United States Prevention, Pesticides EPA 738-R-08-012
Environmental Protection and Toxic Substances Agency (7508P)



# Reregistration Eligibility Decision (RED) Document for

Tetramethrin

Revised April 2010TABLE 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 III. Summary of Tetramet hrin Risk Assessments ........................................................................ 6

A. Human Health Risk Assessment ......................................................................................... 6

1. Toxicity of Tetramethrin ........................................................................................... 7

2. Carcinogenicity of Tetramethrin ............................................................................ 10

3. Metabolites and Degradates .................................................................................. 10

4. Dietary Exposure and Ri sk (Food and Water) ....................................................... 11

5. Residential Exposure and Risk ............................................................................. 11

6. Aggregate Exposure and Risk ............................................................................... 16

7. Occupational Exposure and Risk ......................................................................... 16

8. Cumulative Exposure and Risk ............................................................................ 18

9. Tetramethrin Human Incident Reports ............................................................... 19

B. Environmental Risk Assessment .................................................................................... 20

1. Environmental Fate and Transport ........................................................................ 20

2. Ecological Exposure and Risk ................................................................................. 21

3. Adverse Ecological Incidents ................................................................................ 24

4. Endangered Species Considerations .................................................................... 25 IV. Risk Management, Reregistration, and Tolerance Reassessment Decision ................... 27 A. Determination of Reregistration Eligibility .................................................................. 27 B. Public Participation ......................................................................................................... 27 C. Regulatory Position ......................................................................................................... 27

1. Regulatory Rationale ............................................................................................. 27

2. Endocrine Disruptor Screening Program ............................................................ 29

3. Endangered Species ............................................................................................... 29 D. Labeling Requirements ................................................................................................... 30 V. What Registrants Need to Do ............................................................................................... 31 A. Manufacturing Use Products ......................................................................................... 31

1. Additional Generic Data Requirements ............................................................... 31

2. Labeling for Manufacturing-Use Products ......................................................... 31

B. End-Use Products ............................................................................................................ 32

1. Additional Product-Sp ecific Data Requirements ................................................ 32

2. Labeling for End-Use Products ............................................................................ 32

C. Labeling Changes Summary Table ............................................................................... 34 Appendix A. Non-Food and Non-Feed Use Patterns Subject to the Reregistration of

Tetramethrin .................................................................................................... 52 Appendix B. Data Supporting Guideline Re quirements for Tetramethrin ...................... 53 Appendix C. Technical Support Documents ........................................................................ 56 Appendix D. Bibliography ..................................................................................................... 57 Appendix E. Tetramethrin Acute Mammalian Toxicity Batching .................................... 64iv 

### 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

LC 50 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/l, mg/kg or ppm.

LD 50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in 50% of

the test animals when admini stered by the route indicated (oral, dermal, inhalation). It is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.

LOC 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 Identificatio n (number). EPA's syst em 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, Pe sticides 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 (Registrati ons Under Section 24(c) of FIFRA) TGAI Technical Grade Active Ingredient USDA United States Department of Agriculture UF Uncertainty Factor

UF db Database Uncertainty Factorv 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 Andersonvi Summary of Revisions to the Tetramethr in Reregistration Eligibility Decision

The Reregistration Eligibility Decision (R ED) document for Tetramethrin was signed on June 23, 2008, and is available on the Federal Dock et Management System (FDMS), available at http://www.regulations.gov (document # EP A-HQ-OPP-2008-0014-0019). Although a public comment period did not follow the RED, the Agency did receive comments from the registrants regarding the need for clarifica tion and corrections in Appendix A, as well as clarification of label statements in Table 12, Summary of Labeling Changes for Tetramethrin . Further, in the 2008 RED, the Agency assessed the indoor aer osol space spray scenario at a maximum application rate of 0.25% active ingredient (a.i). To suppor t indoor aerosol space spray products up to 0.35% a.i., the registrants submitted a re vised Cumulative and Aggr egate Risk Evaluation System (CARES ® ) assessment for this scenario and a short-term incidental oral benchmark dose (BMD) analysis in order to revise the endpoint for incidental oral exposure. Finally, the registrants requested the Agency review existing acute toxicological studies previously submitted to the Agency in order to address data ga ps identified in the 2008 RED document.

As a result of these post-RED discussions with the registrants and th e review of existing and new toxicity data, the Agency has revised the Tetramethrin RED, where appropriate, in order to correct any errors, clarify th e intent of its risk mitigation captured in Table 12, reflect the revised occupational and residential risk assessments , and revise the acute toxicity data gaps and data-call in requirements.

The major revisions to the human health risk assessment and data needs are as follows:

• The Agency reviewed the Guideline 870.2400 Primary Eye Irritation Testing (MRID# 41609611) submitted by Sumitomo Chemical Inc., and found the study to be acceptable. Therefore, in Section III, Summary of Tetramethrin Risk Assessments , the acute toxicity profile (Table 2) was revised to reflect this data requirement as fulfilled and tetramethrin as a category III eye irritant.

• Additionally, the need for Guideline 870.2400 Primary Eye Irritation Testing was removed from Section V, Additional Generic Data Requirements

.

