidney weights

Offspring NOAEL = 118 mg/kg/day (HDT)

Reproductive NOAEL = 118 mg/kg/day (HDT) No 

effect was seen in any of reproductive parameters 

examined.

870.3800 2-Generation 

reproduction study 

in the rat

47372447; (2008, Report)

Acceptable/guideline

40; 220; & 1, 200 ppm 

♂: 3, 15, 83 mg/kg/day 

(premating) 

♀: 3, 18, & 96 mg/kg/day 

(premating).

Parental NOAEL = 15 mg/kg/day

Parental LOAEL = 83 mg/kg/day based on increased 

creatinine, total protein, and albumin, and increased

kidney weight.

Offspring NOAEL = 15 mg/kg/day

Offspring LOAEL= 83 mg/kg/day based on decreased 

body weight (8%) with decreases in spleen and thymus 

weights.

Reproductive NOAEL = 96 mg/kg/day (HDT). No 

effect was seen in any of reproductive parameters 

examined.

870.4100 1-year toxicity study 

in dogs (dietary)

47372449; (2007)

Acceptable/guideline

100; 400; & 2,000 ppm

♂: 3, 13, & 68 mg/kg/day 

♀: 4, 14, & 66 mg/kg/day.

NOAEL = 13 mg/kg/day

LOAEL = 66 mg/kg/day based on ↓ body weight & 

food consumption (M/F), ↑ alkaline phosphatase (M/F), 

Liver: centrilobular hypertrophy.

870.4200 Carcinogenicity 

study in the mouse

47372450; (2007)

Acceptable/guideline

30, 150, & 750 ppm

♂: 4, 21, & 105 mg/kg/day 

♀: 5, 27, & 129 mg/kg/day.

NOAEL = 4 mg/kg/day

LOAEL = 21 mg/kg/day based on follicular cell 

hyperplasia in the thyroid gland, centrilobular to 

panlobular hypertrophy and hepatocellular single cell 

degeneration /necrosis in the liver. 

Thyroid gland follicular cell

adenomas in high dose males.
Fluopyram Human Health Risk Assessment DP No. D421926

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

870.4300 Chronic 

/carcinogenicity 

study in the rat

47372501; (2008)

Acceptable/guideline

30, 150 & 750/375 ppm for

♂; 30, 150 and 1,500 ppm 

for ♀.

♂: 1.2, 6.0, & 29 mg/kg/day 

♀: 1.7, 8.6, & 89 mg/kg/day 

(Due to high mortality in 750 

ppm males, this 

concentration was reduced to 

375 ppm from week 85 

onward)

NOAEL = 1.2 mg/kg/day

LOAEL = 6.0 mg/kg/day based on liver toxicity, 

nephropathy, and follicular cell hypertrophy in the 

thyroid gland.

Liver cell tumors (carcinoma and adenoma) in high 

dose females. 

870.5100 Ames test 47372502; (2006)

Acceptable/guideline

Doses: 16 to 5000 μg/plate

+/- metabolic activation

Negative

870.5100 Ames test 47372503; (2008)

Acceptable/guideline

Doses: 5 to 1581 μg/plate

 16 to 5000 μg/plate

+/- metabolic activation

Negative

870.5300 In-vitro

chromosome 

aberration (V79 

cells).

47372505; (2005)

Acceptable/guideline

Concentrations: 30, 60, 120, 

180, & 240 μg/ml.

Negative

870.5300 HPRT Test (V79 

cells).

47372504; (2006)

Acceptable/guideline

Concentrations: 4 to 256 

μg/ml

+/- metabolic activation.

Negative

870.5385 In-vivo micronucleus test in male 

mice

47372506; (2005)

Acceptable/guideline

Doses: 250, 500, & 1000 

mg/kg.

Negative

870.6200a Acute neurotoxicity 

screening battery

47372507; (2007)

Acceptable/guideline

Initial study

125; 500; and 2,000 

mg/kg/day

NOAEL = 125 for males ; <125 for females

Based on ↓ motor and locomotor activity, clinical 

signs and ↓ body temperature

LOAEL for male = 500 mg/kg/day based on ↓ motor 

and locomotor activity.

Follow-up study using only 

female rats 

25, 50 and 100 mg/kg/day.

NOAEL = 50 mg/kg/day

LOAEL = 100 mg/kg/day based on ↓ motor and 

locomotor activity.
Fluopyram Human Health Risk Assessment DP No. D421926

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

870.6200b Subchronic 

neurotoxicity 

screening battery

47372508; (2008, Report) 

(The study was conducted in 

2007)

Acceptable/guideline

100; 500; & 2,500 ppm 

♂: 7, 33, & 164 mg/kg/day 

♀: 8, 41, & 197 mg/kg/day

NOAEL = 33 mg/kg/day

LOAEL = 164 m/kg/day based on a host of effects 

which included increases in cholesterol and triglyceride 

levels, decrease in glucose level, decreases in 

hemoglobin and hematocrit, and deceases in body 

weight and food consumption.

No evidence of neurotoxicity in either neurobehavioral 

parameter or histopathology.

870.7485 ADME study in rats 47372509; (2008)

Acceptable/guideline

5 & 250 mg/kg (single dose 

by gavage )(14 C on phenyl 

ring)

5 mg/kg (radiolabeled

fluopyram) after 14 days pretreatment

With oral dosing, fluopyram was rapidly absorbed 

(93.2 % of administered radioactivity) from the GI tract 

of male and female rats. The max. plasma 

concentration was reached at 15 hrs in males and 11 

hrs in females post dosing with 5 mg/kg. After 168 hrs 

post dosing 91-99 % of the administered radioactivity 

was eliminated via urine(32-41% of the administered 

dose) and feces (53-65% of the administered dose). The 

ratio of renal and fecal elimination was comparable 

(45% via urine and 47% via feces). The organ which 

contained the highest radioactivity was the liver (0.4 to 

1.0 % of the administered radioactivity.) Considerable 

enterohepatic circulation was demonstrated by the 

results. Fluopyram was extensively metabolized and 29 

metabolites were identified. It was proposed that three 

main metabolite groups were formed in the liver 

(fluopyram-7-OH-GA, 8-OH-GA and enol-GA) 

(GA=glucuronic acid).

870.7485 ADME in the rat 47372511; (2008)

Acceptable/guideline

Single oral dose, 5 mg/kg 

(gavage) (14C in positions 2 

& 6 of the pyridyl ring)

With oral dosing, fluopyram was absorbed rapidly and 

efficiently eliminated from the body (>98% of the 

administered radioactivity was eliminated) after 72 hrs 

post dosing. No significant residues remained in the 

body. Considerable enterohepatic circulation occurred. 

Three main metabolite groups were formed in the liver 

(fluopyram-7-OH-GA, 8-OH-GA and enol-GA) 

(GA=glucuronic acid).

870.7485 Distribution of total 

radioactivity in male 

& female rats

47372513; (2008)

Acceptable/non-guideline

Single dose 14C in the phenyl 

ring of fluopyram at 3 

mg/kg.

Distribution occurred in almost all organs with liver 

reaching the maximal concentration first, and most of 

the tissue reaching the peak concentration at 

approximately 24 hr post-dosing. By 136 hr post dosing 

little of the radioactivity was present in most organs 

except nasal mucosa. 

870.7485 Distribution of 14C 

labeled fluopyram.

47372512; (2008)

Acceptable/non-guideline

3 mg/kg for ♂ & 4.5 mg/kg 

for ♀ (Single oral dose; 14C 

on pyridyl ring of 

fluopyram.)

Fluopyram was readily absorbed from the GI tract and 

distributed among almost all organs. Peak level was 

reached at approximately 1 hr after dosing in most 

organs with liver having the higher concentration than 

other organs. From peak levels, a continuous but slow 

decline of radioactivity concentrations was observed 

for all organs.

870.7485 Metabolism in 

organs and tissues in 

rats

47372509; (2008)

Acceptable/non-guideline 5 

mg/kg (Single oral dose; 14C 

in the 2 & 6 position of the 

pyridyl ring of fluopyram).

