### Fluopyram Human Health Risk Assessment DP No. D421926



### UNITED STAT E S ENVIRONMENTAL PROTE C TION AGENC Y

WASHINGTON

, D

. C

. 20460

M E MORAND U M

DA TE: December 22, 2015 OFFICE OF
CHE M ICAL SAFETY AND
POLLUTION PREVE N TION



### SU B JECT : Fluop y ram : Human Health Risk Assessment for Proposed New Uses on Crop Subgroup 1 B

, Subgroup 1 C

, Crop Group 2, Subgroup 3-07 A, Subgroup 3-07B, Subgroup 4A

, Subgroup 4B, Subgroup SA, Subgroup SB, Subgroup 6A,

S u bgroup 6B, D r ied Beans, Soybean

, Su b group 8 -1 OA

, Subgroup 8-1 O B

, Subgroup 9A, Subgroup 9B, Subgroup 10

- 10

, Group 11

- 10

, Subgroup 12-1 2A, Subgroup 12

- 12B

, Subgroup 12-12C

, Subgroup 13

- 07A, Subgroup 13

- 07B

, Subgroup 13

- 07F, Subgroup 13-07G

, Crop Group 15 (except com and Ric e)

, Crop Group 16, Subgroup l 9A

, Dill Seed, Subgroup 20A, Subgroup 20B

, Subgroup 20C, Art i choke (Globe), Hops

, and Sugarcane (Rotated). Amended

Tolerance Reque s ts for the Registered Uses due to Crop Group / Subgroup Expansion Requ ests

. Proposed New Uses on Turf Grass, Ornamenta l s, and

Christmas Trees, and as a Seed Treatment to Peanut s.

P C Code: 080302

D ec i s i o n No.: 492321 DP Ba r co d e: 0421926

R eg i s tr a ti o n Nos.: 432-RLGI: 432-RLGT ; 432-RLGA; 432-

RLGL: 432- R LGU; 264-1078: 264

- 1084; 264 -1 085; 264-1090;

264-1091

P e tition No.: 4F8284 R eg ul ato r y A ct i o n :

. Section 3 Registration

Case No.: NA R isk Assess m e n t Ty p e : Single Chemica l/ Agg reg ate

T X R No.: NA CAS No.: 658066-35-4

4 0 CF R : 

### § 180 .66 1 MRID No.: NA



### FROM :

T H RO UG H :

TO: Barry O ' Keefe

, Senior Bio l ogist/ R isk Assesso r 

# /3

. O i Jl o{) 

# k

Meheret Negussie

, Chemist 

## / l e i " j

_ ;{-(i

## ;cl~**,,'~** Whang Phang, Senior Toxicologist / "'**}-6~** 

### Risk Assessment Branch 

### fII

H ea lth Effects Di v ision (7S09P)

Christine Olinger

, Chief 

# z**..£ ~**  

# (/ 

# / 1 ' 0' ' / ?

Ri sk Assessment Branch Ill 

# {;-Z1**~** 

# - - -

Hea l th Effects D i vision (7S09P)

Tamue Gibson

, Risk Manager Shaja J oyner, Team Leader Fungicide Herbi cide Branch
Reg i strat i on Division (7S05 P )

Page 1 of 87

### Fluopyram Human Hea l th Risk Assessme nt DP No

. 04 2 1926

The registrant. Bayer CropScience, is requesting new u ses of fluopyram on artic h oke (g lobe ),

Brassica (co l e) leafy vegetables, Brassica (co l e) leafy vegetables head and stem s ubgroup

, bu l b vegetables, cano l a, carTOt, cer ea l gra in s (except r i ce), c itru s, co rn (includi n g field, swee t

, popcorn
, and field corn grow n for seed)

, cotton

, cucurbit vegetables, fruiting vegetables, ginseng,

grapes and other small v i nes fruits (except fuzzy kiw i fru i t), herb s and spices (except black

pepper ), hop s, leafy vegetab l es, l egume vegetab l es ( in cludi n g soybean), peanut

, pome fruits

, potato and other root, tuberous and corm vegetables, s m a ll berr i es (caneber ries and bushbe r ries)

, stone fru i t, strawberry and other low grow in g berries, s ugar beet

, s unflow e r subgroup, tre e nuts;

use as a seed treatment to peanuts ; tu r f grass (golf courses, sod far m s, sports fields

, r eside n t i a l

, indu strial, municipal

, com mer cia l

, and other turf grass areas), ornamenta l s (in residential and

comme r cia l se ttings)

, and Ch ri s tmas tr ees.

The Regis t ration Di vision (RD) of OPP has r equested that the H ealt h Effects Di vision ( H E D )

evaluate the hazard and exposure data and conduct dietar y, aggregate, occupational and

resid e ntial exposure assessments

, as n eede d

, to es timat e the risk to human health th at w ill r es ult

from t h e propo sed uses of fluopyram. This mem orandum serves as HED 's asse ss m ent of those

exposu r es

.

The toxicology reevaluation was per formed by Whang P hang

, the dr i nking wate r assessment was
conducted by Mo hamm ed Ruhm an (EPA E n viron m e nt al Fate and Effects Division (EFED)), the

review of the re s idu e chem i stry data and the die t a r y exposure assessme n t were conducted by

Mehcret Neguss ie

, and the occupational and residen ti al exposu r e assessment and aggrega t e
human health ri sk asse ss m ent we r e cond u cted by Barry O ' Keefe.

