Date:

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

February 18

, 2016 OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

Pirimiphos-methyl. Draft Occupational and Residential Exposure / Risk

Assessment for Registration Review.

PC Code: I 08102

Decision No.: 477390

Petition No.: NA DP Barcode: 431439 Registration No.: NA Regulatory Action: Registration Review

Case No.: 2535 Risk Assessment Type: Exposure Assessment

TXRNo.: NA CAS No.: 29232-93- 7

40 CFR: § 180.409 MRIDNo.: NA

From:

Through:

To:

Introduction /

# Z~ida Figueroa

, DrPH

, Industrial Hygienist 

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R1sk Assessment Branch II**~** Health Effects Division (7509P) 

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Christina Swartz

, Branch Chief 

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Risk Assessment Branch II

Health Effects Division (7509P)

Russell Wasem and Neil Anderson

Risk Management and Implementation Branch 1

Pesticide Re-Evaluation Division (PRD) (7508P)

The Pesticide Re-evaluation Division (PRD) requested that Health Effects Division (HED)

conduct an occupational exposure / risk assessment to estimate the risk to human health that will

result from the currently registered uses of pirimiphos-methyl. This memorandum contains

HED ' s occupational / residential exposure and risk assessment required during registration review

to reflect the updated pirimiphos-methyl ' s hazard assessment

, science policies and procedures.

There are no registered residential uses ; therefore

, this risk assessment only addresses potential occupational/commercial exposures associated with the pirimiphos-methyl ' s registered uses

.

P a g e I of22Page 2 of 22 It is HED policy to use the best available data to assess exposure. Several sources of generic data were used in this assessment as surrogate data in the absence of chemical-specific data, including: Pesticide Handlers Exposure Databa se Version 1.1 (PHED 1.1); the Agricultural Handler Exposure Task Force (AHETF) data base; ExpoSAC Policy 9.1; ExpoSAC Policies 14, 15, and 15.1 (SOPs for Seed Treatment). Some of these data are propriet ary, and subject to the data protection provisions of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Note: This memorandum was reviewed by the Exposure Science Advisory Committee (ExpoSAC) on July 31, 2014 and on December 21, 2015.Page 3 of 22 Table of Contents

1.0 Executive Summary ............................................................................................................. 4

2.0 Risk Assessment Conclusions and Recommendations ........................................................ 8

2.1 Summary of Risk Estimates ............................................................................................. 8

2.2 Label Recommendations from Occupational Assessment ............................................... 8

2.3 Label Recommendations from Residential Assessment .................................................. 8

2.4 Data Deficiencies and Requirements ............................................................................... 8

3.0 Hazard Characterization ....................................................................................................... 9

3.1 Acute Toxicity ................................................................................................................ .. 9

3.2 Toxicological PODs Used for Risk Assessment .............................................................. 9

4.0 Use Profile ................................................................................................................... ...... 11

5.0 Non-Occupational (Residential) Ex posure and Risk Estimates ......................................... 13

5.1 Non-Occupational Spray Drift E xposure and Risk Estimates ....................................... 13

6.0 Occupational Exposure and Risk Estimates ...................................................................... 13

6.1 Occupational Handler Expos ure/Risk Estimates............................................................ 13 6.2 Occupational Post-application Exposure/Risk Estimates ................................................... 21

6.2.1 Occupational Post-application Inhala tion Exposure/Risk Estimates ...................... 21

6.2.2 Occupational Post-application Derm al Exposure/Risk Estimates .......................... 21 Appendix A. Summary of Occupa tional Non-cancer Algorithms ............................................... 22Page 4 of 22 1.0 Executive Summary

Pirimiphos-methyl (O-[2-diethylamino-6- methyl-4-pyrimidinyl] O,O-dimethyl phosphorothioate) is an organophospha te (OP) insecticide regist ered for post-harvest use on stored grains and grain seeds (c orn and sorghum), for spray treatment of empty storage bins and as ready-to use (RTU) ear-tag treatment for livestock.

This memorandum contains HED’s occupational/ residential exposure an d risk assessment required during registration review to reflect the updated pirimi phos-methyl’s hazard assessment, science policies and procedures. It addresses occupational handler exposure and risk associated with the registered uses of pirimiphos -methyl when used as directed.

Exposure Profile Occupational workers may be exposed (dermal and inhalation routes) to pirimiphos-methyl during handling (mixing, loading, and/or applyi ng) activities associated with RTU ear-tag treatments, spray or surface (“top-dressing by spra ying on top of stored grain) treatments to stored grains/seeds and spray treatm ent of empty storage bins. Since the labels state that a spray solution could be applied uniformly as grain ente rs storage or export co ntainers, a quantitative commercial seed treatment assessment (for prim ary and secondary handlers) was also conducted for stored grains/seeds (corn and sorghum). In general, occupational pos t-application exposures are not expected as reentry act ivities are not anticipated for the registered pirimiphos-methyl

uses.

Based on information provided by the registrant , Winfield Solutions, LLC, the major use of pirimiphos-methyl is for the post-harvest control of insects in grain and seeds going into storage or shipping containers in the Sout h and warmer climates. It is a pplied at the point of transfer between August and September and the treated seed grain is usually stored for 8-9 months before planting (May). Currently, there are no reside ntial uses of pirimiphos-methyl; therefore, exposure in non-occupational settings is not expect ed. Exposure via spray dr ift is not anticipated based on the current use pattern.

Pirimiphos-methyl is a member of the OP cl ass of pesticides. For OPs, matching the toxicological endpoint and the exposure duration is different than HED’s approach for conventional chemicals. OPs exhibit a phenom enon known as steady state acetylcholinesterase (AChE) inhibition. After repeated exposure at the same dose, the de gree of inhibition comes into equilibrium with the production of new, uninhi bited enzyme. The steady state approach is appropriate for pirimiphos-methyl given the toxi cological and exposure profile. The “steady state” endpoint selecti on for pirimiphos-methyl overlaps with HED’s traditional short-term exposure duration endpoint selec tion and is considered health protective for occupational handlers that apply pirimiphos-methyl commer cially over longer pe riods of time (i.e., intermediate-term exposures).

