62910
United States Prevention, Pesticides EPA 738-R-06-013
Environmental Protection and Toxic Substances June 2006
Agency (7508C)
Interim Reregistration
Eligibility Decision for
Dichlorvos (DDVP)
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Interim Reregistration Eligibility Decision (IRED) Document for
Dichlorvos (DDVP)
List A
Case Number 0302
Approved by: Date:
Debra Edwards, Ph. D.
Director
Special Review and Reregistration Division
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3:
33
\
UJ
C3
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON D.C., 20460
OFFICE OF
PREVENTION, PESTICIDES AND TOXIC
SUBSTANCES
MEMORANDUM
DATE: July 31,2006
SUBJECT: Finalization of Interim Reregi strati on Eligibility Decisions (IREDs) and Interim
Tolerance Reassessment and Risk Management Decisions (TREDs) for the
Organophosphate Pesticides, and Completion of the Tolerance Reassessment and
Reregi strati on Eligibility Process for the Organophosphate Pesticides
FROM: Debra Edwards, Director
Special Review and Reregi strati on Division
Office of Pesticide Programs
TO: Jim Jones, Director
Office of Pesticide Programs
As you know, EPA has completed its assessment of the cumulative risks from the
Organophosphate (OP) class of pesticides as required by the Food Quality Protection Act of
1996. In addition, the individual OPs have also been subject to review through the individual-
chemical review process. The Agency's review of individual OPs has resulted in the issuance of
Interim Reregi strati on Eligibility Decisions (IREDs) for 22 OPs, interim Tolerance
Reassessment and Risk Management Decisions (TREDs) for 8 OPs, and a Reregi strati on
Eligibility Decision (RED) for one OP, malathion.l These 31 OPs are listed in Appendix A.
EPA has concluded, after completing its assessment of the cumulative risks associated
with exposures to all of the OPs, that:
(1) the pesticides covered by the IREDs that were pending the results of the OP
cumulative assessment (listed in Attachment A) are indeed eligible for reregistration; and
Malathion is included in the OP cumulative assessment. However, the Agency has issued a RED for malathion,
rather than an IRED, because the decision was signed on the same day as the completion of the OP cumulative
assessment.
Page 1 of 3
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(2) the pesticide tolerances covered by the IREDs and TREDs that were pending the
results of the OP cumulative assessment (listed in Attachment A) meet the safety standard under
Section 408(b)(2) of the FFDCA.
Thus, with regard to the OPs, EPA has fulfilled its obligations as to FFDCA tolerance
reassessment and FIFRA reregi strati on, other than product-specific reregi strati on.
The Special Review and Reregi strati on Division will be issuing data call-in notices for
confirmatory data on two OPs, methidathion and phorate, for the reasons described in detail in
the OP cumulative assessment. The specific studies that will be required are:
- 28-day repeated-dose toxicity study with methidathion oxon; and
- Drinking water monitoring study for phorate, phorate sulfoxide, and phorate sulfone
in both source water (at the intake) and treated water for five community water
systems in Palm Beach County, Florida and two near Lake Okechobee, Florida.
The cumulative risk assessment and supporting documents are available on the Agency's website
at www.epa.gov/pesticides/cumulative and in the docket (EPA-HQ-OPP-2006-0618).
Page 2 of 3
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Attachment A:
Organophosphates included in the OP Cumulative Assessment
Chemical
Acephate
Azinphos-methyl (AZM)
Bensulide
Cadusafos
Chlorethoxyphos
Chlorpyrifos
Coumaphos
DDVP (Dichlorvos)
Diazinon
Dicrotophos
Dimethoate
Disulfoton
Ethoprop
Fenitrothion
Malathion
Methamidophos
Methidathion
Methyl Parathion
Naled
Oxydemeton-methyl
Phorate
Phosalone
Phosmet
Phostebupirim
Pirimiphos-methyl
Profenofos
Propetamphos
Terbufos
Tetrachlorvinphos
Tribufos
Trichlorfon
Decision Document
IRED
IRED
IRED
TRED
TRED
IRED
TRED
IRED
IRED
IRED
IRED
IRED
IRED
TRED
RED
IRED
IRED
IRED
IRED
IRED
IRED
TRED
IRED
TRED
IRED
IRED
IRED
IRED
TRED
IRED
TRED
Status
IRED completed 9/2001
IRED completed 10/2001
IRED completed 9/2000
TRED completed 9/2000
TRED completed 9/2000
IRED completed 9/2001
TRED completed 2/2000
IRED completed 6/2006
IRED completed 7/2002
IRED completed 4/2002
IRED completed 6/2006
IRED completed 3/2002
IRED completed 9/2001
IRED addendum completed 2/2006
TRED completed 10/2000
RED completed 8/2006
IRED completed 4/2002
IRED completed 4/2002
IRED completed 5/2003
IRED completed 1/2002
IRED completed 8/2002
IRED completed 3/2001
TRED completed 1/2001
IRED completed 10/2001
TRED completed 12/2000
IRED completed 6/2001
IRED completed 9/2000
IRED completed 12/2000
IRED completed 9/2001
TRED completed 12/2002
IRED completed 12/2000
TRED completed 9/2001
Page 3 of 3
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Table of Contents
Abstract 8
I. Introduction 8
II. Chemical Overview 11
A. Chemical Identity 11
B. Use and Usage Profile 12
III. Links to the DDVP Risk Assessments 13
IV. Interim Risk Management and Reregistration Decision 13
A. Determination of Interim Reregistration Eligibility 13
B. Public Comments and Responses 14
C. Regulatory Position 14
1. Food Quality Protection Act Findings 14
a. "Risk Cup" Determination 14
b. Determination of Safety to U.S. Population (Including Infants and Children) 15
c. Endocrine Disrupter Effects 15
d. Cumulative Risks 16
2. Tolerance Summary 17
D. Regulatory Rationale 20
1. Human Health Risk Management 20
a. Aggregate Risk Mitigation (food, drinking water, and residential exposure) 20
b. Occupational Risk Mitigation 21
2. Ecological Risk Management and Mitigation 21
3. Other Labeling Requirements 22
4. Threatened and Endangered Species Considerations 22
5. General Risk Mitigation 22
V. What Registrants Need to Do 23
A. Manufacturing-Use Products 23
1. Additional Generic Data Requirements 23
2. Labeling for Manufacturing-Use Products 24
B. End-Use Products 24
1. Additional Product-Specific Data Requirements 24
2. Labeling for End-Use Products 24
APPENDIX A: Dichlorvos Use Patterns Eligible For Reregistration 32
APPENDIX B. Table of Generic Data Requirements and Studies Used to Make the
Reregistration Decision for DDVP 46
APPENDIX C: Bibliography 51
APPENDIX D: Technical Support Documents 67
APPENDIX E: Generic Data Call-In 71
APPENDIX E: Product Specific Data Call-In 72
APPENDIX G: EPA's Batching of DDVP Products for Meeting Acute Toxicity Data
Requirements for Reregistration 73
Appendix H: List of Registrants Sent Data Call-ins 80
Appendix I: List of Available Related Documents and Electronically Available Forms .... 81
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APPENDIX J: Dichlorvos (DDVP) HED Chapter of the Reregistration Eligibility Decision
Document (RED) 85
APPENDIX K: Revised EFED risk assessment for the Dichlorvos Reregistration Eligibility
Document 237
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DDVP Interim Reregistration Eligibility Decision Team
EPA Office of Pesticide Programs
Special Review and Reregistration Division
Dayton Eckerson
Eric Olson
Health Effects Division
William Dykstra
Susan Hummel
Ray Kent
David Jaquith
David Hrdy
Environmental Fate and Effects Division
Diana Eignor
Ibrahim Abdel-Saheb
Biological and Economic Analysis Division
Donald Atwood
TJ Wyatt
John Faulkner
Registration Division
George LaRocca
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Glossary of Terms and Abbreviations
AGDCI
ai
aPAD
BCF
CFR
cPAD
CSF
CSFII
DCI
DEEM
DFR
DNT
EC
EDWC
EEC
EPA
EUP
FDA
FIFRA
FFDCA
FQPA
GLN
IR
LCso
LD
50
LOC
LOAEL
MATC
mg/kg/day
mg/L
MOE
MRID
MUP
NOAEL
OPP
Agricultural Data Call-In
Active Ingredient
Acute Population Adjusted Dose
Bioconcentration Factor
Code of Federal Regulations
Chronic Population Adjusted Dose
Confidential Statement of Formulation
USDA Continuing Surveys for Food Intake by Individuals
Data Call-In
Dietary Exposure Evaluation Model
Dislodgeable Foliar Residue
Developmental Neurotoxicity
Emulsifiable Concentrate Formulation
Estimated Drinking Water Concentration
Estimated Environmental Concentration
Environmental Protection Agency
End-Use Product
Food and Drug Administration
Federal Insecticide, Fungicide, and Rodenticide Act
Federal Food, Drug, and Cosmetic Act
Food Quality Protection Act
Guideline Number
Index Reservoir
Median Lethal Concentration. A statistically derived concentration of a
substance that can be expected to cause death in 50% of test animals. It is
usually expressed as the weight of a substance per weight or volume of
water, air, or feed, e.g., mg/1, mg/kg, or ppm.
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.
Level of Concern
Lowest Observed Adverse Effect Level
Maximum Acceptable Toxicant Concentration
Micrograms Per Gram
Micrograms Per Liter
Milligram Per Kilogram Per Day
Milligram Per Liter
Margin of Exposure
Master Record Identification Number. EPA's system for recording and
tracking studies submitted.
Manufacturing-Use Product
No Observed Adverse Effect Level
EPA Office of Pesticide Programs
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OPPTS
PAD
PCA
PDF
PHED
PHI
ppb
PPE
ppm
PRZM/EXAMS
Q*
RAC
RED
REI
RfD
RQ
SCI-GROW
SAP
SF
SLC
TGAI
USDA
USGS
UF
UV
WPS
EPA Office of Prevention, Pesticides, and Toxic Substances
Population Adjusted Dose
Percent Crop Area
USDA Pesticide Data Program
Pesticide Handler's Exposure Data
Pre-harvest Interval
Parts Per Billion
Personal Protective Equipment
Parts Per Million
Tier II Surface Water Computer Model
The Carcinogenic Potential of a Compound, Quantified by the EPA's
Cancer Risk Model
Raw Agriculture Commodity
Reregistration Eligibility Decision
Restricted Entry Interval
Reference Dose
Risk Quotient
Tier I Ground Water Computer Model
Science Advisory Panel
Safety Factor
Single Layer Clothing
Technical Grade Active Ingredient
United States Department of Agriculture
United States Geological Survey
Uncertainty Factor
Ultraviolet
Worker Protection Standard
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Abstract
This document presents EPA's interim reregistration and tolerance reassessment
decisions for the pesticide dichlorvos (DDVP). Final risk management decisions for DDVP will
be issued once the cumulative risks for all of the organophosphate pesticides have been
addressed. EPA may need to pursue further risk management measures for DDVP once the
cumulative risks are considered.
Pending completion of the organophosphate cumulative assessment, EPA has determined
that DDVP will be eligible for reregistration and that tolerances will be reassessed once recent
use deletions and label amendments requested by the registrant become effective. These use
deletions and label amendments are summarized later in this document. EPA has assessed the
human health and ecological risks associated with the remaining uses of DDVP and has
determined that risks do not exceed levels of concern. Therefore, no additional risk mitigation
measures are necessary at this time. Additional data are required to confirm these decisions.
EPA's screening-level ecological risk assessment indicated potential risks of concern
resulting from DDVP use to control flying insects and granular bait uses. However, because the
screening-level assessment methods included conservative assumptions, EPA believes that actual
risks associated with these uses will not exceed levels of concern and no further mitigation is
needed.
Based on EPA's screening-level assessment, potential risks to federally-listed threatened
and endangered species ("listed species") cannot be precluded at this time. In the future EPA
will conduct a species-specific risk analysis. A determination that there is a likelihood of effects
to any listed species may result in further limitations on DDVP use, additional risk mitigation
measures, and/or consultation with the Fish and Wildlife Service and/or the National Marine
Fisheries Service as appropriate.
The Agency is issuing this Interim Reregistration Eligibility Decision (IRED) document
for DDVP, as announced in a Notice of Availability published in the Federal Register. There
will be a 60-day public comment period for this document to allow stakeholders the opportunity
to review and provide comments on this document.
I. Introduction
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 Act calls for the development and submission of data to support the reregistration
of an active ingredient, as well as a review of all data submitted to EPA. 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 a pesticide, to determine the need for additional data on health and environmental effects, and
to determine whether or not the pesticide meets the "no unreasonable adverse effects" criteria of
FIFRA.
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On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into
law. This Act amended FIFRA and the Federal Food Drug and Cosmetic Act (FFDCA) to
require reassessment of all existing tolerances for pesticides in food by August 3, 2006. EPA
decided that, for those chemicals that have tolerances and are undergoing reregistration,
tolerance reassessment would be accomplished through the reregistration process. Under FQPA,
in reassessing these tolerances, the Agency must consider, among other things, aggregate risks
from non-occupational sources of pesticide exposure, whether there is increased susceptibility
among infants and children, and the cumulative effects of pesticides that have a common
mechanism of toxicity. When the Agency determines that risks are not of concern and concludes
that there is a reasonable certainty of no harm to any population subgroup, the tolerances are
considered reassessed.
FQPA requires EPA to consider available information concerning the cumulative effects
of a particular pesticide's residues and "other substances that have a common mechanism of
toxicity" when considering whether to establish, modify, or revoke a tolerance. Potential
cumulative effects of chemicals with a common mechanism of toxicity are considered because
low-level exposure to multiple chemicals causing a common toxic effect by a common
mechanism could lead to the same adverse health effect as would a higher level of exposure to
any one of these individual chemicals. For information regarding EPA's efforts to determine
which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of
such chemicals, see the policy statements released by EPA's Office of Pesticide Programs
concerning common mechanism determinations and procedures for cumulating effects from
substances found to have a common mechanism on EPA's website at
http://epa.gov/pesticides/cumulative/.
DDVP is a member of the organophosphate class of pesticides. The Agency has
classified the organophosphate pesticides and their common degradates as having a common
mechanism of toxicity. The Agency is completing its cumulative risk assessment for this class,
and the cumulative risks of these chemicals are being considered in the Agency's final tolerance
assessment decision for DDVP and the other organophosphates. The Agency may need to
pursue further risk mitigation for DDVP to address any risks identified in the cumulative
assessment for the organophosphate pesticides.
This document presents EPA's revised human health and ecological risk assessments (see
Appendices J and K), its progress toward tolerance reassessment, and the interim reregistration
eligibility decision for DDVP. The document consists of six sections. Section I contains the
regulatory framework for reregistration/tolerance reassessment. Section II provides the chemical
identity and a profile of the use and usage of the chemical. Section III references the revised
human health and ecological risk assessments attached as Appendices to this document. Section
IV presents the Agency's risk management, reregistration eligibility, and tolerance reassessment
decision. Section V summarizes any data requirements necessary to confirm the reregistration
eligibility decision as well as label changes necessary to implement the risk mitigation measures
outlined in the IRED. Section VI provides information on how to access related documents.
Finally, the Appendices list related information and supporting documents and present the
human health and ecological risk assessments. The preliminary and revised risk assessments for
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DDVP in their entirety are available in the Public Docket, under docket number OPP-2002-0302,
and in the Federal Docket Management System (FDMS) at http://www.regulations.gov.
Readers should be aware that the current human health risk assessment reflects recent
changes in the DDVP registration voluntarily requested by the registrant. The changes requested
in the registrant's terms and conditions letter, dated May 9, 2006, are summarized below. The
Agency is in the process of approving the changes as requested in the letter. The full letter is
available in the docket.
Voluntary Deletion of the Following:
Product Types
1. 100 gram (g) pest strip
2. 80 g pest strip (contingent on EPA granting the replacement registration for the 80g pest strip)
3. 65 g pest strip (contingent on EPA granting the replacement registration for the 65g pest strip)
4. 21 g pest strip (contingent on EPA granting the registration for 16 g pest strip)
5. Total release fogger
The registrant will split its end use registrations so that there will be one end use label for
the large pest strips (65 g & 80 g) and another for the small pest strips (10.5 g, 5.25 g, and a new
16 g).
Use Patterns
6. Lawn, Turf, and Ornamentals
7. Crack and Crevice
Application Method
8. Mushroom house hand held fogger
9. Greenhouse hand held fogger
10. Warehouse hand held fogger
Label Amendments
Occupational Exposure — Applicators
1. Mushroom house Hose End Sprayer — add coveralls to personal protective equipment
requirements.
Occupational — Post Application
2. Mushroom houses - 18 hour re-entry interval (REI)
3. Greenhouse —12 hour REI
Pest Strips
65 and 80 g pest strips
Label language to read:
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"For use in unoccupied areas; not for use in homes except garages, attics, crawl spaces, and
sheds occupied for less than 4 hours per day.
Also for use in boathouses, museum collections, animal buildings, and milk rooms, or enclosed
areas thereof, occupied for less than 4 hours per day.
For use in unoccupied areas such as trash dumpsters, catch basins, bulk raw grain bins, storage
bins, insect traps, enclosed utility boxes, and storage units. Also for use in non-perishable
packaged and bagged and bulk stored processed and raw agricultural commodities (including
soybeans, corn, grains, cocoa beans and peanuts).
Also for use in the following unoccupied structures, provided they are unoccupied for more than
4 months immediately following placement of a pest strip: vacation homes, cabins, mobile
homes, boats, farm houses, and ranch houses."
16 g (new), 10.5 g, 5.25 g pest strips
Label language to read:
"Within homes, use only in closets, wardrobes, and cupboards. Also for use in storage units,
garages, attics, crawl spaces, boathouses, museum collections, garbage cans, trash dumpsters,
animal buildings, milk rooms, catch basins, bulk raw grain, and storage bins."
II. Chemical Overview
A. Chemical Identity
Chemical Structure:
Empirical Formula:
Common Name:
CAS Name:
CAS Registry Number:
OPP Chemical Code:
et
C4 H7 C12 04 P
Dichlorvos (DDVP)
2,2-Dichlorovinyl dimethyl phosphate
62-73-7
084001
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Case Number:
Technical or
Manufacturing-Use
Registrants:
Regulatory History
0302
AMVAC Chemical Corporation
First registered for use in 1948.
EPA initiated special review in 1988 (PD1) for
carcinogenicity, liver effects, and cholinesterase inhibition.
Preliminary determinations (PD2/3) issued in 1995,
proposing cancellation of certain uses, and label
modifications for other uses to mitigate risk
B. Use and Usage Profile
The following is information on the currently registered uses of DDVP. A detailed table
of food and feed uses, or uses which require tolerances or tolerance consideration, is contained in
Appendix A.
Pesticide type/target
pests:
Mode of Action:
Formulations:
Methods of Application:
Use Sites:
Application Rates:
Dichlorvos (2, 2-Dichlorovinyl dimethyl phosphate), also known as
DDVP, is an organophosphate insecticide. Target pests are flies,
gnats, mosquitoes, chiggers, ticks, cockroaches, armyworms, chinch
bugs, clover mites, crickets, cutworms, grasshoppers, and sod
web worms.
Inhibition of cholinesterase.
Granules for bait, liquid, resin impregnated, ready to use sprays and
foggers.
Applied with ready to use aerosol spray cans, spray equipment, wall
mounted foggers, and through slow release from impregnated
materials, such as resin strips and pet collars.
DDVP is registered to control insect pests in agricultural sites,
commercial, institutional and industrial sites; in and around homes;
and on pets. DDVP is also used in greenhouses; mushroom houses;
storage areas for bulk, packaged and bagged raw and processed
agricultural commodities; food manufacturing/processing plants;
animal premises; and non-food areas of food-handling establishments.
It is also registered for direct dermal pour-on treatment of cattle and
poultry. DDVP is not registered for direct use on any field grown
commodities.
The maximum rate is 2.0 gm ai/1000 cu. ft. for liquid formulations in
greenhouses and warehouses; and 0.09 Ib ai/1000 cu. ft. for
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impregnated material.
Annual Usage in the Approximately 54% used for commodities in bulk storage,
U.S.: distribution warehouses and processing plants; 28% for livestock and
poultry; and 15% for Pest Control Operator/structural use.
Related Pesticides: DDVP is closely related to naled and trichlorfon, which are members
of the organophosphate class of pesticides. Naled and trichlorfon both
metabolize or degrade to DDVP in food, water, or the environment.
Tolerances Currently, there are 27 tolerances listed in 40 CFR §108.235 for
DDVP on agricultural (food and feed) crops and animal commodities.
See Table 1 for a complete list of the DDVP tolerances.
III. Links to the DDVP Risk Assessments
Please refer to Appendices J and K for the Human Health and Ecological Risk
Assessments for DDVP, dated June 20, 2005, and June 22, 2006, respectively, for details on the
risks associated with the use of DDVP. These documents are also available in the public docket
EPA-HQ-OPP-2002-0302, located on-line in the Federal Docket Management System (FDMS)
http://www.regulations.gov.
IV. Interim Risk Management and Reregistration Decision
A. Determination of Interim Reregistration Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether or not products containing the active
ingredient are eligible for reregistration. The Agency has previously identified and required the
submission of the generic (technical grade) data to support reregistration of products containing
DDVP as an active ingredient. The Agency has completed its review of these generic data, and
has determined that the data are sufficient to support interim reregistration of products containing
DDVP once the use deletions and label amendments discussed above become effective.
Additional data are required to confirm this determination.
The Agency has completed its assessment of the dietary (both food and drinking water),
residential, occupational, and ecological risks associated with the use of pesticide products
containing the active ingredient DDVP. Based on a review of these data and on public
comments on the Agency's assessments for the active ingredient DDVP, the Agency has
sufficient information on the human health and ecological effects of DDVP to make interim
decisions as part of the tolerance reassessment process under FFDCA and reregistration process
under FIFRA, as amended by FQPA. The Agency has determined that products containing
DDVP will be eligible for reregistration provided that (i) label amendments are made to reflect
the use deletions, use amendments, and other measures identified in the registrant's May 9, 2006
terms and conditions letter, and (ii) any additional measures needed to reduce cumulative risks
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are adopted. Label changes and language are listed in Section V. Appendix A provides a
detailed table of those uses eligible for reregistration. Appendix B identifies generic data the
Agency reviewed as part of its interim determination of reregistration eligibility of DDVP, and
lists the studies the Agency found acceptable and that satisfy the data requirement. Data gaps are
identified as either outstanding generic data requirements that have not been satisfied with
acceptable data or additional data requirements necessary to confirm the decision presented here.
Because the Agency has not yet addressed the potential cumulative risk for all of the
organophosphates, this reregistration eligibility decision does not fully satisfy the requirements
for reassessment of the existing DDVP food residue tolerances as called for by FQPA. When the
Agency has addressed potential organophosphate cumulative risks, DDVP tolerances will be
reassessed. At that time, the Agency will also meet the FQPA requirements and make a final
decision on the reregistration eligibility determination for DDVP. Additionally, once an
endangered species assessment is completed, further changes to these registrations may be
necessary as explained in Section IV.D.4 of this document.
B. Public Comments and Responses
During the public comment period on the revised ecological risk assessment, which
closed on June 30, 2005, the Agency received comments from AMVAC Chemical Corporation,
Beyond Pesticides, Natural Resources Defense Council, and Cereal Food Processors, Inc. These
comments in their entirety are available in the public docket EPA-HQ-OPP-2002-0302, located
on-line in the Federal Docket Management System (FDMS) http://www.regulations.gov. During
the public comment period on the human health assessment, which closed on December 11,
2000, the Agency received comments from the Norwegian Agricultural Inspection Service,
Pesticide Applicators Education Program, Natural Resources Defense Council (NRDC),
AMVAC Chemical Corporation, University of Georgia Entomology Department, North
American Miller's Association, California Pistachio Commission, Fumigation Service & Supply,
Inc., U.S. Department of Agriculture (USDA), and California Department of Pesticide
Regulation. The Agency's responses to substantive comments for both comment periods are
available in memoranda in the public docket. It is important to note that the Agency's responses
to the public comments reflected the Agency's position at the time that the responses were
written. This DDVP IRED supersedes previous Agency responses to public comments.
C. Regulatory Position
1. Food Quality Protection Act Findings
a. "Risk Cup" Determination
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated
with DDVP. This assessment is for this individual organophosphate and does not attempt to
fully reassess these tolerances as required under FQPA. FQPA requires the Agency to evaluate
food tolerances on the basis of cumulative risk from substances sharing a common mechanism of
toxicity, such as a common biochemical interaction of organophosphate pesticides with
cholinesterase which may lead to a myriad of cholinergic effects. The Agency will finalize the
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cumulative risk assessment and risk management decisions for the entire class of
organophosphates shortly.
DDVP is closely related to naled and trichlorfon, which are also members of the
organophosphate class of pesticides. Naled and trichlorfon both metabolize or degrade to DDVP
in food, water, or the environment. Therefore, FQPA requires OPP to estimate aggregate risk
from all sources of DDVP, including DDVP derived from naled and trichlorfon. The current
assessment addressed the risks posed by DDVP resulting from the uses of DDVP, naled, and
trichlorfon.
The Agency has made an interim conclusion that tolerances for DDVP meet the FQPA
safety standards and that the risk from aggregate exposure (from food, drinking water, and
residential sources) is within the DDVP "risk cup." The Agency has determined that the human
health risks from these combined exposures are within acceptable levels. In reaching this
determination, EPA has considered the available information on the special sensitivity of infants
and children.
b. Determination of Safety to U.S. Population (Including Infants and
Children)
The Agency has made an interim decision that the established tolerances for DDVP, with
label amendments and changes as specified in this IRED document, meet the safety standards
under the FQPA amendments to Section 408(b)(2)(D) and 408(b)(2)(c) of the FFDCA, and that
there is a reasonable certainty that no harm will result to the general U.S. population, infants,
children, or any other subgroup, from the use of DDVP. The safety determination considers
factors such as the toxicity, use practices and exposure scenarios, and environmental behavior of
DDVP.
In determining whether or not infants and children are particularly susceptible to toxic
effects from DDVP residues, the Agency considered the completeness of the hazard database for
developmental and reproductive effects, the nature of the effects observed, and other
information. The Agency evaluated the hazard and exposure data to determine if the FQPA10X
safety factor should be retained, reduced, or removed. In doing so, the Agency concluded that
the FQPA Safety Factor for DDVP can be reduced to IX, except for certain scenarios, for which
the FQPA factor is retained at 3X to account for the lack of a NOAEL. The exposure scenarios
that have retained a 3X FQPA Safety Factor due to a lack of a NOAEL are: short-term incidental
oral; short-, intermediate-, and long-term dermal; short- and intermediate-term inhalation of
vapors; and short- and intermediate-term inhalation during application. In the case of DDVP, the
Agency has concluded that the FQPA Safety Factor should be reduced based on the lack of pre-
and/or postnatal susceptibility resulting following exposure to DDVP, the lack of residual
uncertainties for pre- and/or postnatal toxicity, and the fact that the DDVP food, drinking water,
and residential assessments are not expected to underestimate exposure. For more details on the
DDVP FQPA Safety Factor, refer to the Human Health Risk Assessment, dated June 22, 2006
(Appendix J).
c. Endocrine Disrupter Effects
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EPA is required under the FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect produced by a naturally
occurring estrogen, or other endocrine effects as the Administrator may designate." Following
recommendations of its Endocrine Disrupter Screening and Testing Advisory Committee
(EDSTAC), EPA determined that there was a scientific basis for including, as part of the
program, the androgen and thyroid hormone systems, in addition to the estrogen hormone
system. EPA also adopted EDSTAC's recommendation that EPA include evaluations of
potential effects in wildlife. For pesticides, EPA will use FIFRA and, to the extent that effects in
wildlife may help determine whether a substance may have an effect in humans, FFDCA
authority to require the wildlife evaluations. As the science develops and resources allow,
screening for additional hormone systems may be added to the Endocrine Disrupter Screening
Program (EDSP). In the available toxicity studies on DDVP, there was no estrogen, androgen,
and/or thyroid mediated toxicity. When additional appropriate screening and/or testing protocols
being considered under the Agency's EDSP have been developed, DDVP may be subjected to
further screening and/or testing to better characterize effects related to endocrine disruption.
d. Cumulative Risks
FQPA stipulates that when determining the safety of a pesticide chemical EPA shall base
its assessment of the risk posed by the chemical on, among other things, available information
concerning the cumulative effects to human health that may result from dietary, residential, or
other non-occupational exposure to other substances that have a common mechanism of toxicity.
The reason for consideration of other substances is due to the possibility that low-level exposures
to multiple chemical substances that cause a common toxic effect by a common mechanism
could lead to the same adverse health effect as would a higher level of exposure to any of the
other substances individually. A person exposed to a pesticide at a level that is considered safe
may in fact experience harm if that person is also exposed to other substances that cause a
common toxic effect by a mechanism common with that of the subject pesticide, even if the
individual exposure levels to the other substances are also considered safe.
For information regarding EPA's efforts to determine which chemicals have a common
mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy
statements released by the Agency concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a common mechanism. These
may be found on EPA's website at http://www.epa.gov/pesticides/cumulative.
DDVP is a member of the organophosphate (OP) class of pesticides. EPA considers
organophosphates to express toxicity through a common biochemical interaction with
cholinesterase and, consequently the organophosphate pesticide risks are considered as a group.
EPA published the final guidance that it now uses for identifying substances that have a common
mechanism of toxicity (FR 64(24) 5796-5799, February 5, 1999), "Proposed Guidance for
Cumulative Risk Assessment for Chemicals that Have a Common Mechanism of Toxicity." This
document was made available for public comment in the Federal Register (65 FR 40644, June
30, 2000) and the Agency presented this approach to the FIFRA/FQPA Science Advisory Panel
16
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in late September, 2000. The revised methods, based on SAP's review, were used to conduct
preliminary and revised cumulative risk assessments for organophosphate pesticides in 2002 (US
EPA, 2002) and can be found at http://www.epa.gov/scipoly/sap/2002/index.htm. The revised
cumulative risk assessment for OPs, (US EPA, 2002a) can be found on the Agency's web site
http://www.epa.gov/pesticides/cumulative/rra-op/. It assesses the cumulative effects of exposure
to multiple OPs, including DDVP.
Once the aggregate, single chemical assessments are completed for all the individual
organophosphates, the Agency will issue the final cumulative risk assessment for these
compounds. For purposes of this interim decision, EPA has considered risks for only DDVP and
its degradates.
2. Tolerance Summary
A tolerance summary and interim tolerance reassessment decision is presented for
DDVP in Table 1 below. Currently there are 27 tolerances listed in 40 CFR §180.235 for DDVP
on agricultural (food and feed) crops and animal commodities. DDVP residues are currently
expressed in terms of the parent compound only, with the exception of cucumbers, lettuce,
mushrooms, and tomatoes, which are expressed as naled. The registrants are not supporting
tolerances for several crops and animal commodities, including cucumbers, lettuce, radishes, and
tomatoes. These tolerances will be proposed to be revoked. EPA will propose to raise the
tolerances for fat, meat, and meat byproducts of cattle, goats, horses, and sheep were raised to
harmonize with the Codex maximum residue limit (MRL).
The tolerances in 40 CFR §180.235 for nonperishable packaged, bagged or bulk raw food
and for packaged or bagged nonperishable processed foods (formerly in 40 CFR §185.1900) do
not refer to specific commodities.
Table 1. Tolerance Reassessment Summary for DDVP.
Commodity
Current
Tolerance, ppm
Tolerance
Reassessment, ppm
Comment/
[Correct Commodity Definition]
Tolerances Listed Under 40 CFR §180.235(a)(l)*
Cattle, fat
Cattle, meat
Cattle, mbyp
Cucumbers
Eggs
Goats, fat
Goats, meat
Goats, mbyp
Horses, fat
0.02(N)
0.02(N)
0.02(N)
0.5 1
0.05(N)
0.02(N)
0.02(N)
0.02(N)
0.02(N)
0.05
0.05
0.05
Revoke
0.05
0.05
0.05
0.05
0.05
EPA will propose to raise the
tolerance to harmonize with the
Codex maximum residue limit
(MRL).
The registrant is not supporting
use of DDVP on this commodity.
Tolerance has been revoked.
EPA will propose to raise the
tolerance to harmonize with the
Codex maximum residue limit
(MRL).
EPA will propose to raise the
17
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Commodity
Horses, meat
Horses, mbyp
Lettuce
Milk
Mushrooms
Poultry, fat
Poultry, meat
Poultry, mbyp
Radishes
Raw agricultural commodities,
nonperishable, bulk stored
regardless of fat content (post-
H)
Raw agricultural commodities,
nonperishable, packaged or
bagged, containing 6 percent
fat or less (post-H)
Raw agricultural commodities,
nonperishable, packaged or
bagged, containing more than
6 percent fat (post-H)
Sheep, fat
Sheep, meat
Sheep, mbyp
Tomatoes (pre- and post-H)
Current
Tolerance, ppm
0.02(N)
0.02(N)
1.0 1
0.02(N)
0.5 1
0.05(N)
0.05(N)
0.05(N)
0.5
0.5
0.5
2.0
0.02(N)
0.02(N)
0.02(N)
0.05 1
Tolerance
Reassessment, ppm
0.05
0.05
Revoke
0.05
0.5
0.05
0.05
0.05
Revoke
4.0
4.0
0.05
0.05
0.05
Revoke
Comment/
[Correct Commodity Definition]
Codex maximum residue limit
(MRL).
The registrant is not supporting
use of DD VP on this commodity.
Tolerance has been revoked.
EPA will propose to raise the
tolerance to harmonize with the
Codex maximum residue limit
(MRL).
The tolerance should be revised to
be expressed in terms of DDVP.
The registrant is not supporting
use of DDVP on this commodity.
The required residue data showed
that a higher tolerance is needed.
EPA will propose to raise the
tolerance. [Raw agricultural
commodities, nonperishable, bulk
stored]
The required residue data showed
that a higher tolerance is needed.
EPA will propose to raise the
tolerance. [Raw agricultural
commodities, nonperishable,
packaged and bagged]
EPA will propose to raise the
tolerance to harmonize with the
Codex maximum residue limit
(MRL).
The registrant is not supporting
use of DDVP on this commodity.
Tolerances Listed Under 40 CFR §180.235(a)(2)
Edible swine tissue 2
0.1
Revoke
Residue data have been required
and not submitted.
Tolerances Listed Under 40 CFR §180.235(a)(3)
Packaged or bagged
nonperishable processed food
0.5
4.0
The required residue data showed
that a higher tolerance is needed,
and the tolerance should be moved
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Commodity
Current
Tolerance, ppm
Tolerance
Reassessment, ppm
Comment/
[Correct Commodity Definition]
to§180.235(a)(l). EPA will
propose to raise the tolerance.
[Processedfood, nonperishable,
packaged or bagged]
Tolerances to be Proposed Under 40 CFR §180.235(a)
Soybean, hulls
15.0
Soybean hulls have been added to
the Agency's list of regulated
processed commodities since
DDVP tolerances were set.
Aspirated grain fractions
20.0
Aspirated grain fractions have
been added to the Agency's list of
regulated processed commodities
since DDVP tolerances were set.
The tolerance is required when
residues in the aspirated grain
fractions are greater than the
residues in soybean grain residues.
N Negligible residues
* Concurrently with the revocation of the tolerance for edible swine tissue in §180.235(a)(2) and the moving of the
tolerance for packaged or bagged nonperishable processed food in §180.235(a)(3), §180.235(a)(l) should be
redesignated §180.235(a).
1 Residues expressed as naled. Another registrant has expressed interest in supporting the tolerance on tomato.
However, data have been required and not submitted.
2 Resulting both from its use as an anthelmintic in swine feed and as an insecticide applied directly to swine;
prescribed by 21 CFR 558.205 as a feed additive in swine, with a tolerance of 0.1 ppm for residues of DDVP in
edible swine tissue listed in 21 CFR 556.180.
The Codex Alimentarius Commission has established several maximum residue limits
(MRLs) for residues of DDVP in/on various commodities. The Codex MRLs are expressed in
terms of DDVP per se and are based on residues likely to be found at harvest or slaughter. The
Codex MRL and the U.S. tolerance expressions are compatible. A comparison of the Codex
MRLs and the corresponding reassessed U.S. tolerances is presented in Table 2.
The following conclusions can be made regarding efforts to harmonize U.S. tolerances
with Codex MRLs: (i) compatibility between the U.S. tolerances and Codex MRLs exists for
milks, mushrooms, meat (from mammals other than marine mammals), and poultry meat; and (ii)
incompatibility of the U.S. tolerances and Codex MRLs remains at present for cereal grains
because of differences in good agricultural practices. However, the difference between the U.S.
tolerance and Codex MRL for cereal grains is relatively small and unlikely to result in trade
concerns in international commerce.
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Table 2. Codex MRLs and Applicable U.S. Tolerances for DDVP
Commodity
Cereal grains
Meat (from mammals other
than marine mammals)
Milks
Mushrooms
Poultry meat
Wheat bran, Unprocessed
Wheat flour
Wheat germ
Wheat wholemeal
MRL
(mg/kg)
5
0.05*
0.02 (*)
0.5
0.05
10
1
10
2
Reassessed U.S.
Tolerance, ppm
4.0
0.05
0.02
0.5
0.05
..
..
..
—
Recommendation
Compatibility exists
Compatibility exists
Compatibility exists
Compatibility exists
1 (*) = At or about the limit of detection.
D. Regulatory Rationale
The Agency has determined that products containing DDVP will be eligible for
reregistration provided that the use deletions, use amendments, worker protections, and label
language amendments included in the IRED and in the registrant's May 9, 2006, terms and
conditions letter for the DDVP registration are implemented.
exposure)
1. Human Health Risk Management
a. Aggregate Risk Mitigation (food, drinking water, and residential
As discussed in the revised human health risk assessment (Appendix J), upon
implementation of the use deletions, use amendments, and the labeling amendments reflected in
the DDVP registrant's May 9th, 2006, letter to EPA, all aggregate (food, drinking water, and
residential) risks of concern from use of DDVP will have been addressed; therefore, no further
risk mitigation will be necessary for this interim reregistration eligibility decision.
The preliminary human health risk assessment indicated the possibility of drinking water
and inhalation exposures of concern from the degradation of trichlorfon into DDVP from
trichlorfon turf use. However, since the preliminary risk assessment was written, the registrant
for trichlorfon submitted soil dissipation data which indicated that, under predominant soil pH
conditions, the actual rate at which trichlorfon degrades into DDVP is significantly lower than
assumed in the preliminary risk assessment. As a result, the Agency does not believe that there
will be significant drinking water or inhalation exposures to DDVP from the use of trichlorfon
on turf. As noted below, confirmatory data in the form of a turf transferable residue (TTR) study
will be required from the trichlorfon registrant to verify that the revised assessment of drinking
water and inhalation exposure is accurate.
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b. Occupational Risk Mitigation
As discussed in the revised human health risk assessment (Appendix J), upon
implementation of the use deletions, use amendments, worker protections, and labeling
amendments reflected in the DDVP registrant's May 9th, 2006, letter to EPA, the occupational
risks of concern from use of DDVP will have been addressed. No further mitigation is
necessary.
2. Ecological Risk Management and Mitigation
As discussed in the ecological risk assessment attached as Appendix K, the following
potential risks of concern were identified by Agency screening-level modeling:
• For use on turf, the chronic level of concern (LOG) was exceeded for birds, and
the chronic and acute endangered species LOCs were exceeded for certain
mammalian species. Turf use modeling also resulted in acute, acute endangered
species, and chronic LOG exceedences for freshwater invertebrates.
• For the flying insect exposure scenario, the chronic level of concern (LOG) was
exceeded for birds, and the chronic and acute endangered species LOCs were
exceeded for certain mammal species.
• For the bait exposure scenario, acute risk and acute endangered species LOCs
were exceeded for birds. Chronic risk from bait use could not be assessed due to
insufficient data.
As noted above, the registrant has requested that all uses on lawns, turf, and ornamentals
be deleted from its registration; therefore, the above-referenced risks from the turf use scenarios
will not occur. Regarding the remaining two uses for which ecological concerns were identified,
flying insect spray and granular bait use, modeling for both uses predicts only small exceedences
of the risk quotients (RQs). For the flying insect exposure scenario, most of the chronic RQs
were below 5, with a high of 8.3 for 15 g short grass-eating mammals. It is important to note
also that the exposure assumptions for the flying insect risk estimate represents an extreme worst
case scenario: the maximum application rate was assumed to be applied 75 times per year. For
the large majority of users, such year-round insect control regimens at the maximum treatment
levels are not necessary. Moreover, even for climates where target insect infestations are a year-
round problem, it is unlikely that treatments will continue uninterrupted every 3 to 5 days for an
entire year.
For the granular bait use, the highest estimated RQ was just under 1 for 20 g birds; the
rest of the estimated RQs were below 0.2. Given these very low exceedences in the Agency's
screening level modeling at maximum use rate, the Agency does not believe that this use of
DDVP presents a risk of concern. Therefore EPA is not requiring additional mitigation
measures.
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3. Other Labeling Requirements
In order to be eligible for reregistration, DDVP use and user safety information also
needs to be included in the labeling of all end-use products containing DDVP. For the specific
label statements and a list of additional data requirements necessary to confirm this decision,
refer to Section V of this RED document.
4. Threatened and Endangered Species Considerations
The Agency has developed the Endangered Species Protection Program to identify
pesticides whose use may cause adverse impacts on threatened and endangered species and to
implement mitigation measures that address these impacts. The Endangered Species Act
requires federal agencies to ensure that their actions are not likely to jeopardize listed species or
adversely modify designated critical habitat. To analyze the potential of registered pesticide uses
that may affect any particular species, EPA uses basic toxicity and exposure data developed for
REDs and then considers ecological parameters, pesticide use information, geographic
relationship between specific pesticide uses and species locations, and biological requirements
and behavioral aspects of the particular species. When conducted, this species-specific analysis
will take into consideration risk mitigation measures that are being implemented as a result of
this IRED.
For the remaining outdoor uses of DDVP flying (insect and granular bait), the Agency's
level of concern for Federally listed threatened and endangered species were exceeded for
endangered bird species and small mammals. There also may be the potential for indirect
adverse effects for some listed species that are dependent on this taxonomic group. These
findings are based on EPA's screening level assessment and do not constitute a may affect
finding under the Endangered Species Act.
Following this future species-specific analysis, a determination that there is a likelihood
of potential effects to a listed species may result in limitations on use of DDVP, other measures
to mitigate any potential effects, or consultations with the Fish and Wildlife Service and/or the
National Marine Fisheries as appropriate. If the Agency determines use of DDVP "may effect"
listed species or their designated critical habitat, EPA will employ the provisions in the Services
regulations (50 CFR Part 402). EPA is not requiring specific DDVP label language at the
present time relative to threatened and endangered species. If, in the future, specific measures
are necessary for the protection of listed species, the Agency will implement them through the
Endangered Species Program.
5. General Risk Mitigation
DDVP end-use products may also contain other registered pesticides. Although the
Agency is not proposing any mitigation measures for products containing DDVP specific to
Federally listed threatened and endangered species, the Agency needs to address potential risks
from other end-use products. Therefore, the Agency requires that users adopt all threatened and
endangered species risk mitigation measures for all active ingredients in the product. If a
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product contains multiple active ingredients with conflicting threatened and endangered species
risk mitigation measures, the more stringent measure(s) must be adopted.
V. What Registrants Need to Do
The Agency has determined that DDVP is eligible for reregistration provided (i) label
amendments are made to reflect the use deletions, use amendments, and other measures
identified in the registrant's May 9, 2006, terms and conditions letter, as well as this IRED, and
(ii) any additional measures needed to reduce cumulative risks are adopted. The Agency intends
to issue Data Call-Ins (DCIs) for generic (technical or manufacturing-use grade) data and
product-specific data. Generally, registrants will have 90 days from receipt of a generic DCI to
complete and submit response forms or request time extension and/or waiver requests with a full
written justification. Table 3 below presents the additional generic data the Agency intends to
require for DDVP to be eligible for reregistration. For product-specific DCIs, registrants will
have eight months to submit data and amend labels. In order for products containing DDVP to
be eligible for reregistration, all product labels must be amended to incorporate the specific
changes and language presented in Table 4 below. Table 4 also describes how the required
language should be incorporated.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic database supporting the reregistration of DDVP has been reviewed and
determined to be complete. However, the following additional data requirements have been
identified by the Agency as confirmatory and are included in the generic DCI for this IRED.
Table 3. Confirmatory Data Requirements for the Reregistration of DDVP
Data Requirement
New OPPTS
Guideline
Number (GLN)
Old Guideline
Number
Storage Stability
The reregistration requirements for storage stability data are not
fulfilled. Information pertaining to the storage intervals and conditions of
samples of the following commodities must be submitted: packaged and
bagged raw agricultural commodities and processed food; bulk stored raw
agricultural commodities; milk; eggs; and meat, fat, and meat byproducts
of dairy cows and poultry. Alternatively, the registrant may demonstrate
that there are sufficient residue data which are supported by storage
stability data to support all registered uses of DDVP.
860.1380
171-4e
Magnitude of Residues: Swine
The reregistration requirements for data pertaining to this guideline topic
are not completely fulfilled. A dermal magnitude of the residue study
must be submitted for swine. No additional data are required for milk and
edible tissues of ruminants, and for eggs and edible tissues of poultry.
860.1480
171-4J
In addition, a confirmatory exposure study will be required for trichlorfon based on the
DDVP risk assessment. A TTR study (GDLN 875.2500) with analyses for trichlorfon and
DDVP in the turf and in the toddler breathing zone above the turf (18") is requested to confirm
23
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the exposure estimates in this document. The study must be conducted at an appropriate pH
(approx. 7). The air concentrations of DDVP must be expressed in mg/L. A field dissipation
study may be substituted, provided it meets these requirements. A DCI for this confirmatory
data will be sent to the trichlorfon registrant.
2. Labeling for Manufacturing-Use Products
To ensure compliance with FIFRA, labeling on manufacturing-use products (MUP)
should be revised to comply with all current EPA regulations, PR Notices, and applicable
policies. The MUP labeling should bear the specific language presented in Table 4 below.
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g) (2) (B) of FIFRA calls for the Agency to obtain any needed product-specific
data regarding the pesticide after a determination of eligibility has been made. The registrant
must review previous data submissions to ensure they meet current EPA acceptance criteria and
if not, commit to conduct new studies. If a registrant believes that previously submitted data
meet current testing standards, then the study MRID numbers should be cited according to the
instructions in the Requirement Status and Registrations Response Form provided for each
product. The Agency intends to issue a separate product-specific Data Call-In outlining specific
data requirements.
2. Labeling for End-Use Products
Labeling changes are necessary to implement measures outlined in the IRED. The
specific changes and language required are presented in Table 4 below.
Except for pest strips, 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.
Please refer to "Existing Stocks of Pesticide Products; Statement of Policy," Federal Register,
Volume 56, No. 123, June 26, 1991.
For large pest strips (80 gram and 65 gram), the registrant shall stop distributing product
with old labels on April 15, 2007, (or 4 months after EPA approves their new labels, which ever
is later); supplemental distributors shall have until December 31, 2007, to sell any old labeled
product. As of January 1, 2008, the registrant and its supplemental distributors may sell only
pest strips with the new label language. After December 31, 2007, the Registrant will reclaim
any old labeled product from its distributors or end use registrants.
For small pest strips (16 gram, 10.5 gram, and 5.25 gram) the new label language is
effective as of the date EPA approves the changes described above. The existing stocks time
frames will be established per the "Existing Stocks of Pesticide Products; Statement of Policy,"
Federal Register, Volume 56, No. 123, June 26, 1991.
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In order to be eligible for reregistration, amend all product labels to incorporate the risk mitigation measures outlined in the
IRED. The following table describes how language on the labels should be amended.
Table 4: Summary of Labeling Changes for DDVP
Description
Amended Labeling Language
Placement on Label
For all Manufacturing
Use Products
"Only for formulation into:
(1) Dry formulations for use in impregnated dispensers, impregnated resin dog and flea collars, and dry
bait formulations:
(2) The following impregnated resin pest strip products: 80, 65, 16, 10.5 and 5.25 grams
(3) Ready to Use aerosol and total release fogger products intended for commercial use;
(4) Liquid formulations for the following agricultural/commercial uses: farm buildings, (farmyards),
manure treatments on farm premises, dairy and farm premises, feed lots, including barns, feeding areas,
shelters and stables, dairy barns (including milk rooms), equipment and barnyards, livestock feeding
areas, pens, poultry droppings, poultry houses (equipment and yards), greenhouses (non-food),
mushroom houses, beef cattle, poultry, dairy cattle, goats, horses (including ponies), sheep, swine and
turkeys, and;
(5) Liquid formulations for use only in commercial application equipment such as conventional or ULV
fogging equipment (space treatment) for warehouses, silos, mushroom houses, greenhouses (non-food)
bulk bins and food/feed processing, food/feed manufacturing, handling and storage plants containing
non-perishable, packaged or bagged raw or processed food/feed commodities or bulk raw or processed
food commodities and non-food feed areas processing/manufacturing plants.
"Not for formulation into:
(1) Products intended for use by residential consumers that contain more than .5% a.i. DDVP;
(2) Ready to Use (RTU) total release fogger products intended for use on residential sites;
(3) Aerosol products intended to be used as crack and crevice or space sprays on residential sites;
(4) Liquid formulations intended for use with hand held fogging or hand held smoke generator
equipment;
(5) Products intended for use in tobacco houses;
(6) Products intended for use in the following types of food/feed manufacturing establishments:
bottling plants (including wineries, breweries, soft drinks, frozen food/feed (including pizza
and ice cream plants;
(7) Products intended for use in the following food/feed processing establishments: meat, poultry
and seafood slaughtering and/or packing plants (including edible fats and oils), frozen
food/feed plants (including fruit and vegetables), dairy product plants (including milk
processing plants);
Directions for Use
25
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(8) Products intended for use on lawns, turf, or ornamentals."
One of these statements
may be added to a label to
allow reformulation of
the product for a specific
use or all additional uses
supported by a formulator
or user
"This product may be used to formulate products for specific use(s) not listed on the MP label if the
formulator, user group, or grower has complied with U.S. EPA submission requirements regarding
support of such use(s)."
"This product may be used to formulate products for any additional use(s) not listed on the MP label if
the formulator, user group, or grower has complied with U.S. EPA submission requirements regarding
support of such use(s)."
Directions for Use
Environmental Hazards
Statements Required by
the IRED and Agency
Label Policies
"This product is toxic to birds, fish, and aquatic invertebrates. Do not discharge effluent containing this
product into lakes, streams, ponds, estuaries, oceans, or other waters unless in accordance with the
requirements of a National Pollution Discharge Elimination System (NPDES) permit and the permitting
authority has been notified in writing prior to discharge. Do not discharge effluent containing this
product to sewer systems without previously notifying the local sewage treatment plant authority. For
guidance contact your State Water Board or Regional Office of the EPA."
Precautionary
Statements
End Use Products Intended for Occupational Use (WPS and Non-WPS)
PPE Requirements
Established by the IRED1
for liquid formulations
(excludes Ready to Use
aerosol products
containing 5% or less a.i.
DDVP)
"Personal Protective Equipment (PPE)"
"Some materials that are chemical-resistant to this product are" (registrant inserts correct chemical-
resistant material). "If you want more options, follow the instructions for category" [registrant inserts
A,B,C,D,E,F,G,or H] "on an EPA chemical-resistance category selection chart."
Mixers, loaders, applications and other handlers must wear:
- long-sleeve shirt,
- long pants,
- shoes and socks, and
- chemical-resistant gloves
- A NIOSH-approved respirator with:
~ an organic-vapor removing cartridge with a prefilter approved for pesticides (MSHA/NIOSH approval
number prefix TC 23 C) or,
~ a canister approved for pesticides (MSHA/NIOSH approval number prefix TC-14G) or,
- an organic-vapor removing cartridge or canister with any N,R,P, or HE prefilter.
Immediately
following^elow
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
PPE Requirements
Established by the IRED
for Ready to Use (RTU)
Aerosol products
containing 5% or less a.i.
DDVP and products
"Personal Protective Equipment (PPE)"
"Some materials that are chemical-resistant to this product are" (registrant inserts correct chemical-
resistant material). "If you want more options, follow the instructions for category" [registrant inserts
A,B,C,D,E,F,G,or H\ "on an EPA chemical-resistance category selection chart."
Applicators and other handlers must wear:
Immediately
following^elow
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
26
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formulated as a granular
baits.
- long-sleeve shirt,
- long pants,
- shoes and socks,
- chemical resistant gloves
PPE Requirements
Established by the IRED
for Ready to Use pest
strips and collars
PPE not required
User Safety Requirements
for all products requiring
PPE (see above)
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions for washables
exist, use detergent and hot water. Keep and wash PPE separately from other laundry."
"Discard clothing and other absorbent materials that have been drenched or heavily contaminated with
this product's concentrate. Do not reuse them."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals immediately
following the PPE
requirements
Engineering Controls
for all Formulations
None Required
User Safety
Recommendations
All products:
"User Safety Recommendations
Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the toilet."
All products requiring PPE:
"Users should remove clothing/PPE immediately if pesticide gets inside. Then wash thoroughly and put
on clean clothing.
Users should remove PPE immediately after handling this product. Wash the outside of gloves before
removing. As soon as possible, wash thoroughly and change into clean clothing."
Precautionary
Statements under:
Hazards to Humans and
Domestic Animals
immediately following
Engineering Controls
(Must be placed in a
box.)
Environmental Hazards
Statements for products
labeled for outdoor uses
"ENVIRONMENTAL HAZARDS"
"This product is toxic to fish, birds, and aquatic invertebrates. Do not apply directly to water, to areas
where surface water is present or to intertidal areas below the mean high water mark. Do not
contaminate water when disposing of equipment wash-waters or rinsate."
Precautionary
Statements under
Environmental Hazards
Environmental Hazards
for Products labeled for
Indoor Use that are
packaged in containers
"ENVIRONMENTAL HAZARDS"
"Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or other
waters unless in accordance with the requirements of a National Pollution Discharge Elimination System
27
Precautionary
Statements under
Environmental Hazards
-------
equal to or greater than 5
gallons or 50 Ibs
(NPDES) permit and the permitting authority has been notified in writing prior to discharge. Do not
discharge effluent containing this product to sewer systems without previously notifying the local
sewage treatment plant authority. For guidance contact your State Water Board or Regional Office of
the EPA."
Restricted-Entry Interval
(REI), Early Entry PPE
and Ventilation
Requirement for products
with use directions for
use within the scope of
the Worker protection
Standard for agricultural
pesticides
"NOTIFICATION: Before the start of the application, notify workers of the application by warning
them orally and by posting fumigant warning signs at all entrances to the building. The signs must bear
the skull and crossbones symbol and state: (1) "DANGER/PELIGRO," (2) "Building under fumigation,
DO NOT ENTER/NO ENTRE," (3) the date and time of fumigation, (4) "DDVP {or use brand name}
Fumigant in use," and name, address, and telephone number of the applicator. Post the fumigant warning
sign instead of the WPS sign for this application, but follow all WPS requirements pertaining to
location, legibility, size, and timing of posting and removal."
"Do not apply this product to a greenhouse or mushroom house that is attached to another structure,
including another greenhouse or mushroom house, unless the greenhouse or mushroom house to be
treated is entirely sealed off from the other structures."
"A trained pesticide handler with immediate access to the PPE that this labeling requires for applicators
must maintain constant visual or voice contact with any handler who is applying this product in a
greenhouse or mushroom house or who enters the treated building before the ventilation is complete to
perform any handling task."
"Entry (including early entry that would otherwise be permitted under the WPS) by any person ~ other
than a correctly trained and equipped handler who is performing a handling task permitted by the WPS
and wearing the personal protective equipment required for handlers - is PROHIBITED in the entire
greenhouse or mushroom house (entire enclosed structure/building) from the start of application until
ventilation is complete in the greenhouse or mushroom house. Ventilation is complete either when 24
hours have elapsed following application and the building has been opened and aired or when a direct-
indication short-term concentration monitoring device (e.g. Draeger tube) indicates that the DDVP air
concentration is equal to, or less than 0.050 ppm (50% of the OSHA PEL). A trained pesticide handler
with immediate access to the PPE that this labeling requires for applicators must maintain constant
visual or voice contact with any handlers entering the treated building before the ventilation is
complete."
"For Greenhouses: If ventilation is complete before 12 hours have elapsed following application (e.g.,
Draeger tub reading), then a restricted-entry interval of 12 hours is in effect. Do not enter or allow
workers to enter during the restricted entry interval of 12 hours. Early entry as permitted by the Worker
Protection Standard is permitted provided:
• the fumigant warning sign is removed, and
• the following personal protective equipment is worn: coveralls, shoes and socks, and
waterproof gloves."
Agrigultural Use
Reqirements Box
28
-------
"For Mushroom Houses:
If ventilation is complete before 18 hours have elapsed following application (e.g., Draeger tub reading),
then a restricted-entry interval of 18 hours is in effect. Do not enter or allow workers to enter during the
restricted entry interval of 18 hours. Early entry as permitted by the Worker Protection Standard is
permitted provided:
• the fumigant warning sign is removed, and
• the following personal protective equipment is worn: coveralls, shoes and socks, and
waterproof gloves."
Entry Restrictions for
products having
occupational uses on the
label not subject to the
WPS (applies to aerosols
applied as a space spray,
fog or smoke)
"NOTIFICATION: Before the start of the application, post fumigant warning signs at all entrances to
the building. The signs must bear the skull and crossbones symbol and state: (1)
"DANGER/PELIGRO," (2) "Building under fumigation, DO NOT ENTER/NO ENTRE," (3) the date
and time of fumigation, (4) "DDVP {or use brand name} Fumigant in use," and name, address, and
telephone number of the applicator. The signs must be located prominently at each entrance, using a sign
size and letter size that makes the sign clearly legible. All signs must be removed after the ventilation is
complete and before routine entry by unprotected persons is permitted.
"Entry by any person ~ other than a correctly trained and equipped handler who is performing a task
related to ventilation or air concentration monitoring and who is wearing the personal protective
equipment required for handlers ~ is PROHIBITED in the entire enclosed structure/building from the
start of application until ventilation is complete. Ventilation is complete either when 24 hours have
elapsed following application and the building has been opened and aired or when a direct-indication
short-term concentration monitoring device (e.g. Draeger tube) indicates that the DDVP air
concentration is equal to, or less than 0.050 ppm (50% of the OSHA PEL)."
If no WPS uses on the
product label, place the
appropriate statement
in the Directions for
Use Under General
Precautions and
Restrictions. If the
product also contains
WPS uses, then create a
Non-Agricultural Use
Requirements box as
directed in PR Notice
93-7 and place the
appropriate statement
inside that box.
Entry Restrictions for
products having
occupational uses on the
label that are only
applied as a surface
spray.
Entry Restriction for non-WPS uses applied as a surface spray:
"Do not enter or allow others to enter until sprays have dried."
If no WPS uses on the
product label, place the
appropriate statement
in the Directions for
Use Under General
Precautions and
Restrictions. If the
product also contains
WPS uses, then create a
Non-Agricultural Use
Requirements box as
directed in PR Notice
93-7 and place the
appropriate statement
inside that box.
29
-------
General Application
Restrictions
Other Application
Restrictions (Risk
Mitigation)
"Do not apply this product in a way that will contact workers or other persons, either directly or through
drift. Only handlers wearing specified PPE may be in the area during application."
Liquid Formulations:
"Use in hand held fogger or hand held smoke generator equipment is prohibited."
"Use in residential sites as a crack and crevice or space spray is prohibited"
"Use on Lawns, turf or ornamentals is prohibited".
Pest Strips (80 and 65 g):
"For use in unoccupied areas; not for use in homes except garages, attics, crawl spaces, and sheds
occupied for less than 4 hours per day.
Also for use in boathouses, museum collections, animal buildings, and milk rooms, or enclosed areas
thereof, occupied for less than 4 hours per day.
For use in unoccupied areas such as trash dumpsters, catch basins, bulk raw grain bins, storage bins,
insect traps, enclosed utility boxes, and storage units. Also for use in non-perishable packaged and
bagged and bulk stored processed and raw agricultural commodities (including soybeans, corn, grains,
cocoa beans and peanuts).
Also for use in the following unoccupied structures, provided they are unoccupied for more than 4
months immediately following placement of a pest strip: vacation homes, cabins, mobile homes, boats,
farm houses, and ranch houses."
Pest Strips (16, 10.5, and 5.25 g):
"Within homes, use only in closets, wardrobes, and cupboards. Also for use in storage units, garages,
attics, crawl spaces, boathouses, museum collections, garbage cans, trash dumpsters, animal buildings,
milk rooms, catch basins, bulk raw grain, and storage bins."
Place in the Direction
for Use directly above
the Agricultural Use
Box.
Directions for Use
End Use Products Intended for Residential Use
30
-------
Application Restrictions
"Do not apply this product in a way that will contact any person, pet, either directly or through drift.
Keep people and pets out of the area during application."
Pest Strips (80 and 65 g):
"For use in unoccupied areas; not for use in homes except garages, attics, crawl spaces, and sheds
occupied for less than 4 hours per day.
Also for use in boathouses, museum collections, animal buildings, and milk rooms, or enclosed areas
thereof, occupied for less than 4 hours per day.
For use in unoccupied areas such as trash dumpsters, catch basins, bulk raw grain bins, storage bins,
insect traps, enclosed utility boxes, and storage units. Also for use in non-perishable packaged and
bagged and bulk stored processed and raw agricultural commodities (including soybeans, corn, grains,
cocoa beans and peanuts).
Also for use in the following unoccupied structures, provided they are unoccupied for more than 4
months immediately following placement of a pest strip: vacation homes, cabins, mobile homes, boats,
farm houses, and ranch houses."
Pest Strips (16, 10.5, and 5.25 g):
"Within homes, use only in closets, wardrobes, and cupboards. Also for use in storage units, garages,
attics, crawl spaces, boathouses, museum collections, garbage cans, trash dumpsters, animal buildings,
milk rooms, catch basins, bulk raw grain, and storage bins."
Directions for Use
under General
Precautions and
Restrictions
Entry Restrictions
Liquids applied as surface sprays:
"Do not allow people or pets to enter the treated area until sprays have dried.'
Directions for use
under General
Precautions and
Restrictions
PPE that is established on the basis of Acute Toxicity of the end-use product must be compared to the active ingredient PPE in this document. The more
protective PPE must be placed in the product labeling. For guidance on which PPE is considered more protective, see PR Notice 93-7.
31
-------
APPENDIX A: Dichlorvos Use Patterns Eligible For Reregistration
Site
Application Type
Formulation
Application Rate, ai
Use Directions and Limitations
Agricultural commodities (bulk storage of nonperishable raw and processed agricultural commodities including raw grains, corn, soybeans, cocoa
beans, and peanuts)
Premise
treatment
20% Impr
20% Impr
]
20% Impr
10.5 g of product/
50-1 00 cu. ft
or
80 g of product/
900-1 200 cu. Ft
Use of product where unwrapped food is stored or allowing the strip to come in contact with food
or cooking utensils is prohibited.
Use in kitchens, restaurants, or areas where food/feed are prepared or processed, use in
food/feed processing or food/feed manufacturing areas of food/feed processing and food/feed
manufacturing plants are prohibited.
Use in kitchens, restaurants, or areas where food is prepared or served and use in edible
product areas of food processing plants are prohibited.
Greenhouses (not containing food commodities)
Fog application
0.37 Ib/gal
EC
0.004 lb/1, 000 cu. ft
Applications may be made using a cold aerosol generator. Hand held foggers are no longer
permitted.
Mushroom houses
Fog application
[hand-held fogger
is no longer
permitted]
Brush on /coarse
spray
50% FIC
0.37 Ib/gal
EC
2 Ib/gal EC
2% finished spray
[6.25 oz/1 0,000 cu.ft]
2% finished spray
[10 oz/1 0,000 cu.ft]
5 g/1 0,000 cu.ft
0.004 lb/1, 000 cu.ft
0.00125 lb/100sq ft
Applications may be made in 1,1,1-trichloroethane using a cold aerosol generator. Applications
may be made twice a week during spawn run; thereafter use as needed. A 1-day PHI has been
established for mushrooms.
Applications may be made in deodorized base kerosene using a cold aerosol generator.
Applications may be made twice a week during spawn run; thereafter use as needed. A 1-day
PHI has been established for mushrooms.
Applications may be made using a cold aerosol generator. Applications may be made twice a
week during spawn run; thereafter use as needed.
Coarse spray or paint on walls, around doors, ventilators & cracks before mushrooms come into
production. Use as 0.5% solution - 1 pint of 0.5% solution per 100 sq ft., up to 10 days before
crop emerges on soil beds. Do not spray inside walls after mushrooms appear on beds. After
mushrooms appear, spray only the outside of the building.
Food-handling establishments (including households; restaurants; theaters; food processing plants; industrial plants; and warehouses)
32
-------
Site
Application Type
Indoor treatment
Directed spray
application
Indoor treatment
Remote Fog
Application
Formulation
4 Ib/gal EC
20% PrL
Application Rate, ai
0.5% finished spray
2.5g/1000cu. ft.
Use Directions and Limitations
Applications may be made with deodorized base oil or water using a low pressure sprayer to
treat localized areas where insects may infest around baseboards, cracks, walls, doors, window
frames, and localized areas of floors. Use in edible product areas of food processing plants,
restaurants, or other areas where food is commercially prepared or processed and use in
serving areas while food is exposed is prohibited
Application made by timer when buildings are unoccupied. Building should be closed and
ventilation kept to a minimum. Lock all entrances, and do not allow unprotected workers to enter
the building when being treated.
Food-handling establishments (including theaters; food processing plants; industrial plants; and warehouses)
Indoor treatment
Space spray
application
[Hand-Held
Foggers are no
longer permitted]
0.37 Ib/gal
EC
1.59 Ib/gal
EC
4 Ib/gal EC
1.1 5 Ib/gal
SC
2 Ib/gal SC
8.39 Ib/gal
SC
1% finished spray
[1 gal/64,000 cu.ft]
Fogging or misting applications may be made with deodorized base oil or water using fogging or
misting equipment to treat indoor areas. Applications are to be made when the plants are not in
operation. Food should be removed and food-handling equipment covered prior to application or
washed with suitable cleaner and potable water after application.
Food-handling establishments [including areas for receiving, storage, packing (canning, bottling, wrapping, boxing), preparing, edible waste storage,
and enclosed processing systems (mills, dairies, edible oils, syrups), and serving areas]
Indoor crack and
crevice
treatment
0.25 Ib/gal
EC
0.5 Ib/gal
EC
0.1% finished spray
Applications may be made in water or oil and may be applied by directing small amounts into
crack and crevices, in points between different elements of construction, and between
equipment legs and bases. Applications in food areas other than crack and crevice treatments
are prohibited.
Nonfood/feed areas of food-handling establishments [including garbage rooms, lavatories, floor drains (sewers), entries and vestibules, offices,
locker rooms, machine rooms, boiler rooms, garages, mop closets, and storage (after canning or bottling)]
33
-------
Site
Application Type
Formulation
Application Rate, ai
Use Directions and Limitations
Indoor treatment
Directed spray
application
0.37 Ib/gal
EC
1.59 Ib/gal
EC
1.15 Ib/gal
SC
2 Ib/gal SC
8.39 Ib/gal
SC
0.5% finished spray
Applications may be made with deodorized base oil or water using a low pressure sprayer to
treat localized areas where insects may infest around baseboards, cracks, walls, doors, window
frames, and localized areas of floors. Use in edible product areas of food processing plants,
restaurants, or other areas where food is commercially prepared or processed and use in
serving areas while food is exposed are prohibited.
4.48 Ib/gal
SC
0.5% finished spray
Applications may be made with deodorized base oil using a low pressure sprayer to treat
localized areas where insects may infest around baseboards, cracks, walls, doors, window
frames, and localized areas of floors. Use in food/feed handling areas of food/feed handling
establishments, restaurants or other areas where food is commercially prepared or served and
use to treat non-perishable bagged or bulk raw or processed commodities is prohibited.
10 Ib/gal SC
0.5% finished spray
For use in warehouses, silos, bulk bins, and food/feed processing, food/feed manufacturing,
handling and storage plants containing non-perishable, packaged or bagged raw or processed
food/feed commodities or bulk raw or processed food commodities. Applications may be made
with deodorized base oil using a low pressure sprayer to treat localized areas where insects may
infest around baseboards, cracks, walls, doors, window frames, and localized areas of floors.
Use of this product in food processing plants, food-handling areas of restaurants, or areas where
food is prepared or served, and use to treat non-perishable bagged and or bulk stored raw or
processed agricultural commodities are prohibited. Contamination of food, water, food
containers, or cooking utensils is prohibited.
Nonfood/feed areas of food-handling establishments [including garbage rooms, lavatories, floor drains (sewers), entries and vestibules, offices,
locker rooms, machine rooms, boiler rooms, garages, mop closets, and storage (after canning or bottling)]
Indoor spot
treatment
0.25 Ib/gal
EC
0.5 Ib/gal
EC
0.1% finished spray
Applications may be made in water or oil and may be applied as a coarse spray or with a paint
brush to areas where pests hide (baseboard areas, around water pipes, surfaces behind and
beneath sinks, lockers, tables, pallets, and similar areas). Applications may be repeated as
needed. Use of this product in edible product areas of food processing plants, restaurants, or
other areas where food is commercially prepared or processed and use in serving areas where
food is exposed are prohibited.
34
-------
Site
Application Type
Indoor treatment
Space spray
application
[Hand-Held
Foggers are no
longer permitted]
Formulation
1.16lb/gal
EC
[
0.5% RTU
4.48 Ib/gal
SC
Application Rate, ai
0.5% finished spray
0.5% spray
1% finished spray
[1 gal/64,000 cu.ft]
Use Directions and Limitations
Applications may be made in water and may be applied to areas where pests hide (around
baseboards, cracks, walls, door and window frames and localized areas of floors). Use of this
product in food processing plants, food-handling areas of restaurants, or areas where food is
prepared or served, and use to treat non-perishable bagged and or bulk stored raw or processed
agricultural commodities are prohibited. Contamination of food, water, food containers, or
cooking utensils is prohibited.
Applications may be made with a pump sprayer to areas where pests hide (dark corners of room
and closets, cracks and crevices in walls, behind and beneath sinks, stoves, refrigerators,
cabinets, washing machines, cupboards, bookcases, and around baseboards). Use of this
product in food areas of food-handling establishments, restaurants, or other areas where food is
commercially prepared or processed and use in serving areas where food is exposed or while
facility is operating are prohibited.
Fogging or misting applications may be made with deodorized base oil using fogging or misting
equipment to treat indoor areas. Use in bottling plants, food contact areas or meat slaughter,
and/or packing plants or in frozen food plants is prohibited.
Nonfood/feed areas of food-handling establishments [including garbage rooms, lavatories, floor drains (sewers), entries and vestibules, offices,
locker rooms, machine rooms, boiler rooms, garages, mop closets, and storage (after canning or bottling)] (continued)
Indoor treatment
Space spray
application
[Hand-Held
Foggers are no
longer permitted]
Indoor premise
treatment
10 Ib/gal SC
0.5% PrL
20% Impr
1% finished spray
[1 gal/64,000 cu.ft]
0.5% spray
10.5 g of product/
50-100 cu. ft
For use in warehouses, silos, bulk bins, and food/feed processing, food/feed manufacturing,
handling and storage plants containing non-perishable, packaged or bagged raw or processed
food/feed commodities or bulk raw or processed food commodities. Fogging or misting
applications may be made with deodorized base oil using fogging or misting equipment to treat
indoor areas. Use in bottling plants, food contact areas or meat slaughter, and/or packing plants
or in frozen food plants is prohibited. When using in food processing, handling, and storage
areas: (I) applications may be made only during times when plant is not in operation and no
food products are exposed; if bulk, unpackaged food is exposed, it must be removed or covered
prior to treatment; (ii) all food processing surfaces should be covered during treatment or
thoroughly cleaned before using.
Use as a space spray is prohibited. Applications may be applied to areas where pests hide
(cracks, around baseboards, cabinets, walls, and woodwork) and repeated as necessary. Use
of this product in edible product areas of food processing plants, restaurants, or other areas
where food is commercially prepared or processed and use to treat non-perishable bagged and
or bulk stored raw or processed agricultural commodities are prohibited. Contamination of
utensils, food, water, and foodstuffs prohibited.
Use in kitchens, restaurants, or areas where food/feed are prepared or processed, use in
food/feed processing or food/feed manufacturing areas of food/feed processing and food/feed
manufacturing plants are prohibited.
Animal Uses (Premises)
35
-------
Site
Application Type
Formulation
Application Rate, ai
Use Directions and Limitations
Farm buildings (including animal shelters, barns, around feed lots, dairy barns, milk sheds, loafing pens, pig pens, poultry houses, hog barns,
stables, and other farm buildings)
Premise
treatment
Directed spray
application
1 Ib/gal EC
2 Ib/gal EC
0.37 Ib/gal
EC
2 Ib/gal EC
4 Ib/gal EC
0.5% finished spray
[1 qt/1,000sq.ft]
0.5% finished spray
[1 qt/1,000sq.ft]
0.5% finished spray
[1 qt/1,000sq.ft]
Applications may be made as a coarse, wet spray to all exterior and interior surfaces, treating
window sills, around doors, fences, and ledges or as a directed spray to floors, baseboards,
crack and crevices in wall, and along base of walls. Applications may be made using water- or
oil-based sprays; applications may be repeated as necessary. A 1-day preslaughter interval
(PSI) has been established.
Applications may be made as a coarse, wet spray to surfaces, treating window sills, doorways,
feed storage rooms, and alleyways. Applications may be made using water; applications may
be repeated as necessary. Animals must be removed prior treatment. Application in areas
where animals have received a direct application of DDVP within the past 8 hours is prohibited.
Applications may be made as a coarse, wet spray to surfaces, treating window sills, doorways,
feed storage rooms, and alleyways. Applications may be made using water; applications may
be repeated as necessary. Animals may be present during treatment. Contamination of water,
feed or foodstuffs, milk or milking utensils is prohibited.
Farm buildings (including animal shelters, barns, around feed lots, dairy barns, milk sheds, poultry houses, hog barns, stables, and other farm
buildings) (continued)
36
-------
Site
Application Type
Premise
treatment
Directed spray
application
Premise
treatment
Space spray
application
[Hand-Held
Foggers are no
longer permitted]
Formulation
1.16lb/gal
EC
1.59lb/gal
EC
1.15lb/gal
SC
4.48 Ib/gal
SC
8.39 Ib/gal
SC
10 Ib/gal SC
2 Ib/gal EC
Application Rate, ai
0.5% finished spray
[1 qt/1,000sq.ft]
1% finished spray
[0.5 qt/8,000 cu.ft]
or
0.5% finished spray
[1 qt/8,000 cu.ft]
Use Directions and Limitations
Applications may be made as a coarse, wet spray to surfaces, treating window sills, doorways,
feed storage rooms, and alleyways. Applications may be made using diesel oil or water;
applications may be repeated as necessary. Direct treatment of animals or humans and
contamination of water, feed or foodstuffs, milk or milking utensils are prohibited.
Fog applications may be made using diesel oil. Animals must be removed prior to treatment.
Prior to application, reduce air movement as much as possible by closing doors, windows, and
other openings. Application in areas where animals have received a direct application of DDVP
within the past 8 hours is prohibited.
Farm buildings (including animal shelters, barns, around feed lots, dairy barns, milk sheds, poultry houses, hog barns, stables, and other farm
buildings) (continued)
37
-------
Site
Application Type
Premise
treatment
Space spray
application
[Hand-Held
Foggers are no
longer permitted]
Premise
treatment
Farm buildings (incluc
buildings) (continued
Premise
treatment
Space spray
application
[Hand-Held
Foggers are no
longer permitted]
Formulation
0.37 Ib/gal
EC
1.1 6 Ib/gal
EC
1.59 Ib/gal
EC
2 Ib/gal EC
4 Ib/gal EC
1.1 5 Ib/gal
SC
4.48 Ib/gal
SC
8.39 Ib/gal
SC
10 Ib/gal SC
1%G
Application Rate, ai
1% finished spray
[0.5 qt/8,000 cu.ft]
or
0.5% finished spray
[1 qt/8,000 cu.ft]
0.04 oz/1, 000 sq.ft
Use Directions and Limitations
Fog applications may be made using diesel oil. Animals must be removed prior to treatment.
Prior to application, reduce air movement as much as possible by closing doors, windows, and
other openings. Application in areas where animals have received a direct application of DDVP
within the past 8 hours is prohibited. Contamination of water, feed or foodstuffs, milk or milking
utensils is prohibited.
Bait applications may be made to clean floor areas, ground areas outside enclosures, window
sills, or other areas where flies congregate. Applications are to be made in such a manner that
stock cannot come into contact with bait.
ding animal shelters, barns, around feed lots, dairy barns, milk sheds, poultry houses, hog barns, stables, and other farm
1 Ib/gal EC
1% finished spray
[0.5 qt/8,000 cu.ft]
Fog applications may be made with animals present, provided a direct animal treatment of
DDVP has not been made in the past 8 hours. Applications may be made using water or
deodorized kerosene. Prior to application, reduce air movement as much as possible by closing
doors, windows, and other openings.
38
-------
Site
Application Type
Formulation
Application Rate, ai
Use Directions and Limitations
Animal buildings (including horse barns, calf parlors, hog parlors, stables, poultry houses, tack rooms, and dog kennels)
Premise
treatment
20% Impr
10.5 g of product/
50-100 cu. ft
Contamination of water, food or foodstuffs, milk or milking equipment is prohibited. Use of
product where unwrapped food is stored or allowing the strip to come in contact with food or
cooking utensils is prohibited.
20% Impr
10.5 g of product/
50-100 cu. ft
Contamination of water, food or foodstuffs, milk or milking equipment is prohibited.
Milk rooms (including bulk storage rooms)
Premise
treatment
20% Impr
10.5 g of product/
50-100 cu. ft
Contamination of milk or milking equipment is prohibited. Use of product where unwrapped food
is stored or allowing the strip to come in contact with food or cooking utensils is prohibited.
20% Impr
10.5 g of product/
50-100 cu. ft
Contamination of milk or milking equipment is prohibited.
Feed lots, stockyards, corrals, and holding pens
Outdoor premise
treatment
1 Ib/gal EC
0.37 Ib/gal
EC
1.16 Ib/gal
EC
1.59 Ib/gal
EC
2 Ib/gal EC
4 Ib/gal EC
1.15 Ib/gal
SC
4.48 Ib/gal
SC
8.39 Ib/gal
SC
10 Ib/gal SC
0.5% finished spray
[5 gal/A]
0.2 Ib/A
Applications may be made as an overall mist spray to fences, feed bunkers, shade areas,
spillage areas, building walls, and other areas where flies congregate. Applications may be
made in water using a mist blower or similar equipment at 3- to 14-day intervals.
Applications may be made as an overall mist spray to fences, feed bunkers, spillage areas, and
building walls. Applications may be made in diesel oil or water using a mist blower or similar
equipment. Animals may be present during treatment.
39
-------
Site
Application Type
Formulation
Application Rate, ai
Use Directions and Limitations
Poultry houses
Premise
treatment
0.37 Ib/gal
EC
1 Ib/gal EC
1.1 6 Ib/gal
EC
1.59 Ib/gal
EC
2 Ib/gal EC
4 Ib/gal EC
1.1 5 Ib/gal
SC
4.48 Ib/gal
SC
8.39 Ib/gal
SC
10 Ib/gal SC
[5481-200]
1%G
[5481-9]
0.5% finished spray
[1 qt/1,000sq.ft]
Not specified on the 2
Ib/gal EC [5481 -73]
product label
0.04 oz/1, 000 sq. ft
Applications may be made to manure, window sills, exterior walls, interior walls, feed room
floors, and walkways. Only crack and crevice treatments are permitted for indoor use and
applications are to be made out of reach of poultry (EPA Reg. No. 5481-41 only).
Bait applications may be made to droppings under cages, on walkways, window sills, alley ways,
and other areas where flies congregate. Applications are to be made out of reach of birds.
Direct Animal Uses
Cattle (beef and dairy
Animal mist spray
treatment
1 Ib/gal EC
[5481-41]
2 Ib/gal EC
[5481-73]
1% finished spray
[2 fl. oz/animal/day]
0.5% finished spray
[4 fl. oz/animal/day]
Application may be made in water as an atomized spray uniformly distributed over each animal.
Do not wet the skin.
Application may be made in water as an atomized spray uniformly distributed over each animal.
Application more than once per day and application to calves less than 6 months of age are
prohibited.
40
-------
Site
Application Type
Formulation
0.37 Ib/gal
EC
1.1 6 Ib/gal
EC
1.59 Ib/gal
EC
2 Ib/gal EC
4 Ib/gal EC
[
1.1 5 Ib/gal
SC
4.48 Ib/gal
SC
8.39 Ib/gal
SC
10 Ib/gal SC
Application Rate, ai
1% finished spray
[2 fl. oz/animal/day]
Use Directions and Limitations
Application may be made in deodorized base oil or water as an atomized spray uniformly
distributed over each animal. Do not wet the hide. Application of more than 2 fl. oz. per animal
per day and application to calves less than 6 months of age are prohibited. A 1-day PSI has
been established (EPA Reg. Nos. 5481-204 and 5481-220 only).