• The Agency determined the “Evaluation of Potential Human Health Risks Associated

with Residential Uses of Tetramethrin: Revised Supplemental – Short-term Oral Benchmark Dose Analysis,” (MRID# 47921601) submitted by the registrant on November 30, 2009 to be acceptable. As a result, the short-term incidental oral endpoint

for use in the human health risk assess ment was revised from 25 mg/kg/day to 61.1 mg/kg/day.

• The occupational handler inhala tion risk assessment was revise d to reflect the increased rate of 0.35% for aerosol space sprays. Th e revised margin of exposure (MOE) of 9,000 is below the Agency’s level of concern (LOC ), and therefore, con tinues to be not of concern to the Agency (MOEs ≥ 1,000 are not of concern).vii • The residential handler risk assessment was also revised to reflect the increased rate of 0.35% for aerosol space sprays. The revi sed MOE of 54,000 is below the Agency’s LOC, and therefore, continues to be not of concern to the Agency. The residential postapplication CARES assessment was also revised to reflect the revised short-term incidental oral end-point and the increased use rate for the indoor aerosol space spray. In the 2008 RED, the inhalation MOE for this scen ario (using a use rate of 0.25% a.i.) was not of concern (MOEs ≥ 1,000) at the 99.88 th percentile. In the revised CARES assessment, this use scenario (w ith an application rate of 0.35 % a.i. and revised incidental oral endpoint) is not of c oncern at the 99.9 percentile (MOE = 1,131), and therefore, is eligible for reregistration. The increased us e rate of 0.35% is speci fied in Appendix A.

Section 5, What Registrants Need to Do , has been amended to require two additional generic data requirements, Guideline 830.7050 UV / Visible Absorption and Guideline 870.7800 Immunotoxicity. Both are new studies whic h are now required for all pesticide active ingredients. The Additional Product-Specific Data Requirements section has also been amended to include efficacy data requirements for public health pests and companion animal studies for tetramethrin products used on domestic animals. The determination of which efficacy studies would be required for tetramethrin was still on- going at the time of publi cation of the June 2008

RED.

A number of revisions have also been made to the Summary of Labeling Changes for

Tetramethrin (Label Table), Table 12, for clarificati on and to reflect updates in labeling on tetramethrin end-use products. Among the updates are the following:

• The Agency is requiring the following label st atements to reduce the potential ecological exposure of tetramethrin. While some of the label statements are additions to the Label Table, others appeared in Table 12 of the June 28, 2008 Tetramethrin RED document; however, they have been revised slightly to be consistent with other pyrethroid nonagricultural outdoor product labeling.

o Incorporation of PR No tice 2008-1, “Environmental Hazard General Labeling

Statements on Outdoor Residential Use Products” on appropriate outdoor nonagricultural end-use products.

o Products labeled for General Outdoor Surface and Space Sprays (except outdoor fogging devices):

“All outdoor applications must be limited to spot or crack-and-crevice treatments only, except for the following permitted uses:

 Treatment to soil or vegetation around structures;

 Applications to building foundations up to a maximu m height of 3 feet.

Other than applications to building f oundations, all outdoor applications to impervious surfaces such as sidewalks, driveways, patios, porches and structural surfaces (such as windows, doors, and eav es) are limited to spot treatments or crack-and-crevice applications, only.”viii o Products labeled for use around or ne ar floor drains must contain the following statement:

“Application is prohibited directly into sewers or drains, or to any area like a gutter where drainage to sewe rs, storm drains, water bodie s, or aquatic habitat can occur. Do not allow the product to ente r any drain during or after application.”

o Products labeled for use in drains or sewers must contain the following

statement:

“Do not apply directly to sewers or dr ains, or to any area like a gutter where drainage to sewers, storm drains, water bodies, or a quatic habitat can occur, except as directed by this label.”

• The Agency is also including the total re lease fogger (TRF) labeling requirements, intended to improve residential safety, in the Label Table (Table 12). The label requirements were sent to the pyrethrins and pyr ethroid registrants in a letter dated March 23, 2010. EPA is requiring the following labeling changes on all TRF by September 30, 2011, except where manufacturers can satisfact orily explain to the Agency that an alternative approach would be adequate to address the causes of bug bomb exposure

incidents:

o Bug bomb labels must be written in plain language with clear headings.

o The new labels must incorporate pictogr ams to illustrate the following list of

restrictions and dire ctions for use:

 do not use multiple canisters in a room

 do not use in small confined areas

 turn off ignition sources

 remove or cover exposed food

 air out the room before entering

o Instructions to vacate upon use and air out upon return must be very prominent.

o Door hang-tags must be provided to inform others to stay out of treated areas.

• The following entry restriction label statemen ts that appear in the “End-Use Products Intended for Occupational Use (WPS and Non- WPS)” section of the Label Table (Table 12) have been added to the “End Use Products Primarily Used by Consumers/Homeowners” section since they apply to applications made by both PCOs

and consumers.

o For products that do not contain directi ons for use that allow people to be present during application:

“Do not enter or allow others to enter treated area until sprays have dried.”ix o For products that contain directions for use that allow people to be present during application AND are labeled fo r use as a directed spray (does not apply to products applied direc tly to domestic animals):

“Except when (insert applica tion method or site that al lows people to be present during application), do not enter or allow ot hers to enter treated area until sprays

have dried.”

o 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 applica tion method or site that al lows people to be present during application), do not enter or allow ot hers to enter until vapors, mists, and aerosols have dispersed, and the treate d area has been thoroughly ventilated.”

o For total release foggers labeled for indoor use:

“Wait at least two (2) hours after app lication, then open windows, vents and doors

for two more hours. If an odor is still de tected additional ventilation is required.”

