US Environmental Protection Agency
Office of Pesticide Programs
Reregistration Eligibility Decision (RED)
for Tetramethrin
June 23, 2008
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?/EPA
United States
Environmental Protection
Agency
Prevention, Pesticides
and Toxic Substances
(7508P)
EPA 738-R-08-008
Re registration
Eligibility Decision
(RED) Document for
Tetramethrin
June 2008
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Reregistration Eligibility Decision (RED) for
Tetramethrin
List B
Case No. 2660
Approved by: t, '
Steven Bradbury, Ph.D., Director
Special Review and Reregistration Division
Date: June 23, 2008
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TABLE OF CONTENTS
I. Introduction 1
II. Chemical Overview 2
A. Regulatory History 2
B. Chemical Identification 2
C. Use Profile 3
D. Estimated Usage of Pesticide 4
HI. Summary of Tetramethrin Risk Assessments 6
A. Human Health Risk Assessment 6
1. Toxicity of Tetramethrin 7
2. Carcinogenicity of Tetramethrin 9
3. Metabolites and Degradates 10
4. Endocrine Disruption 10
5. Dietary Exposure and Risk (Food and Water) 10
6. Residential Exposure and Risk 10
7. Aggregate Exposure and Risk 15
8. Occupational Exposure and Risk 15
9. Cumulative Exposure and Risk 17
10. Tetramethrin Human Incident Reports 18
B. Environmental Risk Assessment 19
1. Environmental Fate and Transport 19
2. Ecological Exposure and Risk 20
3. Adverse Ecological Incidents 23
4. Endangered Species Considerations 24
IV. Risk Management, Reregistration, and Tolerance Reassessment Decision 26
A. Determination of Reregistration Eligibility 26
B. Public Participation 26
C. Regulatory Position 26
1. Regulatory Rationale 26
2. Endocrine Disrupter Effects 27
3. Endangered Species 28
D. Labeling Requirements 28
V. What Registrants Need to Do 30
A. Manufacturing Use Products 30
1. Additional Generic Data Requirements 30
2. Labeling for Manufacturing-Use Products 30
B. End-Use Products 30
1. Additional Product-Specific Data Requirements 30
2. Labeling for End-Use Products 31
C. Labeling Changes Summary Table 32
Appendix A. Non-Food and Non-Feed Use Patterns Subject to the Reregistration of
Tetramethrin 39
Appendix B. Data Supporting Guideline Requirements for Tetramethrin 40
Appendix C. Technical Support Documents 43
Appendix D. Bibliography 44
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Glossary of Terms and Abbreviations
a.i. Active Ingredient
CFR Code of Federal Regulations
CSF Confidential Statement of Formula
DCI Data Call-In
DFR Dislodgeable Foliar Residue
DNT Developmental Neurotoxicity
EC Emulsifiable Concentrate Formulation
EEC Estimated Environmental Concentration
EPA Environmental Protection Agency
EUP End-Use Product
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
G Granular Formulation
GLN Guideline Number
HP High pressure
LC50 Median Lethal Concentration. A statistically derived concentration of a substance that can be expected
to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or
volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in 50% of
the test animals when administered by the route indicated (oral, dermal, inhalation). It is expressed as
a weight of substance per unit weight of animal, e.g., mg/kg.
LOG Level of Concern
LOAEL Lowest Observed Adverse Effect Level
LP Low pressure
mg/kg/day Milligram Per Kilogram Per Day
mg/L Milligrams Per Liter
MOE Margin of Exposure
MRID Master Record Identification (number). EPA's system of recording and tracking studies submitted.
MUP Manufacturing-Use Product
N/A Not Applicable
NDETF Non-Dietary Exposure Task Force
NLAA Not Likely to Adversely Affect
NR Not Required
NOAEL No Observed Adverse Effect Level
OPP EPA Office of Pesticide Programs
OPPTS EPA Office of Prevention, Pesticides and Toxic Substances
PCA Percent Crop Area
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
ppm Parts per Million
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose
RQ Risk Quotient
SF Safety Factor
SLC Single Layer Clothing
SLN Special Local Need (Registrations Under Section 24(c) of FIFRA)
TGAI Technical Grade Active Ingredient
USDA United States Department of Agriculture
UF Uncertainty Factor
UFdb Database Uncertainty Factor
IV
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TETRAMETHRIN TEAM MEMBERS
Office of Pesticide Programs:
Health Effects Risk Assessment
Becky Daiss
Marquea King
Abdallah Khasinawah
Matt Crowley
Susan Hummel
Ecological Fate and Effects Risk Assessment
William Eckel
Wanda Hall
Richard Lee
Ibrahim Abdel-Saheb
Dana Spatz
Biological and Economics Analysis Assessment
LaVerne Dobbins
Nikhil Mallampalli
Jihad Alsadek
Registration Division
Richard Gebken
Carmen Rodia
Risk Management
Jacqueline Guerry
Monica Wait
Neil Anderson
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Abstract
The Environmental Protection Agency (EPA or the Agency) has completed the human
health and environmental risk assessments for tetramethrin and is issuing its risk management
decision. Tetramethrin is not registered for use on food and has no U.S. tolerances associated
with its use; therefore, it is not subject to Food Quality Protection Act (FQPA). The risk
assessments, which are summarized below, are based on the review of the required database
supporting the use patterns of currently registered products and additional data provided by the
technical registrants, Valent BioSciences Corporation and Sumitomo Chemical Company, Ltd.
Tetramethrin is part of the pyrethroid class of pesticides and was first registered in 1968.
It is a broad spectrum, non-systemic, synthetic pyrethroid used to control flying and crawling
insects in a number of commercial, horticultural and residential applications. Commercial
applications include space, broadcast and crack-and-crevice treatment in a variety of
commercial, industrial, residential, and institutional sites. Horticultural applications include
foliar and fogger treatment on non-food plants. Residential uses include pest control in homes
and outdoor domestic structures, on gardens and direct application to cats, dogs and horses. The
registered uses of tetramethrin are not expected to adversely impact groundwater or surface
water; therefore, a drinking water assessment was not performed. There are no food uses of
tetramethrin or potential for dietary exposures, so no dietary risk assessment was conducted.
Therefore, the reregi strati on action considered only potential residential (inhalation and
incidental oral), occupational (inhalation only), and ecological risks. No endpoints were selected
for dermal exposure because no effects were observed at the limit dose in available acceptable
dermal toxicity studies.
For residential handler inhalation risk, calculated Margins of Exposure (MOEs) for all
scenarios assessed were below the Agency's Level of Concern (LOG) (MOEs > 1,000) and
therefore are not of concern. For residential post-application inhalation and incidental oral risks,
the MOEs are all greater than the target MOE of 1,000 at the 99.8 percentile of the CARES
probabilistic risk assessment and are also not of concern.
Occupational handler and post-application inhalation exposures were assessed. All of the
MOEs are greater than the Agency's target occupational MOE of 1,000 without respirators, and
therefore, the inhalation risks are not of concern. The MOEs for the occupational post-
application scenarios assessed exceed the Agency's target MOE of 1,000 and are not of concern.
The Agency evaluated potential ecological risk from both indoor and outdoor uses of
tetramethrin. Although the Agency believes exposure to non-target organisms is unlikely,
tetramethrin is considered highly toxic to aquatic organisms. Therefore, the Agency is limiting
all outdoor uses to localized spot treatments, with the exception of (1) barrier, perimeter or band
applications to soil or vegetation around structures up to a maximum of 10 feet away from the
building; and (2) band applications to building foundations, up to a maximum of 3 feet up the
walls of the building. Since outdoor uses will be limited to spot treatments, no additional
mitigation measures for these uses are required. No direct or indirect effects to endangered
species are expected due to applications of tetramethrin, except the potential for direct effects for
Listed insects or indirect effects to plants if they have an obligate relationship with a Listed
insect pollinator.
VI
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I. Introduction
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988
to accelerate the reregistration of products with active ingredients registered prior to November
1, 1984. The amended Act calls for the development and submission of data to support the
reregistration of an active ingredient, as well as a review of all submitted data by the U.S.
Environmental Protection Agency (referred to as EPA or "the Agency"). Reregistration involves
a thorough review of the scientific database underlying a pesticide's registration. The purpose of
the Agency's review is to reassess the potential risks arising from the currently registered uses of
the pesticide, to determine the need for additional data on health and environmental effects, and
to determine whether or not the pesticide meets the "no unreasonable adverse effects" criterion
of FIFRA.
This document summarizes EPA's human health and ecological risk assessments and
reregistration eligibility decision (RED) for tetramethrin. The document consists of six sections.
Section I contains the regulatory framework for reregistration; Section II provides an overview
of the chemical and a profile of its use and usage; Section III gives an overview of the human
health and environmental effects risk assessments; Section IV presents the Agency's decision on
reregistration eligibility and risk management; and Section V summarizes the label changes
necessary to implement the risk mitigation measures outlined in Section IV. Finally, the
Appendices list related information, supporting documents, and studies evaluated for the
reregistration decision. The risk assessments for tetramethrin and all other supporting documents
are available in the Office of Pesticide Programs (OPP) public docket
(http://www.regulations.gov) under docket number EPA-HQ-OPP-2008-0014.
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II. Chemical Overview
A. Regulatory History
Tetramethrin was first registered in the United States in 1968. Current technical
registrants include Valent BioSciences Company and Sumitomo Chemical Corporation.
Tetramethrin is on reregi strati on List B; thus no Registration Standard was completed.
Currently, there are 58 end-use registrants and approximately 300 end-use products
containing tetramethrin, of which approximately 20 are manufacturing formulations.
Tetramethrin is not registered for direct application to agricultural crops and there are no food
tolerances for specific raw agricultural commodities. There are no proposed new uses by any of
the registrants for tetramethrin as part of this reregi strati on.
Prior to the reregi strati on of this active ingredient, the registrants have requested and the
Agency has approved a number of amendments to delete uses or certain registrations for
products containing tetramethrin. From 1996 through 2007, the registrants canceled all
greenhouse uses of tetramethrin and have also voluntarily canceled certain tetramethrin products.
These regulatory actions were published in the Federal Register for public comment and were
subsequently approved by the Agency.
B. Chemical Identification
TETRAMETHRIN:
Tetramethrin, [(1,3,4,5,6,7-hexahydro-l,3-dioxo-2H-isoindol-2-yl)methyl 2,2-dimethyl-
3-(2-methyl-l-propenyl)cyclopropanecarboxylate] is a mixture of four stereoisomers designated
as 1R - trans, 1R - cis, IS- trans, and 1S - cis in an approximate ratio of 4:1:4:1. The first two
isomers are the most insecticidally active, and a mixture of the two has been termed 'd-
tetramethrin' and has the tradename Neo-Pynamin Forte (Sumitomo). Neo-Pynamin Forte is not
registered in the U.S., but toxicity data on this material have been submitted to fulfill data
requirements for tetramethrin.
Common Name: Tetramethrin
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Chemical Name:
(1,3,4,5,6,7-hexahydro-l,3-dioxo-2H-isoindol-2-yl)methyl 2,2-
dimethyl-3-(2-methyl-l-propenyl)cyclopropanecarboxylate
Chemical Class:
Case Number:
Synthetic pyrethroid
2660
EPA Chemical (PC) Code: 069003
CAS Number: 7696-12-0
Empirical Formula: Ci9H25NO4
Technical Registrants:
Valent BioSciences Corporation
Sumitomo Chemical Company
Table 1. Physicochemical Properties of Technical Grade Tetramethrin.
Parameter
Melting point/range
Molecular Weight
Density
Water solubility
Solvent solubility
Vapor pressure
Dissociation constant, pKa
Octanol/water partition coefficient,
Log(Kow)
UV/visible absorption spectrum
Value
68 - 70 °C
331.4g/mol
1.1 specific gravity at 20 °C
1.83mg/Lat25°C
>2 g/100 mL in acetone, ethanol, methanol, hexane and n-octanol
0.944 mPa at 30 °C
Not available
logPow = 4.6at25°C
Not available
c.
Use Profile
The following information on the currently registered uses includes an overview of use
sites and application methods. A detailed table of the uses of tetramethrin eligible for
reregi strati on is contained in Appendix A.
Type of Pesticide: Tetramethrin is a broad-spectrum, first-generation synthetic pyrethroid
insecticide. Pyrethroids are synthetic esters derived from naturally occurring pyrethrins
(insecticides derived from the extract of chrysanthemum flowers). Tetramethrin is a rapid
knockdown agent against flying and crawling insects. Tetramethrin may be co-formulated with
synergists (e.g., PBO and MGK-264), other active ingredients such as pyrethrins and other
pyrethroids (e.g., permethrin, allethrins, phenothrin, resmethrin, and cypermethrin), and growth
inhibitors (e.g., fenoxycarb) for greater effectiveness and to control a broader spectrum of insect
pests. These other active ingredients are more persistent than tetramethrin and provide residual
activity against insects not exposed initially.
Target Organisms: The primary target pests are flying and crawling insects such as wasps,
hornets, roaches, ants, fleas, and mosquitoes.
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Mode of Action: Tetramethrin is a type 1 pyrethroid (i.e., lacking a cyano group at the a carbon
position of the alcohol moiety). Type 1 pyrethroids act on axons in the peripheral and central
nervous system by interacting with sodium channels in mammals and/or insects. Tetramethrin is
a nerve cell membrane sodium channel modulator, which interferes with entrance of sodium ions
into the channel, leading to hyperactivity of the nervous system which can result in paralysis
and/or death.
Use Sites: Commercial applications include space sprays, broadcast surface treatments, and
crack and crevice treatments in a variety of industrial and institutional sites including: indoor
non-food areas; animal premises (not used for human consumption); and outdoors as localized
space and contact sprays on ornamental plants and perimeter treatments (sidewalks,
entranceways, outside surfaces of buildings, etc.).
