US Environmental Protection Agency
Office of Pesticide Programs
Reregistration Eligibility Decision
for Phosalone
When EPA concluded the organophosphate (OP) cumulative risk assessment in July 2006, all
tolerance reassessment and reregi strati on eligibility decisions for individual OP pesticides were
considered complete. OP Interim Reregistration Eligibility Decisions (IREDs), therefore, are
considered completed REDs. OP tolerance reassessment decisions (TREDs) also are considered
completed.
Combined PDF document consists of the following:
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 (July 31, 2006)
Phosalone TRED
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I
55
V
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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 Reregi strati on Eligibility Decisions (IREDs) and Interim
Tolerance Reassessment and Risk Management Decisions (TREDs) for the
Organophosphate Pesticides, and Completion of the Tolerance Reassessment and
Reregi strati on Eligibility Process for the Organophosphate Pesticides
FROM: Debra Edwards, Director
Special Review and Reregi strati on 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 individual-
chemical review process. The Agency's review of individual OPs has resulted in the issuance of
Interim Reregi strati on Eligibility Decisions (IREDs) for 22 OPs, interim Tolerance
Reassessment and Risk Management Decisions (TREDs) for 8 OPs, and a Reregi strati on
Eligibility Decision (RED) for one OP, malathion.l 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
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 1 of 3
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(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 reregi strati on, other than product-specific reregi strati on.
The Special Review and Reregi strati on 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 2 of 3
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Attachment A:
Organophosphates included in the OP Cumulative Assessment
Chemical
Acephate
Azinphos-methyl (AZM)
Bensulide
Cadusafos
Chlorethoxyphos
Chlorpyrifos
Coumaphos
DDVP (Dichlorvos)
Diazinon
Dicrotophos
Dimethoate
Disulfoton
Ethoprop
Fenitrothion
Malathion
Methamidophos
Methidathion
Methyl Parathion
Naled
Oxydemeton-methyl
Phorate
Phosalone
Phosmet
Phostebupirim
Pirimiphos-methyl
Profenofos
Propetamphos
Terbufos
Tetrachlorvinphos
Tribufos
Trichlorfon
Decision Document
IRED
IRED
IRED
TRED
TRED
IRED
TRED
IRED
IRED
IRED
IRED
IRED
IRED
TRED
RED
IRED
IRED
IRED
IRED
IRED
IRED
TRED
IRED
TRED
IRED
IRED
IRED
IRED
TRED
IRED
TRED
Status
IRED completed 9/2001
IRED completed 10/2001
IRED completed 9/2000
TRED completed 9/2000
TRED completed 9/2000
IRED completed 9/2001
TRED completed 2/2000
IRED completed 6/2006
IRED completed 7/2002
IRED completed 4/2002
IRED completed 6/2006
IRED completed 3/2002
IRED completed 9/2001
IRED addendum completed 2/2006
TRED completed 10/2000
RED completed 8/2006
IRED completed 4/2002
IRED completed 4/2002
IRED completed 5/2003
IRED completed 1/2002
IRED completed 8/2002
IRED completed 3/2001
TRED completed 1/2001
IRED completed 10/2001
TRED completed 12/2000
IRED completed 6/2001
IRED completed 9/2000
IRED completed 12/2000
IRED completed 9/2001
TRED completed 12/2002
IRED completed 12/2000
TRED completed 9/2001
Page 3 of 3
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vvEPA
United States Prevention, Pesticides EPA 738-R-01-001
Environmental Protection And Toxic Substances January 2001
Agency (7508C)
Report on FQPA Tolerance
Reassessment Progress
and Interim Risk
Management Decision for
Phosalone
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United States
Environmental Protection
Agency
Prevention, Pesticides
and Toxic Substances
(7508C)
EPA738-F-01-001
January 2001
Phosalone Facts
EPA has assessed the dietary risks of phosalone and prepared a "Report on FQPA Tolerance
Reassessment Progress and Interim Risk Management Decision" for this organophosphate (OP)
pesticide. Phosalone fits into its own "risk cup"-- its individual risks are within acceptable levels.
Phosalone has no U.S. registrations and nine
import tolerances, on almond (hulls), almonds, apples,
apricots, cherries, grapes, peaches, pears, and plums
(fresh prunes). Phosalone treated crops do not pose
risk concerns, and no risk mitigation is necessary at
this time.
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 phosalone cannot be considered final until this
cumulative assessment is complete. Further risk
mitigation may be warranted 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 in food, drinking water, and other non-
occupational exposures also must be reassessed to
make sure they meet the new FQPA safety standard.
The phosalone interim decision was made through the OP pilot public participation process,
which increases transparency and maximizes stakeholder involvement in EPA's development of risk
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
phosalone.
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.
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Uses
An insecticide/acaricide, phosalone is used to control various insect species in/on almonds,
apples, apricots, cherries, grapes, peaches, pears, and plums in Algeria, Austria, Belgium,
Canada, Croatia, Czech Republic, France, Greece, Hungary, Iraq, Italy, Japan, Kuwait,
Morocco, Poland, Portugal, Russia, Slovak Republic, Spain, Switzerland, Taiwan, Tunisia,
Turkey, and Ukraine. It is not registered under FIFRA and may not be sold, distributed, or
used in the U.S.
