UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

Date:

Subject: June 25, 2013 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

lpconazole: Occupational and Residential Exposure/Risk Assessment for Proposed Seed Treatment Uses on Legume Vegetables.

PC Code: 125618 DP Barcode: D410928

Decision No.: 469403 Reg i stration No.: 400

- 544

Petition No.: 2F8076 Regulatory Action: Section 3 Registration

Risk Assessment Type: ORE Case No.: 7041

TXRNo.:NA CAS No.: 125225-28-7

MRIDNo.: NA 40 CFR: 180.646

REVIEWER:

Expo SAC:

THROUGH:

TO:

Introduction Margarita Collantes, Biologist

## -;/J!a-;pt-~ (2_

## #~ Risk Assessment Branch II

Health Effects Division (7509P)

James Scott Miller, Environmental

# En~i~eer**~** Cassi Walls, Biologist

## ~ )_

## L>~**{J**

Christina Swartz

, Chief

# ~~ Risk Assessment Branch II

Health Effects Division (7509P)

Tony Kish, 

### RM 22

Dominic Schuler, Risk Manager Reviewer Registration Division (750 5P)

The Registration Division (RD) requested that the Health Effects Division (HED) conduct a risk

assessment for proposed uses of ipconazole. Chemtura has proposed a new use of ipconazole for

treatment of legume vegetable seeds. It is HED policy to use the best available data to assess

exposure. Sources of generic data, used as surrogate data in the absence of chemical

- specific
data, include the Standard Operating Procedures (SOPs) for Seed Treatment (Policy 14)

, Amount

of Seed Treated or Planted per Day (Policy 15) and In t erim Guidance " Amount of Commercial

Seed Treated Per Day" (Policy 15.1).

Note: This memorandum was reviewed by the Exposure Science Advisory Committee (ExpoSAC) on April18, 2013.

Page 1 of14Page 2 of 14 Table of Contents

1.0 Executive Summary ............................................................................................................. 3

2.0 Summary of Conclusions/ Data Deficiencies ....................................................................... 3

3.0 Hazard Characterization ....................................................................................................... 5

4.0 Use Profile ................................................................................................................... ........ 7

5.0 Residential Exposure and Risk Estimates ............................................................................ 8

5.1 Spray Drift ................................................................................................................... ..... 8

5.2 Residential Bystander Post-Appli cation Inhalation Exposure ......................................... 8

6.0 Occupational Exposure and Risk Estimates ........................................................................ 8

6.1 Occupational Handler Expos ure/Risk Estimates.............................................................. 8

6.2 Occupational Post-application Exposure/Risk Estimates .............................................. 13

Appendix A. Summary of Occupational AlgorithmsPage 3 of 14 1.0 Executive Summary

The Registration Division (RD) re quested that the Health Eff ects Division (HED) conduct an exposure and risk assessment for the active ingredient (ai), ipcon azole. Chemtura AgroSolutions is requesting a new proposed use for ipconazole as a commercial and on-farm seed treatment for legume vegetable (dried and succulent) seeds. Although the product is proposed for on-farm use, the label specifies that seed s hould be treated using a water-based slurry with other registered

seed treatment insecticides and fungicides through standard slurry or mist-type commercial seed treatment equipment and not for use in hopper, plan ter or slurry boxes at or immediately before planting. Ipconazole is currently registered for seed treatment uses on brassica leafy vegetable, canola, cucurbit vegetable group, le afy vegetable group, mustard, rape , root and tuber vegetable, sorghum, sunflower, cotton, peanut, soybean, dr y shelled peas and beans (subgroup 6C), cereal grain (except rice), ornamental fl owers, conifers, and grass seeds. With the current petition, the registrant is requesting seed tr eatment uses on all of Crop Group 6.

The product, Rancona® 3.8 FS, is a systemic broad spectrum fungicide seed dressing specifically for protection agains t soilborne and seed borne disease of crop plants. Rancona®

3.8 FS is formulated as a flowable concentrate containing 40.7% (ai or 3.77 lb ai per gallon.

There are no registered or propos ed residential uses associated with ipconazole and residential exposure is not expected from the commercial us e of this product; ther efore, only occupational exposure is assessed in this memorandum.