Residential uses include: pest control in homes as a space spray, general surface spray, spot and
crack and crevice applications, on house plants, clothing and bedding, pet premises, and direct
applications to pets. Outdoors it is used as localized space and contact spray on ornamental
plants and perimeter treatments (sidewalks, decks, patios, outside surfaces of buildings, etc.).
Horticultural applications include foliar and fogger treatment on non-food plants. There are no
registered food use applications for tetramethrin.
Use Classification: Tetramethrin products are designated as general use. However, some end
use products indicate they are for use by pest control operators (PCOs) only.
Formulation Types: Pressurized liquid, ready-to-use (RTU) liquids, emulsifiable concentrates,
and liquid concentrates.
Application Methods: Tetramethrin is applied by aerosol can, handheld sprayers, foggers, and
mechanical sprayers.
Application Rates: Tetramethrin application rates vary depending on the use pattern, indoor or
outdoor use, and consumer and professional or commercial operator use. Typical concentrations
of active ingredient (a.i.) in residential use products, including ready to use (RTU) (e.g. ant and
roach sprays, wasp and hornet sprays) and indoor and outdoor aerosols or aqueous sprays for
crawling and flying insects, range between 0.1 % and 0.25%. Indoor total release foggers are
typically around 0.54% a.i. Sprays designed for use on pets are typically 0.063% a.i.
Emulsifiable concentrate formulations are approximately 2.5% a.i. The maximum single
application rate to an outdoor site is 0.00002 Ib a.i./sq ft.
Application Timing: Tetramethrin is typically labeled for use "as needed."
D. Estimated Usage of Pesticide
Based on data provided to the Agency by the tetramethrin registrants, it appears that
tetramethrin usage has increased over the past 5 years. This is likely due to the fact that
pyrethroids are alternatives to several organophosphate pesticides, which are no longer registered
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for indoor residential areas. The Agency estimates annual usage of tetramethrin to be between
15,000 and 30,000 pounds (Ibs) a.i. However, tetramethrin use data is extremely limited and
difficult to interpret because tetramethrin products may be stored for periods of time and
produced only as inventory is exhausted. In addition, based on its localized use pattern and "use
as needed" directions, sales or production data does not accurately reflect usage.
Based on use information provided to the Agency by the tetramethrin registrants, the
majority of tetramethrin use is in residential outdoor spaces. It appears residential indoor use
sites and institutional and industrial sites make up a small percentage of tetramethrin use.
Further, tetramethrin is primarily used by residential consumers as opposed to PCOs. Sources
suggest that less than 1,000 Ibs a.i. are used annually by professional applicators.
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HI. Summary of Tetramethrin Risk Assessments
The following is a summary of EPA's revised human health and ecological risk
assessments for tetramethrin, as presented fully in the documents, Tetramethrin Risk Assessment
for Reregistration Eligibility Decision, dated June 18, 2008 and the Revised Environmental Fate
and Ecological Risk Assessment for the Re-registration Eligibility Decision on Tetramethrin,
dated February 5, 2008, respectively. The purpose of this summary is to assist the reader by
identifying key features and findings of these risk assessments, and to help the reader better
understand conclusions reached in the assessments.
The human health and ecological risk assessment documents and supporting information
listed in Appendix C were used to reach the safety finding and regulatory decision for
tetramethrin. While the risk assessments and related addenda are not included in this document,
they are available from the OPP Public Docket, located at http://www.regulations.gov, under
docket number EPA-HQ-OPP-2008-0014.
EPA's use of human studies in the tetramethrin risk assessment is in accordance with the
Agency's Final Rule promulgated on January 26, 2006, related to Protections for Subjects in
Human Research, which is codified in 40 CFR Part 26.
A. Human Health Risk Assessment
The human health risk assessment incorporates all sources of potential exposure, hazard,
and risks, including both residential and occupational applications. There are no registered food
uses for tetramethrin, and the majority of use is in consumer home products (indoor and outdoor
surface and space sprays). There are also commercial and horticultural uses for tetramethrin.
The EPA released its preliminary risk assessments for tetramethrin for public comment
on February 27, 2008 for a 60-day public comment period (Phase 3 of the public participation
process). The preliminary risk assessments may be found in the tetramethrin public docket. In
response to comments received and additional data submitted during Phase 3, the human health
risk assessment was updated and refined. Major revisions to the tetramethrin human health risk
assessment include the following:
• Elimination of the post-application exposure scenario "outdoor total release
fogger" due to comments received from McLaughlin, Gormley, King Company
that there are no total release aerosols registered for outdoor use.
• Consideration and inclusion of a probabilistic risk assessment model, Cumulative
and Aggregate Risk Evaluation (CARES), for residential post-application
exposure to tetramethrin products in the revised residential exposure risk
assessment.
• Identification of acute inhalation toxicity data, eye and dermal irritation, and skin
sensitization data gaps.
For more information on the revised human health risk assessment, see Tetramethrin Risk
Assessment for Registration Eligibility Decision, dated June 18, 2008, which is available under
docket number EPA-HQ-OPP-2008-0014.
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1. Toxicity of Tetr amethrin
Toxicity assessments are designed to predict whether a pesticide could cause adverse health
effects in humans (including: short-term or acute effects, such as skin or eye damage; and lifetime or
chronic effects, such as cancer, developmental effects, or reproductive effects), and the level or dose at
which such effects might occur.
The toxicity database for tetramethrin contains acceptable acute toxicity, subchronic,
chronic, oncogenecity, and mutagenecity studies. However, the database lacks acceptable
developmental studies and acceptable acute neurotoxicity, subchronic neurotoxicity, and
developmental neurotoxicity (DNT) studies. Although developmental and neurotoxicity studies
are available, these studies are considered inadequate based on the use of
carboxymethylcellulose (CMC) as the dosing vehicle. CMC has been found to decrease the
absorption rate and thereby lessen the potency and toxicity of pyrethroid compounds. Concerns
regarding studies on pyrethroid compounds that used CMC as a vehicle are discussed in
published literature and further emphasized in a EPA report released in a July 18, 2007 draft
document, "Assessing Approaches for the Development of PBPK Models of Pyrethroid
Pesticides" prepared jointly by EPA's Office of Pesticide Programs and Office of Research and
Development. Therefore, new developmental toxicity, and acute, subchronic, and developmental
neurotoxicity studies utilizing an appropriate dosing vehicle are required to fully evaluate
potential risks from exposure to tetramethrin.
Since the tetramethrin database is currently incomplete with respect to data on
developmental and neurotoxicity studies, the Agency applied a ten-fold (lOx) database
uncertainty factor (UFDB) to account for this lack of data.
a.
Acute Toxicity Profile
Tetramethrin is slightly toxic (Toxicity Category III or IV) by the oral and dermal routes
of exposure. However, in acute oral studies in mice with technical tetramethrin and/or
neopynamin forte, clinical signs sometimes included hyper-excitability, muscular fibrillation,
tremor, ataxia, limb paralysis, irregular respiration, lacrimation, and salivation. These effects
were also seen in acute percutaneous studies in rats. Acceptable data on the acute inhalation
toxicity and acute eye and dermal irritation and skin sensitization for technical tetramethrin are
unavailable. The Agency is requiring these data.
Table 2. Acute Toxicity Profile - Tetramethrin (Neopynamin)
Guideline
No.
870.1100
870.1200
870.1200
870.1300
870.2400
870.2500
Study Type
Acute oral [rat]*
Acute dermal [rat]
Acute dermal [rabbit]
Acute inhalation [rat]
Acute eye irritation [rabbit]
Acute dermal irritation
[rabbit]
MRID
42146405
00063574
40276101
Results
LD50 > 5,000 mg/kg
LD50> 5,000 mg/kg
LD50 > 2,000 mg/kg
Toxicity
Category
IV
IV
III
No data
No data
No data
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Table 2. Acute Toxicity Profile - Tetramethrin (Neopynamin)
Guideline
No.
870.2600
Study Type
Skin sensitization [guinea pig]
MRID
Results
Toxicity
Category
No data
* Clinical signs of neurotoxicity (e.g., hyper-excitability, muscular fibrillation, tremor, ataxia etc.) were present at
2,500 and 5,000 mg/kg/day in acute oral studies in rodents.
b. Toxicological Endpoints
The toxicological endpoints used in the human health risk assessment for tetramethrin are
listed in Table 3 below. There are no registered food uses for tetramethrin and dietary and
drinking water exposure to tetramethrin is not expected based on use patterns. Therefore, acute
and chronic reference doses are not required and were not selected for this assessment. Non-
cancer endpoints were selected for inhalation and incidental oral exposures only.
The short-term incidental oral endpoint was selected from a two-generation rat
reproduction study (MRID 00161842) with 1 litter per generation. The systemic toxicity
NOAEL of 25 mg/kg/day was selected based on parental and offspring LOAELs of 150
mg/kg/day. The parental LOAEL is based on decreased body weight and food consumption in
both sexes of FO and Fl parental animals and bile duct hyperplasia in Fl animals. The offspring
LOAEL is based on decreased pup body weight during lactation.
There are no dermal absorption studies available with tetramethrin. However, based on
available dermal absorption studies in pyrethrins/pyrethroid compounds, dermal absorption of
tetramethrin is expected to be very low (i.e., less than 2%). Tetramethrin was tested in a 21-day
dermal toxicity study in rats (MRID 41995004) at doses of 0, 100, 300, or 1,000 mg/kg/day in
5/sex/dose Sprague-Dawley rats. There were no treatment-related systemic toxic effects and a
LOAEL was not established. No endpoints were selected for dermal exposure because no effects
were observed at the limit dose in available acceptable dermal toxicity studies.
The short and intermediate term inhalation exposure endpoint was selected based on two
90-day inhalation toxicity studies in rats conducted in 1991 (MRIDs 42012101 and 41995003).
The systemic toxicity NOAEL of 19.8/20.3 mg/m3 (3.5 mg/kg/day) was selected based on:
increased clinical signs (irregular respiration and bradypnea); decreased body weight gain;
changes in hematology, urinalysis, and blood chemistry; gross necropsy findings in liver;
hepatocellular hypertrophy; and hyaline droplets in kidney in both sexes at the LOAEL of 134
mg/m3 (23.5 mg/kg/day).
A combined uncertainty factor or margin of exposure (MOE) of 1,000 for residential and
occupational scenarios is based on lOx and lOx for interspecies and intraspecies variation plus an
additional database uncertainty factor (UFoe) of lOx for the absence of adequate acute
neurotoxicity, subchronic neurotoxicity, and DNT studies. The neurotoxicity studies are needed
since the target site of tetramethrin is the nervous system and adequate neurotoxicity data are
lacking. The lOx database uncertainty factor is applicable to workers because occupational
exposures may pose neurotoxic and developmental risk concerns. The uncertainty factors (UF)
used to account for interspecies extrapolation and intraspecies variability are also described in Table 3.
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Table 3. Summary of Toxicological Doses and Endpoints for Tetramethrin for Use in Human Risk
Assessments
Exposure
Scenario
Acute and Chronic
Dietary
(general population)
Short-Term
Incidental Oral
(1 - 30 days)
Short-,
Intermediate- Term
Dermal
(1 - 30 days,
1-6 months)
Inhalation
Short-,
Intermediate-Term
(1 - 30 days, 1-6
months)
Cancer (oral,
dermal, inhalation)
Dose Used in Risk
Assessment, UF
Safety Factor and
Level of Concern
Study and Toxicological Effects
Acute and Chronic RfD's were not selected because there are no registered food uses
NOAEL = 25 mg/kg/d
UFA=10
UFH = 10
UFDB = 10
Residential LOC for
MOE = 1,000
Occupational LOC for
MOE = N/A
2-Generation Reproduction (rats)
LOAEL = 150 mg/kg/day based on |
body wt, I food consumption; and bile
duct hyperplasia in Fl females
No risk is expected from this exposure scenario as no hazard was identified in a 21/28 day
dermal toxicity study conducted at the limit dose of 1,000 mg/kg/d.
Inhalation NOAEL =
19.8 mg/m3 (3.5
mg/kg/d (oral
equivalent)
UFA=10
UFH = 10
UFDB = 10
Residential LOC for
MOE = 1,000
Occupational LOC for
MOE = 1,000
90 Day Inhalation Toxicity (rats)
LOAEL = 134 mg/ m3 (23.5
mg/kg/day) based on f clinical signs,
absolute/relative kidney and liver
weights; J, body weight, changes in
hematology, urinalysis, hypertrophic
and gross liver necropsy findings, and
hyaline droplets in the kidney
Group C, possible human carcinogen based on evidence of benign testicular tumors in rats
and increased hepatocellular carcinomas in male mice at the HOT of 1 134 mg/kg/day. Based
on a recent review of the cancer data, HED has determined that tetramethrin would likely be
reclassified under EPA's 2005 Guidelines for Carcinogen Risk Assessment as "Suggestive
Evidence of Carcinogenic Potential."
UF = uncertainty factor (A= Animal/Interspecies, H= Human/Intraspecies, DB=Data Base)
NOAEL = no observed adverse effect level
LOAEL = lowest observed adverse effect level
MOE = margin of exposure
LOC = level of concern
N/A = Not Applicable
2. Carcinogenicity of Tetramethrin
The Agency concluded that, based on the available information, tetramethrin meets the
criteria for Group C, possible human carcinogen. Tetramethrin administered to Sprague-Dawley
rats was associated with a statistically significant dose-related increase in the incidence of
interstitial cell adenomas in the testes in mid- and high-dose males. These results were
reproducible in a second study in Sprague-Dawley rats and another study in Long-Evans rats.