AE C656948 was extensively metabolized, and more 

than 20 metabolites were identified. The major 

metabolic transformation was oxidation and took place 

mainly at the ethylene bridge of the molecule. The 

major metabolites were AE C656948-7-hydroxy and 

AE C656948-pyridyl-acetic acid.
Fluopyram Human Health Risk Assessment DP No. D421926

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

870.7600 In-vitro dermal 

absorption study 

with human and rat 

skin

47372514 (2007)

Acceptable

500 mg AE C656948 & 0.5 

mg AE C656948 (spray 

dilution)

Dermatomed skin membranes from human and rat were 

examined. The report stated that over a period of 24 hrs 

the potentially absorbable [14C] –AE C656948 was 

1.8% and 12.4 % for human and rat skin, respectively. 

This results in approximately 6x difference between 

dermatomed human and rat skin. Rat skin being more 

permeable.

In-vivo dermal 

absorption

47567201 (2008)

Acceptable/guideline

0, 60 μg (spray dilution) and 

60 mg (neat)

The maximal dermal absorption rates for neat 

formulation and spray dilution were 4.5% and 12.8% of 

the applied dose, respectively.

870.7800 28-Day 

immunotoxicity 

study in rats

48239930; (2010)

Acceptable/guideline

0, 200, 600, 1800 ppm

0, 17.2, 53.6, 156.3 

mg/kg/day.

Immunotoxicity NOAEL for anti-SRBC IgM response 

= 156.3 mg/kg/day (HDT).

Mechanistic Studies

Non-guideline 7-Day mechanistic 

study in female rats 

(dietary 

administration)

47372520; (2008)

Acceptable/non-guideline

3,000 ppm (193 mg/kg/day).

Feeding fluopyram at 193 mg/kg/day in the diet to 

female rats did not affect body weight, clinical signs or

food or water consumption. 

Mean absolute and relative liver weights were 

increased (40 to 43%) relative to the controls. This 

increase was associated with enlarged and dark livers 

in 13/15 females. 

At histological examination, minimal to slight 

centrilobular to panlobular hepatocellular hypertrophy 

was found in all treated animals. 

There was a 4x increase in mean BrdU labeling index 

in both the perilobular and centrilobular areas of the 

hepatic lobule in treated animals relative to the 

controls.

A slight increase in total P-450 content and in mean 

EROD activity, a moderate increase in mean PROD 

and BROD activities and a marked increase in mean 

UDPGT activity (all statistically different from the 

control group (p≤0.01)) were seen. The report 

concluded that AE C656948 has the ability to induce 

moderately phenobarbital-inducible hepatic enzymes 

(total cytochrome P-450, BROD and PROD and 

UDPGT) as well as liver hypertrophy and cell 

proliferation in the liver.
Fluopyram Human Health Risk Assessment DP No. D421926

Page 67 of 87

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

Non-guideline 7-Day mechanistic 

study with 

Phenobarbital

Reduction in activity in all treated animals & slight 

reduction in body weight gain. Mean absolute and 

relative liver weights were increased (≈ 22%) relative 

to the controls. Dark liver was found in 5/14 females 

and enlarged liver in 3/14 females. Minimal to slight 

centrilobular to panlobular hepatocellular hypertrophy 

was found in all treated animals. A 2x increase in mean 

BrdU labeling index in the perilobular and centrilobular 

areas in the treated animals. A moderate increase in 

total P-450 content and in mean PROD, BROD and 

UDPGT activities (all statistically different from the 

control group p≤0.01). The report states that 

phenobarbital has the ability to induce hepatic enzymes 

like total cytochrome P-450, PROD, BROD and 

UDPGT activities as well as liver hypertrophy and cell 

proliferation in the liver. 

Non-guideline 14-Day dietary 

administration to the 

mice (hepatotoxicity 

and thyroid hormone 

investigations)

47372519; (2008

Acceptable/non-guideline

2,000 ppm

308 and 314 mg/kg for 3 or 

14 days, respectively.

After 3 days of exposure, mean T3 level was not 

changed, whereas mean T4 level was decreased (-30%) 

while mean TSH level was increased (+18%) relative 

to the controls. Mean absolute and relative liver 

weights were increased by approximately 60%. 

Enlarged liver was found in all the treated animals. 

Diffuse centrilobular to panlobular hepatocellular 

hypertrophy and an increased number of mitoses were 

observed in all examined treated animals. In addition, 

hepatocellular single cell necrosis was observed in 1/5 

treated animals. No significant microscopic change 

was observed in the thyroid gland.

Total cytochrome P-450 content was markedly 

increased (+116%) by the treatment. EROD activities 

were marginally increased (+235%), whereas PROD 

and BROD activities were markedly increased 

(respectively +2890% and +8717%) relative to 

controls. No significant changes were observed in 

UDPGT. 

Non-guideline Phenobarbital 14-

day mechanistic 

study in the mouse 

(gavage)(hepatotoxicity and thyroid 

hormone 

investigations)

47372522; (2008)

Acceptable/non-guideline

80 mg/kg for 3 or 14 days by 

gavage.

The report stated that phenobarbital administration at a 

dose level of 80 mg/kg body weight/day in the mouse 

for 3 and 14 days induced significant liver changes

including increases in hepatic total cytochrome P-450, 

PROD and BROD activities. Phenobarbital also 

induced a modification of the normal thyroid hormone 

balance (in particular by a decrease in T4 and/or T3 

after 3 and/or 14 days of exposure together with a 

concomitant increase in TSH level after 14 days.)

Non-guideline In-vitro studies on 

the potential 

interactions with 

thyroid peroxidasecatalyzed reactions

47372518; (2008)

Acceptable/non-guideline

300 μM

Fluopyram at 300 μM did not affect thyroid peroxidase

(TPO)-catalyzed guaiacol oxidation and TPO-catalyzed

iodine formation. Therefore, the data show that 

fluopyram does not affect thyroid hormone synthesis at 

the level of TPO.

Non-guideline Mechanistic 3-Day 

toxicity study in the 

mouse by gavage 

(thyroid hormone 

investigations)

49005901 (2012)

Acceptable/non-guideline

0, 100 or 300 mg/kg bw/day 

for 3 days.

There were no compound related effects on mortality 

or clinical signs. Plasma T4 levels were significantly 

decreased in treated animals at all time-points with no 

obvious time-related trends, Plasma TSH levels were 

comparable to controls.
Fluopyram Human Health Risk Assessment DP No. D421926

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

Non-guideline Mechanistic 

Investigations in the 

Liver of Female 

Rats Following 

Dietary 

Administration for 

28 days

49005902 (2012)

Acceptable/non-guideline

0, 30, 75, 150, 600 or 1500 

ppm (0, 2.2, 5.6, 11.3, 44.5, 

or 111.4 mg/kg bw/day) for 

28 days. A one month 

recovery period in control 

and high dose animals 

assessed reversibility of 

effects. Phenobarbital was 

used as a positive control at 

80 mg/kg bw/day.

Absolute and relative liver weights were increased at ≥ 

44.5 mg/kg bw/day fluopyram and in the 

phenobarbital-treated group. Following the recovery 

phase, liver weights were nearly identical among 

control, high dose fluopyram- and phenobarbitaltreated rats. Visibly enlarged livers were seen starting 

at 5.6 mg/kg bw/day with red foci and prominent 

lobulation being recorded at higher dose levels. 

Hepatocellular hypertrophy was observed starting at 

44.5 mg/kg bw/day.

After 28 days of treatment, mean liver cell proliferation 

was increased in the fluopyram treated groups starting 

at 5.6 mg/kg bw/day and in the phenobarbital group. 

Enzyme activity was increased in fluopyram- and 

phenobarbital-treated rats. These activity levels showed 

partial reversibility following recovery.