Nine import tolerances are established for residues of phosaone in/on imported almonds,
apples, apricots, cherries, grapes, peaches, pears, and plums. It is estimated that less than
1.5% of the apples (fresh and dried), 0.1% of pears, 0.05% of peaches, and 0.2% of plums
available in the U.S. are imported from countries with phosalone registrations. Total imports
treated with phosalone is approximately 13.0 %; 6.0 % of which is from apple juice.
Health Effects
Risks
Phosalone 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.
Dietary exposures from eating food crops treated with phosalone are below the level of
concern for the entire U.S. population, including infants and children. Dietary exposure through
drinking water is not expected because there is no domestic usage.
Risk Mitigation
Dietary risk from exposure to phosalone does not exceed EPA's level of concern. Therefore,
no mitigation is necessary and no further actions are warranted at this time.
Next Steps
Numerous opportunities for public comment were offered as this decision was being
developed. The phosalone IRED therefore is issued in final (see www.epa.gov/REDs/ or
www.epa.gov/pesticides/op ), without a formal public comment period. The docket remains
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 phosalone and may request further risk
mitigation measures. For all OPs, raising and/or establishing tolerances will be considered once
a cumulative assessment is completed.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
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 related to the
revised risk assessment for the organophosphate pesticide phosalone. 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 the dietary risk from phosalone as part of the
tolerance reassessment process for this chemical, presents a summary of the related food tolerance for
this single chemical, and provides the Agency's current risk management decision based on the risk
assessment. Phosalone is not registered in the U.S. However, there are nine import tolerances. 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 phosalone" is published in the Federal Register. This
document and the technical documents supporting it 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/pesticides/op/phosalone.htm."
This document is based on the updated technical information found in the phosalone public
docket. The docket not only includes background information and comments on the Agency's
preliminary risk assessments, but also now includes the revised risk assessment for phosalone, and a
document summarizing the Agency's Response to Comments. The Response to Comments document
addresses corrections to the preliminary risk assessment submitted by the chemical manufacturer,
Aventis CropScience, as well as comments submitted by the general public and stakeholders during the
comment period on the risk assessment.
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
Food Quality Protection Act of 1996 (FQPA), the Agency is undertaking a special effort to maintain
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open public dockets on the organophosphate pesticides and to engage the public in the reregistation
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 phosalone 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 phosalone 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, John Pates at (703) 308-8195.
Lois A. Rossi, Director
Special Review and
Reregistation Division
Attachment
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Report on FQPA Tolerance Reassessment Progress
and Interim Risk Management Decision
for
Phosalone
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TABLE OF CONTENTS
PHOSALONE TEAM i
GLOSSARY OF TERMS AND ABBREVIATIONS ii
EXECUTIVE SUMMARY v
OVERALL RISK SUMMARY v
I. INTRODUCTION 1
II. CHEMICAL OVERVIEW 2
A. Regulatory History 2
B. Chemical Identification 3
C. Use Profile 4
D. Estimated Usage of Pesticide 5
III. SUMMARY OF PHOSLAONE RISK ASSESSMENT 8
A. Human Health Risk Assessment 8
1. Dietary Risk from Food 8
a. Toxicity 8
b. FQPA Safety Factor 9
c. Population Adjusted Dose (PAD) 10
d. Exposure Assumptions 10
e. Acute Food Risk 11
f. Chronic Food Risk 11
IV. FQPA TOLERANCE REASSESSMENT PROGRESS & INTERIM RISK
MANAGEMENT DECISION 12
A. Tolerance Reassessment Progress & Interim Risk Management Decision.. 12
B. Summary of Phase 5 Comments 13
C. Regulatory Position 13
1. FQPA Assessment 13
a. "Risk Cup" Determination 13
b. Tolerance Summary 14
2. Endocrine Disrupters Effects 15
D. Regulatory Rationale 16
V. WHAT MANUFACTURERS MUST DO 16
A. Additional Data Requirements 16
B. Risk Mitigation Requirements 17
VI. RELATED DOCUMENTS AND HOW TO ACCESS THEM 17
BIBLIOGRAPHY 18
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PHOSALONE TEAM
Office of Pesticide Programs:
Health Effects Risk Assessment
Kristina El-Attar
Bill Hazel
Kit Farwell
Use and Usage Analysis
Jihad Alsadek
Mike Hennessey
Registration Support
N/A
Risk Management
John Leahy
John Pates
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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
ORES 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
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
HOT 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/1, mg/kg or ppm.
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GLOSSARY OF TERMS AND ABBREVIATIONS
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
LOG 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.
NA Not Applicable
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
PCA Percent Crop Area
PDF 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
Q!* 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
RiD Reference Dose
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GLOSSARY OF TERMS AND ABBREVIATIONS
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(c) 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
\ig/g Micrograms Per Gram
jig/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
IV
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Executive Summary
EPA has completed its review of public comments on the revised risk assessment and is issuing
its risk management decisions for phosalone, an organophosphate insecticide. The decisions outlined in
this document do not include the final decisions for phosalone. The revised risk assessment is based on
review of the required target data base supporting the nine phosalone import tolerances and information
received during the public comment periods in the open process developed through the Tolerance
Reassessment Advisory Committee (TRAC).
