United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508C)
EPA738-R-00-017
September 2000
&EPA
Report on FQPA
Tolerance Reassessment
Progress and Interim Risk
Management Decision
Phostebupirim
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United States
Environmental Protection
Agency
Prevention, Pesticides
and Toxic Substances
(7508C)
EPA738-F-00-015
September 2000
Phostebupirim Facts
EPA has assessed the dietary risk of phostebupirim [also known as tebupirimphos] and
prepared a Report on FQPA Tolerance Reassessment Progress and Interim Risk Management
Decision for this organophosphate (OP) pesticide. Phostebupirim fits into its own "risk cup"- its
individual risks are within acceptable levels.
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.aov/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 risk management decisions for individual
OP pesticides, and will make final decisions
through a cumulative OP assessment.
Because phostebupirim was initially
registered after 1984, it is not subject to
reregistration. However, the Agency has
reassessed the occupational risks from
phostebupirim use on corn and is
recommending label modifications at this time.
In addition, the registrant is generating
additional data which will be used to refine the
occupational risk assessment.
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
phostebupirim cannot be considered final until
this cumulative assessment is complete. Further
risk mitigation may be required at that time.
EPA is reviewing the OP pesticides to
determine whether they meet current health and
safety standards. Older OPs need decisions
about their eligibility for reregistration under
FIFRA. OPs with residue limits in food (tolerances) and other non-occupational exposures also must
be reassessed to make sure they meet the new FQPA safety standard.
The phostebupirim interim decision was made through the OP pilot public participation process,
which increases transparency and maximizes stakeholder involvement in EPA's development of risk
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assessments and risk management decisions. EPA worked with affected parties to reach the decisions
presented in this interim decision document, which concludes the OP pilot process for phostebupirim.
Uses
Phostebupirim is an organophosphate insecticide registered for use on field com, seed com,
sweet corn, and popcorn for the control of com rootworms, wireworms, cutworms, seed corn
maggots, seedcorn beetles and white grubs.
Annual domestic use is estimated to be approximately 270,000 pounds of active ingredient per
year.
Formulations
In addition to the technical, there are three end-use formulations: two 2.1% granular
formulations (clay-based and cellulose-based) and a 4.67% granular formulation for use only
with a SmartBox® applicator system.
Health Effects
Phostebupirim can cause cholinesterase inhibition in humans; that is, it can overstirnulate the
nervous system causing nausea, dizziness, confusion, and at very high exposures (e.g., accidents
or major spills), respiratory paralysis and death.
Risks
Dietary risks from food and drinking water are not of concern.
Handler risks under the current risk assessment are of concern without appropriate PPE and
engineering controls during the loading and application processes.
EPA did not quantitatively assess the risks to post application workers. Since phostebupirim is
mainly incorporated into the soil at planting, minimal post application exposure is anticipated.
Risk Mitigation
The Agency is recommending label changes which are intended to mitigate potential
occupational risk from occupational exposure to phostebupirim products. The changes include
a dust/mist respirator for loaders of the 2.1% granular clay-based formulation, emergency PPE
requirements, establishment of an REI if re-entry activities disturb the soil surface, and the
addition of a double notification statement.
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The registrant will need to submit an exposure or dust comparison study to confirm that the
cellulose-based Biodac formulation is sufficiently less dusty than the clay-based formulation.
This study should be submitted to EPA by April 1,2001.
The registrant is conducting a 21-day rat dermal toxicity study to be submitted by April 1,
2001, which will be used to refine both the short and intermediate-term occupational risk
assessments. The Agency believes that this data will provide a more appropriate endpoint for
assessing dermal exposure risks than the studies currently available, and will demonstrate that
occupational risks are adequately mitigated with the measures presently recommended. The
Agency plans to recommend any appropriate additional occupational risk mitigation measures
before the conditional registration is set to expire on July 5,2001, should such measures
remain necessary following refinement of the risk assessment
Next Steps
Numerous opportunities for public comment were offered as this decision was being
developed. The Interim Tolerance Reassessment Evaluation and Risk Management Decision
for phostebupirim is therefore issued in final (see www.epa.gov/pesticides/op). without a formal
public comment period. The docket remains open, however, and any comments submitted in
the future will be placed in this public docket.
To effect the label amendments as quickly as possible, time frames for making the changes
required by the Interim Tolerance Reassessment Evaluation and Risk Management Decision
document are shorter than those in a usual RED. The Agency is asking that all labels be
amended to include the above mitigation and submitted to the Agency within 90 days after
issuance of this document.
When the cumulative risk assessment for all organophosphate pesticides is completed, EPA will
issue its final tolerance reassessment decision for phostebupirim and may require further risk
mitigation measures.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
OCT 2 4 2000
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 preliminary and revised human health risk assessment for the organophosphate
pesticide phostebupiriin (also known as tebupirimphos). The enclosed "Report on FQPA
Tolerance Reassessment and Interim Risk Management Decision for Phostebupirim," which was
approved on September 29, 2000, summarizes the Agency's assessment o"f the dietary and
occupational risk from phostebupirim. Based on its review, EPA has recommended risk
mitigation measures to address the human health risks associated with the current use of
phostebupirim. These risk mitigation measures can be found in the attached document.
The major means by which the Agency reassesses tolerances is through its reregistration
process. Each pesticide registered prior to 1984 is subject to a comprehensive evaluation of its
effects on human health and the environment. Such an evaluation includes a determination of
whether the tolerances are safe. Since phostebupirim was registered after 1984, it is not subject
to reregistration. However, phostebupirim tolerances are subject to reassessment in accordance
with the Federal Food, Drug, and Cosmetic Act (FFDCA) as amended by the Food Quality
Protection Act of 1996 (FQPA). The FQPA requires EPA to re-evaluate existing tolerances to
ensure that children and other sensitive subpopulations are protected from pesticide risk.
When phostebupirim was registered in July 1995, it was granted a conditional registration
contingent on the submission of additional data. All of the data and information requested as
conditions of the registration have been received by the Agency. The Agency decided, hi
addition to reassessing phostebupirim tolerances, to also reassess occupational risks under the
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The Agency has not conducted a
new risk assessment for the effects of phostebupirim on non-target species (e.g., fish and birds)
since it believes that the conclusions reached at the time of the initial decision to register
phostebupirim in 1995 remain unchanged.
The "Report on FQPA Tolerance Reassessment Progress and Interim Risk Management
Decision for Phostebupirim" is based on the revised human health assessment, updated technical
information, and public comments received by the Agency, all of which are available in the
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phostebupirim public docket. The docket includes both the preliminary and revised risk
assessment for phostebupirim as well as comments on the risk assessments submitted by the
general public and stakeholders. A Notice of Availability for this Report on FQPA Tolerance
Reassessment Progress and Interim Risk Management Decision for Phostebupirim is being
published in the Federal Register. To obtain a copy of this document, please contact the OPP
Public Regulatory Docket (7502C), US EPA, Ariel Rios Building, 1200 Pennsylvania Avenue,
N.W., Washington D.C., 20460, telephone (703) 305 - 5805. Electronic copies of this report and
the documents supporting it are available on the internet and can be found on the Agency's web
page, www.epa.gov/pesticides/op.
This document and the process used to develop it are the result of a pilot process to
facilitate greater public involvement and participation in the reregistration and/or tolerance
reassessment decisions for these 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. This open process follows the guidance 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 phostebupirim risk assessment concerns only this particular
organophosphate. It does not address the cumulative effects of other organophosphates as a
class. Because the FQPA directs the Agency to evaluate food tolerances on the basis of
cumulative risk from substances sharing a common mechanism of toxicity, such as the toxicity
expressed by the organophosphates through a common biochemical interaction with the
cholinesterase enzyme, the Agency will evaluate the cumulative risk posed by the entire
organophosphate class of chemicals after completing the risk assessments for individual
organophosphates. The Agency is working towards completion of a methodology to assess
cumulative risk and the individual risk assessments for 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 necessary to address those
human health risks associated with the current uses of phostebupirim. The Agency will issue the
final tolerance reassessment decision for phostebupirim and finalize any other decisions once the
cumulative assessment for all organophosphates is complete.
Based on the phostebupirim risk assessment, the Agency believes that current uses of
phostebupirim may pose unreasonable adverse effects to human health, and that such effects can
be mitigated with the risk mitigation measures identified in this document. Accordingly, the
Agency recommends that registrants implement these risk mitigation measures immediately.
Section IV of this document describes labeling amendments for end-use products and data
requirements necessary to implement these mitigation measures. Instructions for registrants on
submitting revised labeling and the time frame established to do so can be found in Section V of
this document.
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Should a registrant fail to implement any of the recommended occupational risk
mitigation measures, the Agency will continue to have concerns about the risks posed by
phostebupirim. Where the Agency has identified any unreasonable adverse effect to human
health, the Agency may at any time initiate appropriate regulatory action to address this concern.
At that time, any affected person (s) may challenge the Agency's action.
If you have questions on this document or the label changes, please contact the Special
Review and Reregistration Division representative, Stacey Milan, at (703) 305-2505.
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
Phostebupirim
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Table of Contents
Phostebupirim Team i
Glossary of Terms and Abbreviations ifi
Executive Summary • 1
I. Introduction 3
BE. Chemical Overview • 6
A. Regulatory History 6
B. Chemical Identification 6
C. Use Profile 7
D. Estimated Usage of Pesticide 7
m. Summary of Phostebupirim Risk Assessments 8
A. Dietary Risk from Food 8
1. Toxicity 8
2. FQPA Safety Factor 8
3. Population Adjusted Dose (PAD) 9
4. Exposure Assumptions 9
5. Food Risk Characterization 10
B. Dietary Risk from Drinking Water 11
1. Surface water 11
2. Ground water — 11
3. Drinking Water Levels of Comparison (DWLOCs) 12
C. Aggregate Risk 12
D. Occupational Risk 12
1. Toxicity 13
2. Exposure • 14
3. Risk Assessment 15
a. Short-Term Risks .16
b. Intermediate-Term Risk 17
4. Post-Application Risk 19
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IV. FQPA Tolerance Reassessment Progress and Interim Risk
Management Decision 19
A. Determination of Tolerance Reassessment & Interim Risk
Management Decision 19
B. Summary of Phase 3 Comments and Revisions to Preliminary
Assessment 20
C. Summary of Phase 5 Comments and Responses 21
D. Regulatory Position 22
1. FQPA and Occupational Risk Assessment 22
a. "Risk Cup" Determination 22
b. Tolerance Summary 23
2. Endocrine Disrupter Effects .24
3. Recommended Label Modifications 25
E. Regulatory Rationale 26
1. Dietary Mitigation 26
a. Dietary (Food) Risk Mitigation „ 26
b. Dietary (Water) Risk Mitigation 26
c. Aggregate (Food + Water) Risk Mitigation 26
2. Occupational Risk Mitigation 26
3. Post Application Risk Mitigation 28
V. Recommended Mitigation Measures 29
A. Manufacturing Use Products 29
B. End-Use Products 29
1. Labeling Changes for End-Use Products 29
2. Procedure and Tuning for Label Amendment 33
C. Existing Stocks 33
VI. Related Documents and How to Access Them 33
VH. APPENDICES 35
A: Citations Supporting the FQPA Tolerance Reassessment and Interim
Occupational Risk Management Decision (Bibliography) 37
B: EPA's Batching of Phostebupirim Products for Meeting Acute
Toxicity Data Requirements for Reregistration 47
C:
List of Available Related Documents " 49
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Phostebupirim Team
Office of Pesticide Programs:
Health Effects Risk Assessment
Robert Fricke
Christina Jarvis
Renee Sandvig
Environmental Fate (Prinking Waterl Risk Assessment
Patricia Jennings
Use and Usage Analysis
David Brassard
David Widawsky
Registration Support
Marilyn Mautz
Risk Management
Jason Klug
Nancy Zahedi
Stacey Milan
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Glossary of Terms and Abbreviations
AE Acid Equivalent
a.i. Active Ingredient
AGDCI Agricultural Data Call-In
ai Active Ingredient
aPAD Acute Population Adjusted Dose
AR Anticipated Residue
ARC Anticipated Residue Contribution
BCF Bioconcentration Factor
CAS Chemical Abstracts Service
CI Cation
CNS Central Nervous System
cPAD Chronic Population Adjusted Dose
CSF Confidential Statement of Formula
CFR Code of Federal Regulations
CSFII USDA Continuing Surveys for Food Intake by Individuals
DCI Data Call-in
DEEM Dietary Exposure Evaluation Model
DFR Dislodgeable Foliar Residue
ORES Dietary Risk Evaluation System
DWEL Drinking Water Equivalent Level (DWEL) The DWEL represents a medium specific
(i.e., drinking water) lifetime exposure at which adverse, noncarcinogenic health effects
are not anticipated to occur.
