Reregistration Eligibility Decision
(RED) Document for Nitrapyrin
April 29, 2005
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United States Prevention, Pesticides EPA-738-F-05-003
Environmental Protection And Toxic Substances April 2005
Agency (7508C)
xvEPA
Re registration Eligibility
Decision
Nitrapyrin
List [B]
Case No. 0213
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Reregistration Eligibility Decision (RED) Document for
Nitrapyrin
Approved by:
Debra Edwards, Ph. D.
Director
Special Review and Reregistration Division
Date: April 29, 2005
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TABLE OF CONTENTS
Nitrapyrin Reregistration Eligibility Decision Team i
Glossary of Terms and Abbreviations ii
Executive Summary iv
I. Introduction 1
II. Chemical Overview 2
A. Regulatory History 2
B. Chemical Identification 2
C. Use Profile 3
D. Estimated Usage of Pesticide 4
III. Summary of Nitrapyrin Risk Assessments 4
A. Human Health Risk Assessment 5
1. Dietary Risk from Food 5
a. Toxicity of Nitrapyrin 5
b. FQPA Safety Factor 8
c. Population Adjusted Dose 8
1) Acute PAD 8
2) Chronic PAD 9
d. Exposure Assumptions 9
e. Dietary (Food) Risk Assessment 9
1) Acute Dietary Risk 9
2) Chronic Dietary Risk 9
3) Dietary Cancer Risk 10
2. Dietary Risk from Drinking Water 10
a. Surface Water 11
b. Groundwater 12
3. Residential (Non-dietary) Risk 12
4. Aggregate Risk 12
a. Chronic Aggregate Risk 13
b. Cancer Aggregate Risk 13
5. Cumulative Risk Assessment 14
6. Occupational Risk 14
a. Occupational Toxicity 15
b. Occupational Handler Exposure 16
c. Occupational Handler Risk Summary 16
d. Occupational Postapplication Risk Summary 18
e. Human Incident Data 18
B. Environmental Risk Assessment 18
1. Environmental Exposure 19
a. Environmental Fate and Transport 19
b. Aquatic Organism Exposure 19
c. Terrestrial Organism Exposure 20
2. Environmental Effects (Hazard) 21
a. Toxicity to Aquatic Organisms 21
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b. Toxicity to Terrestrial Organisms 22
3. Ecological Risk Estimation (RQs) 24
a. Risk to Aquatic Organisms 25
b. Risk to Non-target Terrestrial Organisms 26
c. Endangered Species 29
d. Assumptions, Uncertainties, Strengths, and Limitations 29
IV. Risk Management, Reregistration, and Tolerance Reassessment Decision 30
A. Determination of Reregistration Eligibility 30
B. Public Comments and Responses 31
C. Regulatory Position 31
1. Food Quality Protection Act Findings 31
a. "Risk Cup" Determination 31
b. Determination of Safety to U.S. Population 31
c. Determination of Safety to Infants and Children 32
d. Endocrine Disrupter Effects 32
e. Cumulative Risks 32
2. Tolerance Summary 33
a. Tolerances Currently Listed Under 40 CFR §180.350 33
b. Codex Harmonization 34
c. Residue Analytical Methods - Plants and Livestock 35
D. Regulatory Rationale 35
1. Human Health Risk Management 35
a. Dietary (Food) Risk Mitigation 35
b. Drinking Water Risk Mitigation 35
c. Aggregate Risk Mitigation 36
1) Acute Aggregate Risk 36
2) Chronic Aggregate Risk 36
3) Cancer Aggregate Risk 36
d. Occupational Risk Mitigation 36
1) Handler Exposure 36
2) Post-application Risk Mitigation 37
2. Environmental Risk Mitigation 37
3. Other Labeling 37
4. Endangered Species Program 37
V. What Registrants Need to Do 38
A. Manufacturing Use Products 39
1. Additional Generic Data Requirements 39
2. Labeling for Manufacturing Use Products 40
B. End-Use Products 40
1. Additional Product-Specific Data Requirements 40
2. Labeling for End-Use Products 40
C. Label Summary Table 41
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VI. Appendices 45
Appendix A. Food/Feed Use Patterns Subject to Reregistration for Nitrapyrin (Case 0213)
46
Appendix B. Table of Generic Data Requirements and Studies Used to Make the
Reregistration Decision 47
Appendix C. Technical Support Documents 53
Appendix D. Citations Considered to be Part of the Database Supporting the
Reregistration Eligibility Decision (Bibliography) 55
Appendix E. Generic Data Call-In 68
Appendix F. Product Specific Data Call-in 69
Appendix G. EPA's Batching of Nitrapyrin Products for Meeting Acute Toxicity Data
Requirements for Reregistration 70
Appendix H. List of Registrants Sent This Data Call-in 72
Appendix I. List of Available Related Documents and Electronically Available Forms .... 73
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Nitrapyrin Reregistration Eligibility Decision Team
Office of Pesticide Programs:
Biological and Economic Analysis Assessment
Nicole Zinn
Environmental Fate and Effects Risk Assessment
Amer Al-Mudallal
Christine Hartless
Health Effects Risk Assessment
John Doherty
David Soderberg
Seyed Tadayon
Registration Support
Joanne Miller
Risk Management
Stephanie Plummer
Laura Parsons
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Glossary of Terms and Abbreviations
AGDCI
ai
aPAD
AR
BCF
CFR
cPAD
CSF
CSFII
DCI
DEEM
DFR
DWLOC
EC
EEC
EPA
EUP
FDA
FIFRA
FFDCA
FQPA
FOB
G
GENEEC
GLN
HAFT
IR
LD,
'50
LOC
LOD
LOAEL
MATC
mg/kg/day
mg/L
Agricultural Data Call-In
Active Ingredient
Acute Population Adjusted Dose
Anticipated Residue
Bioconcentration Factor
Code of Federal Regulations
Chronic Population Adjusted Dose
Confidential Statement of Formula
USDA Continuing Surveys for Food Intake by Individuals
Data Call-In
Dietary Exposure Evaluation Model
Dislodgeable Foliar Residue
Drinking Water Level of Comparison.
Emulsifiable Concentrate Formulation
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
Functional Observation Battery
Granular Formulation
Tier I Surface Water Computer Model
Guideline Number
Highest Average Field Trial
Index Reservoir
Median Lethal Concentration. A statistically derived concentration of a
substance that can be expected to cause death in 50% of test animals. It is
usually expressed as the weight of substance per weight or volume of
water, air or feed, e.g., mg/1, mg/kg or ppm.
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
Limit of Detection
Lowest Observed Adverse Effect Level
Maximum Acceptable Toxicant Concentration
Micrograms Per Gram
Micrograms Per Liter
Milligram Per Kilogram Per Day
Milligrams Per Liter
11
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MOE
MRID
MUP
NA
NAWQA
NPDES
NR
NOAEL
OP
OPP
OPPTS
PAD
PCA
PDF
PHED
PHI
ppb
PPE
ppm
PRZM/EXAMS
Qi*
RAC
RED
REI
RfD
RQ
SCI-GROW
SAP
SF
SLC
SLN
TCPSA
TGAI
TRR
USDA
USGS
UF
UV
WPS
Margin of Exposure
Master Record Identification (number). EPA's system of recording and
tracking studies submitted.
Manufacturing-Use Product
Not Applicable
USGS National Water Quality Assessment
National Pollutant Discharge Elimination System
Not Required
No Observed Adverse Effect Level
Organophosphate
EPA Office of Pesticide Programs
EPA Office of Prevention, Pesticides and Toxic Substances
Population Adjusted Dose
Percent Crop Area
USDA Pesticide Data Program
Pesticide Handler's Exposure Data
Preharvest 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
Reregi strati on Eligibility Decision
Restricted Entry Interval
Reference Dose
Risk Quotient
Tier I Ground Water Computer Model
Science Advisory Panel
Safety Factor
Single Layer Clothing
Special Local Need (Registrations Under Section 24(c) of FIFRA)
2,3,3-trichloroprop-2-ene sulfonic acid (nitrapyrin Metabolite)
Technical Grade Active Ingredient
Total Radioactive Residue
United States Department of Agriculture
United States Geological Survey
Uncertainty Factor
Ultraviolet
Worker Protection Standard
in
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Executive Summary
This document presents the Environmental Protection Agency's (hereafter the Agency or
EPA) decision regarding the reregi strati on eligibility of the registered uses of nitrapyrin [2-
chloro-6-(trichloromethyl) pyridine]. The Agency made its reregi strati on eligibility
determination based on the required data, the current guidelines for conducting acceptable
studies to generate such data, and published scientific literature. The Agency has found that
currently registered uses of nitrapyrin are eligible for reregi strati on, provided that the changes
specified in this document are made to the label.
Nitrapyrin is a nitrification inhibitor used on corn, sorghum, and wheat. There are tolerances
for nitrapyrin on corn, wheat, sorghum, livestock, and poultry. The Agency estimates that
approximately 99% of nitrapyrin is used on corn, with the remaining 1% used on sorghum and
wheat.
Risks summarized in this document are those that result only from the use of nitrapyrin. The
Food Quality Protection Act (FQPA) requires that the Agency consider available information
concerning the cumulative effects of a particular pesticide's residues and 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 toxic mechanism could lead to the same adverse health effect as would
a higher level of exposure to any of the substances individually. Unlike other pesticides for
which EPA has followed a cumulative risk approach based on a common mechanism of toxicity,
EPA has not made a common mechanism of toxicity finding for nitrapyrin and any other
substances, and nitrapyrin does not appear to produce a toxic metabolite produced by other
substances. For the purposes of this action, therefore, EPA has assumed that nitrapyrin does not
have a common mechanism of toxicity with other substances. 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://www.epa.gov/pesi ci des/cumul ati ve/.
Dietary Risk from Food
No acute dietary assessment was performed for nitrapyrin. The chronic (non-cancer) dietary
risks are less than 100% of the Chronic Population Adjusted Dose (cPAD) for all population
subgroups and are therefore not of concern.
Dietary Risk from Drinking Water
Drinking water exposure to pesticides can occur through groundwater and surface water
contamination. All modeled surface water EECs (which are < 1.71 ppb) and ground water EECs
(which are < 278.82 ppb) are less than the chronic DWLOCs (300 or greater) and therefore are
not of concern.
iv
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Residential Risk
There are currently no nitrapyrin products registered for residential use; therefore, a
residential risk assessment was not conducted.
Aggregate Risk
A chronic aggregate risk assessment was conducted for nitrapyrin. The chronic aggregate
risk assessment looked at the combined risk from dietary exposure (food and drinking water
pathways), since there are no residential uses. Chronic risks from food exposures were below
the Agency's level of concern, with a cPAD of less than 100%.
Occupational Risk
The Agency identified two major occupational scenarios where exposures might occur: (1)
mixing/loading liquids for groundboom application; and (2) applying sprays via groundboom.
Occupational risks were assessed for short and intermediate term exposures only because use
patterns for nitrapyrin do not suggest any long term use. For the two exposure scenarios, all
margin of exposure (MOE) values calculated did not exceed EPA's level of concern.
Workers would be expected to be exposed to nitrapyrin, which is classified as "likely to be a
human carcinogen" based on the mouse study that demonstrated liver tumors, stomach tumors,
and Harderian gland neoplasm. The Qi* was determined to be 4.25 X 10"2 (mg/kg/day)"1 human
equivalents. At baseline PPE, cancer risks for workers mixing/loading liquids for groundboom
application exceed the Agency's level of concern; however, when the PPE that is required on
current labels is worn (long pants, long sleeved shirt, and gloves), the cancer risk is considered to
be at an acceptable level for non-commercial and commercial handlers, who would use the
product more than 30 days.
Ecological Risk
Nitrapyrin hydrolyzes and photodegrades rapidly, and hence should not persist in most
environments. It is shown to be mobile to moderately mobile in mineral soils, and also prone to
volatilize from the application site, so it could leave application sites through leaching or
volatilization. 6-CPA, the primary degradate of nitrapyrin, is mobile and degrades via
hydroxylation (breaking the pyridine ring) and microbial mineralization.
EPA concludes that nitrapyrin presents ecological risks of concern only when soil
incorporation does not occur immediately after incorporation. In order for nitrapyrin to be
eligible for reregi strati on, the Agency has determined that the product labels must require
immediate soil incorporation. The implementation of this mitigation measure should result in
decreased exposure values, leading to much lower RQs for both terrestrial and aquatic
organisms. When soil incorporation occurs immediately after application, ecological risks are
below the Agency's levels of concern for terrestrial and aquatic organisms, and EPA has
therefore determined that no further risk mitigation is necessary for environmental concerns.
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Endangered Species
The screening level risk assessment for nitrapyrin resulted in no acute risks above EPA's
level of concern to any listed species and no chronic risks above EPA's level of concern for any
listed terrestrial organisms if nitrapyrin is incorporated immediately post-treatment. However,
at this time, the Agency does not have chronic toxicity data for estuarine aquatic organisms.
Therefore, EPA concludes that there is "no effect" from direct acute risks for any listed species
and from direct chronic risks for any listed terrestrial species when nitrapyrin is soil incorporated
immediately post-treatment. The EPA cannot, at this time, make a clear "no effect" finding for
indirect effects or for direct chronic effects for listed estuarine organisms.
The general risk mitigation required through this RED will serve to protect listed species of
potential concern until such time as the Agency refines its risk assessment for plants and for
chronic effects to avian species. If in the future specific measures are necessary for the
protection of listed species, the Agency will implement them through the Endangered Species
Protection Program.
Risk Mitigation Summary
The only risks of concern from current uses of nitrapyrin are risks to birds and mammals.
Currently all end-use product labels except one require soil incorporation to take place during or
immediately after application. One product (EPA Reg. No. 34701-804) allows for a delay of up
to 48 hours. By changing this label to also require immediate incorporation, all ecological risks
of concern are reduced to acceptable levels. Therefore, EPA will require the registrant to revise
its label.
Next Steps
The Agency is announcing issuance of the Reregi strati on Eligibility Document (RED) for
nitrapyrin in the Federal Register', with a 60-day public comment period. This RED document
includes guidance and time frames for complying with any required label changes for products
containing nitrapyrin. With the addition of the label restrictions and amendments detailed in this
document, the Agency has determined that all currently registered uses of nitrapyrin are eligible
for reregistration. If substantive information is received during the comment period that
indicates a need to refine any of EPA's assumptions or a need for additional risk mitigation, then
this decision will be modified as appropriate through an amendment to the RED.
In the future, EPA will issue a generic data call-in (DCI) for additional data necessary to
confirm the conclusions of this RED for the active ingredient nitrapyrin. EPA will also issue a
product specific DCI for data necessary to complete reregistration for products containing
nitrapyrin.
VI
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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 amended Act calls for the development and submission of data to
support the reregistration of an active ingredient, as well as a review of all submitted data by
the U.S. Environmental Protection Agency (hereafter referred to as EPA or the Agency).
Reregistration involves a thorough review of the scientific database underlying a pesticide's
registration. The purpose of the Agency's review is to reassess the potential risks arising
from the currently registered uses of the pesticide, to determine the need for additional data
on health and environmental effects, and to determine whether or not the pesticide meets the
"no unreasonable adverse effects" criteria of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into
law. This Act amends FIFRA to require reassessment of all tolerances in effect on the day
before it was enacted. EPA decided that, for those chemicals that have tolerances and are
undergoing reregistration, tolerance reassessment will be accomplished through the
reregistration process. FQPA also amended the FFDCA to require a safety finding in
tolerance reassessment based on factors that include an assessment of cumulative effects of
chemicals with a common mechanism of toxicity. The reason for consideration of other
substances is that the possibility exists that low-level exposures to multiple chemicals that
cause a common toxic effect by a common mechanism could lead to the same adverse health
effect as would a high level of exposure to any one of the other substances individually.
FQPA requires that the Agency consider available information concerning the cumulative
effects of a particular pesticide's residues and 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 of toxicity could lead to the same adverse health effect
that would occur at a higher level of exposure to any of the substances individually. Unlike
other pesticides for which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for
nitrapyrin and any other substances, and nitrapyrin does not appear to produce a toxic
metabolite produced by other substances. For the purposes of this action, therefore, EPA has
assumed that nitrapyrin does not have a common mechanism of toxicity with other
substances. 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://www.epa.gov/pesticides/cumulative.
This document presents EPA's revised human health and ecological risk assessments and
its progress toward tolerance reassessment, and the reregistration eligibility decision for
nitrapyrin. The document consists of six sections: section I contains the regulatory
framework for reregistration/tolerance reassessment; section II provides a profile of the use
and usage of the chemical; section III gives an overview of the revised human health and
environmental effects risk assessments based on data, public comments, and other
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information received in response to the preliminary risk assessments, section IV presents the
Agency's reregi strati on eligibility and risk management decisions; section V summarizes
label changes necessary to implement the risk mitigation measures outlined in Section IV;
and section VI provides information on how to access related documents. Finally, the
Appendices list related and supporting documents and Data Call-In (DCI) information. The
revised risk assessment documents and related addenda are not included in this document,
but are available on the Agency's web page http://www.epa.gov/pesticides, and in the Public
Docket under docket number OPP-2004-0283.
II. Chemical Overview
A. Regulatory History
Nitrapyrin has been registered in the United States since 1974 for use as a nitrification
inhibitor. During the second phase of reregi strati on, the Agency conducted a review of the
scientific data base underlying pesticide registrations and identified any missing or
inadequate studies. Subsequent Data Call-Ins (DCIs) were issued in 1991 and 1995 for
nitrapyrin. This Reregi strati on Eligibility Decision (RED) reflects a reassessment of all data
submitted to date.
There are four products containing nitrapyrin registered under Section 3 of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA). Currently, there are no Section 18
(Emergency Exemption) uses, or Section 24(c) (Special Local Need) uses registered for
nitrapyrin. This Reregistration Eligibility Decision document evaluates risks from all
currently registered uses.
A close-out conference call was conducted on April 28, 2005, with EPA, USD A, and the
registrant, to discuss the risk management decisions and resultant changes to the nitrapyrin
labels.
B.
Chemical Identification
Figure A. Chemical structures of Nitrapyrin Residues of Concern.
CCI3
Nitrapyrin
C02H
6-Chloropicolinic Acid
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Common Name: Nitrapyrin
Chemical Name: 2-chloro-6-(trichloromethyl) pyridine
Chemical Family: Pyridine
Empirical Formula: CeHsCUN
CAS Registry Number: 1929-82-4
Case Number: 0213
OPP Chemical Code: 069203
Molecular weight: 230.9
Trade Names: N-Serve TG®, N-Serve 24E®, N-Serve 24®, Stay-N 2000®
Basic Manufacturers: Dow AgroSciences, LLC
Nitrapyrin is a white crystalline solid with a mildly sweet odor. It has a melting point of
62-63 degrees Celsius, a solubility of 92 ppm in water 25 degrees Celsius and a vapor
pressure of 2.8 x 10"5 mm Hg.
C. Use Profile
The following is information on the currently registered uses of nitrapyrin, including an
overview of use sites and application methods. A detailed table of the uses of nitrapyrin
eligible for reregi strati on is contained in Appendix A.
Type of Pesticide: Nitrification inhibitor, bacteriostat, plant growth
regulator
Summary of Use: Used as a nitrification inhibitor and soil bactericide,
and can delay the nitration of ammonium ion in soil
when used together with urea and nitrogen fertilizer.
Soil incorporation is currently required immediately
after application for all products except one, for
which soil incorporation can be delayed up to 48
hrs, provided that conditions exist where the soil
contains at least 3% organic matter and soil
temperatures do not exceed 65 °F.
Food uses: Corn, sorghum, wheat
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Formulation Type:
Registrants:
All products are formulated as emulsifiable
concentrates, ranging from 19.8% to 22.2% active
ingredient.
Dow AgroSciences LLC and Loveland Products,
Inc.
Method and Rates of Application:
Application Methods:
Application Rates:
Application Timing:
Applied as a broadcast treatment, soil band
treatment, soil incorporated broadcast treatment, top
dressing treatment, soil injection, and soil sidedress.
Current maximum application rates are a single
application of 0.9 Ib a.i./A to sorghum and wheat
and two applications of 0.45 Ib a.i./A at a 30 day
interval to corn.
Applied pre-plant, at plant, post-plant, and/or post
harvest for all use sites.
Use Classification:
General
D. Estimated Usage of Pesticide
The technical registrant requested that EPA consider any market data for nitrapyrin as
Confidential Business Information, and as such, an estimate of pounds applied annually is
not disclosed in this document.