Pag e 2 

### of87

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 3 of 87 TABLE OF CONTENTS

1.0 Executive Summary

................................ ................................ ................................ ........... 5

2.0 HED Recommendations

................................ ................................ ................................ .... 9

2.1 Da ta Deficiencies

................................ ................................ ................................ ............ 9

2.2 Tolerance Considerations

................................ ................................ .............................. 9

2.2.1 Enforcement Analytical Method

................................ ................................ ............... 9

2.2.2 International Harmonization

................................ ................................ ..................... 9

2.2.3 Recommended Tolerances

................................ ................................ ....................... 10

2.2.4 Revisions to Petitioned

- For Tolerances

................................ ................................ .. 15

2.3 Label Recommendations

................................ ................................ .............................. 17

3.0 Introduction

................................ ................................ ................................ ...................... 18

3.1 Chemical Identity

................................ ................................ ................................ ......... 18

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 Do se

- 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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 4 of 87 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 Es timates

..... 74 Appendix E. Occupational Handler and Post

- application Exposure/Risk Summary Tables

................................ ................................ ................................ ................................ ....................... 76 Appendix F. International Residue Limit Status Sheet

................................ .......................... 84

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 5 of 87 1. 0 Executive Summary

Fluopyram, ( N

- [2

- [3

- chloro

- 5

- (trifluoromethyl)

- 2

- pyridinyl]ethyl]

- 2

- (trifl uoromethyl)benzamide) is a broad

- spectrum syste mic fungicide of the pyridinyl ethylbenzamide group. It acts by inhibiting succinate dehydrogenase in the cell respir ation 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 fie ld 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 th e following multi

- active ingredient labels: 1) Propulse TM 

### (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) Lun a ® 

### 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 th e 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 variou s pre

harvest 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 additio n, 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 greenhous es, 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 5 00 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)

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 6 of 87 [EPA File Symbol 432

- RLGA] which con tains 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 pro posed 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 us e 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 c otton 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 derma l and inhalation exposure to fluopyram during handling tasks (mixing, loading, and application) and during post

application activities. Long

- term occupational exposure is not expected for the proposed use patterns associated with fluopyram. There is a po tential for residential short

- term dermal and inhalation exposure to fluopyram to adults during handling tasks. During residential post

application activities there is a potential for short

- term dermal exposure to adults, youths, and

children and incident al oral exposure to children 1 to <2 years old.

H azard Characterization

The l iver was the target organ following fluopyram exposure across specie s and exposure duration s . Treatment

- related thyroid effects were also observed at dose levels causing adverse liver perturbations in rats and mice. Decreased body weight w as 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 pro liferation 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

b ecause there are no residual uncertainties with regard to pre

- and postnatal su sceptibility, the toxicology database is complete, and there is no evidence of neurotoxicity

.

A n acute dietary endpoin t for the general population (including infants and children) was

selected from the acute neurotoxicity study in rats based on decreased motor and locomotor

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 7 of 87 activity ( no observed adverse effect level ( NOAEL = 50 mg/kg). Because t his 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 derm al 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 i nhalation and short

- term incidental

oral endpoints were selected from the multi generation reproduction study in rats based on clinical chemistry and kidney effects in the parental generation (NOAEL = 1 4. 5 mg/kg/day)

. I nhalation toxicity is assumed to be equivalent to o ral 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 include s tolerance residue level s, the assumption of 100% crop treated, and processing factors (empirical and default)

. The acute

e stimated 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 95 th


### percentile of exposure utilized 19 % of the acute population adjusted dose (aPAD) for the genera l US population, and 3 5 % 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, projected
percent crop treated, and processing factors (empirical and default)

. The chronic EDWC was incorporated d irectly 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 8 1 % o f 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

inhalatio n 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 MOE s 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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 8 of 87 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

a ggregate a cute and chronic risk s are equivalent to the acute and chronic dietary risk s 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 MOE s for small children and for adults are both 1,500, and are there fore

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

n ot 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 exp osures, 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. Addit ionally, 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 e xceed 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 post

application 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 exposur e

.

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.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 9 of 87 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) and a revised Section F (see Section 2.2.3

, Recommended Tolerances), 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 Defic iencies

There are no data deficiencies.

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

, t he 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 ( 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 analyt e 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 f or all plant and

livestock commodities.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 10 of 87 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 represen tative 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 sultan as 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 petition s and the MRLs are harmonized for almost all proposed crops, except soyb ean seed, crop subgroup 6C, crop subgroup 8

- 10A, crop subgroup 9B, crop group 15, herb subgroup 19A, and s ubgroup 20A (Refer to Appendix F ). Mainly, the differences

are due to different use pattern s and polic ies

.

The US and Codex/Canadian livestock MRLs are not harmonized due to different diet s 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.

Table 2 .2.3 .1. Tolera nce 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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 11 of 87 Table 2 .2.3 .1. Tolera nce Summary for Fluopyram.

Commodity Proposed Tolerance (ppm) Recommended/

Harmonized Tolerance (ppm) Comments; Correct Commodity

Definition

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, chrysa n themum , corn salad, cress, dandelion, endive, orach and purslane 1 40.0

VEGETABLES LEAFY, Celery, including Chinese celery and S wiss 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

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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 12 of 87 Table 2 .2.3 .1. Tolera nce Summary for Fluopyram.

Commodity Proposed Tolerance (ppm) Recommended/

Harmonized Tolerance (ppm) Comments; Correct Commodity

Definition

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 v ine 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

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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 13 of 87 Table 2 .2.3 .1. Tolera nce Summary for Fluopyram.

Commodity Proposed Tolerance (ppm) Recommended/

Harmonized Tolerance (ppm) Comments; Correct Commodity

Definition

Dill seed, Including

– Caraway seed, celery seed, coriael seed, lovage seed, mustard seed and poppy seed 1 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. 20 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

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

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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 14 of 87 Table 2.2. 3

. 2. Tolerance Summary for Fluopyram

. Commodity Established

Tolerance (ppm) Proposed

Tolerance (ppm) HED

Recommended

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

as crop

group 0.05 Revoke existing tolerance upon 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

.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 15 of 87 Table 2.2. 3

. 2. Tolerance Summary for Fluopyram

. Commodity Established

Tolerance (ppm) Proposed

Tolerance (ppm) HED

Recommended

Tolerance (ppm) Comments

( correct commodity definition )

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

15 0.03

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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 16 of 87 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, tre e 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 1 5 (sorghum) and rapeseed subgroup 20A (canola), the petitioner excluded a field trial as an outlier based on statistical tests. However, the trial s could not be excluded by the Agency since there were no abnormal field conditions. In addition, f or crop g roup 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.

