UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460 

OFFICE OF 

PREVENTION, PESTICIDES AND TOXIC 

SUBSTANCES 

MEMORANDUM

DATE: July 31, 2006 

SUBJECT: Finalization of Interim Reregistration Eligibility Decisions (IREDs) and Interim 

Tolerance Reassessment and Risk Management Decisions (TREDs) for the 

Organophosphate Pesticides, and Completion of the Tolerance Reassessment and 

Reregistration Eligibility Process for the Organophosphate Pesticides 

FROM: Debra Edwards, Director 

Special Review and Reregistration Division 

Office of Pesticide Programs 

TO: Jim Jones, Director 

Office of Pesticide Programs 

As you know, EPA has completed its assessment of the cumulative risks from the 

organophosphate (OP) class of pesticides as required by the Food Quality Protection Act of 

1996. In addition, the individual OPs have also been subject to review through the individualchemical review process. The Agency’s review of individual OPs has resulted in the issuance of 

Interim Reregistration Eligibility Decisions (IREDs) for 22 OPs, interim Tolerance 

Reassessment and Risk Management Decisions (TREDs) for 8 OPs, and a Reregistration 

Eligibility Decision (RED) for one OP, malathion.1

 These 31 OPs are listed in Appendix A. 

EPA has concluded, after completing its assessment of the cumulative risks associated 

with exposures to all of the OPs, that: 

(1) the pesticides covered by the IREDs that were pending the results of the OP 

cumulative assessment (listed in Attachment A) are indeed eligible for reregistration; and 

 

Page 1 of 3 

1 Malathion is included in the OP cumulative assessment. However, the Agency has issued a RED for malathion, 

rather than an IRED, because the decision was signed on the same day as the completion of the OP cumulative 

assessment. 
Page 2 of 3 

(2) the pesticide tolerances covered by the IREDs and TREDs that were pending the 

results of the OP cumulative assessment (listed in Attachment A) meet the safety standard under 

Section 408(b)(2) of the FFDCA. 

 

Thus, with regard to the OPs, EPA has fulfilled its obligations as to FFDCA tolerance 

reassessment and FIFRA reregistration, other than product-specific reregistration. 

The Special Review and Reregistration Division will be issuing data call-in notices for 

confirmatory data on two OPs, methidathion and phorate, for the reasons described in detail in 

the OP cumulative assessment. The specific studies that will be required are: 

− 28-day repeated-dose toxicity study with methidathion oxon; and 

− Drinking water monitoring study for phorate, phorate sulfoxide, and phorate sulfone 

in both source water (at the intake) and treated water for five community water 

systems in Palm Beach County, Florida and two near Lake Okechobee, Florida. 

The cumulative risk assessment and supporting documents are available on the Agency’s website 

at www.epa.gov/pesticides/cumulative and in the docket (EPA-HQ-OPP-2006-0618). 
Page 3 of 3 

Attachment A: 

Organophosphates included in the OP Cumulative Assessment 

Chemical Decision Document Status 

Acephate IRED IRED completed 9/2001 

Azinphos-methyl (AZM) IRED IRED completed 10/2001 

Bensulide IRED IRED completed 9/2000 

Cadusafos TRED TRED completed 9/2000 

Chlorethoxyphos TRED TRED completed 9/2000 

Chlorpyrifos IRED IRED completed 9/2001 

Coumaphos TRED TRED completed 2/2000 

DDVP (Dichlorvos) IRED IRED completed 6/2006 

Diazinon IRED IRED completed 7/2002 

Dicrotophos IRED IRED completed 4/2002 

Dimethoate IRED IRED completed 6/2006 

Disulfoton IRED IRED completed 3/2002 

Ethoprop IRED IRED completed 9/2001 

IRED addendum completed 2/2006 

Fenitrothion TRED TRED completed 10/2000 

Malathion RED RED completed 8/2006 

Methamidophos IRED IRED completed 4/2002 

Methidathion IRED IRED completed 4/2002 

Methyl Parathion IRED IRED completed 5/2003 

Naled IRED IRED completed 1/2002 

Oxydemeton-methyl IRED IRED completed 8/2002 

Phorate IRED IRED completed 3/2001 

Phosalone TRED TRED completed 1/2001 

Phosmet IRED IRED completed 10/2001 

Phostebupirim TRED TRED completed 12/2000 

Pirimiphos-methyl IRED IRED completed 6/2001 

Profenofos IRED IRED completed 9/2000 

Propetamphos IRED IRED completed 12/2000 

Terbufos IRED IRED completed 9/2001 

Tetrachlorvinphos TRED TRED completed 12/2002 

Tribufos IRED IRED completed 12/2000 

Trichlorfon TRED TRED completed 9/2001 

 
United States Prevention, Pesticides EPA 738-R-00-012

Environmental Protection And Toxic Substances October 2000

Agency (7508C)

Report on FQPA Tolerance

Reassessment Progress

and Interim Risk 

Management Decision 

 for 

 Fenitrothion
UNITED STATES ENVIRONMENTAL PROTECTION AGE

WASHINGTON, D.C. 20460

OFFICE OF 

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

CERTIFIED MAIL July 5, 2000

Dear Registrant:

This is to inform you that the Environmental Protection Agency (hereafter referred to as EPA or

the Agency) has completed its review of the available data and public comments received concerning

the revised risk assessment for the organophosphate pesticide fenitrothion. The public comment period

on the revised risk assessment phase of the tolerance reassessment process is closed. The attached

document summarizes the Agency’s assessment of dietary risk from fenitrothion as part of the tolerance

reassessment process for this chemical, presents a summary of the revised food tolerances for

fenitrothion, and provides the Agency’s current risk management position, based on the risk

assessment. Fenitrothion is not registered for use on food or feed crops in the U.S. It has only one

import tolerance, for wheat gluten imported from Australia, and the dietary risk analysis indicates that

the risk is below the Agency’s level of concern. Therefore, no mitigation is necessary at this time. 