A number of revisions have been made to Appendix A, Non-Food and Non-Feed Use Patterns Subject to the Rere gistration of Tetramethrin , to reflect the maximu m use rates assessed for aerosol space sprays. Furthermore, the Ag ency clarified Appendix A by including Outdoor Jet Sprays (intended for wasp and hornet use) in its own row, with a maximum of 0.20% a.i. and 1 to 2 second bursts per application.x Abstract

The Environmental Protection Agency (EPA or the Agency) has completed the human

health and environmental risk assessments for te tramethrin and is issuing its risk management

decision. Tetramethrin is not re gistered 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 register ed products and additiona l data provided by the technical registrants, Valent BioSciences Corporation and Sum itomo Chemical Company, Ltd.

Tetramethrin is part of the pyrethroid class of pesticides and was first registered in 1968. It is a broad spectrum, non-syst emic, synthetic pyrethroid used to control flying and crawling

insects in a number of commer cial, horticultural and resident ial applications. Commercial applications include space, broadcast and crack-and-crevice treatment in a variety of commercial, industrial, residentia l, and institutional sites. Ho rticultural applications include foliar and fogger treatment on non-food plants. Resi dential 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 expe cted 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 di etary exposures, so no dietary risk assessment was conducted. Therefore, the reregistration action consider ed only potential residential (inhalation and incidental oral), occupational (i nhalation only), and ecological risks. No endpoints were selected for dermal exposure because no effects were obs erved at the limit dose in available acceptable dermal toxicity studies.

For residential handler inhalation risk, calcu lated Margins of Exposure (MOEs) for all scenarios assessed were below the Agen cy’s Level of Concern (LOC) (MOEs ≥ 1,000) and therefore, are not of concern. Fo r residential post-application inhala tion and incidental oral risks, the MOEs are all greater than the target MOE of 1,000 at th e 99.9 percentile of the CARES probabilistic risk assessment and are also not of concern.

Occupational handler and post-applic ation inhalation exposures were assessed. All of the MOEs are greater than the Agency’s target occupational MO E of 1,000 without respirators, and therefore, the inhalation risks are not of concern. The MOEs for the occupational postapplication 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 e xposure 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 and crack a nd crevice treatments, with the exception of (1) barrier, perimeter or band applic ations to soil or vegetati on around structures; and (2) band applications to building foundati ons, 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. Although th ese limitations will reduce exposur e to tetramethrin, there could be a potential for direct effects fo r Listed insects or indirect eff ects to plants if they have an obligate relationship with a Listed insect pollinator.1 I. Introduction

The Federal Insecticide, Fungicide, and R odenticide Act (FIFRA) was amended in 1988 to accelerate the reregistration of products with active ingredient s registered prior to November 1, 1984. The amended Act calls for the developm ent and submission of data to support the reregistration of an active ingredient, as well as a review of all submitted data by the EPA. Reregistration involves a thorough re view of the scientific data base underlying a pesticide’s registration. The purpose of the Agency’s review is to reassess the poten tial 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 tetram ethrin. The document consists of six sections. Section I contains the regulator y framework for reregistration; Section II provides an overview of the chemical and a profile of its use and us age; 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 managemen t; and Section V summarizes the label changes necessary to implement the risk mitigation m easures 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 Pe sticide Programs (OPP) public docket (http://www.regulations.gov) unde r docket number EPA-HQ-OPP-2008-0014.2 II. Chemical Overview

A. Regulatory History

Tetramethrin was first registered in the United States in 1968. Current technical registrants include Valent BioSciences Comp any and Sumitomo Chemical Corporation. Tetramethrin is on reregistration List B; thus no Registration Standard was completed.

Currently, there are 58 end-use registra nts and approximately 300 end-use products containing tetramethrin, of which approximately 30 are ma nufacturing formulations. Tetramethrin is not registered for direct application to agricu ltural 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 reregistration.

Prior to the reregistration of this active ingr edient, 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 vo luntarily 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:

N

O O O O

Tetramethrin, [(1,3,4,5,6,7-hexahydro-1,3-dioxo-2 H-isoindol-2-yl)methyl 2,2-dimethyl3-(2-methyl-1-propenyl)cyclopropanecarboxylate] is a mixture of four stereoisomers designated as 1R - trans, 1R – cis, 1S – trans, and 1S – cis in an approximate ratio of 4:1:4:1. The first two isomers are the most insecticidally active, a nd a mixture of the two has been termed ‘dtetramethrin’ and has the trade name Neo-Pynami n 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: Tetramethrin3 Chemical Name: (1,3,4,5,6,7-hexahydro-1,3-dioxo- 2H-isoindol-2-yl)methyl 2,2- dimethyl-3-(2-methyl-1-pr openyl)cyclopropanecarboxylate

Chemical Class: Synthetic pyrethroid

Case Number: 2660

EPA Chemical (PC) Code: 069003

CAS Number: 7696-12-0

Empirical Formula: C 19 H 25 NO 4

Technical Registrants: Valent BioSciences Corporation Sumitomo Chemical Company

Table 1. Physicochemical Properties of Technical Grade Tetramethrin.