III.
Summary of Nitrapyrin Risk Assessments
The following is a summary of EPA's human health and ecological risk findings and
conclusions for nitrapyrin, as presented fully in the documents "Nitrapyrin. Revised HED
Chapter of the Reregi strati on Eligibility Decision Document (RED)" written by S. Tadayon,
D. Soderberg, and J. Doherty (3/1/05) and "Environmental Fate and Effects Division Revised
Risk Assessment for the Nitrapyrin Reregi strati on Eligibility Decision" written by C.
Hartless and A. Al-Mudallal (3/1/05).
The purpose of this section is to summarize the key features and findings of the risk
assessment in order to help the reader better understand the risk management decisions
reached by the Agency. While the risk assessments and related addenda are not included in
this document, they are available in the public docket (docket number OPP-2004-0283) and
on the Agency's website at http://www.epa.gov/pesticides/reregistration/status.htni.
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A.
Human Health Risk Assessment
1. Dietary Risk from Food
A brief overview of the toxicity studies used for endpoints in the dietary risk assessments
is outlined below in Table 1. Further details on the toxicity of nitrapyrin can be found in the
revised human health risk assessment dated March 1, 2005.
a. Toxicity of Nitrapyrin
The Agency has reviewed all toxicity studies submitted and has determined that the
toxicity database for nitrapyrin is complete and supports a reregi strati on eligibility
determination for all currently registered uses. The studies have been submitted to support
guideline requirements. Acute toxicity values and categories for the technical grades of
nitrapyrin and 6-CPA are summarized in Tables 1 and 2, respectively.
Note: The technical acute toxicity values included in this document are for informational
purposes only. The data may not be appropriate for product reregi strati on citation.
Table 1. Acute Toxicity Data on Nitrapyrin
Old
Guideline
No.
81-1
81-2
81-3
81-4
81-5
81-6
New Guideline
No.
870.1100
870.1200
870.1300
870.2400
870.5200
870.2600
Study Type
Acute Oral - rat
Acute Dermal -
rabbit
Acute Inhalation
Primary Eye Irritation
Primary Skin
Irritation
Dermal Sensitization
MRID #(s)
00037519
(1972)
00158904
(1986)
00158901
(1986)
00158902
(1986)
00037519
(1972)
00158903
(1986)
Results
LD50= 1.07gm/kgo*
1.23 gm/kg 9
LD50 > 2000 mg/kg
LC50 > 0.03 m/L
no effects
(technically limited
atmospheric cone.)
Cornea! opacity to day 14
(2/6), conjunctivitis today
21, iritis to day 7.
Very slight erythema and
slight exfoliation.
Toxicily
Category
III
III
Cannot
Classify*
II
IV
Positive in the modified Maguire method.
*The waxy physical nature of technical nitrapyrin precludes generating aerosols of appropriate atmospheric
concentration to meaningfully assess inhalation toxicity.
No appropriate endpoints (effects) attributable to a single exposure (dose) were identified
in any study, including developmental studies in rabbits or rats. Therefore, an acute RfD was
not established and EPA has not assessed acute dietary risk for nitrapyrin.
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In longer term studies, the liver was demonstrated to be the principle target organ in rat,
mouse, and dog. Decreases in body weight were demonstrated in subchronic and chronic
studies. In addition to the liver, the kidney was also demonstrated to be a target organ in
male rats only and the weight of evidence indicated that nitrapyrin affects the kidney in a
manner consistent with the alpha 2// globulin model. Consistent with this model, kidney
non-neoplastic pathology was evident and there were increases in kidney tumors in male rats.
Induction of kidney pathological changes in the alpha 2// globulin model is not related to
human risk assessment.
In a dermal absorption (rat) study conducted with nitrapyrin, dermal absorption was
found to be 46% at 24 hours. Since an oral NOAEL was selected, 46% dermal absorption
should be used for route-to-route extrapolation. A dermal absorption value of 46% was
calculated to represent the residual chemical that could be absorbed and for use in route-to-
route extrapolation.
For nitrapyrin, the Agency selected the developmental oral study for rabbits to be the
basis for short-term inhalation risk assessment. Also, an assumption is made that 100% of
the estimated inhalation dose will be absorbed. Risk estimates are based on the NOAEL dose
of 10 mg/kg/day and LOAEL of 15 mg/kg/day, based on decreased body weight gain and
increased liver weight.
The intermediate-term inhalation risk assessment is based on the chronic dog study,
considering liver enzymes, liver weights and liver lesions at a LOAEL of 15 mg/kg/day. The
NOAEL is 3 mg/kg/day. As in the short-term inhalation risk assessment, an assumption is
made that 100% of the estimated inhalation dose will be absorbed. All toxicological
endpoints used for risk assessment are presented in Table 2 below.
Table 2. Summary of Doses and Toxicological Endpoints for Nitrapyrin
Guideline No,/ Study Type
870.4200
Carcinogenicity mice
870.4300
Combined chronic feeding and
carcinogenicity study - rats
870.5100
Gene Mutation - Ames Test
870.5300
Cytogenetics - Mammalian gene
mutation.
870.5375
Cytogenetics - Micro-nucleus test.
MRID/Accession No.
41651601
41345403
Accession No. 259818.
MRID No. 00163805
Accession No. 259818
Results
The Carcinogenicity Peer Review Committee
determined that the high dose in this study was
not adequate for carcinogenicity evaluation.
NOAEL = 5 mg/kg/day
LOAEL = 20 mg/kg/day based on decreased
body weight gain in males.
Increase in kidney tumors related to the alpha 2/j,
globulin model (not relevant to humans).
No evidence of mutagenic activity in strains TA-
97, TA-98, TA-100 and TA 1535 in the presence
or absence of activation.
Negative for genotoxic effect.
No evidence of mutagenic potential in the mouse
micronucleus test at a dose of 800 mg/kg.
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Guideline No,/ Study Type
870.5550
Other Effects
MRID/Aecession No.
MRID No. 00109456.
Results
No increase in unscheduled DNA synthesis.
Nitrapyrin did not demonstrate increased sensitivity to fetuses and offspring. Maternal
toxicity consisted of decreases in body weight and liver effects and kidney effects in the rat
reproduction study. There were no indications of impaired reproductive performance. Fetal
and offspring toxicity was slight and included increased incidence of crooked hyoid in
rabbits, ossification decreases in rats and body weight decreases and evidence of hepatic
centrilobular hypertrophy with fatty changes in rats in the reproduction study.
Table 3. Summary of Toxicological Doses and Endpoints for Nitrapyrin for Use in
the Dietary Exposure Assessment
Exposure Scenario
Acute Dietary
(All Populations)
Chronic Dietary
(All Populations)
Cancer (oral, dermal,
inhalation)
Dose Used in Risk
Assessment, UF
Special FQPA SF*
and Level of Concern
for Risk Assessment
Study and Toxicological
Effects
No study was selected for this scenario since neither the rat nor the rabbit
demonstrated definite toxicity following a single dose and developmental toxicity
was not a concern for nitrapyrin.
NOAEL = 3
mg/kg.day
UF = 100
Chronic RfD =
.03 mg/kg/day
FQPA SF = IX
cPAD =
chronic RfD
FQPA SF
= 0.03 mg/kg/day
Chronic feeding - dog
LOAEL =15 mg/kg/day based
on liver effects
Classified as "likely to be a carcinogen in humans" as per May 5, 2000 and April
26, 2005 CARC reports. Ql* = 4.25xlO'2 human equivalents (refer to TXR #
0014035 memo dated 3/9/00).
A classification of "likely to be carcinogenic to humans" was assigned by the Cancer
Assessment Review Committee (CARC) dated May 5, 2000, using the criteria in the Draft
Guidelines for Carcinogen Risk Assessment (July, 1999). The Qi* was determined to be
4.25 x 10"2 (mg/kg/day)"1 human equivalents. The CARC also met on February 9, 2005, to
reconsider the cancer classification of nitrapyrin, based on a rebuttal report submitted by the
technical registrant during the Phase 3 public comment period. As a result of this meeting,
the CARC reaffirmed the cancer classification, noting, however, that the Harderian gland
tumors seen in the mouse study are no longer considered a response to treatment with
nitrapyrin, and that the forestomach tumors are not relevant to human health risk assessment.
The CARC did retain its concern for the epididymal tumors and did not accept the
registrant's proposed mechanism for liver tumors.
Under a two year dietary study 6-chloropicolinic acid (6-CPA) was considered not to be
carcinogenic to male and female mice [Cancer Assessment Review Committee Report for
Nitrapyrin (2nd Review), May 5, 2000]. A cancer risk assessment was done for
occupational, but not dietary, exposures to nitrapyrin, because dietary exposures are to 6-
CPA only, whereas occupational exposures are to parent nitrapyrin.
-------
The mutagenicity data base for nitrapyrin satisfies the current recommendations for
testing. However, there is one study conducted by the National Toxicology Program (NTP)
that reports that nitrapyrin is mutagenic in the Salmonella typhimurium strains TA97, TA98,
and TA100 in the presence of S9 metabolite activation. The results of the NTP study are in
contrast with the submitted study, which did not demonstrate positive mutagenicity effects in
these strains. In addition, certain structural activity factors would predict that nitrapyrin
could have mutagenic potential.
The technical registrant has expressed interest in developing new data that may affect the
cancer classification. If they choose to submit such data to the Agency, the Agency will
review the data according to the scheduling guidelines of the Pesticide Registration
Improvement Act, and revise the cancer classification if appropriate. However, at this time,
the Agency has no data that would warrant changing the current cancer classification for
nitrapyrin.
Neither the subchronic, chronic, developmental, or reproductive rat, mouse, dog or rabbit
studies indicates that nitrapyrin was associated with either a specific or an indirect neurotoxic
or immunotoxic response or endocrine disruption.
b. FQPA Safety Factor
The FQPA Safety Factor (as required by the Food Quality Protection Act of 1996) is
intended to provide up to an additional 10-fold safety factor (10X), to protect for special
sensitivity in infants and children to specific pesticide residues in food, drinking water, or
residential exposures. In the case of nitrapyrin, the Agency has concluded that the FQPA
Safety Factor should be removed (which would make it equivalent to IX) based on a
conclusion of no increased susceptibility and no residual uncertainty. In addition, there is not
a concern for neurotoxicity or for pre- and/or postnatal toxicity resulting from exposure to
nitrapyrin. On this basis, the Agency concluded that the special FQPA safety factor should
be removed (i.e., reduced tolX) for all potential exposure scenarios to nitrapyrin.
c. Population Adjusted Dose
A population adjusted dose, or PAD, is the reference dose (RfD) adjusted for the FQPA
safety factor. A risk estimate that is less than 100% of the acute PAD, the dose at which an
individual could be exposed over the course of a single day and no adverse health effects
would be expected, does not exceed EPA's level of concern. Likewise, a risk estimate that is
less than 100% of the chronic PAD, the dose at which an individual could be exposed over
the course of a lifetime and no adverse health effects would be expected, does not exceed
EPA's level of concern.
1) Acute PAD
As discussed in Section III. A.I.a of this document, EPA has not assessed acute dietary
risk for nitrapyrin because no appropriate endpoint attributable to a single exposure (dose)
could be identified. As a result, an acute dietary RfD was not established.
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2) Chronic PAD
Dietary risk for nitrapyrin was assessed by comparing chronic dietary exposure estimates
(in mg/kg/day) to the nitrapyrin cPAD. Dietary risk is expressed as a percent of the cPAD,
which is the chronic Reference Dose (3 mg/kg/day) modified by an uncertainty factor of 100
(10X for inter-species extrapolation and 10X for intra-species variability). Therefore, the
theoretical cPAD for nitrapyrin would be 0.03 mg/kg/day. The cPAD was derived from a
chronic dog study, in which nitrapyrin was administered to beagles (4/sex/dose) in the diet at
dose levels at 0.5, 5.0, 125, and 250 mg/kg/day for up to 53 weeks, with aNOAEL of 3
mg/kg/day as noted in Table 3 above.
d. Exposure Assumptions
A refined chronic dietary exposure assessment was performed in order to determine the
exposure risk assessment to nitrapyrin for use in chronic dietary risk assessment from all
registered uses. The assessment was conducted using the Dietary Exposure Evaluation
Model software with the Food Commodity Intake Database (DEEM-FCID™, Version 1.3),
which incorporates consumption data from USDA's Continuing Surveys of Food Intakes by
Individuals (CSFII), 1994-1996 and 1998. Field trial data, estimated percent crop treated
information, and processing factors, where available, were used. The chronic and cancer
dietary exposure estimates were also conducted using the Lifeline™ model (Version 2.0).
These Lifeline™ assessments were conducted using the same consumption data as the
DEEM-FCID™ (CSFII, 1994-1996 and 1998 consumption data with FCID). Lifeline™ uses
the recipe file to relate RACs to foods "as-eaten" (D299299, March 04, D Soderberg).
Exposure estimates are reported in milligrams per kilogram of body weight per day, and risk
is expressed as a percent of the cPAD.
e. Dietary (Food) Risk Assessment
1) Acute Dietary Risk
Acute dietary risk was not assessed for nitrapyrin, since no appropriate endpoint
attributable to a single dose has been identified.
2) Chronic Dietary Risk
Chronic dietary risk was calculated by using the average consumption value for food and
average residue values on those foods. For all commodities, the results of both the DEEM-
FCID™ and Lifeline™ analyses for chronic dietary exposure (food only) yielded exposure
results <1% cPAD for the US Population and for all population subgroups, which is below
EPA's level of concern. Dietary exposure results <100% of the cPAD are below EPA's
level of concern. A summary of chronic dietary risk estimates are presented in Table 4.
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Table 4. Summary of Chronic Dietary Exposure and Risk for Nitrapyrin
Population Subgroup
General U.S. Population
All Infants (< 1 year old)
Children 1-2 years old
Chronic Dietary Exposure and Risk
DEEM
Dietary Exposure
(mg/kg/day)
0.000013
0.000015
0.000027
%
cPADa
<1
<1
<1
Lifeline
Dietary Exposure
(mg/kg/day)
0.000012
0.000012
0.000026
% cPADa
<1
<1
<1
"Percent of cPAD = (Exposure - cPAD) x 100%.
For more information on the chronic dietary risk assessment, please refer to the Chronic
Dietary Exposure and Risk section of the revised human health chapter for nitrapyrin, dated
March 1, 2005.
3) Dietary Cancer Risk
A dietary cancer risk assessment was not conducted for nitrapyrin because exposure to
nitrapyrin, per se, in the diet is negligible (zero). Human exposure to residues of nitrapyrin is
only through the grains and grain products of corn, sorghum, and wheat, and the only
residues detected on these grain products are free or conjugated forms of 6-chlorpicolinic
acid. Nitrapyrin, per se, has never been detected. The cancer endpoint is relevant only to
nitrapyrin, per se, and not to 6-CPA.
2. Dietary Risk from Drinking Water
Dietary water exposure to pesticides can occur through ground and surface water
contamination. In assessing drinking water risks EPA considers acute (one day), chronic
(long-term) and, if applicable, cancer (overall mean) exposure, and uses either modeling or
monitoring data if available, to estimate those risks. To determine the maximum contribution
from water allowed in the diet, EPA first looks at how much of the overall allowable risk is
contributed by food and then calculates a "drinking water level of comparison" (DWLOC) to
determine whether modeled or monitoring exposure estimates exceed the allowable risk
level. Estimated environmental concentrations (EECs) that are above the corresponding
DWLOC exceed the Agency's level of concern.
Estimated Environmental Concentrations (EECs) of parent nitrapyrin and its major
degradate 6-CPA from ingestion of drinking water were assessed by modeling because there
are no monitoring data available to the Agency for nitrapyrin and 6-CPA in surface and
ground water. The Agency modeled nitrapyrin and 6-CPA separately because a combined
residue approach was not possible. 6-CPA was not detected or adequately quantified in any
of the environmental fate studies that are used in the PRZM/EXAMS input parameters;
therefore, no combined residue half-lives (nitrapyrin + 6-CPA) could be determined.
10
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a.
Surface Water
Nitrapyrin can be transported to surface water during or after application via run-off and
soil leaching from ground applications. Estimated surface water (drinking water)
concentrations are based on two models coupled together, PRZM and EXAMS. Tier II
PRZM-EXAMS modeling was performed using index reservoir (IR) scenarios with percent
crop area (PCA) adjustment factors for the use of nitrapyrin on corn, sorghum, and wheat.
The application rate for corn is 0.45 Ibs ai/A with 2 applications per year at a 30 day interval,
and the application rate for sorghum and wheat is 0.90 Ibs ai/A with 1 application per year.
The default PCA factor of 0.87 was used in the modeling to reflect the possibility of having
more than one crop treated with nitrapyrin within the same water shed. For the modeling of
6-CPA in drinking water, the application rate was corrected for the difference in molecular
weight between parent nitrapyrin and 6-CPA. Due to the lack of environmental fate data for
6-CPA, EPA assumed that 6-CPA is stable to all abiotic and biotic routes of degradation,
thus producing very conservative estimates of 6-CPA concentrations in drinking water.
The Texas sorghum scenario produced the highest estimated concentration of nitrapyrin
in surface water among the modeled scenarios. The estimated concentration of nitrapyrin in
water is not expected to exceed 1.21 ppb for the 1 in 10 year annual peak concentration, 0.03
ppb for the 1 in 10 year annual daily mean concentration, and 0.01 ppb for the 30 year annual
average concentration.
The Oregon wheat scenario produced the highest estimated concentration of 6-CPA in
surface water among the modeled scenarios. The estimated concentration of 6-CPA in water
is not expected to exceed 1.71 ppb for the 1 in 10 year annual peak concentration, 1.63 ppb
for the 1 in 10 year annual daily mean concentration, and 1.02 ppb for the 30 year annual
average concentration.
Table 5. Estimated Concentrations of Nitrapyrin and 6-CPA in Surface Drinking
Water Using IR/PCA PRZM/EXAMS Scenarios
Crop Scenario
1 in 10 year peak
concentration
ppb
Nitrapyrin
6-CPA
1 in 10 year annual daily
average concentration
ppb
Nitrapyrin
6-CPA
30-year annual daily
average
ppb
Nitrapyrin
6-CPA
Corn
Pennsylvania Corn
Texas Corn
0.158
0.868
0.568
1.182
0.005
0.024
0.359
0.374
0.001
0.014
0.134
0.194
Sorghum
Kansas Sorghum
Texas Sorghum
0.685
1.214
0.944
1.431
0.020
0.032
0.338
0.459
0.009
0.014
0.165
0.236
Wheat
North Dakota Wheat
Oregon Wheat
0.451
0.343
0.743
1.705
0.011
0.011
0.489
1.627
0.005
0.004
0.286
1.023
11
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Crop Scenario
1 in 10 year peak
concentration
ppb
Nitrapyrin
6-CPA
1 in 10 year annual daily
average concentration
ppb
Nitrapyrin
6-CPA
30-year annual daily
average
ppb
Nitrapyrin
6-CPA
Corn
Texas Wheat
1.057
0.781
0.026
0.260
0.010
0.117
b.
Groundwater
In the absence of monitoring data, the Screening Concentration in Ground Water (SCI-
GROW) model was used to estimate potential ground water concentrations of nitrapyrin and
6-CPA. SCI-GROW estimates likely groundwater concentrations assuming the pesticide is
used at the maximum allowable rate in areas where groundwater is exceptionally vulnerable
to contamination. In most cases, a large majority of the use area will have groundwater that
is less vulnerable to contamination than the areas used to derive the SCI-GROW estimate.
Application of nitrapyrin to corn, sorghum, and wheat was modeled. The estimated
concentration of nitrapyrin in shallow ground water sources is 0.073 ppb. For 6-CPA, EPA
assumed the compound to be stable to aerobic soil metabolism and used a half-life range of
360 to 10,000 days. The estimated concentration of 6-CPA in shallow ground water sources
ranged from 30.87 ppb to 278.82 ppb. However, The EPI Suite program (structure
estimation program) estimated the biodegradation half-life for 6-CPA to be in the range of
days to weeks.
For more information on drinking water risks and the DWLOC calculations, see the
Water Exposure/Risk Pathway section of the revised human health risk assessment, dated
March 1, 2005.
3. Residential (Non-dietary) Risk
There are no residential uses of nitrapyrin.