A Notice of Availability for this “Report on FQPA Tolerance Reassessment Progress

and Interim Risk Management Decision for Fenitrothion” will be published in the Federal Register. 

This document and supporting technical documents are available for viewing in the Office of Pesticide

Programs' Public Docket and can also be found on the Agency’s web page, "www.epa.gov/opp/op."

 This document presents an update of the Reregistration Eligibility Decision (RED), which was

issued in July 1995, taking into account the provisions of the Food Quality Protection Act (FQPA) of

1996. The docket includes background information on the risk assessments. No comments affecting

the risk assessments were received during the Phase 3 or Phase 5 public comment periods. Therefore,

the risk assessments were not revised. 

This document and the process used to develop it are the results of a pilot process to facilitate

greater public involvement and participation in the reregistration and/or FQPA tolerance reassessment

decisions on pesticides. As part of the Agency’s effort to involve the public in the implementation of the

FQPA, the Agency is undertaking a special effort to maintain open public dockets on the

organophosphate pesticides and to engage the public in the reregistration and tolerance reassessment

processes for these chemicals. The idea of using such an open process was developed by the

Tolerance Reassessment Advisory Committee (TRAC), a large multi-stakeholder advisory body which

advised the Agency on implementing the new provisions of the FQPA. The reregistration and tolerance

reassessment reviews for the organophosphate pesticides are following this new process. 
Please note that the fenitrothion risk assessment concerns only this particular organophosphate. 

Because the FQPA directs the Agency to consider available information on cumulative risk from

substances sharing a common mechanism of toxicity, such as the toxicity expressed by the

organophosphates through a common biochemical interaction with cholinesterase, the Agency will

evaluate the cumulative risk posed by the entire organophosphate class of chemicals, after completing

risk assessments for the individual organophosphates. The Agency is working to complete a

methodology to assess cumulative risk, and individual assessments of each organophosphate are likely

to be necessary elements of any cumulative assessment. The Agency has decided to move forward

with individual assessments and to identify mitigation measures, where necessary. The Agency will

issue the final tolerance reassessment decision for fenitrothion once the cumulative assessment for all of

the organophosphates is complete.

If you have questions on this document, please contact the Special Review and Reregistration

Division representative for fenitrothion, Stephanie Nguyen at (703) 605-0702.

Lois A. Rossi, Director

Special Review and 

 Reregistration Division

Attachment
Report on FQPA Tolerance Reassessment Progress

and Interim Risk Management Decision

for

Fenitrothion
TABLE OF CONTENTS

Fenitrothion Team ............................................................. ii

Glossary of Terms and Abbreviations ............................................ iii

Executive Summary ........................................................... 1

I. Introduction ............................................................ 1

II. Chemical Overview ...................................................... 3

A. Regulatory History ................................................ 3

B. Chemical Identification ............................................. 4

C. Use Profile ....................................................... 4

D. Estimated Usage of Pesticide ........................................ 5

III. Summary of Fenitrothion Risk Assessment .................................. 5

A. Human Health Risk Assessment ..................................... 6

1. Dietary Risk from Food ...................................... 6

a. Toxicity ............................................. 6

b. FQPA Safety Factor ................................... 6

c. Population Adjusted Dose (PAD) ......................... 6

d. Exposure Assumptions ................................. 7

e. Acute Food Risk ...................................... 8

f. Chronic Food Risk .................................... 8

2. Residential Risk ............................................ 9

3. Aggregate Risk ............................................. 9

IV. FQPA Tolerance Reassessment Progress & Interim Risk Management Decision ... 9

A. Tolerance Reassessment Progress & Interim Risk Management Decision ... 9

B. Summary of Phase 5 Comments ..................................... 10

C. Regulatory Position ............................................... 10

1. FQPA Assessment ......................................... 10

a. “Risk Cup” Determination ............................. 10

b. Tolerance Summary .................................. 11

2. Endocrine Disruptor Effects .................................. 12

D. Regulatory Rationale ............................................. 12

V. What Manufacturers Must Do ............................................ 12

A. Additional Data Requirements ...................................... 12

B. Risk Mitigation Requirements ...................................... 13

VI. Related Documents and How to Access Them ............................... 13

Fenitrothion Team
i

Office of Pesticide Programs:

Health Effects Risk Assessment

Christine L. Olinger

Christina Swartz

Use and Usage Analysis

Frank Hernandez

Registration Support

Marilyn Mautz

Risk Management

Margaret Rice

Stephanie Nguyen
ii

Glossary of Terms and Abbreviations

AE Acid Equivalent

a.i. Active Ingredient

AGDCI Agricultural Data Call-In

ai Active Ingredient

aPAD Acute Population Adjusted Dose

AR Anticipated Residue

ARC Anticipated Residue Contribution 

BCF Bioconcentration Factor 

CAS Chemical Abstracts Service

CI Cation

CNS Central Nervous System

cPAD Chronic Population Adjusted Dose

CSF Confidential Statement of Formula

CFR Code of Federal Regulations

CSFII USDA Continuing Surveys for Food Intake by Individuals

DCI Data Call-In

DEEM Dietary Exposure Evaluation Model

DFR Dislodgeable Foliar Residue

DRES Dietary Risk Evaluation System

DWEL Drinking Water Equivalent Level (DWEL) The DWEL represents a medium specific

(i.e., drinking water) lifetime exposure at which adverse, noncarcinogenic health effects

are not anticipated to occur.