Overall Risk Summary
All phosalone containing products registered in the U.S., as of 1992, have been canceled;
human exposure to this pesticide is strictly through the consumption of imported foods. This risk
assessment involves consideration of only the hazard component of the risk and food sources of dietary
exposure. Residential and occupational exposures as well as dietary exposure through drinking water
are not expected because there is no domestic use of phosalone. Therefore, aggregate acute and
chronic risks are attributable only to food sources of dietary exposure. EPA's revised risk assessment
for phosalone indicates that acute and chronic dietary risk is below the Agency's level of concern;
therefore, no risk mitigation is necessary at this time.
The tolerance reassessment decision for phosalone will be issued once the cumulative
assessment for all of the organophosphates is completed. The Agency may need to issue further risk
management measures for phosalone at the time the organophosphate cumulative assessment is
finalized.
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VI
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I. Introduction
This report on the progress toward tolerance reassessment of phosalone is the result of the pilot
process developed through the TRAC to facilitate greater public involvement in the ongoing FIFRA
reregistation and FQPA tolerance reassessment initiatives on pesticides. Phosalone is subject only to
FQPA because it has only import tolerances and is not registered for use in the U.S. However, some
history and background of FIFRA is included here for informational purposes and to provide a
discussion of the existing laws governing pesticides.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into law.
This Act amended FFDCA to require that all tolerances be reassessed within a 10-year period and that
those, which are considered to be the riskiest, are reassessed first and foremost. 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. Since organophosphates share a common mechanism of toxicity and are considered some of
the riskiest of all chemicals, it has been deemed necessary that these particular chemicals be grouped
together. The Agency will evaluate the cumulative risk posed by the entire organophosphate class of
chemicals after completing risk assessments for the individual organophosphates. Although not subject
to the reregi station process, due to no domestic registrations, phosalone does have import tolerances
that could factor into dietary risk. 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 individual dietary assessment for the
organophosphate phosalone has been completed, and will be used in the cumulative assessment of all of
the organophosphate chemicals, to satisfy the requirements of FQPA.
Phosalone is not registered for use in the United States; however, there are nine import
tolerances on almonds, grapes, pome and stone fruits for this chemical. Because it is not registered in
the U.S., it is not subject to the reregistation process. It is subject to the requirements of FQPA;
therefore, a dietary risk assessment was completed. This document presents the Agency's dietary risk
assessment for phosalone, 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 phosalone 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 being published in the Federal Register. The Phase 6 of
the pilot process did not include a public comment period; however, for some chemicals, the Agency
may provide for another comment period, depending on the content of the risk management decision.
The 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. The
1
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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
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 the 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 the chemical. Section m gives an overview of the dietary risk assessment for
phosalone, including a discussion of any revisions that were 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/pesticides/op/phosalone.htm), and in the Public Docket.
II. CHEMICAL OVERVIEW
A. Regulatory History
Phosalone is an organophosphate insecticide/acaricide first registered in 1969. All U.S.
registrations were voluntarily canceled in 1989 by the registrant at that time, Rhone-Poulenc Ag
Company (RPAC). The Agency proposed to revoke all phosalone tolerances in 1998 (63 FR 3057).
However, in response to this proposal, RPAC (now Aventis CropScience) requested that the Agency
not revoke tolerances for phosalone residues in/on almonds, grapes, pome fruits (apples and pears),
and stone fruits (apricots, cherries, peaches, and plums) so that these commodities bearing phosalone
could continue to be imported legally into the U.S. In the Final Rule published in the Federal Register
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of 10/26/98, the Agency maintained existing tolerances for residues of phosalone in/on the specified
commodities: almond (hulls), almonds, apples, apricots, cherries, grapes, peaches, pears, and plums
(fresh prunes), while revoking the remaining phosalone tolerances under (40 CFR §180.263) and (40
CFR §186.4800).
Permanent tolerances of 0.1 to 50.0 ppm(s) have been established by the U.S. EPA under 40
CFR §180.263 for residues of phosalone in/on almonds, almond hulls, grapes, apples, apricots,
cherries, peaches, pears, and plums imported into this country. Products containing the active
ingredient phosalone are registered and marketed in a number of countries (mostly in Europe), primarily
to tree crops and grapes, which may be treated and exported from those countries to the U.S.
However, the current use pattern is very limited in comparison to what may be specified on the label
because of the entry of other pest control products, use within IPM systems, marketing strategies and
changed grower practices.
B.
Chemical Identification
Common Name:
Phosalone
Chemical Name:
Chemical Family:
CAS Registry Number:
OPP Chemical Code:
(O,O-diethyl S-[(6-chloro-2-oxobenzoaxzolin-
3-yl)methyl] phosphorodithioate)
Organophosphate
2310-17-0
097701
Empirical Formula:
Molecular Weight:
C,?H,,CINOJ>S?
367.80
Trade and Other Names: Zolone, Rubitox
Basic Manufacturers:
Aventis CropScience
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A detailed discussion on the physical properties of phosalone can be found in the EPA
document entitled "Phosalone: Preliminary Human Health Risk Assessment," dated November 1, 1999.