Gene transcript expression was increased for both 

fluopyram- and phenobarbital-treated rats, though there 

were notable differences in expression between 

compounds. Partial reversibility was evident after a 

month without treatment.

Non-guideline 28-Day Toxicity 

Study for 

Proliferation 

Assessment in the 

male Mouse

49005904 (2012)

Acceptable/non-guideline

0 or 750 ppm (0 or 127 

mg/kg bw/day) for 28 days

Phenobarbital (gavage) as 

positive control

Enlarged and dark livers were present in treated mice. 

Phenobarbital-treated mice also exhibited dark thyroids 

without microscopic correlates.

The BrdU labeling index was increased in the 

fluopyram group, but not the phenobarbital group.

Non-guideline 28-Day Toxicity 

Study for Thyroid 

Cell Proliferation in 

the Mouse

49005905 (2013)

Acceptable/non-guideline

0, 30, 75, 150, 600, 750 or 

1500 ppm (0, 5, 13, 25, 99, 

124 or 247 mg/kg bw/day) 

for 28 days.

(28-day recovery groups 

consisted of control and high 

dose animals) 

There were no compound related effects on mortality, 

clinical signs, body weight, food or water consumption, 

organ weights, or gross and histologic pathology. The 

proliferation index in the thyroid was increased starting 

at 25 mg/kg bw/day.
Fluopyram Human Health Risk Assessment DP No. D421926

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

Non-guideline 28-Day Dietary 

Study to Determine 

Potential Role of the 

Nuclear Pregnane X 

Receptor (PXR) and 

Constitutive 

Androstane 

Receptor (CAR) on 

the Thyroid 

Changes Following 

the Administration 

of Fluopyram to 

Male Mice 

(C57BL/6J and PXR

KO/CAR KO).

49005906 (2013)

Acceptable/non-guideline

0, 750 or 1500 ppm (125 or 

256 mg/kg bw/day for wild 

type and 130 or 247 mg/kg 

bw/day for knockout) for 28 

days.

There were no effects on mortality, clinical signs, body 

weight or food or water consumption. Liver weights 

were increased in all fluopyram-treated mice. Enlarged 

livers were observed in the wild type groups, but not in 

controls or knockout groups. In treated wild type mice, 

there was an increase in hepatocellular hypertrophy. 

There were no similar treatment-related effects in the 

knockout mice.

Thyroid cell proliferation was increased in wild type 

mice, while the knockout mice had a slight decrease in 

proliferation index that was likely incidental.

Total cytochrome P-450 content was increased in 

treated wild type mice, but not in treated knockout 

mice. PROD activity was greatly increased in treated 

wild type mice and slightly increased in treated 

knockout mice. BQ activity was increased in wild type 

mice while the knockout mice showed slight decreases. 

Thyroxine glucuronosyl transferase (T4-GT) and 

bilirubin glucuronidation (BIL-GT) activities were 

increased in treated wild type mice, but showed no 

change in treated knockout mice except for a slight 

decrease in T4-GT activity at 247 mg/kg bw/day.

There was a significant increase of Tsh beta transcript 

in the pituitary gland of treated wild type mice and a 

slight decrease in the same measure for high dose 

knockout mice.

Non-guideline Enzyme and DNASynthesis Induction 

in Cultured Human 

Hepatocytes, Main 

Study

49005907 (2013)

Acceptable/non-guideline

0, 1, 3, 10, 30, 100 or 300 

μM fluopyram or at 10, 100 

or 1000 μM phenobarbital 

for 96 hours.

Epidermal growth factor, at 

25 ng/mL, was used as a 

positive control

ATP concentration in the fluopyram groups indicated 

that cytotoxicity begins around 100 μM fluopyram. 

Phenobarbital did not affect ATP levels.

There was no effect on DNA synthesis with either 

fluopyram or phenobarbital. The positive control 

substance generated a large increase in DNA synthesis.

There was no dose-related increase in PROD activity 

with fluopyram treatment, though all dose levels up to 

cytotoxic levels showed an approximate 2-fold increase 

over controls. The same general effect was seen with 

phenobarbital. There was a dose-dependent increase in 

BROD activity following fluopyram treatment. 

Phenobarbital treatment also produced an increase at 

the high dose. There was a slight increase in BQ 

activity at low dose levels of fluopyram. Phenobarbital 

caused a dose-related increase at the mid and high dose 

level.
Fluopyram Human Health Risk Assessment DP No. D421926

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

Non-guideline Enzyme and DNASynthesis Induction 

in Cultured Rat 

Hepatocytes, Main 

Study

49005908 (2013)

Acceptable/non-guideline

0, 1, 3, 10, 30, 100 or 300 

μM fluopyram or at 10, 100 

or 1000 μM phenobarbital 

for 96 hours. The test vehicle 

was DMSO. Epidermal 

growth factor, at 25 ng/mL, 

was used as a positive 

control.

ATP concentration in the fluopyram groups was 

comparable to controls until cytotoxic levels. 

Phenobarbital did not appear to have an effect on ATP 

levels.

DNA synthesis was increased with fluopyram and 

phenobarbital. Cytotoxicity at 100 and 300 μM 

fluopyram impacted the results. The positive control 

substance generated a large increase in DNA synthesis.

There was an increase in PROD, BROD and BQ 

activity following fluopyram and phenobarbital 

treatment until cytotoxic levels.

Non-guideline Mechanistic 3-Day 

Toxicity Study in 

the Mouse by Oral 

Gavage (Thyroid 

Hormone 

Investigations)

49005909 (2011)

Acceptable/non-guideline

0, 100 or 300 mg/kg bw/day 

for 3 days. Phenobarbital was 

used as a positive control at 

80 mg/kg bw/day.

There were no compound related effects on mortality, 

clinical signs, body weight or gross pathology. There 

were small decreases in body weight gains in all treated 

groups, though this effect lacked a dose-response 

relationship in the fluopyram groups.

Plasma T4 levels were significantly decreased in all 

fluopyram- and phenobarbital-treated mice, but plasma 

TSH levels were comparable to controls. There was an 

increase in Tsh beta transcript in the pituitary in all 

treated groups.
Fluopyram Human Health Risk Assessment DP No. D421926

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile for Fluopyram.

Guideline No. Study Type MRID No. (year)/ 

Classification/Doses

Results

Non-guideline Mechanistic 28-Day 

Toxicity Study in 

the Mouse by 

Dietary 

Administration 

(Hepatotoxicity and 

Thyroid Hormone 

Investigations)

49005911 (2012) (28-day 

dietary study)

49005903 (2013) (PROD and 

BQ assessment)

Acceptable/non-guideline

0, 30, 75, 150, 600 or 750 

ppm (0, 5, 13, 25, 102 or 128 

mg/kg bw/day) for 28 days. 

Phenobarbital was used as a 

positive control at 80 mg/kg 

bw/day.

There were no treatment-related clinical signs or 

mortalities in the fluopyram groups. The phenobarbital 

group showed reduced motor activity during the dosing 

phase and there were three deaths between days 2 and 

7. There were no treatment-related clinical signs in any 

group during the recovery phase. There was no effect 

on body weight related to fluopyram treatment. 

Decreased body weight and body weight gain were 

noted in phenobarbital-treated mice during treatment 

followed by increased body weight gains compared to 

controls during the recovery phase. There was no effect 

on food consumption in the fluopyram-treated groups. 

The phenobarbital group had a small reduction in food 

consumption during the first week of dosing.

Plasma T4 levels were decreased in fluopyram- and 

phenobarbital-treated animals while plasma TSH levels 

were comparable amongst all groups. Following the 

recovery phase, plasma hormone levels were 

comparable across groups.

Absolute and relative liver weights were increased in 

both fluopyram-treated mice starting at 25 mg/kg 

bw/day and the phenobarbital-treated mice following 

the dosing phase. After the recovery phase, all groups 

had comparable liver weights.