T he 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 reques ted 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 exposure s from these

c ommodities are insignificant. However, separate tolerances, at 70 ppm, are needed for d ill, seed; caraway seed; celery seed; coriander, seed ; lovage seed; mustard seed; and poppy seed

.

For harmonization purposes, t olerances for sugar beet roots, melon su bgroup 9A, and subgroup

13

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

Separate tolerances were proposed for herbs and spices, subgroup 19A and dried herbs. Only 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 pro posed 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 prop ose 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.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 17 of 87 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. Generally, the Agency does not consider PPE and clothing requirements to be enforceable on consumer lawn products. If prod ucts 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 u ses).

 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 restri ctions 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 aft er treating with 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, mu stard 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 applicatio n 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 gra ze treated area for 14 days and do not harvest for food or feed within 14 days of application” “Under barley; corn (sweet corn,

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 18 of 87 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, “C hinese 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 unde r 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 vegeta bles (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 In troduction

Fluopyram (AE C656948) is a Group 7 fungicide with a broad spectrum of activity against numerous fungal diseases, including Ascomycetes, leaf spots, molds, sc a b, Alternaria, Septoria,

Mon i linia, 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.

3.1 Chemical Identity

Table 3.1. Fluopyram Nomenclature

. Chemical structure

Common name Fluopyram

Company experimental name AE C656948

IUPAC name N

- [2

- [3

- c hloro

- 5

- (trifluoromethyl)

- 2

- pyridyl]ethyl]

- α,α,α

- trifluoro

- o

- toluamide

CAS name N

- [2

- [3

- c hloro

- 5

- (trifluoromethyl)

- 2

- pyridinyl]ethyl]

- 2

- (trifluoromethyl)benzamide

CAS registry number 658066

- 35

- 4

End

- use product (EP) 264

- 1 167 Fluopyram ST; 264

- 107 8 Luna® Privilege ; 264

- 1084 Propulse; 264

- 1085 Luna Tranquility; 264

- 1090 Luna Sensation; 264

- 1091 Luna Experience

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 19 of 87 Table 3.1. Fluopyram Nomenclature

. Chemical structure of AE

C656948

- benzamide

metabolite (included in the

toler ance expression for livestock commodities)

2

- (T rifluoromethyl)

- benzamide



### 3.2 Physical/Chemical Characteristics

Fluopyram is not a highly lipophilic molecule (log K OW 

### = 3.3) and is not expected to pass the dermal barrier, pass through human milk

, or bioaccumulate in significant quantity. Emp i rical 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. Fluopyra m is persisten t in soil ( its half

- life is 4 64 days) w ith 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 u ses of fluopyram on registered liquid formulation product labels, as follows:

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 bee t, sunflower subgroup, and tree nuts. Additionally, the Luna Privilege label is also proposed for use as a seed treatment to peanuts.

2) The Propulse TM 

### 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 g rowing berries (except strawberries and cranberries), millet (pearl and proso), oats, rapeseed, rye, soybean, triticale, and wheat (spring, durum, and winter).

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 20 of 87 3) The Luna ® 

### Tranquility label (1.04 lb ai/gal) [EPA Reg. No. 264

- 1085] contains the active ing redients 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 low

growing berrie s (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), Brassic a (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

- 109 1] 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 vegetab les, 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 pro ducts 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, interiors capes, 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 proposed uses on citrus, grapes and small v ine 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 43 2

- 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

- R LUG] 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 propos ed labels the proposed REI for new uses is 12 hours.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 21 of 87 The proposed uses and application rates are described in detail in Table 3.3 .1.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 22 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

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 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)

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 h ybrids 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. Inc luding 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 forag e 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 sw eet), 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. 0.12 5 (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 14

0 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

- 1 078] 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 Summ er 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/o r 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 2 7 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 Summ er 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/o r 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 (i ncludes 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, Sunber ry, 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, Tr ee 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/A

13.7 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/A

17.1 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), Chin ese chive, Chive, Cinnamon, Clary, Clove (buds), Coriander (cilantro or Chinese parsley leaves),

Cori an der seed (cilantro seed), Costmary, Cilantro (leaf and seed), Cumin, Curry leaf, Dill (seed), Dillweed, Fennel [common and Florence (seed)], Fenugreek, G rains 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), Swee t 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

- 109 1] 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

fenn el (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.

Groun d, 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 (imm ature 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, Crowd er 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, Mayh aw, 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/A

13.7 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/A

17.1 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 (Turnip

rooted), 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 thornle ss 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, Rangebe rry, 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 raspb erry, 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), Blueber ry (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 cultivar s, 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, Phenome nalberry, 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 Baba bery, 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 buckth orn, 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 C urrant, 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

the se. 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/A

13.7 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/A

17.1 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 oi l 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 days. Ground,

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/A

13.7 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/A

17.1 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/A

15.3 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/A

309 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 ft 2
(0.04 to 0.31 fl oz/1000 ft 2 ) (0.0566 to 0.439 lb ai /A)

NS 0.3145 fl oz/1000

ft 2

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 ft 2
(0.05 to 0.6 fl oz/1000 ft 2 ) (0.0557 to 0.429 lb ai/A) 0.6267 fl oz/1000

ft 2

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 ft 2
(1.5 to 12.6 fl oz/1000 ft 2 ) (0.0531 to 0.446 lb ai/A) 12.6 fl oz/1000 ft 2

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 ft 2
(1.5 to 12.6 fl oz/1000 ft 2 ) (0.0531 to 0.446 lb ai/A) 12.6 fl oz/1000 ft 2

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 ft 2
(0.05 to 0.39 fl oz/1000 ft 2 ) (0.0566 to 0.444 lb ai/A) 0.393 fl oz/1000 ft 2

