Date :

Subject: UNITED STATES ENVIRONMENTAL PROTECTION AGEN CY WASHINGTON
, D.C. 2 0460

September 1 5, 20 15 OFFICE OF CHEMICA L SAFETY AND POLLU T ION PREVEN T ION

C hl orp y ri fo s- me th yl. Occupational and R esident i al Expos u re / Risk Assess m ent for R eg i s trati o n R ev ie w.

PC Code: 059102
D ec i s i o n No.: 503280
P etit i on No.: NA DP Barcodc: 0426987
R eg i s tr a t i o n No.: NA
R eg ul a t ory Action: Rcgi s rration Review Ca se No.: 2535 Ri sk A ssess m e nt T y pe : Expo s ure Assessment
TX R No.: NA CAS No.: 5598-13-0
40 C FR: 180.419 MR ID No.: NA

Fro m:

Thro u g h :

To:

Introducti o n 

### Matthew Lloyd, C IH 

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Risk Assessmen t Branch V II Health Effec t s Division (7509P)

D anette Dr ew, Ri s k

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M i c h ae l S. Me t zge r , Chief 

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Risk Assessme nt Branch V Health Effects Division (7509 P )

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Joshua Godshall, Ex poSA C R eviewe r /

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-- Exposure Science Adv i sory Committe

Jo el Wolf

, Che mi ca l R eview Manager
R i sk Mana ge m e n t a nd Impl e m e ntation Branch I I
P est i cide Re -eva luation Divi s i o n (7508 P )

The Pest i cide R e

- eva lu at i o n Divi s i o n (PRO) requested that H ea lth Effects Di v i s i o n ( HED )

co ndu ct a n occ up at i onal expos ure / risk assessment to estimate the ri sk to h u man h e alth that w i II
result from the c urrentl y ac ti ve l y registered uses of chlorpyrifos-methy l. T hi s memorandum contains 1 I ED"s occupational / r esidential exposure and ri sk a s sessme nt required during registration review to reflect the updated chlorpy ri fos -m et h yl hazard assessme nt
, scie n ce pol i cies

Pa g e I of 18 \

.Page 2 of 18

and procedures

. There are no registered residential uses; therefore, this risk assessment only addresses potential occupational/commercial exposures associated with the registered uses of chlorpyrifos

- methyl

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

- specific data, including : Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1) ; and the Agricultural Handler Exposure Task Force (AHET F) database

. Some of these data are proprietary, and subject to the data protection provisions of the Federal Insecticide, Fungicide, and Rodenticide Act ( FIFRA). Note: This memorandum was reviewed by the Exposure Science Advisory Committee (ExpoSAC ) on August 6

, 201 5

.Page 3 of 18 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 4 2.0 Risk Assessment Conclusions and Recommendations

................................ ........................ 6 2.1 Summary of Risk Estimates

................................ ................................ ............................. 6 2.2 Label Recommendations from Occupational Assessment

................................ ............... 6 3.0 Hazard Characterization

................................ ................................ ................................ ....... 7 3.1 Acute Toxicity

................................ ................................ ................................ .................. 7 3.2 Toxicological PODs Used for Risk Assessment

................................ .............................. 8 4.0 Use Profile

................................ ................................ ................................ ......................... 10 5.0 Resident ial Exposure and Risk Estimates

................................ ................................ .......... 11 6.0 Spray Drift

................................ ................................ ................................ ...................... 11 7.0 Non

- Occupational Bystander Post

- Application Inhalation Exposure and Risk Estimates 11 6.0 Occupational Exposure and Risk Estimates

................................ ................................ ...... 12 6.1 Occupational Handler Exposure/Risk Estimates

................................ ............................ 12 6.2 Occupational Post

- application Exposure/Risk Estimates

................................ .............. 17 Appendix A. Summary of Occupational Non

- cancer Algorithms

................................ ............... 18Page 4 of 18

1.0 Executive Summary

Chlorpyrifos

- methyl [ O,O

- dimethyl O

- 3,5,6

- trichloro

- 2

- pyridyl phosphorothioate ] is an organophosphate (OP) insecticide limited for use as a post

- harvest treatment of stored grains or to treat empty grain bins and warehouses where grain i s stored

. Currently, there are no registered uses of chlorpyrifos

- methyl (CPM) anticipated to result in residential exposure.