Cattle (beef and dairy) (continued)
Animal face paint
treatment
1 Ib/gal EC
0.5% bait slurry
[1 tsp/face]
Applications may be made to the animal's forehead daily for 14 days and thereafter as needed.
41
-------
Site
Application Type
Formulation
0.37 Ib/gal
1.16lb/gal
EC
1.59 Ib/gal
EC
2 Ib/gal EC
4 Ib/gal EC
1.1 5 Ib/gal
SC
4.48 Ib/gal
SC
8.39 Ib/gal
SC
10 Ib/gal SC
Application Rate, ai
1% bait slurry
[3 mL/face]
Use Directions and Limitations
Application is to be made as a 6-inch line to the animal's forehead with a paint brush.
Cattle (beef and dairy) (continued)
42
-------
Site
Application Type
Manure treatment
Formulation
0.37 Ib/gal
EC
1 Ib/gal EC
1.1 6 Ib/gal
EC
1.59 Ib/gal
EC
2 Ib/gal EC
4 Ib/gal EC
1.1 5 Ib/gal
SC
4.48 Ib/gal
SC
8.39 Ib/gal
SC
10 Ib/gal SC
Application Rate, ai
0.5% finished spray
[2qt/100sq.ft]
or
1% finished spray
[1 qt/100sq.ft]
Use Directions and Limitations
Applications may be made in water to control maggots in manure piles and garbage dumps.
Poultry
Manure treatment
1 Ib/gal EC
[5481-41]
0.5% finished spray
[2qt/100sq.ft]
Applications may be made in diesel oil or deodorized kerosene to control flies and maggots in
poultry droppings.
Animal Uses - Oral Dosing (Drug Use)
Swine
Feed treatment
N/A3
12.5-20.6 mg/kg body
weight
Application is to be made by mixing active ingredient into feed and may be repeated in 4-5
weeks.
Wide Area and General Outdoor Treatment
Outdoor areas (including outside picnic areas, patios, and eating areas of drive-in restaurants)
Outdoor spray
application
2 Ib/gal SC
0.5-1% finished spray
Applications may be made in deodorized spray base oil and repeated monthly or as needed.
Outdoor areas (including picnic grounds, parking areas, loading docks, refuse areas, garbage collection and disposal areas, around drive-in
restaurants, food processing plants, and warehouses)
43
-------
Site
Application Type
Outdoor spray
application
Formulation
1 Ib/gal EC
Application Rate, ai
0.5% finished spray
[1 qt/1,000sq. ft]
Use Directions and Limitations
Applications may be made in water and repeated as needed. Direct use on animals and
contamination of feed, foodstuffs, or water are prohibited.
Outdoor areas (including picnic grounds, parking areas, loading docks, refuse areas, garbage collection and disposal areas, around drive-in
restaurants, food processing plants, and warehouses) (continued)
Outdoor spray
application
0.37 Ib/gal
EC
1.1 6 Ib/gal
EC
1.59 Ib/gal
EC
2 Ib/gal EC
4 Ib/gal EC
1.1 5 Ib/gal
SC
4.48 Ib/gal
SC
8.39 Ib/gal
SC
10 Ib/gal SC
0.5% finished spray
[1 qt/1,000sq. ft]
Applications may be made in diesel oil or water and repeated as needed. Direct use on animals
or humans and contamination of water, food, food containers or cooking utensils are prohibited.
Outdoor areas (including picnic grounds, parking areas, loading docks, refuse areas, garbage collection and disposal areas, around drive-in
restaurants, food processing plants, and warehouses) (continued)
44
-------
Site
Application Type
Outdoor fogging
application
[Hand-Held
Foggers are no
longer permitted]
Formulation
0.37 Ib/gal
EC
1.1 6 Ib/gal
EC
1.59 Ib/gal
EC
2 Ib/gal EC
4 Ib/gal EC
1.1 5 Ib/gal
SC
4.48 Ib/gal
SC
8.39 Ib/gal
SC
10 Ib/gal SC
Application Rate, ai
1% finished spray
[5-10 pt/A]
or
0.05-0.1 Ib/A
Use Directions and Limitations
Fogging or misting applications may be made with diesel oil or water using fogging or misting
equipment to treat outdoor living areas, picnic areas, backyard areas, patios, loading docks,
outdoor latrines, parking areas, refuse areas around service stations, open air drive-ins, ice
cream stands, and garbage collection and disposal areas. Use in areas where food or feed
crops are growing is prohibited.
Catch basins
Outdoor
treatment
20% Impr
One strip
One strip (10.5 or 80 g of product) is to be suspended 10 inches above water level for control of
mosquitoes breeding in catch basins.
45
-------
APPENDIX B. Table of Generic Data Requirements and Studies Used to Make the
Reregistration Decision for DDVP
GUIDE TO APPENDIX B
Appendix B contains a listing of data requirements which support the
reregistration for active ingredients within the case DDVP covered by this RED. In
contains generic data requirements that apply nitrapyrin in all products, including data
requirements for which a "typical formulation" is the test substance.
The data table is organized in the following formats:
1. Data requirement (Column 1). The data requirements are listed in the order in
which they appear in 40 CFR 158. The reference numbers accompanying each
test refer to the test protocols set in the Pesticide Assessment Guidance, which is
available from the National Technical Information Service, 5285 Port Royal
Road, Springfield, VA 22161. (703)487-4650.
2. Use Pattern (Column 2). This column indicates the use patterns for which the
data requirements apply. The following letter designations are used for the given
use patterns.
A. Terrestrial food
B. Terrestrial feed
C. Terrestrial non-food
D. Aquatic food
E. Aquatic non-food outdoor
F. Aquatic non-food industrial
G. Aquatic non-food residential
H. Greenhouse food
I. Greenhouse non-food
J. Forestry
K. Residential
L. Indoor food
M. Indoor non-food
N. Indoor medical
O. Indoor residential
3. Bibliographic Citation (Column 3). If the Agency has acceptable data in its files, this
column lists the identifying number of each study. This normally is the Master Record
Identification (MRID) number, but may be a "GS" number is no MRID number has been
assigned. Refer to the Bibliography appendix for a complete citation of the study.
46
-------
Appendix B. Data Sup
New
Guideline
Number
Old
Guideline
Number
porting Guideline Requirements for the Reregistration of DDVP
Description
Use
Patterns
Citations
PRODUCT CHEMISTRY
830.1550
830.1600
830.1620
830.1670
830.1700
830.1750
830.1800
830.6302
830.6303
830.6304
830.6313
830.6367
830.6320
830.7000
830.7050
830.7200
830.7220
830.7300
830.7550
830.7840
830.7950
61-1
6 1-2 A
61-2B
61-2B
62-1
62-0
62-3
63-2
63-3
63-4
63-13
63-17
63-20
63-12
None
63-5
63-6
63-7
63-11
63-8
63-9
Product Identity and Composition
Description of materials used to
produce the product
Description of production process
Formation of Impurities
Preliminary Analysis
Certification of Limits
Analytical Method
Color
Physical State
Odor
Stability to normal and elevated
temperatures, metals, and metal ions
Storage Stability
Corrosion Characteristics
pH
UV/Visible Absorption
Melting Point
Boiling Point
Density
Partition coefficient, shake flask
method
Solubility
Vapor Pressure
All
All
Al
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
40798101
40798101
40798101
40798101
40798102
40798102
40798102
40798103
40798103
40798103
40798103, 41232401,
43890401
40798103
40798103
40798103
40798103
40798103
40798103
40798103
40798103
ENVIRONMENTAL TOXICITY
850.2100
850.2100
850.2200
850.2200
850.2300
850.2300
850.1075
850.1075
850.1075
850.1075
850.1010
850.1075
850.1025
850.1035
850.1300
850.1350
71-1A
71-1A
7 1-2 A
71-2B
7 1-4 A
71-4B
72-1A
72-1B
72-1C
72-1D
72-2A
72-3A
72-3B
72-3C
72-4
72-3D
72-3E
72-3F
72-4B
Avian Acute Oral Toxicity - Quail
Avian Acute Oral Toxicity - Duck
Avian Dietary Toxicity - Quail
Avian Dietary Toxicity - Duck
Avian Reproduction - Quail
Avian Reproduction - Duck
Fish Toxicity Bluegill
Fish Toxicity Bluegill - TEP
Freshwater Fish Toxicity Rainbow
Trout
Freshwater Fish Toxicity Rainbow
Trout - TEP
Freshwater Invertebrate Toxicity
Estuarine/Marine Toxicity - Fish
Estuarine/Marine Toxicity - Mollusk
Estuarine/Marine Toxicity - Shrimp
Freshwater Invertebrate Toxicity -
Chronic
Estuarine/Marine Toxicity - Fish, TEP
Estuarine/Marine Toxicity - Mollusk,
TEP
Estuarine/Marine Toxicity - Shrimp,
TEP
Estuarine/Marine Invertebrate Life
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
00160000, 40818301
00160000
00022923
00022923
43981701
44233401
40094602
43284701
40098001
43284702
40098001
43571403
43571404
43571405
43890301
43571406
43571407
43571408
43854301
47
-------
New
Guideline
Number
850.1400
850.3020
850.5400
Old
Guideline
Number
72-4
141-1
122-2
Description
Cycle
Freshwater Fish Early-Life Stage
Honey Bee Acute Contact
Aquatic Plant Growth
Use
Patterns
ALL
ALL
ALL
Citations
43788001
00036935
40228401=40098001
TOXICOLOGY
870.1100
870.1200
870.1300
870.2400
870.2500
870.3100
870.6100
870.3700
870.3700
870.3800
870.4100
870.4100
870.4200
870.4300
870.6100
870.6200
870.6300
870.7485
870.7600
870.8223
Non-
Guideline
Non-
guideline
81-1
81-2
81-3
81-4
81-5
82-1A
83-3A
83-3B
83-4
83-1A
83-1B
83-2B
83-5
82-5A
81-8
83-6
85-1
85-3
Human
Studies
Acute Oral Toxicity - Rat
Acute Dermal Toxicity - Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Skin Irritation
Subchronic Oral Toxicity: 90-Day
Study Rodent
Subchronic Neurotoxicity Study in Hens
Developmental Toxicity - Rat
Developmental Toxicity - Rabbit
2-Generation Reproduction - Rat
Chronic Feeding Toxicity Study - Rat
Chronic Feeding Toxicity Study - Non-
rodent
Carcinogenicity Mice
Combined Chronic
Toxicity/Carcinogenicity: Rats
Acute Delayed Neurotoxicity - Hen
Neurotoxicity Screening Battery
Developmental Neurotoxicity
General Metabolism
Dermal Penetration and Absorption
Time Course of Cholinesterase
Inhibition in Preweaning and Adult
Wistar Rats/870. 8223
Preliminary Developmental
Neurotoxicity - Rat
Multiple Oral Dosing on Erythrocyte
Cholinesterase Inhibition in Healthy
Male Volunteers
Cholinestrase Inhibition Following
Oral Administration to Healthy Male
Volunteers
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
00005467, 45805701,
45805702, 45805703,
45842301
00005467
00137239
00146921
00146920
41004701
41004702
41951501
41802401
42483901
41593101
00057695, 00632569,
40299401
40299401
43433501, 41004702
42958101,42655301
46153302, 46239801
41228701,41839901
41435201
46153303
46153301
44248801
44416201
ENVIRONMENTAL FATE
835.2120
835.2240
835.2410
835.4100
835.4200
835.1240
835.6100
161-1
161-2
161-3
162-1
162-2
163-1
164-1
Hydrolysis
Photodegradation - Water
Photodegradation - Soil
Aerobic Soil Metabolism
Anaerobic Soil Metabolism
Leaching/ Adsorption/Desorption
Terrestrial Field Dissipation
ALL
ALL
ALL
ALL
ALL
ALL
ALL
41723101
43326601
43642501
41723102
43835701
41723103,40034904,
41354105
44297701, 44386701
48
-------
New
Guideline
Number
Old
Guideline
Number
Description
Use
Patterns
Citations
RESIDUE CHEMISTRY
860.1000
860.1300
860.1300
860.1340
860.1340
860.1380
860.1500
860.1360
860.1460
170-1
171-4A
171-4B
171-4C
171-4D
171-4E
171-4K
171-4M
171-41
Reduction of Residue
Dried Beans
Cocoa Beans
Coffee Beans
Tomato
Meat, Eggs, Pasteurized Milk
Degradation - Packaged and Bagged
Raw and Processed Commodities
Degradation - Bulk Stored Raw and
Processed Commodities
Nature of Residue - Plants
Nature of Residue - Livestock
Residue Analytical Method - Plants
Residue Analytical Method - Livestock
Storage Stability
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
42910701
42910701
42910701
42910701
42910701
42858201
42903801
00013545, 00074844
00013546, 00066696,
00117261,00117262,
00126462, 00126463,
42721601,42951701
00042702, 00042704,
00042706, 00047472,
00049086, 00049971,
00049975,00051556,
00074706, 00074777,
00107572,00115993,
00117747,00118115,
00139845
00042702, 00042704,
00049086, 00049087,
00049975, 00060469,
00060470, 00060472,
00074706,00115939,
00115993,00117257,
00117747,00118113,
00118592,00118639,
00140392
00074776, 00076809,
00140392, 43377701,
Data Gap
Crop Field Trials
Radishes
Lettuce
Cucumbers
Mushrooms
Multiresidue Methods
Food Handling
A,B
A,B
A,B
A,B
A,B
00118572,00119536
00033139,00082271,
00118572,00119536
00082271, 00107572,
00118572
00074658,00117686,
00117690
42611001
Grain Processing and Manufacturing Establishments
Bulk Stored Raw and Processed
Commodities
Bulk stored peanuts
A,B
A,B
00117747,42916601
43003101
A,B
49
-------
New
Guideline
Number
860.1480
860.1520
Old
Guideline
Number
171-4J
171-4L
Description
Packaged and Bagged Raw and
Processed Commodities
Magnitude of Residue in Meat, Milk,
Poultry and Eggs
Use
Patterns
A,B
Citations
00056593, 00056595,
00056596, 42853701
Milk and the Fat, Meat, and Meat Byproducts of Cattle, Goats, Hogs, Horses,
and Sheep
Eggs and the Fat, Meat, and Meat
Byproducts of Poultry
Magnitude of Residue in Processed
Food/Feed
A,B
00118639,00119537,
00139843, 00139844,
43047901, Data Gap
Corn, field
Cottonseed
Rice
Peanuts
Soybeans
Wheat
Wheat
A,B
A,B
A,B
A,B
A,B
A,B
42993501
42993501
42952601
42993501
42993501
42993501
OCCUPATIONAL/RESIDENTIAL EXPOSURE
A,B
A,B
50
-------
APPENDIX C: Bibliography
1. 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.
2. 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.
3. 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.
4. 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.
b. 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
51
-------
document. When the date appears as (19??), the Agency was unable to
determine or estimate the date of the document.
c. 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.
Chemistry Bibliography
40798101 Feiler, W. (1988) DDVP: Product Identity and Composition. Unpublished
compilation prepared by Amvac Chemical Corp. 25 p.
40798102 Feiler, W. (1988) DDVP: Analysis and Certification of Product Ingredients.
Unpublished compilation prepared by Amvac Chemical Corp. 13 p.
40798103 Feiler, W. (1988) DDVP: Physical and Chemical Characteristics.
Unpublished study prepared by Amvac Chemical Corp. 3 p.
41232401 Feiler, W. (1988) Supplement to: Stability of Technical Grade DDVP.
Unpublished study prepared by Amvac Chemical Corp. 4 p.
43890401 Marsh, J. (1996) DDVP-Stability: Lab Project Number: 4506-95-0071-AS-
001: 4506-95-0071-AS-OOO: 4506-95-0071-AS. Unpublished study prepared
by Ricerca, Inc. 48 p.
Ecological Effects Bibliography
52
-------
00022923
00036935
00160000
40094602
40098001
40818301
43284701
43284702
43571403
43571404
43571405
43571406
Hill, E.F.; Heath, R.G.; Spann, J.W.; et al. (1975) Lethal Dietary Toxicities of
Environmental Pollutants to Birds: Special Scientific Report—Wildlife No.
191. (U.S. Dept. of the Interior, Fish and Wildlife Service, Patuxent Wildlife
Research Center; unpublished report)
Atkins, E.L.; Greywood, E.A.; Macdonald, R.L. (1975) Toxicity of Pesticides
and Other Agricultural Chemicals to Honey Bees: Labo- ratory Studies. By
University of California, Dept. of Entomology. UC, Cooperative Extension.
(Leaflet 2287; published study.)
Johnson, W.; Finley, M. (1980) Handbook of Acute Toxicity of Chemicals to
Fish and Aquatic Invertebrates: Resource Publi- cation 137. US Fish and
Wildlife Service, Washington, D.C. 106 p.
Mayer, F.; Ellersieck, M. (1986) Manual of Acute Toxicity: Interpretation and
Data Base for 410 Chemicals and 66 Species of Freshwater Animals. US Fish
& Wildlife Service, Resource Publication 160. 579 p.
Grimes, J.; Jaber, M. (1988) DDVP: An Acute Oral Toxicity Study with the
Bobwhite: Final Report: Project No. 246-102. Unpub- lished study prepared
by Wildlife International Ltd. 21 p.
Jones, F. (1994) DDVP 4-E Emulsifiable Concentrate: Acute Toxicity to
Bluegill (Lepomis machrochirus) under Flow-Through Test Conditions: Lab
Project Number: J9403007D. Unpublished study prepared by Toxikon
Environmental Sciences. 49 p.
Jones, F. (1994) DDVP 4-E Emulsifiable Concentrate: Acute Toxicity to
Rainbow Trout (Oncorhynchus mykiss) (sic) under Flow-Through Test
Conditions: Lab Project Number: J9403007E. Unpublished study prepared by
Toxikon Environmental Sciences. 49 p.
Jones, F.; Davis, J. (1994) DDVP Technical Grade: Acute Toxicity to
Sheep shead Minnow (Cyprinodon variegatus) Under Flow-through Test
Conditions: Lab Project Numbers: J9403007F: J9403007B. Unpublished
study prepared by Toxikon Environmental Sciences. 59 p.
Jones, F.; Davis, J. (1995) DDVP Technical Grade: Acute Effect on New
Shell Growth of the Eastern Oyster (Crassostrea virginica): Lab Project
Numbers: J9403007H: J9403007B. Unpublished study prepared by Toxikon
Environmental Sciences. 63 p.
Jones, F.; Davis, J. (1994) DDVP Technical Grade: Acute Toxicity to the
Mysid (Mysidopsis bahia) Under Flow-through Test Conditions: Lab Project
Numbers: J9403007G: J9403007B. Unpublished study prepared by Toxikon
Environmental Sciences. 61 p.
Jones, F.; Davis, J. (1994) DDVP 4-E Emulsifiable Concentrate: Acute
53
-------
43571407
43571408
43788001
43854301
43890301
43981701
44233401
Toxicity to Sheepshead Minnow, Cyprinodon variegatus, Under Flow-
through Test Conditions: Lab Project Numbers: J9403003I: J9403007B.
Unpublished study prepared by Toxikon Environmental Sciences. 60 p.
Jones, F.; Davis, J. (1994) DDVP 4-E Emulsifiable Concentrate: Acute Effect
on New Shell Growth of the Eastern Oyster (Crassostrea virginica): Lab
Project Numbers: J9403007K: J9403007C. Unpublished study prepared by
Toxikon Environmental Sciences. 58 p.
Jones, F.; Davis, J. (1994) DDVP 4-E Emulsifiable Concentrate: Acute
Toxicity to the Mysid, Mysidopsis bahia, Under Flow-through Test
Conditions: Lab Project Numbers: J9403007J: J9403007B. Unpublished
study prepared by Toxikon Environmental Sciences. 60 p.
Davis, J. (1995) DDVP Technical Grade: Toxicity to Embryos and Larvae of
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30, 1973 under 201-341; CDL: 001044-J)
Shell Chemical Co. (1971) The Results of Tests To Determine Whether
Vapona Insecticide Residues Are Incurred in Food Products De- rived from
Livestock Treated with Vapona, Including a Description of the Analytical
Methods Used. (Compilation; unpublished study received Sep 8, 1969 under
9F0788; CDL:091359-A)
Williams, M. (1992) Multiresidue Methods Testing for DDVP: DEGS
Column Chromatography (Method C) and Method D: Lab Project Number:
10029. Unpublished study prepared by Horizon Laboratories, Inc. 125 p.
Krautter, G. (1993) The Metabolism of (vinyl-1-(carbon 14)) DDVP in the
Lactating Goat Following Dermal Application for 3 Consecutive Days: Lab
Project Number: 1381: 498. Unpublished study prepared by PTRL East, Inc.
207 p.
Schofield, C. (1993) Magnitude of Residue for Dichlorvos in Food Handling
Establishments: Oat Processing Facility: Final Report: Lab Project Number:
SARS 92-14A: 40598. Unpublished study prepared by Stewart Agricultural
Research Services, Inc. and Analytical Bio-Chemistry Labs, Inc. 234 p.
Schofield, C. (1993) Magnitude of Residue for Dichlorvos in Food Handling
Establishments: Corn Processing Facility: Lab Project Number: SARS-92-
14C: SARS-92-IA-14C: 40628. Unpublished study prepared by Stewart Ag.
Research Services, Inc. and ABC Labs, Inc. 191 p.
Schofield, C. (1993) Magnitude of Residue for Dichlorvos in Nonperishable
Raw Agricultural Commodities and Processed Foods: Warehouse Storage on
Packaged and Bagged Commodities: Final Report: Lab Project Number:
SARS-92-16A. Unpublished study prepared by Stewart Agricultural
Research Services, Inc., Horizon Labs, Inc., and Analytical Bio-Chemistry
Labs, Inc. 493 p.
Schofield, C. (1993) Half-Life Determination of Dichlorvos in Nonperishable
Raw Agricultural Commodities and Processed Foods: Warehouse Storage of
Packaged and Bagged Commodities: Final Report: Lab Project Number:
SARS-92-16B. Unpublished study prepared by Stewart Pesticide
Registration Associates, Inc. 329 p.
Feiler, W. (1993) Magnitude of Residues for Dichlorvos in Animal Feed
Streams of Food Handling Establishments: Oat Processing Facility: Final
Report: Supplemental Study of Fines Stream: Lab Project Number: AMV 002
RES: 40658. Unpublished study prepared by ABC Labs. 74 p.
Schofield, C. (1993) Half-Life Determination of Dichlorvos in Nonperishable
Raw Agricultural Commodities and Processed Foods: Bulk Stored
Commodities: Final Report: Lab Project Number: SARS-93-17B.
64
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42910701
42910801
42910901
42916601
42951701
42952601
42993501
43003101
43037401
Unpublished study prepared by Stewart Agricultural Research Services, Inc.,
Horizon Labs., Inc., and Analytical Bio-Chemistry Labs., Inc. 338 p.
Williams, M. (1993) DDVP Residues in Uncooked and Cooked/Processed
Commodities: Meat, Eggs, Dry Beans, Milk, Cocoa Beans, Coffee Beans, and
Tomato Paste: Lab Project Number: 10043. Unpublished study prepared by
Horizon Laboratories, Inc. 133 p.
Schofield, C. (1993) Magnitude of Residue for Dichlorvos in Food Handling
Establishments: Oat Manufacturing Facility: Final Report: Lab Project
Number: SARS-92-14B: SARS-92-IA-14B: 40627. Unpublished study
prepared by Stewart Agricultural Research Services, Inc. and Analytical Bio-
Chemistry Labs, Inc. 204 p.
Schofield, C. (1993) Magnitude of Residue for Dichlorvos in Food Handling
Establishments: Wheat Manufacturing Facility: Final Report: Lab Project
Number: SARS-92-14D: 10038: SARS-92-IL-14D. Unpublished study
prepared by Stewart Agricultural Research Services, Inc. and Horizon Labs,
Inc. 309 p.
Schofield, C. (1993) Magnitude of Residue for Dichlorvos in Nonperishable
Raw Agricultural Commodities and Processed Foods: Bulk Stored
Commodities: Lab Project Number: SARS-93-17A. Unpublished study
prepared by Horizon Labs., Inc.; Analytical Bio-Chemistry Labs., Inc.;
Stewart Agricultural Research Services, Inc. 316 p.
Krautter, G. (1993) The Metabolism of (vinyl-1-(carbon 14))DDVP in Laying
Hens Following Dermal Application for 3 Consecutive Days: Lab Project
Number: 1536: 497. Unpublished study prepared by PTRL East, Inc. 204 p.
Hofen, J.; Warnke, J. (1993) Magnitude of Residue for Dichlorvos in
Processed Fraction of Peanuts: Field Test Site and Processing Laboratory:
Lab Project Number: SARS-92-13. Unpublished study prepared by Stewart
Agricultural Research Services, Inc.; Horizon Labs, Inc. 310 p.
Hofen, J.; Warnke, J. (1993) Magnitude of Residue for Dichlorvos in
Processed Fractions of Raw Agricultural Commodities: Field Corn, Wheat,
Rice, Cottonseed and Soybeans: Final Report: Lab Project Number: SARS-
93-18: SARS-93-MO-18: 10016. Unpublished study prepared by Horizon
Labs, Inc., Analytical Bio-Chemistry Labs, Inc. and Stewart Agricultural
Research Services, Inc. 581 p.
Hofen, J.; Warnke, J. (1993) Magnitude of Residue for Dichlorvos in Food
Handling Establishments: Bulk Stored Peanuts: Final Report: Lab Project
Number: SARS-92-12: SARS-92-GA-12: 10035. Unpublished study
prepared by Stewart Agricultural Research Services, Inc. and Horizon Labs,
Inc. 309 p.
March, K.; Noland, P.; Roesel, L.; et al. (1993) Magnitude of the Residue of
65
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Dichlorvos in Milk and Dairy Cow Tissues: Final Report: Lab Project
Number: 40872: M-9134-MB. Unpublished study prepared by ABC Labs,
Inc. 96 p.
43047901 March, K.; Noland, P.; Chickering, D. (1993) Magnitude of the Residues of
Dichlorvos in Eggs and Laying Hen Tissues: Lab Project Number: 40873: M-
9133. Unpublished study prepared by ABC Labs., Inc. 102 p.
43377701 Matheson, W. (1993) Amendment #1 of the Analytical Report for Magnitude
of Residue for Dichlorvos in Food Handling Establishments: Bulk Stored
Peanuts: Lab Project Number: 10035: SARS/92/12. Unpublished study
prepared by Horizon Lab., Inc. 10 p.
Exposure Bibliography
45870701 Jacobs, L; Driver, J.; Pandian, M. (2003) Residential Exposure Joint Venture:
National Pesticide Use Survey-Design, Implementation, Analysis Methods and
Results: Lab Project Number: 03-REJV-4M-001: 030-REJV-4M-001: 8D.
Unpublished study prepared by NFO WorldGroup and infoscientific.com, Inc. 8515 p.
46099001 Jacobs, L.; Driver, J.; Pandian, M. (2003) Residential Exposure Joint Venture
National Pesticide Use Survey - Design, Implementation, Analysis Methods and
Results. Project Number: 03/REJV/12M/002. Unpublished study prepared by NFO
Worldgroup and lnfoscientific.com, Inc. 155 p.
66
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APPENDIX D: Technical Support Documents
Additional documentation in support of this RED is maintained in the OPP docket EPA-HQ-
OPP-2002-0302. This docket may be accessed in the OPP docket room located at Room S-4900,
One Potomac Yard, 2777 S. Crystal Drive, Arlington, VA. It is open Monday through Friday,
excluding Federal holidays, from 8:30 a.m. to 4:00 p.m. All documents may be viewed in the
OPP docket room or downloaded or viewed via the Internet at the following site:
http://www.regulations.gov.
The Agency documents in the docket include:
1. Dichlorvos (DDVP) HED Chapter of the Reregistration Eligibility Decision Document (RED)
2. Weight of Evidence Comparison of Human and Animal Toxicology Studies and Endpoints
for DDVP
3. Ethical Review of DDVP Human Study
4. Response to AMVAC's pre-Phase 5 error only comments on the DDVP human health effects
risk assessments
5. Response to Public Comments on the Dichlorvos (DDVP) Preliminary Risk Assessment
6. Drinking Water Assessment for Dichlorvos (Revised)
7. Summary of HED's Reviews of Outdoor Residential Exposure Task Force (ORETF)
Chemical Handler Exposure Studies; MRID 44972201. ORETF Study
Numbers OMA001, OMA002, OMA003, OMA004., DP Barcode 261948,
memo dated April 30, 2001.
8. Memorandum: Review of Poison Control Center Data Call In. To Joshua First, December 5,
1994. US EPA.
9. Review of Comments on Dichlorvos Incidences. Memo to D. Utterback. May 17, 1996.
10. Determination of the Quantity of Carbaryl Removed by Petting Dogs Wearing 16% Carbaryl
Dog Collars: Lab Project Number: TR-506. Unpublished study prepared by Zoecon Industries,
Inc. 14 p. (OPPTS 875.1500} MRID 45792201.
11. DDVP (Vapona) QUA, Memorandum to D. Pillitt (RD) dated October 2, 1985.
12. Dichlorvos (084001). Anticipated Residues for Dichlorvos resulting from use of Dichlorvos
andNaled. June 15, 1998.
67
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12. Dichlorvos (084001). Refined Anticipated Residues and Dietary Exposure and Risk for
Residues of Dichlorvos resulting from use of Dichlorvos, Trichlorfon, and Naled. June 7, 2000.
13. Assessment of Exposures of Residents to Dichlorvos Applied as a Total Release Fogger.
May 10, 1993.
14. Review of Exposure Monitoring Study for Use of DDVP in Food Processing
Establishments, DP Barcode D191571, December 6, 1993.
15. Exposures from Dichlorvos (DDVP) Resin Strips. D246131. March 5, 1998.
16. Re-entry Exposures to Dichlorvos Resulting from Application to Residential Turf and
Recreational Areas. D246126. March 16, 1998.
17. Exposures to Dichlorvos (DDVP) from Flea Collars. March 18, 1998.
18. Exposure Assessment for Dichlorvos (DDVP) Applied to Greenhouse and Mushroom
Houses. April 22, 1998.
19. Exposure to Dichlorvos resulting from the Use of Bait Products. D246128. April 28, 1998.
20. Inhalation Exposures from Dichlorvos (DDVP) Resin Strips. June 12, 1998.
21. Revised Applicator Exposures to Dichlorvos resulting from Crack and Crevice Use and the
Use of Aerosol Products. D261140. April 30, 1998.
22. Revisions of Exposures from Dichlorvos (DDVP) Resin Strips. D250069. September 30,
1998.
23. Exposures to Dichlorvos Resulting from the Use of Bait Products. D251336. January 27,
1999.
24. Response to Comments from EXPOSAC on Exposure Assessment for Dichlorvos (DDVP)
from Flea Collars. D 246127. November 6, 1998.
25. Response to EXPOSAC Comments on Exposure Assessment for Total Release Foggers
Containing Dichlorvos (DDVP). D251333. December 31, 1998.
26. Revised Applicator Exposures to Dichlorvos (DDVP) Resulting from Dairy Barn and
Animal Spray Uses. D251330. January 27, 1999.
27. Response to Comments from the EXPOSAC and Others on Assessment of Re-entry
Exposures to Dichlorvos Resulting from Application to Residential Turf and Recreation Areas.
D251909. January 28, 1998.
68
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28. Revised Exposure Assessment for Greenhouses and Mushroom Houses. D251337. January
27, 1999.
29. Response to Amvac Comments on HED Interim Risk Assessment for DDVP. D255064.
March 17, 1999.
30. Examination of Recent Submissions from Amvac regarding Dichlorvos (DDVP) and
Rationale for Not Including Them in the Exposure/Risk Assessment. May 27, 1999.
31. Dislodgeable Foliar Residues and Exposure Assessment for Residential/Recreational Turf
Applications of Dichlorvos (DDVP), PC Code 084001, Barcodes D248456, D248596, D255253,
August 13, 1999.
32. Calculation Error - Dichlorvos Resin Strips, D257002, August 16, 1999.
33. Dichlorvos (DDVP) Resin Strip Exposure Assessment for Individuals Exposed for a 2 Hour
Period, PC Code 084001. July 21, 2000.
34. Revision of Exposure Assessment for DDVP applied to Warehouses and Food Processing
Plants. D226572. June 7, 2000.
35. Response to Comments on the Preliminary Risk Assessment (PRA) for Dichlorvos (PC
Code 084001, DP Barcode D271993). May 31,2001.
36. Addendum to Residential Turf Assessment for Dichlorvos (DDVP) PC Code 084001, DP
Barcode D288914. March 28, 2003.
37. Review of Protocol for Study Monitoring Indoor Air Concentrations of DDVP Using Pest
Strips in Confined and Unoccupied Areas. DP Barcode D288575. March 14, 2003.
38. Exposure Assessment for Workers Applying DDVP to Rail Cars and Stationary Trucks and
Subsequently Loading Cargo onto the Treated Vehicles (PC Code 084001, DPBarcode
D289191), January 27, 2005.
39. HED's Revision of the Trichlorfon Residential Exposure/Risk Assessment. PC Code
057901. DP Barcode D268125. August 9, 2000.
40. Vapona (DDVP) Exposure Potential to Workers in Mushroom houses in Ventura County,
California in 198l.HS-861.
41. Trichlorfon (057901): HED Revised Preliminary Risk Assessment for Trichlorfon. DP
Barcode D268728. Case 0104. September 19, 2000.
42. Dichlorvos (DDVP)- Report of the Cancer Assessment Review Committee, March 7, 2000.
69
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43. Benchmark dose analysis of cholinesterase inhibition data in neonatal and adult rats (MRID
no. 46688914) following exposure to DDVP PC Code: 084001. DP Barcode DP
328793. TXRNo. 0054223 June 9, 2006
44. Qualitative Assessment of Dichlorvos (DDVP) in Drinking Water and Volatilization from
Use of Trichlorfon Turf, May 18, 2006
45. Biological and Economic Analysis of Dichlorvos in Greenhouses
46. Biological and Economic Analysis of Residential Indoor Use of Dichlorvos
47. Biological and Economic Analysis of Dichlorvos for Residential Outdoor Pests
48. Biological and Economic Analysis of Dichlorvos for Pet Collars
49. Biological and Economic Analysis of Dichlorvos for Bulk Stored Commodities
50. Biological and Economic Analysis of Dichlorvos in Mushroom Houses
51. Biological and Economic Analysis of Dichlorvos for Food Storage Areas
52. Request for Voluntary Cancellations and Amended Registrations; Letter from Amvac
Chemical Corp. to EPA, May 9, 2006
53. Petition to Conclude Special Review, Reregistration, and Tolerance Reassessment Process
and to Revoke All Tolerances and Cancel All Registrations for the Pesticide DDVP, Filed June
2, 2006
70
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APPENDIX E: Generic Data Call-In
Note that a Data Call-In (DCI), with all pertinent instructions, will be sent to the registrants.
71
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APPENDIX F: Product Specific Data Call-In
Note that a Data Call-In (DCI), with all pertinent instructions, will be sent to the registrants.
72
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APPENDIX G: EPA's Batching of DDVP 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 DDVP as the 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 that the Agency is not describing
batched products as "substantially similar" since some products within 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. Notwith-standing the batching process, the Agency reserves the right to
require, at any time, acute toxicity data for an individual product should the 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 a batch, or to generate all the required
acute toxicological studies for each of their own products. If a 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 a
registrant chooses to rely upon previously submitted acute toxicity data, he/she may do so
provided that the data base is complete and valid by today's 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,
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.
73
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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 a registrant supplies the data to support a
batch of products, he/she must select 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 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.
Ninety eight products were found which contain DDVP as the active ingredient.
These products have been placed into twenty batches and a No Batch group in
accordance with the active and inert ingredients and type of formulation.
Batching Instructions:
Batch 1A: Products listed in this Batch may cite data from Batch 1.
Batch 3: EPA Reg. Nos. 769-632 and 61483-75 may not cite data generated with lower
percentage a.i. products within this batch.
Batch 4: EPA Reg. Nos. 5481-73 and 5481-334 may not cite data generated with lower
percentage a.i. products within this batch
Batch 10: EPA Reg. No. 2517-37 may not cite data generated with lower percentage a.i.
products within this batch.
Batch 13: EPA Reg. No. 769-924 must conduct own primary eye irritation study.
Batch 15: EPA Reg. Nos. 769-640, 5481-9, & 47000-43 may not cite data generated
with EPA Reg. No. 769-568.
No Batch: Each product in this Batch should generate their own data.
NOTE: The technical acute toxicity values included in this document are for
informational purposes only. The data supporting these values may or may not meet the
current acceptance criteria.
Page 74 of 338
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Batch 1
EPA Reg. No.
5481-461
5481-462
Percent Active Ingredient
98.0
98.0
Batch 1A
EPA Reg. No.
769-629
5481-96
5481-200
19713-353
19713-356
Percent Active Ingredient
90.00
93.00
90.00
90.00
90.09
Batch 2
EPA Reg. No.
769-727
769-795
5481-202
47000-137
Percent Active Ingredient
50.0
50.0
50.0
50.0
Batch 3
EPA Reg. No.
655-692
769-632
5481-204
47000-17
61483-75
Percent Active Ingredient
41.76
44.50
41.10
44.50
40.20
Batch 4
EPA Reg. No.
769-625
769-627
769-798
2217-291
5481-73
5481-205
5481-334
47000-135
47000-138
51036-55
Percent Active Ingredient
23.70
23.70
23.70
24.60
25.00
24.62
25.24
23.70
23.68
23.70
Batch 5
EPA Reg. No.
5481-338
5481-344
5481-348
Percent Active Ingredient
18.6
18.6
18.6
Page 75 of 338
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5481-475
18.6
Batch 6
EPA Reg. No.
655-492
47000-130
Percent Active Ingredient
18.6
18.5
Batch 7
EPA Reg. No.
2217-463
5481-207
5481-208
Percent Active Ingredient
15.0
15.0
15.0
Batch 8
EPA Reg. No.
769-796
5481-41
Percent Active Ingredient
12.50
13.01
Batch 9
EPA Reg. No.
8730-50
65458-6
Percent Active Ingredient
10.0
10.0
Batch 10
EPA Reg. No.
2517-37
5481-341
5481-343
5481-346
Percent Active Ingredient
9.6
9.0
9.0
9.0
Batch 1 1
EPA Reg. No.
9444-32
19713-344
Percent Active Ingredient
7.0
7.0
Batch 12
EPA Reg. No.
1015-68
5481-220
47000-74
Percent Active Ingredient
5.0
5.0
5.0
Batch 13
EPA Reg. No.
769-924
6218-57
Percent Active Ingredient
5.37
5.00
Page 76 of 338
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67517-38
4.65
Batch 14
EPA Reg. No.
2517-38
5481-342
5481-345
5481-347
Percent Active Ingredient
4.7
4.7
4.7
4.7
Batch 15
EPA Reg. No.
769-568
769-640
5481-9
47000-43
Percent Active Ingredient
0.47
1.00
1.00
1.00
Batch 16
EPA Reg. No.
655-702
47000-23
47000-52
Percent Active Ingredient
0.93
0.50
1.00
Batch 17
EPA Reg. No.
228-103
2217-332
47000-114
Percent Active Ingredient
0.93
1.00
1.00
Batch 18
EPA Reg. No.
19713-306
19713-354
Percent Active Ingredient
1.0
1.0
Batch 19
EPA Reg. No.
4-159
47000-129
47000-136
Percent Active Ingredient
0.5
1.0
0.5
Batch 20
EPA Reg. No.
572-246
769-797
Percent Active Ingredient
DDVP: 0.230
Pyrethrin: 0.034
Piperonyl Butoxide: 0.277
DDVP: 1.000
Page 77 of 338
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4866-3
47000-108
47000-112
Pyrethrin: 0.300
Piperonyl Butoxide: 0.500
DDVP: 0.500
Pyrethrin: 0.050
Piperonyl Butoxide : 0.100
DDVP: 0.465
Pyrethrin: 0.025
Piperonyl Butoxide: 0.025
DDVP: 1.000
Pyrethrin: 0.010
Piperonyl Butoxide : 0.100
No Batch
EPA Reg. No.
769-628
769-644
769-821
1327-36
5011-49
5481-13
5481-201
5481-203
5481-206
5481-340
6218-21
6959-98
8536-40
8536-41
19713-357
47000-2
47000-54
47000-71
47000-131
Percent Active Ingredient
50.000
DDVP: 1.000
Malathion: 1.500
4.980
12.740
9.800
0.500
80.000
50.000
20.000
DDVP: 0.500
Pyrethrin: 0.030
Piperonyl Butoxide: 0.060
MGK264: 0.102
10.000
18.600
4.650
7.440
20.000
DDVP: 0.500
Phenothrin: 0.200
d-trans Allethrin: 0.323
DDVP: 0.500
Pyrethrin: 0.050
Piperonyl Butoxide : 0.100
MGK264: 0.160
MGK326: 0.200
18.600
DDVP: 0.500
Pyrethrin: 0.100
Piperonyl Butoxide: 0.400
Page 78 of 338
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51036-5
61483-50
61483-79
65458-5
33.7
DDVP: 5.300
Tetrachlorvinphos: 23.000
19.200
6.980
Page 79 of 338
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Appendix H: List of Registrants Sent Data Call-Ins
BONIDE PRODUCTS, INC.
NUFARM AMERICAS INC.
VALUE GARDEN SUPPLY LLC
PRENTISS INC
VALUE GARDENS SUPPLY, LLC
DOUGLAS PRODUCTS AND
PACKAGING COMPANY
FULLER SYSTEM, INC.
PBI/GORDON CORP
SERGEANT'S PET CARE
PRODUCTS, INC.
INTAGRA, INC.
AIRE-MATE INC
AMVAC CHEMICAL CORP
SUMMIT CHEMICAL CO
CESSCOINC
SOIL CHEMICALS CORPORATION
ABERDEEN ROAD COMPANY
WATERBURY COMPANIES INC
DREXEL CHEMICAL CO
CHEM-TECH LTD
MICRO-FLO COMPANY LLC
CALIFORNIA DEPT. OF FOOD AND
AGRICULTURE
KMG-BERNUTH INC
PLATO INDUSTRIES, LTD
PM RESOURCES INC
JOHN WISE & ASSOCIATES, LTD
REGGUIDE
STEVEN E. ROGOSHESKE
TECHNOLOGY SCIENCES CROUP, INC.
6301 SUTLIFF ROAD ORISKANY
150 HARVESTER DRIVE SUITE 200 BURR RIDGE
PO Box 585 ST. JOSEPH
C.B.2000 FLORAL PARK
PO Box 585 SAINT JOSEPH
PO Box 1295 LIBERTY
PO Box 3053 WOBURN
PO Box 014090 1217 WEST 12TH STREET KANSAS CITY
509 TOWER VALLEY DRIVE HILLSBORO
16719IREDALE PATH LAKEVILLE
PO Box 406 WESTFIELD
4695 MACARTHUR COURT, SUITE 1250 NEWPORT BEA(
235 S KRESSON STREET BALTIMORE
3609A RIVER RD JOHNS ISLAND
PO Box 782 HOLLISTER
PO Box 435 EMIGSVILLE
PO Box 640129 CALHOUN STREET INDEPENDENCE
PO Box 133271700 CHANNEL AVENUE MEMPHIS
1479 W POND RD EAGAN
530 OAK COURT DRIVE MEMPHIS
1220 N STREET SACRAMENTO
10611 HARWIN DRIVE, #402 HOUSTON
115018TH STREET, NW, SUITE 1000 WASHINGTON
13001 ST. CHARLES ROCK RD BRIDGETON
Page 80 of 338
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Appendix I: List of Available Related Documents and Electronically Available
Forms
Pesticide Registration Forms are available at the following EPA internet site:
http ://www. epa. gov/opprdOO 1 /forms/.
Pesticide Registration Forms (These forms are in PDF format and require the Acrobat
reader)
Instructions:
1. Print out and complete the forms. (Note: Form numbers that are bolded can be
filled out on your computer then printed.)
2. The completed form(s) should be submitted in hardcopy in accord with the
existing policy.
3. Mail the forms, along with any additional documents necessary to comply with
EPA regulations covering your request, to the following address for the Document
Processing Desk.:
Document Processing Desk (distribution code)*
Office of Pesticide Programs (7504P)
Environmental Protection Agency
1200 Pennsylvania Ave, NW
Washington, DC 20460-0001
* Distribution Codes are as follows:
(APPL) Application for product registration
(AMEND) Amendment to existing registration
(CAN) Voluntary Cancellation
(EUP) Experimental Use Permit
(DIST) Supplemental Distributor Registration
(SLN) Special Local Need
(NEWCO) Request for new company number
(NOTIF) Notification
(PETN) Petition for Tolerance
(XFER) Product Transfer
DO NOT fax or e-mail any form containing "Confidential Business Information" or
"Sensitive Information."
If you have any problems accessing these forms, please contact Nicole Williams at (703)
308-5551 or by e-mail at williams.nicole@epamail.epa.gov. If you want these forms
mailed or faxed to you, please contact Lois White, white.lois@epa.gov or Floyd Gayles,
gayles.floyd@epa.gov.
If you have any questions concerning how to complete these forms, please contact OPP's
ombudsperson for conventional pesticide products: Linda Arrington, (703) 305-5446
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The following Agency Pesticide Registration Forms are currently available via the
Internet at the following locations:
8570-1
8570-4
8570-5
8570-17
8570-25
8570-27
8570-28
8570-30
8570-32
8570-34
8570-35
8570-36
8570-37
Application for Pesticide
Regi stration/ Amendment
Confidential Statement of Formula
Notice of Supplemental Registration of
Distribution of a Registered Pesticide
Product
Application for an Experimental Use
Permit
Application for/Notification of State
Registration of a Pesticide To Meet a
Special Local Need
Formulator's Exemption Statement
Certification of Compliance with Data
Gap Procedures
Pesticide Registration Maintenance
Fee Filing
Certification of Attempt to Enter into
an Agreement with other Registrants
for Development of Data
Certification with Respect to Citations
of Data (in PR Notice 98-5)
Data Matrix (in PR Notice 98-5)
Summary of the Physical/Chemical
Properties (in PR Notice 98-1)
Self-Certification Statement for the
Physical/Chemical Properties (in PR
Notice 98-1)
http://www.epa.sov/opprd001/forms/8570-l.pdf
http://www.epa.sov/opprd001/forms/8570-4.pdf
http://www.epa.sov/opprd001/forms/8570-5.pdf
http://www.epa.sov/opprd001/forms/8570-17.pdf
http://www.epa.sov/opprd001/forms/8570-25.pdf
http://www.epa.sov/opprd001/forms/8570-27.pdf
http://www.epa.sov/opprd001/forms/8570-28.pdf
http://www.epa.sov/opprd001/forms/8570-30.pdf
http://www.epa.sov/opprd001/forms/8570-32.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
5.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
5.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
l.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
l.pdf
Pesticide Registration Kit http://www.epa.gov/pesticides/registrationkit/
Dear Registrant:
For your convenience, we have assembled an online registration kit which
contains the following pertinent forms and information needed to register a pesticide
product with the U.S. Environmental Protection Agency's Office of Pesticide Programs
(OPP):
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1. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal
Food, Drug and Cosmetic Act (FFDCA) as Amended by the Food Quality
Protection Act (FQPA) of 1996.
2. Pesticide Registration (PR) Notices
a. 83-3 Label Improvement Program-Storage and Disposal Statements
b. 84-1 Clarification of Label Improvement Program
c. 86-5 Standard Format for Data Submitted under FIFRA
d. 87-1 Label Improvement Program for Pesticides Applied through Irrigation
Systems (Chemigation)
e. 87-6 Inert Ingredients in Pesticide Products Policy Statement
f 90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement
g. 95-2 Notifications, Non-notifications, and Minor Formulation Amendments
h. 98-1 Self Certification of Product Chemistry Data with Attachments (This
document is in PDF format and requires the Acrobat reader.)
Other PR Notices can be found at http://www.epa.gov/opppmsdl/PR_Notices.
3. Pesticide Product Registration Application Forms (These forms are in PDF format
and will require the Acrobat reader.)
a. EPA Form No. 8570-1, Application for Pesticide Registration/Amendment
b. EPA Form No. 8570-4, Confidential Statement of Formula
c. EPA Form No. 8570-27, Formulator's Exemption Statement
d. EPA Form No. 8570-34, Certification with Respect to Citations of Data
e. EPA Form No. 8570-35, Data Matrix
4. General Pesticide Information (Some of these forms are in PDF format and will
require the Acrobat reader.)
a. Registration Division Personnel Contact List
b. Biopesticides and Pollution Prevention Division (BPPD) Contacts
c. Antimicrobials Division Organizational Structure/Contact List
d. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data
Requirements (PDF format)
e. 40 CFR Part 156, Labeling Requirements for Pesticides and Devices (PDF
format)
f. 40 CFR Part 158, Data Requirements for Registration (PDF format)
g. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27,
1985)
Before submitting your application for registration, you may wish to consult some
additional sources of information. These include:
1. The Office of Pesticide Programs' Web Site
2. The booklet "General Information on Applying for Registration of Pesticides in
the United States", PB92-221811, available through the National Technical
Information Service (NTIS) at the following address:
National Technical Information Service (NTIS)
5285 Port Royal Road
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Springfield, VA 22161
The telephone number for NTIS is (703) 605-6000.
3. The National Pesticide Information Retrieval System (NPIRS) of Purdue
University's Center for Environmental and Regulatory Information Systems. This
service does charge a fee for subscriptions and custom searches. You can contact
NPIRS by telephone at (765) 494-6614 or through their website.
4. The National Pesticide Telecommunications Network (NPTN) can provide
information on active ingredients, uses, toxicology, and chemistry of pesticides.
You can contact NPTN by telephone at (800) 858-7378 or through their website:
http://npic.orst. edu
The Agency will return a notice of receipt of an application for registration or
amended registration, experimental use permit, or amendment to a petition if the
applicant or petitioner encloses with his submission a stamped, self-addressed
postcard. The postcard must contain the following entries to be completed by
OPP:
• Date of receipt
• EPA identifying number
• Product Manager assignment
Other identifying information may be included by the applicant to link the
acknowledgment of receipt to the specific application submitted. EPA will stamp
the date of receipt and provide the EPA identifying File Symbol or petition
number for the new submission. The identifying number should be used whenever
you contact the Agency concerning an application for registration, experimental
use permit, or tolerance petition.
To assist us in ensuring that all data you have submitted for the chemical are
properly coded and assigned to your company, please include a list of all
synonyms, common and trade names, company experimental codes, and other
names which identify the chemical (including "blind" codes used when a sample
was submitted for testing by commercial or academic facilities). Please provide a
CAS number if one has been assigned.
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APPENDIX J: Dichlorvos (DDVP) HED Chapter of the Reregistration Eligibility
Decision Document (RED)
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33
\
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
June 22, 2006
MEMORANDUM
SUBJECT: Dichlorvos (DDVP) HED Chapter of the Reregistration Eligibility
Decision Document (RED). PC Code: 084001, Case #: 0310, DP
Barcode: D330262
Regulatory Action: Phase 5 Reregistration
Risk Assessment Type: Single Chemical/Aggregate
FROM: Susan V. Hummel, Chemist, Branch Senior Scientist
Reregistration Branch IV
Health Effects Division (7509C)
and
William Dykstra, Ph. D., Toxicologist
David Hrdy, Biologist
David Jaquith, Industrial Hygienist
Reregistration Branch IV
Health Effects Division (7509C)
THROUGH: Ray Kent, Ph. D., Branch Chief
Reregistration Branch IV
Health Effects Division (7509C)
TO: Eric Olson, CRM #61
Special Review Branch
Special Review and Reregistration Division (7508C)
Attached please find the revised Human Health Risk Assessment for dichlorvos
(DDVP). The Risk Assessment uses some endpoints based on human studies, found to
be in compliance with the human studies rule. This document has been revised to address
error only comments provided by the registrant (AMVAC). Additionally, on May 9,
2006, AMVAC requested voluntary cancellation and/or amendments, through
incorporation of terms and conditions to current dichlorvos registrations. These
modifications are summarized below:
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Voluntary deletion of the following:
Product Types
1. 100 gram (g) pest strip
2. 21 g pest strip (contingent on the granting of registration for 16 g pest strip)
3. Total release fogger
Use Patterns
4. Lawn, Turf, and Ornamentals
5. Crack and Crevice
Application Method
6. Mushroom house hand held fogger
7. Greenhouse hand held fogger
8. Warehouse hand held fogger
Label Amendments
Occupational Exposure ~ Applicators
1. Mushroom house Hose End Sprayer — add coveralls to personal protective equipment
requirements.
Occupational ~ Post Application
2. Mushroom houses - 18 hour re-entry interval (REI)
3. Greenhouse —12 hour REI
Pest Strips
Registrant will split its end use registrations so that there will be one end use label for the
large pest strips (65 g & 80 g) and another for the small pest strips (10.5 g, 5.25 g, and a
new 16 g)
65 and 80 g pest strips
Label language to read:
"For use in unoccupied areas; not for use in homes except garages, attics, crawl spaces,
and sheds occupied for less than 4 hours per day.
Also for use in boathouses, museum collections, animal buildings, and milk rooms, or
enclosed areas thereof, occupied for less than 4 hours per day.
For use in unoccupied areas such as trash dumpsters, catch basins, bulk raw grain bins,
storage bins, insect traps, enclosed utility boxes, and storage units. Also for use in non-
perishable packaged and bagged and bulk stored processed and raw agricultural
commodities (including soybeans, corn, grains, cocoa beans and peanuts).
Also for use in the following unoccupied structures, provided they are unoccupied for
more than 4 months immediately following placement of a pest strip: vacation homes,
cabins, mobile homes, boats, farm houses, and ranch houses."
16 g (new), 10.5 g, 5.25 g pest strips
Label language to read:
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"Within homes, use only in closets, wardrobes, and cupboards. Also for use in storage
units, garages, attics, crawl spaces, boathouses, museum collections, garbage cans, trash
dumpsters, animal buildings, milk rooms, catch basins, bulk raw grain, and storage bins."
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Table of Contents
1.0 Executive Summary 91
1.1 Use and Major Formulations 91
1.2 Regulatory History 91
1.3 Hazard Identification and Dose-Response Assessment 93
1.4 Exposure/Risk Assessment and Risk Characterization 94
1.5 Human Studies 95
2.0 Ingredient Profile 96
2.1 Summary of Registered/Proposed Uses 97
2.2 Structure and Nomenclature 117
2.3 Physical and Chemical Properties 117
3.0 Metabolism Assessment 119
3.1 Comparative Metabolic Profile 119
3.2 Nature of the Residue in Foods 119
3.2.1. Description of Primary Crop Metabolism 119
3.2.2 Description of Livestock Metabolism 119
3.2.3 Description of Rotational Crop Metabolism, including
identification of major metabolites and specific routes of biotransformation 120
3.3 Environmental Degradation 120
3.4 Summary of Residues for Tolerance Expression and Risk Assessment 122
4.0 Hazard Characterization/Assessment 122
4.1 Hazard Characterization 122
4.2.1 Adequacy of the Toxicity Data Base 128
4.2.2 Evidence of Neurotoxicity 128
4.2.3 Developmental Toxicity Studies 128
4.2.4 Reproductive Toxicity Study 128
4.2.5 Pre-and/or Postnatal Toxicity 128
4.3 Hazard Identification and Toxicity Endpoint Selection 130
4.3.1. Acute Reference Dose (aRfD) 130
4.3.2. Chronic Reference Dose (cRfD) 132
4.3.3. Incidental Oral Exposure (Short and Intermediate Term) 133
4.3.4. Dermal Absorption 133
4.3.5. Dermal Exposure (Acute) 134
4.3.6. Dermal Exposure (Short- and Intermediate- Term) 134
4.3.7. Inhalation Exposure (Acute) 134
4.3.8. Inhalation Exposure (Short and Intermediate Term) 134
4.3.9. Inhalation Exposure (Long Term) 135
4.3.10. Margins of Exposure 135
4.3.11. Recommendation for Aggregate Exposure Risk Assessments 136
4.3.12. Classification of Carcinogenic Potential 136
4.4 FQPA Safety factor 139
4.5. Endocrine Disruption 140
5.0 Public Health Data 141
5.1 Incident Reports 141
5.2 Other 141
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6.0 Exposure Characterization/Assessment 143
6.1 Dietary Exposure/Risk Pathway 143
6.1.1 Residue Profile 143
6.1.2 Acute and Chronic Dietary Exposure and Risk 147
6.2 Water Exposure/Risk Pathway 152
6.3 Residential (Non-Occupational) Exposure/Risk Pathway 159
6.3.1 Home Uses 159
6.3.2 Recreational Uses 164
6.3.3 Other (Spray Drift, etc.) 164
7.0 Aggregate Risk Assessments and Risk Characterization 169
7.1 Acute Aggregate Risk 170
7.2 Short-Term Aggregate Risk 171
7.3 Intermediate-Term Aggregate Risk 173
7.4 Long-Term Aggregate Risk 173
7.5 Aggregate Cancer Risk 173
8.0 Cumulative Risk Characterization/Assessment 174
9.0 Occupational Exposure/Risk Pathway 175
10.0 Data Needs and Label Requirements 189
10.1 Toxicology 189
10.3 Residue Chemistry 189
10.4 Occupational and Residential Exposure 189
REFERENCES 191
Appendices 200
1.0 Toxicology Data Requirements
2.0 Toxicology Studies
3.0 Residue Chemistry Data Requirements
4.0 Tolerance Reassessment
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1.0 Executive Summary
The Health Effects Division (HED) has conducted a human health risk assessment for the
active ingredient dichlorvos (2,2-dichlorovinyl dimethyl phosphate), also known as DDVP, for
the purposes of making a reregistration eligibility decision. Cumulative risk assessment
considering risks from other pesticides or chemical compounds having a common mechanism of
toxicity is not addressed in this document. This risk assessment updates the Phase 3 Preliminary
Human Health Risk Assessment, dated August 9. 2000, addresses the Public Comments
submitted in accordance with Phase 3 of the Tolerance Reassessment Advisory Committee
(TRAC) Organophosphate (OP) Pilot Process, and additional error correction comments on a
June 14, 2005 assessment, and uses endpoints based on human studies for some scenarios. The
intentional dosing, human toxicity study used in this risk assessment has been reviewed by
EPA's Human Studies Review Board (HSRB), on April 5, 2006, as required by EPA's Human
Subjects Protections rule, 40 CFR part 26 (effective April 7, 2006). Exposures and risks for all
exposure scenarios have been recalculated. Exposure to dichlorvos from the use of naled and
trichlorfon (which metabolize to dichlorvos) is included in this document.
1.1 Use and Major Formulations
Dichlorvos is an organophosphate insecticide and fumigant registered for use in
controlling flies, mosquitos, gnats, cockroaches, fleas, and other insect pests. Formulations of
dichlorvos include pressurized liquids, granulars, emulsifiable concentrates, total release
aerosols, and impregnated materials. Dichlorvos is applied with aerosols and fogging
equipment, with spray equipment, and through slow release from impregnated materials, such as
resin strips and pet collars.
Dichlorvos is registered to control insect pests on agricultural sites; commercial,
institutional and industrial sites; and for domestic use in and around homes (i.e., resin strips) and
on pets. Dichlorvos is used preplant in mushroom houses, and postharvest in storage areas for
bulk, packaged and bagged raw and processed agricultural commodities, food
manufacturing/processing plants, animal premises, and non-food areas of food-handling
establishments. It is also registered for direct dermal treatment of cattle and poultry, and swine,
sheep, and goats.
The mechanism of pesticidal action of dichlorvos is inhibition of cholinesterase. The
Agency has determined that the adverse effects caused by dichlorvos that are of primary concern
to human health are neurological effects related to inhibition of cholinesterase activity.
1.2 Regulatory History
The Agency initiated a Special Review for pesticide products containing dichlorvos on
February 24, 1988, by publishing Position Document 1 (PD 1). At that time, the Agency was
concerned that exposure to dichlorvos from registered uses posed an unreasonable carcinogenic
risk and that there were inadequate margins of exposure for cholinesterase inhibition and liver
effects to exposed individuals. After evaluation of information submitted through the Special
Review Process, the Agency conducted another risk assessment for dichlorvos. In 1995, the
Agency concluded that dichlorvos posed carcinogenic risks of concern to the general population
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from dietary exposure. The Agency also concluded in 1995 that dichlorvos posed risks of
concern for cholinesterase inhibition to residents and to individuals mixing, loading, and
applying this pesticide, as well as to those reentering treated areas. Subsequently, the Agency
issued a Preliminary Determination to Cancel Certain Registrations and Draft Notice of Intent to
Cancel the dichlorvos uses which posed the greatest risks, also called Position Document 2/3 or
PD 2/3 (60 FR 50338, September 28, 1995). In its 1995 Preliminary Determination (PD 2/3),
the Agency concluded that the risks outweighed the benefits for most uses of dichlorvos and,
therefore, recommended a variety of measures to reduce those risks. The Agency proposed
cancellation of certain uses of dichlorvos and cancellation of other uses unless certain labeling
modifications were made to reduce risk.
The PD 2/3 Federal Register Notice provided for a formal comment period, which closed
on December 28, 1995. Comments were received, and are contained in a public docket
identified as "OPP-30000/56." Major comments to the PD 2/3 were submitted to the Agency by
Amvac Chemical Corporation, the Japanese Resin Strip Manufacturer's Association, grower
groups, and the general public. Some of the comments contained additional data pertaining to
the risks posed by dichlorvos.
The Agency has also identified newer exposure and toxicity data pertaining to dichlorvos
that have become available since publication of the Notice of Preliminary Determination to
Cancel certain Registrations and Draft Notice of Intent to Cancel (PD 2/3). In addition to the
newer data and information described above, the Food Quality Protection Act of 1996 has
effectively modified the considerations the Agency uses to assess the risks of pesticides.
Therefore, the Agency has re-evaluated the toxicology and exposure databases for dichlorvos to
make a determination of potential special susceptibility of infants and children, as mandated by
FQPA. In addition, the Agency has reviewed new information pertaining to dietary exposure
and performed a refined dietary exposure assessment. The Agency has also refined the
occupational and residential exposure assessment for dichlorvos with new information and new
methodologies that were previously unavailable.
The following issues pertaining to the ongoing dichlorvos risk assessment were presented
to the FIFRA Science Advisory Panel (SAP) on July 28, 1998: (1) the selection of an FQPA
safety factor for dichlorvos and (2) how the Agency conducted the resin strip exposure
assessment.
This risk assessment has been conducted for dichlorvos in conjunction with the public
review and comment process for all of the organophosphate pesticides. The public process for
dichlorvos was initiated on December 3, 1998, when the Phase 1 risk assessment was provided to
the registrant for "error only" review. In Phase 2 of the OP pilot process, the error correction
comments from the registrant were incorporated. On October 11, 2000, the Preliminary Risk
Assessment for dichlorvos was issued for public comment. This revision incorporates Agency
response to the public comments submitted in Phase 3 of the OP pilot process. Comments on the
dichlorvos Preliminary Risk Assessment were received from Amvac, NRDC, and dichlorvos
users. Additional exposure analyses were conducted for different sizes of resin strips and for pet
collars. Comments were received from a second registrant "error correction" comment period
and from the HSRB from an April 5, 2006 meeting.
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1.3 Hazard Identification and Dose-Response Assessment
The toxicology database for dichlorvos is complete with respect to the OPPTS Guideline
requirements. For acute toxicity, technical dichlorvos was placed in Toxicity Categories II, I and
II, respectively, for the oral, dermal and inhalation routes and in Toxicity Category III and IV for
eye and dermal irritation, respectively. Dichlorvos did not cause organophosphate induced
delayed neurotoxicity (OPIDN) in the hen following single or multiple (28 days) exposures.
Following a single oral dose to rats, dichlorvos was associated with a variety of neurological and
physiological changes. Subchronic and chronic oral exposures in rats and dogs as well as
chronic inhalation exposure in rats resulted in significant decreases in plasma, red blood cell
and/or brain cholinesterase activity. The carcinogenic potential of dichlorvos has been classified
as "suggestive" under the 1999 Draft Agency Cancer Guidelines and no quantitative assessment
of cancer risk is required. There was no evidence of increased susceptibility following in utero
exposures to rats and rabbits as well as pre/post natal exposure to rats. Also, there was no
evidence of abnormalities in the development of the fetal nervous system in the
frbrlopmrnysl/neurotoxicity studies submitted to the Agency.
The toxicity endpoints used in this document to assess risks include acute and chronic
dietary reference doses (RfDs), and short-, intermediate- and long-term dermal LOAELs and
inhalation no observed adverse affect levels (NOAELs). Endpoints based on human studies
have been used to assess some scenarios.
Inhibition of cholinesterase activity was the toxicity endpoint selected for acute and
chronic dietary, as well as, short term, intermediate term, and long term (chronic) occupational
and residential risk assessments. The Uncertainty Factor(s) ranged from 30 to 100 depending on
the route and duration of exposures.
The HED dichlorvos team evaluated the hazard and exposure data to determine if the
FQPAlOx safety factor should be retained, reduced or removed focusing primarily on the
following points: 1) the standard developmental and reproductive toxicity studies and the
developmental neurotoxicity study submitted to the Agency showed no residual concern for
increased susceptibility of rats, or rabbits to in utero and/or postnatal exposure to dichlorvos; 2)
in single dose (acute) studies with dichlorvos in rats, there were no differences with respect to
either RBC or brain cholinesterase inhibition between preweaning and adult rats; 3) in repeated
dose studies with dichlorvos in rats, young rats were no more sensitive than adult rats with
respect to inhibition of RBC and brain cholinesterase; and 4) sufficient data were available to
ensure that the dietary (food and drinking water) and non-dietary (residential) risk assessments
do not underestimate potential exposures and risks for infants and children from the use of
dichlorvos. Some scenarios used endpoints ased on a LOAEL, and the 3x uncertainty factor
used is considered part of the FQPA safety factor.
The dichlorvos team determined that there no residual concerns for increased
susceptibility of infants and children. An FQPA safety factor of Ix is considered appropriate.
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1.4 Exposure/Risk Assessment and Risk Characterization
Dietary exposure to dichlorvos residues may occur as a result of use of dichlorvos on or
at a variety of sites, including mushroom houses, bulk-stored and packaged or bagged
nonperishable processed and raw food, commercial food processing plants, direct dermal pour-
on treatment to livestock, and livestock premises treatment. Two other pesticides, naled and
trichlorfon, degrade to dichlorvos through plant and animal metabolism and other processes.
Residues of dichlorvos from the use of naled on crops are included in the dichlorvos dietary
exposure assessment. All trichlorfon field crop food uses have been canceled and associated
tolerances revoked; therefore, the Agency does not expect measurable dichlorvos residues from
use of trichlorfon on field crops. The trichlorfon tolerances on livestock commodities remain;
dermal use on beef cattle is supported as an import use. Non-detectable dichlorvos residues in
livestock commodities are expected as a result of trichlorfon use, and dichlorvos was not a
significant metabolite in the trichlorfon dermal metabolism study. Therefore, dietary (food)
exposure to dichlorvos residues resulting from use of trichlorfon is considered negligible for the
purposes of this risk assessment.
Most product and residue chemistry data requirements for dichlorvos have been fulfilled.
However, the reregistration data requirements for storage stability (Guideline 860.1380), for
meat, milk, poultry, and egg studies (Guideline 860.1480), and directions for use (Guideline
860.1200) have not been fulfilled.
Dietary (food only) exposure estimates for dichlorvos have been refined with residue data
from USDA's Pesticide Data Program (PDF), FDA surveillance monitoring data and FDA Total
Diet Study (TDS) data. Anticipated residues for dichlorvos have been revised to incorporate
these residue data. The acute and chronic dietary exposure analyses for dichlorvos (including
contribution from naled and negligible contribution from trichlorfon) were conducted using the
Dietary Exposure Evaluation Model (DEEM™) software. Acute dietary exposure did not
exceed the Agency's level of concern for the 99.9th percentile of the population. Chronic dietary
exposure did not exceed 2% of the cPAD for all subpopulations, which is below the Agency's
level of concern of 100%.
The Environmental Fate and Effects Division (EFED) evaluated the potential for
dichlorvos to contaminate water from the use of dichlorvos, naled or trichlorfon. EFED has
limited ground water monitoring data for dichlorvos, naled, and trichlorfon from the states of
California and Hawaii in the "Pesticides in Groundwater" database. These data indicate that
naled, dichlorvos, or trichlorfon have not been detected in groundwater; however, these data
were not targeted to the pesticide use area. Therefore, the SCIGROW model was used to
estimate concentrations of dichlorvos, naled, and trichlorfon in groundwater. OPP does not have
any surface monitoring data on the concentrations of dichlorvos, naled, or trichlorfon at the
present time. Therefore, the Tier II screening models PRZM and EXAMS with the Index
Reservoir and Percent Crop Area adjustment (IR-PCA PRZM/EXAMS) were used to estimate
surface water concentrations for dichlorvos resulting from the use of naled, trichlorfon and
dichlorvos.
Although PDF water monitoring data were available, and all samples had non-detectable
residues (LODs ranged from 6 to 22.5 ppt), these data were not considered sufficiently
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representative. In the absence of sufficient water monitoring data, estimated drinking water
concentrations (EDWCs) of dichlorvos from the use of dichlorvos, naled, and trichlorfon in
water were compared with Drinking Water Levels of Comparison (DWLOCs) for acute or
chronic systemic toxicity. EDWCs of dichlorvos in ground and surface water were derived from
conservative screening level models. A DWLOC is a theoretical upper limit on a pesticide's
concentration in drinking water in light of total aggregate exposure to a pesticide in food,
drinking water, and through residential uses. HED uses DWLOCs internally in the risk
assessment process as a surrogate measure of potential exposure associated with pesticide
exposure through drinking water.
Residential and occupational exposure scenarios can be described as acute, short term (1-
30 days), intermediate term (1 month to 6 months), and long term or chronic (6 months to a
lifetime). The dichlorvos residential exposure scenarios for aerosol spray cans (both homeowner
application and post-application) are considered acute exposure scenarios. Lawn post-
application from treatment with trichlorfon is considered a short-term exposure scenario. Resin
pest strips and pet flea collars are long term exposure scenarios. Occupational exposure
scenarios are typically acute or short-term, except for a few intermediate term occupational
exposure scenarios, applications in mushroom houses and direct application to livestock.
Exposure assessments for a number of occupational and residential scenarios were
derived from limited data from the scientific literature, textbooks, knowledge of cultural
practices, and the Residential SOPs (U.S. EPA, 1997a). Other estimates, particularly in the
residential environment, were derived from surrogate data from the Pesticide Handlers Exposure
Database (PHED, version 1.1), chemical specific data included in the Outdoor Residential
Exposure Task Force (ORETF) database, Residential Exposure Joint Venture (REJV) data, and
additional chemical specific monitoring data, including biomonitoring of a urinary metabolite, in
combination with models and literature studies.
Residential exposure scenarios do not exceed the Agency's level of concern. Residential
exposure from the use of the pressurized aerosol has been recalculated due to new data from the
Residential Exposure Joint Venture (REJV).
Residential and occupational exposures to dichlorvos may also result from uses of naled
and trichlorfon. The only naled residential use is a mosquitocide public health use. For this use,
the application rate of naled is very low, and we expect that any dichlorvos formed dissipates
rapidly. Further discussion is found in the exposure assessment section of this document.
Approximately 25% of trichlorfon is expected to degrade to dichlorvos at the pH of a typical
lawn.
None of the aggregate risks exceed our level of concern, considering food, water, and
residential exposures, for all residential exposure scenarios. Food and water exposure were very
small compared to the residential exposure estimates.
Occupational handler scenarios do not exceed the Agency's level of concern, after
voluntary cancellations, addition of additional PPE, and longer reentry intervals (REIs).
1.5 Human Studies
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This risk assessment relies in part on data from studies in which adult human subjects were
intentionally exposed to a pesticide or other chemical. These studies, listed below, have been
determined to require a review of their ethical conduct, and EPA is currently preparing these
ethics reviews in accordance with EPA Human Subjects Protections rule, 40 CFR part 26.
Gledhill, A., 1997. Dichlorvos: A Single Blind, Placebo Controlled, Randomised Study
to Investigate the Effects of Multiple Oral Dosing on Erythrocyte Cholinesterase
Inhibition in Healthy Male Volunteers: Lab Project Number: CTL/P/5392: XH6063.
Unpublished study prepared by Zeneca Central Toxicology Lab. 52 p. MRID 44248801.
Emlay, D.; Rudolph, R. (1977) Determination of the Quantity of Carbaryl Removed by
Petting Dogs Wearing 16% Carbaryl Dog Collars: Lab Project Number: TR-506.
Unpublished study prepared by Zoecon Industries, Inc. 14 p. (OPPTS 875.1500} MRID
45792201.
Klonne, D. (1999) Integrated Report for Evaluation of Potential Exposures to
Homeowners and Professional Lawn Care Operators Mixing, Loading, and Applying
Granular and Liquid Pesticides to Residential Lawns: Lab Project Number: OMAOO5:
OMAOO1: OMAOO2. Unpublished study prepared by Ricerca, Inc., and Morse
Laboratories. 2213 p. (MRID 44972201) (ORETF study)
McDonald, E., 1991. Indoor Fogger Dermal and Inhalation Exposure Study with DDVP:
Lab Project Number: 4-02-333. Unpublished study prepared by British Columbia
Research Corp. 331 p. MRID 41928801.
The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1.
Electronic Database. Task Force members Health Canada, U. S. Environmental
Protection Agency, and the National Agricultural Chemicals Association, released
February, 1995.
In addition, the Human Subjects Protections rule requires that the Gledhill study - an
intentional dosing, human toxicity study on which EPA is relying in this risk assessment - be
reviewed by the Human Studies Review Board (HSRB). The Agency presented the Gledhill
study to the HSRB at a meeting on April 2-4, 2006. The HSRB discussed the Gledhill study
extensively during this meeting and has prepared a draft written report summarizing its
discussions. The Agency believes that the oral comments of the HSRB and the draft report
provided a sufficient indication of the conclusions likely to appear in the HSRB's final report
that EPA could confidently move ahead. Accordingly, the Agency has decided to issue this risk
assessment prior to receiving the final written report of the HSRB. The Agency will carefully
review the HSRB's final report on DDVP prior to issuing its final reregistration eligibility
decision to determine whether the HSRB's report contains conclusions that warrant
reconsideration of this risk assessment
2.0 Ingredient Profile
Page 96 of 338
-------
Dichlorvos is a chlorinated organophosphorus insecticide, with technical and
manufacturing use products registered to Amvac Chemical Corporation and Drexel Chemical
Company. Formulations and EPA Reg. Nos. are summarized below in table 2.0.
Table 2.0. Registered Manufacturing-Use Products of Dichlorvos, as described in OPPIN.
Formulation
93% T
98% T 1'2
98% T 1'2
90% Fl 3
EPA Reg. No.
5481-96
5481-461
5481-462
19713-353
Registrant
Amvac Chemical Corporation
Drexel Chemical Company
Repackaged from an EPA-registered product. We note that there is not another EPA registered
product containing 98% dichlorvos. This discrepancy must be cleared up.
2 OPPIN currently identifies this product as an Fl; however, it is correctly identified as a T.
3 Sequentially transferred from EPA Reg. Nos. 8521-126, 904-396, and 44215-139.
T = Technical Product Fl = Formulation intermediate
2.1 Summary of Registered/Proposed Uses
The basic producer of dichlorvos is Amvac Chemical Corporation. According to an
OPPIN search, conducted on 6/12/06, there are 98 active end-use products (EPs) registered under
FIFRA Section 3 containing dichlorvos, 29 of which are registered to Amvac; there is one
Special Local Need (SLN) registration under FIFRA Section 24(c) associated with these Amvac
EPs, and one Special Local Need (SLN) registration under FIFRA Section 24(c) associated with
another EP. The registered food and feed use patterns of dichlorvos EP labels subject to
reregistration are presented in table 2.1. Residential use patterns are discussed in Section 6 of
this document. Occupational use patterns are discussed in Section 9 of this document. In
addition, Amvac submitted copies of two product labels for the technical formulation (EPA Reg.
Nos. 5481-461 and 5481-462) which include directions for use for various sites.
Page 97 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Application Rate, ai
Use Directions and Limitations
Formulation
[EPA Reg.
No.]
Agricultural commodities (bulk storage of nonperishable raw and processed agricultural commodities including raw grains, corn, soybeans, cocoa
beans, and peanuts)
20% Impr Use of product where unwrapped food is stored or allowing the strip to come in contact
[5481-338] with food or cooking utensils is prohibited.
Use in kitchens, restaurants, or areas where food/feed are prepared or processed, use in
food/feed processing or food/feed manufacturing areas of food/feed processing and
food/feed manufacturing plants are prohibited.
Use in kitchens, restaurants, or areas where food is prepared or served and use in edible
product areas of food processing plants are prohibited.
Premise treatment
20% Impr
[5481-344]
20% Impr
[5481-348]
Greenhouses (not containing food commodities)
Fog application
[hand-held fogger is no
longer permitted]
10.5 g of product/
50-100 cu. ft
or
80 g of product/
900-1200 cu. ft
0.37 Ib/gal
EC
[5481-220]
Applications may be made using a cold aerosol generator. Hand held foggers are no
0.004 lb/1,000 cu. ft longer permitted.
Mushroom houses
Fog application
[hand-held fogger is no
longer permitted]
Brush on /coarse spray
Tobacco Warehouse:
50% FIC
[5481-203]
0.37 Ib/gal
EC
[5481-220]
2 Ib/gal EC
[72-365]
(canceled)
Applications may be made in 1,1,1-trichloroethane using a cold aerosol generator.
2% finished spray Applications may be made twice a week during spawn run; thereafter use as needed. ^
[6.25 oz/10,000 cu.ft] 1-day PHI has been established for mushrooms.
2% finished spray
[10 oz/10,000 cu.ft] Applications may be made in deodorized base kerosene using a cold aerosol generator.
Applications may be made twice a week during spawn run; thereafter use as needed. ^
5 g/10,000 cu.ft 1-day PHI has been established for mushrooms.
0.004 lb/1,000 cu.ft
0.00125 lb/100sq ft
Applications may be made using a cold aerosol generator. Applications may be made
twice a week during spawn run; thereafter use as needed.
Coarse spray or paint on walls, around doors, ventilators & cracks before mushrooms
come into production. Use as 0.5% solution - 1 pint of 0.5% solution per 100 sq ft., up to
10 days before crop emerges on soil beds. Do not spray inside walls after mushrooms
appear on beds. After mushrooms appear, spray only the outside of the building.
Page 98 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Space treatment in
closed warehouses
[Hand-Held Foggers are
no longer permitted]
Formulation
[EPA Reg.
No.]
1.59lb/gal
EC
[5481-206]
4 Ib/gal EC
[5481-204]
1.15 Ib/gal
SC
[5481-207]
8.39 Ib/gal
SC
[5481-201]
0.37 Ib/gal
EC
[5481-220]
Application Rate, ai
Use Directions and Limitations
2% finished spray
[ 19-38 fl.oz/10,000
cu.ft]
or
10-20 g/10,000 cu. ft
0.37 lb/336,000 cu.ft
Fogging applications may be made with odorless oil or other non-flammable oil solvents
known to be safe for use in tobacco warehouses. Applications may be repeated as
needed. Applications may be made only in warehouses storing unfinished tobacco.
Fogging applications may be repeated as needed. Applications may be made only in
warehouses storing unfinished tobacco.
Food-handling establishments (including households; restaurants; theaters; food processing plants; industrial plants; and warehouses)
Applications may be made with deodorized base oil or water using a low pressure
sprayer to treat localized areas where insects may infest around baseboards, cracks,
walls, doors, window frames, and localized areas of floors. Use in edible product areas
of food processing plants, restaurants, or other areas where food is commercially
prepared or processed and use in serving areas while food is exposed is prohibited
Indoor treatment
Directed spray
application
4 Ib/gal EC
[5481-204]
0.5% finished spray
Application made by timer when buildings are unoccupied. Building should be closed
Indoor treatment 20% PrL 2.5 g/1000 cu. ft. and ventilation kept to a minimum. Lock all entrances, and do not allow unprotected
Remote Fog Application [47000-71] workers to enter the building when being treated.
Food-handling establishments (including theaters; food processing plants; industrial plants; and warehouses)
Page 99 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Indoor treatment
Space spray application
[Hand-Held Foggers are
no longer permitted]
Formulation
[EPA Reg.
No.]
0.37 Ib/gal
EC
[5481-220]
1.59 Ib/gal
EC
[5481-206]
4 Ib/gal EC
[5481-204]
1.15 Ib/gal
SC
[5481-207]
2 Ib/gal SC
[5481-334]
Application Rate, ai
Use Directions and Limitations
8.39 Ib/gal
SC
[5481-201]
1% finished spray
[1 gal/64,000 cu.ft]
Fogging or misting applications may be made with deodorized base oil or water using
fogging or misting equipment to treat indoor areas. Applications are to be made when
the plants are not in operation. Food should be removed and food-handling equipment
covered prior to application or washed with suitable cleaner and potable water after
application.