DWLOC Drinking Water Level of Comparison.
EC Emulsifiable Concentrate Formulation
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an
environment, such as a terrestrial ecosystem.
EP End-Use Product
EPA U.S. Environmental Protection Agency
FAO Food and Agriculture Organization
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
FQPA Food Quality Protection Act
FOB Functional Observation Battery
G Granular Formulation
GENEEC Tier I Surface Water Computer Model
GLC Gas Liquid Chromatography
GLN Guideline Number
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
HDT Highest Dose Tested
IR Index Reservoir
LCSO 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
MRJDD 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
PC A 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
Qj* 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
TMRC Theoretical Maximum Residue Contribution
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torr
TOR
UF
/ig/L
USDA
USGS
UV
WHO
WP
WPS
Glossary of Terms and Abbreviations
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
VI
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Executive Summary
EPA has completed its review of public comments on the revised risk assessment for
phostebupirim, and is, in this document, setting forth its interim decision on the risk mitigation for this
chemical. The revised dietary risk assessment includes the Agency's review of additional studies and a
revision of the FQPA safety factor based on the study reviews. The Agency identified the risk
management measures set forth in this report after inviting stakeholders to provide proposals and
suggestions on appropriate mitigation measures. This report on FQPA Tolerance Reassessment
Progress and Interim Pusk Management Decision will not be considered final until the cumulative risk
assessment of all organophosphate pesticides is complete. The cumulative assessment may result in
further risk mitigation measures for phostebupirim.
Phostebupirim is an organophosphate insecticide registered for use on field com, seed com,
sweet corn, and popcorn for the control of com rootworms, wireworms, cutworms, seed corn
maggots, seedcom beetle and white grubs. It was first registered in the United States in 1995 and is
registered as a 2.1% and 4.67% granular end-use .product (Aztec® 2.1G and 4.67G), although only the
Aztec® 2.1G product is currently being marketed. The Aztec® 2.1G product has two formulations: a
new cellulose-based Biodac formulation along with a clay-based granular formulation. Phostebupirim
is used on average once a season at planting, at a maximum rate of 0.15 Ibs ai/acre. Annual domestic
usage of phostebupirim is estimated to be approximately 270,000 pounds active ingredient. Between
3-6% of all corn acreage is treated.
Overall Pusk Summary
EPA's dietary (food) risk assessment for phostebupirim indicates that neither the acute nor
chronic risks exceed the Agency's level of concern, i.e., less than 100% of the acute or chronic
Population Adjusted Dose (PAD) is utilized for the general U.S. population and all population
subgroups, including infants and children using a Tier 1 screening level assessment (100% crop treated
and tolerance levels).
Acute and chronic dietary risks from drinking water are also below the Agency's level of
concern. Surface water and ground water estimated environmental concentrations (EECs) do not
exceed the Agency's drinking water levels of comparison (DWLOC) for acute and chronic aggregate
dietary exposure. Aggregate risk, based on food and water exposure, does not exceed the Agency's
level of concern; therefore, no risk mitigation based on dietary risk estimates is necessary at this time.
The Agency has determined that there is potential exposure to handlers for use-patterns
associated with phostebupirim. Occupational handler risk estimates are based on two separate studies
for estimating short-term and intermediate-term exposure risks and PHED exposure studies. With the
exception of intermediate-term risks for applicators, the risks in all exposure scenarios generally do not
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exceed the Agency's level of concern when the appropriate PPE and engineering controls are utilized
during the loading and application processes.
EPA did not quantitatively assess the risks to post application workers. Minimal post-
application exposure is anticipated since phostebupirim is typically incorporated into the soil, is applied
at planting and is not systemic in the plant and degrades readily.
Based on the phostebupirim risk assessment, the Agency believes that label changes requiring
use of dust/mist respirators (or comparable mitigation) by loaders of the Aztec® 2.1G clay-based
formulation would mitigate inhalation exposures. Loaders of the Aztec® 4.67G SmartBox® system
must have a dust/mist respirator immediately available for use in case of an emergency. The Agency is
not requiring the use of dust/mist respirators for handlers who use the cellulose-based formulation.
EPA believes this formulation is sufficiently less dusty than the clay-based formulation that there will not
be a risk concern for loaders.
The registrant will need to submit an exposure or dust comparison study to confirm that the
Biodac formulation is. sufficiently less dusty than the clay-based formulation. This study should be
submitted to EPA by April 1,2001.
Under current label restrictions, EPA does have risk concerns for the short and intermediate-
term inhalation risk for applying granular phostebupirim with an open cab tractor drawn spreader
(MOE=79). However, the risk was calculated using low confidence PHED data (one study with a
small number of replicates using only a broadcast spreader). In actual use, phostebupirim will typically
be applied in-farrow or T-Band. These methods of application should make the granular formula less
available for exposure than in the broadcast spreader scenario. Therefore, the Agency believes the
MOE of 79 is an overestimate of the risk for this specific phostebupirim use scenario and inhalation
risks for applicators are likely to be acceptable. Therefore, no risk mitigation is required to address
applicator risk.
Currently available data suggests that dermal occupational risk is also of concern. However,
EPA believes the current risk assessment overestimates this risk to workers as well. The registrant will
initiate a 21-day rat dermal toxicity study using the 4.67% granular formulation to better characterize
dermal risk from occupational exposure to phostebupirim products. The Agency believes that this
study will provide a more appropriate dermal endpoint for regulating both short and intermediate-term
worker exposures and that worker risk under current label conditions does not exceed the Agency's
level of concern. This study should be submitted to EPA by April 1,2001.
However, in me event that these studies do not adequately demonstrate that worker risk is not
a concern, the Agency will recommend that the registrant implement additional label amendments to
mitigate remaining worker risks that exceed the Agency's level of concern. The Agency will review the
phostebupirim data prior to July 5,2001, the date the conditional registration expires.
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I.
Introduction
This report on the progress toward tolerance reassessment for phostebupirim is the result of the
pilot process developed through the Tolerance Reassessment Advisory Committee (TRAC) to facilitate
greater public involvement in the ongoing FIFRA reregistration and/or FQPA tolerance reassessment
initiatives on pesticides. Since phostebupirim was first registered in 1995, it is currently not subject to
the reregistration process, only to the requirements of FQPA. However, some history and
background on reregistration and 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 of all existing tolerances. The Agency has
decided that, for those chemicals that have tolerances and are undergoing reregistration, the tolerance
reassessment will be initiated primarily through this reregistration process. It also requires that by
2006, EPA must review all tolerances in effect on the day before the date of the enactment of the
FQPA, which was August 3, 1996. FQPA also amends the FFDCA to require a safety finding in
tolerance reassessment based on factors including an assessment of cumulative effects of chemicals with
a common mechanism of toxicity. Phostebupirim belongs to a group of pesticides called
organophosphates, which share a common mechanism of toxicity - they all affect the nervous system by
inhibiting cholinesterase. Although FQPA significantly affects the Agency's reregislration process, it
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 phostebupirim has been completed, and will be used in the
cumulative assessment of all of the organophosphate chemicals to satisfy the requirements of FQPA.
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This document presents the Agency's revised dietary risk assessment for phostebupirim, as part of the
tolerance reassessment process. The Agency has also revised occupational risk estimates for
phostebupirim.
As part of the EPA's effort to involve the public in the implementation of 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
public process was discussed by 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 organophosphates are following this new process.
Phases 1 through 4 of the pilot process address the development and refinement of the risk
assessments. Phases 5 and 6 are concerned with the development and implementation of risk
management plans and provide opportunity for the registrants, user community, and general public to
propose risk mitigation based on the revised risk assessments. During phase 6 of the process, the
Agency prepares an Interim Reregistration Eligibility Decision (RED) Document or a Report on FQPA
Tolerance Reassessment and Interim Risk Management Decision Document, from which risk
management will be implemented Prior to finalizing a risk management decision, the Agency typically
arranges a conference call with USDA, growers, registrants, and other interested parties to assess the
feasibility of proposed mitigation measures.
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
phosetebupirim has already been subject to numerous public comment periods and a further comment
period was deemed unnecessary. A Notice of Availability for this document, however, has been
published in the Federal Register.
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
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.
In addition to the policy issues that resulted from the TRAC process, the Agency published in
the Federal Register on August 12,1999, a draft Pesticide Registration Notice that presents EPA's
proposed approach for managing risks from organophosphate pesticides to occupational users. This
notice describes the Agency's baseline approach to managing risks to handlers and workers of
organophosphate pesticides. Generally, basic protective measures such as closed mixing and loading
systems, enclosed cab equipment, or protective clothing, as well as increased reentry intervals will be
required for most uses where current risk assessments indicate a risk and such protective measures are
feasible. The draft guidance policy also slates that the Agency will assess each pesticide individually,
and based upon the risk assessment, determine the need for specific measures tailored to the potential
risks of the chemical. The measures included in this interim document are consistent with that draft
Pesticide Registration Notice.
This document consists of six sections. Section I contains the regulatory framework for
reregistration/tolerance reassessment as well as descriptions of the process developed by TRAC for
public comment on science policy issues for the organophosphate pesticides and the worker risk
management PR notice. Section H provides a profile of the use and usage of the chemical. Section ffl
gives an overview of the revised human health risk assessment resulting from public comments and
other information. Section IV presents the Agency's interim risk management decisions. Section V
summarizes required label changes based on the risk mitigation measures outlined in Section IV.
Section VI provides information on how to access related documents. Finally, the Appendices list Data
Call-In (DCI) information. The revised risk assessments and related addenda are not included in this
document, but are available on the Agency's web page, www.epa.gov/pesticides/op, and in the Public
Docket.
-------
Chemical Overview
A. Regulatory History
Phostebupirim was first registered in the United States in July 1995 for at-plant control of a
variety of soil-dwelling insect pests in or on corn.
B. Chemical Identification
PHOSTEBUPIRIM
Common Name:
Chemical Name:
Chemical Family:
CAS Registry Number:
.OPP Chemical Code:
Empirical Formula:
Molecular Weight:
Vapor Pressure:
Trade and Other Names:
Phostebupirim
O.-[2
-------
Technical phostebupirim is a colorless liquid. Phostebupirim is soluble in water at 5.5 mg/mL
and is completely miscible with all solvents tested at 20° C.
C. Use Profile
The following information is based on the currently registered uses of phostebupirim:
Type of pesticide: Insecticide.
Summary of Use Sites and Target Pests: Phostebupirim is only registered for use on
corn. Phostebupirim is used for the control of
com rootworms, cutworms, and other soil
insect pests in com commodities (forage and
fodder, pop, and sweet).
