&EPA
United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508C1
EPA 738-R-01-001
January 2001
        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)
EPA 738-F-01-001
January 2001
4>EFW   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 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 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 andnsk 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.

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  Uses
         An msecticide/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/o 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
        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.
 Risks
        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/RF.Ds/ or
       www.epa.gov/pe.sficides/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:
FCB
        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 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

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 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
                                          Reregistration 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 	
  GLOSSARY OF TERMS AND ABBREVIATIONS	«
  EXECUTIVE SUMMARY	    '.'.'.'.".	
  OVERALL RISK SUMMARY	V

  I.     INTRODUCTION 	                  l

  H.    CHEMICAL OVERVIEW	                         2
       A.    Regulatory History	      	2
       B.    Chemical Identification	                          	*
       C.    UseProfile	'.'.'.".*"".'""!.'!."!.".*.".*.".".'.""]	4
       D.    Estimated Usage of Pesticide	5

 HI.   SUMMARY OF PHOSLAONE RISK ASSESSMENT	8
       A.    Human Health Risk Assessment	8
            1. Dietary Risk from Food	        	o
                 a.    Toxicity	   	8
                 b.    FQPA Safety Factor	........!.....!!!!!. 9
                 c.    Population Adjusted Dose (PAD)	10
                 d.    Exposure Assumptions	  10
                 e.    Acute Food Risk	    H
                 f.     Chronic Food Risk	   H

 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	                                  ,0
                                    	lo

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                              PHOSALONE TEAM
 Office of Pesticide Programs:

 Health Effects Risk Assessment

 Kristina El-Attar
 Bill Hazel
 KitFarwell

 Use and Usage Analysis

 Jihad Alsadek
 Mike Hennessey

 Registration Support

N/A

Risk Management

John I^ahy
John Pates

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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
 ORES
 DWEL
 DWLOC
 EC
 EEC

 EP
 EPA
 FAO
 FDA
 FIFRA
 FFDCA
 FQPA
 FOB
 G
 GENEEC
 GLC
 GLN
 GM
 GRAS
 HA

 HAFT
 HOT
 BR
LC50
  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
 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.

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GLOSSARY OF TERMS AND ABBREVIATIONS

LDj0           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 EP A's Cancer Risk Model
RAC           Raw Agriculture Commodity
RBC           Red Blood Cell                          :
RED           Reregistration Eligibility Decision
REI            Restricted Entry Interval
RfD            Reference Dose
                                                 ID.

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 GLOSSARY OF TERMS AND ABBREVIATIONS
 RQ
 RS
 RUP
 SAP
 SCI-GROW
 SF
 SLC
 SLN
 TC
 TD
 TEP
 TGAI
 TLC
 TMRC
 torr
 TRR
 UF
 Hg/g
USDA
USGS
UV
WHO
WP
WPS
 Risk Quotient
 Registration Standard
 Restricted Use Pesticide
 Science Advisory Panel
 Tier I Ground Water Computer Model
 Safety Factor
 Single Layer Clothing
 Special Local Need (Registrations Under Section 24(c) of FIFRA)
 Toxic Concentration. The concentration at which a substance produces a toxic effect.
 Toxic Dose. The dose at which a substance produces a toxic effect.
 Typical End-Use Product
 Technical Grade Active Ingredient
 Thin Layer Chromatography
 Theoretical Maximum Residue Contribution
 A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
 Total Radioactive Residue         "•*-  '
 Uncertainty Factor
 Micrograms Per Gram
 Micrograms Per Liter
 United States Department of Agriculture
 United States Geological Survey
Ultraviolet
World Health Organization
Wettable Powder
Worker Protection Standard
                                              IV

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  Executive Summary
its risk
 te nskmamgem
       °f PUMC COmmentS °n fce revised risk ««««*
for phosalone, an organophosphate insecticide,
                                                                                    issuing
                                                    Ph°salone                     non

                        comment periods in the open process developed ftraugh the Tolerance
 Reassessment Advisory Committee (TRAC).                                    luicrdnce



 OveraU 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



 ZSTl^T'l^^
 ZnoT^n Tdr  ^ ?*?*«»* ensures' as well as dietary exposure through drinking watT

 are not expected because there * no domestic use of phosalone. Therefore, aggregate acute and


      C n   "
fh  ,                                                sure-      se
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.                                concern,




*«    ^e tole^^essment 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

nmentmeasuresforphosdone^^^

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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 FTFRA
  reregistration 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 reregistration 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 reregistration 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

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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 Safely 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 n provides a
 profile of the usage of the chemical.  Section IH 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.
H.    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 8180 263) and (40
CFR§ 186.4800).                                                                   V

       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:

                    Chemical Name:
                            Phosalone

                            (O,O-diethylS-[(6-chloro-2-oxobenzoaxzolin-
                            3-yl)methyl] phosphorodithioate)
                    Chemical Family:

                    CAS Registry Number:

                    OPP Chemical Code:

                    Empirical Formula:

                    Molecular Weight:
                            Organophosphate

                            2310-17-0

                            097701

                            C12HI5CIN04PS2

                            367.80

Trade and Other Names:    Zolone, Rubitox

Basic Manufacturers:       Aventis CropScience

                       3

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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

 Mport 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 leafrniner, 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, bkck cherry aphid, green peach aphid, hop
 aphid, black pecan aphid, pecan spittiebug,
 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:
                                                   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.
Method and Rates of Application:
              Equipment-

              Method and Rate -
                                           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.

        Use Classification:                 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

-------
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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-------
 IIL    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 phosalbrie 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.

-------
        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 (fflARC) evaluated the toxicological
 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 t _:
Plasma ChE inhibition
Study " i_
Acute neurotoxicity
In rats
UF=300 Acute RfD = Acute PAD = 0.03 mg/kg/day
Developmental
NOAEL = 1
Post-implantation loss
Developmental
toxicity in rabbits
UF = 1 00 Acute RfD = Acute PAD = 0.01 rag/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

-------
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 (CSFIT), 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, Ihe
 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, Ihe 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

-------
 beef (3 /o 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 avSable berf supplytuld


 P^cootam phosalone residue, As a result, tolerances for phosalone residues in iLk


 coZl   TT? SSaiy" Conse c°™*™ *»* » «** chanc* of
 getting a high or low dose residue level. A risk estimate that is less than 100% of the (aPAD) the dose


               ^^

                   .    ^ 6XCeed ^ AgCnCy'S ^ COnCem" Results at *e "-^ P-entile of

 noed    A       n ? b8K>qPS ^°-740/0 °f ^ ^^ C°llfinn ^ &e CUCTent «^c levels do
 not exceed theAgency's nsk concern. This estimate has been highly ^refined using Monte Carlo

 analysis and FDA monitoring data as the principal source of anticipated residues.



       TheaPAD for the general population (including infants and children) is 0.03 mg/kg/day This

 endpoin is from an acute neurotoxicity study in the rats with a LOAEL of 10 mg^g/dfy SwS


Sir^  °^LN?^Lforpl^chofc^^^
LOAEL is beheved to be close to a NOAEL, as neither brain nor RBC cholinesterase were  tatisticaUv

^cmnyin^itedatlOmg^gor25mS/kginthiSstudy.  Unce^ty factors total 3Z (^X for "

interspecies extrapolation, 10X for intraspecies variation, and 3X for lack of a NOAEL).



                   f.     Chronic Food Risk




                ^ ^ aSSessment is achieved by combining the average consumption values

                             f°r flM8e f°0dS' f°r Cach P^^011 sub, over a 70-year
nh                                   rODCay eXp°Sed to Phosalone at a kvel less thar the











                            •" pI>plllMi0
                                                    £0.74% of to aPAD md chronic


                                          CPAD' WeU W°«"i- Agency's levels
            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 *
j 1
• * — "£-"'_,
^ *- "fy-"!
Population Subgroup
-' - "" '"H" , rt
, "- k j!
General U.S. Population
All Infants (<1 yr)
Children (1 -6 yrs)
Children (7-12 yrs)
Females (13-50 yrs)
Males (13-19 yrs)
Males (20+ yrs)
Acute Assessment (99.9th %-ile of Exp'osure) '
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
%raPAD
0.16
0.28
0.74
0.44
0.05
.0.05
0.06
r ? *
> , t
Females 13+ '
Exposure
(mg/kg/day)
N/A
N/A
N/A
N/A
0.000017
N/A . .
N/A
!
%aPADi
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
% cJPAl}
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, '

                                            13

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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)0,0,-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-oxobenzo-xazolin-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 Hie 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, chemes, peaches, and plums. In response to Aventis' comments, the Agency has decided to
  wave 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.
                                             14

-------
       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
1 (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
TBD"
Almond, nutmeat
Almond hulls are not imported.
The available data indicate that the established
tolerances 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
prunes, data are needed from field trials on plums.
Phosalone residues concentrate by a maximum of ~2x in
prunes.
The available residue data on imported apples, pears,
3each.es, and cherries suggest that crop group
tolerances may be appropriate for pome and stone
fruits. If the requested residue data on pome and stone
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

-------
  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 Disruptor
  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 aUow 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

-------
       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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Fox, S.E.; Herrera, R. (1980) Research Report: Residue Determination of Metabolites
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                                         25

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                                         26

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