Parameter Value
Melting point/range 68 - 70 °C

Molecular Weight 331.4 g/mol

Density 1.1 specific gravity at 20 °C

Water solubility 1.83 mg/L at 25 °C

Solvent solubility >2 g/100 mL in acetone, ethanol, methanol, hexane and n-octanol

Vapor pressure 0.944 mPa at 30 °C
Dissociation constant, pK

a Not available

Octanol/water partition coefficient, Log(K OW ) log P

ow = 4.6 at 25 °C

UV/visible absorption spectrum Not available

C. Use Profile

The following information on the currently regi stered uses includes an overview of use sites and application methods. A detailed table of the uses of tetramethrin eligible for reregistration 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 chry santhemum flowers). Te tramethrin is a rapid knockdown agent against flying and cr awling insects. Tetramethrin may be co-formulated with synergists (e.g., PBO and MGK-264) , other active ingred ients such as pyrethrins and other pyrethroids (e.g., permethrin, alle thrins, phenothrin, resmethrin, and cypermethrin), and growth inhibitors (e.g., fenoxycarb) for gr eater effectiveness and to contro l a broader spectrum of insect pests. These other activ e ingredients are more persistent than tetramethrin and provide residual activity against insects no t exposed initially.

Target Organisms: The primary target pests are flying and crawling insects such as wasps, hornets, roaches, ants, fleas, and mosquitoes.4 Mode of Action: Tetramethrin is a type 1 pyrethroi d (i.e., lacking a cyano group at the α carbon position of the alcohol moiety). Type 1 pyrethr oids act on axons in th e peripheral and central nervous system by interacting with sodium channels in mammals and/or insects. Tetramethrin is a nerve cell membrane sodium channel modulator, wh ich interferes with en trance of sodium ions into the channel, leading to hype ractivity 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 institu tional sites including: indoor non-food areas; animal premises (not used for human consumption); and outdoors as localized space and contact sprays on ornamental plan ts 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 be dding, pet premises, and direct applications to pets. Outdoor s 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 incl ude 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 enduse 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 comme rcial operator use. Typical concentrations of active ingredient (a.i.) in residential use pr oducts, 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, ra nge between 0.1 % and 0.35%. Indoor total release foggers are typically around 0.54% a.i. Sprays designe d 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 lb 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 regi strants, it appears that tetramethrin usage has increased over the past fe w years. This is likely due to the fact that pyrethroids are alternatives to several organophosphate pesticides, which are no longer registered5 for indoor residential areas. The Agency estima tes annual usage of tetramethrin to be between 15,000 and 30,000 pounds (lbs) a.i. However, tetram ethrin use data is extremely limited and difficult to interpret because tetramethrin pr oducts may be stored for periods of time and produced only as inventory is exhausted. In addi tion, 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 Ag ency by the tetramethrin registrants, the majority of tetramethrin use is in residential outdoor spaces. It appears residential indoor use

sites and institutional and industr ial sites make up a small percentage of tetramethrin use. Further, tetramethrin is primarily used by resi dential consumers as opposed to PCOs. Sources suggest that less than 1,000 lb s a.i. are used annually by professional applicators.6 III. Summary of Tetram ethrin Risk Assessments

The following is a summary of EPA’s re vised 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 subsequent supplemental

assessments discussed below 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 a ssessment documents and supporting information listed in Appendix C were used to reach th e safety finding and re gulatory decision for

tetramethrin. While the risk assessments and rela ted 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.

Tetramethrin risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pest icide to determine their dermal and inhalation exposure. Many such studies, i nvolving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pest icide Handlers Exposure Database (PHED). EPA

has reviewed all the studies in these multi-pesticide generic exposur e databases, and on the basis

of available evidence has found them to have been neither fundamentally unethical nor significantly deficient relative to standards of ethical research c onduct prevailing when they were conducted. There is no regulator y barrier to continued relian ce on these studies, and all applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied.

A. Human Health Risk Assessment

The human health risk assessment incorporat es all sources of potential exposure, hazard, and risks, including both resident ial and occupational applications . There are no registered food uses for tetramethrin, and the majority of us e is in consumer home products (indoor and outdoor surface and space sprays). There are also commerci al and horticultural uses for tetramethrin.

The Human Health Tetramethrin Risk Assessment for Registration Eligibility Decision document was completed on June 18, 2008. Since the completion of the Human Health Risk Assessment, the registrant s requested the Agency review existing acute primary eye irritation data, and also submitted a benchmark dose (BMD) analysis of the toxicity endpoint for incidental oral exposures. The Agency’s review of the BMD analysis, Tetramethrin: Benchmark Dose Analysis of Toxicity Endpoint for Incidental Oral Exposure , dated January 6, 2010, found the BMD analysis to be acceptable, and consequently, the short-term incidental oral end point was revised. The Agency also revised the occupational and residential handler risk assessments, as well as the residential post-application CARES portion of the Tetramethrin: Phase IV Revised Occupational and Residential Exposure Assessment and Recommendations for the Reregistration Eligibility Decision, dated June 13, 2008. Major revi sions to the tetramethrin human health risk assessment include the following:7 • The acute toxicity profile (T able 2) was revised to reflect the acute eye irritation data requirement as fulfilled and tetramet hrin as a category III eye irritant.