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 ft 2
(0.04 to 0.28 fl oz/1000 ft 2 ) (0.0566 to 0.396 lb ai/A)

NS 0.2847 fl oz/1000

ft 2

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 ft 2
(0.05 to 0.56 fl oz/1000 ft 2 ) (0.0557 to 0.400 lb ai/A) 0.5647 fl ozi/1000

ft 2

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 ft 2
(1.5 to 11.4 fl oz/1000 ft 2 ) (0.0531 to 0.404 lb ai/A) 11.4 fl oz/1000 ft 2

497 fl oz/A 2

0.404 lb ai/A

FLU+TFS SC 32.5 (0.104 lb ai/gal) 0.00121 to 0.00926 lb ai/1000 ft 2
(1.5 to 11.4 fl oz/1000 ft 2 ) 11.4 fl oz/1000 ft 2

497 fl oz/A

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 37 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

- 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 ft 2
(0.05 to 0.3558 fl oz/1000 ft 2 ) (0.0566 to 0.404 lb ai/A) 0.3558 fl oz/1000

ft 2

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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 38 of 87 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, applic ators 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 exposure s for workers re

- entering treated field s

. Additionally, there are proposed uses of fluopyram on turf and ornamentals; and therefore, exposure in residential or non

- occupational settings is likely, and

w ill result in short

- term dermal and inhalation exposure s fo r adult handl ers a nd dermal (for adults and small children) and incidental oral (for small children) exposures from post

application 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," ( htt p://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 s ubgroups 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 categoriz ed 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 expos ures 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 ha s 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 Septe mber, 201 4 ( D414231, B. O’Keefe, 09 /2 2 /201 4 )

. The toxicology database is complete and the hazard characterization is unchanged from the last assessment. This assessment includes summaries of prior hazard

characterization.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 39 of 87 4.1 Toxicological Effects

L iver effects and d ecreased body weight were the most common and sensitive findings in the subchronic and chronic oral toxicity studies in rats, mice, and dogs. L iver effect s were characterized by increased liver weight, hepatocellular hypertrophy, hepatocellular vacuolation,

increased mitosis and hepatocellular necrosis

. Increased liver tumors were also observed i n female rats in the carcinogenicity study. Live r 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 . C hanges in thyroid hormon e level s (T 3 

### & T 4 

### ) 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 t o have no genotoxic potential.

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

No evi dence of qualitative or quantitative susceptibility w as observed in these studies

.

In an acute neurotoxicity study, transient decreased motor activity was seen only on the day of treatment, but no other finding s demonstrating neurotoxicity w ere found. I n 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 ; t he percentage absor bed was approximately 93% of the administered dose. The

max imal plasma concentration was reached at 15 h ou rs in males and 11 h ou rs in females post dosing (5 mg/kg). The ab sorbed 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 small er extent to the kidney s. T he elimination results showed that 53

- 65% o f 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 h ou r s 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 metab olized and more than 29

metabolites were identified. T hree 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 methyl

sulfoxide, demonstrated less acute toxic potential than the parent compound. Mutagenicity tests on these two metabolites were negative.

A parallel approach was used to e stimate 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.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 40 of 87 4.2 Safety F actor for Infants and Children (FQPA Safety Factor)

The FQPA safety factor can be reduced to 1x b ecause (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 uncertain ties in the exposure database.

4.2.1 Completeness o f the Toxicology Database

T he toxic ology database for fluopyram is complete, and the available studies are adequate to characterize potential pre

- and/or post

- natal risk s 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 N eurotoxicity

The fluopyram toxicology database did not demonstrate evidence o f 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 gen eral 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 o f Sensitivity/Su sc eptibility in the Developing o r 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 e xposed during pre

- or post

- natal periods.

4.2.4 Residual Uncertainty in the Exposure Datab ase

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 processin g 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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 41 of 87 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 ra tes 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 D eparture 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,

a n acute neurotoxicity study in rats has been used to select t he 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

exposure s . The LOAEL of 82. 8 mg /kg/day was based on c linical 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 e xposure 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 toxicologic al effects w ere 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. The refore, it is not appropriate to combine these routes of exposure for risk assessment.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 42 of 87 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 base d on convincing evidence that non

- genotoxi c mode s of action for liver tumors in rats and thyroid

tumors in mice ha ve 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 con cern for mutagenicity.

4.3.4 Summary of P oints 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 Non

Occupational Human Health Risk Assessments

.

Exposure/

Scenario Point of

Departure Uncertainty/FQP

A 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 UF A = 10 X

UF H =10 X FQPA SF=1 X 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 UF A = 10 X

UF H =10 X FQPA SF=1 X Chronic RfD

= 0.0 12 mg/kg/day

cPAD =

0.0 12 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

Intermediate

Term (1

- 6 months) NOAEL=

14.5 mg/kg/day UF A = 10 X

UF H =10 X FQPA SF=1 X 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

.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 43 of 87 Table 4

. 3

. 4. 1

. Summary of Toxicological Doses and Endpoints for Fluopyram for Use in Dietary and Non

Occupational Human Health Risk Assessments

.

Exposure/

Scenario Point of

Departure Uncertainty/FQP

A Safety Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Dermal Short

Term (1

- 30 days) and

Intermediate

Term (1

- 6 months) NOAEL=

300 mg/kg/day UF A = 10 X

UF H =10 X FQPA SF=1 X 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

Intermediate

Term (1

- 6 months) NOAEL=

1 4 .5 mg/kg/day UF A = 10 X

UF H =10 X FQPA SF=1 X 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 w eights 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 c ancer 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. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the hu man 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 Short

Term (1

- 30 days) and

Intermediate

Term (1

- 6 months) NOAEL=

300 mg/kg/day UF A = 10 X

UF H =10 X 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

Intermediate

term (1

- 6 months) NOAEL=

1 4 .5 mg/kg/day UF A =10 X

UF H =10 X 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 decr eased 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 prolifera tion 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

Page 44 of 87 exposures. NOAEL = no ob served adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = 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 ro tational 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 compo und 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 oi lseed 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

involve s 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 an d 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 co ncern in ruminants are fluopyram and its metabolites AE C656948

- benzamide, AE C656948

- E

- olefine, AE C656948

- Z

olefine and AE C656948

- 7

- hydroxy, and in hens are fluopyram and its metabolites AE C656948

- benzamide, AE C656948

- E

- olefine, and AE C656948

- Z

- olefi ne.