DWLOC Drinking Water Level of Comparison.

EC Emulsifiable Concentrate Formulation

EEC Estimated Environmental Concentration. The estimated pesticide concentration in an

environment, such as a terrestrial ecosystem.

EP End-Use Product

EPA U.S. Environmental Protection Agency

FAO Food and Agriculture Organization

FDA Food and Drug Administration

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FFDCA Federal Food, Drug, and Cosmetic Act

FQPA Food Quality Protection Act

FOB Functional Observation Battery

G Granular Formulation

GENEEC Tier I Surface Water Computer Model

GLC Gas Liquid Chromatography

GLN Guideline Number

GM Geometric Mean

GRAS Generally Recognized as Safe as Designated by FDA
iii

HA Health Advisory (HA). The HA values are used as informal guidance to municipalities

and other organizations when emergency spills or contamination situations occur.

HAFT Highest Average Field Trial

HDT Highest Dose Tested

IR Index Reservoir

LC50 Median Lethal Concentration. A statistically derived concentration of a substance that

can be expected to cause death in 50% of test animals. It is usually expressed as the

weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or

ppm.

LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause

death in 50% of the test animals when administered by the route indicated (oral, dermal,

inhalation). It is expressed as a weight of substance per unit weight of animal, e.g.,

mg/kg.

LEL Lowest Effect Level

LOC Level of Concern

LOD Limit of Detection 

LOAEL Lowest Observed Adverse Effect Level

MATC Maximum Acceptable Toxicant Concentration

MCLG Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to

regulate contaminants in drinking water under the Safe Drinking Water Act.

mg/kg/day Milligram Per Kilogram Per Day

mg/L Milligrams Per Liter

MOE Margin of Exposure 

MP Manufacturing-Use Product

MPI Maximum Permissible Intake

MRID Master Record Identification (number). EPA's system of recording and tracking

studies submitted.

N/A Not Applicable

NAWQA USGS National Water Quality Assessment

NOEC No Observable Effect Concentration

NOEL No Observed Effect Level

NOAEL No Observed Adverse Effect Level

NPDES National Pollutant Discharge Elimination System

NR Not Required

OP Organophosphate

OPP EPA Office of Pesticide Programs

OPPTS EPA Office of Prevention, Pesticides and Toxic Substances

Pa pascal, the pressure exerted by a force of one newton acting on an area of one square

meter.

PAD Population Adjusted Dose

PADI Provisional Acceptable Daily Intake

PAG Pesticide Assessment Guideline

PAM Pesticide Analytical Method
iv

PCA Percent Crop Area

PDP USDA Pesticide Data Program

PHED Pesticide Handler's Exposure Data 

PHI Preharvest Interval

ppb Parts Per Billion

PPE Personal Protective Equipment

ppm Parts Per Million

PRN Pesticide Registration Notice

PRZM/EXAMS Tier II Surface Water Computer Model 

Q1* The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk

Model

RAC Raw Agriculture Commodity

RBC Red Blood Cell

RED Reregistration Eligibility Decision

REI Restricted Entry Interval

RfD Reference Dose

RQ Risk Quotient

RS Registration Standard

RUP Restricted Use Pesticide

SAP Science Advisory Panel

SCI-GROW Tier I Ground Water Computer Model

SF Safety Factor

SLC Single Layer Clothing

SLN Special Local Need (Registrations Under Section 24© of FIFRA)

TC Toxic Concentration. The concentration at which a substance produces a toxic effect. 

TD Toxic Dose. The dose at which a substance produces a toxic effect.

TEP Typical End-Use Product

TGAI Technical Grade Active Ingredient

TLC Thin Layer Chromatography

TMRC Theoretical Maximum Residue Contribution

torr A unit of pressure needed to support a column of mercury 1 mm high under standard

conditions.

TRR Total Radioactive Residue

UF Uncertainty Factor

μg/g Micrograms Per Gram

μg/L Micrograms Per Liter

USDA United States Department of Agriculture

USGS United States Geological Survey

UV Ultraviolet 

WHO World Health Organization

WP Wettable Powder

WPS Worker Protection Standard
v

Executive Summary

The U.S. Environmental Protection Agency (hereafter referred to as EPA or the Agency) has

completed its review of public comments on the risk assessment for fenitrothion, and is, in this

document, issuing its interim decision on the risk mitigation for this chemical. This risk assessment is

based on review of the required target data base supporting the single fenitrothion import tolerance and

information received during the public comment periods in the open process developed through the

Tolerance Reassessment Advisory Committee (TRAC). Fenitrothion is registered in the U.S. for use

in ant and roach baits. There are no food uses registered in the U.S. The product is manufactured by

Sumitomo Chemical Corporation. 

EPA's revised risk assessment for fenitrothion indicates that the dietary risk does not exceed the

Agency’s level of concern; therefore, no risk mitigation is necessary at this time. This assessment does

not address residential, ecological, drinking water, or worker risks, because little or no exposure to

residents, workers, or the environment is likely from the current limited domestic use of fenitrothion in

ant and roach baits.