Hazard Profile HED has determined that the toxicology data base for pirimiphos-methyl is complete and adequate for risk assessment. Pirimiphos-methyl has low toxicity (Toxicity Category III) viaPage 5 of 22 oral, dermal, and inhalation routes of exposure. It is an eye irritant (Toxicity Category II) and moderate dermal irritant (Toxicity Cate gory III); it is not a dermal sensitizer.

Like other OPs, the initiating ev ent in the adverse outcome pathwa y (AOP), also often called the mode of action (MOA), for pirimiphos-methyl in volves inhibition of the enzyme AChE via phosphorylation of the serine residu e at the active site of the enzyme. This inhibition leads to accumulation of acetylcholine and ultimately to ne urotoxicity in the central and/or peripheral nervous system. For pirimiphos-methyl, AChE i nhibition is the most sensitive endpoint in the toxicology database in multiple species, durations , lifestages, and routes. Clinical signs of neurotoxicity can be found throughout the pirimi phos-methyl toxicology data base at doses much higher than those causing inhibition of AChE.

None of the guideline developmental and repr oduction toxicity studies for pirimiphos-methyl demonstrated quantitative and/or qualitative susceptibility. However, in the acute comparative CCA study, pups were more sensitive than adult animals to AChE inhibition. In the repeat comparative CCA study, adult and pup AChE in hibition were generally comparable. The available CCA studies for pirimiphos-methyl do not contain a gestational component and a DNT study is not available. Therefor e, no AChE data are available for comparative AChE evaluation of pregnant dams and fetuses.

The points of departure (PoD) selected are ba sed on the most sensitive endpoint red blood cell (RBC) acetylcholinesterase (ACh E) inhibition and are protecti ve of the clinical signs (neurotoxicity) observed in the toxicology database.

For steady state dermal risk assessment, a no observed adverse effects level (NOAEL) of 25 mg/kg/day was selected based on decreased RBC AChE inhibition from a 21- day dermal rat toxicity study that contains AC hE inhibition data. Since the st eady state dermal PoD was based on a route-specific toxicity study, an absorption factor was not necessary to estimate dermal exposure. Inhalation AChE data are not availabl e for pirimiphos-methyl; therefore, an oral study was used for endpoint selection. For inhalation ri sk assessment, an inhalation PoD was selected from a repeat comparative cholinesterase study based on RBC AChE inhibition in pups (Benchmark Dose Level (BMDL 10 ) = 0.73 mg/kg/day or 0.00062 mg/L/day; Benchmark Dose (BMD 10 ) = 1.01 mg/kg/day). Since the NOAEL for inha lation risk assessment was chosen from an oral study, it was assumed that toxicity via the inhala tion route is equivalent to oral toxicity.

HED has determined that a subchronic inhala tion study is now require d for pirimiphos-methyl (HASPOC, TXR # 0053947).

The level of concern (LOC) for occupational dermal exposure is equal to a margin of exposure (MOE) of 1,000 (10X to account for interspecies extrapolation, 10X for intraspecies variation, and 10X for FQPA SF due to uncertainty in the human dose-response relationship for neurodevelopmental effects and th e lack of gestational data). The LOC for i nhalation exposure is 3,000X (10X for interspecies extrapolation, 10X for intraspeci es variation, and 30X database uncertainty factor incorporating uncertainty in the human dose-response relationship for neurodevelopmental effects, lack of gestational component, and abse nce of the inhalation study).Page 6 of 22 For pirimiphos-methyl, the risk assessment fo r inhalation exposure is based on RBC AChE inhibition. For dermal exposure, an endpoint was not identified for the dermal study used for risk assessment, as no treatment related effects we re seen at doses up to the highest dose tested (HDT) of 25 mg/kg/day. However, since the derm al study did not test up to the limit dose, there is potential for treatment related effects on AChE inhibition at higher doses . Therefore, dermal

and inhalation routes can be combined. The inha lation and dermal routes have different LOCs; therefore, in order to combine exposure from both routes, the aggr egate risk index (ARI) is used to estimate exposure and risk. ARIs ≥ 1 are not of concern.

Pirimiphos-methyl is classified as “not likely to be carcinogenic to humans.” Treatment-related

increase in tumors was not obser ved in carcinogenicity studies in rats and mice and there is no concern for mutagenicity.

Residential Exposure There are no registered residential uses, or co mmercial/professional uses at residential sites associated with pirimiphos-methyl at this time. Residential exposures are not expected from the current uses; therefore, a quantitative residentia l handler and post-application assessment was not

conducted.

Spray Drift HED determined that pirimiphos-methyl is not regist ered on use sites that ar e likely to result in spray drift. Therefore, a quantitative spray drift assessment was not conducted for pirimiphosmethyl.

Occupational Handler Exposure Generic, surrogate handler data were used in the assessment. A female body weight of 69 kg was assumed to account for potentially pregnant wo rkers. Dermal and inhalation risk estimates

were combined for risk assessment because e ffects on AChE inhibition were observed in both

routes. Since the inhalation and dermal routes have different LOCs, the aggregate risk index (ARI) is used to estimate exposure and risk. ARIs ≥ 1 are not of concern.

Impregnated ear-tag : Negligible dermal and inhalation exposures are expected for workers applying RTU impregnated ear-tag to cattle with use of labe l required personal protective equipment or PPE (i.e., chemical-resistant gloves) ; therefore, no risks of concern are expected.

Stored grains/seeds and empty storage bins : Steady state dermal and inhalation exposures and risks were calculated for occupational handlers for the registered use on stored grain/seeds or in empty grain storage bins. Piri miphos-methyl may be applied to grain with handheld equipment as a surface spray to control insects. It may be applied via handheld equipment to empty storage

bins.

Risk concerns were identified fo r all handler scenario s (mixer/loader/applicator) using handheld equipment (i.e., manually-pressurized handwand a nd backpack sprayer) when treating stored grain/seeds as a surface spray (“top-dressing”) using label-required clothing (e.g., long-sleeved shirt, long pants, shoes plus socks) and PPE (i.e., chemical-resistant gloves and protective eyewear). Risks for manually-pressurized ha ndwand obtained an ARI=1.0 when using label-Page 7 of 22 required clothing and PPE plus a PF10 respirator. Risks for backpack sprayer treatments remain of concern (ARI=0.39) despite consideration of additional levels of PPE (e.g., double layer clothing and PF10 respirator).