This memorandum contains HED’s occupational/residential exposure and risk assessment required during registration review to reflect the updated Chlorpyrifos

- methyl hazard assessment, and to incorporate updated science policies and procedures. It addresses occupational handler exposure and risk associated with the registered uses of Chlorpyrifos

methyl when used as directed.

Exposure Profile:

Occupational dermal and inhalation exposures are expected for workers when mixing, loading, and applying Chlorpyrifos

- methyl as a surface spray to stored grain, stored seed, or to treat empty grain bins and warehouses where grain i s stored. C hlorpyrifos

- methyl is formulated as an emulsifiable concentrate (EC) . O nly one end

- use product is currently registered containing C hlorpy rifos

- methyl (21.6%) and deltamethrin (3.7%) . Deltamethrin, the other active ingredient in the registered end

- use product, will be addressed in separate assessment. The C hlorpyrifos

methyl product label direct mixers, loaders, applicators and other handl ers to wear long

- sleeved shirt s, long pants, chemical resistant gloves, and protective eyewear

. Empty grain bin applications require handlers to wear “a NIOSH

- approved respirator with any N, R, P or HE filter”.

C hlorpyrifos

- methyl is a member of the OP class of pesticides. For OPs , match ing the toxicological endpoint and the exposure duration is different than HED’s approach for conventional chemicals. OPs exhibit a phenomenon known as steady state a cetylcholinesterase ( AChE ) inh ibition. After repeated exposure at the same dose, the degree of inhibition comes into equilibrium with the production of new, uninhibited enzyme. The steady sta te approach is appropriate for chlorpyrifos

- methyl given the toxicological and exposure profi le. The “steady state” endpoint selection for chlorpyrifos

- methyl overlaps with HED’s traditional short

- term exposure duration endpoint selection and is considered health protective for occupational handlers that apply commercially over longer periods of time (i.e., intermediate

- term exposures).

Hazard Profile :

C hlorpyrifos

- methyl is a member of the OP class of pesticides. Like other OPs, the initiating event in the adverse outcome pathway (AOP), also often called the mode of action (MOA), for chlorpy rifos

- methyl involves inhibition of the enzyme AChE via phosphorylation of the serine residue at the active site of the enzyme. This inhibition leads to accumulation of acetylcholine and ultimately to neurotoxicity in the central and/or peripheral nervous system . For c hlorpyrifos

methyl , AChE inhibition is the most sensitive endpoint in the toxicology database in multiple species, durations, lifestages, and routes

.Page 5 of 18

For risk assessment, the same co

- critical studies were selected for endpoints for the dermal and inhalation routes of exposure. A rat chronic toxicity study measuring AChE inhibition was selected co

- critically with a rat developmental study for dermal and inhalation risk assessment. The lowest observed adverse effect levels ( LOAELs ) from those studies were 50 and 12.5 mg/kg/day

, respectively

, and both were based on based on red blood cell (RBC) cholinesterase AChE inhibition at a no observed adverse effect level ( NOAEL ) of 1 mg/kg/day. No information on an appropriate dermal absorption fa ctor was available, so 100% dermal absorption is assumed. AChE data via the inhalation route of exposure are not available for

c hlorpyrifos

- methyl ; therefore

, the same PoD was selected co

- critically for the dermal assessment was selected for assessing the inhalation route of exposure

. Since the NOAEL for inhalation risk assessment was chosen from an oral study, it was assumed that toxicity via the inhalation route is equivalent to oral toxicity. Since the dermal and inhalation PoDs are both based on RBC AChE inhibition, these routes of exposure can be combined for risk assessment
purposes using the Combined MOE approach

.
A total uncertainty factor of 3, 00 0 X is appropriate for the dermal route of exposure [10X for interspecies extra polation, 10X for intraspecies variation] and a total uncertainty factor of 3

, 000 X is appropriate for the inhalation route of exposure [10X for interspecies extrapolation, 10X for intraspecies variation, 3 0X for database uncertainty factor ]. Chlorpyrifos methyl is classified as "not likely to be carcinogenic to humans”

.
Residential Exposure

There are no registered residential uses, or commercial/professional uses at residential sites associated with c hlorpyrifos

- methyl at this time. Therefore, a quantitative residential exposure assessment is not required.