This increase was outside the historical control range for Sprague-Dawley rats. No historical
control data were available on Long-Evans rats. Tetramethrin administration to BeCsFi mice did
not alter the spontaneous tumor profile for this strain of mice. Therefore, the Agency determined
that no chronic cancer risk assessment was necessary. The Agency based its decision on the fact
that this type of tumor (interstitial cell adenomas of the testes) is a benign tumor that does not
progress to a malignant tumor in rats; the tumors occurred at a later stage of the study; the
exposure started in utero; and the treatment did not cause reduction in latency.
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3. Metabolites and Degradates
The Agency reviewed the metabolism of tetramethrin (MRIDs 42448901 and 42448902), and
concluded that for risk assessment, the parent compound, tetramethrin, is the only residue of
lexicological concern. For additional details, refer to the Tetramethrin Risk Assessment for
Registration Eligibility Decision, dated June 18, 2008.
4. Endocrine Disruption
EPA is required under the FFDCA, to develop a screening program to determine whether
certain substances (including all pesticide active and other ingredients) "may have an effect in humans
that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effects
as the Administrator may designate." Following recommendations of its Endocrine Disrupter and
Testing Advisory Committee (EDSTAC), EPA determined that there was a scientific basis for
including, as part of the program, the androgen and thyroid hormone systems, in addition to the
estrogen hormone system. EPA also adopted EDSTAC's recommendation that the Program include
evaluations of potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the
extent that effects in wildlife may help determine whether a substance may have an effect in humans,
FFDCA authority to require the wildlife evaluations. As the science develops and resources allow,
screening of additional hormone systems may be added to the Endocrine Disrupter Screening
Program (EDSP).
When additional appropriate screening and/or testing protocols being considered under the
Agency's EDSP have been developed, tetramethrin may be subjected to further screening and/or
testing to better characterize effects related to endocrine disruption.
5. Dietary Exposure and Risk (Food and Water)
Tetramethrin currently has no registered food uses and there are no tolerances for specific
raw agricultural commodities. Tetramethrin is not registered for direct application to agricultural
crops, livestock animals, or livestock premises, where livestock are used for food. Although
there are no registered food uses for tetramethrin, there are uses in the home where food may be
exposed (e.g., kitchens), but labels for these uses have restrictions to prevent / limit food
exposure such as, "In the home, all food-processing surfaces and utensils should be covered
during treatment or thoroughly washed before use. Cover exposed food." Therefore, dietary
exposure is not of concern.
The Agency did not conduct a quantitative drinking water assessment for tetramethrin,
given the limited extent of potential exposure and the chemical's environmental fate properties.
Tetramethrin is used by individual homeowners or industrial / commercial property owners, in
individual, isolated areas, and in small amounts as opposed to wide scale uses (i.e., for
agriculture or mosquito abatement by public authorities). Because tetramethrin products are not
expected to adversely impact groundwater or surface water (the sources of drinking water), a
quantitative drinking water assessment is not warranted.
6. Residential Exposure and Risk
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Residential exposure assessments consider all potential non-occupational pesticide
exposure. Tetramethrin has a wide variety of residential uses, including use in/on indoor and
outdoor surfaces, and use on pets. Therefore, the Agency has determined that there is a potential
for exposure to tetramethrin in residential settings for homeowners who handle (mix, load, and
apply) products containing tetramethrin, as well as post-application exposure from entering
tetramethrin-treated areas. Non-occupational post-application exposures can result following use
of pesticides by homeowners themselves or following applications by professional pest control
operators in residential or non-residential settings.
Risk assessments have been completed for both residential handler (inhalation only) and
post-application scenarios (inhalation and incidental oral). Though dermal exposure is possible
and expected for residential handler and post-application scenarios of tetramethrin, the Agency
determined a dermal assessment was not necessary because no systemic effects were observed at
the limit dose in dermal toxicity studies in animals.
To estimate residential (inhalation and incidental oral) risks, the Agency calculates a
margin of exposure (MOE), which is the ratio of the toxicity endpoint (NOAEL) selected for risk
assessment to the exposure value. The MOE is then compared to a level of concern (LOG),
which is the same value as the uncertainty factor (UF) applied to a particular toxicity study. The
standard UF is lOOx (lOx to account for interspecies extrapolation and lOx for intraspecies
variation). However, since the tetramethrin database is currently incomplete the Agency applied
a ten fold (lOx) database uncertainty factor (UFDB) to account for this lack of data; thus, for
residential exposures to tetramethrin, MOEs greater than the target LOG of 1,000 are not of
concern to the Agency. For detailed information on the residential risk assessment, see the
Tetramethrin Risk Assessment for Registration Eligibility Decision, dated June 18, 2008.
a. Residential Handler Risks
The Agency determined that exposure to homeowners handling a tetramethrin product is
likely to occur via the inhalation route during the residential use of tetramethrin in a variety of
indoor and outdoor settings. The risk assessment considered three major residential exposure
scenarios, based on the types of equipment and techniques that can potentially be used to make
tetramethrin applications. While some tetramethrin products are packaged as RTU trigger
sprayer bottles, the handler risks calculated from aerosol can application are protective of risks
from trigger sprayer applications because the unit exposure values are lower for trigger sprayer
application. The Agency only considered short-term (1-30 days) inhalation exposure due to
infrequency of use associated with homeowner products and the non-persistence of tetramethrin.
Additionally, as discussed above, dermal exposures were not assessed, because no effects were
observed at the limit dose in available acceptable dermal toxicity studies. The following
scenarios were assessed:
• Mix / Load / Apply liquids with a backpack sprayer or low pressure hand wand.
• Aerosol can application
• Load / Apply liquids with a trigger-pump sprayer.
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Pesticide handler exposure database (PHED) unit exposure values were used to assess
exposures, because chemical-specific monitoring data were not available. The following
assumptions were also used in estimating risks from residential handler exposure to tetramethrin:
• The body weight of an adult handler is 70 kg.
• The amount handled per day is based on formulation type:
o Aerosol can: One 16 ounce can is used per day.
o Trigger- pump Sprayer: 1 gallon of diluted solution per day.
o Low-pressure handwand sprayer: 5 gallons of diluted solution per day.
Table 4 summarizes the inhalation risk estimates for residential handlers of tetramethrin
products. All MOEs are well below the Agency's LOG (MOEs > 1,000 are not of concern), with
values ranging from 75,000 to 100,000.
Table 4. Residential Handler Risk Estimates from General Spray Applications
Exposure Scenario
M/L/A Liquids with
LP Hand-wand or
Backpack Sprayer
Aerosol Can
Application
L/A RTU with a
Trigger-pump
Sprayer
Application Rate
0.02 Ib a.i./gallon
solution
0.25% a.i.
0.02 Ib a.i./gallon
solution
Amount Sprayed per
Day
5 gallons
1 can (16 ozea)
1 gallon
Pound a.i.
handled per day
0.1
0.0025
0.02
Inhalation MOE
82,000
75,000
100,000
M/L/A = Mix / load / apply
LP = Low pressure
L/A = Load / apply
RTU = Ready-to-use
b.
Residential Post-Application Risks
The Agency uses the term "post-application" to describe exposures to individuals that
occur as a result of being in an area that has been previously treated with a pesticide. Unlike
residential handler exposure, where the Agency assumed only adults will be handling and
applying tetramethrin products, individuals of varying ages can potentially be exposed when
reentering or performing activities in areas that have been previously treated. Tetramethrin can
also be used on pets, which can lead to exposure by contact with the treated animals.
Tetramethrin post-application incidental oral exposures may occur after applications are
made to residential areas resulting in residues on surfaces, such as carpets and vinyl flooring.
Post-application inhalation exposures are possible from residue concentrations in air following
applications such as space sprays and fogging applications. Post-application incidental oral
exposures were assessed for children only, and inhalation exposures were assessed for both
adults and children. Again, dermal exposures were not assessed, because no effects were
observed at the limit dose in available acceptable dermal toxicity studies. The following
scenarios were assessed.
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• Inhalation exposure (adults and children) indoors:
o Space spray and total release fogger;
• Inhalation exposure (adults and children) outdoors:
o Handheld foggers and aerosols;
• Incidental oral ingestion (children only) of residues indoors:
o Total release aerosol fogger treatment,
o Aerosol and spray surface treatments,
o Aerosol and spray treatments to pets; and,
• Incidental oral ingestion (children only) of residues outdoors:
o Handheld fogger applications, and
o Aerosol surface treatments.
The Agency assessed the post-application exposure to tetramethrin using two approaches:
a deterministic approach and a probabilistic approach. A deterministic approach uses a point
estimate from a data set, e.g., a single maximum value or an average value, as an input variable
in the exposure model. This approach does not consider the range of potential exposures
incurred by members of a population and does not describe the potential or probability of
exposure to individuals within a population. Rather, the deterministic approach produces an
output value that represents the potential exposure or risk of a group; depending on how the
estimate was generated, the output value may reflect a "central tendency," a "high-end," or an
"upper-bound." In contrast, a probabilistic approach uses the full range of available data and
produces a distribution of values as output, and is recognized as a refinement over the
deterministic assessment. More detail is provided below regarding the probabilistic risk
assessment.
i. Deterministic Risk Approach and Assessment
The February 5, 2008, Tetramethrin: Phase 1 Revised Occupational and Residential
Exposure Assessment and Recommendations for the Reregistration Eligibility Decision presented
results of the Agency's deterministic post-application risk assessment. Risks of concern were
identified for hand-to-mouth exposures following indoor aerosol can space spray treatments
(MOEs of 290 and 430 for children on carpet and vinyl, respectively), inhalation exposure
following indoor aerosol can treatments (MOE of 850 for children), and hand-to-mouth exposure
following indoor ready-to-use liquid spray treatments (MOEs of 570 and 840 for children on
carpet and vinyl, respectively).
ii. Probabilistic Risk Approach and Assessment
In the Tetramethrin Risk Assessment for Registration Eligibility Decision, dated June 18,
2008, the Agency presents the results of the probabilistic exposure assessment, using the
Cumulative and Aggregate Risk Evaluation System (CARES® Version 3.0; http://cares.ilsi.org/),
a publicly available software program. Probabilistic exposure assessment is recognized as a
refinement over deterministic assessment because it allows users to identify percentiles of risk by
using inputs in the form of distributions rather than point estimates.
a. Tetramethrin CARES Post-Application Risk Assessment
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The Agency completed a CARES probabilistic residential exposure and risk assessment,
which verified the CARES assessment that was submitted by tetramethrin registrants Valent
BioSciences Corporation, Sumitomo Chemical Company, LTD, S. C. Johnson & Son, Inc., and
McLaughlin Gormley King Company. CARES utilizes a reference population of 100,000
individuals selected from the 1990 U.S. Census. It is considered appropriate for use in exposure
analysis due to its similarity with the U.S. Census Public Use Micro Data Sample (PUMS), a
statistically representative dataset that contains data for statistical weights from sampled
individuals of the general U.S. population, provided by the U.S. Department of Commerce,
Bureau of the Census, Economics and Statistics Administration. Key sub-populations relevant to
exposure analysis within CARES include different races (e.g., white, black, Hispanic, etc.) and
different age groups (e.g., children 1-3 years old, male 20-54 years old, etc.) (Driver et al, 2008).
CARES simulates daily (24-hour) exposures over the course of one calendar year for
each person in the specified sub-population based on user-specified routes of exposure (e.g.,
dietary, dermal, non-dietary ingestion), empirical data, and exposure algorithms. It can provide
cumulative exposures for more than one chemical, aggregate across exposure routes, and provide
results for different exposure patterns (e.g., acute or chronic exposures). Additionally, each input
(e.g., chemical residue, exposure duration, and mouthing behavior) is described and used as a
distribution in a Monte Carlo simulation to identify percentiles of risk and enable users to
conduct analyses to identify major exposure contributors.
The calculations and algorithms used to estimate exposure for the various scenarios and
routes are consistent with standard Agency practice for residential pesticide exposure
assessment. Risks of concern were not identified for residential handler scenarios in the
deterministic assessment; therefore, the CARES assessment considered only post-application
exposure routes. The tetramethrin exposure scenarios were assessed using standard EPA
algorithms for exposure estimation. Distributional inputs were included in the probabilistic
assessment where possible. The probabilistic assessment assumes post-application exposure
occurs on the "day of application," which is the most conservative assumption.
The tetramethrin CARES assessment calculated risk for adults (defined as males and
females 20 - 49 years old) and children (defined as males and females 1-2 years old). Though
older or younger children may be exposed to tetramethrin, the selection of 1 - 2 year olds is
appropriate since this age group exhibits the highest degree of mouthing behavior - a major route
of exposure for this assessment (Tulve et al., 2002). Combined male/female populations are also
appropriate since the toxicological endpoints used in the risk assessment are not gender specific.
The risk percentages generated by the CARES model correspond only to those individuals who
use tetramethrin as a pesticide (i.e., the population is "users only") and those that reside within
the home. The assessment does not characterize risk relative to the percentage of the population
that does not use tetramethrin.
Exposure factors used in the CARES assessment were determined based on consultation
between EPA and the tetramethrin registrants. Many of the non-tetramethrin-specific
distributional inputs are based on EPA's n-methyl Carbamate Revised Cumulative Risk
Assessment (NMCCRA), the most recent EPA publication using probabilistic methods and
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distributional inputs for residential exposure assessment. Refer to the Tetramethrin: Phase IV
Revised Occupational and Residential Exposure Assessment and Recommendations for the
Reregistration Eligibility Decision, dated June 13, 2008, for more information on the inputs and
distributions considered for the CARES assessment.