Food-handling establishments [including areas for receiving, storage, packing (canning, bottling, wrapping, boxing), preparing, edible waste storage,
and enclosed processing systems (mills, dairies, edible oils, syrups), and serving areas]
0.25 Ib/gal
EC
[5481-217] Applications may be made in water or oil and may be applied by directing small amounts
into crack and crevices, in points between different elements of construction, and
Indoor crack and crevice 0.5 Ib/gal EC between equipment legs and bases. Applications in food areas other than crack and
treatment [5481-216] 0.1% finished spray crevice treatments are prohibited.
Nonfood/feed areas of food-handling establishments [including garbage rooms, lavatories, floor drains (sewers), entries and vestibules, offices,
locker rooms, machine rooms, boiler rooms, garages, mop closets, and storage (after canning or bottling)]
Page 100 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Indoor treatment
Directed spray
application
Formulation
[EPA Reg.
No.]
0.37 Ib/gal
EC
[5481-220]
1.59 Ib/gal
EC
[5481-206]
1.15 Ib/gal
SC
[5481-207]
2 Ib/gal SC
[5481-334]
8.39 Ib/gal
SC
[5481-201]
4.48 Ib/gal
SC
[5481-202]
10 Ib/gal SC
[5481-200]
Application Rate, ai
0.5% finished spray
0.5% finished spray
0.5% finished spray
Use Directions and Limitations
Applications may be made with deodorized base oil or water using a low pressure
sprayer to treat localized areas where insects may infest around baseboards, cracks,
walls, doors, window frames, and localized areas of floors. Use in edible product areas
of food processing plants, restaurants, or other areas where food is commercially
prepared or processed and use in serving areas while food is exposed are prohibited.
Applications may be made with deodorized base oil using a low pressure sprayer to treat
localized areas where insects may infest around baseboards, cracks, walls, doors,
window frames, and localized areas of floors. Use in food/feed handling areas of
food/feed handling establishments, restaurants or other areas where food is
commercially prepared or served and use to treat non-perishable bagged or bulk raw or
processed commodities is prohibited.
For use in warehouses, silos, bulk bins, and food/feed processing, food/feed
manufacturing, handling and storage plants containing non-perishable, packaged or
bagged raw or processed food/feed commodities or bulk raw or processed food
commodities. Applications may be made with deodorized base oil using a low pressure
sprayer to treat localized areas where insects may infest around baseboards, cracks,
walls, doors, window frames, and localized areas of floors. Use of this product in food
processing plants, food-handling areas of restaurants, or areas where food is prepared or
served, and use to treat non-perishable bagged and or bulk stored raw or processed
agricultural commodities are prohibited. Contamination of food, water, food containers,
or cooking utensils is prohibited.
Nonfood/feed areas of food-handling establishments [including garbage rooms, lavatories, floor drains (sewers), entries and vestibules, offices,
locker rooms, machine rooms, boiler rooms, garages, mop closets, and storage (after canning or bottling)]
Page 101 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Indoor spot treatment
Indoor treatment
Space spray application
[Hand-Held Foggers are
no longer permitted]
Formulation
[EPA Reg.
No.]
0.25 Ib/gal
EC
[5481-217]
0.5 Ib/gal EC
[5481-216]
1.16 Ib/gal
EC
[5481-208]
0.5% RTU
[5481-240]
4.48 Ib/gal
SC
[5481-202]
Application Rate, ai1
0.1% finished spray
0.5% finished spray
0.5% spray
1% finished spray
[1 gal/64,000 cu.ft]
Use Directions and Limitations
Applications may be made in water or oil and may be applied as a coarse spray or with a
paint brush to areas where pests hide (baseboard areas, around water pipes, surfaces
behind and beneath sinks, lockers, tables, pallets, and similar areas). Applications may
be repeated as needed. Use of this product in edible product areas of food processing
plants, restaurants, or other areas where food is commercially prepared or processed
and use in serving areas where food is exposed are prohibited.
Applications may be made in water and may be applied to areas where pests hide
(around baseboards, cracks, walls, door and window frames and localized areas of
floors). Use of this product in food processing plants, food-handling areas of restaurants,
or areas where food is prepared or served, and use to treat non-perishable bagged and
or bulk stored raw or processed agricultural commodities are prohibited. Contamination
of food, water, food containers, or cooking utensils is prohibited.
Applications may be made with a pump sprayer to areas where pests hide (dark corners
of room and closets, cracks and crevices in walls, behind and beneath sinks, stoves,
refrigerators, cabinets, washing machines, cupboards, bookcases, and around
baseboards). Use of this product in food areas of food-handling establishments,
restaurants, or other areas where food is commercially prepared or processed and use in
serving areas where food is exposed or while facility is operating are prohibited.
Fogging or misting applications may be made with deodorized base oil using fogging or
misting equipment to treat indoor areas. Use in bottling plants, food contact areas or
meat slaughter, and/or packing plants or in frozen food plants is prohibited.
Nonfood/feed areas of food-handling establishments [including garbage rooms, lavatories, floor drains (sewers), entries and vestibules, offices,
locker rooms, machine rooms, boiler rooms, garages, mop closets, and storage (after canning or bottling)] (continued)
For use in warehouses, silos, bulk bins, and food/feed processing, food/feed
manufacturing, handling and storage plants containing non-perishable, packaged or
bagged raw or processed food/feed commodities or bulk raw or processed food
commodities. Fogging or misting applications may be made with deodorized base oil
using fogging or misting equipment to treat indoor areas. Use in bottling plants, food
contact areas or meat slaughter, and/or packing plants or in frozen food plants is
prohibited. When using in food processing, handling, and storage areas: (I) applications
may be made only during times when plant is not in operation and no food products are
exposed; if bulk, unpackaged food is exposed, it must be removed or covered prior to
treatment; (ii) all food processing surfaces should be covered during treatment or
thoroughly cleaned before using.
Indoor treatment
Space spray application
[Hand-Held Foggers are
no longer permitted]
10 Ib/gal SC
[5481-200]
1% finished spray
[1 gal/64,000 cu.ft]
Page 102 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Formulation
[EPA Reg.
No.]
0.5% PrL
Indoor premise treatment [5481-340]
20% Impr
[5481-344]
Farm buildings (including animal shelters,
stables, and other farm buildings)
Premise treatment
Directed spray
application
1 Ib/gal EC
[5481-41]
2 Ib/gal EC
[5481-73]
0.37 Ib/gal
EC
[5481-220]
2 Ib/gal EC
[5481-205]
Application Rate, ai
Use Directions and Limitations
Use as a space spray is prohibited. Applications may be applied to areas where pests
hide (cracks, around baseboards, cabinets, walls, and woodwork) and repeated as
necessary. Use of this product in edible product areas of food processing plants,
restaurants, or other areas where food is commercially prepared or processed and use to
treat non-perishable bagged and or bulk stored raw or processed agricultural
commodities are prohibited. Contamination of utensils, food, water, and foodstuffs
prohibited.
Use in kitchens, restaurants, or areas where food/feed are prepared or processed, use in
food/feed processing or food/feed manufacturing areas of food/feed processing and
food/feed manufacturing plants are prohibited.
Animal Uses (Premises)
barns, around feed lots, dairy barns, milk sheds, loafing pens, pig pens, poultry houses, hog barns,
0.5% spray
10.5 g of product/
50-100 cu. ft
0.5% finished spray
[1 qt/1,000sq.ft]
0.5% finished spray
[1 qt/1,000sq.ft]
Applications may be made as a coarse, wet spray to all exterior and interior surfaces,
treating window sills, around doors, fences, and ledges or as a directed spray to floors,
baseboards, crack and crevices in wall, and along base of walls. Applications may be
made using water- or oil-based sprays; applications may be repeated as necessary. A 1-
day preslaughter interval (PSI) has been established.
Applications may be made as a coarse, wet spray to surfaces, treating window sills,
doorways, feed storage rooms, and alleyways. Applications may be made using water;
applications may be repeated as necessary. Animals must be removed prior treatment.
Application in areas where animals have received a direct application of DDVP within the
past 8 hours is prohibited.
Applications may be made as a coarse, wet spray to surfaces, treating window sills,
doorways, feed storage rooms, and alleyways. Applications may be made using water;
applications may be repeated as necessary. Animals may be present during treatment.
Contamination of water, feed or foodstuffs, milk or milking utensils is prohibited.
Farm buildings (including animal shelters, barns, around feed lots, dairy barns, milk sheds, poultry houses, hog barns, stables, and other farm
buildings) (continued)
4 Ib/gal EC
[5481-204]
0.5% finished spray
[1 qt/1,000sq.ft]
Page 103 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Premise treatment
Directed spray
application
Formulation
[EPA Reg.
No.]
1.16lb/gal
EC
[5481-208]
1.59lb/gal
EC
[5481-206]
1.15lb/gal
SC
[5481-207]
4.48 Ib/gal
SC
[5481-202]
8.39 Ib/gal
SC
[5481-201]
10 Ib/gal SC
[5481-200]
Application Rate, ai
Premise treatment
Space spray application
[Hand-Held Foggers are
no longer permitted]
0.5% finished spray
[1 qt/1,000sq.ft]
1% finished spray
[0.5 qt/8,000 cu.ft]
or
0.5% finished spray
[1 qt/8,000 cu.ft]
Use Directions and Limitations
Applications may be made as a coarse, wet spray to surfaces, treating window sills,
doorways, feed storage rooms, and alleyways. Applications may be made using diesel
oil or water; applications may be repeated as necessary. Direct treatment of animals or
humans and contamination of water, feed or foodstuffs, milk or milking utensils are
prohibited.
Fog applications may be made using diesel oil. Animals must be removed prior to
treatment. Prior to application, reduce air movement as much as possible by closing
2 Ib/gal EC 0.5% finished spray doors, windows, and other openings. Application in areas where animals have received
[5481-73] [1 qt/8,000 cu.ft] a direct application of DDVP within the past 8 hours is prohibited.
Farm buildings (including animal shelters, barns, around feed lots, dairy barns, milk sheds, poultry houses, hog barns, stables, and other farm
buildings) (continued)
Page 104 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Premise treatment
Space spray application
[Hand-Held Foggers are
no longer permitted]
Premise treatment
Formulation
[EPA Reg.
No.]
0.37 Ib/gal
EC
[5481-220]
1.16 Ib/gal
EC
[5481-208]
1.59 Ib/gal
EC
[5481-206]
2 Ib/gal EC
[5481-205]
4 Ib/gal EC
[5481-204]
1.15 Ib/gal
SC
[5481-207]
4.48 Ib/gal
SC
[5481-202]
8.39 Ib/gal
SC
[5481-201]
10 Ib/gal SC
[5481-200]
[5481-9]
Farm buildings (including animal shelters,
buildings) (continued)
Application Rate, ai
Use Directions and Limitations
1% finished spray
[0.5 qt/8,000 cu.ft]
or
0.5% finished spray
[1 qt/8,000 cu.ft]
0.04 oz/1,000 sq.ft
Fog applications may be made using diesel oil. Animals must be removed prior to
treatment. Prior to application, reduce air movement as much as possible by closing
doors, windows, and other openings. Application in areas where animals have received
a direct application of DDVP within the past 8 hours is prohibited. Contamination of
water, feed or foodstuffs, milk or milking utensils is prohibited.
Bait applications may be made to clean floor areas, ground areas outside enclosures,
window sills, or other areas where flies congregate. Applications are to be made in such
a manner that stock cannot come into contact with bait.
barns, around feed lots, dairy barns, milk sheds, poultry houses, hog barns, stables, and other farm
Page 105 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Formulation
[EPA Reg.
No.]
Application Rate, ai
Premise treatment
Space spray application
[Hand-Held Foggers are 1 Ib/gal EC 1% finished spray
no longer permitted] [5481-41] [0.5 qt/8,000 cu.ft]
Animal buildings (including horse barns, calf parlors, hog parlors,
Premise treatment
20% Impr
[5481-338]
20% Impr
[5481-344]
[5481-348]
Milk rooms (including bulk storage rooms)
10.5 g of product/
50-100 cu. ft
10.5 g of product/
50-100 cu. ft
Premise treatment
10.5 g of product/
50-100 cu. ft
20% Impr
[5481-338]
20% Impr
[5481-344]
[5481-348]
Feed lots, stockyards, corrals, and holding pens
0.5% finished spray
Outdoor premise 1 Ib/gal EC [5 gal/A]
treatment [5481-41]
10.5 g of product/
50-100 cu. ft
Use Directions and Limitations
Fog applications may be made with animals present, provided a direct animal treatment
of DDVP has not been made in the past 8 hours. Applications may be made using water
or deodorized kerosene. Prior to application, reduce air movement as much as possible
by closing doors, windows, and other openings.
stables, poultry houses, tack rooms, and dog kennels)
Contamination of water, food or foodstuffs, milk or milking equipment is prohibited. Use
of product where unwrapped food is stored or allowing the strip to come in contact with
food or cooking utensils is prohibited.
Contamination of water, food or foodstuffs, milk or milking equipment is prohibited.
Contamination of milk or milking equipment is prohibited. Use of product where
unwrapped food is stored or allowing the strip to come in contact with food or cooking
utensils is prohibited.
Contamination of milk or milking equipment is prohibited.
Applications may be made as an overall mist spray to fences, feed bunkers, shade areas,
spillage areas, building walls, and other areas where flies congregate. Applications may
be made in water using a mist blower or similar equipment at 3- to 14-day intervals.
Page 106 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Formulation
[EPA Reg.
No.]
0.37 Ib/gal
EC
[5481-220]
1.16 Ib/gal
EC
[5481-208]
1.59 Ib/gal
EC
[5481-206]
2 Ib/gal EC
[5481-205]
4 Ib/gal EC
[5481-204]
1.15 Ib/gal
SC
[5481-207]
4.48 Ib/gal
SC
[5481-202]
8.39 Ib/gal
SC
[5481-201]
10 Ib/gal SC
[5481-200]
Application Rate, ai
0.2 Ib/A
Use Directions and Limitations
Applications may be made as an overall mist spray to fences, feed bunkers, spillage
areas, and building walls. Applications may be made in diesel oil or water using a mist
blower or similar equipment. Animals may be present during treatment.
Poultry houses
Page 107 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Premise treatment
Formulation
[EPA Reg.
No.]
0.37 Ib/gal
EC
[5481-220]
1 Ib/gal EC
[5481-41]
1.1 6 Ib/gal
EC
[5481-208]
1.59 Ib/gal
EC
[5481-206]
2 Ib/gal EC
[5481-73]
[5481-205]
4 Ib/gal EC
[5481-204]
1.1 5 Ib/gal
SC
[5481-207]
4.48 Ib/gal
SC
[5481-202]
8.39 Ib/gal
SC
[5481-201]
10 Ib/gal SC
[5481-200]
[5481-9]
Application Rate, ai
Use Directions and Limitations
0.5% finished spray
[1 qt/1,000sq.ft]
Not specified on the 2
Ib/gal EC [5481-73]
product label
0.04 oz/1,000 sq. ft
Applications may be made to manure, window sills, exterior walls, interior walls, feed
room floors, and walkways. Only crack and crevice treatments are permitted for indoor
use and applications are to be made out of reach of poultry (EPA Reg. No. 5481-41
only).
Bait applications may be made to droppings under cages, on walkways, window sills,
alley ways, and other areas where flies congregate. Applications are to be made out of
reach of birds.
Page 108 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
„.. Formulation
' 6A ,. .. -r- [EPA Reg. Application Rate, ai1 Use Directions and Limitations2
Application lype ^Q ,
Direct Animal Uses
Cattle (beef and dairy)
Animal mist spray 1 Ib/gal EC 1% finished spray Application may be made in water as an atomized spray uniformly distributed over each
treatment [5481-41] [2 fl. oz/animal/day] animal. Do not wet the skin.
Application may be made in water as an atomized spray uniformly distributed over each
2 Ib/gal EC 0.5% finished spray animal. Application more than once per day and application to calves less than 6 months
[5481-73] [4 fl. oz/animal/day] of age are prohibited.
Page 109 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Formulation
[EPA Reg.
No.]
0.37 Ib/gal
EC
[5481-220]
1.16 Ib/gal
EC
[5481-208]
1.59 Ib/gal
EC
[5481-206]
2 Ib/gal EC
[5481-205]
4 Ib/gal EC
[5481-204]
1.15 Ib/gal
SC
[5481-207]
4.48 Ib/gal
SC
[5481-202]
8.39 Ib/gal
SC
[5481-201]
10 Ib/gal SC
[5481-200]
Cattle (beef and dairy) (continued)
Animal face paint
treatment
1 Ib/gal EC
[5481-41]
Application Rate, ai
Use Directions and Limitations
1% finished spray
[2 fl. oz/animal/day]
0.5% bait slurry
[1 tsp/face]
Application may be made in deodorized base oil or water as an atomized spray uniformly
distributed over each animal. Do not wet the hide. Application of more than 2 fl. oz. per
animal per day and application to calves less than 6 months of age are prohibited. A 1-
day PSI has been established (EPA Reg. Nos. 5481-204 and 5481-220 only).
Applications may be made to the animal's forehead daily for 14 days and thereafter as
needed.
Page 110 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Formulation
[EPA Reg.
No.]
0.37 Ib/gal
[5481-220]
1.16 Ib/gal
EC
[5481-208]
1.59 Ib/gal
EC
[5481-206]
2 Ib/gal EC
[5481-205]
4 Ib/gal EC
[5481-204]
1.15 Ib/gal
SC
[5481-207]
4.48 Ib/gal
SC
[5481-202]
8.39 Ib/gal
SC
[5481-201]
10 Ib/gal SC
[5481-200]
Cattle (beef and dairy) (continued)
Application Rate, ai
Use Directions and Limitations
1% bait slurry
[3 mL/face]
Application is to be made as a 6-inch line to the animal's forehead with a paint brush.
Page 111 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Manure treatment
Poultry
Formulation
[EPA Reg.
No.]
0.37 Ib/gal
EC
[5481-220]
1 Ib/gal EC
[5481-41]
1.16 Ib/gal
EC
[5481-208]
1.59 Ib/gal
EC
[5481-206]
2 Ib/gal EC
[5481-73]
[5481-205]
4 Ib/gal EC
[5481-204]
1.15 Ib/gal
SC
[5481-207]
4.48 Ib/gal
SC
[5481-202]
8.39 Ib/gal
SC
[5481-201]
10 Ib/gal SC
[5481-200]
Application Rate, ai
Use Directions and Limitations
0.5% finished spray
[2qt/100sq.ft]
or
1% finished spray
[1 qt/100sq.ft]
Applications may be made in water to control maggots in manure piles and garbage
dumps.
Page 112 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Manure treatment
Formulation
[EPA Reg.
No.]
1 Ib/gal EC
[5481-41]
Application Rate, ai
Use Directions and Limitations
0.5% finished spray Applications may be made in diesel oil or deodorized kerosene to control flies and
[2 qt/100 sq.ft] maggots in poultry droppings.
Animal Uses - Oral Dosing (Drug Use)
Swine
Feed treatment
12.5-20.6 mg/kg body Application is to be made by mixing active ingredient into feed and may be repeated in 4-
N/A3 weight 5 weeks.
Wide Area and General Outdoor Treatment
Outdoor areas (including outside picnic areas, patios, and eating areas of drive-in restaurants)
Outdoor spray 2 Ib/gal SC Applications may be made in deodorized spray base oil and repeated monthly or as
application [5481-334] 0.5-1% finished spray needed.
Outdoor areas (including picnic grounds, parking areas, loading docks, refuse areas, garbage collection and disposal areas, around drive-in
restaurants, food processing plants, and warehouses)
Outdoor spray 1 Ib/gal EC 0.5% finished spray Applications may be made in water and repeated as needed. Direct use on animals and
application [5481-41] [1 qt/1,000 sq. ft] contamination of feed, foodstuffs, or water are prohibited.
Outdoor areas (including picnic grounds, parking areas, loading docks, refuse areas, garbage collection and disposal areas, around drive-in
restaurants, food processing plants, and warehouses) (continued)
Page 113 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Outdoor spray
application
Formulation
[EPA Reg.
No.]
0.37 Ib/gal
EC
[5481-220]
1.16 Ib/gal
EC
[5481-208]
1.59 Ib/gal
EC
[5481-206]
2 Ib/gal EC
[5481-205]
4 Ib/gal EC
[5481-204]
1.15 Ib/gal
SC
[5481-207]
4.48 Ib/gal
SC
[5481-202]
8.39 Ib/gal
SC
[5481-201]
10 Ib/gal SC
[5481-200]
Application Rate, ai
Use Directions and Limitations
Applications may be made in diesel oil or water and repeated as needed. Direct use on
0.5% finished spray animals or humans and contamination of water, food, food containers or cooking utensils
[1 qt/1,000 sq. ft] are prohibited.
Outdoor areas (including picnic grounds, parking areas, loading docks, refuse areas, garbage collection and disposal areas, around drive-in
restaurants, food processing plants, and warehouses) (continued)
Page 114 of 338
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Table 2.1. Food/Feed Use Patterns on EP Labels Subject to Reregistration for Dichlorvos (Case 0310).
Site
Application Type
Outdoor fogging
application
[Hand-Held Foggers are
no longer permitted]
Catch basins
Outdoor treatment
Formulation
[EPA Reg.
No.]
0.37 Ib/gal
EC
[5481-220]
1.16 Ib/gal
EC
[5481-208]
1.59 Ib/gal
EC
[5481-206]
2 Ib/gal EC
[5481-205]
4 Ib/gal EC
[5481-204]
1.15 Ib/gal
SC
[5481-207]
4.48 Ib/gal
SC
[5481-202]
8.39 Ib/gal
SC
[5481-201]
10 Ib/gal SC
[5481-200]
20% Impr
[5481-338]
[5481-344]
[5481-348]
Application Rate, ai
Use Directions and Limitations
1% finished spray
[5-10 pt/A]
or
0.05-0.1 Ib/A
One strip
Fogging or misting applications may be made with diesel oil or water using fogging or
misting equipment to treat outdoor living areas, picnic areas, backyard areas, patios,
loading docks, outdoor latrines, parking areas, refuse areas around service stations,
open air drive-ins, ice cream stands, and garbage collection and disposal areas. Use in
areas where food or feed crops are growing is prohibited.
One strip (10.5 or 80 g of product) is to be suspended 10 inches above water level for
control of mosquitoes breeding in catch basins.
Page 115 of 338
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1 Application rates in brackets refer to amount of finished spray to be applied per listed area.
2 The product label for EPA Reg. No. 5481-41 prohibits treatment of more than 5 application sites per day and prohibits DDVP applications more
than once per week (we note that this is in conflict with use directions forfeedlots, stockyards, corrals, and holding pens which allow
applications to be made at 3-day intervals). A similar statement was required to be added to the product label for EPA Reg. No. 5481-200.
No other products listed in this table bear this restriction.
3 DDVP is registered for use as an anthelmintic in swine feed; use pattern is defined in 21 CFR §520.600(e)(2).
Page 116 of 338
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2.2 Structure and Nomenclature
TABLE 2.2. Test Compound Nomenclature
Chemical Structure
Empirical Formula
Common name
Company experimental
name
IUPAC name
CAS name
CAS Registry Number
End-use product/EP
Chemical Class
Known Impurities of
Concern
PC Code No.
0
^P^ ^^^ ^^1
RCO^/ ^cr ^r^
OCH3
Cl
C4H7Cl204P
Dichlorvos (ISO) or DDVP
2,2-dichlorovinyl dimethyl phosphate
2,2-dichloroethenyl dimethyl phosphate
62-73-7
Alco, Amvos
organophosphate
none
084001
2.3 Physical and Chemical Properties
Dichlorvos is a liquid with high vapor pressure at room temperature and is used for
fumigation. The high vapor pressure suggests that residues in food and environmental surfaces
will dissipate rapidly.
Page 117 of 338
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TABLE 2.3. Physicochemical Properties
Parameter
Molecular Weight
Physical State
Boiling point/range
PH
Specific gravity
Water solubility (20 C)
Solvent solubility (temperature not
specified)
Vapor pressure (25 C)
Dissociation constant, pKa
Octanol/water partition coefficient,
log Kow (25 C)
UV/visible absorption spectrum
Value
221.0
liquid
1 17 Cat 10mm Hg
~ 4 as 1% aqueous solution
1 .424 at 25 C
~1.5g/100g
~0.5% in glycerine; miscible with aromatic
hydrocarbons, chlorinated hydrocarbons,
alcohols, ketones, and esters. Essentially
insoluble in kerosene and aliphatic
hydrocarbons
0.032 mm Hg at 32 C
N/A
38.4
log KOW = 1 -58
N/A
Reference
40798103
40798103
40798103
40798103
40798103
40798103
40798103
40798103
Page 118 of 338
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3.0 Metabolism Assessment
3.1 Comparative Metabolic Profile
A rat metabolism study has been conducted. The overall metabolic profile suggests the
involvement of the one-carbon pool biosynthetic pathway as evidenced by the presence of a
relatively large amount of radioactivity in the form of expired 14CC>2 and the presence of
dehalogenated metabolites as well as urea and hippuric acid. Plant metabolism studies show that
dichlorvos hydrolyzes to dimethyl phosphate and dichloroacetaldehyde, and is incorporated into
natural plant constituents. Oral and dermal livestock metabolism studies show that dichlorvos
metabolizes to desmethyl dichlorvos in livestock animals. The major environmental degradates
were 2,2-dichloroacetic acid, 2,2-dichloroacetaldehyde, desmethyl dichlorvos, and glyoxylic
acid.
3.2 Nature of the Residue in Foods
3.2.1. Description of Primary Crop Metabolism
Nature of the Residue - Plants (GLN 860.1300}: The reregistration requirements for plant
metabolism are fulfilled. The Agency determined that the available data depicting the
metabolism of naled in plants are sufficient to delineate the metabolism of dichlorvos in plants
because dichlorvos is the initial metabolite of naled. In plants, naled is metabolized to
dichlorvos which is hydrolyzed to dimethyl phosphate and dichloroacetaldehyde. Dimethyl
phosphate is sequentially degraded to monomethyl phosphate and inorganic phosphates, and
dichloroacetaldehyde is converted to 2,2-dichloroethanol which is then conjugated and/or
incorporated into naturally occurring plant components. The residue of concern in plant
commodities is dichlorvos.
3.2.2 Description of Livestock Metabolism
Nature of the Residue -Animals (GLN 860.1300): The reregistration requirements for
animal metabolism are fulfilled. Acceptable studies depicting the qualitative nature of the
residue in ruminants and poultry following dermal treatment with dichlorvos have been
submitted and evaluated. Because dichlorvos is the initial metabolite of naled, the available
metabolism studies reflecting oral dosing of ruminants and hens with naled are sufficient to
delineate the metabolism of orally dosed dichlorvos in animals. The residue of concern in
animal commodities is dichlorvos.
In the lactating goat treated orally with naled, no naled or dichlorvos was identified in milk
(<0.005 ppm) or tissues (<0.05 ppm). Dichloroethanol conjugates and desmethyl-dichlorvos
were not identified in milk (<0.05 ppm). Liver and kidney contained up to 0.3 ppm
dichloroethanol conjugates and 0.1 ppm desmethyl-dichlorvos; other tissues showed only traces
of both of these metabolites.
Page 119 of 338
-------
In laying hens treated orally with naled, the sulfate conjugate of dichloroethanol was the
major component (0.1 ppm in fat to 10 ppm in kidney) identified in all tissues. The parent
compound, naled, was not identified (<0.01 ppm) in any tissues except gizzard. Naled plus
mostly dichlorvos were found in gizzard (0.6 ppm) after 2 hours in singly dosed hens and as a
minor metabolite (0.01-0.46 ppm) in tissue samples of multi-dosed hens.
In both lactating goats and laying hens treated orally with naled, naled is initially
debrominated to yield dichlorvos. The major pathway is cleavage of dichlorvos to
dimethylphosphate and dichloroacetaldehyde. A minor pathway is O-demethylation to form
desmethyl-dichlorvos. In part, dichloroacetaldehyde is reduced to dichloroethanol which is
conjugated with endogenous sulfate to form the sulfate ester conjugate of dichloroethanol.
Dichloroacetaldehyde is dechlorinated and oxidized sequentially to form glyoxal and then
glyoxylic acid which is incorporated into amino acids (glycine, alanine, serine, etc.) and proteins.
Metabolism of dichlorvos in ruminants, following dermal exposure, is adequately understood.
Dichlorvos is extensively metabolized following dermal exposure. No dichlorvos or primary
metabolites of dichlorvos were found in milk or tissues of treated goats, furthermore,
incorporation of 14C into endogenous milk (as lactose) and tissue components (as glycerol) of the
treated goats was demonstrated.
Metabolism of dichlorvos in poultry, following dermal exposure, is adequately understood.
Dichlorvos is extensively metabolized following dermal exposure. Limited amounts of
dichlorvos and des-methyl dichlorvos were identified in breast muscle and fat, with the majority
of the TRR incorporated into tissue. Radioactivity found in internal tissues accounted for 0.3%
of the administered dose.
3.2.3 Description of Rotational Crop Metabolism, including identification of major
metabolites and specific routes of biotransformation
Dichlorvos is not registered for field crop uses; therefore no rotational crop data have
been required.
3.3 Environmental Degradation
Dichlorvos. A major route of dissipation is volatilization (vapor pressure = 0.032 mm Hg at
32 C). Dichlorvos also appears to degrade through aerobic soil metabolism and abiotic
hydrolysis as well, but is secondary to volatilization. Hydrolysis is pH dependant where the
half-lives were 11 days at pH 5, 5 days at pH 7 and 21 hours at pH 9. The major degradates were
2,2-dichloroacetic acid, 2,2-dichloroacetaldehyde, desmethyl dichlorvos, and glyoxylic acid.
Aerobic soil metabolism data showed a half-life of 10 hours with the major metabolite being
2,2-dichloroacetic acid (62.8% of applied at 48 hours). Other metabolites present at less than
12% of applied were 2,2-dichloroacetaldehyde, and dichloroethanol. Extensive mineralization
took place as CC>2 accounted for 60% of applied at 360 hours post-treatment. Due to rapid
degradation of dichlorvos leaching/adsorption/desorption data were declared supplemental due to
the inability to establish a soil/solution phase equilibrium. However, a soil TLC study (MRID
41354105) indicates that dichlorvos is moderately mobile (Kd's ranging 0.3 to 1.2) based on the
Page 120 of 338
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Heiling and Turner's mobility classification. The potential of dichlorvos to leach to ground water
is mitigated by its rapid degradation. However, dichlorvos does have the potential to contaminate
surface waters because of a low Koc value and high water solubility (10 X 103 ppm, or 1%).
Substantial fractions of run-off will more than likely occur via dissolution in run-off water rather
than adsorption to eroding soil. Dichlorvos should not be persistent in any surface waters due to
its susceptibility to rapid hydrolysis.
Naled. Chemical hydrolysis and biodegradation are the major processes involved in the
transformation of naled and its degradates in the environment. While direct photolysis in water is
not a major degradative pathway for naled, indirect photolysis in the presence of photosensitizer
may play an important role in the photodegradation of naled in aqueous media and soils. The
degradate dichlorvos does not form under abiotic hydrolysis nor by direct photolysis in water,
but forms by indirect photolysis in water and soils. In the presence of photosensitizer in water, as
much as 20% of the applied dose of naled can be found as dichlorvos after 1 day, with rapid
decline of dichlorvos residues afterwards. Under aerobic conditions, naled mineralizes rapidly to
CC>2 and degrades to dichloroacetic acid and dichloroethanol, but dichlorvos is not detected. This
is likely to be the result of the rapid degradation and mineralization of any dichlorvos that may
form from naled. However, under anaerobic aquatic conditions, dichlorvos can be as high as
15% of the applied naled dose after 1 day. The degradation of dichlorvos, once formed, was
slower than that of parent naled. During the first 1-2 days after application of naled, the half-life
of dichlorvos was about 0.9 days.
Trichlorfon. Dichlorvos is formed from trichlorfon in both soil and water by aerobic soil
metabolism. Environmental fate data indicate that trichlorfon degrades rapidly in aerobic soil (ti/2
1.8 days) under non-sterile conditions; however, in a sterile soil, trichlorfon was stable (ti/2 > 40
days). Abiotic hydrolysis studies indicate that trichlorfon degrades rapidly in aqueous media and
that the rate of conversion is pH dependent. The estimated half-life of trichlorfon is 31 minutes at
pH 9, and 34 hours at pH 7, and 104 days at pH 5. This indicates the stability of trichlorfon under
acidic conditions. The maximum amount of dichlorvos formed from trichlorfon by aerobic
aquatic metabolism is approximately 56 percent of the amount of trichlorfon originally applied at
pH8.5.
Page 121 of 338
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3.4 Summary of Residues for Tolerance Expression and Risk Assessment
Tolerances for residues of dichlorvos are published in 40 CFR 180.235. The current
tolerance expression includes only dichlorvos [2,2-dichlorovinyl dimethyl phosphate].
Table 3.6. Summary of Metabolites and Degradates to be included in the Risk Assessment and
Tolerance Expression
Matrix
Plants
Livestock
Primary Crop
Rotational Crop
Ruminant
Poultry
Drinking Water
Residues included in Risk
Assessment
dichlorvos
N/A
dichlorvos
dichlorvos
dichlorvos
Residues included in
Tolerance Expression
dichlorvos
N/A
dichlorvos
dichlorvos
Not Applicable
4.0 Hazard Characterization/Assessment
4.1 Hazard Characterization
Dichlorvos is a chlorinated organophosphate pesticide cholinesterase inhibitor, which inhibits
plasma, erythrocyte, and brain cholinesterase in a variety of species, but does not cause
organophosphate-induced delayed neurotoxicity (OPIDN) in the hen. Concern for potential
developmental neurotoxicity arose based on a study in the open literature (Mehl et al, 1994),
which reported decreased total brain weight in two litters of guinea pigs from dichlorvos-
exposed dams. However, in developmental neurotoxicity studies in rats, decreased brain weight
was not associated with gavage doses of dichlorvos administered to pups during PNDs 8-22. In
acute and 90-day neurotoxicity studies in rats, there was no neuropathology associated with
changes in FOB and motor activity. Subchronic and chronic oral exposures in rats and dogs as
well as chronic inhalation exposure in rats resulted in significant decreases in plasma, red blood
cell and/or brain cholinesterase activity. Repeated, oral subchronic exposures in male humans
were associated with statistically and biologically significant decreases in red blood cell
cholinesterase depression.
There was no evidence of increased susceptibility following in utero exposure to rats and
rabbits as well as pre/post natal exposure to rats in developmental and reproduction studies. The
FQPA safety factor was reduced to Ix. Some scenarios used endpoints based on a LOAEL, and
the 3x uncertainty factor used is considered part of the FQPA safety factor.
The carcinogenic potential of dichlorvos has been classified as "suggestive" under the 1999
Draft Cancer Guidelines and no quantitative assessment of cancer risk is required. Dichlorvos
has been shown to be a direct acting mutagen in in vitro mammalian test systems. Dichlorvos
seems to also have clastogenic activity in Chinese hamster ovary (CHO) cells in vitro with or
without metabolic activation. On the other hand, studies showed that dichlorvos was not
clastogenic in in vivo micronucleus tests.
Page 122 of 338
-------
Inhibition of cholinesterase activity was the toxicity endpoint selected to assess hazards for all
acute and chronic dietary reference doses (RfDs), as well as short-, intermediate-, and long-term
(chronic) dermal and inhalation occupational and residential risk assessments. The no observed
adverse effect levels (NOAELs), lowest observed adverse effect levels (LOAELs), or BMDLios
were selected in light of Agency policy on the use of toxicology studies employing human
subjects. Therefore, HED selected doses and endpoints for risk assessment based on both human
and animal studies.
Table 4.1 a Acute Toxicity of Dichlorvos
Guideline
No.
8701.1100
870.1200
870.1300
870.2400
870.2500
870.2800
870.6100
870.6200
Study Type
Acute Oral
Acute Dermal
Acute Inhalation
Primary Eye Irritation
Primary Skin Irritation
Dermal Sensitization
Acute Delayed
Neurotoxicity-Hen
Acute Neurotoxicity-
Rat
MRID#(S).
00005467
00005467
00137239
00146921
00146920
none
41004702
42655301
Results
LD50 = 80 mg/kg (M)
56 mg/kg (F)
LD50 = 107 mg/kg (M)
> 75 mg/kg (F)
LC50> 0. 1 98 mg/L
mild irritant
mild irritant
no study available
Negative for acute delayed
neurotoxicity
NOAEL = 0.5 mg/kg; LOAEL
= 35 mg/kg (changes in
FOB, motor activity ) no
neuropathology
Toxicity Category
II
I
II
III
IV
NA
NA
NA
Page 123 of 338
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Table 4.1b. Guideline Toxicology Studies for Dichlorvos in Experimental Animals
Guideline No./Study Type
MRID No.
Results
Acute Oral Cholinesterase Inhibition
Study (1st) in Adult SD Rats/
870.1100 (non-guideline)
45805701
Acceptable
ChEl NOAEL (RBC and Brain) = not established
ChEl LOAEL (RBC and Brain) = 2.1 mg/kg/day
Acute Oral Cholinesterase Inhibition
Study (2nd) in Adult SD Rats/
870.1100 (non-guideline)
45805702
Acceptable
ChEl NOAEL (RBC and Brain) = 1 mg/kg
ChEl LOAEL (RBC and Brain) = not established
Acute Oral Cholinesterase Inhibition
Study (3rd) in Adult Wistar Rats/
870.1100 (non-guideline)
45805703
Acceptable
RBC Cholinesterase Inhibition
NOAEL = 1 mg/kg
LOAEL =5 mg/kg
BMD/BMDLio = 1.7/1.3 (M) mg/kg
BMD/BMDLio = 1.5/1.2 (F) mg/kg
Brain Cholinesterase Inhibition
NOAEL = 1 mg/kg
LOAEL =5 mg/kg
BMD/BMDLio = 1.6/1.0 (M) mg/kg
BMD/BMDLio = 1.6/0.8 (F) mg/kg
Acute Oral Cholinesterase Inhibition
Study in Preweaning Wistar Rat
Pups/870.1100 (non-guideline)
45842301
Acceptable
RBC Cholinesterase Inhibition
ChEl NOAEL (RBC) = not established
ChEl LOAEL (RBC) = 1 mg/kg
Postnatal day 8 BMD/BMDL10 = 1.8/1.3 (M) mg/kg;
Postnatal day 8 BMD/BMDL10 = 1.5/1.0 (F) mg/kg;
Brain Cholinesterase Inhibition
ChEl NOAEL (Brain) = 1 mg/kg
ChEl NOAEL (Brain) = 5 mg/kg
Postnatal day 8 BMD/BMDL10 = 1.8/1.5 (M) mg/kg;
Postnatal day 8 BMD/BMDL10 = 2.2/1.6 (F) mg/kg;
Time Course of Cholinesterase
Inhibition in Preweaning and Adult
Wistar Rats/870.8223 (Non-
Guideline)
46153303
Acceptable
Brain and RBC enzyme activities were maximally
inhibited one hour after single dosing in both adult and
preweaning female rats. Thereafter, ChE inhibition in
both compartments decreased to approximately control
levels by 8 hours post dosing.
Repeat Dose Cholinesterase
Inhibition Study in Preweaning (PND
18) and Adult (PND 48) Wistar
Rats/(Non-Guideline)
46153304
Acceptable
1.41/1.66 mg/kg/d RBC ChEl (M)
1.31/1.63 mg/kg/d RBC ChEl (M)
0.83/1.47 mg/kg/d RBC ChEl (F)
1.26/1.55 mg/kg/d RBC ChEl (F)
1.40/1.50 mg/kg/d Brain ChEl
1.80/2.02 mg/kg/d Brain ChEl (F)
1.26/1.55 mg/kg/d Brain ChEl (F)
PND18BMD/BMDL1tr
PND48 BMD/BMDL10=
PND18BMD/BMDL1tr
PND48 BMD/BMDL10=
PND18BMD/BMDL1tr
(M)
PND48 BMD/BMDL10=0.76/1.46 mg/kg/d Brain ChEl
(M)
PND18BMD/BMDL1tr
PND48 BMD/BMDL10=
Page 124 of 338
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Table 4.1 b. Guideline Toxicology Studies for Dichlorvos in Experimental Animals
Guideline No./Study Type
Dichlorvos: A single blind, placebo
controlled, randomized study to
investigate the effects of multiple oral
dosing on erythrocyte cholinesterase
inhibition in healthy male volunteers
(non-guideline)
Dichlorvos: A study to investigate
erythrocyte cholinesterase inhibition
following oral administration to
healthy male volunteers (non-
guideline)
Dichlorvos: A study to investigate the
effect of a single oral dose on
erythrocyte cholinesterase inhibition
in healthy male volunteers (non-
guideline)
Dermal Absorption/870.7600
28-Day Delayed Neurotoxicity-
Hen/870.6100
90-Day Subchronic Oral Toxicity -
Rat/870.3100
90-Day Neurotoxicity - Rat/870.6200
Chronic-Feeding-Dog/870.4100
2-Year Inhalation toxicity/
carcinogenicity - Rat/870.4200
Chronic toxicity/
Carcinogenicity-F344 Rats (NTP
study)/870.4300
Carcinogenicity-Mouse/870.4200
MRID No.
44248801
Acceptable
44317901
Unacceptable
44248802
Unacceptable
41435201
Acceptable
43433501
Acceptable
41004701
Acceptable
42958101
Acceptable
41593101
Acceptable
00057695,
00632569
Acceptable
40299401
Acceptable
40299401
Acceptable
Results
RBC cholinesterase inhibition
LOAEL = 0.1 mg/kg/day
NOAEL = not established
RBC cholinesterase inhibition
NOAEL = not determined (missed time of peak effect)
RBC cholinesterase inhibition
NOAEL = not determined (missed time of peak effect)
Dermal absorption rate for dichlorvos was estimated to
be approximately 11% in 10 hours of exposure.
Cholinesterase inhibition (brain ChEl)
NOAEL = 0.1 mg/kg/day
LOAEL = 0.3 mg/kg/day
No neuropathology.
NOAEL = 0.1 mg/kg/day
LOAEL = 1.5 mg/kg/day (plasma and RBC ChEl)
NOAEL = 0.1 mg/day
LOAEL = 7.5 mg/kg/day (plasma, red blood cell (RBC)
and brain ChEl).
NOAEL = 0.05 mg/kg/day
LOAEL = 0.1 mg/kg/day (plasma and RBC ChEl in both
sexes).
BMD/BMDLio = 0.15/0.07 mg/m3 RBC ChEl (F)
BMD/BMDLio = 0.14/0.04 mg/m3 RBC ChEl (M)
BMD/BMDLio = 0.29/0.29 mg/m3 Brain ChEl (F)
BMD/BMDLio = 0.31/0.30 mg/m3 Brain ChEl (M)
NOAEL = Not established
LOAEL = 4.0mg/kg/day (plasma and RBC ChEl)
Suggestive evidence of carcinogenicity (mononuclear
cell leukemia in male rats)
NOAEL = Not established
LOAEL = 10 mg/kg/day (plasma and RBC ChEl in
males)
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Table 4.1 b. Guideline Toxicology Studies for Dichlorvos in Experimental Animals
Guideline No./Study Type
MRID No.
Results
Developmental Toxicity-
Rat/870.3700
41951501
Acceptable
Maternal toxicity NOAEL = 3 mg/kg/day
LOAEL = 21 mg/kg/day
(clinical signs, decreased body weight gain and
reductions in food consumption and efficiency)
Developmental toxicity NOAEL = > 21 mg/kg/day (HOT)
Developmental Toxicity-
Rabbit/870.3700
41802401
Acceptable
Maternal toxicity NOAEL = 0.1 mg/kg/day
LOAEL = 2.5 mg/kg/day
(mortality, decreased body weight gain at LOAEL)
Developmental toxicity NOAEL= > 7 mg/kg/day (HOT)
ChEl was not measured in main study
Range-Finding: Doses were 0, 0.1, 1.0, 2.5, 5.0, 10
mg/kg/day
Maternal toxicity
ChE NOAEL = 0.1 mg/kg/day
ChE LOAEL = 1.0 mg/kg/day
Reproductive Toxicity - Rat/870.3800
42483901
Acceptable
Parental/Systemic NOAEL = 2.3 mg/kg/day
LOAEL = 8.3 mg/kg/day
(decreased % of females with estrous cycle and
increased % of females with abnormal cycling)
Offspring NOAEL = 2.3 mg/kg/day
LOAEL = 8.3 mg/kg/day
(reduced # dams bearing litter, fertility index, pregnancy
index and pup weight).
Preliminary Developmental
Neurotoxicity - Rat/(Non-Guideline)
46153301
Acceptable
Systemic NOAEL = 7.5 mg/kg/day Maternal
Systemic LOAEL = not identified Maternal
RBC ChEl NOAEL = 0.1 mg/kg/day Maternal
RBC ChEl LOAEL = 1.0 mg/kg/day Maternal
Brain ChEl NOAEL = 1.0 mg/kg/day Maternal
Brain ChEl LOAEL = 7.5 mg/kg/day Maternal
Systemic NOAEL = 7.5 mg/kg/day Offspring
Systemic LOAEL = not identified Offspring
RBC ChEl NOAEL = 1.0 mg/kg/day Fetuses (GD 22)
RBC ChEl LOAEL = 7.5 mg/kg/day Fetuses (GD 22)
Brain ChEl NOAEL = 1.0 mg/kg/day Fetuses (GD 22)
Brain ChEl LOAEL = 7.5 mg/kg/day Fetuses (GD22)
Offspring (Pups) did not demonstrate ChEl during PND
2-22
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Table 4.1 b. Guideline Toxicology Studies for Dichlorvos in Experimental Animals
Guideline No./Study Type
MRID No.
Results
Developmental Neurotoxicity -
Rat/870.6300
46153302
Acceptable
(Study
RR0886)
Maternal toxicity NOAEL = 7.5 mg/kg/day (HOT)
No treatment related effects
Developmental toxicity NOAEL= 1.0 mg/kg/day
LOAEL = 7.5 mg/kg/day
(increases in auditory startle reflex habituation Vmax in
PND 23 high dose males in both studies)
ChEl was not measured in main study
Developmental Neurotoxicity -
Rat/870.6300
46239801
Acceptable
(Study
RR0988)
Maternal NOAEL is 7.5 mg/kg/day (HOT). A maternal
LOAEL was not established.
Offspring/developmental NOAEL is 1.0 mg/kg/day
(based on study RR0886) and the
Offspring/developmental LOAEL is 7.5 mg/kg/day
(based on both studies RR0886 and RR0988) with the
effect being increases in auditory reflex habituation
Vmax in PND 23 high dose males in both studies.
Mutagenicity/Genetic Toxicity Test
Guidelines-870.5000
Acceptable
Dichlorvos has been shown to be a direct acting
mutagen by common in vitro bacterial genetic toxicity
assays and in in vitro mammalian test systems.
Conflicting evidence was seen for clastogenic activity in
vivo.
Metabolism-Rat/870.7485
41228701
41839901
Acceptable
The overall metabolic profile suggests the involvement
of the one-carbon pool biosynthetic pathway as
evidenced by the presence of a relatively large amount
of radioactivity in the form of expired 14CO2 and the
presence of dehalogenated metabolites as well as urea
and hippuric acid.
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4.2FQPA Hazard Considerations
4.2.1 Adequacy of the Toxicity Data Base
The toxicology database for dichlorvos is complete. The FQPA database includes
acceptable developmental studies in rats and rabbits, an acceptable 2-generation rat reproduction
study, two developmental neurotoxicity studies, and single dose gavage cholinesterase studies in
adult and preweaning rats and repeat dose gavage studies in young adult and preweaning rats.
4.2.2 Evidence of Neurotoxicity
There is a concern for neurotoxicity resulting from exposure to dichlorvos. Dichlorvos is a
chlorinated organophosphate pesticide cholinesterase inhibitor, which inhibits plasma, erythrocyte,
and brain cholinesterase.
4.2.3 Developmental Toxicity Studies
In the rat study (MRID 41951501), the maternal toxicity LOAEL was 21 mg/kg/day based
on clinical signs of toxicity, reduced body weight gain, and food efficiency; the maternal NOAEL
was 3 mg/kg/day. The developmental LOAEL was not established; the NOAEL was 21 mg/kg/day.
In the rabbit developmental study (MRID 41802401), groups of NZW rabbits (16/dose)
received oral administration of dichlorvos (97%) in distilled water at dose levels of 0, 0.1, 2.5, or
7.0 mg/kg/day during gestation days 7 through 19, inclusive. The maternal LOAEL was 2.5
mg/kg/day based on maternal deaths and decreased body weight gain; the NOAEL was 0.1
mg/kg/day. No developmental toxicity was noted; therefore, the NOAEL for developmental
toxicity was 7 mg/kg/day.
4.2.4 Reproductive Toxicity Study
In a two generation reproduction study in rats (MRID 42483901), the parental/systemic
NOAEL was 2.3 mg/kg/day and the LOAEL was 8.3 mg/kg/day based on a decreased incidence of
estrous cycling and increased abnormal cycling in Fl females, reduced water intake in both sexes,
and decreased plasma, and RBC ChE activity at all dosage levels in both sexes in both generations.
In addition brain ChE was decreased in both sexes at 2.3 mg/kg/day. The NOAEL for brain ChE
was 0.6 mg/kg/day and the NOAEL for plasma and RBC ChE depression was less than 0.6
mg/kg/day. The NOAEL/LOAEL for reproductive/offspring toxicity 2.3/8.3 mg/kg/day based on a
decrease in the number of dams bearing litters, reduced fertility indices, pregnancy index, and pup
body weights on lactation Day 4 in both Fl matings. The offspring were not examined for effects
on cholinesterase.
4.2.5 Pre-and/or Postnatal Toxicity
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There is no concern for pre- and/or postnatal toxicity resulting from exposure to dichlorvos.
There was no evidence for increased susceptibility of the rat and rabbit offspring to prenatal or
postnatal exposure to dichlorvos (MRID 41951501, 41802401 and 42483901, respectively) . In
both rat and rabbit developmental studies, no developmental effects were observed. In the
reproduction study, the parental/systemic NOAEL/LOAEL was 2.3/8.3 mg/kg/day which was
identical to the reproductive/offspring NOAEL/LOAEL. In the DNT studies, at doses much higher
than used for regulation, increase in auditory startle reflex habituation Vmax in PND 23 high dose
males was noted.
4.2.5.1 Determination of Susceptibility
The mode of action for dichlorvos is neurotoxicity through the inhibition of
cholinesterase via phosphorylation of the active site of the enzyme. Inhibition of cholinesterase
provides the most sensitive endpoint for dichlorvos. There are acute and repeated dosing studies
which evaluate cholinesterase inhibition in juvenile and young adult rats. The Agency has
completed a benchmark dose (BMD) analysis of these data. The Agency's draft BMD technical
guidance indicates that the BMD approach is a preferable alternative to the NOAEL/LOAEL
approach (USEPA, 2000). The Office of Pesticide Programs is increasing its use of BMD
techniques in its hazard assessments and risk characterizations for use in developing points of
departure and in considering relative sensitivity of adult and juvenile animals. BMDs are preferred
over the NOAEL/LOAEL as NOAELs/LOAELs are highly dependent on dose selection in that they
are limited to the doses included in a study. BMD analysis also considers the entire dose response
curve and not just a single point. Moreover, the NOAEL/LOAEL approach does not account for
the uncertainty in the estimate of the dose-response. The dichlorvos BMD analysis was developed
using the exponential model provided in EPA's OPCum Risk software. The application of the
exponential model to cholinesterase data from OPs and TV-methyl carbamate pesticides has been
reviewed by the FIFRA Scientific Advisory Board on multiple occasions. This model and the
supporting computer code are publicly available for download, review, and use at
www.epa.gov/pesticides/cumulative/EP A_approach_methods.htm.
The Agency calculated the estimated dose to result in 10% inhibition (BMDio) and the lower
95% confidence limit on the BMDio (BMDLio). Brain and RBC ChE data from acute dosing to
post-natal day 8 (PND8) and young adult rats were extracted from MRID nos. 45805703 and
45842301. The acute BMDsio range from approximately 1.3 mg/kg to 2.0 mg/kg for each
compartment, sex and age group. Regarding repeated exposures, brain and RBC ChE data from the
repeated dosing studies in juvenile and young adult rat were extracted from MRID nos. 46433201
and 46153304. As described in detail in the Data Evaluation Record (DER) for these studies, the
ChE activity measurements in some control groups are unusually high for the laboratory which
conducted the repeated exposure study. The registrant, AMVAC, provided historical control values
for brain and RBC ChE activity. BMD estimates were developed using both the concurrent and
pooled historical control values. It is preferred to evaluate relative sensitivity using concurrent
controls however in this case use of the historical control values provides helpful characterization.
Overall, for the repeated exposure, the BMDs ranged from approximately 0.5 mg/kg to 1.2 mg/kg
when using the historical or concurrent controls and are thus similar between compartments, sexes
and age groups.
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4.2.5.2 Degree of Concern Analysis and Residual Uncertainties for Pre and/or
Post-natal Susceptibility
Based on the BMD analysis summarized above, the dichlorvos risk assessment team
has determined that the FQPA Safety Factor can be reduced to IX for acute and repeated exposures
of dichlorvos. The BMD estimates are similar for juvenile and adult rats, and thus indicates no
sensitivity to young animals (Lowit, A., 2006).
4.2.6. Traditional Safety Factors
Any traditional safety factors other than that standard uncertainty factors, the interspecies
extrapolation factor, and the intraspecies variability factor, are considered to be FQPA safety
factors. For dichlorvos, a LOAEL from a human 21-day oral study is used as an endpoint for short
term residential exposure scenarios. The LOAEL to NOAEL factor of 3x is considered to be an
FQPA Safety Factor.
4.3 Hazard Identification and Toxicity Endpoint Selection
4.3.1. Acute Reference Dose (aRfD) - General Population
Study Selected: Acute Cholinesterase Study in Rats Non-guideline
MRID: 45805703
Title: Dichlorvos: Third Acute cholinesterase inhibition study in rats; Twomey, K. June 26,
2002.
Executive Summary: In the third acute oral cholinesterase toxicity study in rats (MRID
45805703J, groups of 15 male and 15 female Wistar-derived rats were administered single oral
doses of dichlorvos (purity of 99.0%) at dose levels of 0 (control), 1 mg/kg, or 5 mg
dichlorvos/kg on Day 1 of the study. Nine males were dosed with 35 mg dichlorvos/kg, but due
to the severe cholinergic signs, no further dosing at this level was conducted. Two additional
groups of 15 females were dosed with 0 or 15 mg dichlorvos/kg as a single oral dose. All
animals were observed prior to the start of the study and on Day 1 at time of expected peak
effect (30 minutes post dose) for any changes in clinical condition. Body weights were
measured at Day 1, 8, and 15. At scheduled termination at 1 hour post dosing, 5/sex/dose
animals were sacrificed and brains were removed and weighed. Cardiac blood samples were
taken post mortem for determination of erythrocyte cholinesterase activity. The cerebellum,
cerebral cortex, hippocampus, half and remainder of the brain were dissected out and sent for
determination of cholinesterase activity. Dose analysis measurements were acceptable. On day 1
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of dosing, severe toxicity in 9 males of the high-dose group (35 mg/kg) was observed. Four of
these males were killed for humane reasons within 1 hour of dosing. Those sacrificed and the
remaining animals in this group displayed some or all of the following signs: decreased activity,
irregular breathing, clonic convulsions, fasiculations, prostration, decreased righting and splay
reflexes, and salivation. One female dosed with 15 mg/kg had miosis and fasiculations. There
were no meaningful (i.e., miosis) treatment related clinical signs in animals of the 1 or 5 mg/kg
dose groups. Body and brain weight comparisons between treated groups of both sexes and their
respective controls were not statistically significantly affected. Statistically significant
cholinesterase depression occurred at the following doses in blood or brain segments for each
sex: cerebellum (males, 35 mg/kg; females, 5 and 15 mg/kg), cortex (males, 5 and 35 mg/kg;
females, 5 and 15 mg/kg), hippocampus (males, 35 mg/kg; females, 5 and 15 mg/kg), remainder
(males 35 mg/kg; females 5 and 15 mg/kg), half-brain (males, 35 mg/kg; females, 5 and 15
mg/kg), erythrocyte (males, 5 and 35 mg/kg; females, 5 and 15 mg/kg). There was no
meaningful cholinesterase depression at 1 mg/kg on erythrocyte or brain segments for both sexes
killed at 1 hour post-dosing on day 1 or on day 8 or day 15 in comparison to controls. Due to a
lack of cholinesterase inhibition in some animals on day 1, the animals scheduled for
cholinesterase measurement on day 8 and 15 were sacrificed.
The LOAEL for erythrocyte and brain cholinesterase inhibition is 5 mg/kg in both sexes.
The NOAEL for erythrocyte and brain cholinesterase inhibition is 1 mg/kg in both sexes.
This acute oral cholinesterase toxicity study is classified acceptable/non-guideline. This study
does satisfy the requirement (modified OPPTS 870.1100; OECD 401) for an acute oral
cholinesterase toxicity study on the technical.
Dose and endpoint for establishing the aRfD: A Benchmark Dose Analysis (BMD) was
conducted for the dichlorvos cholinesterase inhibition data by RRB4 (Daiss B., 2004). The
Agency's BMDS program (Benchmark Dose Software version 1.3.2) was used to derive the
BMDLio, the estimated dose that results in 10% inhibition of cholinesterase, and the BMDLio,
the lower 95% confidence interval on the BMDLio, for the RBC cholinesterase data. For this
analysis, the polynomial continuous model default option of relative deviation was used for the
benchmark response (BMR) type, with a corresponding BMR factor of 0.1 used as a basis for
BMD and BMDLio derivation.
The BMDLio of 0.8 mg/kg based on Day 1 female brain ChE depression was selected as the
lowest value of all the studies available which were analyzed by BMD.
A second BMD analysis was done for dichlorvos to be used in the OP cumulative analysis. This
BMD analysis was done using the OPCumRisk software. Similar results were obtained. The
decision algorithm and technical details of the "basic" exponential model used in this BMD
analysis can be obtained at www.epa.gov/scipoly/sap/2001/september/rpfappendixl.pdf
Uncertainty factor: 100 (lOx for interspecies differences and lOx for intraspecies variation).
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FQPA Safety Factor: The FQPA Safety Factor has been reduced to Ix, since BMD analysis of
studies with pup and adult ChE depression results did not demonstrate any substantial numerical
differences in BMDL values (all values were approximately 1 mg/kg) for either RBC or brain
cholinesterase.
Comments about Study/Endpoint/Uncertainty Factor: There are no specific issues of concern in
the assessment of the rat acute cholinesterase studies.
Acute
PAD
(General
population) —
O.I
? ms/ks =
0
008
mg/kg
100
4.3.2. Chronic Reference Dose (cPAD)
Study Selected: Chronic Toxicity-Dog 870.4100 (formerly §83-lb)
MRIDNo. 41593101
Executive Summary: In a chronic feeding study, groups of beagle dogs were administered
dichlorvos by capsule for 52 weeks at dose levels of 0, 0.1, 1.0 and 3.0 mg/kg/day. The 0.1
mg/kg/day dose was lowered to 0.05 mg/kg/day on day 22 due to the inhibition of plasma
cholinesterase noted after 12 days (plasma cholinesterase was decreased in males (21.1%) and
females (25.7%) at week 2 in the 0.1 mg/kg/day group). At time points after week 2, plasma
cholinesterase activity was only significantly reduced in males (39.1 to 59.2%) and females
(41.0 to 56.7%) in the mid-dose group and in males (65.1 to 74.3%) and females (61.1 to 74.2%)
in the high dose group. Although RBC cholinesterase activity was reduced in males (23.6%)
and females (50.1%) at week 6 in the low-dose group, this was believed to be an effect on RBC
cholinesterase of the higher dose of 0.1 mg/kg/day. Much lower levels of inhibition were
observed in this group after week 6. At time points after week 6, RBC cholinesterase activity
was only significantly decreased in males (43.0 to 53.9) and females (38.0 to 51.9) in the mid-
dose group and in males (81.2 to 86.9%) and females 79.2 to 82.5%) in the high-dose groups.
Brain cholinesterase activity was significantly reduced in males (22%) in the mid-dose group
and in males (47%) and females (29%) in the high dose group. The NOAEL was 0.05
mg/kg/day and the LOAEL was 0.1 mg/kg/day based on plasma and RBC cholinesterase
inhibition in males and females.
Dose and Endpoint for Establishing cRfD: NOAEL = 0.05 mg/kg based on plasma and RBC
cholinesterase inhibition in males and females at 0.1 mg/kg/day (LOAEL).
Uncertainty Factor: lOOx (lOx for interspecies variation, lOx for intraspecies extrapolation)
FQPA Safety Factor: Ix.
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Comments about Study/Endpoint/Uncertainty Factor: The human data (discussed in the next
section) were not used since RBC cholinesterase inhibition did not demonstrate a steady state
(equilibrium) by the end of the study at three weeks, i.e. the inhibition of cholinesterase was
progressive and a NOAEL was not achieved. This conclusion was supported by the HSRB.
Chronic PAD = 0.05 mg/kg/dav = 0.0005 mg/kg/day
100
4.3.3. Incidental Oral Exposure (Short Term)
Incidental Oral Exposure: Short-Term (1-30 days)
Study Selected: Subchronic oral toxicity study in human subjects § Non-guideline
MRID No.: 44248801
Executive Summary: In a single blind oral study 6 fasted male volunteers were administered 7
mg of dichlorvos in corn oil (equivalent to approximately 0.1 mg/kg/d) via capsule daily for 21
days. Three control subjects received corn oil as a placebo. Baseline values for RBC
cholinesterase activity for each study participant were determined. After dosing started, RBC
cholinesterase activity was monitored on days 2, 4, 7, 9, 11, 14, 16, and 18, then on day 25 or 28
post dosing. No clinical signs attributable to administration of dichlorvos was reported. Mean
RBC cholinesterase activity was statistically significantly reduced in treated subjects on days 7,
11, 14, 16, and 18. These values were 8, 10, 14, 14, and 16 percent below the pre-dose mean.
Under the study conditions, a LOAEL for RBC cholinesterase inhibition was established at 0.1
mg/kg/d. A NOAEL was not established.
Dose and Endpoint for Risk Assessment: The LOAEL of 0.1 mg/kg/d based on statistically
significant decreases in RBC cholinesterase inhibition.
Comments about Study/Endpoint: The human study was selected because it is a subchronic
study of appropriate duration and is the lowest LOAEL established for RBC cholinesterase
inhibition in a repeated oral exposure to dichlorvos. Uncertainty factors account for intraspecies
variability (lOx). Since the study was conducted in human subjects, there was no need to
account for interspecies extrapolation.
FQPA Safety Factor: 3x A 3x for lack of a NOAEL is considered an FQPA safety factor.
Target MOE: 30
4.3.4. Dermal Absorption
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Dermal Absorption Factor: The dermal absorption rate for dichlorvos was estimated to be
approximately 11% in 10 hours of exposure based on an acceptable dermal absorption study in rats
(MRID 41435201).
4.3.5. Dermal Exposure (Acute)
Study Selected: Acute Cholinesterase Study in Rats Non-guideline
MRID: 45805703 (see discussion under Section 4.3.1 Acute Reference Dose)
Target MOE: 100
4.3.6. Dermal Exposure (Short-, Intermediate-, and Long- Term)
Study Selected: Subchronic oral toxicity study in human subjects § Non-guideline
MRID No.: 44248801
Executive Summary: (See discussion above)
Dose and Endpoint for Risk Assessment: The LOAEL of 0.1 mg/kg/d based on statistically
significant decreases in RBC cholinesterase inhibition.
Comments about Study/Endpoint: The human study was selected because it is a subchronic
study of appropriate duration and is the lowest LOAEL established for RBC cholinesterase
inhibition in a repeated oral exposure to dichlorvos. Since the study was conducted in human
subjects, there was no need to account for the interspecies extrapolation. Uncertainty factors
account for intraspecies variability (10x).
FOPA Safety Factor: 3x A 3x for lack of a NOAEL is considered an FQPA safety factor.
Target MOE: 30
4.3.7. Inhalation Exposure (Acute)
Study Selected: Acute Cholinesterase Study in Rats Non-guideline
MRID: 45805703 (see discussion under Section 4.3.1 Acute Reference Dose)
Target MOE: 100, or 30 if RfC methodology is used. If RfC methodology is used, the
interspecies extrapolation factor is reduced from lOx to 3x.
4.3.8. Inhalation Exposure (Short and Intermediate Term)
Study Selected: Subchronic oral toxicity study in human subjects § Non-guideline
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MRID No.: 44248801 (See discussion above under dermal exposure)
Comments about Study/Endpoint: The uncertainty factors are the same as discussed above under
Dermal Exposure.
4.3.9. Inhalation Exposure (Long Term)
Study Selected: 2-year Rat Inhalation/carcinogenicity870.4200a (formerly §83-2a)
MRID No. 0057695, 00632569
Executive Summary: The critical study for inhalation risk assessment for Dichlorvos is an
inhalation carcinogenicity study in rats. Groups of 50/sex/group Carworth rats were exposed to
atmospheres containing Dichlorvos vapor for 23 hours/day, 7 days/week at concentrations of 0,
0.05, 0.5, and 5 mg/m3 equivalent to 0.055, 0.5, and 5.0 mg/kg/day for 2 years. Animals were
observed for clinical signs of toxicity, hematology, and clinical chemistry. Plasma, RBC and
brain cholinesterase activity were determined at study termination. There were no toxic signs,
and no organ weight or organ to body weight changes, or hematological changes attributable to
administration of Dichlorvos. Body weights were significantly decreased in mid and high dose
males up to study termination, and in high dose females throughout the study. Plasma, RBC, and
brain cholinesterase activity were significantly reduced in the mid and high dose groups (76, 72,
and 90 and 83, 68, and 90 percent of control in mid dose males and females, and to 38, 4, and
21, and 22, 5, and 16 percent of control in the high dose male and female groups, respectively).
RBC cholinesterase activity was reduced to 88 percent of control in the low dose females. The
BMDio for RBC cholinesterase inhibition in female rats was 0.15 mg/m3 and the BMDLio was
0.07 mg/m3.
Comments about Study/Endpoint: This is the same inhalation study which has been used by the
Agency RfD/RfC Work Group in deriving the Reference Concentration (RfC) for Dichlorvos.
An Agency RfC document is available on IRIS.
The BMDLio of 0.07 mg/m3 (or 0.00007 mg/L) was selected for chronic inhalation risk
assessment scenarios. Uncertainty factors account for intraspecies variation (lOx) and 3x for
interspecies variation. (The interspecies extrapolation factor is reduced to 3x when the endpoint
is expressed in concentration units (RfC methodology)).
FQPA Safety Factor: Ix
Target MOE: 30
4.3.10. Margins of Exposure
A summary of target Levels of Concern for dichlorvos risk assessment is provided in Table
4.3.10.
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Table 4.3.10. Target Levels of Concern (i.e., Margins of Exposure) for Dichlorvos Exposure Scenarios
Route
Acute
(<1 Day)
Short-Term
(1-30 Days)
I ntermed i ate-Term
(1 - 6 Months)
Long -Term
(> 6 Months)
Occupational (Worker) Exposure
Dermal
Inhalation
100
100/30*
30
30
30
30
N/A
N/A
Residential (Non-Dietary) Exposure
Oral
Dermal
Inhalation
100
100
100/30*
30
30
N/A
N/A
30
N/A
N/A
30
30
* The higher target MOE is used when the endpoint is expressed in mg/kg/day (for exposure during application).
The lower target MOE is used when the endpoint is expressed in concentration units (RfC methodology, used
for post-application risk assessment). There is no long term residential inhalation exposure during application.
For short- and intermediate- term oral and dermal exposures, the uncertainty factor is based on
the conventional uncertainty factor of 10X for intraspecies variability. No factor is needed for
interspecies extrapolation because the endpoint is based on a human study. A 3x factor for lack
of a NOAEL is considered an FQPA safety factor.
For short- and intermediate- term inhalation exposure, the uncertainty factor is based on the
conventional uncertainty factor of lOx for intraspecies extrapolation, 3x for the use of a LOAEL.
For long term inhalation exposure, the uncertainty factor is based on the conventional uncertainty
factor of lOx for intraspecies extrapolation, 3x for interspecies extrapolation (based on air
concentrations), The FQPA safety factor is reduced to Ix for residential exposure assessments.
For acute inhalation exposure, the uncertainty factor is based on the conventional uncertainty
factor of lOOx (10X for interspecies extrapolation and lOx for intraspecies variability), when the
endpoint is expressed in mg/kg/day. When the endpoint is expressed in concentration units, the
interspecies extrapolation factor is reduced to 3x. The FQPA Safety Factor has been reduced to Ix.
The target MOE is 30.
4.3.11. Recommendation for Aggregate Exposure Risk Assessments
Under FQPA, when there are potential residential exposures to the pesticide, aggregate risk
assessment must consider exposures from residues in food commodities and drinking water, as well
as exposures arising from non-dietary sources (e.g., incidental oral, dermal and inhalation
exposures) from the residential scenarios. Since there are residential uses of dichlorvos and the
effect is cholinesterase inhibition for all endpoints, aggregation of risk from non dietary sources is
required. Since the target MOEs differ, aggregation of risk will be assessed using the aggregate
risk index (ARI). The target ARI is 1.
4.3.12. Classification of Carcinogenic Potential
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Dichlorvos has been classified as a category C carcinogen based primarily on increased
incidences of forestomach tumors in female mice and mononuclear cell leukemia (MCL) in male
Fischer 344 rats. Both tumor types have been used at various times to derive qi* s for quantitation
of cancer risk. After lengthy deliberations and consultations with EPA's Scientific Advisory Panel
(SAP) and cancer experts with the National Toxicology Program, HED's Cancer Assessment
Review Committee has classified dichlorvos as "suggestive" and not requiring quantitation of
cancer risks based on the following rationale:
1) MCL in the male Fischer rat has certain properties in terms of variability and reliability which
limit its usefulness for human risk assessment.
2) The forestomach tumors in mice observed at gavage doses causing inhibition of plasma and
red blood cell cholinesterase and cholinergic signs, are also limited in their use for human risk
assessment.
3) The fact that dichlorvos is only positive by the gavage route and negative by the inhalation
route, which is the major route of human exposure, indicates that any classification by the oral
route may be limited since localized effects in the forestomach may not be applicable to human
risk assessment.
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4.4 Summary of Toxicology Endpoint Selection for Dichlorvos
Table 4.4. Summary of lexicological Doses and Endpoints for Dichlorvos for Use in Dietary and Non-Occupational Human Health
Risk Assessments
Exposure
Scenario
Acute Dietary
(General population
including infants and
children)
Chronic Dietary
(All populations)
Short-Term
Incidental Oral (1-30
days)
Acute Dermal and
Acute Incidental Oral
Short-, Intermediate-
and Long-Term
Dermal
Acute Inhalation (1
day)
Short- and
Intermediate-term
Inhalation of vapors
Short- and
Intermediate-Term
Inhalation during
application
Long-Term Inhalation
of vapors
Cancer (oral, dermal,
inhalation)
Point of
Departure
BMDL10 = 0.8
mg/kg/day
NOAEL= 0.05
mg/kg/day
LOAEL=0.1
mg/kg/day
BMDL10 = 0.8
mg/kg/day
dermal
absorption=11%
Oral study
LOAEL=
0.1 mg/kg/day
dermal
absorption=11%
Oral study
BMDL10= 0.8
mg/kg/day
(inhalation
absorption rate
= 1 00%)
Air
concentration
Equivalent = 0.8
mg/m3*
Oral study
LOAEL=
0.1 mg/kg/day
UF=30
Concentration
equivalent= 0.35
mg/m3*
LOAEL=0.1
mg/kg/day
BMDL10 = 0.07
mg/m3
Uncertainty/FQPA
Safety Factors
UFA= 10x
UFH = 10x
FQPASF = 1x
UFA=10x
UFH = 10x
FQPASF = 1x
UFH=10x
FQPASF = 3x(UFL)
UFA= 10x
UFH = 10x
FQPASF = 1x
UFH = 10x
FQPASF = 3x(UFL)
UFA=10x
UFH = 10xor3x**
FQPASF = 1x
UFH = 10x
FQPASF = 3x(UFL)
UFH = 10x
FQPASF = 3x(UFL)
UFA= 10x
UFH = 3x"
FQPASF = 1x
Level of Concern
for Risk
Assessment
Acute RfD = 0.008
mg/kg/day
aPAD = 0.008
mg/kg/day
Chronic RfD =
0.0005 mg/kg/day
cPAD = 0.0005
mg/kg/day
Residential LOC
MOE = 30
Residential LOC
MOE = 100
Residential LOC
MOE = 30
Residential LOC
MOE = 100/30"
Residential LOC
MOE = 30
Residential LOC
MOE = 30
Residential LOC =
30
Study and Toxicological Effects
Rat acute oral cholinesterase studies -
RBC and Brain ChE depression. NOAEL =
1 mg/kg/day, LOAEL = 5 mg/kg/day, BMD
= 1 .6 mg/kg/day for brain ChE depression
(F)
1-Year Dog study
LOAEL = 0.1 mg/kg/day based on Plasma
and RBC ChE depression
Human 21 -day oral study
LOAEL = 0.1 mg/kg/day based on RBC
ChE depression
Rat acute oral cholinesterase studies -
RBC and Brain ChE depression. NOAEL =
1 mg/kg/day, LOAEL = 5 mg/kg/day, BMD
= 1 .6 mg/kg/day for brain ChE depression
(F)
Human 21 -day oral study
LOAEL = 0.1 mg/kg/day based on RBC
ChE depression
Rat acute oral cholinesterase studies -
RBC and Brain ChE depression. NOAEL =
1 mg/kg/day, LOAEL = 5 mg/kg/day, BMD
= 1 .6 mg/kg/day for brain ChE depression
(F)
Human 21 -day oral study
LOAEL = 0.1 mg/kg/day based on RBC
ChE depression
Human 21 -day oral study
LOAEL = 0.1 mg/kg/day based on RBC
ChE depression
2-year Rat Inhalation
BMD = 0.15 mg/m3 based on RBC ChE
depression (F)
"suggestive" evidence of carcinogenicity not quantifiable under the 1 999 Draft Agency Cancer Guidelines
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Table 4.4. Summary of Toxicological Doses and Endpoints for Dichlorvos for Use in Dietary and Non-Occupational Human Health
Risk Assessments
Exposure
Scenario
Point of
Departure
Uncertainty/FQPA
Safety Factors
Level of Concern
for Risk
Assessment
Study and Toxicological Effects
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and
used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human
exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF =
uncertainty factor. UFA = extrapolation from animal to human (intraspecies). UFn = potential variation in sensitivity
among members of the human population (interspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of
a short-term study for long-term risk assessment. UFoe = to account for the absence of key date (i.e., lack of a critical
study). FQPAsp = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference
dose. MOE = margin of exposure. LOG = level of concern. N/A = Not Applicable
* Calculation of concentration equivalent BMDL-io and LOAEL
Acute Inhalation BMDL-io
0.8 mg/kg/day x 0.35 kg / 0.34 m3/day = 0.8 mg/m3
Short- and Intermediate-term inhalation of vapors LOAEL
0.1 mg/kg/day x 70 kg / 20 m3/day = 0.35 mg/m3
**Since the NOAEL is expressed in concentration units (RfC methodology), the interspecies extrapolation factor is 3x (for
the acute and long term inhalation scenarios), for a total UF of 30 for acute inhalation and long term inhalation. The
residential target MOE is 30 for acute inhalation, since the FQPA safety factor has been reduced to 1. The Residential
target MOE is 30 for long term inhalation, since the FQPA safety factor is 1.
4.4 FQPA Safety factor
The HED dichlorvos team evaluated the hazard and exposure data to determine if the FQPAlOx
safety factor should be retained, reduced or removed focusing primarily on the following points:
• The standard developmental and reproductive toxicity studies and the developmental
neurotoxicity study submitted to the Agency showed no residual concern for sensitivity or
susceptibility of rats, or rabbits to in utero and/or postnatal exposure to dichlorvos;
• In repeated dose studies with dichlorvos in rats, young rats were less sensitive than adult rats
with respect to inhibition of RBC cholinesterase; in repeated dose studies with dichlorvos in
rats, based on the BMD analysis, there was no difference between young rats and adult rats with
respect to inhibition of brain cholinesterase; in repeated dose studies, the BMDs are similar
between compartments, sexes and age groups.
• Some exposure scenarios are based on a LOAEL.
• The dietary food exposure assessment utilizes a combination of monitoring data, field trial data,
and tolerance level residues. Percent crop treated information is used where available. These
data will not underestimate chronic exposures/risks.
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• The dietary drinking water assessment (Tier 2 estimates) utilizes values generated by model and
associated modeling parameters which are designed to provide conservative, health protective,
high-end estimates of water concentrations.
• The residential exposure assessment utilizes dichlorvos specific monitoring data, activity
specific transfer coefficients and chemical-specific turf transferable residue (TTR) studies for
the post-application turf scenario (use of trichlorfon). The refined residential assessment is
based on reliable data and is unlikely to underestimate exposure/risk.
The dichlorvos team concluded that the FQPA Safety Factor can be reduced to Ix, except for short
term oral and dermal scenarios, for which the FQPA factor is retained at 3x to account for the lack
ofaNOAEL.
4.5. Endocrine Disruption
EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to
determine whether certain substances (including all pesticide active and other ingredients) "may
have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or
other such endocrine effects as the Administrator may designate." Following recommendations of
its Endocrine Disrupter and Testing Advisory Committee (EDSTAC), EPA determined that there
was a scientific basis for including, as part of the program, the androgen and thyroid hormone
systems, in addition to the estrogen hormone system. EPA also adopted EDSTAC's
recommendation that the Program include evaluations of potential effects in wildlife. For pesticide
chemicals, EPA will use FIFRA and, to the extent that effects in wildlife may help determine
whether a substance may have an effect in humans, FFDCA authority to require the wildlife
evaluations. As the science develops and resources allow, screening of additional hormone systems
may be added to the Endocrine Disrupter Screening Program (EDSP). In the available toxicity
studies on dichlorvos, there was no estrogen, androgen, and/or thyroid mediated toxicity. When
additional appropriate screening and/or testing protocols being considered under the Agency's
EDSP have been developed, dichlorvos may be subjected to further screening and/or testing to
better characterize effects related to endocrine disruption.
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5.0 Public Health Data
The Agency has conducted a review of reported poisoning incidents associated with human
exposure to dichlorvos. The Agency has consulted the following data bases for the poisoning
incident data on the active ingredient dichlorvos: (1) the OPP Incident Data System, which contains
anecdotal reports of incidents from various sources, including registrants, other federal and state
health and environmental agencies and individual consumers, submitted to OPP since 1992, (2)
Poison Control Center Data for 28 organophosphate and carbamate chemicals for the years 1985
through 1992, (3) California Department of Food and Agriculture reports (superceded by the
Department of Pesticide Regulation), which contain uniform data on suspected pesticide poisonings
collected since 1982, and (4) National Pesticide Telecommunications Network (NPTN), which is a
toll-free information service supported by OPP. In addition, the Agency has received public
comments regarding poisoning incidences associated with dichlorvos as comments to the Proposed
Notice of Intent to Cancel (PD 2/3) and in Phase 3 of the RED process. Specific comments on
incidences were received from Amvac Chemical Corporation, the Japanese Resin Strip
Manufacturer's association, and two private citizens, Arturo Haran and Eric Levine.
Exposure to dichlorvos has resulted in poisoning incidents. Dichlorvos has widespread use
patterns in the home and agricultural environments. Many of these uses (e.g., poultry houses) are
atypical of most organophosphates, which make it difficult to compare the risk. According to
California data, it appears that a majority of cases involved illnesses to workers indoors that entered
a facility previously fumigated with dichlorvos. Often exposure results from inadequate ventilation
before persons are allowed in or near the treated area or lack of proper personal protective
equipment (PPE).
Dichlorvos can cause systemic illness, including respiratory effects, to individuals who are
exposed after fumigation.
5.1 Incident Reports
Incidents with dichlorvos are discussed in a separate review. Blondell, J and Spann, M.
1998. More recent information is available. However, the more recent information is very similar
to that reported in 1998, and doesn't change our conclusions (J. Blondell, personal communication
with S. Hummel, 1/4/2005).
5.2 Other
The Agency received additional information on poisoning incidents associated with
dichlorvos as comments to the PD 2/3 and to Phase 3 of the RED. Specific comments on incidents
were received from Amvac Chemical Corporation, the Japanese Resin Strip Manufacturer's
Association, and two private citizens, Arturo Haran and Eric Levine. Amvac submitted a review of
human incident data for Dichlorvos (Feiler 1995), and the Japanese Resin Strip Manufacturer's
Association submitted data on poisoning incidences involving dichlorvos resin strips. Arturo Haran
submitted an anecdotal report of health effects and Eric Levine submitted a comment about the
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potential carcinogenicity of dichlorvos. The Agency has reviewed this new information (Blondell
1996). The Agency's conclusions are summarized below.
