v>EPA
United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508C)
EPA738-R-00-012
October 2000
Report on FQPA Tolerance
Reassessment Progress
and Interim Risk
Management Decision
for
Fenitrothion
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United States
Environmental Protection
Agency
Prevention, Pesticides
and Toxic Substances
(7508C)
EPA738-F-00-010
October 2000
Fenitrothion Facts
EPA has assessed the risks of fenitrothion and completed a "Report on FQPA Tolerance
Reassessment Progress and Interim Risk Management Decision for Fenitrothion" for this
organophosphate (OP) pesticide. Without risk mitigation, fenitrothion fits into its own "risk cup"- its
individual, aggregate risks are within acceptable levels. Fenitrothion also is eligible for reregistration,
pending a full reassessment of the cumulative risk from all OPs.
In July 1995 a RED was issued for
fenitrothion. Most uses were canceled during the
RED process or subsequent to the issuance of the
RED. Currently used in Australia on stored wheat
and in the U.S. in containerized ant and roach baits in
child resistant packaging, fenitrothion residues in
food do not pose risk concerns and exposure
resulting from use of the containerized ant and roach
baits is expected to be insignificant. Without
-mitigation fenitrothion fits into its own "risk cup."
EPA's next step under the Food Quality
Protection Act (FQPA) is to complete a cumulative
risk assessment and risk management decision
encompassing all the OP pesticides, which share a
common mechanism of toxicity. The interim
decision on fenitrothion cannot be considered final
until this cumulative assessment is complete. Further
risk mitigation may be required at that time.
EPA is reviewing the OP pesticides to
determine whether they meet current health and
safety standards. Older OPs need decisions about
their eligibility for reregistration under FIFRA. OPs
with residues hi food, drinking water, and other non-
occupational exposures also must be reassessed to make sure they meet the new FQPA safety
standard.
The OP Pilot Public Participation Process
The organophosphates are a group of
related pesticides that affect the functioning of the
nervous system. They are among EPA's highest
priority for review under the Food Quality
Protection Act.
EPA is encouraging the public to
participate in the review of the OP pesticides.
Through a six-phased pilot public participation
process, the Agency is releasing for review and
comment its preliminary and revised scientific risk
assessments for individual OPs. (Please contact
the OP Docket, telephone 703-305-5805, or see
EPA's web site, www.epa.gov/pesticides/op.)
EPA is exchanging information with
stakeholders and the public about the OPs, their
uses, and risks through Technical Briefings,
stakeholder meetings, and other fora. USDA is
coordinating input from growers and other OP
pesticide users.
Based on current information from
interested stakeholders and the public, EPA is
making interim risk management decisions for
individual OP pesticides, and will make final
decisions through a cumulative OP assessment.
The fenitrothion interim decision was made through the OP pilot public participation process,
which increases transparency and maximizes stakeholder involvement in EPA's development of risk'
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assessments and risk management decisions. EPA worked extensively with affected parties to reach
the decisions presented in this interim decision document, which concludes the OP pilot process for
fenitrothion.
Uses
An insecticide/acaricide, fenitrothion is used in Australia on stored wheat and there is a U.S.
tolerance for imported wheat gluten. The only registered use in the U.S. is for containerized
ant and roach baits in child resistant packaging.
Annual domestic use is low. 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. No data are available on percent crop treated in Australia.
Health Effects
Fenitrothion can cause cholinesterase inhibition in humans; that is, it can overstimulate the
nervous system causing nausea, dizziness, confusion, and at very high exposures (e.g.,
accidents or major spills), respiratory paralysis and death.
Risks
Dietary exposures from consuming wheat gluten treated with fenitrothion are below the level
of concern for the entire U.S. population, including infants and children. Drinking water is not
a source of exposure.
Risks are not of concern for the 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.
Risk Mitigation
No risk mitigation is necessary at this time.
