Page 1 of 22 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

Date : May 30 , 201 4

Subject: Fluopyram

. Occupational and Residential Exposure Assessment for New Use as

a Soil/In

- Furrow Treatment for Cotton and Peanut, and as a Seed Treatment to Cotton and Soybean

.

PC Code: 080302 DP Barcode: D 419530

Decision No.: 4 81199 Registration No. : 264

- 107 8 ,264

- RRAT

Petition No.: NA Regulatory Action: Section 3 Risk Assessment Type: Occupational /Residential Exposure Assessment Case No.: NA

T XR No.: NA CAS No.: 658066

- 35

- 4

MRID No.: NA 40 CFR: §180. 661

From: Barry O’Keefe, Senior Biologist

Risk Assessment Branch III Health Effects Division (7509P)

Through: Christine Olinger, Branch Chief

Risk Assessment Branch III Health Effects Division (7509P)

and

Kelly O’Rourke

, ExpoSAC Reviewer Jennifer Tyler

, ExpoSAC Reviewer Exposure Science Advisory Committee (ExpoSAC) / HED

To: Barry O’Keefe , Risk Assessor

Risk Assessment Branch III

Health Effects Division (750 9 P)

Introduction The Health Effects Division (HED) of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human health from exposure to pesticides. The Registration Division (RD) of OPP has requested that HED evaluate the hazard and exposure data and conduct occupational

and residential exposure assessments, as needed, to estimate the risk to human health that willPage 2 of 22

result from the proposed uses of fluopyram

. This memorandum serves as HED’s assessment of the occupational and residential exposure a nd risk from the se proposed uses

.

It is HED policy to use the best available data to assess exposure. Several sources of generic data were used in this assessment as surrogate data in the absence of chemical

- specific data, including Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1) ; the Agricultural Handler Exposure Task Force (AHETF) database; ExpoSAC Policy 14 , 15, and 15.1 (SOPs for Seed Treatment), The Reviewer’s Aid to Calculating Occupational Exposure from Activities Related to Agricultu ral Seed Treatment, and the Agricultural Reentry Task Force (ARTF)

database

. Some of these data are proprietary, and subject to the data protection provisions of the Federal Insecticide, Fungicide, and Rodenticide Act ( FIFRA).

Note: This memorandum wa s reviewed by the Exposure Science Advisory Committee (ExpoSAC) on May 15 , 201 4

.Page 3 of 22 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 4

2.0 Risk Assessment Conclusions and Recommendations

................................ ........................ 6

2.1 Summary of Risk Estimates

................................ ................................ ............................. 6

2.2 Data Deficiencies and Requirements

................................ ................................ ............... 6

2.3 Label Recommendations

................................ ................................ ................................ .. 7

3.0 Hazard Characterization

................................ ................................ ................................ ....... 7

4.0 Use Profile

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

5.0 Residential Exposure and Risk Estimates

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

6.0 Occupational Exposure and Risk Estimates

................................ ................................ ...... 11

6.1 Occupational Handler Exposure/Risk Estimates

................................ ............................ 11

6.2 Occupational Post

- application Exposure/Risk Estimates

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

6.2.1 Occupational Post

- application Inhalation Exposure/Risk Estimates

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

6.2.2 Occupational Post

- application Dermal Exposure/Risk Estimates

.......................... 19 Appendix A. Summary of Occupational and Residential Non

- cancer Algorithms

..................... 22Page 4 of 22

1.0 Executive Summary

The active ingredient, f

luopyram ( N

- [2

- [3

- chloro

- 5

- (trifluoromethyl)

- 2

- pyridinyl]ethyl]

- 2

- (trifl uoromethyl)benzamide) is a pyridylethylamide SDH (succinate

- dehydrogenase

- inhibitor, complex II) fungicide with broad spectrum of activity against fungal diseases in a wid e range of

crops

.

Use Profile The registrant, Bayer CropScience is requesting new uses of fluopyram as a soil/in

- furrow treatment for cotton and p eanut, and as a seed treatment to cotton and soybean

. The at

- planting

soil/in

- furrow treatment for cotton and p eanut is an amendment to the Luna ® Privilege label (EPA Reg. No. 264

- 1078). Additionally, post

- emergent application to peanut by overhead chemigation is proposed on the Luna ® Privilege label. The proposed Luna ® Privilege label requires occupational handlers to wear the following personal protective equipment (PPE): long sleeved shirts, long pants, shoes, socks, and chemical resistant gloves. The proposed restricted entry interval (REI) is 12 hours.

The seed tr eatment to cotton and soybean is on the new end

- use product Fluopyram ST (EPA Reg. No. 264

- RRAT ). The proposed Fluopyram ST label requires occupational handlers to wear the following PPE: long

- sleeved shirt, long pants, shoes plus socks, and waterproof gl oves

.

Both products (Luna ® Privilege and Fluopyram ST) are liquid formulations containing 41.5 % ai ( 4.16 lb ai /gal) and 48.4% ai (5 lb ai/gal), respectively

.

Fluopyram is currently registered on a vari ety of agricultural food crops

, including apple, c herry (sweet and tart), dried beans, peanut, potato

, strawberry , sugar beets, tree nuts, watermelon, and viniferous variety grapes

. There are no existing or pro po sed residential uses of fluopyram.