The product label EPA Reg No. 1381-170 is unclear about the potential treatment of empty storage bins. Therefore, this assessment quantita tively calculates risk estimates using handheld equipment (i.e., mechanica lly-pressurized handg un, manually-pressurized handwand and backpack sprayer) to treat empty storage bins. Risk concerns were id entified for all handler scenarios. Total ARIs range from 0.001-0.09 for mixers/loaders/app licators treating empty storage bins using handheld equipment. Risks for these scenarios remain of concern despite consideration of additional PPE (e.g., doubl e layer clothing and PF10 respirator).

Seed Treatment Assessment : All risk estimates for commercial seed treatment handlers were not of concern (i.e., MOEs ≥ 1,000 for dermal and MOEs ≥ 3,000 for inhalation) when wearing single layer clothing + gloves for loader/applicat or and multiple activities worker; and single layer clothing + no gloves for sewe r and bagger. All Total ARIs ar e greater than 1 and therefore,

are not of concern.

Occupational Post-app lication Exposure Post-application exposure from treated stored grai ns/seeds is unlikely because sustained levels of contact with treated stored grain/ seed after application is not e xpected. Commercial applicators rarely have direct contact with the stored grain during testing of grain, maintenance, or other

intermittent activities. Therefor e, post-application exposure is expected to be negligible and a quantitative post-application as sessment was not required for pi rimiphos-methyl from treated stored grains/seeds.

Also, post-application exposures are not expected for workers removing ear-tags from treated cattle. No REI is listed on the available pr oduct label as the label-de fined use sites are not subject to the Worker Pr otection Standard (WPS).

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 PHED 1.1; the AHETF database; ExpoSAC Policy 14 (SOPs for Seed Treatment); these studies 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 et hics review may have included review by the Human Stud ies Review Board. Descriptions of data sources, as well as guidance on their use, can be found at the Agency website 1

.

1 Available at: http://www2.epa.gov/pesticide-science-and- assessing-pesticide-risks/occupational-pesticide-handlerexposure-data and http ://www2.epa.gov/pesticide- science-and-assessing-pesticide-risks/occupational-pesticide-postapplication-exposure.Page 8 of 22 2.0 Risk Assessment Conclusions and Recommendations

2.1 Summary of Risk Estimates

There are no risks of concern for workers applying RTU impregnated ear-tag to cattle with use of label required personal protectiv e equipment or PPE (i.e., chem ical-resistant gloves). In addition, all risk estimates for commercial seed treatment handlers were not of concern.

However, there are risk of concern for occ upational handlers when mixing/loading/applying pirimiphos-methyl when using handheld equipmen t. Based on the occupational risk estimates, additional PPE will be needed in the registered la bels. Detailed risk estimates description is

available in Section 6.0.

2.2 Label Recommendations from Occupational Assessment

Based on the occupational risk estimates, additional PPE will be needed on the registered labels to protect occupational handlers when mixing/lo ading/applying pirimiphos-methyl during spray or surface (“top-dressing”) treatments usi ng manually-pressurized handwand (i.e., PF 10 respirator). Risks for backpack sprayer tr eatments remain of concern (ARI=0.39) despite

consideration of additional leve ls of PPE (e.g., double layer clot hing and PF10 respirator).

The registered label EPA Reg No. 1381-170 is un clear about the potentia l treatment of empty storage bins. This assessment quantitatively calc ulates risk estimates for empty storage bins treatment using handheld equipment (i.e., mechanically-pressur ized handgun, manuallypressurized handwand and backpack sprayer). If the label is clarified about the potential treatment of empty storage bins, th at scenario will not be appli cable and the occupational risk

estimates for that scenario will not be applicable for risk assessment.

2.3 Label Recommendations from Residential Assessment

None.

2.4 Data Deficiencies and Requirements

None.Page 9 of 22 3.0 Hazard Characterization

The toxicology database for pirimiphos-methyl is adequate for risk assessment. Pirimiphosmethyl is a member of the organophosphate (OP) class of pesticides. Like other OPs, the initiating event in the advers e outcome pathway (AOP)/mode of action (MOA), for pirimiphosmethyl involves inhibition of th e enzyme AChE via phosphorylation of the serine residue at the active site of the enzyme. This inhibition l eads to accumulation of acet ylcholine and ultimately to neurotoxicity in the central and/or peripheral nervous system and is th e endpoint of concern.

Cholinesterase inhibition is the e ndpoint of concern for pirimiphos-methyl.

3.1 Acute Toxicity

Pirimiphos-methyl has low toxicity (Toxicity Category III) via oral, dermal, and inhalation routes of exposure. It is an eye irritant (Toxicity Category II ) and moderate dermal irritant (Toxicity Category III); it is not a dermal sensitizer. The acute toxicity for pirimiphos-methyl is

summarized in Table 3.1.

Table 3.1. Acute Toxicity Studies for Pirimiphos-methyl.

Guideline No./Study Type MRID No. Results Toxicity Category

870.1100 Acute oral toxicity (rat) 00126257 LD 50 =2.4 g/kg III

870.1200b Acute dermal toxicity (rabbit) 00126257 LD50 = M: 2.2-3.5 g/kg F: >3.5 g/kg III

870.1300 Acute inhalation toxicity (rat) 41556304 LC 50 >4.7 mg/L IV

870.2400 Acute eye irritation (rabbit) 00126257 Irritant II

870.2500 Acute dermal irritation (rabbit) 00126257 Moderate Irritant III

870.2600 Skin sensitization (guinea pig) 00126257 Non-sensitizer NA

NA = Not applicable.

3.2 Toxicological PODs Us ed for Risk Assessment

For risk assessment, a 21- day dermal rat t oxicity study, with a NOA EL of 25 mg/kg/day, was selected for dermal exposure. However, an e ndpoint was not determined for the study since no treatment-related effects were observed at any do se. The study is approp riate for the route and duration of exposure; there is no concern for in creased sensitivity afte r repeated exposure.

Since inhalation AChE data are not available fo r pirimiphos-methyl, an oral study was used for endpoint selection. A steady stat e inhalation PoD was selected from the repeat comparative cholinesterase study based on RBC AChE inhibition in pups (BMDL 10 = 0.73 mg/kg/day or 0.00062 mg/L/day; BMD 10 = 1.01 mg/kg/day). HED determin ed that a subchronic inhalation study is required for pirimiphos-methyl.

