United States Prevention, Pesticides EPA 738-R-00-005
Environmental Protection And Toxic Substances June 2000
Agency (7508C)
oEPA Report on FQPA
Tolerance Reassessment
Progress and Interim Risk
Management Decision
Cadusafos
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\
uj
UNITED ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON D.C.,
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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"^-
% 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 cadusafos. 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 cadusafos 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. Cadusafos has no U.S. registrations and only one import tolerance on bananas, and the
dietary risk analysis indicates that the risk is below the Agency's level of concern. Therefore, no
mitigation is necessary at this time.
A Notice of Availability for this "Report on FQPA Tolerance Reassessment Progress
and Interim Risk Management Decision for Cadusafos" 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."
This document is based on the updated technical information found in the cadusafos 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 cadusafos, 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, FMC
Corporation, 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
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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 cadusafos 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 cadusafos 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, Jacqueline McQueen at (703) 308-8164.
Sincerely yours,
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
Cadusafos
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TABLE OF CONTENTS
CADUSAFOS TEAM i
GLOSSARY OF TERMS AND ABBREVIATIONS iii
EXECUTIVE SUMMARY 1
I. INTRODUCTION 1
II. CHEMICAL OVERVIEW 3
A. Regulatory History 3
B. Chemical Identification 3
C. Use Profile 4
D. Estimated Usage of Pesticide 5
III. SUMMARY OF CADUSAFOS RISK ASSESSMENT 6
IV. FQPA TOLERANCE REASSESSMENT PROGRESS AND INTERIM RISK
MANAGEMENT DECISION 9
A. Tolerance Reassessment Progress & Interim Risk Management Decision... 9
B. Summary of Phase 5 Comments 10
C. Regulatory Position 10
1. FQPA Assessment 10
a. "Risk Cup" Determination 10
b. Tolerance Summary 11
2. Endocrine Disrupters Effects 11
D. Regulatory Rationale 12
V. WHAT MANUFACTURERS MUST DO 12
A. Additional Data Requirements 12
B. Risk Mitigation Requirements 12
VI. RELATED DOCUMENTS AND HOW TO ACCESS THEM 13
BIBLIOGRAPHY 15
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CADUSAFOS TEAM
Office of Pesticide Programs:
Health Effects Risk Assessment
Richard Griffin
JohnPunzi
Nicole Paquette
Use and Usage Analysis
Michael Hennessey
Stephen Smearman
Registration Support
Marylin Mautz
Risk Management
Angel Chiri
Jacqueline McQueen
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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 USD A 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
111
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GLOSSARY OF TERMS AND ABBREVIATIONS
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.
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
IV
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GLOSSARY OF TERMS AND ABBREVIATIONS
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
PRZM7
EXAMS Tier H 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
RfD Reference Dose
RQ Risk Quotient
RS Registration Standard
RUP Restricted Use Pesticide
SAP Science Advisory Panel
SCI-GROW Tier I Ground Water Computer Model
SF Safety Factor
SLC Single Layer Clothing
SLN Special Local Need (Registrations Under Section 24(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
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GLOSSARY OF TERMS AND ABBREVIATIONS
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
|ig/L Micrograms Per Liter
USD A United States Department of Agriculture
USGS United States Geological Survey
UV Ultraviolet
VI
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EXECUTIVE SUMMARY
EPA has completed its review of public comments on the revised risk assessment for
cadusafos, and is, in this document, issuing its interim decision on the risk mitigation for this chemical.
The revised risk assessment is based on review of the required target data base supporting the single
cadusafos import tolerance and information received during the public comment periods in the open
process developed through the Tolerance Reassessment Advisory Committee (TRAC). Cadusafos is
not registered under FIFRA and may not be sold, distributed, or used in the U.S. One import tolerance
for cadusafos in/on bananas was established through a petition submitted by FMC Corporation, the
manufacturer of this chemical, in 1986. EPA's revised risk assessment for cadusafos indicates that the
dietary risk does not exceed the Agency's level of concern; therefore, no risk mitigation is necessary at
this time.
The tolerance reassessment decision for cadusafos will be issued once the cumulative
assessment for all of the organophosphates is completed. The Agency may need to issue risk
management measures for cadusafos at the time the organophosphate cumulative assessment is
finalized.