Formulation Types Registered:
In addition to the technical, there are three end-
use formulations: two 2.1% granular
formulations (clay-based and cellulose-based)
and a 4.67% granular formulation for use only
with a SmartBox® applicator system.
Method and Rates of Application:
Equipment -
Phostebupirim can be applied to com only with tractor drawn spreader.
Method and Rate - At-plant band and T-Band application with soil incorporation, and in-
furrow application. Application rates vary from 0.11 to 0.15 pounds
active ingredient per acre.
Timing -
At-plant.
Use Classification: Phostebupirim is a restricted use chemical, registered only for use on
com.
D. Estimated Usage of Pesticide
This section summarizes the best estimates available for phostebupirim use, based on available
pesticide usage information for 1990 through 1997 as obtained by EPA and USDA - NASS. As
discussed in the February 8, 1999, "Quantitative Usage Analysis," approximately 270,000 pounds of
phostebupirim active ingredient are applied annually to com. Approximately 3% of com acreage
receive applications of phostebupirim, with up to 6% crop treated as a maximum estimate. The
-------
majority of phostebupirim use (85%) occurs in the states of Iowa, Nebraska, Illinois, Indiana, Ohio,
and Minnesota. Phostebupirim use has been steadily increasing in the years for which data were
available.
m. Summary of Phostebupirim Risk Assessments
Following is a summary of EPA's human health risk findings and conclusions for the
organophosphate phostebupirim, as fully presented in the documents, "Phostebupirim: Dietary Risk
Assessment Update," dated April 9,1999, and "Occupational Exposure and Risk Assessment
Regarding the Use of Phostebupirim," dated May 5, 1999. The purpose of this summary is to assist the
reader by identifying the key features and findings of these risk assessments, and to better understand
the conclusions reached in the assessments.
EPA's preliminary risk assessments for phostebupirim were made available for public comment
on May 26,1999 (Phase 3 of the TRAC process). Comments submitted during the Phase 3 comment
period did not support any revisions to the Agency's risk assessments, as discussed in "Phostebupirim:
HED's Response to Comments Submitted During Phase 3 (Public Comment Period)," dated
September 22,1999. Thus, the preliminary and final risk assessments for phostebupirim are the same.
On March 27,2000, the Agency requested public comment on risk management for phostebupirim.
The risk assessments presented here form the basis of the Agency's interim risk management
decision for phostebupirim only; the Agency must complete a cumulative assessment of the dietary risks
of all the organophosphate pesticides before any final tolerance decisions can be made for the
organophosphate pesticides, including phostebupirim.
A. Dietary Risk from Food
1. Toxicity
The Agency has reviewed all toxicity studies submitted and has determined that the toxicity
database is complete, and that it supports an interim human health risk determination for all currently
registered uses. Further details on the toxicity of phostebupirim can be found in the April 9, 1999,
"Phostebupirim: Dietary Risk Assessment Update." A brief overview of the studies used for the
dietary risk assessment is outlined in Table 1 in this document.
2. FQPA Safety Factor
The FQPA safety factor is IX. The toxicity database includes an acceptable two-generation
reproduction study in rats, acceptable developmental toxicity studies in rats and rabbits, and acceptable
acute and subchronic neurotoxicity studies in the rat. These studies show no increased susceptibility of
rat or rabbit fetuses to in utero exposure to phostebupirim. There was no indication of increased
-------
susceptibility in the offspring as compared to parental animals in the two generation reproduction study.
In these studies, effects in the fetuses/offspring were observed only at or above treatment levels which
resulted in evidence of parental toxicity. Therefore, the additional 10X factor for the protection of
infants and children as required by FQPA was reduced to IX as discussed in the March 30, 1999,
"Phostebupirim - Report of the FQPA Safety Factor Committee." As the dietary assessments were
based on water modeling, tolerance levels and a 100% crop treated assumption, the Agency also found
that the exposure assessments will not underestimate the potential dietary (food and water) exposures
for infants and children from the use of phostebupirim and no non-dietary (residential) exposures are
expected.
3. Population Adjusted Dose (PAD)
The Reference Dose (RfD) is derived from an exposure level at which there are no statistically
or biologically significant increases in the frequency or severity of adverse effects between the exposed
population and its appropriate control, along with the application of uncertainty factors. 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). In the case of phostebupirim, the FQPA safety factor is 1; therefore, the acute or
chronic RfD = 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 level of risk concern.
4. Exposure Assumptions
Dietary risk analyses for phostebupirim were conducted with the Dietary Exposure Evaluation
Model (DEEM™). DEEM incorporates consumption data generated in USDA's Continuing Surveys
of Food Intakes by Individuals (CFSH), 1989-1992.
The Tier I acute dietary analysis used tolerance levels and assumed 100% of the registered
commodities were treated. The chronic dietary analysis for phostebupirim was also a Tier 1 estimate
with all residues at tolerance levels and 100% of the commodities assumed to be treated with
phostebupirim. Further refinements to the dietary risk assessment were not conducted, given the low
dietary risk estimates based on the tolerance-level residues and 100% crop treated screening
assumptions.
-------
Table 1: Summary of lexicological Endpoints and Other Factors Used in the Human Dietary
Risk Assessment of Phostebupirim
Assessment
Acute Dietary
Chronic
Dietary
Dose
LOAEL = O.S
mg/kg/daya
NOAEL=
0.02
mg/kg/day
Endpoint
Plasma and
RBCChEIb
Plasma, RBC
and brain ChEI
Study
Acute rat
neurotoxicity
(MRID
43473001)
1 -year dog
feeding study
(MRID
42005452 and
42119301)
Uncertainty !
Factor(UF)
UF = 300
lOOXinter-
and
intraspecies
variation and
3X lack of
NOAEL
UF=100
100X inter-
and
intraspecies
variation
FQPA Safety
Factor
IX
IX
PADC
0.002 mg/kg
(same as acute
RfD)
0.0002
mg/kg/day
(same as
chronic RfD)
NOAEL not achieved in males '
bChEI" Cholinesterase Inhibition
c PAD = Population Adjusted Dose = Acute or Chronic RfD
FQPA Safety Factor
5.
Food Risk Characterization
Generally, a dietary risk estimate that is less than 100% of the acute or chronic Population
Adjusted Dose does not exceed the Agency's risk concerns. The phostebupirim acute dietary risk
fiom food is well below the Agency's level of concern- that is, less than 100% of the acute PAD is
utilized. For example, the percent of the acute PAD utilized for the most exposed subpopulation group,
children (1-6 years), is <5% at the 95th percentile. The 95* percentile is reported here because a Tier
1 deterministic assessment was conducted. A probabilistic assessment was not conducted at this time
because the results of the Tier I assessment were so low.
Similarly, the chronic dietary risk from food alone is well below the Agency's level of concern.
For the most exposed subpopulation group, children (1-6 years old), the percent of the chronic PAD
utilized is 17.6%. La summary, both acute and chronic dietary exposure and risk associated with
phostebupirim-treated foods are considered to be well below the Agency's level of concern, even
when tolerance-level residue values are used along with a 100% crop treated assumption.
Refinements to the dietary analyses can be made using monitoring data and percent crop
treated data for the chronic dietary analysis, and a probabilistic assessment for acute dietary analysis;
however, given the low dietary risk estimates based on tolerance level residues and 100% crop treated
assumptions, the Agency determined that further refinements are not warranted at this time.
Refinements will be considered when the cumulative assessment for all of the organophosphates is
conducted.
10
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B. Dietary Risk from Drinking Water
Drinking water exposure to pesticides can occur through ground water and surface water
contamination. EPA considers both acute (one day) and chronic (lifetime) drinking water risks and
uses either modeling or actual monitoring data, if available, to estimate those risks. Modeling is
considered to be an unrefined assessment and provides a high-end estimate of risk. In the case of
phostebupirim, no monitoring data for either ground or surface water were available; therefore,
modeling was used to estimate drinking water risks from these sources.
The GENEEC model was used to estimate surface water concentrations, and SCI-GROW
was used to estimate groundwater concentrations of phostebupirim in drinking water. Both of these
models are considered to be screening models which provide high end estimates of water
concentrations. These drinking water assessments are described in greater detail in "Tier 1 Screen for
Drinking Water Assessment for Phostebupirim," dated December 8,1997.
Based on available environmental fate data regarding half-lives under environmental conditions,
phostebupirim appears to be quite persistent in the environment. Based on relatively high K^ values,
phostebupirim also appears to be quite immobile in soil. Two phostebupirim metabolites have been
identified: TBHP (2-[l,l-dime%ne%l]-5-hydroxypyrirnidine) andOMAT (2-[l,l-dimethylethyl]-5-
pyrimidinyl ethyl 1-methylethyl phosphate). The OMAT metabolite is structurally very similar to
phostebupirim; however it appears to be quite mobile in soil.
1.
Surface water
EPA used a Tier 1 GENEEC model to estimate the upper-bound phostebupirim concentrations
in drinking water derived from surface water based on phostebupirim use on com. This model is the
least refined model, based on the most conservative assumptions, which is used as an initial screening
tool. The highest estimated concentrations of phostebupirim in surface water, based on this screening
model, were a peak acute concentration of 1.89 ppb and a chronic concentration of 0.86 ppb.
2.
Ground water
Drinking water concentrations from ground water were estimated with SCI-GROW, also a
Tier 1 unrefined assessment tool. For ground water, the maximum acute and chronic estimated
concentration of phostebupirim is 0.3 ppb. This screening model does not provide different values for
acute and chronic estimated residue values.
11
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3. Drinking Water Levels of Comparison (DWLOCs)
To determine the maximum allowable contribution of water containing pesticide residues
permitted in the diet, EPA first looks at how much of the overall allowable risk is contributed by food
(and if appropriate, residential uses) then determines a "drinking water level of comparison" (DWLOC)
to determine whether modeled or monitored levels exceed this level. The Agency uses the DWLOC as
a surrogate to capture risk associated with exposure from pesticides in drinking water. The DWLOC
is the maximum concentration in drinking water which, when considered together with dietary exposure,
does not exceed a level of concern.
OPP has calculated DWLOCs for acute exposure to phostebupirim in surface and ground
water for the U.S. general population and children (ages 1-6). These DWLOCs are 68.36 ppb and
19.04 ppb, respectively. For chronic (non-cancer) exposure to phostebupirim in surface and ground
water, the DWLOCs are 6.48 ppb for the U.S. general population, and 1.65 ppb for children (ages 1-
6).
Estimated maximum concentrations of phostebupirim in surface and ground water are 1.89 ppb
and 0.3 ppb, respectively. Estimated average concentrations of phostebupirim in surface and ground
water are 0.86 ppb and 0.3 ppb, respectively.
The maximum and average drinking water estimated concentrations in surface and ground
water are less than OPP's levels of comparison for phostebupirim in drinking water. As residues of
phostebupirim in drinking water are less than calculated drinking water levels of comparison, the
Agency concludes that drinking water risk from phostebupirim use is not of concern.
C. Aggregate Risk
Aggregate risk consists of the combined risk from exposure through food, drinking water, and
non-occupational uses of a pesticide. For phostebupirim, acute and chronic aggregate risk is limited to
food and water exposure because phostebupirim is not used in residential settings or other areas that
are frequented by the general public. Generally, the combined risks from these different exposures
must be less than 100% of the acute or chronic PAD, respectively. Since the ground and surface water
estimated concentrations are substantially below the DWLOCs based on screening models, acute and
chronic aggregate (food and water) exposure to phostebupirim is not of concern for any population
sub-group. There are no residential uses of phostebupirim, and no residential exposures resulting from
phostebupirim use on com.