The tolerance reassessment decision for fenitrothion will be issued once the cumulative

assessment for all of the organophosphates is completed. The Agency may need to issue risk

management measures for fenitrothion at the time the organophosphate cumulative assessment is

finalized. 
1

I. Introduction

This report on the progress toward tolerance reassessment of fenitrothion is the result of the

pilot process developed through the TRAC to facilitate greater public involvement in the ongoing

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) reregistration and FQPA tolerance

reassessment initiatives on pesticides. A Reregistration Eligibility Document (RED) was issued in July

1995. This assessment presents an update of the RED, taking into account the provisions of the Food

Quality Protection Act of 1996. Fenitrothion is not used on food or feed crops in the U.S. It has only

one tolerance, for wheat gluten imported from Australia. This assessment does not address residential,

ecological, drinking water, or worker risks, because little or no exposure to residents, workers, or the

environment is likely from the current limited domestic use of fenitrothion in ant and roach baits. Thus,

this assessment relates only to the requirements of FQPA. However, some history and background of

FIFRA is included here for informational purposes and to provide a discussion of the existing laws

requiring action on pesticides.

The FIFRA was amended in 1988 to accelerate the reregistration of products with active

ingredients registered prior to November 1, 1984. The amended act calls for the development and

submission of data to support the reregistration of an active ingredient, as well as a review of all 

submitted data by the Agency. Reregistration involves a thorough review of the scientific database

underlying a pesticide’s registration. The purpose of the Agency’s review is to reassess all potential

hazards arising from the currently registered uses of the pesticide; determine the need for additional data

on health and environmental effects; and determine whether the pesticide meets the “no unreasonable

adverse effects” criteria of FIFRA. 

On August 3, 1996, the FQPA was signed into law. This Act amends FIFRA to require

tolerance reassessment during reregistration. It also requires that, by August 2006, EPA review all

tolerances in effect on the day before the date of the enactment of the FQPA. FQPA amends both

FIFRA and the Federal Food, Drug, and Cosmetic Act (FFDCA), but does not amend any of the

existing reregistration deadlines. Therefore, the Agency is continuing its reregistration program while it

resolves remaining issues associated with the implementation of FQPA. The Agency is also continuing

its progress toward tolerance reassessment as required by FQPA for all of the organophosphate

chemicals, whether or not they are subject to the reregistration process. While the methodology for

completion of the cumulative assessment for all of the organophosphates is being developed, individual

risk assessments and risk mitigation measures, where appropriate, are being conducted. The

Fenitrothion RED, reflecting decisions of the reregistration process, was issued in July 1995. The

revised individual dietary assessment for fenitrothion has been completed, and will be used in the

cumulative assessment of all of the organophosphate chemicals, in order to satisfy the requirements of

FQPA.

The import tolerance for fenitrothion is subject to the requirements of FQPA; therefore, a

dietary risk assessment was completed. This document presents the Agency’s dietary risk assessment

for fenitrothion, as part of the tolerance reassessment process. Note that there is no comment period
2

for this document. As part of the process developed by the TRAC, which sought to open up the

process to interested parties, the Agency’s risk assessment for fenitrothion has already been subject to

numerous public comment periods, and a further comment period was deemed unnecessary. A Notice

of Availability for this document is published in the Federal Register. Phase 6 of the pilot process

does not include a public comment period. However, for some chemicals, the Agency may provide

another comment period, depending on the content of the risk management decision.

 Implementation of FQPA has required the Agency to revisit some of its existing policies

relating to the determination and regulation of dietary risk, and has also raised a number of new issues

for which policies need to be created. These issues were refined and developed through collaboration

between the Agency and the Tolerance Reassessment Advisory Committee (TRAC), which was

composed of representatives from industry, environmental groups, and other interested parties. TRAC

identified the following science policy issues it believed were key to the implementation of FQPA and

tolerance reassessment:

C Applying the FQPA 10-Fold Safety Factor

C Whether and How to Use "Monte Carlo" Analyses in Dietary Exposure Assessments 

C How to Interpret "No Detectable Residues" in Dietary Exposure Assessments

C Refining Dietary (Food) Exposure Estimates

C Refining Dietary (Drinking Water) Exposure Estimates

C Assessing Residential Exposure

C Aggregating Exposure from all Non-Occupational Sources

C How to Conduct a Cumulative Risk Assessment for Organophosphate or Other Pesticides with

a Common Mechanism of Toxicity

C Selection of Appropriate Toxicity Endpoints for Risk Assessments of Organophosphates

C Whether and How to Use Data Derived from Human Studies

The process developed by TRAC calls for EPA to provide one or more documents for public

comment on each of the policy issues described above. Each of these issues is evolving and in a

different stage of refinement. Some issue papers have already been published for comment in the

Federal Register and others will be published shortly.

This document consists of six sections. Section I contains the regulatory framework for

reregistration/tolerance reassessment as well as a description of the process developed by TRAC for

public comment on science policy issues for the organophosphate pesticides. Section II provides a

profile of the usage of this chemical. Section III gives an overview of the dietary risk assessment for

fenitrothion, including a discussion of any revisions made to the preliminary assessment. Section IV

presents the Agency's progress towards tolerance reassessment, its interim decision, and the regulatory

position on this chemical. Section V discusses what the manufacturer’s obligations are with respect to

further actions required, and finally, Section VI provides information on how to access related

documents. The entire revised risk assessment is not included in this document, but is available on the

Agency's web page (www.epa.gov/opp/op), and in the Public Docket. 
3

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P

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O

O2N

OCH3

OCH3

II. Chemical Overview

A. Regulatory History

Fenitrothion, an organophosphate, is a cholinesterase inhibiting insecticide/acaricide registered

for use in the U.S. in ant and roach baits. In the July 1995 RED a tolerance of 15 ppm was

recommended for residues of fenitrothion in wheat gluten resulting from post-harvest application to

stored wheat in Australia. The Agency has reassessed the tolerance for residues of fenitrothion in

wheat gluten and is lowering it to 3 ppm, and will revise the tolerance expression to include only the

parent compound.

