Page 2 of 29

Table of Contents

Executive Summary

................................ ................................ ................................ ...................... 3

1.0 Exposure/Risk Assessment

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

1.1 Hazard Concerns

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

1.2 Proposed U se Profile

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

1.3 Existing Use Profile for Golf Course Turf

................................ ................................ ... 8

2.0 Occupational Exposures and Risk Estimates

................................ ................................ .. 9 2.1 Occupational Handler Exposure Data

................................ ................................ .............. 9 2.2 Occupational Handler Non

- Cancer Risk Estimates

................................ ...................... 10 2.2.1 Occupational Handler Exposure and Non

- Cancer Risk Assumptions

................. 10 2.2.2 Occupational Handler Non

- Cancer Risk Estimate Calculations

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

2.2.3 Occupational Handler Non

- Cancer Risk Estimates

................................ .......... 12

2.3 Occupational Handler Cancer Risk Estimat es

................................ .......................... 14 2.3.1 Occupational Handler Exposure and Cancer Risk Assumptions

......................... 14 2.3.2 Occupational Handler Cancer Risk Calculations

................................ ................... 14 2.3.3 Occupational Handler Cancer Risk Estim ates

................................ ....................... 15 3.0 Occupational Postapplication Exposures and Risk Estimates

................................ .......... 18 3.1 Occupational Postapplication Exposure and Non

- Cancer Risk Estimates

................. 18 3.2 Occupational Postapplication Cancer Risk Estimates

................................ .................. 19 3.2.1 Occupational Postapplication Exposure and Cancer Risk Assumptions

............. 19 4.0 Residential Exposure

................................ ................................ ................................ ............ 20 4.1 Residential Handler Exposure

................................ ................................ ......................... 20 4.3 Use of TTR Data for Iprodione Post

- application Exposure Assessments

................... 20 4.2 Residential Postapplication Exposure and Non

- cancer Risk Estimates

...................... 21

4.4 Residential Po stapplication Exposure and Cancer Risk Estimates

............................. 24

5.0 Label Recommendation

................................ ................................ ................................ ........ 27

APPENDIX A: IPRIDION E DFR STUDY SUMMARY

................................ ........................ 28Page 3 of 29

Executive Summary The Health Effects Division (HED) has conducted an occupational exposure assessment for the proposed new use s of the fungicide and nematicide active ingredient (ai) ipr odione on cucurbits and fruiting vegetables . The new agricultural use s are for the product Enclosure TM 4 Flowable,

a liquid concentrate formulation (41.6% iprodione; 4 lbs iprodione per gallon) and are intended

as a nematicide

. Ipr o dione a pplication s can be made mechanically (groundboom) or by chemigation. This memorandum addresses the occupational exposure and risk from this label

amendment and the revised residential exposure assessment that is needed for a aggregate risk

assessment

.

The new use l abel

- required personal protective equipment (PPE) for mixers/loaders is long

sleeved shirt, long pants, chemical

- resistant footwear plus socks, chemical

- resistant apron and

chemical

- resistant gloves

.

Hazard Summary

Non

- cancer s hort

- and intermediate

- term dermal and inhalation risk estimates in this assessment

are based on systemic effects observed in the rat pubertal assay at the Lowest Observed Adverse Effect Level (LOAEL) of 50 mg/kg/day

.

The non

- cancer level of concern is an MOE of < 1000 for the short

- and intermediate

- term exposure duration s, respectively . The level of concern is based on uncertainty factors of 10x to account for intraspecies variability , a 10x for interspecies variability , and a factor of 10x to
account for the LOAEL to NOAEL extrapolation for both short

- and intermediate

- term

exposures

.

Iprodione is also classified as a “Likely” human carcinogen based on a Q 1 * value assigned to ipr o dione based on testicular tumors (Leydig Cell) in rats of 4 .4 x 10 - 2 (mg/kg/day) - 1 ; was used for assessing cancer risk. Additionally, iprodione has a degradate (3,5

- DCA) with an established Q 1 *, although that Q 1 * value is not relevant to th e exposure assessment on the new agricultural

uses or the updated residential cancer risk assessment

.

Occupational Handler Risk Summary The occupational handler risk estimates were calculated using the label maximum application

rate of 2 lb ai/acre, and assumptions regarding the agricultural equipment and work practices

. For non

- cancer risk estimates

, inhalation and dermal exposures were combined since the endpoints were based on the same effect

. For cancer risk estimates

, inhalation and dermal exposures are assessed; dermal and inhalation exposure s were combin ed. Based upon the proposed label PPE, non

- cancer risk estimates were not of concern at the proposed label PPE

. For the private grower scenario, cancer risk estimates range from 1 .0 x 10 - 6 to 1.0 x 10 - 5 at the proposed label PPE. For the commercial grower scenario, cancer risk estimates range from 6.8 x 10 - 6 to 3.0 x 10 - 5 at the proposed label PPE.

Occupational Postapplication Risk Summary Occupational short

- and intermediate

- term non

- cancer dermal ri sk estimates were qualitatively

assessed for postapplication activities. The proposed use pattern indicates pre

- plant and soilPage 4 of 29

incorporated applications of iprdione. Therefore, the standard “foliar

- based” transfer coefficient

metho do logy does not apply. HED believes the proposed soil incorporation is expected to keep exposures low. Based on the Agency's current practices, a quantitative non

- cancer occupational postapplication inhalation exposure assessment was not performed for iprodione at this time.

S imilarly, a review of the labeled use pattern indicates that because of negligible postapplication

worker contact with treated soi l , a quantitative postapplication cancer risk assessment is not necessary at this time

.

Restricted Entry Interval : Technica l iprodione is classified as toxicity category III/IV for acute dermal toxicity, primary eye, and skin irritation. Under the WPS, active ingredients classified as acute toxicity categories III or IV for these exposure routes are assigned a 12

- hour restric ted entry interval

. The proposed product label identifies a 24 hour restricted entry interval for curcurbits and fruiting vegetables.

Residential Exposure HED assessed residential golf course turf exposure in this assessment in order to complete the

aggregate assessment. While the agricultural uses of iprodione for curcurbits and fruiting vegetables are as a nematicide, the golf course use of iprodione asses sment is as a fungicide.

I prodione can be applied to golf course turf where there is potential for postapplication residential exposure to golfers. Cancer and n on

- cancer postapplication risk estimates were

calculated for non

- occupational postapplication e xposure to treated golf course turf. Non

- cancer risk estimates for the residential golfer scenario ranged from 3,200 to 4,800; all the risk estimates are above the LOC of 1,000 and therefore, not of concern.

C ancer risk estimates for the golfer scenario r ange from 3 .2 x10 - 6 to 1.8x10 - 5

.

Human 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

, w hich include studies from

the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler Exposure Task Force (AHETF) database

, are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements. For cer tain studies that 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 http://www.ep a.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.html

.

Label Recommendation

HED recommends t he proposed pro duct label should be modified to clarify that foliar application is prohibited for the proposed new uses on curcurbits and fruiting vegetables

. While

the c rop specific parts of the label indicate clear use directions, other parts of the label appear to

all ow for aerial application (page 6 and other places) which is contrary to the crop specific curcurbit and fruiting vegetable uses on the proposed label.Page 5 of 29

1.0 Exposure/Risk Assessment

The registrant requests new use s of iprodione on cucurbits and fruiting vegetables . This memorandum addresses the occupational exposure and risk from this label amendment. HED assessed post

- application residential golf course turf exposure in this assessment in order to complete the aggregate assessment.

1.1 Hazard Concerns

Acute Toxicity

The results of acute toxicity testing are given in Table 1.1a. These results indicate that technical iprodione has low to moderate acute toxicity , is a mild eye irritant, and is not a dermal sensitizer.