C.
Use Profile
The following information is based on the current uses of phosalone outside of the United
States, and includes an overview of use sites and application methods. Phosalone is registered in:
Algeria, Austria, Belgium, Canada, Croatia, Czech Republic, France, Greece, Hungary, Iraq, Italy,
Japan, Kuwait, Morocco, Poland, Portugal, Russia, Slovak Republic, Spain, Switzerland, Taiwan,
Tunisia, Turkey, and Ukraine for use on almonds, grapes, pome and stone fruits. Phosalone is not
registered under FIFRA and may not be sold, distributed, or used in the U.S.
Type of Pesticide:
Summary of Use Sites:
Target Pests:
Insecticide/Acaricide
Import only: Almond (hulls), Almonds, Apples,
Apricots, Cherries, Grapes, Peaches, Pears, Plums
(fresh prunes).
Phosalone is used to control mites, apple rust mite,
broad mite, brown almond mite, brown mite, spruce
spider mite, citrus red mite, European red mite, Pacific
spider mite, two-spotted spider mite, thrips, citrus
thrips, Colorado potato beetle, plum curculio, pecan
weevil, chrysanthemum leafminer, cherry fruit fly,
walnut husk fly, apple maggot, whiteflies, aphids, citrus
aphids, pecan aphids, buckthorn aphid, apple aphid,
green apple aphid, leafcurl plum aphid, thistle aphid,
black peach aphid, walnut aphid, rosy apple aphid,
wooly apple aphid, potato aphid, rose, aphid, filbert
aphid, black cherry aphid, green peach aphid, hop
aphid, black pecan aphid, pecan spittlebug,
leafhoppers, potato leafhopper, grape, leafhopper,
variegated leafhopper, pecan phylloxera, grape
phylloxera, pear psylla, European apple sawfly, peach
twig borer, potato tuberworm, green fruitworm,
orangedog, plume moths, pecan nut casebearer,
mineola moth, European corn borer, fruittree leafroller,
redbanded leafroller, obliquebanded leafroller,
omnivorous leafroller, European leafroller, filbert
leafroller, oriental fruit moth, hickory shuckworm,
codling moth, filbert worm, grape berry moth,
eyespotted bud moth.
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Formulation Types:
Method and Rates of Application:
Equipment-
Method and Rate -
Use Classification:
There are three basic formulations
manufactured: emulsifiable concentrate (2.91
Ib/gallon/ai), flowable concentrate (4.17
Ib/gallon/ai), and wettable powder (30%). In a
very few countries, a local formulation is used.
Local formulations are simply more dilute
versions of either the (2.91 Ib/gallon/ai) EC or
the 30% WP, using the same inerts but in
higher quantity to achieve a lower assay.
Ground and/or aerial equipment.
Phosalone is applied as broadcast foliar applications
using ground or aerial equipment. The maximum use
rate per season on labels ranges from 1.6 Ib
ai/acre/season to 4.0 Ib ai/acre/season, however, labels
for non-EU countries (Turkey, Czech Republic, and
Slovak Republic) do not specify the maximum number
of applications allowed.
Actual use practices typically result in significantly
longer (<35 days) preharvest intervals, no more than 2-
3 applications per year at timings determined by pest
pressure and official recommendations.
N/A Not registered for use in the U.S.
D. Estimated Usage of Pesticide
This section summarizes the best estimates available for the pesticide uses of phosalone. 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.
The market share of phosalone among the exporting countries (preceding section labeled:
Summary of Use Sites) is minimal. The percent of almonds, apples, apple juice, apricots, cherries,
grapes, raisins, peaches, pears, and plums derived from countries possessing phosalone registrations
was assessed using statistics submitted by RPAC (now Aventis CropScience) quantifying the amount of
each commodity available for U.S. consumption from both domestic and foreign sources. It is
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estimated that less than 1.5% of the apples (fresh and dried), 0.1% of pears, 0.05% of peaches, and
0.2% of plums available in the U.S. are imported from countries with phosalone registrations. These
statistics, which reflect U.S. production data from the USDA National Agricultural Statistics Service
averaged from 1992-1996 plus U.S. import data from the U.S. Department of Commerce averaged
from 1992-1996, were used to generate the values summarized in Table 1. The FDA monitoring data
for 1992-1998 support these numbers.
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Table 1. Phosalone Usage Information
Crop
Almonds
Apples
Apricots
Cherries
(Sweet & Tart
Varieties)
Grapes
Peaches
(including
nectarines)
Pears
Plums
Commodity
nutmeat
fresh + dried
juice
fresh + dried + pulp/prepared
or preserved + kernel (peach,
plum or other stone fruits)
fresh
fresh + juice + wine
raisins (fresh basis)
fresh
fresh (including quince) +
nesoi
fresh + dried (fresh basis)
Total Available for
U.S. Consumption
from Domestic +
Foreign Sources
(1000 Ibs.)
532,714
8,332,009
4,913,086
222,569
184,006
11,005,780
3,282,885
1,583,569
9,413,574
1,589,478
Total from
Domestic
Sources
(1000 Ibs.)