Spray Drift

Chlorpyrifos

- methyl is not registered on use sites that are likely to result in spray drift ; it is only used inside grain storage facilities . Therefore, a quantitative spray drift assessment was not conducted for chlorpyrifos

- methyl

.
Occupational Exposure

Handler

Based on the use profile of c hlorpyrifos methyl, occupational handler exposure is possible during mixing/loading of automated sy stems and the use of handheld equipment to treat grain bins/warehouse s

. C hemical

- specific handler exposure data were not submitted in support of this registration; therefore, HED relied on surrogate unit exposure data in accordance with standard policies. Default assumptions established by the HED Science Advisory Council for Exposure (ExpoSAC) were used for parameters such as body weight and amount handled. Steady state exposure and risks were calculated for occupational handlers of c hlorpyrifos

- methyl for a variety of exposure scenarios depending on the application pattern identified on the product label.Page 6 of 18

Risk concerns were identified for all handler scenarios (combined MOEs <3,000) with label

specified PPE (single layer plus gloves and PF5 respirator ); the automated equipment MOE was 350, and the handheld equipment MOEs range from 12 to 28. Risks for these scenarios remain of concern despite consideration of additional PPE.

Post

- application

Commercial applicators do not typically return to the tre ated areas after indoor commercial pesticide applications and thus an occupational post

- application inhalation exposure assessment was not performed for commercial applicators. Bystander exposure through dust may be possible for either the employee of a grain elevator or farmer/operator who operates a portable auger to load treated grain into a bin ; inhalation exposure in these cases are anticipated to be significantly lower than occupational handler exposures. A Restricted Entry Interval ( REI ) is not lis ted on the available product label as the label

- defined use sites are not subject to the Worker Protection Standard (WPS).

Human Studies Review

This risk assessment relies in part on data from studies in which adult human subjects were intentionally expo sed to a pesticide or other chemical. These data, which include studies from PHED 1.1; the AHETF database; 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

r equirements. For certain studies, the ethics review may have included review by the Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be found at the Agency website 1

.

2.0 Risk Assessment Conclusions and Recommendations

2.1 Summary of Risk Estimates

 Risk concerns were identified for all scenarios (combined MOEs <3,000 based on a LOC of 3,000) with both label

- specified PPE (single layer plus gloves and PF5 respirator):

o Mix/load/apply (M/L/A) for Mechanically

- pressurized hand wand equipment (Combined MOE of 12)

o M/L/A for Manually

- pressurized hand wand equipment (Combined MOE of 14)

o M/L/A Backpack Sprayer scenario (Combined MOE of 14)

o M/L for automated application (combined MOE of 350)

2.2 Label Re commendations from Occupational Assessment

The existing label is unclear and sometimes contradictory on the equipment per use scenario, particularly for the treatment of grain bin s and warehouses. This assessment quantitatively

1 http://www.epa.gov/pesticides/science/handler

- exposure

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

- app

- exposure

- data.htmlPage 7 of 18

calculates risk estimates using handheld equipment. If the label language is clarified to clearly restrict handheld equipment scenarios, those scenarios would not be applicable. Also, the label allows for open pour mixer/loader scenarios for automated spray equipment application

. The label should clearly restrict the presence of handlers or bystanders in the treated area.

3 .0 Hazard Characterization

The toxicology database for c hlorpyrifos

- methyl is adequate for risk assessment. Chlorpyrifos

methyl is a member of the OP clas s of pesticides. Like other OPs, the initiating event in the adverse outcome pathway (AOP/ mode of action (MOA, for c hlorpyrifos

- methyl involves inhibition of t he enzyme AChE via phosphorylation of the serine residue at the active site of the
enzyme. This inhibition leads to accumulation of acetylcholine and ultimately to neurotoxicity in the central and/or peripheral nervous system and is the endpoint of concern . Cholinesterase inhibition is the endpoint of concern for c hlorpyrifos

- methyl

.

3.1 Acute Toxicity

Chlorpyrifos

- methyl has low toxicity (Toxicity Category III) via oral, dermal, and inhalation routes of exposure. It is a slight eye and dermal irritant (Toxicity Category I I I); it is not a dermal sensitizer. The acute toxicity for the te chnical c hlorpyrifos

- methyl is summarized in Table 3 .1.