Table 1.1a. Acute Toxicity of Ipr odione

Guideline

No. Study Type MRID Results Toxicity Category

870.1100 Acute Oral

– rat 423063

- 01 LD 50 = 4468 mg/kg III

870.1200 Acute Dermal

– rabbit 405676

- 01 LD 50 > 2000 mg/kg III

870.1300 Acute Inhalation

- rat 429461

- 01 LC 50 >5.16 mg/L IV

870.2400 Primary Eye Irritation

– rabbit 418673

- 01 Mild irritant III

870.2500 Primary Skin Irritation

– rabbit 418673

- 02 Not an irritant IV

870.2600 Dermal Sensitization

– guinea pig 405676

- 02

425246

- 01 Not a dermal sensitizer N/A

Toxicological PODs Used for Risk Assessment

A summary of the toxicological points of departure (PODs) that are relevant to occupational exposure is included in Table 1.1b

.

A single endpoint was selected to cover the dermal and inhalation short

- and intermediate

- term occupational exposure scenarios. The endpoint for the occupational exposure scenarios was selected from the male rat pubertal assay (MRID 48279201) where the LO AEL is 50 mg/kg/day,

based on reduced serum testosterone. The 69 kg bodyweight is appropriate to use for the occupational assessment because the endpoint is an in utero effect occurring during prenatal

exposure

.

HED’s level of concern for non

- cancer risk estimates is defined by the uncertainty factors that are applied to the assessment. The level of concern for short

- and intermediate

- term iprodione occupational exposures is 1000, based on the inter

- and intra

- sp ecies factors as well as a 10x uncertainty factor for the lack of a NOAEL in the study

.Page 6 of 29

For the non

- cancer residential exposure assessment, the standard inter

- and intra

- species factors are applicable. Additionally, HED recommends that the 10X FQPA safet y factor be retained for

the short

- and intermediate

- term dermal and inhalation exposure points of departure (for the protection of infants and children), based on the LOAEL to NOAEL extrapolation. Therefore the level of concern for residential exposure is an MOE of <1,000.

Based on the available toxicity database and the Agency’s current practices, the inhalation risk

for iprodione was assessed using an oral study. The toxicity sought expert advice and input on issues related to this route to route extrap olation approach (i.e., the use of oral toxicity studies for inhalation risk assessment) from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report
on March 2, 2 010 ( http://epa.gov/scipoly/meetings/20091220109meeting.html ). The Agency is in the process of evaluating the SAP report and may, as appropriate, re

- examine and develop new policies and procedures for conducting inhalation risk assessments, including route to route extrapolation of toxicity data. If any new policies o r procedures are developed, the Agency may revisit the need for an inhalation toxicity study for iprodione and/or a re

- examination of the

inhalation toxicity risk assessment.

In accordance with the EPA Proposed Guidelines for Carcinogen Risk Assessment ( April 10, 1996), the Cancer Assessment Review Committee classified Iprodione as a "likely" human carcinogen based on the combined hepatocellular adenomas/carcinomas in mice and testicular tumors in male rats with a linear low dose extrapolation approach an d a 3/4 s interspecies scaling factor for human risk characterization. The CARC determined that for the Leydig cell tumors in male rats, the Q 1 * is 4.39 x 10

- 2 (selected by HED’s CARC Committee; TXR 0054534, 3/22/07)

. HED policy doesn’t define a “level of concern” when evaluating cancer risk estimates. The cancer risk estimates are presented based on the Q 1 * value for OPP risk managers to evaluate and mitigate as needed.Page 7 of 29

Table 1.1b. Toxicological PODs for Occupational Exposure Assessment of Iprodione

Exposure Scenario Point of Departure

(POD) Uncertainty

Factors Study and Toxicological Effects

Dermal Short

- Term (1

- 30 days)

Dermal

Intermediate

- Term

Inhalation Short

Term (1

- 30 days)

Inhalation

Intermediate

- Term LOAEL = 50

mg/kg/day Dermal absorption

factor = 5%

Since no inhalation toxicity data are available, toxicity by the

inhalation route is

considered to be equivalent to toxicity by

the oral route of

exposure UF A 10x

UF H 10x

UF LOAEL→NOAEL =10X Co

- critical studies

Male pubertal toxicity (rat )

MRID 48279201 LOAEL = 50 mg/kg/day, based on significant , dose

- related reductions in

serum testosterone levels (↓73%)

Chronic oral toxicity (rat)

MRID 42637801/42787001 LOAEL = 12.4 mg/kg/day, based on increases in generalized enlargement of the cells of the zona glomerulosa in males and females, in fine vacuolation of the zona fasciculata and in generalized fine

vacuolation of the zone reticularis in males in the adrenal cortex, an increased

incidence o f interstitial cell hyperplasia, reduced spermatozoa in the epididymides, reduced secretion of the seminal vesicles, increased hemosiderosis in the spleen in females, and increased liver weight.

NOAEL = 6.1 mg/kg/day

Inhalation Short

Term (1

- 30 days)

Inhalation

Intermediate

- Term LOAEL = 50

mg/kg/day UF A 10x

UF H 10x

UF LOAEL→NOAEL =10X Male pubertal assay (rat)

MRID 48279201 LOAEL = 50 mg/kg/day, based on reduced serum

testosterone levels

Dermal Absorption

Factor 5 percent of the oral dose Based on the value measured at 10 hours in a dermal absorption study (MRID 43535003). Carcinogenicity Q 1 * = 4.4 x 10 - 2 (mg/kg/day) - 1 Iprodione is classified as a “Likely” human carcinogen, based on findings in the Rat Leydig

cells (CARC

- based Q1*)

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. LOAEL = lowest observ able adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies).

1.2 Proposed Use Profile

The proposed new use s for the product Enclosure TM 4 Flowable, a liquid concentrate formulation (41.6% iprodione; 4 lbs ai per gallon) , are on cucurbits and fruiting vegetables . The maximum application rate allowed on this label for cucurbits and fruiting vegetables is 4 pints of

Enclosure TM 4 Flowable per acre ( 2 lb ai/acre) per application and up to 3 app lications arePage 8 of 29

allowed per season . The maximum application rate per season is 6 pints per acre (3 lb ai/A/season). The pre

- harvest interval (PHI) for cucurbits and fruiting vegetables is 14 days (the final application can be made up to 14 days before harv est). Application consists of a soil

directed pre

- plant or post

- plant mechanical incorporation . T he application timings and methods

are described below.

Cucurbits and fruiting vegetables , transplanted crops : The application is specified to be a preplant and post plant soil treatment. For transplanted crops, the label specifies that the 1 st
application should be made 4

- 7 days prior to transplant and that the product should be thoroughly incorporated (mechanically or through drip irrigation) into the bed at least 3

- 5 inches deep. The 2 nd application is specified to be made through drip chemigation 7

- 10 days after transplanting

. The 3 rd application is specified to be made through drip chemigation 12

- 14 days

after the 2 nd application.

Cucurbits and fruiting vegetables , seeded crops: The application is specified to be a pre plant and post plant soil treatment. For seeded crops, the label specifies that the 1 st application be

made 4

- 7 days prior to seeding. The product should be thoroughly incor porated (mechanically or through drip chemigation) into the bed at least 3

- 5 inches. The 2 nd application is specified to be made through drip chemigation 10

- 14 days after seedling emergence. The 3 rd application is specified to be made through drip chemig ation 12

- 14 days after the 2 nd application.

The label specifie s that for nematode su pplemental control , the product should be applied through drip chemigation 14

- 21 days after transplanting, and that subsequent applications through drip chemigation should be made on 14

- day intervals.

The label specifies that when the high rate of 4 pints per acre is used, only one subsequent application at 2 pints per acre is allowed. This application should be made 7

- 10 days after transplanting or 10

- 14 days after seed ling emergence.