A summary of m etabolites and d egradates to be included in the r isk a ssessment and t olerance

e xpressions 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 R isk 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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 45 of 87 Table 5.1. Summary of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expressions.

Matrix R isk 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, o range 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 ca ttle, 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 pr ovided by the EFED ( D427985 M

, 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 c urrently 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 c hronic (non

- cancer) value is 1 7 .3 ppb.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 46 of 87 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 wate r. For the human health risk assessment, the highest relevant EDWCs are recommended.

Table 5.3

. Estimated Surface and Ground W at er Concentrations for Fluopyram

.
Scenario Surface Water Conc., ppb Ground Wa ter Conc., ppb

Acute 

### 50.6 97.6 a

Chronic (non

- cancer) 

### 17.3 90.5 a

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

T he acute dietary analysis i s 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 u g/ L ) and was calculate d by PRZM

- GW modeling.

T he chronic dietary analysis i s a refined assessment that included average residue level s, projected % 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 projected percent crop treated data for new uses ( P PCTn) for fluopyram (DP# 427397, 0 9 / 2 2/201 5) , which includes both average and maximum PCT values . In addition, the previous PCTn (2010 and 2011) were consider ed acceptable (DP# 370371 (2010); DP# 381225 (2011); DP# 387 227 (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:

po tatoes 64%; sugar beets 48%; celery 60%; head lettuce 67%; leaf lettuce 62%; spinach 43% ( BEAD recommends using USDA/NASS spinach PCT values a s a proxy for Brassica leafy vegetables and leafy vegetables) ; broccoli 24%; snap beans 44%; dry beans/peas 7%; so ybeans 17%; fresh tomatoes 64%; processed tomatoes 57%; cantaloupes 22%; cucumbers 41%; pumpkins 45%; squash 47%; watermelons 54%; oranges 39%; apples 40%; pears 43%; peaches

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 47 of 87 56%; grape table 84%; grape raisin 95%; grape wine 79% (used for grape, wine and sherry); strawberries 75%; almonds 33%; corn

, field 9%; corn, sweet 15 % (email from Alsadek Jihad, 12/22/15) ; 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 95 th 

### percentile o f exposure is estimated to be

0.096117 mg/kg/day for the overall U.S. population, equivalent to 19% 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 95 th 

### percentile of 0.175170 mg/kg/day, equivalent to 3 5 % 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 gener al 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 8 1 % 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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 48 of 87 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

Youth 13

- 19 years old 0.073266 15 0.002617 22

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

1 The 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 environmen t that has been previously treated with fluop yram. 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 hig h contact lawn activities,

 Children (1 to <2 years old) incidental oral exposure as a result of contacting treated turf,

 Adults and y ouths (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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 49 of 87  Adults and children (6 to <11 years old) dermal exposure to treated gardens.

Exposures are expected to be short

- term in duration. Short

- term dermal and incidental oral exposure and risk est imates 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.

Di slodgeable F

oliar R esidue (D FR ) 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 Secti on 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 associa ted 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.

Table s 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 post

application 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 tre ated 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 33,00 0.

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

inhalation handler exposure from treat ing lawns from by hose

- end sprayer

.

 The recommended residential exposure for use in the children (1 to <2 years old)

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 50 of 87 aggregate assessment reflects incidental oral hand

- to

- mouth post

- application exposure to

treated lawns

.

The residential risk estimates from these exposures are presented in T able 6.3.1.

Table 6

. 3 .1. Recommendations for the Residential Exposures for the Fluopyram Aggregate Assessment.

Lifestage Dose (mg/kg/day) 4 MOE 5

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

, 4 00



### 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 rece ived 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 Ana lysis (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 r equired for fluopyram.

In addition to this screen, t he 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

- Occup ational 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 sour ce 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 spr ay 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 Procedure s For Residential Risk Assessment (SOPs)

- Residential Exposure Assessment Standard Operating Procedures Addenda 1: Consideration of Spray Drift. This

document outlines the quantification of indirect non

- occupational exposure to drift.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 51 of 87 7.0 Aggregate Expo sure/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 sou rces 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 p roposed residential uses so short

- term residential exposures are likely to occur ; and t herefore, 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 r isks 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. Th e 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 MOE s 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 LOC 1 Max Exposure 2 Residential

Exposure mg/kg/day Average

Dietary Exposure mg/kg/day Total

Exposure mg/kg/day Aggregate

MOE 2

Child 1 to <2 yr I ncidental oral hand

- to

- mouth post

- application exposure to treated lawns 14.5 100 0.145 0.000056 0.009733 0.009789 1,500

Adult I nhalation 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 ÷ ( A verage 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.,

<100% cPAD for the general U.S. population and all population subgroups )

. See Section 5.4.4

for details.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 52 of 87 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 toxici ty f inding as to fluopyram and any othe r 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 to xicity 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 Pesticid e 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 d ocument 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. Base d 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 v ia 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 mec hanically

- 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.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 53 of 87 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, withou t 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 o f 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. R isk estimates for dermal and inhalation short

- term occupational handler exposures all resulted in MOE s ≥100, and therefore, do not exceed HED’s level of concern, with MOEs ranging from 1, 4 0 0 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 re

entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop p roduction, 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 f or all post

application 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

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 54 of 87 23,000. A ll 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. A lthough 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 t hese 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

tr igger 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, t he 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 fo liar 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,

g reenhouse 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 transfe r after a foliar application (F AR 

