?/EPA
United States Office of Prevention, Pesticides EPA 739-R-05-010
Environmental Protection and Toxic Substances September 2005
Agency (751OC)
Reregistration
Eligibility Decision for
Azadioxabicyclooctane
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
This is to inform you that the Environmental Protection Agency (hereafter referred to as
EPA or the Agency) has completed its review of the available data and public comments
received related to the preliminary risk assessments for the antimicrobial preservative referred to
as azadioxabicyclooctane. The enclosed Reregistration Eligibility Decision (RED) document was
approved on September 30, 2005. Public comments and additional data received were
considered in this decision.
Based on its review, EPA is now publishing its Reregistration Eligibility Decision (RED)
and risk management decision for azadioxabicyclooctane and its associated human health and
environmental risks. A Notice of Availability will be published in the Federal Register
announcing the publication of the RED.
The RED and supporting risk assessments for azadioxabicyclooctane are available to the
public in EPA's Pesticide Docket OPP-2005-0186 at: http://www.epa. gov/edockets.
The azadioxabicyclooctane RED was developed through EPA's public participation
process, published in the Federal Register on July 20, 2005, which provides opportunities for
public involvement in the Agency's pesticide reassessment and reregistration programs.
Developed in partnership with USDA and with input from EPA's advisory committees and
others, the public participation process encourages robust public involvement starting early and
continuing throughout the pesticide risk assessment and risk mitigation decision making process.
The public participation process encompasses full, modified, and streamlined versions that
enable the Agency to tailor the level of review to the level of refinement of the risk assessments,
as well as to the amount of use, risk, public concern, and complexity associated with each
pesticide. Using the public participation process, EPA is attaining its strong commitment to both
involve the public and meet statutory deadlines.
Please note that the azadioxabicyclooctane risk assessment and the attached RED
document concern only this particular pesticide. This RED presents the Agency's conclusions
on the dietary, drinking water, occupational and ecological risks posed by exposure to
azadioxabicyclooctane alone. This document also contains both generic and product-specific
data that the Agency intends to require in Data Call-Ins (DCIs). Note that DCIs, with all
pertinent instructions, will be sent to registrants at a later date. Additionally, for product-specific
-------
DCIs, the first set of required responses will be due 90 days from the receipt of the DCI letter.
The second set of required responses will be due eight months from the receipt of the DCI letter.
As part of the RED, the Agency has determined that azadioxabicyclooctane will be
eligible for reregistration provided that all the conditions identified in this document are satisfied,
including implementation of the risk mitigation measures outlined in Section IV of the
document. Sections IV and V of this RED document describe labeling amendments for end-use
products and data requirements necessary to implement these mitigation measures. Instructions
for registrants on submitting the revised labeling can be found in the set of instructions for
product-specific data that accompanies this document.
Should a registrant fail to implement any of the risk mitigation measures outlined in this
document, the Agency will continue to have concerns about the risks posed by
azadioxabicyclooctane. Where the Agency has identified any unreasonable adverse effect to
human health and the environment, the Agency may at any time initiate appropriate regulatory
action to address this concern. At that time, any affected person(s) may challenge the Agency's
action.
If you have questions on this document or the label changes necessary for reregistration,
please contact the Chemical Review Manager, Tom Luminello, at (703) 308-8075. For questions
about product reregistration and/or the Product Specific DCI that accompanies this document,
please contact Marshall Swindell at (703) 308-6341.
Sincerely, D
Frank T. Sanders D
Director, D
Antimicrobials DivisionD
-------
-------
REREGISTRATION ELIGIBILITY
DECISION
for
AZADIOXABICYCLOOCTANE
ListC
CASE 3023
Approved By:
Frank T. Sanders
Director,
Antimicrobials Division
Date
Attachment
-------
Table of Contents
Azadioxabicyclooctane Reregistration i D
Team D
Glossary of Terms and Abbreviations ii D
Executive Summary v D
I. Introduction 1 D
II. Chemical Overview 3 D
A. Regulatory History 3 D
B. Chemical Identification 3 D
1. Technical Azadioxabicyclooctane 4 D
C. Use Profile 4 D
D. Estimated Usage of Pesticide
III. Summary of Azadioxabicyclooctane Risk Assessments 5 D
A. Human Health Risk Assessment 5 D
1. Toxicity of 5 D
Azadioxabicyclooctane D
2. FQPA Safety 8 D
3. Population Adjusted Dose (PAD) 8 D
a. Acute PAD 8 D
b. Chronic PAD 9 D
4. Exposure Assumptions 9 D
5. Dietary (Food) Risk Assessment 10 D
a. Acute Dietary Risk 10 D
b. Chronic (Non-Cancer) Dietary Risk 10 D
c. Dietary Risks from Drinking Water 10 D
6. Residential 11 D
a. Toxicity 11 D
b. Residential Handler 12 D
c. Residential Application 14 D
7. Aggregate Risk 14 D
a. Short-Term Aggregate Risk 14 D
8. Occupational Risk 14 D
a. Occupational Toxicity 15 D
b. Occupational Handler Exposure 15 D
c. Occupational Handler Risk Summary 15 D
d. Occupational Post-Application Risk Summary 17 D
B. Environmental Risk Assessment 17 D
1. Environmental Fate and Transport 17 D
2. Ecological Risk 18 D
3. Listed Species Consideration 21 D
IV. Risk Management, Reregistration, and Tolerance Reassessment Decision... 23 D
A. Determination of Reregistration Eligibility 23 D
B. Public Comments and Responses 23 D
C. Regulatory Position 24 D
-------
1. Food Quality Protection Act Findings 24 D
a. "Risk Cup" Determination 24 D
b. Determination of Safety to U. S. Population 24 D
c. Determination of Safety to Infants and Children 24 D
d. Endocrine Disrupter Effects 25 D
e. Cumulative Risks 25 D
D. Regulatory Rationale 26 D
1. Human Health Risk Management 26 D
a. Dietary (Food) Risk Mitigation 26 D
b. Drinking Water Risk Mitigation 26 D
c. Residential Risk Mitigation 26 D
d. Occupational Risk Mitigation 26 D
i. Handler Exposure 27 D
ii. Post-Application Risk Mitigation 27D
2. Environmental Risk Management 27D
3. Other Labeling Requirements 27D
4. Threatened and Endangered Species Considerations 27 D
a. The Endangered Species Program 27 D
b. General Risk Mitigation 28 D
V. What Registrants Need to Do 29 D
A. Manufacturing Use-Products 31 D
1. Additional Generic Data Requirements 31 D
2. Labeling for Technical and Manufacturing-Use Products 32 D
B. End-Use Products 32 D
1. Additional Product Specific Data Requirements 32 D
2. Labeling for End-Use Products 32 D
a. Label Changes Summary Table 34 D
VI. Appendices 36 D
A. Table of Use Patterns for Azadioxabicyclooctane 37 D
B. Table of Generic Data Requirements and Studies Use to Make theD
Reregistration Decision 39 D
C. Technical Support Documents 45 D
D. Bibliography Citations 47 D
E. Generic Data Call-In 53 D
F. Product Specific Data Call-In 54 D
G. Batching of End-Use Products 55 D
H. List of All Registrants Sent the Data Call-In 56 D
I. List of Available Forms 57 D
-------
-------
Azadioxabicyclooctane Reregistration Team
Health Effects Risk Assessment
Timothy Leighton
Timothy McMahon
Talia Milano
Bob Quick
Cassi Walls
Ecological Risk Assessment
Kathryn Montague
Product Chemistry
Najm Shamim
Risk Management
Ben Chambliss
Tom Luminello
-------
GLOSSARY OF TERMS AND ABBREVIATIONS D
a.i. Active Ingredient
aPAD Acute Population Adjusted Dose
ADTC Antimicrobials Division Toxicology Endpoint Selection Committee
APHIS Animal and Plant Health Inspection Service
ARTF Agricultural Re-entry Task Force
BCF Bioconcentration Factor
CDC Centers for Disease Control
CDPR California Department of Pesticide Regulation
CFR Code of Federal Regulations
ChEI Cholinesterase Inhibition
CMBS Carbamate Market Basket Survey
cPAD Chronic Population Adjusted Dose
CSFII USDA Continuing Surveys for Food Intake by Individuals
CWS Community Water System
DCI Data Call-in
DEEM Dietary Exposure Evaluation Model
DL Double layer clothing (i.e., coveralls over SL}
DWLOC Drinking Water Level of Comparison
EC Emulsifiable Concentrate Formulation
EDSP Endocrine Disrupter Screening Program
EDSTAC Endocrine Disrupter Screening and Testing Advisory Committee
EEC Estimated Environmental Concentration. The estimated pesticide concentration
in an environment, such as a terrestrial ecosystem.
EP End-Use Product
EPA U.S. Environmental Protection Agency
EXAMS Tier II Surface Water Computer Model
FDA Food and Drug Administration
FFDCA Federal Food, Drug, and Cosmetic Act
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FOB Functional Observation Battery
FQPA Food Quality Protection Act
FR Federal Register
GL With gloves
GPS Global Positioning System
HIARC Hazard Identification Assessment Review Committee
IDFS Incident Data System
IGR Insect Growth Regulator
IPM Integrated Pest Management
RED Reregistration Eligibility Decision
LADD Lifetime Average Daily Dose
LCso Median Lethal Concentration. Statistically derived concentration of a substance
expected to cause death in 50% of test animals, usually expressed as the weight of
substance per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
LCO Lawn Care Operator
ii
-------
LOAEC
LOAEL
LOG
LOEC
mg/kg/day
MOE
MP
MRID
MRL
N/A
NASS
NAWQA
NG
NMFS
NOAEC
NOAEL
NPIC
NR
OPP
ORETF
PAD
PCA
PDCI
PDF
PF10
PF5
PHED
PHI
ppb
PPE
PRZM
RBC
RED
REI
RfD
RPA
RPM
RQ
RTU
RUP
SCI-GROW
SF
SL
SLN
Median Lethal Dose. Statistically derived single dose causing death in 50% of the
test animals when administered by the route indicated (oral, dermal, inhalation),
expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
Lowest Observed Adverse Effect Concentration
Lowest Observed Adverse Effect Level
Level of Concern
Lowest Observed Effect Concentration
Milligram Per Kilogram Per Day
Margin of Exposure
Manufacturing-Use Product
Master Record Identification (number). EPA's system of recording and tracking
studies submitted.
Maximum Residue Level
Not Applicable
National Agricultural Statistical Service
USGS National Water Quality Assessment
No Gloves
National Marine Fisheries Service
No Observed Adverse Effect Concentration
No Observed Adverse Effect Level
National Pesticide Information Center
No respirator
EPA Office of Pesticide Programs
Outdoor Residential Exposure Task Force
Population Adjusted Dose
Percent Crop Area
Product Specific Data Call-In
USDA Pesticide Data Program
Protections factor 10 respirator
Protection factor 5 respirator
Pesticide Handler's Exposure Data
Pre-harvest Interval
Parts Per Billion
Personal Protective Equipment
Pesticide Root Zone Model
Red Blood Cell
Reregistration Eligibility Decision
Restricted Entry Interval
Reference Dose
Reasonable and Prudent Alternatives
Reasonable and Prudent Measures
Risk Quotient
(Ready-to-use)
Restricted Use Pesticide
Tier I Ground Water Computer Model
Safety Factor
Single layer clothing
Special Local Need (Registrations Under Section 24C of FIFRA)
-------
STORE! Storage and Retrieval
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TRAC Tolerance Reassessment Advisory Committee
TTRS Transferable Turf Residues
UF Uncertainty Factor
USD A United States Department of Agriculture
USFWS United States Fish and Wildlife Service
USGS United States Geological Survey
WPS Worker Protection Standard
IV
-------
EXECUTIVE SUMMARY
The Environmental Protection Agency (hereafter referred to as EPA or the Agency) has
completed its review of public comments on the human health and environmental risk
assessments for azadioxabicyclooctane and is issuing its risk management decision. The Agency
has decided that azadioxabicyclooctane is eligible for reregistration provided all measures
outlined in this document are implemented. Azadioxabicyclooctane consists of an equilibrium
mixture of three chemicals (I: 5-hydroxymethoxymethyl-l-aza-3,7-dioxabicyclo(3,3,0)octane;
II: 5-hydroxymethyl-l-aza-3,7-dioxabicyclo(3,3,0)octane; III: 5-hydroxypoly(methylene-
oxy)methyl-l-aza-3,7-dioxabicyclo(3,3,0)octane). These chemicals cannot be divided into
components for individual testing and the three of them will be referred to as
azadioxabicyclooctane in this Reregistration Eligibilty Decision. This mixture is registered as a
preservative for antimicrobial control in the following use sites: oil recovery drilling muds and
flooding fluids; industrial adhesives and coatings (natural based and synthetic); latex and
polymer emulsions; metalworking cutting fluids; latex paints; paper coatings; caulks and
sealants; inks; pigment dispersion and pigment slurry; and textile fiber finishes that are not
intended as clothing. Azadioxabicyclooctane has been cleared by the US Food and Drug
Administration (US FDA) for use as an antibacterial preservative in paper and paperboard
products that are limited to dry food contact only in 21CFR 176.180 as well as a component in
paper adhesives in 21CFR 175.105.
Overall Risk Summary
The Agency's human heath risk assessment indicates no risks of concern for dietary or
drinking water exposures. Acute and chronic dietary risk estimates are below the Agency's level
of concern for the general U.S. population and all population subgroups.
Azadioxabicyclooctane is not likely to contaminate surface and ground waters based on
its use patterns. Thus, a drinking water assessment was not conducted.
Residential risks for handlers were calculated for short- and intermediate-term dermal
and inhalation exposures. All exposure and risk estimates for residential handler scenarios are
below the Agency's level of concern with the exception of the risks associated with application
of paint using an airless sprayer at the maximum application rate. Based on the use patterns of
azadioxabicyclooctane there are no potential dermal post application exposures to assess.
Inhalation post application exposures are expected to be minimal because the paint is dry and the
vapor pressure of azadioxabicyclooctane is negligible.
For the occupational handler dermal and inhalation risk assessment, the short- and
intermediate- term risks calculated were above target MOEs for all scenarios. Post-application
exposure is expected to be minimal based on the use patterns of this chemical with the exception
of metal working fluids. Occupational risks from post-application exposure were calculated for
long-term dermal and inhalation exposures to machinists resulting from metal working fluid use.
