Fosthiazate Human Health Risk Assessment DP No. 405448 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: March 5, 2013 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Fosthiazate. Preliminary Human Health Risk Assessment for Registration 

Review 

PC Codei 129022 

Decision No.: NA 

Petition No.: NA 

Risk Assessment Type: Single 

Chemical/ Aggregate 

TXRNo.:NA 

MRIDNo.: NA 

DP Barcode: D405448 

Registration No.: NA 

Regulatory Action: Registration Review 

Case No.: 7604 

CAS No.: 98886-44-3 

40 CFR: 180.596 

FROM: Charles Smith, Senior Envirorunental Scientist/Risk Assess 

Risk Assessment Branch I 

Health Effects Division (7509P) 

and 

Donald Wilbur, Chemist 

Risk Assessment Branch VI 

Health Effects Division (7509P) 

THROUGH: Felecia Fort, Branch Chief ..f · ' p-.._ 1 ;S} rjJ "3 

Risk Assessment Branch VI ~U...O. 0 4 vr' l ~ Health Effects Division (7509P) 

TO: Khue Nguyen, Chemical Review Manager 

Risk Management and Implementation Branch I 

Pesticide Re-evaluation Division (7508P) 

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F osthiazate Human Health Risk Assessment DP No. 405448 

The Health Effects Division (HED) ofthe Office of Pesticide Programs (OPP) is charged with 

estimating the risk to human health from exposure to pesticides. As part of Registration Review, 

the Pesticide Re-evaluation Division (PRD) of OPP has requested that HED evaluate the hazard 

and exposure data and conduct dietary, occupational, residential, and aggregate exposure 

assessments, as needed, to estimate the risk to human health that will result from the registered 

uses of fosthiazate. 

HED has evaluated the toxicity and exposure databases for the active ingredient, fosthiazate, and 

has conducted a human health risk assessment in support of Registration Review. Based on this 

assessment, HED has determined that there are potential risk estimates of concern to 

mixer/loaders for the currently registered use of fosthiazate on tomatoes. 

A summary of the findings and an assessment of human health risk resulting from the currently 

registered uses of fosthiazate are provided in this document. The HED team members 

contributing to this risk assessment include Charles Smith (risk assessment) and Donald Wilbur 

(chemistry assessment). Keara Moore of the Environmental Fate and Effects Division (EFED) 

performed the drinking water assessment for fosthiazate. 

Page 2 of 18 
Fosthiazate Human Health Risk Assessment DP No. 405448

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

2.0 Ingredient Profile ....................................................................................................................... 6

2.1 Structure and Nomenclature................................................................................................... 6

2.2 Physical/Chemical Characteristics......................................................................................... 6

2.3 Summary of Existing Uses..................................................................................................... 6

2.4 Anticipated Exposure Pathways............................................................................................. 7

2.5 Consideration of Environmental Justice ................................................................................ 7

3.0 Hazard Characterization and Dose-Response Assessment........................................................ 7

3.1 Points of Departure and Toxicity Endpoints Used in Human Risk Assessment.................... 7

3.2 Endocrine Disruption ............................................................................................................. 9

4.0 Dietary Exposure and Risk Assessment .................................................................................. 10

4.1 Degradate Residue Profile.................................................................................................... 10

4.1.1 Summary of Environmental Degradation ..................................................................... 10

4.1.2 Residues of Concern Summary and Rationale.............................................................. 10

4.2 Food Residue Profile............................................................................................................ 11

4.3 Water Residue Profile .......................................................................................................... 11

4.4 Dietary Risk Assessment...................................................................................................... 12

4.4.1 Description of Residue Data Used in Dietary Assessment........................................... 12

4.4.2 Percent Crop Treated Used in Dietary Assessment ...................................................... 12

4.4.3 Acute Dietary Risk Assessment.................................................................................... 12

4.4.4 Chronic Dietary Risk Assessment ................................................................................ 12

4.4.5 Cancer Dietary Risk Assessment.................................................................................. 13

4.4.6 Dietary Risk Assessment Summary Table.................................................................... 13

5.0 Residential (Non-Occupational) Exposure/Risk Characterization .......................................... 13

6.0 Aggregate Exposure/Risk Characterization............................................................................. 14

7.0 Cumulative Exposure/Risk Characterization........................................................................... 14