UDPGT enzymatic activity towards bilirubin was 

increased in all treated animals and reached statistical 

significance at 102 and 128 mg/kg bw/day of 

fluopyram. Similar results were noted for UDPGT 

activity towards thyroxine, though the dose-response 

relationship was not strong at the high dose. Following 

the recovery phase, the UDPGT activities were roughly 

comparable to controls. PROD and BQ activities were 

increased in fluopyram- and phenobarbital-treated mice 

at 28 days. The activities of both PROD and BQ were 

statistically comparable to controls following the 

recovery period.

There was an increase of Tsh beta transcript in the 

pituitary gland of fluopyram- and phenobarbital-treated 

animals following the dosing phase. After the recovery 

phase, the fluopyram-treated mice had slightly elevated 

relative tsh b, but the phenobarbital-treated mice were 

similar to controls.
Fluopyram Human Health Risk Assessment DP No. D421926

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Appendix B. Physical/Chemical Properties

Table B1. Physicochemical Properties of Fluopyram.

Parameter Value Reference

Melting point 118 oC MRID 47372240

pH 6.6 (1% aqueous solution; pure substance) MRID 47372236

Density 1.53 MRID 47372242

Water solubility (20 °C) Distilled water (pH 6.7) = 16 mg/L

pH 4 = 15 mg/L

pH 7 = 16 mg/L

pH 9 = 15 mg/L

MRID 47372247

Solvent solubility (g/L at 20 °C) heptane 0.66

toluene 62.2

dichloromethane >250

methanol >250

acetone >250

ethyl acetate >250

dimethyl sulfoxide >250

MRID 47372248

Vapor pressure 1.2 x 10-6 Pa at 20 oC

3.1 x 10-6 Pa at 25 oC

2.9 x 10-4 Pa at 50 oC

MRID 47372249

Dissociation constant (pKa) 0.5 (23 oC) MRID 47372243

Octanol/water partition coefficient 

Log(KOW)

3.3 MRID 47372245

UV/visible absorption spectrum Peak max at 270 nm MRID 47372237
Fluopyram Human Health Risk Assessment DP No. D421926

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Appendix C. Review of Human Research

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. 

Electronic Database. Task Force Members: Health Canada, U.S. EPA, and the National 

Agricultural Chemicals Associations, released February 1995. 

The Agricultural Handler Exposure Task Force (AHETF), 2011. The Occupational Handler Unit 

Exposure Surrogate Reference Table. U.S. EPA. Released June 21, 2011. 

Data from the Outdoor Residential Exposure Task Force (ORETF). 

HED Residential Standard Operating Procedures (2012). 
Fluopyram Human Health Risk Assessment DP No. D421926

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Appendix D. Residential Handler and Post-application Exposure and Risk Estimates

Table D.1. Residential Handler Short-term Exposure and Risk Estimates for Fluopyram.

Use Site

Equipment/

Application Method

Application 

Rate1

Area 

Treated 

or 

Amount 

Handled

Daily2

Exposure 

Route

Unit 

Exposure 

(mg/lb ai)

Daily Dose3

(mg/kg/day) MOE4

Gardens / 

Trees

Manually-Pressurized 

Handwand

0.00223 lb 

ai/gal 5 gal

Dermal 63 0.0088 34,000

Inhalation 0.018 0.0000025 5,800,000

Gardens / 

Trees

Manually-Pressurized 

Handwand

0.000005119 

lb ai/ft2 1200 ft2 Dermal 63 0.0048 62,000

Inhalation 0.018 0.0000014 10,000,000

Gardens / 

Trees Hose-End Sprayer 0.00223 lb ai/gal 11 gal

Dermal 58 0.018 17,000

Inhalation 0.0014 0.00000043 34,000,000

Gardens / 

Trees Hose-End Sprayer 0.000005119 lb ai/ft2 1200 ft2 Dermal 58 0.0045 67,000

Inhalation 0.0014 0.00000011 130,000,000

Gardens / 

Trees Backpack 0.00223 lb ai/gal 5 gal

Dermal 130 0.018 17,000

Inhalation 0.14 0.000020 740,000

Gardens / 

Trees Backpack 0.000005119 lb ai/ft2 1200 ft2 Dermal 130 0.010 30,000

Inhalation 0.14 0.000011 1,300,000

Gardens / 

Trees Sprinkler Can 0.00223 lb ai/gal 5 gal

Dermal 58 0.0081 37,000

Inhalation 0.0014 0.00000020 74,000,000

Gardens / 

Trees Sprinkler Can 0.000005119 lb ai/ft2 1200 ft2 Dermal 58 0.0045 67,000

Inhalation 0.0014 0.00000011 130,000,000

Lawns / 

Turf

Manually-Pressurized 

Handwand

0.00404 lb 

ai/gal 5 gal

Dermal 63 0.016 19,000

Inhalation 0.018 0.0000045 3,200,000

Lawns / 

Turf Hose-End Sprayer 0.404 lb ai/A 0.5 A

Dermal 13.4 0.034 8,900

Inhalation 0.022 0.000056 260,000

Lawns / 

Turf Backpack 0.00404 lb ai/gal 5 gal

Dermal 130 0.033 9,100

Inhalation 0.14 0.000035 410,000

Lawns / 

Turf Sprinkler Can 0.000009285 lb ai / ft2 1000 ft2 Dermal 13.4 0.0016 190,000

Inhalation 0.022 0.0000026 5,700,000

1 Maximum Single Application Rate.

2 Units Treated taken from Science Advisory Council for Exposure, Standard Operating Procedure 9.1, Standard Values for Daily Acres Treated 

in Agriculture, Rev. 25 SEP 2001.

3 Daily Dose = Unit Exposure x Application Rate x Units Treated  Body Weight (80 kg).

4 Margin Of Exposure (MOE) = NOAEL (mg/kg/day)  Daily Dose (mg/kg/day); where the NOAEL = 300 mg/kg/day for dermal exposure & 

14.5 mg/kg/day for inhalation exposure.
Fluopyram Human Health Risk Assessment DP No. D421926

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Table D.2. Residential Post-Application Dermal Short-Term Exposure and Risk Estimates from Turf.

Scenario Application 

Rate (lb ai/A)

TTR1

(μg/cm2)

Exposure 

Time (hr) Population TC (cm2/hr)

Daily Dose2

(mg/kg/day) MOE3

Golf Course 

Turf 0.446 0.0496 4

Adults 5,300 0.0131 23,000

Youths 11 to <16 yr old 4,400 0.0153 20,000

Children 6 to <11 yr old 2,900 0.0180 17,000

High 

Contact 

Activities

0.404 0.0449 1.5

Adults 180,000 0.152 2,000

Children 1 to <2 yr old 49,000 0.300 1,000

Mowing 

Turf 0.404 0.0449 1

Adults 5,500 0.00309 97,000

Youths 11 to <16 yr old 4,500 0.00355 85,000

1 TTR derived as follows: 0.446 lb ai/A x 4.54E+8 μg/lb x 2.47E-8 A/cm2

x 0.01 (fraction of transferable ai) = 0.0496 μg/cm2or 0.404 lb ai/A x 

4.54E+8 μg/lb x 2.47E-8 A/cm2x 0.01 (fraction of transferable ai) = 0.0449 μg/cm2.

2 Daily Dose = [TTR (μg/cm2

) x (0.001 mg/μg) x Dermal Transfer Coefficient x Exposure Time] / [Body weight (80 kg for adults, 57 kg for 

youths 11 to <16 yr, 32 kg for children 6 to <11 yr, and 11 kg for children 1 to <2 yr old)].

3 MOE = NOAEL/Daily Dose. Short-Term NOAEL = 300 mg/kg/day.

Table D.3. Residential Post-Application Incidental Oral Exposure and Risk Estimates to 1 to <2 Year Olds 

from Turf.

Scenario

Application Rate 

(lb ai/A)

Daily Dose (mg/kg/day) MOE

Hand-to-Mouth 0.404 0.00615 2,400

Object-to-Mouth 0.404 0.000187 78,000

Soil Ingestion 0.404 0.000014 1,100,000

1 TTR derived as follows: 0.404 lb ai/A x 4.54E+8 μg/lb x 2.47E-8 A/cm2

x 0.01 (fraction of transferable ai) = 0.0449 μg/cm2.