Risks of concern were identified for this use pattern at the maximum application rate of 0.3%
product by weight of material treated.
v
-------
The indoor uses of azadioxabicyclooctane are not likely to pose risk to fish, wildlife or
plants due to the low likelihood of exposure and the low toxicity of the compound. The offshore
oil production use drilling fluid treatment and flooding fluid treatment is considered unlikely to
adversely affect aquatic organisms due to the low toxicity and large dilution factor. The Agency
assumes that the waste streams occurring from terrestrial oil production are actively managed
under local environmental regulations to prevent adverse ecological effects.
Dietary Risk
The Agency has conducted a dietary exposure and risk assessment for use of
azadioxabicyclooctane as a preservative in paper coatings and paper adhesives each of which
may end in indirect food contact scenarios. For both the acute and chronic dietary exposure, the
risk is highest for children (12% of the acute PAD and 39.6% chronic PAD). For an adult, the
acute and chronic dietary exposures are 5.1% and 17% of the acute and chronic PADs
respectively. All dietary exposures calculated are below the Agency's level of concern (100% of
aPAD or cPAD) for non-cancer risk. A dietary cancer risk assessment could not be performed as
there are no carcinogenicity data for azadioxabicyclooctane.
Drinking Water Risk
None of the uses associated with azadioxabicyclooctane are expected to impact either
surface or ground water resources. Therefore, no drinking water assessment was performed.
Residential Handler Risk
Residential risks for handlers were calculated for short- and intermediate-term dermal
and inhalation exposures. All exposure and risk estimates for residential handler scenarios are
below the Agency's level of concern with the exception of the risks associated with application
of paint using an airless sprayer at the maximum application rate.
Aggregate Risk
The aggregate short-term risk assessment is designed to provide estimates of risk likely to
result from exposures to the pesticide or pesticide residues in food, water, and from residential
(or other non-occupation) pesticide uses. For adults, the aggregate assessment includes dietary
(oral) and residential inhalation exposures from painting. An assessment was not conducted for
children since there are no residential exposures expected for this subgroup.
Since exposures to residential handlers for the paint scenario are of concern at the highest
application rate, short-term aggregate risks are also of concern.
Occupational Risk
The short- and intermediate-term exposure scenarios identified for occupational workers
are the liquid pour and liquid pump applications of this chemical when it is used as a
preservative for the label-specified materials. There are also occupational painter scenarios
(which result from the chemical being incorporated as a preservative into paints) that involve the
vi
-------
methods of applications of airless painting and brush painting. All exposure and risk estimates
for occupational handler scenarios are below the Agency's level of concern. Therefore, no risk
mitigation measures are required for these handler scenarios.
For azadioaxabicyclootane, exposures are expected to be minimal except for the metal
working fluid scenario. Occupational risks from post-application exposure were calculated for
long-term dermal and inhalation exposures to machinists resulting from metal working fluid use.
Risks of concern were identified for this use pattern at the maximum application rate of 0.3%
product by weight of material treated.
Ecological Risk
The indoor uses of azadioxabicyclooctane are not likely to pose risk to fish, wildlife or
plants due to the low likelihood of exposure and the low toxicity of the compound. Most uses of
azadioxabicyclooctane are indoor uses, with little chance of exposure to the environment. The
oil production uses do occur outdoors; however, the Agency does not have an available model
for estimating exposure from those uses. The risk from offshore oil drilling uses of
azadioxabicyclooctane was previously addressed (Agency review July 14, 1983), and the
application of 500-2000 ppm drilling fluid treatment or 100-1000 ppm flooding fluid treatment
was considered "unlikely to adversely affect aquatic organisms due to the low toxicity and large
dilution factor." Discharge of waste streams occurring from terrestrial oil recovery operations
would be regulated at the local level in order to prevent undue environmental exposure.
Regulatory Decision
The Agency has completed its review and has determined that the data are sufficient to
support reregistration of all supported products containing azadioxabicyclooctane. The Agency
is issuing this RED for azadioxabicyclooctane, as announced in a Notice of Availability
published in the Federal Register. This RED document includes guidance and time frames for
making any necessary label changes for products containing azadioxabicyclooctane.
Summary of Mitigation Measures
The Agency has determined that azadioxabicyclooctane is eligible for reregistration
provided the mitigation measures described in this document and the label changes included in
Table 13 in Section V of the RED are implemented.
Residential:
To reduce residential exposure, the Agency has determined that the following mitigation
and label changes for specific scenarios are appropriate and required for reregistration eligibility:
• D Reduce the maximum application rate for paint uses to 0.4% product by weight of
material treated.
vn
-------
Occupational:
To reduce post-application exposure, the Agency has determined that the following
mitigation and label changes for specific scenarios are appropriate and required for reregistration
eligibility:
• D Reduce the maximum application rate for paint uses to 0.2% product by weight of
material treated.
Data Requirements
Confirmatory data is required to complete the reregistration of azadioxabicyclooctane as
outlined in Section V of this document. A complete list of data gaps is presented in Appendix B
(Table of Generic Data Requirements) as well as in Appendix E (the Generic Data Call-In) at the
end of this document.
Vlll
-------
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 and amended again by the Pesticide Registration Improvement Act of 2003 to set time
frames for the issuance of Reregistration Eligibility Decisions. 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 (EPA or the
Agency). Reregistration involves a thorough review of the scientific database underlying a
pesticide's registration. The purpose of the Agency's review is to reassess the potential hazards
arising from the currently registered uses of the pesticide; to determine the need for additional
data on health and environmental effects; and to determine whether 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 tolerance reassessment. The Agency has decided that,
for those chemicals that have tolerances and are undergoing reregistration, the tolerance
reassessment will be initiated through this reregistration process. The Act also requires that by
2006, EPA must review all tolerances in effect on the day before the date of the enactment of the
FQPA. FQPA also amends the Federal Food, Drug, and Cosmetic Act (FFDCA) to require a
safety finding in tolerance reassessment based on factors including consideration of cumulative
effects of chemicals with a common mechanism of toxicity. This document presents the
Agency's revised human health and ecological risk assessments; and the Reregistration
Eligibility Decision (RED) for azadioxabicyclooctane.
Azadioxabicyclooctane is a materials preservative registered for use on oil recovery
drilling muds and flooding fluids; industrial adhesives and coatings (natural based and synthetic);
latex and polymer emulsions; metalworking cutting fluids; latex paints; paper coatings; caulks
and sealants; inks; pigment dispersion and pigment slurry; and textile fiber finishes that are not
intended as clothing.
The Agency has concluded that the FQPA safety factor should be retained at 10X. The
toxicology database is not complete with respect to assessing the increased susceptibility to
infants and children as required by FQPA for azadioxabicyclooctane. There is an absence of
adequate developmental toxicity data and an absence of reproductive toxicity data for this
chemical. There is one prenatal dermal developmental toxicity study available for
azadioxabicyclooctane. While the developmental study showed no evidence of susceptibility of
offspring, the dermal route of administration is not a good indicator of potential effects from oral
exposures and the available data do not examine potential reproductive effects of the chemical.
Risks summarized in this document are those that result only from the use of the active
ingredient azadioxabicyclooctane. 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 that would occur at a higher level of exposure to any
1
-------
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 azadioxabicyclooctane and any other substances.
Azadioxabicyclooctane does not appear to produce a toxic metabolite produced by other
substances. For the purposes of this action, therefore, EPA has not assumed that
azadioxabicyclooctane has 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 the Agency's decision regarding the reregistration eligibility of
the registered uses of azadioxabicyclooctane. In an effort to simplify the RED, the information
presented herein is summarized from more detailed information which can be found in the
technical supporting documents for azadioxabicyclooctane referenced in this RED. The risk
assessments and related addenda are not included in this document, but are available in the
Public Docket at http://www.epa.gov/edocket.
This document consists of six sections. Section I is the introduction. Section II provides
a chemical overview, a profile of the use and usage of azadioxabicyclooctane, and its regulatory
history. Section III, Summary of azadioxabicyclooctane Risk Assessment, gives an overview of
the human health and environmental assessments, based on the data available to the Agency.
Section IV, Risk Management, Reregistration, and Tolerance Reassessment Decision, presents
the reregistration eligibility and risk management decisions. Section V, What Registrants Need
To Do, summarizes the necessary label changes based on the risk mitigation measures outlined
in Section IV. Finally, the Appendices list all use patterns eligible for reregistration,
bibliographic information, related documents and how to access them, and Data Call-In (DCI)
information.
-------
II.
Chemical Overview
A. Regulatory History
Azadioxabicyclooctane has been registered since October 30, 1975. The registration and
all data to support reregistration were transferred from Tenneco Chemicals on December 22,
1982 to Nuodex Inc. The Nuosept 95 product was purchased by International Specialty Products
on March 26, 2002. There are currently two products registered with azadioxabicyclooctane as
the active ingredient (one technical product and one end-use-product).
B. Chemical Identification
1. Technical Azadioxabicyclooctane
6542-37-6
0
O
O
,OH
Azadioxabicyclooctane is an equilibrium reaction mixture of three
Azadioxabicyclooctanes in a 50% aqueous solution.
Common name:
Chemical names:
Azadioxabicyclooctane
5 -Hydroxymethoxymethyl-1 -aza-3,7-dioxabicyclo (3,3,0)octane;
5-Hydroxymethyl-l-aza-3,7-dioxabicyclo(3,3,0)octane;
5-Hydroxypoly(methylene-oxy)*methyl-1-aza-3, 7-
dioxabicyclo(3.3.0)octane *(74%C2, 21%C3, 4%C4, 1%C5)
-------
CAS Registry No.:D 107001: 59720-42-2 D
107002: 6542-37-6 D
107003: 56709-13-8 D
OPP Chemical Code: 107001, 107002, 107003
Case Number: 3023
Chemical Family: Bicyclic Oxazolidine
Empirical formula: CyHoC^N
Molecular weight: 170.5
Trade name: Nuosept 95 Preservative
Basic manufacturer: International Specialty Products
Technical azadioxabicyclooctane is in the form of a liquid and is clear yellow in color.
The solubility of azadioxabicyclooctane in organic solvents range from 0.2 g/100 g at 25°C
(Hexane) to 28.0 g/100 g at 25°C (Ethyl ether). Azadioxabicyclooctane has a vapor pressure of
20.44 mm Hg at 90 °C and <2.1 x 10'5 mm Hg at 20°C.
C. Use Profile
The following is information on the currently registered uses of azadioxabicyclooctane
and an overview of use sites and application methods. A detailed table of the uses of
azadioxabicyclooctane eligible for reregistration is contained in Appendix A.
Type of Pesticide: Preservative
Summary of Use:
Food: Paper coatings and paper adhesives.
Non-Food: Adhesives (natural and synthetic), caulks, metalworking fluids, drilling
muds and flooding fluids, paper coatings, latex emulsions, wax emulsions.
Latex paint, inks, pigment dispersion, pigment slurry, sealants, textile fiber
finishes.
Residential: Paints and caulks.
Target Pests: Used to control slime forming bacteria and fungi.
Formulation Types: The end-use product is a liquid.
Method and Rates of Application:
-------
Equipment: Open pour, liquid pump.
Application Rates: 0.05 to 0.5 percent by weight.
Timing: Added to water phase or post addition during manufacturing process.
-------
III. Summary of Azadioxabicyclooctane Risk Assessments
The purpose of this summary is to assist the reader by identifying the key features and
findings of these risk assessments, and to help the reader better understand the conclusions
reached in the assessments. The human health and ecological risk assessment documents and
supporting information listed in Appendix C were used to formulate the safety finding and
regulatory decision for azadioxabicyclooctane. While the risk assessments and related addenda
are not included in this document, they are available from the OPP Public Docket and may also
be accessed on the Agency's website at http://epa.gov/dockets. Hard copies of these documents
may be found in the OPP public docket under docket number OPP-2005-0186. The OPP public
docket is located in Room 119, Crystal Mall II, 1801 S. Bell Street, Arlington, VA, and is open
Monday through Friday, excluding Federal holidays, from 8:30 a.m. to 4:00 p.m.
A. Human Health Risk Assessment
1. Toxicity of Azadioxabicyclooctane
A brief overview of the toxicity studies used for determining endpoints in the dietary risk
assessments are outlined in Table 2. Further details on the toxicity of azadioxabicyclooctane can
be found in the azadioxabicyclooctane docket and include, "AD Preliminary Risk Assessment
for the Reregistration Eligibility Decision" dated September 28, 2005; and "Report of the
Antimicrobials Division Toxicology Endpoint Selection Committee", dated April 20, 2005.
These documents are available on the Agency's website in the EPA Docket at
http ://www/epa. gov/edockets.
The Agency has reviewed all toxicity studies submitted for azadioxabicyclooctane and
has determined that the toxicological database is sufficient for reregistration. Major features of
the toxicology profile are presented below. The acute oral and dermal toxicities of
azadioxabicyclooctane are low. The acute inhalation toxicity showed a median lethal dose
range of between 0.441 mg/L and 0.819 mg/L in males, and between 0.819 mg/L and 1.397
mg/L in females, with epistaxis, labored breathing, rales, and rhinorrhea in all dose groups.
Corneal opacity was observed in the primary eye irritation study resulting in a Toxicity Category
I classification. Moderate dermal irritation effects were noted in the primary dermal irritation
study, leading to a Toxicity category III classification.
Table 1. Acute Toxicity Profile for Azadioxabicyclooctane
Guideline
Number
870.1100
(§81-1)
870.1200
(§81-2)
870.1300
(§81-3)
Study Type/
Test substance (% a.i)
Acute Oral- Rat Nuosept® 95
(50% a.i.)
Acute Dermal- Rabbit
Nuosept® 95 (50% a.i.)
Acute Inhalation- Rat
Nuosept® 95 (50% a.i.)
MRID Number/
Citation
MRID 41641601
MRID 41671801
MRID 42650901
Results
LD50 = 1940 mg/kg/day
LD50 > 2000 mg / kg
Combined LC50. >0.441
mg/L<0.819mg/L
Toxicity
Category
III
III
II
-------
Guideline
Number
870.2400
(§81-4)
870.2500
(§81-5)
870.2600
(§81-6)
Study Type/
Test substance (% a.i.)