Table 5. CARES Residential Post-Application Assessment - Tetramethrin MOEs for Adults (20 - 49 years)
Percentile
100
99.9
99.8
99.7
99.6
99.5
Exposure Scenario and Route
Outdoor Treatment
Inhalation
1,690
2,051
2,117
2,150
2,188
2,215
Indoor Treatment (Spray)
Inhalation (Applicator)
37,336
47,342
48,848
48,848
48,848
48,848
Inhalation (Post-
application)
5,834
6,726
7,162
7,432
7,510
7,673
Table 6. CARES Residential Post-Application Assessment - Tetramethrin MOEs for Children (1-2 years)
Percentile
100
99.9
99.88
99.8
99.7
99.6
99.5
Exposure Scenario and Route
Outdoor Treatment
Ingestion
1,808
2,123
2,188
2,387
2,603
2,771
2,870
Inhalation
,034
,040
,042
,045
,045
,046
,048
Indoor Treatment
Fogger
Ingestion
3,351
5,347
5,487
6,085
6,952
7,951
8,475
Spray
Ingestion
492
942
947
1,092
1,144
1,249
1,333
Inhalation
3,007
3,113
3,130
3,160
3,221
3,246
3,285
Pet Care
Ingestion
3,725
5,135
5,207
5,770
6,131
6,482
6,719
For the tetramethrin CARES probabilistic residential exposure assessment, MOEs below
1,000 were identified only for indoor non-dietary ingestion at the 100, 99.9, and 99.88
percentiles for children 1-2 years old following a spray application. The MOE for this scenario
is greater than 1,000 at the 99.8th percentile (MOE = 1,092). The Agency does not have a current
policy on a "percentile of regulation" for probabilistic residential non-dietary exposure
assessment; however, considering this assessment still reflects the standard, conservative practice
of assessing "users only" on the "day of application," risks do not exceed the Agency's LOG.
7. Aggregate Exposure and Risk
For tetramethrin, short term aggregate risk potentially involves adding exposure estimates
for incidental oral exposure and inhalation exposure pathways for young children. However,
exposures from incidental oral and inhalation pathways may not be aggregated for tetramethrin
because the toxicity endpoints for these exposure routes are not based on common toxic effects
(i.e., body weight changes are considered to be non-specific, and there are no common specific
target organ effects observed in the oral and inhalation toxicity studies.)
8. Occupational Exposure and Risk
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The occupational risk assessment addresses risks to workers who may be exposed to
tetramethrin when mixing, loading, or applying a pesticide (i.e., handlers), and when entering
treated sites for routine tasks (post-application). Exposure for workers generally occurs via the
dermal or inhalation route. However, for tetramethrin, only inhalation exposures were calculated
since there were no treatment related systemic toxic effects at the highest dose tested in the 21
day dermal toxicity study. The target MOE is 1,000 for occupational exposures.
Occupational exposure to tetramethrin was assessed using data from the Pesticide
Handler Exposure Database (PHED), and worker exposure and risk estimates are based on the
best data currently available to the Agency. In addition, standard default assumptions pertaining
to average body weight, work day, and area treated daily were used to calculate risk estimates.
Application rates used in this assessment are derived directly from current tetramethrin labels.
The occupational risk assessment is summarized here. For further detail, see the Tetramethrin
Risk Assessment for Registration Eligibility Decision, dated June 18, 2008.
a. Occupational Handler Exposure and Risks
The term "handler" applies to individuals who mix, load, and apply the pesticide product.
Because most tetramethrin products are packaged in aerosol cans, most of the uses will involve
application only (i.e., there is no mixing or loading activities for aerosol cans). However, some
products are packaged as ready-to-use liquids or liquid concentrates, which are applied with
mechanical sprayers, compressed air sprayers or foggers (i.e., equipment and formulation that do
require mixing and loading activities). Based upon the currently registered product labels, the
Agency assessed the following occupational handler scenarios:
Pesticide Control Operator Scenarios
1. Mix/Load/Apply (M/L/A) liquids with a backpack sprayer or low pressure handwand
2. M/L/A liquids with handheld fogging equipment
3. Applying with an aerosol can
4. Load/Apply (L/A) liquids with a trigger-pump sprayer
Occupational handler exposure assessments are conducted by the Agency using different
levels of protection. The Agency typically evaluates all exposures with minimal protection and
then adds protective measures in a tiered approach to determine the level of protection necessary
to obtain appropriate MOEs. Dermal exposures were not assessed because no systemic effects
were observed at the limit dose in available acceptable dermal toxicity studies. Inhalation
exposures were assessed at the minimum level of protection, which is no respirator. Risk
estimates (i.e., MOEs) for the general surface and space sprays and handheld fogger handler
scenarios are summarized in Tables 7 and 8. All MOEs are above the target MOE of 1,000
(ranging from 10,000 to 50,000), and therefore, are not of concern.
Table 7. Short / Intermediate-term Inhalation MOEs for Occupational Handlers Applying General Surface
and Space Sprays
Exposure Scenario
Unit
ExposureA
(jig/lb a.i.)
Application
Rate8
Amount
Sprayed
per Day
Ib a.i.
handled
per day
Inhalation
DoseE
(mg/kg/day)
Inhalation
MOEF
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Table 7. Short / Intermediate-term Inhalation MOEs for Occupational Handlers Applying General Surface
and Space Sprays
Exposure Scenario
M/L/A liquids with LP
hand-wand or backpack
sprayer
L/A liquids with Trigger-
pump Sprayer
Aerosol can application
Unit
ExposureA
(jig/lb a.i.)
30
123
1300
Application
Rate8
0.02 Ib
a.i./gallon
solution
0.25% a.i.
Amount
Sprayed
per Day
40 gallons0
2 gallons0
6 cansD
Ib a.i.
handled
per day
0.8
0.04
0.015
Inhalation
DoseE
(mg/kg/day)
0.00034
0.00007
0.00028
Inhalation
MOEF
10,000
50,000
13,000
A. Unit Exposure values are from PHED (See Table A12)
B. Application rates are from labels 769-939 (0.02 Ib a.i./gallon solution) and 73049-165 (0.25%)
C. Based upon ExpoSAC Policy 9.
D. Screening level estimate based upon professional judgment.
E. Inhalation dose (mg/kg/day) = [unit exposure (ug/lb a.i.) * 0.001 mg/ g * Ib a.i. handled per day)] / Body weight
(70 kg).
F. MOE = NOAEL (3.5 mg/kg/day) / Dose
Table 8. Inhalation MOEs for Occupational Handlers Applying Sprays using Handheld Fogging Equipment
Application Rate
(Ib a.i./ft3)A
0.00000001
(mg/m3)8
0.218
Inhalation
Exposure0
(mg/day)
0.0174
Inhalation DoseD
(mg/kg/day)
0.00025
Inhalation
MOEE
14,000
A. Based on EPA Reg. No. 73049-432: 1 fluid ounce of 0.10% RTU solution per 600 square feet at an
approximate spray height of 8 feet. [1 fl.oz./600 ft2] * [1 gallon/128 fl.oz.] * [8.35 Ib soln/gallon] * [0.1% a.i.] /
8 ft = 0.0000000 llba.i./ft3
B. Application rate (mg/m3) = 0.00000001 Ib a.i./ft3 * [454000 mg/lb] * [35 ft3/m3] = 0.218 mg/m3
C. Inhalation Exposure (mg/day) = [Application Rate (mg/m3) * Breathing Rate (1 m3/hr) * Exposure Time (8
hours/day)] / Outdoor Dilution Factor (100)
D. Inhalation Dose (mg/kg/day) = Inhalation Exposure (mg/day) / Body Weight (70 kg)
E. MOE = NOAEL/Dose where the NOAEL is 3.5 mg/kg/day.
b. Occupational Post-Application Exposure and Risk
The Agency uses the term "post-application" to describe exposures to individuals that
occur as a result of being in an environment that has been previously treated with a pesticide
(also referred to as re-entry exposure). The Agency did not conduct a post-application risk
assessment for tetramethrin for occupational exposures. Although dermal exposure is possible
and expected, no occupational post-application assessment was conducted because no systemic
effects were observed at the limit dose in available acceptable dermal toxicity studies in animals.
Additionally, inhalation post-application exposures were not assessed because tetramethrin is
applied in areas where prolonged occupational presence in areas with low ventilation following
application (e.g., following greenhouse applications) is not expected.
9. Cumulative Exposure and Risk
Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish,
modify, or revoke a tolerance, 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."
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Tetramethrin is a member of the pyrethroid class of pesticides. Although all pyrethroids
alter nerve function by modifying the normal biochemistry and physiology of nerve membrane
sodium channels, EPA is not currently following a cumulative risk approach based on a common
mechanism of toxicity for the pyrethroids. Although all pyrethroids interact with sodium
channels, there are multiple types of sodium channels, and it is currently unknown whether the
pyrethroids have similar effects on all channels. Nor do we have a clear understanding of effects
on key downstream neuronal function e.g., nerve excitability, nor do we understand how these
key events interact to produce their compound specific patterns of neurotoxicity. There is
ongoing research by the EPA's Office of Research and Development and pyrethroid registrants
to evaluate the differential biochemical and physiological actions of pyrethroids in mammals.
When available, the Agency will consider this research and make a determination of common
mechanism as a basis for assessing cumulative risk. For information regarding EPA's
procedures for cumulating effects from substances found to have a common mechanism on
EPA's website at http://www.epa.gov/pesticides/cumulative/.
10. Tetramethrin Human Incident Reports
The OPP Incident Data System (IDS) and Poison Control Centers (PCC) databases were
consulted for poisoning incident data on the active ingredient tetramethrin. Reports submitted to
the IDS and PCC typically represent anecdotal reports or allegations only; therefore, no
conclusions can be drawn implicating tetramethrin as a cause of any of the reported health
effects unless supported by results from other data sources or unless the individual incidents are
well documented.
There are approximately 98 reported incidents in the IDS database over the last five years
(2002 to the present) for products containing tetramethrin. Since there are no pesticide products
for which tetramethrin is the sole active ingredient, reported incidents cannot be solely attributed
to exposure to tetramethrin. The incidents are classified as mild to moderate human incidents
(less than 1% involved major effects). The majority (approximately 85%) of incidents with
documented health effects reported either no effects or mild effects resulting from tetramethrin-
related exposures. The majority of the symptoms included respiratory irritation, shortness of
breath, blisters, welts, hives, dizziness, rashes, coughing, and eye irritation, which are similar to
that of other pyrethroid compounds. The PCC incidents involved a wide range of effects
including cardiovascular, gastrointestinal, respiratory, dermal, and ocular effects.
The Agency believes the number of reported incidents is small in relation to the estimated
usage of tetramethrin, which is approximately 15,000 to 30,000 pounds per year. Tetramethrin
applications are primarily residential localized or spot treatments via aerosol or RTU sprays on
an "as needed" basis (residential exposures accounted for 98% of the reported cases involving
tetramethrin); therefore, given this broad spectrum residential use pattern, the Agency estimates
the number of applications per year could range in the hundreds of thousands or greater.
While the incident report does inform the Agency further regarding possible dermal and
respiratory irritations attributed to pyrethroids, it does not garner greater concern for the active
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ingredient tetramethrin solely. The Agency is currently investigating the pyrethroid class of
chemicals and aggravated dermal and asthmatic reactions.
B. Environmental Risk Assessment
Tetramethrin is used in residential and industrial/commercial areas in relatively small
quantities through aerosols, foggers, and space sprays. On a nationwide basis, tetramethrin use is
relatively limited. It is not used on a wide scale, such as agriculture or in mosquito abatement by
public authorities. The use pattern is therefore in individual, isolated areas, and again, in small
amounts. Tetramethrin also decomposes rapidly by photolysis and hydrolysis. The localized use
pattern of tetramethrin, combined with the low total pounds used on a national basis, and rapid
degradation due to photolysis and hydrolysis, make it highly unlikely that non-target organisms
will be exposed at harmful levels. Non-target organism exposure is most likely to result from
outdoor uses, such as spraying wasp or hornet nests under the eaves of houses, and backyard
foggers for flying insects. Further, because of the very rapid photolytic decomposition of
tetramethrin, only those organisms present at the time of spraying are likely to be exposed and
are at risk of acute effects.
The standard models (GENEEC, PRZM-EXAMS, T-REX, Terrplant) used to calculate
and quantify risks to terrestrial and aquatic organisms do not fit with the localized use patterns of
tetramethrin. As a result, tetramethrin's ecological risk assessment did not follow the standard
methodology and the acute risks will be characterized qualitatively rather than quantitatively. A
summary of the Agency's environmental fate and effects risk assessment is presented below.
For detailed discussion of all aspects of the environmental risk assessment, please see the
February 5, 2008 Revised Environmental Fate and Ecological Risk Assessment Chapter in
Support of Phase I of the Re-registration Eligibility Decision on Tetramethrin, which is available
under docket number EPA-HQ-OPP-2008-0014.
1. Environmental Fate and Transport
Tetramethrin is not a persistent pyrethroid in the environment. It may be co-formulated
with synergists, other active ingredients such as pyrethrins and pyrethroids, and growth
inhibitors. These other ingredients are more persistent than tetramethrin and provide residual
activity against insects not initially exposed. Tetramethrin decomposes rapidly by photolysis and
hydrolysis in shallow, non-turbid water. Photolysis in air is expected to be rapid (half-life 30
minutes) based on reaction with ozone. Tetramethrin is more susceptible to hydrolysis at pH 7
and 9 than pH 5. The half-lives were 15.9 - 19.7 days (pH 5), 0.89 - 1.06 days (pH 7), and
0.009 - 0.014 days (pH 9). Tetramethrin is slightly mobile in soil (Koc value range from 1,249-
2,939), has a vapor pressure of 7.1x10-6 mm Hg, water solubility of 1.83 mg/L, and an estimated
Henry's law constant of 1.7x10-6 atm-m3/mol-l.