I. INTRODUCTION
This report on the progress toward tolerance reassessment of cadusafos is the result of the pilot
process developed through the TRAC to facilitate greater public involvement in the ongoing FIFRA
reregistration and FQPA tolerance reassessment initiatives on pesticides. Cadusafos is subject only to
FQPA because it has only an import tolerance 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 requiring action on pesticides.
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988 to
accelerate the reregistration of products with active ingredients registered prior to November 1, 1984.
The amended act calls for the development and submission of data to support the reregistration of an
active ingredient, as well as a review of all submitted data by the U.S. Environmental Protection Agency
(referred to as EPA or "the Agency"). Reregistration involves a thorough review of the scientific
database underlying a pesticide's registration. The purpose of the Agency's review is to reassess the
potential hazards arising from the currently registered uses of the pesticide; to determine the need for
additional data on health and environmental effects; and to determine whether the pesticide meets the
"no unreasonable adverse effects" criteria of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into law.
This Act amends FIFRA to require tolerance reassessment during reregistration. It also requires that
by August 2006, EPA review all tolerances in effect on the day before the date of the enactment of the
1
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FQPA. FQPA amends both FIFRA and the Federal Food, Drug, and Cosmetic Act (FFDCA), but
does not amend any of the existing reregistration deadlines. Therefore, the Agency is continuing its
reregistration program while it resolves the remaining issues associated with the implementation of
FQPA. The Agency is also continuing its progress toward tolerance reassessment as required by
FQPA for all of the organophosphate chemicals, whether or not they are subject to the reregistration
process. While the methodology for completion of the cumulative assessment for all of the
organophosphates is being developed, individual risk assessments and risk mitigation measures, where
appropriate, are being conducted. Although not subject to the reregistration process, the individual
dietary assessment for the organophosphate cadusafos has been completed, and will be used in the
cumulative assessment of all of the organophosphate chemicals, to satisfy the requirements of FQPA.
Cadusafos is not registered for use in the United States; however, there is one import tolerance
on bananas 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 cadusafos, 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 cadusafos has already been subject to numerous public comment periods,
and a further comment period was deemed unnecessary. A Notice of Availability for this document is
published in the Federal Register. 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
TRAC identified the following science policy issues it believed were key to the implementation of
FQPA and tolerance reassessment:
Applying the FQPA 10-Fold Safety Factor
Whether and How to Use "Monte Carlo" Analyses in Dietary Exposure Assessments
How to Interpret "No Detectable Residues" in Dietary Exposure Assessments
Refining Dietary (Food) Exposure Estimates
Refining Dietary (Drinking Water) Exposure Estimates
Assessing Residential Exposure
Aggregating Exposure from all Non-Occupational Sources
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How to Conduct a Cumulative Risk Assessment for Organophosphate or Other Pesticides with
a Common Mechanism of Toxicity
Selection of Appropriate Toxicity Endpoints for Risk Assessments of Organophosphates
Whether and How to Use Data Derived from Human Studies
The process developed by 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 m gives an overview of the dietary risk assessment for
cadusafos, 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), and in the Public Docket.
II.
CHEMICAL OVERVIEW
A. Regulatory History
Cadusafos, a nematicide and soil insecticide, is not registered under FIFRA and may not be
sold, distributed, or used in the United States. However, a permanent tolerance of 0.01 ppm has been
established by the U.S. EPA under 40 CFR §180.461 for residues of cadusafos in/on bananas
imported into this country.
B.
Chemical Identification
CADUSAFOS:
HX
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Common Name:
Cadusafos
! Chemical Name:
! Chemical Family:
! CAS Registry Number:
! OPP Chemical Code:
Empirical Formula:
Molecular Weight:
O-ethyl S,S-bis (1-methylpropyl)
phosphorodithioate
Organophosphate
95465-99-9
128864
C10H2302PS2
270.39
Trade and Other Names: Rugby, Apache
Basic Manufacturers:
FMC Corporation
A detailed discussion on the physical properties of cadusafos can be found in the EPA
document entitled "Cadusafos: HED Risk Assessment for the Risk Management Proposal," dated
December 17, 1998.
C. Use Profile
The following information is based on the current uses of cadusafos outside of the United
States, and includes an overview of use sites and application methods.