Based on the proposed use pattern, short- and intermediate-term durations of exposure are expected for occupational handler s. HED has new information to suggest that in commercial

seed treatment facilities with high throughput for various seed types (e.g., corn or soybean), the durations of exposure for occupational handlers mightexceed those typically considered in shortand intermediate-term assessments. However, HE D decided not to conduct a long-term exposure

assessment due to the conservative nature of the unit exposures which are based on open-pour systems rather than the closed and/or automated systems that would be us ed in larger facilities operating over longer durations. HED also notes that it would be unlikely for a single chemical to be used continuously, even in high throughpu t facilities, over long term durations. Using conservative assumptions, the short- and intermed iate-term scenarios are considered protective of longer-term exposure and risk.

Hazard Characterization Ipconazole may cause local, portal-of-entry ir ritation following oral, dermal, or inhalation exposure. Systemic effects that were obser ved in laboratory animals following exposure to ipconazole include decreases in body weight, bod y weight gain, and food consumption; liver and kidney effects; and developmental e ffects (the latter being in the pr esence of maternal toxicity). Carcinogenicity studies showed no treatment-related increases in tu mors in rats and mice after exposure to ipconazole.

The 28-day dermal study in the rat was selected for assessing short-and intermediate-term dermal exposure and risk. The no observed adverse eff ect level (NOAEL) of 150 mg/kg/day and the lowest observed adverse effect level (LOAEL) of 1000 mg/kg/day were based on decreased bodyPage 4 of 14 weight, and body weight gains, food consumption, as well as increased incidences of dermal irritation. The 28-day inhalation rat study was selected for the short- and intermediate-term

inhalation risk assessment. An inhalation P OD was selected for adults based on epithelial hyperplasia in the hard palate in males, epith elium hyperplasia in the larynx mucosa of both sexes, and mixed inflammatory cells in the trachea of females.

Since the short- and intermediate-term dermal and inhalation points of departure (PODs) were based on route-specific toxicity st udies, no absorption factors were needed to estimate exposure. Furthermore, dermal and inhalation exposur e estimates were not combined since the toxicological effects are different for these routes of exposure.

Based on the available toxicity and exposure data, HED has r ecommended that the 10X Food Quality Protection Act (FQPA) Safety Factor (for the protection of infants and children) be reduced to 1X. Therefore, the level of concern (L OC) for dermal risk assessments is a margin of exposure (MOE) of 100, based on the combined in terspecies (10X) and intraspecies (10X) uncertainty factors. The LOC fo r all inhalation occupational scen arios is equal to a MOE of 300, based on the combined uncertainty factors: 10X for lack of a NOAEL in the inhalation study, 10X for intraspecies variabilit y, and a 3X uncertainty factor for interspecies variability.

Occupational Handler Exposure and Risk Estimates The proposed label-required pers onal protective equipm ent (PPE) states that all handlers must wear long-sleeved shirt and long pants, chemical -resistant gloves, and socks and shoes.

Commercial handler dermal and inhalation risk estimates are not of concern (Dermal LOC =

MOE ≥ 100 and Inhalation LOC = MOE ≥ 300) for the proposed legume seed treatment use with label required PPE. The short-term handler MOEs for treating seed ranged from 2000 for inhalation exposure to 74,000 for dermal exposur e, with the lowest MOE resulting from performing multiple activities with baseline clot hing (long-sleeved shirt and long pants, socks and shoes) and gloves. The seed planter expos ure estimates resulted in MOEs ranging from 20,000 for inhalation to 140,000 for dermal using base line clothing and gloves (note that gloves are only assumed to be used duri ng loading of seed into the plan ter, and not during planting seed into the field using a tractor).