Table 3. 1 . Acute Toxicity Studies for Chlorpyrifos

- Methyl

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

81

- 1 (870.1100)

Acute Oral Toxicity 242152* LD 50 = 2140 (1530

- 2990) mg/kg for males = 1090 (694

- 1710) mg/kg for females III

81.2 (870.1200)

Acute Dermal Toxicity 242152* LD 50 > 2000 mg/kg. III

81.3 (870.1300)

Acute Inhalation Toxicity Not available on the technical product, however, a formulation had an LC 50 of 4.8 mg/L in males and 5.2 mg/L in females NA

81.4 (870.2400) Acute Eye Irritation 242152* Slight irritation in all eyes, with

c learing in 5/6 rabbits in seven days. III

81.5 (870.2500)

Acute Dermal Irritation 242152* Irritation in 2 /3 rabbits on days 4

- 7 after exposure III

81.6 (870.26 00)

Skin Sensitization 44906901 44989001 Delayed Contact Hyper

sensitization Study in the Guinea Pig [Unacceptable/ not upgradable] NAPage 8 of 18

* Study conducted prior to the 1984 Subdivision F Guidelines The skin sensitization study may be waived according to M. Lewis, 12/4/09 email communication to J. Doherty NA = Not applicable due to lack of data.

3.2 Toxicological PODs Used for Risk Assessment

The PoDs selected are also based on the most sensitive endpoint (AChE inhibition) and are protective of the clinical signs (neurotoxicity) observed in the toxicology database. For risk assessment, a rat chronic toxicity study with AChE inhibition data is avai lable and was selected for dermal and inhalation risk assessment

, co

- critical with a rat developmental study. The LOAELs from those studies were 50 and 12.5 mg/kg/day respectively and both were based on based on red blood cell (RBC) cholinesterase AChE inh ibition at the NOAEL of 1 mg/kg/day. The endpoint and PoD are appropriate for steady state dermal exposure for Chlorpyrifos

- methyl (which is reached approximately 21 days after exposure). Since inhalation AChE data are not available for Chlorpyrifos

- meth yl

, the same co

- critical studies were used for inhalation e ndpoint selection.

For chlorpyrifos

- methyl occupational (inhalation and dermal) exposures (there are currently no scenarios that would result in non

- occupational, residential exposures to chlor pyrifos

- methyl )

, a total database uncertainty factor (UF DB ) of 30X (to account for the uncertainty in the human dose

- response relationship for neurodevelopmental effects

, the lack of a CCA study , and lack of

a route

- specific inhalation stud y ) is applied

. A total UF of 3000X (10X to account for interspecies extrapolation, 10X for intra

- species variation, and 30X UF DB ) is applicable to occupational scenarios.

Prenatal developmental toxicity in rats and rabbits and the rat reproduction studies provided no evidence of increased susceptibility of the fetuses or offspring. There is no developmental neurotoxicity study with chlorpyrifos

- methyl . The developmental ne urotoxicity study with the closely

- related chlorpyrifos ethyl did not provide clear indications of increased quantitative susceptibility in the offspring, although there were concerns for qualitative susceptibility in offspring. However, the DNT study tog ether with a growing body of studies in the open literature suggest that gestational and early postnatal exposure to chlorpyrifos ethyl to pups may result in persistent alterations as indicated by various assessments of the laboratory animals when they rea ch adulthood. The 2014 risk assessment for chlorpyrifos ethyl retained a 10X FQPA factor for potential neurodevelopmental toxicity

, based primarily on the Columbia University epidemiology study ( D424485). Since chlorpyrifos

- methyl is so closely related to chlorpyrifos ethyl in structure and because HED already recognizes the similarity between these two organophosphates (memos dated 7/8/2003: D291405 and D289974, TXR 0051734) , HED considers that the conclusions regarding possible adverse developmental effects for chlorpyrifos also applies to chlorpyrifos

- methyl . Therefore, a 10X FQPA factor will also be retained for chlorpyrifos

- methyl

. Since the dermal and inhalation PoDs are both based on RBC AChE inhibition, these routes of exposure can be combined for risk assessment purposes.

Chlorpyrifos

- methyl is classified as “not likely to be carcinogenic to humans.” Chlorpyrifos

methyl was evaluated for carcinogenic potential in bot h rats and mice. There was no evidence of carcinogenicity following oral exposure. Chlorpyrifos

- methyl is not mutagenic in vitro inPage 9 of 18

bacteria (Ames test) or in a CHO/HGPRT mammalian cells tests. No evidence of a clastogenic effect was found in either an in vitro cytogenetics test or in an in vivo mouse micronucleus test. There was also no evidence of unscheduled DN A synthesis. Therefore, a quantitative cancer risk assessment is not required for chlorpyrifos methyl.

Table 3 .2

. Summary of Toxicological Do ses and Endpoints for Chlorpyrifos

- methyl for Use in Occupational Human Health Risk Assessments

.