1.3 Existing Use Profile for Golf Course Turf

HED conducted a cancer risk assessment based on non

- occupational exposure to treated golf

course turf to contribute an aggregate human health risk assessment. A variety of existing product labels for turf were reviewed. Because iprodione can be used to prevent disease or to control disease infestation, product labels indicate a range of potential application rates depending on seasonality or dis ease pressure. Some product labels have differential application rates for golf course greens and fairways. For example, 9198

- 229 indicates an application rate of 8.2 and 5.5 lbs ai/A for tees and greens and fairways, respectively. Granular formulations ar e to be applied using a light rate (1.4 lb ai/acre) to prevent certain fungi such as pink or gray snow mold or leaf spot. Other liquid product labels indicate a normal (2.7 lb ai/acre) to heavy application rate (4.1 lb ai/acre) to control fungi such as lea f spot, brown patch and red leaf spot ( representative label: EPA Reg. No. 538

- 159).Page 9 of 29

2.0 Occupational Exposures and Risk Estimate s

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.

Tasks associated with occupational pesticide handlers are categorized using one of the following

terms: Mixers and/or Loaders: these individuals perform tasks in preparation for an application. For example, mixers/loaders would mix and prepare the nemat ici de product prior to application. Applicators: these individuals are involved in the pesticide application process (they do job functions related to a pesticide application event). These individuals would complete the product application.

The following occupational handler exposure scenarios were assessed:

1

– Mix/ Load Liquid for Chemigation

2

– Mix/Load Liquid for Groundboom Application

3

– Apply spray by Groundboom Sprayer

A chemical can produce different effects based on how long a person is exposed, how frequently exposures occur, and the level of exposure. HED classifies exposures from 1 to 30 days as short

term and exposures 30 days to six months as intermediate

- term. HED completes both short

- and

intermediate

- term assessments for occupational scenarios in all cases because these kinds of exposures are likely and acceptable use/usage data are not available to justify deleting

intermediate

- term scenarios. Based on use d ata and label instructions, HED believes that occupational exposures may occur over a single day or up to weeks at a time for many use

patterns and that intermittent exposure over several weeks may also occur. Some applicators may apply these products ove r a period of weeks, because they are commercial applicators who are completing multiple applications for multiple clients. Long

- term (greater than six months) handler exposures are not expected for iprodione based on the proposed use pattern.

Occupation al handler exposure assessments are completed by HED using different levels of risk mitigation. Typically, HED uses a tiered approach evaluating various levels of personal protective equipment. This approach is used to ensure that the lowest level of risk mitigation that provides adequate protection is selected, since the addition of PPE and engineering controls involves an additional expense to the user and (in the case of PPE) also involves an additional

burden to the user due to decreased comfort and de xterity and increased heat stress and respiratory stress.

2.1 Occupational Handler Exposure DataPage 10 of 29

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

- specific data, include the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the Agricultural Handler Exposure Task Force (AHETF) database, the Outdoor Residential Exposure Task Force (ORETF) database, or other registrant

- submitted occ upational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “ unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ( http://www.epa.gov/opp00001/science/handler

- exposure

table.pdf ), whi ch, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at http://www.epa.gov/pesticides/scienc e/handler

- exposure

- data.html

.

The appropriate u nit exposure data are listed below in Table 2.1.

Table 2.1. Iprodione Occupational Handler Dermal and Inhalation Unit Exposures used for

Non

- Cancer and Cancer Risk Assessments

Exposure

Scenario Dermal Unit Exposure (mg/ lb ai) Inhalation Unit Exposure (mg/ lb ai)

Baseline A Single Layer

plus Gloves B Double Layer

Plus Gloves C Engineering

Control D Baseline

E PF5 Respirator PF10

Respirator Engineering

Control F

Mixer/Loader Scenarios

Mixing/Loading Liquids for Chemigation Application 0.22 0.0 376 0.0 291 Closed System:

0.0 0 86 0.00 0219 0.000 04 4 0.000 02 2 Closed System:

0.000083

Mixing/Loading Liquids for

Groundboom Application 0.22 0.0 376 0.0 291 Closed System:

0.0 0 86 0.00 0219 0.000 04 4 0.000 02 2 Closed System:

0.000083

Applicator Scenarios

Applying Spray via Open Cab

Groundboom 0.0 786 0.01 61 0.01 26 Enclosed

Cab:

0.005 1 0.000 34 0.000 07 0.0000 3 Enclosed Cab:

0.000043

A. Baseline dermal unit exposures represent long pants, long sleeved shirts, shoes, and socks, no gloves.

B. Single Layer plus gloves (minimum PPE) dermal unit exposure represent long pants, long sleeved shirts, shoes, socks and chemi cal

- resistant gloves.

C. Double layer plus gloves (Maximum PPE) dermal unit exposure represent long pants, long sleeved shirt, shoes, socks, coveralls , and chemical resistant gloves.

D. Engineering control includes closed mixing and loading for mixer/loaders and an enclosed cab for applicators.

E. Baseline inh alation unit exposures represent no respirator protection (baseline).

F. Engineering control includes closed mixing and loading for mixer/loaders and an enclosed cab for applicators.

2.2 Occupational Handler Non

- Cancer Risk E stimate s

2.2.1 Occupational Handler Exposure and Non

- Cancer Risk Assumptions

The assumptions and factors used in the risk calculations include: The application rate is 2 lbs ai per acre [proposed curcurbit/vegetable use]

.Page 11 of 29

Unit exposure data are outlined above in Table 2.1. The area treated per day is 350 acres for chemigation application short/intermediate

- term exposures and 80 acres for groundboom application short/intermediate

- term exposures. These values were derived from ExpoSAC policy 3.1. The body weight for short

- and intermediate

- term non

- cancer exposure assessment is 69 kg because the effects are based on developmental effects

.

2. 2.2 Occupational Handler Non

- Ca n cer Risk Estimate Calculations

Average Daily Dose (ADD): Potential daily exposures for occupational handlers were calculated using the following formula:

Daily Exposure (mg ai /day) = UE (mg ai / lb ai) * AR (lb ai /A) * AT (A /day)

Where:

UE = Unit Exposure (from PHED)

, AR = maximum application rate according to proposed lab el , and

AT = daily acres treated

.

The daily doses were calculated using the following formula:

Average Daily Dose (mg ai/kg/day) = [Daily Exposure (mg ai/day) * Absorption ( %)] Body Weight (kg)

Margin of Exposure : Non

- cancer inhalation risk estimates for each 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. Risk estimates were calculated for inhalation exposure, as there was no dermal endpoint.

MOE = PoD (typically a NOAEL or LOAEL in mg/kg/day) / ADD (mg/kg/day)

Where:

MOE = Margin of Exposure: value used by HED to represent risk or risk estimates (unitless)

, PoD = Point of Departure

, NOAEL = No Observed Adverse Effect Level: Dose level in a toxicity study

, LOAEL = Lowest Observed Adverse Effect Level; and

ADD = Average Daily Dose: the absorbed dose received from exposure to a pesticide in a given scenario

.

A combined dermal and inhalation MOE was calculated to show combined dermal and

inhalation risk estimates. Combined risks of concern are identified by an MOE < 100 0

.

Combined MOE = Dermal and Inhalation PoD (typically a NOAEL /LOAEL in mg/kg/day)

Dermal ADD (mg/kg/day) + Inhalation ADD (mg/kg/day)

Where:

MOE = Margin of Exposure: value used by HED to represent risk or risk estimates (unitless),

PoD = Point of Departure,

NOAEL = No Observed Adverse Effect Level (mg/kg/day): Dose level in a toxicity study, where

no observed adverse effects occurred in the study, andPage 12 of 2 9 ADD = Average Daily Dose (mg/kg/day) : the absorbed dose received from exposure to a

pesticide in a given scenario

.