Type of Pesticide:
Summary of Use Sites:
Nematicide and soil insecticide.
Cadusafos is registered in Ecuador, Costa Rica,
Honduras, Guatemala, Columbia and Mexico for use
in/on bananas. Cadusafos is not registered under
FIFRA and may not be sold, distributed, or used in the
U.S.
Target Pests:
Plant parasitic nematodes and soil insects.
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Formulation Types: FMC Corporation produces a 10% granular
formulation for use in banana-producing countries.
Method and Rates of Application:
Method and Rate - The established maximum seasonal rate is 6 grams of
active ingredient (ai.) per mat per year, applied to the
base of the plants.
Timing - Cadusafos is applied at the beginning of the banana
planting season. It may also be applied a second time,
as needed.
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 cadusafos. 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.
In the current risk assessment, the Agency estimated that cadusafos is used on about 10-15%
of the annual banana imports into the U.S. The principal countries exporting bananas treated with
cadusafos to the U.S. are Guatemala, Costa Rica, Ecuador, Columbia, Mexico and Honduras. Since
the risk assessment was completed, more current information on the percent of imported bananas
treated with cadusafos was submitted by the International Banana Association (IBA). This organization
worked with banana growers to more accurately estimate the amount of cadusafos-treated bananas
imported into the U.S. The estimates provided by the IBA range from a typical or average of 5.1%
imported, to a high-end estimate of 7% for the years 1997 to 1998. These estimates are consistent
with new information received by EPA from outside economic sources. Although the risk assessment
was not updated again to include these figures, they will be considered for use in both the acute and
chronic risk assessments at the time the cumulative assessment is conducted for all of the
organophosphates.
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III. SUMMARY OF CADUSAFOS RISK ASSESSMENT
Following is a summary of EPA's revised human health risk findings and conclusions for the
organophosphate pesticide cadusafos, as fully presented in the revised risk assessment document,
"Cadusafos: Dietary Risk Assessment Update for FQPA Requirements," dated December 17, 1998.
The risk assessment presented here forms the basis of the Agency's interim risk management decision
for cadusafos only; the Agency must complete a cumulative assessment of the risks of all
organophosphate pesticides before it can complete its reassessment of the cadusafos tolerance.
Because cadusafos 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.
Human Health Risk Assessment
During the comment period on the cadusafos preliminary risk assessment, FMC Corporation,
the manufacturer, submitted comments noting that the decision to retain the 10X FQPA safety factor
was based on the assumption that there were data gaps for all required neurotoxicity studies, although
the company had previously submitted an acute delayed neurotoxicity study. FMC Corporation re-
submitted this study and requested that the Agency evaluate the data and consider reducing the FQPA
Factor. The Agency reviewed the study, and it was found to be acceptable and to show no delayed
neurotoxicity and no evidence of neuropathology. Based on this information, the FQPA safety factor
was reduced from 10X to 3X; the 3X was retained due to continuing data gaps for acute and
subchronic neurotoxicity studies in rats. This was the only major revision to the risk assessment.
Dietary Risk from Food
Toxicity
The Agency has reviewed all toxicity studies submitted and has determined that the toxicity
database supports a dietary risk assessment for cadusafos as well as a future FQPA tolerance
reassessment for the import tolerance on bananas. Further details on the toxicity of cadusafos can be
found in the December 17, 1998 FLED Risk Assessment. A brief overview of the studies used for the
dietary risk assessment is outlined in Table 1 of this document.
FQPA Safety Factor
The FQPA Safety Factor was reduced to 3X. As stated earlier in this document, the safety
factor was initially 10X because of data gaps for three neurotoxicity studies: an acute delayed
neurotoxicity study in hens, and acute and subchronic studies in rats. The acute delayed neurotoxicity
study in hens was received and reviewed by the Agency, found to be acceptable, and to show no
neurotoxicity and no delayed neuropathology in the treated animals. It was determined that adequate
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actual data, surrogate data, and/or modeling outputs were available to satisfactorily assess exposure
through food, and that the assumptions and models used in the assessments do not underestimate the
potential risk for infants and children. Results of the study allowed for a reduction in the safety factor;
however, because data gaps for the acute and subchronic rat neurotoxicity studies remain; an FQPA
safety factor of 3X was retained.