HED assumes that the commercial seed treatment risk assessment is protective of on-farm seed treatment exposure and risk because the equipment is similar but the on-farm throughput is significantly less than th e commercial throughput. Therefore, risk estimates for on-farm seed

treatment have not been separately quantified.

Occupational Post-Application Exposure and Risk Estimates A quantitative post-application exposure assessment is not required for seed treatment, as the exposure is expected to be negligible, since th ere will be no residue on foliage from contact once plants are grown.Page 5 of 14 Restricted Entry Interval No quantitative post-application assessment is re quired for exposure to treated seeds that have already been planted. Therefore, the labeling properly states the exception to the Agricultural Use Requirements restricted entr y interval (REI) of 12 hours.

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. Thes e data, which include studies from SOPs for Seed Treatment, Policy 14, 15, and 15.1 are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that 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 s ources, as well as guidanc e on their use, can be

found at http://www.epa.gov/pesticides/scien ce/handler-exposure-data.html and http://www.epa.gov/pesticides/sci ence/post-app-exposure-data.html

.

2.0 Summary of Conclusions and Data Requirements

There are no residential/occupational risk estimates of concern associated with the proposed new uses of ipconazole. There are no data gaps in the exposure database.

2.1 Summary of Risk Estimates

Occupational exposure scenarios as sessed resulted in MOEs that do not exceed HED's level of concern (Dermal MOEs ≥ 100 and Inhalation MOE ≥ 300) for ipconazole dermal and inhalation exposures; no changes are needed for the label-required PPE.

2.2 Label Recommendations from Occupational Assessment

There are no label recommendations ba sed on the occupational assessment.

2.3 Label Recommendations from Residential Assessment

There are no proposed or register ed residential uses associated with ipconazole at this time.

2.4 Data Deficiencies and Requirements

There are no outstanding exposure data defici encies or data requirements for the active ingredient, ipconazole.

3.0 Hazard Characterization

Acute Toxicity Acute exposure to ipconazole resulted in low toxi city via the oral, dermal and inhalation routes of exposure and it was classified as Category III fo r these routes. Ipconazole is classified asPage 6 of 14 Category IV for dermal irritation, is a low to mild eye irritant and is not a dermal sensitizer. A summary of the acute toxicity prof ile is provided in Table 3.1 below.

Table 3.1 Acute Toxicity Profile - Ipconazole

Guideline

No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral [rat] 45552702 LD50 M = 1338 mg/kg LD50 F = 888 mg/kg III

870.1200 Acute dermal [rabbit] 45552703 LD50 > 2000 mg/kg (both sexes) III

870.1300 Acute inhalation [rat] 46110501 LD50 > 1.88 mg/L (both sexes) III

870.2400 Acute eye irritation [rabbit] 45552705 Eye irritation present at 24 hours, cleared by day 7 III

870.2500 Primary dermal irritation [rabbit] 45552706 Primary irritation index = 0.8 IV

870.2600 Skin sensitization [guinea pig] 45552707 Non-sensitizer NA

Toxicological PODs Used for Risk Assessment

The 28-day dermal study in the rat was selected for short- and intermediate term dermal exposure and risk assessment. The NOAEL of 150 mg/kg/day and the LOAEL of 1000 mg/kg/day were based on decrea sed body weight, and body weight gains, food consumption, as

well as increased incidences of dermal irritation.

The 28-day inhalation rat study was selected for th e short- and intermediate-term inhalation risk

assessment. An inhalation NOAEL was not identifie d; therefore, the selected POD was based on the lowest dose tested, 0.03 mg/L. The LOAEL was based on epithelial hyperplasia in the hard palate in males, epithelium squamous/squamoid hype rplasia in the larynx mucosa of both sexes, and mixed inflammatory cells in the trachea of females. For purposes of estimating inhalation risk resulting from occupational exposure, a hu man equivalent concentration (HEC) and human equivalent dose (HED) were derived in accordan ce with standard methodology that results in a reduction in the interspecies uncertainty factor (UF) from 10X to 3X. The HED determined for occupational inhalation risk assessment is 0.2832 mg/kg/day.