At least nine degradates were detected in a column leaching study, and in an aerobic soil
metabolism study, seven degradates were identified including one (acid-NPY) that retains the
entire ester structure and possibly the mode of action of the parent tetramethrin. However, it too
is subject to rapid hydrolysis, and therefore, exposure to acid-NPY is unlikely. In two acceptable
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field dissipation studies, tetramethrin dissipated from the upper 15 cm of soil with a DT50 (time
to 50% degradation) of 3 hours in a California study, and less than one hour in a Florida study.
No toxicity data are available for tetramethrin degradates.
Indoor uses of tetramethrin are not expected to result in significant exposure pathways to
terrestrial and aquatic ecosystem as they are confined indoors, and tetramethrin rapidly degrades
in hours. While there are numerous outdoor uses, these applications are limited to spot
treatments in localized areas and, again, the degradation of tetramethrin to non-toxic degradates
is rapid. There is potential for tetramethrin residues to be transported to aquatic systems from
use in drainage systems, but only in acidic water where hydrolysis is slower. However, the
Agency believes exposure is unlikely because product labels prohibit direct application to water.
2. Ecological Exposure and Risk
The possible exposure mechanisms considered following tetramethrin applications were
runoff, spray drift, and direct spray. Only direct spray is considered to be a completed exposure
pathway, since tetramethrin is too non-persistent to be transported via runoff, and it is not used in
sufficient quantities for spray drift to be of concern. As stated above, neither indoor nor outdoor
uses of tetramethrin are expected to result in significant exposure pathways to terrestrial and
aquatic ecosystems since they are limited and tetramethrin degrades rapidly. Given that
degradation of tetramethrin to non-toxic degradates is rapid, the primary risk will be acute
exposure to tetrramethrin at the time of application and a brief period thereafter.
Acute toxicity data from studies submitted by pesticide registrants along with the
available open literature were used to evaluate the potential direct effects of tetramethrin aquatic
and terrestrial organisms. This includes toxicity data on the technical grade active ingredient,
degradates, and formulated products when available. The open literature studies are indentified
through EPA's ECOTOX database (https://cfpub.epa.gov/ecotox/X which employs a literature
search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife.
The evaluation of both sources of data can also provide insight into the direct and indirect effects
of tetramethrin on biotic communities from loss of species that are sensitive to the chemical and
from changes in structure and functional characteristics of affected communities.
a. Terrestrial Organisms
No terrestrial modeling was conducted for tetramethrin because exposure of non-target
organisms to harmful levels is unlikely based on the localized use patterns, low total pounds used
on a national basis, and rapid degradation due to photolysis and hydrolysis. Instead, the Agency
conducted a qualitative assessment using submitted studies and review of the literature.
The Agency developed an effects characterization, which describes the potential effects a
pesticide can produce in a terrestrial organism, and is based on registrant-submitted studies that
describe acute effects toxicity information for various terrestrial animals. Table 9 summarizes
the specific measurement endpoint value selected to evaluate risks for tetramethrin to mammals
and birds.
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Table 9. Summary of Specific Measurement Endpoint Values Selected to Evaluate Risk for the Associated
Terrestrial Animal Assessment Endpoints
Assessment
Ends
Survival and
Reproduction
of Birds,
Reptiles and
Amphibians
Survival and
Reproduction
of Terrestrial
Mammals
Survival of
Terrestrial
Invertebrates
and Beneficial
Insects
Acute
Measurement
Endpoint
(most
sensitive)
Acute oral
toxicity
Acute dietary
toxicity
Acute oral
toxicity, LD50
Dermal
toxicity, LD50
Inhalation
toxicity, LC50
Reproduction
NOAEL
Contact LD50
(ug/bee)
Foliar residue
toxicity (honey
bee)
Selected Measurement Endpoint Values and Source
Species
Bobwhite
quail
Bobwhite
quail and
Mallard
duck
Rat
Rat
Rat
Rat
Honey bee
(Apis
mellifera)
Honey bee
(Apis
mellifera)
Study
Duration
Single oral
dose
8 days
Single oral
dose
Not
available
Not
available
Two-
generation
48 hours
24 hours
post
treatment
Toxicity
Value
LD50 >2250
mg/kg-bw
LC50 >5620
mg/kg/-diet
LD50 >5000
mg/kg-bw
LD50 >5000
mg/kg-bw
LC50 >L18
mg/L
25
mg/kg/day
LD50 0.155
ug/bee
< 3 hours
post
treatment
Most Sensitive
Endpoint
(MRID)
Mortality*
(416096-04/
Acceptable)
Mortality*
(416096-05,
416096-06/
Acceptable)
Mortality*
(00063 574/
Acceptable)
Mortality*
(00063 574/
Acceptable)
Mortality*
(42 1464-0 1/
Acceptable)
Mortality*
(161842/
Acceptable)
Mortality
(416096-137
Acceptable)
Mortality
(419408-017
Acceptable)
Acute
Toxicity
Classification
Practically
non-toxic
Practically
non-toxic
Highly Toxic
*None observed at the highest dose
Birds and Mammals
Non-target terrestrial animals are not likely to be subject to mortality from the use of
tetramethrin because it is practically non-toxic to birds and mammals on an acute exposure basis.
The limitation of outdoor applications to spot treatments and the non-persistent nature of
tetramethrin make it unlikely that exposure sufficient to cause the chronic effects seen in
laboratory studies would occur in the field. The Agency's conceptual model for assessing risk to
terrestrial animals assumes that the animals derive the entirety of their diet from treated feed
items. The use of tetramethrin as a spot treatment in residential and/or commercial settings is
unlikely to result in extensive treatment of potential feed items. In addition, although chronic
toxicity studies are not designed to determine how long an exposure is necessary to cause
adverse chronic effects, the quick degradation of tetramethrin would reduce the amount of time
that toxic residues are available for potential dietary exposure.
Given that tetramethrin is an insecticide, it is considered highly toxic to invertebrates,
including beneficial insects, such as honey bees, on an acute contact exposure basis. Non-target
21
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invertebrates present at the time of spraying and shortly thereafter are considered to be at risk of
acute effects.
Terrestrial Plants
Toxicity data are not available for terrestrial plants. Therefore, the potential for risk to
terrestrial plants from exposure to tetramethrin cannot be assessed, and remains an uncertainty.
However, any toxicity to plants would occur for reasons other than tetramethrin's insecticidal
mode of action, because tetramethrin works in insects as a neural toxin. Unlike insects, plants do
not have neural networks that could be affected. In addition, the Agency also believes there is a
low likelihood of exposure to non-target terrestrial plants because outdoor applications are
limited to spot treatments.
b. Aquatic Organisms
No aquatic exposure modeling was conducted for tetramethrin because exposure of non-
target organisms to harmful levels is unlikely based on the localized use patterns, low total
pounds used on a national basis, and rapid degradation due to photolysis and hydrolysis. Also,
the aquatic exposure models assume that the chemical is applied to a ten-acre watershed draining
to a one-acre pond, which is unlikely for current use scenarios for tetramethrin. Instead, the
Agency conducted a qualitative assessment using submitted studies and review of the literature.
The Agency developed an effects characterization, which describes the potential effects a
pesticide can produce in an aquatic organism, and is based on registrant-submitted studies that
describe acute effects for various aquatic animals. Table 10 summarizes the toxic effects and
reference values used to assess risks for tetramethrin to aquatic organisms.
Table 10. Summary of Specific Measurement Endpoint Values Selected to Evaluate Risk for the Associated
Terrestrial Animal Assessment Endpoints
Assessment
Ends
Survival and
Reproduction
of Freshwater
Vertebrates
(fishes, etc.)
Survival and
Reproduction
of Freshwater
Invertebrates
Acute
Measurement
Endpoint
(most
sensitive)
Freshwater
fish or
amphibian
LC50
Freshwater
invertebrates
Selected Measurement Endpoint Values and Source
Species
Rainbow
trout
(Oncorhyn
chus
mykiss)
Water flea
(Daphnia
magna)
Study
Duration
96hrLC50
48hrEC50
flow-
through
Toxicity
Value
3.7ppb
45ppb
Most Sensitive
Endpoint
(MRID)
Mortality
(416096-087
Acceptable)
Immobilization and
mortality
(416096-097
Supplemental)
Acute
Toxicity
Classification
Veiy Highly
Toxic
Veiy Highly
Toxic
Freshwater and Estuarine/Marine Fish and Invertebrates
The acute toxicity of tetramethrin was tested in two species of freshwater fish (rainbow
trout and bluegill sunfish) and one freshwater invertebrate. Based on submitted studies,
tetramethrin is classified as very highly toxic to fish and invertebrates on an acute exposure
22
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basis. No chronic toxicity data were available for freshwater fish or invertebrates. However,
the limitation of outdoor applications to spot treatments and the non-persistent nature of
tetramethrin make it unlikely that exposure sufficient to cause the chronic effects would occur.
The use of tetramethrin as a spot treatment in residential and/or commercial settings is unlikely
to result in spray drift or run-off activities that would lead to exposure to non-target aquatic
organisms. In addition, although chronic toxicity studies are not designed to determine how
long an exposure is necessary to cause adverse chronic effects, the quick degradation of
tetramethrin would reduce the amount of time that toxic residues are available for potential
dietary exposure.
Additionally, no acute or chronic toxicity data were available for estuarine/marine fish or
invertebrates. The Agency is not requesting this toxicity data for estuarine/marine fish or
invertebrates because the outdoor uses of tetramethrin should not pose an acute risk to aquatic
animals (fish, aquatic-phase amphibians, and invertebrates) since exposure levels are not
expected to reach thresholds where adverse effects would be likely for such uses. Additionally,
based on the rapid photolytic and hydrolytic degradation of tetramethrin, and its demonstrated
rapid dissipation in field studies, the exposure duration is not expected to be sufficient to cause
reproductive effects. There are potential acute risks to non-target aquatic organisms from direct
application to drainage systems, but only in acidic waters where hydrolysis is slower. This
remains an uncertainly in the risk assessment; however, the Agency believes exposure is unlikely
because product labels prohibit direct application to water.
Aquatic Plants
Toxicity data are lacking for vascular and nonvascular aquatic plants. However,
tetramethrin is not expected to reach water bodies in sufficient concentrations to induce
phytotoxic effects in aquatic plants. Runoff exposure is not expected due to very short
photolysis, hydrolysis, and field dissipation half-lives. Spray drift exposure is expected to be
minimal based on use patterns and label restrictions. Additionally, similar to terrestrial plants,
any toxicity to plants would occur for reasons other than tetramethrin's insecticidal mode of
action, because tetramethrin works in insects as a neural toxin. Unlike insects, plants do not
have neural networks that could be affected.
c. Data Gaps
As stated above, the Agency does not have chronic toxicity data for either terrestrial or
aquatic organisms, acute or chronic toxicity data for terrestrial or aquatic plants, nor acute
toxicity data for are estuarine/marine animals. Although these data are guideline requirements,
the available effects data, non-persistent nature of tetramethrin, and low potential for
environmental exposure indicate this data would not affect the outcome of the risk assessment.
No additional environmental fate studies are needed to complete this assessment.
3. Adverse Ecological Incidents
A search of the EIIS (Environmental Incident Information System) database for
ecological incidents (run on Dec. 2, 2005) identified no ecological incidents involving
23
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tetramethrin. The number of documented incidents in EIIS is believed to be a very small fraction
of total mortality caused by pesticides for a variety of reasons. An absence of reports does not
necessarily equate to an absence of incidents given the nature of the incident reporting.
4. Endangered Species Considerations
Table 11 provides a matrix that depicts the potential for direct and indirect effects to
listed species resulting from the use of tetramethrin. No direct or indirect effects to endangered
species are expected, except the potential for direct effects for Listed insects or indirect effects to
plants if they have an obligate relationship with a Listed insect pollinator.
Table 11. Listed Species Associated With Direct or Indirect Effects Due to Applications of Tetramethrin for
all Outdoor Uses1
Listed Taxon
Terrestrial and semi-aquatic plants - monocots
Terrestrial and semi-aquatic plants - dicots
Insects
Birds
Terrestrial phase amphibians
Reptiles
Mammals
Aquatic vascular plants
Freshwater fish
Aquatic phase amphibians
Freshwater crustaceans
Mollusks
Marine/estuarine fish
Marine/estuarine crustaceans
Direct Effects
None (1)
None (1)
Yes (acute)
None (3)
None (3)
None (3)
None (5)
None (1)
None (6)
None (6)
None (6)
None (6)
None (6)
None (6)
Indirect Effects
Possible (2)
Possible (2)
None
None (4)
None (4)
None (4)
None (4)
None
None (4)
None (4)
None (4)
None (4)
None (4)
None (4)
(1) Direct effects to plants are not anticipated based on lack of incident reports, registration on ornamental plants,
and no identified mechanism of toxicity.
(2) Indirect Effects on plants are possible if they have an obligate relationship with a Listed insect pollinator.
(3) Direct Effects are considered unlikely due to low toxicity to birds and low exposure.
(4) Indirect effects via loss of prey base (insects and invertebrates) not likely due to low magnitude of effect.
(5) Direct effects are considered unlikely due to low toxicity to mammals and low exposure.
(6) Direct Effects are not anticipated due to low exposure, despite high toxicity to freshwater fish and invertebrates.
Specific levels of concern could not be evaluated for the supported use of tetramethrin
because RQs were not calculated in this assessment. However, acute risks from tetramethrin's
outdoor uses to listed aquatic species are not expected due to low application rates, the localized
and spatially fragmented use patterns, and rapid dissipation of the chemical stressor due to
photolysis and hydrolysis.