Exposure/
Scenario Point of

Departure Uncertainty/FQPA

Factors Level of

Concern for
Risk
Assessment Study and Toxicological Effects

Dermal Steady State (21 days and longer) NOAEL = 1

mg/kg/day UF A = 10x

UF H = 10x
UF DB = 3 0x (to protect for potentially pregnant females) Occupational

LOC= 3 ,000 Chlorpyrifos

- methyl Rat Chronic Study

NOAEL = 1.0 mg/kg/day LOAEL = 50 mg/kg/day, based on RBC

ChE Inhibition

Co

- Critical Study Chlorpyrifos

- methyl Rat Developmental Study

NOAEL = 1.0 mg/kg/day LOAEL = 12.5 mg/kg/day, based on

inhibition of RBC cholinesterase

Inhalation Steady State (21 days and longer) NOAEL = 1

mg/kg/day UF A = 10x

UF H = 10x
UF DB = 3 0x (to protect for potentially pregnant females) Occupational

LOC= 3 ,000 Chlorpyrifos

- methyl Rat Chronic Study

NOAEL = 1.0 mg/kg/day LOAEL = 50 mg/kg/day, based on RBC

ChE Inhibition

Co

- Critical Study Chlorpyrifos

- methyl Rat Developmental Study

NOAEL = 1.0 mg/kg/day LOAEL = 12.5 mg/kg/day, based on

inhibition of RBC cholinesterase

Cancer (oral, dermal, inhalation) Classification: Classification: "Not likely to be carcinogenic to humans.”Page 10 of 18

Point of Departure (PoD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human
exposures. NOAEL = no obs erved 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

. *30x FQPA safety factor (SF) for females of child

- bearing age (13

- 49 years old), infants, children, and youths to account for 1) uncertainties introduced by the lack of sufficient data to quantify potential neurodevelopmen tal effects observed in epidemiology data for OPs and 2) the lack of lifestage

- specific data for determining sensitivity of the young to chlorpyrifos

- methyl (i.e., comparative cholinesterase assay). The assessment of the above lifestages is protective of a ll other lifestages. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. BMDL = benchmark dose level. BMD = benchmark dose.

Absorption

There are no dermal absorption studies available for chlorpyrifos

- methyl ; a 100% dermal absorption factor is assumed.

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

- spec ific body weight of 69 kg was used . While the endpoint of concern, RBC AChE inhibition, is not sex

- specific, the female body weight was used to protect for pregnant women due to uncertainty in the human dose

- response relationship for neurodevelopmental ef fects

.

4 .0 Use Profile

Chlorpyrifos

- methyl is an OP insecticide used to protect stored grain, including wheat, barley, oats, rice, and sorghum.

The only currently registered end

- use product is Storcide II ( 264

- 992 )

. It is formulat ed as an emulsifiable concentrate containing two active ingredients c hlorpyrifos

- methyl and deltamethrin (3.7%)

. The 2 1.6 % EC may be applied to stored grains at 0.18 lb a.i/1

, 000 bushels to provide a concentration of 3 ppm of c hlorpyrifos

- methyl on stored grains. Deltamethrin

, the other active ingredient in th is registered end

- use product

, will be a ddressed in a separate assessment

.
Workers may be exposed to c hlorpyrifos

- methyl during mixing, loading, and applying activities associated with stored grains, bins and warehouses. Currently there are no registered uses of

c hlorpyrifos

- methyl that could result in residential exposure.

The use directions of the c hlorpyrifos

- methyl product is summarized in Table 4.0

.

Table 4.0 . Summary of Directions for Use of Chlorpyrifos

- 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

Automated Grain Application (wheat, barley, rice, sorghum, oats)Page 11 of 18

Table 4.0 . Summary of Directions for Use of Chlorpyrifos

- 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

Automated spray equipment Storicide TM II
264

- 992 0. 18 lbs ai/ 1,000

bushels [all grains except oats] N/A N/A N/A  For protection against grain insect pests/empty grain bins

 Do not make more than one application to stored grain or seed Handheld Equipment to treat empty grain bins [ mechanically pressurized handwand, manually pressurized handwand

, backpack] Storicide TM II
264

- 992 0.03 lbs ai/gallon

[all grains except oats] 500 gallons of

spray solution/day for mechanically pressurized equipment;

2 0 gallons of spray solution assumed/day for manually pressurized and backpack
sprayers N/A N/A  Fumigate as necessary to control existing populations

 Apply for residual control as a course spray to deposit 3 ppm CPM and 0.5 ppm deltamethrin on grain

 Clean and treat storage areas prior to storage of seed 0.02 lbs ai/gallon [oats]

1. Storicide TM II 264

- 992 is co

- formulated with deltamethrin (3.7%)

.