HED has recommended that the 10X FQPA Safety Factor (for the protection of infants and children) be reduced to 1X. Therefore, the leve l of concern (LOC) for dermal risk assessments is a margin of exposure (MOE) of 100, based on the combined interspecies (10X) and intraspecies (10X) uncertainty factors. The LOC for all inhalation occupational scenarios is equal to a MOE of 300, based on the following uncer tainty factors: 10X for lack of a NOAEL, 10X for intraspecies variabilit y, and 3X for interspecies vari ability. A summary of the toxicological endpoints and doses for ipc onazole is provided in Table 3.2 below.Page 7 of 14 Table 3.2. Summary of Toxicological Doses and Endpoints for Ipconazole Use in Occupational Human

Health Risk Assessments

Exposure

Scenario Point of Departure Uncertainty

Factors Level of Concern

for Risk

Assessment Study and Toxicological Effects

Dermal

Short-Term (1 - 30 days)

and

Intermediateterm (1 - 6 months) NOAEL = 150 mg/kg/day UF A =10X

UF H =10X LOC for MOE =100 28-day Dermal Toxicity Study in Rats LOAEL = 1000 mg/kg /day, based on

decreased body weight, body weight gain, and food consumption, as well as, increased incidences of dermal

irritation

Inhalation

Short-Term (1 - 30 days)

and

Intermediateterm (1 – 6 months) LOAEL = 0.03 mg/L

HEC = 0.00531 mg/L

HED = 0.2832 mg/kg/day UF A = 3X

UF H = 10X

UF L = 10X LOC for MOE =300 28-Day Inhalation Toxicity Study in

Rats LOAEL = 0.03 mg/L, based on

epithelial hyperplasia in the hard palate in males, epithelium squamous/squamoid hyperplasia in the larynx mucosa of both sexes, and mixed inflammatory cells in the

trachea of females Cancer (oral, dermal, inhalation) No Evidence of Carcinogenicity. Classified as “Not Likely to be Carcinogenic to Humans.”

Point of Departure (POD) = A data point or an estimated poin t that is derived from observed dose-response data and used to mark the beginning of extrapolation to determin e risk associated with lowe r, environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). UF L = use of a LOAEL to extrapolate a NOAEL. MOE = margin of exposure. LOC = level of concern.

Absorption

Since the short- and intermediate-term dermal and inhalation points of departure (PODs) were based on route-specific toxicity studies, no absorption factors were needed to estimate exposure.

Body Weight The standard body weight for the general population (80 kg) was used for a ll exposure scenarios covered in this risk assessment since the endpoi nts selected were not based on developmental

and/or fetal effects.

4.0 Use Profile

Chemtura AgroSolutions is requesting a new propos ed use for ipconazole as a commercial and on-farm seed treatment for legume vegetable (dri ed and succulent) seeds. The proposed product label specifies that seed should be treated using a water-based slu rry with other registered seed treatment insecticides and fungicides through st andard slurry or mist-type commercial seed treatment equipment and not for use in hopper, plan ter or slurry boxes at or immediately before planting. Rancona® 3.8 FS is form ulated as a flowable concentr ate containing 40.7% ai or 3.77 lb ai per gallon. The PPE statement on the propose d label requires applicators and other handlersPage 8 of 14 to wear the following: long-sleeved shirt and long pants, socks, shoes, and chemical-resistant gloves. The proposed use directio ns are summarized in Table 4.1.

1 Rate = Maximum application rate s specified on proposed labels. *Maximum Application Rate (lb ai/lb seed) = (.085fl oz /cwt x 3.77 lb ai/gal x 1 gal/128 fl. oz)/100 cwt

5.0 Residential Exposure and Risk Estimates

There are currently no registered or propos ed residential uses of ipconazole.

5.1 Spray Drift and Residential Bystander Post-Application Inhalation Exposure

A quantitative post-application exposure assessment is not required since there is no application of pesticide to the fields (seeds are previously tr eated in seed treatment fa cilities). Therefore, exposure is expected to be negligible.