The level of concern (LOC) for occupational dermal exposure is equal to a margin of exposure (MOE) of 1,000 (10X to account for interspecies extrapolation, 10X for intraspecies variation,Page 10 of 22 and 10X for FQPA SF due to uncertainty in the human dose-response relationship for neurodevelopmental effects and th e lack of gestational data). The LOC for i nhalation exposure is 3,000 (10X for interspecies ex trapolation, 10X for intraspecies variation, and 30X database uncertainty factor incorporating uncertainty in the human dose-response relationship for neurodevelopmental effects, lack of gestational component, and abse nce of the inhalation study).

For pirimiphos-methyl, the risk assessment fo r inhalation exposure is based on RBC AChE inhibition. For dermal exposure, an endpoint was not identified for the dermal study used for risk assessment, as no treatment related effects we re seen at doses up to the highest dose tested (HDT) of 25 mg/kg/day. However, since the derm al study did not test up to the limit dose, there is potential for treatment related effects on AChE inhibition at higher doses . Therefore, dermal

and inhalation routes can be combined. The inha lation and dermal routes have different LOCs; therefore, in order to combine exposure from both routes, the aggr egate risk index (ARI) is used to estimate exposure and risk. ARIs ≥ 1 are not of concern.

Pirimiphos-methyl is classified as “not likely to be carcinogenic to humans.” No treatmentrelated increase in tumors was observed in carcinogenicity studies in rats and mice. Additionally, there is no concer n for mutagenicity.

Table 3.2. Summary of Toxicological Doses and Endpoints for Pirimiphos-methyl for Use in Occupational

Human Health Risk Assessments.

Exposure/

Scenario Point of Departure Uncertainty/FQP

A Factors Level of Concern

for Risk

Assessment Study and Toxicological Effects

Dermal Steady State (21 days and longer) NOAEL = 25 mg/kg/day UF A = 10x

UF H = 10x

UF DB = 10x (covers epi, gestational) Occupational LOC=1,000 21-day dermal toxicity study (MRID 45764501) in rats

LOAEL= not determined

Inhalation Steady State (21 days and longer) BMDL 10 = 0.73 mg/kg/day UF A = 10x

UF H = 10x

UF DB = 30x (covers epi, gestational, and inhalation) Occupational LOC=3,000 Repeat CCA Study (MRID 49037406) in the rat

BMD 10 = 1.01mg/kg/day

Inhibition of RBC AChE in pups

on PND 21

Cancer (oral, dermal, inhalation) Classification: Classification: "Not likely to be carcinogenic to humans.”

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 en vironmentally 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 DB =database uncertainty factor. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. BMDL = benchmark dose level. BMD =

benchmark dose.Page 11 of 22 Absorption: Since the dermal PoDs were based on rout e-specific toxicity studies, no absorption factors were necessary to estimate dermal exposur e. Furthermore, no inhalation absorption data are available; therefore, toxicity by the inhalati on route is considered to be equivalent to the estimated toxicity by the oral route of exposure.

Body Weight: For adults, when an endpoint is not sex-specific (i.e., the endpoints are based on developmental or fetal effects) a body weight of 80 kg is typically used in risk assessment; however, in this case, a female-specific body wei ght of 69 kg was used. While the endpoint of concern, RBC AChE inhibition, is not sex-specific, the female-specific body weight was used to protect for pregnant women due to uncertainty in the human dose-response relationship for neurodevelopmental effects.

4.0 Use Profile

Pirimiphos-methyl is registered as a post-harvest treatment to cont rol insects on stored grain and seeds going into storage or shipping containers or to treat empty grai n bins where grain is stored.

There were also two special loca l need labels registered for th e use of pirimiphos-methyl on iris and gladiolas bulbs in Washington state and Michigan state. Both labels were cancelled or the registration has been expired. Cu rrently, there are no registered uses of pirimiphos-methyl that

could result in reside ntial exposure.

The pirimiphos-methyl is also registered for ear-tag treatment of livestock (Dominator® Insecticide Ear Tag [EPA Reg. No. 773-68] and Double Barrel® VP Inse cticide Ear Tag [EPA Reg. No. 773-81]) and the labels di rect handlers to wear long-sl eeved shirt and long pants, shoes plus socks, and chemical-resistant gloves.

The registered product labels Actellic® 5E In secticide [EPA Reg. N o. 1381-170] and Executive S-PTM Insecticide Emulsifiable Concentrate [EPA Reg. No. 1381-198] direct mixers, loaders, and

other handlers to wear long-sleeved shirt and long pants, shoes plus socks, chemical-resistant gloves and protective eyewear. A ll other mixers, loaders, applic ators and other handlers must wear: coveralls over long-sleeved shirt and long pants, chemical-r esistant footwear plus socks, chemical-resistant gloves and protective eyewear. In addition, mixers and loaders must wear a chemical-resistant apron.

The use directions of the pirimiphos-methyl products are summarized in Table 4.0.Page 12 of 22 Table 4.0. Summary of Directions for Use of Pirimiphos-methyl.

Applic. Timing, Type, and Equip. Formulation [EPA Reg. No.] Max. Single Applic. Rate Max. No. Applic. per

Season Max.

Seasonal Applic.

Rate

(lb ai/A) PHI (days) Use Directions and

Limitations

Cattle Ear Tags

Animal treatment; Impregnated material (controlled release). Dominator ® Insecticide Ear Tag

(20% ai)

[EPA Reg. No. 773- 68] 2 ear tags/animal

(9.6 g/tag or 1.92 g ai/tag) 1 appl. /year N/A N/A Apply when flies appear in Spring. Effective for 5 months, remove in fall. Apply with ALLFLEX Tagging System. Animal treatment; Impregnated material (controlled release). Double Barrel ® VP Insecticide EarTag

(14% ai)

[EPA Reg. No. 773- 81] 1 2 ear tags/animal

(9.5 g/tag or 1.92 g ai/tag) 1 appl./year N/A N/A

Stored Corn (field and pop); Grain So rghum (including bulk and bagged seed)

Spray treatment using large tanks as grain

enters storage or export containers. Actellic ® 5E

Insecticide

Water Soluble

Packets (WPS)/Emulsifiable Concentrate (EC) 3

(57% ai)

(5 lb ai/gal)

[EPA Reg. No.