Exposure Profile There is a potential for short

- and intermediate

- term occupational dermal and inhalation exposure

to fluopyram during handling tasks ( m ixing, loading, and application ) and during post

application activities . Long

- term occupational exposure is not expected for the proposed use patterns associated with fluopyram

.

Hazard Concerns

Short

- and intermediate term dermal risks are based on increased cholesterol in females, increased prothrombin time in males, increased liver weight (both sexes) and liver hypertrophy effects observed

at the Lowest Observed Adverse Effect Level ( LOAEL ) of 1000 mg/kg/day ( No Observed Adverse

Effect Level ( NOAEL ) of 3 00 mg/kg/day) from a 28

- day dermal toxicity study in rats

. Short

- and

intermediate

- term inhalation risks are b ased on decreased pup body weight and body weight gain

, and decrease in spleen and thymus weight effects observed at the LOAEL of 82.8 mg/kg/day ( NOAEL of

14

. 5 mg/kg/day) from a 2

- generation reproduction study in rats. The subchronic inhalation study data requirement was waived by the Hazard and Science Policy Council (HASPOC) (K. Rury, 1/30/13, TXR No. 0056523). Since the dermal and inhalation endpoints are not based on developmental effects, t he average body weig ht of an adult ( 8 0 kg) was used in the exposure assessment s. Further,Page 5 of 22

s ince the toxicological effects for dermal and inhalation routes are not similar, the risks from both

routes are not combined together

.

Fluopyram has low acute toxicity by the oral and de rmal routes of exposure (Toxicity Category III) and also by the inhalation route of exposure (Toxicity Category IV). It is not a dermal or eye

irritant and is not a dermal sensitizer.

The cancer classification is “ not like ly to be carcinogenic to humans

. ” There is no mutagenic concern for fluopyram.

Occupational Exposure

No chemical

- specific handler exposure data were submitted in support of th e s e Section 3 registration s . To assess handler exposures for regulatory actions when chemical

- specific monitoring data are not available, HED relie d on the most scientifically

- reliable surrogate data currently available from various sources such as the PHED, and the AHETF

. Some of this data, such as the industry task force data, is compensatory, subject to the data protection provisions of

FIFRA. For the in

- furrow uses on cotton and peanut, n on

- cancer risk estimates for dermal (with gloves) and inhalation (no respirator) s hort

- and intermediate

- term occupational handler

exposures all resulted in MOE ≥100, and therefore, do not exceed HED’s level of concern , with MOEs ranging from 8,200 to 84,000 for dermal exposures with gloves and from 68,000 to 300,000 for inhalation exposures. For the seed treatment uses on soybean and cotton seeds, n on

cancer risk esti mates for dermal and inhalation s hort

- term occupational handler exposures all resulted in MOE ≥100, and therefore, do not exceed HED’s level of concern, with MOEs ranging from 480 to 7,300 for dermal exposures and from 620 to 26,000 for inhalation exposure s.

Short

- and intermediate

- term d ermal 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 (T C ) used for all post

- a pplication activities were

the TC s established by ExpoSAC in the revised SOP No. 3.1. The dislodgeable foliar residue (DFR) levels for agricultural crops were estimated using HED standard values where it is

assumed that the initial residue on treated foli age is 2 5 % of the application rate and the residues degrade at a rate of 10 % per day. The occupational post

- application non

- cancer MOEs do not exceed HED’s level of concern (MOEs ≥100)

, with dermal MOEs ranging from 2 ,600 to 69,00 0

.

Based on the Agency's current practices, a quantitative non

- cancer 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: When post

- application risk estimate s a re not a concern on day 0 (12 hours following application), the REI is based on the acute tox icity of fluopyram technical

material. Fluopyram is classified as T oxicity C ategory III by the acute dermal route of exposure

, and Toxicity Category IV for acute eye irritation potential and skin irrita tion potential. Under the WPS for Agricultural Pesti cides, 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 would be adequate.Page 6 of 22

Residential Exposure Based on product labels, the products are not intended for use by homeowners, or by occupational handlers in residential settings. Additionally, there are no existing uses in residential settings. Therefore, non

- occupational/residential r isk assessments have not been completed.

Hu man Studies Review 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 data, which include studies from PHED 1.1; the AHETF database; the ARTF database; and ExpoSAC Polic ies 14 , 15, and 15.1 (SOPs for Seed Treatment), and The Reviewer’s Aid to Calculating Occupational Exposure from Activities Related to Agricultural Seed Treatment are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received th at review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review may have included review by the Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be

found at the A gency website 1

.

2.0 Risk Assessment Conclusions and Recommendations

2.1 Summary of Risk Estimates

There are no occupational risk estimates of concern assoc iated with the proposed use s of

fluo pyram

.

2. 2 Data Deficiencies and Requirements

There are no data deficiencies or requirements missing from the fluopyram database at this time.

Turf Transferable Residue (TTR): A TTR study is not required for fluopyram at this time

, since

there is no proposed or registered use on turf.

Dislodgeable Foliar Residue (DFR): A DFR study is not required for fluopyram at this time.