2.2.3 Occupational Handler Non

- Cancer Risk Estimates

The occupational handler non

- cancer risk estimates are included in Table 2.2.3

. Combined

MOEs for the handler non

- cancer risk estimates exceed the level of concern of 100 0 with the proposed label personal protective equipment (i.e., gloves, no respirator) , which means that the

non

- cancer risk estimates are not of concern to HED

.Page 13 of 29 Table 4. 1.1. Short

- and Intermediate

- term Exposure & Risk to Occupational Handlers F or Iprodione Proposed New Use Sites

. Crop or Target Unit Exposure 1
(mg ai/lb handled) Applic. Rate 2

(lb ai/A) Units Treated 3

(A/day) Avg. Daily Dose 4

(mg ai/kg /day) MOE 4 Combined MOEs 4

Mixer/Loader

–

Liquids

– Chemigation Applications

Fruiting vegetables/curcurbits Dermal

Baseline: 0.220

PPE

- G: 0.0376 2 350 Dermal

Baseline: 0.39

PPE

- G: 0. 067 Dermal

Baseline: 450

PPE

- G: 2,600 Baseline dermal + inhalation:

440

PPE

- G dermal + Baseline

inhalation: 2,600 Inhal.

Baseline: 0.0002 19 Inhal.

Baseline: 0.000 77 Inhal.

Baseline: 23,000

Mixer/Loader

–

Liquids

– Groundboom Applications

Fruiting vegetables/curcurbits Dermal

Baseline: 0.220

2 80 Dermal

Baseline: 0.0 9 Dermal

Baseline: 2,000 Baseline dermal + inhalation:

1900

PPE

- G dermal + Baseline

inhalation: 11,000 Inhal.

Baseline: 0.0002 19 Inhal:

Baseline: 0.000 18 Inhal.

Baseline: 98,000

Applying Sprays via Groundboom Equipment

Fruiting vegetables/ curcurbits Dermal

Baseline: 0.0786

2 80 Dermal

Baseline: 0.032 Dermal

Baseline: 9

, 000

Baseline dermal + inhalation: 1,900 Inhal.

Baseline: 0.00034 Inhal.

Baseline: 0.00027 Inhal.

Baseline : 14,000

Inhal.

Baseline: 0.00035 Inhal.

Baseline: 0.0012 Inhal.

Baseline: 5,500

1. See Section 2.1 for additional information

2. See Section 1.2 for additional information

3. See Section 2.2.1 for additional information

4. See Section 2.2.2 for additional informationPage 14 of 29

2.3 Occupational Handler Cancer Risk Estimates

2.3.1 Occupational Handler Exposure and Cancer Risk Assumptions

The assumptions and factors used in the risk calculations include: The application rate is 2 lbs ai per acre [proposed curcurbit/vegetable use]. The area treated per day is 350 acres for chemigation application and 80 acres for groundboom application. These values were derived from ExpoSAC policy 3.1.

To calculate cancer risk estimates , it is assumed that private growers would be exposed 10 days pe r year and commercial applicators would be exposed 30 days per year. It is assumed that handlers would be exposed for 35 years out of a 70 year lifespan. The body weight for cancer risk calculations is 8 0 kg (average bodyweight for U.S. adults)

A 5% dermal absorption factor is used for the handler cancer assessment

2.3.2 Occupational Handler Ca n cer Risk Calculations

EPA conducted an assessment of the carcinogenic risk estimates associated with iprodione following exposures to occupational handlers.

The occupational handler exposure and cancer risk calculations are presented in this section.

Cancer risk estimates were calculated using a linear low

- dose extrapolation approach in which a Lifetime Average Daily Dose (LADD) is first calculated and the n compared with a Q 1 * that has been calculated for iprodione based on dose response data in the appropriate toxicology study ( 0.044 (mg/kg/day) - 1 )

. Absorbed average daily dose (ADD) levels were used as the basis for calculating the LADD values. Dermal and inhalation ADD values were first added together to obtain combined ADD values. LADD values were then calculated and compared to the Q 1 * to

obtain cancer risk estimates.

Lifetime Average Daily Dose: After the development of the ADD values, the next step required to calculate the carcinogenic risk is to amortize these values over the working lifetime of occupational handlers based on use patterns, which results in the LADD for that use. LADD

values were calculated using the following equation:

LADD = ADD x Treatment Frequency x Working Duration

365 days/year Lifetime

Where:
Lifetime Average Daily Dose = the amount as absorbed dose received from exposure to a pesticide in a given scenario over a lifetime (mg pesticide active ingredient/kg body weight/day, also referred to as LADD)

, Average Daily Dose = the amount as absorbed dose received from exposure to a pesticide in a given scenario on a daily basis (mg pesticide active ingredient/kg body weight/day, also referred to as ADD)

, Treatment Frequency = the annual frequency of an application by an individual (days/year)

, Working Duration = t he amount of a lifetime that an individual spends engaged in a career involving pesticide exposure (35 years) , andPage 15 of 29

Lifetime = t he average life expectancy of an individual (7 8 years)

.

Cancer Risk Estimate s: C ancer risk calculations were completed by comparing the LADD

v alues calculated above to the Q 1 * values for iprodione (Q 1 * = 0.044 (mg/kg/day) - 1 ). The Agency considered more typical users in these calculations (i.e., private growers at 10 events per year) as well as more frequent users that might represent commercial applicators (i.e., 30 events per year). Cancer risk values were calculated using the following equation:

Total Risk = (Dermal LADD + Inhalation LADD) x Q 1 *

Where:

Risk = Probability of excess cancer cases over a lifetime (unitless)

, Dermal Lifetime Av erage Daily Dose = t he amount as absorbed dose received from dermal exposure to a pesticide in a given scenario over a lifetime (mg pesticide active ingredient/kg body weight/day, also referred to as LADD)

, Inhalation Lifetime Average Daily Dose = t he amou nt as absorbed dose received from inhalation exposure to a pesticide in a given scenario over a lifetime (mg pesticide active ingredient/kg body weight/day, also referred to as LADD) , and Q 1 * = Quantitative dose response factor used for linear, low

- dose re sponse cancer risk calculations (mg/kg/day) - 1

.

For this assessment, cancer risk estimates were calculated at the proposed label PPE for occupational handlers and then with increasing tiers of personal protective equipment for review by the risk manager.

2. 3.3 Occupational Handler Cancer Risk Estimates

All of the cancer risk calculations for occupational iprodione handlers completed in this assessment are included in Tables 2.3.3a and 2.3.3b. The specifics of each table and a brief summary of results are provided below.

- Table 2.3.3: Iprodione Occupational Handler Cancer Risk Estimates for Private Growers:

Presents cancer risk estimates for combined dermal and inhalation for private growers (i.e., 10 applications per year) with each possible combinatio n of dermal and respiratory protection considered in this assessment.

- Table 2.3. 4 : Iprodione Occupational Handler Cancer Risk Estimates for Commercial Applicators: Presents cancer risk estimates for combined dermal and inhalation for commercial applicator s (i.e., 30 applications per year) with each possible combination of dermal and respiratory protection considered in this assessment.

The LADD values were applied to the Q 1 * value to calculate the cancer risk estimates as described above. Cancer risk est imates were calculated for different exposure scenarios at different levels of personal protecti ve equipment

. For the private grower scenario, cancer risk estimates range from 1 .0 x10 - 6 to 1.0x10 - 6 at the proposed label PPE. For the commercial grower scenario, cancer risk estimates range from 6.8 x10 - 6 to 3. 0 x10 - 5 at the proposed label PPE.