8.0 Occupational Exposure/Risk Characterization ........................................................................ 14

8.1 Occupational Handler Exposure and Risk ........................................................................... 14

8.1.1 Short-/Intermediate-Term Non-Cancer Handler Exposure and Risk............................ 15

8.2 Occupational Postapplication Exposure and Risk................................................................ 16

8.2.1 Postapplication Inhalation Exposure............................................................................. 16

9.0 References................................................................................................................................ 17

Appendix A: Review of Human Research.......................................................................................... 18
Fosthiazate Human Health Risk Assessment DP No. 405448

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1.0 Executive Summary

As part of Registration Review, the Pesticide Re-evaluation Division (PRD) of the Office of 

Pesticide Programs (OPP) has requested that the Health Effects Division (HED) evaluate the 

hazard and exposure data and conduct dietary, occupational, residential, and aggregate exposure 

assessments, as needed, to estimate the risk to human health that will result from the registered

uses of fosthiazate. A summary of the findings and an assessment of human health risk resulting 

from the currently registered uses of fosthiazate are provided in this document.

Use Profile: Fosthiazate is an organophosphate (OP) nematicide and insecticide that is currently 

registered as a liquid formulation for drip irrigation use on tomatoes.

Hazard Assessment: The toxicology database for fosthiazate is complete as described in 40 

CFR, Part 158. Overall, the studies available for consideration of fosthiazate toxicity provide a 

comprehensive database. Like other OPs, fosthiazate causes neurotoxicity through the inhibition 

of acetylcholinesterase leading to changes in clinical signs and behavior. The FQPA Safety 

Factor for fosthiazate was reduced to 1X since available data indicate that fetuses and juvenile 

rats are not more sensitive than adult rats.

Dietary Exposure (Food and Drinking Water): The residue chemistry data and environmental 

fate data are adequate to assess human exposure. Estimated drinking water concentrations 

(EDWCs) were generated by the Environmental Fate and Effects Division (EFED) using 

computer modeling methods. The highest surface water EDWCs values are 75.2 ppb (1-in-10 

year acute) and 7.8 ppb (1-in-10 year annual average). The groundwater EDWC value was 0.04 

ppb.

Acute: A slightly refined acute dietary exposure assessment was performed that directly 

incorporated potential drinking water residues. The estimated exposure to the highest population 

subgroup (all infants < 1 year old) resulted in an estimated risk of 15% of the acute population 

adjusted dose (aPAD). The estimated exposure to the general U.S. population resulted in an 

estimated risk of 5.6% of the acute population adjusted dose (aPAD).

Chronic: An unrefined chronic dietary exposure assessment was performed that directly 

incorporated potential drinking water residues. The estimated exposure to the highest population 

subgroup (all infants < 1 year old) resulted in an estimated risk of 45% of the chronic population 

adjusted dose (cPAD). The estimated exposure to the general U.S. population resulted in an 

estimated risk of 19% of the chronic population adjusted dose (cPAD). 

Residential Exposure: There are currently no registered residential uses associated with 

fosthiazate; therefore, a residential/non-occupational exposure assessment is not required. 

Aggregate Risk: Aggregate risk assessments evaluate the combined risk from dietary exposure 

(food and water) and any non-occupational (residential) uses. There are currently no registered 

residential uses associated with fosthiazate; therefore, a residential/non-occupational exposure 

assessment is not required. As a result, the fosthiazate aggregate risk assessment includes only 
Fosthiazate Human Health Risk Assessment DP No. 405448

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dietary exposure (food and water). The acute and chronic dietary exposure estimates from food 

and drinking water do not exceed HED’s level of concern.

Occupational Exposure/Risk: Occupational handler exposures to the existing uses of 

fosthiazate may occur via the dermal and inhalation route. The short- and intermediate-term risk 

estimates for all occupational handler scenarios exceed HED’s level of concern (Margins of 

Exposure or MOEs < 100) even with the use of engineering controls.

Occupational postapplication exposures are not expected based on the currently registered uses 

of fosthiazate. Fosthiazate is applied to the soil prior to planting. HED expects that 

postapplication exposure to fosthiazate soil will be negligible and thus an occupational 

postapplication exposure assessment is not required.

