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Appendix 1. Representative Exposure Estimates For Chlorpyrifos 

This appendix presents representative chlorpyrifos exposure and absorbed dose estimates for a number 

of residential and occupational scenarios in order to provide context for the discussions of 

pharmacokinetic modeling, adverse outcome pathways, and epidemiological research in this document. 

In most cases, the values have been excerpted from the 2011 risk assessment which was completed as 

part of the registration review process.1 In the others, values were excerpted from 2000 risk assessment 

which served as the basis for the reregistration decision for chlorpyrifos2 because it addressed the uses 

of chlorpyrifos in a residential environment that were removed as of late 2001. These are important to 

consider, however, because at the time epidemiological cohorts of interest were initiated while 

chlorpyrifos was still allowable in residential settings that would be reflective of their anticipated 

exposure patterns (e.g., Columbia University cohort of lower income women in New York City initiated 

in 1997). The remaining uses of chlorpyrifos have remained relatively stable since that time and risk 

assessment methods and inputs have evolved since 2000 so it is more appropriate for the 2011 values to 

be considered for the remaining exposure scenarios.

Table App1-1 contains exposure estimates that would be predicted for the general population including 

dietary intake estimates, estimates that represent the use of consumer products, and estimates that 

represent those living in areas which have been previously treated. Additional information is being 

developed that will impact how they are calculated (e.g., water treatment influence on residues). The 

values include dietary estimates of exposure to chlorpyrifos that can be thought of as what would be 

received on a high exposure day (i.e., acute exposure) or a more typical day (i.e., chronic exposure). 

These are based on dietary consumption information for the population and information that details 

possible chlorpyrifos residues in the food supply. The estimates for residential exposures reflects those 

associated with pesticides that can be used in an indoor environment. In this case, measures of dermal, 

inhalation, and oral exposures were calculated as well as associated absorbed dermal doses. Absorbed 

dermal doses were calculated using a 3 percent dermal absorption factor and it is assumed that all 

inhalation exposure can be absorbed (i.e., a 100% inhalation absorption which is protective in lieu of 

more definitive data). Risks are based on someone wearing shorts and a short sleeved shirt which are 

reflective of typical clothing that would be worn at home in the summer. Users are assumed to apply a 

can or less of typical homeowner pesticide product (e.g., 16 ounce volume and 1% or less 

concentration). Exposures that could have occurred from the residential application of a chlorpyrifos 

were determined by assuming that those who could be exposed were involved in high contact activities 

including adults exercising and children playing on the floor and putting their hands in their mouths. 

 1 www.regulations.gov docket ID EPA-HQ-OPP-2008-0850-0025 2 Smegal and Leighton (10/5/99) D259612
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Table App1-1: Dose Estimates Based on Passive Dosimetry Anticipated in the General Population to Chlorpyrifos

Activity Exposure Conditions

Chlorpyrifos (μg/kg/d)

Dermal 

Exposure On 

the Skin

Absorbed Dose 

From Dermal 

Exposure

Absorbed Dose From 

Inhalation Exposure

Absorbed Dose 

From Oral Exposure

Adults Applying Pest 

Control Products Indoors 

At Home (Source: 

Leighton & Smegal, 1999)

0.01 lb chlorpyrifos applied (entire 16 oz can 

containing 1 % active ingredient) 31.4 0.94 0.34 NA

0.005 lb chlorpyrifos applied (entire 16 oz can 

containing 0.5 % active ingredient) 15.7 0.47 0.17 NA

Adults Daily Activities On 

Carpeted Floor In 

Previously Treated Area 

(Source: Leighton & 

Smegal, 1999)

Based on the highest values observed in a study 

which monitored the air concentration and 

deposition of chlorpyrifos in 3 houses after a 

typical application of 0.5% chlorpyrifos spray for 

cockroach control

56.5 1.70

0.18

(1 day TWA)

0.15

(10 day TWA)

NA

Children

Playing On Carpeted Floor 

In Previously Treated Area

(Source: Leighton & 

Smegal, 1999)

53.4 1.60

0.76

(1 day TWA)

0.28

(10 day TWA)

1.67

Children

Dietary Exposure From 

Food Only

(Source: USEPA, 2011)

<1 yr old Chronic NA NA NA 0.016

Acute NA NA NA 0.190

1-2 yr old Chronic NA NA NA 0.034

Acute NA NA NA 0.323

3-5 yr old Chronic NA NA NA 0.027

Acute NA NA NA 0.275

Adults, Dietary Exposure 

From Food Only

(Source: USEPA, 2011)