4. Aggregate Risk
The Food Quality Protection Act amendments to the Federal Food, Drug, and Cosmetic
Act (FFDCA, Section 408(b)(2)(A)(ii)) require 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 will typically include exposures from food, drinking water, residential
uses of a pesticide, and other non-occupational sources of exposure.
For nitrapyrin, aggregate risk assessments were conducted for chronic (several months to
lifetime) exposures only, and this aggregate assessment includes a non-cancer and a cancer
risk assessment. An acute aggregate assessment was not performed because an endpoint
could not be selected for the acute dietary exposure scenario, based on available studies.
12
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In the case of nitrapyrin, there are no residential uses, so the aggregate assessments include
exposures via food and drinking water only. Furthermore, food exposures were considered
to be negligible, and EPA concludes with reasonable certainty that residues of nitrapyrin and
6-CPA in drinking water will not contribute to aggregate risks of concern.
a. Chronic Aggregate Risk
Chronic aggregate risk was considered by aggregating chronic food and drinking water
exposure. The chronic DWLOCs range from 300 ug/L for the population subgroup with the
highest food exposure (Children 1 to 2 years old) to 1050 ug/L for the subgroups U.S.
Population, Adults 20 to 49 years old, and Adults 50+ years old. The chronic EECs (highest
value) generated are less than EPA's calculated chronic DWLOCs for 6-CPA and nitrapyrin
in drinking water. Thus, the Agency concludes with reasonable certainty that residues of
nitrapyrin in drinking water will not contribute significantly to the aggregate chronic human
health risk and that the chronic aggregate exposure from nitrapyrin residues in food and
drinking water will not exceed the Agency's level of concern (100% of the cPAD) for any
population subgroup. For more information on how nitrapyrin concentrations in surface
water were modeled, see the drinking water assessment in the environmental fate and effects
risk assessment for nitrapyrin, dated March 1, 2005.
Table 6. Summary of Chronic DWLOC Calculations for Nitrapyrin and 6 CPA
Population Subgroup
General U.S. Population
All Infants (< 1 year old)
Children 1-2 years old
Chronic Scenario
Theoretical
cPAD
mg/kg/day
0.03
Chronic
Food Exp
mg/kg/day
0.000013
0.000015
0.000027
Max Chronic
Water Exp
mg/kg/day1
0.029987
0.029985
0.029973
6-CPA
Surface
Water
EDWC
(Mg/i)
1.6
6-CPA
Ground
Water
EDWC
(Ug/L)
280
Chronic
DWLOC
(Mg/L)
1050
300
300
b. Cancer Aggregate Risk
The Agency used multi-year mean water concentration values to calculate cancer (Qi*)
exposures. The cancer DWLOC is the concentration in drinking water as a part of the
aggregate chronic exposure that is expected to result in a negligible cancer risk (10"6).
An aggregate cancer risk assessment for the U.S. Population based on nitrapyrin was
conducted in which food exposure was assumed to be negligible, but water exposures were
not. The EECs used for the cancer aggregate risk assessment are 0.01 ug/L (surface water)
and 0.07 ug/L (groundwater). Both values are below the cancer DWLOC of 0.84 ug/L;
therefore, the Agency concludes that aggregate exposure to nitrapyrin in food and drinking
water will not result in a cancer risk of concern. The cancer endpoint is relevant only to
13
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nitrapyrin and not to 6-CPA. A summary of cancer DWLOC calculations for nitrapyrin is
presented in Table 7 below.
Table 7. Summary of Cancer DWLOC Calculations for Nitrapyrin
Population
U.S. Pop
Q*
4.25e-02
Negligible
Risk Level
l.Oe-06
Target Max
Exposure
mg/kg/day
0.000024
Chronic
Food
Exposure
mg/kg/day
NA
Max Water
Exposure
mg/kg/day
0.000024
Surface
Water
EDWC
(^g/L)
0.01
(corn)
Ground
Water
EDWC
(Ag/I)
0.07
Cancer
DWLOC
Cug/L)
0.84
5.
Cumulative Risk Assessment
Risks summarized in this document are those that result only from the use of nitrapyrin.
The Food Quality Protection Act (FQPA) requires that the Agency consider available
information concerning the cumulative effects of a particular pesticide's residues and 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 toxic mechanism could lead to the same
adverse health effect as would a higher level of exposure to any of the substances
individually. Unlike other pesticides for which EPA has followed a cumulative risk approach
based on a common mechanism of toxicity, EPA has not made a common mechanism of
toxicity finding for nitrapyrin and any other substances, and nitrapyrin does not appear to
produce a toxic metabolite produced by other substances. For the purposes of this action,
therefore, EPA has assumed that nitrapyrin does not have a common mechanism of toxicity
with other substances. 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://www.epa.gov/pesi ci des/cumul ative/.
6. Occupational Risk
Workers can be exposed to a pesticide through mixing, loading, and/or applying a
pesticide, or re-entering treated sites. Occupational handlers of nitrapyrin include mixers,
loaders, and applicators in agricultural settings only. Occupational risk for all of these
potentially exposed populations is measured by a Margin of Exposure (MOE), which
determines how close the occupational exposure comes to a No Observed Adverse Effect
Level (NOAEL). In the case of nitrapyrin, MOEs greater than 100 do not exceed the
Agency's level of concern. For workers entering a treated site, MOEs are calculated for each
day after application to determine the minimum length of time required before workers can
safely re-enter.
For nitrapyrin, a dermal absorption value of 46% was used, based on a rat dermal
absorption study, to represent the residual chemical that could be absorbed. An absorption
14
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factor of 100% was applied for inhalation exposures. Nitrapyrin MOEs are determined by a
comparison of specific exposure scenario estimates to the dermal and inhalation NOAEL of
10 mg/kg/day (from the oral developmental toxicity study with rabbits) for short-term
assessment, or 3 mg/kg/day (from the chronic feeding toxicity study with dogs) for
intermediate-term assessment. For nitrapyrin users, an MOE of 100 has been determined to
be adequately protective (for both short- and intermediate-term exposure), based on the
standard uncertainty factors of 10X for interspecies extrapolation and 10X for intraspecies
variability. Long-term worker exposure is not expected for nitrapyrin.
Occupational risk is assessed for exposure at the time of application (termed "handler"
exposure) and following application, or post-application exposure. Application parameters
are generally defined by the physical nature of the formulation (e.g., formula and packaging),
by the equipment required to deliver the chemical to the use site, and by the application rate
required to achieve an efficacious dose. Post-application risk is assessed for activities such
as scouting, irrigating, pruning, and harvesting, and is based primarily on dermal exposure
estimates. Note that occupational risk estimates are intended to represent pesticide workers,
and on this basis assumptions are made concerning acres treated per day and the seasonal
duration of exposure.
For more information on the assumptions and calculations of potential risk of nitrapyrin
to workers, see the Occupational Exposure Assessment (Section 7.0) in the "Revised FED
Chapter of the Reregi strati on Eligibility Decision Document (RED)," dated March 1, 2005.
a. Occupational Toxicity
Table 8 below provides a listing of the toxicological endpoints used in the nitrapyrin
occupational risk assessment.
Table 8. Toxicological Endpoints for the Nitrapyrin Occupational Risk Assessment
Exposure
Scenario
Short-Term
(1-30 days)
Dermal and
Inhalation
Intermediate-Term
(1-6 months)
Dermal and
Inhalation
Cancer (oral,
dermal, inhalation)
Dose used in
Risk
Assessment
(mg/kg/day)
NOAEL= 10
NOAEL= 3
Margin of Exposure
(MOE) for Risk
Assessment
MOE = 100
MOE = 100
Study and Toxieological Effects
Developmental Toxicity -Rabbits
LOAEL = 30 mg/kg/day based on decreased body
weight gain and increased liver weights
Chronic feeding study - Dogs
LOAEL =15 mg/kg/day based on liver enzymes,
liver weights and liver lesions.
Classified as "likely to be a carcinogen in humans."
15
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b. Occupational Handler Exposure
Occupational handler risk estimates have been assessed for both short- and intermediate-
term exposure durations. Due to the use patterns for nitrapyrin, long term exposures are not
expected. However, since the duration of exposure is uncertain, intermediate-term risk
estimates are provided as an upper-bound assessment.
Occupational handler assessments are conducted using increasing levels of protection.
The Agency typically evaluates all exposures with minimal protection and then considers
additional protective measures using a tiered approach in an attempt to obtain an adequate
MOE. The lowest tier is represented by the baseline clothing scenario (i.e., single layer
clothing, socks, and shoes), followed by increasing levels of risk mitigation such as personal
protective equipment (PPE) and engineering controls (EC). In the case of nitrapyrin, all
potential non-cancer exposure scenarios provide a total MOE greater than or equal to 100
either at the baseline, using open systems, or with PPE while using closed systems. All
current labels require handlers to wear a long sleeve shirt, long pants, chemical-resistant
gloves, shoes plus socks, and protective eyewear when mixing, loading, or applying products
containing nitrapyrin. End-use product PPE will be assessed on a product-by-product basis.
c. Occupational Handler Risk Summary
The Agency has determined that there are potential exposures to individuals who mix,
load, apply, and otherwise handle nitrapyrin during the usual use patterns associated with the
pesticide's use. Based on the use patterns, two major occupational handler exposure
scenarios were identified as follows:
(1) mixing/loading liquids for groundboom application
(2) application of sprays via groundboom application.
Occupational Handler Exposure Assumptions:
The assumptions for daily areas treated are taken from the Health Effects Division
Science Advisory Committee on Exposure Policy 9: Standard Values for Daily Acres
Treated in Agriculture (July 5, 2000).
Chemical-specific data for assessing human exposures during pesticide handling
activities were not submitted to the Agency in support of the reregi strati on of nitrapyrin. In
such instances, it is the policy of the EPA to use data from the Pesticide Handlers Exposure
Database (PHED) Version 1.1 to assess handler exposures for regulatory actions when
chemical-specific monitoring data are not available.
The following assumptions and factors were used in order to complete the exposure and
risk assessments for occupational handlers and applicators:
Average body weight of an adult handler is 70kg;
• Average occupational workday is 8 hours;
16
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Treatments for all crops are assessed at the maximum labeled single application
rates of 0.45 Ib a.i./A for corn and 0.9 Ib a.i./A for sorghum and wheat.
Summary of Risk Concerns and Data Gaps for Handlers
Non-cancer MOEs for all potential exposure scenarios are greater than or equal to 100
either at the baseline, using open systems, or using PPE (single layer and gloves, no
respirator) while using closed systems. All current labels require handlers to wear a long
sleeve shirt, long pants, chemical-resistant gloves, shoes plus socks, and protective eyewear.
Short-term MOEs for the two scenarios assessed are 250 for mixers/loaders and 420 for
applicators with PPE, and intermediate-term MOEs are 100 for mixers/loaders and 150 for
applicators with PPE. Therefore, short- and intermediate-term occupational risk is not of
concern. Chronic occupational risks were not assessed because long term exposures are not
expected. Table 9 provides a listing of the short- and intermediate-term risk estimates for
handlers.
Table 9. Summary of Occupational Handler Risks for Nitra
Exposure Scenario
(Scenario #)
Crop
Application
Rate Ib ai/A
Daily
Treated
Acres/
day
Total
Baseline
Short-term
MOE1 -2
pyrin
Total
Baseline
Intermediate
-term
MOE1'2
Total
PPE1
Short-
term MOE
Total
PPE1
Intermedi
ate-term
MOE
Mixer/Loader
Mixing/loading
liquids for
groundboom
application (1)
Wheat,
corn,
sorghum
1
200
22
1
250
100
Applicator
Sprays for
groundboom
application (2)
Wheat,
corn,
sorghum
1
200
420
150
420
150
Baseline dermal attire scenarios include long pants, long sleeved shirt, and no gloves.
2Baseline inhalation attire represents no respirator.
3PPE1 dermal attire includes long pants, long sleeved shirt, and gloves for mixers/loaders only.
-v-4
For occupational cancer risks, EPA begins mitigation at < 1.0 x 10" , and attempts to
mitigate risks to < l.Ox 10"6 when feasible. The results of the occupational handler cancer
assessment (Table 10) for nitrapyrin indicate that the cancer risks for all of the exposure
scenarios considered do not exceed the Agency's level of concern, with the exception of
commercial handlers at baseline PPE. All current labels require workers handling nitrapyrin
to wear the equivalent of the PPE1 scenario (long pants, long sleeved shirt, plus gloves).
Assessments with additional PPE or engineering controls did not significantly reduce the
cancer risk estimates. In addition, cancer risk was assessed at two application frequencies;
the first (3 applications) represents the maximum number of applications per site per season,
and represents private use. In the second application frequency, a factor often was applied,
to represent commercial handlers making multiple applications per site per season, resulting
in an assumption of 30 applications. The Agency considers this to be a conservative
assumption, and given that the cancer risk is at an acceptable level for commercial and non-
commercial handlers using PPE1, the Agency believes this current level of PPE is adequate.
17
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Table 10. Summary of Occupational Handler Cancer (Q*) Risks for Nitrapyrin
Exposure Scenario
App. Rate Ib
ai/A
Acres Treated
A/day
Crop Type
Baseline Risk
3/30
PPE1 Risk
3/30
Mixer/Loader
Mixing/Loading
Liquids for
Groundboom
Application
1.00
200
Wheat, Corn,
Sorghum
6.66e-4/ 6.66s-
o
J
5.88e-6/
5.88e-5
Applicator
Sprays for
Groundboom
Application
1.00
200
Wheat, Corn,
Sorghum
3.6e-6/
3.6e-5
3.6e-6/
3.6e-5
Baseline dermal unit exposure scenarios includes long pants, long sleeved shirts and no gloves.
PPE1 long pants, long sleeved shirts and gloves (no respirator)
d. Occupational Postapplication Risk Summary
A postapplication assessment was not conducted for nitrapyrin because the expectation
for postapplication exposures is low. Because nitrapyrin is applied directly to the soil and
mechanically soil incorporated well before the plants are mature, and because nitrapyrin is
usually applied pre-plant, significant exposure during harvesting or any other late season
activities is not likely. Further, the timing of the application greatly reduces the potential for
post application exposure to treated soil. Also, many agricultural operations mechanically
plant seeds early in the season, which minimizes the potential for contact. It should be noted,
however, that the Restricted Entry Interval will remain at 24 hours for all crops, based on the
fact that this chemical is a Toxicity Category II Eye Irritant.
e.
Human Incident Data
In evaluating incidents to humans, the Agency reviewed reports from the National Poison
Control Centers (PCC), the Agency's Office of Pesticide Program's Incident Data System
(IDS), and the California Department of Pesticide Regulation. Relatively few incidents of
illness have been reported due to nitrapyrin. Some of the reports suggest that nitrapyrin can
be an eye and skin irritant.
B.
Environmental Risk Assessment
A summary of the Agency's environmental risk assessment for nitrapyrin is presented
below. Nitrapyrin has the following registered uses, which result in environmental
exposures: soil applications to corn, sorghum, and wheat. More detailed information
associated with the environmental risk from the use of nitrapyrin can be found in the
Environmental Fate and Effects Division Revised Risk Assessment for the Nitrapyrin
Reregi strati on Eligibility Decision, dated October 7, 2004. The complete environmental risk
assessment is not included in this RED, but may be accessed in the OPP Public Docket
(docket number OPP-2004-0283) and on the Agency's website at
http://www.epa.gov/pesticides/reregistration/status.htm.
18
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1. Environmental Exposure
a. Environmental Fate and Transport
Nitrapyrin hydrolyzes and photodegrades rapidly and hence should not persist in most
environments. In aerobic mineral soils half lives ranged from 11 to 17.9 days, and in
anaerobic aquatic environments, nitrapyrin had a half-life of less than 3 hours. 6-CPA was
identified as the major degradate in both hydrolysis and photolysis. 6-CPA appears to
degrade through hydroxylation (breaking the pyridine ring) and microbial mineralization.
Nitrapyrin was shown to be mobile to moderately mobile in several soils, according to
available mobility studies. The adsorption coefficient (Kd) for nitrapyrin ranged from 0.947
to 19.9 with Koc values ranging from 254 to 360, respectively. The major degradate 6-CPA
is mobile in mineral soils and high organic matter soils, with approximate Kd values ranging
from 0.387 (mineral soils) to 1.02 (high organic matter soils). Nitrapyrin also has a high
vapor pressure (2.8 e-3 torr) and hence is prone to volatilize from the application site.
Nitrapyrin volatilization from soil appears to be dependent on the depth of incorporation as
well as air-flow rates and soil temperatures. Hence, nitrapyrin could move off site through
leaching and volatilization.
Nitrapyrin accumulated in bluegill sunfish (303 X BCF) after a 21 day exposure period.
However, the bioaccumulated residues were almost completely eliminated from fish tissues
(82%) during a 2 week depuration period.
b. Aquatic Organism Exposure
For exposure to aquatic fish and invertebrates, EPA considers surface water only, since
most aquatic organisms are not found in groundwater. Surface water models are used to
estimate exposure to freshwater aquatic animals, since monitoring data are generally not
from studies targeted on small water bodies and primary streams, where many aquatic
animals are found. The modeling results used in risk calculations for nitrapyrin are detailed
in the "Environmental Fate and Effects Division Revised Risk Assessment for the Nitrapyrin
Reregi strati on Eligibility Decision," dated March 1, 2005.
The Agency used modeling to derive estimated environmental concentrations (EECs) for
nitrapyrin in surface water. Unlike the drinking water assessment described in the human
health risk assessment section of this document, the ecological water resource assessment
does not include the Index Reservoir (IR) and Percent-Crop Area (PCA) factor refinements.
The IR and PC A factors represent a drinking water reservoir, not the variety of aquatic
habitats, such as ponds adjacent to treated fields, relevant to a risk assessment for aquatic
animals. Therefore, the EEC values used to assess exposure to aquatic animals are not the
same as the values used to assess human dietary exposure from drinking water sources.
Several scenarios were modeled for each use and can be found in the environmental fate and
effects assessment for nitrapyrin. The Texas scenarios gave the maximum EECs, and so
were chosen for regulatory purposes. The EEC values used to assess exposure to aquatic
animals can be found in Table 10 below.
19
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Table 11. Estimated Environmental Concentrations (ug ai/L) of Nitrapyrin in Surface
Water (PRZM-EXAMS) for Ecological Assessment.
Crop Scenario
Peak
21-day Average
60-day Average
Incorporated Applications
Texas Corn
Texas Sorghum
Texas Wheat (Winter Wheat)
0.41
0.59
0.50
0.19
0.24
0.20
0.07
0.10
0.08
Unincorporated Applications
Texas Corn
28.89
11.93
4.78
c. Terrestrial Organism Exposure
The Agency assessed exposure to terrestrial organisms by first predicting the amount of
nitrapyrin residues found on animal food items and then using information on typical food
consumption by various species of birds and mammals to determine the amount of pesticide
consumed. The amount of residues on animal feed items are based on the Fletcher
nomogram, which is a model developed by Hoerger and Kenaga (1972) and modified by
Fletcher (1994), and the current maximum application rate for nitrapyrin. Current labels
allow a maximum single application of 0.9 Ib a.i./Acre per year for sorghum and wheat, and
two applications per year for corn at a rate of 0.45 Ibs a.i./Acre, for a seasonal maximum
application rate of 0.9 Ibs a.i./Acre. For every pound of nitrapyrin applied per acre, the
resulting maximum concentration on short grass is 240 ppm (mean is 85 ppm), on tall grass
is 110 ppm (mean is 36 ppm), on broad-leaved plants/small insects is 135 ppm (mean is 45
ppm), and on seeds/large insects is 15 ppm (mean is 7 ppm).
Birds and Mammals
For birds and mammals, predicted maximum and mean EECs for food items resulting
from multiple applications are calculated from the FATES program. FATES estimates the
highest one-day residue, based on the maximum or mean initial EEC from the first
application, the total number of applications, interval between applications, and a first-order
degradation rate, consistent with EPA policy. Acute RQs are calculated from these EECs.
For this assessment, fruit, pods, seeds, and insects are the only food items of concern, since
nitrapyrin is applied to the ground and incorporated into the soil.
Non-target Terrestrial Plants
Based on a screening assessment using non-guideline terrestrial plant toxicity data, it
appears unlikely that adverse effects in plants would be observed at the current labeled rates
of nitrapyrin.