Review of Human Research: 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 studies 

(listed in Appendix A) have been determined to require a review of their ethical conduct and all 

of the studies utilized in this assessment have received the appropriate review.
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2.0 Ingredient Profile

Fosthiazate is an organophosphate nematicide and insecticide that is currently registered for use 

on tomatoes.

2.1 Structure and Nomenclature

Table 2.1: Fosthiazate Nomenclature

Chemical Structure

Fosthiazate: O-Ethyl S-(1-methylpropyl)(2-oxo-3-thiazolidinyl)phosphonothioate

ASC-67131: (RS)-S-sec-Butyl O-ethyl N-[2-(methylsulfonyl)ethyl] phosphoramidothioate

IUPAC name (RS)-[S-(RS)-sec-butyl O-ethyl 2-oxo-1,3-thiazolidin-3-ylphosphonothioate]

CAS Name O-ethyl S-(1-methylpropyl) P-(2-oxo-3-thiazolidinyl)phosphonothioate

CAS Registry Number 98886-44-3

2.2 Physical/Chemical Characteristics

Fosthiazate’s vapor pressure (2.7 x 10-6 mm Hg) and Henry's Law Constant (1.76 X 10-05 Pa m3

mol-1) indicate that the compound is relatively non-volatile under field conditions. It is generally 

considered to be moderately persistent in water and soil. In two studies, fosthiazate was found to 

have low sorption to soil and has been classified as mobile to moderately mobile. Based on the 

use pattern and environmental fate parameters, there is the potential for fosthiazate to reach 

water resources.

2.3 Summary of Existing Uses

Fosthiazate is formulated as an emulsifiable concentrate (EC) at 75% active ingredient (ai) and 

47.2% ai. The product has the trade names; FOSTHIAZATE 900EC (71512-4), 

NEMATHORIN 500EC (71512-5), and FOSTHIAZATE 75%EC (71512-17). Tomatoes are 

the only currently registered use site. Applications are made once per season, either prior to or 

at transplanting for tomatoes. It may only be applied through drip (trickle) irrigation systems. 

The maximum application rate is 1.5 lb a.i. /acre and the label restricts applicators to treating 

only 25 acres per day.

According to a Biological and Economic Analysis Division (BEAD) memo (R. Prieto, 

01/30/2012), there is no reported usage of fosthiazate seen in any of the available usage 

databases, including the USDA-NASS (United States Department of Agriculture's National 

Agricultural Statistics Service); private pesticide market research pesticide usage data from 2001 

N

P

S

O

CH3

CH3

OC2H5

S

O

H3C

S

N

H

P

S

O

OC2H5

CH3

CH3

O

O
Fosthiazate Human Health Risk Assessment DP No. 405448

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to 2008; and the California Department of Pesticide Regulation (DPR) Pesticide Use Reporting 

(PUR) system.

2.4 Anticipated Exposure Pathways

Humans may be exposed to fosthiazate in their diet resulting from residues present in foods 

treated with fosthiazate. Further, given the environmental fate parameters of fosthiazate and the 

registered agricultural uses, the potential exists for fosthiazate to reach water resources resulting 

in potential residues in drinking water. There are currently no residential uses of fosthiazate, so 

exposure in residential and non-occupational settings is not likely. There is a potential for 

occupational handler exposures.

2.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations,” 

(http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf. As a part of every pesticide risk 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture’s National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a 

pesticide. These data are analyzed and categorized by subgroups based on age and ethnic group. 

Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and 

exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

postapplication are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

3.0 Hazard Characterization and Dose-Response Assessment

3.1 Points of Departure and Toxicity Endpoints Used in Human Risk Assessment

HED updated the hazard characterization and endpoint selection for fosthiazate in 2008 (J. 

Facey; TXR0054845; 06/02/2008). The 2008 document incorporated new fosthiazate 

toxicological studies in adults and juvenile rats describing the time- course and dose-response for 

brain and red blood cell (RBC) cholinesterase (ChE) inhibition. These studies included the 

following: 1) a comparative cholinesterase assessment (CCA) study in which ChE activity was 

measured following gestational exposure, describing time of peak effect, and following acute 
Fosthiazate Human Health Risk Assessment DP No. 405448

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exposures (postnatal day, PND 11, 42) and repeated exposures (PND 11-21 and 42-52) and 2) a 

28 day inhalation toxicity study with blood and brain ChE measurements.

