### Page 1 of 5 

## 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 chlorpyrifos 2 

### 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 Unive rsity 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 201 1 values to be considered for the remaining exposure scenarios.

Table App1

- 1 contains exposure estimates that would be predicted fo r 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 pe sticides 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 fa ctor 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 typic al 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 applicatio n 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

### Page 2 of 5 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

### Page 3 of 5 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

n umber 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. W orker 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 treate d 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 , a bsorbed 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 i n 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 mit igate 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
h igher 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 c hlorpyrifos 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 b ecause 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 work ers.

### Page 4 of 5 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

### Page 5 of 5 

## 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