In accordance with 40 CFR158, DFR data are required for all occupational (e.g., crop, nursery, greenhouse use sites) or residential (e.g., ornamental and vegetable gardens, pick your own farms, retail tree farms) uses that could result in post

- application exposure to foliage. In the

absence of chemical

- sp ecific DFR data, EPA uses default values. The 2012 Standard Operating Procedures for Residential Pesticide Exposure Assessment includes an analysis of a number of DFR studies, which resulted in the selection of a revised default values for the fraction of the application rate available for transfer after a foliar application (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 appl ication rate error made in the

1 http://www.epa.gov/pesticides/science/handl er

- exposure

- data.html and http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.htmlPage 7 of 22

original submission of “ARF039

– Determination of Dermal and Inhalation Exposure to Reentry Workers During Chrysanthemum Pinching in a Greenhouse” (EPA MRID 45344501). As a result, the range of F AR values was revised from 2%

- 89% to 2%

- 47%. In the data, a large range of transferability is observed and this variability can potentially be attributable to many factors such as active ingredient; formulation; field conditions in the studies; weather conditions (e.g., humidity) ; or many other difficult to quantify factors. Although witnessed across multiple 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. Because DFR data are not available for fluopyram , EPA is using the default value of 25%. Although there may be a small degree of uncertainty in the use

of the default DFR value for fluopyram (i.e., there is a smal l chance that the F AR value may exceed the applicable default value ), it is likely that the health

- protective aspects of EPA’s occupational post

- application assessment methodology will more than compensate for this potential uncertainty. For example, whe n assessing residential and occupational post

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 doesn’t rain, etc); individuals perform

the same post

- application activities performed in the transfer coefficient study day after day (e.g., weeding, harvesting, pruning, etc.); and individuals engage in these pos t

- application activities for a high

- end amount of time every day (represented by data reflecting time spent gardening based on survey data).

Given the conservatisms discussed above and the potential compounding nature of these conservatisms, EPA is able t o rely upon the calculated exposure estimates with confidence that exposure is not being underestimated.

Since the highest estimated occupational post

- application exposure using default DFR values for fluopyram is minimal in comparison to the level of concern (i.e., the calculated MOE is greater than 2 times higher than the level of concern, MOE = 2,600 compared to the LOC of 100 ); EPA is waiving the 40 CFR DFR data requirement. In this instance, it is unlikely that chemical

specific DFR data would be needed to further refine exposure assessments or would add appreciably to our overall understanding of the availability of dislodgeable foliar pesticide

residues for fluopyram

.

2. 3 Label Re commendations

There are no label recommendations associated with these actions.

3 .0 Hazard Characterization

Acute Toxicity The acute toxicity for fluopyram is summarized in Table 3. 1

. Fluopyram has low acute toxicity by the oral and dermal routes of exposure (Toxicity Category III) and by the inhalation route of exposure (Toxicity Category IV). It is not a dermal or eye irritant and is not a dermal sensitizer.Page 8 of 22

TABLE 3. 1. Acute Toxicity Profile of Fluopyram Technical

.

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

870.1100 Acute Oral 47372430 LD50 > 2000 mg/kg in

females III

870.1200 Acute Dermal 47372432 LD50 > 2000 mg/kg in males &, females III

870.1300 Acute Inhalation (4 hr) 47372434 LC50 > 5.112 mg/L in males

& females IV

870.2400 Primary Eye Irritation 47372436 No positive scores at 24 hr; not irritating IV

870.2500 Primary Skin Irritation 47723701 Not irritating IV

870.2600 Dermal Sensitization 47372440 Not sensitizing N/A

870.2600 Dermal Sensitization 47753403 Not sensitizing N/A

Toxicological PODs Used for Risk Assessment

Short

- and intermediate term dermal risks are based on increased cholesterol in females, increased prothrombin time in males, increased liver weight (both sexes) and liver hypertrophy

effects observed at the LOAEL of 1000 mg/kg/day ( NOAEL of 3 00 mg/kg/day) from a 28

- day dermal toxicity study in rats

. Short

- and intermediate

- term inhalation risks are based on decreased pup body weight and body weight gain

, and decrease in sp leen and thymus weight

effects observed at the LOAEL of 82.8 mg/kg/day ( NOAEL of 14

. 5 mg/kg/day) from a 2

- generation reproduction study in rats. The subchronic inhalation study data requirement was waived by the Hazard and Science Policy Council (HASPOC) (K. Rury, 1/30/13, TXR No. 0056523). Since no inhalation absorption data are available, toxicity by the inhalation route is considered to be equivalent to the estimated toxicity by the oral route of exposure. Since the dermal and inhalation endpoints are not based on developmental effects, t he average body weig ht of an adult (80 kg) was used in the exposure assessment s. Further, s ince the toxicological effects

for dermal and inhalation routes are not similar, the risk estimate s from both routes are not

c ombined together

.

There is no mutagenic concern for fluopyram

. The CARC classified fluopyram as “Not Likely to be Carcinogenic to Humans” at doses that do not induce cellular proliferation in the liver or thyroid glands

. This classification was based on convincing evidence that non

- genotoxic modes of action for liver tumors in rats and thyroid tumors in mice have been established and that the carcinogenic effects have been demonstrated as a result of a mode of action dependent

on activation of the CAR/ PXR receptors. The CARC has determined that quantification of risk is not required.Page 9 of 22

A summary of the toxicological doses and endpoints for occupational human health risk assessment is provided in Table 3. 2

.