Overall, the studies available for consideration of fosthiazate toxicity provide a comprehensive 

database. Like other OPs, fosthiazate causes neurotoxicity through the inhibition of 

acetylcholinesterase leading to changes in clinical signs and behavior. The FQPA Safety Factor

for fosthiazate was reduced to 1X since available data indicate that fetuses and juvenile rats are 

not more sensitive than adult rats.

No new toxicological data have been submitted to the Agency since the 2008 document. As a 

result no changes to the fosthiazate endpoints or hazard characterization were required for 

Registration Review. Tables 3.1.1 and 3.1.2 provide the toxicological doses and endpoints for 

use in fosthiazate dietary and occupational assessments, respectively.

Table 3.1.1: Toxicological Doses and Endpoint for Use in Fosthiazate Dietary Human Health Risk 

Assessments

Exposure Scenario Point of 

Departure 

Uncertainty/FQPA 

Safety Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(Children)

0.65 mg/kg/day UFA= 10x

UFH= 10x

FQPA SF = 1x

Acute RfD= 0.0065

aPAD= 0.0065

Comparative Cholinesterase Rat 

Study (MRID 46744902)

BMD10=1.26 mg/kg/day and 

BMDL10 = 0.65 mg/kg/day, 

based on RBC ChE inhibition in 

postnatal day 11 (PND 11) pups

Acute Dietary

(Adults)

0.87 mg/kg/day UFA= 10x

UFH= 10x

FQPA SF = 1x

Acute RfD= 0.0087

aPAD= 0.0087

Comparative Cholinesterase Rat 

Study (MRID 46744902)

BMD10=1.29 mg/kg/day and 

BMDL10 = 0.87 mg/kg/day, 

based on RBC ChE inhibition in 

young adult rats following acute 

exposure 

Chronic Dietary

(all populations)

0.096 mg/kg/day UFA= 10x

UFH= 10x

FQPA SF = 1x

Chronic RfD= 

0.00096

aPAD= 0.00096

Comparative Cholinesterase Rat 

Study (MRID 46744902)

BMD10= 0.10 mg/kg/day and 

BMDL10 = 0.096 mg/kg/day, 

based on RBC ChE inhibition in 

young adult rats exposed for 11 

days

Cancer (oral, dermal, 

inhalation)

Classification: “Not likely to be carcinogenic to humans.” 

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect 

level, PAD = population adjusted dose (a = acute, c = chronic), RfD = reference dose, LOC = level of concern, NA = Not Applicable. UFA= 

extrapolation from animal to human (interspecies), UFH = potential variation in sensitivity among members of the human population 

(intraspecies).
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Table 3.1.2: Toxicological Doses and Endpoint for Use in Fosthiazate Occupational Human Health 

Risk Assessments

Exposure Scenario Point of Departure Uncertainty/FQPA 

Safety Factors

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Dermal

(short and 

intermediate term)

0.44 mg/kg/day UFA= 10x

UFH= 10x

MOE = 100 21 Day Dermal Rat study 

(MRID 43916806) BMD10= 1.00

mg/kg/day and BMDL10 = 0.44

mg/kg/day, based on RBC ChE 

inhibition in rats (females)

Inhalation (short and 

intermediate term)

0.0025 mg/kg/day UFA= 10x

UFH= 10x

MOE = 100 28 Day Inhalation study (MRID 

46744901) BMD10= 0.0047 

mg/kg/day and BMDL10 = 

0.0025 mg/kg/day, based on 

RBC ChE inhibition in rats 

Cancer (oral, dermal, 

inhalation)

Classification: “Not likely to be carcinogenic to humans.” 

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect 

level, PAD = population adjusted dose (a = acute, c = chronic), RfD = reference dose, LOC = level of concern, NA = Not Applicable. UFA= 

extrapolation from animal to human (interspecies), UFH = potential variation in sensitivity among members of the human population 

(intraspecies).

3.2 Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of registration review, EPA will review these data and select the most 

sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. 

However, as required by FFDCA section 408(p), fosthiazate is subject to the endocrine screening 

part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 
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Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. In November 

of 2010, issued test orders/data call-ins for the second group of 134 chemicals, which contains 51

pesticide active ingredients. Fosthiazate is not among the 109 pesticide active ingredients on the 

first and second lists to be screened under the EDSP. For further information on the status of the 

EDSP, the policies and procedures, the list of chemicals, future lists, the test guidelines and the 

Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/.