1381-170] 12.3 fl.oz/30 tons of grain equivalent to

0.016 lb ai/ton of grain,

0.000008 lb ai/lb of

seed 1 appl./stored

crop N/A N/A Treated seed for planting at point of transfer (8-9 months before planting). Treatment is only off-farm (or in a facility were the seed is bagged).

Surface treatment (or “top dressing”) by spraying on top of stored grain. Handheld sprayers. 0.12 lb ai /1,000 ft 2

of surface area Apply as a split treatment before and after raking.

Empty bins spray

treatment. Handheld

sprayers. 0.059 lb ai/gal 1 appl./bin N/A N/A Apply to clean and treat empty storage bins prior to storage of seeds.

Spray treatment as grain enters storage or export containers. Executive S-P TM

Insecticide

Emulsifiable

Concentrate

(57% ai)

(5 lb ai/gal)

[EPA Reg. No.

1381-198] 2 0.0078 lb ai/ton of grain; 0.0000039 lb ai/lb of grain 1 appl./stored

crop N/A N/A Treated seed for planting at point of transfer (8-9 months before planting). Treatment

of seed is off-farm in a facility where seed is bagged. Do not use as a “top dressing” treatment. Product

not for use as a seed

treatment to control insects. No bins treatment; always start with clean storage bins.

1. Mixture with lambda-cyhalothrin 6.8%. 2. Double pack with Spinosad (EPA Reg. No. 62719-294 (22.8% ai or 2 lb spinosad technical/gal). The two products are mixed at the time of treatment (i.e., “admixture”). 3. Statements on product label: 1) For the product label Actellic® 5E Insecticide [EPA Reg. No. 1381-170], the EC formulation i s to be used with a closed system/loading system designed by the manufacturer to prevent pesticide from contacting handlers. This product is form ulated in a container designed for closed mi xing and loading. 2) For the product Actellic® 5E Insecticide [EPA Reg. No. 1381-170] when pack aged in water soluble packets (WSP), when used correctly, qualify as a closed mixing/loading system under th e description of 40 CFR 170.240(d )(4). Mixers and loaders using water soluble packets must wear the PPE require d for mixers/loaders, and must be provided, must have immediat ely available and must use in an emergency (such as a broken package, spill or equipment breakdown) the following PPE: coveralls and chemical -resistant

footwear.Page 13 of 22 5.0 Non-Occupational (Residential ) Exposure and Risk Estimates

There are no registered residential uses, or co mmercial/professional uses at residential sites associated with pirimiphos-methyl at this time. Therefore, a quantitati ve residential exposure assessment is not required.

5.1 Non-Occupational Spray Drift Exposure and Risk Estimates

All the pirimiphos-methyl uses were evalua ted as part of the Registration Review process to ensure that the potential for spray drift from all re gistered uses have been considered in the risk assessment. Based on the use-pattern, HED determ ined that pirimiphos-met hyl is not registered on use sites or applied via equipment or methods th at would result in spray drift. Therefore, a quantitative spray drift assessment wa s not conducted for pirimiphos-methyl.

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 PPE protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

Pirimiphos-methyl is currently registered for us e on impregnated ear tags for cattle, as a postharvest treatment to control of insects on stor ed grains as a surface spray (or “top-dressing”) using handheld equipment. Also, grain storag e workers may apply liquid pirimiphos-methyl to the walls of empty grain storage bins using handh eld sprayers. Since the labels state that the products could be use in off-farm facilities and that a spray solution could be applied uniformly as grain enters storage or export containers, a quantitative commercial se ed treatment assessment (for primary and secondary handlers) was also conducted for stored gr ains/seeds (corn and sorghum). Both labels state that the products are not intended for use to control of soil insects.

Based on the anticipated use patterns and curr ent labeling, types of equipment and techniques that can potentially be used, occupational handler e xposure is expected from the registered uses. The quantitative exposure/risk a ssessment developed for occupati onal handlers is based on the following scenarios:

 Applicator of RTU (i mpregnated) ear tags;

 Mixing/Loading/Applying Liqui ds using Manually-pressuri zed Handwand Equipment for Empty Storage Bins Treatment Applications;

 Mixing/Loading/Applying Liqui ds using Backpack Sprayer Equipment for Empty Storage Bins Treatment Applications;

 Mixing/Loading/Applying Liqui ds using Mechanically-pre ssurized Handgun EquipmentPage 14 of 22 for Empty Storage Bins Treatment Applications;

 Mixing/Loading/Applying Liqui ds using Manually-pressuri zed Handwand Equipment for Spray or Surface (“Top-dressing”) Treatment A pplications on Stored Grains or Seeds;

 Mixing/Loading/Applying Liqui ds using Backpack Sprayer Equipment for Spray or Surface (“Top-dressing”) Treatment Appli cations on Stored Grains or Seeds;

 Primary Handler Seed Treatment Scenarios (i .e., activities associated to treating the seed); and

 Secondary Handler Seed Treatment Scenarios (i.e., activities associated with planting treated seed).

No mechanically-pressurized handgun equipmen t was assessed for surface spray (or “Topdressing”) treatment applications on stored grains/seeds, because the equipment (hand-gun sprayer) is not suitable (i.e., to treat a thin la yer of solution on stored grains/seeds) for that

scenario.

Primary Handler (Treating Seed)

Potential primary occupational handler exposure scenarios from the use of pirimiphos-methyl as

a commercial seed treatment include:

 Mixing, loading, applying liquid formulations;

 Bagging treated seed;

 Sewing bags; and

 Multiple activities.

Typically, for large-scale commercial seed tr eatments, workers perform only those specific individual tasks listed above; however, it is assumed that workers also may perform multiple activities throughout the day. As a result a “multiple activities” s cenario (i.e., where one worker performs all seed treatment tasks such as loading/applying, sewing, bagging, cleaning, calibration, repair, forklift driver , etc.) was addressed. Furtherm ore, the grain is treated only once with pirimiphos-methyl; however , repeat treatment of grain by workers at storage silos and shipping ports may result in re peated worker exposures.

Secondary Handler (Planting Treated Seed)

Potential secondary occupational handler exposur e scenarios from the use of pirimiphos-methyl as a commercial seed treatment include planting treated seed.