Data reported by the American Association of Poison Control Centers (AAPCC) concerning
exposure to single products with dichlorvos often contain other active ingredients. AAPCC
reported 21,006 exposures to single products containing dichlorvos. Most of these exposures
involve homeowner use products that contained dichlorvos in combination with other insecticides
such as propoxur, pyrethrins, or piperonyl butoxide. In these cases involving dichlorvos in
combination with other pesticides it is incorrect to attribute any resulting toxicity solely to
dichlorvos.
Dichlorvos resin strips account for a very small proportion of total incidents, about 33 cases
per year (1% of total incidences). Incident reports involving exposure to resin strips usually do not
involve any significant acute symptoms that would require medical treatment (Blondell 1996).
Eric Levine commented on epidemiological evidence linking use of dichlorvos resin strips
with childhood cancer. Two epidemiologic studies have reported an association between exposure
to dichlorvos resin strips and childhood cancer. These studies by Liess and Savitz (1995) and
Davis et al (1993) have been reviewed by the Agency (Blondell 1996). Reviews of these studies
have identified biases and confounders that could explain the observed associations. The Agency
concludes that the biases are a more likely explanation for the findings of increased cancer than
exposure to resin strips. Additional studies that correct for the control of potential biases and
problems of exposure determination are needed before an association between dichlorvos and
childhood cancer can be established.
A statistically significant excess risk for prostate cancer and dichlorvos exposure was
reported in the recent Agricultural Health Study (AHS) by Alavanja et al., (2003). The reported
excess risk was based on a small number of cases (n=16) and only seen in the men who had a
family history of prostate cancer. The odds ratio reported was 1.75, (75% excess) with confidence
interval 1.0-3.06, meaning the risk could be as high as 206%. Dichlorvos was one of seven
chemicals positive for prostate cancer among fifty chemicals tested. There is no AHS chemical
specific report on dichlorvos at this time. Follow-up studies are planned to examine the interaction
effect on family history and genetic susceptibility factors. The AHS is a prospective pesticide
epidemiology study that includes over 90,000 certified pesticide applicators and their families from
Iowa and North Carolina. Additional analyses will examine dichlorvos findings, as part of the high
pesticide exposure event studies and work practices assessments. Dichlorvos is not one of the
current National Health and Nutrition Examination Surveys (NHANES) chemicals being examined
by the Centers for Disease Control (CDC) National Center for Health Statistics (NCHS).
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6.0 Exposure Characterization/Assessment
6.1 Dietary Exposure/Risk Pathway
6.1.1 Residue Profile
The reregistration requirements for plant and livestock metabolism are fulfilled. The Agency
determined that the available data depicting the metabolism of naled in plants are sufficient to
delineate the metabolism of dichlorvos in plants because dichlorvos is the initial metabolite of
naled. In plants, naled is metabolized to dichlorvos which is hydrolyzed to dimethyl phosphate and
dichloroacetaldehyde. Dimethyl phosphate is sequentially degraded to monomethyl phosphate and
inorganic phosphates, and dichloroacetaldehyde is converted to 2,2-dichloroethanol which is then
conjugated and/or incorporated into naturally occurring plant components. The residue of concern
in plant commodities is dichlorvos.
Acceptable studies depicting the qualitative nature of the residue in ruminants and poultry
following dermal treatment with dichlorvos have been submitted and evaluated. Because
dichlorvos is the initial metabolite of naled, the available metabolism studies reflecting oral dosing
of ruminants and hens with naled are sufficient to delineate the metabolism of orally dosed
dichlorvos in animals. The residue of concern in animal commodities is dichlorvos.
Adequate field trial and processing data are available for the reregistration of dichlorvos,
although not all the field trial data are adequately supported by storage stability data, and there is an
outstanding data requirement for a dermal study in swine. Finite residues are reported in the field
trials, but residues are generally non-detectable in monitoring data. Non-detectable residues were
generally reported in livestock tissues, milk, and eggs. Adequate enforcement analytical methods
are available in PAMI and II. Dichlorvos is recovered by PAMI Luke multiresidue method
(protocol D), provided "early eluter" conditions are used. The Pesticide Analytical Manual (PAM)
Vol. II lists a GC method (with flame photometric detection; Method I) for the determination of
dichlorvos in plant and animal commodities. An additional GC method (Method II) using electron
capture detection is listed for the determination of dichlorvos and naled in plant and animal
commodities; this method is also an enforcement method for naled. A GC method using
microcoulometric detection is listed as Method A. This method determines total residues of
dichlorvos and naled via conversion of naled residues to dichlorvos; however, the method can be
modified to determine naled and dichlorvos separately. Data collection methods were similar to the
available enforcement methods, and were adequately validated.
Dietary exposure to dichlorvos residues may occur as a result of use on or at a variety of
sites, including mushroom houses, warehouses containing bulk-stored and packaged or bagged
nonperishable processed and raw food, commercial food processing plants, groceries, direct animal
treatment, and livestock premise treatment. As a result, dichlorvos residues may be found in bulk
stored and packaged or bagged non perishable processed or raw food. Dichlorvos residues may also
be found in mushrooms and in livestock commodities, such as meat, milk, meat byproducts,
poultry, and eggs. In addition, a dichlorvos registrant has expressed interest in supporting use on
tomatoes.
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Two other pesticides, naled and trichlorfon, degrade to dichlorvos through plant and
livestock metabolism, and non-biological reactions. The Agency does not expect measurable
dichlorvos residues from trichlorfon because all trichlorfon food uses on field crops have been
canceled and associated tolerances revoked, and non-detectable residues were found in livestock
dermal studies.
Three factors will significantly affect dietary exposure to dichlorvos from registered uses of
naled; these include the pre-harvest interval (PHI), the condition and length of storage, and cooking
and processing. Plant metabolism studies show that dichlorvos residues are formed 1 to 3 days
after treatment with naled; however, dichlorvos residues decline to less than the limit of detection
(0.01 to 0.05 ppm) 7 days after treatment. In general, registered uses of naled have PHIs of less
than 7 days. Because of the short PHIs for naled products, measurable residues of dichlorvos may
be present in the diet from naled treated food. As a result, the dietary (food) exposure assessment
for dichlorvos includes residues of dichlorvos resulting from the application of naled.
Dietary exposure estimates for acute and chronic dietary exposure assessments have been
refined with residue data from USDA's Pesticide Data Program (PDF), FDA surveillance
monitoring data, and FDA Total Diet Study (TDS) data, processing and cooking studies, and
percent of crop treated information.
Sources of data to estimate the levels of residues of pesticides in food include the
following: tolerances (legal limits), controlled field trial data, Food and Drug Administration
(FDA) surveillance and compliance monitoring data, FDA Total Diet Study data (market basket
survey based on a random sampling of residues on food in grocery stores), US Department of
Agriculture (USDA) Pesticide Data Program (PDF), and USDA/FSIS (Food Safety Inspection
Service) livestock monitoring data (Hummel, 1998a, Hummel 2000). The estimated levels of
residues can then be adjusted for the effects of processing using processing studies, including
commercial processing studies, washing studies, cooking studies, and residue degradation studies.
Of these sources, the Agency relied on tolerance levels and field trial data (adjusted for the effects
of processing and cooking) to estimate dietary exposure to dichlorvos in the PD 2/3. At the time of
the PD 2/3, the monitoring data available for dichlorvos were very limited. In this updated
assessment, anticipated residues based on some tolerances plus field trial and monitoring data were
used.
(a). Field Trial Data. Data from controlled field trials which reflect currently
registered uses are available for mushrooms. Data from direct dermal treatments to cattle and
poultry are discussed in the Dichlorvos Registration Standard. Field trial data are available for
packaged or bagged food, use in food manufacturing and processing facilities, and for secondary
residues in livestock commodities. Adequate field trial data are not available for tomatoes.
(b). FDA Surveillance and Compliance Monitoring Data. The FDA Surveillance
and Compliance Monitoring Program is designed to ensure that pesticide residues do not exceed
established tolerances. Naled and dichlorvos are included in the FDA surveillance and compliance
monitoring programs. However, dichlorvos is only detected using the Luke method on non-fatty
foods, and only when "early eluter" column conditions are used (low column temperature). Thus,
the number of samples analyzed for dichlorvos is low compared to the samples analyzed for other
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pesticides, although the number of analyses done by FDA that will detect dichlorvos have increased
significantly in the last few years. FDA Surveillance and Compliance monitoring data were
obtained from FDA for 1990 through 1998. From 1994 through 1998, FDA analyzed over 3000
surveillance monitoring samples for dichlorvos. The limit of quantitation (LOQ) for dichlorvos in
fruits and vegetables is approximately 0.01 ppm, and the limit of detection (LOD), approximately
0.003 ppm.
All residues of dichlorvos reported were non-detectable, with the following exceptions:
three samples of strawberries (which had low levels of detectable residues of dichlorvos), one
sample of red raspberries (0.08 ppm dichlorvos); one tomato sample from Mexico with a trace
residue (> LOD, but
-------
temperature programming which would allow detection of "early eluters." Therefore, if dichlorvos
is present, it would be detected, and one detectable residue of dichlorvos was reported. The LOD
for dichlorvos in total diet samples is 0.001 ppm (personal communication, B. McMahon, FDA).
(d). USDA Pesticide Data Program Data. The USDA Pesticide Data Program
(PDF) collects residue data primarily for fresh fruits and vegetables, plus wheat grain, beef
commodities, poultry commodities, and milk. A few canned and frozen commodities have been
tested. Samples are collected in terminal markets and large distribution centers. The commodities
included in the PDF changes annually. Sampling dates and sites are selected at random following a
statistically designed sampling plan. Participating laboratories meet rigorous quality
assurance/quality control (QA/QC) criteria including following good laboratory practices (GLP), a
check sample program, and confirmation of residue findings. Sampling and analyses are done
through a cooperative agreement with nine states and two USDA laboratories. These states
represent about 50% of the population of the US and a large percentage of the fresh fruits and
vegetables grown in the US. Food commodities collected in the PDF are prepared as normally
would be done for consumption, washed and peeled, although not cooked. Canned and frozen
commodities are not further cooked before analysis, although they may have been blanched or
cooked in the canning or freezing process.
The USDA PDF analyzes for dichlorvos, which would include dichlorvos resulting from
naled since the analytical method used generally converts naled to dichlorvos prior to or during the
analysis. The LOD for the analyses varied, depending on the laboratory conducting the analyses,
and ranged from 3 ppb to 280 ppb. All samples analyzed for dichlorvos had non-detectable
residues, except for (1) one peach sample analyzed in 1992, which had a dichlorvos residue of
0.059 ppm; (2) one green bean sample analyzed in 1994, which had a dichlorvos residue of 0.012
ppm; (3) one grape sample analyzed in 1996, which had a dichlorvos residue of 0.003 ppm, which
was below the LOQ; (4) one milk sample analyzed in 1996, which had a dichlorvos residue of
0.003 ppm, which was below the LOQ; (5) one pear sample analyzed in 1997, which had a
dichlorvos residue of 0.005 ppm, which was below the LOQ; and (5) 15 strawberry samples in
1998, on which the maximum dichlorvos residue was 0.02 ppm. PDF data were used in the
dichlorvos dietary exposure assessment for commodities which could be treated with naled, beef
commodities, poultry commodities, and for milk. The PDF data on wheat grain were not used,
because packaged and bagged commodities made from wheat grain could have been treated again
with dichlorvos after the PDF samples would have been collected. The PDF does not analyze for
naled because initial method validation indicated that naled is converted to dichlorvos during the
analysis. The PDF does, however, identify unknown residues, and would report a residue of naled
if found.
(e). Processing and Cooking Study Data. Residues for raw commodities can be
modified by processing factors to account for changes during commercial or other processing and
cooking. Processing, cooking and decline (half-life) studies were available for cocoa beans, dry
pinto beans, tomato juice, ground roasted coffee beans, raw hamburger meat, raw eggs, and raw
whole milk. The resulting cooking factors were used to reduce the Agency's estimate of residues
for these commodities and were translated to other commodities based on similarity of cooking time
and temperature. Additional cooking studies were available and discussed in the Residue
Chemistry Chapter of the Registration Standard. Half-lives of dichlorvos in various commodities
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ranged from 0 to over 1,000 hours. The reduction of dichlorvos upon cooking appeared to be
related to the length of time and temperature used in cooking. Residues were adjusted based on
these cooking factors to obtain the Anticipated Residue Estimate for the cooked commodity.
(f). Percent of crop treated data. OPP has refined its estimates of dietary exposure
for various commodities based on percent of crop treated. The Biological and Economic Analysis
Division (BEAD) of OPP provided updated percent of crop treated (% CT) information that were
incorporated into the acute dietary (food) exposure analysis as appropriate (Hummel, et. al. 2000).
Where a range of percent crop treated estimates are supplied for this analysis, the upper end of that
range is assumed for acute dietary (food) exposure analysis, and the typical or average % CT is
used for the chronic dietary (food) exposure analysis.
6.1.2 Acute and Chronic Dietary Exposure and Risk
Anticipated residues are a realistic estimate of actual pesticide residues in foods
based on available data. Reliable data are available for dichlorvos, including the USDA's PDF
data, the FDA Total Diet Study and the FDA monitoring data. These data were not available at the
time of the PD 2/3, Notice of Intent to Cancel, published in 1995. Anticipated residues used in the
dietary risk assessment are presented in separate memo (Hummel S, Hrdy D, and Sahafayen M,
2000). The methods for deriving anticipated residues for dichlorvos are described below.
(a) From Use of Dichlorvos. All dichlorvos tolerances in 40 CFR §180.235 were
evaluated as potential sources of dichlorvos residues. For the updated dichlorvos dietary exposure
assessment, FDA Total Diet Study data were used for residues resulting from the use of dichlorvos
per se, where appropriate, by grouping similar commodities made from grain products, sugar, dried
eggs, coffee and tea, and dried fruits. These are summarized below.
Raw Agricultural Commodities. The following uses have been canceled by
AMVAC: tomatoes, cucumbers, lettuce, and radishes, and the associated tolerances recommended
for revocation. Therefore, these uses are not included in the exposure assessment. One dichlorvos
registrant has proposed supporting use on tomatoes, and tomatoes still appears on one product label,
EPA Reg. No. 5011-49. No residue data were provided to support this use. No detectable
residues of dichlorvos were detected on tomatoes in 1996-1998 in the PDF or from 1994-1998 in
the FDA Surveillance Monitoring Program.
Meat, Milk, Poultry and Eggs. Residues in livestock tissues, including milk and
eggs, may result from consumption of dichlorvos treated livestock feeds, direct dermal treatments,
livestock premise treatments, or from use as a drug in swine. Livestock metabolism studies done at
exaggerated rates in ruminants and poultry have demonstrated that oral ingestion of dichlorvos,
naled, and trichlorfon by cattle and poultry will not result in detectable residues. This conclusion
can be translated to the drug use of dichlorvos in swine. Secondary residues in livestock and
poultry from consumption of treated feed fall under category 3 of 40 CFR §180.6(a), having no
reasonable expectation of finite residues. Data reflecting dichlorvos direct livestock treatments are
discussed in the Residue Chemistry Chapter of the Dichlorvos Registration Standard. Data from
direct dermal studies indicate that detectable residues are not expected, except in skin. Residues are
non-detectable (<0.01 ppm) in cattle tissue and milk, and non-detectable (<0.05 ppm) in poultry
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tissues and eggs. For the PD 2/3 dietary exposure assessment, the Agency used one-half the limit
of detection as the residue estimate in both cases.
PDF monitoring data were available for meat (beef and poultry) commodities, and milk.
Non-detectable residues of dichlorvos were found in all beef commodities (<0.001 ppm) and
poultry commodities (<0.006 ppm), Ratios of dichlorvos residues found in livestock tissues in
dermal metabolism studies to residues of dichlorvos found in milk in the livestock dermal
metabolism studies were calculated. These ratios were then used with the PDF monitoring data in
milk to estimate residues of dichlorvos in livestock tissues (lower than the PDF limit of quantitation
for beef commodities). The dietary exposure estimates in poultry commodities are based on the
non-detectable residues (<0.006 ppm) reported in PDF monitoring data. A cooking factor of 0.3x
was then applied. The dietary exposure estimate for eggs was the non-detectable residue found in
cooked eggs in the FDA Total Diet Study.
Bulk Stored, Packaged or Bagged Commodities, Food and Feed Handling Uses. The
anticipated residues used in the Dichlorvos PD 2/3 exposure assessment for packaged, bagged or
bulk stored food were based on field studies submitted by AMVAC (Hummel 1994b). Residue data
were submitted for many commodities. For those commodities where data were not submitted, the
Agency translated residue data from similar commodities. For example, data on dry beans are
translated to other legumes; data on wheat flour are translated to all flours and meals, etc. In
addition, residue data were provided for corn and oats at various points during processing, and for
flour, sugar, dried milk, dried eggs, shortening, and baking mix from a treated manufacturing
facility. Bulk stored commodities are assumed to be uncovered when treated. Although pesticide
labels state that bulk or unpackaged foods should be covered or removed before spraying, it is not
possible to assess the effect of covering food since the type of material used in the cover is not
specified and the manner in which food is covered would vary considerably. Therefore, food is
assumed to be uncovered, which is likely to overestimate residues. Since the proportion of
commodities stored in bulk vs. packaged/bagged is unknown, the anticipated residues are based the
residues found in packaged/bagged food, because foods are expected to be packaged/bagged closer
to the time of consumption.
FDA TDS data were used for the dichlorvos dietary exposure assessment on grain products
and sugar, eggs, coffee and tea. In the 43 samples of 126 commodities in which dichlorvos would
be detected, only one sample had a detectable residue, one sample of rye bread at 0.01 ppm, which
is below the LOQ of 0.03 ppm.
The tolerances in 40 CFR §180.235 for nonperishable packaged, bagged or bulk raw food
and for packaged or bagged nonperishable processed foods (formerly in 40 CFR §185.1900) do not
refer to specific commodities. Therefore, the Agency has developed a list of commodities likely to
be treated with dichlorvos that are covered by tolerances. Because these tolerances were
established to cover residues resulting from use at different sites (for example, wheat could be
treated in its raw form in a silo, later as flour, during processing into cake mixes, and finally as a
stored packaged commodity), cancellation of any one of the site-specific uses does not necessarily
eliminate the risk of a commodity from dichlorvos treatment. The Agency did not combine the
residues from different sites in creating the anticipated residues, although the cumulative residues
from treating a commodity at different sites were considered in the estimation of percent of crop
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treated for the PD 2/3; however, the Agency position has changed. Now we expect that sufficient
time will pass between treatments that only the maximum residue from one type of treatment needs
to be considered.
(b) From Use ofNaled. All naled tolerances in 40 CFR §180.215 were evaluated as
potential sources of dichlorvos residues. Anticipated residues are based on either tolerance level
equivalents or field trials or monitoring data from FDA (Regulatory monitoring or Total Diet
Study) or USDA (PDF). These data sources were used for both acute and chronic dietary exposure
estimates. Naled and dichlorvos residue estimates were reduced when data were available to
account for the effects of washing, cooking, and processing. In addition, wide area application of
naled in mosquito and fly control use could result in residues potentially on all crops in the
Agency's DEEM™ software. The Agency did not include all these crops in its estimate of
anticipated dichlorvos residues for the chronic dietary exposure assessment. Although it is possible
that dichlorvos residues could occur on any raw agricultural commodity from this use of naled, it is
unlikely that residues would be found on all commodities. As a result, this inclusion of residues of
dichlorvos from all raw crops would present a possible source of overestimation of dietary
exposure. A sensitivity analysis was conducted for naled and dichlorvos from naled, done
separately from the dichlorvos risk assessment, showing that the mosquito and fly control use was
not a substantial source of exposure.
(c) From Use of Trichlorfon. All trichlorfon tolerances in 40 CFR 180.198 were evaluated
as a potential source of dichlorvos residues. All tolerances for trichlorfon have been revoked, with
the exception of tolerances in beef cattle commodities, which are being retained to cover potential
residues from imported meat commodities. In trichlorfon cattle feeding studies, residues of
trichlorfon and dichlorvos were non-detectable (<0.05 ppm) in livestock commodities at pre-
slaughter intervals of 1, 3, and 7 days (T. Morton, 1999). This would result in residue estimates of
the same order of magnitude as those for dichlorvos alone and naled-derived dichlorvos.
Measurable residues of dichlorvos from the use of trichlorfon are not expected, because it has no
crop tolerances or registered crop food uses (Hummel, 1998b), and non-detectable residues are
expected on livestock commodities.
6.1.2.1 Acute Dietary Exposure and Risk
A DEEM™ analysis was performed to estimate acute dietary exposure and risk from
dichlorvos; and to estimate dietary exposures and risks for chronic systemic toxicity from residues
of dichlorvos (Hummel, S. V., D. Hrdy, M. Sahafayen. 2000). Because dichlorvos residues on food
may be derived from use of either dichlorvos or naled, the dietary risk analyses included both
dichlorvos and naled-derived dichlorvos. Trichlorfon-derived dichlorvos was considered. All
domestic field crop uses of trichlorfon have been canceled. The trichlorfon tolerances have been
revoked, except for tolerances in livestock commodities, which were retained as import uses. The
DEEM™ analyses were done for all commodities supported for reregistration.
A highly refined acute dietary analysis was performed, which combined the acute exposure
from dichlorvos residues resulting from the use of dichlorvos, naled-derived dichlorvos (including
residues of naled, which could be converted in the body to dichlorvos), but excluding the naled
public health mosquito use (Hummel, et. al. 2000). Residues of dichlorvos from the use of
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trichlorfon were estimated to be negligible. For assessing risk use of dichlorvos, anticipated
residues based on field trials and monitoring data were used. For assessing risk from naled-derived
dichlorvos, anticipated residues based on some tolerances, some field trials, and monitoring data
were used. The acute probabilistic dietary analyses used individual food consumption as reported
by respondents in the USDA 1989-91 Continuing Survey of Food Intake by Individuals (CSFII) in
the DEEM™ software. Results are reported as a percentage of the aPAD for the 99.9th percentile of
the population. The % aPAD is calculated as the ratio of the exposure to the aPAD (% aPAD =
exposure/aPAD x 100%).
Highly refined anticipated residues which incorporated percent of crop treated (% CT),
monitoring data from the PDF, the FDA Surveillance Monitoring Program, the FDA TDS, field
trial data, and a few tolerances were used to estimate acute dietary exposure. The acute
exposure/risk estimate did not exceed HED's level of concern for either the general US population
or any of the sub-populations. The sub-population with the highest exposure was children 1-6 with
estimated exposure of 4% of the aPAD (0.000021 mg dichlorvos/kg bwt/day), while the estimated
exposure for the U. S. Population was 2% of the aPAD (0.000009 mg dichlorvos/kg bwt/day) at the
99.9th percentile. The results are provided in Table 6.2.1.1.
Table 6.1.2.1. Acute Dietary (Food Only) Tier 3 Exposure and Risk Estimates for Dichlorvos.
Population Subgroup"
U.S. pop - all seasons:
All infants (
-------
Highly refined anticipated residues (which also incorporated % CT information, monitoring
data from the PDF and the FDA Surveillance Monitoring Program, and field trial data) were used to
estimate chronic dietary exposure. The chronic exposure/risk estimate did not exceed HED's level
of concern for either the general US population or any of the sub-populations. The resulting risk
estimate for all sub-populations and the general US population was below 100% of the cPAD. The
sub-population with the highest exposure was children 1-6 with 1% of the chronic population
adjusted dose (cPAD) (0.0000013 mg dichlorvos/kg bwt/day), while the estimated risk to the U.S.
Population was <1% of the cPAD (0.0000007 mg residue/kg bwt/day). The results are provided
below in Table 6.2.1.2.
Table 6.2.1.2. Chronic Dietary (Food Only) Tier 3 Exposure and Risk Estimates for Dichlorvos.
Population Subgroup1
U.S. Population (total)
All infants (< 1 year)
Children 1-6 yrs
Children 7-1 2 yrs
Females 13-50 yrs
cPAD, mg/kg/day2
0.0005
Exposure, mg/kg/day
0.0000007
0.0000013
0.0000013
0.0000007
0.0000003
% cPAD
<1
1
1
<1
<1
1 Population subgroups shown include the U.S. general population, and those of infants, children, and women of child-bearing
age, and other, representative populations whose exposure exceeds that of the U.S. general population.
2 % cPAD = Exposure (mg/kg) •*• cPAD (mg/kg) x 100
6.2.1.3. Dietary Cancer Risk Estimates
No dietary cancer risks for dichlorvos were estimated. The carcinogenic potential of
dichlorvos has been classified as "suggestive" under the 1999 Draft Agency Cancer Guidelines and
no quantitative assessment of cancer risk is required. (Diwan, S. 2000).
6.2.2. Uncertainties in Dietary Exposure Assessment
The Agency believes the exposure and risk assessment presented in this document is the most
refined to date for acute and chronic dietary exposure to dichlorvos as a result of use of dichlorvos,
naled, and trichlorfon. However, there are some uncertainties associated with this exposure
assessment as follows:
(a). The dietary exposure analyses relied primarily on monitoring data obtained either "at the
farm gate," in the case of FDA surveillance monitoring data, or in regional distribution warehouses
for PDF data. Residues potentially present on items purchased at roadside produce stands or farmer's
markets are not represented in this analysis. Although cooking data were available and were used,
there may be differences in the amount of reduction of dichlorvos residues as a result of cooking.
(b). Samples collected for the FDA Total Diet Study were collected in supermarkets in only
four cities per year. Residues found in food in other locations may be different.
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(c). Very little monitoring data are available for fumigated commodities. Extensive
translation was done from one fumigated commodity to another.
(d). For the commodities for which field trial data were used, the residues of dichlorvos are
probably over-estimated. Dichlorvos is expected to dissipate fairly rapidly.
6.2 Water Exposure/Risk Pathway
Dichlorvos residues can be present in ground and/or surface water as a result of use of three
pesticides: dichlorvos (DDVP), naled, and trichlorfon (dichlorvos is a degradate of naled and
trichlorfon). The Environmental Fate and Effects Division (EFED) discussed the environmental
fate of dichlorvos, naled and trichlorfon and evaluated the potential for dichlorvos to contaminate
water from these sources (Abdel-Saheb I, 2003, Jones, R. D., 2006). The environmental fate
properties of dichlorvos, naled, and trichlorfon are indicators of the potentials of these compounds
to migrate to ground or surface water. These fate properties are described below.
6.2.1 Fate Properties of Dichlorvos, Naled, and Trichlorfon
6.2.1.1. Dichlorvos
The major mode of dissipation of dichlorvos is volatilization from soils because
dichlorvos has a vapor pressure of 1.2 X 10"2 mm Hg under field conditions. Also, acceptable
laboratory studies indicate rapid dissipation through volatilization. Dichlorvos appears to degrade
through aerobic soil metabolism and abiotic hydrolysis as well, but these processes are secondary to
volatilization. Hydrolysis is pH dependent where the half-lives were 11 days at pH 5, 5 days at pH
7 and 21 hours at pH 9. Aerobic soil metabolism data showed a half-life of 10 hours; 2,2-
dichloroacetic acid was the major metabolite. An acceptable soil TLC study indicates that
dichlorvos is moderately mobile (Kd's ranging 0.3 to 1.2), based on the Heiling and Turner's
mobility classification. The potential of dichlorvos to leach to ground water is mitigated by its
rapid degradation. Dichlorvos has the potential to contaminate surface waters because of a low Koc
value and high water solubility (10 x 103 ppm, or 1 %). Substantial fractions of run-off will more
than likely occur via dissolution in run-off water rather than adsorption to eroding soil. Despite the
potential for contamination, dichlorvos should not be persistent in any surface waters due to its
susceptibility to rapid hydrolysis and volatilization.
6.2.1.2. Naled
Chemical hydrolysis and biodegradation are the major processes involved in the
transformation of naled and its degradates in the environment. Dichlorvos forms from naled by
indirect photolysis in water and soil. In the presence of photosensitizer in water, as much as 20% of
the applied dose of naled can be found as dichlorvos after 1 day, with rapid decline of dichlorvos
residues afterwards. Under anaerobic aquatic conditions, dichlorvos can be as high as 15% of the
applied naled dose after 1 day. The degradation of dichlorvos formed from naled under anaerobic
conditions is slower (half-life 0.9 days) than under aerobic conditions.
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6.2.1.3. Trichlorfon
Dichlorvos is formed from trichlorfon in soil by aerobic soil metabolism, and in
water hydrolysis studies. Environmental fate data indicate that trichlorfon degrades rapidly in
aerobic soil (ti/2 -1.8 days) under non-sterile conditions; however, in a sterile soil, trichlorfon was
stable (ti/2 > 40 days). Trichlorfon degradation is strongly influenced pH. In the hydrolysis study at
25° C, the trichlorfon degradation half-life was 104 days at pH 5; 34 hours at pH 7; and 31 minutes
at pH 9. The maximum measured dichlorvos formed from trichlorfon also varied with pH, with a
maximum percentage converted of 2.1% at pH 5; 25% at pH 7; and 52% at pH 9. The formation of
dichlorvos from trichlorfon is not a 'hydrolysis reaction' per se, but a dehydrochlorination. The
other degradates found in the hydrolysis study are des-methyldichlorvos, and dichloroacetaldehyde,
resulting from hydrolysis of dichlorvos directly. There is no acceptable field dissipation study for
trichlorfon, because the submitted studies had recovery problems.
6.2.2. Groundwater
EFED has limited monitoring data on the concentrations of dichlorvos, naled or trichlorfon
in groundwater. Validated monitoring data for dichlorvos, naled, and trichlorfon are available for
the states of California and Hawaii from the Pesticides in Groundwater Database (USEPA 1992).
These data indicated that naled, dichlorvos, or trichlorfon have not been detected in groundwater.
However, the monitoring studies were not targeted to the pesticide use area. These data are
presented in Table 6.2.2a. below.
Table 6.2.2a. Groundwater monitoring data for Dichlorvos, Naled, and Trichlorfon showing number of
wells sampled (number of wells with residues) (USEPA 1992)
California
Hawaii
Naled
83(0)
3(0)
Dichlorvos
20(0)
7(0)
Trichlorfon
280 (0)
Because the groundwater monitoring data for dichlorvos are limited, EFED used the Tier I
SCI-GROW screening model to estimate concentrations of dichlorvos in groundwater. This model
predicts that dichlorvos, naled, and trichlorfon will not be found in significant concentrations in
groundwater. Concentrations of these compounds were calculated based on a maximum annual
application rate of 0.2 Ib a.i./acre for dichlorvos (wide area treatment), 9.375 Ib a.i/acre for naled
(the maximum seasonal use rate on Cole crops, 5 applications of 1.87 Ib a.i./acre), and 3 times per
year at 8.17 Ib a.i./acre for trichlorfon (turf). The amount of dichlorvos formed as a degradate of
naled was estimated to be 20% of naled. Therefore, a conservative dichlorvos use rate was
estimated by using naled's use rate multiplied by 0.20. The amount of dichlorvos formed as a
degradate of trichlorfon was estimated to be 56% of trichlorfon, which is the maximum percent of
dichlorvos (56%) formed as a trichlorfon degradate determined from the trichlorfon aerobic aquatic
metabolism at pH 8.5. The amount of dichlorvos formed as a trichlorfon degradate was estimated
by multiplying the maximum application rate for trichlorfon (8.17 Ib a.i/acre) by 56%. Because
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groundwater concentrations of dichlorvos were estimated using a Tier I screening model, EFED has
moderate confidence in the groundwater assessment.
Table 6.2.2b. Estimated Dichlorvos Concentrations in Groundwater.
Source of Dichlorvos Residues
Dichlorvos Applied 1/week
Dichlorvos Applied Every Other
Day
Dichlorvos (from Naled)
Dichlorvos (from Trichlorfon)
Modeled Groundwater Concentration,
ug/l_
0.004
0.015
0.0002
0.01
There may be exceptional circumstances under which groundwater concentrations could
exceed the SCI-GROW estimates. However, such exceptions should be quite rare since the SCI-
GROW model is based exclusively on maximum groundwater concentrations from studies
conducted at sites and under conditions which are most likely to result in groundwater
contamination. The groundwater concentrations generated by SCI-GROW are based on the largest
90-day average recorded during the sampling period. Since there is relatively little temporal
variation in groundwater concentrations compared to surface water, the concentrations can be
considered as appropriate for acute and chronic risk assessment.
6.2.3. Surface Water
Dichlorvos may reach surface water as a result of use of three pesticides: dichlorvos
(DDVP), naled and trichlorfon. In the event that all of these pesticides are used in the same use
area, then the contribution for each chemical should be incorporated in any risk assessment.
OPP does not have any surface water monitoring data on the concentrations of dichlorvos,
naled, or trichlorfon at the present time. Therefore, the Tier IIPRZM/EXAMS model was used for
dichlorvos, naled and trichlorfon. The turf scenario with the Index Reservoir and Percent Crop
Area adjustment (IR-PCA PRZM/EXAMS) was used to estimate surface water concentrations for
trichlorfon.
The results from the index reservoir represent potential drinking water exposure from a
specific area (Illinois) with specific cropping patterns, weather, soils, and other factors. Use of the
index reservoir for areas with different climates, crops, pesticides used, sources of water (e.g. rivers
instead of reservoirs, etc), and hydrogeology creates uncertainties. In general, because the index
reservoir represents a fairly vulnerable watershed, the exposure estimated with the index reservoir
will likely be higher than the actual exposure for most drinking water sources. However, the index
reservoir is not a worst case scenario; communities that derive their drinking water from smaller
bodies of water with minimal outflow, or with more runoff prone soils would likely get higher
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drinking water exposure than estimated using the index reservoir. Areas with a more humid climate
that use a similar reservoir and cropping patterns may also get more pesticides in their drinking
water than predicted using this scenario.
A single steady flow has been used to represent the flow through the reservoir. Discharge
from the reservoir also removes chemical so this assumption will underestimate removal from the
reservoir during wet periods and overestimates removal during dry periods. This assumption can
underestimate or overestimate the concentration in the pond depending upon the annual
precipitation pattern at the site.
The index reservoir scenario uses the characteristics of a single soil to represent the soil in
the basin. In fact, soils can vary substantially across even small areas, and this variation is not
reflected in these simulations.
The index reservoir scenario does not consider tile drainage. Areas that are prone to
substantial runoff are often tile drained. Tile drainage contributes additional water and in some
cases, additional pesticide loading to the reservoir. This may cause either an increase or decrease in
the pesticide concentration in the reservoir. Tile drainage also causes the surface soil to dry out
faster. This will reduce runoff of the pesticide into the reservoir. The watershed used as the model
for the index reservoir (Shipman City Lake) does not have tile drainage in the cropped areas.
Turf was used as the site of interest for trichlorfon. General outdoor uses were used as the
site of interest for dichlorvos. Eight crops were simulated for naled. The modeling results indicate
that all these compounds have the potential to contaminate surface waters by runoff, for short
periods of time especially in areas with large amounts of annual rainfall. However, based on its
environmental fate characteristics, naled will degrade/dissipate rapidly (ti/2 < 1 day), trichlorfon and
dichlorvos will persist slightly longer (ti/2 1.4 and ~ 5 days, respectively). Mitigation practices that
reduce runoff could be effective in reduction of these chemicals transport into surface waters.
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Table 6.2.3a. Estimated Drinking Water Concentrations in Surface Water for
Dichlorvos, Dichlorvos from Naled, and Dichlorvos from Trichlorfon use on Turf
using Tier II PRZM/EXAMS.
Surface water/ peak (90th percentile annual
daily max. for acute exposure analysis)
Surface water/ 90th percentile annual mean
for chronic exposure analysis
use(s) modeled
PCA
model EDWCs (ug/L)
Dichlorvos1
3.46
0.17
4 applications
@0.20lb
ai/acre, spray
appl.
from Naled2
33.0
1.83
5 applications
@1.87lb
ai/acre, spray
appl.
from
Trichlorfon3*
60
1.56
3 applications @
8.2 Ib ai/acre,
spray appl.
0.87
' Dichlorvos from wide area treatment
2 Naled from treatment of brassica crops
3 Trichlorfon turf treatment
* Dichlorvos from trichlorfon is adjusted for a 25% conversion at pH 7, a pH typical of soils
growing turf.
The maximum amount of dichlorvos formed from naled is approximately 20% of the applied
naled. Therefore, a conservative dichlorvos use rate was selected as naled's use rate multiplied by
0.20.
The application rate used on turf for trichlorfon based on 25 percent conversion to dichlorvos
adjusted for differences in MW. A maximum of 25% degradation of trichlorfon to dichlorvos was
assumed because 25% degradation was the maximum observed in a hydrolysis study at pH 7, a pH
typical of soils used to grow turf.
Table 6.2.3b shows the input parameters used in PRZM/EXAMS.
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Table 6.2.3b. Input parameters for Dichlorvos, Dichlorvos from Naled, and
Dichlorvos from Trichlorfon used in PRZM/EXAMS models.
Chemical
PC Code for parent chemical
Molecular weight (g/mole)
Solubility (ppm)
Hydrolysis half-life, pH 7 (days)
Soil Photolysis half-life (days)
Aerobic Soil Metabolism half-life (days)
Aerobic Aquatic Metabolism half-life (days)
Soil Organic Carbon Partitioning (KoC)(l/kg)
Use
Application Rate (Ib a.i. /acr/yr)
Number Of Applications/year
Interval between appl. (day)
Application Method
Dichlorvos Information
From Naled
34401
220.9
10000
5.2
0.65
0.42
no data
37
Brassica
1.87
5
30
Spray
From
Trichlorfon
57901
220.9
10000
5.2
0.65
0.42
no data
37
Turf
8.2
3
7
Spray
Dichlorvos
84001
220.9
10000
5.2
0.65
0.42
no data
37
Wide Area
Treatment
0.20
4
30
Spray
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6.2.4. Drinking Water Risk Estimates
The Pesticide Data Program (PDF) in USD A-Agricultural Marketing Service has sampled
finished drinking water collected after disinfection, and just before distribution to customers, from
community water systems in a few states from 2001 through 2004, and raw and finished drinking
water from community water systems in a few states in 2004. In 2001, PDF analyzed 214
finished drinking water samples from CA and NY. In 2002 and 2003, PDF sampled 371 and 699
finished drinking water samples, respectively, in CA, CO, KS, NY, and TX. In 2004, PDF
sampled raw and finished water from 171 community water systems from MI, NC, OH, OR, PA,
and WA. Dichlorvos was one of the analytes. No detectable residues of dichlorvos were found
at limits of detection (LOD) of 0.4 - 22.5 pptrillion. Naled and trichlorfon were not among the
analytes tested, but PDF would have detected dichlorvos coming from naled and trichlorfon.
The PDF monitoring of water from community water systems does not reflect the drinking
water consumed by the population for the following reasons:
- The PDF samples large community water systems in a limited number of states. The sampling
sites are not necessarily in dichlorvos, naled, and trichlorfon use areas, and the data may not be
reflective of drinking water concentrations in areas of high dichlorvos use.
- The community water systems sampled by PDF are generally deep ground water or surface
water systems. The PDF does not sample individual, private wells. Use of the PDF data would
not be protective of people whose drinking water source is a private well.
The Agency currently lacks sufficient water-related exposure data from monitoring to
complete a quantitative drinking water exposure analysis and risk assessment for dichlorvos.
Therefore, the Agency is presently relying on computer-generated estimated environmental
concentrations (EDWCs). The Tier II PRZM/EXAMS model turf scenario with the Index
Reservoir and Percent Crop Area adjustment (IR-PCA PRZM/EXAMS) was used to generate
EDWCs for surface water and SCI-GROW (an empirical model based upon actual monitoring
data collected for a number of pesticides that serve as benchmarks) predicts EDWCs in ground
water. These models take into account the use patterns and the environmental profile of a
pesticide, but do not include consideration of the impact that processing raw water for distribution
as drinking water would likely have on the removal of pesticides from the source water. The
primary use of these models by the Agency at this stage is to provide a coarse screen for
determining that pesticides residues (and metabolites) in water are not of concern.
For any given pesticide, the SCI-GROW model generates a single EDWC for pesticide
concentration in ground water. That EDWC is used in assessments of both acute and chronic
dietary risk. It is not unusual for the ground water EDWC to be significantly lower than the
surface water EDWCs. The tier II PRZM/EXAMS model provides long duration (up to 36-year)
pesticide concentrations in surface water and is mainly used when a refined EDWC is needed.
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6.3 Residential (Non-Occupational) Exposure/Risk Pathway
Dichlorvos is registered for several residential uses. Residential handlers may be exposed to
dichlorvos during application of dichlorvos in pressurized aerosol spray cans. Residential post
application exposure may occur after use of the following products containing dichlorvos:
pressurized aerosol spray can, resin pest strips, and pet flea collars. Residential post application
exposure to dichlorvos may also occur after lawn treatment with trichlorfon. Residential Exposure
and Risk Estimates are summarized in Table 6.3 below. Information sources and major
assumptions for each residential scenario are described below, with additional information in the
table endnotes. Additional information is available in the referenced documents (Jaquith D., 1993b,
Jaquith D 1998a through n, Jaquith D. 1999 through d, Jaquith, D, 2000, and Jaquith, D., 2001 and
2003). Dichlorvos exposure from the use of Naled is covered by the Naled Risk Assessment.
Dichlorvos exposure from the use of trichlorfon is included in this document. Although residential
bystander exposure could result from the use of naled, both on field crops and as a mosquitocide,
any exposure to dichlorvos from the use of naled would be covered by the Naled Risk Assessment.
Residential Scenarios which were evaluated were of acute, short term, or long term duration.
A BMDLio of 0.8 mg/kg/day from a rat acute oral cholinesterase study is used for the acute oral,
dermal, and inhalation risk assessment. An 11% dermal absorption is assumed for the dermal risk
assessment. The target MOE for residential acute risk assessments is 100.
A LOAEL of 0.1 mg/kg/day from a human 21-day oral study is used for short term
incidental oral, dermal, and inhalation (during application) risk assessment. An 11% dermal
absorption is assumed for the dermal risk assessment. The target MOE for residential short term
risk assessments is 30.
A BMDLio of 0.07 mg/m3 from a 2 year rat inhalation study is used for the long term, post-
application inhalation risk assessment. The target MOE for residential long term inhalation risk
assessment is 30.
6.3.1 Home Uses
6.3.1.1. Residential Handler
(a). Pressurized Aerosol Spray Can
The exposure assessment for pressurized spray cans was derived from data in the
Pesticide Handlers Exposure Database (PJdED VI. 1) and the Residential SOPs for aerosol
application. Residential use of pressurized aerosol product is based on application of 2 ounces from
an aerosol can of 0.5 percent dichlorvos (Jaquith 2001; Jaquith 1998f; REJV, 2002). This is an
acute exposure scenario.
Pressurized aerosol products containing dichlorvos do not list any clothing requirements;
therefore the Agency is assuming that dichlorvos is applied during hot weather when an individual
will be wearing the least amount of clothing (i.e., shorts, short sleeve shirt, and shoes). Using the
Residential SOPs, unit dermal exposures were 220 mg/lb ai handled, and 1.3 mg / Ib ai handled for
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inhalation exposure (adjusted for the NAFTA breathing rate of 1.0 m3/hr, with an absorbed dermal
dose of 0.00022 mg/kg/day. Respiratory exposure was estimated to be 1.2 x 10"5 mg/kg/day. The
total exposure was 2.3 x 10"4 mg/kg/day, with an MOE of 3500 (target MOE = 100), which is not of
concern.
6.3.1.2. Residential Post-application
(a). Pressurized Aerosol
Post application data from a total release fogger application were used as a surrogate
for the post application exposure from pressurized aerosol applications. The total release fogger
treatments in the home have been canceled. However the data are still being used to assess the use
of the aerosol spray, after adjustment for application rate.
Indoor residential post-application exposures for short term exposure scenarios were derived
from a single study measuring the exposures of individuals performing defined activity patterns (20
minute Jazzercise® routine) following the activation of a total release fogger, containing dichlorvos.
This study provides a conservative estimate for short term exposure scenarios from indoor
applications of dichlorvos (Jaquith 1993b). The multi-phase study measured deposition on whole
body dosimeters and (in a separate phase) the urinary concentrations of the metabolite dimethyl
phosphate (DMP), a metabolite of dichlorvos. The biomonitoring gave estimates of exposure of 14
In order to estimate the potential oral exposure from hand to mouth activity of children, the
amount of dichlorvos measured on the hands in the passive dosimetry phase was considered to be
available for ingestion. The passive dosimetry dose on the hands had to be added because the
Jazzercise® routine does not include hand-to-mouth activity. The estimated exposure due to hand
to mouth ingestion, was 0.61 ug/kg (Jaquith 1998k), or a total exposure of 15 ug/kg when the
potential oral component was included. This is considered to be a short-term exposure scenario.
This study only measured exposures to adults; however, exposure to children is expected to be
similar to that of an adult.
For post-application exposure and risk estimates from the use of the pressurized aerosol, it
was assumed that there would be 2 oz of product (containing 0.5% ai) used in a 1000 sq. ft. house
(from the Residential Exposure Joint Venture (REJV) survey (REJV, 2002)). This amount was
compared to the amount that was used for a total release fogger, and the ratio used to adjust the
amount of the biomonitoring study that was conducted. The MOE was 100, which is not of
concern, compared to the target MOE of 30.
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(b). Resin Pest Strips
Several sizes of resin pest strips are marketed. The full size, room size strip is 65 or
80 g, containing 12.1 or 14.9 g of dichlorvos, used to treat 1000 ft3. The full size strip may no
longer be used in spaces occupied more than 4 hours per day. Examples of spaces which may not
be occupied more than 4 hours per day were attics, crawl spaces, and garages. Other sizes of resin
pest strips are the large closet strip, 16 g, containing 3.0 g dichlorvos; the small closet strip, 10.5 g,
containing 1.8 g dichlorvos, and the cupboard strip, 5.25 g, containing 0.97 g dichlorvos.
The dichlorvos label for the smaller size resin strips will have these limitations.
"Only available in the following sizes: 16 g (0.56 oz), 10.5 g (0.37 oz), and 5.25 g (0.9 oz)
pest strip sizes"
Household use. "Use only in Closets, Wardrobes, and Cupboards. Do not use in areas of a
home where people will be present for an extended period of time (e.g., Living Room,
Family Room). Do not use in any rooms or closets of rooms where infants, children and the
sick or aged are or will be present for any extended period of confinement. Do not use
where unwrapped food is stored, or allow the strip to come into contact with food or
cooking utensils. Do not allow children or pets to play or sleep in these areas when
treatment is in progress."
Storage Units, Attics, Garages, Sheds, and Enclosed Crawl Spaces. "Do not use in areas of
a home where people will be present for an extended period of time. [Keep] out of reach of
children and pets, in an open space of an enclosed area, away from windows."
The largest pest strip, 100 g, will no longer be registered. The large 80 g and 65 g pest
strips will be separated into a separate registration, where the label will state:
"Only available in 65 g and 80 g pest strip sizes."
"DIRECTIONS FOR USE" "For use in unoccupied areas, not for use in homes except
garages, attics, crawl spaces, and sheds occupied for less than 4 hours per day.
"Also for use in the following unoccupied structures, provided they are unoccupied for more
than 4 months immediately following placement of a pest strip: vacation homes, cabins,
mobile homes, boats, farm houses, and ranch houses."
Respiratory exposures resulting from the use of resin pest strips were estimated using a
study found in the scientific literature (Collins and DeVries, 1973). Fifteen homes were monitored
at various time intervals for a period of 91 days. Air monitoring was done in one place in each of
the homes, in the same room with the full sized resin pest strip (80 or 100 g strips). A decay curve
measuring the decline of airborne residues was derived for each of these homes. The resulting
equations were integrated over a 91 day period and an average concentration was calculated
(Jaquith 1998a, 1999d, and 2000). The average air concentration, over this time period was
estimated to be 0.015 mg/m3. Smaller sized resin strips placed in a closet or cupboard would be
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expected to have lower concentrations by direct proportion, assuming that the residue of dichlorvos
in the air would equilibrate between the closet or cupboard and the room.
Margins of Exposure were calculated for the resin pest strips using the 90 day average air
concentration in the house (0.015 mg/m3) from a 65 -80 g pest strip containing 12.09 - 14.9 g
dichlorvos in a 1000 ft3 room (Collins, R. D. and DeVries, D. M. 1973), and the BMDLio from a
chronic rat inhalation study of 0.07 mg/m3, based on RBC cholinesterase, and 23 hours of exposure.
The margins of exposure will vary, depending on the exposure time and the size of the pest strip, as
shown in Table 6.3.1.2. below.
Table 6.3.1.2. Exposures/MOEs for dichlorvos resin strips, based on size
of resin strip and time exposed
BMDL10: 0.07 mg/m3 for RBC cholinesterase from 2 year rat inhalation study
Exposure duration: 23 hours per day, 7 days a week
90-day average concentrations of 0.015 mg/m3
Target MOE = 30
Size of Resin Strip
g product
g dichlorvos
Hours exposed per day
1
2
4
6
8
10
12
14
16
18
20
22
24
Full size
65
12.09
Closet
16
3.0
Closet
10.5
1.95
Cupboard
5.25
0.975
Margin of Exposure (MOE)
110
54
27
18
13
11
9
8
7
6
5
5
4
470
240
120
78
60
35
40
34
30
26
24
21
20
660
330
170
110
83
67
55
48
42
37
33
30
28
1300
660
330
220
170
130
110
95
83
74
67
60
55
The MOEs in table 6.3.1.2 are calculated as follows.
23 hr/dav
MOE = 0.07 mg/nr x _
0.015 mg/m3 Hr exposed per day
x 65 g dichlorvos in full size strip
g dichlorvos in product
The dichlorvos label has been changed to allow use of resin strips in areas occupied up to 4
hours per day (garages, attics, ...). Although this use would be allowed by the label, there is no
expectation that individuals will actually be exposed at this level routinely.
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AMVAC has proposed a study to measure air concentrations from use of the smaller resin
strips in closets and cupboards. The study has been required by California, but not EPA. A
protocol was submitted by the registrant to EPA and reviewed (Jaquith, 2003a). The Agency's
comments were provided to AMVAC. Some suggestions were made to improve the study,
including diagrams of the houses, placement of the air monitors, and monitoring of fabric in the
closets with a closet sized strip. To date, the study has not been submitted to EPA.
(c). Pet Flea Collars
A flea collar is placed on the pet's neck to protect the pet from fleas over the life of the
collar. It is expected that the flea collar will be replaced when it is no longer efficacious, which is
assumed to be 120 days.
In this assessment, inhalation exposure was estimated for the flea collars, considering them to be
a mobile resin strip, because the formulation is similar to the resin strip formulation. A dog collar,
containing 2.2 g dichlorvos, would contain (2.2/12.1) or 18 % of the amount of dichlorvos
contained in a full sized resin strip. The air concentration in the room with the pet is estimated to
average 0.0027 mg/m3 for 8 hours per day.
In addition, dermal exposure and children's hand-to-mouth exposure assessments were done,
using a draft ExpoSAC policy. The calculations for the assessment are shown in the footnote for
table 6.3. The dermal exposure was estimated to contribute 0.0011 mg/kg/day and hand-to-mouth
exposure was estimated to be 0.0001 mg/kg/day.
Combining the dermal and hand-to-mouth exposure results in an exposure estimate of 0.0012
mg/kg/day, and an MOE of 83. The inhalation MOE is 74, and the total MOE is 39, which is
greater than the target MOE of 30, and not of concern.
(d). Lawns and Turf - Post-Application
Dichlorvos from the use of Naled. Naled is used as a mosquitocide, and may result in
residues on home lawns. This use was considered in the Naled Risk Assessment.
Dichlorvos from the use of Trichlorfon. Post application exposure to dichlorvos from the
use of trichlorfon has been assessed. (Leighton, T., 2000). This is a short-term exposure scenario.
Trichlorfon is applied to home lawns at 8.2 Ib ai/acre as a granular formulation, which is watered in
with 0.25" water. The assessment for dichlorvos from trichlorfon use utilized an environmental
fate model to predict residues of a parent and a metabolite, based on the trichlorfon half-life from a
trichlorfon turf transferable residue study (TTR) and the dichlorvos half-lives from a turf
transferable residue study for dichlorvos. The turf assessment has been modified to assume 25%
degradation of trichlorfon to dichlorvos, based on the 25% maximum conversion in a hydrolysis
study of trichlorfon at pH 7, a pH typical of home lawns. Trichlorfon degrades less at lower pH's
and up to 50% at pH 8.4 (Jones, R. D., 2006).
Hand-to-mouth residues were estimated using the Residential SOPs. Trichlorfon was
applied at 8.1 Ib ai/A (registered rate is 8.2 Ib ai/a). The initial TTR of trichlorfon was 0.0829
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ug/cm2. Exposure from hand-to-mouth activity for toddlers was added to arrive at total estimated
exposure. The maximum amount of dichlorvos was estimated to occur 11 hours after application.
(Leighton, 2000). Toddler dermal plus hand to mouth MOEs ranged from 430 to 710, compared to
a target MOE of 30.
Inhalation exposure from this scenario could not be assessed, because air concentrations in
the breathing zone of toddlers were not provided in the trichlorfon study. For comparison purposes,
inhalation estimates from the equivalent dichlorvos dermal exposure is provided in the table. These
inhalation exposure estimates are expected to overestimate inhalation exposure because of
differences in the application method between dichlorvos and trichlorfon, and because the
maximum dichlorvos formed was predicted to occur 11 hours after application. "Wetting in" the
trichlorfon granules is expected to reduce the amount of dichlorvos available for volatilization
(Jones, R. D., 2006).
A trichlorfon TTR study with analyses for dichlorvos in the turf and in the toddler breathing
zone above the turf (18") is being requested to confirm these exposure estimates. The study must
be conducted at an appropriate pH (approx. 7). A field dissipation study may be substituted,
provided it meets these requirements.
6.3.2 Recreational Uses
The dichlorvos and trichlorfon turf uses could also be recreational uses. They are addressed
above in Section 6.3.1 Home uses. The same exposures would be expected for recreational uses as
home lawn uses.
6.3.3 Other (Spray Drift, etc.)
Spray drift is always a potential source of exposure to residents nearby to spraying
operations. This is particularly the case with aerial application, but, to a lesser extent, could also be
a potential source of exposure from ground application methods. However, there are no field crop
applications employed for dichlorvos. The Agency has been working with the Spray Drift Task
Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to
develop the best spray drift management practices. On a chemical by chemical basis, the Agency is
now requiring interim mitigation measures for aerial applications that must be placed on product
labels/labeling. The Agency has completed its evaluation of the new data base submitted by the
Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on
how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for
pesticides applied by air, orchard airblast and ground hydraulic methods. After the policy is in
place, the Agency may impose further refinements in spray drift management practices to reduce
off-target drift with specific products with significant risks associated with drift.
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Table 6.3. Summary of Residential Exposure and Risk Estimates for Dichlorvos
USES
NOTES
EXPOSURE
PATTERN1
Current Exposure (mg/kg/day)
Dermal
Inhalation
Total
Current MOE
Dermal
Inhalation
MOE
Total
RESIDENTIAL EXPOSURE All Target MOEs for all Residential Scenarios are 30, except for acute dermal and handler exposure scenarios, where the target MOE is 100.
RESIDENTIAL HANDLER
(a) Pressurized aerosol spray can
RESIDENTIAL POST-APPLICATION
(a) Pressurized aerosol (toddler)
Same rate as fogger
Adjusted rate
(b) Resin pest strips
Full size strip 65 g (4 hr exposure)
Smaller strips (14 hr exposure)
Closet strip 16 g
Small Closet strip 10. 5g
Cupboard strip 5.25g
(c) Pet flea collars
toddler(includes hand-to-mouth)
(d) Lawns, Trichlorfon use 8.1 Ib
ai/A Post -application
Toddler - high end
Toddler - low end
2
3
Acute
0.00022
0.000012
0.00023
3600
67000
3500
4
5
6
7
Short-term
Long-term,
Inhalation
Long-term
Dose is 0.90 ug/kg/day based on
urinary dimethyl phosphate +
incidental oral of 0.038 ug/kg/day
N/A
N/A
N/A
N/A
0.0012
0.015 mg/m3.
0.0048 mg/m3.
0.0024 mg/m3
0.001 2 mg/m3.
0.000949 mg/m3
0.00098
83
27
34
48
95
74
Although inhalation exposure is not assessed, rough estimates were made by comparison with
dichlorvos turf study, which we expect to result in an over-estimate of the exposure & risk.
Short-term (adding
incidental oral of
0.0004 mg/kg/day
0.00023
0.00014
not assessed
not assessed
430
710
(100)
(150)
100
27
34
48
95
39
NOTES: The following notes define the assumptions used in calculating the margins of exposure.
Risk is expressed as a Margin of Exposure (MOE)
MOE = NOAEL , where both the NOAEL and the Exposure are expressed in common units
Exposure
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1. Doses and toxicological endpoints for assessment of short term dermal, incidental oral and inhalation (applicator) residential risks are based on an oral LOAEL of 0.1 mg/kg/day from a
human 21-day repeated dose study. A dermal absorption factor of 11% was used in assessing risks from dermal exposure. The applicator is assumed to weigh 70 kg. The target
MOE for these scenarios is 30 (1 Ox for intraspecies variability, 3x for use of the LOAEL).
Doses and toxicological endpoints for assessing risks from long-term inhalation of dichlorvos vapors are based on an inhalation BMDL10 of 0.07 mg/m3 from a 2 year rat inhalation
study. The target MOE for this scenario is 30 (1 Ox for intraspecies variability, 3x for interspecies extrapolation).
Acute Dermal and Inhalation endpoints are based on the 0.8 mg/kg/day BMDLio from a rat acute oral cholinesterase study, with an 11 % dermal absorption factor for the dermal
exposure. The target MOEs are 100 (10x for interspecies extrapolation, and 10x for intraspecies variability)
2. Residential handler assumptions. An average resident applicator weighs 70 kg and has a respiratory volume of 1.0 m3/hour (NAFTA value for moderate activity). Assume applicator
wears short pants, short sleeves, and no gloves.
3. Pressurized aerosol spray - residential handler. Residential use of pressurized aerosol product is based on application of 2 ounces of 0.5 percent dichlorvos pressurized aerosol
(0.00063 Ib ai). Pressurized aerosol products containing dichlorvos do not have any clothing requirements; therefore EPA is assuming that dichlorvos is applied during hot weather
when an individual will be wearing only shorts, short sleeve shirt, and shoes. From the Residential SOPs unit dermal exposures are 220 mg/lb ai handled, and 1.3 mg / Ib ai handled
for inhalation exposure (after correction for the NAFTA breathing rate). The risk assessment is based on application by a 70 kg resident applicator. (Jaquith, 2001).
Dermal exposure = 220 mg/lb ai handled x 0.005 x 2 oz/16 oz/lbxO.11 (dermal absorption factor) •*• 70 kg = 0.00022 mg/kg/day
Inhalation Exposure = 1.3 mg/lb ai x 0.000625 Ib ai H- 70 kg = 1.2 E-5 mg/kg/day
Total exposure = 0.00022 + 0.000012 = 0.00023 mg/kg/day
Total MOE = 0.8/0.00023 = 3500
4. Pressurized Aerosol - Post application. The assessment is based on biomonitoring data (urinary excretion of DMP from exposure to dichlorvos) from the use of the Total Release
Fogger and represents the total dose to the individual from all routes. To account for children's hand-to-mouth exposure, an estimate of incidental oral exposure was obtained by
assuming that all material on hands (from passive dosimetry data) is available for ingestion. (Jaquith, 1998k) The oral exposure from passive dosimetry is added to the dermal
exposure from biomonitoring. (Jaquith, 1993b) Children, performing the same activities as adults were considered to have the same exposure as an adult on a mg per kg basis.
Total Exposure (ug/kg/day) = Biomonitoring Exposure ( ug/kg/day) + Hand-to-mouth Exposure ( ug/kg)
15 ug/kg/day + 0.61 ug/kg = 16 ug/kg
In the biomonitoring study, an average of 1.7 mg dichlorvos was released into a room of 16.8 m2
A lower application rate is used for the pressurized aerosol, compared to the total release fogger. The risk assessment is done by using the results of the biomonitoring study, and the
ratio of the application rate expected to be used for the pressurized aerosol to the rate that was used in the biomonitoring study.
The 2 oz application rate for the pressurized aerosol in a typical 1000 sq ft house is from the REJV data.
Application rate for aerosol = 2 oz x 0.5% = = 6.2 x 10"7 Ib/ sq. ft.
16ozx1000ft2
Application rate in biomonitoring study = 0.77 g dichlorvos = 9.9 x 10"6 Ib/sq. ft.
16.8 m2 x (3.2 ft /m)2 x 454 g/lb
Ratio of application rates = 6.2 x 10'7 Ib/sq. ft. = 0.063
9.9 x10'6 Ib/sq. ft
Total Exposure incl. Hand-to-mouth = 15.6 ug/kg/day x 0.063 = 0.98 ug/kg/day
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MOE = 0.1 mg/kg/dav = 100 (Target = 30)
0.00098 mg/kg/day
5. Resin Strips MOEs were based on the average air concentration (0.015 mg/m3) in 15 houses over a 90-day period (Collins and DeVries 1973, in Jaquith 1998h) and the BMDLio of
0.07 mg/m3 from 2 year rat inhalation study. Exposure estimates are adjusted to 14 hours in the house. Exposure estimates for smaller resin strips assume air concentrations are
proportional to the weight of the ai in the strip. The target MOE for inhalation exposure is 100.
MOE (full sized strips) = 0.07/0.015 x 23 hr exposure/14 hr = 8
Table 6.3.1.2 shows Exposures and MOEs for different exposure times to different sizes of resin pest strips.
6. Inhalation assessment assumes that a flea collar is like a mobile resin strip, and the resident spends 8 hours per day in the room with the pet. The air concentration is obtained by
proportion based on the ratio of ai in the collar to the ai in the full sized resin strip. MOEs for many different times of exposure are found in Table 6.3.1.2.
A full size resin strip of 65 g (12.09 g ai) results in an air concentration of 0.015 mg/m3. The point of departure (POD) is 0.07 mg/m3 from 23 hours of exposure. The inhalation
exposure is
0.015 mg/m3 x 2.2 g dichlorvos x 8 hr = 0.000949 mg/m3
12.09gai 23 hr The MOE is 0.07 mg/m3/0.000949 mg/m3 = 74
Dermal exposure is estimated as follows from draft ExpoSAC policy
The amount of dichlorvos available per dog per day is 2.2 g in the collar, divided by the 120 days that the collar is effective, 2.2 g x 1000 mg/g/120 days = 18.3 mg/dog/day.
The draft ExpoSAC policy assumes 20% of the residue is transferrable, but a carbaryl study (MRID 45792201) showed 2.6% transferrable.
18.3 mg/dog/dav x .026 transferrable
5986 cm2 surface area on a 30 Ib dog
18.3 mg/dog/dav x .026 transferrable = 0.00008 mg/ cm2 transferrable residue
A child is assumed to hug a dog and contact 1875 cm2 of the dog's fur. The dermal absorption is 11 %. A toddler is assumed to weigh 15 kg.
0.00008 mg/ cm2 transferrable residue x 1875 cm2 x .11 dermal absorption factor = 0.0011 mg/kg/day
15 kg child
For the hand-to-mouth component, 1 event per hour is assumed. The surface area of a child's hand which goes into the mouth is 20 cm2. The child is assumed to play with the dog
for 2 hours per day. The saliva extraction factor is 50%.
0.00008 mg/cm2x 1 event/hr x 20 cm2 x 0.5 x 2 hr/dav = 0.0001 mg/kg/day
15 kg child
Combining the dermal and hand-to-mouth exposure results in an exposure estimate of 0.0012 mg/kg/day, and an MOE of 83
7. The calculations for incidental oral and dermal exposure to children playing on turf have been updated to be consistent with the revised Residential SOPs. Activities on the lawn
are assumed to start 1 hour or more after spraying, and last 2 hours per day.
The assessment for dichlorvos from trichlorfon use relied on the dichlorvos half-lives from the same TTR study for dichlorvos, trichlorfon total transferable residues (TTR) residues from
a trichlorfon DFR study, and the Residential SOPs. TTRs of dichlorvos were estimated using the calculated half-lives of trichlorfon and dichlorvos (0.53 hours- 3.7 hours). The
calculations were done using a spreadsheet-based model developed by EFED to estimate the decay rate of a chemical and its degradate applied to short grass for single or multiple
applications. The initial trichlorfon concentration was derived from a Trichlorfon TTR study. A first order decay assumption is used to determine the concentration at each day after
initial application based on the concentration resulting from the initial and additional applications. Exposure from hand-to-mouth activity for toddlers was added to arrive at total
estimated exposure. (Leighton, 2000). The formulas are presented below, (a) is the exponential form, and (b) is the log transformed versions.
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(a) CPT = Cp,ek1T
(b) In (CpT/Cpi) = k,T
For the degradate Cd, = (kiCpi)e~k1T -e"k2T)/(k2ki)
Where:
CpT = parent concentration at time T = day T.
Cpi = parent concentration at time T = day zero (0.0138 bcg/cn from trichiorton HR study; MRID 45067201).
ki = parent degradation rate constant determined from the trichlorfon TTR study using half life data of 0.93 and 2.5 days (MRID 45067201).
k2 = DDVP degradation rate constant determined from the DDVP TTR studies using a half life of 0.156 days (MRIDs 44591901, 44610501, and 44794901).
The high end exposure (daily dermal dose) for dichlorvos from trichlorfon, adjusting for 25% conversion to dichlorvos was 0.00019 mg/kg/day. Hand-to-mouth exposure was 0.00004
mg/kg/day, totaling 0.00023 mg/kg/day.
This results in an MOE of BMDLin = 0.8 mg/kg/dav = 3500
Exposure 0.00023 mg/kg/day
The inhalation MOEs presented in the table are based on the ratio of the dermal exposure to dichlorvos after treatment of dichlorvos to the dermal exposure to dichlorvos after
treatment with trichlorfon. These estimates are expected to overestimate the exposure and risk.
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7.0 Aggregate Risk Assessments and Risk Characterization
The Food Quality Protection Act amendments to the Federal Food, Drug, and Cosmetic Act
(FFDCA, Section 408(b)(2)(A)(ii)) require that for establishing a pesticide tolerance "that there is
reasonable certainty that no harm will result from aggregate exposure to pesticide chemical residue,
including all anticipated dietary exposures and other exposures for which there are reliable
information." Aggregate exposure is the total exposure to a single chemical (or its residues) that
may occur from all sources. Typically these are dietary (i.e., food, and drinking water), residential
and other non-occupational sources, and from all known or plausible exposure routes (oral, dermal
and inhalation).
In an aggregate assessment, estimated exposures from relevant sources are added together and
compared to quantitative estimates of hazard (e.g., aNOAEL, LOAEL, BMDL, or PAD), or the
risks themselves can be aggregated. When aggregating estimated exposures and risks from various
sources, FED considers both the route and duration of exposure. Aggregate risk assessments are
typically conducted for acute (1 day), short-term (1-30 days), intermediate-term (30 days to 6
months), and chronic (6 months to lifetime) exposure.
Dichlorvos residues may be present in water and/or food as a result of use of three pesticides:
dichlorvos (DDVP), naled, and trichlorfon. Dichlorvos is a degradate of naled and trichlorfon. The
Environmental Fate and Effects Division (EFED) evaluated the potential for dichlorvos to
contaminate water from these sources. The environmental fate properties of dichlorvos, naled, and
trichlorfon are an indicator of the potential of these compounds to migrate to ground or surface
water. EFED has limited monitoring data on the concentrations of dichlorvos, naled, or trichlorfon
in groundwater. Validated monitoring data for dichlorvos, naled, and trichlorfon are available for
the states of California and Hawaii from the Pesticides in Groundwater Database, and from a few
other states in the PDF. These data indicated that neither naled, dichlorvos, nor trichlorfon, have
been detected in groundwater nor drinking water; however, these data were not targeted to the
pesticide use area. OPP does not have sufficient ground or surface water monitoring data on the
concentrations of dichlorvos, naled, or trichlorfon at the present time. Therefore, the Tier I
screening model SCI-GROW was used to estimate ground water concentrations for naled,
trichlorfon and dichlorvos. The Tier II PRZM/EXAMS model was used to estimate drinking water
concentrations from surface water.
A probabilistic acute dietary exposure assessment was conducted without the water contribution.
The chronic dietary exposure assessment was also conducted without the water contribution.
Sufficient water modeling data were available to use for probabilistic assessment if needed.
For residential exposure and risk assessment, deterministic exposure assessments were done.
Exposure estimates for a number of occupational and residential scenarios were derived from
limited data from the scientific literature, textbooks, and knowledge of cultural practices. Other
estimates, particularly in the residential environment, were derived from chemical specific
monitoring data, including biomonitoring, in combination with models and literature studies.
The route of exposure which results in the greatest exposure to residents depends on the use
pattern. For resident applicators and reentry after use of an aerosol spray, the dermal route of
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exposure results in the highest estimated risk. For the pest strip and reentry onto lawns, the
inhalation risk is estimated to be the highest. In general, the residential risks are estimated to be
much higher than food and water combined.
Drinking Water Levels of Comparison (DWLOCs). For dichlorvos (and most pesticide active
ingredients), water monitoring data are considered inadequate to determine surface and ground
water drinking water exposure estimates, so model estimates have been used to estimate residues in
drinking water (Estimated Drinking Water Concentrations, or EDWCs, see Table 6.2.3a and
6.2.3b). In order to determine if aggregate risks are of concern, HED then calculates drinking water
levels of comparison, or DWLOCs. The DWLOC is the maximum amount of a pesticide in
drinking water that would be acceptable in light of combined exposure from food and residential
pathways. The calculated DWLOCs are then compared to the EDWCs provided by EFED; if
model-derived EDWCs exceed the DWLOCs for surface or ground water, there may be a concern
for exposure to residues in drinking water.
HED has calculated drinking water levels of comparison (DWLOCs) associated with acute and
chronic exposure to dichlorvos in drinking water. These DWLOCs are compared with the estimated
drinking water concentrations (EDWCs) of dichlorvos in water.
7.1 Acute Aggregate Risk
The acute aggregate risk estimate to dichlorvos includes exposures from food and drinking
water. Although there are several acute residential exposure scenarios, these will be included in
the short term aggregate risk assessment because it is highly unlikely that high exposure from food,
water, and residential use will co-occur. For the highly refined acute probabilistic dietary exposure
analysis, PDF and FDA monitoring data and FDA TDS data were used to the greatest extent
possible, along with field trial data, cooking and processing factors, and degradation studies to
assess dietary exposures.
The acute DWLOC for dichlorvos includes aggregate exposure from food and water only. The
DWLOCacute was calculated for the general population, All Infants, Children (1-6 years) who are the
most highly exposed population subgroup, and for females (13-50 years). Acute water exposures
and DWLOC calculations are summarized in Table 7.2.4.1. below.
DWLOCacute (|^g/L) = acute drinking water exposure (mg/kg/day) x body weight (kg)
Water consumption (L/day) x (10"3 mg/ug)
where body weight is 70 kg for adults, 60 kg for females (13-50) and 15 kg for children and water
consumption is 2 L per day for adults and 1 L per day for children.
acute water exposure = aPAD - acute food exposure
where aPAD is 0.008 mg/kg/day.
Table 7.1. Summary of DWLOCacute Calculations for Dichlorvos.
i i i
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DEEM
Population
Subgroup
US Population
All Infants
Children (1-6)
Females (13-
50)
Acute Dietary
Exposure to
Dichlorvos at 99.9th
%tile, mg/kg/day
0.00014
0.00031
0.00033
0.000085
Acute aPAD,
mg/kg/day
0.008
0.008
0.008
0.008
Allowable Water
Exposure,
mg/kg/day
DWLOCacute, ug/L
280
120
120
240
Maximum
EDWCacute
M9/L
60
60
60
60
For acute drinking water exposure, the modeled groundwater concentrations of 0.0002 to 0.015
ug/L for dichlorvos resulting from the use of dichlorvos, naled, and trichlorfon are not of risk
concern, when compared to the DWLOCAcuiE, shown above in Table 7.1. There is no risk concern
from the estimated drinking water concentration of dichlorvos in surface water, resulting from the
use of dichlorvos, of 3.46 ug/L, from naled, of 33.0 ug/L, nor from trichlorfon, of 60 ug/L.
7.2 Short-Term Aggregate Risk
The short-term aggregate risk estimate includes chronic dietary (food and water) from
dichlorvos uses, and acute and short-term non-occupational exposures (i.e., residential/recreational
uses).
There are two short-term residential exposure scenarios which could be aggregated with food
and water: the application of the aerosol spray and the resulting post-application exposure , and
post-application exposure to dichlorvos from turf treatment with trichlorfon. Since the exposures
from the aerosol spray and the exposures from treated lawns are so short-lived (a week or less), it is
extremely unlikely that an individual would be exposed concurrently. Accordingly, two separate
aggregate scenarios are presented. It should be noted that the contribution of food and water to the
short-term aggregate risk is considered to be negligible occupying less than one percent of the risk
cup. Consequently, the short-term aggregate risk is mainly a result of the residential exposures
presented in each of the scenarios.
The first scenario includes the residential use of the aerosol spray can. Exposure from the
application of the aerosol spray is considered to be negligible (i.e., an MOE of 3500 was calculated
vs. a target MOE of 100) with the majority of the exposure occurring post- application. The MOE
calculated from post-application exposures was 100 vs. the target MOE of 30. When these
residential exposures are combined (aggregated) with the exposures from food and water and
compared to the short-term endpoint, our risk level of concern is not exceeded.
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Table 7.2. Short-Term Aggregate Risk and DWLOC Calculations
Population
Adult
Female
Child
Short-Term Scenario (post application from spraying with an aerosol can)
Target MOE = 30
Short-term LOAEL = 0.1 mg/kg/day
Target
Aggregate
MOE
30
30
MOE
Food1
330000
77000
MOE
residen-
tial2
100
100
Aggregate
MOE
(food and
residential)3
100
100
MOE
Water4
43
43
Allowable
water
exposure5
(mg/kg/day)
0.0023
0.0023
Ground
Water
EDWC6
(PPb)
0.01
0.01
Surface
Water
EDWC6
(PPb)
1.83
1.83
DWLOC7
(ug/L)
69
34
MOE food = [(short or intermediate-term oral NOAEL)/(chronic dietary exposure)] = 0.1mg/kg/day/0.0000003 mg/kg/day for adult females = 330000
= 0.1 mg/kg/day/0.0000013 mg/kg/day = 77000
2 MOE residential = [(short or intermediate-term oral NOAEL)/(residential exposure)]
3 Aggregate MOE (food and residential) = 1-[ [(1-MOE food) + (1-MOE oral) + (1-MOE dermal) + (1-MOE inhalation)]]
4 Water MOE = 1^- [[(1^- Target Aggregate MOE) - (^Aggregate MOE (food and residential)]]
5 Allowable water exposure = Short or Intermediate Term Oral NOAEL •*• MOE water
6 The crop producing the highest level was used.
7 DWLOC(ug/L) = [allowable water exposure (mq/kq/dav) x body weight (kq)1
[water consumption (L) x 10-3 mg/ug]
Where body weight = 15 kg for a child, and 60 kg for a woman.
The other scenario involves the post-application exposure to dichlorvos from the use of trichlorfon on turf. As discussed previously,
data from trichlorfon are not available to calculate exposures resulting from this use and the Agency has used available data and modeling
from dichlorvos to estimate these exposures. The MOEs calculated did not exceed our level of concern (i.e., were greater than our target
MOE of 30) and the Agency expects that, given the negligible contribution from food and water, short-term aggregate risks do not exceed
our level of concern. Data for the use of trichlorfon on turf will be required to confirm these conclusions.
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7.3 Intermediate-Term Aggregate Risk
The intermediate-term aggregate risk estimate includes chronic dietary (food and water) from
dichlorvos uses, and intermediate-term non-occupational exposures (i.e., residential/ recreational
uses). There are no residential/recreational uses with an intermediate-term exposure scenario.
Therefore, intermediate-term aggregate risks were not evaluated.
7.4 Long-Term Aggregate Risk
The long-term aggregate risk estimate for dichlorvos combines chronic exposures from food,
drinking water, and long-term residential exposures. There are two long-term residential scenarios:
resin strips and pet (flea) collars. While it is possible that an individual could be exposed
concurrently to dichlorvos from the use of resin strips, have a pet that wears a dichlorvos collar and
consume food and drink water with dichlorvos residues, the probability of these simultaneous
exposures is fairly low, especially considering the market share of these residential uses.
Consequently, two separate scenarios are discussed for long-term aggregate risk.
The contribution of dichlorvos in food occupies less than one percent of the risk cup for long-
term exposure. When potential exposure to water is added, approximately 23 percent of the risk
cup is occupied leaving 77 percent (equating to an MOE of 39) for any additional exposures
resulting from residential use.
The first scenario considers the pet collar. As discussed previously in this document, the
Agency has made a number of conservative assumptions in deriving a risk estimate for this use.
Included in these assumptions is that the pet collar acts as a miniature resin strip which results in
inhalation exposure proportional to that of larger resin strips and that the pet is in the same room as
an individual for 8 hours a day. Additionally, exposures were calculated based on dermal contact
(from hugging and petting activities) as well as incidental oral (hand to mouth) exposures exhibited
by children. The inhalation MOE is calculated to be 74 and the dermal and incidental oral MOE of
83 for a comined MOE of 39 vs. our target MOE of 30. Therefore, the long-term aggregrate risk
does not exceed our level of concern given that this conservative estimate from the pet collar does
not exceed the amount left in the risk cup after considering food and water.
The second scenario considers the largest resin strip. The registrant recently voluntarily
amended its registration to limit where these strips can be used. No use will be permitted in living
areas and the labeling warns of exposure to the strips for more than 4 hours. The Agency believes
that given the location of where these strips may be used (e.g., attics, crawl spaces, garages, etc),
exposure times will be much less than 4 hours a day and/or that daily exposure (repeated exposure)
may not be likely depending on the site of application (e.g., crawl spaces). Consequently,
considering the room available in the risk cup after consideration of food and water and that
exposures are not expected either daily or for significant periods of time, our risk of concern is not
exceeded from this long-term exposure scenario.
7.5 Aggregate Cancer Risk
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No aggregate cancer risk assessment is needed. Dichlorvos shows "suggestive" evidence of
carcinogenicity under the 1999 Draft Agency Cancer Guidelines. No quantitation is required. No
aggregate cancer risk assessment is required.
8.0 Cumulative Risk Characterization/Assessment
Section 408(b)(2)(D)(v) of the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by
the Food Quality Protection Act (1996) stipulates that when determining the safety of a pesticide
chemical, EPA shall base its assessment of the risk posed by the chemical on, among other things,
available information concerning the cumulative effects to human health that may result from
dietary, residential, or other non-occupational exposure to other substances that have a common
mechanism of toxicity. The reason for consideration of other substances is due to the possibility that
low-level exposures to multiple chemical substances that cause a common toxic effect by a
common mechanism could lead to the same adverse health effect as would a higher level of
exposure to any of the other substances individually. A person exposed to a pesticide at a level that
is considered safe may in fact experience harm if that person is also exposed to other substances
that cause a common toxic effect by a mechanism common with that of the subject pesticide, even
if the individual exposure levels to the other substances are also considered safe.
Dichlorvos is a member of the organophosphate (OP) class of pesticides. Other members of this
class of pesticides are numerous and include azinphos methyl, chlorpyrifos, chlorpyrifos-methyl,
diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, methamidophos, methidathion,
monocrotophos, naled, oxydemeton-methyl, phorate, phosmet, pirimiphos-methyl, and trichlorfon
to name a few. EPA considers organophosphates to express toxicity through a common biochemical
interaction with cholinesterase which may lead to a myriad of cholinergic effects and, consequently
the organophosphate pesticides should be considered as a group when performing cumulative risk
assessments. FLED published the final guidance that it now uses for identifying substances that have
a common mechanism of toxicity (FR 64(24) 5796-5799, February 5, 1999) "Proposed Guidance of
Cumulative Risk Assessment for Chemicals that have a Common Mechanism of Toxicity" was
made available for public comment in the Federal Register (65 FR 40644, June 30, 2000 . The
Agency presented this approach to the FIFRA/FQPA Science Advisory Panel in late September,
2000. The SAP reviewed revised methods used to conduct a preliminary cumulative risk
assessment for organophosphate pesticides in 2002 (US EPA, 2002), found at
http://www.epa.gov/scipoly/sap/2002/index.htm.
The Agency has completed a cumulative risk assessment for OPs, (US EPA, 2001) and a revised
cumulative risk assessment for OPs, (US EPA, 2002a) which can be found on the Agency's web site
http://www.epa.gov/pesticides/cumulative/rra-op/. It assesses the cumulative effects of exposure to
multiple OPs, including dichlorvos.
Dichlorvos is closely related to naled and trichlorfon, which are members of the
organophosphate class of pesticides. Naled and trichlorfon both metabolize or degrade to dichlorvos
in food, water, or the environment. Therefore, FQPA requires OPP to estimate aggregate risk from
consumption of food and water, containing dichlorvos derived from naled and trichlorfon and from
residential exposure to dichlorvos from the use of those pesticides. The current assessment
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addressed only the risks posed by dichlorvos, resulting from the uses of dichlorvos, naled, and
trichlorfon.