In the July 1995 RED, greenhouse, outdoor ornamental, and containerized ant and roach baits

in child resistant packaging were the only registered domestic uses assessed. The RED required an

extensive amount of risk mitigation for the greenhouse and outdoor ornamental uses as well as a

considerable amount of additional data. Subsequent to the issuance of the RED, these uses were

voluntarily canceled, leaving ant and roach baits as the only registered domestic use.

B. Chemical Identification

 FENITROTHION:

! Common Name: Fenitrothion 

! Chemical Name: O,O-dimethyl O-(4-nitro-m-tolyl)

phosphorothioate

! Chemical Family: Organophosphate

! CAS Registry Number: 122-14-5

! OPP Chemical Code: 105901

! Empirical Formula: C9H12 NO5 PS

! Molecular Weight: 277.2
4

! Trade and Other Names: Tat Ant Trap X, Tat Roach Bait V, Sumithion

! Basic Manufacturers: Sumitomo Chemical Co.TDT., Osaka, Japan

(Fenitrothion is not manufactured in the U.S.)

C. Use Profile

The following information is based on the current uses of fenitrothion both within and outside of 

the United States, and includes an overview of use sites and application methods.

Type of Pesticide: Insecticide/Acaricide

Summary of Use Sites:

Food: There are no registered food uses in the U.S.

Fenitrothion is used in Australia on stored wheat and

there is a U.S. tolerance for imported wheat gluten.

Residential: The only registered use in the U.S. is for containerized

ant and roach baits in child resistant packaging.

Target Pests: Ants, roaches, palmetto bugs, waterbugs

Formulation Types: Emulsifiable concentrate (not registered in the U.S.),

and as pellets and granular baits 

Method and Rates of Application:

Method and Rate - Baits contain either 0.01563% or 1.0% active

ingredient (a.i.). For stored wheat, fenitrothion

emulsifiable concentrate is applied at 12 mg a.i./kg

grain, prior to bin storage (not registered in the U.S.)

D. Estimated Usage of Pesticide

This section summarizes the best estimates available for the pesticide uses of fenitrothion. 

These estimates are derived from a variety of published and proprietary sources available to the

Agency. The data, reported on an aggregate and site (crop) basis, reflect annual fluctuations in use

patterns as well as the variability in using data from various sources.
5

Annual U.S. consumption of wheat gluten by the food industry is about 250 million pounds;

currently approximately 26% (65 million pounds) is imported from Australia. Because no data are

available on percent crop treated, for the purpose of this reassessment, EPA has assumed that all of the

wheat gluten imported from Australia could be treated with fenitrothion. (Note: Wheat gluten is the

natural protein derived from wheat. It is essentially wheat flour with the starch removed. It is used by

the baking industry to improve consistency in bread products, and has other industrial uses.) 

III. Summary of Fenitrothion Risk Assessment

Following is a summary of EPA’s revised human health risk findings and conclusions for the

organophosphate pesticide fenitrothion, as fully presented in the revised risk assessment document,

"Fenitrothion HED RED Chapter; Revised Risk Assessment (PC Code 105901)," dated May 19,

1999. The risk assessment presented here forms the basis of the Agency’s interim risk management

decision for fenitrothion only; the Agency must complete a cumulative assessment of the risks of all

organophosphate pesticides before it can complete its reassessment of the fenitrothion tolerance. 

The revised risk assessment for fenitrothion presents the individual dietary assessment for

fenitrothion resulting from its use on wheat gluten imported from Australia. This assessment does not

address residential, ecological, drinking water, or worker risks, because little or no exposure to

residents, workers, or the environment is likely from the current limited domestic use of fenitrothion in

ant and roach baits.

A. Human Health Risk Assessment

 No comments affecting the risk assessment were received during the Phase 3 or Phase 5

public comment periods; therefore, the risk assessments were not revised.

1. Dietary Risk from Food

a. Toxicity

The Agency has reviewed all toxicity studies submitted and has determined that the toxicity

database supports a dietary risk assessment for fenitrothion as well as a future FQPA tolerance

reassessment for the import tolerance on wheat gluten. Further details on the toxicity of fenitrothion

can be found in the May 19, 1999 HED Red Chapter; Revised Risk Assessment. A brief overview of

the studies used for the dietary risk assessment is outlined in Table 1 of this document.
6

b. FQPA Safety Factor

The FQPA Safety Factor was removed based on a complete toxicity data base and adequate

exposure information, which allowed reasonable understanding in predicting possible effects on infants

and children, and the lack of increased susceptibility in the fetuses and/or pups in the developmental and

reproduction studies. The Agency has granted a waiver for the developmental neurotoxicity (DNT)

study for fenitrothion. The Agency has determined that exposure to any population group of concern

under the FQPA is very low for the currently registered and labeled uses of fenitrothion, given the

amount used, how it is used, and information available to the Agency regarding levels to which people

are exposed.

c. Population Adjusted Dose (PAD)