The proposed label require s that mixer/loaders wear long

- sleeve shirt and long pants, chemical resistant glo ves, chemical resistant footwear plus socks, and a chemical resistant apron (single layer plus gloves and no respirator). The label requires applicators using mechanical groundPage 16 of 29

equipment wear long

- sleeve shirt and long pants and shoes plus socks (single l ayer, no gloves and no respirator y protection ).

Table 2.3.3. Iprodione Occupational Handler Cancer Risk Estimates

- Private Grower

Exposure

Scenario Amount of

Ai Applied per Day PPE Total Average Daily Dose A
(mg/kg/day) Lifetime

Average Daily

Dose B
(mg/kg/day) Cancer Risk C

Q1*=0.044 mg/kg/day - 1

Mixer/ Loader Scenarios

Mix/Load Liquid for Chemigation 2 lb ai/acre X

350 acres/day

= 700 lb ai/day Dermal

– Double

Layer Gloves

Inhalation

– Baseline 0.0 17 0.0002 3 1.0x 10 - 5

(required label PPE)

Dermal

– Double Layer Gloves

Inhalation

– PF5 Respirator 0.01 455 0.000 2 9.0 x 10 - 6

Dermal

– Double Layer Gloves

Inhalation

– PF 10 Respirator 0.019 0.00026 1.1 x 10 - 5

Mix/Load Liquid

for Groundboom Application 2 lb ai/acre X

80 acres/day

= 1 6 0 lb

ai /day Dermal

– Double

Layer Gloves

Inhalation

– Baseline 0. 0033 0.000052 1.0 x 10 - 6

(required label PPE)

Dermal

– Double Layer Gloves

Inhalation

– PF5 Respirator 0.0034 0.000047 7.6 x 10 - 7

Dermal

– Double Layer Gloves

Inhalation

– PF 10 Respirator 0.0034 0.000059 7.1 x 10 - 7

Applicator Scenarios

Apply Spray by Open Cab

Groundboom 2 lb ai/acre X

80 acres/day

= 1 6 0 lb ai/day Dermal

–

Baseline

Inhalation

– Baseline 0.0098 1.3E

- 04 4.6 x 10 - 6

(required label PPE)

A. Dermal dose (mg/kg/day) = [unit exposure (mg/lb ai) * lb ai handled per day * Dermal absorption factor (0.05))] / BW ( 8 0 kg) Inhalation dose (mg/kg/day) = [unit exposure (mg/lb ai) * lb ai handled per day)] / BW ( 8 0 kg) Total average daily dose (mg/kg/d ay) = dermal dose (mg/kg/day) + inhalation dose (mg/kg/day) B. Lifetime Average daily dose (mg/kg/day) = Total Average Daily Dose * (10 days for private grower/ 365 days) * (35 years/ 8 0 years) C. Cancer Risk = Lifetime Average Daily Dose (mg/kg/day) * Q 1 *( 0.044 mg/kg/day

- 1 )Page 17 of 29

Table 2.3.4. Iprodione Occupational Handler Cancer Risk Estimates

- Commercial

Grower

Exposure Scenario Amount of Ai Applied per Day PPE Total Average Daily Dose A
(mg/kg/day) Lifetime

Average Daily

Dose B
(mg/kg/day) Cancer

Risk C

Q1*=0.044
mg/kg/day - 1

Mixer/ Loader Scenarios

Mix/Load Liquid for Chemigation/ Aerial Application 2 lb ai/acre X 350 acres/day = 700 lb ai/day Dermal

– Double

Layer Gloves

Inhalation

– Baseline 0.017 0.00069 3.0 x 10 - 5

(required label PPE)

Dermal

– Double Layer Gloves

Inhalation

– PF5 Respirator 0.015 0.00061 2.7 x 10 - 5

Dermal

– Double Layer Gloves

Inhalation

– PF 10 Respirator 0.019 0.00061 2. 4 x 10 - 5

Mix/Load Liquid for Groundboom Application 2 lb ai/acre X 80 acres/day = 1 6 0 lb

ai /day Dermal

– Double

Layer Gloves

Inhalation

– Baseline 0. 0038 0.00016 6. 8 x 10 - 6

(required label PPE)

Dermal

– Double Layer Gloves

Inhalation

– PF5 Respirator 0.0034 0.00014 6.2 x 10 - 6

Dermal

– Double Layer Gloves

Inhalation

– PF 10 Respirator 0.0034 0.00014 6. 2 x 10 - 6

Applicator Scenarios

Apply Spray by Open Cab

Groundboom 2 lb ai/acre X 80 acres/day = 1 6 0 lb ai/day Dermal

–

Baseline

Inhalation

– Baseline 0.0098 4.0E

- 04 1. 4 x 10 - 5

(required label PPE)

A. Dermal dose (mg/kg/day) = [unit exposure (mg/lb ai) * lb ai handled per day * Dermal absorption factor (0.05))] / BW ( 8 0 kg) Inhalation dose (mg/kg/day) = [unit exposure (mg/lb ai) * lb ai handled per day)] / BW ( 8 0 kg) Total average daily dose (mg/kg/d ay) = dermal dose (mg/kg/day) + inhalation dose (mg/kg/day) B. Lifetime Average daily dose (mg/kg/day) = Total Average Daily Dose * ( 3 0 days for private grower/ 365 days) * (35 years/7 8 years) C. Cancer Risk = Lifetime Average Daily Dose (mg/kg/day) * Q 1 *( 0.044 mg/kg/day

- 1 )Page 18 of 29

3.0 Occupational Postapplication Exposures and Risk Estimate s

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 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 applica tions, relative to harvest activities, can greatly reduce the potential for postapplication exposure.

Post

- application exposures to the proposed iprodione uses on curcurbits and fruiting vegetables

uses have not been assessed in this document as the expos ure potential is low. The proposed label is for chemigation /soil incorporation applications that are watered in to the top 3

- 5 inches

of soil. In cases like iprodione where the proposed uses do not follow the standard “foliar

- based”

transfer coefficient me thodology, exposure assessors reference ExpoSAC policy 3.1 on guidance

on crop

- activity combinations utilizing an alternate transfer coefficient method.

Due to the method and timing of applications and typical agricultural practices for these crops,

HED has determined that a specific post

- application exposure assessment is not necessary for these scenarios. This determination is based on the following: (1) routine hand labor activities that involve significant contact with the treated soil/planting medium are not required, or are not required for several weeks or months after the application, and (2) reentry activities that may be necessary are likely to result in relatively low levels of dermal exposure because contact with the treated medium (soil) is mi nimal or infrequent.

3.1 Occupational Postapplication Exposure and Non

- Cancer Risk Estimate s

Occupational Postapplication Dermal Exposure

Based on a review of the non

- cancer hazard database, HED believes that the potential for dermal postapplication worker exposure is low, provided at least a 12

- hour restricted entry interval (REI) and other proposed restrictions based on worker reentry are observed

.

As noted above, the proposed use pattern is for soil directed/soil

- incorporated applications of ip rodione and thus no foliage will be contacted. Additionally, reentry activities that may be necessary are likely to result in negligible dermal exposure because contact with the treated medium is infrequent.

Occupational Postapplication Inhalation Exposure

Based on the Agency's current practices, a quantitative postapplication inhalation exposure assessment was not performed for iprodione at this time primarily because it has a low vaporPage 19 of 29

pressure (3.8 x 10 - 9 mm H g 1 ). However, volatilization of pesticides may be a potential source of

post

- application inhalation exposure to individuals nearby to pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The Agency is in the

pro cess of evaluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or proced ures are put into place, the Agency may revisit the need for a quantitative postapplication inhalation exposure assessment

for iprodione

.

Although a quantitative postapplication inhalation exposure assessment was not performed, an inhalation exposure asse ssment was performed for occupational/commercial 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 ex posure estimates would be protective of most occupational postapplication inhalation exposure

scenarios.