4.0 Dietary Exposure and Risk Assessment

4.1 Degradate Residue Profile

4.1.1 Summary of Environmental Degradation

Based on laboratory studies, fosthiazate is expected to degrade slowly in the environment, with 

the major routes of dissipation being aerobic soil and anaerobic aquatic soil metabolisms with 

half-lives of approximately 45 and 37 days, respectively. Under alkaline conditions, fosthiazate 

may also dissipate quite rapidly via hydrolysis with a half-life of less than 1 week. Photodegradation in water is not significant.

Although mobile in all soils tested under laboratory conditions, in the field fosthiazate residues 

were seen to remain mostly on the surface soils. Insignificant amounts of residues (< 10% of 

total applied) were found in the deeper 15-30 cm. soil layers, and no residues were found in soil 

below the 30 cm. layer. Fosthiazate’s half-life ranged from 10-17 days in the avaialbel terrestrial 

field dissipation studies.

4.1.2 Residues of Concern Summary and Rationale

The HED Metabolism Assessment Review Committee (MARC) considered the available data on 

the nature and magnitude of residues in fosthiazate and has concluded that for plants, the parent 

compound and its ASC-67131 metabolite should be included for tolerance enforcement and 

dietary risk assessment (S. Kinard; D285024; 08/27/2002). There are no significant animal 

feedstuffs associated with the current use pattern, so the committee had no recommendation on 

residues of concern in livestock. For drinking water, the MARC recommended including the 

parent compound only for risk assessment. The residues of concern for fosthiazate are 

summarized in Table 4.1.2.

Table 4.1.2: Summary of Metabolites and Degradates to be included in the Risk 

Assessment and Tolerance Expression for Fosthiazate

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants Primary Crop Parent, ASC-67131 Parent, ASC-67131

Rotational Crop Parent, ASC-67131 Parent, ASC-67131

Livestock Ruminant NA NA

Poultry NA NA

Drinking Water Parent only NA
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4.2 Food Residue Profile

The submitted data on the metabolism of fosthiazate in potato, peach, and tomato demonstrate 

that residues are generally low, but do translocate throughout the plants. The highest residues 

are generally found in the foliage (leaves and stems), and not in the fruit (edible portion) of the 

commodity. Field trial data submitted for tomato showed no quantifiable residues of fosthiazate

in any tomato sample.

Adequate residue chemistry data have been provided for fosthiazate. Field trials are of adequate 

number and geographic representation, were generated using adequate analytical methods and 

are supported by adequate storage stability data. Adequate studies were submitted for tomato to 

elucidate the fate of fosthiazate in processed commodities. The Agency has determined that the 

current use of fosthiazate on tomato does not have any associated animal feedstuffs and therefore

no exposure from animal commodities is expected. Confined rotational crops studies show that 

the metabolism of fosthiazate in rotated crops is similar to that in primary crops. The available 

field trial data for fosthiazate in/on tomato indicate that following application via drip irrigation 

at 4 and 6 lb a.i./A, residues of fosthiazate and its metabolite ASC-67131 were below the LOQ 

(<0.01 ppm each) in/on all tomato samples. 

4.3 Water Residue Profile

Estimated drinking water concentrations (EDWCs) for fosthiazate (K. Moore; D340347 and 

D340348; 02/26/2008) were previously generated by the Environmental Fate and Effects 

Division (EFED). The fosthiazate concentrations in surface water were simulated in an Index 

Reservoir, with 30 years of scenario specific weather data, using the linked PRZM (v3.12.2, May 

12, 2005) and EXAMS (v2.98.04.06, April 25, 2005) models with a national default PCA of 

0.87. Estimated groundwater EDWCs were calculated using the screening model SCI-GROW 

(Screening Concentrations in Ground Water, version 2.3, 07/29/03). Additional information 

about model assumptions and uncertainties, input guidance, and scenario metadata are available 

at the Agency’s water modeling website, http://www.epa.gov/oppefed1/models/water/.

The modeling was conducted using application of fosthiazate to tomatoes by ground spray, 

banded application, or through drip irrigation at a maximum application rate of 4.5 lb a.i./A, with 

all methods requiring either incorporation to 4 inches or cover with plastic mulch. It is important 

to note that the currently labeled use rate is only 1.5 lbs a.i./A and thus the EDWCs calculated by 

EFED should be considered highly conservative. The recommended fosthiazate EDWCs for the 

human health risk assessment are summarized in Table 4.3.