532,600
8,024,340
2,458,660
193,644
172,384
9,463,988
3,199,120
1,482,580
9,279,200
1,543,604
Total from
Foreign
Sources a
114
307,669
2,454,426
28,925
11,622
1,541,792
83,765
100,989
134,374
46,874
Total from
Exporting Countries
with Phosalone
Registered
(1000 Ibs.)
1
117,171
294,785
857
938
418,220
14,861
845
6,051
2,756
Total from Exporting
Countries without
Phosalone Registered a
(1000 Ibs.)
113
190,498
1,775,168
28,068
10,684
1,046,579
68,904
100,144
128,323
44,118
% from
Countries
with
Phosalone
Registered
0.0002 %
1.41%
6.0 %
0.39 %
0.51 %
3.8 %
0.45 %
0.05 %
0.06 %
0.17%
a The values in these columns do not account for countries without phosalone registrations that are responsible for <1% of the corresponding commodity imported
by the U.S.
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III. Summary of Phosalone Risk Assessment
Following is a summary of EPA's revised human health risk findings and conclusions for the
organophosphate pesticide phosalone, as fully presented in the revised risk assessment document,
"Phosalone: Revised Human Health Risk Assessment," dated June 12, 2000. The risk assessment
presented here forms the basis of the Agency's interim risk management decision for phosalone only;
the Agency must complete a cumulative assessment of the risks of all organophosphate pesticides
before it can complete its reassessment of the phosalone tolerances.
Because phosalone is not currently registered for use in the U.S., only a human health dietary
assessment from exposure to this chemical through food was necessary.
A. Human Health Risk Assessment
During the comment periods on the phosalone human health risk assessment, the only
comments received were from the registrant, Aventis CropScience. The Agency reviewed the
comments and no substantive revisions were made to the risk assessment. However, based on these
comments and recently submitted data, the Agency has decided to waive and/or reduce the number of
field trials required to support tolerance reassessment. Since phosalone has no U.S. registrations, the
assessment did not address ecological, drinking water, or occupational risk issues. The only source of
possible human exposure is through residues in imported foods and the conclusion of the assessment
indicated that food risk from phosalone is below the Agency's level of concern.
1. Dietary Risk from Food
a. Toxicity
EPA has determined that it is appropriate to treat the organophosphates (OPs) as sharing a
common mechanism of toxicity because of their common mode of action, which inhibits cholinesterase
(ChE) activity. As required by FQPA, a cumulative assessment will need to be conducted to evaluate
the risk from food, water, and non-occupational exposure resulting from all uses of OPs.
Information from blood cholinesterase inhibition data is considered to provide important insights
into potential hazard. Although red blood cell (RBC) measures of acetylcholinesterase (AchE) are
generally preferred over plasma measures of cholinesterase activity, the Agency may use plasma
cholinesterase inhibition data under certain circumstances, such as if red blood cell data are insufficient,
of poor quality, or unavailable; if there is a lack of dose-dependency for the red blood cell
acetylcholinesterase inhibition; or, if the dose responses for inhibition of plasma cholinesterase more
closely approximate those for AchE inhibition in the nervous system than do the dose responses for
RBC acetylcholinesterase inhibition.
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NOAELs were not determined for plasma ChE inhibition in the acute rat neurotoxicity study;
for systemic effects or plasma, RBC, or brain ChE inhibition in the subchronic rat neurotoxicity study;
for plasma ChE inhibition in the chronic dog study; for plasma or RBC ChE inhibition in the mouse
carcinogenicity study; or for RBC ChE inhibition in the reproduction study. The lack of NOAELs in
these studies did not interfere with endpoint selection and the toxicology database is considered
adequate and of good quality.
The Hazard Identification Assessment Review Committee (HIARC) evaluated the lexicological
database for phosalone and selected toxicity endpoints for dietary exposure. The ensuing table (Table
2) contains a summary of the doses and toxicity endpoints selected for use in the human health risk
assessment.
Table 2. Summary of Toxicological Endpoints and Other Factors Used in the Human Dietary
Risk Assessment of Phosalone.
Exposure
Acute Dietary
(General population including
infants and children)
Acute Dietary
(Females 13+)
Chronic Dietary
Dose
(mg/kg/day)
LOAEL = 10
Endpoint
Plasma ChE inhibition
Study
Acute neurotoxicity
in rats
UF =300 Acute RfD = Acute PAD = 0.03 mg/kg /day
Developmental
NOAEL = 1
Post-implantation loss
Developmental
:oxicity in rabbits
UF = 1 00 Acute RfD = Acute PAD = 0. 01 mg/kg /day
NOAEL = 0.2
Plasma and RBC ChE inhibition (both sexes),
decreased testicular weight and lesions
2-Year Rat Study
UF = 1 00 Chronic RfD = Chronic PAD = 0.002 mg/kg/day
b. FQPA Safety Factor
The FQPA Safety Factor was reduced to IX. The toxicity database includes an acceptable
two-generation reproduction study in rats and acceptable prenatal developmental toxicity studies in rats
and rabbits. These studies show no increased sensitivity to fetuses as compared to maternal animals
following acute in utero exposure in the developmental rat and rabbit studies and no increased
sensitivity to pups as compared to adults in a multi-generation reproduction study in rats. There was no
evidence of abnormalities in the development of the fetal nervous system in the pre/post natal studies.