It is the policy of HED to use the best available data to assess handler exposure. Sources of generic handler data for seed treatment are in corporated in HED ExpoSAC Policy 14: SOPs for Seed Treatment. The amount of active ingredient handled depends on the application rate (lb ai/lb seed or lb ai/seed), the pounds of seed trea ted in a day, and the pounds of seed that can be planted in a day, all of which va ry depending upon the seed type. Values for the amount of seed treated and planted per day were obtained fr om HED ExpoSAC Policy 15.1: Interim Guidance – Amount of Commercial Seed per Day and th e Biological and Economic Analysis DivisionPage 15 of 22 (BEAD) memo: “Acres Planted per Day and S eeding Rates of Crops Grown in the United States.” (J. Becker, March 2011).

Occupational Handler Exposure Data and Assumptions

A series of assumptions and exposure factors serv ed as the basis for completing the occupational handler risk assessments. Each assumption and fact or is detailed below on an individual basis.

Application Rate : The maximum single application rates on the registered labels were used to assess the handler exposure scenario s. Refer to Table 4.0 for a comp lete use pattern description.

Unit Exposures: It is the policy of HED to use the best av ailable data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical-specific data, include PHED 1.1, the AHETF database, and ExpoSAC Policy 14 for Seed Treatment, or other registrant-submitted occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protecti on provisions of FIFRA. The standard values recommended for use in predicting handler exposur e that are used in th is assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Ha ndler Unit Exposure Surrogate

Reference Table 2 ”, which, along with additional informa tion on HED policy on use of surrogate data, including descriptions of the various so urces, can be found at the Agency website 3

.

Amount Handled: The amount handled is based on the spec ifications on the registered labels and guidance in ExpoSAC Policy 9.1, Po licy 15.1: Interim Guidance – Amount of Commercial Seed per Day and the BEAD memo “Acres Planted Per Day and Seeding Rates of Crops Grown in the United States” (J. Becker, March 2011).

Exposure Duration: HED classifies exposures from 1 to 30 days as short-term and exposures 30 days to six months as intermediate-term. Exposure duration is determined by many things, including the exposed population, the use site, the pest pressure triggeri ng the use of the pesticide, and the cultural prac tices surrounding that use site. Fo r the OP pesticides, the match between the toxicological endpoint selection and the exposure durat ion is different than HED’s approach for conventional chemicals. The e ndpoint selection for OP pesticides involves a “single day” and “steady state” approach based on an individual chemical’s cholinesterase inhibition. The steady state approach is appropriate fo r pirimiphos-methyl given the toxicological and exposure profil e. The “steady state” endpoint selection for pirimiphos-methyl overlaps HED’s traditional short-term exposure dur ation endpoint selecti on and is considered health protective for occupational handlers that apply commercially over longer periods of time (i.e., intermediate-term exposures).

Based on the anticipated use patterns and curr ent labeling, types of equipment and techniques that can potentially be used, steady state exposures are expected for occupational handlers. The steady state toxicological endpoints can be found in Table 3.2.

2 Available at: http://www2.epa.gov/sites/production/file s/2015-09/documents/handler-exposure-table-2015.pdf.

3 Available at: http://www2.epa.gov/pesticide-science-and- assessing-pesticide-risks/occupational-pesticide-handlerexposure-data.Page 16 of 22 Mitigation/Personal Protective Equipment: Estimates of dermal and inhalation exposure were calculated for various levels of PPE dependi ng on the scenario. The pirimiphos-methyl registered products for ear-tag treatment of liv estock (Dominator® Inse cticide Ear Tag [EPA Reg. No. 773-68] and Double Barrel® VP Insect icide Ear Tag [EPA Re g. No. 773-81]) direct handlers to wear baseline clothing (i.e., long-sleeved shirt and long pants, shoes plus socks) and chemical-resistant gloves. The pirimiphos-methyl product labels Actellic® 5E Insecticide [EPA Reg. No. 1381-170] and Executive S-PTM Insecticid e Emulsifiable Concentrate [EPA Reg. No. 1381-198] direct mixers, loaders, an d other handlers to wear baseline clothi ng, chemical-resistant gloves and protective eyewear. A ll other mixers, loaders, applic ators and other handlers must wear: coveralls over long-sleeved shirt and long pants, chemical-r esistant footwear plus socks, chemical-resistant gloves and protective eyewear. In addition, mixers and loaders must wear a chemical-resistant apron.

Occupational Handler Non-Cancer E xposure and Risk Estimate Equations

The algorithms used to estimat e non-cancer exposure and dose fo r occupational handlers can be found in Appendix A.

Combining Exposures/Risk Estimates A total aggregated risk index (ARI) was used since the LOC values for dermal exposure (1,000) and inhalation exposure (3,000) are di fferent. The target ARI is 1; therefore, ARIs of less than 1 are risk estimates of concern. The aggregate risk index (ARI) was calculated as follows:

Aggregate Risk Index (ARI) = 1÷ [(Dermal LOC ÷ Dermal MOE) + (Inhalation LOC ÷ Inhalation MOE)]

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

Tables 6.1a and b present the estimated steady st ate dermal and inhalation risk estimates for occupational handlers. Dermal and inhalation risk estimates were combined for risk assessment

because effects on AChE inhibition were observe d in both routes. Since the inhalation and

dermal routes have different LO Cs, the aggregate risk index (ARI) is used to estimate exposure

and risk. ARIs ≥ 1 are not of concern.

Impregnated ear-tag : Negligible dermal and inhalation exposures are expected for workers applying RTU impregnated ear-tag to cattle with use of labe l required personal protective equipment or PPE (i.e., chemical-resistant gloves) ; therefore, no risks of concern are expected.

Stored grains/seeds and empty storage bins : Steady state dermal and inhalation exposures and risks were calculated for occupational handlers for the registered use on stored grain/seeds or in empty grain storage bins. Piri miphos-methyl may be applied to grain with handheld equipment as a surface spray to control insects. It may be applied via handheld equipment to empty storage

bins.