• The short-term incidental oral toxici ty end point has been revised to 61.1 mg/kg/day based on the BMD analysis.

• Occupational and residential handler expos ure and risks were revised from the previous assessment to reflect use of the 0.35% tetramethrin aerosol space spray.

• Revision of the CARES portion of th e Residential Exposure Assessment

considered the revised incidental or al endpoint and the use of the 0.35% tetramethrin aerosol space spray.

For more information on the human health risk assessment, and the revisions to toxicity and residential portions, see Tetramethrin Risk Assessment for Registration Elig ibility Decision, dated June 18, 2008; HED Review of Evaluation of Potent ial Human Health Risks Associated with Residential Uses of Tetramethrin: Supplemental Assessment for Indoor Space Spray , dated April 27, 2009; Tetramethrin: Benchmark Dose Analysis of Toxicity Endpoi nt for Incidental Oral Exposure, dated January 6, 2010; and the HED Review of Evaluation of Potential Human

Health Risks Associated with Residential Uses of Tetramethrin: Revised Supplemental – ShortTerm Oral Benchmark Dose Analysis, dated February 25, 2010, which are available under docket number EPA-HQ-OPP-2008-0014.

1. Toxicity of Tetramethrin

Toxicity assessments are desi gned to predict whether a pestic ide could cause adverse health effects in humans (includi ng: short-term or acute ef fects, such as skin or eye damage; and lifetime or chronic effects, such as cancer, de velopmental effects, or reproductive effects), and the level or dose at which such effects might occur.

The toxicity database for tetramethrin c ontains acceptable acute toxicity, subchronic, chronic, oncogenecity, and mutagenecity studi es. However, the database lacks acceptable developmental studies and acceptable acute ne urotoxicity, subchronic neurotoxicity, and developmental neurotoxicity ( DNT) studies. Although developmen tal and neurotoxicity studies are available, these studies are consid ered inadequate based on the use of carboxymethylcellulose (CMC) as the dosing vehicl e. CMC has been found to decrease the absorption rate and thereby lessen the poten cy 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 Deve lopment of PBPK Models of Pyrethroid Pesticides” prepared jointly by EPA’s Office of Pesticide Program s and Office of Research and Development. Therefore, new developmental to xicity, and acute, subchr onic, and developmental neurotoxicity studies utilizing an appropriate dosing vehicle are required to fully evaluate potential risks from e xposure to tetramethrin.

Since the tetramethrin database is curren tly incomplete with respect to data on developmental and neurotoxicity studies, the Agency applied a ten-fold (10x) database uncertainty factor (UF DB ) to account for this lack of data.8 a. Acute Toxicity Profile

Tetramethrin is slightly toxic (Toxicity Cate gory III or IV) by the oral and dermal routes of exposure, and is a Category III eye irritant. However, in acute oral studies in mice with technical tetramethrin and/or neopynamin fort e, clinical signs sometimes included hyperexcitability, muscular fibril lation, tremor, ataxia, limb para lysis, irregular respiration, lacrimation, and salivation. These effects were also seen in acute percutaneous studies in rats. As presented in Table 2, acceptable data on the ac ute inhalation toxicity, acute dermal irritation,

and skin sensitization for technical tetramethrin are unavailable. The Agency is requiring these

data.

Table 2. Acute Toxicity Prof ile – Tetramethrin (Neopynamin)

Guideline

No. Study Type MRID Results Toxicity Category

870.1100 Acute oral [rat]* 42146405 LD50 > 5,000 mg/kg IV

870.1200 Acute dermal [rat] 00063574

42146405 LD50 > 5,000 mg/kg IV

870.1200 Acute dermal [rabbit] 40276101 LD50 > 2,000 mg/kg III 870.1300 Acute inhalation [rat] -- -- No data 870.2400 Acute eye irritation [rabbit] 41609611 -- III 870.2500 Acute dermal irritation [rabbit] -- -- No data 870.2600 Skin sensitization [guinea pig] -- -- 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 a ssessment for tetramethrin are listed in Table 3 below. There are no register ed food uses for tetram ethrin and dietary and drinking water exposure to tetramet hrin is not expected based on us e patterns. Therefore, acute

and chronic reference doses are not required and were not select ed for this assessment. Noncancer endpoints were selected for inhalation and incident al 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 no observed adverse effect level (NOAEL) is 50 mg/kg/day and the lo west observed adverse effect level (LOAEL) is 300 mg/kg/day based on decreased body weight and food consumpti on in both sexes of F0 and F1 parental animals and decreased pup body wei ght during lactation. A benchmark dose (BMD) analysis was performed to determine the short-term incidental oral endpoin t. A BMD is defined as an exposure due to a dose of a substance asso ciated with a specified low incidence of risk, generally in the range of 1% to 10%, of a health effect; or the dose associated with a specified measure or change of a biological effect. The selected toxicological e ndpoint of 61.1 mg/kg/day was based on decreased offspr ing body weight on day 21 in the F0 and F1 generations.