D. Occupational Risk
Occupational workers can be exposed to a pesticide through mixing, loading, and/or applying a
pesticide, or re-entering treated sites. Risk to workers handling phostebupirim is measured by a
12
-------
Margin of Exposure (MOE) which determines how close the occupational or residential exposure
comes to a No Observed Adverse Effect Level (NOAEL). Generally, MOEs greater than 100 do not
exceed the Agency's level of concern.
1. Toxicity
Table 2 presents the acute toxicity categories for phostebupirim.
Table 2. Toxicity Categories
Study Type
Acute Oral Toxicity
Acute Dermal Toxicity
Acute Inhalation Toxicity
Primary Eye Irritation
Primary Dermal Irritation
Dermal Sensitization
Toxicity Category
(technical)
I
I
I
Not Available
Not Available
Not Available
Toxicity
Category
(Aztec 4:67%);.
n
m
m
m
IV
slight
The phostebupirim endpoints were obtained from the Agency's "Risk Assessment for Use of
Aztec 2.1% Granular on Com Commodities," dated February 16, 1995, and they indicate that there
are toxicological endpoints of concern for phostebupirim. Phostebupirim is not expected to be used on
a continuous long-term basis (greater than 6 months a year) resulting in chronic exposure. Therefore,
the risk assessments were conducted for short- (1-7 days) and intermediate- (one week- several
months) term occupational exposure scenarios. Dermal and inhalation endpoints of concern have been
identified for short-term and intermediate-term exposures.
Table 3 lists the toxicity endpoints selected for the phostebupirim risk assessment These are
based primarily on plasma, red blood cell., and brain cholinesterase inhibition. While a 21-day rabbit
dermal toxicity study was submitted by the registrant, this could not be relied on for risk assessment
since phostebupirim is a sulfur-containing organophosphate and detoxification can occur in rabbits when
dermally exposed to sulfur-containing organophosphates. Phostebupirim is classified as a Group E
chemical, indicating that it is "Not Likely" to be carcinogenic in humans via relevant routes of exposure.
This classification is supported by adequate carcinogenicity studies in rats and mice.
13
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Table 3. Phostebupirim Hazard Endpoints and Uncertainty Factors
Route/
Duration
Dermal
short term
Dermal
intermediate term
Inhalation (short
and intermediate
term)
NOAEL
(mg/kg/day)
0.1
0.02
0.043
(0.16 mg/nf)a
Effect
Increased Number
ofFetal
Resorptions
Red Blood Cell
Cholinesterase
Inhibition
Red Blood Cell
Cholinesterase
Inhibition
Study
developmental
toxicity in rabbits.
1 -year chronic dog
study
28 day inhalation
study in rats.
Uncertainty Factors
Interspecies: lOx
Intraspecies: lOx
Interspecies: lOx
Intraspecies: lOx
Interspecies: lOx
Intraspecies: lOx
Absorption
Factor
100 percent
dermal
assumed.
100 percent
dermal
assumed.
Wistar Rats, 6
hrs/day
exposure, 100
percent lung
absorption
assumed.
a O.lo'mgVm-' was converted to 0.043 mg/kg/day by the following formula: NOAEL (mg/kg/day) = NOAEL (mg/mj) *
Conversion Factor (1m3 / 1000 L) * Wistar Rat Respiratory Volume for Males and Females (8.46 L/hr) * Body Weight of ' '
Wistar Rats for Males and Females (1/0.187 kg) * Exposure Duration per day (6 hrs/day).4
2. Exposure
Chemical-specific exposure data were not available for phostebupirim; therefore, risks to
pesticide handlers were assessed using data from the Pesticide Handlers Exposure Database
(PHED), and standard assumptions about average body weight, work day, daily areas treated, volume
of pesticide used, etc. to calculate risk estimates. The quality of the data and exposure factors
represents the best sources of data currently available to the Agency for completing these kinds of
assessments; the application rates are derived directly from phostebupirim labels. The exposure factors
(e.g., body weight, amount treated per day, protection factors, etc.) are all standard values that have
been used by the Agency over several years, and the PHED unit exposure values are the best available
estimates of exposure. Some PHED unit exposure values are high quality while others represent low
quality, but are the best available data. The quality of the data used for each scenario assessed is
discussed in "Occupational Exposure and Risk Assessment Regarding the Use of Phostebupirim,"
dated May 5,1999, which is available in the public docket.
The following general assumptions are made:
Average body weight of an adult handler is 70 kg. An average body weight of 60 kg
was used for an adult female for short-term dermal exposure since the NOAEL is
based on a reproductive study. Since the dermal and inhalation NOAELs for the short-
term were not based on identical effects, the doses were not combined in this risk
assessment to identify a total MOE. However, the MOEs were combined for the
intermediate-term since the effect was the same.
14
-------
Average work day interval represents an 8 hour workday (e.g., the acres treated or
volume of spray solution prepared in a typical day).
Calculations of handler scenarios are completed using the application rates
recommended by the available phostebupirim labels.
PHED Version 1.1 data were used to estimate exposures for all scenarios.
Due to a lack of scenario-specific data, the Agency calculated unit exposure values
using generic data from the Pesticide Handler Exposure Database (PHED) and, in lieu
of PHED data for a scenario, using protection factors that are applied to represent
various risk mitigation options (i.e., the use of PPE and engineering controls).
Exposures were estimated for handlers using 213 acres per day maximum acreage (20
row planter) and 69 acres per day typical acreage (8 row planter) for a tractor drawn
spreader at the minimum and maximum application rates, since these data were
available from the "Corn Insecticide Cluster Risk Assessment for Occupational
Exposure," dated November, 1993.
3.
Risk Assessment
Occupational exposure scenarios identified for phostebupirim were (1) loading phostebupirim
granulars and (2) applying phostebupirim granulars with a tractor drawn spreader. Within each of these
occupational categories, further analyses were conducted to determine the MOE at minimum and
maximum application rates, and at maximum and typical acreage. The Agency assessed the exposure
and risks for the two scenarios considering both inhalation and dermal exposure. Phostebupirim is not
expected to be used on a continuous long-term basis (greater than 6 months a year) resulting in chronic
exposure. Therefore, the risk assessments were conducted for short- (1-7 days) and intermediate-
(one week - several months) term occupational exposure scenarios.
Based on the available toxicity data, it is not appropriate to combine short-term dermal and
inhalation MOEs because the effects observed at the LOAELs are different. However, it is necessary
to combine the intermediate-term dermal and inhalation MOEs, since the effects observed at the
LOAELs were identical. The short-term and intermediate-term MOE for dermal exposure were
calculated using a NOAEL of 0.1 mg/kg/day and a NOAEL of 0.02 mg/kg/day, respectively. Both the
short-term and intermediate-term MOE for inhalation exposure were calculated using a NOAEL of
0.16 mg/m3 which translates to 0.043 mg/kg/day. Since a developmental study was used to determine
the short-term dermal NOAEL, the body weight used to calculate short-term dermal dose was 60 kg,
the average weight of an adult female. No chronic scenarios were identified. All of the risk calculations
for handlers completed in this assessment are described in the document entitled, "Occupational
Exposure and Risk Assessment
15
-------
Regarding the Use of Phostebupirim," dated May 5, 1999, available in the public docket. The results
are summarized in Tables 5-6 of this document. Table 4 summarizes the PPE requirements on current
phostebupMm labels.
Table 4: PPE on Current PhostebuDirim Labels
Formulation
Aztec 2.1% Granular
Insecticide
Aztec 4.67% Granular
Insecticide
Loaders
Long pants, long sleeved shirt,
waterproof gloves and shoes
plus socks.
Long pants, long sleeved shirt,
waterproof gloves and shoes
plus socks. Smart Box®
required.
Applicators
Long pants, long sleeved shirt,
waterproof gloves and shoes
plus socks.
Long pants, long sleeved shirt,
waterproof gloves and shoes
plus socks.
a.
Short-Term Risks
Table 5 presents the MOEs for short-term worker exposures. Under current phostebupirim
labels, short-term dermal MOEs exceed the Agency's level of concern for all worker handler
scenarios, with the exception of loading granules with the Smart Box formulation and at the minimum
application rate and typical acreage for the 2.1 G formulation. Additional personal protective equipment
(double layer of clothing for loaders and respirators for applicators) partially addresses these MOEs,
while engineering controls (closed loading systems and enclosed cabs) result in MOEs greater than 100
for all use scenarios with the exception of application at maximum rates and for the maximum acreage.
16
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Table 5: Short-Term Dermal and Inhalation Exposure to PhostebupirinV*
Scenario
Loading
granules
Loading
granules
Applying
granules
with
tractor
drawn
spreader
Applying
granules
with
tractor
drawn
spreader
Acres3
69
213
69
213
Rateb
(pounds
ai/acre)
0.11
0.15
0.11
0.15
0.11
0.15
0,11
0.15
Short-Term Dermal MOEs
Current
Label0
110
110
-«£ v -
*»*».'
\^i
i. "a&V-t
$ **Svfc,
5 ^
"^
*.r
i, t;^
"^fter *•*>«>
Jfc^"
<., «
Current label
+ additional
PPE?
230
170
75.
55 , • ,
190
140
61
45
Engineering
controls e
4700
3400
1500
1100
380
280
120
«*V-" -V
V "
Short-Term Inhalation MOEs
Current
Label0
230
170
330
240
110
^ >^r»^^
•Mif^ •»
Current
Label*
addn
PPE? ' ' ; ;;.
1200
860
380
280
1700
1200
-540
390
Engineering
Controls*
12000
8600
3800
2800
1800
1300
580
430
Dermal and inhalation exposures were riot combined due to the difference in effects observed at the LOAELs.
a Typical acreage = 69 acres; Maximum acreage = 213 acres.
b Minimum application rate = 0.11 Ibs ai/Acre; Maximum application rate = 0.15 Ibs ai/Acre.
c Current labels reflect risks for loaders, and applicators of the 2.1%G products, but only applicators for the 4.67%G product
(risks for loaders of the 4.67%G are reflected under engineering controls due to the Smart Box®). Current label specified PPE for
dermal unit exposure are long pants, long sleeved shirt, water-proof gloves, open mixing/loading, open cab tractor. Inhalation
exposure represents no respirator.
d Additional PPE for all dermal scenarios includes double layer of clothing (50% Protection Factor for clothing). Additional PPE
for all inhalation scenarios includes a dust/mist respirator (80% Protection Factor).
e Engineering controls for dermal scenarios include closed mixing/loading (e.g., Lock and Load ® or Smart Boxes® 98% protection
factor), single layer clothing, chemical resistant gloves. Engineering controls for inhalation scenarios include enclosed cab, single
layer clothing, no gloves (98% protection factor). '
b.
Intermediate-Term Risk
Table 6 presents MOEs for intermediate-term worker exposures. There are intermediate-term
risks of concern for all use scenarios under current labels and with additional PPE, except for the Smart
Box formulation which has MOEs greater than 100 for loaders. Use of closed loading systems brings
all MOEs to greater than 100 for loaders, while use of enclosed cabs results in MOEs for applicators
ranging from 20 to 84, which exceed the Agency's level of concern.
17
-------
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4. Post-Application Risk
The present labels for phostebupirim establish a re-entry interval (REI) of 0 hours. -The -
Agency's decision to establish the REI at this level is reflected in the memorandum entitled "Requested
Waiver of WPS Label Statements for Aztec 2.1% Granular Insecticide," dated September 13,1994.
This decision was based on the belief that soil incorporated insecticides, such as phostebupirim, would
not result in any dermal exposure after incorporation.