Population Adjusted Dose (PAD)
The PAD is a relatively new term that characterizes the dietary risk of a chemical, and reflects
the Reference Dose, either acute or chronic, that has been adjusted to account for the FQPA safety
factor (i.e., RfD/FQPA safety factor). For the acute dietary assessment, risk is calculated considering
what is eaten in one day (consumption) and maximum, high-end residue values in food. For chronic
exposures, dietary risk is calculated by using the average consumption value for food and average
residue value. In the case of cadusafos, the FQPA safety factor is 3X; therefore, the acute or chronic
RfD / 3 = the acute or chronic PAD. A risk estimate that is less than 100% of the acute or chronic
PAD does not exceed the Agency's risk concern.
Exposure Assumptions
Residues of cadusafos in banana pulp were not detected in field trials conducted in seven sites.
Further, no detections have been reported by the Food and Drug Administration, based on analysis of
hundreds of samples from approximately a dozen countries. For this assessment, the Limit of Detection
(LOD) of 0.001 ppm was used for the acute dietary assessment. For the chronic dietary assessment,
l/2 of the LOD, or 0.0005, was used. The value of 0.001 ppm represents a probable upper-end
estimate of cadusafos residues in banana pulp.
Dietary risk analyses for cadusafos were conducted with the Dietary Exposure Evaluation
Model (DEEM). DEEM incorporates consumption data generated in USDA's Continuing Surveys
of Food Intakes by Individuals (CSFII), 1989-1992.
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Table 1. Summary of Toxicological Endpoints and Other Factors Used in the Human Dietary
Risk Assessment of Cadusafos.
Assessment
Acute Dietary
Chronic
Dietary
Study
14-day (range
finding) oral
toxicity study in
dogs (MRID
40017902)
One-year
feeding study in
dogs (MRIDs
40017901/40017
902)
Dose
NOAEL=
0.02
mg/kg/day
NOAEL=
0.001
mg/kg/day
Endpoint
Plasma ChE
inhibition
Plasma ChE
inhibition
UF
100
100
FQPA
Safety
Factor
3X
3X
PAD
0.00007
mg/kg/
day
0.000003
mg/kg/
day
Acute Food Risk
An acute dietary assessment was conducted for cadusafos. The assessment used a residue
estimate of 0.001 ppm, the LOD, and a distribution of consumption values. The acute risk estimates
are considered upper-end estimates since the residue level assumed is a point estimate rather than a
range, and because 100% of the crop treated is assumed. Based on the above parameters, DEEM
estimates that the "Average U.S. Population" and the population subgroups of "All Infants (<1 year)"
and "Children (1-6 years)" are exposed to cadusafos (per day) at a level less than the cadusafos acute
PAD; that is, less than 100% of the aPAD is utilized. At the 99.9th percentile of exposure, the % acute
PAD utilized is 21%, 31%, and 39%, respectively. Because these values are significantly lower than
100%, the acute dietary risk is not of concern to the Agency. The population group "All Infants" is
noted since this group is typically estimated to be the most highly exposed group. This analysis satisfies
the FQPA requirement for the special consideration of pesticide risk to children.
Chronic Food Risk
The chronic risk estimates are based on the residue level of 1A LOD (0.0005 ppm), the
upper-end of the crop treated estimate (10-15%), and averaged food consumption estimates. The
resultant risk estimate is not considered upper-end since the estimate is refined by the percent crop
treated data. Based on these parameters, DEEM estimates that the "Average U.S. Population" and all
population subgroups including "All Infants (<1 year)" are chronically exposed to cadusafos at a level
less than the cadusafos chronic PAD. The percent of the chronic PAD utilized is less than 5% for all
population groups; the % cPAD for infants less than 1 year and children 1-6 years were 4% and 2%,
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respectively. Because these levels are significantly lower than 100%, the chronic dietary risk is not of
concern.
In summary, the potential acute and chronic dietary exposures to cadusafos-treated bananas
are below the level of concern for all U.S. citizens, including infants and children. As discussed in the
"Chemical Overview" section of this document, the Agency has recently received updated information
on the percent of bananas imported into the United States. This information indicates that 5-7% is
imported, not 10-15%, as the Agency's previous information indicated. This updated information will
be considered for the acute and chronic risk assessments at the time that the cumulative assessment for
all of the organophosphates is conducted.