9.0 Occupational Exposure/Risk Pathway
Risk is expressed as a Margin of Exposure (MOE)
MOE = NOAEL
Exposure
where both the NOAEL and the Exposure are expressed in the same units (mg/kg/day for dermal or
inhalation exposure during application or mg/m3 for exposure to dichlorvos vapors). Dermal
exposures include a dermal absorption factor of 11%, because the exposure is compared to an oral
NOAEL. The target MOE for occupational scenarios varies from 30 to 100. (See Table 4.4).
The risk assessment has been changed from previous versions to use the North American Free
Trade Agreement (NAFTA) recommended breathing rate of 1.0 m3 /hr rather than the rate
recommended in the guidelines or the default breathing rate used in PHED. This change increases
the inhalation MOEs, and therefore decreases the estimated risk to occupational and residential
handlers. The risk assessment uses the recommended body weight of 70 kg for the acute, short
term, and intermediate term risk assessments.
AMVAC has requested voluntary cancellation of the following uses.
Mushroom house, greenhouse, and warehouse hand held fogger
Lawn, Turf, and Ornamental uses
Total release fogger
Crack and Crevice uses
The following label changes will be made:
A Restricted Entry Interval (REI) of 18 hours for mushroom houses, and 12 hours for
greenhouse uses.
Toxicological Doses and Endpoints for Occupational Exposure Assessment are presented in
Table 9.0. Occupational exposure and risk estimates for applicators are presented in Table 9.1
below. Occupational post-application exposure and risk estimates are presented in Table 9.2
below.
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Table 9.0. Summary of Toxicological Doses and Endpoints for Dichlorvos for Use in Occupational Human Health Risk
Assessments
Exposure
Scenario
Acute Dermal
Short-, Intermediate-
and Long-Term
Dermal
Acute Inhalation (1
day)
Short- and
Intermediate-term
Inhalation of vapors
Short- and
Intermediate-Term
Inhalation during
application
Long-Term Inhalation
of vapors
Cancer (oral, dermal,
inhalation)
Point of Departure
BMDL10 = 0.8
mg/kg/day
dermal
absorption=11%
Oral study LOAEL=
0.1 mg/kg/day
dermal bsorption=1 1%
Oral study BMDL10 =
0.8 mg/kg/day
(inhalation absorption
rate = 100%)
Air concentration
Equivalent = 0.8
mg/m3*
Oral study LOAEL=
0.1 mg/kg/day UF=30
Concentration
equivalent= 0.35
mg/m3*
LOAEL=0.1
mg/kg/day
BMDL10 = 0.07 mg/m3
Uncertainty
Factors
UFA=10x
UFH = 10x
UFH = 10x
UFL = 3x
UFA= 10x
UFH = 10xor3x**
UFH = 10x
UFL = 3x
UFH = 10x
UFL = 3x
UFA=10x
UFH = 3x"
Level of Concern
for Risk
Assessment
Occupational
LOG MOE = 100
Occupational
LOG MOE = 30
Occupational
LOG MOE =
100/30"
Occupational
LOG MOE = 30
Occupational
LOG MOE = 30
Occupational
LOG = 30
Study and Toxicological Effects
Rat acute oral cholinesterase studies -
RBC and Brain ChE depression. NOAEL =
1 mg/kg/day, LOAEL = 5 mg/kg/day, BMD
= 1 .6 mg/kg/day for brain ChE depression
(F)
Human 21 -day oral study
LOAEL = 0.1 mg/kg/day based on RBC
ChE depression
Rat acute oral cholinesterase studies -
RBC and Brain ChE depression. NOAEL =
1 mg/kg/day, LOAEL = 5 mg/kg/day, BMD
= 1 .6 mg/kg/day for brain ChE depression
(F)
Human 21 -day oral study
LOAEL = 0.1 mg/kg/day based on RBC
ChE depression
Human 21 -day oral study
LOAEL = 0.1 mg/kg/day based on RBC
ChE depression
2-year Rat Inhalation
BMD = 0.15 mg/m3 based on RBC ChE
depression (F)
"suggestive" evidence of carcinogenicity not quantifiable under the 1 999 Draft Agency Cancer Guidelines
Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and
used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human
exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF =
uncertainty factor. UFA = extrapolation from animal to human (intraspecies). UFH = potential variation in sensitivity
among members of the human population (interspecies). UF|_ = use of a LOAEL to extrapolate a NOAEL. UFS = use of
a short-term study for long-term risk assessment. UFDB = to account for the absence of key date (i.e., lack of a critical
study). MOE = margin of exposure. LOG = level of concern. N/A = Not Applicable
* Calculation of concentration equivalent BMDL-io and LOAEL
Acute Inhalation BMDL-io
0.8 mg/kg/day x 0.35 kg / 0.34 m3/day = 0.8 mg/m3
Short- and Intermediate-term inhalation of vapors LOAEL
0.1 mg/kg/day x 70 kg / 20 m3/day = 0.35 mg/m3
**Since the NOAEL is expressed in concentration units (RfC methodology), the interspecies extrapolation factor is 3x (for
the acute and long term inhalation scenarios), for a total UF of 30 for acute inhalation and long term inhalation.
Page 176 of 338
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9.0.1. Mushroom House
(a). Application
Application of dichlorvos to mushroom houses may be made by coarse spray and paint-on
applications. Foggers would be permitted if the applicator is outside the mushroom house. The
exposures for coarse spray applications were derived from ORETF data. The Outdoor Residential
Exposure Task Force (ORETF) has recently completed several surrogate mixer/loader/applicator
studies addressing lawn care operators (LCOs). (Bangs, 2001; Jaquith, 2001). The hose-end sprayer
scenario from the ORETF studies will be used to estimate exposures to applicators in mushroom
houses. Estimates of the surface areas that would be painted or sprayed during dichlorvos
application were derived from mushroom culture textbooks and are considered to be conservative
(Jaquith 1998d and n). This application scenario is considered to be intermediate term (several
months) because a single individual may treat different mushroom houses on different days due to
the cyclic nature of mushroom culture.
Coarse Spray and Paint-on Applications. For the coarse spray, data from the ORETF lawn
care study were used; protective clothing varied with the application method, and included long
pants, long sleeved shirt and gloves, or coveralls plus long pants, long sleeved shirt and gloves. The
label does not specify protective clothing needed. Dermal and inhalation exposure and total
exposure resulting in an MOE of 46 is not considered to be of concern, compared to the target MOE
of 30. If an additional layer of protective clothing were added, the absorbed dermal dose would be
cut approximately in half, and the MOE of 88 would be adequate.
(b). Post-application
For reentry exposure, it was assumed that a worker reenters a ventilated mushroom house
12 or 24 hours after treatment and is exposed for 8 hours. This is a short term exposure because
workers may be exposed multiple times on subsequent days. The MOE at a 12 hour REI of 23 is
less than the target MOE of 30, and is of concern. The MOE at a 24 hour REI of 58 is greater than
the target MOE of 30, and is not of concern. AMVAC has submitted an amendment, changing the
label REI to 18 hours.
9.0.2. Greenhouse
(a). Application
There are currently no end use product labels with directions for use for greenhouses.
However, the technical label for Dichlorvos allows use of up to 2.0 g/1000 cu. ft. Previously,
smoke generators were registered, and were considered to result in negligible applicator exposure
since the applicator vacates the premises immediately upon activation of the smoke generator. This
application scenario is considered to be short term because treatment would not be expected to
occur in a given greenhouse more than once a week. The baseline MOE is 46, which is not of
concern.
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(b). Post-application
The dermal exposure for reentry into greenhouses following the use of dichlorvos was
obtained using data from a greenhouse culture textbook, data on turf transferable residues from a
chlorpyrifos/dichlorvos study (Goh, K. S., et. al. 1986), and a standard transfer coefficient of 2500
cm2/hr, from ExpoSAC Policy 003. Inhalation exposure estimates were modeled assuming the
initial concentration at the maximum rate, assuming first order kinetics and an air exchange rate
from a textbook (Mastalerz, 1977). This is considered to be a short-term exposure scenario
(Jaquith, 1998d).
The total daily dermal exposure that would occur after a 2 hour REI is estimated to be 1.2
ug/kg/day. The dichlorvos concentrations available for inhalation exposure were modeled (Jaquith,
1998d), and concentrations depended on the ventilation used. The estimated respiratory component
of exposure would be 0.00035 mg/m3. The resulting MOE with a 2 hour REI of 78 is not of
concern, compared to the target MOE of 30. At a 12 hr REI, the total MOE is >650 and is not of
concern, compared to the target MOE of 30.
9.0.3. Domestic Animal Premises (food and nonfood) and Direct Animal Sprays,
Feedlots, Manure Treatment, Garbage Dumps, and Baits
(a). Application
Dairy barn application and direct application to dairy cattle were used as the reference
facility for these exposure assessments (Jaquith 19981). There are no data addressing the use of
dichlorvos in other types of animal facilities. Worker exposure from direct application to animals is
based on dairy cattle treatment. Although permitted on product labels, the Agency does not believe
that direct application to livestock animals with a handheld sprayer is used. Rather, some type of
automated equipment is used to apply dichlorvos directly to animals. Space and premise treatments
also help control insects on animals. Since several registered products provide guidance on use
with a handheld sprayer, the exposure and risk are estimated here for that application method,
which is expected to result in a much higher exposure than automated methods. While some labels
indicate that daily application (probably for direct application to cattle) is allowable, the use
assessment indicates that the material is applied at 2 week intervals (Dow, M., 1985). This
assessment assumes daily applications over several months, and is therefore considered to be an
intermediate term scenario.
Cattle. Exposure assessments for direct application to dairy cattle using hand-held sprayers
as a surface spray or space spray were conducted using PHED Vl.l. Applicators were assumed to
be wearing long sleeved shirt, long pants, and gloves. Gloves are not currently required on the
label. Absorbed dermal doses were estimated to range from 0.009 to 0.22 ug/kg/day and respiratory
doses from 0.008 to 0.039 ug/kg/day, depending on application equipment. These total MOEs
would range from 440 to 59000, and are not considered to be of concern.
Poultry. Applicator exposure data for cattle cannot be extrapolated to poultry, because of
the different application method and less frequent applications. Individual animals are less likely to
be treated directly and the equipment is more likely to be automated. As a result, exposure from
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applying dichlorvos to poultry is expected to be much lower than for cattle. Therefore, no separate
assessment has been done.
Domestic Animal Premises. Barn sizes were obtained from the dichlorvos Qualitative Use
Assessment (QUA) (Dow, M., 1985). Assuming that a worker wears long sleeve shirt, long
trousers, shoes and impervious gloves at a minimum, risks from dichlorvos application to domestic
animal premises are lower than the risks from direct application to cattle, with total MOEs from 440
to 5900, and do not exceed the Agency's level of concern. Gloves are not currently required on all
dichlorvos labels.
Feedlots include stockyards, corrals, holding pens and other areas where large groups of
animals are contained. EPA assumes that some type of power sprayer capable of treating a large
number of animals in a short time is probably used. A short application time period in an outdoor
or partially enclosed area would minimize exposure to less than that of dairy applications.
Manure Treatment. The application equipment used for manure applications may be similar
to those used in a dairy barn; however, the application time would probably be less and the treated
area would be well ventilated - either outdoors or in a partially enclosed area. The MOE for
applicators is expected to be greater than the target MOE for manure use.
(b). Reentry
There are no data addressing potential reentry into animal facilities. Re-entry exposure to
animal premises would not be expected to exceed reentry exposure for greenhouses, and would be
expected to be considerably less, since animal premises are usually outdoors or well ventilated,
where minimal dermal contact is expected.
9.0.4. Food Manufacturing Plant, Warehouse Treatment
(a). Application
Dichlorvos can be applied to warehouses with wall-mounted automatic foggers. Exposure
to mixer/loaders through automatic application is expected to be negligible; however, there would
still be reentry exposure.
(b). Post-application
In estimating reentry exposure, EPA assumed 24 hours elapsed before reentry is allowed,
the label REI; and that workers in food manufacturing plants spend 8 hours per day in the treated
area, and 2 hours per day in warehouses. Absorbed dermal exposure was measured for the hands
only, which is likely to be the greatest route of dermal exposure, and represents an average of the
total exposure measured for three work stations, and was negligible compared to the inhalation
exposure. This exposure scenario was considered to be acute due to rapid dissipation of dichlorvos
(1 day) and sporadic use. (Jaquith, D., 2000a; Jaquith, D, 1993c).
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The dermal exposure estimate is 0.00022 mg/kg/day for food manufacturing plants. The mean
air concentration of dichlorvos in a food manufacturing plant is estimated to be 0.053 mg/m3, 24
hours after application, which results in an exposure of 0.006 mg/kg/day. The estimated air
concentration in a warehouse after a 24 hour REI is 0.074 mg/m3 . This is an acute exposure
scenario with an MOE of 130 (target MOE is 100) for food manufacturing plants, and 650 for
warehouses, neither of which is of concern.
9.0.5. Railcars and Trucks
(a). Application
Dichlorvos can be applied to railcars and trucks as a fog or as a surface spray. This is a
short term exposure scenario. One to ten railcars or trucks could be treated in a single day.
Application with a surface spray would have MOEs of 320, compared to a target MOE of 30, which
would not be of concern.
(b). Post-application
In estimating reentry exposure, EPA assumed 6 hours elapsed before reentry is allowed, and
that workers could spend 1 hour per truck or railcar and could load 4 railcars or trucks per day.
Workers loading rail cars or trucks would not be expected to have dermal exposure to dichlorvos.
The air concentration was estimated using initial air concentrations calculated from the application
rate, and assuming ventilation similar to a food processing establishment. This exposure scenario
was considered to be short term due to rapid dissipation of dichlorvos. (Jaquith, D., 2005). The air
concentration 6 hours after treatment is estimated to be 0.018 mg/m3. The MOE would be 94,
which is not of concern, compared to the target MOE of 30. There is considerable uncertainty
about the air exchange rate. Under the conditions described, the air exchange rate could be as low
as 1/3 per hour.
9.0.6. Insect Traps
Exposure is believed to be negligible since the pesticide is in the form of an impregnated
strip in a sealed package, which is opened and the applicator leaves, and the traps are placed in
outdoor areas (such as forests) where there is no human exposure.
9.0.7. Occupational Uses of Resin Strips
The dichlorvos label contains the following use patterns and restrictions.
Garbage Cans, Trash Dumpsters, Catch Basins, Utility Enclosures. Keep lid on can and
dumpster closed.
Animal Buildings, Milk Rooms. Do not contaminate food, water or foodstuffs. Do not
contaminate milk or milking equipment.
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Agricultural Commodities: Bulk Storage of raw grains, corn, soybeans, cocoa beans, and
peanuts. No restrictions.
Reptile Houses and Terrariums. Make sure that the reptiles can not touch or contact the
strip.
Exposure to dichlorvos from these use patterns is expected to be small compared to the use
of resin strips in homes, provided that workers are in the facilities treated for short periods of time.
Refer to table 6.3 for exposure and risk information.
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Table 9.1 Occupational Applicator Exposure and Risk Estimates1
Scenario
Mushroom house & Greenhouse
- ORETF Hose End Sprayer
- ORETF Hose End Sprayer +
coveralls
Direct animal treatment
- Hand Held Sprayer
- Backpack Sprayer (471 )
- Backpack Sprayer (416)
- Portable Sprayer on Cart
Dairy barns - space spray
- Hand Held Sprayer
- Backpack Sprayer (471 )
- Backpack Sprayer (416)
- Portable Sprayer on Cart
Dairy barns - surface spray
- Hand Held Sprayer
- Backpack Sprayer (471 )
- Backpack Sprayer (416)
- Portable Sprayer on Cart
Rail cars and trucks
- Surface Spray
Feedlots
Manure
Garbage Dumps
End- Duration
note
2
Intermediate
term
Intermediate
term
3
Intermediate
term
Intermediate
term
Intermediate
term
Intermediate
term
4
Short term
Short term
Short term
Short term
Short term
Short term
Short term
Short term
5
Short term
6 Short term
7 Short term
8 Short term
# ai/day
2.6
2.6
0.092
0.092
0.092
0.092
0.033
0.033
0.033
0.033
0.053
0.053
0.053
0.053
0.28
Dermal unit Inhalation unit
exposure
0.52
0.27
0.17
2.6
0.27
0.69
0.17
2.6
0.27
0.69
0.17
2.6
0.27
0.69
0.67
exposure
0.001
0.001
0.017
0.017
0.017
0.052
0.017
0.017
0.017
0.052
0.017
0.017
0.017
0.052
0.0032
No data
Dermal
Exposure
0.00212
0.00110
0.000025
0.000376
0.000039
0.000100
0.000009
0.000135
0.000014
0.000036
0.000014
0.000217
0.000022
0.000057
0.00030
not expected
nhalation
Exposure
0.00004
0.00004
0.000023
0.000023
0.000023
0.000068
0.000008
0.000008
0.000008
0.000025
0.000013
0.000013
0.000013
0.000039
0.000013
to exceed
Total
Exposure
0.0022
0.00061
0.000047
0.000399
0.000062
0.000168
0.000017
0.000143
0.000022
0.000060
0.000027
0.000230
0.000036
0.000097
0.00031
Dermal
MOE
47
91
4100
270
2600
1000
11000
740
7100
2800
7100
460
4400
1700
330
Inhalation
MOE
2700
2700
4400
4400
4400
1500
12000
12000
12000
4100
7600
7600
7600
2500
7700
Total
MOE
46
88
2100
250
1600
600
5900
700
4500
1700
3700
440
2800
1000
320
dairy barn exposure
NOTES: The parameters and assumptions used in calculating the margins of exposure are found in the endnotes below
Risk is expressed as a Margin of Exposure (MOE)
MOE = NOAEL , where both the NOAEL and the Exposure are expressed in mg/kg/day or mg/m3
Exposure
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The target MOE for occupational exposure scenarios is 30.
1. Occupational Exposure assumptions. An average worker weighs 70 kg and has a respiratory volume of 1.0 m3 /hour (NAFTA Value). At a minimum, the following
protective clothing was used in the exposure scenarios: gloves, long-sleeve shirt, long pants
2. Mushroom Houses and Greenhouses
Mushroom Houses - coarse spray. Atypical mushroom operation is believed to consist of 10 houses, each with a volume of 30000 ft3 (850 m3). The label does not
specify protective clothing needed. If an individual treats all 10 houses at a rate of 2 grams per 1000 ft3 the amount handled in a day would be:
Amount handled (Ib ai/day) = 30000 ft3/house x 10 houses/day x 2 q/1000 ft3 = 1.3lbai/day
454 g/lb ai
Workers are assumed to be wearing a single layer of clothing and gloves. A second assessment was done for applicators wearing coveralls. Data from the
ORETF lawn care study were used (liquid formulation, hose end sprayer).
AMVAC does not have a coarse spray registered. There was a canceled product, EPA Reg. No. 72-375 that had use directions for the coarse spray or paint-on
application to mushroom houses. The use specified 0.25 Ib of a 0.5% solution to treat 100 sq ft. If we assume that atypical mushroom house is 6000 sq ft, the
amount handled per day would be aboutl.5 Ib ai/day. Thus, the mushroom/greenhouse assessment presented in this table estimates a somewhat higher exposure
than what would be expected.
Greenhouse - The average greenhouse has an estimated volume was 85,000 ft3 A typical operation was assumed to consist of 10 greenhouses which could be
treated in a single day. Treatment was estimated to be 3.75 minutes per house or 26 minutes (0.44 hrs) per day. Dichlorvos is applied at the rate of 1.4 grams of
active ingredient per 1,000 ft3. Workers were assumed to be a single layer of clothing and gloves. Treatment would not be expected to occur in a given
greenhouse more than once a week, resulting in a short term exposure scenario. Workers are assumed to weigh 70 kg. The unit exposures were 14 mg/lb ai
handled for dermal exposure, and 0.19 mg/lb ai handled for inhalation exposure.
The typical application rate for dichlorvos in a greenhouse is 1.4 g per 1000 ft3. The amount handled per greenhouse would be:
Amount handled (Ib ai/greenhouse) = 1.4gai/1000 ft3 x 85000 ft3/greenhouse
= 120 g ai/greenhouse = 0.26 Ib ai/greenhouse
The amount handled per day would be:
Amount handled (Ib ai/day) = 0.26 Ib ai/greenhouse x 10 greenhouses/day _ 2.6 Ib ai/day
3. Domestic Food/Non-food Animals (non-poultry). Worker exposure from direct application to animals is based on dairy cattle treatment. A one percent solution of
dichlorvos is applied with a handheld sprayer. An average herd of dairy cattle consists of 65 head, each requiring 24 seconds to spray, two times per day during
treatment. Fly control is required from May to October with application expected to be occurring weekly rather than 2 x per day during this time (26 times per
year). Although permitted on product labels, EPA does not believe that direct application with a handheld sprayer is used. Rather, some type of automated
equipment is used to apply dichlorvos directly to animals. Space and premise treatments also help control insects on animals. Since several registered products
provide guidance on use with a handheld sprayer, the exposure and risk are estimated here for that application method, which is expected to result in a much
higher exposure than automated methods. The exposure assessment for direct application to dairy cattle using a handheld sprayer was conducted using PHED
V1.1. Applicators were assumed to wear long sleeve shirts, long pants, and gloves.
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Domestic Food/Non-food Animals (poultry). Data for cattle cannot be extrapolated to poultry, because of the different application method and less frequent
applications. However, individual animals are less likely to be treated directly and the equipment is more likely to be automated. As a result, exposure from
applying dichlorvos to poultry is expected to be much lower than for cattle, and no separate assessment is done.
4. Domestic Animal Premises - Dairy Barns. An average dairy barn has the dimensions 30 ft x 100 ft x 9 ft (total area covered is 5,340 ft2). (Dow, M., 1985).
Dichlorvos is applied at two week intervals for 22 weeks, one barn per day. A 1.0 percent solution of dichlorvos is applied using a low pressure hand sprayer at a
rate of 0.0115 Ib a.i. per 1000 ft2. A worker wears long sleeve shirt, long trousers, shoes and impervious gloves at a minimum. The unit exposure varies
depending on the equipment used.
5. Rail cars and trucks. Calculation is shown for treating 10 rail cars or trucks per day. Dermal absorption is assumed to be 11 percent. Applicators are assumed to
wear long sleeve shirts, long pants, gloves, and a respirator (90% protection). Coveralls, although required on some labels, are not included for surface
application. An applicator treating 10 rail cars per day handles 0.28 Ib ai/day. The dermal unit exposure is 0.67 mg/lb ai, and the inhalation unit exposure is
0.0032 mg/lb ai.
0.28 Ib dichlorvos x 0.67 mq/lb ai x 0.11 (dermal absorptinq factor) - 0.00030 mg/kg/day
70 kg applicator
0.28 Ib dichlorvos x 0.0032 mq/lb ai = 0.000013 mg/kg/day
70 kg applicator
6. Feedlots include stockyards, corrals, holding pens and other areas where large groups of animals are contained. EPA assumes that some type of power sprayer
capable of treating a large number of animals in a short time is probably used. A short application time period in an outdoor or partially enclosed area would
minimize exposure to less than that of dairy applications.
7. Manure. The MOE is expected to be greater than 100 for manure use. Application equipment may be similar to those used in a dairy barn; however, the
application time would probably be less and the treated area would be well ventilated - either outdoors or in a partially enclosed area.
8. Garbage Dumps. Exposure at a garbage dump is believed to be less than dairy exposure.
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Table 9.2. Summary of Occupational Post-Application Exposure and Risk Estimates for Dichlorvos
USES
OCCUPATIONAL
EXPOSURE
i. Mushroom house
Reentry (12-hour REI)
Reentry (24-hour REI)
ii. Greenhouse
Reentry (2 hour REI)
Reentry (12 hour REI)
Reentry (24 -hour REI)
iii. Food Manufacturing Plant -
Reentry (24 hour REI)
iv. Warehouse treatment -
Reentry (24 hour REI, 1 hr
exposure)
v. Railcars and trucks
(8 hr REI)
NOTES
1
2
3
4
5
6
EXPOSURE
PATTERN1
Current Exposure (mg/kg/day)
Dermal
Inhalation
Current MOE
Dermal
Inhalation
MOE
Total
Target MOEs for all short term post-application Occupational Scenarios are 30, and for acute
post-application scenarios, are 100.
Short-term
Short-term
0.0002
0.0002
0.044 mg/m3
0.016 mg/m3
450
450
24
66
23
58
Short-term
Short-term
Short-term
acute
acute
Short-term
0.0012
0.00012
<0. 00012
0.00022
0.00022
0.00035 mg/m3
<0. 00035 mg/m3
<0. 00035 mg/m3
0.053 mg/m3
(0.006 mg/kg/day)
0.074 mg/m3
(0.001 mg/kg/day)
0.01 87 mg/m3
(0.0010
mg/kg/day)
80
800
>800
3600
3600
3000
>3000
>3000
130
800
94
78
>650
>650
130
650
94
NOTES: The following notes define the assumptions used in calculating the margins of exposure.
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1. Risk is expressed as a Margin of Exposure (MOE)
MOE = NOAEL .where both the NOAEL and the Exposure are expressed in mg/kg/day or mg/m3
Exposure
The target MOE for all short term post-application occupational exposure is 30, and for all acute post-application scenarios is 100.
Occupational Exposure assumptions. An average worker weighs 70 kg and has a respiratory volume of 1.0 m3 /hour (NAFTA Value). At a minimum, the following
protective clothing was used in the exposure scenarios: gloves, long-sleeve shirt, and long pants. Addition of a respirator to the PPE requirements would reduce
estimated inhalation exposure by 90%, which would not change the MOEs by more than a factor of 2.
2. Mushroom Houses - reentry. For reentry exposure, it was assumed that a worker reenters a ventilated mushroom house 12 or 24 hours after treatment and is
exposed for 8 hours. The post-application exposures for mushroom houses were derived from a study conducted by the California Department of Food and
Agriculture (CDFA) (now the California EPA) in which air and surface residues were measured in mushroom houses where dichlorvos had been applied (Maddy
1981, Jaquith 1998d). This was a limited study measuring surface residues and air concentrations in 2-4 mushroom houses over 24 hours.
Wipe sampling was only conducted in 2 mushroom houses, preventing any analysis of the distribution of surface residues in these facilities. The highest surface
concentration, 0.026 ug/cm2, was reported 3 hours after application. The last sampling point was at 12 hours after application, when the surface residues
averaged 0.007 ug/cm . There was no clear trend in the air concentrations. Air samples were collected at 30 minutes, and 1, 3, 6 12, and 24 hours. Only two
samples were taken at the 24 hour sampling period. The air concentrations of dichlorvos averaged 0.022, 0.044, and 0.016 mg/m , at 6, 12, and 24 hours after
treatment, respectively. The transfer coefficient was obtained from the ExpoSAC policy 003, to be 2500 cm2/hr. Because of the aeration pattern of mushroom
houses, the volatility of dichlorvos, and dissipation of dichlorvos in mushroom houses, this is considered to be a short term exposure scenario. Respirators are not
worn during reentry.
Dermal Exposure (ug/kg/day) = 0.007 ug/cm2 x 2500 cm2/hrx8 hr/dayx 1/70 kg x 0.11 (Absorb)
= 0.22 ug/kg/day
= 0.00022 mg/kg/day
Estimated dermal post-application risk = NOAEL = 0.1 mq/kq/dav = 450 (Target MOE = 30, ARI = 450/30 = 15)
Exposure 0.00022 mg/kg/day
The inhalation risk estimate includes a factor to adjust for the hours of exposure. The endpoint converted to concentration units assumed 24 hours exposure per
day. Workers in mushroom houses are exposed for 8 hours.
Estimated inhalation post-application risk = NOAEL = 0.35 mq/m3x 24hr = 24 (Target MOE = 30)
(12hourREI) Exposure 0.044 mg/m3 8 hr
The label REI is now 18 hours.
3. Greenhouse - reentry. The dermal exposure for reentry into greenhouses following the use of dichlorvos was obtained using data from a greenhouse culture
textbook, data on turf transferable residues from a chlorpyrifos/dichlorvos turf study (Goh, K. S., et. al. 1986), and a transfer coefficient of 2500 cm2/hr, from the
ExpoSAC Policy 003. Inhalation exposure estimates were modeled assuming the initial concentration at the maximum rate, assuming first order kinetics and an air
exchange rate from a textbook (Mastalerz, 1977). This is considered to be a short-term exposure scenario (Jaquith, 1998d).
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The dislodgeable foliar residues reported in the Goh study were 0.04 ug/cm2, 2-6 hours after application, and 0.004 ug/cm2, 10 hours after application of 2 g
dichlorvos/IOOOft3
The total daily dermal exposure that would occur after a 2 hour REI is estimated to be:
Dermal Exposure (ug/kg/day) = 0.04 ug/cm2 x 2500 cm2/hrx 8 hrs/dayx 0.11 (dermal absorption factor) x 1/70 kg = 1.25 ug/kg/day (0.00125 mg/kg/day)
Dermal MOE = NOAEL = 0.1 mq/kq/dav =80
Exposure 0.00125 mg/kg/day
Estimated inhalation post-application risk = NOAEL = 0.35 mq/m3 x 24 hr = 3000
(2 hour REI) Exposure 0.00035 mg/m3 8 hr
4. Reentry - Food manufacturing plant. Dichlorvos can be applied to food processing facilities with wall-mounted automatic foggers. In estimating reentry exposure to
food processing facilities, EPA assumed 24 hours elapsed before reentry is allowed, as required on labels; and that workers spend 8 hours per day on the day
following treatment. Dichlorvos is applied at the rate of 2.0 grams active ingredient per 1,000 ft3 over a period of 125 minutes per application. Hand rinses were
done and air concentrations were measured at 0, 3, 6, 10, 22, and 42 hours after application. Dermal exposure was measured for the hands only and represents
an average of the total exposure measured for three work stations. Because significant exposure occurs for only one day and occurs sporadically, this is
considered an acute reentry scenario and MOEs are calculated using the BMDL-io of 0.8 mg/kg for inhibition of rat cholinesterase.
The dermal exposure calculated in the original review (Jaquith 1993c), 0.00027 mg/kg/day, has been corrected for the application rate (2.0/2.4), resulting in a
dermal exposure estimate of 0.00022 mg/kg/day.
The dermal MOE = 0.8/.00022 = 3600
Mean air concentrations of dichlorvos in a food handling establishment following treatment using a fogger at 2.4 g ai/1000 ft3. Means include samples from all sites
and two different heights. (Jaquith, D., 2000a; Jaquith, D, 1993c).
Hours After Application Mean Cone, (mg/m3) Cone. Corrected for application rate (mg/m3)
0 10.0 8.3
3 2.7 2.2
6 0.62 0.52
10 0.37 0.31
22 0.13 0.11
42 0.052 0.043
An exponential decay curve C = C0x e"kt was fit to the data where C0 = 0.93 mg/m3 and k = 0.10/hour. The corresponding equation for average concentration over
the interval from t-i to t.2 is Cavg = Co x (e"kt1 - e-kt2) / k(t.2-ti). For the interval from 24 to 32 hours, the average concentration is 0.053 mg/m3. The dose on a mg/kg
basis is:
Page 187 of 338
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Dose (mg/kg) = 0.053 mg/m3x 1.0 m3/hrx8 hr^-70 kg = 0.006 mg/kg.
The acute inhalation MOE is: MOE = 0.8 •*• 0.006 = 130
5. Reentry - warehouse. Dichlorvos can be applied to food warehouses with wall-mounted automatic foggers. In estimating reentry exposure to warehouse facilities,
EPA assumed 24 hours elapsed before reentry is allowed, as required on labels; and that workers spend 60 minutes per day in the treated area. Dichlorvos is
applied at the rate of 2.0 grams active ingredient per 1,000 ft3 over a period of 125 minutes per application. Dermal exposure was measured for the hands only
and represents an average of the total exposure measured for three work stations. Because significant exposure occurs for only one day and occurs sporadically,
this is considered an acute reentry scenario and MOEs are calculated using the BMDL-io of 0.8 mg/kg for inhibition of rat cholinesterase.
The dermal exposure is described in footnote (4).
The methodology for inhalation exposure and risk are described in footnote (4). Assuming a worker reenters a treated warehouse 24 hours after application and
works for one hour, the average dichlorvos concentration in the interval from 24 to 25 hours is 0.074 mg/m3. The dose on a mg/kg basis is:
0.074 mg/m3x1.0 m3/hrx 1 hr/70 kg = 0.0010 mg/kg/day
MOE = 0.8 mq/kq/dav = 800
0.0010 mg/kg/day
6. Reentry - railcars and trucks. Dichlorvos can be applied to railcars and trucks as a space spray, or as a surface spray. Some labels allow up to 2 g ai/1000 ft3,
others allow up to 2.5 g ai/1000 ft3. The initial concentration of dichlorvos from 2.5 g ai/1000 ft would be 88 mg/m3. The concentration at later time intervals can
be calculated from the equation, Ct= C0x e"kt, where k= 1, based on an assumed air exchange rate of 1 air change per hour. In estimating reentry exposure, EPA
assumed 8 hours elapsed before reentry is allowed, and that workers could spend 1 hour per truck or railcar and could load 4 railcars or trucks per day. Workers
loading rail cars or trucks would not be expected to have dermal exposure to dichlorvos. The air concentration was estimated using initial air concentrations
calculated from the application rate, and assuming ventilation similar to a food processing establishment (k=1). This exposure scenario was considered to be short
term due to rapid dissipation of dichlorvos. (Jaquith, D., 2005).
Integrating the equation for a period of 8 to 9 hours,
Ct = -88 mg/m3x (e9 - e8) = 0.0187 mg/m3
0.0187 mg/m3 x 1.0 m3/hrx1 hr/truckx4 trucks / 70 kg = 0.0011 mg/kg/day
MOE = 0.1 mq/kq/dav = 94
0.0011 mg/kg/day
There is considerable uncertainty about the air exchange rate. Under the conditions described, the air exchange rate could be as low as 1/3 per hour
Page 188 of 338
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10.0 Data Needs and Label Requirements
10.1 Toxicology
There are no outstanding toxicology data requirements.
10.2 Product Chemistry
The discrepancy in the percent of active ingredient in several of the technicals must be
resolved.
10.3 Residue Chemistry
The residue chemistry database for dichlorvos is reasonably complete. All labels must
conform to the use pattern reflected in the residue data submitted. The following data requirements
remain outstanding.
GLN 860.1380: Storage Stability Data
The Reregistration requirements for storage stability data are not fulfilled. Information
pertaining to the storage intervals and conditions of samples of the following commodities, from
studies that were reviewed in the Residue Chemistry Chapter of the Guidance Document, must be
submitted: packaged and bagged raw agricultural commodities and processed food; bulk stored raw
agricultural commodities; milk; eggs; and meat, fat, and meat byproducts of dairy cows and poultry.
Alternatively, the registrant may demonstrate that there are sufficient residue data which are
supported by storage stability data to support all registered uses of dichlorvos.
The available storage stability data indicate that residues of dichlorvos are stable under frozen
storage conditions for up to 90 days in/on plant commodities, up to 4.5 months in/on peanuts, and
up to 8 weeks in animal commodities.
GLN 860.1480: Meat, Milk, Poultry, Eggs
The Reregistration requirements for data pertaining to this guideline topic are not completely
fulfilled. A dermal magnitude of the residue study must be submitted for swine. No additional data
are required for milk and edible tissues of ruminants, and for eggs and edible tissues of poultry.
Swine use is on the labels for EPA Reg. Nos. 572-246 and 47000-130.
10.4 Occupational and Residential Exposure
All labels must conform to the parameters used in this risk assessment. Protective clothing
requirements at least as stringent as that used in this risk assessment must be added to the label.
Labels permitting fogging must be clarified to state that hand-held foggers are not permitted, and
that the applicator must be outside the treated area during application.
Page 189 of 338
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The greenhouse exposure study requirement has been satisfied by a generic study on malathion,
which allowed the Agency to determine a transfer coefficient for harvesting greenhouse grown cut
flowers. MRID 46513901, (Dole, T and M. Lloyd, 2005)
Dichlorvos from trichlorfon.
Outstanding exposure data requirements exist for trichlorfon. A TTR study with analyses for
trichlorfon and dichlorvos in the turf and in the toddler breathing zone above the turf (18") is
requested to confirm the exposure estimates in this document. The study must be conducted at an
appropriate pH (approx. 7). A field dissipation study may be substituted, provided it meets these
requirements.
GDLN 875.2100 Foliar Residue Dissipation Study (replaces GDLN132-1 (a))
GDLN 875.2400 Dermal Exposure (replaces GDLN 133-3, Dermal Passive Dosimetry)
GDLN 875.2500 Inhalation Exposure (replaces GDLN 133-4, Inhalation Passive Dosimetry)
Page 190 of 338
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Page 193 of 338
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Reregistration Eligibility Document. April 27, 1998.
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Exposure and Risk for Residues of Dichlorvos resulting from use of Dichlorvos and Naled. April 7,
2000.
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28-29 Meeting. Memo to D. Campt. October 16, 1989.
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Jaquith D. 1987b. Refinement of Exposure Assessment for Dichlorvos. August 7, 1987.
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Fogger. MRID 41928801. May 10, 1993.
Jaquith D. 1993c. Review of Exposure Monitoring Study for Use of DDVP in Food Processing
Establishments, DP Barcode D191571, December 6, 1993.
Jaquith D. 1996. Response to Public Comments on Dichlorvos PD 2/3. June 4, 1996.
Jaquith D. 1998a. Exposures from Dichlorvos (DDVP) Resin Strips. D246131. March 5, 1998.
Jaquith D. 1998b. Re-entry Exposures to Dichlorvos Resulting from Application to Residential Turf
and Recreational Areas. D246126. March 16, 1998.
Jaquith D. 1998c. Exposures to Dichlorvos (DDVP) from Flea Collars. March 18, 1998.
Jaquith D. 1998d. Exposure Assessment for Dichlorvos (DDVP) Applied to Greenhouse and
Mushroom Houses. April 22, 1998.
Page 194 of 338
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Jaquith D. 1998e. Exposure to Dichlorvos resulting from the Use of Bait Products. D246128. April
28, 1998.
Jaquith D. 1998f Inhalation Exposures from Dichlorvos (DDVP) Resin Strips. June 12, 1998.
Jaquith D. 1998g. Revised Applicator Exposures to Dichlorvos resulting from Crack and Crevice
Use and the Use of Aerosol Products. D261140. April 30, 1998.
Jaquith D. 1998h. Revisions of Exposures from Dichlorvos (DDVP) Resin Strips. D250069.
September 30, 1998.
Jaquith D. 1998L Exposures to Dichlorvos Resulting from the Use of Bait Products. D251336.
January 27, 1999.
Jaquith D. 1998J. Response to Comments from EXPOS AC on Exposure Assessment for Dichlorvos
(DDVP) from Flea Collars. D 246127. November 6, 1998.
Jaquith D. 1998k. Response to EXPOSAC Comments on Exposure Assessment for Total Release
Foggers Containing Dichlorvos (DDVP). D251333. December 31, 1998.
Jaquith D. 19981. Revised Applicator Exposures to Dichlorvos (DDVP) Resulting from Dairy Barn
and Animal Spray Uses. D251330. January 27, 1999.
Jaquith D. 1998m. Response to Comments from the EXPOSAC and Others on Assessment of Re-
entry Exposures to Dichlorvos Resulting from Application to Residential Turf and Recreation
Areas. D251909. January 28, 1998.
Jaquith D. 1998n. Revised Exposure Assessment for Greenhouses and Mushroom Houses.
D251337. January 27, 1999.
Jaquith, D. 1999a. Response to Amvac Comments on HED Interim Risk Assessment for DDVP.
D255064. March 17, 1999.
\
Jaquith, D. 1999b. Examination of Recent Submissions from Amvac regarding Dichlorvos (DDVP)
and Rationale for Not Including Them in the Exposure/Risk Assessment. May 27, 1999.
Jaquith, D., 1999c. Dislodgeable Foliar Residues and Exposure Assessment for
Residential/Recreational Turf Applications of Dichlorvos (DDVP), PC Code 084001, Barcodes
D248456, D248596, D255253, August 13, 1999.
Jaquith, D., 1999d. Calculation Error - Dichlorvos Resin Strips, D257002, August 16, 1999.
Jaquith, D, 2000. Dichlorvos (DDVP) Resin Strip Exposure Assessment for Individuals Exposed
for a 2 Hour Period, PC Code 084001. July 21, 2000.
Page 195 of 338
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Jaquith, D., 2000a. Revision of Exposure Assessment for DDVP applied to Warehouses and Food
Processing Plants. D226572. June 7, 2000.
Jaquith, D., 2001. Response to Comments on the Preliminary Risk Assessment (PRA) for
Dichlorvos (PC Code 084001, DP Barcode D271993). May 31, 2001.
Jaquith, D., 2003. Addendum to Residential Turf Assessment for Dichlorvos (DDVP) PC Code
084001, DP Barcode D288914. March 28, 2003.
Jaquith, D., 2003 a. Review of Protocol for Study Monitoring Indoor Air Concentrations of DDVP
Using Pest Strips in Confined and Unoccupied Areas. DP Barcode D288575. March 14, 2003.
Jaquith, D., 2005. Exposure Assessment for Workers Applying DDVP to Rail Cars and Stationary
Trucks and Subsequently Loading Cargo onto the Treated Vehicles (PC Code 084001, DPBarcode
D289191), January 27, 2005.
Johnston, Jason , et al, A Re-analysis of Observations on Occupants of Arizona Homes Containing
20% Vapona Insecticide Resin Strips (Arizona II Home Study):, Exponent, Inc. December 4, 2002.
Exponent, Inc. (Washington, D.C.).Laboratory Study No. Dichlorvos 02-01. MRID 45812001.
Unpublished.
Jones, R. D., 2006. Qualitative Assessment of Human Exposure to Dichlorvos formed from
Trichlorfon through Drinking Water and Inhalation Routes. EPA Memorandum to Dayton
Eckerson and Sue Hummel, dated May 17, 2006.
Kent, R. 2001. Use of Human Toxicity Studies on Dichlorvos (DDVP) to Decrease the Interspecies
Scaling Factor (PC Code 084001, DP Barcode D278926). TXR: 0050250. November 1, 2001.
Khasawinah, A. and Diwan, S. 1999. Trichlorfon and Dichlorvos (DDVP): Reassessment of the
Requirements for the Prenatal Developmental Studies in Guinea Pig - Report of the Hazard
Identification Assessment Review Committee. August 10, 1999. HED Document No. 013989.
Klonne, D. (1999) Integrated Report for Evaluation of Potential Exposures to Homeowners and
Professional Lawn Care Operators Mixing, Loading, and Applying Granular and Liquid Pesticides
to Residential Lawns: Lab Project Number: OMAOO5: OMAOO1: OMAOO2. Unpublished study
prepared by Ricerca, Inc., and Morse Laboratories. 2213 p. (MRID 44972201)
Knox, B.; Askaa, J.; Basse, A.; Bitsch, V.; Mandrup, M.; Ottosen, H.; Overby, E.; Pedersen, K.;
Rasmussen, F. 1978. Congenital ataxia and tremor with cerebellar hypoplasia in piglets borne by
sows treated with NeguvonR vet. (Metrifonate, Trichlorfon) during pregnancy. Nord. Vet. Med.
30:538-545.
Leighton, T. 2000. HED's Revision of the Trichlorfon Residential Exposure/Risk Assessment.
PC Code 057901. DP Barcode D268125. August 9, 2000.
Lewis. P. 1998. Transmittal of the Final Report of the FIFRA Scientific Advisory Panel Meeting
Held July 29-30, 1998. Memorandum to M. Mulkey, Director, Office of Pesticide Programs.
Page 196 of 338
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(MRID 46688914) following exposure to DDVP. June 9, 2006.
Maddy KT, Schneider F, Lowe J, Ochi E, Frederickson S, and Margotich S. 1981. Vapona (DDVP)
Exposure Potential to Workers in Mushroom houses in Ventura County, California in 1981. HS-
861. As cited in Jaquith 1998d.
Mastalerz, J.W. 1977. The Greenhouse Environment. John Wiley & Sons, New York, Table 2.1,
page 14.
Mehl, N.; Schanke, T.; Johnsen, B.; Fonnum, F. 1994. The effect of Trichlorfon and other
organophosphates on prenatal brain development in the guinea pig. Neurochem. Res.
19(5):569-574.
Morton, T. 1999. Trichlorfon (057901): Nature of Residue in Livestock(GLN 860.1300), Residue
Analytical Method (GLN 860.1340), Storage Stability Data (GLN 860.1380), Magnitude of
Residue in Livestock (GLN 860.1480), and Residue Depletion after Dermal Application (GLN
860.1300). DP Barcode # D244279, D254894. Case 0104; MRID Nos. 44500701, 44500702,
44500703, 44500704, 44781401, June 24, 1999.
Morton, T. 2000. Trichlorfon (057901): HED Revised Preliminary Risk Assessment for
Trichlorfon. DP Barcode D268728. Case 0104. September 19, 2000.
Nigg, H. N., J. H. Stamper, W. D. Mahon. 1987. Pesticide Exposure to Florida Greenhouse
Applicators. Grant No. CR-810743. Sponsored by EPA.
Parker RD, Nelson, HP, and Jones D. 1995. GENEEC: a Screening Model for Pesticide
Environmental Exposure Assessment. The International Symposium on Water Quality Monitoring.
American Society of Agricultural Engineers. P. 485.
Pope, A.; Heavner, J.; Guarnieri, J; Knobloch, C. 1986. Trichlorfon induced congenital cerebellar
hypoplasia in neonatal pigs. JAVMA 189(7):781-783.
Rambo, G. 1987. Personal communication between George Rambo of the National Pest Control
Association (NPCA) and David Jaquith of OPP.
REJV, 2002. Residential Exposure Joint Venture, electronic database, study period May 2001 -
April 2002.
Reregistration Branch 4, 2002. Dichlorvos Resin Pest Strips - Additional Exposure and Risk
Analyses. Addendum to Human Health Risk Assessment. DP Barcode D286338. October 23,
2002.
Rowland J. 1998. Dichlorvos (DDVP) - RE-EVALUATION - Report of the Hazard Identification
Assessment Review Committee. June 3, 1998.
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Rowland J. 1999. Dichlorvos (DDVP) - RE-EVALUATION - Report of the Hazard Identification
Assessment Review Committee. June 2, 1999. HED Document No. 013434
Sahib I. 1998. Drinking Water Assessment for Dichlorvos. March 25, 1998.
Schaible, S. 1994. and Chronic Dietary Exposure Analysis for Dichlorvos. December 2, 1994.
Sette, W. F. 1998a. Dichlorvos (084001): Pathology Working Group Peer Review of 28 day
Neurotoxicity Study. April 9, 1998.
Sette, W.F. 1998b. Dichlorvos (084001), Trichlorfon (057901). D237270: Summary Review of
Published studies on Metrifonate, a drug metabolized to Dichlorvos, and their relevance to
Dichlorvos risk assessment (MRID 44308001). April 10, 1998.
Sette, W.F. 1999a. DDVP (084001): Response to AMV AC letter of 1/19/99 related to EPA's basis
for concern for potential developmental neurotoxic effects, and revised HED testing
recommendations. D252753. May 3, 1999.
Stewart J. 1993. Review of Human Toxicology Data on Dichlorvos (DDVP). TXR 010157.
Memorandum dated April 8, 1993.
Stewart J. 1998. Review of Toxicity Studies on Dichlorvos Using Human Volunteers. March 24,
1998. MRIDs 44317901, 4416201, 44248801, 44248802.
Stewart 1996a. Dichlorvos Special Studies. MRID 42880101, 42881101. May 30, 1996.
Stewart J. 1996b. Review of Supplementary Pathology Data: Staging of Severity of Mononuclear
Cell Leukemia observed in Male fisher 344 Rats in the Two Year Carcinogenicity Study. MRID
43565601. June 20, 1996
Stewart J. 1996. Dichlorvos. Transmittal of the Quantitative Risk Assessment and Response to
Registrant's questions concerning Neurotoxicity Study and Cancer Peer Review. October 4, 1996.
Stewart J. and W. Burnam 1996. Fifth Carcinogenicity Peer Review of Dichlorvos. Tox Chem #
328, PC Code 084001. August 28, 1996.
Stewart J. 1997. Toxicology Branch Response to Public Comments on the PD 2/3 for Dichlorvos.
April 16, 1997.
Stewart J. 1998. Review of Toxicity Studies on Dichlorvos Using Human Volunteers. March 24,
1998. MRIDs 44317901, 4416201, 44248801, 44248802.
Tarplee B. and Rowland J. 1998. Dichlorvos (DDVP) - Report of the FQPA Safety Factor
Committee. June 2, 1998.
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Tarplee, B. 2000. Dichlorvos (DDVP) - Reassessment Report of the FQPA Safety Factor
Committee. February 23, 2000.
USEPA 1992. Pesticides in Groundwater Database - A Compilation of Monitoring Studies from
1971 to 1991. US Environmental Protection Agency, Office Of Pesticides, Prevention, and Toxic
Substances. EPA Document Number 734-12-92-0001.
US EPA 1997. Reregistration Eligibility Decision (RED): Trichlorfon. US Environmental
Protection Agency, Office Of Pesticides, Prevention, and Toxic Substances. EPA Document
Number 738-R-96-017.
US EPA. 1997a. Draft Standard Operating Procedures (SOPs) for Residential Exposure
Assessments. December 19, 1997. (See also ExpoSAC, 2001)
USEPA. 1998. FIFRA Scientific Advisory Panel. 7/30/98. A Set of Scientific Issues Being
Considered by the Agency in Connection with DDVP (Dichlorvos) Risk Issues, pp 14-26 .
US EPA. 1998a. PHED Surrogate Exposure Guide. Estimate of Worker Exposure from the
Pesticide Handlers Exposure Database, Version 1.1. August, 1998.
US EPA, 2000. "Benchmark Dose Technical Guidance Document" Draft report. Risk Assessment
Forum, Office of Research and Development, U.S. Environmental Protection Agency. Washington,
DC. EPA/630/R-00/001
US EPA 2001. Preliminary OP Cumulative Risk Assessment. December 3, 2001.
http ://www. epa. gov/pesticides/cumulative/pra-op/
US EPA, 2002. Methods Used to Conduct a Preliminary Cumulative Risk Assessment for
Organophosphate Pesticides. Report from the FIFRA Scientific Advisory Panel Meeting of
February 5-7, 2002 (Report dated March 19, 2002). SAP Report 2002-01.
http://www.epa.gov/scipoly/sap/index.htnrfjune.
US EPA 2002a. Revised Organophosphorus Pesticide Cumulative Risk Assessment. Office of
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http://www.epa.gov/pesticides/cumulative/rra-op/
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Appendices
1.0 TOXICOLOGY DATA REQUIREMENTS
The toxicology data requirements (40 CFR 158.340) for food uses for dichlorvos are in Table 1.
Use of the new guideline numbers does not imply that the new (1998) guideline protocols were
used.
Test
Technical
Required
Satisfied
870.1100 OralToxicity
870.1200 Dermal Toxicity
870.1300 Inhalation Toxicity
870.2400 Primary Eye Irritation
870.2500 Primary Dermal Irritation
870.2600 Dermal Sensitization
870.3100 Oral Subchronic (rodent)
870.3150 Oral Subchronic (nonrodent)
870.3200 21-Day Dermal
870.3250 90-Day Dermal
870.3465 90-Day Inhalation
870.3700a Developmental Toxicity (rodent)
870.3700b Developmental Toxicity (nonrodent)
870.3800 Reproduction
870.4100a Chronic Toxicity (rodent)
870.4100b Chronic Toxicity (nonrodent)
870.4200a Oncogenicity (rat)
870.4200b Oncogenicity (mouse)
870.4300 Chronic/Oncogenicity
870.5100 Mutagenicity—Gene Mutation - bacterial
870.5300 Mutagenicity—Gene Mutation - mammalian
870.5xxx Mutagenicity—Structural Chromosomal Aberrations.
870.5xxx Mutagenicity—Other Genotoxic Effects
870.6100a Delayed Neurotox. (hen)
870.6100b 90-Day Neurotoxicity (hen)
870.6200a Neurotox. Screening Battery (rat)
870.6200b 90 Day Neuro. Screening Battery (rat)
870.6300 Developmental Neurotoxicity
870.7485 General Metabolism
870.7600 Dermal Penetration
Special Studies for Ocular Effects
Oral (rat)
Subchronic Oral (rat)
Six-month Oral (dog)
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
no
no
yes
yes
yesa
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yesb
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
no
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
no
no
no
a = Subchronic (oral) dog study is satisfied by chronic dog study
b = chronic toxicity in rats and Oncogenicity in rats are satisfied by chronic toxicity/carcinogenicity
rat study
Page 200 of 338
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2.0 REFERENCES FOR TOXICOLOGY STUDIES
Alternative Selection for Acute RfD:
Study Selected: Acute Cholinesterase Study - Humans Non-guideline
MRID: 44248802
Title: Dichlorvos: A Study to Investigate the Effect of a Single Oral Dose on Erythrocyte
Cholinesterase Inhibition in Healthy Male Volunteers; Gledhill, AJ; March 25, 1997
Executive Summary: Dichlorvos was administered in a single oral dose of 70 mg (equivalent to 1
mg/kg bw) in corn oil by capsule to fasted young healthy male volunteers. Prior to dosing, baseline
RBC Cholinesterase activity was measured on study days -22, -20, -18, -15, -13, -11, -8, -6, -4 and
immediately prior to dosing. The study subjects were medically supervised for clinical signs and
body temperature changes for 24 hours and for RBC Cholinesterase inhibition for up to fourteen
days after administration of the DDVP capsules. Plasma Cholinesterase was not measured in this
study.
Under study conditions, no adverse clinical signs or changes in body temperature were reported.
When the group mean RBC Cholinesterase activities were analyzed, there were statistically
significant reductions (p<0.01) from the predose mean on days 5/6, day 7, and day 14. These
statistically significant reductions represent percent decreases of 10, 12, and 11%, respectively. No
reduction in RBC Cholinesterase activity was apparent at other reporting periods. The individual
predose values used to calculate the mean RBC Cholinesterase activity varied by 17% for volunteer
1, 16% for volunteer 2, 6% for volunteer 3, 10% for volunteer 4, 7% for volunteer 5, and 9% for
volunteer 6.
The NOAEL for RBC Cholinesterase depression is 1.0 mg/kg bw and a LOAEL was not established
in the study.
Although the study results indicate that a significant decrease in mean RBC Cholinesterase was first
observed at 5/6 days after treatment, with significance also seen at 7 and 14 days posttreatment,
measurements at posttreatment days 1 and 3 were not significantly different from baseline. These
results are inconsistent with known information on the chemical. Namely, given the rapid
bioavailability and metabolism of dichlorvos, it is unlikely that a significant decrease in RBC
Cholinesterase would first be observed at day 5/6 posttreatment and not also at days 1 and 3
posttreatment. The statistical significance observed could be attributed to variation among
individual participants.
Lack of information on time of peak effect.
In the acute human study, the first Cholinesterase measurement was recorded 24 hours after dosing.
In the study (MRID 46153303) on the measurement of RBC and brain ChE activity in pre-weaning
and adult female rats treated with a single dose of 15 mg/kg dichlorvos, time-course data
Page 201 of 338
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demonstrate that the time of peak effect for both RBC and brain ChE measurements is 1-3 hours
post-dosing. Therefore, the absence of biologically significant RBC ChE depression in the human
study may be due to the absence of blood sampling at the time of peak effect (1-3 hours), since in
the human study, the first measurement did not occur until 24 hours after dosing.
Based on the information on time to peak effect, we conclude that the lack of cholinesterase
measurements prior to 24 hours post-treatment in the acute human study may have influenced the
apparent NOAEL. We have therefore opted not to use the acute human study for regulatory
purposes.
CITATION: G. Milburn (2003) Dichlorvos: developmental neurotoxicity study in rats.
Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Laboratory report number CTL/RR0886/Regulatory/Report, November 10,
2003. MRID 46153302. Unpublished.
G. Milburn (2003) Dichlorvos: preliminary developmental neurotoxicity study
in rats. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire,
UK. Laboratory report number CTL/RR00885/Regulatory/Report, October
13,2003. MRID 46153301. Unpublished.
SPONSOR: Amvac Chemical Corporation.
EXECUTIVE SUMMARY:
In a developmental neurotoxicity study (2003, MRID 46153302, study RR0886) Dichlorvos (99.0%
a.L, batch #81120700) was administered to 30 time-mated female Alpk:APfSD (Wistar-derived)
rats per group by gavage in de-ionized water at dose levels of 0, 0.1, 1.0, or 7.5 mg/kg bw/day from
gestation day (GD) 7 through postnatal day (PND) 7 and direct treatment of the Fl offspring was
carried out during PND 8-22, inclusive. On PND 5, litters were culled to 8 pups (4/sex as closely as
possible), and litters containing fewer than 7 pups and/or fewer than 3 pups of each sex were
removed from the study. The dams were subjected to a functional observational battery (FOB) on
GDs 10 and 17 and on PNDs 2 and 9. The Fl offspring were observed for attainment of preputial
separation or vaginal patency. Animals were allocated from within litters for use in the following
investigations: functional observational battery assessments (PNDs 5, 12, 22, 36, 46, and 61);
locomotor activity assessment (PNDs 14, 18, 22, and 60); auditory startle habituation (PNDs 23 and
61), water maze testing (PND 24-27 or PND 59-62); and post mortem investigations including brain
weight, neuropathology, and morphometry (PNDs 12 and 63). Dosing was based on a preliminary
developmental neurotoxicity study in rats (MRID 46153301).
One high-dose female was sacrificed on LD 3 due to clinical signs (pallor, piloerection, and slightly
hunched posture and thin appearance) and had a pale liver at necropsy. One mid-dose female died
on GD 24 due to parturition difficulties. There were no treatment-related effects on maternal body
weight, FOB parameters, or gestation length. The maternal NOAEL is 7.5 mg/kg/day, the highest
dose tested. A maternal LOAEL was not established.
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During LD 1-5, the control, low-, mid-, and high-dose groups, respectively, had pup mortality of
22.6, 17.4, 17.5, and 28.1%, and there were total litter losses of 20.0, 10.0, 17.9, and 18.5% of the
litters in these same respective groups. There were 2 total litter resorptions in the high-dose group.
The number of litters available which were used for Fl offspring was 23, 21, 21, and 14 and the
viability indices were 77.4, 82.6, 82.5, and 69.0% for the control, low, mid, and high dose groups,
respectively.
Due to the low number of pups available in the high dose group, it was necessary to combine this
study (RR0886) with a repeat study (2004, MRID 46239801; study No. RR0988) consisting of
controls and a dose level of 7.5 mg/kg in order to have sufficient pups for all assessments.
The DNT Committee determined that the two DNT studies combined (RR0886 and RR0988) had
acceptable numbers of total pups examined in the controls and high dose groups (> 35 pups/sex
examined in combined studies) and, therefore, the developmental results of the combined studies
could be evaluated for the NOAEL/LOAEL. The classification of the studies taken together was
changed from unacceptable/non-guideline to Acceptable/non-guideline. A comparison of the
developmental findings showed that the auditory startle reflex habituation Vmax in PND 23 high
dose males in study RR0886 had statistically significant increases (37-49%) in 4 out of 5 blocks and
study RR0988 had increases (7-15%), although not statistically significant, in this same Vmax
parameter in PND 23 high dose males in 5 out of 5 blocks in comparison to controls for each study.
Therefore, the developmental/offspring NOAEL was determined to be 1.0 mg/kg/day (based on
study RR0886) and the developmental/offspring LOAEL was 7.5 mg/kg/day (based on both studies
RR0886 and RR0988) with the effect being increases in auditory startle reflex habituation Vmax in
PND 23 high dose males in both studies.
This study when combined with the accompanying study is classified Acceptable/non-guideline and
may be used for regulatory purposes. It does satisfy the guideline requirement for a developmental
neurotoxicity study in rats [OPPTS 870.6300, §83-6; OECD 426 (draft)], pending review of the
positive control data.
CITATION: G.M. Milburn (2004) Dichlorvos: supplemental developmental neurotoxicity
study in rats. Central Toxicology Laboratory, Alderley Park, Macclesfield,
Cheshire, UK SK10 4TJ. Laboratory report number
CTL/RR0988/Regulatory/Report, January 28, 2004. MRID 46239801.
Unpublished.
SPONSOR: Amvac Chemical Corporation.
EXECUTIVE SUMMARY: In a preliminary developmental neurotoxicity study (MRID
46153301) Dichlorvos (99.0% a.L, batch #ST120700) was administered by gavage in de-ionized
water to 15 time-mated female Alpk:APfSD (Wistar-derived) rats per dose at dose levels of 0, 0.1,
1.0, or 7.5 mg/kg bw/day from gestation day (GD) 7 through postnatal day (PND) 22. In-life
observations included maternal clinical signs, body weight, and food consumption (during
gestation) and the number, survival, clinical signs, and body weight of the pups. Erythrocyte (RBC)
and whole brain acetylcholinesterase (AChE) activities were measured as follows: in 5 dams/group
Page 203 of 338
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on GD 22; in 5 dams/group on PND 22; in selected fetuses from the dams killed on GD 22 (blood
from sufficient fetuses to attain adequate pooled sample volume and whole brain from 4
fetuses/sex/litter); and in 5 pups/sex/group (1 per litter where possible) on each of PNDs 2, 8, 15,
and 22. Plasma AChE activity was not measured.
There were no maternal deaths during the study. Three dams had abnormal clinical signs: one
control dam with piloerection on day 26; one mid-dose dam with observations of paleness (days 24-
26), hunched, subdued behavior (day 26), and a total litter loss by day 26 (LD 3); and one high-dose
dam with irregular breathing on days 25-27. There were no treatment-related effects on maternal
food consumption, maternal body weight, or gestation length. The study author mentioned body
weight decreases in high-dose dams beginning on LD 11, but these were of insufficient magnitude
to be considered biologically significant (just 3-4% less than controls). Under the conditions of
this study, the LOAEL for maternal systemic toxicity (other than acetylcholinesterase inhibition) is
not identified, and the NOAEL is greater than or equal to 7.5 mg/kg bw/day.
There were no treatment-related effects on the overall proportion of pups born alive, the mean
percentage of live pups per litter, or live litter size on LD 1. Pup survival, body weight, and clinical
signs were unaffected by treatment. Two dams had total litter losses: one mid-dose dam had a total
litter loss by LD 3, and one low-dose dam had a total litter loss (of 1 pup) by LD 2. An increased
proportion of male pups in the mid-dose group (64.8% vs. 46.2% for controls; p<0.01) was
considered incidental to treatment because there was no similar finding at the highest dose level.
Under the conditions of this study, the LOAEL for offspring toxicity (other than
acetylcholinesterase inhibition) is not identified, and the NOAEL is greater than or equal to 7.5
mg/kg bw/day.
In maternal animals, RBC AChE activity was biologically significantly inhibited at the mid- and
high-dose treatment levels on GD 22 by 25% and 48%, respectively (p<0.01) and on LD 22 by 24%
and 50%, respectively (p<0.05 and p<0.01). RBC AChE activity was also inhibited in high-dose
male and female (GD 22) fetuses by 28% (p<0.5) [p<0.05] and 21% (n.s.), respectively. There
were no treatment-related effects on RBC AChE activity in male or female pups. The LOAEL for
dichlorvos erythrocyte acetylcholinesterase inhibition in maternal rats is 1.0 mg/kg bw/day, with a
NOAEL of 0.1 mg/kg bw/day. The LOAEL for erythrocyte acetylcholinesterase inhibition in
offspring or fetuses is 7.5 mg/kg bw/day (based on male and female fetuses on GD 22), and the
NOAEL is 1.0 mg/kg bw/day.
In maternal animals, whole brain AChE activity was biologically significantly inhibited in high-
dose animals on GD 22 and LD 22 by 59% and 67%, respectively (p<0.01). Brain AChE activity
was also inhibited in high-dose male and female (GD 22) fetuses by 16% (p<0.5) [p<0.05] and
21%, respectively (p<0.01). There were no treatment-related effects on brain AChE activity in
male or female pups. The LOAEL for brain acetylcholinesterase inhibition in maternal animals is
7.5 mg/kg bw/day, with a NOAEL of 1.0 mg/kg bw/day. The LOAEL for brain
acetylcholinesterase inhibition in offspring or fetuses is 7.5 mg/kg bw/day (based on male and
female fetuses on GD 22), and the NOAEL is 1.0 mg/kg bw/day.
Based on the results of this study, dose levels of 0, 0.1, 1.0, and 7.5 mg/kg bw/day were chosen for
the main study.
Page 204 of 338
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CITATION: Milburn, G.M.. (2003) Dichlorvos: time course of cholinesterase inhibition in
pre-weaning and adult rats. Central Toxicology Laboratory, Cheshire, UK
SK10 4TJ. Doc. No. CTL/AR7310/Regulatory/Report. 26-SEPT-2003. MRID
46153303. Unpublished.
Twomey, K. (2002) Dichlorvos (DDVP): Acute cholinesterase inhibition study in
rats. Central Toxicology Laboratory, Cheshire, UK SK104T3. Laboratory
report number CTL/AR7079/SUM/Regulatory/Report; Study No. AR7079, 30-
MAY-2002. MRID 45805701. Unpublished.
Twomey, K. (2002) Dichlorvos (DDVP): Second acute cholinesterase inhibition
study in rats. Central Toxicology Laboratory, Cheshire, UK SK104TJ.
Laboratory report number CTL/AR7126/SUM/Regulatory/Report; Study No.
AR7126, 19-JUNE-2002. MRID 45805702. Unpublished.
Twomey, K. (2002) Dichlorvos (DDVP): Third acute cholinesterase inhibition
study in rats. Central Toxicology Laboratory, Alderley Park, Macclesfield,
Cheshire, UK SK104TJ. Laboratory report number
CTL/AR7138/Regulatory/Report; Study No. AR7138, 26-JUNE-2002. MRID
45805703. Unpublished.
Moxon, M.E. (2002) Dichlorvos: Acute cholinesterase inhibition study in pre-
weaning rats. Central Toxicology Laboratory, Cheshire, UK SK104T3.
Laboratory report number CTL/AR7147/Regulatory/Report; Study No.
AR7147, 22-NOV-2002. MRID 45842301. Unpublished.
Moxon, M.E. (2003) Dichlorvos: Repeat dose cholinesterase inhibition study in
pre-weaning and young adult rats. Central Toxicology Laboratory, Cheshire,
UK SK104TJ. Laboratory report number CTL/KR1490/Regulatory/Report;
Study No. KR1490, 24-OCT-2002. MRID 46153304. Unpublished.
SPONSOR: AMVAC, Los Angeles, CA
EXECUTIVE SUMMARY: In a series of special comparative cholinesterase inhibition (ChEI)
studies, Dichlorvos (DDVP; 99% a.L, lot #ST 120700) was administered by gavage to groups of
either Sprague-Dawley or Wistar rats. For time-course evaluation (MRID 46153303) 5
females/group were given a single oral dose of 0 or 15 mg/kg on PND 15 or 42 and sacrificed 1,3,
8, 24, or 72 hours later. In three acute studies (MRIDs 45805701, 45805702, 45805703) groups of
5 adult rats/sex were given a single oral dose of 0, 1, 5, 15, or 35 mg/kg and sacrificed one hour
post-dosing or on post-dosing days 8 and 15. In a fourth acute study, groups of 5 pre-weaning
rats/sex were given a single oral dose of 0, 1, 5, or 15 mg/kg on PND 8, 15, or 22 and terminated
one hour post-dosing. Finally repeated administration was studied by giving seven daily doses of 0,
0.1, 7.5, or 15 mg/kg/day to groups of 5 rats/sex beginning on either PND 12 or 42; animals were
Page 205 of 338
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sacrificed one hour after the last dose. RBC and brain ChE activities were measured in all animals
in each study. Plasma enzyme activity was not measured in any study.
Based on the analytical data for MRID 45805701, the low-dose animals were actually dosed with
2. 1 mg/kg, rather than the desired dose of 1 .0 mg/kg/day. For the remaining studies, the analytical
data indicated that the mixing procedure was adequate and that the difference between nominal and
actual dosage to the study animals was acceptable for all studies.
At a single dose of 35 mg/kg, one female died with cholinergic signs and four males were killed for
humane reasons due to severe toxicity. The remaining animals of both sexes given 35 mg/kg
displayed some or all of the following signs: decreased activity, lachrymation, miosis, irregular
breathing, clonic convulsions, tremors/fasciculations, prostration, decreased righting and splay
reflexes, and salivation. A single dose of 15 mg/kg resulted in miosis and fasciculations in one
adult female, and tremors in one male and one female on PND 8 and one female on PND 22. No
treatment related clinical signs were observed in animals of the 1 or 5 mg/kg dose groups following
acute exposure.
Following repeated exposure of pre-weaning rats, tremors were observed in 5/5 males and 5/5
females at 15 mg/kg/day on 3-5 days of the dosing interval. In young adult rats at 15 mg/kg/day,
tremors were observed in 3/5 males and 5/5 females on one to four days of the dosing interval. In
addition, tremors were seen in one adult male after the last dose of 7.5 mg/kg/day. No clinical signs
of toxicity were observed in the remaining groups.
Acute exposure to doses >5 mg/kg resulted in clear dose-related inhibition of enzyme activity in
both compartments in all groups. At 1 mg/kg, RBC enzyme activity was significantly inhibited in
PND 8 females, and PND 15 males and females, but not adults. Brain enzyme activity from
animals treated with 1 mg/kg was not significantly inhibited in adult or pre-weaning males and
females. Although there was inhibition of brain enzyme activity at the low dose in MRID
45805701, the actual analytical dose at this level was 2.1 mg/kg and not 1 mg/kg. Repeat of the 1
mg/kg dose level was identified as a NOAEL for brain enzyme inhibition as demonstrated in other
acute studies.
Two studies included recovery groups held for up to 15 days post-exposure. RBC enzyme activity
of males and females treated with 35 mg/kg remained slightly inhibited by 9-15% at 8 days after
exposure. This is not considered biologically significant. No inhibition of RBC enzyme activity
was seen at any other dose at 8 or 15 days post-dosing. Brain enzyme activity was not affected at
any dose during the recovery interval. Brain and RBC enzyme activities were maximally inhibited
one hour after dosing in both adult and pre-weaning female rats. Thereafter, ChE inhibition in both
compartments decreased to approximately control levels by 8 hours post-dosing.
Dose-related inhibition of RBC and brain ChE activities was also apparent after repeated dosing in
both adult and pre-weaning rats. Biologically significant inhibition of RBC enzyme activity
(>50%) occurred at doses of 7.5 and 15 mg/kg/day in both sexes of adults and pre-weaning and at
the low dose for adult animals (11-17%). Brain enzyme activity was statistically and biologically
inhibited in both sexes at doses of 7.5 and 15 mg/kg/day for adults (>50%) and at all doses for pups
Page 206 of 33 8
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For acute exposure:
the adult LOAEL for brain ChEI is 5 mg/kg for males and females
the adult NOAEL for brain ChEI is 1 mg/kg for males and females;
the offspring LOAEL for brain ChEI is 5 mg/kg (both sexes)
the offspring NOAEL for brain ChEI is 1 mg/kg (both sexes)
the adult LOAEL for red blood cell ChEI is 5 mg/kg (both sexes)
the adult NOAEL for red blood cell ChEI is 1 mg/kg (both sexes);
the offspring LOAEL for red blood cell ChEI is 1 mg/kg (both sexes)
the offspring NOAEL for red blood cell ChEI is not identified.
For acute exposure, the overall adult LOAEL for cholinesterase inhibition in rats is 5 mg/kg based
on enzyme inhibition in brain and red blood cells; the adult NOAEL is 1 mg/kg.
For acute exposure, the overall offspring LOAEL for cholinesterase inhibition in rats is 1 mg/kg
based on enzyme inhibition in red blood cells; the offspring NOAEL was not identified.
For repeated exposure:
the adult LOAEL for brain ChEI is 7.5 mg/kg/day (both sexes)
the adult NOAEL for brain ChEI is 0.1 mg/kg/day;
the offspring LOAEL for brain ChEI is 0.1 mg/kg/day (both sexes)
the offspring NOAEL for brain ChEI is not identified;
the adult LOAEL for red blood cell ChEI is 0.1 mg/kg/day (both sexes)
the adult NOAEL for red blood cell ChEI is not identified;
the offspring LOAEL for red blood cell ChEI is 7.5 mg/kg/day (both sexes)
the offspring NOAEL for red blood cell ChEI is 0.1 mg/kg/day;
For repeated exposure, the overall adult LOAEL for cholinesterase inhibition in rats is 0.1
mg/kg/day based on enzyme inhibition in red blood cells; the adult NOAEL is not identified.
For repeated exposure, the overall offspring LOAEL for cholinesterase inhibition in rats is 0.1
mg/kg/day based on enzyme inhibition in brain; the offspring NOAEL is not identified.
The cholinesterase activity measurements following an acute oral dose of dichlorvos demonstrate
approximately equal susceptibility between juvenile and adult rats. In contrast, results from
repeated exposures show that juvenile rats are more susceptible than adults for brain ChEI. In pups
the brain ChE activity appeared to be more sensitive than RBC enzyme activity. This susceptibility
for brain cholinesterase was observed in terms of the dose level at which an effect was observed
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(i.e., the LOAEL for brain cholinesterase inhibition was lower for juveniles than for adults).
However, the LOAEL for RBC enzyme inhibition was lower for adults than for juvenile rats. The
fact that brain enzyme activity in young animals was the most sensitive to inhibition by the test
article is of concern for potential developmental neurotoxicity.
Taken together these studies are classified Acceptable/Non-guideline for the determination of RBC
and brain cholinesterase activities following treatment with dichlorvos in adult and juvenile rats.
Main deficiencies include omission of plasma measurements and lack of assessment in dams and
fetuses on GD 20.
870.6100 (81-7) Acute Delayed Neurotoxicitv - Hen. MRID 41004702
CITATION: Beavers, J.; Driscoll, C.; Dukes, V.; et al. (1988) DDVP: An Acute Delayed
Neurotoxicity Study in Chickens: Final Report: Project No. 246-103.
Unpublished study prepared by Wildlife International Ltd. 86 p. (MRID
41004702
EXECUTIVE SUMMARY: In an acceptable acute delayed neurotoxicity study (MRID
41004702), groups often chickens were exposed either to vehicle (distilled water), DDVP at 16.5
mg/kg, or the positive control, Tri-o-tolyl Phosphate (TOCP), at 600 mg/kg in corn oil. All birds
treated with DDVP were administered an intramuscular injection of atropine sulfate at 5 mg/kg
concurrent with DDVP dosing (the oral LDso value of DDVP in chickens not administered atropine
is reported at 16.15 mg/kg); atropine also was administered at 2 mg/kg on an individual basis as
needed to DDVP-treated birds.
After 21 days, DDVP-treatment and vehicle control birds were redosed (with atropine
treatment as previously) and observed for an additional 21 days before sacrifice. TOCP-treated
birds were sacrificed 21 days after the initial dose.
During the first forced locomotor activity evaluation on day 3, two hens (G30 and G37)
of the DDVP-treated group displayed slight to moderate ataxia, and refused to walk or perform the
second walk. By day 7 (the second evaluation) hen G37 was noted as being slightly ataxic when
dropped, appeared normal during the hop, but refused to walk alone. This bird appeared normal
when standing or walking in a group, but refused to move when alone; this hen continued to refuse
to walk alone at each evaluation except for day 25. On days 36 and 39, the same hen also refused to
hop. However, when observed in a group, this bird did not appear ataxic, and appeared to move in
a normal manner.
On histopathological examination, bird G37 showed swelling of the axis cylinder and
nerve fiber degeneration in the sciatic nerve. Nerves from 5/10 positive control (TOCP-treated)
hens showed evidence of peripheral neuropathy, while those from 5/10 hens showed no significant
neural degenerative lesions; however, 3/5 of these hens had exhibited slight to moderate ataxia
during locomotor assessments. In summary, there were no brain or spinal cord degenerative
changes in any of the control, TOC, or DDVP-treated groups. However, there were sciatic nerve
degenerative changes in 0/10, 5/10, and 1/10 in the negative control, TOCP, and DDVP groups,
respectively.
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Although the authors considered the results equivocal, the findings have been interpreted
by HED as indicating a positive result for DDVP for acute delayed neurotoxicity.
870.3100 (82-1) 13-Week Gavage Study in Sprague-Dawlev Rats - MRID 41004701
CITATION: Kleeman, J. (1988) 13-Week Gavage Toxicity Study with DDVP in Rats: Final
Report: Project ID: HLA 6274-102. Unpublished study pre- pared by Hazleton
Laboratories America, Inc. 294 p. MRID 41004701.
EXECUTIVE SUMMARY: In an acceptable 13-week subchronic study (MRID 41004701),
Crl:CDR(SD)BR rats, 10/sex/group, were gavaged with 0, 0.1, 1.5 or 15 mg DDVP/kg/day, 5
days/week, "for at least 13 weeks." The following (Table 5) summarizes possible effects:
Table 5.
Effect
Reduced RBC count,
hemoglobin & hematocrit
Week 14
Higher Mean Corpuscular
Volume
Higher Cholesterol
Reduced Plasma ChE
Week?
Week 14
Reduced RBC ChE
Week?
Week 14
Reduced Brain ChE
(termination)
Controls
M
-
-
_
-
-
-
F
-
-
_
-
-
-
0.1 mg
DDVP/kg/day
M
-
-
_
-
-
-
F
-
-
_
-
-
-
1.5 mg
DDVP/kg/day
M
+
-
_
+
;
-
F
-
-
_
+
;
-
15 mg
DDVP/kg/day
M
+
-
+
*
I
+
F
+
+
_
*
I
+
In addition, salivation and/or urine stains were noted in some high-dose males and
females at approximately 30 to 60 minutes post-dosing. According to Table 12 (p. 52) of MRID
41004701, at terminal sacrifice 2/10 high-dose and 1/10 low-dose females (but no control females)
had generalized retinal atrophy. On page 79 "unilateral retinal degeneration" occurred in 1/9
control females, 1/10 in the low-dose group, 0/10 in the mid-dose, and 2/10 in the high-dose. Males
in the high-dose group had a noticeably (but not significantly) elevated mean liver weight at
termination (14.14 g vs. a control value of 12.46 g). However, the mean liver-to-body weight ratio
was significantly (p < 0.05) elevated (to a value of 0.0293 vs. a control value of 0.0267).
Page 209 of 338
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The following mean plasma and RBC cholinesterase measurements were obtained for
weeks 7 and 14:
Table 6.
Dosage
Level
(mg/kg/day)
0
0.1
1.5
15
Males (Week 7)
Plasma ChE
mu/mL
Mean (S.D.)
318(67.3)
285 (32.0)
226*(48.5)
112*(24.2)
RBC ChE
mu/mL
Mean (S.D.)
1195(163.1)
1166(244.3)
903*(138.0)
629*(109.3)
Females (Week 7)
Plasma ChE
mu/mL
Mean (S.D.)
813(326.2)
933(382.1)
692 (89.7)
338*(79.0)
RBC ChE
mu/mL
Mean (S.D.)
1269(246.9)
1148(125.9)
956*(145.8)
740*(95.4)
*Reported as statistically significant, with p < 0.05.
Data are from Tables 13 and 14, p. 53 and 54 of MRID 41004701.
Table 7.
Dosage
Level
(mg/kg/day)
0
0.1
1.5
15
Males (Week 14)
Plasma ChE
mu/mL
Mean (S.D.)
314(56.7)
282 (59.9)
259 (69.9)
204*(45.1)
RBC ChE
mu/mL
Mean (S.D.)
1358(145.5)
1247(113.9)
101 4* (62. 6)
787*(103.6)
Females (Week 14)
Plasma ChE
mu/mL
Mean (S.D.)
1091 (462.0)
1150(485.2)
1020(257.0)
575*(142.2)
RBC ChE
mu/mL
Mean (S.D.)
1321 (82.3)
1212*(81.4)
1002*(81.5)
874*(86.8)
*Reported as statistically significant, with p < 0.05.
Data are from Tables 13 and 14, p. 53 and 54 of MRID 41004701.
According to MRID 41004701 (p. 29): "The apparent decrease of inhibitory effect at
week 14 [as compared to week 7] may have been due to a longer post-treatment interval before
blood collection and partial recovery of cholinesterase activity."
The following mean brain cholinesterase measurements were obtained at termination:
Table 8.
T
T
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Dosage
Level
(mg/kg/day)
0
0.1
1.5
15
Males
Brain ChE
mu/mL
Mean (S.D.)
1105(376.6)
1213(656.4)
1060(183.2)
791*(290.0)
Females
Brain ChE
mu/mL
Mean (S.D.)
1338(490.0)
1290(376.2)
1290(336.5)
680*(216.6)
*Reported as statistically significant, with p < 0.05.
In the review [HED Doc. No. 007448] it is stated that: "The data presented demonstrate
that administration of DDVP at doses of 0, 0.1, 1.5 and 15 mg/kg[/day] resulted in no adverse effect
on body weight or food consumption. Although hematology parameters were reduced, it is doubtful
whether the reductions were biologically significant, because the reductions were within ten percent
of control values. Plasma and RBC cholinesterase activity [sic] were reduced in mid and high dose
animals, and RBC cholinesterase activity was reduced in 0.1 mg/kg[/day] females at 14 weeks.