6.0 Occupational Exposure and Risk Estimates

6.1 Occupational Handler Ex posure/Risk Estimates

HED uses the term handlers to describe those individuals who are invo lved in the pesticide application process. HED believe s that there are distinct job functions or tasks related to applications, and exposures can vary depending on the specifics of each task. 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 ha ndler can cause exposure levels to differ in a manner specific to each application event.

Based on the anticipated use patterns and curr ent labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the proposed uses. Typically, for large-scale commercial seed trea tments, workers perform only specific individual tasks; however, it is assumed that workers al so may perform multiple activities throughout the day. As a result a “multiple activities” scenario (i.e. where one worker performs all seed treatment tasks such as loading/applying, baggi ng, cleaning, calibration, re pair, forklift driver, etc.) was addressed. The quant itative exposure/risk assessmen t developed for occupational handlers is based on the following scenarios:

 Mixing, loading, applying liquid formulations for commercially and on-farm treated seeds;

 Multiple activities; and Table 4.1. Summary of Directions for Use of Ipconazole For Seed Treatment

Crop/ Use Site Product/ Formulation (EPA Reg. No.) Treatment Type Maximum Application Rate 1

(lb ai/ lb seed)*

Legume Vegetables (Crop Group 6) Rancona® 3.8 FS (400-544) Commercial and

On-Farm 0.000025 (0.085fl oz/cwt seed)Page 9 of 14  Planting treated seed.

Occupational Handler Exposure Data, and Assumptions A series of assumptions and exposure factors serv ed as the basis for completing the occupational handler (seed treatment and planti ng) risk assessments. Each assu mption and factor is detailed

below on an individual basis.

Application Rate The maximum application rate lis ted on the proposed label provid ed by the Registration Division was used for all exposure assessments. The maximum rate is 0.000025 lbs ai/lb seed for legume vegetable seeds.

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 su rrogate data in the absence of chemical-specific data, include HED Exposure SAC Policy 14: SOPs for Seed Treat ment. Some of these data are proprietary (e.g., Agricultural Handler Exposure Task Force (AHETF) data), and subject to the data protection provisions of FIFRA. The standard values recommende d for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the SOP 14. The registrant has not submitted a chemical-speci fic exposure study in support of this action.

Amount Handled: The AHETF is currently conducting surveys for use in seed treatment exposure assessment, providing daily seed treatment throughput data along with information on seed treating equipment and worker activities. The HE D Interim Guidance (SOP 15.1) “Amount of Commercial Seed Treated Per Day” provides up dated additional inform ation regarding these throughput data which will ultimately be incorporat ed into a final revised Seed Treatment SOP 15. Since the AHETF surveys only include informa tion for the five major field crops (canola, corn, rice, soybean and wheat), throughput values for non-surveyed crops are assigned based on a combination of “best professional judgement;” sim ilarity of seed size to that of the surveyed crops; and general knowledge of each crop and its production. The amount of seed treated per day at a commercial facility is summarized below for each crop:

 281,250 lbs of legume vegetables (succulent or dried) for short -term exposure (no survey data available; based on daily soybean throughput values)

Amount of Seed Planted Per Day: The amount of seed planted per day is based on information provided in the HED Reviewer’s Aid to Calculating Occupational Exposures from Activities Related to Agricultural Seed Treatment (November 29, 2012) and the BEAD Acre s Planted per Day and Seeding Rates of Crops Grown in the United States, Appendix B, Table B-1:

 13,280 lbs of legume vegetable (surrogate – soybeans) seeds planted per acre [(250,000 seed/A × 1 lb seed/ 1,500 seeds) × 80 A (legumes) = 13,280]Page 10 of 14 Note: Although soybeans served as a surroga te for legumes and are considered a high acreage crop which therefore assu mes that 200 acres will be pl anted, legumes are considered a typical acreage crop. Therefore 80 acres were used to refine the amount of legume seeds planted per day in place of 200 acres.