20
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Non-target Terrestrial Insects
EPA currently does not quantify risks to terrestrial non-target insects. Risk quotients are
therefore not calculated for these organisms. Since the method of application is ground spray
with incorporation or soil injection, the likelihood of exposure to honey bees is low. In
addition, one study evaluating toxicity to earthworms was submitted to the Agency, and
based on this study, exposure was not likely significant for adverse effects.
2. Environmental Effects (Hazard)
a. Toxicity to Aquatic Organisms
Freshwater and Esturarine/Marine Fish
Toxicity studies conducted using technical nitrapyrin demonstrate that it is moderately
toxic to freshwater fish under acute exposure with definitive LC50 values ranging from 3.4 to
9.29 mg a.i./L. A single toxicity study conducted using technical nitrapyrin demonstrated
that it is moderately toxic to estuarine/marine fish under acute exposure with a definitive
LCso of 4.28 mg ai/L. Table 12 summarizes the data that support the acute toxicity endpoints
used in assessing the risks to fish. No fish early-life stage toxicity studies were submitted to
the Agency.
Table 12. Acute Toxicity Endpoints for Freshwater and Estuarine/Marine Fish
Test Species
% a.i.
96-hr
LCSO
(mg/L)
NOAEC
(mg/L)
Measured/nominal
Flow-through/static
Toxicily
Classification
MRIDor
Accession
Number
Freshwater Fish
Bluegill
92.4
3.4
1.5
Mean measured,
flow-through
Moderately
toxic
420776-01
Estuarine/Marine Fish
Silverside
minnow
91.2
4.28
<1.26
Mean measured,
flow-through
Moderately
toxic
420776-04
Freshwater and Estuarine/Marine Invertebrates
Toxicity studies conducted using technical nitrapyrin demonstrate that it is moderately
toxic to freshwater invertebrates under acute exposure with definitive LCso values ranging
from 2.2 to 5.8 mg a.i./L. Toxicity studies conducted using technical nitrapyrin demonstrate
that it is moderately to highly toxic to estuarine/marine invertebrates under acute exposure
with definitive ECso values and LCso values ranging from 0.41 to 3.1 mg a.i./L. Table 13
summarizes the data that support the acute toxicity endpoints used in assessing the risks to
aquatic invertebrates. No invertebrate full-life-cycle toxicity studies were submitted to the
Agency.
21
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Table 13. Acute Toxicity Endpoints for Freshwater and Estuarine/Marine Invertebrates
Test Species
% at
48- or 96-
hrLC50
(mg/L)
NOAEC
(mg/L)
Measured/nominal
Flow-through/static
Toxicity
Classification
MRIDor
Accession
Number
Freshwater Invertebrates (48-hr LC50)
Daphnia magna
92.4
2.2
1.5
Mean measured,
flow through
Moderately
toxic
420776-03
Estuarine/Marine Invertebrates (96-hr LC50)
Grass shrimp
Easter oyster,
shell deposition
Eastern oyster,
shell deposition
91.2
90
91.2
3.1
1.5
0.41
2.19
0.7
0.16
Mean measured,
flow through
Mean measured,
flow through
Mean measured,
flow through
Moderately
toxic
Moderately
toxic
Highly toxic
420776-06
430262-01
420776-05
Aquatic Plants
No aquatic plant data were submitted to the Agency for nitrapyrin. However, toxicity of
nitrapyrin to green algae can be estimated using the ECOSAR model. ECOSAR predicted a
96-hr ECso for green algae of 0.263 mg ai/L. The highest modeled peak EECs (incorporated
= 0.00059 mg/L and unincorporated = 0.03622 mg/L) are equal to 0.22% of the 96-hr EC50 in
the incorporated use scenario and 14% of the 96 hr ECso in the unincorporated scenario.
b. Toxicity to Terrestrial Organisms
Birds
Nitrapyrin is classified as moderately toxic to practically non-toxic to birds on an acute
basis, since the LDso value is between 118 and greater than 2510 mg/kg. Additionally, since
the LC50 values fall within the range of 820 to 2131 ppm, nitrapyrin is classified as
moderately toxic to slightly toxic to birds on a subacute basis. Table 14 summarizes the data
that support the acute toxicity endpoints used in assessing the risks to birds. No avian
chronic data were submitted to the Agency for nitrapyrin.
Table 14. Avian Toxicity Endpoints for Nitrapyrin
Toxicity
Study
Acute Single
Oral Dose
Subacute
Dietary
Species
Beltsville
small white
turkey
poults
Japanese
quail
% a.i.
93.6
93.6
Toxicity
Endpoint
LD50=H8
mg/kg - bwt
(85,164)
LC50 = 820
mg/kg-diet
(754, 894)
NOAEC/
NOAEL
NA
NOAEC =
600
mg/kg-
diet
Toxicity
Classification
Moderately toxic
Moderately toxic
MRID
Ace. 116870
Ace. 116899
22
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Table 15. Avian Acute Toxicity Endpoints for 6-CPA
Toxicity
Study
Acute
Dietary
Acute
Dietary
Test Species
Nlallard
duck
Japanese
quail
% a.i.
99
99
Toxicity
Endpoint
LC50 > 4640
mg/kg-diet
LC50 > 5000
mg/kg-diet
NOAEC/
NOAEL
1000 mg/
kg-diet
5000 mg/kg-
diet
Toxicity
Classification
practically
non-toxic
practically
non-toxic
MRID
Ace. 117016
Ace. 116899
Mammals
Nitrapyrin is classified as slightly toxic to mammals on an acute basis; however, adverse
effects were demonstrated in the mammalian subchronic, developmental, and 2-generation
toxicity studies (see Table 16).
Subchronic toxicity data for mammals from the 1-year feeding study with dogs indicate
increases in alkaline phosphatase, cholesterol, absolute and relative (to body) liver weights,
and liver hypertrophy. The LOAEL was 15 mg a.i./kg-bwt/day and the NOAEL was 3 mg
a.i./kg-bwt/day. Other subchronic mammalian studies had treatment related effects with
NOAELs ranging from 5 to 200 mg ai/kg-bwt/day and LOAELs ranging from 20 to 400 mg
ai/kg-bwt/day. Effects observed in these studies included increased liver weights and
hypertrophy.
Pre-natal developmental toxicity studies with rats and rabbits also demonstrated toxic
effects, including decreased body weight gains, increased absolute and relative (to body)
liver weights, and increased incidences of crooked hyoid (NOAEL =10 mg ai/kg-bwt/day).
Chronic toxicity data for mammals from the 2-generation rat reproduction study indicate
increases in liver and kidney weight and hepatic centrilobular diffuse hypertrophy (NOAEL
= 5 mg ai/kg-bwt/day, LOAEL = 20 mg ai/kg-bwt/day). No treatment-related reproductive
effects were observed; therefore, the parental NOAEL was set at the highest treatment level,
75 mg ai/kg-bwt/day. The offspring NOAEL was set at 20 mg ai/kg-bwt/day based on
decreased body weights and increased hepatic centrilobular vacuolation consistent with fatty
change in both sexes and generations.
Table 16. Summary of Acute Toxicity Endpoints for Mammals
Test Species
Rat
% a.i.
90
Toxicity Endpoint
LD50 (mg/kg-bwt) = 1070
(males)
1230 (females)
Toxicity
Classification
Slightly toxic
MRID
Ace. 37519
23
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Table 17. Summary of Subchronic and Chronic Toxicity Endpoints for Mammals
Toxicity Study
Test Species
% a.i.
NOAEL/
LOAEL
(mg/kg-bwt)
MRID
Subchronic
24-month Oral
Toxicity
90-day Feeding
52-week Oral
Toxicity
Rat
Mouse
Dog
93.3
90-92.05
92.8
5/20
200/300 (males) and
400 (females)
3/15
41345403
44231802
41345401
Chronic (reproductive)
Prenatal
Developmental
Toxicity
Prenatal
Developmental
Toxicity
2-generation
Reproductive
Rabbit
Rat
Rat
91.9
92
93.3
10/30
50/120
Parental = 5/20
Repro = 75/>75
Offspring = 20/75
Ace. 153543
43210302
40952701
Non-target Insects
No acute contact or dietary honey bee studies for nitrapyrin were submitted to the
Agency.
Non-target Terrestrial Plants
No guideline studies evaluating the toxicity of nitrapyrin to terrestrial plants have been
submitted to the Agency. However, several non-guideline studies evaluating nitrapyrin
phytotoxicity were submitted and one is summarized below.
The phytotoxicity of nitrapyrin was compared to that often commercial herbicides on
both monocots and dicot field crops and vegetables. Because little information is provided in
this study regarding laboratory methodology and quality controls, toxicity endpoints for
nitrapyrin cannot be derived from these data, but this study does provide anecdotal evidence
that nitrapyrin is less phytotoxic than several commercial herbicides.
3. Ecological Risk Estimation (RQs)
The Agency's ecological risk assessment compares toxicity endpoints from ecological
toxicity studies to estimated environmental concentrations (EECs) based on environmental
fate characteristics and pesticide use data. To evaluate the potential risk to non-target
organisms from the use of nitrapyrin products, the Agency calculates a Risk Quotient (RQ),
which is the ratio of the EEC to the most sensitive toxicity endpoint values, such as the
median lethal dose (LD50) or the median lethal concentration (LC50). These RQ values are
then compared to the Agency's levels of concern (LOCs), given in Table 17, which indicate
whether a pesticide, when used as directed, has the potential to cause adverse effects on non-
target organisms. When the RQ exceeds the LOG for a particular category, (e.g., endangered
24
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species), the Agency presumes a risk of concern to that category. These risks of concern may
be addressed by further refinements of the risk assessment or mitigation. Use, toxicity, fate,
and exposure are considered when characterizing the risk, as well as the levels of certainty
and uncertainty in the assessment. EPA further characterizes ecological risk based on any
reported incidents to non-target terrestrial or aquatic organisms in the field (e.g., fish or bird
kills).
Table 18. EPA's Levels of Concern and Associated Risk Presumptions
Risk Presumption
Acute Risk - there is potential for acute risk; regulatory action
may be warranted in addition to restricted use classification.
Acute Restricted Use - there is potential for acute risk, but
may be mitigated through restricted use classification.
Acute Endangered Species - endangered species may be
adversely affected; regulatory action may be warranted.
Chronic Risk - there is potential for chronic risk; regulatory
action may be warranted.
LOC
terrestrial
animals
0.5
0.2
0.1
1
LOC
aquatic animals
0.5
0.1
0.05
1
For a more detailed explanation of the ecological risks posed by the use of nitrapyrin,
refer to the "Environmental Fate and Effects Division Revised Risk Assessment for the
Nitrapyrin Reregi strati on Eligibility Decision", dated March 1, 2005.
a. Risk to Aquatic Organisms
Fish and Aquatic Invertebrates
Acute risks to aquatic species are not of concern when nitrapyrin products are
incorporated immediately upon application. For use without immediate soil incorporation,
the endangered species LOC is exceeded for estuarine/marine invertebrates; however, there
are no listed endangered or threatened estuarine/marine invertebrates at this time.
Chronic effects toxicity data were not available for nitrapyrin; therefore, RQs could not
be calculated. However, chronic risks to freshwater aquatic organisms would not be
expected for applications with either immediate or delayed soil incorporation because of the
low potential acute risks and rapid degradation of nitrapyrin.
The RQs and LOCs for acute risk from nitrapyrin for both freshwater and
estuarine/marine organisms are outlined in Table 18.
25
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Table 19. Acute Risk Quotients for Fish and Aquatic Invertebrates
Use Site
Peak Water
Concentration
(uga.i,/L)
Acute RQ a>b
Freshwater
Fish
Freshwater
Invertebrate
Estuarine/Marine
Fish
Estuarine/Marine
Invertebrate
Immediately Incorporated Application Scenarios
Texas Corn
Texas
Sorghum
Texas Wheat
0.41
0.59
0.50
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
<0.01
Un-incorporated Application Scenarios
Texas Corn
28.89
<0.01
<0.01
0.013
0.070*
a * indicates an exceedance of Endangered Species Level of Concern (LOG); RQ > 0.05.
b Acute toxicity endpoints (LC50 or EC50) were 3.4, 4.28, 2.2, and 0.41 mg ai/L for freshwater fish,
freshwater invertebrates, estuarine/marine fish, and estuarine/marine invertebrates, respectively.
Aquatic Plants
Aquatic plant toxicity data were not available to the Agency for nitrapyrin; therefore, a
quantitative risk assessment could not be conducted. However, adverse effects in green algae
at the current labeled rates of nitrapyrin are unlikely, based on a screening assessment using
predicted toxicity data from the ECOSAR program. An algae study has been submitted, but
has not been reviewed at this time. The review of this study is expected to confirm this
preliminary assessment.
Other Aquatic System Issues
Nitrapyrin disrupts bacterially mediated steps in the nitrogen cycle. Specifically the
compound inhibits the bacterial conversion of ammonia to nitrite. In aquatic systems this
may serve to increase the residence time of ammonia in surface waters. The duration and
magnitude of ammonia in water is a toxic concern in freshwater systems. The quantitative
extent to which runoff and drift of nitrapyrin to surface waters has not been evaluated in this
risk assessment because no data are available to assess the extent to which nitrapyrin inhibits
ammonia conversion in aquatic environments.
b. Risk to Non-target Terrestrial Organisms
RQs for birds and mammals were calculated by two methods: 1) using acute toxicity
endpoints and residues on food items and 2) the LD50/sq foot method. The RQs calculated
by both methods indicate similar risk levels, but the LD50/sq foot method is considered more
appropriate for the purpose of this document, because nitrapyrin is applied directly to soil,
and hence residues on food items are expected to be very low.
For the RQ methodology that utilizes LD50/sq ft, two application scenarios for each crop
scenario were modeled. In one scenario it was assumed that incorporation was delayed and
100% of nitrapyrin was available to birds, and in the second scenario it was assumed that
incorporation occurred immediately after application and only 1% of the chemical remained
available on the soil surface.
26
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Birds
There are no exceedances of any acute LOCs for birds, assuming nitrapyrin was soil
incorporated immediately after application (RQs range from <0.01 to 0.08; see Table 19).
However, if incorporation is delayed, then potential risks to small and medium (i.e., 20 and
100 g) birds are of concern (Endangered Species, Acute Restricted Use, and Acute LOCs are
exceeded) (RQs range from 0.05 to 8.25). There is only one end-use product label (EPA Reg.
No. 34704-804) that permits a delay of incorporation, up to 48 hours.
Potential acute risks to birds from 6-CPA, the major degradate of nitrapyrin, are low,
based on acute dietary bird toxicity studies.
Table 20. Avian Acute RQs Estimated from Nitrapyrin Application Using LD50/Sq Ft
Methodology
Scenario and Bird Weight Class (g)
RQa,b
Delayed Incorporation (100%
Available)
Immediate Incorporation (1%
Available)
Sorghum and Wheat (0.9 Ib a.i./A/app, single app)
20
100
1,000
8.25***
1.29**
0.09
0.08
0.01
<0.01
Corn (0.45 lbs/a.i./A/app, 2 apps at 30 day interval), single app of 0.45 Ibs a.i./A for calculations
20
100
1,000
4 ^2***
0.64***
0.05
<0.01
<0.01
<0.01
a RQ = (mg ai/sq ft) / (adjusted LD50 * wt. of bird, kg) [final units are: LD50/sqft ]
b * indicates an exceedance of Endangered Species Level of Concern (LOG); RQ > 0.10.
** indicates an exceedance of Acute Restricted Use LOG; RQ > 0.20.
*** indicates an exceedance of Acute Risk LOG; RQ > 0.50.
Mammals
There are no exceedances of any acute LOCs for mammals, assuming nitrapyrin is soil
incorporated immediately after application (all RQs were <0.01). If incorporation is delayed,
however, acute LOG exceedances occur for small and medium sized mammals (15 and 35 g)
(RQs range from <0.01 to 0.59). Acute mammal RQs are summarized in Table 21.
Table 21. Acute Mammal RQ Summary (LDso/sq foot)
Scenario and Mammal Weight Class
(g)
RQa-b
Delayed Incorporation (100%
Available)
Immediate Incorporation (1%
Available)
Sorghum and Wheat (0.9 Ib a.i./A/app, single app)
15
35
1,000
0.59***
0.25**
0.01
0.01
0.01
0.01
Corn (0.45 lbs/a.i./A/app, 2 apps at 30 day interval), single app of 0.45 Ibs a.i./A for calculations
15
35
1,000
0.29**
0.13*
0.01
0.01
0.01
0.01
' RQ = (mg ai/sq ft) / (LD50 * wt. of mammal, kg) [final units are: LD50/sqft ]
27
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* indicates an exceedance of Endangered Species Level of Concern (LOG); RQ > 0.10.
** indicates an exceedance of Acute Restricted Use LOG; RQ > 0.20.
*** indicates an exceedance of Acute Risk LOG; RQ > 0.50.
Chronic RQs for mammals were calculated assuming no soil incorporation of nitrapyrin
occurs. For sorghum and wheat applications, when the maximum residue levels are assumed,
the chronic LOG was exceeded for smaller mammals (15 and 35 g) consuming fruit and large
insects. For corn applications, when the maximum residue levels are assumed, the chronic
LOG was exceeded for small mammals (15 g) consuming fruit and large insects. There were
no exceedances of the chronic LOG for mammals consuming seeds and pods with predicted
maximum residues or for mammals when mean residue levels are assumed.
Table 22. Mammal Chronic RQ Summary (Assuming No Soil Incorporation)"'1^
Scenario and
Mammal Weight
Class (g)
RQ (Fruit and Large Insects)
Predicted Max
Residues
Predicted Mean
Residues
RQ (Seeds and Pods)
Predicted Max
Residues
Predicted Mean
Residues
Sorghum and Wheat (0.9 Ibs a.i./A/app, 1 app)
15
35
1,000
Corn (0.45 Ibs ai/A/api
15
35
1,000
1.72+
1.19+
0.28
0.86
0.60
0.14
0.59
0.41
0.10
0.30
0.21
0.05
p, 2 apps at 30 day interval), single app of 0.45 Ibs a.i./A for calculations
1.35+
0.94
0.22
0.25
0.17
0.04
0.47
0.32
0.07
0.08
0.06
0.01
" Chronic toxicity endpoint was NOAEL = 5 mg ai/kg-bwt-day.
b Detailed calculations for chronic RQs are provided in Table G-6 of EFED chapter.
c + indicates an exceedance of Chronic Level of Concern (LOG); RQ > 1.0.
Non-target Insects
EPA currently does not quantify risks to terrestrial non-target insects; therefore, risk
quotients are not calculated for these organisms. The likelihood of exposure to honey bees is
not likely to be significant because the method of application is ground spray with
incorporation, or soil injection. However, nitrapyrin exposure to beneficial ground dwelling
insects and other organisms may be significant. Based on submitted toxicity data, adverse
effects in earthworms are unlikely at the current labeled rates of nitrapyrin.
Non-target Terrestrial Plants
No guideline studies were submitted to the Agency for terrestrial plants; therefore, RQs
were not calculated for nitrapyrin. Adverse effects in terrestrial plants at the current labeled
rates of nitrapyrin are unlikely, based on a screening assessment using non-guideline
terrestrial plant toxicity data. Please refer to the environmental fate and effects risk
assessment for more detailed information.
Terrestrial Organism Risk Characterization
The risk assessment and calculated RQs for nitrapyrin assume 100% of the diet is
relegated to single food types foraged only from treated fields. The assumption of 100% diet
from a single food type may be realistic for acute exposures, but diets are likely to be more
28
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variable over longer periods of time. This assumption is likely to be conservative and will
tend to overestimate potential risks for chronic exposure, especially for larger organisms that
have larger home ranges (e.g., deer and geese).
In addition, exposure routes other than dietary are also possible for animals residing in or
moving through treated areas, including ingestion of contaminated drinking water, ingestion
of contaminated soils, preening/grooming, and dermal contact. Consumption of drinking
water would appear to be inconsequential if water concentrations were equivalent to the
concentrations from PRZM/EXAMS; however, concentrations in puddled water sources on
treated fields may be higher than concentrations in a modeled small water body. Preening
exposures, involving the oral ingestion of material from the feathers, have not been
quantified, but are a potentially important exposure route. Toxicity due to dermal contact is
likely to be of moderate importance because mammal testing revealed nitrapyrin was a
dermal sensitizer (Ace. 158903); however, no dermal effects were noted in the acute dermal
study with rabbits (LDso > 2000 mg ai/kg-bwt, Ace. 158904). If toxicity is expected through
any of these other routes of exposure, then the risks of a toxic response to nitrapyrin is
underestimated in this risk assessment.