Adequate actual data, surrogate data, and/or modeling outputs are available to satisfactorily assess
dietary exposure. The assumptions and models used in the assessments do not underestimate the
potential risk for infants and children. Therefore, the additional 10X factor as required by FQPA was
reduced to IX.
It must be noted that in the prenatal developmental toxicity study in rats and the two-generation
reproduction study in rats, effects in the fetuses/offspring were observed at doses higher than those
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producing maternal/paternal effects. The effects observed in the fetuses/offspring are not considered a
true quantitative increase in fetal sensitivity, due to two reasons. First, the endpoint of 1 mg/kg/day is a
very conservative indicator of toxicity because it is based on total resorptions and is not a litter effect.
Second, although cholinesterase activity was not determined in the study, it is likely that significant
cholinesterase inhibition occurred at 20 mg/kg/day, considering the severity of the maternal clinical signs
(labored breathing, abdominal cramps, extension spasms, prostration). Based upon information from
other studies, it is presumed that cholinesterase activity was also inhibited in the maternal rabbits at 10
mg/kg/day. Therefore, ChE determinations would most likely have shown the maternal NOAEL to be
the same as the developmental NOAEL or lower.
c. Population Adjusted Dose (PAD)
The PAD is a 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 residue values in the food. For chronic exposures, dietary risk is
calculated by using the average consumption value for food and average residue value. In the case of
phosalone, the FQPA safety factor is IX; therefore, the acute or chronic Reference Dose (RfD) = the
acute or chronic Population Adjusted Dose (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
Revised acute and chronic dietary risk analyses for phosalone were conducted with the Dietary
Exposure Evaluation Model (DEEM). DEEM incorporates consumption data generated in USDA's
Continuing Survey of Food Intakes by Individuals (CSFII), 1989-91. Acute and chronic dietary
analyses were also conducted using anticipated residues (ARs) based on FDA Surveillance Monitoring
data. Anticipated residues on almonds and cherries were calculated from field trial results due to lack
of sufficient monitoring data. Although USDA/PDP data were available for some commodities, the
FDA data were preferable due to a larger number of samples of foods imported from countries having
phosalone registrations. In the case of almonds where there were non-detectable residues, /^ the limit
of detection was used in the dietary exposure assessments. The acute and chronic analyses take into
consideration the reduction of phosalone residues in certain processed foods.
Based on available livestock metabolism and feeding studies, it has been determined that there
is no reasonable expectation of finite residues being transferred into livestock commodities from feed
items bearing phosalone residues, i.e., a 180.6(a)(3) classification is appropriate. With regards to wet
apple pomace, the majority of apple imports are in the form of juice (84%), with 9% of apple imports
being fresh fruit. It is unlikely that these imported apples will be used for processing; therefore,
domestic livestock are unlikely to be fed wet apple pomace bearing phosalone residues. In addition, of
the countries with registered uses of phosalone on apples, only Canada exports significant quantities of
10
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beef (3% of available commodity) to the U.S. If the percentage of the apple crop treated with
phosalone in Canada (6.5%) is also considered, then only 0.2% of the available beef supply could
possibly contain phosalone residues. As a result, tolerances for phosalone residues in livestock
commodities are not necessary. Consequently, the dietary exposure assessments reflected no
consumption of livestock commodities.
e. Acute Food Risk
An acute dietary assessment was conducted for phosalone. A Tier 3 probabilistic (Monte
Carlo) technique was used in order that the high-end (or low end) consumer had an equal chance of
getting a high or low dose residue level. A risk estimate that is less than 100% of the (aPAD), the dose
at which an individual could be exposed on any given day that would not be expected to result in
adverse health effects, does not exceed the Agency's risk concern. Results at the 99.9th percentile of
exposure for all population subgroups (<0.74% of the aPAD) confirm that the current residue levels do
not exceed the Agency's risk concern. This estimate has been highly refined using Monte Carlo
analysis and FDA monitoring data as the principal source of anticipated residues.
The aPAD for the general population (including infants and children) is 0.03 mg/kg/day. This
endpoint is from an acute neurotoxicity study in the rats with a LOAEL of 10 mg/kg/day, the lowest
dose tested. Although a NOAEL for plasma cholinesterase was not determined in this study, the
LOAEL is believed to be close to a NOAEL, as neither brain nor RBC cholinesterase were statistically
significantly inhibited at 10 mg/kg or 25 mg/kg in this study. Uncertainty factors total 300X (10X for
interspecies extrapolation, 10X for intraspecies variation, and 3X for lack of a NOAEL).
f. Chronic Food Risk
The chronic dietary risk assessment is achieved by combining the average consumption values
for food and average residue values for those foods, for each population subgroup, over a 70-year
lifetime to determine average exposure in mg/kg/day. Based upon achieved modeling numbers, DEEM
estimates that all population subgroups are chronically exposed to phosalone at a level less than the
phosalone chronic Population Adjusted Dose (cPAD). Chronic risks to all population subgroups was
0.1% or less of the cPAD. The chronic dietary risk from phosalone residues in food alone is also
below the Agency's level of concern.