Risk concerns were identified fo r all handler scenario s (mixer/loader/applicator) using handheld equipment (i.e., manually-pressurized handwand a nd backpack sprayer) when treating stored grain/seeds as a surface spray (“top-dressing”) using label-required clothing (e.g., long-sleeved shirt, long pants, shoes plus socks) and PPE (i.e., chemical-resistant gloves and protectivePage 17 of 22 eyewear). Risks for manually-pressurized ha ndwand obtained an ARI=1.0 when using labelrequired clothing and PPE in addition to a PF 10 respirator. Risks for backpack sprayer treatments remain of concern (ARI=0.39) despite consideration of additional levels of PPE (e.g., double layer clothing and PF10 respirator).

The product label EPA Reg No. 1381-170 is unclear about the potential treatment of empty storage bins. Therefore, this assessment quantita tively calculates risk estimates using handheld equipment (i.e., mechanica lly-pressurized handg un, manually-pressurized handwand and backpack sprayer) to treat empty storage bins. Risk concerns were identified for all handler scenarios. Total ARIs range from 0.001-0.09 for mixers/loaders/app licators treating empty storage bins using handheld equipment. Risks for these scenarios remain of concern despite consideration of additional PPE (e.g., doubl e layer clothing and PF10 respirator).

Seed Treatment Assessment : All risk estimates for commercial seed treatment handlers were not of concern (i.e., MOEs ≥ 1,000 for dermal and MOEs ≥ 3,000 for inhalation) when wearing single layer clothing + gloves for loader/applicat or and multiple activities worker; and single layer clothing + no gloves for sewe r and bagger. All Total ARIs ar e greater than 1 and therefore,

are not of concern.

Seed Treatment Steady state risk estimates for commercial seed treatment (primary and secondary handlers) are presented in Table 6.1b. All MOEs calculated for commercial seed treatment handlers (i.e., loader/applicator, sewer, bagger, and multiple activ ities seed treatment workers) are greater than the LOCs (Dermal LOC=1,000 and Inhalation LOC=3,000 ). All ARIs are greater than 1 and not of concern for workers wearing single layer clothing + gloves for loader/applicator and multiple activities worker; and single layer clothing + no gloves for sewer and bagger. The lowest ARI was 3 for workers conducting multiple activities (primary handlers).Page 18 of 22Table 6.1a. Occupational Handler Exposureand Risk Estimates for Pirimiphos-methyl.ExposureScenario andProductTargetSiteApplicationRateaAmountHandledDermal UnitExposureb(mg/lb)[MitigationLevel]InhalationUnitExposureb(mg/lb)[MitigationLevel]DermalDosec(mg/kg/day)DermalMOEdLOC =1,000InhalationDosee(mg/kg/day)InhalationMOEfLOC =3,000Total ARIgApplicatorRTUImpregnatedmaterial TagEartag(Cattle)1.92 g ai/tag200cattle/dayat 2 tagsper cattleNo data No dataNegligible. PPE requiredon label include chemical-resistant gloves forhandlers.Mixer/Loader/ApplicatorSprays usingManuallypressurizedHandwandEmptyStorageBinTreatment0.059 lbai/gal500 gal100[Baseline; No-G]0.030[No-R]42.8 0.58 0.01280 60 0.000560.430[Baseline; G]0.006[PF5]0.184 140 0.00257 280 0.0560.365[DL-G]0.003[PF10]0.157 160 0.00128 570 0.087Sprays usingMechanicallypressurizedHandgun0.059 lbai/gal500 gal1.8[Baseline; No-G]0.079[No-R]0.770 30 0.0338 20 0.0060.640[Baseline; G]0.0158[PF5]0.274 90 0.00675 110 0.030.365[DL-G]0.0079[PF10]0.157 160 0.00338 220 0.05Sprays usingBackpackSprayer0.059 lbai/gal500 gal2.50[Baseline; G]0.030[No-R]1.1 23 0.0128 57 0.011.6[DL-G]0.006[PF5]0.684 37 0.00257 280 0.0261.6[DL-G]0.003[PF10]0.684 37 0.00128 570 0.031Sprays usingManuallypressurizedHandwandSpray orSurface(Topdressing)Appl. onStoredGrain orSeed0.059 lbai/gal40 gal100[Baseline; No-G]0.030[No-R]3.42 10 0.00103 710 0.010.430[Baseline; G]0.006[PF5]0.0146 1,700 0.000206 3,500 0.690.430[Baseline; G]0.003[PF10]0.0146 1,700 0.000103 7,100 1.0Sprays usingBackpackSprayer0.059 lbai/gal40 gal2.50[Baseline; G]0.030[No-R]0.0858 290 0.00103 710 0.131.6[DL-G]0.006[PF5]0.0548 460 0.000206 3,500 0.33Page 19 of 22Table 6.1a. Occupational Handler Exposureand Risk Estimates for Pirimiphos-methyl.ExposureScenario andProductTargetSiteApplicationRateaAmountHandledDermal UnitExposureb(mg/lb)[MitigationLevel]InhalationUnitExposureb(mg/lb)[MitigationLevel]DermalDosec(mg/kg/day)DermalMOEdLOC =1,000InhalationDosee(mg/kg/day)InhalationMOEfLOC =3,000Total ARIg1.6[DL-G]0.003[PF10]0.0548 460 0.000103 7,100 0.39a. Maximum single application rates are based on registered labels (see Table 4.0).b. Occupational Pesticide Handler Unit Exposure Surrogate Reference Table (March, 2014). Baseline clothing or single layer (SL): long-sleeved shirt, long pants, shoes plus socks. No-G: no gloves. G:chemical-resistant gloves. DL: double layer clothing which includes coveralls or apronplus baseline clothing. No-R: no respirator. PF5 or PF 10 respirator.c. Dermal Dose (mg/kg/day) = [Dermal Unit Exposure (mg/lb ai) * Application Rate * AmountHandled]/Body Weight (69 kg).d. Dermal MOE = NOAEL (25 mg/kg/day)/Dermal Dose (mg/kg/day); LOC= 1,000.e. Inhalation Dose (mg/kg/day) = [Inhalation Unit Exposure (mg/lb ai) * Application Rate * Amount Handled]/Body Weight (69 kg).f. Inhalation MOE = NOAEL (0.73 mg/kg/day)/Inhalation Dose (mg/kg/day); LOC = 3,000.g. ARI = Aggregate Risk Index = 1÷ [(Dermal LOC ÷Dermal MOE) + (Inhalation LOC ÷ Inhalation MOE)]. ARI≥1 not of concern.Page 20 of 22Table 6.1b. Occupational Non-Cancer Primary & Secondary Handlers Exposure and Risk Estimates for Seed-Treatment for Pirimiphos-methyl.ExposureScenarioSeedSpeciesMitigationLevelDermalUnitExposure(mg/lb ai)aInhalationUnitExposure(mg/lb ai)aApplicationRate(lb ai/lb seed)AmountHandledb(lb seedtreated/day)DermalDosec(mg/kg/day)DermalMOEdInhalationDosee(mg/kg/day)InhalationMOEfTotalARIgPrimary HandlersLoader/ApplicatorLoading/ApplyingLiquid forSeed TreatmentCorn SingleLayer,Gloves0.023 0.00034 0.000008 339,500 0.00091 28,000 0.000013 55,000 10Sorghum 360,000 0.00096 26,000 0.000014 51,000 10SewerSewing Seeds afterSeed treatmentCorn SingleLayer,No Gloves0.0062 0.00023 0.000008 339,500 0.00024 100,000 0.0000091 81,000 20Sorghum 360,000 0.00026 97,000 0.0000096 76,000 20BaggerBagging Seedsafter SeedtreatmentCorn SingleLayer,No Gloves0.0091 0.00016 0.000008 339,500 0.00036 70,000 0.0000063 120,000 30Sorghum 360,000 0.00038 66,000 0.0000067 110,000 20Multiple Activities WorkerMultiple Activitiesfor Seed treatmentCorn SingleLayer,Gloves0.042 0.0016 0.000008 339,500 0.00165 15,000 0.000062 12,000 3Sorghum 360,000 0.00175 14,000 0.000067 14,000 3Secondary HandlersPlantersSecondary SeedHandlers: plantingseeds in the fieldCorn SingleLayer,Gloves0.25 0.0034 0.000008 6,000 0.0001714 150,000 0.0000023 310,000 60Sorghum 1,800 0.0000527 470,000 0.0000007 1,000,000 200a. Unit Exposures from HED Exposure Science Advisory Council Policy 14: Standard Operating Procedures for Seed Treatment (baseline inhalation = no respirator).b. HED default for lb seed treated/planted per day from HEDExposure Science Advisory Council Interim Policy 15.1 and the BEADmemo “Acres Planted Per Day and Seeding Rates of Crops Grownin the United States” (J. Becker, March 2011).c. Daily Dermal Dose (mg/kg/day) = Unit Exposure (mg/lb ai) *Application Rate (lb ai/lb seed) * Daily Amount Handled/Body Weight (69 kg).d. Dermal MOE = NOAEL (25 mg/kg/day)/Dermal Dose (mg/kg/day); LOC= 1,000.e. Daily Inhalation Dose (mg/kg/day) = Unit Exposure (mg/lb ai) * Application Rate(lb ai/lb seed) * Daily Amount Handled/BodyWeight (69 kg).f. Inhalation MOE = NOAEL (0.73 mg/kg/day)/Inhalation Dose (mg/kg/day); LOC = 3,000.g. ARI = Aggregate Risk Index = 1÷ [(Dermal LOC ÷Dermal MOE) + (Inhalation LOC ÷ Inhalation MOE)]. ARI≥1 not of concern.Page 21 of 22 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). Such exposures may occur when workers enter previously treated areas to perform job functions, including ac tivities related to crop producti on, such as scouting for pests or harvesting. Post-application e xposure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was trea ted, the type of pesticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for post-application exposure.