Primary Eye Irritation- Rabbit
Nuosept® 95 (50% a.i.)
Primary Dermal Irritation-
Rabbit
Nuosept® 95 (50% a.i.)
Dermal Sensitization
MRID Number/
Citation
MRID 41641602
MRID 41641603
NA
Results
Corrosive
Moderate irritant
Assumed Sensitizer
Toxicity
Category
I
III
no data
available
The doses and toxicological endpoints selected for the dietary exposure scenarios are
summarized in Table 2.
Table 2. Toxicological Endpoints for Azadioxabicyclooctane (Dietary)
Exposure
Scenario
Acute Dietary
(gen. pop.)
Acute Dietary
(females 13+)
Chronic Dietary
(All populations)
Cancer (oral)
Dose Used in
Risk
Assessment, UF
NOAEL = 10.6
mg/kg/day
UF=100
NOAEL = 10.6
mg/kg/day
UF=100
NOAEL = 10.6
mg/kg/day
UF = 300
Special FQPA SF*
and Level of
Concern for Risk
Assessment
FQPA SF = lOx
aPAD = acute RID
FQPA SF
= 0.01 mg/kg/day
FQPA SF = lOx
aPAD = acute RID
FQPA SF
= 0.01 mg/kg/day
FQPA SF = lOx
cPAD =
chronic RID
FQPA SF
= 0.003 mg/kg/day
Study and Toxicological
Effects
90 day oral toxicity in rats
NOAEL = 10.6 mg/kg/day based
on decreased water consumption
at 56.5 mg/kg/day in males.
90 day oral toxicity in rats
NOAEL = 10.6 mg/kg/day based
on decreased water consumption
at 56.5 mg/kg/day in males.
90 day oral toxicity in rats
NOAEL = 10.6 mg/kg/day based
on decreased water consumption
at 56.5 mg/kg/day in males.
No cancer data available
Notes:
UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect
level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose, LOG = level of concern
-------
From the available repeat dose toxicity studies, there was no evidence of neurotoxicity of
azadioxabicyclooctane. There are no reproductive toxicity data available for
azadioxabicyclooctane.
In a dermal developmental toxicity study there was clear evidence of maternal dermal
effects (e.g. erythema, scabbing, edema) in all treatment groups. The LOAEL for maternal
dermal toxicity is 100 mg/kg/day (based on severe dermal irritation); a NOAEL could not be
established. The systemic maternal toxicity NOAEL is greater than or equal to 1000 mg/kg/day.
There were no other embryotoxic or fetotoxic effects observed in this study. The developmental
NOAEL is greater than or equal to 1000 mg/kg/day.
Carcinogenicity Classification
There are no lifetime carcinogenicity studies available for azadioxabicyclooctane.
Mutagenicity
Azadioxabicyclooctane has been tested for mutagenic activity in several assays. Although
the data suggest largely negative responses, the lack of test article characterization (especially in
light of positive responses observed in two studies) points to the need for proper test article
characterization before an adequate conclusion can be made about the mutagenicity of
azadioxabicyclooctane.
Endocrine Disruption Potential
EPA is required under the Federal Food Drug and Cosmetic Act (FFDCA), as amended
by FQPA, to develop a screening program to determine whether certain substances (including all
pesticide active and other ingredients) "may have an effect in humans that is similar to an effect
produced by a naturally occurring estrogen, or other such endocrine effects as the Administrator
may designate." When the appropriate screening and/or testing protocols being considered under
the Agency's Endocrine Disrupting Screening Program (EDSP) have been developed,
azadioxabicyclooctane may be subjected to additional screening and/or testing to better
characterize effects related to endocrine disruption.
2. FQPA Safety Factor
The FQPA Safety Factor (as required by the Food Quality Protection Act of 1996) is
intended to provide 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, or to compensate for an incomplete database for certain exposure pathways. The
FQPA Safety Factor has been retained (i.e., remains 10X) for azadioxabicyclooctane based on
the very limited developmental and reproductive toxicity databases.
The toxicology database for azadioxabicyclooctane with respect to assessing sensitivity
of infants and children is not complete. There is only one study, a developmental toxicity study
in rats conducted by the dermal route, available for this chemical. While the developmental
study showed no evidence of susceptibility of offspring to this chemical, the route of
administration is not a good indicator of potential effects from oral exposures.
-------
3. Population Adjusted Dose (PAD)
Dietary risk is characterized in terms of the Population Adjusted Dose (PAD), which
reflects the reference dose (RfD), either acute or chronic, that has been adjusted to account for
the FQPA Safety Factor (SF). This calculation is performed for each population subgroup. A
risk estimate that is less than 100% of the acute or chronic PAD is not of concern.
a. Acute PAD
Acute dietary risk for azadioxacyclooctane is assessed by comparing acute dietary
exposure estimates (in mg/kg/day) to the acute Population Adjusted Dose (aPAD). Acute dietary
risk is expressed as a percent of the aPAD. The aPAD is the acute reference dose (0.1
mg/kg/day) modified by the FQPA safety factor. The acute reference dose was derived from a
90-day oral toxicity study in rats in which both the NOAEL (10.6 mg/kg/day) and the LOAEL
(56.5 mg/kg/day) were determined. The azadioxacyclooctane aPAD is 0.01 mg/kg/day based on
a reference dose of 0.1 mg/kg/day, and incorporating the FQPA safety factor of 10X for the
overall U.S. population or any population subgroups.
b. Chronic PAD
Chronic dietary risk for azadioxacyclooctane is assessed by comparing chronic dietary
exposure estimates (in mg/kg/day) to the chronic Population Adjusted Dose (cPAD). Chronic
dietary risk is expressed as a percent of the cPAD. The cPAD is the chronic reference dose (0.03
mg/kg/day) modified by the FQPA safety factor. The cPAD was derived from a 90-day oral
toxicity study in rats in which both the NOAEL (10.6 mg/kg/day) and the LOAEL (56.5
mg/kg/day) were determined. However, no chronic studies were available necessitating the use
of an additional 3X uncertainty factor. The azadioxacyclooctane cPAD is 0.003 mg/kg/day
based on a reference dose of 0.03 mg/kg/day, which includes the incorporation of the FQPA
safety factor (10X) for the overall U.S. population or any population subgroups.
4. Exposure Assumptions
The use of antimicrobial chemicals on paper coatings and paper adhesives may result in
pesticide residues in human food. The Agency must determine the risk to human health that may
occur from exposure to these chemicals.
Potential dietary exposures to the active ingredient, azadioxabicyclooctane, from its uses
as paper coating and paper adhesive preservatives were assessed. Azadioxabicyclooctane has
been cleared by the US Food and Drug Administration (US FDA) for use as an antibacterial
preservative in paper and paperboard products contacting dry food only in 21CFR176.180 as
well as, a component in paper adhesives in 21CFR175.105.
US FDA has estimated a Cumulative Dietary Concentration of 12 ppb and a Cumulative
Dietary Exposure Intake (CEDI) of 0.006 mg/kg/day for azadioxabicyclooctane
(http://www.cfsan.fda.gov/~dms/opa-tedi.html) however, the Agency does not have the specific
details (i.e., application rates or residue migration potential) used by US FDA in their review of
this petition. Furthermore, no residue data have been submitted to the Agency in support of the
-------
azadioxabicyclooctane indirect food contact uses. Therefore, a screening-level assessment has
been conducted using the US FDA's Center for Food Safety & Applied Nutrition's (CFSAN)
approach as presented in "Preparation of Food Contact Notifications and Food Additive Petitions
for Food Contact Substances: Chemistry Recommendations" dated April 2002. The Agency
calculated "worst-case" dietary concentration values using the labeled maximum application rate
for the paper coating preservative use (0.25% or 2500 ppm of the paper coating) (EPA Reg. No.
1529-28), US FDA's default assumptions for preservation of paper adhesives, and EPA's
standard values for body weights.
Since azadioxabicyclooctane can be used as a preservative in paper coatings and
adhesives, the dietary exposures resulting from both uses must be added together because both
the coatings and adhesives could be used together within one paper product.
5. Dietary (Food) Risk Assessment
Generally, a dietary risk estimate that is less than 100% of the acute or chronic PAD does
not exceed the Agency's risk concerns. A summary of acute and chronic risk estimates are
shown in Table 3.
a. Acute Dietary Risk
An acute dietary risk assessment was conducted for azadioxabicyclooctane food uses.
The result of the combined assessment for coatings and adhesives showed the risk estimates to
be <12.0% of the aPAD for all population subgroups and therefore are not of concern.
b. Chronic (Non-cancer) Dietary Risk
A chronic dietary risk assessment was conducted for azadioxabicyclooctane food uses.
The risk analysis assumes daily exposure from paper coatings and adhesives. The result of the
combined assessment for coatings and adhesives showed the risk estimates to be <39.6% of the
cPAD for all population subgroups and therefore are not of concern.
Table 3: Acute and Chronic Dietary Exposure and Risk
Use
Paper Coating
Preservative
Paper Adhesive
Preservative
Combined
Daily Dietary
Dose
(mg/kg bw/day)
0.00021 (adult)
0.0005 (child)
0.00030 (adult)
0.00070 (child)
0.00051 (adult)
0.0012 (child)
% aPAD
2.1% (adult)
5% (child)
3% (adult)
7% (child)
5.1% (adult)
12% (child)
%cPAD
7.0% (adult)
16.6% (child)
10% (adult)
23% (child)
17% (adult)
39.6% (child)
10
-------
c. Dietary Risk from Drinking Water
Azadioxabicyclooctane is not likely to contaminate surface and ground waters based on
its use patterns. Therefore, a drinking water assessment was not conducted.
6. Residential Exposure
Residential exposure assessment considers all potential pesticide exposure, other than
exposure due to residues in food or in drinking water. Exposure may occur during painting or
caulking. Each route of exposure (oral, dermal, inhalation) is assessed, where appropriate, and
risk is expressed as a Margin of Exposure (MOE), which is the ratio of estimated exposure to an
appropriate NOAEL. Based on its use patterns, azadioxabicyclooctane has been assessed for the
residential mixing/loading/applicator (or "handler") exposure for applications by homeowners
painting. For azadioxabicyclooctane there are no potential dermal post application exposures to
assess. As for inhalation post application exposures, these are expected to be minimal because
the paint is dry and the vapor pressure of azadioxabicyclooctane is negligible.
a. Toxicity
The toxicological endpoints and associated uncertainty factors used for assessing the non-
dietary risks for azadioxabicyclooctane are listed in Table 4.
A MOE greater than or equal to 3,000 is considered adequately protective for the
residential exposure assessment for the inhalation route of exposure. The MOE of 3,000
includes lOx for interspecies extrapolation, lOx for intraspecies variation, 3x for a lack of
histopathology data and the lOx FQPA factor. The FQPA lOx hazard based safety factor was
retained based on the lack of developmental and reproductive toxicity data for
azadioxabicyclooctane, but was not applied to children's risk assessments for residential
exposure as residential exposures to children are not expected from the uses.
Need to add a discussion for occupational inhalation exposure. The above is all
residential. I assume the discussion would be the same absent the FQPA SF but not sure what
the histopath applies too.
For the dermal route of exposure, a MOE greater than or equal to 300 is considered
adequately protective for the residential exposure assessment. The MOE of 300 includes lOx for
interspecies extrapolation, lOx for intraspecies variation and 3x for lack of a NOAEL.
A MOE greater than or equal to 3,000 is considered adequately protective for the long-
term occupational exposure assessment for the dermal route of exposure. The MOE of 3000
includes lOx for interspecies extrapolation, lOx for intraspecies variation and 3x for lack of a
NOAEL and 3x for the lack of a chronic endpoint.
Table 4: Toxicity Endpoints Selected for Assessing Occupational and Residential Risk for
Azadioxabicyclooctane
11
-------
Exposure
Scenario
Dermal (all
durations)
Inhalation (all
durations )
Cancer
Dose Used in
Risk
Assessment, UF
Dermal LOAEL =
100 mg/kg/day
NOAEL= 10.6
mg/kg/day
(inhalation
absorption rate =
100%)
Special FQPA SF*
and Level of
Concern for Risk
Assessment
Occupational MOE =
300 (ST and IT)
= 3000 (LT)
Residential MOE =
300 (ST and IT)
Occupational MOE =
300
Residential MOE =
3000
Study and Toxicological
Effects
Co-critical studies:
21-day dermal toxicity in
rabbits
LOAEL =100 mg/kg/day (severe
dermal effects)
developmental toxicity in rats
LOAEL = 100 mg/kg/day (severe
dermal effects)
90 day oral toxicity in rats
NOAEL = 10.6 mg/kg/day based
on decreased water consumption
at 56.5 mg/kg/day in males.
No cancer data available
Notes: ST= short-term, IT = intermediate-term, LT= long-term
b Residential Handler
i. Exposure Scenarios, Data and Assumptions
Residential exposure may occur for azadioxabicyclooctane during application as a paint
or caulk. A number of assumptions, or estimates, such as adult body weight and area treated per
application, are made by the Agency for residential risk assessment. Also, note that residential
handlers are sometimes addressed somewhat differently than occupational handlers in that
homeowners are assumed to complete all elements of an application (mix/load/apply) without the
use of personal protective equipment.
The quantitative exposure/risk assessment developed for residential handlers is based on these
scenarios:
(1) painting using a brush or roller,
(2) painting using an airless sprayer
Based on end-use product application methods and use amounts, it is assumed that
exposures while applying paints will be equal to or greater than exposures that may occur when
an individual uses any of the other end use products (i.e., caulks, inks, sealants). Therefore,
residential handler exposures were assessed for the application of paint, as this scenario
represents maximum possible exposure to the chemical.
Brush/Roller
12
-------
The dermal and inhalation unit exposures for this application method were obtained from
the Agency's Residential SOPs. The dermal unit exposure is representative of the handler a tee-
shirt and shorts while applying the paint with a brush and without gloves because this is a
residential use site. The inhalation unit exposure is representative of a painter applying paint
with a brush. The maximum application rate is 0.5% product by weight of material being
treated. The application rates on the label do not account for the product containing only 50%
a.L, so the maximum application results in exposure to 0.25% a.i. by weight of the material
treated.