3.2 Occupational Postapplication Cancer Risk Estimate s

3.2.1 Occupational Postapplication Exposure and Cancer Risk Assumptions

HED typically assesse s dermal postapplication exposure potential for field workers, for both

non

- cancer and cancer assessments (when a Q 1 * has been determined). HED has identified a Q 1 * for the parent compound and one Q 1 * from a iprodione degradate . However, because of review of the proposed label and proposed use pattern, HED has determined that a quantitative post

application exposure assessment is not necessary for these scenarios. The determination is based on the exposure potential (similar to the non

- cancer exposure potential characterization identified above in section 3.0) for the parent compound.

While there is an additional Q 1 * value for a degradate of iprodione (3,5

- DCA 2 ); no quantitative postapplication cancer assessment has been comp leted for the degradate. The proposed label for fruiting vegetables and curcurbits directs applicators to pre

- emergent soil incorporation or post

emergent soil directed sprays. Therefore, there is negligible occupational postapplication dermal potential fo r the parent compound , and no post

- application dermal exposure potential for the 3,5

- DCA degradate.

1 http://www.oehha.org/multimedia/biomon/pdf/0709iprodione.pdf
2 3, 5

- DCA is not a registered pesticide; therefore, there are no FIFRA toxicology data for this compound. In the past, HED has used the Q1 * for

p

- chloroaniline (PCA) to assess the carcinogenic risk for other structurally related chloroanilines. The HED policy on chlor oanilines specifies that chloroaniline metabolites should be considered to be toxicologically equivalent to PCA unless there is sufficient evidence th at the metabolite is not carcinogenic. A Q 1 * of 6.38 X 10

- 2 (mg/kg/day)

- 1 in human equivalents has been calculated for p

- chloroaniline. This Q 1 * is based on the spleen sarcoma rate in male rats from an NTP bioasssay, linearized low dose multistage model, and the 3/4s interspecies body scaling factor.Page 20 of 29

4.0 Residential Exposure

According to the 1998 reregistration eligibility decision (RED) for iprodione , “Based on cancer risk concerns, the Agency has determined that iprodione residential uses on turf, ornamentals and vegetable/small fruit gardens are ineligible for reregistration. The registrant [at the time of the
RED] , Rhone

- Poulenc, has requested to v oluntary cancelation of all residential uses of iprodione.” Therefore, residential turf uses of iprodione are no longer registered by the Agency. However, there are iprodione

- based products that can be professionally applied to golf courses,

where there is potential for non

- occupational postapplication exposure to golfers.

This “golfer” scenario is assessed in this document to update the residential exposure assessment and to be used in the updated aggregate exposure assessment. While the agricultural uses of iprodione for curcurbits and fruiting vegetables are as a nematicide, HED calculated risk estimates for exposure to treated golf course turf to include in the aggregate risk assessment.

4.1 Residential Handler Exposure

There are no registered r esidential products that can be applied by residential handlers; therefore, residential handler exposure has not been quantitatively assessed

.

4. 2 Use of TTR Data for Iprodione Post

- application Exposure Assessments

This assessment contains potentially co mpensable turf transferable residue data generated by

Rhône

- Poulenc . The t ransferable turf residue (TTR) data are available and scientifically sound for

risk assessment (MRID 44968001; reviewed by HED in D389183). The data set measured TTR in 3 locations; Georgia, New York, and California. As data are available, HED evaluated cancer risk estimates based on the potential exposure the highest 14 day average TTR value; from the

California

- based measurements.

There are TTR data available for iprodione (MRID 44968001) and a summary is included in Appendix A . Six applications of 5.45 lb iprodione/A in flowable concentrate formulation were applied by groundboom in three test sites, GA, CA, and NY. For the reside ntial exposure assessment, the predicted TTR values from the California site were used for 14

- and 28

- day averaging to provide a health protective assessment of potential exposure to iprodione parent

residues. Table 4.3.1 details the TTR values used for th e residential exposure assessment.

Calculations of non

- cancer postapplication exposures are typically completed using maximum application rates identified in the label and “day 0” residue values

. In this case, the risk estimates are also shown for the hig hest TTR residue value as a screening level assessment. The maximum application rate for products applied to golf courses is 5.5 lb ai/A; therefore the available TTR data did not need to be adjusted based on the application rate. Calculations of cancer pos t

application exposures are completed using average application rates (2.5 lbs ai/A) identified on product labels to reflect lifetime exposure potential. The available TTR data was adjusted to reflect that application rate

.Page 21 of 29 Table 4.3.1: Use of TTR data Derived from MRID 44968001

Postapplication Exposure Assessment Type TTR value

used (in ug/cm 2 ) Application

Rate Averaging

time Site

Location

Non

- Cancer

Assessment 0.49 M aximum

(5.5 lb ai/A) 14 day California

Cancer Assessment 0.22 A verage ( 2 .5 lb ai/A) 14 day California

0.15 average 28 day California

( 2 .5 lb ai/A)

Upper bound Cancer

Assessment 1 Greens

- 1.98 Fairways

- 0.49 M aximum

( 20/5 .5 lb ai/A )2 14 day California

Green s

- 1.98 Fairways

- 0.49 M aximum

( 20/5.5 lb ai/A) 2 28 day California

1) The upper bound cancer risk assessment reflects a weighted average of residue exposure from time spent on fairways vs. greens & maximum application rates 2) Weighted average application rate

4. 3 Residential Postapplication Exposure and Non

- cancer R isk Estimate s

Residential Post

- application Dermal Exposure

This action covers the new uses of iprodione on fruiting vegetables and curcurbits. However, this document includes qualitative and quantitative exposure assessments for the residential postapplication “golfe r” scenarios because a revised aggregate assessment is needed to complete

this iprodione action.

Iprodione residential post

- application scenarios include individuals playing golf on treated turf. As a result, HED’s Standard Operating Procedures (SOP’s) for Residential Exposure Assessments, (20 12 ), as well as chemical

- specific residue data from a t urf transferable residue (TTR) study (MRID 44968001 ) are used to assess residential golfer exposure. The 2012 residential SOP’s outline quanitatively assessing exposure to the following lifestages: 1) adults

, 2) 11 to < 16 year olds, and 3) 6 to < 11 year olds

.

4. 3 .1 Non

- Cancer Dermal Post

- application Exposure

This scenario assumes that pesticide residues are transferred to the skin of individuals that enter treated areas for recreation or other activities such as golfing. Below are some assumptions about the dermal exposure potential.

Assumptions :

Residential post

- application exposure must be assessed on the same day the pesticide isPage 22 of 29

applied si nce it is assumed that golfers could be exposed to turf grass immediately after application. Therefore, exposures are based on “ day 0 ” residues.

TTR value is assumed to be 0.682 ug/cm 2 based on predicted day 0 residue value calculated by a first

- order dissipation kinetics and decay model from chemical

- specific data. A summary of the TTR study is presented in section 4. 2 of this document. The full study review is available ( D389183 ). An upper bound TTR residue value wa s used as a screening level assessment. Transfer coefficients (TCs) were used to assess dermal exposure resulting from golfing. An average body weight of 69 kg was used to assess dermal exposure for adults. Body weights of 57 and 32 were used to assess dermal exposure for 11 to < 16 yrs and 6 to < 11 yrs old, respectively. Those bodyweights reflect average bodyweights for those age

groups. Duration of exposure on golf course lawns , greens and tees is assumed to be 4 hours.

Equations :

Dermal Dose (mg/kg/day) = [T TR (μg/cm 2 ) x 0.001 (mg/μg) x TC (cm 2 /hr) x ET (hr/day)]/BW (kg)

Where:

Dose = Dermal exposure on day of application attributable for activity in a previously

treated area (mg/kg/day);

TTR = Turf Transferable Residue (μg/cm 2 );

TC = Transfer Coefficient (cm 2 /hr);

ET = Exposure Time (hours); and,

BW = Body Weight (kg).