Table 3.2. 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

Short

- (1

- 30 days) &

Intermediate

Term Dermal (1

- 6 months) NOAEL =

300 mg/kg/day UF A = 10x

UF H = 10x LOC =

MOE ≤ 100 28

- day dermal toxicity study in the rat

LOAEL of 1000 mg/kg/day based on increased cholesterol in females, increased prothrombin time in males, increased liver weight (both s exes) and liver hypertrophy. (low dermal absorption, <1%)

Short

- (1

- 30 days) &

Intermediate

Term (1

- 6 months)

Inhalation NOAEL =

14.5 mg/kg/day UF A = 10x

UF H = 10x LOC =

MOE ≤ 100 2

- generation reproduction study in rats

LOAEL = 82.8 mg/kg/day based on decreased pup body weight and body weight gain and decrease in spleen and thymus weight.

Cancer (oral, dermal, inhalation) Classification: 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

.

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 as sociated 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 var iation in sensitivity among members of the human population (intraspecies). MOE = margin of exp osure. LOC = level of concern.

4 .0 Use Profile

The registrant, Bayer CropScience is requesting new uses of fluopyram as a soil/in

- furrow

treatment for cotton and p eanut, and as a seed treatment to cotton and soybean . The at

- planting

soil/in

- furrow treatment for cotton and p eanut is an amendment to the Luna Privilege label (EPA Reg. No. 264

- 1078). Additionally, post

- emergent application to peanut by ove rhead chemigation is proposed on the Luna ® Privilege label. The proposed Luna ® Privilege label requires occupational handlers to wear the following PPE: long sleeved shirts, long pants, shoes, socks, and chemical resistant gloves. The proposed REI is 12 hours.

The seed treatment to cotton and soybean is on the new end

- use product Fluopyram ST (EPA Reg. No. 264

- RRAT ). The proposed Fluopyram ST label requires occupational handlers to wear the following PPE: long

- sleeved shirt, long pants, shoes plus socks, and waterproof gloves

.

Both products are liquid formulations containing 41.5 % ai ( 4.16 lb ai /gal) and 48.4% ai (5 lb ai/gal), respectively

. The uses and application rates are described in Table 4.1.Page 10 of 22

T able 4

. 1. Summary of Proposed Directions for Use of Fluopyram

. Applic ation Timing, Type, and Equip. Formulation

[EPA Reg. No.] Applic ation

Rate (lb ai/A) Max. No.

Applic.

per Season Max.

Seasonal Applic. Rate (lb ai/A) PHI

(days) Use Directions and

Limitations

Cotton

Seed treatment

with commercial slurry mixture equipment only Fluopyram ST

(5 lb ai /gal) [ 264

- RRAT ] 0.0 03472 a

lb ai/lb seed 0.35 mg ai/seed (1.97 fl oz per 100,000 cotton seeds) 1 0.45 (from all uses) NA Do not use treated

seed for food, feed, or oil purposes.

In

- furrow during planting. Luna Privilege

(4.16 lb ai /gal) [ 264

- 1078 ] 0.22

( 6.84 fl oz/A) 1 NS NA Direct application

into the furrow and

cover with soil. Soybean

Seed treatment

with commercial slurry mixture equipment Fluopyram ST

(5 lb ai /gal) [ 264

- RRAT ] 0. 001983 a

lb ai/lb seed 0.25 mg ai/seed (1.97 fl oz per 140,000 soybean seeds) 1 0.45 (from all uses) NA Do not use treated

seed for food, feed, or oil purposes. Do not graze or feed soybean forage and hay to livestock.

Peanut

In

- furrow during planting or by chemigation
post

- emergent. Luna Privilege

(4.16 lb ai /gal) [ 264

- 1078 ] 0.22

(6.84 fl oz/A) 1 0.45 NA Direct application

into the furrow and

cover with soil.

a Based on seed counts (4

, 500 cotton seeds maximum/lb and 3

, 6 00 soybean seeds maximum/lb) from BEAD memo : “Acres Planted Per Day and Seeding Rates of Crops Grown in the United States.”

.

5 .0 Residential Exposure and Risk Estimates

Based on product labels, the products are not intended for use by homeowners, or by occupational handlers in residential settings. Therefore, non

- occupational/residential r isk

assessments have not been completed.

Spray Drift

S pray drift is always a potential source of exposure to residents nearby to spraying operations. This is particularly the case with aerial application

, but to a lesser extent, could also be a potential source of exposure from the airblast and groundboom application method s additionally employed for fluopyram . The Agency has bee n working with the Spray Drift Task Force, EPA Regional Offices

, and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices. The Agency is now requiring interim mitigation measures for aerial ap plications that must be placed on product labels/labeling. The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast

, and ground hydraulic methods. After the policy is in place, the AgencyPage 11 of 22

may impose further refinements in spray drift management practice s to reduce off

- target drift and risks associated with aerial as well as other application types where appropriate.

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 200 9, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- 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 i s required for fluopyram.