For this scenario, the painter is expected to handle 2 gallons of paint per day. This is
from the AD Residential SOPs (1997 & 2001) in which this value is the 90th percentile value of 8
gallons of latex paint used per year divided by the mean frequency of 4 painting events per year.
The density of paint is assumed to be 10 Ib/gallon, so that the value of 2 gallons is equivalent to
20 pounds of paint.
Airless Sprayer
The dermal and inhalation unit exposures for this application method were obtained from
the Agency's Residential SOPs. The dermal unit exposure is representative of the handler
wearing a tee-shirt and shorts while performing an ungloved airless spray application. The
inhalation unit exposure is representative of a painter applying a material with an airless sprayer.
For this scenario, the painter is expected to handle 15 gallons of paint per day. This is from the
Agency's SOP's in which this value is based on coverage of 200ft2/gal and a house size being 40'
x 30' x 20' (surface area of 2,800ft2). The density of paint is assumed to be 10 Ibs/gallon, so that
the value of 15 gallons is equivalent to 150 Ibs of paint.
ii. Residential Handler Risk Estimates
Based on toxicological criteria and potential for exposure, the Agency has conducted
dermal and inhalation exposure assessments. As noted previously, MOEs greater than or equal to
3,000 for the inhalation route of exposure and 300 for dermal exposure are considered
adequately protective for the residential exposure assessment.
A summary of the residential handler exposures and risk are presented on Table 5. For
residential handlers that handle products containing azadioxabicyclooctane, short-term, and
intermediate-term MOEs were below the target MOEs for painting using an airless sprayer at the
maximum application rate and thus are of concern. MOEs do not exceed the Agency's level of
concern for the painting using a brush or roller or for painting using an airless sprayer at the
minimum application rate.
13
-------
Table 5: Estimates of Exposures and Risks to Residential Handlers of
Azadioxabicyclooctane (Short -Term Duration)
Exposure
Scenario
Paints
Method of
Application
Brush/Roller
Airless
Sprayer
Airless
Sprayer
Application rate (% a.i. by
weight of material being
treated - % product by
weight of material treated x
50% a.i.)
0.25% (max)
0.25% (max)
0.05% (min)1
Daily Dose
(mg a.i./kg per day)
Dermal
Dose
0.1643
0.4232
0.0846
Inhalation
Dose
0.0002
0.004446
0.000889
MOE
Dermal
(target = 300)
609
236
1,181
Inhalation
(target = 3000)
53,000
2.400
12,000
c. Residential Post-Application
Residential post application exposures occur when bystanders contact areas in which the
antimicrobial end use product has recently been applied. For azadioxabicyclooctane there are no
potential dermal post application exposures to assess. As for inhalation post application
exposures, these are expected to be minimal because the paint is dry and the vapor pressure of
azadioxabicyclooctane is negligible.
6. 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 a 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. Since no drinking water estimates
were developed for azadioxabicyclooctane, aggregate assessments include exposure to food and
as a result of residential uses only.
Typically, aggregate risk assessments are conducted for acute (1 day), short-term (1-30
days), intermediate-term (1-6 months) and chronic (6 months to lifetime) exposures. However,
acute and chronic aggregate assessments were not conducted because there are no significant
impacts to drinking water sources, nor are there long-term residential uses. Thus, only short- and
intermediate-term aggregate assessments were conducted. Oral and inhalation exposure and risk
estimates were combined for the aggregate risk assessment because these endpoints are based on
the same toxicity study and effects of concern. Dermal exposures were not aggregated with the
oral or inhalation exposures due to different toxicological endpoints for oral and dermal
exposures.
a. Short-Term Aggregate Risk
The aggregate short-term risk assessment is designed to provide estimates of risk likely to
result from exposures to the pesticide or pesticide residues in food, water, and from residential
14
-------
(or other non-occupation) pesticide uses. For adults, the aggregate assessment includes dietary
(oral) and residential inhalation exposures from painting. An assessment was not conducted for
children since there are no residential exposures expected for this subgroup.
Since exposures to residential handlers for the paint scenario are of concern at the highest
application rate short-term aggregate risks are also of concern.
7. Occupational Exposure and Risk
Workers can be exposed to a pesticide through mixing, loading, and/or applying a
pesticide, or re-entering treated sites. Occupational handlers of azadioxabicyclooctane include
workers in a variety of occupational settings. Additionally, postapplication exposures are likely
to occur in these settings. The representative scenarios selected for assessment were evaluated
using maximum application rates as recommended on the product labels for
azadioxabicyclooctane.
Occupational risk is assessed for exposure at the time of application (termed "handler"
exposure) and is assessed for exposure 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.
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) from toxicological studies. In the case for
azadioxabicyclooctane, MOEs greater than 300 for dermal and inhalation exposures are not of
concern to the Agency for short- and intermediate-term exposures. MOEs greater than 1000 for
dermal and inhalation exposures are not of concern to the Agency for long-term exposures. 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.
a. Occupational Toxicity
Table 4 provides a listing of the toxicological endpoints used in the occupational risk
assessment for azadioxabicyclooctane.
b. Occupational Handler Exposure
The Agency has determined that there is potential fe^dermal and inhalation worker
exposure to azadioxabicyclooctane at various use sites when used as a preservative consistent
with existing labeling. There are also occupational painter scenarios associated with its use as a
preservative in paints. Painting methods evaluated include application with an airless sprayer
and a brush. To assess handler risks, the Agency used surrogate unit exposure data from both the
Pesticide Handlers Exposure Database (PFLED) and proprietary data from the Chemical
Manufacturers (CMA) antimicrobial exposure study.
15
-------
c. Occupational Handler Risk Summary
For the occupational handler dermal and inhalation risk assessment, the short- and
intermediate- term risks calculated were above the target MOEs for all scenarios (i.e., dermal and
inhalation >300). However, the inhalation MOE for the airless sprayer paint scenario falls
below the MOE of 1,000, when the additional 10X route-to-route extrapolation uncertainty factor
is applied. In such cases, an inhalation study would be required to confirm these findings. A
summary of the results of the occupational handler assessment is provided in Table 6.
16
-------
Table 6: Short and Intermediate Term Azadioxabicyclooctane Exposures and MOEs Associated with Occupational Handlers
Substrate Treated/Handled
through Exposure Scenario
Latex Paint
(Latex Emulsions)5
Metalworking cutting fluids
(preservation)
Paper Coating (preservation)
Drilling Muds (end user)
Flooding Fluids (end-user)
Method of
Application
Liquid Pour
(preservation)
Liquid Pump
(preservation)
Airless spraying
(end user)
Airless spraying (end
user)
Brush Painting (end
user)
Liquid Pour
Liquid Pump
Liquid Pump
Liquid Pour
Application rate
(% a.i. by weight
of material being
treated)
0.25 (max)
0.25 (max)
0.25 (max)
0.05 (min)
0.25 (max)
0.1 5 (max)
0.1 5 (max)
0.25 (max)
0.25 (max)
Quantity Handled/Treated
per day (unit as indicated)
19,100 Ibs (2,000 gallons)
191, 000 Ibs (20,000
gallons)
500 Ibs (50 gallons)
500 Ibs (50 gallons)
50 Ibs (5 gallons)
2,865 Ibs (300 gallons)
2,865 lbs(300 gallons)
9,550 Ibs (1000 gallons)
46.7 lbs(5.6 gal (ST))
23.31bs(2.8gal(IT))
Daily Dose (mg a.i./kg per day)
Dermal Dose
0.0921
0.0429
0.25
0.05
0.0429
0.0113
0.0192
0.0015
0.0002
0.0001
Inhalation Dose
0.00236
0.00275
0.0148
0.00296
0.0005
0.000524
0.000214
0.000090
0.000006
0.000003
MOEr
Dermal (target
ST/IT MOE = 300)
1,100
2,300
400
2,000
2,300
8,900
5,200
65,000
440,000
890,000
Inhalation (target MOE
= 300)
4,500
3,800
720
3,600
21,000
20,000
50,000
120,000
1.8x106
3.7x106
a: The maximum application rate of 0.5% product ( 0.25% a.i). by weight of material treated generates an MOE of concern, whereas using materials treated at the minimumD
application rates specified in the table, an MOE that is not of concern is generated. All of these uses in Table 6.2 were assessed at this rate, except for metalworking fluids. This D
treatment was label specified to be 0.3 % product (0.15% a.i.) by weight of the fluid treated. D
b,c : CMA preservative liquid pour, gloved values for dermal and inhalation are 0.135 mg/lb a.i. and 0.00346 mg/lb a. irrespectively. D
d,e : CMA preservative liquid pump, gloved values for dermal and inhalation are 0.00629 mg/lb a.i. and 0.000403 mg/lb a.i., respectively. D
f, g : PHED unit exposure values for a handler wearing gloves and applying paint using an airless sprayer were used, so that the dermal and inhalation values were 14 mg/lb a.i. D
and 0.830 mg/lb a.i., respectively. D
h, i: PHED paintbrush application scenario, gloved values for dermal and inhalation are 24 mg/lb a.i. and 0.28 mg/lb a.i., respectively. D
j, k : CMAMWF liquid pour, gloved values for dermal and inhalation are 0.184 mg/lb a.i. and 0.00854 mg/lb a.i.,respectivelyD
1, m : CMA MWF liquid pump, gloved values for dermal and inhalation are 0.312 mg/lb a.i. and 0.00348 mg/lb a.i., respectively D
n, o : CMA liquid pump for pulp and paper, gloved values for dermal and inhalation are 0.0045 mg/lb a.i. and 0.00027 mg/lb a.i., respectively. D
17
-------
p: For the quantity handled, it is explained in the MOE discussion following, which addresses each scenario individually
q: Daily Dose (mg a.i./kg per day) = Daily Dose (mg a.i./kg per day) = Unit Exposure (mg/lb a.i.) x rate x amount handled x (II body weight (kg))
r: MOE = Toxicity Endpoint (mg/kg/day) / Daily Dose (mg/kg/day); where dermal NOAEL =100 mg/kg/day and the inhalation LOAEL =10.6 mg/kg/day
s: Latex paints are representative for adhesives, caulks, ink dispersions, pigment dispersions, pigment slurries, wax emulsions, textiles, and sealants.
t: There is a chemical metering application (i.e. liquid pump) for drilling muds and flooding fluid uses. However, this was not assessed because appropriate unit exposure values
are not available. This is further discussed in the End User discussion later in the document.
18
-------
d. Occupational Post-application
Occupational painter post-application exposures result when bystanders contact areas in
which the antimicrobial end-use product has been recently applied. For azadioxabicyclooctane,
exposures are expected to be minimal except for the metal working fluid scenario.
Metalworking Fluids:
There is a potential for dermal and inhalation exposure when a worker handles treated
metalworking fluids. This route of exposure occurs after the chemical has been incorporated into
the metal working fluid and a machinist is using/handling this treated end-product. The MOEs
are in Table 7 for this exposure scenario. A screening-level long-term dermal exposure estimate
was derived using the 2-hand immersion model from ChemSTEER. The model is available at
www.epa.gov/opptintr/exposure/docs/chemsteer.htm
Table 7. Post Application Risks to Machinists from Metal Working Fluid Use
Substrate
Treated/Handled
through Exposure
Scenario
Metalworking cutting
fluids
Method of
Application
Liquid Pour
Liquid Pump
Liquid Pour
Liquid Pump
Application Rate (%
a.i. by weight of
material being
treated)
0.15
0.05
Daily Dose
Dermal Dose
0.1854
0.0618
Inhalation Dose
0.00107
0.000357
Long Term MOE
Dermal
540
1,600
Inhalation
9900
30,000
At the maximum application rate (0.3% product by weight of material to be treated,
0.15% a.i.) permitted for metalworking fluids (MWF), there is concern with the dermal exposure
to the worker. The target MOE for long-term exposure is 1,000, and at the maximum rate, the
MOE is 540, which is a concern. However, when the worker comes into contact with fluid that
has been treated at the minimum application rate (0.1% product by weight of material to be
treated, 0.05% a.i.), the MOE is 1,600 which is not of concern since it is greater than 1,000.
B.
Environmental Risk Assessment
A summary of the Agency's environmental risk assessment is presented below. The
following risk characterization is intended to describe the magnitude of the estimated
environmental risks for azadioxabicyclooctane use sites and any associated uncertainties.
1. Environmental Fate and Transport
The environmental fate assessment for azadioxabicyclooctane is based on U.S. EPA's
Estimation Programs Interface (EPI) Suite. EPI Suite provides estimations of physical/chemical
19
-------
properties and environmental fate properties. Azadioxabicyclooctane is a mixture of three acetals
(components a, b and c). EPI Suite lacks estimation of the third of the three isomers (component
C).
Under abiotic conditions, the mixture of these acetals is hydrolytically unstable with half-
lives of 0.347 days at pH 5, 1.74 days at pH 7 and approximately 15 days at pH 9. It is, therefore,
not likely to be persistent in water.
Components A and B of the mixture are likely to volatilize into the atmosphere as their
vapor pressures vary between 0.0004 to 0.003 mm Hg. Component C is likely to have less
volatility as the side chain of CH2O groups are added into the structure. Estimated half lives in
the atmosphere for components A and B are 1.2 and 1.4 hours. Hence, these two chemicals are
not likely to persist in the atmosphere.
Estimated log Kows of components A and B respectively are -2.23 and -1.55 (very highly
miscible in water and show no tendency for dissolving organic solvents); therefore, the mixture
is not likely to bioaccumulate in aquatic organisms.
MITI linear biodegradability (modified linear biodegradation method) for components A
and B indicates a fast biodegradation is highly probable in soils and water. These compounds do
not likely pose a concern for surface and ground water contamination.
2. Ecological Risk
Azadioxabicyclooctane demonstrates low toxicity to birds and mammals and slight
toxicity to freshwater aquatic organisms. All submitted ecological toxicity studies were
conducted with the formulated product Nuosept® 95. Although conducted using a formulated
product and not the TGAI, the submitted studies for avian acute, avian subacute, freshwater
invertebrates and estuarine/marine organisms are considered adequate to support the registered
uses of azadioxabicyclooctane, as Nuosept® 95 is the only end-use product. A summary of
submitted data is provided below.