The PAD is a relatively new term that characterizes the dietary risk of a chemical, and reflects

the Reference Dose, either acute or chronic, that has been adjusted to account for the FQPA safety

factor (i.e., RfD/FQPA safety factor). For the acute dietary assessment, risk is calculated considering

what is eaten in one day (consumption) and maximum, high-end residue values in food. For chronic

exposures, dietary risk is calculated by using the average consumption value for food and average

residue value. In the case of fenitrothion, the FQPA Safety Factor Committee recommended removal

of the 10X safety factor; therefore, the acute or chronic RfD is equal to the acute or chronic PAD. A

risk estimate that is less than 100% of the acute or chronic PAD does not exceed the Agency’s risk

concern. 

d. Exposure Assumptions

A tolerance level of 15 ppm was previously recommended to cover residues of fenitrothion in

wheat gluten imported from Australia. However, the Agency has re-evaluated the magnitude of residue

database for fenitrothion and concluded that the tolerance value for fenitrothion in wheat gluten can be

lowered to 3 ppm. In four trials from four different states in Australia, residues ranged from 0.95 to 2.5

ppm in/on wheat gluten; the average residue was 1.84 ppm. Monitoring data from a commercial wheat

gluten processing facility in Australia showed residues ranging from 0.09 to 0.9 ppm, with an average of

0.38 ppm. FDA has monitored just a few wheat gluten samples from Australia over the last several

years. Most samples showed non-detectable residues of fenitrothion, although trace residues (residues

less than the level which can be reliably quantified) were found in two samples.

The Agency estimates that approximately 65 million pounds of wheat gluten are imported from

Australia each year, according to quotas that were created in 1998. Based on that figure, together with

an annual U.S. consumption estimate for the U.S. food industry of 250 million pounds of wheat gluten, 

the maximum amount of all U.S. wheat gluten which could be treated with fenitrothion is 26%. This

assumes that 100% of wheat gluten imported from Australia has been treated.
7

Dietary risk analyses for fenitrothion were conducted with the Dietary Exposure Evaluation

Model (DEEMTM). DEEM incorporates consumption data generated in USDA’s Continuing Surveys

of Food Intake by Individuals (CSFII), 1989-1992. This model does not contain consumption values

for wheat gluten. EPA used wheat flour consumption data and an adjustment factor (0.0062) to

estimate the amount of wheat gluten consumed. [The adjustment factor represents the estimated amount

of wheat gluten consumed annually as a proportion of the total wheat flour consumed annually]. Use of

this factor assumes that the relative consumption of wheat gluten to wheat flour is the same for all

population subgroups. Residues were estimated using the proposed revised tolerance level (3 ppm)

and average per capita exposure.

Table 1. Summary of Toxicological Endpoints and Other Factors Used in the Human Dietary

Risk Assessment of Fenitrothion

Assessment Study Dose

(mg/kg/day)

Endpoint UF FQPA

Safety

Factor

PAD

Acute

Dietary

Acute

Neurotoxicit

y- Rat

NOAEL = 12.5 

LOAEL = 50

Tremors and impaired

motor coordination

100 1X 0.13 mg/kg/

day

Chronic

Dietary

1-year

Feeding

Study-Dog

NOAEL = 0.125 

LOAEL = 0.25 

Plasma ChE inhibition and

histopathology changes of

the lymph nodes

100 1X 0.0013 

mg/kg/ 

day

e. Acute Food Risk 

 The acute dietary (food) risk of fenitrothion is 0.02% of the aPAD for the general population,

well below the Agency’s level of concern. An acute dietary risk assessment was not performed in the

July 1995 RED because data to estimate single-day consumption of wheat gluten were not available. 

However, using the average U.S. population exposure estimate with the acute dietary NOAEL results

in the above acute dietary risk estimate. Therefore, while there are uncertainties in the estimated risk

due to uncertainties in the consumption estimate, this extremely low percent of the aPAD indicates that

risks from this use will be insignificant. This analysis satisfies the FQPA requirement for the special

consideration of pesticide risk to children.

f. Chronic Food Risk

Use of the average residues from field trials and limited FDA monitoring, together with percent

of commodity treated data discussed above (26%) results in chronic dietary risk estimates of <1% of

the cPAD for the general U.S. population and all population subgroups. The most highly exposed subpopulation is children 1-6 at 0.7% of the cPAD. Note that this estimate is considered to be somewhat

conservative, since 100% crop treatment is assumed for wheat gluten produced in Australia.
8

 In summary, the potential acute and chronic dietary exposures on imported wheat gluten are

well below the level of concern for all population sub-groups, including infants and children. Data on

the actual percentage of stored Australian wheat treated with fenitrothion and the percent of imported

Australian wheat gluten diverted for non-food purposes (e.g., the manufacture of bio-degradable

plastic) would allow EPA to further refine the dietary risk estimates.

2. Residential Risk

Exposure resulting from use of the containerized ant and roach baits in child resistant packaging

is expected to be insignificant. The Agency did not quantitatively estimate risks for this type of use

because of the expected low potential for exposure. Exposure is expected to be insignificant because

the material is not available through the dermal and oral routes; and, due to the small amount of material

which would be available through volatilization, inhalation exposure is expected to be minimal.

3. Aggregate Risk

Because exposure from residential uses is expected to be insignificant, the aggregate exposure

assessment for fenitrothion would include consideration of exposures only from food. Therefore, an

aggregate assessment was not required.