### ). 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 subm ission 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 F AR 

### values was revised from 2%

- 89% to 2%

- 47%. In the data, a large

ra nge 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 factor s. Although witnessed across multiple

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 55 of 87 chemicals, this range in F AR 

### 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. Be cause 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 F AR 

### value may

exceed the a pplicable 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 pos t

application 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 doe sn’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 amoun t 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 residen tial 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

occupa tional 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 appre ciably 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 re sidential turf uses that could result in post

application 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 o f 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 (F AR 

### ). These values are based on an analysis of 5 9 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 F AR 

### values from 0.00 05% 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 ingre dient; formulation; field conditions in the studies; weather

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 56 of 87 conditions (e.g., humidity); or many other difficult to quantify factors. Although witnessed across multiple chemicals, this range in F AR 

### values is not expected when considering TTR data

for a s ingle 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 uncertain ty in the use of the default TTR value for fluopyram (i.e., there is a small chance that the F AR 

### value may exceed the applicable default value ), it is likely that the health

- protective aspects of EPA’s residential and occupational post

- application turf ass essment 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 F AR 

### values exceed the defaults ). For example, when

assessi ng 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

- applicatio n 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 und erestimated.

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 T oxicity C ategory III by the acute oral and dermal route s of exposure and Toxicity Category IV for acute inhalation, eye irritation potential and skin irrita tion 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 label s is adequate.

9.2.2 Inhalation Post

- application Risk

There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- appli cation activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 57 of 87 pesticides. The agency sought expert advice and input on issues related to volatilizat ion 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 ag ency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docke tDetail;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, 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 incorporat e 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 b e 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 / 201 5

, D 4 26622

. 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, fruit ing 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 (g olf c ourses, s od

f arms, s ports f

ields, r esidential, i ndustrial

, m unicipal, c ommercial, and other t urf grass areas ), ornamentals ( in r esidential and c ommercial settings), and Christmas trees

.

Cheng, L., 0 9 / 23 /2011, D387587 and D 389081. Fluopyram. Application for Section 3 Registration for Use on Apple, Banana (Impo rt 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 , D426 6 20. Fluopyram. Tolerances and Registration for Use on Crop Subgroup 1B, Subgroup 1C, Crop Group 2, Subgroup 3

- 07A, Subgroup 3

- 07B, Subgroup 4 A, Subgroup 4 B

, Subgroup 5A, Subgroup 5B, Subgroup 6A, Subgroup 6B, Dry B ean
, 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

- 07 A, Subgroup 13

- 07B, Subgroup

13

- 07F, Subgroup 13

- 07G, Crop G roup 15 (except corn and rice), C rop G roup 16, Sub gr oup 19A, Dill Seed , Subgroup 20A , Subgroup 20B, Subgroup 20C, Ar tichoke (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.

Negussie, M., 11/10/2015

, D 426621

. 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 4 A, Subgroup 4 B

, 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, S ubgroup 12

- 12A, Subgroup

12

- 12B, Subgroup 12

- 12C, Subgroup 13

- 07 A, Subgroup 13

- 07B, Subgroup 13

- 07F, Subgroup

13

- 07G, Crop G roup 15 (except corn and rice), Crop G roup 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 5 9 of 87 Ruhman, M. A., 10/26/ 20 15: 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 Ri sk Assessment.

Ruhman, M. A., 04/01/ 20 15: 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 Hea lth Risk Assessment.

Scollon, E., 7/16/2009, D367115. Fluopyram. Report of the Residues of Concern Knowledgebase Subcommittee (ROCKS).

Rowland, J., 05 / 08 /20 14 , TXR 0056961

. 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

Page 60 of 87 A ppendix 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

- Waived a

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

Page 61 of 87 A.2 Toxicity Profile s

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 LD 50 > 2000 mg/kg III

870.1300 Acute inhalation

- rat 47372435

47372434 LC 50 at 4 hours > 5112 mg/m 3

LC 50 > 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

Page 62 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 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/ova l 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 gl and: ↓ ceroid pigment (M), ↑ cortical vacuolation (F).

Non

- guideline 28

- day oral tox icity

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

tox icity 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 droplet s 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 fe tal body weight (5%), increased incidence

of two minor variations at both the visceral and skeletal

evaluation.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 63 of 87 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 r educed body weight gain and food consumption.

Developmental NOAEL = 25 mg/kg/day Developmental LOAEL = 75 mg/kg/day based on

d ecreased 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 b ased 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 i ncrease d kidney weight.

Offspring NOAEL = 15 mg/kg/day Offspring LOAEL= 83 mg/kg/day based on d ecreased 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

e xamined.

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 b a sed 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

Page 64 of 87 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

/carcino genicity 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 micro

nucleus 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

Page 65 of 87 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 incre ases 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 (radiola beled fluopyram) after 14 days pre

treatment 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 u rine (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 metabolit e 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) ( 14 C in position s 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 14 C 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

lit tle of the radioactivity was present in most organs except nasal mucosa.

870.7485 Distribution of 14 C

labeled fluopyram. 47372512; (2008)

Acceptable/non

- guideline
3 mg/kg for ♂ & 4.5 mg/kg for ♀ (Single oral dose; 14 C on pyridyl ring of

f l uopyram. ) Fluopyram was readily absorbed from the GI tract and distributed among almost all organs. P eak level was reached at approximately 1 hr after dosing in most organs with liver having the higher concentration than other organs. From peak level s, 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; 14 C

in the 2 & 6 p osition 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 a t 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

Page 66 of 87 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 [ 14 C]

– 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 we re 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 hepatocel lular 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 co ntent 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 abilit y 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. Minima l 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 liv er 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) (hepato

toxicity 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 peroxid a se

catalyzed reactions 47372518; (2008)

Acceptable /non

- guideline 300 μM Fluopyram at 300 μM did not affect thyroid per oxidase ( TP O)

- 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

Page 68 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 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. Ab solute 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 phenobarbital

treated 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 followin g 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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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 ( P XR ) and

Constitutive

Androstane Receptor ( C AR ) on the Thyroid Changes Following

the Administration of Fluopyram to

Male Mice (C57BL/6J and P XR

KO/ C AR KO). 49005906 (2013)

Acceptable/non

- guideli ne 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 fluopyra m

- 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 m ice.