The indoor uses of azadioxabicyclooctane are not likely to pose risk to fish, wildlife or
plants due to the low likelihood of exposure and the low toxicity of the compound. Most uses of
azadioxabicyclooctane are indoor uses, with little chance of exposure to the environment. The
oil production uses do occur outdoors; however, the Agency does not have an available model
for estimating exposure from those uses. The risk from offshore oil drilling uses of
azadioxabicyclooctane was previously addressed (Agency review July 14, 1983), and the
application of 500-2000 ppm drilling fluid treatment or 100-1000 ppm flooding fluid treatment
was considered "unlikely to adversely affect aquatic organisms due to the low toxicity and large
dilution factor." Discharge of waste streams occurring from terrestrial oil recovery operations
would be regulated at the local level in order to prevent undue environmental exposure.
20
-------
Table 8. Acute Oral Toxicity of Nuosept® 95 to Birds
,..-.• „• '..•.-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-.
Mallard duck (Anas
platyrhynchos)
'• :lngre1iie:nt:.v;
107001
24.5%
107002
17.7%
107003
7.8%
::.:-.;.. . __, . -. -. -. -. -. -. -. -. -. -. -. -. -. :,
LD50>2,510
NOEL = 25 10
(mortality)
,..-.• .: '..'.•. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-. .-.
Practically non-toxic
.. . •" ;; _ _• •' __ . •' ..•;. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. :.
Beavers, 1983 (ACC #
250533)
Table 9. Subacute Dietary Toxicity of Nuosept® 95 to Birds
:: ... •.-"'• ,.«•• :'±~'- -•• ••-• .• ." •' :• -"".-.• •....', .
= -:- :,:•••::?; v-Species- •••.. ;v\;\r
:: .:• '"'v:.:X •.••!.'•••'"...'.;• .••'"-'^ ^ '.- '.- '.- '^ '.- '
Bobwhite quail
(Colinus virginianus)
Bobwhite quail
(Colinus virginianus)
Mallard duck (Anas
platyrhynchos)
:•:,. 5%:A;cti\f :••;"•
;.-;il%redierit;,;'
3tL;£j;ai)i v™
50%
not reported
not reported
ii-;ysp|p^'ti^- ;^;
LC50 >5,200 a.i.
(>10,400 product)
NOEC 1541 ppm
a.i. (3082 ppm
product)
LC50 > 10,000 ppm
product
NOEC 10,000 ppm
LC50 > 10,000 ppm
product
NOEC 10,000 ppm
: r;:ToMpity:pategoiry; "v-
:. : ^. •..;••':: .. .-^^^.^^^^.^^^^.^^
::- ':"' '... .-\':->. ^. ^. \ ^. ^. ^. \ ^. ^. ^. \ ^. ^.
Practically non-toxic
Practically non-toxic
Practically non-toxic
. /^;:^v;J^reiaSe;>:5. -:•:-
Hakinetal., 1990 (MRID
416848-01)
Truslow Farms, 1974.
(ACC#24878)
Truslow Farms, 1974.
(ACC#24878)
NOAEC= No-observable adverse effect concentration
21
-------
Table 10. Acute Toxicity of Nuosept® 95 to Fish
• V :•.;• ;: ;;.". Sp|cigS:;;<; •;•;•;{
,..-.• .: '.. ':. :. :. :. :. :. :. :. :. :. :. :. :. :. :. :.
Rainbow trout
(Oncorhynchus
mykiss)
Bluegill (Lepomis
macrochims)
Sheepshead minnow
(Cyprinodon
variegatus)
•::^::i%tiye:i>----
: -ringrefeat;:::?.
•Vi-'-.X^V:;-;,-:.-
not reported
not reported
PC code %
107001
24.5%
107002
17.7%
107003
7.8%
I sEft%pims;(plpn''..;;^
;;: Iv;;?r-pr6duetf /; ;;;/v/i
::.:-.;.. . __, . -. -. -. -. -. -. -. -. -. -. -. -. -. :,
LC50 = 240
NOEC = 87
LC50 = 163
NOEC = 87
LC50 = 440 ppm
NOEC = 250 ppm
.:^i^;.(^b&X'
.-••• ". :.'' •'.•.•.'.'•'••"•• ' .v: ••",',":, :, ':, ':, :, :, ':, ':,
,..-.• .: '.. ':. :. :. :. :. :. :. :. :. :. :. :. :. :. :. :.
practically non- toxic
practically non-toxic
practically non-toxic
1 i , " •••V^iSRj^rerifief :f f^- - ^
.. . •" ;; _ _• •' __ . •' ..-;. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. ::.. :.
Bentley and Sleight, 1974
(ACC #247878; MRID
930500-15)
Bently and Bevier, 1974
(ACC#247878; MRID
930500-15)
Ward, 1983. (ACC#
250533)
Table 11. Acute Toxicity of Nuosept® 95 to Invertebrates
"••••.-.•' •••>'"•'«"' " •••''*• .•'• • '".•:'"..••"'' '•'•= ."
i-j:&$^^--j-^'-:-:
••'• •'• ••••- •• • • .. •'•-••• ••;••: ••• ••• ••;••: ••• ••• ••;••: ••
'•'•< ':" '... .-\':->. ^. ^. ^. ^. ^. ^. ^. ^. ^. ^. ^. ^. ^.
Eastern oyster
(Crassostrea
virginica)
Mysid (Americamysis
bahia)
Water flea
(Daphnia magna)
.ii.'%4cti¥f-.;;
:::Iogrj4ieftr:
mm^
PC Code %
107001
24.5%
107002
17.7%
107003
7.8%
107001
24.5%
107002
17.7%
107003
7.8%
107001
24.5%
107002
17.7%
107003
7.8%
1&|^s{f>plv
iiv^Pf^Sf?^fete.
EC50 = 42
NOEC =25
LC50 = 88 ppm
NOEC < 50 ppm\
EC50 = 77
NOEC = 7.7
;;ipMt^e^egfry!i
.-. : ^. ...;• "• . • .':.•:::. :: :: ^ ^ ^ ^ ^ ^ ^ ^ ^
::- ':" '... .-••':\X ^. ^. ^. ^. ^. ^. ^. ^. ^. ^. ^. ^. ^.
slightly toxic
slightly toxic
slightly toxic
:: •,,^,,i^; ••' •' . ••.. '••'•'",» "\v '.'-^' • V. "•„. -. . • •'••• ••
.^;^.-?K/;Refer|not:>:::;-^:;,:>
.'• "••''. ^/- •_. ' ' -. ..•:-::.-::.-::.-::.-::.-::.-::.-::.-::.-::.-::.-::.-:.
Ward, 1983.
(ACC#250533)
Ward, 1983.
ACC#250533
Suprenant, 1983
(ACC# 25053 3/MRID
#930500-16)
22
-------
3. Listed Species Consideration
a. The Endangered Species Act
Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all
federal agencies to consult with the National Marine Fisheries Service (NMFS) for marine and
anadromous listed species, or the United States Fish and Wildlife Services (FWS) for listed
wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species
or their designated habitat. Each federal agency is required under the Act to insure that any
action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a
listed species or result in the destruction or adverse modification of designated critical habitat.
To jeopardize the continued existence of a listed species means "to engage in an action that
reasonably would be expected, directly or indirectly, to reduce appreciably the likelihood of both
the survival and recovery of a listed species in the wild by reducing the reproduction, numbers,
or distribution of the species." 50 C.F.R. § 402.02.
To facilitate compliance with the requirements of the Endangered Species Act subsection
(a)(2) the Environmental Protection Agency, Office of Pesticide Programs has established
procedures to evaluate whether a proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed species in the wild by
reducing the reproduction, numbers, or distribution of any listed species (U.S. EPA 2004). After
the Agency's screening-level risk assessment is performed, if any of the Agency's Listed Species
LOG Criteria are exceeded for either direct or indirect effects, a determination is made to identify
if any listed or candidate species may co-occur in the area of the proposed pesticide use. If
determined that listed or candidate species may be present in the proposed use areas, further
biological assessment is undertaken. The extent to which listed species may be at risk then
determines the need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.
For certain use categories, the Agency assumes there will be minimal environmental
exposure, and only a minimal toxicity data set is required (Overview of the Ecological Risk
Assessment Process in the Office of Pesticide Programs U.S. Environmental Protection Agency -
Endangered and Threatened Species Effects Determinations, 1/23/04, Appendix A, Section II B,
pg.81). Chemicals in these categories therefore do not undergo a full screening-level risk
assessment, and are considered to fall under a "no effect" determination. Due to the low
likelihood of exposure and low toxicity of azadioxabicyclooctane, the indoor uses of the
compound are not likely to adversely affect listed species. Likewise, offshore oil production use
of azadioxabicyclooctane is considered unlikely to adversely affect listed species due to the low
toxicity of the compound and the large dilution factor in offshore operations. Therefore, the
Agency expects no effects to listed species or critical habitat and therefore makes a "No Effect"
determination for this chemical.
b. General Risk Mitigation
Azadioxabicyclooctane end-use products (EPs) may also contain other registered
pesticides. Although the Agency is not proposing any mitigation measures for products
23
-------
containing azadioxabicyclooctane specific to federally listed species, the Agency needs to
address potential risks from other end-use products. Therefore, the Agency requires that users
adopt all listed species risk mitigation measures for all active ingredients in the product. If a
product contains multiple active ingredients with conflicting listed species risk mitigation
measures, the more stringent measure(s) should be adopted.
24
-------
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 reregistration. The Agency has previously identified and required the
submission of the generic (i.e., active ingredient-specific) data required to support reregistration
of products containing azadioxabicyclooctane as an active ingredient. The Agency has
completed its review of these generic data, and has determined that the data are sufficient to
support reregistration of all supported products containing azadioxabicyclooctane.
The Agency has completed its assessment of the dietary, occupational, drinking water,
and ecological risks associated with the use of pesticide products containing the active ingredient
azadioxabicyclooctane. Based on a review of these data and on public comments on the
Agency's assessments for the active ingredient azadioxabicyclooctane, the Agency has sufficient
information on the human health and ecological effects of azadioxabicyclooctane to make
decisions as part of the tolerance reassessment process under FFDCA and reregistration process
under FIFRA, as amended by FQPA. The Agency has determined that all azadioxabicyclooctane
containing products are eligible for reregistration 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 azadioxabicyclooctane
that are eligible for reregistration. Appendix B identifies the generic data requirements that the
Agency reviewed as part of its determination of reregistration eligibility of
azadioxabicyclooctane, 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 azadioxabicyclooctane, the Agency has determined that
azadioxabicyclooctane 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 azadioxabicyclooctane. If all changes outlined in
this document are incorporated into the product labels, then all current risks for
azadioxabicyclooctane will be substantially mitigated for the purposes of this determination.
B. Public Comments and Responses
Through the Agency's public participation process, EPA worked with stakeholders and
the public to reach the regulatory decisions for azadioxabicyclooctane. During the public
comment period on the risk assessments, which closed on September 19, 2005, the Agency
received comments from the registrant, International Speciality Products. These comments in
their entirety are available in the public docket, http://docket.epa.gov/edkpub/index.j sp, (OPP-
2005-0186). These comment have been considered in the writing of this RED.
25
-------
The registrant also submitted comments to the Agency during Phase 1, the error only
comment period. The Agency's responses to these comments are incorporated into the revised
chapters and are available in the public 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 azadioxabicyclooctane. An aggregate assessment was conducted for exposures through
food, drinking water and residential use. The Agency has determined that the human health risks
from these combined exposures are within acceptable levels with the mitigation contained in this
document. 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, water and
residential use.
b. Determination of Safety to U.S. Population
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated
with azadioxabicyclooctane. The Agency has determined that there is a reasonable certainty no
harm will result to the general population or any subgroup from the use of azadioxabicyclooctane
with amendments and changes as specified in this document. In reaching this conclusion, the
Agency has considered all available information on the toxicity, use practices and exposure
scenarios, and the environmental behavior of azadioxabicyclooctane. Both the acute dietary
(food alone) and chronic dietary risks from azadioxabicyclooctane are not of concern.
Azadioxabicyclooctane is not likely to contaminate surface and ground waters based on its use
patterns. Thus, a drinking water assessment was not conducted.
Because the Agency has concerns for residential handler risks for the paint scenario
short- and intermediate-term aggregate risk assessments were not conducted for
azadioxabicyclooctane since this use alone exceeds the Agency's level of concern.
c. Determination of Safety to Infants and Children
EPA has determined that the established tolerances for azadioxabicyclooctane, 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
factors of 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 azadioxabicyclooctane residues in this population subgroup.
A Special FQPA Safety Factor is necessary to protect the safety of infants and children.
In determining whether or not infants and children are particularly susceptible to toxic effects
26
-------
from azadioxabicyclooctane 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 retained (i.e., remains 10X) for
azadioxabicyclooctane based on the very limited developmental and reproductive toxicity
databases.
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 that EPA include evaluations of
potential effects in wildlife. For pesticides, EPA will use FIFRA and, to the extent that effects in
wildlife may help determine whether a substance may have an effect in humans, FFDCA
authority to require the wildlife evaluations. As the science develops and resources allow,
screening of additional hormone systems may be added to the Endocrine Disrupter Screening
Program (EDSP).
When the appropriate screening and/or testing protocols being considered under the
EDSP have been developed, azadioxabicyclooctane may be subject to additional screening
and/or testing to better characterize effects related to endocrine disruption.
e. Cumulative Risks
Risks summarized in this document are those that result only from the use of
azadioxabicyclooctane. 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 azadioxabicyclooctane. 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/.
27
-------
D. Regulatory Rationale
The Agency has determined that azadioxabicyclooctane is eligible for reregistration
provided that additional required data confirm this decision and that the risk mitigation measures
outlined in this document are adopted, and label amendments are made to reflect these measures.
The following is a summary of the rationale for managing risks associated with the use of
azadioxabicyclooctane. Where labeling revisions are warranted, specific language is set forth in
the summary tables of Section V of this document.
1. Human Health Risk Management
a. Dietary (Food) Risk Mitigation
For all supported uses, the acute and chronic dietary exposure estimates are below the
Agency's level of concern. Therefore, no risk mitigation measures are required to address
exposure to azadioxabicyclooctane residues in food.
b. Drinking Water Risk Mitigation
Azadioxabicyclooctane is not likely to contaminate surface and ground waters based on
its use patterns. Thus, a drinking water assessment was not conducted. Therefore, no risk
mitigation measures are required to address azadioxabicyclooctane exposure from drinking
water.
c. Residential Risk Mitigation
Residential risks for handlers were calculated for short- and intermediate-term dermal
and inhalation exposures. Risks of concern were identified for the application of paints using an
airless sprayer at the maximum application rate of 0.5% product by weight of material treated.