However, the investigators did not consider the RBC cholinesterase reduction in low dose females
to be biologically significant since it was less than ten percent below control. The reduction of brain
cholinesterase activity in high dose male and female rats at study termination was biologically
significant."
"No other changes were seen in the test animals which could be attributed to
administration of the test compound. The increased liver/body [weight] ratio seen in high dose
males was not accompanied by any body weight or enzyme changes."
The data presented support a LOAEL of 1.5 mg/kg[/day] based on cholinesterase
inhibition (plasma and RBC in females and RBC in males). The NOAEL is 0.1 mg/kg[/day]. A
NOAEL of 1.5 mg/kg/day may be defined based on decreased brain cholinesterase activity in both
sexes.
870.6100 (82-5) Subchronic Neurotoxicitv Study in Hens - MRID 43433501
CITATION: Redgrave, V. (1994) DDVP: 28-Day Neurotoxicity in the Domestic Hen: Lab
Project Number: AVC 1/921405: RAD 2/942053. Unpublished study prepared
by Huntingdon Research Centre, Ltd. 465 p. MRID 43433501.
EXECUTIVE SUMMARY: Groups of 21 adult domestic hens were given oral daily doses by
gavage of 0, 0.3, 1.0, or 3.0 mg DDVP/kg in distilled water. Fourteen birds from each group were
treated for 28 days; an interim sacrifice of 6 birds/group was performed on day 49 and the final
sacrifice of 6 birds/ group was performed on day 77. Satellite groups of three birds from each
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original group of 21 were sacrificed on day 4 and day 30 for brain cholinesterase and brain and
spinal cord neurotoxic esterase activity. An additional group of four birds was administered 0.1 mg
DDVP/kg for 28 days for cholinesterase determination only. A positive control group of 21 hens
was administered 7.5 mg TOCP/kg, and sacrificed as described above.
Mortality occurred in 1 bird in the 1.0 mg/kg dose group and in 4 birds in the 3.0 mg/kg
dose group. Subdued behavior, unsteadiness, and vomiting were observed in the 3.0 mg/kg group
shortly after dosing from day 4 to day 29. Clinical signs were also observed in 2 birds after dosing
with 1.0 mg/kg on days 2 and 14. No delayed motor ataxia was observes, and there was no clear
evidence of organophosphate induced delayed neuropathy. Decreased body weight was observed
during the first 14 days of dosing at 1.0 and 3.0 mg/kg, but compensatory increases occurred from
day 14 onward. Brain cholinesterase activity was decreased at day 4 in the 1.0 mg/kg and 3.0
mg/kg dose groups (44% and 63% decrease, respectively, compared to controls); and, at day 30,
brain cholinesterase was dose-dependently decreased by 26%, 34%, and 54% in the 0.3, 1.0, and
3.0 mg/kg dose groups, respectively. A slight increase in minimal axonal degeneration was
observed at 1.0 and 3.0 mg/kg. The positive control responded appropriately.
A LOAEL of 0.3 mg/kg can be defined based on decreased brain cholinesterase activity. The
NOAEL is 0.1 mg/kg/day. ANOAEL of 0.3 mg/kg is defined based on axonal degeneration of
more than one level of the spinal cord at 1.0 mg/kg and above of DDVP.
This study meets the guideline requirements of 82-5 and is classified as Acceptable.
870.3200 (83-2a) Two Year Gavage Study in F344 Rats. NTP TR 342, MRID 40299401
CITATION: Chan, P. (1987) NTP Technical Report on the Toxicology and Carcinogenesis
Studies of Dichlorvos (CAS No. 62-73-7) in F344/N Rats and B63F1 Mice:
(Gavage Studies): NTP TR 342. Draft Technical Report of July, 1987 prepared
for public review and comment. US Dept. of Health and Human Services,
Public Health Service, Publication No. NIH 88-2598. 239 p. MRID 40299401.
EXECUTIVE SUMMARY: In an oncogenicity gavage study (MRID 40299401), 4 or 8
mg/kg/day dichlorvos (DDVP) (97.8-98.2% a.L, lot SDC-092179, batch 01) in corn oil (Mazola®
"100% pure") was administered as 5 mL/kg to 60 F344 rats/sex/dose 5 days/week for 103 weeks
followed by a one-week observation period. The controls received corn oil only. Five rats/sex/dose
were used only for plasma and RBC cholinesterase (ChE) determination after 6, 12, 24, 36, 52, 78,
and 104 weeks and 5 rats/sex/dose were used for brain and sciatic nerve histology at study
termination. The doses employed were based on results of a 13-week subchronic study where 10
rats/sex/dose were given 0, 2, 4, 8, 16, 32, or 64 mg/kg/day DDVP. All rats given 32 or 64
mg/kg/day and some rats given 16 mg/kg/day had tremors, diarrhea, and convulsions and died
during the study, whereas the surviving rats had no clinical signs or weight loss.
Mortality and weekly body weight gains were similar in treated and control animals. Clinical signs
among treated males included brown fur around the nose, mouth, and anal areas, leaning head, and
diarrhea, and among treated females included vaginal discharge, wet fur in peri-anal or pelvic area,
and diarrhea. From 6-78 weeks, plasma ChE levels in the 4 and 8 mg/kg/day treated groups were
lower than the respective control levels by 52-72% and 53-72% in males and by 75-85% and 82-
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88% in females, respectively. At 104 weeks, plasma ChE among treated groups of both sexes were
only 4-18% below controls, perhaps due to the intervening week without treatment. RBC ChE
levels were more variable: values were decreased (13-65%) in both dose group females for weeks
6-78 and in the high-dose males (17-90%) for weeks 24-104, but in the low-dose males were
decreased (34-49%) only for weeks 36-78. Treatment time did not appear to be directly related to
ChE inhibition. No gross lesions were found in the control or treated animals. The incidences of
hepatic cytoplasmic vacuolation, renal tubule mineralization, and adrenal cortical vacuolation were
increased in high-dose males and of pancreatic (acinar) atrophy were increased in high-dose
females (p < 0.05); it was unclear whether these effects were treatment-related. Results of the brain
and sciatic nerve histology examinations were not given.
Under the conditions of this study, 4 mg/kg/day was identified as the LOAEL for both sexes of rats
based on decreased RBC and plasma ChE levels. A NOAEL was not identified.
Treatment-related neoplastic lesions were seen in both sexes of rats. Males had an increased
incidence (p < 0.05) of lung adenoma (8 mg/kg/day), mononuclear cell leukemia (both doses), and
pancreatic acinar adenoma (both doses). Females had an increased incidence of mammary gland
fibroadenoma (p < 0.05 for both doses); an additional high-dose female had mammary gland
fibroma.
This study was classified as "supplementary for chronic study; minimum for oncogenicity" when
the Data Evaluation Report was originally prepared (1987). Although this study did not follow the
"Subdivision F" guidelines for chronic toxicity, the most sensitive end-point for toxicity, namely
ChE inhibition, was measured and used as a basis for NOAEL. Therefore, this study should be
valid for performing risk assessment.
870.3200 (83-2b) Two Year Gavage Study in B6C3F1 Mice. NTP TR 342. MRID 40299401
CITATION: Chan, P. (1987) NTP Technical Report on the Toxicology and Carcinogenesis
Studies of Dichlorvos (CAS No. 62-73-7) in F344/N Rats and B63F1 Mice:
(Gavage Studies): NTP TR 342. Draft Technical Report of July, 1987 prepared
for public review and comment. US Dept. of Health and Human Services,
Public Health Service, Publication No. NIH 88-2598. 239 p. MRID 40299401
EXECUTIVE SUMMARY: In an oncogenicity gavage study (MRID 40299401), dichlorvos
(DDVP) (97.8-98.2% a.L, Lot SDC-092179, batch 01) in corn oil (Mazola® "100% pure") was
administered to 60 B6C3F1 mice/sex/dose 5 days/week for 103 weeks followed by a one-week
observation period. Males were given 10 or 20 mg/kg/day DDVP, females 20 or 40 mg/kg/day
DDVP, and controls corn oil only; the dosing volume was 10 mL/kg. Five mice/sex dose were used
only for plasma and RBC cholinesterase (ChE) determination after 6, 12, 24, 36, 52, 78, and 104
weeks and 5 mice/sex/dose were used for brain and sciatic nerve histology at study termination.
The doses employed were based on results of a 13-week study where 10 mice/sex/dose were given
0, 5, 10, 20, 40, 80, or 160 mg/kg/day DDVP; all males and 9 females given 160 mg/kg/day died
during the study. The survivors had no dose-related body weight changes, toxic signs, or
significant pathology.
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No treatment-related mortality or body weight changes were observed, however, all male mice used
for ChE determination died when blood was withdrawn at 24 weeks. Reported clinical signs
consisted of a slight increase of left pelvic masses in high dose males and of distended abdomens in
treated females. Plasma ChE levels in males were 54-62% and 69-76% lower than controls at 10
and 20 mg/kg/day, respectively, from 6-24 weeks (death of mice precluded further analysis).
Plasma ChE levels in females were 64-73% and 79-90% lower than controls at 20 and 40
mg/kg/day, respectively from weeks 6-78, but were similar to or higher than controls at week 104,
perhaps due to the intervening week without treatment. RBC ChE levels were more variable: levels
were decreased (26-46%) at week 24 in both sexes and by 11-33% at weeks 36, 52, and 104 in
females, but were similar to or greater than controls at weeks 6 and 12 (both sexes, both doses) and
78 (females, both doses). Treatment time did not appear to be directly related to ChE inhibition.
No treatment-related gross or microscopic lesions were found and no lesions were seen in the
animals used to investigate brain and sciatic nerve histology.
Under the conditions of this study, a LOAEL of 10 mg/kg/day was identified based on the
decreased RBC and plasma ChE levels in males. A NOAEL was not identified.
The incidence of forestomach squamous cell papilloma was increased in high dose males (5/50 vs.
1/50 for controls, p = 0.06) and females (18/50 vs. 5/50 for controls, p < 0.05); forestomach
carcinoma also occurred in 2/50 high-dose females. Three high-dose males each had one unusual
neoplasm: glandular stomach carcinoid/carcinoma, duodenal adenocarcinoma, or a duodenal
adenomatous polyp.
This oncogenicity study was classified as "core-minimum" when the Data Evaluation Report was
originally prepared (1987).
870.4200 (83-2) 80-Week Feeding/Carcinogenicitv study in Rats - TXR007765, NCI, 1977
EXECUTIVE SUMMARY: In an 80-week feeding/carcinogenicity study (NCI, 1977), groups of
fifty 36-43 day old Osborne-Mendel rats/sex were administered DDVP (94%) at dose levels (time-
weighted average) of 150 or 326 ppm (7.5 and 16.3 mg/kg/day by standard convention methods).
The dosage for the high-dose group was 1000 ppm (50 mg/kg/day) for the first 3 weeks and was
then changed to 300 ppm (15 mg/kg/day) for the remaining 77 weeks due to toxicity. A matched
control group of 10 rats/sex was included. The pooled control group consisted of 60 male and 60
female rats. All animals were observed twice daily for signs of toxicity, weighed at regular
intervals, and palpated for masses at each weighing. Gross and microscopic examination of all
major tissues, organs and gross lesions were made from sacrificed animals, and where feasible,
from animals found dead. Rats were sacrificed at 110-111 weeks.
Severe signs of toxicity including tremors, rough hair coat, diarrhea and poor appearance were
observed in the 1000 ppm DDVP group during the first 3 weeks. All groups showed slight or
moderate degrees of toxicity during the first year. Treated animals showed an increased frequency
of toxic signs during the second year consisting of rough hair coats, epistaxis, hematuria, alopecia,
dark urine, bloating and abdominal distension. No compound-related mortality was reported.
Survival was 64% and 76% in males in the low- and high-dose groups, respectively, for over 105
weeks. Survival was 80% and 84% in females in the low- and high-dose groups, respectively, for
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over 105 weeks. During the first year and a half, body weights of male and female rats in the high-
dose group were consistently lower than the low-dose and matched control groups. Thyroid
follicular hyperplasia was increased in males in the low-dose group (7%) and high-dose group
(10%) when compared to controls (0%). The incidence of alveolar macrophages was increased in
treated males (14-28%) and treated females (42-44%) when compared to controls (0-10%). The
incidence of interstitial fibrosis of the myocardium was increased in treated males (24-32%) and
treated females (30-38%) when compared to controls (10%). Malignant fibrous histiocytoma was
increased in male rats in the low-dose group (8%) and high-dose group (16%) when compared to
pooled controls (3%, linear trend p=0.018). This neoplasm occurred in 10% of the matched
controls. Under the conditions of the study, DDVP was not demonstrated to be carcinogenic in rats.
The study is Unacceptable-Guideline and does not satisfy the guideline requirement (series 83-2)
for a carcinogenicity study in rats. Too few animals (10/sex) were used as matched controls and
only 2 dose levels were employed.
870.4200 (83-2) 94-Week Feeding/Carcinogenicitv Study in B^C^ Mice - TXR 007765, NCL
1977
EXECUTIVE SUMMARY: In a 94-week feeding/carcinogenicity study (NCI, 1977), groups of
fifty BeCsFi mice/sex, 35-36 days of age, were administered DDVP (94%) at dose levels (time-
weighted average) of 318 or 635 ppm (47.7 and 95.3 mg/kg/day by standard convention methods).
The dosage levels for the low- and high-dose mice were 1000 and 2000 ppm (150 and 300
mg/kg/day) for the first 2 weeks, then reduced to 300 and 600 ppm (45 and 90 mg/kg/day) for the
remaining 78 weeks. A matched control group of 10 mice/sex was included. The pooled control
group consisted of 100 males and 80 females. All animals were examined twice daily for signs of
toxicity, weighed at regular intervals, and palpated for masses at each weighing. Gross and
microscopic examination of all major tissues, organs and gross lesions were made from sacrificed
animals and, where feasible, from animals found dead. The mice were sacrificed at 92-94 weeks.
Initially, mice fed DDVP exhibited severe signs of toxicity: tremors, rough coat, diarrhea and poor
general appearance. After doses were reduced, the behavior and appearance of treated mice were
comparable to controls. Survival was 92% and 90% in males in the low- and high-dose groups,
respectively. Survival was 74% and 84% in females in the low- and high-dose groups, respectively.
The body weight of male and female mice in the high-dose group was generally lower after the
initial growth phase than the low-dose and control groups. Two squamous-cell carcinomas of the
esophageal epithelium occurred, 1 in a low-dose male and 1 in a high-dose female. Two low-dose
males had focal hyperplasia of the esophageal epithelium. And one high-dose female had a
papilloma of the esophageal epithelium. There was insufficient information to establish the
association of esophageal tumors with DDVP treatment. Under the conditions of the study, DDVP
was not demonstrated to be carcinogenic in mice.
The study is Unacceptable-Guideline and does not satisfy the guideline requirement (series 83-2)
for a carcinogenicity study in mice. Too few animals (10/sex) were used as matched controls and
only two dose levels were employed.
870.4100 (83-lb) 52-Week Chronic Oral Toxicitv Study in Dogs. MRID 41593101
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CITATION: Markiewicz, V. (1990) A 52-Week Chronic Toxicity Study on DDVP in Dogs:
Lab Project Number: 2534/102. Unpublished study prepared by Hazleton
Laboratories America, Inc. 431 p. MRID 41593101
EXECUTIVE SUMMARY: In a chronic oral toxicity study (MRID 41593101), dichlorvos
(DDVP) (purity not given but was 97.3% in the preceding range finding study; Lot No. 802097)
was administered to 4 beagle dogs/sex/dose by capsule for 52 weeks at doses of 0, 0.1, 1.0, or 3.0
mg/kg/day. Due to excessive plasma cholinesterase inhibition at week 2, the low dose was changed
from 0.1 to 0.05 mg/kg/day in both sexes on treatment day 22 to achieve a NOAEL.
No dogs died during the study. Clinical signs included ataxia, salivation, and dyspnea in one high-
dose male on one day during week 33 and emesis in three high-dose females and one male and/or
female at most other doses. Cumulative body weight gains were lower than that of controls only in
the high-dose males, from approximately weeks 1-8. No treatment-related effects were noted on
the food consumption, ophthalmoscopic examination, hematology, urinalysis, gross or microscopic
pathology, organ weights, or clinical chemistry except for cholinesterase (ChE) measurements.
After 2 weeks of treatment, plasma ChE levels were 21-26% lower than pretreatment values for
both sexes given 0.1 mg/kg/day DDVP, prompting the dose decrease to 0.05 mg/kg/day on day 22.
At subsequent test weeks (6, 13, 26, 39, and 52), plasma ChE levels in the low-dose group were
within 12% of pretreatment values. Plasma ChE levels of dogs given 1.0 and 3.0 mg/kg/day DDVP
were decreased 39-59% and 61-74%, respectively, throughout the study in both sexes. RBC ChE
levels were decreased in low-dose dogs at week 6 (24% in males and 50% in females), likely due to
effects of the earlier higher dose of 0.1 mg/kg/day, but were within 13% of pretreatment values at
all other time points. At 1.0 or 3.0 mg/kg/day DDVP, RBC ChE levels in both sexes were lowered
33-65% and 67-94%, respectively, throughout the study. The % inhibition of neither plasma nor
RBC ChE appeared to change with time. Brain ChE measurements taken at termination were
comparable to concurrent controls for the low dose groups but were decreased at both 1.0
mg/kg/day (22%, p < 0.05 in males; 7%, N.S. in females) and 3.0 mg/ kg/day (47% in males and
29% in females, p < 0.05 for both).
Under the conditions of this study, the NOAEL was identified as 0.05 mg/kg/day for both sexes.
The LOEL was 1.0 mg/kg/day, based on the inhibition of plasma and RBC ChE levels in both sexes
and the inhibition of brain ChE in males. It should be noted that the actual LOAEL could be as low
as 0.1 mg/kg/day since plasma ChE was decreased by nearly 25% after the initial administration of
this dose to the low-dose group during the first two weeks.
This study was classified as acceptable (guideline) for satisfying the guideline requirement for a
chronic oral toxicity study (83-lb) in dogs.
870.3700 (83-3a) Developmental Oral Toxicitv Study in SD Rats.
CITATION: Tyl, R.; Marr, M.; Myers, C. (1991) Developmental Toxicity Evaluation of
DDVP Administered by Gavage to CD (Sprague-Dawley) Rats: Lab Project
Number: 60C-4629-10/20. Unpublished study prepared by Research Triangle
Inst. 305 p. MRID 41951501
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EXECUTIVE SUMMARY: In a developmental toxicity study (MRID 41951501), 25 pregnant
Sprague-Dawley rats per group were administered Dichlorvos (96.86% a.L; Lot No. 802097) by
gavage at doses of 0, 0.1, 3.0, or 21.0 mg/kg/day on gestation days (GD) 6-15, inclusive. On GD
20, all dams were sacrificed and all fetuses were examined for external anomalies. Approximately
one-half of all fetuses were examined for visceral anomalies and the remainder stained and
examined for skeletal anomalies.
All animals survived until scheduled sacrifice. There was no evidence of maternal toxicity at 0.1 or
3.0 mg/kg/day. At the high dose, clinical signs of toxicity were indicative of cholinesterase
inhibition. All high-dose dams exhibited tremors at some time during the dosing period. Other
anticholinesterase-related signs of toxicity included prone positioning, hindlimb splay, circling,
vocalization, excitability, hypoactivity, and labored respiration among others.
Absolute maternal body weights of the high-dose dams were significantly (4-6%; p < 0.05) lower
than the controls on GD 9, 12, and 15 and body weight gains during the dosing period were
significantly (p < 0.01) decreased by 28%. Food consumption and food efficiency of high-dose
dams were significantly (p < 0.01) less than the controls during the dosing interval and overall (GD
0-20).
Therefore, the maternal toxicity LOAEL is 21 mg/kg/day based on clinical signs of toxicity,
reduced body weight gain, and food consumption and efficiency. The maternal toxicity NOAEL is
3 mg/kg/day.
No treatment-related effects were observed for gravid uterine weights, number of fetuses/litter, pre-
and post-implantation loss, numbers of corpora lutea/dam, number of implantations/dam,
resorptions/dam, fetal body weights, or fetal sex ratios. There were no developmental
malformations/variations in any fetus that were attributed to treatment.
Therefore, the developmental toxicity NOAEL is >21 mg/kg/day and the developmental toxicity
LOAEL was not identified.
This study is classified as Acceptable (guideline) and satisfies the guideline requirements for a
developmental toxicity study (83-3a) in rats.
870.3700 (83-3b) Developmental Oral Toxicitv Study in New Zealand Rabbits.
CITATION: Tyl, R.; Marr, M.; Myers, C. (1991) Development Toxicity Evaluation of DDVP
Administered by Gavage to New Zealand White Rabbits: Lab Project Number:
60C-4629-30/40. Unpublished study prepared by Research Triangle Institute.
247 p. MRID No. 41802401
EXECUTIVE SUMMARY: In a developmental (teratology) toxicity study (MRID 41802401), 16
pregnant New Zealand rabbits per group were administered Dichlorvos (97% purity; Lot No.
802097) by gavage at doses 0, 0.1, 2.5, or 7.0 mg/kg/day on gestation days (GD) 7-19. (Dose
selection was based on a range-finding study in which maternal toxicity, including increased
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mortality (5/8 died), decreased weight gain, and clinical signs, were manifested at the highest tested
dose of 10 mg/kg/day.) At study termination (GD 30), the number of does with live fetuses was 14,
12, 11, and 9 in each of the control, 0.1, 2.5, and 7.0 mg/kg/day group, respectively. On GD 30, all
surviving dams were euthanized and all fetuses were weighed and examined for external, skeletal,
and visceral anomalies.
Maternal toxicity (dose-dependent) was evident in the form of dose-dependent increased mortality
(four and two died in the high and mid-dose groups, respectively), decreased mean body weight
gain and typical anticholinesterase-related clinical observations. Mean body weight gain during the
dosing period (GD 7-19) was 67% and 58% below control in the mid and high dose groups,
respectively. Mean body weight gain during the entire gestation period (corrected for gravid uterine
weight) was variable where, compared to the control group, it was higher in the low and mid dose
groups (by 140% and 45%, respectively) and lower (54%, p<0.05) in the high dose group. There
were no abortions but two does in the low-dose group had premature deliveries (GD 23 and 30).
Therefore, based on mortality, and other effects, the maternal toxicity LOAEL is 7.0 mg/kg/day; the
maternal toxicity NOAEL is 2.5 mg/kg/day.
There were no statistically significant treatment-related differences in the number (per doe) of
corpora lutea, implantations, live fetuses, resorptions, or dead fetuses. Though not indicated to be
significantly different than the control group, the low-dose group had fewer implantations/doe (4.9
± 0.8 vs. 7.0 ± 0.8) and fewer live fetuses/doe (4.8 ± 0.8 vs. 6.5 ± 0.8). There were no apparent
developmental malformations or variations that could be attributed to treatment.
Therefore, the developmental toxicity NOAEL is >7 mg/kg/day and the developmental toxicity
LOAEL was not identified.
This study was classified as Core Minimum where all criteria were satisfied except for the
minimum number (12) of available does/group which, due to mortality in the mid and high dose
groups, were 11 and 9, respectively. The reviewer of this study also indicated that individual data
on corpora lutea were not submitted.
870.3800 (83-4) Two-Generation Reproduction Study in SD Rats. MRID No. 42483901
CITATION: Tyl, R.; Myers, C.; Marr, M. (1992) Two-Generation Reproductive Toxicity
Study of DDVP Administered in Drinking Water to CD (Sprague-Dawley)
Rats: Final Report: Lab Project Number 60C-4629-170. Unpublished study
prepared by Research Triangle Institute. 1225 p. MRID No. 42483901
EXECUTIVE SUMMARY: In a 2-generation reproduction study (MRID 42483901) DDVP
(96.86%) was administered to 30 CD (Sprague-Dawley) rats/sex/dose in their drinking water at
concentrations of 0, 5, 20 and 80 ppm. Equivalent dosages were the following:
Table 10.
Water
Cone.
FO&F1 c?
(ug/kg/day)
FO&F1 ?
prebreeding
FO&F1 $
gestation
FO&F1 $
lactation
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(ppm)
5.0
20.0
80.0
476-500
1923-1952
6897-7528
(ug/kg/day)
650-660
2432-2673
9370-9472
(ug/kg/day)
564-590
2124-2420
7035-8150
(ug/kg/day)
930-1176
4280-4596
13238-17468
After at least 10 weeks of continuous exposure, rats were randomly mated within treatment
groups to produce the Fl generation; after mating the FO males were necropsied. Fl litters were
culled to 8 pups (4 $, 4 $ when possible) on post natal day 8 and weaned on day 21. Ten
weanlings/sex/dose were necropsied and 30 weanlings/sex/dose were selected as Fl parents with at
least 11-week prebreeding exposure to DDVP in their water. These rats were about 14-17 weeks old
when mated and their F2(a) litters were culled to 8 pups/litter on post natal day 8. At weaning, 10
F2(a) weanlings/sex/dose level were necropsied.
Due to poor reproductive performance (not treatment or dose-related), Fl females were
evaluated for vaginal estrus cyclicity and then rebred with untreated males to produce F2(b) litters
which were culled on PND 8 (8 pups/litter) and necropsied (10/sex/dose) after weaning.
Systemic toxicity: A NOAEL for cholinesterase inhibition in parental animals was not observed.
Cholinesterase levels were dose-dependently decreased in plasma (by 3.6 to 57.4%), erythrocytes (by
7.0 to 60.5%), and brain (by 1.1 to 60.3%) from FO and Fl animals and, overall, females were more
sensitive than males. No ChE measurements were done on the F2(a) or F2(b) progeny. Water
consumption was also reduced in the 80 ppm dosed animals.
Reproductive toxicity: No effects on reproductive parameters were observed in the FO mating,
although mean pup body weight in the 80 ppm group at weaning (day 21) was significantly lower
than controls (57.02 vs. 62.29 g). In the first mating of the Fl animals, incidences of pregnancies
were low (controls: 17/30; 5 ppm: 14/30; 20 ppm: 16/30; 80 ppm: 11/30). Mean pup body weight in
the 80 ppm group at weaning was noticeably (not significantly) lower than controls (52.22 vs. 57.43
g). As stated in the report conclusions: "Parental reproductive parameters were slightly affected in Fl
animals at 80 ppm, although these changes did not achieve statistical significance. Offspring survival
was also slightly reduced at 80 ppm, associated with accompanying maternal toxicity seen at this dose
level."
Results of the estrous cyclicity assessment showed that in the 80 ppm Fl group, there was a
statistically significant decrease in the percent of females cycling (63.3%, control 86.2%)
accompanied by increased abnormal cycling (68.4%, control 16%).
In the F2(b) mating, incidences of pregnancies were still relatively low (controls: 19/29; 5 ppm:
19/30; 20 ppm: 17/30; 80 ppm: 13/30); in terms of pregnancies/confirmed copulations incidences
were: controls: 19/25 (76%); 5 ppm: 19/27 (70.4%); 20 ppm: 17/27 (63%); 80 ppm: 13/26 (50%).
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The LOAEL for systemic toxicity [drinking water administration] is 5 ppm (488 ug/kg/day in males,
577 ug/kg/day in females), based on RBC and plasma cholinesterase inhibition. The NOAEL is <5
ppm (<488 ug/kg/day in males, <577 ug/kg/day in females).
The reproductive LOAEL [drinking water administration] is 80 ppm (7592 ug/kg/day) based on the
lack of cycling and abnormal cycling due to persistent or prolonged estrus. In addition, parental
reproductive parameters (decreased pregnancy and fertility, and decreased live litters and survival)
were slightly affected in Fl animals at 80 ppm, although these changes did not achieve statistical
significance. Offspring survival was also slightly reduced. The reproductive NOAEL is 20 ppm
(4438 ug/kg/day).
81-8ss Acute Oral Neurotoxicity Study in Rats.
CITATION: Lamb, I. (1993) An Acute Neurotoxicity Study of Dichlorvos in Rats: Final
Report (Text and Summary Data): Lab Project Number: WIL-188003.
Unpublished study prepared by WIL Research Labs., Inc. 984 p. MRID
42655301
EXECUTIVE SUMMARY: In an acute oral neurotoxicity study (MRID 42655301), a single
gavage dose of dichlorvos (97.8% a.L, lot #80209) was administered in deionized water to 12
Sprague-Dawley rats/sex/ group at 0, 0.5, 35, or 70 mg/kg. The animals were observed for up to 14
days. Functional Observational Battery (FOB) tests were done pretest and on study days 0 (15
minutes after compound administration), 7 and 14. Animals surviving to study termination were
sacrificed and perfused in situ for neurohistopathological evaluation. All animals were necropsied.
Two high-dose males and five high-dose females died within four hours of compound
administration. All other animals survived until study termination. No body weight effects were
observed. The FOB and motor activity effects (described below) of dichlorvos were most prevalent
10-20 minutes post-dosing and had essentially resolved by days 7 and 14. Statistically significant
(p<0.05) postural alterations, tremors, salivation, and changes in fur appearance and skin color were
observed in mid- and high-dose males and females. High-dose males exhibited an increased
incidence (p<0.05) of exophthalmus. Group mean time to first step was significantly (p<0.01)
increased in high-dose males (31.7 sec) and females (18.3 sec). Treatment-related (p<0.05)
decreased group mean rearing, impaired mobility, abnormal gait, and decreased arousal level were
also observed in mid- and high-dose males and females. Dose-related (p<0.05) alterations of touch,
tail pinch, pupil response and air righting reflex were observed in mid- and high-dose males and in
high-dose females. Dose-related decreased hindlimb resistance (mid- and high-dose, p<0.05), grip
strength (high-dose, p<0.01), and rotarod performance (mid- and high-dose, p<0.01) were observed
in male and female rats. Decreased (p<0.01) mean body temperature was observed in mid- and
high-dose males and females, and increased (p<0.01) group mean catalepsy values were observed in
high-dose animals of both sexes. No brain weight, brain dimension, or neurohistopathological
effects were observed.
Under the conditions of this study, the LOAEL for dichlorvos is 35 mg/kg and the NOAEL is 0.5
mg/kg based on changes in the FOB, decreased motor activity, and decreased body temperature.
This study is classified as acceptable (guideline) for an acute neurotoxicity study in rats (81-8ss).
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81-8ss Subchronic Oral Neurotoxicity Study in Rats.
CITATION: Lamb, I. (1993) A Subchronic (13 Week) Neurotoxicity Study of Dichlorvos in
Rats: Final Report: Lab Project Number: WIL-188004. Unpublished study
prepared by WIL Research Labs, Inc. 1199 p. MRID 42958101.
EXECUTIVE SUMMARY: In a Subchronic oral neurotoxicity study (MRID 42958101),
dichlorvos (97.87% a.L, lot No. 802097) was administered in deionized water to 15 Sprague-
Dawley rats/sex/group at gavage doses of 0, 0.1, 7.5, or 15.0 mg/kg/day for 90 days. Within each
dose group, 10 rats/sex were allocated for brain cholinesterase determination and 5 rats/sex were
allocated for neuropathology evaluation. Additionally, blood samples were collected for
cholinesterase measurements prestudy and on study weeks 3, 7, and 13. Five rats/sex/dose from the
cholinesterase group and 5/sex/dose from the neuropathology group were evaluated with the
Functional Observational Battery (FOB) and motor activity tests pretest and on study weeks 3, 7,
and 12. Body weight and food consumption were measured weekly.
There was no treatment-related mortality. Mean body weight in high-dose females was consistently
lower than the control (11-21%) throughout the study. No body weight effects were observed in
any other animals, and there was no treatment-related effect on food consumption. Tremors,
salivation, exophthalmos, lacrimation, and clear material on the forelimbs were observed in high-
dose males and females approximately 15 minutes post-dosing. Rales, chromodacryorrhea, and
red/yellow/orange material around the nose and mouth were also seen in high-dose rats. Tremors
were observed in three mid-dose males and nine mid-dose females. Generally, the clinical signs
occurred during the third week of treatment in the mid-dose animals, and as early as the first week
of dosing and throughout the study in the high-dose rats. Cholinesterase activity was decreased in
mid- and high-dose male and female rats as follows: plasma 30-58%; erythrocyte 8-35%; brainstem
and brain cortex 10-16%. There were no treatment-related effects in the FOB or motor activity
tests. No treatment-related neurohistopathological lesions and no apparent changes in brain weight
or size were observed.
Based on decreased cholinesterase activity and clinical cholinergic signs, the LOAEL for dichlorvos
is 7.50 mg/kg and the NOAEL is 0.1 mg/kg. This study is classified as acceptable (guideline) for a
Subchronic neurotoxicity study in rats (81-8ss).
g. Mutagenicity
Mutagenicity Studies with Positive Results
Several in vitro and in vivo mutagenicity studies were reviewed and presented to the Cancer Peer
Review Committee (CPRC) by Kerry Deerfield in a Memorandum entitled, "Review of the in vivo
mutagenicity studies concerning Dichlorvos" (dated August 10, 1988). Another review may be
found in the more recent Memorandum entitled, "Fifth carcinogenicity peer review of Dichlorvos"
by Jocelyn Stewart (dated August 28, 1996). Though lacking sufficient detail, these two reviews
provide some information about the types and variety of mutagenicity/ genotoxicity studies that
were considered by the Agency since DDVP has been registered.
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DDVP has been shown to be a direct acting mutagen by common in vitro bacterial genetic toxicity
assays. For instance, DDVP is mutagenic in the base-substitution Salmonella strain, TA100 as well
as in the E. coli WP2 mutation assay (Moriya et al, 1983). In this study, 238 pesticides including
DDVP were tested by the Ames plate incorporation method in five Salmonella strains (TA1535,
TA100, TA1537, TA1538, and TA98) as well as in E. Coli (WP2 her) both in the presence or
absence of an S-9 metabolizing system. DDVP (technical, unknown purity) was added (0.1 mL in
DMSO) at 0, 100, 500, 1,000, 5,000 or 10,000 jig/plate and all plates were incubated for two days
at 37°C prior to counting revertant colonies. In Salmonella TA100, DDVP gave rise to a dose-
dependent response from 100 to 5000 jig/plate with a maximum increased mutation of nearly 4.5-
fold over control in the absence of S-9 activation while complete toxicity was seen at the highest
dose tested. Addition of S-9 metabolizing system reduced the mutation frequency to a maximum of
nearly 2-fold (at 5000 jig/plate) over background. DDVP was also positive in E. coli WP2 her,
though no actual data were provided. The other tested strains failed to respond to DDVP in the
presence or absence of S-9 activation. Therefore, DDVP was shown to be a direct acting mutagen
in TA100 (and in E. coli WP2 her) where, compared to 44 other direct acting mutagens in the same
study, DDVP ranked 26 with a mutagenic potency of 0.027 revertants/nmole (most and least potent
were Captan in TA100 and ETU in TA1535 scoring 93.7 and 0.00065 revertants/nmole,
respectively) (Moriya et al., 1983).
A single dose of apparently 5000 |ig DDVP (>97% a.i.) in cultures of E. coli (B/r WP2 and WP2
her) and in S. typhimurium (TA1535 and TA1538) was tested with or without S-9 metabolic
activation. (According to HED doc. # 007765, p. 143, 0.1 mL of pesticide solution containing 22.6
jiM DDVP was used. However, the author of this document interprets this to mean that 22.6
(imoles, equaling 5000 jig, of DDVP in 0.1 mL solution was used; otherwise, the amount of DDVP
in 0.1 mL of the 22.6 jiM solution would be only 0.5 jig.) Water served as negative (solvent)
control. In the absence of S-9 activation, DDVP was positive in both the E. coli and TA1535
strains (10-30 fold increased revertants above background). S-9 metabolic activation abolished
DDVP's mutagenicity in TA1535 but not in E. coli (Moriya et al., 1978).
This study was considered acceptable despite using one dose only and no reporting of concurrent
control values (HED doc. # 007765).
Positive mutation findings were also reported in two E. coli WP2 strains (trp" and the plasmid-
containing CM881) in another study which only tested DDVP (a.i. not specified) at concentrations
from 0.1 |ig/mL (in the agar incorporation method) to 2000 |ig/mL (in the treat and plate method) in
the absence of S-9 metabolic activation. DDVP induced reversion by base substitution in both the
agar (5 |ig/mL agar) or the standard treat and plate method (2000 jig/mL) (Bridges, 1978).
This study was judged inconclusive as a comprehensive test of mutagenicity because it was not also
performed with mammalian metabolic activation (HED doc. # 007765).
An earlier study screened US. typhimurium histidine-requiring strains and seven E. coli
tryptophan-requiring strains by spot testing DDVP (% a.i. not specified) and 139 other
organophosphorus compounds by adding 5-10 jil of each chemical to each bacterial strain and
counting revertants compared to controls after 48 and 72 hr incubation at 37°C. Results were
represented qualitatively using +/- designation. DDVP was positive (+) in strains that were
designed to detect base-pair substitution mutagens (such as TA1530, TA1535, WP2, uvrA, and
Page 222 of 338
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WP67) but was negative (-) in strains that detect frame-shift mutagens (e.g., TA1536, TA1537, and
TA1538) (Hanna and Dyer, 1975). This study was judged acceptable without metabolic activation
but, overall, was considered inconclusive (HED doc. # 007765).
In addition, DDVP is a direct acting mutagen in some in vitro mammalian test systems. For
instance, in the forward mutation assay at the TK locus (L5178Y/TK+/") of cell cultured mouse
lymphoma cells, DDVP (technical, 97.5% a.L, Lot No. 11381-23-5) was tested in up to 20 doses
ranging from 0.0089 to 1.0 |il/mL, both in the presence or absence of metabolic activation.
Concurrent negative controls (DMSO) and positive controls were run using ethylmethanesulfonate
(EMS) for nonactivated and 7,12-dimethylbenz[a]anthracene (DMBA) for activated cultures. The
test article was completely cytotoxic (0% growth) at doses > 1 |il/mL and, therefore doses < 0.33
|il/mL were used to ascertain cloning and mutagenesis. In the absence of metabolic activation,
there was a dose-related (0.024- 0.33 jil/mL) increase in mutant frequencies of 2.3-13.3 times that
of DMSO control. Addition of metabolic activation seemed to diminish the mutation frequency
where at the two highest tested doses of 0.24 and 0.18 jil/mL the mutant frequency was 3.7 and 2.7
times DMSO, respectively. Similar results were seen when the test was repeated in a second series
of experiments with and without metabolic activation. Positive control chemicals elicited
appropriate responses where, relative to solvent control, mutant frequency was induced by 6.8 to
16.3x with EMS in nonactivated cultures and by 2.2 to 6.3x with DMBA in S-9 activated cultures
(Microbiological Associates, Inc., Study No.T-5211.702003, dated 10/14/86, Ace. No. 265524).
This study was considered acceptable (TXR # 005663).
Positive results were also described in another TK mouse lymphoma forward mutation assay where
DDVP (% a.i. not specified) was tested at seven concentrations ranging from 6.25-250 nl/mL in the
absence of metabolic activation only. No cells survived at the two highest doses of 200 and 250
nl/mL but at the dose 100 nL/mL the mutant frequency was 7.6x the solvent control (EtOH) while
the positive control (methylmethanesulfonate) responded appropriately yielding 5.4x the mutation
frequency of EtOH. A repeat test gave similar qualitative results. (Study performed by Litton
Bionetics under contract to NTP/NIEHS, report dated 8/27/85, Ace. No. 259463).
Despite the apparent direct acting mutagenicity results by DDVP, this study was considered
inconclusive as a "comprehensive mutagenicity test in this system" because no S-9 metabolic
activation was done (TXR # 004376).
DDVP seems to also have clastogenic activity by inducing chromosomal aberrations (AB), sister
chromatid exchanges (SCE), and polyploidy in cultured Chinese hamster ovary (CHO) cells
(Tezuka et al, 1980). To 3xl05 pre-cultured CHO cells, DDVP (a.i. > 98%) in DMSO (final
concentration of solvent in culture was kept to 1%) was added at a final DDVP concentration of 0,
1x10"4,2xlO"4, 5xlO"4, and IxlO"3 M. After adding 5-bromomodeoxyuridine to a final concentration
of 2 jiM, each culture was incubated for 26.5 hr in the dark. All doses were run in duplicate using
established procedures, where 50 and 100 metaphases were generally used for scoring and detecting
SCEs and ABs, respectively, at each concentration. There was a statistically significant (<0.001)
dose-dependent increase in the mean number of SCE/cell with a maximum increase over control of
nearly 5-fold at the 5xlO"4M concentration (no data was available at the highest dose tested and no
explanation given). Chromosomal aberrations also were induced (p<0.001) at the 5xlO"4M DDVP
concentration where, of 100 scored cells, AB were found in 34 cells compared to 9/200 for control
and 4/100 for each of the two lowest DDVP doses (no data and no explanation were available for
Page 223 of 338
-------
the highest dose tested). There were no cells with 10 or more AB per cell. Increased polyploidy
was also observed at the three lowest DDVP doses (no data was available for the highest dose)
where the per cent of examined cells with polyploidy ranged from 9.3 to 15.7 %, compared to 2.5%
in control cells. According to the "Discussion" in this article, previous studies with DDVP in
cultured human lymphocytes or fibroblasts did not show inductions of SCE or AB, and this
apparent divergence with the results of this study was attributed to possible differences in
sensitivity among the different test systems (Tezuka et al, 1980).
According to a Memorandum (dated August 10, 1988) entitled, "Review of in vivo mutagenicity
studies concerning Dichlorvos" that was presented to the Cancer Peer Review Committee (CPRC)
by Kerry Deerfield, DDVP is also clastogenic (causing AB and SCE) in CHO cells with or without
metabolic activation (NTP draft report, 1987, TR 342, NIH pub. No. 88-2598). [The review by K.
Dearfield mistakenly cites that the test system in the above study by Tezuka et al., 1980 used V79
cells (hamster fibroblasts) rather than CHO cells.] This NTP study is not available to this reviewer
to clarify and provide more details.
As shown below, however, an in vivo study by Microbiological Associates, Inc. (Study dated
9/26/85) failed to show that DDVP has clastogenic activity in mice.
Mutagenicity Studies with Negative Results
In a micronucleus test, DDVP (98.5% a.L, in corn oil) was administered (i.p.) at 0 (vehicle), 4, 13,
or 40 mg/kg/day to adult CD-I mice (5/sex/dose/scheduled sacrifice) on two consecutive days and
bone marrow polychromatic erythrocytes (PCE) were examined for micronuclei at 30, 48, and 72 hr
after the last dose. A group (5/sex) of positive control mice were administered (i.p.) a single dose
(0.15 mg/kg) of the mutagen triethylene melamine (TEM) in water at 30 hr prior to killing. From a
preliminary DDVP dose-range finding study (8 doses from 1 to 100 mg/kg) the LDso for both sexes
is 56 mg/kg. In the main assay, two males and three females in the high dose group and one male in
the mid dose group died prior to scheduled killing. (Dead animals in the high dose group were
replaced.) Also lethargy and tremors were seen in the high dose group. Therefore, a clinical MTD
seems to have been achieved.
In none of the 18 DDVP test groups were micronuclei significantly increased (range 0-1.2 per 1000
scored PCE) compared to negative control (0-1). There was a significant response in the TEM
positive control group with a mean of 15.6 (males) and 13.2 (females) micronuclei/1000 PCE.
(Microbiological Associates, Inc., Study dated 8/15/85)
This study was classified as acceptable/current guideline (HED doc. # 004376).
In another in vivo mutagenicity study, DDVP (98.5% a.L, in corn oil) was tested for sister
chromatid exchange (SCE) induction in B6C3F1 mice (5/sex/group) which were implanted (s.c.)
with 50 mg bromodeoxyuridine pellet four hours prior to receiving a single injection (i.p.) of 0
(corn oil), 3, 10, or 30 mg DDVP/kg. Dose-selection for this study was based on a preliminary
study in which mice received one of eight doses ranging from 1-100 mg DDVP/kg where the
combined (male/female) LDso was calculated as 47 mg/kg. A positive control group (5/sex)
received an i.p. injection of cyclophosphamide (CP) at 10 mg/kg in water. After 24 hours, bone
marrow from both femurs was removed and processed to determine SCE by standardized methods
Page 224 of 338
-------
where fifty second-division metaphase cells per animal were scored for SCE. No animals died in
the main SCE assay and no clinical signs of toxicity were observed except for lethargy in the high
dose group. The mean SCE/cell/animal were similar among all animals in the negative control and
the DDVP-treated groups (males: 4.9-5.9/females: 5.6-6.3); also the mitotic indices (% of
metaphase cells in first, second, and third division) in all DDVP treated groups were comparable to
the negative control group indicating that there was no cell cycle delay even at the highest DDVP
dose. As expected, CP was positive with a mean SCE/cell/ animal of 29.9 in males and 18.1 in
females. (Microbiological Associates, Inc., Study dated 9/26/85)
This study was classified as acceptable and HED concluded that "although no evidence for target
cell toxicity (mitotic delay) was reported even at a dose causing clinical toxicity, the study was
otherwise conducted adequately, and thus the negative results for SCE are supportable." (HED
doc. # 004376)
This reviewer partly disagrees since the highest tested dose of 30 mg/kg was below the MTD as
judged by an LDso of 47 mg/kg (preliminary study) and a lack of clinical signs of toxicity with the
exception of lethargy.
Another in vivo study (MRID no. 42619901) assessed the potential for genotoxic effects in the
germ cells and in bone marrow in male ICR mice (10/group) by administering daily oral (gavage)
doses of 0, 12.5, 25, or 50 mg/kg/day of DDVP (a.i. 98.1%, dissolved in water to give a constant
dosing volume of 20 mL/kg) for five consecutive days. Cyclophosphamide (CP) was also
administered (10 mice/group) at a single oral dose of 40 or 150 mg/kg (in water, dosing volume 20
mL/kg). All animals also received a single i.p. injection (1.6 mg/kg) of the spindle inhibitor
colchicine two hours before killing. Bone marrow cells and spermatogonia were prepared
according to established procedures; from each animal, fifty metaphase cells were examined,
structural aberrations were recorded, and the mitotic index (MI) was determined. There were no
indication of a clastogenic effect in either germinal (spermatogonia) or somatic cells (bone marrow)
harvested 24 hours following the final administration of the test material. The positive control
group responded appropriately. The reviewer of this study concluded that the maximally tolerated
dose was achieved based on a preliminary test where there was 80 % mortality after a single dose of
70 mg DDVP/kg (100% mortality after a single dose of > 90 mg/kg); furthermore, the five repeated
doses of DDVP "allowed a slightly reduced dosing load while challenging the animals without
excessive mortality" as was seen at >70mg/kg.
This study (MRID No. 42619901) was judged acceptable and, therefore, it satisfied the requirement
for in vivo cytogenetic mutagenicity data (HED doc. # 010446).
h. Metabolism
CITATION: Cheng, T. (1989) Metabolism of (Carbon 14)-DDVP in Rats: Project ID HLA
6274-105. Unpublished study prepared by Hazleton Laboratories America, Inc.
322 p. MRID 41228701.
Cheng, T. (1991) Supplement to: Metabolism of carbon 14|-DDVP in Rats
(Preliminary and Definitive Phases) (...): Lab Project Number: HLA
Page 225 of 338
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6274-105-1. Unpublished study prepared by Hazleton Laboratories America,
Inc. 89 p. MRID 41839901.
EXECUTIVE SUMMARY: Groups of Sprague-Dawley rats (5/sex/group) were administered a
single dose of 20 jiC; [14C]DDVP (radiolabelled at the vinyl position and purified to 100%) either
intravenously (1 mg/kg), orally (1 or 20 mg/kg; low and high doses, respectively), or orally (1
mg/kg) after 15 daily oral doses of unlabeled DDVP (1 mg/kg) and a control group (2/sex) were
orally dosed with water (vehicle). Of the total orally administered dose (low or high), nearly 88-
94% was absorbed through the gastrointestinal tract and, within 24 hr, nearly 43-57% of the original
dose (low or high) was eliminated in expired air and excreta. After seven days, the total
excreted/air expired recovery was approximately 60-77%; and, of the original dose, 11-17% was
recovered in urine/cage washes, 4-7% in feces, and 41-58% as expired 14CC>2. The relative amounts
of radioactivity retained in carcass, liver, and other tissues combined were 13-26%, 3-5%, and 1-
2%, respectively. During the seven days post-dosing period (low or high single dose), males
expired slightly less 14CC>2 than females (41-45% vs. 52-54%, respectively). The excretion patterns
were similar after i.v. or oral administration and little, if any, other differences relating to sex or
dose were found in the excretion or distribution of [ 14C]DDVP. Of the five radiolabelled
compounds that were detected in urine, two were identified by mass spectrometry as hippuric acid
(HA) and urea. Relative to total urinary radioactivity, the concentration of HA ranged from 6.8-
10.5 % (low dose group) to 4.2-5.6 % (high dose group), while the amount of urea was 19.6-33.1%
(low dose group) and 41.1-51.1% (high dose group). Urea and HA also seemed to be present in
feces, albeit at lower concentrations than were found in urine. Three other urinary compounds were
not identified but were assumed to be dehalogenated metabolites. Other metabolites, representing
nearly 8 to 19% of total urinary radioactivity, were considered to be glucuronide conjugates (not
identified).
The overall metabolic profile suggests the involvement of the one-carbon pool biosynthetic
pathway as evidenced by the presence of a relatively large amount of radioactivity in the form of
expired 14CO2 and the presence of dehalogenated metabolites as well as urea and hippuric acid.
These studies (MRID # 41228701 and 41839901) were considered acceptable and should satisfy the
guideline requirement for a metabolism study (HED doc. # 008132 and 009444).
It should be noted that the above metabolism summary was based on the specified subject MRID
and HED documents and, as a result, subtle differences or disagreements (for instance, relative
amounts of metabolites) are inevitable between this summary and other metabolism summaries
(e.g., the document dated August 28, 1996 and entitled, "fifth carcinogenicity peer review of
dichlorvos" prepared by Joycelyn Stewart).
It should also be pointed out that, according to the IRIS summary on dichlorvos dated 09/01/96,
there are several additional published studies on the availability, distribution, and metabolism
following administration of DDVP by different routes to different species.
I. Human Studies
CITATION: Gledhill, A. (1997) Dichlorvos: A Study to Investigate the Effect of a Single Oral
Dose on Erythrocyte Cholinesterase Inhibition in Healthy Male Volunteers:
Page 226 of 338
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Lab Project Number: CTL/P/5393: XH6064. Unpublished study prepared by
Zeneca Central Toxicology Lab. 44 p. MRID 44248802.
Gledhill, A. (1997) Dichlorvos: A Single Blind, Placebo Controlled, Randomised
Study to Investigate the Effects of Multiple Oral Dosing on Erythrocyte
Cholinesterase Inhibition in Healthy Male Volunteers: Lab Project Number:
CTL/P/5392: XH6063. Unpublished study prepared by Zeneca Central
Toxicology Lab. 52 p. MRID 44248801.
Gledhill, A. (1997) Dichlorvos: A Study to Investigate Erythrocyte
Cholinestrase Inhibition Following Oral Administration to Healthy Male
Volunteers: Lab Project Number: XH5170: Y09341: C05743. Unpublished
study prepared by Zeneca Central Toxicology Lab. 104 p. MRID 44416201.
EXECUTIVE SUMMARY: Dichlorvos (lot no. 608002S074, a.i. 98%, dissolved in corn oil and
packed in capsule) was administered in a single oral dose of 70 mg (equivalent to 1 mg/kg) to six
fasted young healthy male volunteers. RBC cholinesterase (ChE) activity was measured prior to
dosing on days -22, -20, -18, -15, -13, -11, -8, -6, -4, and 0 (immediately prior to dosing), and after
DDVP administration on days 1, 3, 5/6, 7, and 14. All subjects were medically supervised for
clinical signs and body temperature changes for twenty four hours after dosing. Under the study
conditions, no adverse clinical signs and no body temperature variations were reported. Mean RBC
ChE activity was statistically significantly inhibited by 12% or less on days 5/6, day 7, and day 14.
The reduction in RBC ChE was not considered to be biologically meaningful.
This study is considered non-guideline (MRID # 44248802).
In a single blind oral study, each of six fasted male volunteers was administered a daily dose of 7
mg DDVP (equivalent to about 0.1 mg/kg/day) in corn oil via a capsule over 21 days. Three
control subjects received corn oil as a placebo. The activity of RBC ChE was measured for each
participant prior to dosing, to establish baseline levels, and also after dosing on days 2, 4, 7, 9, 11,
14, 16, 18, 25, and 28. There were no reported toxicity attributable to DDVP administration.
Compared to pre-dosing mean value, the mean RBC ChE activity was statistically significantly
reduced by 8, 10, 14, 14, and 16 percent on days 7, 11, 14, 16, and 18, respectively. Under the
study conditions, the LOAEL for RBC ChE inhibition was established at 0.1 mg/kg/day (MRID No.
44248801). As discussed below, this study was used for intermediate-term dermal exposure risk
assessment.
In another human study (MRID 44416201), DDVP (lot no. 402010A, a.i., 98%, dissolved in corn
oil and packed in a capsule) was administered to each of six fasted healthy male Caucasian males
over two experimental phases where each phase was followed by repeated measurements of RBC
ChE. In the first phase, volunteers ingested a capsule of 35 mg DDVP on day 1, and on day 8 or 9
they received a corn oil capsule and finally they received another 35 mg DDVP capsule, eight or
nine days after the corn oil. Measurements of RBC ChE were performed pretest (days -7, -5, and -
3) and after administration of each DDVP capsule (24, 72, 120, and 168 hr post each dose) or corn
oil (at 24, 72, and 120 hr). Adverse physical signs and symptoms including body temperature were
recorded for each volunteer. After 24 hr and 120 hr of the first DDVP dosing, group mean RBC
ChE activities were significantly depressed to 88% (not 93% as reported by original reviewer in
Page 227 of 338
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DER #22) and 90 %, respectively, of predosing levels. (There seems to be an error in computing
the day 1 group mean ChE level after the first DDVP dosing which should be 15098 I.U., or 88%,
instead of 15908 I.U., or 93%, as shown in Table 2 of DER #22.) However, following the second
dose of DDVP, there were no statistically significant changes in group mean RBC ChE activity at
any time (94 - 98% of predose activity). Also, no changes in ChE values were seen after dosing
with corn oil (96 - 105% of predosing). Individual post-dose ChE activity ranged from 80% to
103% (not 85 to 100% as per DER #22) of predose values at all reporting periods. There were no
changes in body temperature and no symptoms were attributed to DDVP.
In the second phase of this study, the same volunteers were administered repeated daily doses of 21
mg DDVP for 12 or 14 days and RBC ChE activity was monitored every two or three days up to
day 29, and also on days 33, 40 and 55 (Table 3, DER #22) or on days 33, 40, 47, and 54, instead of
days 33, 40 and 55 (as specified under Section 2 entitled "Study Design" in DER #22). Plasma was
also prepared from all blood samples and immediately frozen and stored at -20°C; however, plasma
ChE was not measured. Compared to the group mean pretest value, group mean RBC ChE activity
was significantly decreased (<0.01) from day 5 through day 33, reaching a minimum of 69% on day
22 after which it seemed to gradually recover until the last measurement on day 54 (or 55) when it
was 91% of pretest activity. Four of the six subjects reported various symptoms; one felt tired
(days 5-9) with headache and nausea (day 6), another felt anxious one hour after the first dose, a
volunteer had an abdominal colic (day 12), and one subject developed an upper respiratory tract
infection (days 7 thru 12). Despite the fact that these symptoms (with the possible exception of
upper respiratory tract infection) are typical indicators of cholinesterase poisoning, the investigators
ruled out DDVP as a possible cause.
According to DER #22, the HED study reviewer concluded that, based on no decrease in RBC ChE
in phase 1, NOAEL is 35 mg/person (or 0.5 mg/kg for an average 70 kg person). This reviewer,
however, does not think that NOAEL was achieved since, compared to pretest value, the group
mean RBC ChE was statistically significantly depressed to 88% (day 1) and 90% (day 5) and also
because, at day 1, one individual (# IV) had this enzyme activity drop to nearly 80% of pretest level
(Table 1 in DER #22); furthermore, the reported physical symptoms in four subjects (three if the
upper respiratory tract infection is deemed unrelated) appear to be characteristic of ChE poisoning.
In phase 2, based on the steady decline in RBC ChE activity, the original HED reviewer concluded
that "NOAEL has not been established for this portion of the study."
This study is considered non-guideline (MRID No. 44416201).
Other human studies (journal articles) were also reviewed and were considered supplementary due
to employing too few subjects and/or lacking individual data (Stewart, 1993; HED document No.
010157andDannon, 1998)
Page 228 of 338
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3.0 Residue Chemistry Science Assessments for Reregistration of Dichlorvos.
GLN: Data Requirements
860.1200: Directions for Use
860.1300: Plant Metabolism
860.1300: Animal Metabolism
Current
Tolerances, ppm
[40 CFR]
N/A = Not
Applicable
N/A
N/A
860.1340: Residue Analytical Methods
- Plant commodities
- Animal commodities
860.1360: Multiresidue Methods
860.1380: Storage Stability Data
N/A
N/A
N/A
N/A
Must Additional
Data Be
Submitted?
Yes2
No
No
No
No
No
Yes6
860.1500: Crop Field Trials
Root and Tuber Vegetables Group
- Radishes
0.5
[180.235(a)]
No8
References 1
00013545, 00074844,
00013546,00066696,
00117261, 00117262,
00126462, 00126463,
42721601 3, 42951701 4
00042702, 00042704,
00042706, 00047472,
00049086,00049971,
00049975,00051556,
00074706, 00074777,
00107572,00115993,
00117747,00118115,
00139845
00042702, 00042704,
00049086, 00049087,
00049975, 00060469,
00060470, 00060472,
00074706,00115939,
00115993,00117257,
00117747,00118113,
00118592,00118639,
00140392
42611001 5
00074776, 00076809,
00140392,43377701 7
00118572, 00119536
Page 229 of 338
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GLN: Data Requirements
Current
Tolerances, ppm
[40 CFR]
Leafy Vegetables (except Brassica Vegetables') Group
- Lettuce
18
[180.235(a)]
Fruitinq Veqetables (except Cucurbits') Group
- Tomatoes
Cucurbit Veqetables Group
- Cucumbers
Miscellaneous Commodities
- Mushrooms
- Tobacco
0.05 9
[180.235(a)]
0.5 9
[180.235(3)]
0.5 9
[180.235(3)
None established
Must Additions!
Dsts Be
Submitted?
No8
No8
No8
No
No10
References 1
00033139,00082271,
00118572,00119536
00033144, 00107572,
00115993, 00117686,
00118169, 00118572
00082271,00107572,
00118572
00074658, 00117686,
00117690
860.1520: Processed Food/Feed
- Corn, field
- Cottonseed
- Rice
- Peanuts
- Soybeans
0.5 (processed
food) ™ [185.1900]
0.5 (processed
food) 11
[185.1900]
0.5 (processed
food) 11
[185.1900]
0.5 (processed
food) 11
[185.1900]
0.5 (processed
food) 11
[185.1900]
No
No
No
No
No
42993501 13
42993501 13
42993501 13
42952601 7
42993501 13
Page 230 of 338
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GLN: Data Requirements
- Wheat
Current
Tolerances, ppm
[40 CFR]
0.5 (processed
food) 11
[185.1900]
Must Additions!
Dsts Be
Submitted?
No
References 1
42993501 IJ
860.1480: Meat, Milk, Poultry, Eggs
- Milk and the Fat, Meat, and Meat
Byproducts of Cattle, Goats, Hogs,
Horses, and Sheep
- Eggs and the Fat, Meat, and Meat
Byproducts of Poultry
860.1400: Water, Fish, and Irrigated
Crops
860.1460: Food Handling
- Food Service Establishments
- Grain Processing and Manufacturing
Establishments
- Bulk Stored Raw and Processed
Commodities 15
- Bulk stored peanuts 15
- Packaged and Bagged Raw and
Processed Commodities
0.02 (milk and the
fat, meat, and
meat byproducts of
cattle, goats,
horses, and
sheep)
[180.235(a)]
0.1 (edible tissue
of swine)
[180.235(b)]
0.05
[180.235(a)]
None established
None established
0.5 (RAC) 14
[180.235(3)]
0.5 (RAC) 14
[180.235(3)]
0.5
[180.235(3)]
0.5 (RAC, <6%
fat) 11
2 (RAC, >6% fat)
[180.235(3)]
0.5 (processed
food) 11
Yes12
No
No
No
No
No
No
00115945, 00116436,
43037401 13
00118639, 00119537,
00139843, 00139844,
43047901 13
42768702 13, 42775901 13,
42878801 13, 42910801 13,
42910901 13
00117747,42916601 7
43003101 7
00056593, 00056595,
00056596, 42853701 7
Page 231 of 338
-------
GLN: Data Requirements
- Crack and Crevice Treatments
860.1000: Reduction of Residue
- Dried Beans
- Cocoa Beans
- Coffee Beans
- Tomato
- Meat, Eggs, Pasteurized Milk
- Degradation - Packaged and Bagged
Raw and Processed Commodities
- Degradation - Bulk Stored Raw and
Processed Commodities
860.1850: Confined Rotational Crops
860.1900: Field Rotational Crops
Current
Tolerances, ppm
[40 CFR]
[185.1900]
None established
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
None
Must Additional
Data Be
Submitted?
No16
No
No
No
No
No
No17
No17
No8
No8
References 1
42910701 13
42910701 13
42910701 13
42910701 13
42910701 13
42858201 13
42903801 7
Page 232 of 338
-------
1 References without endnotes were reviewed in the Residue Chemistry Chapter of the Dichlorvos
Reregistration Standard dated 2/26/86. All other references were reviewed as noted.
2. Label amendments are required to incorporate the parameters of use patterns reflected in the
submitted data and to reflect the use patterns that the registrant wishes to support which are
supported by residue data. Product labels with uses in mushroom houses must be amended to
reflect a 1-day PHI. All uses in greenhouses (food use only) and tobacco warehouses must be
deleted from product labels. Product labels which allow uses in food-handling establishments must
be amended to specify that applications may only be made in: in warehouses, silos, bulk bins, and
food/feed processing, food/feed manufacturing, handling and storage plants containing non-
perishable, packaged or bagged raw or processed food/feed commodities or bulk raw or processed
food commodities; or in non-food areas of food-handling establishments [including garbage rooms,
lavatories, floor drains (sewers), entries and vestibules, offices, locker rooms, machine rooms,
boiler rooms, garages, mop closets, and storage (after canning or bottling)]. Use in food handling
establishments - food service areas must be canceled. There are no tolerances or data supporting
this use.
3 CB No. 11768, DP Barcode D190450, 7/21/93, D. McNeilly.
4. CB No. 12766, DP Barcode D196572, 12/17/93, D. McNeilly.
5. CB No. 11244, DP Barcode D187061, 9/29/93, D. McNeilly.
6. Information pertaining to the storage intervals and conditions of samples of the following
commodities, from studies that were reviewed in the Residue Chemistry Chapter of the
Registration Standard (1987), must be submitted: packaged and bagged raw agricultural
commodities and processed food; bulk stored raw agricultural commodities; milk; eggs; and meat,
fat, and meat byproducts of dairy cows and poultry. Alternatively, the registrant may demonstrate
that there are sufficient residue data supported by storage stability data to support all registered
uses of dichlorvos.
7. CB Nos. 12658, 13230, 13296, and 13297; DP Barcodes D195720 , D199212, D199977, and
D199979; 6/2/94; S. Hummel.
8. The registrant is not supporting any agricultural uses of dichlorvos. Another registrant has
indicated a willingness to support dichlorvos use on tomatoes. If this use is to be supported,
residue data are required. We note that the tomato use is no longer on any dichlorvos labels.
9. Residues are expressed as naled.
10. The registrant is not supporting use of dichlorvos in tobacco warehouses.
11. Resulting from application to packaged or bagged nonperishable commodities.
12. A dermal magnitude of the residue study must be submitted for swine. Swine dermal use remains
on dichlorvos labels.
13. CB Nos. 13006, 13294, 13295, 13296, and 13427; DP Barcodes D197522 , D199975, D199976,
D199979, and D200905; 7/18/94; S. Hummel. Non-detectable residues were reported from direct
dermal uses and from secondary residues in livestock feeds.
14. Resulting from application to bulk stored nonperishable commodities, regardless of fat content.
Page 233 of 338
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15. See also "860.1520: Processed Food/Feed."
16. Data had been required reflecting crack and crevice treatment of food handling establishments;
however, because this use is more restrictive than the registered use on bulk stored and packaged
and bagged commodities, these data are no longer required.
17. Although no additional data are required concerning this guideline topic for the purposes of
reregistration, the Agency's risk assessment could be better refined if the registrant provides
information concerning the typical length of time commodities remain in storage following
treatment. This information would include typical total storage times, frequency of applications, and
rates of application (g/1000 cu. ft.).
Page 234 of 338
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4.0 Tolerance Reassessment
Table C. Tolerance Reassessment Summary for Dichlorvos.
Commodity
Current
Tolerance, ppm
Tolerance
Reassessment, ppm
Comment/
[Correct Commodity Definition]
Tolerances Listed Under 40 CFR §180.235(a)(1)*
Cattle, fat
Cattle, meat
Cattle, mbyp
Cucumbers
Eggs
Goats, fat
Goats, meat
Goats, mbyp
Horses, fat
Horses, meat
Horses, mbyp
Lettuce
Milk
Mushrooms
Poultry, fat
Poultry, meat
Poultry, mbyp
Radishes
0.02(N)
0.02(N)
0.02(N)
0.5 1
0.05(N)
0.02(N)
0.02(N)
0.02(N)
0.02(N)
0.02(N)
0.02(N)
11
0.02(N)
0.5 1
0.05(N)
0.05(N)
0.05(N)
0.5
0.05
0.05
0.05
Revoke
0.05
0.05
0.05
0.05
0.05
0.05
0.05
Revoke
0.05
0.5
0.05
0.05
0.05
Revoke
Harmonize with CODEX.
Harmonize with CODEX.
Harmonize with CODEX.
The registrant is not supporting
use of dichlorvos on this
commodity. Tolerance has been
revoked.
Harmonize with CODEX.
Harmonize with CODEX.
Harmonize with CODEX.
Harmonize with CODEX.
Harmonize with CODEX.
Harmonize with CODEX.
The registrant is not supporting
use of dichlorvos on this
commodity. Tolerance has been
revoked.
Harmonize with CODEX.
The tolerance should be revised to
be expressed in terms of
dichlorvos.
The registrant is not supporting
use of dichlorvos on this
commodity.
Page 235 of 338
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Commodity
Raw agricultural commodities,
nonperishable, bulk stored
regardless of fat content
(post-H)
Raw agricultural commodities,
nonperishable, packaged or
bagged, containing 6 percent
fat or less (post-H)
Raw agricultural commodities,
nonperishable, packaged or
bagged, containing more than
6 percent fat (post-H)
Sheep, fat
Sheep, meat
Sheep, mbyp
Tomatoes (pre- and post-H)
Current
Tolerance, ppm
0.5
0.5
2.0
0.02(N)
0.02(N)
0.02(N)
0.05 1
Tolerance
Reassessment,
ppm
4.0
4.0
0.05
0.05
0.05
Revoke
Comment/
[Correct Commodity Definition]
[Raw agricultural commodities,
nonperishable, bulk stored]
[Raw agricultural commodities,
nonperishable, packaged and
bagged]
Harmonize with CODEX.
Harmonize with CODEX.
Harmonize with CODEX.
The registrant is not supporting
use of dichlorvos on this
commodity.
Tolerances Listed Under 40 CFR §180.235(a)(2)
Edible swine tissue 2
0.1
Revoke
Residue data have been
required and not submitted.
Tolerances Listed Under 40 CFR §180.235(a)(3)
Packaged or bagged
nonperishable processed food
0.5
4.0
The tolerance should be moved
to§180.235(a)(1).
[Processed food,
nonperishable, packaged or
bagged]
Tolerances to be Proposed Under 40 CFR §180.235(a)
Soybean, hulls
Aspirated grain fractions
—
~
15.0
20.0
Concurrently with the revocation of the tolerance for edible swine tissue in §180.235(a)(2) and the
moving of the tolerance for packaged or bagged nonperishable processed food in §180.235(a)(3),
§180.235(a)(1) should be redesignated §180.235(a).
Residues expressed as naled. Another registrant has expressed interest in supporting the
tolerance on tomato. However, data have been required and not submitted.
Resulting both from its use as an anthelmintic in swine feed and as an insecticide applied
directly to swine; prescribed by 21 CFR 558.205 as a feed additive in swine, with a tolerance of
0.1 ppm for residues of dichlorvos in edible swine tissue listed in 21 CFR 556.180.
Page 236 of 338
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APPENDIX K: Revised EFED risk assessment for the Dichlorvos Reregistration
Eligibility Document
Page 237 of 338
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES AND
TOXIC SUBSTANCES
PC Code: 084001
DP Barcodes: D318301
MEMORANDUM June 20, 2005
Subject: Revised EFED risk assessment for the Dichlorvos Reregistration Eligibility Document
To: Bob McNally, Branch Chief/Eric Olson, Chemical Review Manager
Special Review Branch
Special Review and Reregistration Division (7508C)
From: Diana Eignor
Ibrahim Abdel-Saheb
Environmental Risk Branch II
Environmental Fate and Effects Division (7507C)
Through: Tom Bailey, Chief, ERB II
Environmental Fate and Effects Division (7507C)
EFED has completed a revised screening level ecological risk assessment for the reregistration of
dichlorvos. Attached is the dichlorvos ecological risk assessment.
Risk conclusions can be found in the Executive Summary on page 4.
Page 238 of 338
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DICHLORVOS (DDVP)
Revised Ecological Risk Assessment
Of"\ _ pM
, U L-rli
X
C=CH— 0 0— CH
Cl
Diana Eignor
Ibrahim Abdel-Saheb
Approved By:
Thomas A. Bailey, Chief
Environmental Risk Branch 2
Environmental Fate and Effects Division
June 20, 2005
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TABLE OF CONTENTS
I. EXECUTIVE SUMMARY 4
II.PROBLEM FORMULATION 6
A. Introduction 6
B. Stressor Source and Distribution 6
i. Chemical and Physical Properties 6
2. Mode of Action 6
3. Regulatory History 7
4. Use Characterization 7
5. Measurement Endpoints 9
6. Endangered Species 10
C. Conceptual Model 10
i. Terrestrial Environment 10
2. Aquatic Environment 11
D. Key Uncertainties and Information Gaps 15
i. Ecotoxicity Information Gaps 15
2. Environmental Fate Information Gaps 15
E. Analysis Plan 15
i. Specific Considerations 15
2. Assessment Endpoints 15
3. Planned Analyses 16
III. ANALYSIS 19
A. Exposure Characterization 19
i. Environmental Fate and Transport Characterization 19
2. Aquatic Resource Exposure Assessment 21
3. Terrestrial Organism Exposure Modeling 23
B. Ecological Effects Characterization 24
i. Evaluation of Aquatic Ecotoxicity Studies 24
2. Evaluation of Terrestrial Ecotoxicity Studies 29
3. Terrestrial Field Testing 32
4. Use of the Probit Slope Response Relationship 33
5. Incident Data Review 33
IV. RISK CHARACTERIZATION 34
A. Risk Estimation - Integration of Exposure and Effects Data 35
i. Non-target Aquatic Animals 35
2. Non-target Terrestrial Animals 37
3. Non-target Terrestrial Invertebrates 41
4. Non-target Terrestrial and Aquatic Plants 41
5. Non-target Terrestrial Animals - Bait Formulation 41
B. Risk Description - Interpretation of Direct Effects 42
i. Risks to Aquatic Animals 42
2. Risks to Terrestrial Animals 43
C. Threatened and Endangered Species Concerns 44
i. Taxonomic Groups Potentially at Risk 44
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2. Probit Slope Analysis 46
3. Critical Habitat 47
4. Indirect Effect Analyses 47
D. Description of Assumptions, Uncertainties, Strengths, and Limitations 49
i. Assumptions and Limitations Related to Exposure for all Taxa 49
2. Assumptions and Limitations Related to Exposure for Aquatic Species 49
3. Assumptions and Limitations Related to Exposure for Terrestrial Species 50
4. Assumptions and Limitations Related to Effects Assessment 52
5. Assumptions Associated with the Acute LOCs 53
6. Data Gaps and Limitations of the Risk Assessment 53
REFERENCES 55
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APPENDICES
Appendix A: Ecotoxicity Data Requirements
Appendix B: Environmental Fate Data Requirements
Appendix C: PRZM/EXAMS Modeling
Appendix D: Terrestrial Exposure and RQ Calculation - T-REX Model
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I. EXECUTIVE SUMMARY
Dichlorvos (2,2-Dichlorovinyl dimethyl phosphate), also known as DDVP , is an organophosphate
insecticide first registered for use in 1948. Dichlorvos is used in various scenarios for pest control but
there are no agricultural crop uses for this chemical. Target pests are flies, gnats, mosquitoes,
chiggers, ticks, cockroaches, armyworms, chinch bugs, clover mites, crickets, cutworms,
grasshoppers, and sod webworms. Dichlorvos is registered for domestic indoor, terrestrial non-
food, greenhouse (non-food) and domestic outdoor use. This document includes an assessment of
risks to terrestrial animals resulting from the use of dichlorvos on the federal-label listed uses for dry
granular bait use in animal premise areas and liquid spray use for turf and flying insects. Risks to aquatic
organisms are assessed based on modeled EECs for the turf scenario.
Terrestrial Exposure
• Immediately following granular bait application, granules and/or residues are expected to be
around animal premises. Birds and small mammals may be exposed from application to this
site.
• Terrestrial animals may be exposed to dichlorvos resulting from application of liquid
products used as a coarse spray to turf or to outdoor areas for flying insect control (e.g., sites
such as recreational parks and trails).
Aquatic Exposure
• Aquatic animals may be exposed to dichlorvos resulting from drift from ground spray
application to the turf and outdoor flying insect sites.
• It is unlikely that aquatic organisms will be directly exposed to dry granular bait.
Risk to Terrestrial Organisms
• The chronic risk endangered species LOCs are exceeded for turf applications (both i and 4
applications) for birds that consume short grass, tall grass, and broadleaf plants/small
insects.
• For the flying insect scenario, chronic RQs exceed endangered species for birds consuming
short grass, tall grass, and broadleaf plants/small insects.
• The acute risk, acute restricted use, and acute endangered species LOCs for a small bird (20 g
weight) are exceeded for the bait formulation scenario .
• The chronic LOG is exceeded for 15 g, 35 g, and 1000 g mammals that consume short grass,
tall grass, and broadleaf plants/small insects in the turf scenario.
• For turf application, there are acute endangered species LOG exceedences for the 15 g and 35
g mammals that consumes short grass.
• Chronic risk to birds and mammals from the bait formulation can not be assessed at this
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time.
Risks to Aquatic Organisms
• The acute risk, acute restricted use, and acute endangered species LOCs for freshwater invertebrates
are exceeded for turf scenarios in FL and PA for both one and four applications of dichlorvos.
In addition, the chronic level of concern is exceeded for freshwater invertebrates [egg
production and growth (length and weight) endpoint] for all of the turf scenarios (one and
four applications).
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II.PROBLEM FORMULATION
A. Introduction
Dichlorvos (2,2-Dichlorovinyl dimethyl phosphate), also known as DDVP , is an organophosphate
insecticide first registered for use in 1948. Dichlorvos is used in various scenarios for pest control but
there are no agricultural crop uses for this chemical.
The objectives of the current ecological risk assessment were to identify current registered dichlorvos
uses, identify potential exposure pathways and ecological receptors, estimate exposure concentrations,
identify ecological endpoints, and characterize risks for ecological receptors. This screening-level risk
assessment follows the Agency's Ecological Risk Assessment Guidelines (USEPA, 2000). This
document includes an assessment of risks to terrestrial animals resulting from the use of dichlorvos on the
federal-label listed uses for dry granular bait use in animal premise areas and liquid spray use for turf and
flying insects. Risks to aquatic organisms are assessed based on modeled EECs for the turf scenario.
B. Stressor Source and Distribution
1. Chemical and Physical Properties
Common Name:
Chemical Name:
Trade Names:
CAS No.
Molecular Formula:
Molecular Weight:
Physical state:
Boiling Point:
Vapor Pressure:
Solubility:
Henry's Law Const.:
Formulations:
2.
Mode of Action
Dichlorvos (DDVP)
2,2-Dichlorovinyl dimethyl phosphate
Dichlorvos, DDVP, and Vapona
62-73-7
Q H7 Q2 04 P
220.98 g/mol
colorless to amber liquid with a mild chemical odor
140° C at o.oi mm Hg
1.2 x lO'2 mm Hg at 2O°C
15,000 mg/L (25 °C)
5.O1E-8 atm m3/mole (measured)
Granules for Bait (e.g. Active ingredient 7.44%,
Inert ingredients 92.56%); Liquid (e.g. Active
ingredient 40.2%, Inert ingredients 59.8%)
Dichlorvos is an organophosphate insecticide which is a potent cholinesterase (ChE) inhibitor.
Acetylcholinesterase is an enzyme necessary for the degradation of the neurotransmitter acetylcholine
(ACh) and subsequent cessation of synaptic transmission. Inhibition of these enzymes results in the
accumulation of ACh at cholinergic nerve endings and continual nerve stimulation, which can result in
death. For non-target organisms, it causes reversible inhibition of erythrocyte acetylcholinesterase (RBC
ChE) as well as plasma butyryl ChE by binding to the active site of the enzyme.
3.
Regulatory History
Dichlorvos was first registered in 1948.
DDVP is now in the Special Review process.
EPA published a Notice of Preliminary Determination (Position Document 2/3) in the
Federal Register on September 28,1995.
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Dichlorvos is currently banned or restricted in 6 countries. The bans in Angola, Fiji, and Denmark; the
cancellation in Sweden; and restrictions in Kuwait all occurred in 1999 (Source: PIC Circular X,
Appendix V: Synopsis of Notifications of Control Actions, United Nations Environment
Programme, December, 1999,
http://www.fao.org/AG/AGP/AGPP/Pesticid/PIC/circular.htm)..
> Angola's control action applies to the banning of the product Vapona 24 EC.
> Dichlorvos is banned for all uses in Fiji with no remaining uses allowed because of the
potential health hazard.
> In Denmark, all authorizations for products containing dichlorvos as an active substance
have been withdrawn from the market 31 December 1997 and a further use has been
banned from 01 August 1998. No uses are allowed. Dichlorvos is assessed to be
carcinogenic in category 3 (cars., 3 cat., 3) and the formulated products are highly acute
toxic (T+ and T classified respectively) in Denmark. The products are therefore assessed
to be harmful to health.
> In Sweden , registration was cancelled (voluntarily withdrawn). This substance was
restricted due to its mutagenic properties in Sweden.
> In Kuwait, dichlorvos use is severely restricted.. Import of this chemical was stopped from
June 1994. Action was taken for health reasons.
All uses of dichlorvos in the UK/were suspended 4/19/2002. See r
nttp://www.don.gov.uk/com/aicmorvos:htm. Extant approval is for storage by any persons
and for use by persons other than the approval holder or their agents of existing stocks
(approvals expire 18 April 2004). (Source: Banned and Non-Authorized Pesticides in the UK,
Pesticides Safety Directorate, June 21, 2002,
http://www.pesticides.gov.uk/Blue_Book/Contents.htm.)
4. Use Characterization
Dichlorvos is an organophosphate insecticide registered for indoor, terrestrial non-food, greenhouse (non-food) and domestic
indoor and outdoor use. There are no agricultural crop uses for this chemical. Although the LUIS report classifies catch basin as
an aquatic non-food site for dichlorvos, it is more appropriately considered a terrestrial non-food outdoor use based on target pest
(flying or resting adult mosquitoes), formulation type (resin strip), placement of strip (10 inches above water level) and mode of
action (fumigant).
Target pests are flies, gnats, mosquitoes, chiggers, ticks, cockroaches and other nuisance insect
pests. For the turf and ornamental uses target pests also include armyworms, chinch bugs,
clover mites, crickets, cutworms, grasshoppers, and sod webworms. Formulation types include
baits, liquids and impregnated materials.
The majority of dichlorvos uses are indoors; including mushroom houses, greenhouses,
commercial, residential and industrial buildings, farm buildings, food handling establishments,
trash receptacles, and wine cellars. Ecological risk assessments are not performed for indoor
uses.
In the 1987 Dichlorvos Registration Standard, EFED addressed the two major outdoor sites, figs
and mosquito adulticide/larvicide. A third major outdoor site, turf, was not considered because
all registered products containing dichlorvos for that site were multiple active ingredient (MAI)
products, and policy at that time was not to consider MAI products. The current assessment
addresses outdoor flying insects (including mosquitoes), turf, and bait formulations used
around animal premises. The mosquito larvicide and fig uses have been canceled.