Since the phostebupirim REI of zero hours was established in 1994, the Agency has clarified
implementation of the Worker Protection Standards and when an REI must be established. As part of
its reassessment of occupational risks for phostebupirim, EPA has reevaluated potential postapplication
exposures and risks following soil-incorporated applications during planting of corn. The Agency has
determined that the Worker Protection Standard and current Agency policy indicate that a restricted-
entry interval must be established for this use pattern. The Agency notes that phostebupirim does not
qualify as a low risk pesticide, because of its high acute toxicity and because it is classified as an
organophosphate. Therefore, the restricted-entry interval will be established based on available data on
its dermal toxicity and its skin and eye irritation potential.
Under the Worker Protection Standard (WPS), restricted entry intervals for all uses within the
scope of the WPS are based on the acute toxicity of the active ingredient. The toxicity categories of
the active ingredient for acute dermal toxicity, eye irritation, and skin irritation are used to determine the
WPS REI. If one or more of the three acute toxic affects are in toxicity category I, the WPS REI is
established at 48 hours (72 hours in areas that receive less than 25 inches of rainfall per year). Since
phostebupirim has a toxicity category of 1 for acute dermal, the REI should be 48 hours (72 hours in
areas that receive less than 25 inches of rainfall per year) to comply with the Worker Protection
Standard.
IV. FQPA Tolerance Reassessment Progress and Interim Risk Management Decision
A. Determination of Tolerance Reassessment & Interim Risk Management
Decision
This interim evaluation presents the Agency's current position on products containing the active
ingredient phostebupirim. The Agency has sufficient information on the human health effects of
phostebupirim to make interim decisions as part of the tolerance reassessment process under FQPA
and to reassess occupational risks under FTFRA. Should a registrant fail to implement any of the
recommended risk mitigation measures outlined in this document, the Agency will continue to have
concerns about the risks posed by phostebupirim. Where .the Agency has identified any unreasonable
adverse effect to human health, the Agency may at any time initiate appropriate regulatory action to
address this concern. At that time, any affected person(s) may challenge the Agency's action.
19
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Based on its current evaluation of phostebupirim alone, the Agency has determined that
phostebupirim products, labeled and used as specified in this document, will not present unreasonable
dietary and occupational risks. Occupational risks can be brought above the Agency's level of concern
with additional personal protective equipment. In addition, data from both an exposure or dust
comparison study and a new dermal toxicity study will allow the Agency to refine its occupational risk
assessment.
The Agency will finalize the decision for phostebupirim after evaluating the cumulative risk of the
organophosphate class. Because the Agency has not yet completed the cumulative risk assessment for
the organophosphates, this interim decision does not fully address the reassessment of the existing
phostebupirim food residue tolerances as required by section 408(q) of the FQPA. When the Agency
has completed the cumulative assessment, phostebupirim tolerances will be reassessed along with the
other organophosphate pesticides and a final determination will be made. 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.
This interim evaluation does not limit the Agency from making further FQPA determinations and
tolerance-related rulemakings that may be required on this pesticide or any other in the future. If the
Agency determines, as a result of this later implementation process, that any of the determinations
described in this Report on FQPA Tolerance Reassessment Progress and Interim Risk Management
document are no longer appropriate, the Agency will pursue appropriate action, including but not
limited to, reconsideration of any portion of this interim document.
B. Summary of Phase 3 Comments and Revisions to Preliminary Assessment
The Agency solicited comments on the preliminary human health assessment for phostebupirim.
In response to the May 26,1999, Federal Register Notice (64 FR 28469) announcing the availability
of the preliminary risk assessment and supporting documents, comments on the risk assessment were
submitted by the phostebupirim registrant, Bayer Corporation. The registrant disagreed with the
selection of a developmental toxicity study in rabbits for establishing the acute RfD and with the
selection of a developmental toxicity study for evaluating dermal exposure to workers. The Agency
acknowledged that it was more appropriate to use an acute neurotoxicity study for the acute dietary
endpoint and noted that the 3X FQPA safety factor had been reduced to IX by the Hazard
Identification Assessment Review Committee as a result of its March 25,1999, meeting based on the
Agency's review of that data However, the Agency noted that it was not appropriate to use the 21-
day dermal toxicity study in rabbits submitted by the registrant instead of the developmental toxicity
study to determine the endpoint for short-term dermal exposure. This is because the use of rabbits to
evaluate the dermal toxicity of sulfur-containing organophosphates is not appropriate because
detoxification can occur in rabbits when dermally exposed to sulfur-containing organophosphates. The
20
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registrant also disagreed with the use of technical phostebupirim to measure inhalation exposure, rather
than use of a formulated product. The Agency determined that comments received during Phase 3 did
not warrant further revisions to the risk assessment. A fuller discussion of the registrant comments and
the Agency's response can be found in "Phostebupirim: HED's Response to Comments Submitted
During Phase 3 (Public Comment Period), dated September 22,1999.
C. Summary of Phase 5 Comments and Responses
The availability of the revised risk assessment and supporting documents was announced on
March 27,2000, in Federal Register Notice (65 FR 16197). Interested parties were provided a 60-
day period to submit comments, including risk mitigation proposals. Only two submissions were
received during this public comment period, one from the President of the Illinois Corn Growers
Association and the other from the phostebupirim registrant, Bayer Corporation. These comments are
available in their entirety in the docket. A brief summary of the comments and the Agency response is
noted here.
1) Comment. The President of the Illinois Corn Growers Association noted that Aztec plays an
important role in managing corn pests and objected to EPA's use of maximum rates and worst-case
scenarios in conducting risk assessments as unrealistic. He also expressed the opinion that EPA's use
of exposure data derived from a broadcast study was inappropriate because phostebupirim is applied
through in-furrow or banded application methods which are more targeted than broadcast application.
Response. This comment provided no specific mitigation suggestions. However, the Agency's policy is
to use the maximum labeled application rates and maximum daily treated acreage for calculating short
and intermediate-term occupational risks. Since the endpoint of concern for phostebupirim results from
a short and intermediate-term exposure, it is appropriate to protect workers who use the maximum
recommended application rates and who are applying it to larger corn fields. The Agency has reviewed
acreage information for corn and. believes that the 213 acres used is a realistic estimate of the maximum
number of acres of corn which may be treated with phostebupirim in a given day (based on the Com
Cluster analysis and follow-up information).
While the Agency does not agree that it was inappropriate to use exposure data derived from a
broadcast study in the risk assessment, EPA does agree that this has Likely resulted in an overestimate
of exposure. This likely overestimate of exposure has been factored into the risk mitigation
recommended in this document.
2) Comment. Bayer Corporation did not provide any risk mitigation suggestions; instead Bayer
reiterated many of the same comments on the risk assessment raised in its Phase 3 comments.
Specifically, (1) Bayer alleged that the Agency had chosen different lexicological endpoints in 1999
than in 1995 to assess occupational risk despite the submission of no new studies, (2) Bayer suggested
that the use of in-furrow and T-Band application data could reduce calculated exposure values, (3)
21
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Bayer reiterated its objection to the Agency's rejection of the 21-day dermal toxicity study in rabbits for
regulating occupational dermal exposure, (4) Bayer objected to the Agency's assumption of 100%
dermal absorption, suggesting sufficient information was available to estimate a lower dermal absorption
value, (5) Bayer suggested that the Agency amortize intermediate-term exposure from the 1-year
chronic dog study to more accurately represent the shorter-term intermediate-term exposure, and (6)
Bayer proposed that 150 acres should be used for maximum daily acres treated rather than the 213
used by the Agency.
Response. As discussed more fully in the Agency's June 23,2000, Response to Bayer's Comments
found in the docket and on the internet, (1) the Agency used the exact same toxicological endpoints in
both its 1995 and 1999 occupational risk assessment, (2) the Agency's exposure data included the use
of in-furrow and T-Band application studies, (3) it is inappropriate to use dermal toxicity studies in
rabbits for sulfur-containing organophosphates such as phostebupirim, (4) the Agency does not have
sufficient information to estimate an appropriate dermal absorption value and therefore assumes 100%
dermal absorption in the absence of additional data, (5) the Agency agrees that a 1-year chronic dog
study is not the ideal study for estimating intermediate-term worker risk; however, the Agency does not
have sufficient information to amortize intermediate-term exposure from the 1-year chronic dog study
and in the absence of a more appropriate study, the 1-year chronic dog study is a more appropriate
duration study than the other available studies, and (6) the data available to the Agency indicates that
213 acres is an appropriate maximum daily acres treated value for com and does not result in an overly
conservative estimate of risk.
D. Regulatory Position
1. FQPA and Occupational Risk 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 the 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 phostebupirim is within its own "risk cup." In
other words, if phostebupirim did not share a common mechanism of toxicity with other chemicals,
EPA would be able to conclude today that the proposed tolerances for phostebupirim on com meet 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 conducted for exposures through food and drinking water (there are no
22
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residential uses). Results of this aggregate assessment indicate that the human health risks from these
combined exposures are considered to be within acceptable levels; that is, combined risks from all
exposures to phostebupirim "fit" within the individual risk cup. Therefore, unless phostebupirim can be
shown to meet the Agency's Threshold of Regulation policy such that no tolerances are required, the
Agency will consider establishing phostebupirim tolerances after EPA has completed a full assessment
of the cumulative risk from all organophosphates.
b. Tolerance Summary
Time-limited tolerances of 0.01 parts per million (ppm) were established July 5,1995, in 60
FR 34871 for phostebupirim residues in or on field corn, sweet com, pop corn and corn forage and
fodder. The tolerances were set at the Limit of Detection (LOD). There have been no detected
residues of phostebupirim at the LOD in food monitoring programs or field trials where phostebupirim
was applied at the label rate.
The time-limited tolerances for phostebupirim expired July 6,1999, while the conditional
registration for phostebupirim was extended through July 5,2001. The Agency was not able to
establish or extend tolerances for phostebupirim at the time the time-limited tolerance expired due to the
requirements under the FQPA to establish a reasonable certainty of no harm from the cumulative effects
of the residues of all organophosphates that show a common mechanism of toxicity, a level of
assessment which the Agency has not yet completed. However, the Agency believed it was
appropriate to allow for the continued conditional registration of phostebupirim for pre-plant
applications on corn since there is no reasonable expectation of finite residues of phostebupirim. This
determination was made before the Agency issued its Threshold of Regulation (TOR) policy for
deciding whether a pesticide food use pattern needs a tolerance. The Agency believes that
phostebupirim complies with the spirit of the policy because no phostebupirim residues in com
commodities have been detected in either com metabolism studies, crop field trials, or in sampling
programs.
Under the TOR policy, a tolerance or an exemption from the tolerance requirement is not
necessary for a pesticide use that results in no detected residues in food and for which the degree of
potential risk posed by any theoretically possible residues is so minimal that tolerance setting serves no
purpose. While phostebupirim does not meet the TOR policy based on currently available data, Bayer
may be able to generate data which would support a finding under the policy that no tolerances are
required. In order to allow the EPA to make such a determination, it would be necessary to conduct
additional field trial studies using a more sensitive, validated, analytical method, along with exaggerated
application rates. For phostebupirim to be considered under the policy, the registrant should submit a
request in writing, along with any supplemental data to support its request, asking the Agency to
determine whether phostebupirim uses need a tolerance under the TOR policy.
23
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The time-limited tolerances for residues of phostebupirim in/on plant commodities were
expressed in terms of residues of phostebupirim per se. Based upon the lack of phostebupirim residues
measured in field corn, popcorn, and sweet com commodities (<0.01 ppm), there is no reasonable
expectation of finite residues of phostebupirim in meat, milk, poultry or eggs and no tolerances would
be needed for these commodities if the tolerances for the raw agricultural commodities were
established. If Hie Agency is able to establish phostebupirim tolerances after it completes its cumulative
dietary risk assessment from all organophosphates, Table 7 provides the appropriate tolerance levels
for phostebupirim [Q-[2<14-dime%le%l)-5-pvrimidinyl] £)-ethyl Q-(l-methylethyl)
phosphorothioate], as supported by submitted residue data. Sufficient data are available to ascertain
the adequacy of these tolerances for the following commodities, as defined in 40 CFR § 180.486.