Next Steps
Numerous opportunities for public comment were offered as this decision was being
developed. The fenitrothion IRED therefore is issued as final (see
www.epa.gov/pesticides/op), without a formal public comment period. The docket remains
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open, however, and any comments submitted in the future will be placed in this public docket.
When the cumulative risk assessment for all organophosphate pesticides is completed, EPA
will issue its final tolerance reassessment decision for fenitrothion and may require further risk
mitigation measures. The Agency will amend the only tolerance for fenitrothion now The
tolerance for wheat gluten imported from Australia will be lowered to 3 ppm and the tolerance
expression will be modified to include only the parent compound. For all OPs, raising and/or
establishing tolerances will be considered once a cumulative assessment is completed
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^^7 «
UK,
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MATT.
Dear Registrant:
NOV 0 7
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
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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.
ois A. Rossi, Director
Special Review and
Reregistration Division
Attachment
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Report on FQPA Tolerance Reassessment Progress
and Interim Risk Management Decision
for
Fenitrothion
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TABLE OF CONTENTS
Fenitrothion Team y
*
Glossary of Terms and Abbreviations iii
Executive Summary j
I. Introduction j
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 g
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 IQ
a. "Risk Cup" Determination 10
b. Tolerance Summary H
2. Endocrine Disrupter 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
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Fenitrothion Team
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
11
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Glossary of Terms and Abbreviations
AE
a.i.
AGDCI
ai
aPAD
AR
ARC
BCF
CAS
CI
CNS
cPAD
CSF
CFR
CSFII
DCI
DEEM
DFR
DRES
DWEL
DWLOC
EC
EEC
EP
EPA
FAO
FDA
FIFRA
FFDCA
FQPA
FOB
G
GENEEC
GLC
GLN
GM
GRAS
Acid Equivalent
Active Ingredient
Agricultural Data Call-In
Active Ingredient
Acute Population Adjusted Dose
Anticipated Residue
Anticipated Residue Contribution
Bioconcentration Factor
Chemical Abstracts Service
Cation
Central Nervous System
Chronic Population Adjusted Dose
Confidential Statement of Formula
-Code of Federal Regulations
USDA Continuing Surveys for Food Intake by Individuals
Data Call-In
Dietary Exposure Evaluation Model
Dislodgeable Foliar Residue
Dietary Risk Evaluation System
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.
Drinking Water Level of Comparison.
Emulsifiable Concentrate Formulation
Estimated Environmental Concentration. The estimated pesticide concentration in
an environment, such as a terrestrial ecosystem.
End-Use Product
U.S. Environmental Protection Agency
Food and Agriculture Organization
Food and Drug Administration
Federal Insecticide, Fungicide, and Rodenticide Act
Federal Food, Drug, and Cosmetic Act
Food Quality Protection Act
Functional Observation Battery
Granular Formulation
Tier I Surface Water Computer Model
Gas Liquid Chromatography
Guideline Number
Geometric Mean
Generally Recognized as Safe as Designated by FDA
in
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HA
HAFT
HOT
IR
LC50
LD
'so
LEL
LOG
LOD
LOAEL
MATC
MCLG
mg/kg/day
mg/L
MOE
MP
MPI
MRID
N/A
NAWQA
NOEC
NOEL
NOAEL
NPDES
NR
OP
OPP
OPPTS
Pa
PAD
PADI
PAG
PAM
Health Advisory (HA). The HA values are used as informal guidance to
municipalities and other organizations when emergency spills or contamination
situations occur.
Highest Average Field Trial
Highest Dose Tested
Index Reservoir
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/1,
mg/kg or ppm.
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.
Lowest Effect Level
"Level of Concern
Limit of Detection
Lowest Observed Adverse Effect Level
Maximum Acceptable Toxicant Concentration
Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency
to regulate contaminants in drinking water under the Safe Drinking Water Act.
Milligram Per Kilogram Per Day
Milligrams Per Liter
Margin of Exposure
Manufacturing-Use Product
Maximum Permissible Intake
Master Record Identification (number). EPA's system of recording and tracking
studies submitted.