5 .0 Residential Exposure and Risk Estimates

There are no registered residential uses, or commercial/professional uses at residential sites associated with c hlorpyrifos

- methyl at this time. Therefore, a quantitative residential exposure assessment is not required.

6.0 Spray Drift

Based on the use

- pattern , HED determined that c hlorpyrifos

- methyl is not registered on use sites that would result in spray drift. Therefore, a quantitative spray drift assessment was not conducted for c hlorpyrifos

- methyl

.

7.0 Non

- Occupational Bystander Post

- Applicat ion Inhalation Exposure and Risk Estimates

Volatilization of pesticides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The agency h as evaluated the SAP report and has developed a Volatilization Screening Tool and a subsequent Volatilization Screening Analysis (http://www.regulations.gov/#!docketDetail;D=EPA

- HQ

- OPP

- 2014

- 0219).Page 12 of 18

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

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

- methyl

.

6 .0 Occupational Exposure and Risk Estimates

6 .1 Occupational Handler Exposure/Risk Estimates

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

Chlorpyrifos

- methyl is current ly registered for treatment of stored grain /seed and grain bin s (See Section 4.0 for a detail ed use pattern description ). The quantitative exposure/risk assessment developed for occupational handlers is based on the fol lowing scenarios:

(1) mixing/loading liquid formulation for automated application equipment (admixture) [open loading systems] ; (2) mixing/loading/applying liquid formulation using hand

- held equipment :

 Mechanically pressurized handwand (grain bin treatments)

 Manually pressurized handwand (warehouse treatments)

 Backpack sprayer (warehouse treatments)

Grain elevator workers are known to apply this product in liquid form to a moving stream of grain (i.e., conveyor or auger) using automate d equipment. Only mixing and loading are expected to contribute significantly to worker exposure when using an automated process. Grain storage workers and farm workers also may apply liquid c hlorpyrifos

- methyl to the walls of empty grain storage contain ers using hand sprayers such as backpack and manually

- pressurized handwand equipment. The potential for occupational bystander exposure is addressed in Section 6.2

Occupational Handler Exposure Data and Assumptions

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

Application Rate : The maximum single application rates on the registered label was used to

assess the handler exposure scenarios. Refer to Table 4.0 for a complete use pattern description.

Automated admixtures: Storcide ® (22.46% a.i.)Page 13 of 18

Final spray volume is 5 gallons of water per 1000 bushels of grain to provide treatment with 3 ppm concentration of chlorpyrifos

- methyl (0.18 lb ai./1000 bushels). This assumed 26,000 bushels were treated per day (Brad Berven, SD Department of Agriculture).

1.92 lb ai x 12 oz/conc x 5 gal water x gal/conc = 0.18 lbs ai gal/conc. 5 gal. of water 1000 bushels 128 oz/conc 10 00 bushels

Grain, Bin, and Warehouse applications : Based on the application rate identified on the label, HED conducted the assessment using 0.03 lbs ai/gallon

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

- specific data, include PHED 1.1, and the AHETF database

. 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 Exposur e Surrogate Reference Table 2 ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of the various sources, can be found at the Agency website 3

.

Amount Handled : The amount handled is based on the specifications on the registered labels and a citation from a previous risk assessment

. For the automated treatment scenarios (open loading), it is assumed that 26,000 bushels of stored grain are treated per day 4

.

Th e product label provides an applic ation rate of 12.4 fluid oz per 1,000 bushels of grain treated. HED assessed the label maximum rate (for treating wheat; 12.4 fl. oz / 1,000 bushels of grain) For the handheld application scenarios, the following is assumed:

 Backpack spra yer and manually pressurized handwand

– 20 gallons per day 4

 Mechanically pressurized handwand

– 500 gallons per day 5

Exposure Duration: HED typically 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 triggering the use of the pest icide, and the cultural practices surrounding that use site. For the OP pesticides, the match between the toxicological endpoint selection and the exposure duration is different than HED’s approach for conventional chemicals. The endpoint selection for O P pesticides involves a “single day” and “steady state” approach based on an individual chemical’s cholinesterase inhibition. T he steady state approach is appropriate for c hlorpyrifos