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 k nockout 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 DNA

Synthesis 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 cytotoxici ty 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 activit y 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

Page 70 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 Enzyme and DNA

Synthesis 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. Epide rmal growth factor, at 25 ng/mL, was used as a positive

contro l. 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 f luopyram 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 phenobarbita l 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 relat ionship 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

treate d groups

.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 71 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 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

gr oup 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 treat ment. 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

- trea ted 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. Foll owing 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 fo r 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 pheno barbital

- 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

anima ls 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

Page 72 of 87 Appendix B

. Physical/Chemical Properties

Table B 1. 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 (pK
a ) 0.5 (23 oC) MRID 47372243

Octanol/water partition coefficient Log(K OW ) 3.3 MRID 47372245

UV/visible absorption spectrum Peak max at 270 nm MRID 47372237

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 73 of 87 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 Feb ruary 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

Page 74 of 87 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

Rate 1 Area

Treated

or Amount

Handled Daily 2 Exposure

Route Unit

Exposure (mg/lb ai) Daily Dose 3

(mg/kg/day) MOE 4

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/ft 2 1200 ft 2 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/ft 2 1200 ft 2 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/ft 2 1200 ft 2 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/ft 2 1200 ft 2 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 / ft 2 1000 ft 2 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 A cres Treated in Agriculture, Rev. 25 SEP 2001.

3 Daily Dose = Unit Exposure x Application Rate x Units Treated  Body Weight (80 k g).

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

Page 75 of 87 Table D .2. Residential Post

- Application Dermal Short

- Term Exposure and Risk Estimates from Turf.

Scenario Application

Rate (lb ai/A) TTR 1

(μg/cm 2 ) Exposure

Time (hr) Population TC (cm 2 /hr) Daily Dose 2

(mg/kg/day) MOE 3

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/cm 2 x 0.01 (fraction of transferable ai) = 0.0496 μg/cm 2 or 0.404 lb ai/A x 4.54E+8 μg/lb x 2.47E

- 8 A/cm 2 x 0.01 (fraction of transferable ai) = 0.0449 μg/cm 2

. 2 Daily Dose = [TTR (μg/cm 2 ) 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/cm 2 x 0.01 (fraction of transferable ai) = 0.0449 μg/cm 2

. 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) DFR 1

(μg/cm 2 ) Exposure

Time (hr) Population TC (cm 2 /hr) Daily Dose 2

(mg/kg/day) MOE 3

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/cm 2 x 0.25 (fraction of transferable ai) = 0.625 μg/cm 2

. 2 Daily Dose = [DFR (μg/cm 2 ) 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

Page 76 of 87 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

Rate a (lb ai/A) Area

Treated Daily b (A/day) Unit Exposure d Daily Exposure e (mg/kg/day) MOE f

Baseline

Dermal c (mg/lb ai) PPE

- G

Dermal c (mg/lb ai) Baseline

Inhalation c (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 F ruit; Strawberry and Other

Low

- Growing Berries 0.22 2 350

0.22 0.0376 0.219 0.214 0.0365 2

. 13 E

- 4 1,400 8,200 68,000

Brassica Leafy Vegetables Head and

Stem Subgroup 0.125 350 0.120 0.0206 1

. 20 E

- 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 0.22 2 1200 0.733 0.125 7

. 29 E

- 4 410 2,400 20,000

Nursery (ornamentals, vegetables,

trees, container stock) 0.131 60 0.0216 0.00370 2

. 15 E

- 5 14,000 81,000 670,000

Sod 0.446 350 0.429 0.0734 4

. 28 E

- 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; Smal l 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

. 86 E

- 5 6,00 36,000 300,000

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 77 of 87 Table E .1 . Occupational Short

- and Intermediate

- Term Dermal and Inhalation Exposures and Risk Estimates For Fluopyram

Exposure

Scenario Crop or Target Maximum Application

Rate a (lb ai/A) Area

Treated Daily b (A/day) Unit Exposure d Daily Exposure e (mg/kg/day) MOE f

Baseline

Dermal c (mg/lb ai) PPE

- G

Dermal c (mg/lb ai) Baseline

Inhalation c (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 80 0.0275 0.00470 2

. 7 4E

- 5 11,000 64,000 530,000

Canola Subgroup; Cereal grains; Forage, Fodder, or Straw from Cereal Grains; Cotton; Legume Vegetables (including Soybean) ; Potato; Sugar Beet; Sunflower

subgroup 0.222 200 0.122 0.0209 1

. 22 E

- 4 2,500 14,000 120,000

Field Grown Ornamentals 0.131 40 0.0144 0.00246 1

. 44 E

- 5 21,000 120,000 1

. 0 E+6 Nursery (ornamentals, vegetables, trees, container stock) 0.131 60 0.0216 0.0037 2

. 15 E

- 5 14,000 81,000 670,000

Sod 0.446 80 0.0981 0.0168 9

. 76 E

- 5 3,100 18,000 150,000

Turf 0.446 40 0.0490 0.00839 4

. 89 E

- 5 6,100 36,000 300,000 Mixing/Loading Liquids

Concentrates for

Airblast Applications Nursery (ornamentals, vegetables, trees, container stock) 0. 131 2 0

0.22 0.0376 0.219 0.00720 0.00123 7

. 18 E

- 6 42,000 240,000 2

. 0 E+6

Grapes and Small Vine Fruits (except Fuzzy Kiwifruit); Pome Fruit; Stone Fruit; 0.222 40 0.0244 0.00418 2

. 43 E

- 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; Smal l Berries (Caneberries and Bushberries); Stone Fruit; Strawberry and Other