There are no dermal absorption studies availa ble with tetramethrin. However, based on available dermal absorption studies in pyrethr ins/pyrethroid compounds, dermal absorption of tetramethrin is expected to be ve ry low (i.e., less than 2%). Te tramethrin was tested in a 21-day9 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 derm al exposure because no effects

were observed at the limit dose in available ac ceptable dermal toxicity studies.

The short and intermediate term inhalation exposure endpoint was selected based on two 90-day inhalation toxicity st udies in rats conducted in 1991 (MRIDs 42012101 and 41995003). The systemic toxicity NOAEL of 19.8/20.3 mg/m 3 (3.5 mg/kg/day) was se lected based on: increased clinical signs (irre gular respiration and bradypnea) ; decreased body weight gain; changes in hematology, urinalysis, and blood ch emistry; gross necropsy findings in liver; hepatocellular hypertrophy; and hyaline droplets in kidney in both sexe s at the LOAEL of 134 mg/m 3 (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 the standard 10x for interspecies ex trapolation and 10x for intraspecies variation, plus an additio nal database uncertainty factor (UF DB ) of 10x for the absence of adequate neurotoxicity studies, sin ce the nervous system is the target site for tetramethrin. Based on the Agency’s review of existing pyrethroid data, EPA has come to the conclusion that the development neurotoxicity st udy (DNT) is not a par ticularly sensitive study for comparing the sensitivity of young and adul t animals to pyrethroids. EPA has recently determined that, as an alternative to the generation and submission of a new DNT study, pyrethroid registrants may instead choose to cite the six previously submitted DNT studies for pyrethroid pesticides 1 . The Agency is also investigating the need for additional experimentation, specific to the mode of action and pharmacokinetic characteristics of pyrethr oids, to evaluate the potential for increased susceptibility of young orga nisms. Therefore, the Agency is maintaining the 10x database uncertaintly factor to account fo r the outstanding neurotoxicity data gap. The 10x database uncertainty factor is also appli cable to workers because occupational exposures may pose neurotoxic and developmental risk concerns. The uncertainty factors (UF) used to account for interspecies extrapolation and intraspeci es variability are also described in Table 3.

Table 3. Summary of Toxicological Doses and Endpoints for Tetramethrin for Use in Human Risk

Assessments

Exposure

Scenario Dose Used in Risk Assessment, UF Safety Factor and

Level of Concern Study and Toxicological Effects

Acute and Chronic Dietary (general population) Acute and Chronic RfD’s were not selected b ecause there are no registered food uses

Short-Term

Incidental Oral (1 - 30 days) BMDL 5 = 61.1 mg/kg/day

UF A =10

UF H = 10

UF DB = 10 Residential LOC for MOE = 1,000 Occupational LOC for

MOE = N/A 2-Generation Reproduction (rats) The NOAEL is 50 mg/kg/day and the LOAEL is 300 mg/kg/day based on decreased body weight and food consumption in both sexes of F0 and F1 parental animals and decreased pup body weight during lactation.

1 These conclusions and determinations were communicated to registrants of some pyrethroid active ingredients in a letter from EPA dated September 4, 2009 (available from the public docket EPA-HQ-OPP-2008-0331-0027).Further details are also available from the website http://www.epa.gov/oppsrrd1/reevaluation/pyrethroidspyrethrins.html

.10 Table 3. Summary of Toxicological Doses and Endpoints for Tetramethrin for Use in Human Risk

Assessments

Exposure

Scenario Dose Used in Risk Assessment, UF Safety Factor and

Level of Concern Study and Toxicological Effects

Short-,

Intermediate- Term

Dermal (1 - 30 days, 1-6 months) No risk is expected from this exposure scenar io 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 Short-,

Intermediate-Term (1 - 30 days, 1-6 months) Inhalation NOAEL = 19.8 mg/m3 (3.5 mg/kg/day (oral equivalent)

UF A =10

UF H = 10

UF DB = 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 ↑ clinical signs, absolute/relative kidney and liver weights; ↓ body weight, changes in hematology, urinalysis, hypertrophic and gross liver necropsy findings, and hyaline droplets in the kidney Cancer (oral, dermal, inhalation) Group C, possible human carcinogen based on evidence of benign testicular tumors in rats and increased hepatocellular carci nomas in male mice at the HDT of 1134 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 av ailable 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 anot her 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 B 6 C 3 F 1 mice did not alter the spontaneous tumor prof ile 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; a nd the treatment did not cause reduction in latency.