2 Based on HED’s 2012 Residential SOPs: Lawns/Turf (http://www.epa.gov/pesticides/science/residential-exposure-sop.html).

3 MOE = NOAEL/Daily Dose. Short-Term NOAEL = 14.5 mg/kg/day.

Table D.4. Residential Post-Application Dermal Short-Term Exposure and Risk Estimates from Gardens, 

Ornamentals and Fruit Trees.

Scenario Application 

Rate (lb ai/A)

DFR1

(μg/cm2)

Exposure 

Time (hr) Population TC (cm2/hr)

Daily Dose2

(mg/kg/day) MOE3

Gardens 0.223 0.625

2.2 Adults 8,400 0.143 2,100

1.1 Children 6 to <11 yr old 4,600 0.0980 3,100

Trees 0.223 0.625

1.0 Adults 1,700 0.0132 23,000

0.5 Children 6 to <11 yr old 930 0.0090 33,000

1 DFR derived as follows: 0.223 lb ai/A x 4.54E+8 μg/lb x 2.47E-8 A/cm2

x 0.25 (fraction of transferable ai)= 0.625 μg/cm2. 

2 Daily Dose = [DFR (μg/cm2

) x (0.001 mg/μg) x Dermal Transfer Coefficient x Exposure Time] / [Body weight (80 kg for adults and 32 kg for 

children 6 to <11 yr)].

3 MOE = NOAEL/Daily Dose. Short-Term NOAEL = 300 mg/kg/day.
Fluopyram Human Health Risk Assessment DP No. D421926

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Appendix E. Occupational Handler and Post-application Exposure/Risk Summary Tables

Table E.1. Occupational Short- and Intermediate-Term Dermal and Inhalation Exposures and Risk Estimates For Fluopyram

Exposure 

Scenario Crop or Target

Maximum 

Application

Ratea

(lb ai/A)

Area 

Treated 

Dailyb

(A/day) 

Unit Exposured Daily Exposuree(mg/kg/day) MOEf

Baseline 

Dermalc

(mg/lb ai)

PPE-G 

Dermalc

(mg/lb ai)

Baseline 

Inhalationc

(μg/lb ai)

Baseline 

Dermal

PPE-G 

Dermal

Baseline 

Inhalation

Baseline 

Dermal

PPE-G 

Dermal

Baseline 

Inhalation

Mixer/Loader

Mixing/Loading 

Liquid 

Concentrates for 

Aerial and 

Chemigation 

Applications

Artichoke (globe); Brassica (cole) 

Leafy Vegetables; Bulb Vegetables; 

Carrot; Citrus; Cucurbit Vegetables;

Fruiting Vegetables; Ginseng; 

Grapes and Small Vine Fruits 

(except Fuzzy Kiwifruit); Herbs and 

Spices (except Black Pepper); Hops; 

Leafy Vegetables; Pome Fruit; Other 

Root, Tuberous and Corm 

Vegetables; Small Berries 

(Caneberries and Bushberries); 

Stone Fruit; Strawberry and Other 

Low-Growing Berries

0.222 350

0.22 0.0376 0.219

0.214 0.0365 2.13E-4 1,400 8,200 68,000

Brassica Leafy Vegetables Head and 

Stem Subgroup 0.125 350 0.120 0.0206 1.20E-4 2,500 15,000 120,000

Canola Subgroup; Cereal grains; 

Forage, Fodder, or Straw from 

Cereal Grains; Cotton; Legume 

Vegetables (including Soybean); 

Potato; Sugar Beet; Sunflower 

subgroup

0.222 1200 0.733 0.125 7.29E-4 410 2,400 20,000

Nursery (ornamentals, vegetables, 

trees, container stock) 0.131 60 0.0216 0.00370 2.15E-5 14,000 81,000 670,000

Sod 0.446 350 0.429 0.0734 4.28E-4 700 4,100 34,000

Mixing/Loading 

Liquids 

Concentrates for 

Groundboom 

Applications

Artichoke (globe); Brassica (cole) 

Leafy Vegetables; Bulb Vegetables; 

Carrot; Citrus; Cucurbit Vegetables; 

Fruiting Vegetables; Ginseng; 

Grapes and Small Vine Fruits 

(except Fuzzy Kiwifruit); Herbs and 

Spices (except Black Pepper); Hops; 

Leafy Vegetables; Pome Fruit; Other 

Root, Tuberous and Corm 

Vegetables; Small Berries 

(Caneberries and Bushberries); 

Stone Fruit; Strawberry and Other 

Low-Growing Berries

0.222 80 0.22 0.0376 0.219 0.0489 0.00835 4.86E-5 6,00 36,000 300,000

Brassica Leafy Vegetables Head and 0.125 80 0.0275 0.00470 2.74E-5 11,000 64,000 530,000
Fluopyram Human Health Risk Assessment DP No. D421926

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Table E.1. Occupational Short- and Intermediate-Term Dermal and Inhalation Exposures and Risk Estimates For Fluopyram

Exposure 

Scenario Crop or Target

Maximum 

Application

Ratea

(lb ai/A)

Area 

Treated 

Dailyb

(A/day) 

Unit Exposured Daily Exposuree(mg/kg/day) MOEf

Baseline 

Dermalc

(mg/lb ai)

PPE-G 

Dermalc

(mg/lb ai)

Baseline 

Inhalationc

(μg/lb ai)

Baseline 

Dermal

PPE-G 

Dermal

Baseline 

Inhalation

Baseline 

Dermal

PPE-G 

Dermal

Baseline 

Inhalation

Stem Subgroup

Canola Subgroup; Cereal grains; 

Forage, Fodder, or Straw from 

Cereal Grains; Cotton; Legume 

Vegetables (including Soybean); 

Potato; Sugar Beet; Sunflower 

subgroup

0.222 200 0.122 0.0209 1.22E-4 2,500 14,000 120,000

Field Grown Ornamentals 0.131 40 0.0144 0.00246 1.44E-5 21,000 120,000 1.0E+6

Nursery (ornamentals, vegetables, 

trees, container stock) 0.131 60 0.0216 0.0037 2.15E-5 14,000 81,000 670,000

Sod 0.446 80 0.0981 0.0168 9.76E-5 3,100 18,000 150,000

Turf 0.446 40 0.0490 0.00839 4.89E-5 6,100 36,000 300,000

Mixing/Loading 

Liquids 

Concentrates for 

Airblast 

Applications

Nursery (ornamentals, vegetables, 

trees, container stock) 0.131 20

0.22 0.0376 0.219

0.00720 0.00123 7.18E-6 42,000 240,000 2.0E+6

Grapes and Small Vine Fruits 

(except Fuzzy Kiwifruit); Pome 

Fruit; Stone Fruit; 

0.222 40 0.0244 0.00418 2.43E-5 12,000 72,000 600,000

Applicator

Applying 

Sprays via 

Aerial 

Equipment

Artichoke (globe); Brassica (cole) 

Leafy Vegetables; Bulb Vegetables; 

Carrot; Citrus; Cucurbit Vegetables; 

Fruiting Vegetables; Ginseng; 

Grapes and Small Vine Fruits 

(except Fuzzy Kiwifruit); Herbs and 

Spices (except Black Pepper); Hops; 

Leafy Vegetables; Pome Fruit; Other 

Root, Tuberous and Corm 

Vegetables; Small Berries 

(Caneberries and Bushberries); 

Stone Fruit; Strawberry and Other 

Low-Growing Berries

0.222 350

0.00208g No Data 0.0049g

0.00203 No Data 4.76E-6 150,000 No Data 3.0E+6

Brassica Leafy Vegetables Head and 

Stem Subgroup 0.125 350 0.00114 No Data 2.68E-6 260,000 No Data 5.4E+6

Canola Subgroup; Cereal grains; 