6 .0 Occupational Exposure and Risk Estimates

6 .1 Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and exposures can vary depending on the specifics of each t ask. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

In

- Furrow Use on Cotton & Peanut , and Post

- Emergent Chemigation to Peanuts Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, occupational handler dermal and inhalation exposure s ar e expected

from the proposed uses of fluopyram . The quantitative dermal and inhalation exposure/risk assessment developed for occupational handlers is based on the following scenarios:

1) Mixing/loading liquids for chemigation, 2) Mixing/loading liquids for g roundboom application, and 3) Applying sprays via groundboom equipment.

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors served as the basis for completing the occupational

handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate : A summary of the m aximum application rates for each crop or use site are provided in Table 4.1.

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical

- specific data,Page 12 of 22

include PHED 1.1, the AHETF database, or other registrant

- submitted occupational exposure studies. Some of these data are proprieta ry (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 2 ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 3

.

Area Treated or Amount Handled : The d aily areas treated or amounts handled were defined for each handler scenario (in appropriate units) by determining the amount that can be reasonably treated by an individual in a single day. When possible, the assumptions for daily areas treated

or amount s handled are taken from the HED’s ExpoSAC Policy 9 .1 : “Standard Values for Daily Acres Treated in Agriculture”. Values used for area treated or amount handled include the following:

1) 35 0 acres for mixing/loading for chemigation applications to typical field crops (peanuts)

, 2) 8 0 ac res for groundboom applications to typical field crops (e.g. peanuts)

, and

3 ) 200 acres for groundboom applications to high acreage field crops (i.e. cotton)

.

Exposure Duration: HED classifies exposures from 1 to 30 days a s short

- term and exposures 30 days to six months as intermediate

- term. Exposure duration is determined by many things, including the exposed population, the use site, the pest pressure triggering the use of the pesticide, and the cultural practices surrou nding that use site. For most agricultural uses, it is reasonable to believe that occupational handlers will not apply the same chemical every day for

more than a one

- month time frame; however, there may be a large agribusiness and/or commercial applicato rs who may apply a product over a period of weeks (e.g., completing multiple applications for multiple clients within a region).

For fluopyram , based on the existing labeled use patterns

, short

- and intermediate

- term exposures are expected

. Long

- term e xposure is therefore not expected.

Mitigation/Personal Protective Equipment: Occupational handler exposure assessments are completed by HED using different levels of risk mitigation. Typically, HED uses a tiered approach. The lowest tier is designed as the baseline exposure scenario (i.e., long

- sleeve shirt, long pants, shoes, socks, no respirator). If risk estimates are of concern at baseline attire, then increasing levels of PPE (i.e., gloves, respirators) are evaluated. This approach is used to ens ure that the lowest level of risk mitigation that provides adequate protection is selected

. Estimates of

dermal and inhalation exposure were calculated for “baseline,” defined as a single layer of clothing consisting of a long sleeved shirt, long pants, s hoes plus socks, no protective gloves, and no respirator. The fluopyram product label direct mixers, loaders, applicators and other handlers

to wear long

- sleeved shirt and long pants, and chemical resistant gloves

.

Occupational Handler Non

- Cancer Exposure and Risk Estimate Equations

2 Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

3 Available: http://www.epa.gov/pes ticides/science/handler

- exposure

- data.htmlPage 13 of 22

The algorithms used to estimate non

- cancer exposure and dose for occupational handlers can be found in Appendix A

.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates

For all exposure scenarios the risk estimates do not exceed HED’s LOC (MOEs ≥100) at baseline PPE (i.e. without gloves or a respirator). The MOEs ranged from 1, 4 00 (for dermal exposure) to 3 00,000 (for inhalation exposure) . See Table 6.1 .1 for the summary of occupational

handler risk estimates.Page 14 of 22 Table 6.1.1. Non

- Cancer Occupational Short

- and Intermediate

- Term Dermal and Inhalation Exposures and Risk Estimates For Fluopyram

Exposure Scenario Crop or Target 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 Chemigation Applications Peanut 0.22 350 0.22 0.0376 0.219 0.2 1 4 0.0 366 0.00021 3 1,400 8,200 68,000

Mixing/Loading Liquids

Concentrates for Groundboom Applications Peanut 0.22 80 0.22 0.0376 0.219 0.0 489 0.00 836 0.0000 486 6,100 36,000 300,000

Cotton 0.22 200 0.22 0.0376 0.219 0.122 0.0209 0.000122 2,500 14,000 120,000

Applicator

Applying Sprays via Groundboom Equipment Peanut 0.22 80 0.0 786 0.01 61 0. 3 4 0.01 75 0.00 358 0.0000 756 17,000 84,000 190,000

Cotton 0. 22 200 0.0786 0.0161 0.34 0.0436 0.00895 0.000189 6,900 34,000 77,000

a. Application Rates are based on proposed uses from the fluopyram label ( Luna ® Priviledge)

. b. Science Advisory Council Policy No. 9.1.

c. Baseline Dermal: Long

- sleeve shirt, long pants, and no gloves. PPE

- G Dermal: Baseline plus chemical

- resistant gloves. Baseline Inhalation: no respirator. d. Unit Exposures are based on the “Occupational Pesticide Hand ler Unit Exposure Surrogate Reference Table” (May 2013)