3. Metabolites and Degradates

The Agency reviewed the metabolism of tetramethr in (MRIDs 42448901 and 42448902), and

concluded that for risk assessment, the parent compound, tetr amethrin, is the only residue of toxicological concern. For additional details, refer to the Tetramethrin Risk Assessment for Registration Eligibility Decision

, dated June 18, 2008.11 4. Dietary Exposure and Risk (Food and Water)

Tetramethrin currently has no registered food uses and there are no to lerances for specific raw agricultural commodities. Tetramethrin is not registered for direct application to agricultural crops, livestock animals, or livestock pr emises, where livestock are used for food

. Although there are no registered food uses for tetramethri n, 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-proces sing 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 dr inking water assessment for tetramethrin, given the limited extent of poten tial exposure and the chemical’s en vironmental fate properties. Tetramethrin is used by individu al homeowners or industrial / commercial property owners, in individual, isolated areas, and in small amount s as opposed to wide scale uses (i.e., for agriculture or mosquito abatement by public author ities). Because tetramethrin products are not expected to adversely impact gr oundwater or surface water (the sources of drinking water), a quantitative drinking water a ssessment is not warranted.

5. Residential Exposure and Risk

Residential exposure assessments consider all potential non-o ccupational pesticide exposure. Tetramethrin has a wide variety of residential uses, includi ng use in/on indoor and outdoor surfaces, and use on pets. Therefore, the Ag ency has determined that there is a potential for exposure to tetramethrin in residential set tings for homeowners who handle (mix, load, and apply) products containing tetr amethrin, as well as post-appl ication exposure from entering

tetramethrin-treated areas. N on-occupational post-app lication exposures can result following use of pesticides by homeowners themselves or fo llowing 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 incide ntal oral). Though dermal exposure is possible and expected for residential handl er and post-application scenario s of tetramethrin, the Agency determined a dermal assessment was not necessary because no systemic effects were observed at

the limit dose in dermal toxici ty studies in animals.

To estimate residential (inhalation and incide ntal oral) risks, the Agency calculates a margin of exposure (MOE), which is the ratio of the toxicity endpoint (NOAEL or BMDL) selected for risk assessment to the exposure valu e. The MOE is then compared to a level of concern (LOC), which is the same value as the un certainty factor (UF) applied to a particular toxicity study. The standard UF is 100x (10x to account for interspecies extrapolation and 10x for intraspecies variation). However, since the te tramethrin database is currently incomplete, the Agency applied a ten fold (10x) database uncertainty factor (UF DB ) to account for this lack of certain data; thus, for residential exposures to te tramethrin, MOEs greater than the target LOC of 1,000 are not of concern to the Agency. For de tailed information on the residential risk assessment, see the Tetramethrin Risk Assessment for Registration Eligibility Decision

, dated12 June 18, 2008 ; HED Review of Evaluation of Potentia l Human Health Risks Associated with Residential Uses of Tetramethrin: S upplemental Assessment for Indoor Space Spray , dated April 27, 2009; and the HED Review of the Evaluation of Pote ntial Human Health Risks Associated with Residential Uses of Tetramethrin: Revise d Supplemental Short-Term Oral Benchmark Dose Analysis, dated February 25, 2010.

a. Residential Handler Risks

The Agency determined that exposur e 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 assessmen t considered three majo r residential exposure scenarios, based on the types of equipment and t echniques that can potentia lly be used to make tetramethrin applications. While some tetramethrin products are packaged as RTU trigger sprayer bottles, the handler risk s calculated from aerosol can a pplication are prot ective of risks from trigger sprayer applications because the un it exposure values are lower for trigger sprayer application. The Agency only considered shor t-term (1-30 days) inhalation exposure due to infrequency of use associated w ith homeowner products and the non- persistence of tetramethrin. Additionally, as discussed above, dermal exposur es 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 backp ack sprayer or low pressure hand wand.

• Aerosol can application

• Load / Apply liquids with a trigger-pump sprayer.

Pesticide handler exposure database (PHED) unit exposure values were used to assess exposures, because chemical-specific monitori ng data were not available. The following assumptions were also used in estimating risks from residential handler e xposure 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 ga llon 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 LOC (MOEs ≥ 1,000 are not of concern), with values ranging from 54,000 to 100,000.

Table 4. Residential Handler Risk Estimates from General Spray Applications

Exposure Scenario Application Rate Amount Sprayed per Day Pound a.i. handled per day Inhalation MOE

M/L/A Liquids with

LP Hand-wand or Backpack Sprayer 0.02 lb a.i./gallon

solution 5 gallons 0.1 82,000

Aerosol Can 0.35% a.i. 1 can (16 oz ea) 0.0025 54,00013 Table 4. Residential Handler Risk Estimates from General Spray Applications

Application

L/A RTU with a

Trigger-pump Sprayer 0.02 lb a.i./gallon

solution 1 gallon 0.02 100,000

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 tr eated 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 potentia lly be exposed when reentering or performing activities in areas that have been previ ously treated. Tetramethrin can also be used on pets, which can lead to e xposure by contact with the treated animals.

Tetramethrin post-applicati on incidental oral exposures ma y occur after a pplications are

made to residential areas resul ting 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 a pplications. 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:

• Inhalation exposure (adults and children) indoors:

o Space spray and tota l release fogger;

• Inhalation exposure (adults and children) outdoors:

o Handheld foggers and aerosols;

• Incidental oral ingestion (child ren 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 (child ren only) of residues outdoors:

o Handheld fogger applications, and

o Aerosol surface treatments.