Females

13-49 years old

Chronic NA NA NA 0.008

Acute NA NA NA 0.150
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Table App1-2 contains exposure estimates that would be predicted for workers involved with a variety 

of tasks. Workers may be involved in any facet of the application process such as mixing, loading, 

application itself or some combination of activities. Additionally, workers may be involved in any 

number of hand labor activities that are required in production agriculture that can occur in previously 

treated areas such as the hand harvest of fruit and vegetables, scouting for pest presence, or 

maintenance activities such as irrigation or weeding. Worker exposure has been predominantly 

demonstrated to be via the dermal route because product/sprays deposit on the skin during the 

application process and also because field workers contact treated foliage during hand labor activities in 

previously treated areas. Inhalation exposures are also calculated for those involved in application and 

they too can represent substantive exposures for certain scenarios. Like above with the residential 

exposures, absorbed dermal doses were calculated using a 3 percent dermal absorption factor and it is 

assumed that all inhalation exposure can be absorbed (i.e., a 100% inhalation absorption which is 

protective in lieu of more definitive data). Like with Table App1-1 above, the specific exposure condition 

is described in Table App1-2. One distinct difference between the exposure conditions in residential 

settings is that occupational exposures are based on workers wearing typical work clothing (long pants, 

long sleeved shirts, socks and shoes). If needed to further mitigate exposure, for those involved in 

applications, workers can also be required to wear additional clothing (i.e., coveralls, chemical resistant 

gloves) or use protective equipment such as respirators or engineering controls (e.g., closed loading 

systems). Chlorpyrifos labels require coveralls, gloves, and respirators be worn in addition to normal 

clothing. Field worker risks are also actively managed. Use of additional clothing and protective 

equipment is not viable in these settings for many reasons. As such, rather than use additional clothing 

or equipment risks are managed by precluding field labor activities until suitable time has passed to 

allow residues to dissipate to appropriate levels for each task of concern. For example, harvesting is a 

higher exposure activity than scouting immature plants because of the foliage level and level of contact 

with plants so the specified time to wait would be longer prior to entry into fields for harvesting (i.e., the 

Restricted Entry Interval or REI). For chlorpyrifos the days required before activities can occur varies 

based on the crop, application rate, and the type of activity. In many cases, crops themselves cannot be 

harvested after application for weeks which also precludes high harvester exposures because residues 

must dissipate prior to harvest. For activities other than harvest the label specifies REIs that range from 

24 hours to several days. The values presented in Table App1-2 reflect the current label requirements 

for risk mitigation for workers.
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Table App1-2: Dose Estimates Anticipated in Representative Occupational Populations To Chlorpyrifos

Activity Exposure Conditions

Chlorpyrifos (μg/kg/d)

Dermal 

Exposure On 

the Skin

Absorbed Dose 

From Dermal 

Exposure

Absorbed Dose From 

Inhalation Exposure

For Those Involved In Applications 

(All based on use of normal work clothing, chemical resistant gloves, respirator, and coveralls)

Mixing/loading liquid product for 

aerial spray applications

Application rate of 6 lb chlorpyrifos/acre

Treatment of 350 acres 873 26.2 0.66

Application to citrus grove

(CA/AZ)

Open cab tractor/airblast sprayer

Application rate of 3.5 lb chlorpyrifos/acre

Treatment of 80 acres

260 7.8 0.90

Application to field and seed corn

Open cab tractor/ground sprayer

Application rate of 3 lb chlorpyrifos/acre

Treatment of 200 acres

108 3.2 0.29

Application to utility & fence poles

High pressure handgun sprayer

Concentration of 0.17 lb chlorpyrifos/gallon

Treatment using 1000 gallons/day

3885 117 29.1

For Those Involved In Hand Labor Activities in Previously Treated Fields

(All based on use of normal work clothing)

Scouting & Pruning Citrus Application rate of 6 lb chlorpyrifos/acre

Activity conducted 5 days after application 7.28 0.218 NA

Scouting Strawberry Application rate of 1 lb chlorpyrifos/acre

Activity conducted 1 day after application 15.0 0.450 NA

Irrigating Mint Application rate of 2 lb chlorpyrifos/acre

Activity conducted 1 days after application 41.7 0.563 NA

Detasseling Corn Application rate of 1.5 lb chlorpyrifos/acre

Activity conducted 1 days after application 271 8.13 NA
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Appendix 2. AChE/ChE data in gestational studies

Table App2-1. Summary of repeated studies evaluating gestational exposure to maternal rats and fetuses.

Study Route

(vehicle)

Time of 

exposure

Time of 

measurement 

post-dosing

Dose Fetal

inhibition

Maternal

inhibition Compartment

Mattsson et 

al., 1998, 

2000

oral gavage

(corn oil) GD6-20 4 hrs 1 mg/kg/day

8% (NS) 10%/7% 

(p<0.02) forebrain 

0% 12%/7% (NS) hindbrain 

5% (NS) 87%/85% 

(p<0.02) RBC 

4% (NS) 77%/60% 

(p<0.02) plasma 

0% 49%/50% 

(p<0.02) heart 

Hoberman 

et al.,

1998a,b;

Maurissen 

et al., 2000

oral gavage 

(corn oil) GD6-20 4-5 hrs 1 mg/kg/day

N/A 68.9% plasma 

N/A 84.4% RBC 

N/A 17.9% brain 

Mattsson et 

al., 1998, 

2000

oral gavage

(corn oil) GD6-PND1 2 hrs 1 mg/kg/day

5% (NS) 6% (NS) forebrain 

0% 6% (NS) hindbrain 

0% 90% (p<0.02) RBC 

5% (NS) 80% (p<0.02) plasma

2% (NS) 40% (p<0.02) heart 

Qiao et al.,

2002

s.c. injection 

(DMSO) GD 17-20 GD 21 1 mg/kg/day

3% (NS) brainstem N/A

6% (NS) forebrain N/A