Note that these tolerances cannot be established, or considered "reassessed" as required by FQPA,
until the cumulative risk assessment of all organophosphates is completed.
Table 7: Tolerance Summary for Phostebupirim
Commodity
Com, field, forage
Com, field, stover
Corn, pop, forage
Com, pop, stover
Com, sweet, forage
Com, sweet, stover
Com, field, grain
Com, pop, grain
Com, sweet, kernel plus cob with husks
removed
Parts per million '.'.-.:•;'' 7;x
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
2. Endocrine Disrupter Effects
EPA is required to develop a screening program to determine whether certain substances
(including all pesticides and inerts) "may have an effect in humans that is similar to an effect produced by
a naturally occurring estrogen, or such other endocrine effect...". The Agency is currently working with
interested stakeholders, including government agencies, public interest groups, industry and research
scientists in developing a screening and testing program and a priority setting scheme to implement this
program. The EPA may require further testing of phostebupirim for endocrine disraptor effects when
this program is in place.
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3.
Recommended Label Modifications
The Agency recommends the following measures, in addition to the existing label requirements,
to clarify and strengthen the existing label language to help minimize worker risks. These measures are
expected to result in minimal impact on grower costs and ability to effectively use phostebupirim
products.
Labels should state that for granular products packaged in the SmartBox® closed loading
system (or any other closed loading system that meets the requirements of the WPS), loaders,
applicators and other handlers must wear long-sleeved shirt, long pants, shoes plus socks, and
chemical resistant gloves such as or made out of any waterproof material. In addition, loaders
must be provided with and have immediately available for use in case of an emergency, a
NIOSH approved dust/mist respirator.
Labels should state that for clay-based products not packaged in the SmartBox® closed
loading system (or any other closed loading system that meets the requirements of the WPS),
loaders, applicators and otherhandlers must wear long-sleeved shirt, long pants, shoes plus
socks and chemical resistant gloves such as or made out of any waterproof material. In
addition, loaders must wear a dust/mist respirator.
• Labels should state that for cellulose-based products not packaged in the SmartBox® closed
loading system (or any other closed loading system that meets the requirements of the WPS),
loaders, applicators and other handlers must wear long-sleeved shirt, long pants, shoes plus
socks and chemical resistant gloves such as or made out of any waterproof material.
The REI should be 48 hours or 72 hours where there is less than 25 inches of rainfall.
Labels should state that PPE during early re-entry consists of coveralls, chemical resistant
gloves such as or made out of any waterproof material, socks plus shoes, and protective eye
wear.
Labels should include a "double notification" statement. Double notification requires that
workers are advised about the application both orally and by posting warning signs at entrances
to treated areas during the REI.
The Agency is not recommending any further label modifications, beyond the above listed
measures, to mitigate occupational risks from phostebupirim use at this time. Bayer has agreed to
implement the above label modifications for the 2001 use season and the Agency believes that
remaining worker risk concerns will be adequately addressed as a result of confirmatory data, which
will be submitted by April 1,2001, to refine the occupational risk assessment The Agency will review
the phostebupirim data prior to July 5,2000, the date the conditional registration expires.
25
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E. Regulatory Rationale
The following is a summary of the rationale for managing risks associated with the use of
phostebupirim. Where labeling revisions are recommended, specific language is set forth in the
summary tables of Section V of this document.
1. Dietary Mitigation
a. Dietary (Food) Risk Mitigation
Acute and chronic dietary risk from food is well below the Agency's level of concern - a Tier
1 DEEM™ analysis yielded percent acute and chronic PAD values that are only 4.79% and 17.6%
respectively at the 95th percentile of exposure for the most exposed population subgroup (children 1-6
years old). Therefore, no mitigation measures are recommended at this time to address acute or
chronic dietary risk from food.
b. Dietary (Water) Risk Mitigation
Acute and chronic dietary risk from water is not of concern based on the comparison of the
DWLOC against the estimated concentrations from surface and ground water modeling, based on Tier
1 screening models which provide an upper-bound unrefined estimate of drinking water concentrations.
Therefore, no mitigation measures are recommended at this time to address acute or chronic drinking
water risks.
c. Aggregate (Food + Water) Risk Mitigation
For phostebupirim, the aggregate risk is limited to food and water. No risk mitigation for
aggregate risk is necessary at this time because food and drinking water estimates indicate that the
Agency's level of concern is not exceeded for any subgroup.
2. Occupational Risk Mitigation
Under the current label, the Agency's risk assessment shows a risk concern for short and
intermediate-term exposures for both granular loaders and applicators. Adding a dust/mist respirator
requirement to the 2.1G clay-based formulation product labels for loaders would address inhalation risk
concerns. The Agency believes the inhalation risks for applicators are overstated because the MOEs
were calculated with low confidence PHED data based on a broadcast spreader study. Phostebupirim
is applied in-furrow or T-Band, which will have lower exposures. Therefore, no risk mitigation is
necessary to address applicator inhalation risk.
26
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Although dermal risks are of concern, the registrant has agreed to initiate a 21-day rat dermal
toxicity study which the Agency believes will confirm that its current dermal risk assessment
overestimates the potential for worker exposure for the following reasons:
(1) In the absence of an acceptable dermal toxicity study, .the Agency is regulating worker dermal
exposures based on an oral developmental study. The Agency's preference is to use route-
specific studies when possible, and thus a dermal toxicity study would be preferred over an oral
study especially when coupled with the more conservative 100% dermal absorption
assumption. While it is not appropriate to use a rabbit dermal toxicity study for sulphur-
containing organophosphates like phostebupirim, it would be appropriate to use a rat dermal
toxicity study.
(2) The registrant is conducting its dermal toxicity study using the granular (4.67% a.i.) rather than
the technical (98% a.i.) formulation. The Agency believes this is appropriate since only a 2.1%
and 4.67% a.i. granular formulation are registered. This will provide a more realistic picture of
the impacts of the granular product, which has a much lower percent active ingredient than the
liquid technical product.
(3) Since short-term worker exposures are 1-7 days while intermediate-term exposures are 7 days
to several months, the Agency had to use two different studies to approximate these different
exposure durations. One, the oral rabbit developmental study, provided an acute (short-term)
exposure, while the other, the 1-year chronic dog study, provided a longer-term exposure
duration, although the Agency believes intermediate-term exposures to phostebupirim do not
exceed 30 days. By conducting a 21-day rat dermal toxicity study, the registrant will provide a
study which better represents both the short-term and intermediate-term worker exposure
durations. Thus, the Agency will be able to use a single, more appropriate, study to establish a
NOAEL for both short-term and intermediate-term exposure durations.
Thus, for the above-mentioned reasons, the Agency believes that a 21-day rat dermal toxicity
study will provide a more appropriate endpoint for regulating both short-term and intermediate-term
occupational dermal exposures and will provide a more refined occupational risk assessment.
In conclusion, to mitigate inhalation risks to loaders, the Agency is recommending label
amendments to require the use of a dust/mist respirator when loading the Aztec® 2.1G granular clay-
based formulation. The Agency believes that handlers of Aztec® 2.1G cellulose-based products are
exposed to comparatively lower levels via inhalation. As a result, no mitigation is recommended at this
time for the Biodac cellulose-based formulation. However, to confirm the Agency's belief that
cellulose-based formulations pose less inhalation risk than the clay-based formulation, the registrant has
agreed to submit an exposure or dust comparison study by April 1,2001.
27
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The Agency is not requiring further risk mitigation to address applicator inhalation risk.
Although the risk assessment shows a risk concern for this exposure (MOE=79), the Agency believes
this risk is overstated. This is because the risk was calculated using low confidence PHED data (one
study with a small number of replicates using only a broadcast spreader). In actual use, phostebupirim
will typically be applied in-furrow or T-Band. These methods of application should make the granular
formula less available for exposure.
With regard to dermal risks, the Agency believes that the 21-day rat dermal toxicity study using
the 4.67G formulation, which the registrant will submit by April 1,2001, will demonstrate that the
NOAEL is substantially higher and that worker dermal MOEs no longer exceed the Agency's level of
concern. As a result, the Agency is not recommending any additional measures at this time to address
worker risks from dermal exposure. However, in the event that there are risk concerns after results of
the new studies are reviewed, the Agency will recommend additional mitigation measures to the
registrant
3. Post Application Risk Mitigation
Since the phostebupirim REI of 0 hours was established in 1995, the Agency has clarified
implementation of the Worker Protection Standards and when an REI must be established. For
phostebupirim, EPA has reevaluated potential postapplication exposures and risks following
soil-incorporated applications during planting of corn. The Agency has determined that the Worker
Protection Standard and current Agency policy indicate that a restricted-entry interval should be
established for this use pattern. The Agency notes that phostebupirim does not qualify as a low risk
pesticide, because of its high acute toxiciry and because it is classified as an organophosphate.
Therefore, the restricted-entry interval will be established based on available data on its dermal toxiciry
and its skin and eye irritation potential. The restricted-entry interval (REI) is the time immediately after
a pesticide application when entry into the treated area is limited. The current REI on phostebupirim
end-use products of 0 hours must be replaced by 48 hours or 72 hours where average rainfall is less
than 25 inches per year in order to comply with the Worker Protection Standard (WPS). Early re-
entry PPE, as required by WPS, must also be specified on labels and include coveralls over long-
sleeved shirt, long pants, chemical resistant gloves such as or made out of any waterproof material,
chemical resistant footwear plus socks and protective eye wear. Protective eye wear is being required
because the active ingredient (a.i.) is assumed to be Toxicity Category I for Acute Eye Irritation in the
absence of available data. A double notification requirement for re-entry is required because the a.i. is
assumed to be Toxiciry Category I for Dermal Irritation in the absence of available data.
28
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V. Recommended Mitigation Measures
A. Manufacturing Use Products
The generic database supporting the registration of phostebupirim for use on com has been
reviewed and determined to be substantially complete. However, the registrant is conducting a 21-day
rat dermal toxicity study and an exposure or dust comparison study which will provide further
refinement of the current risk assessment. Theses studies are to be submitted to the Agency by April 1,
2001.
B. End-Use Products
1. Labeling Changes for End-Use Products
The Agency recommends the following label language and modifications detailed in Table 8 to
mitigate occupational risks.
29
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"Loaders, applicators and other handlers must wear:
-- Long-sleeved shirt and long pants
-- Chemical resistant gloves such as or made out of any waterproof
— Shoes plus socks
In addition, loaders must wear:
- A NIOSH-approved dust mist filtering respirator with MSHA/NK
NIOSH-approved respirator with any N2 R, P, or HE filter."
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2. Procedure and Timing for Label Amendment
Registrants should submit applications for amended registration. This application should
include the following items: EPA application form 8570-1 (filled in), five copies of each revised label,
and a description on the application, such as, "Responding to Interim Tolerance Reassessment
Evaluation and Risk Management Document." Registrants should send applications for amendment to
the appropriate following address within 90 days after receipt of this document
Document Processing Desk (APPL)
Office of Pesticide Programs
Room 266A, Crystal Mail 2
1921 Jefferson Davis Highway
Arlington, VA 22202
Attn: Marilyn Mautz
Insecticide-Rodenticide Branch (7504C) ._ ._ . - — _.._...-.
C. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling for 12 months
from the date of the issuance of this Report on FQPA Tolerance Reassessment and Interim Risk
Management Decision. Persons other than the registrant may generally distribute or sell such products
for 24 months from the date-of the issuance of this Report on FQPA Tolerance Reassessment Progress
and risk management decision. However, existing stocks time frames will be established case-by-case,
depending on the number of products involved, the number of label changes, and other factors. Refer
to "Existing Stocks of Pesticide Products; Statement of Policy"; Federal Register. Volume 56, No.
123, June 26, 1991.
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 4:00 PM.
The docket initially contained the preliminary risk assessment and related documents as of
January 15,1999. On March 15, the first public comment period closed. EPA then considered
comments, revised the risk assessment, and placed the revised risk assessment in the docket on August
18,1999. All documents, in hard copy form, may be viewed in the OPP docket room or viewed or
downloaded via the Internet (http://www.epa.gov/oppsrrdl/op/).
33
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34
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VII. APPENDICES
35
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36
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Appendix A: Citations Supporting the FQPA Tolerance Reassessment and Interim
Occupational Risk Management Decision (Bibliography)
GUIDE TO APPENDIX A
CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated elsewhere in the
Reregistration Eligibility Document. Primary sources for studies in this bibliography have been
the body of data submitted to EPA and its predecessor agencies in support of past regulatory
decisions. Selections from other sources including the published literature, in those instances
where they have been considered, are included.
UNITS OF ENTRY. The unit of entry in this bibliography is called a "study." In the case of
published materials, this corresponds closely to an article. In the case of unpublished materials
submitted to the Agency, the Agency has sought to identify documents at a level parallel to the
published article from within the typically larger volumes in which they were submitted. The
resulting "studies" generally have a distinct title (or at least a single subject), can stand alone for
purposes of review and can be described with a conventional bibliographic citation. The
Agency has also attempted to unite basic documents and commentaries upon them, treating
them as a single study.
IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted numerically by
Master Record Identifier, or "MRID" number. This number is unique to the citation, and should
be used whenever a specific reference is required. It is not related to the six-digit "Accession
Number" which has been used to identify volumes of submitted studies (see paragraph 4(d)(4)
below for further explanation). In a few cases, entries added to the bibliography late in the
review may be preceded by a nine character temporary identifier. These entries are listed after
all MRID entries. This temporary identifying number is also to be used whenever specific
reference is needed.
FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry consists
of a citation containing standard elements followed, in the case of material submitted to EPA, by
a description of the earliest known submission. Bibliographic conventions used reflect the
standard of the American National Standards Institute (ANSI), expanded to provide for certain
special needs.
a. Author. Whenever the author could confidently be identified, the Agency has chosen to
show a personal author. When no individual was identified, the Agency has shown an
identifiable laboratory or testing facility as the author. When no author or laboratory
could be identified, the Agency has shown the first submitter as the author.
37
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b.
c.
Document date. The date of the study is taken directly from the document. When the
date is followed by a question mark, the bibliographer has deduced the date from the
evidence contained in the document. When the date appears as (1999), the Agency
was unable to determine or estimate the date of the document
Title. In some cases, it has been necessary for the Agency bibliographers to create or
enhance a document title. Any such editorial insertions are contained between square
brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the trailing
parentheses include (in addition to any self-explanatory text) the following elements
describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears
immediately following the word "received."
(2) Administrative number. The next element immediately following the word
"under" is the registration number, experimental use permit number, petition
number, or other administrative number associated with the earliest known
submission.
(3) Submitter. The third element is the submitter. When authorship is defaulted to
the submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the trailing
parentheses identifies the EPA accession number of the volume in which the
original submission of the study appears. The six-digit accession number
follows the symbol "CDL," which stands for "Company Data Library." This
accession number is in turn followed by an alphabetic suffix which shows the
relative position of the study within the volume.
38
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BIBLIOGRAPHY
MRID
CITATION
42408000 Miles, Inc. (1992). Submission of product chemistry data on a metabolite of MAT
7484 (phostebupirim).
42408001 Sheets, L.; Phillips, S. (1992). Acute Oral Toxicity Study with
2-(l J-Dimethyl-2-Hydroxe%l)-5-Hydroxypyrimidine (a Metabolite of MAT 7484) in
Rats: Lab Project Number: 92-012-MV. Unpublished study prepared by Miles Inc.
18 p.
42457800 Miles, Inc. (1992). Submission of toxicity data in support of FDFRA 6(a)(2)
requirements for MAT 7484 Technical.
42457801 Thornton, J. (1992). Letter Sent to Office of Pesticide Programs dated August 26,
1992 providing an addendum in German to a rabbit teratology study for MAT 7484.
Prepared by Miles, Inc. 54 p.
42521100 Miles, Inc. (1992). Submission of leaching data for Aztec 2.1 Granular to support the
registration of MAT Technical and Aztec 2.1.
42521101 Lin, I; Toll, P. (1991). Field Measurement of Phostebupirim and Cyfluthrin Runoff
from a Corn Field in Jackson County, Illinois Treated with Aztec 2.1 G: Lab Project
Number: M4222402: 101309. Unpublished study prepared by Mobay Corp. 86 p.
42649900 Miles (1993). Submission of environmental data in support of the registration for MAT
7484 Technical and MAT 7484 2.1 Granular.
42649901 Lin,J. (1992). Supplement—Report Corrections: Field Measurement of
Phostebupirim and Cyfluthrin Runoff From a Corn Field in Jackson County, Illinois
Treated with Aztec 2.1 G: Lab Project Number: 101309-1: M4222402. Unpublished
study prepared by Miles Inc. 6 p.
42752600 Miles Inc. (1993) Submission of toxicity data in support of the EUP for AZTEC 2.1%
Granular.
42754000 Miles (1993). Submission of residue analytical data in support of the petition and EUP
for MAT 7484.
39
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BIBLIOGRAPHY
MRID
CITATION
42754001 Gronberg, R.; Pfankuche, L. (1990). An Analytical Residue Method for the
Determination of MAT 7484 and MAT 7484 Oxygen Analog in Corn: Lab Project
Number: M4121601: 100202. Unpublished study prepared by Mobay Corp. 179 p.
42905300 Miles, Inc. (1993). Submission of Chronic Toxicity Data in Support of FIFRA 6(a)(2)
Requirements for MAT 7484 Technical. •
42905301 Gagliano, G. (1993). Chronic Toxicity of (Carbon 14)-MAT 7484 to the Waterflea
(Daphnia magna) Under Static Renewal Conditions: Lab Project Number: 106217:
M4840702. Unpublished study prepared by Miles, Inc. 45 p.
42912600 Miles Inc. (1993). Submission of toxiciry data in support of FIFRA 6(a)(2)
requirements for Aztec 2.1% G.
42959000 Miles Inc. (1993). Submission of Product Chemistry Data in Response to EPA
Questions in Regard to Tolerance Petition for Bay MAT 7482, Aztec 2.1% G.
42959001 Fontaine, L. (1993). Supplement to MRID: Product Chemistry (Manufacturing
Process) of BAY MAT 7484 Technical: Lab Project Number: BR 1841: ANR-00793.
Unpublished study prepared by Miles Inc. 10 p.
42959002 Fontaine, L. (1993). Supplement to MRID: Product Chemistry (Physical and Chemical
Characteristics) of BAY MAT 7484 Technical: Lab Project Number BR 1842:
106262. Unpublished study prepared by Miles Inc. 14 p.
42981900 Miles, Inc. (1993). Submission of Toxicology Data on Tebupirimphos in Support of
FIFRA 6(a)(2).
42981901 Bartmann, K. (1993). Study of the Embryotoxic Effect (of Tebupirimphos) on Rabbits
After Oral Administration—Addenda B, C & D: Lab Project Number:
T4024648/T2030621: MAT 7484: 99812-1. Unpublished study prepared by Bayer
AG Fachbereich Toxikologie. 63 p.
43048200 Miles Agricultural Division (1993). Submission of toxicology and risk to endangered
species assessment data in support of registration for MAT 7484 Technical and
AZTEC 2.1%G and of tolerance petition.
40
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BIBLIOGRAPHY
MRID
CITATION
43092700 Miles Inc. (1994). Submission of Residue Chemistry Data for Phostebupirim in
Support of Registration for MAT Technical and AZTEC 2.1%G and of Tolerance
Petition.
43092701 Yen, P.; Wendt, S. (1994). Leaching of Aged Residues of (carbon
14)-Phostebupirim: Lab Project Number: M4092101: 105173. Unpublished study
prepared by Miles Inc., Environmental Research Dept. and Research & Development
Dept. 45 p.
43092702 Dehart, B.; Mattem, G. (1994). Field Dissipation of phostebupirim (sic) (MAT 7484)
on Illinois Soil: Lab Project Number: M4022104: 91-4811: 106240. Unpublished
study prepared by Agri-Growth Research, Inc.; Miles Inc., Research & Development
Dept. and Environmental Fate Analytical Dept. 105 p.
43092703 Valadez, S.; Dehart, B. (1994). Terrestrial Field Dissipation of Phostebupirim (MAT
7484) on Minnesota Soil: Lab Project Number: M4022103: 91-1820: 106241.
Unpublished study prepared by Agri-Growth Research, Inc.; Miles Inc., Agriculture
Division and Miles Environmental Fate Analytical. 93 p.
43188300 Miles Inc. (1994). Submission of Product Chemistry Data for BAY MAT 7484
Technical in Support of Petition and Registration.
43188301 Fontaine, L. (1994). Product Chemistry of BAY MAT 7484 Technical: Lab Project
Number: BR 1870. Unpublished study prepared by Miles Inc. 68 p.
43456500 Miles, Inc. (1994). Submission of Pesticide Use Data in Support of Registration of and
Petitions for AZTEC 2.1% Granular and MAT Technical.
43456501 Standart, V.; Fontaine, L.; Fischer, D.; et al. (1994). Potential Benefits Resulting From
the Registered Use of Aztec (Tebupirimphos plus Cyfluthrin) on Com: Lab Project
Number: 106522. Unpublished study prepared by Miles, Inc. 57 p.
43473000 Miles, Inc. (1994). Submission of Toxicity Data in Support of FTFRA 6(a)(2),
Registration, and Petitions for MAT 7484 Technical.
41
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BIBLIOGRAPHY
MRID
CITATION
43473001 Sheets, L.; Hamilton, B. (1994) An Acute Oral Neurotoxicity Screening Study with
Technical Grade Phostebupirim (MAT 7484) in Fischer 344 Rats: Lab Project
Number: 106804: 93-412-UV. Unpublished study prepared by Miles, Inc. 404 p.
43582200 Miles, Inc. (1995). Submission of Product Use and Efficacy Data in Support of an
Experimental Use Permit for AZTEC 2.1% G.
43582201 Kroll, T.; Wollam, J. (1995). Aztec 2.1G: 1994 Experimental Use Program: Lab
Project Number: 106690. Unpublished study prepared by Miles, Inc. 66 p.
43597000 Miles, Inc. (1995). Submission of Environmental Fate Data in Support of Application
for Registration of MAT 7484 Technical and AZTEC 2.1% Granular and Petition for
Tolerances.
43597001 Dehart, B.; Lam, C.; Clay, V. (1995). Recalculation of the Field Dissipation Half-life
of Phostebupirim (MAT 7484) in Illinois Soil: Supplement: Lab Project Number:
106240-3: M4022103:106240. Unpublished study prepared by Miles, Inc. 21 p.
43597002 Dehart, B.; Lam, C.; Clay, V. (1995). Recalculation of the Field Dissipation Half-life
of Phostebupirim (MAT 7484) in Minnesota Soil: Supplement: Lab Project Number:
106241-3: M4022103:106241. Unpublished study prepared by Miles, Inc. 21 p.
43656300 Bayer Corp. (1995) Submission of Toxicology Data in Support of Tolerance Petitions
for and tfie Registrations of MAT 7484 Technical and AZTEC 2.1% Granular.