IV. FQPA Tolerance Reassessment Progress & Interim Risk Management Decision

A. Tolerance Reassessment Progress & Interim Risk Management Decision

The Agency has completed its assessment of the dietary risk of fenitrothion but has not

considered the cumulative effects of organophosphates as a class. Based on review of the generic and

other data, EPA has sufficient information on the human health effects of fenitrothion to make an interim

decision as part of the tolerance reassessment process under FQPA. Although the Agency has not yet

completed its cumulative risk assessment for the organophosphates, the Agency has completed its

assessment of risk from dietary exposure to fenitrothion alone in order to determine whether any risk

reduction measures are necessary to allow the continued importation of wheat gluten containing

fenitrothion, pending completion of the cumulative assessment. 

As a result of its assessment, EPA has determined that dietary risk from exposure to

fenitrothion does not exceed the Agency’s level of concern. Therefore, no mitigation is necessary and

no further actions are warranted at this time. The Agency may determine that further action is

necessary after assessing the cumulative risk of the organophosphate class. At that time, the Agency

will also address any other outstanding risk concerns that may arise. Such an incremental approach to

the tolerance reassessment process is consistent with the Agency’s goal of improving the transparency

of the implementation of FQPA. By evaluating each organophosphate in turn and identifying
9

appropriate risk reduction measures, the Agency is addressing the risks from organophosphates in as

timely a manner as possible.

Because the Agency has not yet completed the cumulative risk assessment for the

organophosphates, this interim decision does not specifically address the reassessment of the existing

fenitrothion food residue import tolerance as called for by the FQPA. When the Agency has

completed the cumulative assessment, the fenitrothion tolerance will be reassessed in that light. At that

time, the Agency will reassess fenitrothion along with the other organophosphate pesticides to complete

the FQPA requirements. Nothing in this report will preclude the Agency from making further FQPA

determinations and tolerance-related rulemaking that may be required on this pesticide or any other in

the future. 

If the Agency determines, before finalization of the FQPA assessment for fenitrothion, that any

of the determinations described in this document are no longer appropriate, the Agency will pursue

appropriate action, including but not limited to, reconsideration of any portion of this document. 

B. Summary of Phase 5 Comments

EPA released its revised risk assessment for fenitrothion to the public in September, 1999, and 

provided a 60 day comment period for interested parties to submit information, including risk mitigation

suggestions or proposals. No comments were received. Sumitomo Chemical Company, the registrant,

submitted a dietary toxicity study using human volunteers, on April 25, 2000. This study has not been

reviewed.

C. Regulatory Position

1. FQPA Assessment

a. “Risk Cup” Determination 

As part of the FQPA tolerance reassessment process, EPA assessed the risks associated with

this individual organophosphate. FQPA also requires the Agency to consider available information on

cumulative risk from substances sharing a common mechanism of toxicity, such as the toxicity

expressed by the organophosphates through a common biochemical interaction with cholinesterase

enzyme. The Agency will evaluate the cumulative risk posed by the entire class of organophosphates

once the methodology is developed and the policy concerning cumulative assessments is resolved. 

EPA has determined that risk from exposure to fenitrothion is within its own “risk cup.” In

other words, if fenitrothion did not share a common mechanism of toxicity with other chemicals, EPA

would be able to conclude today that the import tolerance for fenitrothion on wheat gluten meets the 

FQPA safety standards. In reaching this determination, EPA considered available information on the

special sensitivity of infants and children, as well as chronic and acute food exposure. An aggregate
10

assessment was not conducted for fenitrothion, because little or no exposure is likely from the current

limited domestic use of fenitrothion in containerized ant and roach baits in child resistant packaging. 

Exposure is expected to be insignificant because the material is not available through the dermal and

oral routes; and, due to the small amount of material which would be available through volatilization,

inhalation exposure is expected to be minimal. Results of the acute and chronic food assessments

indicate that exposures are within acceptable levels; that is, risk from exposure to fenitrothion “fits”

within the individual risk cup. Therefore, the import tolerance remains in effect until a full reassessment

of the cumulative risk from all organophosphates is completed.

b. Tolerance Summary 

A tolerance level of 30 ppm, of which no more than 15 ppm is O,O-dimethyl O-(4-nitro-mtolyl) phosphorothioate or O,O-dimethyl O-(4-nitro-m-tolyl) phosphate, is established for combined

residues of the insecticide O,O-dimethyl O-(4-nitro-m-tolyl) phosphorothioate and its metabolites

O,O-dimethyl O-(4-nitro-m-tolyl) phosphate and 3-methyl-4-nitrophenol in wheat gluten resulting from

postharvest application of the insecticide to stored wheat in Australia. However, the Agency has reevaluated the magnitude of residue database for fenitrothion and concluded the tolerance can be

lowered to 3 ppm, as shown in Table 2. Residues in four field trials from four different states in

Australia resulted in residues ranging from 0.95 to 2.5 ppm in/on wheat gluten; the average residue was

1.84 ppm. The tolerance expression should be modified to include only the parent compound. 

Although 3-methyl-4-nitrophenol is of potential toxicological concern based on data relative to similar

compounds, the risk assessment conducted for the cholinesterase-inhibiting metabolite(s) is expected

to be more sensitive. Therefore, only cholinesterase-inhibiting metabolites need to be regulated and 3-

methyl-4-nitrophenol should be deleted from the current tolerance expression. Although O,O-dimethyl

O-(4-nitro-m-tolyl) phosphate is expected to be of greater toxicological concern than the parent, finite

residues of O,O-dimethyl O-(4-nitro-m-tolyl) phosphate are not expected in/on wheat grain or in

wheat gluten resulting from the postharvest use of fenitrothion on stored wheat in Australia; therefore,

O,O-dimethyl O-(4-nitro-m-tolyl) phosphate should be deleted from the current tolerance expression. 