IV. FQPA TOLERANCE REASSESSMENT PROGRESS AND INTERIM RISK
MANAGEMENT DECISION
A. Tolerance Reassessment Progress & Interim Risk Management Decision
The Agency has completed its assessment of the dietary risk of cadusafos 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 cadusafos,
EPA has sufficient information on the human health effects of cadusafos 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 cadusafos alone in order to determine whether any risk
reduction measures are necessary to allow the continued importation of bananas containing this
chemical, pending completion of the cumulative assessment.
As a result of its assessment, EPA has determined that dietary risk from exposure to cadusafos
does not exceed the Agency's level of concern. Therefore, no mitigation is necessary and no further
actions are warranted at this time. The Agency may determine that action is necessary after assessing
the cumulative risk of the organophosphate class. At that time, the Agency will also address any other
outstanding risk concerns that may arise. Such an incremental approach to the tolerance reassessment
process is consistent with the Agency's goal of improving the transparency of the implementation of
FQPA. By evaluating each organophosphate in turn and identifying 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
cadusafos food residue import tolerance as called for by the FQPA. When the Agency has completed
the cumulative assessment, the cadusafos tolerance will be reassessed in that light. At that time, the
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Agency will reassess cadusafos 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 fmalization of the FQPA assessment for cadusafos, 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 cadusafos to the public in July, 1999 and
provided a 60 day comment period for interested parties to submit information, including risk mitigation
suggestions or proposals. No comments were received.
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 cadusafos is within its own "risk cup." In other
words, if cadusafos did not share a common mechanism of toxicity with other chemicals, EPA would
be able to conclude today that the import tolerance for cadusafos on bananas meets the FQPA safety
standards. In reaching this determination, 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 cadusafos, 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 cadusafos "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.
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b. Tolerance Summary
The established tolerance for residues of cadusafos in/on plant commodities is currently
expressed in terms of residues of cadusafos per se (O-ethyl S,S-di-sec-butyl phosphorodithioate) [40
CFR § 180.461]. It should be noted, however, that the preferred chemical name for cadusafos is O-
ethyl S,S-bis(l-methylpropyl) phosphorodithioate.
Sufficient residue field trial data are available to assess the established import tolerance on
bananas. These trials were conducted in the Ivory Coast, Costa Rica, the Philippines, Guatemala, and
Honduras using the granular formulation according to the maximum use patterns registered to foreign
countries which export bananas to the United States. The tolerance for residues of cadusafos in/on
imported bananas is 0.01 ppm, as shown in Table 2.
Table 2. Tolerance Summary for Cadusafos
Commodity
Bananas
Tolerance Listed Under 40
CFR § 180.461
0.01 ppm
Reassessed
Tolerance*
0.01 ppm
Comment
Banana, whole fruit
* The term "reassessed" here is not meant to imply that the tolerance has been reassessed as required by FQPA,
since this tolerance may be reassessed only upon completion of the cumulative risk assessment of all
organophosphates, as required by this law. Rather, it provides a tolerance level for this single chemical, if no
cumulative assessment was required, that is supported by all of the submitted residue data.
2. Endocrine Disrupter Effects
EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to
determine whether certain substances (including all pesticide active and other ingredients) "may have an
effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such
endocrine effects as the Administrator may designate." Following the recommendations of its
Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC), EPA determined that
there was scientific bases for including, as part of the program, the androgen and thyroid hormone
systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation
that the Program include evaluations of potential effects 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, cadusafos may be subjected to additional screening and/or testing to
better characterize effects related to endocrine disruption.
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D. Regulatory Rationale
Cadusafos has only one import tolerance, 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.). These chemicals are not subject to Data
Call-In (DCI) requirements under FIFRA. Although cadusafos has no U.S. registrations and therefore
is not subject to a FIFRA DCI, it does have a tolerance for bananas 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.
B. Risk Mitigation Requirements
As discussed in this document, the acute and chronic food risk from the use of cadusafos on
imported bananas is not of concern to the Agency; therefore, no mitigation is necessary at this time. The
Agency may need to pursue risk management measures for cadusafos once the cumulative assessment
is finalized.
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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."
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14
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15
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BIBLIOGRAPHY
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16
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17
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