United States Prevention, Pesticides EPA 738-R-00-005

Environmental Protection And Toxic Substances June 2000

Agency (7508C)

Report on FQPA

Tolerance Reassessment

Progress and Interim Risk

Management Decision

Cadusafos
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
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 multistakeholder 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
Report on FQPA Tolerance Reassessment Progress

and Interim Risk Management Decision

for

Cadusafos

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 Disruptors 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

i

CADUSAFOS TEAM

Office of Pesticide Programs:

Health Effects Risk Assessment

Richard Griffin

John Punzi

Nicole Paquette

Use and Usage Analysis

Michael Hennessey

Stephen Smearman

Registration Support

Marylin Mautz

Risk Management

Angel Chiri

Jacqueline McQueen
ii
iii

GLOSSARY OF TERMS AND ABBREVIATIONS

AE Acid Equivalent

a.i. Active Ingredient

AGDCI Agricultural Data Call-In

ai Active Ingredient

aPAD Acute Population Adjusted Dose

AR Anticipated Residue

ARC Anticipated Residue Contribution 

BCF Bioconcentration Factor 

CAS Chemical Abstracts Service

CI Cation

CNS Central Nervous System

cPAD Chronic Population Adjusted Dose

CSF Confidential Statement of Formula

CFR Code of Federal Regulations

CSFII USDA Continuing Surveys for Food Intake by Individuals

DCI Data Call-In

DEEM Dietary Exposure Evaluation Model

DFR Dislodgeable Foliar Residue

DRES Dietary Risk Evaluation System

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

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

are not anticipated to occur.

DWLOC Drinking Water Level of Comparison.

EC Emulsifiable Concentrate Formulation

EEC Estimated Environmental Concentration. The estimated pesticide concentration in an

environment, such as a terrestrial ecosystem.

EP End-Use Product

EPA U.S. Environmental Protection Agency

FAO Food and Agriculture Organization

FDA Food and Drug Administration

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FFDCA Federal Food, Drug, and Cosmetic Act

FQPA Food Quality Protection Act

FOB Functional Observation Battery

G Granular Formulation

GENEEC Tier I Surface Water Computer Model

GLC Gas Liquid Chromatography

GLN Guideline Number
iv

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

HDT Highest Dose Tested

IR Index Reservoir

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

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

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

ppm.

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

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

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

mg/kg.

LEL Lowest Effect Level

LOC Level of Concern

LOD Limit of Detection 

LOAEL Lowest Observed Adverse Effect Level

MATC Maximum Acceptable Toxicant Concentration

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

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

mg/kg/day Milligram Per Kilogram Per Day

mg/L Milligrams Per Liter

MOE Margin of Exposure 

MP Manufacturing-Use Product

MPI Maximum Permissible Intake

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

studies submitted.

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
v

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

PDP USDA Pesticide Data Program

PHED Pesticide Handler's Exposure Data 

PHI Preharvest Interval

ppb Parts Per Billion

PPE Personal Protective Equipment

ppm Parts Per Million

PRN Pesticide Registration Notice

PRZM/

EXAMS Tier II Surface Water Computer Model 

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

Model

RAC Raw Agriculture Commodity

RBC Red Blood Cell

RED Reregistration Eligibility Decision

REI Restricted Entry Interval

RfD Reference Dose

RQ Risk Quotient

RS Registration Standard

RUP Restricted Use Pesticide

SAP Science Advisory Panel

SCI-GROW Tier I Ground Water Computer Model

SF Safety Factor

SLC Single Layer Clothing

SLN Special Local Need (Registrations Under Section 24(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
vi

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

μg/g Micrograms Per Gram

μg/L Micrograms Per Liter

USDA United States Department of Agriculture

USGS United States Geological Survey

UV Ultraviolet
1

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
2

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:

C Applying the FQPA 10-Fold Safety Factor

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

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

C Refining Dietary (Food) Exposure Estimates

C Refining Dietary (Drinking Water) Exposure Estimates

C Assessing Residential Exposure

C Aggregating Exposure from all Non-Occupational Sources
3

H3C

S

CH3

P

S

CH3

CH3

O

O

CH3

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

a Common Mechanism of Toxicity

C Selection of Appropriate Toxicity Endpoints for Risk Assessments of Organophosphates

C Whether and How to Use Data Derived from Human Studies

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

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

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

Federal Register and others will be published shortly.

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

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

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

profile of the usage of the chemical. Section III 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: 
4

! Common Name: Cadusafos 

! Chemical Name: O-ethyl S,S-bis (1-methylpropyl)

phosphorodithioate

! Chemical Family: Organophosphate

! CAS Registry Number: 95465-99-9

! OPP Chemical Code: 128864

! Empirical Formula: C10H23O2PS2

! Molecular Weight: 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: Nematicide and soil insecticide.

Summary of Use Sites: 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.
5

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. 
6

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 resubmitted 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 HED 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
7

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,

1⁄2 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 (DEEMTM). DEEM incorporates consumption data generated in USDA’s Continuing Surveys

of Food Intakes by Individuals (CSFII), 1989-1992. 
8

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

Risk Assessment of Cadusafos. 

Assessment Study Dose Endpoint UF FQPA

Safety

Factor

PAD

Acute Dietary 14-day (range

finding) oral

toxicity study in

dogs (MRID

40017902)

NOAEL=

0.02

mg/kg/day

Plasma ChE

inhibition

100 3X 0.00007 

mg/kg/

day

Chronic

Dietary

One-year

feeding study in

dogs (MRIDs

40017901/40017

902)

NOAEL=

0.001

mg/kg/day

Plasma ChE

inhibition

100 3X 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 1⁄2 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%,
9

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
10

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 finalization 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. 
11

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 Oethyl S,S-bis(1-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 Tolerance Listed Under 40

CFR § 180.461

Reassessed

Tolerance*

Comment

Bananas 0.01 ppm 0.01 ppm 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 Disruptor Effects

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

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

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

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

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

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

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

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

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

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

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

Screening Program (EDSP).

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

EDSP have been developed, cadusafos may be subjected to additional screening and/or testing to

better characterize effects related to endocrine disruption.
12

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. 
13

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."
14
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