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For the outdoor sites listed below, EFED finds minimal potential for exposure to terrestrial and
aquatic animals based on the fate properties of dichlorvos and treatment sites being small and
localized. Maximum application rates and reapplication intervals for outdoor sites are listed
below. No risk assessments were performed for these sites:
Around agricultural premises/structures (liquids): (spot or band treatment only):
liquid spray -0.0115 Ib/iooo sq. ft2; 0.5 Ib ai/A; 7 day reapplication interval for
commercial sites and 30 day reapplication interval for residential sites.
Catch basin - Insect traps, impregnated resin strips (including the insecticidal
strip suspended 10 inches above water in catch basin areas to control flying
insects): i x 8og strip/loooft 3 ; (8og strip contains 18.6% dichlorvos = I4.88g
dichlorvos/strip =0.0327 Ib/strip; usual control last 10 to 15 weeks.
Manure treatment/garbage/refuse areas (liquids and baits): Dry bait: 0.046
Ib/iooo ft2; Liquid spray: 0.046 Ib/iooo ft2; 2 Ib ai/A; i day reapplication
interval.
Direct treatment to Animals: Liquid spray: 0.0013 Ib ai/animal (livestock): 0.02
g/animal (poultry); i day reapplication interval. (Maximum use rate for birds is
from Amvac 1/12/98 letter clarifying uses); also registered labels state to spray at
rate of i quart/1000 sq. ft. (2 Ib and 4 Ib/gal EC formulations; birds may be
present).
The maximum application rates and reapplication intervals for outdoor sites considered in this
risk assessment are listed below:
Liquid sprays for turf and flying insects (including mosquitoes): 0.0046 Ib/iooo
ft2 ( 0.2 Ib ai/A); i day reapplication interval for commercial sites and 7 day
reapplication interval for residential sites; ground application only; coarse sprays
only. According to BEAD, a worse case scenario for turf is 4 applications with
30 day application interval and 75 applications per year for flying insect control.
Dry bait formulations around animal premise areas: 0.0025 Ib/iooo ft2
(equivalent to o.i Ib ai/a) Some of the labels bear directions to reapply every 3 to
5 days until control is achieved. Therefore, a worse case scenario would be 120
applications per year based on label specifications.
For the outdoor flying insect (including mosquitoes) site, some of the labels have specificity of
where to apply, e.g., recreational areas, trails, outdoor living areas, eating areas of drive-in
restaurants, refuse areas, garbage collection/disposal areas, outdoor latrines, refuse areas
around service stations, loading docks, animal feedlots, stockyards, corrals, holding pens, lawns,
turf and ornamental plants. On the other hand, many of the labels have vague directions for
use, e.g., apply outdoors where pests are a problem. Dichlorvos does not appear to be used in
this country for adult mosquito control. It is not listed in State Management recommendations
for mosquito control, and the American Mosquito Control Association (AMCA) has indicated "as
far as they could tell", it wasn't being used in this country. It appears a worst case scenario for
insect control is around 75 applications to a given site over a year period (personal
communication with Douglas Sutherland, 4/15/98). For turf use, dichlorvos would normally be
10
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applied only once or twice per season. It is possible that up to four applications may be made,
but this would be unusual (Douglas Sutherland, BEAD entomologist, personal communication,
4/13/98). However, since the label does not limit the number of applications, the high end
estimate of 4 applications per season is modeled in addition to i application per season.
5. Measurement Endpoints
Each assessment endpoint requires one or more "measures of ecological effect," which are
defined as changes in the attributes of an assessment endpoint itself or changes in a surrogate
entity or attribute in response to pesticide exposure. Ecological measurement endpoints for the
screening level risk assessment are based on a suite of registrant-submitted toxicity studies, as
well as open literature review (U.S. EPA. 20043). The ECOTOX (ECOTOXicity) database is used to
identify additional data from the open literature. The ECOTOX database is a user-friendly, publicly-
available, quality-assured, comprehensive tool for locating toxicity data from the open literature and is
maintained by the EPA Mid-Atlantic Ecology Division. However, for this risk assessment for
dichlorvos, a detailed open literature search was not conducted.
Toxicity studies are usually performed on a limited number of organisms in the following broad
groupings:
Birds (mallard duck and bobwhite quail) used as surrogate species for terrestrial-phase
amphibians and reptiles
Mammals (laboratory rat)
Freshwater fish (bluegill sunfish and rainbow trout) used as a surrogate for aquatic
phase amphibians
Freshwater invertebrates (water flea - Daphnia magna)
Estuarine/marine fish (sheepshead minnow)
Estuarine/marine invertebrates (Eastern oyster and mysid shrimp)
Terrestrial plants (corn, onion, ryegrass, wheat, buckwheat, cucumber, soybean,
sunflower, tomato, and turnip)
Algae and aquatic plants (algae, diatoms, and duckweed)
6. Endangered Species
Potential risks posed by dichlorvos use on listed or endangered species must be evaluated. The potential for individual effects at
exposure levels equivalent to the level of concern (LOG) is made based on the median lethal dose estimate and dose-response
relationship established for the effects study corresponding to each taxonomic group for which the LOCs are exceeded.
C. Conceptual Model
A conceptual model (CM), which summarizes graphically the results of the problem formulation for evaluating risks to
ecological receptors following application of dichlorvos as a dry granular bait around animal premise areas is provided in Figure
1. The CM for the application of dichlorvos as a liquid spray for turf and flying insects is presented in Figure 2. The CMs are
working hypotheses about how dichlorvos is likely to reach (i.e., exposure pathways) and affect ecological entities (i.e., attribute
changes) of concern on and adjacent to a treated area. In order for a pesticide stressor to pose an ecological risk, it must reach an
ecological receptor in biologically significant concentrations. The CMs outline specifically which measures of exposure,
ecological receptors, and measures of effects or measurement endpoints will be used to estimate risks from proposed
reregistration uses of dichlorvos.
Based on the registered uses, dichlorvos is used on areas located in a wide diversity of ecoregions and habitats spanning the
continental United States, Hawaii, Alaska, and Puerto Rico. The wide diversity of land forms and vegetation types across
dichlorvos use areas also provides for a large diversity of mammals, birds, reptiles, amphibians, terrestrial invertebrates, and
freshwater and estuarine/marine fish and invertebrates that could potentially be exposed.
11
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1. Terrestrial Environment
a. Exposure
Immediately following granular bait application, granules and/or residues are expected to be around animal premises. Birds and
small mammals may be exposed from application to this site. Wildlife exposure Could result from mistakenly
ingesting granules as seeds or ingesting them as part of incidental soil ingestion while foraging
for food. Wildlife exposure could also result from a number of other exposure pathways and
wildlife actions or behaviors including inhalation of dust particulates; dermal uptake via direct
contact of skin with the granules and residues in soil and turf; contact with residues in puddles
present in the area at the time of application or formed after a rain event; or ingestion of water
from residues in puddles. Currently, terrestrial wildlife exposure for granular bait formulations are
estimated via the amount of toxicant per unit area in a screening-level risk assessment. This index was
developed considering these other routes of exposure; however, they are not separately accounted for in
the index calculation.
Terrestrial animals may be exposed to dichlorvos resulting from application of liquid products
used as a coarse spray to turf or to outdoor areas for flying insect control, including mosquitoes
(e.g., sites such as recreational parks and trails). Use is by ground application (e.g., back-pack
sprayers or truck-mounted sprayers) using coarse sprays directed to the vegetation. One day
reapplication intervals are permitted for both sites, except for homeowner where it is seven
days. Continuous year-round exposure is possible in some areas of the country, e.g., Florida, for
both sites.
Currently registered labels for turf and flying insects allow for fogging and misting, and there are
no label prohibitions against aerial application. Labels do not specify maximum numbers of
applications or reapplication intervals. Drift can be minimized by prohibiting aerial application,
and restricting application to coarse sprays. However, for the turf site, BEAD sources indicate a
typical application is only twice per year (with a thirty day reapplication interval), with four
applications representing worst-case. For the flying insect (including adult mosquitoes) use, it
does not appear that dichlorvos is being used in this country. BEAD sources indicate a worst
case scenario for a pesticide used for adult mosquito control would be around 75 applications to
a given site over a year period. There are no label restrictions for the use of granular bait. Based
on the label directions to reapply every 3 to 5 days until control is achieved, a worse case
scenario would be 120 applications per year.
b. Receptors of Concern
Ecological receptors of concern identified for consideration in the terrestrial environment include primary
producers, represented by both upland and wetland/riparian vegetation, and primary and secondary
consumers, both vertebrates and invertebrates, representing common ecological functional feeding groups
(i.e., herbivores and insectivores). Herbivores as used here include animals that feed on foliage (stems
and leaves), seeds, and/or fruit; the term granivore is sometimes used to identify animals that feed
primarily on seeds. Omnivores (i.e., consumers that feed on a mixed diet of animals and plants) are also
potentially exposed but are not specifically included in the receptor list for a screening level risk
assessment because exposure concentrations and risk levels will fall between the exclusive feeding
groups.
12
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Based on the sources/transport pathways, exposure media, and potential receptors of concern,
specific questions or risk hypotheses formulated to characterize direct effects of dichlorvos
following application on areas to selected assessment endpoints is provided below.
c. Terrestrial Environment Risk Hypotheses for Dichlorvos Uses
Birds and mammals are subject to reduced survival or reduced reproduction when exposed to
dichlorvos as a result of labeled use.
Upland and riparian/wetland plants are subject to adverse effects (reduced survival) when
exposed to dichlorvos as a result of labeled use.
2. Aquatic Environment
c. Exposure
Aquatic animals may be exposed to dichlorvos resulting from drift from ground spray
application to the turf and outdoor flying insect sites. Following a rain event, dichlorvos may reach
aquatic environments from areas of spray application in sheet and channel flow runoff since dichlorvos is
soluble in water. Direct exposure to aquatic animals from misapplication of the pesticide is also
possible. Aquatic organisms could also be exposed to dichlorvos from groundwater that is subsequently
discharged into a surface water body. Continuous year-round exposure to aquatic animals is
possible in some areas of the country, e.g., Florida, for both the turf and flying insect scenarios.
It is unlikely that aquatic organisms will be directly exposed to dry granular bait, therefore that pathway is
not evaluated.
Currently registered labels for turf and flying insects allow for fogging and misting, and there are
no label prohibitions against aerial application. Labels do not specify maximum numbers of
applications or reapplication intervals. Drift can be minimized by prohibiting aerial application,
and restricting application to coarse sprays. However, for the turf site, BEAD sources indicate a
typical application is only twice per year (with a thirty day reapplication interval), with four
applications representing worst-case. For the flying insect (including adult mosquitoes) use, it
does not appear that dichlorvos is being used in this country. BEAD sources indicate a worst
case scenario for a pesticide used for adult mosquito control would be around 75 applications to
a given site over a year period.
b. Receptors of Concern
For the aquatic ecosystem, ecological receptors include all aquatic life (fish, amphibians, invertebrates, plants) and those
terrestrial animals (e.g., birds and mammals) that consume aquatic organisms. Based on the above sources/transport
pathways, exposure media, and potential receptors of concern, specific questions or risk hypotheses
formulated to characterize direct effects of dichlorvos application to selected assessment endpoints is
provided below.
c. Aquatic Environment Risk Hypotheses for Dichlorvos Uses
Aquatic invertebrates and fish are subject to adverse effects such as reduced survival and reduced reproduction when
exposed to dichlorvos as a result of labeled use.
Aquatic plants are subject to adverse effects (reduced survival) when exposed to dichlorvos as a result
of labeled use.
13
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14
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Figure 1. Ecological conceptual model for the
bait. Solid arrows indicate pathways addressed
application of dichlorvos as dry granular
in assessment.
-------
16
-------
17
-------
Figure 2. Ecological conceptual model for the application of dichlorvos as liquid spray. Solid arrows indicate
pathways addressed in assessment.
18
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D. Key Uncertainties and Information Gaps
The following uncertainties and information gaps were identified as part of the problem
formulation:
1. Ecotoxicity Information Gaps
There are no terrestrial plant data for dichlorvos which leads to uncertainty in the evaluation of
plant risk and indirect effects to other organisms. Appendix A at the end of this document
provides the summary status of all the ecotoxicological data requirements
2. Environmental Fate Information Gaps
There are no data gaps in the environmental fate information. Appendix B at the end of this
document provides the summary status of all the environmental fate data requirements
E. Analysis Plan
1. Specific Considerations
This document includes an assessment of risks to terrestrial animals resulting from the use of dichlorvos as a bait formulation and
spray application for the turf and flying insect scenarios. Risks to aquatic organisms are assessed based on modeled EECs for
liquid spray application for the turf scenario. For the flying insect scenario, current models are inappropriate
to use so a quantitative assessment for flying insects can not be performed. It is likely the EECs in the
surface water for the flying insect scenario would be less than the turf scenario since the treatment area
would be smaller.
Ecological risk assessment is a process that evaluates the likelihood that adverse ecological
effects may occur or are occurring as a result of exposure to one or more stressors (US EPA,
19923). This risk assessment examines the ecological risk of dichlorvos use, and attempts to
determine at what level dichlorvos can be used to minimize deleterious effects on the
environment. These negative effects include structural and/or functional characteristics or
components of ecosystems. In order to estimate the ecological risk associated with dichlorvos
use, use information, chemical and physical properties, and fate/transport data were evaluated.
2. Assessment Endpoints
Assessment endpoints are defined as "explicit expressions of the actual environmental value that
is to be protected." Two criteria are used to select the appropriate ecological assessment
endpoints: (i) identification of the valued attributes of the environment that are considered to
be at risk, and (2) the operational definition of assessment endpoints in terms of an ecological
entity (i.e., a community offish and aquatic invertebrates) and its attributes (i.e., survival and
reproduction). Therefore, the selection of assessment endpoints is based on valued entities (i.e.,
ecological receptors), the ecosystems potentially at risk, the migration pathways of pesticides,
and the routes by which ecological receptors are exposed to pesticide-related contamination.
The selection of clearly defined assessment endpoints is important because they provide
direction and boundaries in the risk assessment for addressing risk management issues of
concern.
a. Toxicity Endpoints
19
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Aquatic and terrestrial non-target toxicity endpoints (animals and plants) are provided by the
acute and, where appropriate, chronic toxicity data. These toxicity endpoints are compared with
the environmental concentrations of dichlorvos, based on fate properties, exposure method, etc.
For this assessment, the most sensitive toxicity endpoints for each surrogate taxa (ie. freshwater
fish and invertebrates, estuarine/marine fish and invertebrates, aquatic plants, terrestrial
plants, birds, and mammals) will be used in Risk Quotient (RQ) calculation with various
exposure values.
An acute and chronic endpoint is selected from the available test data as the data sets allow.
Endpoints used in this assessment are listed in Table i.
Table i. Summary of Assessment and Measurement Endpoints used in
calculations
Assessment Endpoint
1 . Survival, reproduction, and growth of birds
2. Survival, reproduction, and growth of mammals
3. Survival and reproduction of freshwater fish
and invertebrates
4. Survival and reproduction of
estuarine/marine fish and invertebrates
5. Perpetuation of non-target terrestrial plants
(crops and non-crop species)
6. Survival of beneficial insect populations
7. Maintenance and growth of aquatic plants
from standing crop or biomass
Measurement Endpoint
Acute oral Mallard duck LD50 = 7.78 mg/kg
Subacute dietary Pheasant LC50 = 568 mg/kg
Chronic Mallard Duck NOEC = 5 ppm
Oral Rat LD50 = 56 mg/kg (female)
Chronic Rat NOEC = 20 ppm
Acute Lake Trout LC50 = 183 ppb
Acute Daphnia EC50 = 0.07 ppb
Chronic Rainbow trout NOAEC = 5.2 ppb
Chronic Daphnia NOEAC = 0.0058 ppb
Acute Sheepshead minnow LC50 = 735O ppb
Chronic Sheepshead minnow NOAEC = 960 ppb
Acute Mysid LC50 = 19.1 ppb
Chronic Mysid NOAEC = 1.48 ppb
NA
Honey bee (acute contact basis) LD50 = 0.495 ug/bee
Acute algae 48 hr EC50 = 14000 ppb
LD50 = Lethal dose to 50% of test population
NOAEC = No observed adverse effect concentration
LOAEC = Lowest observed adverse effect concentration
LC5o = Lethal concentration to 50% of the test population
EC5o/EC25 = Effect concentration to 5096/25% of the test population
4. Planned Analyses
a. Fate and Exposure
Terrestrial Environment
20
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Ingestion of granular bait used in animal premise areas represents a significant exposure pathway in
terrestrial animals. In addition, terrestrial organisms may be exposed in treated areas (turf and flying
insect areas) via spray applications. Therefore, the terrestrial screening-level risk assessment examined
exposure to granular bait using the maximum labeled use rate. Turf use was assessed using four
applications as the worse case scenario. For the flying insect scenario, weekly applications over a year
period was chosen as a worst-case scenario. A terrestrial foliar dissipation half life of 0.0875 days
was used in the terrestrial modeling for liquid spray. This half life was based on data from acceptable
studies submitted to the Health and Effects Division (HED), titled "Dislodgeable foliar residues
and exposure assessment for residential/recreational turf applications of dichlorvos (DDVP),
Barcodes 0248456, 0248596, 0255253). Only parent dichlorvos was modeled for terrestrial
exposure scenarios.
Aquatic Environment
OPP generally uses computer simulation models to estimate exposure of aquatic organisms, such as
plants, fish, aquatic-phase amphibians, and invertebrates, to a pesticide. These models calculate estimated
environmental concentrations (EECs) in surface water using laboratory data that describe the rate at
which the pesticide breaks down and how it moves into the environment. Monitoring data, if available,
may also be used to determine EECs or to support the model's calculations. The PRZM-EXAMS model is
initially used to calculate high-end estimates of surface water concentrations of pesticide in a generic
pond. This model was used to generate EECs of dichlorvos in surface water for the turf scenarios. The
User's Manual and PRZM-EXAMS Model Description can be consulted for additional information at:
www.epa.gov/oppefedl/models/water/index.htm. No EECs are generated in instances where no toxicity
was observed at concentrations above the active ingredient's water solubility at or above the
recommended limit concentration for a particular type of study.
The Florida and Pennsylvania turf scenarios were used in the standard Pesticide Root Zone Model and
Exposure Analysis Modeling System (PRZM-EXAMS) modeling. Both one application and 4
applications were modeled. The rationale for choosing four applications for turf was based on
information received from BEAD indicating a worst-case scenario would probably be about four
applications. The PRZM model input called "decay rate on foliage" was based on data from
acceptable studies submitted to the Health and Effects Division (HED), titled "Dislodgeable
foliar residues and exposure assessment for residential/recreational turf applications of
dichlorvos (DDVP), Barcodes 0248456, 0248596, 0255253).
For the flying insect (including adult mosquitoes) use, the GENEEC model is inappropriate to
use. It is likely EECs found in surface water from treatment for flying insects (including adult
mosquitoes) would likely be lower than EECs from treatment to turf, since the treatment area
would likely be less. Since the applications for flying insect control are ground applications
(e.g., back-pack sprayers or truck-mounted sprayers) using coarse sprays directed to the
vegetation (no fogging or misting), EFED cannot perform a quantitative assessment.
It is unlikely that aquatic organisms would be directly exposed to the dry granular bait use in animal
premise areas, therefore that pathway is not evaluated.
c. Risk Quotient and Levels of Concern
21
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Risk characterization integrates exposure and ecotoxicity data to evaluate the likelihood of
adverse effects. For ecological effects, the Agency accomplishes this integration using the
quotient risk method. Risk quotients (RQs) are calculated by dividing exposure estimates by
acute and chronic ecotoxicity values.
RQ = EXPOSURE / TOXICITY
RQs are then compared to the Office of Pesticide Program's levels of concern (LOCs) to assess
potential risk to non-target organisms and the need to consider regulatory action. Calculation of
an RQ that exceeds the LOG indicates that a particular pesticide use poses a presumed risk to
non-target organisms. LOCs currently address the following categories of presumed risk:
acute - potential for acute risk is high and regulatory action beyond restricted
use classification may be warranted
acute restricted - the potential for acute risk is high, but may be mitigated
through restricted use classification
acute endangered species - threatened and endangered species may be
adversely affected
chronic risk - the potential for chronic risk is high and regulatory action may be
warranted.
The ecotoxicity values used in the acute and chronic risk quotients are endpoints derived from
required laboratory toxicity studies. Ecotoxicity endpoints derived from short-term laboratory
studies that assess acute effects are:
LC50 - fish and birds
LD50 - birds and mammals
EC50 - aquatic plants and aquatic invertebrates
EC25 - terrestrial plants
The NOAEC (No Observable Adverse Effect Concentration) is the endpoint used to assess
chronic effects. Table 2 gives formulas for calculating RQs and LOCs for various risk
presumptions.
Table 2. Formulas for RQ calculations and LOG used for risk assessment of
dichlorvos
Risk Presumption
Acute Risk
Acute Restricted Use
Acute Endangered Species
Chronic Risk
RQ
Birds and Wild Mammals
EEC'/LCso or LD50/ft2* or LD50/day2
EEC/LCso or LD50/ft2 or LD50/day (or LD50<50 mg/kg)
EEC/LCso or LD50/ft2 or LD50/day
EEC/NOAEC5
LOC
0.5
0.2
0.1
1.0
Aquatic Animals
Acute Risk
EEC3/LC5oorEC5o
0.5
22
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Acute Restricted Use
Acute Endangered Species
Chronic Risk
EEC/LCsoOrECso
EEC/LCsoOrECso
EEC/NOAEC
0.1
0.05
1.0
Terrestrial and Plants Inhabiting Semi-Aquatic Areas
Acute Risk
Acute Endangered Use
EEC4/EC25
EEC/ECos or NOAEC
1.0
1.0
Aquatic Plants
Acute Risk
Acute Endangered Species
EEC3/EC50
EEC/ECos or NOAEC
1.0
1.0
*mg/fp
'Abbreviation for Estimate Environmental Concentration (ppm) on avian/mammalian food items
2 mg of toxicant consumed/day
3 EEC = ppm or ppb in water
4 EEC = Ibs ai/A
s No chronic risk was calculated for terrestrial animals based on the LD50/ft2 index
III. ANALYSIS
A. Exposure Characterization
i. Environmental Fate and Transport Characterization
Acceptable studies for dichlorvos are available for all guidelines. The status of the data
requirements is described in Appendix B. Selected physical and chemical properties are
summarized in Table 3.
Table 3. Selected physical and chemical properties of dichlorvos
Property
Molecular Formula
Molecular Weight
Physical State
Odor
Boiling point
Vapor pressure
Henry's Law coefficient
Solubility
CAS Number
Value
C4 H7 C12 04 P
220.98 g/mol
colorless to amber liquid
mild chemical odor
140° C at o.oi mm Hg
1.2 x io-2 mm Hg at 2O°C
S.oiE-8 Atm. m 3 /mol (measured)
in water at 25° C= 15000 mg/L
62-73-7
a. Persistence
23
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Metabolic transformation is the major mode of dissipation of dichlorvos under field conditions.
Acceptable laboratory and field studies also indicate rapid dissipation through volatilization
(vapor pressure = 1.2 x 10 ~2 mmHg). Volatility is not going to be a major route of dissipation
under field conditions when the soil is moist and the pesticide is wetted in. It appears
dichlorvos degrades through aerobic soil metabolism and abiotic hydrolysis as well, but is
secondary to volatilization. Hydrolysis is pH dependant where the half-lives were 11.6 days at
pH 5, 5.5 days at pH 7 and 21.1 hours at pH 9.
Acceptable lab and field studies indicate that the major modes of dissipation of dichlorvos are
volatilization (vapor pressure 1.2 x 10 ~2 torr) and microbial degradation in an aerobic soil.
Dichlorvos is unstable to hydrolysis at 25°C at pH 9. Under field conditions when the soil is
moist and the pesticide is wetted, volatilization is not going to be a major route of dissipation.
These mechanisms of dissipation indicate dichlorvos has low persistence in the environment.
Hydrolysis is pH dependent where the half-life is 11.65 days at pH 5, 5.19 days (124.62 hours) at
pH 7, and 0.88 days (21.12 hours) at pH 9 respectively at 25° C. Major degradates were 2,2-
dichloroacetic acid (DCA), 2,2-dichloroacetaldehyde (DAA), des-methyl dichlorvos, and
glyoxylic acid. The guideline requirement for hydrolysis (163-2) is fulfilled (MRID 41723101).
Aqueous photolysis found that dichlorvos dissipated with half-lives 10.2 days in the irradiated
samples and 8.9 days in the dark control samples. Major degradates of dichlorvos in the Day 15
irradiated samples were 2,2-dichloroacetaldehyde (32.7%) and des-methyl dichlorvos (17.8%) of
the applied radiocarbon. Under dark condition, major degradates were 2,2-
dichloroacetaldehyde (42.0%) and desmethyl dichlorvos (16.3%). The guideline requirement for
photodegradation in water (163-2) is fulfilled (MRID 43326601).
Soil photolysis study showed that dichlorvos photodegraded with a half-life of 15.5 hours on a
sandy loam soil surface (pH 7). Dichlorvos had a half life of 16.5 hours when incubated in
darkness under similar conditions. After 72 hours of irradiation, 97% of the applied dichlorvos
had dissipated from the soil by a combination of degradation and volatilization. Degradates
identified in the irradiated soil were 2,2-dichloroacetic acid (26.6%) and 2,2-dichloroethanol
(4.4%). The only degradation product formed under dark condition was 2,2-dichloroacetic acid
of which 34% volatilized and 54.2% remained in soil. The guideline requirement for
photodegradation on soil (161-3) is fulfilled (MRID 43642501).
Dichlorvos metabolized with a half-life of 10.18 hours in a sandy loam soil (pH 6.2) incubated in
the dark under aerobic conditions. The major non-volatile metabolites formed during this
aerobic metabolism were 2,2-dichloroacetaldehyde and dichloroethanol (each accounted for less
than 12% of the initially applied radioactivity). 2,2-dichloroacetic acid accounted for up to 62.8%
of the initially applied radioactivity at 48 hours post-treatment. The only volatile metabolite
was 14 CO2 which accounted for 60.8% of the initially applied radiocarbon at 360 hours post-
treatment. The guideline requirement for aerobic soil metabolism (162-1) is fulfilled (MRID
41723102).
Dichlorvos metabolized with half-life of 6.3 days in sandy loam soil (pH 6.8) that was incubated
in the dark under anaerobic conditions (flooding plus nitrogen atmosphere) at 25° C for up to 60
days . The major nonvolatile degradates in the water phase and soil extracts were 2,2-
dichloroaceticacid (which accounted for up to 50.9% of the applied radioactivity at day 60), 2,2-
dichloroacetaldehyde (which accounted for up to 12.6% of the applied radioactivity at day 5),
24
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and 2,2-dichloroethanol (which accounted for up to 24.7% at day 60.0). The guideline
requirement for anerobic soil metabolism (162-2) is fulfilled (MRID 43835701).
Terrestrial field dissipation studies (164-1) showed that dichlorvos dissipated too rapidly within
the time taken to perform the sampling process. Dichlorvos degraded rapidly to 2,2-
dichloroacetic acid (DCA), which was detected only in the 0-4 inch soil. There was no dichlorvos
or 2,2-dichloroethanol (DCE) detected at any soil depth. DCA residues were detected in the soil
below 0-4 inches at levels similar to that of the control samples. A good mass balance of DDVP
was reported in this study through air filters and cellulose cards trapping. The guideline
requirement for terrestrial field dissipation (164-1) is fulfilled (MRIDs 44297701 and 44386701).
b. Mobility
Leaching/adsorption/desorption study indicated that due to the rapid degradation of dichlorvos
an equilibration time for dichlorvos between the soil and solution phases could not be
established. The high water solubility (10 x 10 3 ppm) and low organic carbon coefficient (Koc =
36.9 cm 3 /g) for dichlorvos indicate its high potential for leaching. The Koc calculation was
based on Kd values reported in an acceptable soil TLC (MRID # 41354105). DDVP is not,
however, persistent enough in sand to trigger any studies to assess its potential for leaching to
ground water. Therefore, no groundwater concern is anticipated for dichlorvos. Under field
conditions, dichlorvos dissipated rapidly through volatilization and thus, residues of dichlorvos
are not likely to contaminate groundwater by leaching. The guideline requirement for leaching
and adsorption/desorption (163-1) is fulfilled (MRID 41723103, 40034904, 41354105).
2. Aquatic Resource Exposure Assessment
Aquatic Organism Exposure Modeling
Dichlorvos residues can be present in water as a result of use of three pesticides: dichlorvos,
naled, and trichlorfon. Dichlorvos is a degradate of naled and trichlorfon. This assessment
discusses the potential for dichlorvos to contaminate water from the use of dichlorvos as the sole
active ingredient. Although these estimates are only for dichlorvos, there are several dichlorvos
degradates that have been identified including desmethyl dichlorvos (methyl O-(2,2-
dichlorovinyl) phosphate), dichlorethanol, and dichloroacetic acid; this latter degradate is very
mobile. Turf and general outdoor (flying insect) were the sites of interest. Concentrations were
calculated based on a maximum application rate of 0.2 Ib a.i/A for both sites.
Turf Scenario
Tier II Estimated Environmental Concentrations (EECs) for dichlorvos for the turf scenarios
were estimated using EFED's aquatic models PRZM-EXAMS (Exposure Analysis Modeling
System). PRZM is used to simulate pesticide transport as a result of runoff and erosion from an
lo-ha agricultural field, and EXAMS considers environmental fate and transport of pesticides in
surface water and predicts EECs in a standard pond (io,ooo-m2 pond, 2-m deep), with the
assumption that the small field is cropped at 100%. Calculations are carried out with the linkage
program shell - PE4VOi.pl - which incorporates the standard scenarios developed by EFED.
Additional information on these models can be found at:
http://www.epa.gov/oppefedi/models/water/index.htm.and in Appendix C. Representative
inputs for the model are shown in Table 4, and results are tabulated in Table 5. For a more
detailed explanation and outputs from this model, see Appendix C.
25
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Table 4. PRZM/EXAMS Input parameters
Input Parameter
PC Code
Molecular weught (g/mole)
Water Solubility
Hydrolysis half-life (pH 7)
Aerobic Soil Half-life
Photolysis half -life
Aerobic Aquatic Metabolism Half- Life
Kd
Soil Organic Carbon Partitioning (Koc)
(i/kg)
Organic Carbon Percentage
Use
Application Rate (Ib ai/A)
Application Date
Application Method
Number of Applications/Year
Value
84001
220.9
10000 ppm
5.2 days
0.42 days
10.2 days
No data
0.3
37
0.812
Turf
O.2
May 15
Ground Spray
turf at one application
turf at four applications (at so-day retreatment interval)
! Parameters were selected in accordance with the Proposed Interim Guidance for Input Values document, dated April 6, 2000.
Table 5. Estimated Environmental Concentrations (EECs) For Aquatic Exposure
Based on PRZM/EXAMS
Site
Turf (FL)
Turf(FL)
Applicatio
n Method
ground
ground
Applicatio
n Rate
(Ibs ai/A)
O.2
O.2
No. Apps./
Interval
Between
Apps.
lapp.
4 apps at 30
Initial
(PEAK)
EEC (ppb)
O.112
O.169
21-day
average
EEC (ppb)
0.037
0.061
6o-day
average
EEC (ppb)
0.014
0.036
26
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Turf (PA)
Turf (PA)
ground
ground
0.2
0.2
day interval
lapp.
4 apps at 30
day interval
O.112
0.147
0.037
0.054
0.014
0.034
Less than 20% (4% -17%) of Estimated Environmental Concentrations (EEC) reached aquatic
media were as contribution of spray drift; the remaining (>8o%) is due to runoff (Table 5).
Flying Insect Scenario
For the flying insect (including adult mosquitoes) use, EFED currently has no models that would
be appropriate for modeling EECs. PRZM/EXAMS and the GENEEC model are inappropriate
to use. It is likely EECs found in surface water from treatment for flying insects (including adult
mosquitoes) would likely be lower than EECs from treatment to turf, since the treatment area
would likely be less. Since the applications for flying insect control are ground applications
(e.g., back-pack sprayers or truck-mounted sprayers) using coarse sprays directed to the
vegetation (no fogging or misting), EFED cannot perform a quantitative assessment.
Granular Bait Scenario
For the granular bait scenario in animal premise areas, it is unlikely that aquatic organisms will be directly
exposed, therefore that pathway is not evaluated and a quantitative assessment is not performed.
3. Terrestrial Organism Exposure Modeling
Terrestrial wildlife exposure estimates are typically calculated for birds and mammals,
emphasizing a dietary exposure route for uptake of the pesticide. For obtaining EECs for acute
exposure from multiple applications and chronic exposure from both single and multiple
applications of liquid dichlorvos and granular bait products, the T-REX v 1.1 (U.S. EPA. 2OO4b)
program was used.
For the liquid spray application to turf, the maximum application rate modeled was 0.2 Ib ai/A.
One application and four applications (with 30 day application interval) were modeled for turf.
The rationale for choosing four applications for turf was based on information received from
BEAD indicating a worst-case scenario of four applications.
For liquid spray application for flying insects (including adult mosquitoes), the maximum
application rate modeled was 0.2 Ib ai/A. for 75 applications per year. The rationale for choosing
weekly applications for mosquito control was based on information received from BEAD
indicating a worst case scenario for adult mosquito control would probably be around 75
applications to a given site over a year period.
For the granular bait scenario, the maximum application rate modeled was o.i Ib ai/A. A single
application and a worse case scenario of 120 applications per year were modeled. The rationale
for choosing 120 applications per year is based on label specifications bearing directions to
reapply every 3 to 5 days until insect control is achieved.
A foliar dissipation half-life of 0.0875 days was used for liquid spray application scenarios based
on Dichlorvos Total Residue in Turf data on studies conducted in Florida and Canada (MRID
No. 44610501, and 44794901 respectively).
27
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Terrestrial EECs were calculated using T-REX v 1.1 (U.S. EPA. 2OO4b) and are shown in Tables
6, 7, and 8.
Table 6. Estimated Environmental Concentrations for Modeled Scenarios for Turf
(1 application and 4 applications)
Upper Bound Kenega Value
for Turf (i application)
(ppm)
Upper Bound Kenega Value
for Turf (4 applications
with 30 day application
interval) (ppm)
Food Item
Short Grass
Tall Grass
Broadleaf plants/sm Insects
Fruits/pods/seeds/lg insects
19.30
8.84
10.85
1.21
19.30
8.84
10.85
1.21
Predicted maximum residues are based on Hoerger and Kenaga (1972) as modified by Fletcher et al. (1994).
Table 7. Estimated Environmental Concentrations for Modeled Scenarios for
Flying Insects ( 75 applications with 5 day application interval)
Upper Bound Kenega Value for Flying
Insects (75 applications with 5 day
application interval) (ppm)
Food Item
Short Grass
Tall Grass
Broadleaf plants/sm Insects
Fruits/pods/seeds/lg insects
19.30
8.84
10.85
1.21
Predicted maximum residues are based on Hoerger and Kenaga (1972) as modified by Fletcher et al. (1994).
Table 8. Estimated Environmental Concentrations for Modeled Scenarios for Bait (
1 application)
Crop
Bait
(single application)
Application method
Broadcast
Application
rate
(Ibs ai/A)3
0.1
% Unincorporated
100
EEC
(mg ai/ft2)
0.08
28
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B. Ecological Effects Characterization
In screening-level ecological risk assessments, effects characterization describes the types of
effects a pesticide can produce in an organism or plant. This characterization is based on
registrant-submitted studies that describe acute and chronic toxicity information for various
aquatic and terrestrial animals and plants. In addition, other sources of information, including
the Ecological Incident Information System (EIIS), are conducted to further refine the
characterization of potential ecological effects.
Toxicity testing reported in this section does not represent all species of birds, mammals, or
aquatic organisms. Only a few surrogate species for both freshwater fish and birds are used to
represent all freshwater fish (2000+) and bird (680+) species in the United States. Mammalian
acute studies are usually limited to Norway or New Zealand rat or the house mouse.
Estuarine/marine testing is usually limited to a crustacean, a mollusk, and a fish. Also, neither
reptiles nor amphibians are tested. The risk assessment assumes that avian and reptilian
toxicities are similar. The same assumption is used for fish and amphibians.
i. Evaluation of Aquatic Ecotoxicitv Studies
a. Toxicity to Freshwater Animals
Freshwater Fish, Acute
Two freshwater fish toxicity studies using the TGAI are required for all pesticides to establish
their toxicity to fish. TEP testing was required on the 1987 Standard to support the mosquito
adulticide/larvacide use pattern. The preferred species are rainbow trout (a coldwater fish) and
bluegill sunfish (a warmwater fish). Results of these studies are tabulated below in Table 9.
Table 9. Acute Toxicity Endpoints for Freshwater Fish
Species
Rainbow trout
(Oncorhynchus
mykiss)
Rainbow trout
(Oncorhynchus
mykiss)
Lake trout
(Salvelinus
namaycush)
Bluegill sunfish
(Lepomis
macrochirus)
Bluegill sunfish
(Lepomis
%ai
100
42(EC)
100
100
98
42(EC)
96-hour LC5O
(ppb)
500 (24 hours
only)
320 (=750 for
formulated
product)
187
183
869
1860 (=4300 for
formulated
Toxicity
Category
Highly toxic
Highly toxic for
formulated
product
Highly toxic
Highly toxic
Highly toxic
Moderately
toxic for the
MRID
Author/Year
40098001
(Mayer &
Ellersieck 1986)
43284702
(Jones 1994)
40098001
(Mayer &
Ellersieck 1986)
40094602
(Johnson 1980)
43284701
(Jones 1994)
Study
Classification
Supplemental
Supplemental
Supplemental
Core
Supplemental
29
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macrochirus)
product)
formulated
product
There are no core studies available for the rainbow trout. Mayer and Ellersieck (40098001) cite
a 24-hour LC5O of 500 ppb for rainbow trout. The two 96-hour lake trout LCsos of 187 ppb and
183 ppb showed 24-hour LCsos of 486 ppb and 667 ppb, respectively. The studies are classified
"supplemental" because they were not performed using standard test species. Mayer and
Ellersieck state (p. 9) the correlation coefficient (r) between rainbow and lake trout for acute
static LCsos is 0.99. Since the results are comparable within the limits of the toxic category (i.e.,
highly toxic), the lake trout studies will be substituted for the rainbow trout study. Since the
LCsos are less than i ppm, dichlorvos is categorized as highly toxic to freshwater fish on an
acute basis.
Two studies were performed with an emulsifiable concentrate formulation (42.3% ai). Since the
TEP and TGAI demonstrated similar toxicities (on an active ingredient basis), it does not appear
inerts in the EC formulation are toxic.
Freshwater Fish, Chronic
A freshwater fish early life stage toxicity test was required in the 1987 Dichlorvos Registration
Standard to support the mosquito larvicide use. Results of this test are provided in Table 10.
Table 10. Chronic Toxicity Endpoints for Freshwater Fish
Species/Stu
dy Duration
Rainbow trout
(Oncorhynchu
s mykiss)
Early Life-
Stage (Flow-
through)
%ai
98.0
NOEC/LOAEL
(ppb)
5.2/10.1
MATC1
(ppb)
7.2
Endpoints
Affected
Larval
survival
MRID
Author/Year
43788001
Davis 1995)
Study
Classificatio
n
Core
1 defined as the geometric mean of the NOEC and LOAEL.
Freshwater Invertebrates, Acute
A freshwater aquatic invertebrate toxicity study using the TGAI is required to establish the
toxicity of dichlorvos to aquatic invertebrates. TEP testing was required on the 1987 Standard to
support the mosquito adulticide/larvicide use pattern. The preferred species is Daphnia
magna. Results are presented in Table 11.
Table ll. Acute Toxicity Endpoints for Freshwater Invertebrates
Species
Waterflea
(Daphnia pulex)
Waterflea
(Simocephalus
%ai
100
100
48-hour ECso
(ppb)
0.07
0.28
Toxicity
Category
Very highly
toxic
Very highly
toxic
MRID
Author/Year
40098001
(Mayer &
Ellersieck 1986)
40098001
(Mayer &
Study
Classification
Core
Supplemental
30
-------
serrulatus)
Waterflea
(Simocephalus
serrulatus)
100
0.26
Very highly
toxic
Ellersieck 1986)
40098001
(Mayer &
Ellersieck 1986)
Supplemental
Since the EC5O values are less than 100 ppb, dichlorvos is categorized as very highly toxic to
aquatic invertebrates on an acute basis. A study with the TEP was not submitted.
Freshwater Invertebrates, Chronic
A freshwater aquatic invertebrate life-cycle study was required in the 1987 Dichlorvos
Registration Standard to support the mosquito larvacide use.
Table 12. Chronic Toxicity Endpoints for Freshwater Invertebrates
Species
Waterflea
(Daphnia
magna)
%ai
98.0
21-day
NOEC/LOAEL
(ppb)
0.0058/0.0122
MATC1
(ppb)
0.0084
Endpoints
Affected
Egg production
and growth
(length and
weight)
MRID
Author/Yea
r
43890301
(Ward and
Davis 1995)
Study
Classificatio
n
Core
1 defined as the geometric mean of the NOEC and LOAEL.
b. Toxicity to Estuarine and Marine Animals
Estuarine and Marine Fish, Acute
Acute toxicity studies with estuarine/marine fish using both TGAI and TEP were required in the
1987 Registration Standard to support the mosquito larvicide use.
Table 13. Acute Toxicity Endpoints for Estuarine and Marine Fish
Species
Sheepshead
minnow
(Cyprinodon
variegatus)
Sheepshead
minnow
(Cyprinodon
variegatus)
%ai
98
42.39
96-hour LC5O
(ppb)
7350
6146 (=14500
for formulated
product)
Toxicity
Category
Moderately
toxic
Moderately
toxic for
formulated
product
MRID
Author/Year
43571403
(Jones and
Davis 1994)
43571406
(Jones and
Davis 1994)
Study
Classification
Core
Core
Since the LCso falls in the range 1000 to 10000 ppb ai, dichlorvos is categorized as moderately
toxic to estuarine/marine fish on an acute basis. One study was performed with an emulsifiable
concentrate formulation (42.3% ai). Since the TEP and TGAI demonstrated similar toxicities
(on an active ingredient basis), the inerts in the EC formulation are probably not toxic.
Estuarine and Marine Fish, Chronic
31
-------
An estuarine fish early life stage toxicity test was required in the 1987 Dichlorvos Registration
Standard to support the mosquito larvacide use.
Table 14. Chronic Toxicity Endpoints for Estuarine and Marine Fish
Species/Stu
dy Duration
Sheepshead
Minnow
(Cyprinodon
variegatus)
%ai
98
NOEC/LOAEL
(ppb)
960/1840
MATC1
(ppb)
1330
Endpoints
Affected
Survival and
length
MRID
Author/Year
43790401 (Ward
and Davis 1995)
Study
Classificatio
n
Core
1 defined as the geometric mean of the NOEC and LOAEL.
Estuarine and Marine Invertebrates, Acute
Acute toxicity studies with estuarine/marine invertebrates (mysid and eastern oyster) using
both TGAI and TEP were required in the 1987 Registration Standard to support the mosquito
larvacide use.
Table 15. Acute Toxicity Endpoints for Estuarine and Marine Invertebrates
Species/Static
or Flow-
through
Eastern oyster
(shell
deposition)
(Crassostrea
virginica)
Eastern oyster
(shell
deposition)
(Crassostrea
virginica)
Mysid
(Aniericamysis
bahia)
Mysid
(Aniericamysis
bahia)
%ai.
98
42 (EC)
98
42 (EC)
96-hour LC5O
/EC50 (ppb)
89100
920 (2180 for
formulated
product)
19.1
18.7(44.0 for
formulated
product)
Toxicity
Category
Slightly toxic
Moderately
toxic for
formulated
product
Very highly
toxic
Very highly
toxic for
formulated
product
MRID
Author/Year
43571404
(Jones & Davis
1994)
43571407
(Jones & Davis
1994)
43571405
(Jones & Davis
1994)
43571408
(Jones & Davis
1994)
Study
Classification
Core
Supplemental
Core
Core
Since the LC5O for the most sensitive species (mysid) is less than 1000 ppb, dichlorvos is
categorized as very highly toxic to estuarine/marine animals on an acute basis. Two studies
were performed with an emulsifiable concentrate formulation (42.3% ai). Based on similarity
between toxicity of the TGAI and TEP for the mysid, it does not appear that the inerts in the
formulation are toxic. However, in the case of the oyster, a large discrepancy exists, with toxicity
of the EC formulation (on an active ingredient basis) almost lo-fold greater than that of the
TGAI. No explanation for this was provided by the performing laboratory or registrant. Since
both the TGAI and TEP studies were scientifically sound, they do not have to be repeated.
32
-------
Estuarine and Marine Invertebrate, Chronic
An estuarine aquatic invertebrate life-cycle study was required in the 1987 Dichlorvos
Registration Standard to support the mosquito larvicide use.
Table 16. Chronic Toxicity Endpoints for Estuarine and Marine Invertebrates
Species/(St
atic
Renewal or
Flow-
through)
Mysid
(Americamys
is bahia)
%ai
98
21-day
NOEC/LOA
EL (ppb)
1.48/3.25
MATC1
(ppb)
2.19
Endpoints
Affected
Weight and
length
MRID
Author/Yea
r
43854301
(Ward and
Davis 1996)
Study
Classificati
on
Core
1 defined as the geometric mean of the NOEC and LOAEL.
c. Toxidty to Aquatic Plants
Currently, terrestrial and aquatic plant studies are not required for pesticides other than
herbicides, except on a case-by-case basis (e.g.,, labeling bears phytotoxicity warnings, incident
data or literature that demonstrate phytotoxicity). Plant testing is not required for dichlorvos.
Supplemental data are available (F.L. Mayer, 1986; 40228401) showing 48 hour ECso values of
>iooooo ppb for green algae, 14000 ppb for algae (the species were not given) and 17000-
28000 ppb for marine diatom.
Table 17. Toxicity Endpoints for Aquatic Plants
Species
Green algae
Algae (unknown species)
Marine diatom
Endpoint
48hrEC50>100000ppb
48hrEC50= 14000 ppb
48 hr EC50 = 17000 - 28000 ppb
MRID/Reference
MRTD No. 40228401 (U.S. EPA, F.L.
Mayer 1986)
MRID No. 40228401 (U.S. EPA, F.L.
Mayer 1986)
MRID No. 40228401 (U.S. EPA, F.L.
Mayer 1986)
2. Evaluation of Terrestrial Ecotoxicity Studies
a. Toxicity to Terrestrial Animals
Birds. Acute and Subacute
An acute oral toxicity study using the technical grade of the active ingredient (TGAI) is required to establish the toxicity of
dichlorvos to birds. The preferred test species is either mallard duck (a waterfowl) or bobwhite quail (an upland gamebird).
Results of acute oral testing are tabulated in Table 18.
Table 18. Toxicity Endpoints for Avian Acute Oral
Species
Pheasant
%a.i.
93
LDso (mg/kg)
H-3
Toxicity
Category
Highly toxic
MRID No.
Author/Year
00160000
Study
Classification
Core
33
-------
(Phasianus
colchicus)
Northern
bobwhite quail
(Colinus
virginianus)
Mallard duck
(Anas
platyrhynchos)
96.5
93
8.8
7.78
Very highly
toxic
Very highly
toxic
(Hudson et
01.1984)
40818301
(Grimes and
Aber 1988)
00160000
(Hudson et
01.1984)
Core
Core
Since the LDso of the most sensitive species (mallard) is less than 10 mg/kg, dichlorvos is
categorized as being very highly toxic to avian species on an acute oral basis.
Two subacute dietary studies using the TGAI are required to establish the toxicity of dichlorvos
to birds. The preferred test species are mallard duck and bobwhite quail. Results of subacute
testing are in Table 19.
Table 19. Avian Subacute Dietary Toxicity Endpoints
Species
Pheasant
(Phasianus
colchicus)
Mallard duck
(Anas
platyrhynchos)
Mallard duck
(Anas
platyrhynchos)
%a.i.
94.8
94.8
94.8
5-Day LC5O
(ppm)l
568
1317
(5 -day old test
species)
>5OOO
(l6-day old test
species)
Toxicity
Category
Moderately
toxic
Slightly toxic
Practically non-
toxic
MRID No.
Author/Year
00022923
(Hill etal 1975)
00022923
(Hill etal 1975)
00022923
(Hill etal 1975)
Study
Classification
Core
Core
Core
Since the LCso of the most sensitive species (pheasant) falls in the range of 501 to 1000 ppm,
dichlorvos is categorized as being moderately toxic to avian species on a subacute dietary basis.
Birds, Chronic
Avian reproduction studies were required in EPA's 1987 Dichlorvos Standard to support the
registered terrestrial and aquatic non-food use patterns. Results of the submitted tests are
tabulated below.
Table 20. Chronic Endpoints for Avian Reproduction
Species
Northern
bobwhite quail
(Colinus
virginianus)
%a.i.
98
NOEC/LOAEL
(ppm)
30/100
LOAEL
Endpoints
eggs laid, viable
embryos and
live three week
embryos,
normal
hatchlings,
fourteen day old
MRID No.
Author/Year
43981701
(Cameron 1996)
Study
Classification
Core
34
-------
Mallard duck
(Anas
platyrhynchos)
98
5/15
survivors
eggshell
thickness, eggs
laid, viable
embryos, live
three week
embryos
44233401
(Redgrave and
Mansell 1997)
Core
Based on (i) no adverse effects noted at the i and 5 ppm treatment levels, and (2) statistically
significant reductions in eggshell thickness, numbers of eggs laid, numbers of eggs set, numbers
of viable embryos, and numbers of live three week embryos at the 15 ppm treatment level, the
NOEC for mallards exposed to dichlorvos in the diet for 20 weeks is 5 ppm and the LOAEL is 15
ppm. Based on (i) no adverse effects noted at the 12 and 30 ppm treatment levels, and
statistically significant reductions in fourteen day old survivor weight, terminal male and female
body weight, numbers of eggs laid, numbers of viable embryos, numbers of live three week
embryos, and numbers of normal hatchlings at the 100 ppm treatment level, the NOEC for
bobwhite exposed to dichlorvos in the diet for 20 weeks is 30 ppm and the LOAEL is 100 ppm.
There is some scientific literature on related organ ophosphates showing adverse reproductive
effects to birds from short-term exposures. These effects include reduced egg production within
days after initiation of dietary exposure, and effects on eggshell quality, incubation and brood
rearing behavior (Bennett and Ganio 1991).
Mammals. Acute and Chronic
Wild mammal testing is required on a case-by-case basis, depending on the results of lower tier
laboratory mammalian studies, intended use pattern and pertinent environmental fate
characteristics. In most cases, rat or mouse toxicity values obtained from the Agency's Health
Effects Division (HED) substitute for wild mammal testing. Dichlorvos human toxicity
endpoints for dietary exposure and occupational/residential exposure are reported in HED's
document entitled: Dichlorvos: Hazards Identification Committee Report (G. Ghali to S. Lewis
dated 12/19/97). The mammalian toxicity endpoint value used for ecological risk assessment
purpose is reported below.
Table 21. Mammalian Toxicity Endpoints
Species/
Study
Duration
laboratory rat
(Rattus
norvegicus)
laboratory rat
(Rattus
norvegicus)
laboratory rat
(Rattus
norvegicus)
%ai
Dichlorvos
technical
96 unspecified
Dichlorvos
technical
% unspecified
Dichlorvos
technical
% unspecified
Test Type
acute oral
acute inhalation
acute dermal
Toxicity Value
LDso=8o
mg/kg (M)
LDso=56
mg/kg (F)
LCso > 0.218
mg/L
LDso = 107
mg/kg (M)
LDso = 75
mg/kg (F)
Affected
Endpoints
MRID
0005467
00137239
0005467
35
-------
laboratory rat
(Rattus
norvegicus)
98.3%
2 generation
reproduction
NOEC = 20
ppm
fertility, pup
weight
Ace # 010174,
MRID
42483901
Dichlorvos is categorized moderately toxic to small mammals on an acute oral basis and highly
toxic on an acute dermal basis. In of a 2-generation reproduction study using Sprague-Dawley
rats (where dichlorvos was administered in the drinking water), the reproductive toxicity NOEL
was found to be 20 ppm based on reduced dams bearing litters, fertility index, pregnancy index,
and pup weight on day-4.
Insects
Results of a honey bee acute contact study using the TGAI are tabulated below.
Table 22. Nontarget Insect Acute Contact Toxicity
Species
Honey bee (Apis
mellifera)
%ai
technical %
unspecified
LDso (ug/bee)
0-495
Toxicity
Category
highly toxic
MRID
Author/Year
00036935
(Atkins et al
1975)
Study
Classification
Core
An analysis of the results indicate that dichlorvos is categorized as being highly toxic to bees on
an acute contact basis.
A study on the toxicity of residues on foliage to honey bees (guideline 141-2) using the typical
end-use product was required for dichlorvos in the 1987 Standard to support the terrestrial non-
food and domestic outdoor sites. The study submitted showed residues of dichlorvos 4E applied
at 0.5 Ib ai/A were practically nontoxic to honey bees at three hours posttreatment.
b.
Toxicity to Terrestrial Plants
Currently, terrestrial and aquatic plant studies are not required for pesticides other than herbicides, except on a case-by-case basis
(e.g. „ labeling bears phytotoxicity warnings, incident data or literature that demonstrate phytotoxicity). Plant testing is not
required for dichlorvos.
Table 23 summarizes the most sensitive ecological toxicity endpoints for aquatic and terrestrial
organisms. Discussions of the effects of dichlorvos on aquatic and terrestrial taxonomic groups
are presented below.
Table 23. Toxicity Endpoints Used in the Risk Assessment
Toxicity Test/Species
Avian acute oral/ Mallard duck
Avian subacute dietary/Pheasant
Avian reproduction /Mallard duck
Mammalian acute oral/ rat
Toxicity Endpoint
LD50 = 7-78 mg/kg
LC50 = 568 mg/kg
NOEC = 5 ppm
LD50 = 56 mg/kg (female)
MRID Number and References
MRID # 00160000 (Hudson et
01.1984)
MRID # 00022923 (Hill et al 1975)
MRID # 44233401 (Redgrave and
Mansell 1997)
MRID # 0005467
36
-------
Toxicity Test/Species
Mammalian chronic (reproduction)/rat
Honey bee acute (acute contact basis)
Terrestrial Plants
Fish (freshwater) acute/ Lake trout
Fish (freshwater) chronic/Rainbow trout
Fish (estuarine) acute/ Sheepshead minnow
Fish (estuarine) chronic/Sheepshead
minnow
Invertebrate (freshwater) acute/Daphnia
pulex
Invertebrate (freshwater) chronic/ Daphnia
magna
Invertebrate (estuarine) acute/Mysid shrimp
Invertebrate (estuarine) chronic/ Mysid
shrimp
Aquatic plants/ Algae
Toxicity Endpoint
NOEC = 20 ppm
LD50 = 0.495 ug/bee
N/A
LC50= 183ppb
NOAEC = 5.2 ppb
LC50 = 7350 ppb
NOAEC = 960 ppb
EC50 = 0.07 ppb
NOAEC = 0.0058 ppb
LC50= 19.1 ppb
NOAEC =1.48 ppb
EC50 = 14000 ppb
MRID Number and References
MRID #42483901
MRID # 00036935 (Atkins et al
1975)
MRID # 40098001 (Mayer &
Ellersieck 1986)
MRID # 43788001 (Davis 1995)
MRID # 43571403 (Jones and Davis
1994)
MRID # 43790401 (Ward and Davis
1995)
MRID # 40098001 (Mayer &
Ellersieck 1986)
MRID # 43890301 (Ward and Davis
1995)
MRID # 43571405 (Jones & Davis
1994)
MRID # 43854301 (Ward and Davis
1996)
MRID # 40228401 (F.L. Mayer,
1986)
3. Terrestrial Field Testing
No terrestrial field testing studies are available for dichlorvos.
4. Use of the Probit Slope Response Relationship
The Agency uses the probit dose response relationship as a tool for providing additional
information on the endangered and threatened animal species acute levels of concern (LOG).
The acute listed species LOCs of o.i and 0.05 are used for terrestrial and aquatic animals,
respectively. As part of the risk characterization, an interpretation of acute LOCs for listed
species is discussed. This interpretation is presented in terms of the chance of an individual
event (i.e., mortality or immobilization) should exposure at the estimated environmental
concentration actually occur for a species with sensitivity to dichlorvos on par with the acute
toxicity endpoint selected for RQ calculation. To accomplish this interpretation, the Agency
uses the slope of the dose response relationship available from the toxicity study used to
establish the acute toxicity measurement endpoints for each taxonomic group. The individual
effects probability associated with the LOCs is based on the mean estimate of the slope and an
assumption of a probit dose response relationship. In addition to a single effects probability
estimate based on the mean, upper and lower estimates of the effects probability are also
provided to account for variance in the slope. The upper and lower bounds of the effects
probability are based on available information on the 95% confidence interval of the slope. A
statement regarding the confidence in the applicability of the assumed probit dose response
37
-------
relationship for predicting individual event probabilities is also included. Studies with good
probit fit characteristics (i.e., statistically appropriate for the data set) are associated with a high
degree of confidence. Conversely, a low degree of confidence is associated with data from studies
that do not statistically support a probit dose response relationship. In addition, confidence in
the data set maybe reduced by high variance in the slope (i.e., large 95% confidence intervals),
despite good probit fit characteristics.
Individual effect probabilities are calculated based on an Excel spreadsheet tool IECVi.1
(Individual Effect Chance Model Version 1.1) developed by Ed Odenkirchen of the U.S. EPA,
OPP, Environmental Fate and Effects Division (June 22, 2004). The model allows for such
calculations by entering the mean slope estimate (and the 95% confidence bounds of that
estimate) as the slope parameter for the spreadsheet. In addition, the LOG (o.i for terrestrial
animals and 0.05 for aquatic animals) is entered as the desired threshold.
5. Incident Data Review
There have been 6 incidents related to dichlorvos reported in the Environmental Incident Information System (EDS) database
(reported to the Agency from 1991 to 2002). Of these 6 incidents, 3 were of undetermined use, and 3 were registered uses.
Avian Incidences
Five of the incidences were terrestrial, with 4 related to bird kills. One incident involved an avian outdoor exposure from a site
(apples) for which dichlorvos was never registered. Two bluebird chicks died in their nest box in the town of
Redhook New York. The nest was within 300 yards of an apple orchard. The cause of death was
dichlorvos poisoning (Reported by: Wildlife Pathology Unit, NY State Dept. Of Environmental
Conservation Annual Report 1/1/94 -5/3/95- Ward Stone, Wildlife Pathologist. 1994 incident).
Another incident involved a registered use of dichlorvos crystals in treated feed than resulted in
8 mallard ducks dying in an agricultural area. The last two incidents involved the use of
dichlorvos in the home residence resulting in canary deaths (6 total deaths).
Mammalian Incidences
There is one mammalian incidence reported involving indoor exposure to animals. Amvac
Chemical Corp. (Letter to Agency Dated 7/3/95) reported potential adverse effects exposure
relating to a pest strip in which several exotic and wild native and non-native animals that
included skunks and several fennis foxes (native of Egypt) were in a room roughly 4000 cubic
feet. The room had a pest strip placed in it 3-4 days previous to control insects. The pest strip
was labeled as covering 1000 cubic feet. Four fennis fox pups died. A veterinarian treated three
other pups with atropine; two recovered. The foxes were the only animals that recovered. Two
of the animals recovered after treating with atropine, indicating it is possible that the cause of
poisoning was exposure to dichlorvos fumes.
Aquatic Incidence
One aquatic incident of undetermined use in Tennessee involving fish kills was reported
affecting 379 organisms (species undetermined). No residue analysis was conducted.
Currently, no systematic or reliable mechanism exists for the accurate monitoring and reporting
of wildlife kill incidents to the Agency. Moreover, before a pesticide incident can be reported or
investigated, the dead animals must first be found. In the absence of monitoring following
pesticide applications, kills are not likely to be noticed in agro-environments which are generally
38
-------
away from human activity. Even if onlookers are present, dead wildlife species, particularly
small song birds and mammals, are easily overlooked, even by experienced and highly motivated
observers. Even in sparse vegetative cover, wildlife carcass detection is difficult and as vegetative
cover increases the difficulty in detection is exacerbated. Under some circumstances intoxicated
animals may seek heavy cover before dying which decreases the probability of detection further.
Poisoned birds may fly from the sites, succumbing outside of the area or scavengers may remove
carcasses before they can be observed, significantly reducing the chance of detection.
Balcomb (1986) reported that songbird carcasses removal rate ranged from 62 to 92 percent in
the first 24 hours following placement, with a mean loss at 24 hours of 75% (S.D. = 12.4).
Overall, by the end of the 5-day monitoring period, 72 of the 78 carcasses had been removed by
scavengers. In addition, the number of birds per acre alone, not considering these other factors,
makes detection of kills difficult. Best (1990) reported from 0.57 live birds per acre in the center
to 2.8 live birds per acres in the perimeter of corn fields in Iowa and Illinois. Even if all the birds
in a field were killed and remained on the field, the probability of observing carcasses,
particularly when not systematically searching, at these densities, is not high. Research has
shown that even when intense systematic searches are conducted by highly trained individuals
for placed carcasses in agro-environments, recovery rates rarely exceed 50 percent (Madrigal et
aZ.1996).
Even if dead animals are observed, they might not be reported to the Agency. Persons unfamiliar
with the toxicity of pesticides to non-target species may fail to associate the finding with the
pesticide application, especially if the two events are separated by several days and only a few
birds are observed dead. Even if the association is made, the observer must be aware or have
the motivation to find out where to report the incident. Therefore, the reporting of a few dead
birds associated with the use of a chemical is believed to provide evidence that substantial
effects may be occurring.
6. RISK CHARACTERIZATION
Risk characterization is the integration of exposure and effects characterization to determine the
ecological risk from the use of dichlorvos and the likelihood of effects on aquatic life, wildlife,
and plants based on varying pesticide-use scenarios. The risk characterization provides an
estimation and a description of the risk; articulates risk assessment assumptions, limitations,
and uncertainties; synthesizes an overall conclusion; and provides the risk managers with
information to make regulatory decisions.
A. Risk Estimation - Integration of Exposure and Effects Data
Results of the exposure and toxicity effects data are used to evaluate the likelihood of adverse ecological effects on non-target
species. For the assessment of dichlorvos risk, the risk quotient (RQ) method is used to compare exposure and measured toxicity
values. Estimated environmental concentrations (EECs) are divided by acute and chronic toxicity values. The RQs are compared
to the Agency's levels of concern (LOCs). These LOCs are the Agency's interpretive policy and are used to analyze potential
risk to non-target organisms and assess the need to consider regulatory action. These criteria are used to indicate when a
pesticide's directed label use has the potential to cause adverse effects on non-target organisms. Table 2 of this document
summarizes the LOCs used in this risk assessment.
1. Non-target Aquatic Animals
a. Freshwater Fish
39
-------
An analysis of the results show that for single and multiple applications of dichlorvos to turf at
the maximum application rate of 0.2 Ib ai/A, no freshwater fish acute or chronic LOCs are
exceeded. Freshwater fish risk quotients are listed in Table 24.
Table 24. Acute and chronic risk quotients for freshwater fish for turf scenarios (Risk Quotients
for Freshwater Fish Based On a Lake Trout LCso of 183 ppb and a Rainbow Trout NOAEL of 5.2 ppb).
EEC values are calculated based on the maximum labeled application rate.
Site
(No.
Apps. /Inter
val
Between
Apps.)
FLTurf(l
app.)
FLTurf(4
app./30 day
interval)
PA Turf (1
app.)
PA Turf (4
app./so day
interval)
LCso (ppb)
183
183
183
183
NOAEL
(ppb)
5-2
5-2
5-2
5-2
EEC
Initial/Pea
k
(ppb)
O.112
O.169
O.112
0.147
EEC
6o-dayAve.
(ppb)
0.014
0.036
0.014
0.034
Acute RQ
(Initial
EEC/LC50
)
O
O
0
O
Chronic RQ
(6o-dayAve.
EEC/NOAEL
)
O
O
0
O
* exceeds endangered species LOG (LOG = 0.05)
"exceeds endangered species and acute restricted use LOG (LOG = 0.1)
***exceeds endangered species, restricted use and acute risk LOG (LOG = 0.5)
""exceeds chronic LOG (LOG = 1)
b.
Freshwater Invertebrates
An analysis of the results show that for single and multiple applications of dichlorvos to turf
(both FL and PA scenarios) at the maximum application of 0.2 Ib ai/A, the freshwater
invertebrate acute endangered species, restricted use and acute risk LOG is exceeded. The chronic
LOCs is exceeded for freshwater invertebrates (Table 25).
Table 25. Acute and Chronic Risk Quotients for Freshwater Invertebrates for turf scenarios
Risk quotients for freshwater invertebrates based on based on a waterflea ECso of 0.07 ppb and NOAEL of
0.0058 ppb.
Site
(No.
Apps. /Inter
val
Between
EC50 (ppb)
NOAEL
(ppb)
EEC
Initial/Pea
k
(ppb)
EEC
21-day Ave.
(ppb)
Acute RQ
(Initial
EEC/EC50)
Chronic RQ
(21-day
Ave.
EEC/NOAE
L
40
-------
Apps.)
FLTurf(l
app.)
FLTurf(4
app./30 day
interval)
PA Turf (1
app.)
PA Turf (4
app./so day
interval)
0.07
0.07
0.07
0.07
0.0058
0.0058
0.0058
0.0058
O.112
O.169
O.112
0.147
0.037
0.061
0.037
0.054
1.6***
2.41***
1.6***
2 ^***
6.38****
10.52****
6.38****
Q 01****
* exceeds endangered species LOG (LOG = 0.05)
"exceeds endangered species and acute restricted use LOG (LOG = 0.1)
***exceeds endangered species, restricted use and acute risk LOG (LOG = 0.5)
""exceeds chronic LOG (LOG = 1)
c. Estuarine/Marine Fish
An analysis of the estuarine/marine fish species results show that for single and multiple applications of
dichlorvos to turf at the maximum application rate of 0.2 Ib ai/A, no acute or chronic LOCs are
exceeded. Estuarine/marine risk quotients are listed in Table 26.
Table 26. Acute and chronic risk quotients for estuarine/ marine fish for turf scenarios
Risk quotients for estuarine/marine fish based on a sheepshead minnow LCso of 7350 ppb and NOAEL of 960
)pb.
Site
(No.
Apps. /Inter
val
Between
Apps.)
FLTurf(l
app.)
FLTurf(4
app./3O day
interval)
PA Turf (1
app.)
PA Turf (4
app./so day
interval)
LCso (ppb)
7350
7350
7350
7350
NOAEL
(ppb)
960
960
960
960
EEC
Initial/Pea
k
(ppb)
O.112
O.169
O.112
0.147
EEC
6o-dayAve.
(ppb)
0.014
0.036
O.O14
0.034
Acute RQ
(Initial
EEC/LC50)
o
o
o
0
Chronic RQ
(6o-day
Ave.
EEC/NOAE
L)
o
o
o
0
*exceeds endangered species LOC (LOC = 0.05)
"exceeds endangered species and restricted use LOC (LOC = 0.1)
***exceeds endangered species, restricted use and acute risk LOC (LOC = 0.5)
""exceeds chronic LOC (LOC = 1)
d.
Estuarine/Marine Invertebrates
41
-------
An analysis of the results show that for single and multiple applications of dichlorvos to turf at
the maximum application of 0.2 Ib ai/A, no acute or chronic LOCs are exceeded.
Table 27. Acute and chronic risk quotients for estuarine/ marine invertebrates for turf
scenarios
Risk quotients for estuarine/marine invertebrates based on a Mysid LCso of 19.1 ppb and NOAEL of 1.48 ppb.
Site
(No.
Apps. /Inter
val
Between
Apps.)
FLTurf(l
app.)
FLTurf(4
app./30 day
interval)
PA Turf (1
app.)
PA Turf (4
app./so day
interval)
LCso (ppb)
19.1
19.1
19.1
19.1
NOAEL
(ppb)
1.48
1.48
1.48
1.48
EEC
Initial/Pea
k
(ppb)
O.112
O.169
O.112
0.147
EEC
21-day Ave.
(ppb)
0.037
O.O61
0.037
0.054
Acute RQ
(Initial
EEC/LC50)
0.0059
0.0088
0.0059
O.OO77
Chronic RQ
(21-day
Ave.
EEC/NOAE
L)
0.025
O.O41
0.025
0.036
*exceeds endangered species LOG (LOG = 0.05)
"exceeds endangered species and restricted use LOG (LOG = 0.1)
***exceeds endangered species, restricted use and acute risk LOG (LOG = 0.5)
""exceeds chronic LOG (LOG = 1)
1.
Non-target Terrestrial Animals
a.
Liquid Formulations
For liquid formulations, risk assessments were performed for two major categories of dichlorvos
outdoor uses, turf and outdoor flying insects (including mosquitoes).
i. Birds
Turf Scenarios
An analysis of the results for a single broadcast application of dichlorvos to turf at the maximum
application rate of 0.2 Ib ai/A, no avian acute LOG is exceeded (Table 28). The avian chronic
level of concern is exceeded for birds that consume short grass, tall grass, and broadleaf
plants/small insects.
Table 28. Avian Acute and Chronic Risk Quotients for Single Application of
Dichlorvos to Turf (Dietary based RQs based on Pheasant LCso of 568 ppm and Mallard
NOAECofsppm).
42
-------
Site/App.
Method
Turf/Spray/i
app
App. Rate
(Ibs ai/A)
0.2
Food Items
Short grass
Tall grass
Broadleaf plants/Small Insects
Fruits/Pods/Large Insects
Acute RQ
(EEC/LCso)
0.03
O.O2
O.O2
O.OO
Chronic RQ
(EEC/NOAEC
)
3.86****
•4 rj rj 'X1 'X1 'X1 'X1
Q -| ry-X- -X- -X- -X-
O.24
*exceeds endangered species LOG (LOG = O.l)
**exceeds endangered species and acute restricted use LOG (LOG = 0.2)
***exceeds endangered species, restricted use and acute risk LOG (LOG = 0.5)
****exceeds chronic LOG (LOG = l)
An analysis of the results for four applications of dichlorvos to turf at the maximum application
rate of 0.2 Ib ai/A, no avian acute LOG is exceeded (Table 29). The avian chronic level of
concern is exceeded for birds that consume short grass, tall grass, and broadleaf plants/small
insects.
Table 29. Avian Acute and Chronic Risk Quotients for Four Applications of
DichlorvOS to Turf (Dietary based RQs based on Pheasant LC5O of 568 ppm and Mallard NOAEC
of 5ppm).
Site/App.
Method
Turf/Spray/4
app with 30
day
application
interval
App. Rate
(Ibs ai/A)
0.2
Food Items
Short grass
Tall grass
Broadleaf plants/Small Insects
Fruits/Pods/Large Insects
Acute RQ
(EEC/LCso)
0.03
O.O2
O.O2
O.OO
Chronic RQ
(EEC/NOAEC
)
3.86****
•4 rj rj "X1 -X1 -X1 -X1
Q -| ry-X1 •& •& •&
O.24
*exceeds endangered species LOG (LOG = O.l)
**exceeds endangered species and acute restricted use LOG (LOG = 0.2)
***exceeds endangered species, restricted use and acute risk LOG (LOG = 0.5)
****exceeds chronic LOG (LOG = l)
Flying Insect Scenario
An analysis of the results for 75 applications of dichlorvos for flying insect control at the
maximum application rate of 0.2 Ib ai/A, no avian acute LOG is exceeded (Table 30). The avian
chronic level of concern is exceeded for birds that consume short grass, tall grass, and broadleaf
plants/small insects.
43
-------
Table 30. Avian Acute and Chronic Risk Quotients for 75 Applications of
DichlorvOS for Flying Insect Control (Dietary based RQs based on Pheasant LC5O of 568 ppm
and Mallard NOAEC of 5 ppm).
Site/App.
Method
Flying
Insects/Spray
/75 app with 5
day
application
interval
App. Rate
(Ibs ai/A)
0.2
Food Items
Short grass
Tall grass
Broadleaf plants/Small Insects
Fruits/Pods/Large Insects
Acute RQ
(EEC/LCso)
0.03
O.O2
O.O2
O.OO
Chronic RQ
(EEC/NOAEC
)
3.86****
•4 rj rj 'X1 'X1 'X1 'X1
<-) -| ry-X- -X- -X- -X-
O.24
*exceeds endangered species LOG (LOG = O.l)
**exceeds endangered species and acute restricted use LOG (LOG = 0.2)
***exceeds endangered species, restricted use and acute risk LOG (LOG = 0.5)
****exceeds chronic LOG (LOG = l)
ii. Mammals
Turf Scenarios
An analysis of the results for a single broadcast application of dichlorvos to turf at the maximum
application rate of 0.2 Ib ai/A, the mammalian endangered species LOG is exceeded for the 15 g
and 35 g mammals that consumes short grass(Table 31). The mammalian chronic level of
concern is exceeded for 15 g, 35 g, and 1000 g mammals that consume short grass, tall grass,
and broadleaf plants/small insects.
Table 31. Mammalian Acute and Chronic Risk Quotients for Single Application of
DichlorvOS to Turf (Dose-based RQs based on Rat LD5O of 56 mg/kg and Rat NOAEC of 5 ppm).
Short grass
Tall grass
Broadleaf plants/Small
Insects
Fruits/Pods/Large Insects
15 g mammal
Acute
RQ
0.15s
0.07
0.08
O.Ol
Chronic
RQ
g_34****
0 Qo****
4.69****
0.52
35 g mammal
Acute
RQ
0.13*
0.06
0.07
O.Ol
Chronic
RQ
7.16****
o 28****
4.03****
0.45
1000 g mammal
Acute
RQ
0.07
0.03
0.04
O.OO
Chronic
RQ
0 rjfo****
-1 rj^****
2 10****
O.24
44
-------
Seeds (granivore)
o.oo
0.12
o.oo
o.io
o.oo
0.05
*exceeds endangered species LOG (LOG = O.l)
**exceeds endangered species and acute restricted use LOG (LOG = 0.2)
***exceeds endangered species, restricted use and acute risk LOG (LOG = 0.5)
****exceeds chronic LOG (LOG = l)
An analysis of the results for four broadcast application of dichlorvos to turf at the maximum
application rate of 0.2 Ib ai/A, the mammalian endangered species LOG is exceeded for the 15;
and 35 g mammals that consume short grass(Table 32). The mammalian chronic level of
concern is exceeded for 15 g, 35 g, and 1000 g mammals that consume short grass, tall grass,
and broadleaf plants/small insects.
Table 32. Mammalian Acute and Chronic Risk Quotients for Four Applications of
Dichlorvos to Turf (Dose-based RQs based on Rat LD5O of 56 mg/kg and Rat NOAEC of 5 ppm).
Short grass
Tall grass
Broadleaf plants/Small
Insects
Fruits/Pods/Large Insects
Seeds (granivore)
15 g mammal
Acute
RQ
0.15s
0.07
0.08
O.Ol
o.oo
Chronic
RQ
8.34****
0 Qo****
4.69****
0.52
O.12
35 g mammal
Acute
RQ
0.13*
0.06
0.07
O.Ol
o.oo
Chronic
RQ
7.16****
o 28****
4.03****
0.45
O.IO
1000 g mammal
Acute
RQ
0.07
0.03
0.04
o.oo
o.oo
Chronic
RQ
3.76***
-[ rj^***
2 -[o***
O.24
0.05
*exceeds endangered species LOG (LOG = O.l)
**exceeds endangered species and acute restricted use LOG (LOG = 0.2)
***exceeds endangered species, restricted use and acute risk LOG (LOG = 0.5)
****exceeds chronic LOG (LOG = l)
Flying Insect Scenario
An analysis of the results for 75 applications of dichlorvos for flying insect control at the
maximum application rate of 0.2 Ib ai/A, the mammalian endangered species LOG is exceeded
for 15 g and 35 mammals consuming short grass (Table 33). The mammalian chronic level of
concern is exceeded for mammals (15 g, 35 g, 1000 g) that consume short grass, tall grass, and
broadleaf plants/small insects.
Table 33. Mammalian Acute and Chronic Risk Quotients for 75 Applications of
Dichlorvos for Flying Insect Control (Dose-based RQs based on Rat LD50 of 56 mg/kg and
Rat NOAEC of 5 ppm).
15 g mammal
Acute
RQ
Chronic
RQ
35 g mammal
Acute
RQ
Chronic
RQ
1000 g mammal
Acute
RQ
Chronic
RQ
45
-------
Short grass
Tall grass
Broadleaf plants/Small
Insects
Fruits/Pods/Large Insects
Seeds (granivore)
0.15s
0.07
0.08
O.Ol
o.oo
g_34****
o go****
4.69****
0.52
O.12
0.13*
0.06
0.07
O.Ol
o.oo
7.16****
o 28****
4.03****
0.45
O.1O
0.07
0.03
0.04
o.oo
o.oo
0 yf.****
-. rj<2****
2 10****
O.24
0.05
*exceeds endangered species LOG (LOG = O.l)
**exceeds endangered species and acute restricted use LOG (LOG = 0.2)
***exceeds endangered species, restricted use and acute risk LOG (LOG = 0.5)
****exceeds chronic LOG (LOG = l)
3 Non-target Terrestrial Invertebrates
Honeybee acute contact toxicity values indicate that dichlorvos is highly toxic to this insect species.
Toxicity tests using residues on foliage indicate dichlorvos is practically non-toxic to honey bees.
The overall acute risk to honeybees and other non-target and beneficial insects is expected to be
very high for applications of liquid products at 0.2 Ib ai/a. Since dichlorvos is very highly toxic
to bees (LD5o)= 0.495 Mg/bee, it is expected that bees, as well as other non-target and beneficial
insects, could be harmed if exposed to dichlorvos during treatment.
4. Non-target Terrestrial and Aquatic Plants
As described in the analysis section, there were no registrant-submitted terrestrial plant studies so risk to
terrestrial plants can not be assessed.
There are supplemental aquatic plant studies that can be used descriptively to discuss potential risk to
aquatic plants. The 48 hour EQjO values of >iooooo ppb for green algae, 14000 ppb for algae
(the species were not given) and 17000-28000 ppb for marine diatom are reported by Mayer et
al. 1986. The modeled peak EEC value for turf is 2.33 ppb. Comparisons of the toxicities and the
aquatic EEC values indicate minimal aquatic plant risk.
5. Non-target Terrestrial Animals - Bait Formulations
An acute risk assessment for bait formulations was performed for dichlorvos outdoor use
around animal premises. Birds and mammals may be exposed to the bait by ingesting granules.
The number of lethal doses (LDso's) that are available within one square foot immediately after
application can be used as a risk quotient (LDso's/ft 2) for the exposure to bait pesticides.
Chronic risk assessments are not performed for bait products.
The acute risk quotients for birds and mammals are tabulated in Table 34. The results indicate
that for applications of bait products applied at the maximum rate of 0.0025 Ib/iooo ft2, the
acute avian RQs exceed endangered species, restricted use and acute risk LOCs for 20 g birds. The
endangered species LOC is exceeded for 100 g birds.
46
-------
Granular bait can be applied up to 120 applications (worse case scenario) with 3 day application
interval. However, for the bait application, dichlorvos can only be applied to animal premise
areas (soil, near buildings) and not applied directly to grass and turf. When evaluating the aerobic
soil half life of 0.42 days, it becomes clear that in a 3 day application interval, the original 0.1 Ibs/A of
dichlorvos would have gone through approximately 7 half life cycles, leaving only approximately 0.0008
Ibs/A of the original parent product. Therefore, we assume that the risk quotients calculated for 1
application at 0.1 Ibs/A approximate the risk quotients for 120 applications with 3 day application
interval.
Table 34. Avian and Mammalian Acute Risk Quotients for i application of Bait
Products (based on a Mallard LDso of 7.78 mg ai/kg and Rat LDso of 56 mg/kg).
Granular Bait ( i application at o.i Ibs/A) Acute RQ
(LD50/ft2)
Avian
20 g bird
100 g bird
1000 g bird
O-959***
0.151*
0.011
Mammals
15 g mammal
35 g mammal
1000 g mammal
0.042
O.O22
0.002
*exceeds endangered species LOG (LOG = O.l)
**exceeds endangered species and acute restricted use LOG (LOG = 0.2)
***exceeds endangered species, restricted use and acute risk LOG (LOG = 0.5)
B. Risk Description - Interpretation of Direct Effects
i. Risks to Aquatic Animals
Summary of Major Conclusions
Acceptable data on dichlorvos indicates it is very highly toxic to freshwater fish (LC5O = 183 ppb
for most sensitive species), moderately toxic to estuarine/marine fish (EC5O = 7350 ppb for the
one species tested), very highly toxic to freshwater invertebrates (LC5O = 0.28 ppb for most
sensitive species) and very highly toxic to estuarine invertebrates (LC5O = 19.1 ppb for most
sensitive species). Chronic studies established NOAEL values of 5.2 ppb (rainbow trout), 960
ppb (sheepshead minnow), 0.0058 ppb (daphnid) and 1.48 ppb (mysid shrimp).