Table 4.3: Maximum EDWCs (μg/L) from proposed uses of fosthiazate applied as 

ground spray, corrected for Percent Cropped Area

Surface Water a Groundwater b

Use Acute

[1-in-10 year peak]

Chronic

[1-in-10 year average]

Cancer Chronic

[30-year average] Acute and Chronic

Tomato 75.2 7.8 3.4 1.8

a Generated using Tier II linked simulation models PRZM (3.12.2) /EXAMS (2.98.04.06).

b Generated using Tier I model SCIGROW (2.3). 

EDWCs used for acute and chronic dietary exposure assessments are bolded
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4.4 Dietary Risk Assessment

Fosthiazate acute and chronic dietary risk assessments were conducted using the Dietary 

Exposure Evaluation Model DEEM-FCIDTM, Version 3.16 which uses food consumption data 

from the U.S. Department of Agriculture’s National Health and Nutrition Examination Survey, 

What We Eat in America, (NHANES/WWEIA)

4.4.1 Description of Residue Data Used in Dietary Assessment

Fosthiazate tolerance level residue inputs (combined parent and metabolite ASC-67131) were 

used to estimate the acute and chronic dietary risk for all commodities included in the 

assessment. DEEM default processing factors were used for all processed tomato commodities 

with the exception of tomato juice and puree. A 30-year water distribution of daily values was 

used as the input for indirect and direct drinking water exposure in the acute assessment, and the 

1 in 10 year point estimate average drinking water value was used as the input for indirect and 

direct drinking water exposure for the chronic assessment (D340347 and D340348, Moore, 

02/26/2008).

4.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and chronic dietary risk assessment assumed 100% crop treated for all commodities 

included in the assessment.

4.4.3 Acute Dietary Risk Assessment

A slightly refined acute dietary risk assessment was conducted which used tolerance level 

residues, 100% crop treated (% CT) for all commodities, DEEM default and empirical 

processing factors, and a distribution of modeled drinking water estimates from the Tier II 

PRIZM-EXAMS model. This conservative exposure assessment showed no risks of concern 

(<100% of the acute population adjusted dose (aPAD)) for the U.S. General Population or any 

subpopulation at the 95th percentile of exposure. The estimated exposure to the U.S. General 

Population resulted in a risk estimate equivalent to 5.5% of the aPAD. The estimated exposure 

to all infants, the most highly exposed subpopulation, resulted in a risk estimate equivalent to 

15% of the aPAD. Results for all subpopulations are summarized in Table 4.4.6 below.

4.4.4 Chronic Dietary Risk Assessment

An unrefined chronic dietary risk assessment was conducted which used tolerance level residues, 

100% crop treated (% CT) for all commodities, DEEM default and empirical processing factors, 

and an average drinking water estimate from the Tier II PRIZM-EXAMS model. This highly 

conservative risk assessment showed no risks of concern (<100% of the chronic population 

adjusted dose (cPAD)) for the U.S. General Population or any subpopulation. The estimated 

exposure to the U.S. General Population resulted in a risk estimate equivalent to 19% of the 

cPAD. The estimated exposure to all infants, the most highly exposed subpopulation, resulted in 

a risk estimate equivalent to 45% of the cPAD. Results for all subpopulations are summarized 

in Table 4.4.6 below.
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4.4.5 Cancer Dietary Risk Assessment

The Agency has classified fosthiazate as “Not likely to be carcinogenic to humans”; therefore, a 

cancer assessment was not performed.

4.4.6 Dietary Risk Assessment Summary Table

Table 4.4.6: Summary of Dietary (Food and Drinking Water) 

Exposure and Risk for Fosthiazate

Population Subgroup

Acute Dietary

(95th Percentile) Chronic Dietary

Dietary 

Exposure 

(mg/kg/day)

% aPAD

Dietary 

Exposure

(mg/kg/day)

% cPAD

General U.S. Population 0.000361 5.6 0.000184 19

All Infants (< 1 year old) 0.000948 15 0.000435 45

Children 1-2 years old 0.000534 8.2 0.000278 29

Children 3-5 years old 0.000498 7.7 0.000244 25

Children 6-12 years old 0.000348 5.4 0.000173 18

Youth 13-19 years old 0.000273 4.2 0.000139 14

Adults 20-49 years old 0.000357 5.5 0.000182 19

Adults 50+ years old 0.000342 5.3 0.000177 18

Females 13-49 years old 0.000356 5.5 0.000180 19

* Most highly exposed subpopulation is highlighted in bold.