Because nitrapyrin is a volatile compound (v.p. 2.8xlO"3 torr) and does not have a strong
tendency to bind to organic matter in soil (Koc ranges between 278 and 360 based on
experimental data submitted by the registrant), inhalation of gas phase nitrapyrin may be a
significant contributor to overall exposure. For mammals, no toxic effects were seen in
available inhalation studies (Ace. 158901). For birds, however, there would be a potential
for adverse acute effects due to inhalation of the test chemical, if the amount inhaled was
close to or greater than the dietary LD50. If the amount inhaled was much smaller than the
LD50, however, then it is unlikely that adverse effects would be triggered.
c. Endangered Species
The screening level risk assessment for nitrapyrin resulted in no acute risks above EPA's
level of concern to any listed species and no chronic risks above EPA's level of concern for
any listed terrestrial organisms if nitrapyrin is incorporated immediately post-treatment.
However, at this time, the Agency does not have chronic toxicity data for estuarine aquatic
organisms. Therefore, EPA concludes that there is "no effect" from direct acute risks for any
listed species and from direct chronic risks for any listed terrestrial species when nitrapyrin is
soil incorporated immediately post-treatment. The EPA cannot, at this time, make a clear
"no effect" finding for indirect effects or for direct chronic effects for listed estuarine
organisms.
d. Assumptions, Uncertainties, Strengths, and Limitations
There are a number of areas of uncertainty in the terrestrial and the aquatic organism risk
assessments that could potentially cause an underestimation of risk. First, risks to terrestrial
and aquatic organisms from exposures to parent nitrapyrin, but not its degradates, have been
(with the exception of acute avian risk) have been assessed. The Metabolism Assessment
Review Committee (MARC) of the EPA has determined that the major degradate, 6-CPA is
of toxicological concern for mammals. Second, the risk assessment only considers the most
29
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sensitive species tested and only considers a subset of possible use scenarios. Third, the
effect of volatility of nitrapyrin on non-target organisms should be viewed as a source of
uncertainty in the ecological risk assessment for nitrapyrin. For the aquatic organism risk
assessment, there are uncertainties associated with the PRZM/EXAMS model, input values,
and scenarios, as well as uncertainties in the potential for modifications to the surface water
concentration of ammonia; however, these uncertainties cannot be quantified. The potential
impacts of these uncertainties are outlined in the Environmental Fate and Effects Division
Revised Risk Assessment for the Nitrapyrin Reregi strati on Eligibility Decision.
IV. Risk Management, Reregistration, and Tolerance Reassessment Decision
A. Determination of 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 reregi strati on. The Agency has previously identified and required
the submission of the generic (i.e., active ingredient-specific) data required to support
reregi strati on of products containing nitrapyrin as an active ingredient. The Agency has
completed its review of these generic data, and has determined that the data are sufficient to
support reregi strati on of all products containing nitrapyrin.
The Agency has completed its assessment of the dietary, occupational, residential, and
ecological risk associated with the use of pesticide products containing the active ingredient
nitrapyrin. Based on a review of these data and on public comments on the Agency's
assessments for the nitrapyrin, the Agency has sufficient information on the human health
and ecological effects to make decisions as part of the tolerance reassessment process under
FFDCA and reregi strati on process under FIFRA, as amended by FQPA. The Agency has
determined that products containing nitrapyrin are eligible for reregi strati on provided that: (i)
current data gaps and confirmatory data needs are addressed; (ii) the risk mitigation measures
outlined in this document are adopted; and (iii) label amendments are made to reflect these
measures. Label changes are described in Section V. Appendix A summarizes the uses of
nitrapyrin that are eligible for reregi strati on, and Appendix B identifies the generic data
requirements that the Agency reviewed as part of its determination of reregi strati on eligibility
of nitrapyrin, and lists the submitted studies that the Agency found acceptable. Data gaps are
identified as generic data requirements that have not been satisfied with acceptable data.
Based on its evaluation of nitrapyrin, the Agency has determined that nitrapyrin products,
unless labeled and used as specified in this document, would present risks inconsistent with
FIFRA. Accordingly, should a registrant fail to implement any of the risk mitigation
measures identified in this document, the Agency may take regulatory action to address the
risk concerns from the use of nitrapyrin. If all changes outlined in this document are
incorporated into the product labels, then all current risks for nitrapyrin will be adequately
mitigated for the purposes of this determination.
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B. Public Comments and Responses
Through the Agency's public participation process, EPA worked extensively with
stakeholders and the public to reach the regulatory decisions for nitrapyrin. During the
public comment period on the risk assessments, which closed on January 3, 2005, the
Agency received only one set of comments from Dow AgroSciences, the technical registrant.
These comments are available in the EPA's public docket, www. gov/.edocket (OPP-
2004-0283). An individual response to these comments will also be made available in the
docket.
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 nitrapyrin. EPA has determined that risk from dietary (food sources only) exposure to
nitrapyrin fits within its own "risk cup." An aggregate assessment was conducted for
exposures through food and drinking water uses (nitrapyrin is not registered for residential
use), and the Agency has determined that the human health risks from these combined
exposures are within acceptable levels. In other words, EPA has concluded that the
tolerances for nitrapyrin meet FQPA safety standards. In reaching this determination, EPA
has considered the available information on the special sensitivity of infants and children, as
well as aggregate exposure from food and water.
b. Determination of Safety to U.S. Population
The Agency has determined that the established tolerances for nitrapyrin, with
amendments and changes as specified in this document, meet the safety standards under the
FQPA amendments to section 408(b)(2)(D) of the FFDCA, and that there is a reasonable
certainty no harm will result to the general population or any subgroup from the use of
nitrapyrin. In reaching this conclusion, the Agency has considered all available information
on the toxicity, use practices and exposure scenarios, and the environmental behavior of
nitrapyrin. As discussed in Chapter 3, the total acute dietary (food alone) risk was not
assessed because no acute oral endpoint was observed. Further, the chronic non-cancer and
cancer dietary (food alone) risks from nitrapyrin are not of concern.
Acute and chronic risks from drinking water exposures are not of concern. Models have
been used to estimate ground and surface water concentrations. The DWLOC calculated to
assess the surface water contribution to chronic (non-cancer) dietary exposure is a range from
300 ug/L (Children 1 to 2 years old) to 1050 ug/L for the subgroups U.S. Population, Adults
20 to 49 years old, and Adults 50+ years old, and the DWLOC calculated to assess the
surface water contribution to chronic (cancer) dietary exposure is 0.84 ug/L.
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c. Determination of Safety to Infants and Children
EPA has determined that the established tolerances for nitrapyrin, with amendments and
changes as specified in this document, meet the safety standards under the FQPA
amendments to section 408(b)(2)(C) of the FFDCA, that there is a reasonable certainty of no
harm for infants and children. The safety determination for infants and children considers
the toxicity, use practices and environmental behavior noted above for the general
population, but also takes into account the possibility of increased dietary exposure due to the
specific consumption patterns of infants and children, as well as the possibility of increased
susceptibility to the toxic effects of nitrapyrin residues in this population subgroup.
In determining whether or not infants and children are particularly susceptible to toxic
effects from nitrapyrin residues, the Agency considered the completeness of the database for
developmental and reproductive effects, the nature of the effects observed, and other
information. The FQPA Safety Factor has been removed (i.e., reduced to IX) for nitrapyrin
because: 1) there is no indication of quantitative or qualitative increased susceptibility of rats
or rabbits to in utero or postnatal exposure; 2) a DNT study with nitrapyrin is not required;
and 3) the dietary and non-dietary (residential) exposure assessments will not underestimate
the potential exposures to infants and children.
d. Endocrine Disrupter Effects
EPA is required under the FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect produced by a
naturally occurring estrogen, or other 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 to 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 of additional hormone systems may be added to the Endocrine Disrupter
Screening Program (EDSP).
Neither the subchronic, chronic, developmental or reproductive rat, mouse, dog or rabbit
studies indicated that nitrapyrin was associated with either a specific or an indirect
neurotoxic or immunotoxic response or endocrine disruption.
e. Cumulative Risks
Risks summarized in this document are those that result only from the use of nitrapyrin.
The Food Quality Protection Act (FQPA) requires that the Agency consider available
information concerning the cumulative effects of a particular pesticide's residues and "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
32
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substances that cause a common toxic effect by a common toxic mechanism could lead to the
same adverse health effect as would a higher level of exposure to any of the substances
individually. Unlike other pesticides for which EPA has followed a cumulative risk approach
based on a common mechanism of toxicity, EPA has not made a common mechanism of
toxicity finding for nitrapyrin. 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://www.epa.gov/pesticides/cumulative/.
2. Tolerance Summary
Tolerances of nitrapyrin in/on plant and livestock commodities (40 CFR § 180.350) are
presently expressed in terms of the parent compound, as well as the major metabolite, 6-
CPA, because EPA has determined 6-CPA to be the major residue in all registered or rotated
crops.
a. Tolerances Currently Listed Under 40 CFR §180.350
Sufficient field trial data have been submitted (or were translated when appropriate) to
reassess the established tolerances for corn, sorghum, and wheat. The Agency plans to set
new tolerances for wheat, for some crop factions of wheat, and for one crop faction of corn,
because studies submitted since the last Registration Standard have shown higher residues
than were considered before. In addition, there is no reasonable expectation of residues in
livestock or poultry, and so the Agency plans to revoke tolerances for livestock commodities.
A tolerance summary for nitrapyrin is presented in Table 23.
Table 23. Tolerance Summary for Nitrapyrin
Commodity
Cattle, Fat
Cattle, Meat Byproducts
Cattle, Meat
Corn, Forage
Corn, Fresh, K+C, With Husks
Removed
Corn, Grain
Corn, Stover
Goat, Fat
Established Tolerance
(ppm)
0.05 (N)
0.05 (N)
0.05 (N)
1.0
0.1 (N)
0.1 (N)
1.0
0.05 (N)
Reassessed Tolerance
(ppm)
Revoke
Revoke
Revoke
1.0
0.1
0.1
1.0
Revoke
Comments (correct commodity
definition)
No anticipated residues
No anticipated residues
No anticipated residues
[Corn, field, forage} and
[Corn, sweet, forage}
[Corn, sweet, kernel plus cob
with husks removed}
[Corn, field, grain} and [Corn,
pop, grain}
[Corn, field, stover} ; [Corn,
pop, stover}', and [Corn, sweet,
stover}
No anticipated residues
33
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Commodity
Goat, Meat Byproducts
Goat, Meat
Hog, Fat
Hog, Meat Byproducts
Hog, Meat
Horse, Fat
Horse, Meat Byproducts
Horse, Meat
Poultry, Fat
Poultry, Meat Byproducts
Poultry, Meat
Sheep, Fat
Sheep, Meat Byproducts
Sheep, Meat
Sorghum, Forage
Sorghum, Grain
Sorghum, Grain, Stover
Wheat, Forage
Wheat, Grain
Wheat, Straw
Established Tolerance
(ppm)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.05 (N)
0.1 (N)
0.1 (N)
0.5
0.5
0.1 (N)
0.5
Reassessed Tolerance
(ppm)
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
Revoke
0.5
0.1
0.5
2.0
0.5
6.0
Comments (correct commodity
definition)
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
No anticipated residues
[Sorghum, grain, grain]
Based on field trial data
Based on field trial data
Tolerances To Be Established Under 40 CFR §180.350(a)
Corn, Milled Byproducts
Wheat, Bran
Wheat, Milled Byproducts
None
None
None
0.2
3.0
2.0
Based on processing studies
[Corn, field, milled
byproducts]
Based on processing studies
Based on processing studies
JEPA expects to remove the "(N)" designation from all entries to conform to current Agency administrative
practice ["(N)" designation means negligible residues].
b. Codex Harmonization
No Codex maximum residue levels (MRLs) have been established for nitrapyrin.
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c. Residue Analytical Methods - Plants and Livestock
The reregi strati on requirements for residue analytical methods are fulfilled. Adequate
methods are available for data collection and for the enforcement of tolerances for residues of
nitrapyrin per se in/on plant commodities. Since there is no reasonable expectation of
residues in livestock or poultry, enforcement methods for the determination of nitrapyrin
residues in livestock commodities are not needed. However, should new uses of nitrapyrin
be requested that lead to higher residues in livestock or poultry, additional data may be
required to support a tolerance enforcement method for livestock.
D. Regulatory Rationale
The Agency has determined that nitrapyrin is eligible for reregi strati on provided that: 1)
additional data that the Agency intends to require confirm this decision, 2) the risk mitigation
measures outlined in this document are adopted, and 3) label amendments are made to reflect
these measures.
The following is a summary of the rationale for managing risks associated with the use of
nitrapyrin. Where labeling revisions are warranted, specific language is set forth in the
summary tables of Chapter V of this document. Immediate incorporation of nitrapyrin is
expected to reduce risks to occupational handlers, as well as wildlife. The risk reduction
from this action has not been completely quantified, but will reduce exposure to nitrapyrin.
1. Human Health Risk Management
a. Dietary (Food) Risk Mitigation
No adverse effects attributed to a single exposure were identified in any available study
for nitrapyrin, including developmental studies in rabbits or rats. Therefore, no acute dietary
assessment was conducted and no mitigation is needed.
The chronic (non-cancer) dietary analysis indicates all risk estimates are below the
Agency's level of concern for all population subgroups for nitrapyrin. The highest chronic
dietary risk estimates are less than 1% of the chronic population adjusted dose (PAD).
Therefore, the chronic dietary (food) risk estimate is not of concern, and no risk reduction
measures are necessary.
b. Drinking Water Risk Mitigation
Estimated environmental concentrations (EECs) of nitrapyrin and its degradates for both
groundwater and surface water sources of drinking water are below the Agency's drinking
water levels of concern (DWLOCs). Therefore, no mitigation is needed for drinking water.
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c. Aggregate Risk Mitigation
1) Acute Aggregate Risk
There are no adverse effects expected from a single exposure to nitrapyrin; therefore, an
acute aggregate risk assessment was not conducted.
2) Chronic Aggregate Risk
The chronic aggregate risk assessment addresses only exposure to nitrapyrin residues in
food and water; since there are no nitrapyrin uses that could result in residential exposure.
The estimated environmental concentrations (EECs) do not exceed the drinking water level
of comparison (DWLOC). Chronic dietary aggregate risk are below the Agency's level of
concern,and therefore, no mitigation is required.
3) Cancer Aggregate Risk
An aggregate cancer risk assessment for the U.S. Population based on nitrapyrin was
conducted in which food exposure was assumed to be negligible, but water exposures were
not. The EECs do not exceed the DWLOC. Aggregate cancer risk is below the Agency's
level of concern, and therefore, no mitigation is required.
d. Occupational Risk Mitigation
1) Handler Exposure
Non-cancer handler exposure assessments are completed by EPA using a baseline (long-
sleeved shirt and long pants) exposure scenario and, if required, increasing levels of
mitigation Personal Protective Equipment (PPE) and engineering controls] to achieve an
adequate margin of exposure (MOE). Analyses for handler/applicator exposures were
performed using data from the Pesticide Handlers Exposure Database. Short- and
intermediate-term dermal and inhalation risks to occupational handlers are below the
Agency's level of concern (i.e., MOE > 100) at the baseline (i.e., no respirator) for
applicators. For mixing/loading to support ground boom application, MOEs are <100 for
short- and intermediate-term exposures at baseline, but are >100 when chemical resistant
gloves were added. Current labels require chemical resistant gloves; therefore, no further
mitigation is required.
The Agency's level of concern for occupational cancer risks begins at > 1.0 x 10"4, with
all attempts to mitigate risks to < l.Ox 10"6 when possible. The results of the occupational
handler cancer assessment (Table 10) for nitrapyrin indicate that none of the cancer risks for
any of the exposure scenarios considered exceeds the Agency's level of concern. In addition,
all current labels require workers handling nitrapyrin to wear the equivalent of the PPE1
scenario (long pants, long sleeved shirt, plus gloves), and the Agency believes this level of
PPE is adequate.
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2) Post-application Risk Mitigation
A post-application assessment was not conducted for nitrapyrin because there is a low
potential for occupational postapplication exposure when a soil directed pesticide is used.
2. Environmental Risk Mitigation
EPA's screening level ecological risk assessment shows some exceedances of the Acute,
Acute Restricted Use, and the Endangered Species LOCs for small and medium birds and
mammals and the Chronic LOG for smaller mammals when soil incorporation of nitrapyrin
does not occur immediately after application. However, there are no LOG exceedances when
incorporation is immediate. There is currently only one nitrapyrin label that allows delayed
incorporation (up to 48 hours), and that label will be changed to require immediate
incorporation. This mitigation is expected to substantially reduce risks of concern to wildlife
from nitrapyrin use.
3. Other Labeling
In order to be eligible for reregi strati on, various use and safety information will be
included in the labeling of all end-use products containing nitrapyrin. For the specific
labeling statements and a list of outstanding data, refer to Section V of this RED document.
4. Endangered Species Program
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 that may affect any particular species, EPA uses basic toxicity and exposure
data developed for the REDs and 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. This analysis will consider the
risk mitigation measures that are being implemented as a result of this RED.
The screening level risk assessment for nitrapyrin resulted in no acute risks above EPA's
level of concern to any listed species and no chronic risks above EPA's level of concern for
any listed terrestrial organisms if nitrapyrin is incorporated immediately post-treatment.
However, at this time, the Agency does not have chronic toxicity data for estuarine aquatic
organisms. Therefore, EPA concludes that there is "no effect" from direct acute risks for any
listed species and from direct chronic risks for any listed terrestrial species when nitrapyrin is
soil incorporated immediately post-treatment. The EPA cannot, at this time, make a clear
"no effect" finding for indirect effects or for direct chronic effects for listed estuarine
organisms.
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V. What Registrants Need to Do
The use of currently registered products containing nitrapyrin in accordance with
approved labeling will not pose unreasonable risks or adverse effects to humans or the
environment if the risk mitigation measures and label changes outlined in the RED are
implemented. Therefore, all uses of these products are eligible for reregistration. These
products will be reregistered once the required confirmatory generic data, product specific
data, CSFs, and revised labeling are received and accepted by EPA. Products which contain
other ingredients in addition to nitrapyrin will be reregistered when all of their other active
ingredients are also reregistered.
A. For nitrapyrin technical grade active ingredient products, the registrant needs to
submit the following items:
Within 90 days from receipt of the generic data call in (DCI):
1. Completed response forms to the generic DCI (i.e., DCI response form
and requirements status and registrant's response form); and
2. Any time extension and/or waiver requests with a full written justification.
Within the time limit specified in the generic DCI:
1. Citations of any existing generic data which address data requirements or
submit new generic data responding to the DCI.
Please contact Stephanie Plummer at (703) 305-0076 with questions regarding generic
reregistration.
By U.S. Mail: By express or courier service:
Document Processing Desk (DCI/SRRD) Document Processing Desk (DCI/SRRD)
Stephanie Plummer Stephanie Plummer
U. S. EPA (7508C) Office of Pesticide Programs (7508C)
1200 Pennsylvania Ave., NW Room 266A, Crystal Mall 2
Washington, DC 20460 1801 South Bell Street
Arlington, VA 22202
B. For end-use products containing the active ingredient nitrapyrin, the registrant
needs to submit the following items for each product:
Within 90 days from the receipt of the product-specific data call-in (PDCI):
(1) completed response forms to the PDCI (i.e., PDCI response form and
requirements status and registrant's response form); and
(2) any time extension or waiver requests with a full written justification.
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Within eight months from the receipt of the PDCI:
(1) two copies of the confidential statement of formula (EPA Form 8570-4);
(2) a completed original application for reregi strati on (EPA Form 8570-1).
Indicate on the form that it is an "application for reregi strati on";
(3) five copies of the draft label, incorporating all label amendments outlined
in Table 24 of this document;
(4) a completed form certifying compliance with data compensation
requirements (EPA Form 8570-34);
(5) if applicable, a completed form certifying compliance with cost share offer
requirements (EPA Form 8570-32); and
(6) the product-specific data responding to the PDCI.