In summary, acute risks to all population subgroups were <0.74% of the aPAD and chronic
risks to all population subgroups were <0.1% of the cPAD, well below the Agency's levels of concern.
Below in Table 3 is a representation of these risk estimates.
11
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Table 3. Summary of Phosalone Acute & Chronic Non-cancer Dietary Exposure and Risk
Estimates l
Population Subgroup
General U.S. Population
All Infants (<1 yr)
Children (1-6 yrs)
Children (7-1 2 yrs)
Females (13-50 yrs)
Males (13- 19 yrs)
Males (20+ yrs)
Acute Assessment (99.9th %-ile of Exposure)
General U.S. Population
Including All Infants and
Children Subgroups
Exposure
(mg/kg/day)
0.000049
0.000084
0.000221
0.000132
0.000016
0.000014
0.000017
% aPAD
0.16
0.28
0.74
0.44
0.05
0.05
0.06
Females 13+
Exposure
(mg/kg/day)
N/A
N/A
N/A
N/A
0.000017
N/A
N/A
% aPAD
N/A
N/A
N/A
N/A
0.17
N/A
N/A
Chronic Assessment
Exposure
(mg/kg/day)
0.000001
0.000001
0.000002
0.000001
0.000000
0.000000
0.000000
% cPAD
0.0
0.1
0.1
0.0
0.0
0.0
0.0
'The Acute Population Adjusted Doses (aPADs) are 0.03 mg/kg/day for the "General U.S. Population Including All
Infants and Children Subgroups" and 0.01 mg/kg/day for "Females 13+." The Chronic PAD (cPAD) is 0.002
mg/kg/day for all population subgroups.
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 phosalone but has not
considered the cumulative effects of organophosphates as a class. Based on a review of these generic
data and public comments on the Agency's revised risk assessment for the active ingredient phosalone,
EPA has sufficient information on the human health effects of phosalone to make some interim decisions
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 phosalone alone in order to determine whether any risk
reduction measures are necessary to allow the continued importation of almonds, apples, apricots,
cherries, grapes, peaches, pears, and plums containing this chemical, pending completion of the
cumulative assessment.
As a result of its assessment, EPA has determined that dietary risk from exposure to phosalone
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, however, 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
12
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of the implementation of FQPA. By evaluating each organophosphate in turn and identifying
appropriate risk reduction measures, the Agency is addressing the risks from the 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
phosalone food residue import tolerances as called for by the FQPA. When the Agency has
completed the cumulative assessment, the phosalone tolerances will be reassessed in that light. At that
time, the Agency will reassess phosalone 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 phosalone, 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 phosalone to the public in July 26, 2000, and
provided a 60 day comment period for interested parties to submit information, including risk mitigation
suggestions or proposals. During this time, no comments were received in relation to this comment
period.
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 phosalone is within its own "risk cup." In other
words, if phosalone did not share a common mechanism of toxicity with other chemicals, EPA would
be able to conclude today that the import tolerance for phosalone on almonds, grapes, apples, apricots,
cherries, peaches, pears, and plums meets the FQPA safety standards. In reaching this determination,
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EPA has considered the available information on the special sensitivity of infants and children, as well as
chronic and acute food exposure. An aggregate assessment was not conducted for phosalone, because
there are no domestic uses. But, results of the acute and chronic food assessments indicate that
exposures are within acceptable levels; that is, risk from exposure to phosalone "fits" within the
individual risk cup. Therefore, the import tolerance remains in effect and unchanged until a full
reassessment of the cumulative risk from all organophosphates is completed.
b. Tolerance Summary
The established tolerance for residues of phosalone in/on plant commodities is currently
expressed in terms of residues of phosalone per se (S-(6-chloro-3-(mercaptomethyl)-2-
benzoxazolinone)O,O,-diethyl phosphorodithioate) [40 CFR §180.263]. It should be noted, however,
that the preferred chemical name for phosalone is (O,O-diethyl S-[(6-chloro-2-oxobenzoxazolin-3-
yl)methyl] phosphorodithioate). The referenced tolerances for residues of phosalone in/on plant
commodities are outlined in Table 4 of this document.
Because the grape use will be deleted from French labels in the near future, it has been decided
that additional field trial studies need to be conducted solely in Canada reflecting their Good
Agricultural Practices (GAP). The tolerances are to reflect the Canadian use pattern on grapes, apples,
pears, cherries, peaches, and plums. In response to Aventis' comments, the Agency has decided to
waive pear field trials and reduce the number of trials required on peaches and plums. However,
several side-by-side field trials have been determined necessary to compare residues resulting from the
application of two major formulation classes.
It is recommended that both the EC and either the WP or FLC be applied in side-by-side
studies involving two major grape growing regions and that the re-treatment intervals being tested
should mirror common commercial practice.
The same scenario is true for side-by-side studies involving apples, but only one additional trial,
conducted in Canada in one major grape growing region, is recommended. The field trial is to
encompass the EC and either the WP or FLC to be applied in side-by-side Canadian trials. In
conjunction, due to the very low percentage of imported pears available for consumption, the Agency
has decided not to require pear field trials. It is important to state that a pome fruit crop group
tolerance may not be established without the additional two pear field trials which would reflect the
Canadian GAP.