. e. Daily Exposure (mg/kg/day) = Application Rate (lb ai/A) * Unit Exposure (mg/lb ai) * Area Treated or Amount Applied (acre/ day) / 8 0 kg. f. MOE = NOAEL (mg/kg/day) / Daily Exposure (mg/kg/day); wh ere dermal NOAEL = 300 mg/kg/day and inhalation NOAEL = 14.5 mg/kg/day.Page 15 of 22

Seed Treatment Use on Cotton & Soybean Seeds Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the proposed seed treatment use. The quantitative exposure/risk assessment developed for occupational handlers is based on the following scenarios:

1. Mixing/loading liquids f or commercial seed treatment,

2. Bagging treated seed,

3. Sewing bags,

4. Multiple activities, and

5. Planting treated seed.

Occupational seed treatment handlers may experience short

- and intermediate

- term exposure to fluopyram while performing seed treatment activities in commercial settings. In addition, occupational secondary handlers may experience short

- and intermediate

- term exposure while planting fluopyram

- treated seeds. No chemical

- specific handler exposure data were submitted in support of this use pattern. For assessing commercial seed treatment and seed planting activities, unit exposure data were taken from HED ExpoSAC Policy 14: SOPs for Seed Treatment. The

amoun t of ai handled depends on the application rate (lb ai/lb seed) and the pounds of seed treated in a day (or the pounds of seed that can be planted in a day), all of which vary depending upon the seed type. Values for the amount of seed treated and planted per day were obtained from HED ExpoSAC Policy 15 and 15.1.

Treating Seed (Primary Handler) Potential occupational exposure scenarios from the use of fluopyram as a commercial seed treatment include: mixing, loading, applying liquid formulations; bagging treated seed; sewing bags; and multiple activities. Typically, for large

- scale commercial seed treatments, workers perform only those specific individual tasks listed above; however, it is assumed that workers also may perform multiple activities througho ut the day. As a result a “multiple activities” scenario (i.e. where one worker performs all seed treatment tasks such as loading/applying, sewing, bagging, cleaning, calibration, repair, forklift driver, etc.) was addressed.

Planti ng Treated Seed (Secondary Handler) Potential occupational exposure scenarios from the use of fluo pyram as a commercial seed treatment include planting treated seed (secondary handler). Planting treated seed consists of the farmer purchasing bags of treat ed seed, placing the seed in the hopper and applying seed to fields (considered a secondary handler exposure scenario).

Occupational Handler Exposure Data and Assumptions A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate : Refer to the proposed use pattern table in Section 4.0.Page 16 of 22

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure.

Chemical

- specific data for assessing exposure during commercial seed treatment and seed planting were not submitted to the Agency in support of these applications. Unit exp osures are from ExpoSAC Policy 14: SOPs for Seed Treatment (May 1, 2003) and are based on data for open mixing/loading/application systems.

Amount Handled: HED is currently in the process of revising ExpoSAC Policy 15: Amount of Seed Treated or

Planted per Day (March 2, 2004) in efforts to update the daily amount of seed treated in commercial seed treatment facilities. With the increasing demand for hybridized treated seeds, there have been modifications not only in the seed treatment equipment, but in the market shares of new and currently registered pesticide products. HED understands that due to the high cost of producing hybrid seeds, direct seeding is done in a precision manner which requires lower volumes of seed per acre. However, this does not provide a direct correlation to the amount of

seed which is treated in the commercial seed treatment facilities.

The amount of seed handled (for both primary/treater and secondary/planter handlers) is based on HED ExpoSAC Policy 15, HED ExpoSAC Policy SOP 15.1, and the BEAD memo: “Acres Planted Per Day and Seeding Rates of Crops Grown in the United States.”

The amount of seed treated per day at a commercial facility for short

- term exposure durations are

summarized below:

 Soybean

– 281,250 lb, and

 Co tto n

– 339,500 lb.

Amount of Seed Planted (ASP, lb seed/A)

 Soybean

– 133 lb seed/A = 200,000 seeds/A x lb soybean seeds/1,500 soybean seeds

 Cotton

– 18.9 lb seed/A = 85,000 seeds/A x lb cotton seeds/4,500 cotton seeds

The amount of seed planted per day is s ummarized below:

 Soybean

– 2 6, 6 00 lb ( 133 lb seed/A × 200 A/day).

 Cotton

– 3776 lb (18.9 lb seed/A × 200 A/day).

Exposure Duration: HED classifies exposures from 1 to 30 days as short

- term and exposures 30 days to six months

as intermediate

- term.

Mitigation/Personal Protective Equipment: Results are presented for PPE (gloves); defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, protective gloves, and no respirator for all scenarios, except bagging and sewing, for which “baseline ” attire

was evaluated

.