All other exposure and risk estimates for residential handler scenarios are below the Agency's
level of concern.
To reduce residential exposure, the Agency has determined that the following mitigation
and label change for specific scenarios is appropriate and required for reregistration eligibility:
• D Reduce the maximum application rate for paint uses to 0.4% product by weight of
material treated.
d. Occupational Risk Mitigation
i. Handler Exposure
Occupational risks from handler and applicator exposures were calculated for short-term
and intermediate-term dermal and inhalation exposures. All exposure and risk estimates for
28
-------
occupational handler scenarios are below the Agency's level of concern. Therefore, no risk
mitigation measures are required for these handler scenarios.
ii. Post-Application Risk Mitigation
Occupational risks from post-application exposure were calculated for long-term dermal
and inhalation exposures to machinists resulting from metal working fluid use. Risks of concern
were identified for this use pattern at the maximum application rate of 0.3% product by weight of
material treated.
To reduce post-application exposure, the Agency has determined that the following
mitigation and label change for specific scenarios is appropriate and required for reregistration
eligibility:
• D Reduce the maximum application rate for paint uses to 0.2% product by weight of
material treated
2. Environmental Risk Management
As the uses of azadioxabicyclooctane considered in this RED make it unlikely that any
appreciable exposure to terrestrial or aquatic organisms would occur, no risk mitigation measures
are required to address environmental exposure to azadioxabicyclooctane.
3. Other Labeling Requirements
In order to be eligible for reregistration, various use and safety information will be
included in the labeling of all end-use products containing azadioxabicyclooctane. For the
specific labeling statements and a list of outstanding data, refer to Section V of this RED
document.
4. Threatened and Endangered Species Considerations
a. The 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
to affect any particular species, EPA puts basic toxicity and exposure data developed for risk
assessments into context for individual listed species and their locations by evaluating important
ecological parameters, pesticide use information, the geographic relationship between specific
pesticide uses and species locations, and biological requirements and behavioral aspects of the
particular species. A determination that there is a likelihood of potential impact to a listed
species may result in limitations on use of the pesticide, other measures to mitigate any potential
impact, or consultations with the Fish and Wildlife Service and/or the National Marine Fisheries
Service as necessary.
29
-------
Due to the low likelihood of exposure and low toxicity of azadioxabicyclooctane, the
indoor uses of the compound are not likely to adversely affect listed species. Likewise, offshore
oil production use of azadioxabicyclooctane is considered unlikely to adversely affect listed
species due to the low toxicity of the compound and the large dilution factor in offshore
operations. Therefore, the Agency expects no effects to listed species or critical habitat and
therefore makes a "No Effect" determination for this chemical.
b. General Risk Mitigation
Azadioxabicyclooctane end use products (EPs) may also contain other registered
pesticides. Although the Agency is not proposing any mitigation measures for products
containing azadioxabicyclooctane specific to federally listed threatened and endangered species,
the Agency needs to address potential risks from other end-use products. Therefore, the Agency
requires that users adopt all threatened and endangered species risk mitigation measures for all
active ingredients in the product. If a product contains multiple active ingredients with
conflicting threatened and endangered species risk mitigation measures, the more stringent
measure(s) should be adopted.
30
-------
V. What Registrants Need to Do
The Agency has determined that azadioxabicyclooctane is eligible for reregistration
provided that: (i) additional data that the Agency intends to require confirm this decision; and
(ii) the risk mitigation measures outlined in this document are adopted, and (iii) label
amendments are made to reflect these measures. To implement the risk mitigation measures, the
registrants must amend their product labeling to incorporate the label statements set forth in the
Label Changes Summary Table in Section B below (Table 13). The additional data requirements
that the Agency intends to obtain will include, among other things, submission of the following:
For azadioxabicyclooctane 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. Submit any time extension and/or waiver requests with a full written justification.
Within the time limit specified in the generic DCI:
1. Cite any existing generic data which address data requirements or submit new generic
data responding to the DCI.
Please contact Tom Luminello at (703) 308-8075 with questions regarding generic reregistration. D
By US mail: D By express or courier service: D
Document Processing Desk (DCI/AD) D Document Processing Desk (DCI/AD) D
Tom Luminello D Tom Luminello D
US EPA (7510C)D Office of Pesticide Programs (7510C)D
1200 Pennsylvania Ave., NW D Room 266A, Crystal Mall 2 D
Washington, DC 20460D 1801 S. Bell StreetD
Arlington, VA 22202 D
31
-------
For end use products containing the active ingredient azadioxabicyclooctane, 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 (PDCI response form and requirements status
and registrant's response form); and,
2. Submit any time extension or waiver requests with a full written justification.
Within eight months from the receipt of the PDCI:
1. Two copies of the confidential statement of formula (CSF) (EPA Form 8570-4);
2. A completed original application for reregistration (EPA Form 8570-1). Indicate on
the form that it is an "application for reregistration";
3. Five copies of the draft label incorporating all label amendments outlined in Table 13
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 Marshall Swindell at (703) 308-6341 with questions regarding product
reregistration and/or the PDCI. All materials submitted in response to the PDCI should be
addressed as follows:
By US mail: By express or courier service:
Document Processing Desk (PM-31) Document Processing Desk (PM-31)
Marshall Swindell Marshall Swindell
US EPA (75 IOC) Office of Pesticide Programs (75 IOC)
1200 Pennsylvania Ave., NW Room 266A, Crystal Mall 2
Washington, DC 20460 1801 South Bell Street
Arlington, VA 22202
32
-------
A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic database supporting the reregistration of azadioxabicyclooctane has been
reviewed and determined to be substantially complete. However, the following additional data
requirements have been identified by the Agency as confirmatory data requirements. A generic
data call-in will be issued at a later date. The 90-day inhalation study is being required to
confirm the Agency's conclusions on residential risks.
EPA requires that the registrant submit carcinogenicity data for azadioxabicyclooctane to
support the metal working fluid use. Conversely, the registrant may claim that a carcinogenicity
study would not be required for the metalworking fluid use if the use is for "enclosed
metalworking systems". Under this scenario, it has been determined that certain toxicology data
requirements including carcinogenicity testing would be held in reserve pending review of
worker exposure in such enclosed systems.
The Agency has established an interim two-tiered system for toxicology testing
requirements. Tier I toxicology data requirements would apply to all indirect food additives that
result in residue concentrations ranging from 0-200ppb which applied to azadioxabicyclooctane.
The requirements would consist of an acute toxicity testing battery, subchronic toxicity study in
the rodent, a developmental toxicity study in the rat, and a mutagenicity testing battery. The
Agency also conducts a literature search and can also conduct a Structural Activity Relationship
analysis (S AR) if appropriate. The Agency also will hold in reserve a two-generation
reproduction toxicity study in the rat and a subchronic toxicity studies in a non-rodent which
would become data requirements if the Agency's evaluation of the Tier 1 data warranted. A 2-
generation reproduction study and a subchronic toxicity study in a non-rodent species are being
held in reserve for azadioxabicyclooctane.
Tier II studies would be triggered by the presence of significant (i.e. >200ppb) residues in
food or evidence of significant toxicity from the Tier I data set, which may include
developmental / reproductive, or other systemic toxicity such as presence of neoplastic growth or
significant target organ toxicity. In such cases, chronic toxicity and carcinogenicity testing would
be required.
The risk assessment noted deficiencies in the surrogate dermal and inhalation exposure
data available from the Chemical Manufacturers Association (CMA) data base. Therefore, the
Agency is requiring confirmatory data to support the uses assessed with the CMA exposure data
within this risk assessment. The risk assessment also noted that many of the use parameters
(e.g., amount handled and duration of use) were based on professional judgments. Therefore,
descriptions of human activities associated with the uses assessed are required as confirmatory.
33
-------
Table 12. Confirmatory Data Requirements for Reregistration
Guideline Study Name
Skin Sensitization
90-Day Inhalation Toxicity Study-Rat
Freshwater Fish Acute Toxicity with a warmwater species,
preferably Bluegill sunfish, using TGAI
Indoor Inhalation Exposure and Applicator Exposure
Monitoring Data Reporting
Indoor Dermal Exposure and Applicator Exposure
Monitoring Data Reporting
Descriptions of Human Activity
Carcinogenicity
New OPPTS
Guideline No.
870.2600
870.3465
850.1075
875. 1400 and 875. 1600
875. 1200 and 875. 1600
875.2800
870.4200
Old Guideline No.
81-6
82-4
72-1
234 and 236
233 and 236
133-1
83-2
Studies Held in Reserve
2-Generation Reproduction
90-Day Oral Toxicity in Non-Rodents
870.3800
870.3150
83-4
82-1
2. Labeling for Technical and Manufacturing Use Products
To ensure compliance with FIFRA, technical and manufacturing use product (MP)
labeling should be revised to comply with all current EPA regulations, PR Notices and
applicable policies. The Technical and MP labeling should bear the labeling contained in Table
13, Label Changes Summary Table.
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, will follow this RED
at a later date.
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 13.
Registrants may generally distribute and sell products bearing old labels/labeling for 26
months from the date of the issuance of this Reregistration Eligibility Decision document.
34
-------
Persons other than the registrant may generally distribute or sell such products for 52 months
from the approval of labels reflecting the mitigation described in this RED. However, existing
stocks time frames will be established case-by-case, depending on the number of products
involved, the number of label changes, and other factors. Refer to "Existing Stocks of Pesticide
Products; Statement of Policy," Federal Register, Volume 56, No. 123, June 26, 1991.
a. Label Changes Summary Table
In order to be eligible for reregistration, amend all product labels to incorporate the risk
mitigation measures outlined in Section IV. The following table describes how language on the
labels should be amended.
35
-------
Table 13. Labeling Changes Summary Table
Summary of Labeling Changes for Azadioxabicyclooctane
Description
Reduce rate for paint
applications
Reduce rate for metal working
fluids applications
Amended Labeling Language
Maximum rate for paint applications is 0.4% product by weight of material treated
Maximum rate for metal working fluids applications is 0.2% product by weight of material
treated
Placement on Label
Directions for Use
Directions for Use
36
-------
37
-------
VI. APPENDICES D
38
-------
Appendix A. Table of Use Patterns for Azadioxabicyclooctane
Use Site
Formulation
Method of
Application
Application Rate
(Range)3
Use Limitations
Industrial and Manufacturing Facilities
Adhesives (natural-based)
Adhesives (synthetic)
Caulks
Drilling Muds
Flooding Fluids
Latex Emulsion
Wax Emulsion
Latex Paint
1529-28
1529-28
1529-28
1529-28
1529-28
1529-28
1529-28
1529-28
Open pour
Open pour
Open pour
Open pour
Open pour
Open pour
Open pour
Open pour
0.2-0.5 % by weight of
formulation
0.1-0.5 % by weight of
formulation
0.1-0.5 % by weight of
formulation
0.05 -0.2% by weight
of formulation
0.01-0.1 % by weight
of formulation
0.05-0.3 % by weight
of formulation
0.05-0.3 % by weight
of formulation
0.1-0.5 % by weight of
formulation
Add to water phase or post addition.
Add to water phase or post addition.
Add to water phase during manufacture.
Add to water phase or post addition.
Post addition.
Post addition.
Post addition.
Add at any point during manufacture.
a The optimum amount of Nuosept 95 Preservative required for adequate preservation is best determined by conducting a series of test
loadings and making adjustments. The maximum level permitted for metal-working fluids is 0.3%. The maximum level permitted for
all other applications is 0.5%
39
-------
Use Site
Inks
Paper Coatings
Pigment Dispersion
Pigment Slurry
Sealants
Metalworking Fluids
Textile Fiber Finish
Formulation
1529-28
1529-28
1529-28
1529-28
1529-28
1529-28
1529-28
Method of
Application
Open pour
Open pour
Open pour
Open pour
Open pour
Open pour
Open pour
Application Rate
(Range)3
0.1-0.5 % by weight of
formulation
0.1-0.5 % by weight of
formulation
0.1-0.3 % by weight of
formulation
0.05-0.1 % by weight
of formulation
0.1-0.5 % by weight of
formulation
0.1-0.3 % by weight of
formulation
0.05-0.1 % by weight
of formulation
Use Limitations
Post addition.
Must be limited to contact with dry food.
Add to water phase or post addition.
Add at any point during manufacture.
Add to water phase or post addition.
Add to water phase during manufacture.
Add to water phase during manufacture and
service.
For use on fibers that are not in direct
contact with skin.
Add at any point during manufacture.
a The optimum amount of Nuosept 95 Preservative required for adequate preservation is best determined by conducting a series of test
loadings and making adjustments. The maximum level permitted for metal-working fluids is 0.3%. The maximum level permitted for
all other applications is 0.5%.
40 D
-------
APPENDIX B: Azadioxabicyclooctane (Case 3023)
Appendix B lists the generic (not product specific) data requirements which support the re-registration of azadioxabicyclooctane.
These requirements apply to azadioxabicyclooctane in all products, including data requirements for which a technical grade active
ingredient is the test substance. The data table is organized in the following formats:
1. D Data Requirement (Columns 1 and 2). The data requirements are listed by Guideline Number. The first column lists the new Part 158
Guideline numbers, and the second column lists the old Part 158 Guideline numbers. Each Guideline Number has an associated test
protocol set forth in the Pesticide Assessment Guidance, which are available on the EPA website.
2. D Guideline Description (Column 3). Identifies the guideline type.
3. D Use Pattern (Column 4). This column indicates the standard Antimicrobial Division use patterns categories for which the generic (not
product specific) data requirements apply. The number designations are used in Appendix B.
(1) Agricultural premises and equipment
(2) Food handling/ storage establishments premises and equipment
(3) Commercial, institutional and industrial premises and equipment
(4) Residential and public access premises
(5) Medical premises and equipment
(6) Human water systems
(7) Materials preservatives
(8) Industrial processes and water systems
(9) Antifouling coatings
(10) Wood preservatives
(11) Swimming pools
(12) Aquatic areas
3. D Bibliographic Citation (Column 5). If the Agency has data in its files to support a specific generic Guideline requirement, this column
will identity each study by a "Master Record Identification (MRID) number. The listed studies are considered "valid" and acceptable for
satisfying the Guideline requirement. Refer to the Bibliography appendix for a complete citation of each study.