5.0 Residential (Non-Occupational) Exposure/Risk Characterization

There are currently no registered residential uses associated with fosthiazate; therefore, a 

residential/non-occupational exposure assessment is not required. 

5.1 Spray Drift

Spray drift is not likely for fosthiazate as drip irrigation is the only application method allowable 

on the current fosthiazate labels.

5.2 Inhalation Postapplication Exposure

Based on the Agency's current practices, a quantitative residential postapplication inhalation 

exposure assessment was not performed for fosthiazate at this time primarily because 

fosthiazate’s vapor pressure (4.20X10-6 mm Hg at 25 deg C) and Henry's Law Constant (1.76 X 

10-05, Pa m3 mol-1) indicate that the compound is relatively non-volatile under field conditions. 

However, volatilization of pesticides may be a potential source of postapplication 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 is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 
Fosthiazate Human Health Risk Assessment DP No. 405448

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identify the need for and, subsequently, the way to incorporate postapplication inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative postapplication inhalation exposure assessment 

for fosthiazate.

6.0 Aggregate Exposure/Risk Characterization

Aggregate risk assessments evaluate the combined risk from dietary exposure (food and water) 

and any non-occupational (residential) uses. There are currently no registered residential uses 

associated with fosthiazate; therefore, a residential/non-occupational exposure assessment is not 

required. As a result, the fosthiazate aggregate risk assessment includes only dietary exposure 

(food and water). The acute and chronic dietary exposure estimates from food and drinking 

water do not exceed HED’s level of concern (see Sections 4.4.3 and 4.4.4).

7.0 Cumulative Exposure/Risk Characterization

The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative risks of 

chemicals sharing a common mechanism of toxicity. Fosthiazate is a member of the 

organophosphate common mechanism group. The most recent cumulative risk assessment for the 

organophosphates was published on July 31, 2006 and is available at 

http://www.epa.gov/pesticides/cumulative/2006-op/op_cra_main.pdf.

As discussed above in Section 2.3, according to a BEAD memo (R. Prieto, 01/30/2012), there is 

no reported usage of fosthiazate seen in any of the available usage databases. In addition, the 

available field trial data for fosthiazate in/on tomato indicate that following application via drip 

irrigation, residues of fosthiazate and its metabolite ASC-67131 were below the LOQ (<0.01 

ppm each) in/on all tomato samples. Thus, based on the current use pattern and available residue 

data, fosthiazate will not contribute exposure to the organophosphate cumulative risk assessment.

8.0 Occupational Exposure/Risk Characterization

Fosthiazate is currently registered for use as in drip irrigation equipment on tomatoes. Based on 

the existing use pattern for fosthiazate, there is potential for occupational handler exposure to 

occur.

8.1 Occupational Handler Exposure and Risk

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 protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

Based on the currently registered use patterns and types of equipment and techniques that can 

potentially be used, occupational handler exposure is expected for fosthiazate. The quantitative 
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exposure/risk assessment developed for occupational handlers is based on the following 

scenarios: 

1) Mixing/loading liquids for drip irrigation.

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic occupational handler data, used as surrogate data in the absence of chemical-specific 

data, include the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1), the 

Agricultural Handler Exposure Task Force (AHETF) database, the Outdoor Residential 

Exposure Task Force (ORETF) database, or other registrant-submitted occupational exposure 

studies. 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 occupational 

handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the 

“Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” 

(http://www.epa.gov/opp00001/science/handler-exposure-table.pdf), which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at http://www.epa.gov/pesticides/science/handler-exposuredata.html.

8.1.1 Short-/Intermediate-Term Non-Cancer Handler Exposure and Risk

Handler exposure is expected to be short- or intermediate-term in duration based on information 

provided on the proposed labels. The short- and intermediate-term toxicological endpoints are 

the same for the respective routes of exposure; therefore, the estimates of risk for short-term 

duration exposures are protective of those for intermediate-term durations. Long-term exposures 

are not expected; therefore, a long-term assessment was not conducted. 