Please contact Karen Jones at (703) 308-8047 with questions regarding product
reregi strati on and/or the PDCI. All materials submitted in response to the PDCI should be
addressed:
By US mail: By express or courier service only:
Document Processing Desk (PDCI/PRB) Document Processing Desk (PDCI/PRB)
Karen Jones Karen Jones
US EPA (7508C) Office of Pesticide Programs (7508C)
1200 Pennsylvania Ave., NW Room 266A, Crystal Mall 2
Washington, DC 20460 1801 South Bell Street
Arlington, VA 22202
A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregi strati on of nitrapyrin for the above eligible
uses has been reviewed and determined to be substantially complete. However, the
following data requirements are necessary to confirm the reregi strati on eligibility decision
documented in this RED:
Environmental Fate
835.2410 Soil photolysis (nitrapyrin)
835.4300 Aerobic aquatic metabolism (nitrapyrin)
835.6100 Terrestrial field dissipation (nitrapyrin)
835.2120 Hydrolysis (6-CPA)
835.2240 Aqueous photolysis (6-CPA)
835.4100 Aerobic soil metabolism (6-CPA)
835.4300 Aerobic aquatic metabolism (6-CPA)
835.1410 Laboratory volatilization (6-CPA)
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Ecological Effects
850.1350 Estuarine/marine invertebrates, life cycle
850.1400 Estuarine/marine fish, early-life stage
2. Labeling for Manufacturing Use Products
To ensure compliance with FIFRA, manufacturing use product (MUP) labeling should be
revised to comply with all current EPA regulations, PR Notices, and applicable policies. The
MUP labeling should bear the labeling contained in the labeling table, which will be issued
separately.
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 that 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 Registrants
Response Form provided for each product.
A product-specific data call-in, outlining specific data requirements, accompanies this
RED.
2. Labeling for End-Use Products
Labeling changes are necessary to implement measures outlined in Section IV above.
Specific language to incorporate these changes is specified in Table 24.
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C. Label Summary Table
Table 24. Summary of Labeling for Nitrapyrin
Description
Amended Labeling Language
Placement on Label
Manufacturing Use Products
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
group.
"Only for formulation into a nitrification inhibitor for use on corn, sorghum, and
wheat."
"This product may be used to formulate products for specific use(s) not listed on this
label if the formulator, user group, or grower has complied with U.S. EPA submission
requirements regarding the support of such use(s)."
Directions for Use
Directions for Use
Environmental
Hazards Statements
Required by the
RED and Agency
Label Policies
"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."
Directions for Use
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Description
Amended Labeling Language
Placement on Label
End Use Products Intended for Occupational Use
PPE Requirements
Established by the
RED for liquid
formulations
"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, applicators and other handlers must wear:
Long-sleeved shirt and long pants,
Chemical-resistant gloves, and
Shoes plus socks."
Immediately
following/below
Precautionary
Statements: Hazards
to Humans and
Domestic Animals
User Safety
Requirements
"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."
Precautionary
Statements: Hazards
to Humans and
Domestic Animals
immediately
following the PPE
Requirements
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Description
Amended Labeling Language
Placement on Label
User Safety
Recommendations
"User Safety Recommendations
Users should wash hands before eating, drinking, chewing gum, using tobacco, or
using the toilet.
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 User
Safety Requirements
(Must be placed in a
box.)
Environmental
Hazards
"Do not apply directly to water, or 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 washwaters or rinsate."
Precautionary
Statements
immediately
following the User
Safety
Recommendations
Restricted-Entry
Interval
"Do no enter of allow worker entry into treated areas during the restricted entry interval
(REI) of 24 hours."
Directions for Use,
Under Agricultural
Use Requirements
Box
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Description
Amended Labeling Language
Placement on Label
Early Re-Entry
Personal Protective
Equipment
established by the
RED
"PPE required for early entry to treated areas that is permitted under the Worker
Protection Standard and that involves contact with anything that has been treated, such
as plants, soil, or water, is:
* coveralls
* shoes plus socks
* chemical-resistant gloves made of any waterproof material
* protective eyewear."
Direction for Use
Agricultural Use
Requirement Box
"Do not apply this product in a way that will contact workers or other persons, either
directly or through drift. Only protected handlers may be in the area during
application."
General Application
Restrictions
Place in the
Direction for Use
directly above the
Agricultural Use
Box.
Other Application
Restrictions (Risk
Mitigation)
"Must be injected or incorporated in a zone or band in the soil with the fertilizer at a
minimum depth of 2 to 4 inches during or immediately after application."
Place in the
Directions for Use
under Application
Instructions for Each
Crop
44
-------
VI. Appendices
45
-------
Appendix A. Food/Feed Use Patterns Subject to Reregistration for Nitrapyrin (Case 0213)
Site
Application Timing
Application Type
Application Equipment
Maximum
Single
Application
Rate
(Ib a.i./A)
Maximum
Number of
Applications
Per Year
Maximum
Yearly Rate
(Ib a.i./A)
Preharvest
Interval (Days)
Use Directions and Limitations
Corn
Preplant
Broadcastfaand soil incorporated
Sprayer, injection equipment
Postplant
Soil side dress
Sprayer, injection equipment
0.45
0.45
2
1
0.9
0.9
NS
NS
Applications may be made in 1 to 2 pints (band)
or 1 to 4 pints (broadcast) of water or liquid
fertilizer per acre. Product must be soil injected
or incorporated at a minimum of 2 to 4 inches
during or immediately after application. A split
application, with one pre-plant and one post-
plant, is allowed for corn only.
Applications may be made in 1 to 2 pints of
water or liquid fertilizer per acre. Product must
be soil injected or incorporated at a minimum of
2 to 4 inches during or immediately after
application. May be applied up to 30 days post-
plant. A split application, with one pre-plant
and one post-plant, is allowed for corn only.
Sorghum
Preplant
Broadcastfaand soil incorporated
Sprayer, injection equipment
0.9
1
0.9
NS
See corn.
Wheat
Preplant
Broadcastfaan soil incorporated
Sprayer injection equipment
0.9
1
0.9
NS
See corn.
46
-------
Appendix B. Table of Generic Data Requirements and Studies Used to Make the
Reregistration Decision
GUIDE TO APPENDIX B
Appendix B contains a listing of data requirements which support the
reregi strati on for active ingredients within the case Nitrapyrin 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.
47
-------
Appendix B. Data Supporting Guideline Requirements for the Reregistration of Nitrapyrin
New
Guideline
Number
Old
Guideline
Number
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
830.6314
830.6316
830.6367
830.6320
830.7000
830.7050
830.7200
830.7300
830.7370
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
63-12
None
63-5
63-7
63-10
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
Oxidation/reduction: Chemical
Incompatibility
Explodability
Storage Stability
Corrosion Characteristics
pH
UV/Visible Absorption
Melting Point
Density
Dissociation Constants in Water
Partition coefficient, shake flask
method
Solubility
Vapor Pressure
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
00156504
00156504
00156504
00156504
00163516
00163516
00163516
00156505, 40099501
00156505, 40099501
00156505, 40099501
00156505, 40099501
40099501
40099501
40099501,41563104
40099501,41563104
00156505
Data Gap
00156505, 40099501,
41563102
00156505, 40099501,
41563101
00156505
00156505, 40099501,
41563106
00156505,40099501
00156505, 40099501
ECOLOGICAL EFFECTS
850.2100
850.2200
850.2200
850.2300
850.2300
850.1075
850.1075
850.1075
850.1010
71-1A
7 1-2 A
71-2B
7 1-4 A
71-4B
72-1A
72-1C
72-1D
72-2A
Avian Acute Oral Toxicity
Avian Dietary Toxicity - Quail
Avian Dietary Toxicity - Duck
Avian Reproduction - Quail
Avian Reproduction - Duck
Fish Toxicity Bluegill
Freshwater Fish Toxicity
Rainbow Trout
Freshwater Fish Toxicity
Rainbow Trout - TEP
Freshwater Invertebrate Toxicity
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
Ace. 110296, Ace.
116879
Ace. 79565, Ace.
116898, Ace. 116899
Ace. 118934, Ace.
117016
Data gap
Data gap
42077601, 42077602,
00116894,
Ace. 110297
00116894,42077601,
42077602
00116895,00129370,
00042005
42077603, Ace.
48
-------
New
Guideline
Number
850.1075
850.1025
850.1035
850.1350
850.1450
850.5400
850.6200
Old
Guideline
Number
72-3A
72-3B
72-3C
72-4B
72-4D
122-2
None
Description
Estuarine/Marine Toxicity - Fish
Estuarine/Marine Toxicity -
Mollusk
Estuarine/Marine Toxicity -
Shrimp
Estuarine/Marine Invertebrate
Life Cycle
Estuarine/Marine Fish Early -Life
Stage
Aquatic Plant Growth
Earthworm Toxicity
Use Patterns
A,B
A,B
A,B
A,B
A,B
A,B
A,B
Citations
110295, Ace. 110298
42077604
43026201, 42077605,
0074042
42077606
Data gap
Data gap
46411401
46411402
TOXICOLOGY
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
870.3100
870.3150
870.3200
870.4100
870.3700
870.3700
870.3800
870.4100
870.4100
870.4200
870.4300
870.5100
870.5375
870.5550
870.7485
81-1
81-2
81-3
81-4
81-5
81-6
82-1A
82-1B
82-2
83-1
83-1B
83-3A
83-3B
83-4
83-1A
83-1B
83-2B
83-5
84-2
84-2B
84-2
85-1
Acute Oral Toxicity - Rat
Acute Dermal Toxicity -
Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Skin Irritation
Dermal Sensitization
Subchronic Oral Toxicity: 90-
Day Study Rodent
Subchronic Oral Toxicity: 90-
Day Study Non-rodent
21 -Day Dermal - Rabbit/Rat
Chronic Feeding Toxicity - Rat
Chronic Feeding Toxicity - Non-
rodent
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
Bacterial Reverse Gene Mutation
Cytogenetics
Unscheduled DNA Synthesis in
Mammalian Cells in Culture
General Metabolism
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
Ace. 37519
Ace. 37519, 00158904
Ace. 37519, 00158901
Ace. 37519, 00158902
Ace. 37519
00158903
44231802
41345401
42239301
00163217,40339301,
41345401,41345403
41345401,41345403
00163792, 42050101,
43210301,43210302,
Ace. 153543
Ace. 153543
40952701
41345403
41345401
40339301,41345403,
44231803,41651601,
44231801
41651601,41345403
00104957,00151627,
00151628,00163805
00104957,00151627,
00151628,00163805
00163805
44282501,40305501,
44679301
49
-------
New
Guideline
Number
870.7600
Old
Guideline
Number
85-3
Description
Dermal Penetration and
Absorption
Use Patterns
A,B
Citations
44282501
ENVIRONMENTAL FATE
835.2120
835.2240
835.2410
835.4100
835.4200
835.4400
835.4300
835.1240
835.1410
835.6100
None
161-1
161-2
161-3
162-1
162-2
162-3
162-4
163-1
163-2
164-1
165-4
Hydrolysis
Photodegradation - Water
Photodegradation - Soil
Aerobic Soil Metabolism
Anaerobic Soil Metabolism
Anaerobic Aquatic Metabolism
Aerobic Aquatic Metabolism
Leaching/ Adsorption/Desorption
Laboratory Volatilization
Terrestrial Field Dissipation
Bioaccumulation in Fish
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
40515302
(Data gap for 6-CPA)
40515303
(Data gap for 6-CPA)
Data gap
00117010,00117998
00117010
40515303
Data gap for nitrapyrin
and 6-CPA
00079381, 40339401,
00110294
00110294
(Data gap for 6-CPA)
Data gap
00101635
RESIDUE CHEMISTRY
860.1300
860.1300
860.1340
860.1340
171-4A
171-4B
171-4C
171-4D
Nature of Residue - Plants
Nature of Residue - Livestock
Residue Analytical Method -
Plants
Residue Analytical Method -
Livestock
A,B
A,B
A,B
A,B
00110311,00116907,
Ace. 37878, Ace.
37873, Ace. 88727,
Ace. 37876, Ace.
37870, Ace. 37872,
40370401
Ace. 37875, Ace.
38480,00116901,
00116902,00116919,
40339402, 40339403,
42815101,42815102,
43512101,43781501
40339402, 40339403,
40370401, 42740102,
Ace. 37881, Ace.
37886, Ace. 37887,
Ace. 39620, Ace.
39624, Ace. 39625,
Ace. 40046, Ace.
40049, Ace. 52343,
Ace. 52964, Ace.
88737,00109457,
00110314,40515301,
42740102, 42740103,
42740104,42815101,
42815102,43356402
43356405, 43356406,
40407201, 40572301,
40407203, 40363803,
40363802, 42229201
Ace. 37882, Ace.
37885, Ace. 37886,
50
-------
New
Guideline
Number
860.1380
860.1500
860.1360
860.1480
Old
Guideline
Number
171-4E
171-4K
171-4M
171-4J
Description
Storage Stability
Crop Field Trials
Corn, Grain
Corn, Stover
Corn, Forage
Corn, Sweet
Sorghum, Grain
Sorghum, Stover
Sorghum, Forage
Wheat, Grain
Wheat, Forage
Wheat, Straw
Multiresidue Methods
Magnitude of Residue in Meat,
Milk, Poultry and Eggs
Cattle, Goats, Horses and Sheep
Meat
Cattle, Goats, Horses and Sheep
Use Patterns
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
Citations
Ace. 37888,
40515301,41461103,
41461104,42740102,
43356401, 43356402,
43356403, 43356404,
43512101,43781501,
43810601
Ace. 40049, Ace.
40054, Ace. 76728,
Ace. 52343, Ace.
40056, Ace. 40057,
00039619,00110311,
GS0213001,
GS0213002,
40407202, 40968601,
41461103,41461104,
42776601, 42795901,
43849001, 43849002,
43849003
Ace. 40048, Ace.
40050,00110318,
40407201
Ace. 40046, Ace.
40050,00110318,
40407201
Ace. 40046, Ace.
40048, Ace. 40050,
00110318,40407201
40363802
Ace. 39619, 40363803
Ace. 39619, Ace.
40046, 40363803
Ace. 39619, Ace.
40046, 40363803
Ace. 37881, Ace.
39620, 40407203,
40572301, 42229201
Ace. 37881, Ace.
40046, Ace.
39620,40407203,
40572301
ace. 37881, Ace.
39620, 40407203,
40572301
43094501
Ace. 40054
Ace. 40054
51
-------
New
Guideline
Number
860.1520
860.1850
860.1900
Old
Guideline
Number
171-4L
165-1
165-2
Description
Meat Byproducts
Cattle, Goats, Horses and Sheep
Fat
Hog Meat
Hog Meat Byproducts
Hog Fat
Poultry Meat
Poultry Meat Byproducts
Poultry Fat
Milk
Eggs
Magnitude of Residue in
Processed Food/Feed
Corn, Field
Corn, Sweet
Sorghum
Wheat
Confined Accumulation in
Rotational Crops
Field Accumulation in Rotational
Crop Study
Use Patterns
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
Citations
Ace. 40054
Ace. 40055
Ace. 40055
Ace. 40055
Ace. 40057
Ace. 40057
Ace. 40057
Ace. 40056, 42740101
Ace. 40057
41951101,42815102
43356408
43356407
42176001
00156610
41563101
OTHER
Non-
guideline
870.7200
86-1
Hepatocyte Proliferation and
Apoptosis
Unscheduled DNA Synthesis
Determination of
Bioconcentration Factor -
Bluegill
Domestic Animal Safety
Phytotoxicity
A,B
A,B
A,B
A,B
A,B
44231801
00109456
00101635
Ace. 116879
Ace. 116917, 116918
52
-------
Appendix C. Technical Support Documents
Additional documentation in support of this RED is maintained in the OPP
docket, located in Room 119, Crystal Mall 2, 1801 S. Bell Street, Arlington, VA. It is
open Monday through Friday, excluding legal holidays, from 8:30 AM to 4:30 PM.
The nitrapyrin docket initially contained preliminary risk assessments and related
documents as of October 27, 2004. Sixty days later, the comment period closed. The
Agency considered the comments and added the formal "Response to Comments"
documents to the docket. All documents, in hard copy form, may be viewed in the OPP
docket room or downloaded or viewed via the Internet at the following website:
http://www.epa.gov/pesticides/reregistration/status.htm.
These documents include:
HED Documents:
Nitrapyrin: Revised HED Chapter of the Reregi strati on Eligibility Decision Document.
(Tadayon, Seyed, David Soderberg, and John Doherty. 3/1/2005)
- Nitrapyrin Chronic Dietary Exposure Assessment for the Reregi strati on
Eligibility Decision. (Soderberg, David 5/14/2004)
-Nitrapyrin. Reregi strati on Action. Corrected Summary of Analytical Chemistry
and Residue Data. (Soderberg, David 9/29/2004)
- Review of Nitrapyrin Incident Reports. (Blondell, Jerome and Monica S.
Hawkins 9/29/2004)
- Nitrapyrin: Second Revision of the Toxicology Chapter for the RED. (Doherty,
John. 2/24/2004)
- Reviews of a Number of Studies Submitted in Support of the Reregi strati on of
Nitrapyrin. (Soderberg, David 5/25/2004)
- Nitrapyrin - 1st Report of the Hazard Identification Assessment Review
Committee. (Doherty, John. 3/1/2004)
- Nitrapyrin: Team Review of Metabolism Information. (Soderberg, David, John
Doherty, and Seyed Tadayon. 2/23/2004)
- Nitrapyrin RED - Reregi strati on Eligibility Decision Product Chemistry
Considerations. (Soderberg, David. 2/19/2004)
53
-------
EFED Documents:
- Environmental Fate and Effects Division Revised Risk Assessment for the
Nitrapyrin Reregi strati on Eligibility Decision. (Hartless, Christine and Amer Al-
Mudallal. 3/1/2005)
- Drinking Water Assessment for Nitrapyrin and Its Major Degradate 6-
Chloropicolinic Acid (6-CPA). (Al-Mudallal, Amer, Pat Jennings, and Sid Abel.
4/14/2004.)
54
-------
Appendix D. Citations Considered to be Part of the Database Supporting the
Reregistration Eligibility Decision (Bibliography)
GUIDE TO APPENDIX D
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of
all studies considered relevant by EPA in arriving at 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. Selection
from other sources, including 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 a s single
studies.
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 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 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.
55
-------
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
document. When the date appears as (1999), 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.