All other metabolites were determined not to be potential cholinesterase inhibitors and/or were present

at such low levels compared to the parent that they were deemed insignificant and do not need to be

regulated. 

Table 2. Tolerance Summary for Fenitrothion

Commodity Tolerance Currently Listed

Under 40 CFR § 185.2200

Reassessed

Tolerance *

Comment

Wheat Gluten 30 ppm 3 ppm Wheat Gluten, imported

The tolerance should be expressed as parent

only and the tolerance will be listed in 180.540

* The term “reassessed” is not meant to imply that the tolerance has been reassessed as required by FQPA, since

this tolerance may be reassessed only upon completion of the cumulative risk assessment of all organophosphates,

as required by this law. Rather, it provides a tolerance level for this single chemical, if no cumulative assessment

were required, that is supported by all of the submitted residue data. 
11

2. Endocrine Disruptor Effects

EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to

determine whether certain substances (including all pesticide active and other ingredients) “may have an

effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such

endocrine effects as the Administrator may designate.” Following the recommendations of its

Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), EPA determined that

there was scientific bases for including, as part of the program, the androgen and thyroid hormone

systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC’s recommendation

that the Program include evaluations of potential effects in wildlife. For pesticide chemicals, EPA will

use FIFRA and, to the extent that effects in wildlife may help determine whether a substance may have

an effect in humans, FFDCA authority to require the wildlife evaluations. As the science develops and

resources allow, screening of additional hormone systems may be added to the Endocrine Disruptor

Screening Program (EDSP).

When the appropriate screening and/or testing protocols being considered under the Agency’s

EDSP have been developed, fenitrothion may be subjected to additional screening an/or testing to

better characterize effects related to endocrine disruption.

D. Regulatory Rationale

Fenitrothion has only one import tolerance for wheat gluten, and little or no exposure is likely

from the current limited domestic use of fenitrothion in containerized ant and roach baits in child

resistant packaging. Exposure is expected to be insignificant because the material is not available

through the dermal and oral routes; and, due to the small amount of material which would be available

through volatilization, inhalation exposure is expected to be minimal. Therefore, only a dietary risk

assessment for food was conducted. Based on analyses of both acute and chronic dietary risk, the

Agency has determined that the risk estimates are below the Agency’s level of concern, therefore, no

mitigation measures are necessary at this time. 

V. What Manufacturers Must Do

A. Additional Data Requirements

EPA is requiring acute, subchronic, and developmental neurotoxicity studies for all

organophosphates, including those with no domestic registrations (i.e., tolerances are established only

to allow treated commodities to be imported into the U.S.). However, there are no additional data

required for fenitrothion. The Agency has granted a waiver for the developmental neurotoxicity (DNT)

study for fenitrothion. The Agency has concluded that exposure to any population group of concern
12

under the FQPA is very low for the currently registered and labeled uses of fenitrothion, given the

amount used, how it is used, and information available to the Agency regarding levels to which people

are exposed, as described in EPA’s fenitrothion human health risk assessments.

B. Risk Mitigation Requirements

As discussed in this document, the acute and chronic food risk from the use of fenitrothion on

imported wheat gluten is not of concern to the Agency, therefore, no mitigation is necessary at this

time. The Agency may need to pursue risk management measures for fenitrothion once the cumulative

assessment is finalized. 

VI. Related Documents and How to Access Them

This report is supported by documents that are presently maintained in the OPP docket

(#34197). The OPP docket is located in Room 119, Crystal Mall #2, 1921 Jefferson Davis Highway,

Arlington, VA. It is open Monday through Friday, excluding legal holidays, from 8:30 am to 4 pm. All

documents, in hard copy form, may be viewed in the OPP docket room or downloaded or viewed via

the Internet at the following site: "http://www.epa.gov/pesticides/op."
13

Bibliography for Fenitrothion Docket

1. Christine L. Olinger (USEPA/OPPTS/OPP/HED) Fenitrothion HED RED Chapter;

Revised Risk Assessment, (PC 105901). 5/19/99.

2. John C. Redden (USEPA/OPPTS/OPP/HED) HED RED Chapter for Fenitrothion

(PC 105901). 5/7/94. 

3. Jess Rowland (USEPA/OPPTS/OPP/HED) Fenitrothion-Correction to the Report of

HIARC Review Committee. 2/23/99.

4. Jess Rowland (USEPA/OPPTS/OPP/HED) Fenitrothion - FQPA RequirementReport of the Hazard Identification Assessment review Committee. 10/8/97.

5. Christine Swartz (USEPA/OPPTS/OPP/HED) Chronic Dietary Exposure Analyses for

the Revised HED Reregistration Eligibility Decision Document (RED). 5/28/99.

6. Christine L. Olinger (USEPA/OPPTS/OPP/HED) Anticipated Residue and Tolerance

Reassessment Recommendations. 5/19/99.

7. Michael S. Metzger (USEPA/OPPTS/OPP/HED) Update to Consider FQPA

Requirements. 2/24/98.

8. Frank Hernandez (USEPA/OPPTS/OPP/BEAD) Fenitrothion on Wheat Gluten. 

6/29/99.

9. Robin G. Todd, Ph. D (Sumitomo Chemical Company, Limited) Letter to EPA,

Fenitrothion Human Health Risk Assessment. 7/22/99.