Short- and intermediate-term occupational handler exposure and risks were estimated using 1) 

unit exposures taken from the “Occupational Pesticide Handler Unit Exposure Surrogate 

Reference Table”; 2) the maximum fosthiazate label application rates; and 3) acres treated value 

taken from the current fosthiazate labels as the label restricts applicators to treating a maximum 

of 25 acres per day. HED notes that the current fosthiazate labels require long sleeves, long 

pants, chemical resistant gloves, chemical resistant footwear, and protective eyewear to be worn 

when handling this chemical. In addition, a chemical resistant apron is required to be worn 

during mixing/loading or equipment cleaning activities.
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Table 8.1.1 presents the estimated dermal, inhalation, and combined non-cancer occupational 

handler risk estimates for the currently registered uses of fosthiazate. The short- and 

intermediate-term combined risk estimates for all occupational handler scenarios exceed HED’s 

level of concern (MOEs < 100) even with the use of engineering controls.

Table 8.1.1: Summary of Occupational Handler Short- and Intermediate-term Total MOEs

Exposure Scenario Crop or 

Target

Application 

Rate a

Area 

Treated 

Daily 

Total Dermal + Inhalation MOEs b

Baseline G + 

NR

G,DL 

+ NR

G + 

80%-R

G + 

90%-R

G,DL + 

80%-R

G,DL + 

90%-R

EC

Mixer/Loader

Mixing/Loading Emulsifiable 

Concentrates for Drip Irrigation 

Applications (PHED)

Tomatoes 1.5 lb ai/A 25 A 3.6 12 14 21 25 23 28 40

a Application Rates are based on the maximum application rates listed on the current fosthiazate labels.

b Total MOE (combined dermal and inhalation) = 1 / ((1/dermal MOE) + (1/inhalation MOE))

Baseline = long sleeve shirt, long pants, and chemical resistant footwear

G + NR = baseline PPE plus gloves, no respirator

G, DL + NR = baseline PPE plus gloves and coveralls, no respirator

G + 80%-R = baseline PPE plus gloves, dust-mist respirator

G, DL + 80%-R = baseline PPE plus gloves and coveralls, dust-mist respirator

G + 90%-R = baseline PPE plus gloves, organic vapor respirator

G, DL + 90%-R = baseline PPE plus gloves and coveralls, organic vapor respirator

EC = engineering controls

8.2 Occupational Postapplication Exposure and Risk

Occupational postapplication exposures are not expected based on the currently registered uses 

of fosthiazate. Fosthiazate is applied to the soil prior to planting. HED expects that 

postapplication exposure to fosthiazate soil will be negligible and thus an occupational 

postapplication exposure assessment is not required.

8.2.1 Postapplication Inhalation Exposure

Based on the Agency's current practices, a quantitative residential postapplication inhalation 

exposure assessment was not performed for fosthiazate at this time primarily because 

fosthiazate’s vapor pressure (4.20X10-6 mm Hg at 25 deg C) and Henry's Law Constant (1.76 X 

10-05, Pa m3 mol-1) indicate that the compound is relatively non-volatile under field conditions. 

However, there are multiple potential sources of post-application inhalation exposure to 

individuals performing post-application activities in previously treated fields. 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 is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force and may, as appropriate, develop policies 

and procedures, to identify the need for and, subsequently, the way to incorporate occupational 

post-application inhalation exposure into the Agency's risk assessments. If new policies or 

procedures are put into place, the Agency may revisit the need for a quantitative occupational 

post-application inhalation exposure assessment for fosthiazate.
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9.0 References

Metabolism Assessment Review Committee (MARC) Memo for Fosthiazate, D285024, S. 

Kinard, 08/27/2002

Fosthiazate EFED Drinking Water Memo, D340347 and D340348, K. Moore, 02/26/2008
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Appendix A: Review of Human Research

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 studies, which comprise the 

Pesticide Handlers Exposure Database (PHED), the Outdoor Residential Exposure Task Force 

(ORETF) Database, the Agricultural Handler Exposure Task Force (AHETF), and the 

Agricultural Reentry Task Force (ARTF) have been determined to require a review of their 

ethical conduct, have received that review, and have been determined to be ethically conducted.