41 D
-------
DATA REQUIREMENT
New Guideline
Number
Old Guideline
Number
Study Title
Use Pattern
CITATION(S)
MRID Number
PRODUCT CHEMISTRY
830.1550
830.1600
830.1620
830.1650
830.1670
830.1700
830.1750
830.1800
830.6302
830.6303
830.6304
830.7050
830.7200
830.7220
830.7300
830.7840
830.7860
830.7950
830.7370
61-1
61-2a
61-2b
62-1
62-2
62-3
63-2
63-3
63-4
None
63-5
63-6
63-7
63-8
63-9
63-10
Product Identity and Composition
Starting Materials and Manufacturing Process
Formation of Impurities
Preliminary Analysis
Certification of Limits
Analytical Method
Color
Physical State
Odor
UV/Visible Absorption
Melting Point
Boiling Point
Density
Solubility
Vapor Pressure
Dissociation Constant in Water
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42740801, 41671601, 41671602,41671603
42740801, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42 D
-------
DATA REQUIREMENT
New Guideline
Number
830.7550
830.7560
830.7570
830.7000
830.6313
830.6314
830.6315
830.6316
830.6317
830.7100
830.6319
830.6320
Old Guideline
Number
63-11
63-12
63-13
63-14
63-15
63-16
63-17
63-18
63-19
63-20
Study Title
Partition Coefficient (Octanol/Water)
pH
Stability
Oxidizing/Reducing Action
Flammability
Explodability
Storage Stability
Viscosity
Miscibility
Corrosion Characteristics
Use Pattern
All
All
All
All
All
All
All
All
All
All
CITATION(S)
MRID Number
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
42734301, 41671601, 41671602,41671603
ECOLOGICAL EFFECTS
850.2100
850.2200
850.2200
850.1075
850.1075
850.1010
850.1025
71-1
71-2
71-2b
72-la
72-lc
72-2
72-3B
Avian Acute Oral Toxicity Test (Mallard Duck)
Avian Dietary Toxicity (Bobwhite Quail)
Avian Dietary Toxicity (Mallard Duck)
Fish Acute Toxicity - Freshwater (Blue Gill)
Fish Acute Toxicity - Freshwater (Rainbow Trout)
Acute Aquatic Invertebrate Toxicity (Daphnid)
Estuarine/Marine Toxicity - Mollusk
All
All
129008
4164801,112791
112792
109246
109246
129009
129012
TOXICOLOGY
43 D
-------
DATA REQUIREMENT
New Guideline
Number
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
870.3100
870.3200
870.3250
870.3465
870.4200
870.3700
870.3700a
870.3700b
870.5265
870.5395
870.5450
870.5500
870.5550
Old Guideline
Number
81-1
81-2
81-3
81-4
81-5
81-6
82-la
82-2
82-3
82-4
83-2
83-3
83-3a
83-3b
84-2
84-2
84-2
84-2
84-2
Study Title
Acute Oral - Rat
Acute Dermal - Rabbit
Acute Inhalation - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
Dermal Sensitization
90-Day Feeding-Rodent
21/28-Day Dermal Toxicity - Rat
90-day Dermal Toxicity - Rodent
28/90-Day Inhalation - Rat
Carcinogenicty
Developmental Toxicity -Rat
Prenatal Developmental in Rodents
Developmental Toxicity -Rabbit
Bacterial Reverse Mutation Assay
Micronucleus Assay
Dominant Lethal Rat
Bacterial DNA Damager or Repair
Unscheduled DNA Synthesis Assay
Reserved Studies
Use Pattern
All
All
All
All
All
All
All
All
All
All
All
All
All
All
CITATION(S)
MRID Number
41641601
41671801
42650901
41641602
41641603
41641604
41641606
41641605
DG
DG
41537501
41699001
93050019
42711001
44 D
-------
DATA REQUIREMENT
New Guideline
Number
870.3800
870.3150
Non-Guideline
Old Guideline
Number
83-4
82-lb
84-4
Study Title
2 Generation Repro
90-Day Oral Subchronic in Non-Rodent
Other Genotoxic Studies
In Vitro Cell Transformation Assay
Use Pattern
CITATION(S)
MRID Number
DG, reserved study
DG, reserved study
93050022, 93050024, 93050025
OCCUPATIONAL/RESIDENTIAL EXPOSURE
875.2800
875.1200
875.1600
875.1400
875.1600
133-1
233/236
234/236
Descriptions of Human Activity
Dermal Indoor Exposure
Inhalation Indoor Exposure
All
All
All
DG
DG
DG
ENVIRONMENTAL FATE
835.2120
161-1
Hydrolysis
All
43067001
OTHER DATA REQUIREMENTS
45 D
-------
46 D
-------
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 St., Arlington, VA 22202. It is open Monday
through Friday, excluding legal holidays, from 8:30 AM to 4:00 PM.
The docket initially contained preliminary risk assessments and related documents as of
July 20, 2005. Sixty days later the first public comment period closed. The EPA then
considered comments and revised the risk assessments.
All documents, in hard copy form, may be viewed in the OPP docket room or
downloaded or viewed via the Internet at the following site: http://www.epa.gov/edockets
These documents include:
1. D Azadioxabicyclooctane: AD Preliminary Risk Assessment for the Reregistration
Eligibility Decision Document, Julyl2, 2005
2. Azadioxabicyclooctane: Dietary Exposures and Risks from Antimicrobial Indirect Food
Contact Uses, July 7, 2005
3. D Azadioxabicyclooctane: Occupational and Residential Exposure Chapter for RED,
July, 7, 2005
4. D Azadioxabicyclooctane: Environmental Fate Assessment of Nuosept 95 for RED,
March 1, 2005
5.D Azadioxabicyclooctane: Product Chemistry Science Chapter for RED, April 6,2005
6. Azadioxabicyclooctane: Report of the Antimicrobials Division Toxicology Endpoint
Selection Committee, May 25, 2005
7. D Azadioxabicyclooctane: Ecological Hazard and Environmental Risk Assessment
for 5-hydroxymethoxymethyl-l-aza-3, 7-dioxabicyclooctanes (Aza), May 17, 2005
8. D Epidemiology Assessment based on Incident Reports, May 19, 2005
9.D Hazard Characterization
47
-------
48
D
-------
Appendix D: Generic Data Requirements and Studies Used to Make the Reregistration
Decision (Bibliography)
1. MRID Studies
MRID# Citation
109246 Bentley, R. (1974) Acute Toxicity of Nuosept 95 to Bluegill (Lepomis
macrochirus) and Rainbow Trout (Salmo gairdneri). (Unpublished study received
Jul 19, 1982 under 92-35; prepared by Bionomics EG & G, Inc., submitted by
Tenneco Chemical, Inc., Piscataway, N.J.; CDL:247878-A)
112791 Fink, R. (1974) Final Report: Eight-day Dietary LC50-Bobwhite Quail: Nuosept
95: Project No. 122-101. (Unpublished study received Jul 19, 1982 under 92-35;
prepared by Truslow Farms, Inc., submitted by Tenneco Chemical, Inc.,
Piscataway, NJ; CDL: 247878-B)
112792 Fink, R. (1974) Final Report: Eight-day Dietary LC50-Mallard Ducks: Nuosept
95: Project No. 122-102. (Unpublished study received Jul 19, 1982 under 92-35;
prepared by Truslow Farms, Inc., submitted by Tenneco Chemical, Inc.,
Piscataway, NJ; CDL: 247878-C)
129008 Beavers, J.; Jaber, M.; Joiner, G.; et al. (1983) Acute Oral LD50- Mallard Duck:
Nuosept 95: Project No. 122-105. Final rept. (Unpublished study received Jun 23,
1983 under 1100-82; prepared by Wildlife International Ltd., submitted by
Nuodex, Inc., Piscataway, NJ; CDL:250533-A)
129009 LeBlanc, G.; Surprenant, D. (1983) Acute Toxicity of Nuosept 95 to the Water
Flea ...: Report #BW-83-2-1366. (Unpublished study received Jun 23, 1983 under
1100-82; prepared by EG & G Bionomics, submitted by Nuodex, Inc.,
Piscataway, NJ; CDL:250533-B)
129010 Ward, G.; Hodgson, J. (1983) Acute Toxicity of Nuosept 95 to Sheepshead
Minnows ...: Report No. BP-83-5-56. (Unpublished study received Jun 23, 1983
under 1100-82; prepared by EG & G Bionomics, submitted by Nuodex, Inc.,
Piscataway, NJ; CDL: 250533-C)
129011 Ward, G.; Hodgson, J. (1983) Acute Toxicity of Nuosept 95 to Mysid Shrimp ...:
Report No. BP-83-3-41. (Unpublished study received Jun 23, 1983 under 1100-
82; prepared by EG & G Bionomics, submitted by Nuodex, Inc., Piscataway, NJ,
CDL:250533-D)
49
-------
129012 D Ward, G.; Hodgson, J. (1983) Acute Toxicity of Nuosept 95 to Embryos-larvae of
Eastern Oysters ...: Report No. BP-83-6-64. (Unpublished study received Jun 23,
1983 under 1100-82; prepared by EG & G Bionomics, submitted by Nuodex, Inc.,
Piscataway, NJ; CDL:250533-E)
41537501 D Smith, J.; Masters, R.; John, D.; et al. (1990) A Study of the Effect of Nuosept 95
on Pregnancy of the Rat: Report No. NDX 3/ 88962. Unpublished study prepared
by Huntingdon Research Centre Ltd. 122 p.
41641601 D Dilley, J. (1990) Acute Oral Toxicity of Nuosept 95 in Rats: Interim Progress
Report: Lab Project Number: LSC-8470. Unpublished study prepared by SRI
International, lip.
41641602 D Hershman, R. (1984) Summary of Resilts of a Primary Eye Irritation Study,
Rabbit: Lab Project Number: 84-3988A. Unpublished study prepared by
Bio search Inc. 9 p.
41641603 D Unwin, S. (1983) Primary Dermal Irritation Test on Nuosept 95 in New Zealand
White Albino Rabbits: Final Report: Lab Project Number: 7808-E/l. Unpublished
study prepared by Midwest Research Institute, lip.
41641605 D Elliot, P.; Street, A.; Gibson, W.; et al. (1985) Twenty-One Day Dermal Toxicity
Study in Rabbits with Nuosept 95/Nuosept C: Lab Project Number: NDX 1-
84955-SB. Unpublished study prepared by Huntingdon Research Centre. 103 p.
41641606 D Sasmore, D.; Tyson, C. (1980) Effect of Nuosept 95 in Rats: 90-Day Toxicity
Study-Contains Dose Range Study for Dominant Lethal Study: Final Report: Lab
Project Number: LSC-8654. Unpublished study prepared by SRI Int. 72 p.
41671801 D Liggett, M.; McRae, L. (1990) Acute Dermal Toxicity to Rabbits of Nuosept 95:
Final Report: Lab Project Number: 90591D/NDX 8/AC. Unpublished study
prepared by Huntingdon Research Centre Ltd. 14 p.
41684801 D Hakin, B.; Rodgers, M.; Anderson, A.; et al. (1990) Nuosept 95: LC- 50 to
Bobwhite Quail: Lab Project Number: NDX9/901288. Unpublished study
prepared by Huntingdon Research Centre Ltd. 30 p.
41699001 D Hodgson, J. (1988) A Study of the Effect of Nuosept 95 on Pregnancy of the Rat:
Lab Project Number: HRC NDX 3/88962. Unpublished study prepared by
Huntingdon Research Centre, Ltd. 122 p.
41728601 D O'Loughlin, K. (1990) Measurement of Micronuclei in Bone Marrow
Erythrocytes of Swiss-Webster Mice Following Two Treatments with Nuosept
95: Lab Project Number: 1556-C01-90. Unpublished study prepared by SRI
International. 36 p.
50
-------
42587501 D Popendorf, W.; Selim, M.; Kross, B. (1992) Chemical Manufacturers Association
Antimicrobial Exposure Assessment Study: Second Replacement to MRID
41761201: Lab Project Number: Q626. Unpublished study prepared by The
University of Iowa. 316 p.
42650901 D Cholakis, I; Sprinz, H. (1983) Acute Inhalation Toxicity of Nuosept 95 in
Sprague-Dewley Rats: Lab Project Number: 7808-E(1). Unpublished study
prepared by Midwest Research Institute. 25 p.
42711001 D Hamilton, C. (1993) Measurement of Unscheduled DNA Synthesis in Male
Fischer-344 Rat Hepatocytes Following In-Vivo Treatment with Nuosept 95: Lab
Project Number: LSC 4084-U01-92. Unpublished study prepared by SRI
International. 24 p.
42720801 D Rush, D. (1993) Efficacy/Phytotoxicity Studies Performed with Monocarbamide
Dihydrogensulfate: Lab Project Number: RE-P-GA-10: RE-P-GA-4: RE-FC-GA-
2. Unpublished study prepared by Unocal Agriproducts. 123 p.
42734301 D Mahoney, D. (1993) Product Identity (Confidential Statement of Formula):
Nuosept 95 Preservative: Upgrade to MRID 41671601. Unpublished study
prepared by Huls America, Inc. 6 p.
42740801 D Mahoney, D. (1993) Nuosept 95: Certification of Limits (Gas Chromatogram):
Final Report. Unpublished study prepared by Huls America, Inc. 7 p.
43060701 D Hauswirth, J.; Davis, C. (1993) PrimaryDermal Irritation of M-Pede Insecticide
in Rabbits. Unpublished study prepared by Mycogen Corp. 6 p.
43067001 D Cross, J. (1993) Aqueous Hydrolysis of Nuosept 95: Lab Project Number:
211 SOI. Unpublished study prepared by EPL Bio-Analytical Services, Inc. 120 p.
93050015 D Bentley, R.; Sleight, B. (1990) Huls America, Inc. Phase 3 Reformat of MRID
00109246. Acute Toxicity of Nuosept 95 Preservative to Bluegill and Rainbow
Trout. Prepared by EG&G, Inc. 13 p.