Exposure Duration: Treatment of the proposed seeds is expected to re sult in short- and interm ediate-term exposure. However, since the same dermal and inhalati on endpoints were selected for their respective short- and intermediate-term exposure durations , short-term exposure and risk estimates are considered to be protective of intermediate -term exposure and a sepa rate quantitative risk

assessment for intermediate-term durations was not provided. The AHETF survey reports that 39% of soybean is treated downstr eam for a duration of 49 days (50 th percentile; range 4 to 150 days), while soybean commercial facil ities operate 210 days per year (50 th percentile; range 1 to 270 days). While these durations would be c onsidered to potentially exceed the typical intermediate-term duration used in HED’s occupa tional assessments, HED had no information to

indicate that the same chemical is used cons ecutively for a long-term duration. Therefore, chronic occupational handler expos ure for seed treatment was not assessed. Furthermore, the dermal and inhalation unit exposure values specified in Policy 14 are based on open-pour systems, whereas the majority of the seed treatment facilities w ith large throughputs are equipped with fully or partially automated closed mixing and loading systems. Therefore, HED concluded that a chronic exposure assessment fo r ipconazole seed treat ment would result in overly conservative estimates of exposure.

Combining Exposures/Risk Estimates: Dermal and inhalation exposure estimates were not combined since the toxicological effects were different for these routes of exposure.

Summary of Occupational Handler Non-Cancer Expos ure and Risk Estimates

Commercial handler dermal and inhalation risk estimates are not of concern (Dermal LOC =

MOE ≥ 100 and Inhalation LOC = MOE ≥ 300) for the proposed legume seed treatment use with label required PPE. The short-term handler MOEs for treating seed ranged from 2000 for inhalation exposure to 74,000 for dermal exposur e, with the lowest MOE resulting from performing multiple activities with baseline clot hing (long-sleeved shirt and long pants, socks and shoes) and gloves. The seed planter expos ure estimates resulted in MOEs ranging from 20,000 for inhalation to 140,000 for dermal using base line clothing and gloves (note that gloves are only assumed to be used duri ng loading of seed into the plan ter, and not during planting seed into the field using a tractor). A summary of dermal and inhalation risk estimates for occupational handlers (treaters and plante rs) can be found in Tables 6.1 and 6.2.