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In terrestrial environments, vertebrates such as mammals, birds, reptiles and amphibians
are not expected to be at risk because tetramethrin is practically non-toxic to birds and mammals,
and because of the localized and fragmented use patterns. Insects, if directly exposed, are at risk
of mortality.
The potential for chronic risk to any listed animal cannot be dismissed at this time
because of a lack of available data. However, tetramethrin is not expected to persist long enough
to lead to chronic exposure.
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IV. Risk Management, Reregistration, and Tolerance Reassessment Decision
A. Determination of Reregistration Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether or not products containing the active
ingredient are eligible for reregi strati on. The Agency has previously identified and required the
submission of the generic (i.e., active ingredient-specific) data required to support reregi strati on
of products containing the active ingredient tetramethrin. The Agency has completed its review
of these generic data, and has determined that the data are sufficient to support reregi strati on of
all products containing tetramethrin.
The Agency has completed its assessment of the human health and ecological risks
associated with the use of pesticide products containing the tetramethrin. The Agency has
determined that tetramethrin-containing products are eligible for reregi strati on provided that
label amendments are made as outlined in Chapter V. Appendix A summarizes the uses of the
tetramethrin that are eligible for reregi strati on. Appendix B identifies the generic data
requirements that the Agency reviewed as part of its determination of reregistration eligibility of
tetramethrin, and lists the submitted studies that the Agency found acceptable.
Based on its evaluation of tetramethrin, the Agency has determined that products
containing tetramethrin, 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
label changes identified in this document, the Agency may take regulatory action to address the
risk concerns from the use of tetramethrin. If all changes outlined in this document are
incorporated into the product labels, then all current risks for tetramethrin will be adequately
mitigated for the purposes of this determination under FIFRA.
B. Public Participation
Through the Agency's public participation process, EPA worked with stakeholders and
the public to reach the regulatory decisions for tetramethrin. EPA released the tetramethrin
preliminary risk assessments for public comment on February 27, 2008, for a 60-day public comment
period (Phase 3 of the public participation process). During the public comment period on the risk
assessments, which closed on April 28, 2008, the Agency received comments from: the
registrant McLaughlin, Gormley, King Company; the California Regional Water Quality Control
Board, S.F. Bay Region; the California Stormwater Quality Association (CASQA); California
Tri-TAC; as well as from private citizens. These comments in their entirety, responses to the
comments, as well as the preliminary and revised risk assessments, are available in the public
docket (OPP-2008-0014) at http:www.regulations.gov.
C. Regulatory Position
1. Regulatory Rationale
26
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The Agency has determined that products containing tetramethrin are eligible for
reregi strati on provided that specified label amendments are made. The following is a summary
of the rationale for managing risks associated with the use of tetramethrin. Where labelling
revisions are warranted, specific language is set forth in the summary table of Section V.
a. Human Health Risk Management
There are no human health risks of concern for tetramethrin, and therefore, no risk
mitigation is necessary. The personal protective equipment (PPE) for all occupational handlers
is baseline (long-sleeve shirt, long pants, and shoes plus socks), and the re-entry interval (REI) is
12 hours.
b. Ecological Risk Management
The Agency evaluated potential ecological risk from both indoor and outdoor uses of
tetramethrin. Although the Agency believes exposure to non-target organisms is unlikely,
tetramethrin is considered highly toxic to aquatic organisms. Therefore, the Agency is requiring
the following label statements to reduce the potential exposure of tetramethrin to aquatic
organisms.
• Limit all outdoor applications to spot and crack-and-crevice applications only, except for
the following barrier, perimeter, band or broadcast spray applications, which are
permitted:
(1) Barrier, perimeter or band applications to soil or vegetation around structures up to a
maximum of 10 feet away from the building;
(2) Band applications to building foundations, up to a maximum of 3 feet up the walls of
the building.
• The following statement will be required for liquid and ready-to-use products labeled or
intended for outdoor residential uses:
"Do not apply directly to or near water, storm drains, gutters, sewers, or drainage ditches.
Do not apply when windy. Do not water the treated area(s) to the point of run-off or
apply when raining or when rain is expected that day. Rinse application equipment over
treated area only."
Because outdoor uses will be limited to localized spot treatments, no additional
mitigation measures for these uses are required.
2. Endocrine Disrupter Effects
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
27
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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, individual pesticides may be subject to additional screening and/or
testing. However, in the available toxicity studies for tetramethrin, there was no evidence of
endocrine disruption.
3. Endangered Species
The Endangered Species Act required federal agencies to ensure that their actions are not
likely to jeopardize listed species or adversely modify designated critical habitat. The Agency
has developed the Endangered Species Protection Program to identify pesticides whose use may
cause adverse impacts on federally listed endangered and threatened species, and to implement
mitigation measures that address these impacts. To assess the potential of registered pesticide
uses that may affect any particular species, EPA puts basic toxicity and exposure data developed
for the REDs into context for individual listed species and considers 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.
When conducted, these analyses take into consideration any regulatory changes recommended in
this RED being implemented at that time. A determination that there is a likelihood of potential
effects to a listed species may result in limitations on the use of the pesticide, other measures to
mitigate any potential effects, and/or consultations with the Fish and Wildlife Service or National
Marine Fisheries Service, as necessary. If the Agency determines use of tetramethrin "may
affect" listed species or their designated critical habitat, EPA will employ the provisions in the
Services regulations (50 CFR Part 402).
No direct or indirect effects to endangered species are expected due to tetramethrin
applications, except the potential for direct effects for Listed insects or indirect effects to plants if
they have an obligate relationship with a Listed insect pollinator. The ecological assessment that
EPA conducted for this RED does not, in itself, constitute a determination as to whether specific
species or critical habitat may be harmed by the pesticide. Rather, this assessment serves as a
screen to determine the need for any species specific assessment that will evaluate whether
exposure may be at levels that could cause harm to specific listed species and their critical
habitat. That assessment refines the screening-level assessment to take into account the
geographic area of pesticide use in relation to the listed species, the habits and habitat
requirements of the listed species, etc. If the Agency's specific assessments for tetramethrin
result in the need to modify use of the pesticide, any geographically specific changes to the
pesticide's registration will be implemented through the process described in the Agency's
Federal Register Notice (54 FR 27984) regarding implementation of the Endangered Species
Protection Program.
D. Labeling Requirements
28
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In order to be eligible for reregi strati on, various use and safety information will be
included in the labeling of all end-use products containing tetramethrin. For the specific labeling
statements, refer to Section V of this RED document.
29
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V. What Registrants Need to Do
The Agency has determined that products containing tetramethrin are eligible for
reregi strati on provided that the required label amendments are made. The Agency intends to
issue Data Call-In Notices (DCIs) requiring product-specific data. Generally, registrants will
have 90 days from receipt of a DCI to complete and submit response forms or request time
extension and/or waiver requests with a full written justification. For product-specific data, the
registrant will have eight months to submit data. Additionally, below are the label amendments
that the Agency intends to require for tetramethrin to be eligible for reregi strati on.
A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregi strati on of tetramethrin for currently registered
uses has been reviewed and determined to be substantially complete. However, a few data gaps
remain, and these are listed below.
Product Chemistry
All product chemistry data requirements will be required for the technical grade active ingredient
(see Appendix B).
Toxicology
870.1300 Acute Inhalation
870.2400 Primary Eye Irritation
870.2500 Primary Dermal Irritation
870.2600 Skin Sensitization
870.3700a Developmental Toxicity (rodent)
870.6200a Acute Neurotoxi city
870.6200b Sub chronic Neurotoxi city study
870.6300 Developmental Neurotoxicity study
2. Labeling for Manufacturing-Use Products
To ensure compliance with FIFRA, manufacturing-use product (MUP) labeling should be
revised to comply with all current EPA regulations, PR Notices, and applicable policies. The
MUP labeling should bear the labeling contained in Tables 11 and 12.
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
30
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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. The Agency intends to issue a separate product-specific data call-in (PDCI), outlining
specific data requirements.
2. Labeling for End-Use Products
To be eligible for reregi strati on, labeling changes are necessary to implement measures
outlined in Section IV above. Specific language to incorporate these changes is specified in
Table 12. Generally, conditions for the distribution and sale of products bearing old
labels/labeling will be established when the label changes are approved. However, specific
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.
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C. Labeling Changes Summary Table
In order to be eligible for reregi strati on, amend all product labels to comply with the following table. Table 12 describes how
language on the labels should be amended.
Table 12. Summary of Labeling Changes for Tetramethrin
Description
Amended Labeling Language
Placement on Label
Manufacturing Use Products
For Manufacturing Use Products that
will be formulated into total release
fogger end-use products that contain
directions for use indoors
If information is available that justifies a duration longer than 2 hours
for the waiting period before beginning ventilation following an
application or a duration longer than 2 hours as the length of the
ventilation period, submit that information to the Agency.
Directions for use
For all Manufacturing Use Products
"Only for formulation into an insecticide for the following use(s) [fill
blank only with those uses that are being supported by MP registrant]."
Directions for use
One of these statements may be added
to a label to allow reformulation of the
product for a specific use or all
additional uses supported by a
formulator or user group
"This product may be used to formulate products for specific use(s) not
listed on the MP label if the formulator, user group, or grower has
complied with U.S. EPA submission requirements regarding support of
suchuse(s)."
"This product may be used to formulate products for any additional use(s)
not listed on the MP label if the formulator, user group, or grower has
complied with U.S. EPA submission requirements regarding support of
suchuse(s)."
Directions for Use
Environmental Hazards Statements
"ENVIRONMENTAL HAZARDS"
"This pesticide is highly toxic to fish and aquatic invertebrates. Do not
discharge effluent containing this product into lakes, streams, ponds,
estuaries, oceans, or other waters unless in accordance with the
requirements of a National Pollutant Discharge Eliminations System
(NPDES) permit and the permitting authority has been notified in writing
prior to discharge. Do not discharge effluent containing this product to
sewer systems without previously notifying the local sewage treatment
plant authority. For guidance, contact your State Water Board or Regional
Precautionary Statements:
Environmental Hazards
32
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Table 12. Summary of Labeling Changes for Tetramethrin
Description
Amended Labeling Language
Placement on Label
Office of the Environmental Protection Agency."
End-Use Products Intended for Occupational Use (WPS and Non-WPS)
PPE Requirements for Ready To Use
(RTU) Formulations (RTU Liquids and
Pressurized Liquids)
"Personal Protective Equipment (PPE)"
"Some materials that are chemical-resistant to this product are [registrant
inserts correct material(s)]." For more options, follow the instructions for
category [insert A, B, C, D, E, F, G or H] on the chemical-resistance
category selection chart.
"Applicators and other handlers must wear:
> Long-sleeve shirt and long pants, and
> Shoes plus socks."
Immediately following/below
Precautionary Statements: Hazards
to Humans and Domestic Animals
PPE Requirements for Liquid
Concentrates including Emulsifiable
Concentrates
"Personal Protective Equipment (PPE)"
"Some materials that are chemical-resistant to this product are [registrant
inserts correct material(s)]." For more options, follow the instructions for
category [insert A, B, C, D, E, F, G or H] on the chemical-resistance
category selection chart.
"Mixers, Loaders, Applicators and other handlers must wear:
> Long-sleeve shirt and long pants, and
> Shoes plus socks."
Immediately following/below
Precautionary Statements: Hazards
to Humans and Domestic Animals
User Safety Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no
such instructions for washables exist, use detergent and hot water. Keep
and wash PPE separately from other laundry."
Precautionary Statements: Hazards
to Humans and Domestic Animals
immediately following the PPE
requirements
User Safety Recommendations
"User Safety Recommendations"
"Users should wash hands before eating, drinking, chewing gum, using
tobacco, or using the toilet."
"Users should remove clothing/ PPE immediately if pesticide gets inside,
then wash thoroughly and put on clean clothing."
Precautionary Statements under:
Hazards to Humans and Domestic
Animals
(Must be placed in a box.)
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Table 12. Summary of Labeling Changes for Tetramethrin
Description
Amended Labeling Language
Placement on Label
"Users should remove PPE immediately after handling this product.
the outside of gloves before removing. As soon as possible, wash
thoroughly and change into clean clothing."
Wash
Environmental Hazards Statements for
Products Labeled for Outdoor Uses
"ENVIRONMENTAL HAZARDS"
"This pesticide is toxic to fish and aquatic invertebrates. Do not apply
directly to water, or to areas where surface water is present, or to inter-tidal
areas below the mean high water mark. Do not contaminate water when
cleaning equipment or disposing of equipment washwater or rinsate."
"This product is highly toxic to bees exposed to direct treatment on
blooming crops or weeds. Do not apply this product or allow it to drift to
blooming crops or weeds while bees are actively visiting the area."
Precautionary Statements: Hazards to
Humans and Domestic Animals
Environmental Hazards Statements for
Products Labeled for Indoor Uses Only
"ENVIRONMENTAL HAZARDS"
"This product is highly toxic to fish and aquatic invertebrates. Do not
contaminate water when disposing of equipment, washwater, or rinsate.
See Directions for Use for additional precautions and requirements."
For indoor commercial, industrial or institutional products packaged
in containers equal to or greater than 5 gallons or 50 Ibs add the
following statement:
"Do not discharge effluent containing this product into lakes, streams,
ponds, estuaries, oceans, or other waters unless in accordance with the
requirements of a National Pollution Discharge Elimination System
(NPDES) permit and the permitting authority has been notified in writing
prior to discharge. Do not discharge effluent containing this product to
sewer systems without previously notifying the local sewage treatment
plant authority. For guidance contact your State Water Board or Regional
Office of the EPA."
