Date: 

Subject: 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

September 15, 20 15 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

Chlorpyrifos-methyl. Occupational and Residential Exposure/Risk Assessment 

for Registration Review. 

PC Code: 059102 

Decision No.: 503280 

Petition No.: NA 

DP Barcodc: 0426987 

Registra tion No.: NA 

Regula tory Action: Rcgisrration Review 

Risk Assessment Type : Exposure Assessment Case No.: 2535 

TXR No.: NA CAS No.: 5598-13-0 

MRID No.: NA 40 CFR: 180.419 

From: 

Through: 

To: 

Introduction 

Matthew Lloyd, CIH /'"?,,;! :zd} 

Risk Assessment Branch VII 

Health Effects Division (7509P) 

Danette Drew, Risk Assess~r ~vt1 () ) / fL---

Michael S. Metzger, Chief a_,{ . · /l"'i;J 

Risk Assessment Branch V 

Health Effects Division (7509P) 

and // 

Joshua Godshall, ExpoSAC Reviewer/ A Zaida Figueroa, ExpoSAC Reviewer ~ ........... .-.- r------ Exposure Science Advisory Committe 

Joel Wolf, Chemi cal Review Manager 

Risk Management and Implementation Branch I I 

Pesticide Re-evaluation Division (7508P) 

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

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

result from the currently acti vely registered uses of chlorpyrifos-methyl. This memorandum 

contains 1 IED"s occupational/residential exposure and risk assessment required during 

registration review to reflect the updated chlorpyrifos-methyl hazard assessment, science policies 

Page 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 exposure. Several sources of generic 

data were used in this assessment as surrogate data in the absence of chemical-specific data, 

including: Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); and the Agricultural 

Handler Exposure Task Force (AHETF) 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, 2015.
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 Residential 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............................................... 18
Page 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 is 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 Chlorpyrifosmethyl 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 is stored. Chlorpyrifos-methyl is formulated as an 

emulsifiable concentrate (EC). Only one end-use product is currently registered containing 

Chlorpyrifos-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 Chlorpyrifosmethyl product label direct mixers, loaders, applicators and other handlers to wear long-sleeved 

shirts, 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”. 

Chlorpyrifos-methyl is a member of the OP class of pesticides. For OPs, matching the 

toxicological endpoint and the exposure duration is different than HED’s approach for 

conventional chemicals. OPs exhibit a phenomenon known as steady state acetylcholinesterase

(AChE) inhibition. After repeated exposure at the same dose, the degree of inhibition comes into 

equilibrium with the production of new, uninhibited enzyme. The steady state approach is 

appropriate for chlorpyrifos-methyl given the toxicological and exposure profile. 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:

Chlorpyrifos-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 

chlorpyrifos-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 chlorpyrifosmethyl, 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 factor was available, so 100% dermal 

absorption is assumed. AChE data via the inhalation route of exposure are not available for 

chlorpyrifos-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 3,000X is appropriate for the dermal route of exposure [10X for 

interspecies extrapolation, 10X for intraspecies variation] and a total uncertainty factor of 

3,000X is appropriate for the inhalation route of exposure [10X for interspecies extrapolation, 

10X for intraspecies variation, 30X 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 chlorpyrifos-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 chlorpyrifos methyl, occupational handler exposure is possible during 

mixing/loading of automated systems and the use of handheld equipment to treat grain 

bins/warehouses. Chemical-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 chlorpyrifos-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 labelspecified 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 treated 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 listed 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 exposed 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 

requirements. For certain studies, the ethics review may have included review by the Human 

Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be 

found at the Agency website1. 

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 Recommendations from Occupational Assessment 

The existing label is unclear and sometimes contradictory on the equipment per use scenario, 

particularly for the treatment of grain bins 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.html
Page 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 chlorpyrifos-methyl is adequate for risk assessment. Chlorpyrifosmethyl is a member of the OP class of pesticides. Like other OPs, the initiating event in the 

adverse outcome pathway (AOP/ mode of action (MOA, for chlorpyrifos-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 and is the endpoint of concern. Cholinesterase 

inhibition is the endpoint of concern for chlorpyrifos-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 III); it is not a dermal 

sensitizer. The acute toxicity for the technical chlorpyrifos-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* LD50 = 2140 (1530-2990) mg/kg 

for males

= 1090 (694-1710) mg/kg for 

females

III

81.2 (870.1200)

Acute Dermal Toxicity

242152* LD50 > 2000 mg/kg. III

81.3 (870.1300)

Acute Inhalation Toxicity

Not available on the technical 

product, however, a formulation 

had an LC50 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 

clearing 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 (870.2600)

Skin Sensitization

44906901 

44989001

Delayed Contact Hypersensitization Study in the 

Guinea Pig [Unacceptable/ not 

upgradable]

NA
Page 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 available 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 inhibition 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-methyl, the same co-critical studies were used for inhalation endpoint 

selection. 