Occupational Handler Non

- Cancer Exposure and Risk Estimate Equations The algorithms used to estimate non

- cancer exposure and dose for occupational handlers can be

fo und in Appendix A.Page 17 of 22

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates The results of the occupational handler exposure and risk assessment indicate that short

- term
dermal and inhalation risk estimate s do not exceed HED’s LOC (i.e. an M OE < 100 for short

term exposures). Short

- term exposure risk estimates are protective of intermediate

- term exposure risk estimates because the throughput (amount of seed treated) of short

- term exposure is greater than, or equal to, the throughput of inter mediate

- term exposure. The dermal MOEs range from 480 to 7,300 for handlers (treaters and planters). The inhalation MOEs range from

62 0 to 2 6 ,000 for handlers (treaters and planters). Because the short

- and intermediate

- term
dermal and inhalation PODs a re the same, and the intermediate

- term exposure inputs are less

conservative than the short

- term exposure inputs for seed treatment, short

- term exposure risk estimates are protective of intermediate

- term exposure risk estimates.

Table 6

. 1 .2 . Summary of Short

- and Intermediate

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

. a

Crop 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 = 10 0

Loader/Applicator

Soybean 0.001983 281,250 0.023 0.00034 0.1603 0.002370 1,900 6,100

Cotton 0.003472 339,500 0.3389 0.005010 890 2,900

Sewer

Soybean 0.001983 281,250 0.0062 0.00023 0.04322 0.001603 6,900 9,000

Cotton 0.003472 339,500 0.09135 0.003389 3,300 4,300 Bagger
Soybean 0.001983 281,250 0.0091 0.00016 0.06344 0.001115 4,700 13,000

Cotton 0.003472 339,500 0.1341 0.002357 2,200 6,200 Multiple Activities

Soybean 0.001983 281,250 0.042 0.0016 0.2928 0.01115 1,000 1,300

Cotton 0.003472 339,500 0.6188 0.02357 480 620

Planters

Soybean 0.001983 26,600 0.25 0.0034 0.1648 0.002242 1,800 6,500

Cotton 0.003472 37 76 0.04099 0.0005574 7,300 26,000

a Seed treatment rate calculations are based on the following assumptions: Soybean : 3

, 6 00 seeds per lb; 13 3 lb of seed planted per acre, 200 acres planted per day. Cotton: 4,500 seeds per lb; 18.9 lb of seed planted per acre, 200 acres planted per day.

b Application Rate based on proposed label for fluo pyram (Fluopyram ST, EPA Reg. No. 264

- RRAT ).

c Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment (baseline inhalation = no respirator ; dermal unit exposure includes PPE with gloves for loading /applicator, multiple activities and planter scenari os ).

d HED default for lb seed treated/planted per day from HED Exposure Science Advisory Council I nterim Policy 15.1 and the BEAD memo “Acres Planted Per Day and Seeding Rates of Crops Grown in the United States” (J. Becker, March 2011).

e Daily Dermal Dose (mg/kg/day) = daily dermal unit exposure (mg/ lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) ÷ body weight (80 kg adult).

f Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure (mg/ lb ai) × application rate (lb ai/lb seed) × amount planted (lb seed/day) ÷ body weight (80 kg adult).

g Dermal MOE = NOAEL (300 mg /kg/day for short

- and intermediate

- term exposure) ÷ Dermal Dose (mg/kg/day). Level of concern = 100.

h Inhalation MOE = NOAEL ( 14.5 mg/kg/day for short

- and intermediate

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

100.Page 18 of 22

On

- Farm Seed Treatment

On

- farm seed treatment utilizes similar machinery as commercial seed treatment; the only difference being the size of the equipment. The assessed commercial seed treatment exposure and risk is protective of on

- farm seed treatment scenarios.

6

. 2 Occupational Post

- application Exposure/ Risk Estimates

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 production, such as scouting for pests or harvesting. Post

- application exposure levels vary over time and depen d o n 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, c an greatly reduce the potential for post

- application exposure.

6

. 2 .1 Occupational Post

- application Inhalation Exposure/Risk Estimates

There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The agency ha s evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis ( http://www.regulations.gov/#!docketDetail ;D=EPA

- HQ

OPP

- 2014

- 0219 ). During Registration Review, the agency will utilize this analysis to determine if data (i.e., flux studies, route

- specific inhalation toxicological studies) or further analysis is required for fluopyram ]

.

In addition, the Agency is continuing to evaluate the available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the Agency will continue to identify the need for and, subsequently, the way to incorporate

occup ational post

- application inhalation exposure into the agency's risk assessments.

Although a quantitative occupational postapplication inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commer cial handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposure than postapplication exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational postapplication inhalation exposure scenarios.”Page 19 of 22

6

. 2 .2 Occupational Post

- application Dermal Exposure/Risk Estimates

In

- Furrow Use on Cotton & Peanut

Occupational Post

- application Dermal Exposure Data and Assumptions In addition to the application rate and bodyweight values discussed above in the handler exposure section, the following assumptions were made in assessing short

- and intermediate

term dermal post

- application risks :

Dislodgeable foliar residues:

There wer e no chemical

- specific dislodgeable foliar residue data to assess post

- application risks to workers while performing tasks related to crops treated with fluopyram

. For agricultural

crops, o ccupational post

- application exposures and risks were assessed usi ng HED’s default assumptions that 2 5 % 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.

Transfer Coefficients: HED uses a concept known as the transfer coefficient to numerically represent the post

application exposures one would receive (generally presented as cm 2 /hour). A transfer coefficient is a measure of the residue transferred from a treated surface to a person who is doing

a task or acti vity in a treated area. These values are the ratio of an exposure for a given task or activity to the amount of pesticide residue on treated surfaces available for transfer. HED has developed a series of standard transfer coefficients that are unique for variety of job tasks or

activities that are used in lieu of chemical

- and scenario

- specific data.