93050016 D LeBlanc, G. (1990) Huls America, Inc. Phase 3 Reformat of MRID 00129009.
Acute Toxicity of NUOSEPT 95 to the Water Flea (Daphnia magna): Project No.
BW-83-2-1366. Prepared by EG&G, Bionomics. 18 p.
93050017 D Haworth, S. (1990) Huls America, Inc. Phase 3 Reformat of MRID 00088956.
Salmonella/Mammalian-Microsome Plate Incorporation Mutagenesis Assay:
Project No. 601-257-1. Prepared by EG&G Mason Research Institute. 20 p.
93050018 D Lee, C.; Van Goethem, D. (1990) Huls America, Inc. Phase 3 Reformat of MRID
51
-------
00088974. Mutagenicity Studies on NUOSEPT 95 Salmonella/Microsome Test:
Project No. 4754-B. Prepared by Midwest Research Institute. 14 p.
93050019 Haworth, S. (1990) Huls America, Inc. Phase 3 Reformat of MRID 00088957.
Bacterial DNA Damage/Repair Suspension Assay: Project No. 026-601-257-6.
Prepared by EG&G Mason Research Institute. 17 p.
93050020 Metz, F.; Van Goethem, D. (1990) Huls America, Inc. Phase 3 Reformat of
MRID 00088958. Bacterial DNA Repair Assay of NUOSEPT 95: Project No.
4822-B. Prepared by Midwest Research Institute. 13 p.
93050021 Myhr, B. (1990) Huls America, Inc. Phase 3 Reformat of MRID 00088959.
Evaluation of NUOSEPT 95 in the Primary Rat Hepatocyte Unscheduled DNA
Synthesis Assay: Project No. 20991. Prepared by Litton Bionetics. 21 p.
93050022 Thilager, A. (1990) Huls America, Inc. Phase 3 Reformat of MRID 00088960. An
Evaluation of Carcinogenic Potential of NUOSEPT 95 Employing the C3H/10T
1/2 Cell Transformation Assay: Project No. 601-257-8. Prepared by EG&G
Mason Research Institute. 23 p.
93050023 Schechtman, L. (1990) Huls America, Inc. Phase 3 Reformat of MRID 00088961.
Activity of T 1597 in an vitro Mammalian Cell Transformation Assay in the
Absence of Exogenous Metabolic Activation: Project No. T 1597.122. Prepared
by Microbiological Associates. 22 p.
93050024 Thilager, A. (1990) Huls America, Inc. Phase 3 Reformat of MRID 00088962. An
Evaluation of Carcinogenic Potential of R-l 162 (NUOSEPT 95) Employing
C3H/1OT 1/2 Cell Transformation System: Project No. 026-205-435-8. Prepared
by EG&G Mason Research Institute. 24 p.
93050025 Thilagar, A. (1990) Huls America, Inc. Phase 3 Reformat of MRID 00088963. An
Evaluation of Carcinogenic Potential of R-l 143 (NUOSEPT 95) Employing
C3H/10T 1/2 Cell Transformation System: Project No. 026-205-437-8. Prepared
by EG&G Mason Research Institute. 24 p.
93050026 Jorgenson, T. (1990) Huls America, Inc. Phase 3 Reformat of MRID 00088953.
Dominant Lethal Study of NUOSEPT 95: Project No. LSC-8654. Prepared by
SRI International. 81 p.
2. Open Literature
PHED Surrogate Exposure Guide. D1997. Estimates of Worker Exposure from the Pesticide
Handler Exposure Database Version 1.1. May 1997.
52
D
-------
3. Website References
Environmental Protection Agency (EPA), 2002. ECOTOX User Guide: ECOTOXicology
Database System. Version 3.0. http://www.epa.gov/ecotox/.
Environmental Protection Agency (EPA), 2004. Overview of the Ecological Risk Assessment
Process in the Office of Pesticide Programs U.S. Environmental Protection Agency -
Endangered and Threatened Species Effects Determinations, Appendix A, Section IIB,
pg.81. US Environmental Protection Agency. January 24, 2004.
http://www.epa.gov/oppfeadl/endanger/consultation/ecorisk-overview.pdf
Environmental Protection Agency (EPA), 2005a. Chemical Screening Tool for Exposures and
Environmental Releases. February 2005.
http ://www. epa. gov/opptintr/exposure/docs/chemsteer.htm.
Environmental Protection Agency (EPA), 2005b. Estimation Program Interface (EPI) Suite. US
Environmental Protection Agency, http://www.epa.gov/oppt/exposure/docs/episuite.htm.
Food and Drug Administration (US FDA), Center for Food Safety & Applied Nutrition
(CFSAN). 2002. Preparation of Food Contact Notifications and Food Additive Petitions
for Food Contact Substances: Chemistry Recommendations. April 2002.
http ://www. cfsan. fda. gov/~dms/opa2pmnc. html.
Food and Drug Administration (US FDA), Center for Food Safety & Applied Nutrition
(CFSAN). 2005. CEDI/ADI Table: Publicly Available Database of Cumulative
Estimated Daily Intakes and Acceptable Daily Intakes. May 2005.
http ://www. cfsan. fda. gov/~dms/opa-tedi. html.
4. Supporting Documents
Cinalli, Christina, et al, 1992. A Laboratory Method to Determine the Retention of Liquids on
the Surface of Hands. Prepared for Environmental Protection Agency, Office of
Pollution Prevention and Toxics. EPA Contract No. 68-02-4254. September 1992.
Environmental Protection Agency (EPA), 1997a. Standard Operating Procedures (SOPs) for
Residential Exposure Assessments. Health Effects Division, Office of Pesticide
Programs.
Environmental Protection Agency (EPA), 1997b. The Use of Models for Estimating Exposure
and Risk of Antimicrobials in Metalworking Fluids. Memorandum from Winston Dang.
Environmental Protection Agency (EPA), 1999. Evaluation of the Chemical Manufacturers
Association Antimicrobial Exposure Assessment Study (Amended on December 8,
1992). Memorandum from Siroos Mostaghimi, Ph.D., Environmental Engineer to Julie
Fairfax, PM #36. November 4, 1999.
53 D
-------
Environmental Protection Agency (EPA), 2000. Options for Revising CEB's Model for
Screening Level Estimates of Dermal Exposure. Chemical Engineering Branch:
Economics, Exposure, and Technology Division, Office of Pollution Prevention and
Toxics. June 2000.
Environmental Protection Agency (EPA), 2001. Standard Operating Procedures (SOPs) for
Residential Exposure Assessments. Office of Pesticide Programs.
Environmental Protection Agency, 2005. Summary of Antimicrobial Standard Operating
Procedure (SOP) Assumptions for Residential and Occupational Exposure Assessments,
January 2005.
54 D
-------
Appendix E. Generic Data Call-In
55
-------
Appendix F. Product Specific Data Call-In
56
-------
Appendix G. Batching of Azadioxabicyclooctane Products for Meeting Acute Toxicity
Data Requirements for Reregistration
In an effort to reduce the time, resources and number of animals needed to fulfill the
acute toxicity data requirements for reregistration of products containing azadioxabicyclooctane
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. Not with-standing the batching process, the Agency reserves the right
to require, at any time, acute toxicity data for an individual product should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or
cite a single battery of six acute toxicological studies to represent all the products within that
batch. It is the registrants' option to participate in the process with all other registrants, only
some of the other registrants, or only their own products within a batch, or to generate all the
required acute toxicological studies for each of their own products. If a registrant chooses to
generate the data for a batch, he/she must use one of the products within the batch as the test
material. If a registrant chooses to rely upon previously submitted acute toxicity data, he/she
may do so provided that the data base is complete and valid by today's standards (see acceptance
criteria attached), the formulation tested is considered by EPA to be similar for acute toxicity,
and the formulation has not been significantly altered since submission and acceptance of the
acute toxicity data. Regardless of whether new data is generated or existing data is referenced,
registrants must clearly identify the test material by EPA Registration Number. If more than one
confidential statement of formula (CSF) exists for a product, the registrant must indicate the
formulation actually tested by identifying the corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow
the directions given in the Data Call-In Notice and its attachments appended to the RED. The
DCI Notice contains two response forms which are to be completed and submitted to the Agency
within 90 days of receipt. The first form, "Data Call-In Response," asks whether the registrant
will meet the data requirements for each product. The second form, "Requirements Status and
Registrant's Response," lists the product specific data required for each product, including the
standard six acute toxicity tests. A registrant who wishes to participate in a batch must decide
whether he/she will provide the data or depend on someone else to do so. If a registrant supplies
the data to support a batch of products, he/she must select one of the following options:
Developing Data (Option 1), Submitting an Existing Study (Option 4), Upgrading an Existing
Study (Option 5) or Citing an Existing Study (Option 6). If a registrant depends on another's
data, he/she must choose among: Cost Sharing (Option 2), Offers to Cost Share (Option 3) or
57 D
-------
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.
Two products were found which contain azadioxabicyclooctane as the active ingredient.
These products have been placed into one batch in accordance with the active and inert
ingredients and type of formulation.
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 Registration Number
1528-28
1528-49
Percentage Active Ingredient
50.0
50.0
58
D
-------
Appendix H. List of All Registrants Sent the Data Call-In
International Specialty Products
59
-------
Appendix I. List of Available Related Documents and Electronically Available Forms
Pesticide Registration Forms are available at the following EPA internet site:
http ://www. epa. gov/opprdOO 1 /forms/.
Pesticide Registration Forms (These forms are in PDF format and require the Acrobat reader)
Instructions
1. D Print out and complete the forms. (Note: Form numbers that are bolded can be
filled out on your computer then printed.)
2. D The completed form(s) should be submitted in hardcopy in accord with the
existing policy.
3. D 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 at williams.nicole@epamail.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
8570-28
8570-30
8570-32
8570-34
8570-35
8570-36
8570-37
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
Certification of Compliance with Data Gap Procedures
Pesticide Registration Maintenance Fee Filing
Certification of Attempt to Enter into an Agreement
with other Registrants for Development of Data
Certification with Respect to Citations of Data (in PR
Notice 98-5)
Data Matrix (in PR Notice 98-5)
Summary of the Physical/Chemical Properties (in PR
Notice 98-1)
Self-Certification Statement for the Physical/Chemical
Properties (in PR Notice 98-1)
http://www.epa.sov/opprd001/forms/8570-l.pdf
http://www.epa.sov/opprd001/forms/8570-4.pdf
http://www.epa.sov/opprd001/forms/8570-5.pdf
http://www.epa.sov/opprd001/forms/8570-17.pdf
http://www.epa.sov/opprd001/forms/8570-25.pdf
http://www.epa.sov/opprd001/forms/8570-27.pdf
http://www.epa.sov/opprd001/forms/8570-28.pdf
http://www.epa.sov/opprd001/forms/8570-30.pdf
http://www.epa.sov/opprd001/forms/8570-32.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
5.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
5.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
l.pdf
http://www.epa.sov/opppmsdl/PR Notices/pr98-
l.pdf
60
D
-------
Pesticide Registration Kit
www.epa.gov/pesticides/registrationkit/.
Dear Registrant:
For your convenience, we have assembled an online registration kit that 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. D 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. D Pesticide Registration (PR) Notices
a. D 83-3 Label Improvement Program—Storage and Disposal Statements
b. D 84-1 Clarification of Label Improvement Program
c. D 86-5 Standard Format for Data Submitted under FIFRA
d. D 87-1 Label Improvement Program for Pesticides Applied through
Irrigation Systems (Chemigation)
e. D 87-6 Inert Ingredients in Pesticide Products Policy Statement
f D 90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement
g. D 95-2 Notifications, Non-notifications, and Minor Formulation
Amendments
h. D 98-1 Self Certification of Product Chemistry Data with Attachments.
(This document is in PDF format and requires the Acrobat reader.)
Other PR Notices can be found at http://www.epa.gov/opppmsdl/PR_Notices.
3. D Pesticide Product Registration Application Forms (These forms are in PDF format
and will require the Acrobat reader.)
a. D EPA Form No. 8570-1, Application for Pesticide
Regi stration/Amendment
b. D EPA Form No. 8570-4, Confidential Statement of Formula
c. D EPA Form No. 8570-27, Formulator's Exemption Statement
d. D EPA Form No. 8570-34, Certification with Respect to Citations of Data
e.D EPA Form No. 8570-35, Data Matrix
61
-------
4. D General Pesticide Information (Some of these forms are in PDF format and will
require the Acrobat reader.)
a. D Registration Division Personnel Contact List
b. D Biopesticides and Pollution Prevention Division (BPPD) Contacts
c. D Antimicrobials Division Organizational Structure/Contact List
d. D 53 F.R. 5952, Pesticide Registration Procedures; Pesticide Data
Requirements (PDF format)
e. D 40 CFR Part 156, Labeling Requirements for Pesticides and Devices (PDF
format)
f D 40 CFR Part 158, Data Requirements for Registration (PDF format)
g. D 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:
l.D The Office of Pesticide Programs' Web Site.
2. D 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)D
5285 Port Royal Road D
Springfield, VA 22161 D
The telephone number for NTIS is (703) 605-6000. Please note that EPA is currently in
the process of updating this booklet to reflect the changes in the registration program resulting
from the passage of the FQPA and the reorganization of the Office of Pesticide Programs. We
anticipate that this publication will become available during the Fall of 1998. Their Web site is
www.NTIS.gov.
3. D 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 Web site.
4. D 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 Web site:
ace. orst. edu/info/nptn.
62
-------
The Agency will return a notice of receipt of an application for registration or amended
registration, experimental use permit, or amendment to a petition if the applicant or petitioner
encloses with his submission a stamped, self-addressed postcard. The postcard must contain the
following entries to be completed by OPP:
Date of receipt
EPA identifying number
Product Manager assignment
Other identifying information may be included by the applicant to link the
acknowledgment of receipt to the specific application submitted. EPA will stamp the date of
receipt and provide the EPA identifying File Symbol or petition number for the new submission.
The identifying number should be used whenever you contact the Agency concerning an
application for registration, experimental use permit, or tolerance petition.
To assist us in ensuring that all data you have submitted for the chemical are properly coded and
assigned to your company, please include a list of all synonyms, common and trade names,
company experimental codes, and other names which identify the chemical (including "blind"
codes used when a sample was submitted for testing by commercial or academic facilities).
Please provide a CAS number if one has been assigned.
63 D
------- |