43656301 Sheets, L. (1994). A Motor Activity Historical Control and Method Validation Study
Using Triadimefon and Chlorpromazine in Fischer 344 Rats: Lab Project Number:
93-992-WA: 106815. Unpublished study prepared by Miles, Inc. 53 p.
43656302 Sheets, L. (1995). A Subchronic Dietary Neurotoxicity Screening Study with
Technical Grade MAT 7484 (Phostebupirim) in Fischer 344 Rats: Lab Project
Number: 93-472-VM: 106866. Unpublished study prepared by Miles, Inc. 470 p.
44193600 Bayer Corp. (1996). Submission of Toxicity Data in Support of the FIFRA 6(a)(2)
Requirement for Mat 7484 Technical.
42
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BIBLIOGRAPHY
MRID
CITATION
44299800 Bayer Corp. (1997). Submission of Product Chemistry and Environmental Fate Data
in Support of the Registration of Tebupirimphos (MAT 7484 Technical) Insecticide.
44299801 Fontaine, L. (1997). Product Chemistry of MAT 7484 Technical Insecticide: (Product
Identity and Composition): Lab Project Number: BR 1925: ANR-00397:
ANR-00497. Unpublished study prepared by Bayer Corp. 113 p.
44299802 Fontaine, L. (1997). Product Chemistry of MAT 7484 Technical Insecticide: (Analysis
and Certification of Ingredient Limits): Lab Project Number: BR 1926: 107564:
107565. Unpublished study prepared by Bayer Corp. 327 p.
44299803 Cink, J.; Davis, I; Lin, H. (1997). Aerobic Soil Metabolism of (Pyrirnidinyl-2-(carbon
14))Tebupirimphos in Three Soils and at Three Concentrations: (Final Report): Lab
Project Number:107345: M4042102. Unpublished study prepared by Bayer Corp.
141 p.
44409800 Bayer Corp. (1997). Submission of Product Chemistry and Toxicity Data in Support
of the Application for Registration of Aztec 4.67% Granular Insecticide.
44409801 Fontaine, L. (1997). Product Chemistry of Aztec 4.67% Granular Insecticide: Lab
Project Number: TMC-45.11: 107568: 107289. Unpublished study prepared by
Bayer Corp. 74 p. {OPPTS 830.6302, 830.6303, 830.7000, 830.7300, 830.1800,
830.1750, 830.1670, 830.1600, 830.1550, 830.1620, 830.1650}
44409802 Warren, D.; Halliburton, A. (1997). Acute Oral Toxicity Study with Aztec 4.67 G in
Rats: Lab Project Number: 96-012-JW: 107484: 8098. Unpublished study prepared
by Bayer Corp. 29 p.
44409803 Warren, D.; Gastner, M. (1997). Acute Dermal Toxicity Study with Aztec 4.67 G in
Rats: Lab Project Number: 96-022-JR: 107475: 8075. Unpublished study prepared by
Bayer Corp. 29 p.
44409804 Warren, D.; Halliburton, A. (1997). Acute Four-Hour Inhalation Toxicity Study with
Aztec 4.67 G in Rats: Lab Project Number: 96-042-JT: 107482: 8081. Unpublished
study prepared by Bayer Corp. 36 p.
43
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BIBLIOGRAPHY
MRID
CITATION
44409805
44409806
44409807
44815300
44815305
44870601
44980000
44980001
44980002
44980003
Ivett, J. (1997). Primary Eye Irritation Study in Rabbits with Aztec 4.67G: Amended
Final Report: Lab Project Number: 17848-0-820:8094: 107608. Unpublished study
prepared by Corning Hazleton, Inc. 26 p.
Wakefield, A. (1997). Acute Dermal Irritation/Corrosivity Study in Rabbits with Aztec
4.67G: Second Amended Final Report: Lab Project Number: 17848-0-802: 8171:
107752. Unpublished study prepared by Corning Hazleton, Inc. 24 p.
Warren, D.; Gastner, M. (1996). Dermal Sensitization Study with Aztec 4.67 G in
Guinea Pigs: Lab Project Number: 96-324-IL: 107454:8020. Unpublished study
prepared by Bayer Corp. 27 p.
Bayer Corporation (1999). Submission of Toxicity, and Residue Chemistry Data in
Support of the Registration of Aztec 2.1 Granular Insecticide.
Koch, D. (1998). AZTEC 2.1G-Magnitude of the Residue in Field Corn: Lab
Project Number: AZ19CO02: 107804:43737. Unpublished study prepared by ABC
Laboratories, Inc. and Bayer Corporation. 762 p. {OPPTS 860.1500}
PolakofF, B.; Daniel, A.; Osborn, D. et al. (1999). Interim Report: Organophosphates
Market Basket Survey: Lab Project Number: OPMBS-01: 98-02:. Unpublished study
prepared by Novigen Sciences, Inc. 333 p.
Bayer Corporation (1999). Submission of Product Chemistry and Toxicity Data in
Support of the Registration of Aztec 2.1% G.
Fontaine, L. (1999). Product Chemistry of AZTEC 2.1 G: Lab Project Number: TM
C-45.11-07: BR 2009: 107293. Unpublished study prepared by Bayer Corporation
96 p.
Glaza, S. (1999). Primary Eye Irritation Study in Rabbits with AZTEC 2.1 G: Final
Report: Lab Project Number: 108978: 20001-0-820: 98-C335-UU. Unpublished
study prepared by Covance Laboratories, Inc. 20 p.
Glaza, S. (1999). Primary Dermal Irritation Study in Rabbits with AZTEC 2.1 G: Final
Report: Lab Project Number: 108980: 20001-0-830: 98-C325-UV. Unpublished
study prepared by Covance Laboratories, Inc. 20 p.
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BIBLIOGRAPHY
MRID
CITATION
44980004 Glaza, S. (1999). Dermal Sensitization Study in Guinea Pigs-Closed Patch Technique
with AZTEC 2.1 G: Final Report: Lab Project Number: 108989: 98-C324-US:
81001067. Unpublished study prepared by Covance Laboratories, Inc. 60 p.
{OPPTS 870.2600}
44980005 Pauluhn, J. (1999). Aztec 2.1 G: Study on Acute Inhalation Toxicity in Rats: Lab
Project Number: 109259: 28881: T0068060. Unpublished study prepared by Bayer
Ag. 140 p. {OPPTS 870.1300}
44980006 Sturdivant, W.; Halliburton, A. (1999). Acute Oral Toxicity Study with AZTEC 2.1 G
in Rats: Lab Project Number: 108962: 99-012-WR: 8850. Unpublished study
prepared by Bayer Corporation. 39 p. {OPPTS 870.1100}
44980007 Sturdivant, W.; Avila, V. (1999). Acute Dermal Toxicity Study with AZTEC 2.1 G in
Rats: Lab Project Number: 108959: 99-022-WK: 8848. Unpublished study prepared
by Bayer Corporation. 34 p. {OPPTS 870.1200}
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Appendix B: EPA's Batching of Phostebupirim Products for Meeting Acute Toxicity Data
Requirements for Reregistration
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregistration of products containing Phostebupirim as the primary
active ingredient, the Agency has batched products which can be considered similar for purposes of
acute toxicity. Factors considered in the sorting process include each product's active and inert
ingredients (identity, percent composition and biological activity), type of formulation (e.g., emulsifiable
concentrate, aerosol, wettable powder, granular, etc.), and labeling (e.g., signal word, use classification,
precautionary labeling, etc.). Note the Agency is not describing batched products as "substantially
similar" since some products with in a batch may not be considered chemically similar or have identical
use patterns.
Using available information, batching has been accomplished by the process described in the
preceding paragraph. Notwithstanding the batching process, the Agency reserves the right to require,
at any time, acute toxicity data for an individual product should need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite a
single battery of six acute toxicological studies to represent all the products within that batch. It is the
registrants' option to participate in the process with all other registrants, only some of the other
registrants, or only their own products within in a batch, or to generate all the required acute
toxicological studies for each of their own products. If the registrant chooses to generate the data for a
batch, he/she must use one of the products within the batch as the test material. If the registrant
chooses to rely upon previously submitted acute toxicity data, he/she may do so provided mat the data
base is complete and valid by to-days standards (see acceptance criteria attached), the formulation
tested is considered by EPA to be similar for acute toxicity, and the formulation has not been
significantly altered since submission and acceptance of the acute toxicity data. Regardless of whether
new data is generated or existing data is referenced, the registrants must clearly identify the test material
by EPA Registration Number. If more than one confidential statement of formula (CSF) exists for a
product, the registrant must indicate the formulation actually tested by identifying the corresponding
CSF.
In deciding how to meet the product specific data requirements, registrants must follow the
directions given in the Data Call-In Notice and its attachments appended to the RED. The DCI Notice
contains two response forms which are to be completed and submitted to the Agency within 90 days of
receipt. The first form, "Data Call-in Response," asks whether the registrant will meet the data
requirements for each product. The second form, "Requirements Status and Registrant's Response,"
lists the product specific data required for each product, including the standard six acute toxicity tests.
A registrant who wishes to participate in a batch must decide whether he/she will provide the data or
depend on someone else to do so. If the registrant supplies the data to support a batch of products,
he/she must select the one of the following options: Developing data (Option 1), Submitting an existing
Study (Option 4), Upgrading an existing Study (Option 5), or Citing an Existing Study (Option 6). If a
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registrant depends on another's data, he/she must choose among: Cost sharing (Option 2), Offers to
Cost Share (Option 3) or Citing an Existing Study (Option 6). If a registrant does not want to
participate in a batch, the choices are Options 1,4, 5 or 6. However, a registrant should know that
choosing not to participate in a batch does not preclude other registrants in the batch from citing his/her
studies and offering to cost share (Option 3) those studies.
Four products were found which contain Phostebupirim as the active ingredient. These
products have been placed into one batch and a "No Batch " category in accordance with the active
and inert ingredients and type of formulation.
Batch 1
EPA Reg. No.
3125-412
3125-539
Percent active ingredient
2.0
2.0
Formulation Type
Solid
Solid
No Batch
EPA Reg. No.
3125-411
3125-513
Percent active ingredient
93.0
4.45
Formulation Type
Liquid
Solid
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Appendix C: List of Available Related Documents
These documents are available from the Public Docket Office or at the following web site:
www.epa.gov/pesticides/op/phostebupirim.htm
1. Hazard Assessment of the Organophosphates
2. FQPA Safety Factor Recommendations for the Organophosphates
3. Frequently Asked Questions
4. Federal Register Notice Vol. 65, Number 59, Pages 16197-16199 (Comment period ending
May 26,2000)
5. Federal Register Notice Vol. 64, Number 101, Pages 28469-28471 (Comment period
ending July 26,1999)
6. Health Effects Preliminary Assessment
7. Occupational Exposure and Risk Assessment Regarding the Use of Phostebupirim
8. Dietary Risk Assessment Update
9. HIARC Reevaluation of Acute Dietary RfD
10. Acute and Chronic Dietary Exposure and Risk Analysis
11. Reassessment of Acute and Chronic RfDs
12. Report of the FQPA Safety Factor Committee
13. Tier 1 Screen for Drinking Water Assessment
14. Transmittal Letter to Bayer Corporation Regarding the Preliminary Risk Assessment
15. Phostebupirim Summary
16. Overview of Phostebupirim Revised Risk Assessments
17. Quantitative Usage Analysis
18. HED's Response to Comments on the Preliminary Risk Assessment
19. Letter to Bayer Regarding the Revised Risk Assessment
20. Registrant's Confidential Business Certification Statement
21. Bayer's Initial Response to "Risk Assessment Update for FQPA Requirements"
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