No post

- application data were submitted in support of this registration action; therefore, dermal exposures during post

- application activities were estima ted for the various tasks that post

application workers might perform on each crop g rouping using dermal transfer coefficients from the Science Advisory Council for Exposure Policy Number 3 (http://www.epa.gov/pesticides/science/exposac_policy3.pdf). This policy reflects adoption of all ARTF data. Use of the data in this policy requires compensation to the ARTF under FIFRA. The transfer coefficients used in this assessment were taken from the Agency’s revised Agricultural Transfer Coefficient SOP. Many of the transfer coefficient s in this SOP are based

on work of the ARTF.

Workday: HED assumes an 8 hour workday for post

- application workers

.

Equations and Calculations: Daily Dermal Exposure and default DFR calculations are presented below. Daily Dermal Dose and MOE calculations are the same as presented above in Section 6 .1.

Daily D ermal E

xposure: Daily dermal exposures were calculated on each post

- application day after application using the following equation:Page 20 of 22

DE (t) (mg/day) = (DFR (t) (μg/cm 2 ) x TC (cm 2 /hr) x Hr/Day)/1,000 (μg/mg)

Where: DE(t) = Daily exposure or amount deposited on the surface of the skin at time (t)

a ttributable for activi ty in a previously t reated area, DFR(t) = Dislodgeable foliar residue (or transferable turf residue) at time “t” (μg/cm 2 ),

TC = Transfer Coefficient (cm 2 /hour), and Hr/day = Exposure duration meant to represent a typical workday (8 hours).

Default DFR: Default dislodgeabl e foliar residue (DFR) values were calculated on each post

application day after application using the following equation:

Default DFR (μg/cm 2 ) = AR (lb ai/A) x F x (1

- D) t x CF1 x CF2

Where: AR = Maximum application rate

,

F = Fraction of ai retained on the foliage

, D = Fraction of residue that dissipates daily

, t = Post

- application day

, CF1 = 4.54E+8 μg/lb , and

CF2 = 2.47E

- 8 A/cm 2

.

The post

- application exposure associated with agricultural crops is summarized in Table 6.2.2

. The occupational po st

- application MOEs do not exceed HED’s level of concern (MOEs ≥100) with dermal MOEs ranging from 2,60 0 to 69

, 0 00.

Table 6

. 2.2. Summary of Occupational Non

- Cancer Post

- application Risks (Short

- and Intermediate

- Term) with HED Default Assumptions.

Crop s 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)

Peanut 0.22 0.617 1,900 Irrigation (Hand Set) 0.1172 2,600 210 Scouting 0.01295 23,000 70 Weeding (Hand) 0.004317 69,000

Cotton 0. 22 0.617 210 Scouting 0.01295 23,000

70 Weeding (Hand) 0.004317 69,000

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 2 5 % DFR after in i tial 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 ( 8 0 kg)

d. MOE = NOAEL (300 mg/kg/day) / Daily Dose (mg/kg/day)

Restricted Entry Interval Since post

- application risk estimate s 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 a cute dermal route of exposure and Toxicity Category IV for acute eye irritation potential and skin irrita tion potential. Under the WPS for Agricultural Pesticides, active ingredients classified as acute toxicity categories III or IV forPage 21 of 22

these routes are a ssigned a 12

- hour REI. Therefore, the 12

- hour REI that appears on the proposed Luna ® Privilege label is adequate.

Seed Treatment Use on Cotton & Soybean Seeds With regard to seed treatment, the potential for post

- application exposures following the plant ing of fluopyram

- treated seeds is unlikely because s ustained levels of contact with treated seed after it has been placed in the soil or other planting media would not be expected because no routine cultural practice required for the production of agricult ural commodities involves such an activity

, as defined in the no/low contact criteria in the Worker Protection Standard (WPS)

. Therefore, no quantitative post

- application assessment is required for exposure to treated seeds that have already been planted

.Page 22 of 22

Appendix A. Summary of Occupational Non

- cancer Algorithms

Occupational Non

- cancer Handler Algorithms

Potential daily exposures for occupational handlers are calculated using the following formulas:

E=UE * AR * A * 0.001 mg/ug

where:

E = e xposure (mg ai/day),

UE = u nit e xposure (μ g ai/ lb ai),

AR = m aximum application rate according to proposed label (lb ai A or lb ai/gal ), and

A = a rea treated or amount handled (e.g., A/day, gal/day)

.

The daily doses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose a bsorbed in a given scenario (mg ai/ kg / day),

E = e xposure (mg ai/day),

AF = absorption fa ctor (dermal and/or inhalation), and

BW = body weight (kg)

.

Margin of Exposure: Non

- cancer risk estimates for eac h application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occupational

handlers a re compared to the appropr iate POD ( i.e.

, NOAEL) to assess the risk to occupational handlers for each exposure route. All MOE values a re calculated using the following formula:

MOE= POD

ADD

where:

MOE = m argin of e xposure: value used by HED to represent risk estimates (unitless),

POD = p oint of d eparture (mg/kg/day)

, and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day)

.