6.2.1 Occupational Post-application I nhalation Exposure/Risk Estimates

There are multiple potential sources of post-app lication inhalation exposure to individuals performing post-applicati on activities in previously treated fields. These potential sources

include volatilization of pesticides and resuspension of dusts and/or particulat es that contain pesticides. The Agency sought expert advice an d input on issues relate d to volatilization of pesticides from its Federal Insecticide, Fungicide , and Rodenticide Act Scie ntific Advisory Panel (SAP) in December 2009, and received th e SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SA P/meetings/2009/120109meeting.html). The Agency has evaluated the SAP report and has developed a Vo latilization Screening Tool and a subsequent Volatilization Screening Anal ysis (http://www.regulations .gov/#!docketDetail;D=EPA-HQOPP-2014-0219). During Registration Review, the agen cy will utilize this analysis to determine if data (i.e., flux studies) or further analysis is re quired for pirimiphos-methyl.

A post-application inhalation exposu re assessment is not required as exposure is expected to be negligible. Seed treatment a ssessments provide quantitative i nhalation exposure assessments for primary (i.e., seed treaters) and secondary handler s (i.e., planters). It is expected that these exposure estimates would be protective of any potential low-level post- application inhalation exposure that could result from these types of applications.

6.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

A quantitative post-application dermal exposur e assessment was not conducted since such exposure is also expected to be negligible. Post-application exposur e from treated stored grain/seeds is unlikely because sustained levels of contact with treated stored grain/seed after application is not expected. Comm ercial applicators rarely have direct contact with the storedgrain during testing of grain, maintenance, or other intermittent activities. In addition, a postapplication dermal exposure is not expected fo r workers distributing an d/or removing ear-tags from treated animals (cattle). Therefore, a qua ntitative post-application dermal assessment was

not conducted.

No REI is listed on the registered product labels, as the label-defined use sites are not subject to the Worker Protection Standard (WPS).Page 22 of 22 Appendix A. Summary of Occupational Non-cancer Algorithms

Occupational Non-cancer Handler Algorithms

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

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

where:

E = exposure (mg ai/day), UE = unit exposure (μg ai/lb ai), AR = maximum application rate according to label (lb ai A or lb ai/gal), and

A = area treated or amount ha ndled (e.g., A/day, gal/day).

The daily doses are calculated using the following formula:

ADD= E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day), E = exposure (mg ai/day), AF = absorption factor (der mal and/or inhalation), and BW = body weight (kg).

Margin of Exposure: Non-cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), whic h is a ratio of the to xicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occupational handlers are compared to the a ppropriate POD (i.e., NOAEL) to a ssess the risk to occupational handlers for each exposure route. All MOE values are calculated using the following formula:

MOE= POD

ADD

where:

MOE = margin of exposure: value used by HE D to represent risk estimates (unitless), POD = point of departure (mg/kg/day), and ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).