For chlorpyrifos-methyl occupational (inhalation and dermal) exposures (there are currently no 

scenarios that would result in non-occupational, residential exposures to chlorpyrifos-methyl), a 

total database uncertainty factor (UFDB) 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 study) is applied. A total UF of 3000X (10X to account for 

interspecies extrapolation, 10X for intra-species variation, and 30X UFDB) 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 neurotoxicity 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 together 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 reach 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.” Chlorpyrifosmethyl was evaluated for carcinogenic potential in both rats and mice. There was no evidence of 

carcinogenicity following oral exposure. Chlorpyrifos-methyl is not mutagenic in vitro in 
Page 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 DNA synthesis. Therefore, a quantitative cancer risk 

assessment is not required for chlorpyrifos methyl.

Table 3.2. Summary of Toxicological Doses 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

UFA = 10x

UFH = 10x

UFDB = 30x (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

UFA = 10x

UFH = 10x

UFDB = 30x (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 observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity 

among members of the human population (intraspecies). UFDB=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 neurodevelopmental 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 all 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-specific 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 effects.

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 formulated as an 

emulsifiable concentrate containing two active ingredients chlorpyrifos-methyl and deltamethrin 

(3.7%). The 21.6% EC may be applied to stored grains at 0.18 lb a.i/1,000 bushels to provide a 

concentration of 3 ppm of chlorpyrifos-methyl on stored grains. Deltamethrin, the other active 

ingredient in this registered end-use product, will be addressed in a separate assessment. 

Workers may be exposed to chlorpyrifos-methyl during mixing, loading, and applying activities 

associated with stored grains, bins and warehouses. Currently there are no registered uses of 

chlorpyrifos-methyl that could result in residential exposure. 

The use directions of the chlorpyrifos-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

StoricideTM 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] StoricideTM II

264-992

0.03 lbs ai/gallon

[all grains except 

oats]

500 gallons of 

spray 

solution/day for 

mechanically 

pressurized 

equipment;

20 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. StoricideTM 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 chlorpyrifos-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 chlorpyrifos-methyl is not registered on use sites 

that would result in spray drift. Therefore, a quantitative spray drift assessment was not 

conducted for chlorpyrifos-methyl.

7.0 Non-Occupational Bystander Post-Application 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 has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). 
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 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. 

Chlorpyrifos-methyl is currently registered for treatment of stored grain/seed and grain bins (See 

Section 4.0 for a detailed use pattern description). The quantitative exposure/risk assessment 

developed for occupational handlers is based on the following 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 automated 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 chlorpyrifos-methyl to the walls of 

empty grain storage containers 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 1000 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 Exposure Surrogate 

Reference Table2”, 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 website3.

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 day4.

The product label provides an application 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 sprayer and manually pressurized handwand – 20 gallons per day4

 Mechanically pressurized handwand – 500 gallons per day5

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 

pesticide, 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 OP pesticides involves a 

“single day” and “steady state” approach based on an individual chemical’s cholinesterase 

inhibition. The steady state approach is appropriate for chlorpyrifos-methyl given the 

toxicological and exposure profile. The “steady state” endpoint selection for chlorpyrifos-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 chlorpyrifos-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 

between the total volume assumed per day in HED’s default assumptions
Page 14 of 18

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 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 same 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 chlorpyrifos-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 applications 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 transfer 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 estimates were combined using the Combined MOE approach in this 

assessment, since the toxicological effects for these exposure routes were similar. Dermal and 

inhalation risk estimates were combined using the following formula:

Total MOE = Point of Departure (mg/kg/day) ÷ Combined Dermal + Inhalation dose (mg/kg/day)

Summary of Occupational Handler Non-Cancer Exposure and Risk Estimates

Table 6.1 presents 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 concerns 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 additional PPE. 

Specifically, the addition of additional dermal protection (e.g., coveralls) or a PF10 respirator (in 
Page 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 unclear 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 restrict 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 

Ratea

Amount 

Handled

Dermal Unit 

Exposureb

(ug/lb ai)

[Mitigation 

Level]

Inhalation 

Unit 

Exposureb

(mg/lb ai)

[Mitigation 

Level]

Dermal 

Dosec

(mg/kg/day)

Dermal 

MOEd

LOC = 

3,000

Inhalation 

Dosee

(mg/kg/day)

Inhalation 

MOEf

LOC = 

3,000

Total MOEg

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] 0.00281 360 0.0000165 61,000 350

Mixer/Loader/Applicator

Sprays using 

Mechanicallypressurized 

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 +

gloves]

0.78

[PF5 

Respirator]

0.0624 16 0.00017 5,900 16

Sprays using 

Manuallypressurized 

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.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

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

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

In addition, the Agency is continuing to evaluate the available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force. Given these two efforts, the 

Agency will continue to identify the need for and, subsequently, the way to incorporate 

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

In the case of chlorpyrifos-methyl, bystander exposure may be possible to dusts generated by 

treated grain being conveyed into, out of or within 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 activities. 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 bystander 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 to 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 avoid 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 = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

AR = maximum 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 absorbed in a given scenario (mg ai/kg/day),

E = exposure (mg ai/day),

AF = absorption factor (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 are compared to the appropriate POD (i.e., NOAEL) to assess 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 HED 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).