56
-------
BIBLIOGRAPHY
MRID
CITATION
37519 Norris, J.M.; Plomer, E.; Bourne, J.E.; et al. (1971) Acute Toxico- logical Properties of Dowco
163. (Unpublished study received Apr 29, 1972 under 2F1265; submitted by Dow Chemical
U.S.A., Midland, Mich.; CDL:092163-J)
37870 Redemann, C.T. (1962) Residues from 2-Chloro-6-(trichloromethyl)- 14C-pyridine in Lettuce
and in Soil: GS 510. (Unpublished study received Jun 6, 1973 under 2F1265; submitted by
Dow Chemical U.S.A., Midland, Mich.; CDL:092164-D)
37872 Redemann, C.T. (1962) The Fate of 2-Chloro-6-(trichloromethyl)-14C- pyridine Applied to
Cotton under Greenhouse Conditions: GS 516. (Unpublished study received Jun 6, 1973 under
2F1265; submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092164-F)
37873 Redemann, C.T. (1961) Metabolism of 2-Chloro-6-trichloromethylpyridine by the Corn Plant:
GS-465. (Unpublished study received Jun 6, 1973 under 2F1265; submitted by Dow Chemical
U.S.A., Midland, Mich.; CDL:092164-G)
37875 Redemann, C.T. (1961) Metabolism of 2-Chloro-6-trichloromethyl-14C- pyridine in the Dog:
GS-459. (Unpublished study received Jun 6, 1973 under 2F1265; submitted by Dow Chemical
U.S.A., Midland, Mich.; CDL:092164-I)
37876 Redemann, C.T. (1962) Residues from 2-Chloro-6-(trichloromethyl)- 14C-pyridine in Oats: GS
520. (Unpublished study received Jun 6, 1973 under 2F1265; submitted by Dow Chemical
U.S.A., Midland, Mich.; CDL:092164-J)
37878 Meikle, R.W.; Williams, E.A.; Redemann, C.T. (1966) Residues from 2-Chloro-6-
trichloromethyl-14C-pyridine in Cotton Seed Grown in the Field: GS 755. (Unpublished study
received Jun 6, 1973 under 2F1265; submitted by Dow Chemical U.S.A., Midland, Mich.;
CDL:092164-L)
37881 Jensen, D.J.; Miller, P.W. (1973) Studies To Determine Possible Bound Residues of 6-
Chloropicolinic acid (6-CPA) in Wheat: GH-C 655. (Unpublished study received Jun 6, 1973
under 2F1265; submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092164-P)
37882 Miller, P.W. (1973) A Comparison of Retention Times of 6-Chloropicolinic acid and Some
Commonly Used Herbicides by Gas Chromatog- raphy: GH-C 649. (Unpublished study
received Jun 6, 1973 under 2F1265; submitted by Dow Chemical U.S.A., Midland, Mich.;
CDL: 092164-Q)
37885 Jensen, D.J. (1970) Determination of Residues of 6-Chloropicolinic acid in Milk by Gas
Chromatography. Method ACR 70.1 dated Jan 27, 1970. (Unpublished study received Jun 6,
1973 under 2F1265; submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092164-U)
37886 Swarm, R.L.; Ramsey, J.C., ed. (1972) Determination of Residues of 6-Chloropicolinic acid in
Plant and Animal Tissues. Method ACR 71.8R dated Mar 20, 1972. (Unpublished study
received Jun 6, 1973 under 2F1265; prepared in cooperation with International Research and
Development Corp., submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092164-V)
37887 Ramsey, J.C., ed. (1971) Determination of Residues of 6-Chloropico- linic acid in Corn,
Sorghum, Potatoes, and Sugar Beets by Gas Chromatography. Method ACR 71.9 dated Jun 24,
1971. (Unpub- lished study received Jun 6, 1973 under 2F1265; prepared in cooperation with
WARF Institute, Inc., submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092164-W)
37888 Ramsey, J.C.; Jensen, D.J. (1971) Gas Chromatographic Method for the Determination of 6-
Chloropicolinic acid Residues in Eggs. Method ACR 71.15 dated Aug 23, 1971. (Unpublished
57
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study re- ceived Jun 6, 1973 under 2F1265; submitted by Dow Chemical U.S.A., Midland,
Mich.; CDL:092164-X)
38480 Ramsey, J.C.; Rose, J.Q.; Braun, W.H.; et al. (1973) Fate of 6- Chloropicolinic acid following
Oral Administration in Rats. (Unpublished study received Jun 6, 1973 under 2F1265; submitted
by Dow Chemical U.S.A., Midland, Mich.; CDL:092164-O)
39619 Ramsey, J.C.; Jensen, D.J.; Getzendaner, M.E.; et al. (1971) Residues of 6-Chloropicolinic acid
in Sorghum and Sugar Beets|. (Unpublished study including GH-C 469 and GH-C 471,
received Apr 29, 1972 under 2F1265; submitted by Dow Chemical U.S.A., Midland, Mich.;
CDL:092162-E)
39620 Ramsey, J.C.; Jensen, D.J.; Getzendaner, M.E.; et al. (1971) Wheat. Summary of studies
092162-C, 092162-M and 092162-P. (Unpublished study including GH-C 468, received Apr
29, 1972 under 2F1265; prepared in cooperation with Univ. of Idaho, Dept. of Plant Science
and Farmland Industries, submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092162-
F)
39624 Swann, R.L.; Ramsey, J.C., ed. (1971) Determination of Residues of 6-Chloropicolinic acid in
Plant and Animal Tissues. Method ACR 71.8 dated Jun 7, 1971. (Unpublished study received
Apr 29, 1972 under 2F1265; prepared in cooperation with International Research and
Development Corp., submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092162-M)
39625 Ramsey, J.C., ed. (1971) Gas Chromatographic Method for the Determination of 6-
Chloropicolinic acid Residues in Wheat. Method ACR 71.7 dated Jun 7, 1971. (Unpublished
study received Apr 29, 1972 under 2F1265; prepared in cooperation with WARF Institute, Inc.,
submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092162-P)
40046 Ramsey, J.C. (1971) Residue Studies of 2-Chloro-6-(trichlorome- thyl) pyridine in Corn Stover,
Sorghum Stover, and Wheat Forage from Fields Treated with N-serveA(R)124 Nitrogen
Stabilizer. Includes method dated Dec 20, 1971. (Unpublished study received Apr 29, 1972
under 2F1265; submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092162-Q)
40048 Kutschinski, A.H.; Turner, G.O.; Watson, A. J.; et al. (1964) De- termination of 6-
Chloropicolinic acid Residues in Silage Corn, Sweet Corn Kernels and Field Corn Grain Grown
on Soil Treated with N-serve. (Unpublished study received Apr 29, 1972 under 2F1265;
prepared in cooperation with Purdue Univ., submitted by Dow Chemical U.S.A., Midland,
Mich.; CDL:092162-S)
40049 Dow Chemical Company (1964) Gas Chromatographic Method for the Determination of 6-
Chlorpicolinic acid Residues in Silage Corn, Milk-Stage Kernels, and Field Corn Grain.
Method ACR 64.1 dated Feb 19, 1964. (Unpublished study received Apr 29, 1972 under
2F1265; CDL:092162-T)
40050 Ramsey, J.C.; Jenson, D.J.; Getzendaner, M.E.; et al. (1971) Res- idue Studies of Corn Grain
and Stover from Fields Treated with N-serveA(R)I Nitrogen Stabilizer. (Unpublished study
received Apr 29, 1972 under 2F1265; prepared in cooperation with Ridge- town Technical
College, submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092162-U)
40054 Gentry, W.M.; Bucek, O.C.; Swart, R.W. (1971) Determination of 6-Chloropicolinic acid in
Tissues of Beef Calves Given 6-Chloropicolinic acid in the Feed. (Unpublished study received
Apr 29, 1972 under 2F1265; submitted by Dow Chemical U.S.A., Midland, Mich.;
CDL:092162-Y)
40055 Ramsey, J.C.; Jenson, D.J.; Getzendaner, M.E. (1971) A Residue Study in Swine Tissues from
Swine Fed 6-Chloropicolinic acid. (Unpublished study received Apr 29, 1972 under 2F1265;
submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:092162-Z)
40056 Jensen, D.J. (1971) Assay for residues in milk and cream from cows fed 6-Chloropicolinic acid.
58
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Journal of Agricultural and Food Chemistry 19(5):897-899. (Also~In~unpublished submission
re- ceived Apr 29, 1972 under 2F1265; submitted by Dow Chemical U.S.A., Midland, Mich.;
CDL:092162-AA)
40057 Ramsey, J.C.; Jensen, D.J.; Getzendaner, M.E. (1971) A Residue Study in Chicken Tissues and
Eggs from Chickens Fed 6-Chloropicolinic acid. (Unpublished study received Apr 29, 1972
under 2F1265; submitted by Dow Chemical U.S.A., Midland, Mich.; CDL: 092162-AB)
42005 Parisot, T. J. (1968) Letter sent to E.E. Kenaga dated Sep 27, 1968. Toxicity data of Torgon and
other herbicides onfish|. (U.S. Fish and Wildlife Service, Fish Pesticide Research Laboratory,
unpublished study; CDL:094930-N)
52343 Iwata, Y.; Dinoff, T.M.; Bailey, J.B.; et al. (1979) Determination of Nitrapyrin and 6-
Chloropicolinic acid in Strawberry Fruit and Soil Resulting from a Preplant Soil Application of
N-ServeA(R)I. (Unpublished study received Jun 24, 1980 under 464-432; prepared by Univ. of
California-Riverside, Dept. of Entomology, submitted by Dow Chemical U.S.A., Midland,
Mich.; CDL:099484-D)
52964 Jensen, D.J.; Barringer, V.D.; Bjerke, E.L.; et al. (1978) Determination of 6-Chloropicolinic
acid in Corn, Rice and Cottonseed. Method ACR 77.16 dated Feb 17, 1978. (Unpublished study
received Sep 4, 1980 under 464-432; prepared in cooperation with WARF Institute, Inc.,
submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:099615-M)
74042 Butler, P.A.; Lowe, J.I. (1964) Quarterly Program Progress Report: Effect of Pesticides. (U.S.
Fish and Wildlife Service, Bureau of Commercial Fisheries, Biological Laboratory;
unpublished study; CDL:128498-D)
76728 Getzendaner, M.E.; Daun, R.J. (1968) A Residue Study of 6-Chloropicolinic Acid in or on
Cottonseed from the Use of N-serveA(TM)I 24 Nitrogen Stabilizer. (Unpublished study
received Jun 2, 1981 under 464-432; prepared in cooperation with Wisconsin Alumni Research
Foundation, submitted by Dow Chemical U.S.A., Midland, Mich.; CDL:245291-A)
79381 Hamaker, J.W. (1967) The Sorption of 6-Chloropicolinic Acid by Soils. (Unpublished study
received Jul 30, 1981 under 464-432; submitted by Dow Chemical U.S.A., Midland, Mich.;
CDL:245682-E)
79565 Fink, R.; Beavers, J.B. Brown, R. (1980) Final Report-Eight- Day Dietary LCI50A~Bobwhite
Quail: Project No. 103-201. (Un- published study received Nov 26, 1980 under 464-432;
prepared by Wildlife International, Ltd. and Washington College, submitted by Dow Chemical
U.S.A., Midland, Mich.; CDL:099792-A)
88727 Redemann, C.T. (1961) Metabolism of 2-Chloro-6-trichloromethyl- CA14I-pyridine by the
Tomato Plant. (Unpublished study received Mar 2, 1963 under PP0408; submitted by Dow
Chemical Co., Indianapolis, Ind.; CDL:090440-J)
88737 Dow Chemical Company (1963) Studies of Residues from Various Chemicals in Cottonseed).
(Compilation; unpublished study received Mar 2, 1963 under PP0408; CDL:090440-AA)
101635 Bidlack, H. (1982) Determination of the Bioconcentration Factor for Nitrapyrin 2-Chloro-6-
(trichloromethyl)pyridine| in Blue-gill Sunfish during Continuous Aqueous Exposure: GH-C
1531. (Unpublished study received May 19, 1982 under 464-432; submitted by Dow Chemical
U.S.A., Midland, MI; CDL:247521-A)
104957 Meikle, R.; Griffith, J. (1976) Application of the Ames Test for Mutagenesis to Nitrapyrin: GS-
1451. (Unpublished study received Jun 17, 1977 under7F1970; prepared by Plant Science
Research, submitted by Dow Chemical Co., Indianapolis, IN; CDL:096187-C)
109456 Mendrala, A.; Schumann, A. (1982) N-Serve TG ...: Evaluation of N-Serve TG in the Rat
Hepatocyte Unscheduled DNA Synthesis Assay. (Unpublished study received Jul 26, 1982
under 464-432; submitted by Dow Chemical U.S.A., Midland, MI; CDL:071017-D)
59
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109457 Dow Chemical U.S.A. (1982) Results of Tests on the Amount of Residue Remaining, Including
a Description of the Analytical Method: 6-Chloropicolinic Acid and Nitrapyrin. (Compilation;
unpublished study received Jul 26, 1982 under 464-432; CDL: 071017-E)
110294 McCall, P.; Swann, R. (1978) Nitrapyrin volatility from soil. Down to Earth 34(3):21-27. (Also
In unpublished submission received Jun 2, 1978 under 464-432; submitted by Dow Chemical
U.S.A., Midland, MI; CDL:234113-B)
110295 McCarthy, W. (1977) Toxicity of 6-Chloropicolinic Acid to Daphnids: Laboratory Report Code
ES-173. (Unpublished study received Aug 1, 1978 under 464-432; submitted by Dow Chemical
U.S.A., Midland, MI; CDL:234605-A)
110296 Fink, R.; Beavers, I; Grimes, I; et al. (1978) Final Report: Acute Oral LD50~Mallard Duck:
Nitrapyrin|: Project No. 103-185. (Unpublished study received Jun 21, 1979 under 464-432;
prepared by Wildlife International Ltd., submitted by Dow Chemical U.S.A., Midland, MI;
CDL:238687-A)
110297 McCarty, W. (1978) Toxicity of Nitrapyrin to Rainbow Trout and Bluegill: ES-248.
(Unpublished study received Jun 21, 1979 under 464-430; submitted by Dow Chemical U.S.A.,
Midland, MI; CDL:238687-B)
110298 McCarty, W. (1977) Toxicity of Nitrapyrin to Daphnids: Laboratory Report Code ES-182.
(Unpublished study received Jun 21, 1979 under 464-432; submitted by Dow Chemical U.S.A.,
Midland, MI; CDL:238687-C)
110311 Dow Chemical U.S.A. (1977) The Results of Tests on the Amount of Residues Remaining
Including a Description of the Analytical Methods. (Compilation; unpublished study received
Jun 17, 1977 under 464-433; CDL:096193-A)
110314 Dow Chemical U.S.A. (1979) Residues of 6-Chloropicolinic Acid in or on Cottonseed|.
(Compilation; unpublished study received Jun 21, 1979 under 464-432; CDL:098329-A)
110318 Jensen, D.; Bjerke, E. (1978) A Residue Study: 6-Chloropicolinic Acid in Corn from Fields
Receiving Sidedress Treatments of N- Serve Nitrogen Stabilizer: GH-C 1108. (Unpublished
study re- ceived Jul 12, 1978 under 464-432; submitted by Dow Chemical U.S.A., Midland,
MI; CDL:097381-A)
116879 Stevenson, G. (1968) An Acute Single Dose LD50 Toxicity Study of N-Serve in Turkey Poults
and White Legohorn Cockerel Chicks (Unpublished study; submitted by Dow Chemical Co.,
Midland, MI; 10 p.)
116894 Winston, A. (1961) Letter sent to G. Lynn dated Sep 26, 1961: K-31304 ... toxicity to four
species offish. (Unpublished study received Apr 29, 1972 under 2F1265; submitted by Dow
Chemical Co., Indianapolis, IN; CDL:092161-C)
116895 Batchelder, T.; Mullison, W. (1971) Acute Fish Toxicity of N-serve Formulations and 6-
Chloropicolinic Acid to Three Species of Fish. Rev. (Unpublished study received Apr 29, 1972
under 2F1265; submitted by Dow Chemical Co., Indianapolis, IN; CDL: 092161-D)
116898 Stevenson, G. (1967) An Acute Dietary Feeding Test with N-serve and 6-Chloro Picolinic Acid
in Bobwhite Quail~a Pilot Study: GH-A 348. (Unpublished study received Apr 29, 1972 under
2F1265; submitted by Dow Chemical Co., Indianapolis, IN; CDL:092161-H)
116899 Stevenson, G.; Palm, B.; Lapham, K. (1968) A Game Bird Toxicology Study-Acute Dietary
Feeding of N-serve and 6-Chloropicolinic Acid to Japanese Quail: GH-A 375. (Unpublished
study received Apr 29, 1972 under 2F1265; submitted by Dow Chemical Co., Indianapolis, IN;
CDL:092161-I)
116901 Redemann, C.; Williams, E.; Clark, H.; et al. (1966) The excretion of N-(6-chloropicolinoyl)-
glycine by the dog fed 2-chloro-6- (trichloromethyl) pyridine. Agricultural and Food Chemistry
60
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14 (5):530-532. (Also In unpublished submission received Apr 29, 1972 under 2F1265;
submitted by Dow Chemical Co., Indianapolis, IN; CDL:092161-L)
116902 Redemann, C.; Clark, H. (1967) Fate of 2-chloro-6-(trichloromethyl) pyridine in the rat.
Agricultural and Food Chemistry 15(6): 1127-1128. (Also In unpublished submission received
Apr 29, 1972 under 2F1265; submitted by Dow Chemical Co., Indianapolis, IN; CDL:092161-
M)
116907 Meikle, R.; Austin, S.; Turner, G. (1968) Crop Uptake and Soil Residues from 6-
Chloropicolinic Acid Applied to Field Soil: GS 914. (Unpublished study received Apr 29, 1972
under 2F1265; submitted by Dow Chemical Co., Indianapolis, IN; CDL:092161-S)
116917 Geronimo, I; Smith, L.; Stockdale, G.; et al. (1971) Comparative Phytotoxicity of 2-Chloro-6-
(trichloromethyl)pyridine and Its Principal Metabolite, 6-Chloropicolinic Acid: GS-1170.
(Unpublished study received Apr 29, 1972 under 2F1265; submitted by Dow Chemical Co.,
Indianapolis, IN; CDL:092161-AD)
116918 Goring, C.; Youngson, C. (1968) The Comparative Phytotoxicity of N-serve and Several
Commercial Herbicides to Various Plants: GS 916. (Unpublished study received Apr 29, 1972
under 2F1265; submitted by Dow Chemical Co., Indianapolis, IN; CDL:092161-AE)
116919 Youngson, C. (1969) A Study of the Accumulation of 6-Chloropicolinic Acid by Aquatic Food
Chain Organisms: GS 985. (Unpublished study received Apr 29, 1972 under 2F1265; submitted
by Dow Chemical Co., Indianapolis, IN; CDL:092161-AF)
117010 Regoli, A.; Kurihara, N.; Laskowski, D. (1974) Soil Degradation of 14C-Nitrapyrin, the Active
Ingredient of N-serve Nitrogen Stabilizer. (Unpublished study received Mar 1, 1974 under 464-
322; submitted by Dow Chemical U.S.A., Midland, MI; CDL: 092166-A)
117016 Fink, R. (1974) Eight-day Dietary LC50~Mallard Ducks: 6-Chloro- 2-picolinic Acid: Project
No. 103-108. Final rept. (Unpublished study received Mar 1, 1974 under 464-322; prepared by
Truslow Farms, Inc., submitted by Dow Chemical U.S.A., Midland, MI; CDL:092166-H)
117998 Oliver, G.; Swann, R.; Hertel, J. (1982) Anaerobic Soil Degradation of Nitrapyrin: GH-C 1585.
(Unpublished study received Nov 9, 1982 under 464-432; submitted by Dow Chemical U.S.A.,
Midland, MI; CDL:248798-A)
118934 Fink, R. (1974) Eight-day Dietary LC50~Mallard Ducks: Nitrapyrin: Project No. 103-107.
Final rept. (Unpublished study received Mar 1, 1974 under 464-322; prepared by Truslow
Farms, Inc., submitted by Dow Chemical U.S.A., Midland, MI; CDL:092166-G)
129370 Batchelder, T. (1967) Acute Fish Toxicity of Tricyclohexyltin Hydroxide and N-Serve
Formulations to Three Species of Fish. (Unpublished study received May 11, 1983 under 464-
393; submitted by Dow Chemical U.S.A., Midland, MI; CDL:250328-A)
151627 Kennelly, J. (1985) Study To Determine the Ability of Nitrapyrin To Induce Mutation in Four
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Unpublished study prepared by Microtest Research Limited. 39 p.
151628 Kirkland,D. (1985) Nitrapyrin: Micronucleus Test in Mice: Study No. DCE3/MNT/AR/KF11.
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153543 Berdasco, N.; Lomax, L.; Hanley, T. (1985) Nitrapyrin: Oral Teratology in New Zealand White
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156504 Dow Chemical USA (1986) Product Identity and Composition [of Nitrapyrin Including
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156505 Dow Chemical USA (1986) General Provisions for Physical and Chemical Characteristics
61
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Testing [of Nitrapyrin]. Unpublished study. 4 p.
156610 Bauriedel, W.; Miller, J. (1982) Uptake and Identity of Residues in Replacement Crops Planted
30 Days after the Soil Incorporation of [Carbon-14]-Labeled Nitrapyrin: GH-C 1498.
Unpublished study Prepared by Dow Chemical U.S.A. 23 p.
158901 Nitschke, K.; Schuetz, D.; Johnson, K. (1986) N-Serve Nitrogen Stabilizer: An Acute LC50
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158902 Carreon, R. (1986) 2-Chloro-6-(trichloromethyl)pyridine: Primary Eye Irritation Study in New
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158903 Carreon, R. (1986) 2-Chloro-6-(trichloromethyl)pyridine: Dermal Sensitization Potential in the
Guinea Pig: HET K031304-016C. Unpublished study prepared by Dow Chemical U.S.A. 10 p.
158904 Carreon, R.; Battjes, J.; Zimmer, M. (1986) 2-Chloro-6-(trichloro-methyl)pyridine: Acute
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163217 Szabo, J.; Rachunek, B.; Mensik, D.; et al. (1986) Nitrapyrin (N- Serve): 13-Week Dietary
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163516 Dow Chemical U.S.A. (1986) Product Chemistry: N-Serve TG Nitrogen Stabilizer.