Not Applicable
USGS National Water Quality Assessment
No Observable Effect Concentration
No Observed Effect Level
No Observed Adverse Effect Level
National Pollutant Discharge Elimination System
Not Required
Organophosphate
EPA Office of Pesticide Programs
EPA Office of Prevention, Pesticides and Toxic Substances
pascal, the pressure exerted by a force of one newton acting on an area of one
square meter.
Population Adjusted Dose
Provisional Acceptable Daily Intake
Pesticide Assessment Guideline
Pesticide Analytical Method
IV
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PCA Percent Crop Area
PDF USDA Pesticide Data Program
PHED Pesticide Handler's Exposure Data
PHI Preharyest 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
Qi * 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
Micrograms Per Gram
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
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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.
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
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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 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:
Applying the FQPA 10-Fold Safety Factor
Whether and How to Use "Monte Carlo" Analyses in Dietary Exposure Assessments
How to Interpret "No Detectable Residues" in Dietary Exposure Assessments
Refining Dietary (Food) Exposure Estimates
Refining Dietary (Drinking Water) Exposure Estimates
Assessing Residential Exposure
Aggregating Exposure from all Non-Occupational Sources
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How to Conduct a Cumulative Risk Assessment for Organophosphate or Other Pesticides
with a Common Mechanism of Toxicity
Selection of Appropriate Toxicity Endpoints for Risk Assessments of Organophosphates
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.
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.
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B. Chemical Identification
FENITROTHION:
Common Name:
Chemical Name:
Chemical Family:
CAS Registry Number:
OPP Chemical Code:
Empirical Formula:
Molecular Weight:
Trade and Other Names:
Basic Manufacturers:
Fenitrothion
O,O-dimethyl O-(4-nitro-m-tolyl)
phosphorothioate
Organophosphate
122-14-5
105901
NO5 PS
277.2
Tat Ant Trap X, Tat Roach Bait V,
Sumithion
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
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Summary of Use Sites:
Food:
Residential:
Target Pests:
Formulation Types:
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.
The only registered use in the U.S. is for
containerized ant and roach baits in child resistant
packaging.
Ants, roaches, palmetto bugs, waterbugs
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.L). 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 hi
use patterns as well as the variability in using data from various sources.
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
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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.
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
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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.
Dietary risk analyses for fenitrothion were conducted with the Dietary Exposure
Evaluation Model (DEEM). 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.
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Table 1. Summary of Toxicological Endpoints and Other Factors Used in the Human
Dietary Risk Assessment of Fenitrothion
Assessment
Acute Dietary
Chronic
Dietary
Study
Acute
Neurotoxicity-
Rat
1 -year Feeding
Study-Dog
Dose
NOAEL=
12.5
mg/kg/day
LOAEL=
50
mg/kg/day
NOAEL=
0.125
mg/kg/day
LOAEL=
0.25
mg/kg/day
Endpoint
Tremors and
impaired motor
coordination
Plasma ChE
inhibition and
histopathology
changes of the
lymph nodes
TJF
100
100
-
FQPA
Safety
Factor
IX
IX
PAD
0.13
rag/kg/
day
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 sub-population is children 1-6 at 0.7% of the cP AD. Note that this
estimate is considered to be somewhat conservative, since 100% crop treatment is assumed for
wheat gluten produced hi Australia.
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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
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organophosphate in turn and identifying 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 ralemakmg 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
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acute food exposure. An aggregate 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-
m-tolyl) 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 re-evaluated 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 hi 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-rnethyl-4-nitrophenol is of potential
lexicological 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
Wheat Gluten
Tolerance Currently Listed
Under 40 CFR§ 185.2200
30 ppm
Reassessed
Tolerance"
3 ppm
Comment
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,
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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.
2. Endocrine Disrupter 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 Disrupter 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 hi wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects hi 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 Disrupter
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 tune.
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
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neurotoxicity (DNT) study for fenitrothion. The Agency has concluded 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, 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/opp/op."
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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 Requirement-
Report 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.
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