Forage, Fodder, or Straw from 

Cereal Grains; Cotton; Legume 

Vegetables (including Soybean); 

Potato; Sugar Beet; Sunflower 

subgroup

0.22 1200 0.00693 No Data 1.64E-5 43,000 No Data 880,000

Nursery (ornamentals, vegetables, 

trees, container stock) 0.131 60 0.000204 No Data 4.81E-7 1.5E+6 No Data 3.0E+7

Sod 0.446 350 0.00406 No Data 9.56E-6 74,000 No Data 1.5E+6

Applying Artichoke (globe); Brassica (cole) 0.222 80 0.0786 0.0161 0.34 0.0175 0.00358 7.55E-5 17,000 84,000 190,000
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Table E.1. Occupational Short- and Intermediate-Term Dermal and Inhalation Exposures and Risk Estimates For Fluopyram

Exposure 

Scenario Crop or Target

Maximum 

Application

Ratea

(lb ai/A)

Area 

Treated 

Dailyb

(A/day) 

Unit Exposured Daily Exposuree(mg/kg/day) MOEf

Baseline 

Dermalc

(mg/lb ai)

PPE-G 

Dermalc

(mg/lb ai)

Baseline 

Inhalationc

(μg/lb ai)

Baseline 

Dermal

PPE-G 

Dermal

Baseline 

Inhalation

Baseline 

Dermal

PPE-G 

Dermal

Baseline 

Inhalation

Sprays via 

Groundboom 

Equipment

Leafy Vegetables; Bulb Vegetables; 

Carrot; Citrus; Cucurbit Vegetables; 

Fruiting Vegetables; Ginseng; 

Grapes and Small Vine Fruits 

(except Fuzzy Kiwifruit); Herbs and 

Spices (except Black Pepper); Hops; 

Leafy Vegetables; Pome Fruit; Other 

Root, Tuberous and Corm 

Vegetables; Small Berries 

(Caneberries and Bushberries); 

Stone Fruit; Strawberry and Other 

Low-Growing Berries

Brassica Leafy Vegetables Head and 

Stem Subgroup 0.125 80 0.00983 0.00201 4.25E-5 31,000 150,000 340,000

Canola Subgroup; Cereal grains; 

Forage, Fodder, or Straw from 

Cereal Grains; Cotton; Legume 

Vegetables (including Soybean); 

Potato; Sugar Beet; Sunflower 

subgroup

0.222 200 0.0436 0.00894 1.89E-4 6,900 34,000 77,000

Field Grown Ornamentals 0.131 40 0.00515 0.00106 2.23E-5 58,000 280,000 650,000

Nursery (ornamentals, vegetables, 

trees, container stock) 0.131 60 0.00773 0.00159 3.34E-5 39,000 190,000 430,000

Sod 0.446 80 0.0175 0.00359 7.59E-5 17,000 84,000 190,000

Turf 0.446 40 0.0350 0.00718 1.51E-4 8,600 42,000 96,000

Applying 

Sprays via 

Airblast 

Equipment

Nursery (ornamentals, vegetables, 

trees, container stock) 0.222 20

1.77 1.59 4.71

0.0580 0.0521 1.54E-4 5,200 5,800 94,000

Grapes and Small Vine Fruits 

(except Fuzzy Kiwifruit); Pome 

Fruit; Stone Fruit 

0.131 40 0.196 0.176 5.23E-4 1,500 1,700 28,000

Flagger

Flagging for 

Aerial Sprays 

Applications

Artichoke (globe); Brassica (cole) 

Leafy Vegetables; Bulb Vegetables; 

Carrot; Citrus; Cucurbit Vegetables; 

Fruiting Vegetables; Ginseng; 

Grapes and Small Vine Fruits 

(except Fuzzy Kiwifruit); Herbs and 

Spices (except Black Pepper); Hops; 

Leafy Vegetables; Pome Fruit; Other 

Root, Tuberous and Corm 

Vegetables; Small Berries 

(Caneberries and Bushberries); 

Stone Fruit; Strawberry and Other 

Low-Growing Berries

0.222 350 0.011 0.012 0.35 0.0107 0.0117 3.40E-4 28,000 26,000 43,000
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Table E.1. Occupational Short- and Intermediate-Term Dermal and Inhalation Exposures and Risk Estimates For Fluopyram

Exposure 

Scenario Crop or Target

Maximum 

Application

Ratea

(lb ai/A)

Area 

Treated 

Dailyb

(A/day) 

Unit Exposured Daily Exposuree(mg/kg/day) MOEf

Baseline 

Dermalc

(mg/lb ai)

PPE-G 

Dermalc

(mg/lb ai)

Baseline 

Inhalationc

(μg/lb ai)

Baseline 

Dermal

PPE-G 

Dermal

Baseline 

Inhalation

Baseline 

Dermal

PPE-G 

Dermal

Baseline 

Inhalation

Brassica Leafy Vegetables Head and 

Stem Subgroup 0.125 350 0.00601 0.00656 1.91E-4 50,000 46,000 76,000

Canola Subgroup; Cereal grains; 

Forage, Fodder, or Straw from 

Cereal Grains; Cotton Legume 

Vegetables (including Soybean); 

Potato; Sugar Beet; Sunflower 

subgroup

0.22 1200 0.0366 0.040 0.00117 8,200 7,500 12,000

Nursery (ornamentals, vegetables, 

trees, container stock) 0.131 60 0.00108 0.00118 3.44E-5 280,000 250,000 420,000

Sod 0.446 350 0.0215 0.0234 6.83E-4 14,000 13,000 21,000

Mixer/Loader/Applicator

Mixing/Loading

/Applying 

Liquid 

Concentrates 

with Manually 

Pressurized

Handwand

Greenhouse Ornamentals 0.00131 lb 

ai/gal

40 gal 100 0.43 30

0.0655 2.81E-4 1.96E-5 4,600 1.1E+6 740,000

Nursery (ornamentals, vegetables, 

trees, container stock)

0.00131 lb 

ai/gal 0.0655 2.81E-4 1.96E-5 4,600 1.1E+6 740,000

Christmas Trees 0.00223 lb 

ai/gal 0.112 4.80E-4 3.35E-5 2,700 630,000 430,000

Turf 0.0026 lb 

ai/gal 0.130 5.59E-4 3.90E-5 2,300 540,000 370,000

Mixing/Loading

/Applying 

Liquid 

Concentrates 

with 

MechanicallyPressurized 

Handgun

Greenhouse Ornamentals 0.00131 lb 

ai/gal

1000 

gal 3.5 2.5 120 0.0574 0.0410 0.00196 5,200 7,300 7,400

Nursery (ornamentals, vegetables, 

trees, container stock)

0.00131 lb 

ai/gal

1000 

gal

1.3 0.39 3.9

0.0213 0.00639 6.39E-5 14,000 47,000 230,000

Christmas Trees 0.00223 lb 

ai/gal

1000 

gal 0.0363 0.0109 1.09E-4 8,300 28,000 130,000

Pome Fruit; Stone Fruit 0.0222 lb 

ai/gal

1000 

gal 0.361 0.108 0.00108 830 2,800 13,000

Golf Course; Turf 0.446 5 1.14 0.88 1.9 0.0318 0.0245 5.30E-5 9,400 12,000 270,000

Mixing/Loading

/Applying 

Liquid 

Concentrates 

with a 

Backpack

Nursery (ornamentals, vegetables, 

trees, container stock)

0.00131 lb 

ai/gal

40 gal

13.2 11.2 140

0.00865 0.00734 1.98E-5 35,000 41,000 160,000

Christmas Trees 0.00223 lb 

ai/gal 0.0148 0.0125 1.56E-4 20,000 24,000 93,000

Pome Fruit; Stone Fruit 0.0222 lb 

ai/gal 8.26 8.26 2.58

0.0916 0.0916 2.86E-5 3,300 3,300 510,000

Turf 0.0026 lb 

ai/gal 0.0107 0.0107 3.35E-6 28,000 28,000 4.3E+6

a. Application Rates are based on proposed uses from the fluopyram labels.

b. Science Advisory Council Policy No. 9.1.

c. Baseline Dermal: Long-sleeve shirt, long pants, and no gloves.