Dermal MOE = L OAEL (mg/kg/day)/ Dermal Dose (mg/kg/day)

Post

- application Dermal Exposure and Risk Estimate

Short

- term d ermal post

- application exposure and risk estimates for golfers resulted in MOEs greater than the LOC and therefore are not of concern to HED

. A summary of the residential

short

- term dermal exposure s is shown below in Table 4.2.1

. Risk estimates are presented with the highest predicted r esidue values and the predicted “day 0” residue values; neither present risk
estimates of concern based on the level of concern of 1,000.

Table 4.2.1

. Post

- application Short

- term Dermal Exposure and Risk Estimate s for Iprodione

. Scenario Application

Rate

(lb ai/A) TTR 1

(μg/cm 2 ) CF T C 2

(cm 2 /hr) ET

(hrs) BW (kg) Dose 3

(mg/kg/day) Dermal

MOE 4

Golfer

Adult 5.5 0. 682 0.001 5,300 4 69 0.010 4, 8 00

11 to < 16 yrs old 5.5 0 .682 0.001 4,400 4 57 0.011 4, 7 00

6 to < 11 yrs old 5.5 0. 682 0.001 2,900 4 32 0.012 4,000

Adult 5.5 0.85 0.001 5,300 4 69 0.013 3,800

11 to < 16 yrs old 5.5 0.85 0.001 4,400 4 57 0.013 3,800Page 23 of 29

Table 4.2.1

. Post

- application Short

- term Dermal Exposure and Risk Estimate s for Iprodione

. Scenario Application

Rate

(lb ai/A) TTR 1

(μg/cm 2 ) CF T C 2

(cm 2 /hr) ET

(hrs) BW (kg) Dose 3

(mg/kg/day) Dermal

MOE 4

6 to < 11 yrs old 5.5 0.85 0.001 2,900 4 32 0.015 3, 2 00

1. Turf Transferable Residues (TTR) = 0. 682 ug/cm 2 is based on predicted day 0 residue value calculated from chemical

specific data (MRID No. 44968001 ). 0.85 ug/cm 2 is the highest predicted residue value run as a screening level assessment.

2. Transfer Coefficients are derived from HED’s “Science Advisory Co uncil for Exposure (ExpoSAC) Policy 3

- Revised

March 2012”

3. Dermal Dose (mg/kg/day) = [TTR (μg/cm 2 ) x 0.001 (mg/μg) x TC (cm 2 /hr) x ET (hr/day)]/ BW (kg).

4. Dermal MOE = LOAEL (50 mg/kg/day) / Dermal Dose (mg/kg/day).Page 24 of 29

Spray Drift

Spray drift is a potential source of exposure for residents living in close proximity to spraying operations. This is particularly the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground appl ication method employed for iprodione

. The Agency has been working with the Spray Drift Task Force (a membership of US pesticide registrants), EPA Regional Offices, State Lead Agencies for pesticide regulation, and other parties to develop the best spray d rift management practices. The Agency is now requiring interim mitigation measures for aerial applications that must be placed on product labels/labeling. The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force , and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast, and ground hydraulic methods. After the policy is in place, the Agency may impose

f urther refinements in spray drift management practices to reduce off

- target drift with specific products with significant risk estimate s associated with drift.

Residential Postapplication/ Bystander Inhalation Exposure

Based on the Agency's current practi ces, a quantitative postapplication inhalation exposure assessment was not performed for iprodione at this time. However, volatilization of pesticides may be a potential source of postapplication inhalation exposure to individuals nearby to pesticide appl ications. 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. The Agency received the SAP’s final repor t on March 2, 2010 ( http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html ). The Agency is in the process of evaluating the SAP report and may, as appropriate, developing policies and procedures, to identifying the need for and, subsequently, the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative postapplication inhalation exposure assessment for iprodione

.

4. 4 Residential Postapplication Exposure and Cancer Risk Estimates

There are currently registered products that can be professionally applied to golf courses, where there is potential for postapplication residential exposure to golfers. This scenario is assessed in this document to update the residential exposure assessment and to be used in the updated

aggregate exposure assessment.

HED calculates cancer risk estimates for adults exposed to pesticide products during recreational

activities. In this ca se, pesticide products containing iprodione can be applied commercially to golf courses, and recreational golfers can be exposed to those residues

. Adult cancer risk

estimates were calculated from golfer exposure to previously treated golf course turf

. HE D expects dermal exposure is the primary exposure route for adults exposed through recreational golf.Page 25 of 29

The postapplication cancer assessment reflects exposure to parent iprodione

. No quantitative postapplication cancer assessment has been completed for the iprodione degradate 3,5

- DCA. The Q 1 *for 3,5

- DCA is not relevant to the residential postapplication exposure assessment (i.e., golfer scenario) since iprodione is metabolized to 3,5

- DCA in drinking water.

Below are the algorithms and assumptions used to assess residential post

- application exposure

and cancer risk estimates . Exposure scenarios assessed include:

Adult dermal exposure to treated golf course (adults/ young adults )

Assumptions for Post

- application Exposure Scenarios

General assumptions regarding the residential postapplication scenarios assessed are as follows: The body weight for cancer risk assessment is 8 0 kg HED has developed standard transfer coefficient (TC) values for residential post

appli cation scenarios to ensure consistency in exposure assessments. These standard values were used to calculate post

- application exposures. The TC for golfing exposure is

3400 cm 2 /hr , when chemical

- specific TTR data are used from a TTR study which used

the modified California Roller technique

. There are T TR data available for iprodione (MRID 44968001). The data were used as

outlined above in Table 4 .3.1

. Duration of exposure on golf course lawns , greens and tees is assumed to be 4 hours. For the upper bound cancer assessment, it’s assumed that golfers are exposed on greens for 1 hour and on fairways for 3 hours.

It is assumed that 20 days per year are spent golfing based on golfing survey from United

States Golf Association (USGA).

Golf ers are assumed to be in contact with golf course turf for approximately 50 years

over a 7 8 year life time in determining cancer risk.

Similar to o ccupational handlers, cancer risk estimates were calculated using a linear low

- dose extrapolation approach i n which a Lifetime Average Daily Dose ( LADD) is first calculated and then compared with a Q 1 * that has been calculated for iprodione based on dose response data in the appropriate toxicology study (Q 1 * = 0.0087 (mg/kg/day) - 1 ). Absorbed average daily dose (ADD) levels were used as the basis for calculating the LADD values. After the development of the ADD values, the next step required to calculate the carcinogenic risk is to amortize these values over the working lifetime of the occupational workers with postapplication exposure based on use pattern, which results in the LADD for that use. The Agency assumed postapplication exposure to treated golf courses could occur 20 days per year based on a golfing survey from USGA. Finally, 50 years of golfing acti vity in a 78 year lifespan were used to complete the calculations. LADD values were calculated using the following equation:

LADD = ADD x Exposure Frequency x Activity Duration

365 days/year Lifetime

Where:Page 26 of 29

LADD ( Lifetime Average Daily Dose ) = the amount as absorbed dose received from exposure to a pesticide in a given scenario over a lifetime (mg pesticide active ingredient/kg body weight/day, also referred to as LADD)

, ADD ( Average Daily Dose ) = the amount as absorbed dose received from exposure to a pesticide in a given scenario on a daily basis (mg pesticide active ingredient/kg body weight/day, also referred to as ADD)

, Exposure Frequency = the annual frequency of exposure by an individual ( days/year)

, Activity Duration = the amount of a lifetime that an individual spends engaged in an activity (i.e. golfing) involving pesticide exposure ( 50 years) , and Lifetime = the average life expectancy of an individual ( 7 8 years)

.