Low

- Growing Berries 0.22 2 350

0.00 208 g No Data 0.0 049 g 0.00203 No Data 4

. 76 E

- 6 150,000 No Data 3

. 0 E+6

Brassica Leafy Vegetables Head and

Stem Subgroup 0.125 350 0.00114 No Data 2

. 68 E

- 6 260,000 No Data 5

. 4 E+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

. 64 E

- 5 43,000 No Data 880,000

Nursery (ornamentals, vegetables, trees, container stock) 0.131 60 0.000204 No Data 4

. 81 E

- 7 1

. 5 E+6 No Data 3

. 0 E+7

Sod 0.446 350 0.00406 No Data 9.56E

- 6 74,000 No Data 1.5E+6

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 78 of 87 Table E .1 . Occupational Short

- and Intermediate

- Term Dermal and Inhalation Exposures and Risk Estimates For Fluopyram

Exposure

Scenario Crop or Target Maximum Application

Rate a (lb ai/A) Area

Treated Daily b (A/day) Unit Exposure d Daily Exposure e (mg/kg/day) MOE f

Baseline

Dermal c (mg/lb ai) PPE

- G

Dermal c (mg/lb ai) Baseline

Inhalation c (μg/lb ai) Baseline

Dermal PPE

- G

Dermal Baseline

Inhalation Baseline

Dermal PPE

- G

Dermal Baseline

Inhalation

Applying Sprays via

Groundboom 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, Tube rous and Corm Vegetables; Small Berries (Caneberries and Bushberries); Stone Fruit; Strawberry and Other

Low

- Growing Berries 0.222 80

0.0 786 0.01 61 0. 3 4 0.0175 0.00358 7.55E

- 5 17,000 84,000 190,000

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) 0.22 2 2 0

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); 0.22 2 350 0.011 0.012 0.35 0.0107 0.0117 3.40E

- 4 28,000 26,000 43,000

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 79 of 87 Table E .1 . Occupational Short

- and Intermediate

- Term Dermal and Inhalation Exposures and Risk Estimates For Fluopyram

Exposure

Scenario Crop or Target Maximum Application

Rate a (lb ai/A) Area

Treated Daily b (A/day) Unit Exposure d Daily Exposure e (mg/kg/day) MOE f

Baseline

Dermal c (mg/lb ai) PPE

- G

Dermal c (mg/lb ai) Baseline

Inhalation c (μg/lb ai) Baseline

Dermal PPE

- G

Dermal Baseline

Inhalation Baseline

Dermal PPE

- G

Dermal Baseline

Inhalation

Stone Fruit; Strawberry and Other

Low

- Growing Berries 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 Mechanically

Pressu rized 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.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 80 of 87 c. Baseline Dermal: Long

- sleeve shirt, long pants, and no gloves.

PPE

- G Dermal: Baseline plus chemical

- resistant gloves. Baseline Inhalation: no respirator. 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 Treat ed or Amount Applied (acre/day) / 8 0 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 = enc losed cockpit.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 81 of 87 Table E .2. Summary of Short

- and Intermediate

- Term Handler Exposures and Risk Estimates for Fluopyram Seed Treatment of Peanut Seed. a

Maximum Application

Rate b

lb ai/lb seed Amount of

Seed Treated

or Planted Per Day d lb seed/day Dermal

Unit Exposure c mg/lb Inhalation

Unit Exposure c mg/lb Dermal

Dose e mg/kg/day Inhalation

Dose f mg/kg/day Dermal

MOE f

LOC = 100 Inhalation

MOE h

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/appli cator, 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 m emo “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 Inh alation MOE = NOAEL (14.5 mg/kg/day for short

- and intermediate

- term exposure) ÷ Inhalation Dose (mg/kg/day). Level of concern =

100.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 82 of 87 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 application a (μg/cm 2 ) Work Activity &

Maximum Transfer Coefficient b

(cm 2 /hr) Daily Dose c

(mg/kg/day) MOE d

(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/cm 2 ) = application rate (lb ai/A) x (1

- daily dissipation rate) t x 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)

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 83 of 87 Table E

. 5 . Anticipated Post

- Application Activities and Transfer Coefficients for Cotton Harvesters.

Crop Policy Crop

Group Category Crop

Height Foliage

Density Transfer C oefficients 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 Dose 3

(mg/kg/day) Dermal

MOE 4

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

(cm 2 /hr) & Activities 1 Post Application

Day (t) Turf

Transferable

Residue (TTR) 2 (μg/cm 2 ) Daily Dose 3

(mg/kg/day) Short

- &

Intermediate

- Term

Dermal
MOE 4

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 a re 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/cm 2 x 0.01 (fraction of transferable ai) = 0.05 μg/cm 2

. 3 Daily Dose = [TTR (μg/cm 2 ) 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.

### Fluopyram Human Health Risk Assessment DP No. D421926

Page 84 of 87 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 Mexico 2 

### Codex 3

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



### Commodity 1 

### Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 

### Codex 3
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 s ubgroup 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

Page 85 of 87 Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 

### Codex 3

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 v ine climbing, except fuzzy kiwifruit, subgroup 13

- 07F 2.0 2 2 grapes

Grape, rai sin 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 Grain, cereal, group 15 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

Page 86 of 87 Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 

### Codex 3

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

- chloro

5

- (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

- (trifluorometh yl)benzamid e, expressed as Fluopyram



### Commodity 1 

### Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 

### Codex 3

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. 20 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

Page 87 of 87 Summary of US and International Tolerances and Maximum Residue Limits Residue Definition : US Canada Mexico 2 

### Codex 3

Sheep, meat byproducts 7.5 10 0.5 kidney

3 liver



### US Canada Mexic o 2 

### Codex 3

40CFR§180.661 (d) Indirect or

inadvertent residues 

### Commodity 1 

### Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexic o 2 

### Codex 3

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. MR Ls indicated as proposed have not been finalized by the CCPR and the CAC

.