PPE-G Dermal: Baseline plus chemical-resistant gloves.

Baseline Inhalation: no respirator.
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d. Unit Exposures are based on “Occupational Pesticide Handler Unit Exposure Surrogate Table”.

e. Daily Exposure (mg/kg/day) = Application Rate (lb ai/A) * Unit Exposure (mg/lb ai) * Area Treated or Amount Applied (acre/day) / 80 kg.

f. MOE = NOAEL (mg/kg/day) / Daily Exposure (mg/kg/day); where dermal NOAEL = 300 mg/kg/day and inhalation NOAEL = 14.5 mg/kg/day.

g. Engineering control unit exposure for applying sprays via aerial equipment = enclosed cockpit.
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Table E.2. Summary of Short- and Intermediate-Term Handler Exposures and Risk Estimates for 

Fluopyram Seed Treatment of Peanut Seed.a

Maximum 

Application 

Rateb

lb ai/lb seed

Amount of 

Seed Treated 

or Planted 

Per Dayd

lb seed/day

Dermal

Unit 

Exposurec

mg/lb

Inhalation

Unit 

Exposurec

mg/lb

Dermal 

Dosee

mg/kg/day

Inhalation 

Dosef

mg/kg/day

Dermal 

MOEf

LOC = 100

Inhalation 

MOEh

LOC = 100

Loader/Applicator

0.001245 339,500 0.023 0.00034 0.1215 0.001796 2,500 8,100

Sewer

0.001245 339,500 0.0062 0.00023 0.03276 0.001215 9,200 12,000

Bagger

0.001245 339,500 0.0091 0.00016 0.04808 0.0008454 6,200 17,000

Multiple Activities

0.001245 339,500 0.042 0.0016 0.2219 0.008454 1,400 1,700

Planters

0.001245 18,260 0.25 0.0034 0.07104 0.0009662 4,200 15,000

a Seed treatment rate calculations are based on the following assumptions:

Peanut: 460 seeds per lb; 228 lb of seed planted per acre, 80 acres planted per day.

b Application Rate based on proposed label for fluopyram (Luna Privilege, EPA Reg. No. 264-1078).

c Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment (baseline 

inhalation = no respirator; dermal unit exposure includes PPE with gloves for loading/applicator, multiple activities and planter scenarios).

d HED default for lb seed treated/planted per day from HED Exposure Science Advisory Council Interim Policy 15.1 and the BEAD memo 

“Acres Planted Per Day and Seeding Rates of Crops Grown in the United States” (J. Becker, March 2011).

e Daily Dermal Dose (mg/kg/day) = daily dermal unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) ÷ 

body weight (80 kg adult).

f Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) 

÷ body weight (80 kg adult).

g Dermal MOE = NOAEL (300 mg/kg/day for short- and intermediate-term exposure) ÷ Dermal Dose (mg/kg/day). Level of concern = 100.

h Inhalation MOE = NOAEL (14.5 mg/kg/day for short- and intermediate-term exposure) ÷ Inhalation Dose (mg/kg/day). Level of concern = 

100.
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Table E.3. Summary of Occupational Non-Cancer Post-application Risks (Short- and Intermediate-Term) with HED 

Default Assumptions.

Crops or Crop 

Groups

Application 

Rate

(lb ai/acre)

Default DFR on 0 

days (12 hr) after 

applicationa

(μg/cm2)

Work Activity & 

Maximum Transfer Coefficientb

(cm2/hr)

Daily Dosec

(mg/kg/day)

MOEd

(LOC = 100)

Artichoke 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Brassica Leafy 

Vegetables Head & 

Stem Subgroup

0.125 0.350

4200 Hand Harvesting, Hand 

Weeding, Scouting, Topping, 

Tying/Training

0.147 2,000

Brassica Leafy 

Vegetables 0.222 0.622 4200 Hand Weeding 0.261 1,100

Bulb Vegetables 0.222 0.622 4200 Hand Weeding 0.261 1,100

Canola Subgroup 0.222 0.622 1100 Scouting 0.0684 4,400

Carrot 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Sweet Corn 0.222 0.622 17,600 Hand Detasseling, Hand 

Harvesting 1.09 270

Cereal Grains 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Forage, Fodder or 

Straw from Cereal 

Grains

0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Citrus 0.222 0.622 1400 Hand Harvesting 0.0871 3,400

Cotton 0.222 0.622 210 Scouting 0.0131 23,000

Cucurbits 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Fruiting Vegetables 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Okra 0.167 0.468 1900 Irrigation (Hand Set) 0.0889 3,400

Ginseng 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Small Vine Fruits 0.222 0.622 10,100 Hand Harvesting 0.628 480

Herbs & Spices 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Hops 0.222 0.622 19,300 Harvesting, Mechanically 

Assisted 1.20 250

Leafy Vegetables 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Legume Vegetables 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Soybean 0.222 0.622 1100 Scouting 0.0684 4,400

Pome Fruit 0.222 0.622 3600 Thinning Fruit 0.224 1,300

Root, Tuberous & 

Corm Vegetables 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Small Berries 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Stone Fruit 0.222 0.622 3600 Thinning Fruit 0.224 1,300

Low Growing Berries 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Sugar Beet 0.222 0.622 1100 Hand Harvesting 0.0684 4,400

Sunflower 0.222 0.622 1900 Irrigation (Hand Set) 0.118 2,500

Christmas Trees 0.223 0.625 1900 Irrigation (Hand Set) 0.119 2,500

Nursery Ornamentals 0.131 0.367 1900 Irrigation (Hand Set) 0.0697 4,300

a. Default DFR (μg/cm2) = application rate (lb ai/A) x (1- daily dissipation rate) tx 4.54E+8 μg/lb x 24.7E-9 A/cm

2

x 25% DFR after initial treatment.

b. Crops were assessed using the highest transfer coefficient (TC) available.

c. Daily Dose = DFR x TC x (1 mg/1000 μg) x ET (8 hr/day) / body weight (80 kg)

d. MOE = NOAEL (300 mg/kg/day) / Daily Dose (mg/kg/day)
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Table E.5. Anticipated Post-Application Activities and Transfer Coefficients for Cotton Harvesters.

Crop Policy Crop 

Group Category

Crop 

Height

Foliage 

Density Transfer Coefficients Activities

Cotton Field / row. crop, 

low / medium High Min

900 g cotton boll/hr Mechanical Harvesting 

(Module Builder Operator)

2,400 g cotton boll/hr Mechanical Harvesting 

(Picker Operator and Raker)

5,050 g cotton boll/hr Mechanical Harvesting 

(Tramper)

Table E.6. Occupational Post-application Exposure and Risk Estimates for Cotton Harvesting Activities.

Mechanical Harvesting Activity Appl. Rate

(lb ai/A)

DBR

(μg/g)1

Transfer 

Coefficient

(g/hr)2

Dermal Dose3

(mg/kg/day)

Dermal 

MOE4

Module Builder Operator

0.222 0.000194

900 0.0000175 17,000,000

Picker Operator and Raker 2,400 0.0000466 6,400,000

Tramper 5,0500 0.0000981 3,100,000

1. Cotton Harvesting Dislodgeable Boll Residue (DBR) = (Best fit DBR at 30 days MRID# 42701601 (0.082 μg/50g = 0.00164 

μg/g) x Application Rate (0.222 lb ai/A)) / Study Application Rate (1.875 lb ai/A) = 0.000194 μg/g

2. From Non-Foliar Transfer Coefficient Table: http://epa.gov/pesticides/science/exposac-policy-3-march2013.pdf 

3. Daily Dose (mg/kg/day) = [DBR x Transfer Coefficient x Conv. Factor (0.001 mg/μg) x 8 hr/day] / Body Weight (80 kg). 

4: Short- & Intermediate-term Margin of Exposure (MOE) = Short-term Dermal NOAEL (300 mg/kg/day) / Daily Dose 

(mg/kg/day).