Precautionary Statements: Hazards to
Humans and Domestic Animals
Restricted-Entry Interval for Products
with Directions for use within the
scope of the Worker Protection
Standard for Agricultural Pesticides
"Do not enter or allow worker entry into treated areas during the restricted
entry interval (REI) of 12 hours."
Directions for Use, in the
Agricultural Use Requirements Box
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Table 12. Summary of Labeling Changes for Tetramethrin
Description
Amended Labeling Language
Placement on Label
(WPS)
For Products Subject to WPS as
required by Supplement 3 of PR Notice
93-7
Early Entry Personal Protective
Equipment
For Products Subject to WPS as
required by Supplement 3 of PR Notice
93-7
"PPE required for early entry to treated areas that is permitted under the
Worker Protection Standard and that involves contact with anything that
has been treated, such as plants, soil, or water is coveralls, shoes and
socks, and waterproof gloves."
Directions for Use, in Agricultural
Use Requirements Box
General Application Restrictions
"Do not apply this product in a way that will contact workers or other
persons, either directly or through drift. Only protected handlers may be in
the area during application."
Place in the Directions for Use
directly above the Agricultural Use
Box
Entry Restrictions for NonWPS Uses
For products that do not contain directions for use that allow people
to be present during application:
"Do not enter or allow others to enter treated area until sprays have dried."
For products that contain directions for use that allow people to be
present during application AND are labeled for use as a directed spray
(does not apply to products applied directly to domestic animals):
"Except when (insert application method or site that allows people to be
present during application), do not enter or allow others to enter treated
area until sprays have dried."
For products that contain directions for use that allow people to be
present during application AND are labeled for use as a space spray:
"Except when (insert application method or site that allows people to be
present during application), do not enter or allow others to enter until
vapors, mists, and aerosols have dispersed, and the treated area has been
thoroughly ventilated."
If no WPS uses on the product label,
place the appropriate statement in the
Directions for Use Under General
Precautions and Restrictions. If the
product also contains WPS uses, then
create a Non-Agricultural Use
Requirements box as directed in PR
Notice 93-7 and place the appropriate
statement inside that box.
35
-------
Table 12. Summary of Labeling Changes for Tetramethrin
Description
Amended Labeling Language
Placement on Label
For total release foggers labeled for indoor use:
"Wait at least two (2) hours after application, then open windows, vents
and doors for two more hours. If an odor is still detected additional
ventilation is required."
Application Restrictions for End Use
Products containing directions for use
to food/feed handling and service areas
For applications to food/feed handling and service areas:
"Do not apply when food is present."
"Do not use in food areas of food handling establishments, restaurants, or
other areas where food is commercially prepared or processed. Do not use
in serving areas while food is exposed or facility is in operation. Serving
areas are areas where prepared foods are served, such as dining rooms, but
excluding areas where foods may be prepared or held. In the home, all
food processing surfaces and utensils should be covered during treatment
or thoroughly washed before use. Exposed food should be covered or
removed."
In the directions for use for to
food/feed handling and service areas
General Application Restrictions for all
products that do not contain directions
for use in drains or sewers
Products labeled for use around or near floor drains must contain the
following statement.
"Do not apply directly into sewers or drains, or to any area like a gutter
where drainage to storm sewers, water bodies, or aquatic habitat can occur.
Do not allow the product to enter any drain during or after application."
Directions for Use
General Application Restrictions for all
products that contain directions for use
in drains or sewers
"Except when applying to sewers or drains as directed on this label, do not
apply directly into sewers or drains, or to any area like a gutter where
drainage to storm sewers, water bodies, or aquatic habitat can occur. Do
not allow the product to enter any drain during or after application."
Directions for Use
Additional Application Restrictions For
Outdoor Use
"Applications outdoors are limited to spot treatments or crack and crevice
treatments, except for:
(l)Barrier, perimeter or band applications to soil or vegetation around
structures up to a maximum of 10 feet away from the building;
(2) Band applications to building foundations, up to a maximum of 3 feet
up the walls of the building."
Directions for Use
Application Restrictions for Liquid
Concentrate and Ready to Use End Use
products that contain directions for use
in outdoor residential areas
"Do not apply directly to or near water, storm drains, gutters, sewers, or
drainage ditches. Do not apply when windy. Do not water the treated
area(s) to the point of run-off or apply when raining or when rain is
expected that day. Rinse application equipment over treated area only."
Directions for Use
36
-------
Table 12. Summary of Labeling Changes for Tetramethrin
Description
Amended Labeling Language
Placement on Label
End Use Products Primarily Used by Consumers/Homeowners
Environmental Hazards Statement
General Application Restrictions for all
products that do not contain directions
for use in drains or sewers
General Application Restrictions for all
products that contain directions for use
in drains or sewers
General Application Restrictions
Additional Application Restrictions For
Outdoor Use
Application Restrictions for Liquid
Concentrate and Ready to Use End Use
products that contain directions for use
in outdoor residential areas
"ENVIRONMENTAL HAZARDS"
"This product is highly toxic to fish and aquatic invertebrates. Do not
apply directly to water. Do not contaminate water when cleaning
equipment or disposing of equipment washwaters or rinsate. Drift and
runoff may be hazardous to aquatic organisms in water adjacent to treated
areas."
"This product is highly toxic to bees exposed to direct treatment on
blooming crops or weeds. Do not apply this product or allow it to drift to
blooming crops or weeds while bees are actively visiting the area."
Products labeled for use around or near floor drains must contain the
following statement.
"Do not apply directly into sewers or drains, or to any area like a gutter
where drainage to storm sewers, water bodies, or aquatic habitat can occur.
Do not allow the product to enter any drain during or after application."
"Except when applying to sewers or drains as directed on this label, do not
apply directly into sewers or drains, or to any area like a gutter where
drainage to storm sewers, water bodies, or aquatic habitat can occur. Do
not allow the product to enter any drain during or after application."
"Do not apply this product in a way that will contact adults, children, or
pets, either directly or through drift."
"Applications outdoors are limited to spot treatments or crack and crevice
treatments, except for:
(l)Barrier, perimeter or band applications to soil or vegetation around
structures up to a maximum of 10 feet away from the building;
(2) Band applications to building foundations, up to a maximum of 3 feet
up the walls of the building."
"Do not apply directly to or near water, storm drains, gutters, sewers, or
drainage ditches. Do not apply when windy. Do not water the treated
area(s) to the point of run-off or apply when raining or when rain is
expected that day. Rinse application equipment over treated area only."
Precautionary Statements under
Environmental Hazards
Directions for Use
Directions for Use
Place at the beginning of the
Direction for Use
Directions for Use
Directions for Use
37
-------
Table 12. Summary of Labeling Changes for Tetramethrin
Description
Application Restrictions for End Use
Products containing directions for use
around residential food or feed
handling or service areas
Amended Labeling Language
For applications to food or feed handling or service areas:
"Do not apply when food is present. Exposed food should be covered or
removed. All food preparation surfaces and utensils should be covered
during treatment or thoroughly washed before use."
Placement on Label
In the directions for use for to
food/feed handling and service areas
38
-------
Appendix A. Non-Food and Non-Feed Use Patterns Subject to the Reregistration of Tetramethrin
Product
Type
RTUA
Aerosol can
ECB
TRFC
Use Profile
General indoor spray D
General outdoor spray (spot treatment only) E
Handheld fbgger (PCO use only)
General indoor spray
General outdoor spray (spot treatment only)
Pets
General indoor spray
General outdoor spray (spot treatment only)
Indoor fogger
Maximum Application Rate
% Active
Ingredient (% a.i.)
0.10
0.10
0.25
0.20
0.063
2.5
0.54
Volume-based
0.011ba.i./gal
solution
n/a
n/a
n/a
n/a
0.02 Ib a.i./gal
solution
n/a
Area-based
O.OOOOllbai/ft2
0. 000000 llbai/ft2
0.000003 Ib ai/ft2
0.00002 Ib ai/ft2
n/a
0.0000002 Ib ai/ft2
n/a
Space-
based
n/a
n/a
n/a
n/a
n/a
n/a
6oz can /
4,600 ft3
A RTU - Ready to use (product can be poured directly into a sprayer without mixing with water).
B EC - Emulsifiable concentrate.
c TRF - Total release fogger (aerosol can).
D Use sites include but are not limited to: commercial, industrial, institutional, and residential locations; agricultural structures and
eating establishments; animal kennels and sleeping quarters; empty greenhouses; hospitals.
E Use sites include but are not limited to: commercial, industrial, institutional, and residential locations; compost piles; ornamental
paths.
equipment;
plants; patios;
39
-------
Appendix B. Data Supporting Guideline Requirements for Tetramethrin
Data Supporting Guideline Requirements for the Reregistration of Tetramethrin
Guideline
Number
Study Description
Citation(s)
PRODUCT CHEMISTRY
830.1550
830.1600
830.1620
830.1670
830.1700
830.1750
830.1800
830.6302
830.6303
830.6304
830.6313
830.7000
830.7050
830.7200
830.7220
830.7300
830.7370
830.7550
830.7570
830.7840
830.7860
830.7950
Product Identity and Composition
Description of Materials Used
Description of Production Process
Discussion of Formation of Impurities
Preliminary Analysis
Certified Limits
Enforcement Analytical Method
Color
Physical State
Odor
Stability
pH
UV/Visible Absorption
Melting Point
Boiling Point
Density
Dissociation Constant
Octanol / Water Partition Coefficient
Solubility
Vapor Pressure
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
Required
ECOLOGICAL EFFECTS
850.1010
850.1025
850.1035
850.1045
850.1055
850.1075
850.1300
850.1350
850.1400
850.1500
850.1710
Aquatic Invertebrate Acute
Oyster Acute Toxicity Test
Mysid Acute Toxicity Test
Penaeid Acute Toxicity Test
Bivalve Acute Toxicity Test
Fish Acute Toxicity
Freshwater
Estuarine / Marine
Aquatic Invertebrate Life Cycle (Freshwater)
Aquatic Invertebrate Life Cycle (Marine)
Fish Early Life-Stage (Freshwater and
Marine)
Fish Full Life-Cycle (Freshwater and
Marine)
Oyster BCF
41609609
Data gap
Data gap
Data gap
Data gap
41609608,41609607
Data gap
Data gap
Data gap
Data gap
Data gap
Data gap
40
-------
Data Supporting Guideline Requirements for the Reregistration of Tetramethrin
Guideline
Number
850.1730
850.1850
850.2100
850.2200
850.2300
850.2400
850.3020
850.3030
850.3040
850.4100
850.4150
850.4400
850.4500
850.4550
Study Description
Fish BCF
Aquatic Food Chain Transfer
Avian Acute Oral Toxicity
Avian Subacute Dietary Toxicity
Avian Reproduction Toxicity
Wild Mammal Toxicity
Honey Bee Acute Contact Toxicity
Residues on Foliage Honeybee Toxicity
Honeybee Feeding Toxicity Test
Seedling Emergence and Growth
Vegetative Vigor
Aquatic Plant Growth
Algal Plant Toxicity
Algal Plant Toxicity
Citation(s)
Data gap
Data gap
41609604
41609605,41609606
Data gap
00063574, 00161842
41609613
41940801
Data gap
Data gap
Data gap
Data gap
Data gap
Data gap
TOXICOLOGY
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
870.3100
870.3150
870.3200
870.3465
870.3700
870.3800
870.4100
870.4200
870.4300
870.5265
870.5385
870.5550
870.6200
(a)
(b)
Acute Oral Toxicity
Acute Dermal Toxicity
Acute Inhalation Toxicity
Acute Eye Irritation
Acute Dermal Irritation
Skin Sensitization
90-Day Oral Toxicity in Rodents
90-Day Oral Toxicity in Non-rodents
21/28 -Day Dermal Toxicity
90-Day Inhalation Toxicity
Prenatal Developmental Toxicity
Reproduction and Fertility Effects, 2-
Generation Reproduction
Chronic Toxicity
Carcinogenicity
Combined Chronic Toxicity /Carcinogenicity
Gene Mutation (Ames assay)
Bone Marrow Chromosomal Aberration Test
Unscheduled DNA Synthesis in mammalian
cells in culture
42146405
00063574,40276101
Required
Required
Required
Required
42146404
42146403,41698902
41995004
42012101,41995003
Required
42189202, 41995005, 00114369, 00114370
00114371, 00137656, 00137658, 00161842
41723301, 40009401, 40280401,
00156488, 40007501, 41723302,
42189301,44083501
41723301, 40009401, 40280401,
00156488, 40007501, 41723302
00158951, 40276301, 44096001
40276001,40275801
40275901, 42414401, 42414402, 42414403
40778401,40275801
Neurotoxicity Screening battery
Acute Neurotoxicity
Subchronic Neurotoxicity
Required
42601501, 42601502, 43152701
Required
41
-------
Data Supporting Guideline Requirements for the Reregistration of Tetramethrin
Guideline
Number
870.6300
870.7485
Study Description
Developmental Neurotoxicity Study
Metabolism and Pharmacokinetics
Special Study - motor activity in male and
female mice post-natally exposed by
inhalation
Citation(s)
Required
42448901,42448902
44222801
ENVIRONMENTAL FATE
835.1230
835.1410
835.2120
835.2240
835.2370
835.2410
835.4100
835.4200
835.4300
835.4400
835.6100
835.6200
835.6400
835.7100
835.8100
Leaching and Adsorption / Desorption
Laboratory Volatility
Hydrolysis
Photodegradation in Water
Photodegradation in Air
Photodegradation on Soil
Aerobic Soil Metabolism
Anaerobic Soil Metabolism
Aerobic Aquatic Metabolism
Anaerobic Aquatic Metabolism
Terrestrial Field Dissipation
Aquatic (Sediment) Dissipation
Combination and Tank Mixes Dissipation
Ground Water Monitoring
Field Volatility
41995007,42212901
Data gap
41995006
00164634,43773401
Data gap
Data gap
42563301
Data gap
Data gap
Data gap
42622401,42622402
Data gap
Data gap
Data gap
Data gap
42
-------
Appendix C. Technical Support Documents
Additional documentation in support of the Tetramethrin RED is maintained in the OPP
Regulatory Public Docket, located in Room S-4400 One Potomac Yard (South Building), 2777
S. Crystal Drive, Arlington, VA. It is open Monday through Friday, excluding legal holidays,
from 8:30 a.m. to 4:00 p.m. All documents may be viewed in the OPP Docket room or viewed
and/or downloaded via the Internet at http://www.regulations.gov. The Agency's documents in
support of this RED include the following:
1. Daiss, B. Tetramethrin Health Effects Division's Risk Assessment for Reregi strati on
Eligibility Decision. June 18,2008.