On- Farm Exposure and Risk

HED assumes that the commercial seed treatment risk assessment is protective of on-farm seed treatment because the equipment is similar but the on-farm throughput is significantly less.Page11of14Table 6.1. Occupational Seed-Treatment Handlers Exposure and Risk Estimates for IpconazoleUse SitePPEDermalUnitExposurea(mg/lb ai)InhalationUnitExposurea(mg/lb ai)ApplicationRateb(lb ai/ lb seed)AmountTreatedc(lb seed/day)DermalDosed(mg/kg/day)DailyInhalationDosee(mg/kg/day)DermalMOEfInhalationMOEgLoader/ApplicatorLegumeVegetables(surrogate –soybeans)SingleLayer,Gloves0.023 0.00034 0.000025 281,250 0.0020 0.00003 74,000 9,400Multiple ActivitiesLegumeVegetables(surrogate –soybeans)SingleLayer,Gloves0.042 0.0016 0.000025 281,250 0.0037 0.00014 41,000 2,000a Unit Exposures are based on Policy 14: Standard Operating Procedures for Seed Treatment.b Application Rate is based on ProposedLabel for V-10208 3.2 FS (EPA Reg No. 59639-185.c. Amount of Seed Treated is based on information provided in the HED Interim Guidance SOP 15.1: Amount of Commercial Seed Treated Per Day (November 14, 2012).d. Dermal Dose (mg/kg/day) = (unit exposure (mg/lb ai) × application rate (lb ai/lbseed) × daily amounts treated ÷ body weight(80 kg).e. Inhalation Dose (mg/kg/day) = (unit exposure (mg/lb ai) × application rate (lbai/lb seed) × daily amounts treated ÷ body weight (80 kg).f Short- term Dermal MOE = NOAEL (150mg/kg/day) ÷ dermal dose (mg/kg/day).g. Short-term Inhalation MOE = HED (0.28mg/kg/day) ÷ inhalation dose (mg/kg/day).Page12of14Table 6.2: Seed Planter Exposureand Risk Estimates for IpconazoleUse SiteMitigationLevelDermalUnitExposurea(mg/lb ai)InhalationUnitExposurea(mg/lb ai)ApplicationRateb(lb ai lbseed)AmountPlantedc(lbs seed)DermalDosed(mg/kg/day)DermalMOEeInhalationDosef(mg/kg/day)InhalationMOEgLegumeVegetables(surrogate –soybeans)SingleLayer,Gloves0.25 0.00340.000025 13,2800.0010 140,000 0.000014 20,000a Unit Exposures are based on Policy 14: Standard Operating Procedures for Seed Treatment. Notethe dermal unit exposure is based on exposure resulting from loadingtreated seed into hopper while using glovesand does not represent exposure for driver operating tractor (no gloves required).b Application Rate is based on Proposed Label for V-10208 3.2 FS (EPA Reg No. 59639-185).c. Amount planted is based on information provided in the HEDReviewer’s Aid to CalculatingOccupational Exposures from Activities Related to Agricultural SeedTreatment (November 29, 2012) and the BEAD Acres Planted per Day and Seeding Rates ofCrops Grown in the United States, Appendix B, Table B-1.d. Dermal Dose (mg/kg/day) = (unit exposure (mg/lb ai) × application rate (lbai/lb seed) × daily amounts treated / body weight(80 kg).e. Inhalation Dose (mg/kg/day) = (unit exposure (mg/lb ai) × application rate (lbai/lb seed) × daily amounts treated / body weight (80 kg).f Short- term Dermal MOE = NOAEL (150mg/kg/day) / dermal dose (mg/kg/day).g. Short-term Inhalation MOE = HED (0.28 mg/kg/day) /inhalation dose (mg/kg/day).Page 13 of 14 6.2 Occupational Post-applicat ion 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 pe sticide (also referred to as reentry exposure). The potential for dermal a nd inhalation post-applica tion exposures following the planting of ipconazole-treated seeds is unlik ely because sustained levels of contact with treated seed after it has been pl aced in the soil or other planti ng media would not be expected because no routine cultural practice required fo r the production of agricultural 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. The labeling properly stat es the exception to the Agricultural Use Requirements restrict ed entry interval (REI) of 12 hours.Page 14 of 14 Appendix A. Summary of Occupation al Non-cancer and cancer Algorithms

Occupational Handler Non-Cancer E xposure and Risk Estimate Equations

Potential daily exposures for occupational ha ndlers were calculated using the following

formulas:

Daily Exposure (mg ai /day) = UE (mgai / lb of seed) * AR (lb ai /100 lbs of seed) * AT (Amount of seed treated /day) * 1E-3 mg/μg

Where :

Daily Exposure = Amount (mg ai/day) that is available for dermal or inhalation absorption, UE = Unit Exposure (μg ai / lb ai), AR = maximum application rate according to proposed label (lb ai /100lbs of seed), and AT = daily amount treated (lbs/day).

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)

Where: Average Daily Dose = Absorbed dose received from exposure to a pesticide in a given scenario (mg pesticide active ingredient/kg body weight/day), Daily Exposure = Amount (mg ai/day) that is available for dermal or inhalation absorption, Absorption Factor = A measure of the amount of chemical that crosses a biological boundary such as the skin and lungs (%), and Body Weight = Body weight determined to represent the population of interest in a risk assessment (kg).

MOE = POD (typically a NOAEL 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 (mg/kg/day): Dose level in a toxicity study, where no observed adverse effects occurred in the study, and ADD = Average Daily Dose (mg/kg/day): the absorbed dose received from exposure to a pesticide in a given scenario.