Table E.7. Exposure and Risk Assessment for Occupational Post-Application Activities on Turf.

Application Rate

(lb ai/A)

Dermal Transfer Coefficient 

(cm2/hr) & Activities1

Post 

Application

Day (t)

Turf 

Transferable 

Residue 

(TTR)2(μg/cm2)

Daily Dose3

(mg/kg/day)

Short- & 

Intermediate

-Term 

Dermal 

MOE4

0.446

6,700 (Maintenance, 

Transplanting/Planting, & 

Harvesting Sod)

0 0.05 0.0335 9,000

1 The transfer coefficient is the arithmetic mean value taken from MRID 46734001. It should be noted that a previous study on 

golf course maintenance (MRID 45530101) had been submitted, but had been determined to be unacceptable. Data from MRID 

46734001 are believed to be more appropriate.

2 TTR derived as follows: 0.446 lb ai/A x 4.54E+8 μg/lb x 2.47E-8 A/cm2

x 0.01 (fraction of transferable ai) = 0.05 μg/cm2.

3 Daily Dose = [TTR (μg/cm2

) x (0.001 mg/μg) x Dermal Transfer Coefficient x Exposure Time (8 hr)] / [Body Weight (80 kg)] 

= 0.0335 mg/kg/day.

4 MOE = LOAEL/Daily Dose. Short-/Intermediate-Term LOAEL = 300 mg/kg/day.
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Appendix F. International Residue Limit Status Sheet

Fluopyram (080302)

International Residue Limits 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

40 CFR 180.661 (1)

Plants: fluopyram (N-[2-[3-chloro-5-

(trifluoromethyl)-2-pyridinyl]ethyl]-2-

(trifluoromethyl)benzamide)

N-[2-[3-chloro-5-

(trifluoromethyl)-2-

pyridinyl]

ethyl]-2-

(trifluoromethyl)benzamide

Plants: fluopyram

Commodity1Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex3

Artichoke, globe 4.0 4

Grain, aspirated grain 

fractions 50 None

Peanut 0.20 0.2 0.03

Hop, dried cones 60 60

Vegetable, root, except sugar 

beet, subgroup 1B 0.30 0.3 0.4 carrot

Sugarbeet, roots 0.10 0.10 0.04

Vegetable, tuberous and 

corm, subgroup 1C 0.10 0.1 0.03 potato

Potato, wet peel 0.30 None

Vegetable, leaves of root and 

tuber, group 2 30 30

Onion, bulb, subgroup 3-07A 0.40 0.4 0.07 garlic, onion bulb

Onion, green, subgroup 3-

07B 15 15

50 fresh chive leaves 0.15 leek

Leafy greens subgroup 4A 40 40 15 lettuce (head and leaf)

Leaf petioles subgroup 4B 20 20

Brassica, head and stem, 

subgroup 5A 4.0 4

0.3 broccoli, Brussels 

sprout

0.15 cabbage (head)

0.09 cauliflower

Brassica, leafy greens, 

subgroup 5B 50 50

Soybean, seed 0.30 0.2

Vegetable, legume, edible 

podded, subgroup 6A 4.0 4

Pea and bean, succulent 

shelled, subgroup 6B

0.20 0.2

Bean, dry 0.15 0.7 crop subgroup 6C 0.07 beans, chick-pea, 

lentil, lupin (all dry)

Tomato subgroup 8-10A 1.0 0.5 0.4 tomato
Fluopyram Human Health Risk Assessment DP No. D421926

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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

Pepper/eggplant subgroup 8-

10B

4.0 4

0.5 peppers (proposed)

5 peppers chili, dried 

(proposed)

Melon subgroup 9A 1.0 1

Squash/cucumber subgroup 

9B 0.60 0.3 0.5 cucumber

Fruit, citrus, group 10-10 1.0 1

Citrus, oil 8 8

Fruit, pome, group 11-10 0.80 0.8 0.5

Cherry subgroup 12-12A 2.0 2 0.7 cherries

Peach subgroup 12-12B 1.0 1 1

Plum subgroup 12-12C 0.50 0.5 0.5 (including prunes)

Caneberry subgroup 13-07A 5.0 5

3 blackberries, raspberries 

(red, black)

Bushberry subgroup 13-07B 7.0 7

Fruit, small vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F 2.0 2

2 grapes

Grape, raisin 3.0 3

5 dried grapes (=currants, 

raisins and sultanas)

Berry, low growing, except 

cranberry, subgroup 13-07G 2.0 2 0.4 strawberry

Nut, tree, group 14-12 0.05 0.05 0.04

Almond, hulls 10 10

Grain, cereal, group 15

except corn and rice 4.0 1.5

Corn, field grain 0.02

Corn, pop, grain 0.02

Corn, sweet, kernel plus cob 

with husks removed 0.01

Grain, cereal, forage, fodder 

and straw, except rice, group 

16

20 20

Herb subgroup 19A 40 70-fresh

400 dried

Dill, seed (including 

caraway, seed; celery, seed; 

coriander, seed; lovage,

seed; mustard, seed; poppy,

seed

70 70

Rapeseed subgroup 20A 5.0 1.8 1

Sunflower subgroup 20B 0.70 0.7
Fluopyram Human Health Risk Assessment DP No. D421926

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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

Cottonseed subgroup 20C 0.80 0.8

Cotton, gin by-products 30 30

40 CFR 180.661 (2) Livestock: sum of 

fluopyram (N-[2-[3-chloro-5-

(trifluoromethyl)-2-pyridinyl]ethyl]-2-

(trifluoromethyl)benzamide) and its 

benzamide metabolite [2-

(trifluoromethyl)-benzamide], 

calculated as the stoichiometric 

equivalent of fluopyram

Livestock: sum of 

fluopyram (N-[2-[3-chloro5-(trifluoromethyl)-2-

pyridinyl]ethyl]-2-

(trifluoromethyl)benzamide

) and its benzamide 

metabolite [2-

(trifluoromethyl)-

benzamide], calculated as 

the stoichiometric 

equivalent of fluopyram

Animal commodities: Sum 

of fluopyram and 2-

(trifluoromethyl)benzamid

e, expressed as

Fluopyram

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico2 Codex3

Cattle, fat 0.70 1.5

Cattle, meat

0.80 1.5

0.5 Meat (from mammals 

other than marine 

mammals)

Cattle, meat byproducts 7.5 10 0.5 kidney 

3 liver 

Egg 0.08 0.3

Hog, fat 0.20

Hog, meat

0.02

0.5 Meat (from mammals 

other than marine 

mammals)

Hog, meat byproducts 0.20 0.06 0.5 kidney 

3 liver 

Milk 0.40 2 0.3

Poultry, fat 0.04 0.05

Poultry, meat 0.04 0.2

Poultry, meat byproducts 0.16 0.15 0.7

Goat, fat 0.70 1.5

Goat, meat

0.80 1.5

0.5 Meat (from mammals 

other than marine 

mammals)

Goat, meat byproducts 7.5 10 0.5 kidney 

3 liver 

Horse, fat 0.70 1.5

Horse, meat

0.80 1.5

0.5 Meat (from mammals 

other than marine 

mammals)

Horse, meat byproducts 7.5 10

Sheep, fat 0.70 1.5

Sheep, meat

0.80 1.5

0.5 Meat (from mammals 

other than marine 

mammals)
Fluopyram Human Health Risk Assessment DP No. D421926

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Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico2 Codex3

Sheep, meat byproducts 7.5 10 0.5 kidney 

3 liver 

US Canada Mexico

2 Codex3

40CFR§180.661 (d) Indirect or 

inadvertent residues

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico

2 Codex3

Sugarcane, cane 0.08 0.08

Completed: M. Negussie; 09/24/2015

1

Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and 

not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.