There is acute risk for freshwater invertebrates with RQs of 1.6 (FL turf) and 1.6 (PA turf) for
one spray application. For 4 applications, the RQs are 2.41 (FL turf) and 2.1 (PA turf). These
RQs exceeds the endangered species, restricted use, and acute risk LOG. In addition, the
chronic level of concern is exceeded for freshwater invertebrates [egg production and growth
47
-------
(length and weight) endpoint] for all of the turf scenarios (one and four applications). Based on
these findings, there is a potential for acute and chronic risk to freshwater invertebrates from
applications to turf.
For flying insect (including adult mosquitoes) use, EFED is unable to assess risk quantitatively.
It may be assumed that the exposure to dichlorvos from flying insect use would be less than that
expected from turf use. However, the potential risk to freshwater and marine/estuarine
invertebrates can not be quantified and therefore can not be assessed nor discounted.
Exposure to aquatic animals from bait formulations applied around animal premises is expected
to be minimal because treatment sites are small and localized. Therefore, the bait formulation
scenario for aquatic animals was not addressed in this risk assessment.
2. Risks to Terrestrial Animals
Summary of Major Conclusions
Based on the results of acceptable ecotoxicity studies, dichlorvos is very highly toxic to birds on
an acute oral basis (LD5O= 7.8 mg/kg for most sensitive species), moderately toxic to birds on a
subacute dietary basis (LCso = 568 ppm for most sensitive species) and moderately toxic to
mammals on an acute oral basis (LDso = 56-80 mg/kg). Chronic toxicity studies established
NOAEL values of 5 ppm (mallard), 20 ppm (rat) and 30 ppm (bobwhite).
The chronic risk endangered species LOCs are exceeded on turf applications (both i and 4
applications) for birds that consume short grass, tall grass, and broadleaf plants/small insects
(with RQs ranging from 1.77 to 3.86). For the flying insect scenario, no acute LOCs are
exceeded. Chronic LOCs are exceeded for birds that consume short grass, tall grass, and
broadleaf plants/small insects.
For mammals, for both the i and 4 applications of dichlorvos to turf, the chronic LOG is
exceeded for 15 g, 35 g, and 1000 g mammals that consume short grass, tall grass, and broadleaf
plants/small insects. For turf application, there are acute endangered species LOG exceedences
for the 15 g and 35 g mammals that consumes short grass.
The acute risk, acute restricted use, and acute endangered species LOCs for a small bird (20 g
weight) are exceeded for the bait formulation scenario (Acute RQ = 0.959). The endangered
species OC is exceeded for the 100 g mammals with the bait scenario. Chronic risk to birds from
the bait formulation can not be assessed at this time.
There is a possibility of risk to birds and small mammals from ingestion of the bait product.
Dichlorvos is highly toxic to birds on an acute oral basis (LDso
-------
C. Threatened and Endangered Species Concerns
1. Taxonomic Groups Potentially at Risk
The Agency's levels of concern for endangered and threatened freshwater invertebrates, birds, and mammals are exceeded for
dichlorvos use. A summary of the endangered species taxonomic groups potentially at risk from dichlorvos use are listed in
Table 35. Because turf, flying insect, and bait formulation use are available in all states, the endangered
species listing encompasses all dichlorvos use areas..
The preliminary risk assessment for endangered species indicates that dichlorvos exceeds the endangered
species LOCs for the following combinations of analyzed uses and species:
• Freshwater invertebrates (acute): use on turf ( 1 application and 4 applications, both FL and PA
scenarios)
• Freshwater invertebrates (chronic): use on turf ( 1 application and 4 applications, both FL and PA
scenarios)
• Birds (chronic): use on turf (1 application and 4 applications) for birds consuming short grass, tall
grass, and broadleaf plants/small insects
• Birds (chronic): use as flying insect control for birds consuming short grass, tall grass,and
broadleaf plants/small insects
• Birds (acute): use as bait formulation for 20 g and lOOg bird
• Mammals (acute): use on turf (1 application and 4 applications) 15 g and 35 g mammals that
consumes short grass.
• Mammals (chronic): use on turf (1 application and 4 applications) 15 g, 35 g, and 1OOO g mammals
that consume short grass, tall grass, and broadleaf plants/small insects.
Table 35. Tabulation by taxonomic group and total states of listed species that occur in dichlorvos
use areas
Total Unique Species
Taxonomic Group
Bir
ds
57
1
Mam
mals
61
Rep
tiles
28
Am
phi
bia
ns
19
Fish
113
Cr
us
tac
ea
ns
20
Ar
ac
hn
id
s
12
Inse
cts
44
Sn
ail
s
30
Cl
a
m
s
70
Plant
s
548
1 1 1 1 1 1 1 1 1
49
-------
Total States 49 47 19 12 40 12 4 27 15 28 49
The Agency has developed the Endangered Species Protection Program to identify pesticides whose use
may cause adverse impacts on endangered and threatened species, and to implement mitigation measures
that address these impacts. The Endangered Species Act requires federal agencies to ensure that their
actions are not likely to jeopardize listed species or adversely modify designated critical habitat. To
analyze the potential of registered pesticide uses to affect any particular species, EPA puts basic toxicity
and exposure data developed for REDs into context for individual listed species and their locations by
evaluating important ecological parameters, pesticide use information, the geographic relationship
between specific pesticide uses and species locations, and biological requirements and behavioral aspects
of the particular species. This analysis will take into consideration any regulatory changes recommended
in this RED that are being implemented at this time. A determination that there is a likelihood of
potential impact to a listed species may result in limitations on use of the pesticide, other measures to
mitigate any potential impact, or consultations with the Fish and Wildlife Service and/or the National
Marine Fisheries Service as necessary.
The Endangered Species Protection Program as described in a Federal Register notice (54 FR 27984-
28008, July 3, 1989) is currently being implemented on an interim basis. As part of the interim program,
the Agency has developed County Specific Pamphlets that articulate many of the specific measures
outlined in the Biological Opinions issued to date. The Pamphlets are available for voluntary use by
pesticide applicators on EPA's website at www.epa.gov/espp. A final Endangered Species Protection
Program, which may be altered from the interim program, was proposed for public comment in the
Federal Register December 2, 2002.
2 .Probit Slope Analysis
The probit slope response relationship is evaluated to calculate the change of an individual event
corresponding to the listed species acute LOCs. If information is unavailable to estimate a slope for a
particular study, a default slope assumption of 4.5 is used as per original Agency assumptions of typical
slope cited in Urban and Cook (1986).
Freshwater Invertebrates
Raw data is not provided in the daphnid acute £€50 study (MRID 400980017 Mayer and
Ellersieck 1986) to calculate a slope. RQ exceedances occur for freshwater invertebrate species
for the turf scenario (i application and 4 applications). Based on the default slope assumption of
4.5, the individual mortality associated with the minimum and maximum calculated RQ value
(6.71 and 33.29) result in an estimated chance of individual mortality of i in i (100 %). The
corresponding estimated chance of individual mortality associated with the listed species LOG of
0.05 is i in 4.17E+O8.
Birds
Raw data is not provided in the mallard duck acute LDso study (MRID ooi6oooo/ Hudson et
al. 1984) to calculate a slope. RQ exceedances occur for bird species for the flying insect and
bait formulation scenario. Based on the default slope assumption of 4.5, the individual
mortality associated with the calculated minimum and maximum RQ value (0.17 and 0.36) for
flying insect scenario result in an estimated chance of individual mortality of i in 3-74E+O3 to i
in 4-36E+O1. For the bait scenario, RQ range of 0.151 to 0.959, result in an estimated chance of
individual mortality of i in 9.O8E+O3 to i in 2.14 (50%). The corresponding estimated chance of
individual mortality associated with the listed species LOG of o.i is i in 2.94 £+05.
50
-------
Mammals
Raw data is not provided in the rat acute LD50 study (MRID 0005467) to calculate a slope.
Therefore, the event probability was calculated for mammalian LOG based on a default slope of
4.5. RQ exceedances occur for mammalian species for the turf and flying insect scenario. The
individual mortality associated with the calculated RQ values (0.13 and 0.26) for turf scenario
result in an estimated chance of individual mortality of i in 2.99E+O4 and i in 2.36E+O2,
respectively. For the flying insect scenario, RQ range of 0.33 to 1.58, result in an estimated
chance of individual mortality of i in 6.6iE+oi to i in 1.23E+O (100%).
Based on an assumption of a probit dose response relationship with a mean estimated slope of
4.5, the corresponding estimated chance of individual mortality associated with the mammalian
listed species LOG of o.i is i in 294,000.
It is recognized that extrapolation of very low probability events is associated with considerable
uncertainty in the resulting estimates. To explore possible bounds to such estimates, the upper
and lower values for the mean slope estimate can be used to calculate upper and lower estimates
of the effects probability associated with the listed species LOG. However, since slope is based on
a default assumption of 4.5, the 95 percent confidence intervals for the slopes are unavailable.
3. Critical Habitat
In the evaluation of pesticide effects on designated critical habitat, consideration is given to the physical and biological features
(constituent elements) of a critical habitat identified by the FWS and NMFS as essential to the conservation of a listed species and
which may require special management considerations or protection. The evaluation of impacts for a screening level pesticide risk
assessment focuses on the biological features that are constituent elements and is accomplished using the screening level
taxonomic analysis (risk quotients, RQs) and listed species levels of concern (LOCs) that are used to evaluate direct and indirect
effects to listed organisms.
The screening level risk assessment has identified potential concerns for indirect effects on listed species for those organisms
dependent upon freshwater invertebrates, birds, and mammals, hi light of the potential for indirect effects, the next step for EPA,
FWS, and the NMFS is to identify which listed species and critical habitat are potentially implicated.
Analytically, the identification of such species and critical habitat can occur in either of two ways. First, the agencies could
determine whether the action area overlaps critical habitat or the occupied range of any listed species. If so, EPA would examine
whether the pesticide's potential impacts on non-endangered species would affect the listed species indirectly or directly affect a
constituent element of the critical habitat. Alternatively, the agencies could determine which listed species depend on biological
resources, or have constituent elements that fall into, the taxa that may be directly or indirectly impacted by the pesticide. Then
EPA would determine whether use of the pesticide overlaps with the critical habitat or the occupied range of those listed species.
At present, the information reviewed by EPA does not permit use of either analytical approach to make a definitive identification
of species that are potentially impacted indirectly or critical habitats that are potentially impacted directly by the use of the
pesticide. EPA and the Service(s) are working together to conduct the necessary analysis.
This screening level risk assessment for critical habitat provides a listing of potential biological features that, if the are constituent
elements of one or more critical habitats, would be of potential concern. These correspond to the taxa identified above as being of
potential concern for indirect effects and include the following: freshwater invertebrates, birds, and mammals. This list should
serve as an initial step in problem formulation for further assessment of critical habitat impacts outlined above, should additional
work be necessary.
4. Indirect Effect Analyses
The Agency acknowledges that pesticides have the potential to exert indirect effects upon the listed organisms by, for example,
perturbing forage or prey availability, altering the extent of nesting habitat, creating gaps in the food chain, etc. hi conducting a
screen for indirect effects, direct effect LOCs for each taxonomic group are used to make inferences concerning the potential for
indirect effects upon listed species that rely upon non-endangered organisms in these taxonomic groups as resources critical to
their life cycle.
51
-------
Because screening-level acute RQs for freshwater invertebrates, birds, and mammals exceed the
endangered species acute LOCs, the Agency uses the dose response relationship from the toxicity
study used for calculating the RQ to estimate the probability of acute effects associated with an
exposure equivalent to the EEC. This information serves as a guide to establish the need for and
extent of additional analysis that maybe performed using Services-provided "species profiles" as
well as evaluations of the geographical and temporal nature of the exposure to ascertain if a "not
likely to adversely affect" determination can be made. The degree to which additional analyses
are performed is commensurate with the predicted probability of adverse effects from the
comparison of the dose response information with the EECs. The greater the probability that
exposures will produce effects on a taxa, the greater the concern for potential indirect effects for
listed species dependent upon that taxa, and therefore, the more intensive the analysis on the
potential listed species of concern, their locations relative to the use site, and information
regarding the use scenario (e.g., timing, frequency, and geographical extent of pesticide
application).
Screening-level acute RQs for aquatic invertebrates, birds, and mammals are above the non-
endangered species LOCs. The Agency considers this to be indicative of a potential for adverse
effects to those listed species that rely either on a specific plant species (plant species obligate) or
multiple plant species (plant dependent) for some important aspect of their life cycle. The
Agency may determine if listed organisms for which plants are a critical component of their
resource needs are within the pesticide use area. This is accomplished through a comparison of
Service-provided "species profiles" and listed species location data. If no listed organisms that
are either plant species obligates or plant dependent reside within the pesticide use area, a no
effect determination on listed species is made. If plant species obligate or dependent organism
may reside within the pesticide use area, the Agency may consider temporal and geographical
nature of exposure, and the scope of the effects data, to determine if any potential effects can be
determined to not likely adversely affect a plant species obligate or dependent listed organism.
a. Aquatic Species
Indirect effects to endangered/threatened fish that depend on freshwater invertebrates as a
primary source of food, as well as larger aquatic animals that rely on aquatic (freshwater)
invertebrate populations as a food source may be affected by the direct or chronic effects of
dichlorvos use.
b. Terrestrial Species
Although RQs were not calculated for terrestrial plants, due to dichlorvos' mode of action, use, and the lack of aquatic plant risk,
this assessment concludes that plant-dependent species will not be affected indirectly from dichlorvos use.
The Agency acknowledges that pesticides have the potential to exert indirect effects upon endangered or threatened species, by,
for example, perturbing forage or prey availability, altering the extent of nesting habitat, etc. The screen for indirect effects
includes using direct effect LOCs for non-endangered species to infer the potential for indirect effects upon listed species that rely
upon non-endangered organisms as resources critical to their life cycle.
Because at intended use rates dichlorvos may cause mortality in exposed bird and mammal populations, there are potential
concerns for indirect effects on those listed terrestrial organisms that are dependant upon vertebrate species (birds, mammals,
reptiles) as prey items. Additionally, indirect effects to endangered/threatened fish, invertebrates, and
mammals that depend on freshwater invertebrates as a primary source of food may occur.
52
-------
The high acute toxicity of dichlorvos to honeybees may lead to mortality to this and other insect-
pollinators. Listed plant species dependant upon insect pollination may be indirectly affected by the loss
of all or part of such insect populations. Additionally, the potential risk to bird species from dichlorvos use
could also affect bird-pollinated plant species.
A potential drop in both vertebrate and invertebrate biomass associated with dichlorvos use may reduce a
significant portion of the prey base. If this prey base is removed at a critical life-cycle juncture, over a
large area, or it if is removed for a long enough duration, some species may have difficulty meeting energy
needs. Some species may be particularly sensitive during reproductive or developmental periods.
E. Description of Assumptions, Uncertainties, Strengths, and Limitations
1. Assumptions and Limitations Related to Exposure for all Taxa
a. Maximum Use Scenario
This screening-level risk assessment relies on labeled statements of the maximum rate of dichlorvos
application, the maximum number of applications, and the shortest interval between applications (when
applicable). Together, these assumptions constitute a maximum use scenario and can overestimate risk.
However, the maximum use scenario must be considered because it is a reflection of the allowable use of
dichlorvos.
2. Assumptions and Limitations Related to Exposure for Aquatic Species
a. Lack of Averaging Time for Exposure
For an acute risk assessment, there is no averaging time for exposure. An instantaneous peak concentration, with a 1 in 10 year
return frequency, is assumed. The use of the instantaneous peak assumes that instantaneous exposure is of sufficient duration to
elicit acute effects comparable to those observed over more protracted exposure periods tested in the laboratory, typically 48 to 96
hours, hi the absence of data regarding time-to-toxic event analyses and latent responses to instantaneous exposure, the degree to
which risk is overestimated cannot be quantified.
b. Routes of exposure
Screening-level risk assessments pesticide application for aquatic organisms consider exposure through the gills. Other potential
routes of exposure, not considered in this assessment, are discussed below:
Dietary consumption
The screening assessment does not consider the ingestion pathway. This exposure may occur through ingestion of contaminated
vegetation, invertebrates, or other exposed prey items.
Dermal exposure
The screening assessment does not consider dermal exposure. Dermal exposure may occur through one potential source:
contact with contaminated water. The available measured data related to aquatic wildlife dermal contact with pesticides are
extremely limited.
3. Assumptions and Limitations Related to Exposure for Terrestrial Species
a. The LD50/sq. ft. Index
The LD50/sq.ft. index was developed by Felthousen (1977). The concept was based upon field observations made by DeWitt
(1966) who suggested that ecological effects are expected to occur when exposure residues that equal or exceed the LD50 value for
a pesticide, as determined from laboratory studies, are reached in the field. The index was developed, in response to the
Registration Divisions' request for guidance for classifying use patterns, involving granulated formulations, baits, and seed
53
-------
treatments, for labeling purposes. At that time risk criteria considerations were typically based on the amount of residues likely to
occur, immediately following application, in or on feed items likely to be consumed by non-target wildlife species, hi so much as
granular formulations, baits and seed treatments leave very little residue in or on non-target food items, a hazard index had to be
developed to address theses routes of exposure. It's important to note that the LD50/sq. ft. concept is an index to hazard that
presumes exposure will occur on the treated areas (a deterministic assessment) rather than a tool that attempts to quantify the
temporal and spatial relationship of exposure (i.e., a probabilistic assessment tool) to a non-target organism.
The LD50/sq.ft. index used to predict risk to non-target wildlife species has been peer reviewed by numerous scientists, both within
and outside of the Agency and, in general, has been accepted as a useful tool for addressing ecological hazard from the use of
granulated formulations, hi March of 1992, the Agency used this index in its "Comparative Analysis of Acute Avian Risk from
Granular Pesticides" document. This document provided explanation, discussion and analysis of the index as well as specific
examples of risk quotients derived from the index, hi 1996 the FIFRA Science Advisory Panel (SAP) reviewed and approved the
environmental assessments derived from the index for those chemicals evaluated in the corn cluster document. The SAP even
suggested that the acute risk indices calculated from the index may actually underestimate risk.
Based on this long history of scientific peer review, which has repeatedly supported the use of the LD50/sq. ft. risk index in
ecological hazard assessments, we believe that the index is appropriate for determining and classifying ecological risk to
terrestrial wildlife from the use of bait formulations.
b. Uncertainties Associated with the LD50/sq. ft. Index
Risk quotients based on the LD50/sq.ft. hazard index have been criticized as being too conservative and overestimating "real
world" risk. It has been argued that the method greatly oversimplifies the exposure component to hazard assessment by not
specifically addressing the temporal and spatial situations that non-target wildlife species experience under field conditions.
Although this is somewhat correct there are still many other exposure related and toxicological factors that are not accounted for
by the index which may actually underestimate risk from this method.
For example, the LD50/sq.ft. index is based solely on acute mortality as derived from acute oral exposure from laboratory tests. It
does not address subacute behavioral or physiological effects that may occur prior to mortality and yet can still have a profound
sub-lethal effects on an organisms ability to survive and reproduce. As such, this index may underestimate ecological hazard from
sub-lethal exposures. For instance, it is common in clinical observations, conducted during acute tests, to observe such symptoms
as wing droop, goose-stepping ataxia, dyspnea (labored breathing), diarrhea, apnea, weight loss, salivation, convulsions and
hyperactivity prior to mortality occurring. Even if an organism survives this exposure to the toxicant, these symptoms indicate the
organism is under extreme stress that could greatly affect both its survival (susceptibility to disease and parasites, ability to avoid
predation, nest desertion and abandonment) and ability to reproduce under actual field conditions. Necropsy data also indicate that
many organisms are experiencing extreme physiological changes even though they may not die from exposure to the toxicant.
Liver damage, renal failure, lesions, hemorrhage and other tissue damage are indications of severe physiological impairment that
could adversely affect both the survival and reproductive capability of the organisms. These sub-lethal effects are not really
addressed by the LD50/sq. ft. index, hi fact, although the SAP (1996) approved the LD50/sq.ft. index as a method for determining
and classifying ecological risk to terrestrial wildlife from the use of granular formulations, it questioned the use of mortality as the
primary end-point for addressing ecological risk. The SAP stated that, "Many chemicals evoke toxicity through the interference
with the physiological state of the animal including behaviors important to continued reproduction and survival. Each chemical
may have certain unique qualities that may influence their potential hazard to wildlife." These comments suggest that basing
ecological hazard assessments solely on direct effects, as determined by acute indices, may be under protective for predicting
indirect effects from sub-lethal exposures.
Although it is presumed that the LD50/sq.ft. index accounts for acute exposure from oral, dermal and inhalation exposure, it was
not intended to address exposure from drinking water where runoff, from either rain events or irrigation, to low areas may create
puddles that contain very high concentrations of the pesticide. The contribution of this route of exposure to overall body burden
residues is unknown but it will clearly be additive to exposure from direct consumption of the bait formualtion and/or exposure
from eating contaminated vegetation.
c. The Likelihood of Wildlife Presence at Time of Application
Birds and mammals may utilize outdoor areas and animal premise areas that have been treated with dichlorvos and therefore may
be exposed. Also, birds and mammals foraging for seeds, insects, and annelids (e.g., earthworms) may be unable to avoid
ingesting granular bait dichlorvos. Birds may also ingest granules in treated areas when foraging for grit.
d Significance of Wildlife Utilization of Treatment Areas
54
-------
Characterizing risk to non-target wildlife from the use of dichlorvos on the areas for which it is registered, requires a clear
understanding of the many limitations of identifying exactly what species are most likely to use treated areas and for what purpose.
The simple fact is, wildlife utilization of animal premise areas and general outdoor areas is highly variable and difficult to predict
and, as such, there is a great deal of uncertainty surrounding this issue when conducting an ecological hazard evaluation.
e. Routes of Exposure
The risk assessment findings of acute risk to terrestrial animals is based on risk assessments
where ingestion of contaminated food is considered as the primary route of exposure. The risk
assessment did not consider the other possible routes of exposure, e.g., dermal, preening, and
respiratory pathways. These other paths of exposure have been shown to contribute to acute
toxicity of other organophosphate compounds (Driver et al. 1991). Other routes of exposure, not
considered in this assessment, are discussed below:
• Incidental soil ingestion exposure
This risk assessment does not consider incidental soil ingestion. Available data suggests that up to 15% of
the diet can consist of incidentally ingested soil depending on the species and feeding strategy (Beyer et
al., 1994).
• Inhalation exposure
This risk assessment does not consider respiratory pathways. Since dichlorvos volatilizes rapidly, the
inhalation route of exposure may contribute to acute toxicity. Incidence data reports avian toxicity
due to inhalation exposure.
• Dermal Exposure
The screening assessment does not consider dermal exposure, except as it is indirectly included in
calculations of RQs based on lethal doses per unit of pesticide treated area. Dermal exposure may occur
through two potential sources: (1) incidental contact with contaminated vegetation, or (2) contact with
contaminated water or soil.
The available measured data related to wildlife dermal contact with pesticides are extremely limited. The
Agency is actively pursuing modeling techniques to account for dermal exposure via incidental contact
with vegetation.
• Drinking Water Exposure
Drinking water exposure to a pesticide active ingredient may be the result of consumption of surface water
or consumption of the pesticide in dew or other water on the surface of the treated area. For pesticide
active ingredients with a potential to dissolve in runoff, puddles on the treated area may contain the
chemical. Given its high water solubility, dichlorvos is expected to dissolve in dew and other water
associated with plant surfaces. However, the likelihood of exposure to dichlorvos via drinking water is not
quantified in the exposure modeling.
f Incidental Pesticide Releases Associated with Use
This risk assessment is based on the assumption that the entire treatment area is subject to dichlorvos application at the rates
specified on the label, hi reality, there is the potential for uneven application of the pesticide through such plausible incidents as
changes in calibration of application equipment, spillage, and localized releases.
55
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4. Assumptions and Limitations Related to Effects Assessment
a. Age class and sensitivity of effects thresholds
It is generally recognized that test organism age may have a significant impact on the observed sensitivity to a toxicant. The
screening risk assessment acute toxicity data for fish are collected on juvenile fish between 0.1 and 5 grams. Aquatic invertebrate
acute testing is performed on recommended immature age classes (e.g., first instar for daphnids, second instar for amphipods,
stoneflies and mayflies, and third instar for midges). Similarly, acute dietary testing with birds is also performed on juveniles,
with mallard being 5-10 days old and quail 10-14 days old.
Testing of juveniles may overestimate toxicity at older age classes for pesticidal active ingredients, such as dichlorvos, that act
directly because younger age classes may not have the enzymatic systems associated with detoxifying xenobiotics. The screening
risk assessment has no current provisions for a generally applied method that accounts for this uncertainty, hi so far as the
available toxicity data may provide ranges of sensitivity information with respect to age class, the risk assessment uses the most
sensitive life-stage information as the conservative screening endpoint.
b.. Use of the Most Sensitive Species Tested
Although the screening-level risk assessment relies on a selected toxicity endpoint from the most sensitive species tested, it does
not necessarily mean that the selected toxicity endpoints reflect sensitivity of the most sensitive species existing in a given
environment. The relative position of the most sensitive species tested in the distribution of all possible species is a function of the
overall variability among species to a particular chemical, hi the case of listed species, there is uncertainty regarding the
relationship of the listed species' sensitivity and the most sensitive species tested.
The Agency is not limited to a base set of surrogate toxicity information in establishing risk assessment conclusions. The Agency
also considers toxicity data on non-standard test species when available.
5. Assumptions Associated with the Acute LOCs
The risk characterization section of the assessment document includes an evaluation of the potential for individual effects at an
exposure level equivalent to the LOG. This evaluation is based on the median lethal dose estimate and dose/response relationship
established for the effects study corresponding to each taxonomic group for which the LOCs are exceeded.
6. Data Gaps and Limitations of the Risk Assessment
The following data gaps were identified:
g. Ecotoxicity Data Gaps
There is limited terrestrial and aquatic plant data for dichlorvos, which leads to uncertainty in the
evaluation of plant risk.
C. Environmental Fate Information Gaps
re are no environmental fate data gaps.
Appendices A and B at the end of this document provides the summary status of all the
environmental fate and ecotoxicological data requirement
56
-------
57
-------
REFERENCES
Bennett, R.S. and L. M. Ganio. 1991. Overview of methods for evaluating effects of pesticides on
reproduction in birds. U.S.EPA, Off. Research and Development, Environ. Res. Lab., Corvallis,
Oregon. 106 p.
Best, L.B., R.C. Whitmore and G.M. Booth. 1990. Use of cornfields by birds during the breeding
season: the importance of edge habitat. American Midland Naturalist 123:84-99.
Driver et al. 1991. Routes of Uptake and their relative contribution to the toxicological response
of northern bobwhite (Colinus virginianus) to an organophoshate pesticide. Environmental
Toxicology and Chemistry Vol. 10, pp. 21-33.
Felthousen, R. 1977. Classification of Granulated Formulations. USEPA, September 9,1977
Goh, K.S. et al. 1986. Dissipation of Dislodgeable Foliar Residues of Chlorpyrifos and Dichlorvos
on Turf. Bull. Environ. Contam. Toxicol., 37:27-32.
Madrigal et al. 1996. Have to find the citation
Mayer, F. L. J. and Ellersieck, M. R. 1986. Manual of Acute Toxicity: Interpretation and Data
Base for 410 Chemicals and 66 Species of Freshwater Animals. Resour.Publ.No. 160,
U.S.Dep.Interior, Fish WildLServ., Washington, DC 505 p. (USGS Data File) (EPAMRID #
40098001).
Urban D. J. and N. J. Cook. 1986. Hazard Evaluation Division Standard Evaluation Procedure
Ecological Risk Assessment. EPA 540/9-85-001. U.S. Environmental Protection Agency,
Office of Pesticide Programs, Washington, DC.
U.S. EPA. 1986. Acute Toxicity Handbook of Chemicals to Estuarine Organisms., U.S.EPA, Gulf
Breeze, FL (US EPA MRID 40228401).
U.S. EPA. 1992. Comparative Analysis of Acute Avian Risk from Granular Pesticides. March,
i
9
9
2
U.S. EPA. 20043. Interim Guidance of the Evaluation Criteria for Ecological Toxicity Data in the
Open Literature, Phases I and II. July 16, 2004
U.S. EPA. 2OO4b. T-REX Version 1.1. December 7, 2004
58
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59
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APPENDIX A. ECOLOGICAL DATA REQUIREMENTS FOR DICHLORVOS
Data
Requirements
71-l(a) Acute
Avian Oral,
Quail/Duck
71-2(a)Acute
Avian Diet, Quail
71-2(b) Acute
Avian Diet, Duck
71-4(a) Avian
Reproduction Quail
71-4(b) Avian
Reproduction Duck
72-1 (a) Acute Fish
Toxicity Bluegill
72-l(b) Acute Fish
Toxicity Bluegill
(TEP)
72-l(c) Acute Fish
Toxicity Rainbow
Trout
72-l(d) Acute Fish
Toxicity Rainbow
Trout (TEP)
72-2(a) Acute
Aquatic Invertebrate
72-3 (a) Acute
Est/Mar Toxicity
Fish
72-3 (b) Acute
Est/Mar Toxicity
Mollusk
72-3 (c) Acute
Est/Mar Toxicity
Shrimp
72-3 (d) Acute
Use Pattern 1
3,8,9,11,15
3,8,9,11,15
3,8,9,11,15
3
3
3,8,9,11,15
5
3,8,9,11,15
5
3,8,9,11,15
3
3
3
5
Does EPA Have
Data to Satisfy this
Requirement?
(Yes, No, or
Partially)
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Bibliographic
Citation
40818301,
00160000
00022923
00022923
43981701
44233401
40094602
43284701
40098001
43284702
40098001
43571403
43571404
43571405
43571406
Must Additional
Data be Submitted
under FIFRA
3(c)(2)(B)?
No
No
No
No
No
No
No2
No
No2
No
No
No
No
No2
60
-------
Est/Mar Toxicity
Fish (TEP)
72-3 (e) Acute
Est/Mar Toxicity
Mollusk (TEP)
72-3 (f) Acute
Est/Mar Toxicity
Shrimp (TEP)
72-4(a) Early Life
Stage Fish
72-4(b) Life Cycle
Aquatic Invertebrate
14 1-1 Honey Bee
Acute Contact
14 1-2 Honey bee
Residue on Foliage
5
5
3
3
3, 11
3,11
Yes
Yes
Yes
Yes
Yes
Yes
43571407
43571408
43788001,
43790401
43890301,
43854301
00036935
43366701
No2
No2
No
No
No
No
FOOTNOTES:
1. 1 = Terrestrial Food; 2 = Terrestrial Feed; 3 = Terrestrial Non-Food; 4 = Aquatic Food; 5 = Aquatic Non-Food
(Outdoor); 6 = Aquatic Non-Food (Industrial); 7 = Aquatic Non-Food (Residential); 8 = Greenhouse Food; 9 =
Greenhouse Non-Food; 10 = Forestry; 11 = Residential Outdoor; 12 = Indoor Food; 13 = Indoor Non-Food; 14 =
Indoor Medicinal; 15 = Indoor Residential
2. Although data are available, there is no longer an Aquatic Non-Food (Outdoor) or Terrestrial Food use for this
chemical.
61
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APPENDIX B. ENVIRONMENTAL FATE DATA REQUIREMENTS FOR
DICHLORVOS
Data
Requirements
161-1 Hydrolysis
161-2
Photodegradation in
Water
161-3
Photodegradation
On Soil
162-1 Aerobic Soil
162-2 Anaerobic
Soil
163-1 Leaching -
Adsorption/Desorp.
164-1 Soil
Dissipation
20 1-1 Droplet Size
Spectrum
202-1 Drift Field
Evaluation
Use Pattern l
3,8,9,11
3
1
3,8,9,11
1
3,8,9,11
3,11
3
3
Does EPA Have
Data to Satisfy this
Requirement?
(Yes, No, or
Partially)
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Bibliographic
Citation
41723101
43326601
43642501
41723102
43835701
41723103,
40034904
44386701,
44297701
Must Additional
Data be Submitted
under FIFRA
3(c)(2)(B)?
No
No
No2
No
No2
No
No
No3
No3
FOOTNOTES:
1. 1 = Terrestrial Food; 2 = Terrestrial Feed; 3 = Terrestrial Non-Food; 4 = Aquatic Food; 5 = Aquatic Non-Food
(Outdoor); 6 = Aquatic Non-Food (Industrial); 7 = Aquatic Non-Food (Residential); 8 = Greenhouse Food; 9 =
Greenhouse Non-Food; 10 = Forestry; 11 = Residential Outdoor; 12 = Indoor Food; 13 = Indoor Non-Food; 14 =
Indoor Medicinal; 15 = Indoor Residential
2. Although data are available, there is no longer an Aquatic Non-Food (Outdoor) or Terrestrial Food use for this
chemical.
3. Amvac is a member of the Spray Drift Task Force.
62
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APPENDIX C. PRZM/EXAMS MODELING
FLORIDA TURF 1 APPLICATION at 0.2 Ibs/A
stored as DVPtrfl.out
Chemical: DDVP
PRZM environment: FI_turfC.txt modified Monday,
EXAMS environment: pond298.exv modified Thuday,
Metfile: w12834.dvf modified Wedday, 3 July
concentrations (ppb)
16 June
29 August
2002
Water
Year
1961
1962
1963
1964
1965
1966
1967
1968
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
1979
segment
Peak
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
0.112
96 Hr 21 Day 60 Day 90 Day Yearly
0.0867 0.03732 0.01389 0.009268 0.002285
0.0867 0.03731 0.01389 0.009267 0.002285
0.08675 0.03738 0.01392 0.009283 0.002289
0.0867 0.03732 0.01389 0.009267 0.002279
0.0867 0.03731 0.01389 0.009266 0.002285
0.08672 0.03733 0.0139 0.009272 0.002286
0.0867 0.03731 0.01389 0.009266 0.002285
0.08671 0.03732 0.01389 0.009269 0.002279
0.0867 0.03731 0.01389 0.009266 0.002285
0.0867 0.03731 0.01389 0.009265 0.002285
0.0867 0.03731 0.01389 0.009267 0.002285
0.08671 0.03733 0.0139 0.00927 0.00228
0.08671 0.03732 0.01389 0.009269 0.002286
0.08671 0.03732 0.0139 0.009269 0.002286
0.08671 0.03733 0.0139 0.00927 0.002286
0.08717 0.0377 0.01404 0.009365 0.002303
0.0867 0.03731 0.01389 0.009266 0.002285
0.0867 0.03731 0.01389 0.009266 0.002285
0.0867 0.03731 0.01389 0.009266 0.002285
63
-------
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
Sorted
Prob.
0.03225806
0
0
0
0
0
0
0
0
0
0
0
0
.06451613
.09677419
.12903226
.16129032
.19354839
.22580645
.25806452
.29032258
.32258065
.35483871
.38709677
.41935484
0.
0.
0.
0.
0.
0.1
0.
0.
0.
0.
0.
results
Peak
0.1
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
112
112
112
112
112
122
112
112
112
112
112
96
122
112
112
112
112
112
112
112
112
112
112
112
112
0
0
0
0
Hr
0
0
0
0
0
0
0
0
0
0
0
0
.08677
0.0867
.08671
0.0867
.08691
.08721
0.0867
0.0867
0.0867
0.0867
0.0867
.08721
.08717
.08691
.08677
.08675
.08672
.08671
.08671
.08671
.08671
.08671
.08671
0.0867
0.03737
0.03731
0.03732
0.03732
0.0376
0.03768
0.03731
0.03732
0.03732
0.03731
0.03731
21 Day
0.0377
0.03768
0.0376
0.03738
0.03737
0.03733
0.03733
0.03733
0.03732
0.03732
0.03732
0.03732
0.03732
0
.01391
0.01389
0.0139
0.01389
0.014
0.01403
0
.01389
0.01389
0
.01389
0.01389
0
.01389
60 Day
0.01404
0.01403
0.014
0.01392
0
0
.01391
0.0139
0.0139
0.0139
0.0139
0.0139
.01389
0.01389
0
.01389
0
0
0
0
0
0
0
0
0
90
0
0
0
0
0
0
0
0
0
0.00928
.009265
.009269
.009268
0.00934
.009359
.009267
.009267
.009268
.009265
.009266
Day
.009365
.009359
0.00934
.009283
0.00928
.009272
0.00927
0.00927
.009269
.009269
.009269
.009269
.009268
0.002282
0.002285
0.002286
0.002286
0.002297
0.002308
0.002285
0.002285
0.002279
0.002285
0.002285
Yearly
0.002308
0.002303
0.002297
0.002289
0.002286
0.002286
0.002286
0.002286
0.002286
0.002286
0.002285
0.002285
0.002285
64
-------
0.4516129
0.48387097
0.51612903
0.5483871
0.58064516
0.61290323
0.64516129
0.67741935
0.70967742
0.74193548
0.77419355
0.80645161
0.83870968
0.87096774
0.90322581
0.93548387
0.96774194
0.1
Inputs
Data
Output
Metfile:
PRZM
EXAMS
Chemical
Description
Molecular
Henry's
Vapor
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
Average
.112
.112
.112
.112
.112
.112
.112
.112
.112
.112
.112
.112
.112
.112
.112
.112
.112
.112
generated
used
File:
w12834.dvf
scenario:
environment
Name:
Variable
weight
Law
Pressure
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.0867
0.086896
of
by
for
DVPtrfl
FI_turfC.txt
file:
DDVP
Name
mwt
Const.
vapr
0.03732
0.03732
0.03732
0.03732
0.03731
0.03731
0.03731
0.03731
0.03731
0.03731
0.03731
0.03731
0.03731
0.03731
0.03731
0.03731
0.03731
0.037578
yearly
pe4.pl
this
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.01389
0.013992
averages:
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
.009268
.009268
.009267
.009267
.009267
.009267
.009267
.009266
.009266
.009266
.009266
.009266
.009266
.009266
.009265
.009265
.009265
.009334
.002286
0.002285
0.002285
0.002285
0.002285
0.002285
0.002285
0.002285
0.002285
0.002285
0.002285
0.002285
0.002285
0.002282
0.00228
0.002279
0.002279
0.002279
0.002296
8-Aug-03
run:
pond298.exv
Value
220.9
henry
1 .20E-02
Units
g/mol
5.01 E-08
torr
Comment
s
atm-mA3/mol
65
-------
Solubility
Kd
Koc
Photolysis
Aerobic
Anaerobic
Aerobic
Hydrolysis:
Method:
Incorporation
Application
Application
Spray
Application
Record
Record
Flag
Flag
sol
Kd
Koc
half-life
Aquatic
Aquatic
Soil
PH
CAM
Depth:
Rate:
Efficiency:
Drift
Date
17:00
IPSCND
UPTKF
18:00
PLDKRT
FEXTRC
for
for
10000
mg/L
37
kdp
Metabolism
Metabolism
Metabolism
7
2
DEPI
TAPP
APPEFF
DRFT
Date
F I LIRA
1
PLVKRT
2.64
0.5
Index
runoff
mg/L
mg/L
10.2
kbacw
kbacs
asm
5.2
integer
0
0.224
0.99
0.01
20-05
Res.
calc.
days
0
0
0.42
days
See
cm
kg/ha
fraction
fraction
dd/mm
Run
RUNOFF
Half-life
days
days
days
Half-life
PRZM
of
or
IR
none
Halfife
Halfife
Halfife
manual
applicatio
dd/mmm
Pond
none,
stored as
Chemical: DDVP
PRZM environment FLturfC.txt
FLORIDA TURF 4 APPLICATIONS, 30 DAY INTERVAL, 0.2 Ibs/A
DVPFLtrf.out
modified Monday, 16 June
EXAMS environment pond298.exv modified Thuday, 29 August
w12834.dvf modified Wedday, 3 July 2002
segment concentrations (ppb)
Metfile:
Water
Year
Peak 96 Hr 21 Day 60 Day 90 Day Yearly
1961 0.114 0.09286 0.04047 0.02871 0.0284 0.009295
1962 0.1188 0.1001 0.04436 0.0302 0.0294 0.009537
1963 0.114 0.08831 0.03803 0.02781 0.02781 0.009148
1964 0.114 0.08833 0.03806 0.02782 0.02781 0.00912
1965 0.114 0.08831 0.03804 0.02781 0.02781 0.009143
1966 2.983 2.309 0.9941 0.3839 0.2653 0.06772
66
-------
1967 0.114 0.08832 0.03804 0.02782 0.02781 0.009144
1968 0.1247 0.09659 0.0416 0.02954 0.02897 0.009406
1969 0.114 0.08832 0.03813 0.02785 0.02783 0.00915
1970 0.114 0.08833 0.03805 0.02782 0.02781 0.009144
1971 0.114 0.08831 0.03804 0.02782 0.02781 0.009144
1972 2.374 1.838 0.7913 0.3083 0.2149 0.05513
1973 0.114 0.08832 0.03804 0.02782 0.02781 0.009145
1974 0.114 0.08832 0.03804 0.02782 0.02781 0.009145
1975 0.114 0.08835 0.03806 0.02783 0.02782 0.009147
1976 0.114 0.08831 0.03803 0.02781 0.02781 0.009142
1977 0.114 0.08831 0.03811 0.02784 0.02782 0.009148
1978 0.114 0.08831 0.03803 0.02781 0.0278 0.009143
1979 0.114 0.08832 0.03804 0.02782 0.02781 0.009144
1980 0.114 0.08835 0.03812 0.02784 0.02784 0.009129
1981 0.114 0.08832 0.0381 0.02784 0.02782 0.009147
1982 0.1742 0.135 0.06278 0.03711 0.03401 0.01067
1983 0.114 0.08837 0.03809 0.02783 0.02782 0.009148
1984 0.1222 0.09999 0.04476 0.03035 0.0295 0.009552
1985 0.114 0.09034 0.0392 0.02825 0.0281 0.009239
1986 0.1143 0.09068 0.04065 0.02882 0.02848 0.009309
1987 0.114 0.08835 0.03806 0.02782 0.02781 0.009145
1988 0.114 0.08832 0.03804 0.02781 0.02781 0.009119
1989 0.114 0.08841 0.03808 0.02783 0.02781 0.009145
1990 0.114 0.08831 0.03803 0.02781 0.0278 0.009143
Sorted results
Prob. Peak 96 Hr 21 Day 60 Day 90 Day Yearly
0.03225806 2.983 2.309 0.9941 0.3839 0.2653 0.06772
67
-------
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.06451613
.09677419
.12903226
.16129032
.19354839
.22580645
.25806452
.29032258
.32258065
.35483871
.38709677
.41935484
0.4516129
.48387097
.51612903
0.5483871
.58064516
.61290323
.64516129
.67741935
.70967742
.74193548
.77419355
.80645161
.83870968
.87096774
2.374
0.1742
0.1247
0.1222
0.1
0.1
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
188
143
114
114
114
114
114
114
114
114
114
114
114
114
114
114
114
114
114
114
114
114
1.838
0.135
0.1001
0.09999
0.09659
0.09286
0.09068
0.09034
0.08841
0.08837
0.08835
0.08835
0.08835
0.08833
0.08833
0.08832
0.08832
0.08832
0.08832
0.08832
0.08832
0.08832
0.08831
0.08831
0.08831
0.08831
0.7913
0.06278
0.04476
0.04436
0.0416
0.04065
0.04047
0.0392
0.03813
0.03812
0.03811
0.0381
0.03809
0.03808
0.03806
0.03806
0.03806
0.03805
0.03804
0.03804
0.03804
0.03804
0.03804
0.03804
0.03804
0.03803
0.3083
0.03711
0.03035
0
0.0302
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
.02954
.02882
.02871
.02825
.02785
.02784
.02784
.02784
.02783
.02783
.02783
.02782
.02782
.02782
.02782
.02782
.02782
.02782
.02782
.02781
.02781
.02781
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0.2149
.03401
0.0295
0.0294
.02897
.02848
0.0284
0.0281
.02784
.02783
.02782
.02782
.02782
.02782
.02781
.02781
.02781
.02781
.02781
.02781
.02781
.02781
.02781
.02781
.02781
.02781
0.05513
0.01067
0.009552
0.009537
0.009406
0.009309
0.009295
0.009239
0.00915
0.009148
0.009148
0.009148
0.009147
0.009147
0.009145
0.009145
0.009145
0.009145
0.009144
0.009144
0.009144
0.009144
0.009143
0.009143
0.009143
0.009142
68
-------
0.90322581 0.114 0.08831 0.03803 0.02781 0.02781 0.009129
0.93548387 0.114 0.08831 0.03803 0.02781 0.0278 0.00912
0.96774194 0.114 0.08831 0.03803 0.02781 0.0278 0.009119
0.1
Inputs
Data
Output
Metfile:
PRZM
EXAMS
Chemical
Description
Molecular
Henry's
Vapor
Solubility
Kd
Koc
Photolysis
Aerobic
Anaerobic
Aerobic
Hydrolysis:
Method:
Incorporation
Application
Application
Spray
Application
Interval
Interval
Interval
Record
Record
Flag
Flag
0.16925
Average
generated
used
File:
w12834.dvf
scenario:
environment
Name:
Variable
weight
Law
Pressure
sol
Kd
Koc
half-life
Aquatic
Aquatic
Soil
PH
CAM
Depth:
Rate:
Efficiency:
Drift
Date
1
2
3
17:00
IPSCND
UPTKF
18:00
PLDKRT
FEXTRC
for
for
0.13151
of
by
for
DVPFLtrf
FI_turfC.txt
file:
DDVP
Name
mwt
Const.
vapr
10000
mg/L
37
kdp
Metabolism
Metabolism
Metabolism
7
2
DEPI
TAPP
APPEFF
DRFT
Date
interval
interval
interval
F I LIRA
1
PLVKRT
2.64
0.5
Index
runoff
0.060978
yearly
pe4.pl
this
0.036434
averages:
-
run:
0.033559
0.012728
8-Aug-03
0.010551
pond298.exv
Value
220.9
henry
1 .20E-02
mg/L
mg/L
10.2
kbacw
kbacs
asm
5.2
integer
0
0.224
0.99
0.01
20-05
30
30
30
Res.
calc.
Units
g/mol
5.01E-08
torr
days
0
0
0.42
days
See
cm
kg/ha
fraction
fraction
dd/mm
days
days
days
Run
RUNOFF
Comment
s
atm-mA3/mol
Half-life
days
days
days
Half-life
PRZM
of
or
Set
Set
Set
IR
none
Halfife
Halfife
Halfife
manual
applicatio
dd/mmm
to
to
to
Pond
none,
69
-------
PENNSYLVANIA TURF 1 APPLICATION at 0.2 Ibs/A
stored as DVPtrfPA.out
Chemical: DDVP
PRZM environmentPAturfC.txt modified Satday, 12 October
EXAMS environment pond298.exv modified Thuday, 29 August
Metfile: w14737.dvf modified Wedday, 3 July 2002
Water segment concentration (ppb)
s
Year Peak 96 Hr 21 Day 60 Day 90 Day Yearly
1961 0.112 0.08672 0.03734 0.0139 0.009274 0.002287
1962 0.112 0.08672 0.03734 0.0139 0.009274 0.002287
1963 0.112 0.08672 0.03733 0.0139 0.009273 0.002287
1964 0.112 0.08671 0.03733 0.0139 0.009271 0.00228
1965 0.112 0.08671 0.03733 0.0139 0.009272 0.002287
1966 0.112 0.08672 0.03734 0.0139 0.009273 0.002287
1967 0.112 0.08672 0.03733 0.0139 0.009272 0.002287
1968 0.112 0.08672 0.03734 0.01391 0.009275 0.002281
1969 0.112 0.08671 0.03733 0.0139 0.009271 0.002286
1970 0.112 0.08672 0.03734 0.0139 0.009273 0.002287
1971 0.112 0.08672 0.03734 0.0139 0.009274 0.002287
1972 0.112 0.08672 0.03734 0.0139 0.009274 0.002281
1973 0.112 0.08672 0.03734 0.0139 0.009275 0.002287
70
-------
1974 0.112 0.08672 0.03734 0.0139 0.009274 0.002287
1975 0.112 0.08673 0.03735 0.01391 0.009276 0.002288
1976 0.112 0.08672 0.03733 0.0139 0.009273 0.00228
1977 0.112 0.08671 0.03733 0.0139 0.009271 0.002286
1978 0.112 0.08672 0.03734 0.0139 0.009275 0.002287
1979 0.112 0.08678 0.03742 0.01393 0.009295 0.002292
1980 0.112 0.08672 0.03734 0.0139 0.009273 0.002281
1981 0.112 0.08671 0.03733 0.0139 0.009272 0.002287
1982 0.112 0.08672 0.03734 0.0139 0.009274 0.002287
1983 0.112 0.08686 0.03745 0.01394 0.009301 0.002294
1984 0.4776 0.3698 0.1592 0.05929 0.03955 0.009726
1985 0.112 0.08671 0.03733 0.0139 0.009272 0.002287
1986 0.112 0.08758 0.03798 0.01414 0.009435 0.002327
1987 0.112 0.08672 0.03733 0.0139 0.009272 0.002287
1988 0.112 0.08672 0.03734 0.0139 0.009274 0.002281
1989 0.112 0.08672 0.03734 0.0139 0.009275 0.002287
1990 0.112 0.08672 0.03734 0.0139 0.009273 0.002287
Sorted results
Prob. Peak 96 Hr 21 Day 60 Day 90 Day Yearly
0.03225806 0.4776 0.3698 0.1592 0.05929 0.03955 0.009726
0.06451613 0.112 0.08758 0.03798 0.01414 0.009435 0.002327
0.09677419 0.112 0.08686 0.03745 0.01394 0.009301 0.002294
0.12903226 0.112 0.08678 0.03742 0.01393 0.009295 0.002292
0.16129032 0.112 0.08673 0.03735 0.01391 0.009276 0.002288
0.19354839 0.112 0.08672 0.03734 0.01391 0.009275 0.002287
0.22580645 0.112 0.08672 0.03734 0.0139 0.009275 0.002287
71
-------
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.25806452
.29032258
.32258065
.35483871
.38709677
.41935484
0.4516129
.48387097
.51612903
0.5483871
.58064516
.61290323
.64516129
.67741935
.70967742
.74193548
.77419355
.80645161
.83870968
.87096774
.90322581
.93548387
.96774194
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08672
0.08671
0.08671
0.08671
0.08671
0.08671
0.08671
0.03734
0.03734
0.03734
0.03734
0.03734
0.03734
0.03734
0.03734
0.03734
0.03734
0.03734
0.03734
0.03734
0.03733
0.03733
0.03733
0.03733
0.03733
0.03733
0.03733
0.03733
0.03733
0.03733
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.0139
0.009275
0.009275
0.009274
0.009274
0.009274
0.009274
0.009274
0.009274
0.009274
0.009273
0.009273
0.009273
0.009273
0.009273
0.009273
0.009272
0.009272
0.009272
0.009272
0.009272
0.009271
0.009271
0.009271
0.002287
0.002287
0.002287
0.002287
0.002287
0.002287
0.002287
0.002287
0.002287
0.002287
0.002287
0.002287
0.002287
0.002287
0.002287
0.002286
0.002286
0.002281
0.002281
0.002281
0.002281
0.00228
0.00228
0.1 0.112 0.086852 0.037447 0.013939 0.0093 0.002294
Average of yearly averages: 0.002535
Inputs generated by pe4.pl - 8-Aug-03
72
-------
Data
Output
Metfile:
PRZM
EXAMS
Chemical
Description
Molecular
Henry's
Vapor
Solubility
Kd
Koc
Photolysis
Aerobic
Anaerobic
Aerobic
Hydrolysis:
Method:
Incorporatio
n
Application
Application
Spray
Application
Record
Record
Flag
Flag
used
File:
w14737.dvf
scenario:
environment
Name:
Variable
weight
Law
Pressure
sol
Kd
Koc
half-life
Aquatic
Aquatic
Soil
PH
CAM
Depth:
Rate:
Efficiency:
Drift
Date
17:00
IPSCND
UPTKF
18:00
PLDKRT
FEXTRC
for
for
for
DVPtrfPA
PAturfC.txt
file:
DDVP
Name
mwt
Const.
vapr
10000
mg/L
37
kdp
Metabolism
Metabolism
Metabolism
7
2
DEPI
TAPP
APPEFF
DRFT
Date
F I LIRA
1
PLVKRT
2.64
0.5
Index
runoff
this
pond;
Value
henry
1.2C
mg/L
mg/L
kbacv
kbacj
asm
integ<
i
20-0£
Res.
calc.
PENNSYLVANIA TURF 4 APPLIQ
stored
Chemical:
PRZM
as
DDVP
environment
DVPPAtrf.out
PAturfC.txt
moi
run:
9 Units Comment
s
220.9 g/mol
/ 5.01E-08atm-mA3/mol
1.20E-02 torr
10.2 days Half-life
0 days Halfife
0 days Halfife
0.42 days Halfife
5.2 days Half-life
r See PRZM manual
0 cm
0.224 kg/ha
0.99 fraction
0.01 fraction
5 dd/mm
of
or
applicatio
dd/mmm
Run
IR
RUNOFF none
Pond
none,
;d Satday, 12 October
EXAMS environment pond298.exv modified Thuday, 29 August
Metfile: w14737.dvf modified Wedday, 3 July 2002
Water segment concentrations (ppb)
73
-------
Year Peak 96 Hr 21 Day 60 Day 90 Day Yearly
1961 0.1141 0.08833 0.03807 0.02784 0.02783 0.00915
1962 0.114 0.08832 0.03805 0.02783 0.02782 0.009149
1963 0.1141 0.08865 0.03822 0.02789 0.02786 0.009159
1964 0.1141 0.08833 0.03805 0.02783 0.02782 0.009123
1965 0.114 0.08833 0.03806 0.02783 0.02782 0.009148
1966 0.114 0.08832 0.03804 0.02782 0.02781 0.009147
1967 0.1141 0.08833 0.03806 0.02783 0.02782 0.009149
1968 0.114 0.08833 0.03805 0.02783 0.02782 0.009124
1969 0.1141 0.08833 0.03807 0.02783 0.02783 0.009149
1970 0.1262 0.1047 0.04681 0.03112 0.03001 0.00969
1971 0.114 0.08832 0.03804 0.02782 0.02782 0.009148
1972 0.1142 0.09017 0.04004 0.02893 0.02856 0.009307
1973 0.114 0.08833 0.03805 0.02782 0.02782 0.009149
1974 0.1141 0.08834 0.03806 0.02783 0.02782 0.00915
1975 0.1142 0.09152 0.03976 0.02847 0.02825 0.009256
1976 0.114 0.08832 0.03805 0.02782 0.02782 0.009123
1977 0.26 0.2014 0.08673 0.04596 0.03991 0.01213
1978 0.1141 0.08834 0.03806 0.02783 0.02782 0.00915
1979 0.1141 0.08833 0.03806 0.02783 0.02782 0.009155
1980 0.114 0.08833 0.03805 0.02782 0.02782 0.009123
1981 0.1141 0.08862 0.03827 0.02792 0.02789 0.009164
1982 0.114 0.08833 0.03805 0.02782 0.02782 0.009149
1983 0.1496 0.1192 0.05453 0.03402 0.03195 0.01017
1984 0.4776 0.3698 0.1592 0.07293 0.05792 0.01657
1985 0.114 0.08833 0.03805 0.02783 0.02782 0.009148
1986 0.1141 0.08833 0.03805 0.02785 0.02784 0.009188
74
-------
1987 0.114 0.08833 0.03809 0.02784 0.02784 0.009152
1988 0.1141 0.09001 0.03895 0.02816 0.02804 0.009178
1989 0.1142 0.09185 0.03993 0.02864 0.02837 0.009285
1990 0.114 0.08832 0.03805 0.02782 0.02782 0.009148
Sorted results
Prob. Peak 96
0.03225806 0.4776
Hr 21 Day 60 Day 90 Day Yearly
0.3698 0.1592 0.07293 0.05792 0.01657
0.06451613 0.26 0.2014 0.08673 0.04596 0.03991 0.01213
0.09677419 0.1496 0.1192 0.05453 0.03402 0.03195 0.01017
0.12903226 0.1262 0.1047 0.04681 0.03112 0.03001 0.00969
0.16129032 0.1142 0.09185 0.04004 0.02893 0.02856 0.009307
0.19354839 0.1142 0.09152 0.03993 0.02864 0.02837 0.009285
0.22580645 0.1142 0.09017 0.03976 0.02847 0.02825 0.009256
0.25806452 0.1141 0.09001 0.03895 0.02816 0.02804 0.009188
0.29032258 0.1141 0.08865 0.03827 0.02792 0.02789 0.009178
0.32258065 0.1141 0.08862 0.03822 0.02789 0.02786 0.009164
0.35483871 0.1141 0.08834 0.03809 0.02785 0.02784 0.009159
0.38709677 0.1141 0.08834 0.03807 0.02784 0.02784 0.009155
0.41935484 0.1141 0.08833 0.03807 0.02784 0.02783 0.009152
0.4516129 0.1141 0.08833 0.03806 0.02783 0.02783 0.00915
0.48387097 0.1141 0.08833 0.03806 0.02783 0.02782 0.00915
0.51612903 0.1141 0.08833 0.03806 0.02783 0.02782 0.00915
0.5483871 0.1141 0.08833 0.03806 0.02783 0.02782 0.009149
0.58064516 0.1141 0.08833 0.03806 0.02783 0.02782 0.009149
0.61290323 0.114 0.08833 0.03805 0.02783 0.02782 0.009149
0.64516129 0.114 0.08833 0.03805 0.02783 0.02782 0.009149
75
-------
0.67741935
0.70967742
0.74193548
0.77419355
0.80645161
0.83870968
0.87096774
0.90322581
0.93548387
0.96774194
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
14
14
14
14
14
14
14
14
14
14
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
.08833
.08833
.08833
.08833
.08833
.08832
.08832
.08832
.08832
.08832
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
.03805
.03805
.03805
.03805
.03805
.03805
.03805
.03805
.03804
.03804
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
.02783
.02783
.02783
.02782
.02782
.02782
.02782
.02782
.02782
.02782
0.02782
0.02782
0.02782
0.02782
0.02782
0.02782
0.02782
0.02782
0.02782
0.02781
0.
0.
0.
0.
0.
0.
0.
0.
0.
0.
.009149
.009148
.009148
.009148
.009148
.009147
.009124
.009123
.009123
.009123
Inputs
Data
Output
Metfile:
PRZM
EXAMS
Chemical
Description
Molecular
Henry's
Vapor
Solubility
Kd
Koc
Photolysis
Aerobic
Anaerobic
Aerobic
Hydrolysis:
Method:
Incorporation
Application
Application
Spray
Application
0.1 0.14726
Average of
generated by
0.11775 0.053758 0.03373 0.031756 0.010122
yearly averages: 0.009561
pe4.pl - 8-Aug-03
used
File:
w14737.dvf
scenario:
environment
Name:
Variable
weight
Law
Pressure
sol
Kd
Koc
half-life
Aquatic
Aquatic
Soil
PH
CAM
Depth:
Rate:
Efficiency:
Drift
Date
for
DVPPAtrf
PAturfC.txt
file:
DDVP
Name
this
run:
pond298.exv
Value
Units
mwt
Const.
vapr
mg/L
Comment
s
220.9 g/mol
henry 5.01E-08 atm-mA3/mol
1.20E-02 torr
10000 mg/L
kdp
Metabolism
Metabolism
Metabolism
DEPI
TAPP
APPEFF
DRFT
Date
37 mg/L
10.2 days
kbacw
kbacs
asm
7 5.2 days
2 integer See
0 cm
0.224 kg/ha
0.99 fraction
0.01 fraction
20-05 dd/mm
Half-life
0 days
0 days
0.42 days
Half-life
PRZM
of
or
Halfife
Halfife
Halfife
manual
applicatio
dd/mmm
76
-------
Interval
Interval
Interval
Record
Record
Flag
Flag
1 interval
2 interval
3 interval
17:OOFILTRA
IPSCND 1
UPTKF
18:OOPLVKRT
PLDKRT 2.64
FEXTRC 0.5
for Index Res.
for runoff calc.
30 days
30 days
30 days
Run
RUNOFF
Set
Set
Set
IR
none
to
to
to
Pond
none,
77
-------
APPENDIX D. TERRESTRIAL EXPOSURE AND RQ CALCULATION - T-REX MODEL
T-REX Version 1.1
December 7, 2004
The T-REX spreadsheet has been developed by the Plant, Terrestrial Biology and Exposure Technical
Teams.
For information or questions concerning this spreadsheet, please contact John Ravenscroft or Edward
Odenkirchen.
*NOTE**: Please save the spreadsheet file to you own computer first. Select 'File', then 'Save As' on the
menu bar. Select the destination on your own hard drive (usually set to C:). Do not modify the
spreadsheet on the F: drive.
Scroll down to next section for instructions.
Introduction and Background
This spreadsheet-based model calculates the decay of a chemical applied to foliar surfaces for single or
multiple applications. It uses the same principle as the batch code models FATE and TERREEC that
calculate terrestrial exposure concentration estimates on plant surfaces following pesticide application. A
first order decay assumption is used to determine the concentration at each day after initial application
based on the concentration resulting from the initial and additional applications. The decay is calculated
from the first order rate equation:
CT = Cie-kT
or in log form:
In (CT/Ci) = kT
Where
CT concentration at time T = day zero.
C concentration, in parts per million (PPM), present initially (on day zero) on the surfaces. C is calculated
by multiplying the application rate, in pounds active ingredient per acre, by 240 for short grass, 110
for tall grass, and 135 for broad-leafed plants/small insects and 15 for fruits/pods/large insects
based on the Kenaga nomogram (Hoerger and Kenaga, 1972) as modified by Fletcher (1994).
For maximum concentrations, additional applications are converted from pounds active ingredient
per acre to PPM on the plant surface and the additional mass added to the mass of the chemical
still present on the surfaces on the day of application.
k = If the foliar dissipation data submitted to EFED are found scientifically valid and
statistically robust for a specific pesticide, the 90% upper confidence limit of the mean half-
lives should be used. When scientifically valid, statistically robust data are not available,
EFED recommends the using a default half-life value of 35 days. The use of the 35-day half-
life is based on the highest reported value (36.9 days), as reported by Willis and McDowell
(Pesticide persistence on foliage, Environ. Contam. Toxicol, 100:23-73,1987).
78
-------
T =time, in days, since the start of the simulation. The initial application is on day 0. The simulation is designed to
run for 365 days.
The spreadsheet calculates the pesticide residue concentrations on each type of surface on a daily interval
for one year. The maximum concentration during the year is calculated for both maximum and mean
residues.
The calculated residue concentrations are used to calculate Avian and Mammalian risk quotient (RQ)
values. The maximum calculated concentration is divided by user input values for acute and chronic
endpoints to give RQs for each type of plant surface.
How to use TREX
TREX has been designed to be easy to use, yet maintain a level of flexibility needed for the multitude of
chemicals and use patterns encountered by risk assessors. Throughout the spreadsheet, look for small
red cell tags that contain additional information; just move the cursor over them to display the comment
box. With the exception of the seed treatment exposure worksheet, all necessary data can be entered into
the 'Input' worksheet.
Inputs
An 'Input' worksheet has been included to increase consistency and transparency in the terrestrial
exposure estimation process. The inputs used to calculate the amount of chemical present and estimate
exposure are highlighted in blue, as well as consist of various drop-down menus. These inputs include the
following:
Chemical name:Enter either the chemical or common name used in the assessment
Use:Enterthe crop name and type of use
FormulatiorrEnterthe state of the chemical to be used (e.g., liquid, spray, WP, flowable, etc.)
% A.LEnterthe % A.I. for the formulation (from the label)
Application Rate:The maximum label application rate (pounds ai/acre)
Half-life:The degradation half-life for the dominant process (days)
Application lnterval:The interval between repeated applications, from the label (days)
Maximum # Application per yearFrom the label
Concentration of ConcenrFor graphing purposes, choose an endpoint (mg/kg-diet) that you wish to be
overlaid onto the residue graph
Choose label:From the drop-down menu, choose the label that corresponds to the Concentration of
Concern
NOTE: Pushing the 'reset model' button to the right of the first set of inputs will clear ALL of the
user-supplied information. This button was included to allow the user to more quickly run multiple
scenarios with TREX without having to manually clear each cell.
Endpoints
TREX requires that both the chosen endpoint (entered in the blue cell) and the test species to be
included (chosen from the drop-down menu options). For example, one would enter an avian LD50
of 500 mg/kg-bw and that this endpoint was based on a Bobwhite quail study (i.e., chosen from
the drop-down menu immediately to the right of the LD50 input cell). For now, this requirement is
limited to the avian endpoints.
79
-------
Avian endpoints
Enter the endpoints in the blue cells and choose the corresponding test species from the drop-down
menus.
Mammalian endpoints
For acute endpoints, enter the data in the blue cells. For chronic endpoints, enter the reported number
and then choose whether this datapoint was a dose- or diet-based endpoint from the drop-down menu.
The other endpoint will then be calculated and displayed in the cell below.
LD50 ff2
TREX includes the capability to also calculate an LD50 ft"2 with the above-supplied information.
Choose from the drop-down menu provided whether or not you wish to do so. If 'yes' is chosen,
the type of application method (i.e., broadcast or rows) should be entered. If 'rows' is chosen,
additional input parameters will be required (i.e., row spacing, bandwidth, and % incorporation)
and appear to the right. Next, input whether the application is a granular or liquid application. If
'liquid' is chosen, enter the oz. product per 1000 ft row.
To see the results, choose the LD50 ft"2 worksheet tab. The print area has been pre-set, so choose
the printer button in the toolbar to print.
Terrestrial Exposures
All calculated Estimated Environmental Concentration (EEC) and RQ values are
presented in yellow. Intermediate calculations are displayed in red. Users may find
these intermediate values useful in their assessment, so they are presented.
Upper Bound and Mean Kenaga Residue Worksheets
Both the upper bound and mean Kenaga residues for the various food categories
are provided. Each includes RQs for birds and mammals. The upper bound
residue worksheet is to be used for reporting RQ values in the risk assessment,
while the mean residue worksheet is solely for risk description purposes. Mean
residues are calculated exactly as the maximum residues are, except the
corresponding Kenaga values are 85 for Short Grass, 36 for Tall Grass, and 45
for Broad-leafed plants/small insects and 7 for fruits/pods/large insects.
In both worksheets, dose-based RQs are calculated using a body weight-adjusted
LD50 and consumption-weighted equivalent dose. The scaling factors (USEPA,
1993) used in the consumption-weighted (EECs) are:
Avian consumption
80
-------
Mammal consumption
These consumption-weighted EECs (i.e., EEC equivalent dose) are sorted by food
source and body size. There is a corresponding table for birds and mammals.
The LD50 values entered on the input form are adjusted for animal class (20, 100 and
1000 g birds and 15, 35, and 1000 g mammals) using the following equations:
Avian LD
50
Mammal LD$n
The dose-based RQs are calculated by dividing the daily dose (EEC equivalent dose) by
the adjusted LD50 for each food category and animal class.
For dietary-based RQs, the Kenaga EEC is divided by the LCso (acute RQ) or the
NOAEC (chronic RQ).
Graphs
Each worksheet contains a graph of the calculated residues for the first 100 days and includes the
'Concentration of Concern' overlay from the input form. These can be copy/pasted individually into
a word processing program and used in the risk assessment, if desired. Additionally, graphs
displaying acute and chronic LOCs for both birds and mammals are displayed in the 'Graph'
worksheet.
LD50 ff2
LD50 ft"2 values are calculated for both broadcast and banded (granular and liquid) applications
using the adjusted LD50 method described above. The results are presented by class for both
birds and mammals for each type of application.
81
-------
Seed Treatments
Due to the difference in foliar application and seed treatment uses of pesticides, this worksheet
can be used as a 'stand-alone' tool for estimating avian and mammalian RQs for the various crops
listed. Efforts were made to make this crop list as complete as possible; however, there may be
additional crops added in the future as the need arises. Only those seed treatments needed for
the assessment need to be entered. For example, if rye is not an intended use, then leave it set to
zero, as this will have no impact on the RQ calculations for the other crops.
The seed treatment worksheet contains additional input cells in blue separate from those in the
Input worksheet including:
Name of seed treatment formulation: Labels for seed treatment products differ from foliar
applied formulations.
Percent A.I. in formulation: Enter % A.I. as a whole number (e.g., 24% = 24)
Test body weights: Enter the test organism body weight from the avian and
mammal studies
Application rate (fl oz./cwt): Provided on the label
NOTE: If a liquid rate is not available for a chemical, enter the dry weight application rate in the
adjoining cell. Once this is done; however, the underlying equation in that cell has been replaced.
It is preferable that users input the fl oz/cwt value.
RQs are calculated using the adjusted LD50 for the smallest weight class of animal. Acute RQs
are calculated using two methods:
Method #1: Acute RQ = mg A.I. day'Vadjusted LD50
Method #2: Acute RQ = mg A.I. ft"2/(adjusted LD50 * body weight)
Chronic RQs are calculated using the equation:
Chronic RQ = mg A.I. kg"1 seed/NOAEL
References
Fletcher, J.S., J.E. Nellesson and T. G. Pfleeger. 1994. Literature review and
evaluation of the EPA food-chain (Kenaga) nomogram, an instrument for estimating
pesticide residues on plants. Environ. Tox. And Chem. I3(9):i38s-i39i
Hoerger, F. and E.E. Kenaga. 1972. Pesticide residues on plants: correlation of
respresentative dada as a basis for estimation of their magnitude in the environment.
IN: F. Coulston and F. Corte, eds., Environmental Quality and Safety: Chemistry,
Toxicology and Technology. Vol i. Georg Theime Publishers, Stuttgart, Germany, pp. 9-
28
82
-------
USEPA. 1993. Wildlife Exposure Factors Handbook. Volume I of II. EPA/6oo/R-
93/1873. Office of Research and Development, Washington, D. C. 20460.
Willis and McDowell. 1987. Pesticide persistence on foliage. Environ. Contam.
Toxicol. 100:23-73
83
-------
TURF -1 APPLICATION AT 0.2 LBS/A
Chemical Name:
Use
Formulation
Application Rate
Half-life
Application Interval
Maximum # Apps./Year
Length of Simulation
Concentration of
Concern
Name of Concentration
of Concern
Dichlorvos
Turf
Liquid spray
0.0804 Ibs a.i./acre
0.0875 days
0 days
1
1
year
0.00
FALSE
(ppm)
Endpoints
Avian
Mallard duck LD50 (mg/kg-
bw)
Mallard duck LC50 (mg/kg-
diet)
Bobwhite quail NOAEL
(mg/kg-bw)
Mallard duck NOAEC (mg/kg-
diet)
7.78
568
0
5
Mammals
LD50 (mg/kg-bw)
LC50 (mg/kg-diet)
NOAEL (mg/kg-bw)
NOAEC (mg/kg-diet)
56
0
1
20
EECS (ppm)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
Fruits/pods/seeds/lg
insects
Kenaga
Values
19.30
8.84
10.85
1.21
Avian Results
84
-------
Avian
Class
Small
Mid
Large
Body
Weight
20
100
1000
% body wgt
consumed
114
65
29
Adjusted
LD50
4.04
5.14
7.26
EEC
equivalent
dose
(mg/kg-bw)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
Fruits/pods/lg insects
Avian Classes and Body Weights
small
20 g
22
10
12
1
mid
100 g
13
6
7
1
large
1000 g
6
3
3
0
Dose-based
RQS (daily
dose/LD50)
Short Grass
Tall Grass
Broadleaf plants/sm
insects
Fruits/pods/lg insects
Avian Acute RQs
20 g
5.45
2.50
3.06
0.34
100 g
2.44
1.12
1.37
0.15
1000 g
0.77
0.35
0.43
0.05
Dietary-
based RQs
(EEC/LC50 or
NOAEC)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
Fruits/pods/lg insects
RQs
Acute
0.03
0.02
0.02
0.00
Chronic
3.86
1.77
2.17
0.24
85
-------
Mammalian
Results
Mammalian
Class
Herbivores/
insectivores
Grainvores
Body
Weight
15
35
1000
15
35
1000
% body
wgt
consume
d
95
66
15
21
15
3
Adjusted
LD50
123.08
99.58
43.07
123.08
99.58
43.07
Adjusted
NOAEL
2.20
1.78
0.77
2.20
1.78
0.77
EEC
equivalent
dose
(mg/kg-bw)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
Fruits/pods/seeds/lg
insects
Mammalian Classes and Body weight
Herbivores/
insectivores
15 g 35 g 1000 g
18
8
10
1
13
6
7
1
3
1
2
0
Granivore
s
15 g 35 g 1000 g
0
0
0
Dose-based
RQS (daily
dose/LD50 or
NOAEL)
Short Grass
15 g
mammal
Acute
0.15
Chronic
8.34
35 g mammal
Acute Chronic
0.13 7.16
1000 g mammal
Acute Chronic
0.07 3.76
86
-------
Tall Grass
Broadleaf plants/sm
insects
Fruits/pods/lg insects
Seeds (granivore)
0.07
0.08
0.01
0.00
3.82
4.69
0.52
0.12
0.06
0.07
0.01
0.00
3.28
4.03
0.45
0.10
0.03
0.04
0.00
0.00
1.72
2.12
0.24
0.05
Dietary-
based RQs
(EEC/LC50 or
NOAEC)
Short Grass
Tall Grass
Broadleaf plants/sm
insects
Fruits/pods/seeds/lg
insects
Mammal
RQs
Acute
Chronic
0.96
0.44
0.54
0.06
87
-------
-------
TURF - 4 APPLICATION, 30 DAY APPLICATION INTERVALS, AT 0.2
LBS/A
Chemical Name:
Use
Formulation
Application Rate
Half-life
Application Interval
Maximum # Apps./Year
Length of Simulation
Concentration of
Concern
Name of Concentration
of Concern
Dichlorvos
Turf
Liquid spray
0.0804
0.0875
30
4
1
0.00
FALSE
Ibs a. i. /acre
days
days
year
(ppm)
Endpoints
Avian Mallard duck LD50
(mg/kg-bw)
Mallard duck LC50
(mg/kg-diet)
Bobwhite quail NOAEL
(mg/kg-bw)
Mallard duck NOAEC
(mg/kg-diet)
7.78
568
0
5
Mammals LDSO (mg/kg-bw)
LC50 (mg/kg-diet)
NOAEL (mg/kg-bw)
NOAEC (mg/kg-diet)
56
0
1
20
EECS (ppm)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
Fruits/pods/seeds/lg
insects
Kenaga
Values
19.30
8.84
10.85
1.21
Avian Results
| Avian Body % body Adjusted |
89
-------
wgt
Class
Small
Mid
Large
Weight
20
100
1000
consume
d
114
65
29
LD50
4.04
5.14
7.26
EEC
equivalent
dose
(mg/kg-bw)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
Fruits/pods/lg insects
Avian Classes and Body Weights
small
20 g
22
10
12
1
mid
100 g
13
6
7
1
large
1000g
6
3
3
0
Dose-based
RQS (daily
dose/LD50)
Short Grass
Tall Grass
Broadleaf plants/sm
insects
Fruits/pods/lg insects
Avian Acute RQs
20 g
5.45
2.50
3.06
0.34
100 g
2.44
1.12
1.37
0.15
1000 g
0.77
0.35
0.43
0.05
Dietary-
based RQs
(EEC/LC50 or
NOAEC)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
RQs
Acute
0.03
0.02
0.02
Chronic
3.86
1.77
2.17
90
-------
|Fruits/pods/lg insects
0.00
0.24
91
-------
Mammalian
Results
Mammalian
Class
Herbivores/
insectivores
Grainvores
Body
Weight
15
35
1000
15
35
1000
% body
wgt
consume
d
95
66
15
21
15
3
Adjusted
LD50
123.08
99.58
43.07
123.08
99.58
43.07
Adjusted
NOAEL
2.20
1.78
0.77
2.20
1.78
0.77
EEC
equivalent
dose
(mg/kg-bw)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
Fruits/pods/seeds/lg
insects
Mammalian Classes and Body weight
Herbivores/
insectivores
15 g 35 g 1000 g
18
8
10
1
13
6
7
1
3
1
2
0
Granivore
s
15 g 35 g 1000 g
0
0
0
Dose-based
RQS (daily
dose/LD50 or
NOAEL)
Short Grass
Tall Grass
Broadleaf plants/sm
insects
Fruits/pods/lg insects
Seeds (granivore)
15 g
mammal
Acute
0.15
0.07
0.08
0.01
0.00
Chronic
8.34
3.82
4.69
0.52
0.12
35 g mammal
Acute
0.13
0.06
0.07
0.01
0.00
Chronic
7.16
3.28
4.03
0.45
0.10
1000 g mammal
Acute
0.07
0.03
0.04
0.00
0.00
Chronic
3.76
1.72
2.12
0.24
0.05
92
-------
Dietary-
based RQs
(EEC/LC50 or
NOAEC)
Short Grass
Tall Grass
Broadleaf plants/sm
insects
Fruits/pods/seeds/lg
insects
Mammal
RQs
Acute
Chronic
0.96
0.44
0.54
0.06
93
-------
FLYING INSECT - 0.2 LBS/A
Chemical Name:
Use
Formulation
Application Rate
Half-life
Application Interval
Maximum # Apps./Year
Length of Simulation
Concentration of
Concern
Name of Concentration
of Concern
Dichlor
vos
Flying Insect
Liquid spray
0.0804 Ibs a.i./acre
0.0875 days
5 days
75
1
year
0.00
FALSE
(ppm)
Endpoints
Avian
Mallard duck LD50
(mg/kg-bw)
Mallard duck LC50
(mg/kg-diet)
Bobwhite quail NOAEL
(mg/kg-bw)
Mallard duck NOAEC
(mg/kg-diet)
7.78
568
0
5
Mammals
LD50 (mg/kg-bw)
LC50 (mg/kg-diet)
NOAEL (mg/kg-bw)
NOAEC (mg/kg-diet)
56
0
1
20
EECS (ppm)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
Fruits/pods/seeds/lg
insects
Kenaga
Values
19.30
8.84
10.85
1.21
Avian Results
| Avian Body % body Adjusted |
94
-------
wgt
Class
Small
Mid
Large
Weight
20
100
1000
consume
d
114
65
29
LD50
4.04
5.14
7.26
EEC
equivalent
dose
(mg/kg-bw)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
Fruits/pods/lg insects
Avian Classes and Body Weights
small
20 g
22
10
12
1
mid
100 g
13
6
7
1
large
1000g
6
3
3
0
Dose-based
RQS (daily
dose/LD50)
Short Grass
Tall Grass
Broadleaf plants/sm
insects
Fruits/pods/lg insects
Avian Acute RQs
20 g
5.45
2.50
3.06
0.34
100 g
2.44
1.12
1.37
0.15
1000 g
0.77
0.35
0.43
0.05
Dietary-
based RQs
(EEC/LC50 or
NOAEC)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
RQs
Acute
0.03
0.02
0.02
Chronic
3.86
1.77
2.17
95
-------
|Fruits/pods/lg insects
0.00
0.24
96
-------
Mammalian
Results
Mammalian
Class
Herbivores/
insectivores
Grainvores
Body
Weight
15
35
1000
15
35
1000
% body
wgt
consume
d
95
66
15
21
15
3
Adjusted
LD50
123.08
99.58
43.07
123.08
99.58
43.07
Adjusted
NOAEL
2.20
1.78
0.77
2.20
1.78
0.77
EEC
equivalent
dose
(mg/kg-bw)
Short Grass
Tall Grass
Broadleaf plants/sm
Insects
Fruits/pods/seeds/lg
insects
Mammalian Classes and Body weight
Herbivores/
insectivores
15 g 35 g 1000 g
18
8
10
1
13
6
7
1
3
1
2
0
Granivore
s
15 g 35 g 1000 g
0
0
0
Dose-based
RQS (daily
dose/LD50 or
NOAEL)
Short Grass
Tall Grass
Broadleaf plants/sm
insects
Fruits/pods/lg insects
Seeds (granivore)
15 g
mammal
Acute
0.15
0.07
0.08
0.01
0.00
Chronic
8.34
3.82
4.69
0.52
0.12
35 g mammal
Acute
0.13
0.06
0.07
0.01
0.00
Chronic
7.16
3.28
4.03
0.45
0.10
1000 g mammal
Acute
0.07
0.03
0.04
0.00
0.00
Chronic
3.76
1.72
2.12
0.24
0.05
97
-------
Dietary-
based RQs
(EEC/LC50 or
NOAEC)
Short Grass
Tall Grass
Broadleaf plants/sm
insects
Fruits/pods/seeds/lg
insects
Mammal
RQs
Acute
Chronic
0.96
0.44
0.54
0.06
98
-------
BAIT-1 APPLICATION, 0.1 LBS/A
Chemical:
LDso ft-2
INPUTS
Dichlorvos
Do not overwrite these numbers.
Application Rate:
%A.L:
Avian LDso (2Og):
(lOOg)
(lOOOg)
Mammalian LDso
d5g):
(35g)
(lOOOg)
Row
Spacing:
Bandwidth:
Unincorporation :
0.1
0.0744
4.04
5-14
7.26
123.08
99.58
43-07
0
0
100%
Ibs ai/acre
mg/kg
bw
mg/kg
bw
inches
inches
Broadcast applications
Granular
Intermediate Calculations
mg ai/ft2:
LDSO ft-2
Avian
Mammal
0.08
wgt
class
20 g
100 g
1000 g
15 g
35 g
1000g
0.959
0.151
0.011
0.042
0.022
0.002
99
-------
100
------- |