Cancer Risk Estimate s : Finally, cancer risk calculations were completed by comparing the

LADD values calculated above to the Q 1 * for iprodione (Q 1 * = 0.044 (mg/kg/day) - 1 ). Cancer risk values were calculated using the following equation:

Cancer Risk Estimate = Dermal LADD (mg /kg/day) * Q 1 * (mg/kg/day) - 1

Where:

Risk = Probability of excess cancer cases over a lifetime (unitless)

, Dermal Lifetime Average Daily Dose = The amount as absorbed dose received from dermal exposure to a pesticide in a given scenario over a lifetime (mg pesticide active ingredient/kg body weight/day, also referred to as LADD)

, and Q 1 * = Quantitative dose response factor used for linear , low dose response cancer risk calculations (mg/kg/day ) - 1

.

Table 4. 4 B : Residential Postapplication Cancer Dermal Exposu re and Risk with Q1* value of 0.044 : Scenario TTR A

(ug/cm2) CF

(mg/μg) Tc

(cm 2 /hr ) ET

(hrs) BW (kg) Dose B
(mg/kg/day) LADD C

mg/kg/day Cancer

Risk D

Average Application Rate

Adult Golfer

14

- day TTR avging 0.22 0.001 5300 4 8 0 0.00 29 0.000102 4.5 x10 - 6

Adult Golfer

28

- day TTR avging 0.15 0.001 5300 4 8 0 0.00 20 0.000072 3.2 x10 - 6

Upper Bound Application Rate

Adult Golfer

14

- day TTR avging Greens

-

1.984 Fairways

- 0.49 0.001 5300 4 8 0 0.0049 0.000403 1.8 x10 - 5

A . Turf Transferable Residues (TTR) from study MRID 44968001.

B . Dermal Dose (mg/kg/day) = TTR (μg/cm 2 ) x 0.001 (mg/μg) x TC (cm 2 /hr) x ET (hr/day) x 5% DA BW ( 80 kg)

C

. Life Average Daily Dose (LADD) = Daily Dose (mg/kg/day) x 2 0 days x 50 years 365 days 7 8 lifetime years

D . Cancer Risk = Q 1 * ( 4.4 x 10 - 2 mg/kg/day - 1 ) x LADD (mg/kg/day)

The refined residential post

- application cancer assessment assumes that a golfer is exposed to the same residue pattern 20 golfing days per year over 50 years of assumed golf play activity. The risk estimates range from 3.2 x10 - 6 to 1.8 x10 - 5

. This assessment involves significant refinement over a screening level assessment. Refinements include the use of TTR data, average application rates to reflect an individuals’ lifetime exposure, and residue averaging based on likely product application parameters.Page 27 of 29

The product in the TTR study (Chipco ® 26GT) is one of the most widely used products for turf, and is a good representative end use product for the TTR data. The 14

- and 28

- day average

transferable turf residue s were used to calculate the cancer risk estimates

. The product label

suggests app lication intervals of 14 to 28 days; cancer risk estimates are presented as a range

based on : 1) an upper bound cancer risk estimate based on maximum label application rates and 2) 14

- day and 28

- day TTR averages of an average iprodione application rate.

Sometimes meteorological information like rainfall events, or turf treatment regimes can be used

to characterize an exposure assessment using a TTR data set

. The study report doesn't identify

any out of the ordinary issues that would limit the use of this study for use in human health risk

assessment. Both the timing of rainfall events and the timing of turf mowing are unclear from the iprodione TTR study report . The study report indicated some precipitation during the TTR study.

The treated turf received c are similar to standard industrial turf through typical irrigation and mowing procedures

.

5 .0 Label Recommendation

The product label includes several established uses and proposed new uses on curcurbits. The proposed label (86153

- 3) includes general prod uct directions for both foliar and pre

- plant/soil

incorporated directions for various crops. The label section for the proposed new curcurbit uses instructs users on the pre

- plant and soil

- incorporated applications. There are no instructions for foliar app lications for curcurbits; therefore, this assessment did not include a quantitative occupational postapplication assessment for curcurbits

. Based on the proposed use pattern, the proposed product label should be additionally modified to clarify that foliar application is prohibited for the proposed new uses on curcurbits.Page 28 of 29

APPENDIX A: IPRODIONE DFR STUDY SUMMARY Appendix A: Summaries of Dislodgeable Foliar Residue Studies and Proposed Use in Assessment

DFR Studies Available :

Iprodione: Review of Iprodione: Determination of Transferable Turf Residues on Turf Treated

with CHIPCO® 26GT

, TAF 0

- 5, MRID 44968001. (HED Review: Review of “ Determination of Transferable Turf Residue Dissipation from Turf Treated

with Iprodione” , 04/27/2011, D389183)

The chemical

- specific TTR study included three field trial sites in Georgia, California, and New York. The study was conducted on turf to evaluate the decline of iprodione equivalent residue (i.e., parent + metabolite) af ter six applications of a flowable concentrate iprodione product at a maximum application rate of 5.45 lbs ai/A/application. The re

- treatment interval was approximately 14 days. The Modified California Roller technique was used to evaluate the

amount of tr ansferable residues from turf grass. A summary of the California site TTR values used in the residential exposure assessment is provided in Table A.

There are TTR data available for iprodione (MRID 44968001). Six applications of 5.45 lb iprodione/A in flowable concentrate formulation were applied by groundboom in three test sites, GA, CA, and NY. The highest TTR value from the Georgia site was 5 days after the sixth application; the TTR was 0.63 ug/cm 2 . The 14 day average TTR value after 6 application s was 0.3506 ug/cm 2 . The highest TTR value from the California site was 3 days after the sixth application; the TTR was 0.848 ug/cm 2 . The 14 day average was 0.4924 ug/cm 2 . The highest

TTR value from the New York site was 8

- 12 hours after the sixth appli cation; the TTR was 0.608 ug/cm 2 . The 14 day average was 0.4457 ug/cm 2

.

Peak residue formation occurred at 5DAT6 in Georgia, 3DAT6 in California, and 8

- 12 hrs DAT6 in New York. This phenomenon could possibly be explained by the delayed formation of the iprodione metabolite. The dissipation was only followed for 14 days, and the residues never reached levels less than the LOQ during the timeframe of the study. Immediately following the last application of the test product, the percentage of the original application rate of iprodione transferable to cotton sheeting material was 0.81% for the Georgia site, 1.12% for the California site, and 0.83% for the New York site.

F irst

- order dissipation kinetics were assumed to generate dissipation curves for iprodione

. The individual data points (rather than averages) from postapplication to 14 DAT 6 at the G eorgia and

C alifornia test sites. Due to the extreme variability in TTR for individual days at the New York test site, use of individual data points for re gression analysis was not appropriate. A verage daily

data point s were most appropriate for the New York site.

The estimated half

- life values were 8.1 days (R 2 =0.777) for Georgia, 9.8 days (R 2 =0.618) for

California , and 20.7 days ( R 2 = 0. 626 ) for the New York turf

. While the Registrant did not correct for field recoveries, their calculated half

- lives were similar to Agency calculated half

- lives.

This study is acceptable to be used for risk assessment purposes.Page 29 of 29

Table A : Summary of Predicted TTR Levels Used in Residential Exposure Assessment (5.5 lbs ai/A unadjusted application rate)

Days after last

Treatment CA Site Mean

Residue (ug/cm2)

0 0.777

1 0.724

2 0.674

3 0.628

4 0.585

5 0.545

6 0.508

7 0.474

8 0.441

9 0.411

10 0.383

11 0.357

12 0.333

13 0.310

14 0.289

15 0.269

16 0.251

17 0.234

18 0.218

19 0.203

20 0.189

21 0.176

22 0.164

23 0.153

24 0.143

25 0.133

26 0.124

27 0.115

28 0.107