2. Crowley, M. Tetramethrin: Phase IV Revised Occupational and Residential Exposure
Assessment and Recommendations for the Reregi strati on Eligibility Decision. June 13,
2008.
3. Eckel, W. et al. Revised Environmental Fate and Ecological Risk Assessment for the Re-
registration Eligibility Decision on Tetramethrin. February 5, 2008.
4. Abdel-Saheb, I. Revised Drinking Water Assessment for Tetramethrin Use as a Rapid
Knockdown Agent Against Flying and Crawling Insects. February 5, 2008.
43
-------
Appendix D. Bibliography
In addition to the studies listed in Appendix B, this bibliography contains additional
citations considered to be part of the database supporting the reregi strati on decision for
Tetramethrin.
In addition to the MRID study references listed in Appendix B, this bibliography contains the
expanded study citations as well as additional literature considered to be part of the database
supporting the reregi strati on decision for Tetramethrin.
MRID
Citation Reference
63574
Miyamoto, J.; Kadota, T.; Kohda, H. (1977) Acute Oral and Dermal Toxicities of
Neopynamin in Mice and Rats. (Unpublished study received Apr 21, 1978 under
10308-1; prepared by Sumitomo Chemi- cal Co., Ltd., Japan, submitted by
Sumitomo Chemical Co., Ltd., Baltimore, Md.; CDL:233835-A)
114369
Sato, T.; Narama, K. (1982) Reproduction Test of Neopynamin: Part 2. Teratology
Study in Rats: Doc. Code IT-01-0076. (Transla- tion; unpublished study received Sep
20, 1982 under 10308-1; prepared by Sumitomo Chemical Co., Ltd., Japan,
submitted by Sumitomo Chemical Co., Ltd., Baltimore, MD; CDL:248342-B)
114370
Sato, T.; Narama, K. (1982) Reproduction Test of Neopynamin: Part 3. Teratology
Study in Rabbits: Doc. Code IT-01-0077. (Transla- tion; unpublished study received
Sep 20, 1982 under 10308-1; prepared by Sumitomo Chemical Co., Ltd., Japan,
submitted by Sumitomo Chemical Co., Ltd., Baltimore, MD; CDL:248342-C)
114371
Sato, T.; Tagawa, G.; Narama, K. (1982) Reproduction Test of Neo- pynamin: Part
4. Perinatal and Postnatal Study in Rats: Doc. Code IT-01-0078. (Translation;
unpublished study received Sep 20, 1982 under 10308-1; prepared by Sumitomo
Chemical Co., Ltd., Japan, submitted by Sumitomo Chemical Co., Ltd., Balti- more,
MD; CDL:248342-D)
131413
Gabriel, K. (1981) Guinea Pig Contact Dermal Irritation/Sensitization—Buehler
Method: TL-2252: Project No. 81-2354A. (Unpublished study received Sep 19,
1983 under 1021-1492; prepared by Biosearch, Inc., submitted by McLaughlin
Gormley King Co., Minneapolis, MN; CDL:251313-E)
137656
Hazleton Laboratories America, Inc. (1980) One-generation Reproduc- tion Study--
Rats: Neo-Pynamin: Individual Animal Data: Project No. 343-106; IT-01-0081.
(Unpublished study received Apr 30, 1982 under 10308-1; submitted by Sumitomo
Chemical Co., Ltd., Baltimore, MD; CDL:247530-A)
137658
Rutter, H. (1974) One-generation Reproduction Study—Rats: Neo-Pyn- amin: Project
No. 343-106; IT-41-0042. Final rept. (Unpub- lished study received Apr 30, 1982
under 10308-1; prepared by Hazleton Laboratories, Inc., submitted by Sumitomo
Chemical Co., Ltd., Baltimore, MD; CDL:247530-C)
156488
Pence, D. (1986) Chronic Toxicity Study in Rats: Neopynamin Technical:
Addendum to Final Report: Project No. 343-117. Unpublished study prepared by
Hazleton Laboratories America, Inc. 575 p.
158951
Cox, R. (1986) Combined Chronic Toxicity and Oncogenicity Study in Mice:
Neopynamin: Final Report: Project No. 343-136. Unpublish- ed study prepared by
Hazleton Laboratories America, Inc. 4980 p.
44
-------
MRID
Citation Reference
161842 Pence, D.; Wolfe, G.; Kulwich, B. (1986) Two-generation Reproduction Study in
Rats: Neopynamin Forte: Final Report: Project No. 343-147. Unpublished study
prepared by Hazleton Labo- ratories America, Inc. 418 p. _
164634 Chen, Y.; Casida, J. (1970) Photodecomposition of pyrethrin I, allethrin, phthalthrin,
and dimethrin modifications in the acid moiety. Pyrethum Post 10(3):7-16. _
40007501 Cox, R. (1986) Chronic Toxicity Study in Rats, Neopynamin Techni- cal: Addendum
III to Final Report: Hazleton Project No. 343-1 17. Unpublished study prepared by
Hazleton Laboratories America, Inc. 7 p. _
40009401 Cox, R. (1986) Two-year Dietary Administration in the Rat: Neo Pynamin:
Addendum 1: Final Report: Project No.: 343-107. Unpub- lished study prepared by
Hazleton Laboratories America, Inc. 831 p. _
40275701 Suzuki, H.; Miyamoto, J. (1975) Mutagenicity of Some Synthetic Pyrethroids in
Bacterial Test System: Laboratory Project ID: ET-50-0024. Unpublished study
prepared by Sumitomo Chemical Co., Ltd. 14 p. _
40275801
Ding, C.; Yu, Y.; Zhang, J.; et al. (1985) Genotoxicity of tetramethrin in mammalian
cells and salmonella typhimuriam. Journal of the Zhejiang Univ. of Medicine
40275901 Kogiso, S.; Kara, M.; Yoshitake, A.; et al. (1986) In vivo Chromo- somal Aberration
Test of Neopynamin in Mouse Bone Marrow Cells: Laboratory Project ID: IT-60-
0197. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 12 p. _
40276001 Kogiso, S.; Yamada, F.; Kara, M.; et al. (1987) Reverse Mutation Test of
Neopynamin in Salmonella typhimurium and Escherichia coli: Lab Project No. : IT-
70-0205. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 18 p. _
40276101 Suzuki, T.; Sako, H.; Okuno, Y.; et al. (1987) Acute Dermal Toxicity of
Neopynamin in Rabbits: Lab Project No.: IT-70-0207. Unpublished study prepared
by Takarazuka Research Center. 17 p. _
40276301 Cox, R. (1987) Combined Chronic Toxicity and Oncogenicity Study in Mice:
Neopynamin Technical: Amendment to Final Report (IT-71- 0210). Unpublished
study prepared by Hazleton Laboratories America, Inc. 1487 p. _
40280401 Cox, R.; Jones, S. (1987) Historical Control Data for Liver Adenoma Incidence
among Mice, and Supporting Information: Hazleton Product No. 343-107.
Unpublished study prepared by Hazleton Laboratories America, Inc. 53 p. _
40778401 Kogiso, S. (1988) In vitro Unscheduled DNA Synthesis (UDS) Assay of
Neopynamine in Rat Hepatocytes: Study No. 1280. Unpublished study prepared by
Sumitomo Chemical Co., Ltd. 54 p. _
41054701 Knarr, R.D. (1988) Exposure of Applicators to Propoxur During Trigger-Pump Spray
Application of a Liquid Product. Unpublished study prepared by Mobay
Corporation. 195 p. _
41609604 Culotta, J. et al. (1990) Neo-Pynamin: An Acute Oral Toxicity Study with the
Bobwhite: (IW-0 1-0008): Final Report: Lab Project Number: IW/0 1/0008.
Unpublished study prepared by Sumitomo Chemical Company. 17 p. _
41609605 Long, R. ; Hoxter, K. ; Smith, G. (1990) Neo-Pynamin: A Dietary LC50 Study with
the Northern Bobwhite: Lab Project Number: 166/133. Unpublished study prepared
by Sumitomo Chemical Company. 54 p. _
45
-------
MRID
Citation Reference
41609606 Long, R. ; Hoxter, K. ; Smith, G. (1990) Neo-Pynamin: A Dietary LC50 Study with
the Mallard: Lab Project Number: 166/134. Unpublished study prepared by
Sumitomo Chemical Company. 54 p.
41609607 Bowman, J. (1990) Acute Flow-through Toxicity of Neo-Pynamin to Bluegill:
(Lepomis-macrochirus): Lab Project Number: IW/01/0010. Unpublished study
prepared by Analytical Bio-Chemistry Labora- tories, Inc. 188 p.
41609608 Bowman, J. ; Gormley, M. (1990) Acute Flow-Through Toxicity of Neo- Pynamin to
Rainbow Trout (Oncorhynchus mykiss): Lab Project Number: IW/01/0011.
Unpublished study prepared by Analytical Bio-Chemistry Laboratories, Inc., 189 p.
41609609 Burgess, D. (1990) Acute Flow-through Toxicity of Neo-Pynamin to Daphnia
magna: Lab Project Number: IW/01/0009. Unpublished Study Prepared by
Analytical Bio-Chemistry Laboratories, Inc., 176 p.
41609613 Hoxter, K. ; Smith, G. ; Jaber, M. (1990) Neo-Pynamin: An Acute Contact Toxicity
Study with the Honey Bee: Lab Project Number: 1W/01/0012. Unpublished study
prepared by Sumitomo Chemical Co. Ltd. 13 p.
41698902 Pence, D. ; Hagen, W. ; Alsaker, R. et al. (1981) Subchronic Toxicity in Dogs: Lab
Project No: 343-127. Unpublished study prepared by Hazleton Laboratories
America, Inc. 398 p.
41723301 Cox, R. (1974) Two-Year Dietary Administration in the Rat, Part A: Final Report,
Neo-Pynamin: Lab Project Number: 343-107. Unpub- lished study prepared by
Technology Services Group, Inc. 262 p.
41723302 Pence, H.; Serotam, D.; Alsaker, R.; et al. (1981) Chronic Toxicity Study in Rats:
Neo-Pynamin Technical: Lab Project Number: 343- 117. Unpublished study
prepared by Technology Services Group, Inc. 443 p.
41940801 Hoxter, K.; Lynn, S. (1991) Neo-Pynamin: A Foliage Residue Toxicity Study With
the Honey Bee: Lab Project Number: 166-151C. Unpub- lished study prepared by
Wildlife International Ltd. 23 p.
41995003 Kawaguchi, S. (1991) Three Month Inhalation Toxicity Study of Neo- Pynamin in
Rats (Determination of the no Observed Effect Level): Lab Project Number: 2279.
Unpublished study prepared by Sumitomo Chemical Co., Ltd, Environmental Health
Science Lab. 938 p.
41995004 Osheroff, M. (1991) 21-Day Dermal Toxicity Study in Rats with Neo- Pynamin:
Final Report: Lab Project Number: 343/232. Unpublished study prepared by
Hazleton Laboratories America, Inc. 206 p.
41995005 Robinson, K.; Washer, G.; Noveroske, J. (1991) An Oral Teratology Study of Neo-
Pynamin in the Rabbit: Research Report: Lab Project Number: 95088. Unpublished
study prepared by Bio-Research Labo- ratories Ltd. 325 p.
41995006 Katagi, T.; Mikami, N.; Matsuo, M.; et al. (1991) Hydrolysis of Trans-Neo-Pynamin
in Buffered Aqueous Solutions: Lab Project Number: HYD90001: HYD91001.
Unpublished study prepared by Sumi- tomo Chemical Co., Ltd, Environmental
Health Science Lab. 127 p.
46
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MRID
Citation Reference
41995007 Yoshimura, J.; Mikami, N.; Matsuo, M.; et al. (1991) Adsorption and Desorption of
Tetramethrin in Water-Soil Suspension Systems: Lab Project Number: ADS91001.
Unpublished study prepared by Sumitomo Chemical Co., Ltd, Environ. Health
Science Lab. 60 p.
42012101 Kawaguchi, S. (1991) Three-Month Inhalation Toxicity Study of Neo- Pynamin in
Rats: Lab Project Number: 2189. Unpublished study prepared by Sumitomo Chem.
Co. 1055 p.
42146401 Suzuki, T.; Kohda, H.; Misaki, Y.; et al. (1981) Acute and Sub- acute Inhalation
Toxicity Studies of NeoPynamin Forte in Rats: Lab Project Number: IT-10-0144.
Unpublished study prepared by Sumitomo Chemical Co., Ltd. 78 p.
42146402 Hosokowa, S.; Hiromori, T.; Seki, T.; et al. (1981) Additional 6 Month Sub-chronic
Toxicity Study of Neo-Pynamin Forte in Rats : Lab Project Number: IT-10-0140.
Unpublished study prepared by Sumitomo Chemical Co., Ltd. 61 p.
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