The new Canadian cherry field trials tentatively satisfy the requirements to support an import
tolerance. Depending upon whether or not these side-by-side studies on other crops indicate
differences between residues, resulting from different formulation classes, additional cherry field trials
may be required testing the EC formulation.
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In respect to peaches and plums, EPA is reducing the number of trials to be conducted from
three to two each, but to require side-by-side trials testing the EC and either the FLC or WP. These
trials should reflect the Canadian GAP.
Table 4. Tolerance Reassessment Summary for Phosalone.
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comment/Correct Commodity Definition
Tolerances listed under 40 CFR §180.263:
Almonds
Almonds, hulls
Apples
Apricots
Cherries
Grapes
Peaches
Pears
Plums (fresh prunes)
0.1
50.0
10.0
15.0
15.0
10.0
15.0
10.0
15.0
0.1
Revoke
TBDa
Almond, nutmeat
Almond hulls are not imported.
The available data indicate that the established
:olerances are too high and may be lowered to 1 .0 ppm
for residues in/on grapes and stone fruits, and 2.0 ppm
for residues in/on pome fruits. However, additional
data reflecting the slightly higher use rate of the
Canadian GAP are required before the tolerances can be
reassessed.
Tolerances needed under 40 CFR §180.263
Raisins
Prunes
Pome fruits
Stone fruits
None
None
None
None
TBD
TBD
TBD
TBD
Additional data on grapes are needed to assess an
appropriate tolerance for residues in raisins. Phosalone
residues concentrate by ~2X in raisins.
To assess an appropriate tolerance for residues in
srunes, data are needed from field trials on plums.
Phosalone residues concentrate by a maximum of ~2x in
srunes.
The available residue data on imported apples, pears,
peaches, and cherries suggest that crop group
tolerances may be appropriate for pome and stone
fruits. If the requested residue data on pome and stone
fruits from Canadian studies are similar to the available
data from Europe and Japan, then crop groups should
be established for pome fruits and stone fruits
concomitant with revoking the individual tolerances for
the members of these crop groups.
a TBD = To be determined. Tolerance cannot be determined at this time because additional data are required.
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
15
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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 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 Disrupter
Screening Program (EDSP).
When the appropriate screening and/or testing protocols being considered under the Agency's
EDSP have been developed, phosalone may be subjected to additional screening and/or testing to
better characterize effects related to endocrine disruption.
D. Regulatory Rationale
Phosalone has nine tolerances, and no U.S. registrations; 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.). Although phosalone has no U.S.
registrations and therefore is not subject to a FIFRA DCI, it does have a tolerance or tolerances for
almonds, grapes, pome and stone fruits that are imported into the U.S. EPA is currently working to
require the submission of acute, subchronic, and developmental neurotoxicity studies under the authority
of FFDCA. Results of these studies may further refine the risk assessments.
In addition, the In Vitro Unscheduled DNA Synthesis (UDS) Assay has been recommended to
be repeated in order to confirm the findings of an earlier study indicating weak UDS-inducing activity.
Likewise, the General Metabolism Study (in rats) has been deemed unacceptable, due to the majority
of the radioactivity in urine not being identifiable. Additional data have been requested in order to
upgrade the study to an acceptable status. In compliance with regulatory policy, the registrant (Aventis
CropScience) has planned a new rat metabolism study for initiation in approximately April 2000. This
study is being initiated in connection to the requested additional data, metabolite identification in urine,
which was not possible due to the unavailability of samples for further analysis.
16
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Additional Field Trials:
Peach and Plum field trials have been reduced from three to two each, but to require side-by-
side trials testing the EC and either the FLC or WP. These trials should reflect the Canadian
GAP.
Grape field trials are to include both the EC and either the WP or FLC to be applied in side-
by-side studies involving two major grape growing regions and that the re-treatment intervals
being tested mirror common commercial practice.
An apple field trial study is to be conducted in Canada in one major grape growing region,
involving one additional side-by-side trial encompassing the EC and either the WP or FLC. It
is important to state that a pome fruit crop group tolerance may not be established
without the additional two pear field trials which would reflect the Canadian GAP.
*(New Canadian cherry field trials tentatively satisfy the requirements to support an import
tolerance. Depending upon whether or not these side-by-side studies on other crops indicate
differences between residues, resulting from different formulation classes, additional cherry field
trials may be required testing the EC formulation).
B. Risk Mitigation Requirements
As discussed in this document, the acute and chronic food risk from the use of phosalone on
almonds, grapes, and certain pome and stone fruits is not of concern to the Agency; therefore, no
mitigation is necessary at this time. The Agency may need to pursue further risk management measures
for phosalone 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. 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.
The docket initially contained preliminary risk assessments and related documents as of
September 10, 1998. Sixty days later the first public comment period closed. The EPA then
considered comments, revised the risk assessment, and added the formal "Response to Comments"
document and the revised risk assessment to the docket on July 7, 1999.
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/phosalone.htm."
17
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25
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