- methyl given the toxicological and exposure profile. The “steady state ” endpoint selection for c hlorpyrifos

- methyl overlaps HED’s traditional short

- term exposure duration endpoint selection and is considered

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

- exposure

- table.pdf

3 Available: http://www.epa.gov/pesticides/science/handler

- exposure

- data.html

4 Collantes, 12/21/00; Occupational Exposure and Risk Assessment for Section 18 Use of c hlorpyrifos

- methyl on Stored Grains, Bins and Warehouses. DP Barcode:D268643

5 Assumed total volume per day = 25X higher than backpack/manually pressurized equipment; this is the same ratio b etween the total volume assumed per day in HED’s default assumptionsPage 14 of 18

health protective for occupational handlers that apply commercially over longer periods of time (i.e., intermediate

- te rm exposures).

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, steady state exposures are expected for occupational handlers. The steady state toxicological endpoints are the sam e for the respective routes of exposure , although the uncertainty factors differ between the dermal and inhalation routes of exposure

.
Mitigation/Personal Protective Equipment : Estimates of dermal and inhalation exposure were calculated for various levels of PPE depending on the scenario . The c hlorpyrifos

- methyl product labels direct mixers, loaders, applicators and other handlers to wear long

- sleeved shirt and long pants, chemical resistant gloves, and protective eyewear

. Empty grain bin applicati ons require handlers to wear “a NIOSH

- approved respirator with any N, R, P or HE filter”. Handlers applying directly to grain or stored seed must use an automated admixture system. Those systems must apply the pesticide directly to the grain or seed and t ransfer into stationary storage facilities.

Occupational Handler Non

- Cancer Exposure and Risk Estimate Equations

The algorithms used to estimate non

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

.
Combining Exposures/ Risk Estimates : Dermal and inhalation risk estimate s were combined using the Combined MOE approach in this assessment, since the toxicological effects for these exposure routes were similar. Dermal and inhalation risk estimate s were combined using the followin g formula:

Total MOE = Point of Departure (mg/kg/day) ÷ Combined D ermal + I nhalation dose (mg/kg/day)

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates

Table 6.1 present s the estimated steady state dermal and inhalation risk estimates for occupational handlers. Since the dermal and inhalation PoDs are both based on RBC AChE inhibition, these routes of exposure can be combined (using the combined MOE approach ) for risk assessment purposes.

Risk con cerns were identified for all scenarios (combined MOEs <3,000 based on a LOC of 3,000) with label

- specified PPE (single layer plus gloves and PF5 respirator):

o Mix/load/apply (M/L/A) for Mechanically

- pressurized hand wand equipment (Combined MOE of 12)

o M/L /A for Manually

- pressurized hand wand equipment (Combined MOE of 14)

o M/L/A Backpack Sprayer scenario (Combined MOE of 14)

o M/L for automated application (combined MOE of 350)

Risk estimates for these scenarios remain of concern despite considerations of ad ditional PPE. Specifically, the addition of additional dermal protection (e.g., coveralls) or a PF10 respirator (inPage 15 of 18

the case of the manually

- pressurized handwand scenario) does not increase the combined MOE over the LOC of 3,000

.
The existing label is unc lear and sometimes contradictory on the equipment per use scenario, particularly the grain bin and warehouse uses

. The product label does note that “This product may only be applied to empty grain bins using high

- pressure hand held or automated equipment” although warehouse applications using other handheld equipment appear to be allowed in the Directions for Use section. This assessment quantitatively calculates risk estimates using handheld equipment. If the label language is clarified to clearly restri ct handheld equipment scenarios for a specific use site , those scenarios would not be applicable. Also, the label allows for open pour mixer/loader scenarios for automated spray equipment application.Page 16 of 18

Table 6.1 . Occupational Handler Exposure and Risk Estimates for Chlorpyrifos

- methyl.