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163792 Berdasco, N.; Wolfe, E.; Zimmer, M.; et al. (1986) Nitrapyrin: Oral Teratology Study in
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163805 Linscombe, V.; Gollapudi, B. (1986) Evaluation of Nitrapyrin in the Chinese Hamster Ovary
Cell/Hypoxanthine-guanine-phosphoribosyl Transferase (CHO/HGPRT) Forward Mutation
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40099501 Hemmer, N.; Wichman, K. (1987) Nitrapyrin: Physical and Chemical Characteristics.
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40305501 Timchalk, C.; Dryzga, M.; Cambell, R. (1987) The Metabolism and Tissue Distribution of
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40339301 Zimmer, M.; Eisenbrandt, D.; Cieszlak, F.; et al. (1987) 6-Chloropicolinic Acid: 2-Year Dietary
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40339402 Stafford, L. (1987) The Metabolism of [Carbon 14] Labeled Nitrapyrin in Laying Hens: Dow
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40339403 Stafford, L. (1987) The Metabolism of [Carbon 14] Labeled Nitrapyrin in Lactating Goats:
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40363802 Bjerke, E.; Martin, M. (1987) Residues of Nitrapyrin, 2-chloro-6- (Dichloromethyl) Pyridine
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40363803 Bjerke, E. (1987) A Residue Study of Nitrapyrin, 2-chloro-6-(Dichloromethyl)Pyridine and 6-
62
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chloropicolinic Acid in Sorghum: Project ID: GH-C 1947. Unpublished study prepared by Dow
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40370401 Stafford, L.; Miller, I; Lardie, T. (1987) Metabolism of [Carbon 14] Labeled Nitrapyrin in
Field Corn following at Plant Application at a Rate of 1.0 LB AI/Acre with Solid Fertilizer:
Dow Lab. Project ID: GH-C 1949. Unpublished study prepared by Dow Chemical U.S.A. 50 p.
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40407202 Bjerke, E.; Martin, M.; McGee, G. (1987) Stability of Nitrapyrin, 2-Chloro-6-
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Project ID: GHC-1961. Unpublished study prepared by Dow Chemical U.S.A. 24 p.
40407203 Bjerke, E. (1982) Residues of 6-Chloropicolinic Acid and Ntrapyrin in Wheat from Fields
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40515301 Bjerke, E. (1979) Determination of Nitrapyrin in Potatoes and Sorghum; Rice Green Forage
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40515302 Peterson, J.; Carpenter, M. (1988) Determination of the Hydrolysis Rate of Carbon]-Nitrapyrin:
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40515303 Peterson, J.; Carpenter, M. (1988) Determination of the Photolysis Rate of Carbon]-Nitrapyrin
inpH-7 Buffer: Project ID: GHC-2001. Unpublished study prepared by Dow Chemical U.S.A.
and Analytical Biochemistry Laboratories, Inc. 71 p.
40572301 Bjerke, E.; Martin, M.; VanDyke, M. (1988) A Residue Study of Ni- trapyrin, 2-Chloro-6-
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Unpublished study prepared by Dow Chemical U.S.A. 36 p.
40952701 Zempel, J.; Mensik, D.; Szabo, J. (1988) Nitrapyrin (N-Serve TG): Results of a Two-
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40968601 Bjerke, E. (1989) Stability of Nitrapyrin and 2-Chloro-6-(dichloro-methyl)pyridine in Sweet
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41345401 Barna-Lloyd, T.; Szabo, J.; Rachunek, B. (1989) Nitrapyrin: Chronic (One-Year) Dietary
Toxicity Study in Dogs: Lab Project Number: K-031304-029. Unpublished study prepared by
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41345403 Szabo, J.; Landenberger, B.; Rachunek, R. (1989) Nitrapyrin (N- Serve): Two Year Chronic
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41461103 Bjerke, E. (1990) Stability of 6-Chloropicolinic Acid in Wheat Straw Stored Frozen: Lab
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63
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41563102 Davies, C.; Karris, G.; McDonald, R.; et al. (1980) Physical Property Data for 2,3,5,6,-
Tetrachloropyridine (Sym-Tet), 6-Chloro-2-trichloromethylpyridine (N-SERVE) and 5,6-
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41563104 Kroposki, L. (1977) Technical Grade N-Serve: Stability Studies: Lab Project Number: GP
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41563106 Swann, R.; Laskowski, D.; McCall, K.; etal. (1983) A rapid method for estimation of the
environmental parameters octanol/water partition coefficient, soil sorption constant, water to air
ratio and water solubility. Residue Reviews 85(1983): 17-28.
41651601 Quast, I; Cosse, P.; Corley, R. (1990) Nitrapyrin (N-Serve): Two-Year Dietary Oncogenicity
Study in B6C3F1 Mice: Lab Project Number: K-031304-027. Unpublished study prepared by
The Dow Chemical Co. 812 p.
41951101 Bjerke, E.; McNett, D. (1991) A Residue Study of Nitrapyrin, 2- Chloro-6-(Dichloromethyl)
Pyridine and 6-Chloropicolinic Acid in Corn Process Fractions: Lab Project Number: GH-C
2504: 88061: 88061AN. Unpublished study prepared by DowElanco. 49 p.
42050101 Berdasco, N.; Wolfe, E.; Zimmer, M.; et al. (1986) Nitrapyrin: Oral Teratology Probe Study in
Fischer 344 Rats: Lab Project Number: HET-K-031304-014. Unpublished study prepared by
The Dow Chemical Co. 23 p.
42077601 Weinberg, I; Gorzinski, S.; Richardson,; C.; et al. (1991) Nitrapyrin (Nitrogen Stabilizer):
Evaluation of the Acute Toxicity to the Bluegill, Lepomis macrochirus: Lab Project Number:
ES-DR- 0114-1340-6. Unpublished study prepared by The Environmental Toxicology &
Chemistry Research Laboratory. 26 p.
42077602 Weinberg, I; Gorzinski, S.; Richardson, C.; et al. (1991) Nitrapyrin (Nitrogen Stabilizer):
Evaluation of the Acute Toxicity to the Rainbow Trout, Oncorhynchus mykiss Walbaum: Lab
Project Number: ES-DR-0114-1340-7. Unpublished study prepared by The Environmental
Toxicological & Chemistry Research Laboratory. 26 p.
42077603 Weinberg, I; Milazzo, D.; Servinski, M.; et al. (1991) Nitrapyrin (Nitrogen Stabilizer):
Evaluation of the Acute Toxicity to the Daphnid, Daphnia magna Straus: Lab Project Number:
ES-DR-0114-1340-8. Unpublished study prepared by The Environmental Toxicology &
Chemistry Research Laboratory. 26 p.
42077604 Ward, G. (1991) Nitrapyrin Acute Toxicity to the Tidewater Silver- side, Mendia beryllina
Under Flow-Through Test Conditions: Lab Project Number: J9010006B. Unpublished study
prepared by Toxik- on Environmental Sciences. 25 p.
42077605 Ward, G.; Ward, S. (1991) Nitrapyrin: Acute Toxicity to the Eastern Oyster, Crassostrea
virginca, Under Flow-Through Conditions: Lab Project Number: J9010006D. Unpublished
study prepared by Toxikon Environmental Sciences. 27 p.
42077606 Ward, G. (1991) Nitrapyrin: Acute Toxicity to the Grass Shrimp, Palaemonetes pugio, Under
Flow-Through Conditions: Lab Project Number: J9010006C. Unpublished study prepared by
Toxikon Enviromental Sciences. 25 p.
42176001 Bjerke, E.; Lafever, D.; Willett, S. (1990) A Residue Study of Nitrapyrin, 2-Chloro-6-
(Dichloromethyl) Pyridine and 6-Chloropicolinic Acid in Wheat Process Fractions: Lab Project
Number: GH-C 2376. Unpublished study prepared by DowElanco. 29 p.
42229201 Bjerke, E.; McNett, D. (1991) A Residue Study of 6-Chloropicolinic Acid in Wheat Grain: Lab
Project Number: 86011. Unpublished study prepared by DowElanco. 30 p.
42239301 Cosse, P.; Stebbins, K.; Stewart, H. (1992) Nitrapyrin: Probe and 21-Day Repeated Dose
Dermal Toxicity Study in New Zealand White Rabbits: Lab Project Number: K-031304-031.
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Unpublished study prepared by Dow Chemical Co. 174 p.
42740101 Bjerke, E. (1992) Reregistration of Nitrapyrin-Information Requested in EPA Response of
September 16, 1992 to the Registration Standard Update: Lab Project Number: ELB041693.
Unpublished study prepared by DowElanco. 7 p.
42740102 Bjerke, E. (1992) Determination of 6-Chloropicolinic Acid in Corn, Rice and Cottonseed: Lab
Project Number: ELB041693.1. Unpublished study prepared by DowElanco. 10 p.
42740103 Bjerke, E. (1992) Determination of Nitrapyrin in Corn Forage, Corn Fodder, Wheat Forage, and
Wheat Straw: Lab Project Number: ELB041693.2. Unpublished study prepared by DowElanco.
lip.
42740104 Bjerke, E. (1992) Determination of Nitrapyrin in Corn Oil: Lab Project Number: ELB041693.3.
Unpublished study prepared by DowElanco. 8 p.
42776601 Bargar, E., Bjerke, E. (1993) Frozen Storage Stability of 6-Chloropicolinic Acid in Corn Oil
Stored Frozen: Lab Project Number: 90067. Unpublished study prepared by North American
Environmental Chemistry Lab. 16 p.
42795901 Bargar, E.; Bjerke, E. (1993) Stability of 6-Chloropicolinic Acid in Wheat Grain Stored Frozen:
Supplemental Data to GH-C 1961, MRID #40407202: Lab Project Number: GH-C 2958.
Unpublished study prepared by North American Environmental Chemistry Lab. 16 p.
42815101 Bjerke, E. (1992) Validation of Method ACR 77.16 Using Field Corn Samples from (carbon
14) Metabolism Study: Nitrapyrin: Lab Project Number: RES92089: ACR 77.16. Unpublished
study prepared by DowElanco. 20 p.
42815102 Bjerke, E.; Schotts, B. (1992) Validation of Use of Toluene in Method ACR 79.6.S2 for
Determining Residue of Nitrapyrin and Reanalysis of Corn Oil Samples for Nitrapyrin: Lab
Project Number: RES92019: ACR 79.6.S2. Unpublished study prepared by DowElanco. 23 p.
43026201 Boeri, R.; Magazu, I; Ward, T. (1993) Nitrapyrin: Acute Flow-Through Mollusc Shell
Deposition Test: Lab Project Number: 326/DO: ES/2685. Unpublished study prepared by T. R.
Wilbury Labs, Inc. 25 p.
43210301 Schroeder, R. (1994) A Range-Finding Study to Evaluate the Developmental Toxicity of
Nitrapyrin in the Rat: Lab Project Number: 93-4049: TSN-100172. Unpublished study prepared
by Pharmaco LSR, Inc. 192 p.
43210302 Schroeder, R. (1994) A Developmental Toxicity Study in Rats with Nitrapyrin: Lab Project
Number: 93-4050: TSN-100172: 414. Unpublished study prepared by Pharmaco LSR, Inc. 485
P-
43356401 Jensen, D. (1970) Determination of Residues of 6-Chloropicolinic Acid in Cream by Gas
Chromatography: Lab Project Number: ACR 70.2. Unpublished study prepared by DowElanco.
13 p.
43 3 56402 Swann, R. (1972) Determination of Residues of 6-Chloropicolinic Acid in Plant and Animal
Tissues: Lab Project Number: ACR 71.8R. Unpublished study prepared by DowElanco. 16 p.
43356403 Sulaiman, M. (1994) Second Party Method Validation: Determination of Residues of 6-
Chloropicolinic Acid in Animal Tissues by Gas Chromatography with Electron Capture
Detection: Lab Project Number: RES94106: 379C-109. Unpublished study prepared by
Wildlife International Ltd. 35 p.
43356404 Sulaiman, M. (1994) Second Party Method Validation: Determination of Residues of 6-
Chloropicolinic Acid in Milk and Cream by Gas Chromatography with Electron Capture
Detection: Lab Project Number: RES94107: 379C-108. Unpublished study prepared by
Wildlife International Ltd. 22 p.
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43356405 Olberding, E.; Foster, D. (1994) Determination of Residues of 6-Chloropyridine-2-Carboxylic
Acid in Sorghum Grain, Flour, and Starch by Capillary Gas Chromatography with Mass
Selective Detection: Lab Project Number: RES94040. Unpublished study prepared by
DowElanco North American Environmental Chemistry Lab. 45 p.
43356406 Olberding, E.; Foster, D. (1994) Determination of Residues of 6-Chloropyridine-2-Carboxylic
Acid in Sweet Corn and Processed Products by Capillary Gas Chromatography with Mass
Selective Detection: Lab Project Number: RES94039. Unpublished study prepared by
DowElanco North American Environmental Chemistry Lab. 49 p.
43356407 Schwake, I; Foster, D.; Olberding, E. (1994) Magnitude of the Residue of Nitrapyrin and its
Metabolite in Sorghum Processed Commodities: Lab Project Number: RES93027. Unpublished
study prepared by DowElanco and Texas A&M University. 142 p.
43356408 Schwake, I; Foster, D.; Olberding, E. (1994) Magnitude of the Residue of Nitrapyrin and its
Metabolite in Sweet Corn Processed Commodities: Lab Project Number: RES93028.
Unpublished study prepared by DowElanco. 120 p.
43512101 Hosteller, K.; Markley, B. (1995) Determination of Nitrapyrin (Pyridine: 2-Chloro-6-
(Trichloromethyl)-) in Bovine Tissues (Beef Liver, Beef Kidney, Beef Muscle, Beef Fat) and
Whole Eggs, Whole Milk, and Cream Using Gas Chromatography with NI-63 Electron Capture
Detection (GC/ECD): Lab Project Number: RES94139: 379C-107. Unpublished study prepared
by Wildlife International Ltd. 35 p.
43781501 Sorenson, B. (1995) External Validation of a Method for Determination of Nitrapyrin in Beef
Tissues (Muscle, Liver, Kidney, and Fat), Milk, Cream, and Chicken Eggs Using Gas
Chromatography with Electron Capture Detection: Lab Project Number: RES94118: QMAS
94032: GRM94.08. Unpublished study prepared by Quality Management & Analytical
Services, Inc. 57 p.
43810601 Sorenson, B. (1995) Determination of Nitrapyrin in Beef Tissues (Muscle, Liver, Kidney, and
Fat), Milk, Cream, and Chicken Eggs Using Gas Chromatography with Electron Capture
Detection: Lab Project Number: RES94118: GRM 94.08. Unpublished study prepared by
Wildlife International Ltd. 46 p.
43 849001 McKellar, R. (1995) Determination of the Frozen Storage Stability of 6-Chloropicolinic Acid in
Field Corn Grain, Forage, and Fodder: Lab Project Number: RES92065. Unpublished study
prepared by DowElanco North American Environmental Chemistry Lab. 63 p.
43849002 Atkin, L. (1995) Frozen Storage Stability Study of 6-Chloropicolinic Acid in Field Processed
Fractions: Lab Project Number: RES92094. Unpublished study prepared by DowElanco North
American Environmental Chemistry Lab. 80 p.
43843003 Atkin, L. (1995) Frozen Storage Stability Study of Nitrapyrin in Field Corn Process Fractions,
Sweet Corn, Sorghum, and Wheat: Lab Project Number: RES92110. Unpublished study
prepared by DowElanco North American Environmental Chemistry Lab. 152 p.
44231801 Yano, B.; McFadden, L. (1996) Nitrapyrin (N-Serve Nitrogen Stabilizer): Quantitation of
Hepatocyte Proliferation and Apoptosis in a 2-Week Dietary Toxicity Study in B6C3F1 Mice--
A Retrospective Study: Lab Project Number: K-031304-038. Unpublished study prepared by
The Dow Chemical Co. 22 p.
44231802 Daly, I. (1995) A Subchronic (3-Month) Oral Toxicity Study of Nitrapyrin in the Mouse via
Dietary Administration: Final Report: Lab Project Number: K-031304-034: 93-2278.
Unpublished study prepared by Pharmaco LSR, Inc. 536 p.
44231803 Stebbins, K.; Cosse, P. (1997) Nitrapyrin (N-Serve Nitrogen Stabilizer): Two-Year Dietary
Oncogenicity Study inB6C3Fl Mice: (Final Report): Lab Project Number: K-031304-036.
Unpublished study prepared by The Dow Chemical Co. 946 p. (Relates to L0000134).
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44282501 Domoradzki, J.; Gibson, K. (1997) Nitrapyrin: Dermal Absorption of (carbon-14)-Nitrapyrin in
Male Fischer 344 Rats: Lab Project Number: HET K-031304-039: 17706. Unpublished study
prepared by The Dow Chemical Co. 41 p.
44679301 Domoradzki, J.; Brzak, K. (1998) Nitrapyrin: Metabolism and Tissue Distribution of 14C-
Labeled Nitrapyrin in B6C3F1 Mice: Lab Project Number: 971119. Unpublished study
prepared by The Dow Chemical Company. 56 p. {OPPTS 870.7485}
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Appendix E. Generic Data Call-In
The Generic Data Call-In will be posted at a later date. See Chapter V of the nitrapyrin RED for a list of studies required.
68
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Appendix F. Product Specific Data Call-In
The product specific Data Call-In will be posted at a later date
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Appendix G. EPA's Batching of Nitrapyrin Products for Meeting Acute Toxicity
Data Requirements for Reregistration
EPA'S BATCHING OF NITRAPYRIN 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 reregi strati on of products containing Nitrapyrin
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. Notwithstanding 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.
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
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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.
Four products were found which contain Nitrapyrin as the active ingredient.
These products have been placed into 1 batch and a "No Batch" category in accordance
with the active and inert ingredients and type of formulation.
No Batch: Each product in this Batch should have its own data generated.
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.
Batch 1
EPA Reg. No.
34704-804
62719-19
62719-20
% Active Ingredient
22.0
21.9
22.2
No Batch
EPA Reg. No.
62719-21
% Active Ingredient
90.0
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Appendix H. List of Registrants Sent This Data Call-In
A list of registrants sent this Data Call-In will be posted at a later date.
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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/opprd001/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 address below for the Document
Processing Desk.
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 atwilliams.nicole@epa.gov.
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
Application for Pesticide
Registration/ 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
http://www.epa.gov/opprd001/forms/8570-
l.pdf
htt^Jlw^v^&^a^^v/OQT^rdOO^/forms/SSTO^
4.pdf
http://www.epa.gov/opprd001/forms/8570-
5.pdf
http://www.epa.gov/opprdOO 1 /form s/8 5 70-
17.pdf
http://www.epa.gov/opprdOO 1 /form s/8 5 70-
25.pdf
http://www.epa.gov/opprd001/forms/8570-
27.pdf
73
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8570-28
8570-30
8570-32
8570-34
8570-35
8570-36
8570-37
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 (PR Notice 98-5)
Data Matrix (PR Notice 98-5)
Summary of the Physical/Chemical
Properties (PR Notice 98-1)
Self-Certification Statement for the
Physical/Chemical Properties (PR
Notice 98-1)
http://www.epa.gov/opprd001/forms/8570-
28.pdf
http://www.epa.gov/opprdOO 1 /form s/8 5 70-
30.pdf
http://www.epa.gov/opprd001/forms/8570-
H^df
httEL//wji¥wj;pjyg:^
http://www.epa.gov/opppm sd I /PR N oti ces/
or98-5.pdf
httBI/Mwj¥j|i3c^
http://www.epa.gov/opppm sd 1 /PR N oti ces/
pr98-l.pdf
Pesticide Registration Kit
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):
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 Acrobat reader.)
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Other PR Notices can be found at
http://www.epa.gov/opppmsdl/PR_NoticesPesticide 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' website.
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
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:
ace. orst. edu/info/nptn.
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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:
1. Date of receipt;
2. EPA identifying number; and
3. 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 chemical abstract
system (CAS) number if one has been assigned.
Documents Associated with this RED
The following documents are part of the Administrative Record for this RED
document and may be included in the EPA's Office of Pesticide Programs Public Docket.
Copies of these documents are not available electronically, but may be obtained by
contacting the person listed on the respective Chemical Status Sheet.
1. Health Effects Division and Environmental Fate and Effects Division Science
Chapters, which include the complete risk assessments and supporting documents.
2. Detailed Label Usage Information System (LUIS) Report.
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