Exposure Scenario and Product Crops Application Rate a Amount

Handled Dermal Unit

Exposure b ( u g/lb ai ) [Mitigation Level] Inhalation

Unit Exposure b (mg/lb ai ) [Mitigation Level] D ermal

Dose c (mg/kg/day) Dermal

MOE d LOC = 3 ,000 Inhalation

Dose e (mg/kg/day) Inhalation

MOE f LOC = 3,000 Total MOE g

LOC = 3,000

Mixer/Loader

M/L for automated application [open loading] Stored

Grain/Stored Seed (wheat, barley, rice, sorghum) 0.18

lbs ai/1000 bushels 26,000

bushels 37.6

[Baseline; Gloves] 0.219

[No respirator] 0.00 281 360 0.0000165 61

, 000 350

Mixer/Loader/Applicator

Sprays using M echanically

pressurized Handwand Empty grain

bins 0.03 lb ai/gal 500 gal 390 [Baseline ; Gloves] 0.78

[PF5 Respirator] 0.0838 12 0.00017 5,900 12

390 [Double layer +
g loves] 0.78

[PF5 Respirator] 0.0624 16 0.00017 5,900 16

Sprays using Manually

pressurized Handwand Warehouse 0.03 lb ai/gal 20 gal 8600 [Baseline ; Gloves] 220

[PF5 Respirator] 0.0739 14 0.00191 520 14

6200 [Double layer ; Gloves] 110

[PF10 Respirator] 0.0535 19 0.000957 1,000 18

Backpack Sprayer Warehouse 0.03 lb ai/gal 20 gal 8260 [Baseline ; Gloves] 0.516

[PF5 Respirator] 0.0726 14 0.00000449 220,000 14

8260 [Double layer ; Gloves] 0.516

[PF5 Respirator] 0.0353 28 0.00000449 220,000 28

a. Maximum single application rates are based on registered labels (see Table 4.0). b. Occupational Pesticide Handler Unit Exposure Surrogate Reference Table (March, 2014). c. Dermal Dose (mg/kg/day) = [Dermal Unit Exposure (mg/lb ai) * Application Rate * Amount Handled ] /Body Weight ( 69 kg). d. Dermal MOE = NOAEL ( 1 mg/kg/day)/Dermal Dose (mg/kg/day); LOC= 3 ,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 ( 1 mg/kg/day)/Inhalation Dose (mg/kg/day); LOC = 3 ,000.

g. Total MOE = NOAEL (mg/kg/day) ÷ (Dermal Dose + Inhalation Dose) OR Total MOE = 1 ÷ [(1 / Dermal MOE) + (1 /Inhalation MOE)].Page 17 of 18

6

. 2 Occupational Post

- application Exposure/ Risk Estimates

There are multiple potential sources of post

- application inhalation exposure to individuals performing post

- application activities in previously treated fields or other treated areas

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

- HQ

- OPP

- 2014

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

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

- m ethyl

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

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

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

In the case of c hlorpyrifos

- methyl

, bystander exposure may be possible to dusts generated by treated grain being conveyed into, out of or withi n storage containers, and dermal exposure when sampling treated grain. Personnel rarely have direct contact with the stored grain and therefore dermal exposure is expected the negligible during testing of grain, maintenance, or other intermittent activiti es. Commercial applicators do not typically return to the treated areas after an indoor commercial pesticide application (sites such as warehouses, etc.) and thus an occupational post

- application inhalation exposure assessment was not performed for commercial applicators.

Occupational b ystander inhalation exposure through dust may be possible for either the employee of a grain elevator or farmer/operator who operates a portable auger to load treated grain into a bin but there are no data available t o quantify these exposures. However, bystander exposure in these cases are anticipated to be negligible because of dust management practices for grain dust at on

- farm storage sites. Additionally, the available Storicide II product label directs
users to av oid application at extremely dusty sites.

No REI is listed on the available product label as the label

- defined use sites are not subject to the Worker Protection Standard (WPS).Page 18 of 18

Appendix A. Summary of Occupational Non

- cancer Algorithms

Occupational Non

- cancer Handler Algorithms

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

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

where:

E = e xposure (mg ai/day), UE = u nit e xposure (μ g ai/ lb ai), AR = m aximum application rate according to label (lb ai/gal ), and A = amount handled (e.g., A/day, gal/day)

.
The daily doses are calculated using the following formula:

ADD= E * AF
BW

where:

ADD = average daily dose a bsorbed in a given scenario (mg ai/ kg / day), E = e xposure (mg ai/day), AF = absorption fa ctor (dermal and/or inhalation), and BW = body weight (kg)

.
Margin of Exposure: Non

- cancer risk estimates for 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. The daily dermal and inhalation dose received by occupational handlers a re compared to the appropriate POD ( i.e.

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

MOE= POD
ADD

where:

MOE = m argin of e xposure: value used by HED to represent risk estimates (unitless), POD = p oint of d eparture (mg/kg/day)

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

.