The Agency assessed the post-application exposu re 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 va lue 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 determ inistic approach produces an output value that represents th e potential exposure or risk of a group; depending on how the14 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 pr ovided 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-appli cation risk assessment. Risks of concern were identified for hand-to-mouth exposures followi ng indoor aerosol can space spray treatments (MOEs of 290 and 430 for children on carpet an d 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 tr eatments (MOEs of 570 and 840 for children on carpet and vinyl, respectively). Because these risks of concern were identified using the screening-level deterministic a pproach, a more refined probabi listic assessment was conducted for the residential post-application exposure scenarios.

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 probab ilistic exposure assessment, using the Cumulative and Aggregate Risk Evaluation System (CARES ® Version 3.0; http://cares.ilsi.org/ ), a publicly available software program. Probabi listic 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. In the HED Review of the Evaluation of Potential Human Hea lth Risks Associated with Resi dential Uses of Tetramethrin: Revised Supplemental Short-Term Oral Benchmark Dose Analysis, dated February 25, 2010, the

CARES assessment was revised to reflect the revise d short-term oral endpoint and the use rate of 0.35% a.i. for indoor aerosol applications.

a. Tetramethrin CARES Post-App lication Risk Assessment

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 contai ns data for statistical weights from sampled individuals of the general U.S. population, pr ovided 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).15 CARES simulates daily (24-hour) exposures ove r the course of one calendar year for each person in the specified sub-population base d on user-specified routes of exposure (e.g., dietary, dermal, non-dietary ingest ion), empirical data, and exposur e algorithms. It can provide cumulative exposures for more than one chemical , aggregate across exposu re 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 si mulation to identify percentiles of risk and enable users to conduct analyses to identify major exposure contributors.

The calculations and algorithms used to es timate exposure for the various scenarios and routes are consistent with standard Agency practice for residen tial pesticide exposure

assessment. Risks of concern were not identif ied for residential handler scenarios in the deterministic assessment; therefore, the CARES assessment considered only post-application exposure routes. The tetramethrin exposure scenarios were assesse d using standard EPA algorithms for exposure estimation. Distributiona l inputs were included in the probabilistic assessment where possible. The probabilisti c assessment assumes post-application exposure occurs on the “day of application,” wh ich is the most c onservative assumption.

The tetramethrin CARES assessment calculate d 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 tetr amethrin, the selection of 1 - 2 year olds is appropriate since this age group e xhibits the highest de gree of mouthing behavior – a major route of exposure for this assessment (Tulve et al., 20 02). Combined male/female populations are also appropriate since the toxicological endpoints used in the risk asse ssment 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 percen tage of the population

that does not use tetramethrin.

Exposure factors used in the CARES assessm ent were determined based on consultation between EPA and the tetramethrin registrant s. Many of the non-tetramethrin-specific distributional inputs are base d on EPA’s n-methyl Carbamate Revised Cumulative Risk Assessment (NMCCRA), the most recent EPA pub lication using probabi listic methods and distributional inputs for residen tial exposure assessment. For mo re information on the inputs and

distributions considered for the children’s non -dietary ingestion expos ure following use of 0.35% tetramethrin aerosol spa ce sprays, refer to the HED Review of “Evaluation of Potential Human

Health Risks Associated with Residential Uses of Tetramethrin: Revised Supplemental – Shortterm Oral Benchmark Dose Analysis,” dated February 25, 2010. For all other post-application scenarios, 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.16 Table 5. CARES Residential Post-App lication Assessment – Tetramethrin MOEs for Adults (20 - 49 years) Exposure Scenario and Route

Outdoor Treatment Indoor Treatment (Spray) Percentile

Inhalation Inhalation (Applicator) Inhalation (Postapplication)
100 1,690 37,336 5,834
99.9 2,051 47,342 6,726
99.8 2,117 48,848 7,162
99.7 2,150 48,848 7,432
99.6 2,188 48,848 7,510
99.5 2,215 48,848 7,673

Table 6. CARES Residential Post-A pplication Assessment – Tetramethrin MOEs for Children (1 - 2 years) Exposure Scenario and Route

Indoor Treatment Outdoor Treatment Fogger Spray Pet Care Percentile

Ingestion Inhalation Ingestion Ingestion Inhalation Ingestion
100 1,808 1,034 3,351 754 3,007 3,725
99.9 2,123 1,040 5,347 1,131 3,113 5,135
99.88 2,188 1,042 5,487 1,247 3,130 5,207
99.8 2,387 1,045 6,085 1,455 3,160 5,770 99.7 2,603 1,045 6,952 n/a 3,221 6,131 99.6 2,771 1,046 7,951 n/a 3,246 6,482 99.5 2,870 1,048 8,475 n/a 3,285 6,719

n/a- The “Evaluation of Potential Human Health Risks Associated with Residential Uses of Tetramethrin: Revised Supplemental – Short-term Oral Benchmark Dose Analysis” submitted by the registrant in November 2009 only provi ded MOEs down to the 99.8 percentile, which were all below the Agency’s LOC (MOE >1000).

As demonstrated in Tables 5 and 6, for the tetramethrin CARES pr obabilistic residential exposure assessment, all MOEs were above 1,000 at the 99.9 percentile for al l scenarios assessed

for both adults and children.

6. 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 a nd inhalation pathways may not be aggregated for tetramethrin because the toxicity endpoints for these exposur e 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.)

7. Occupational Exposure and Risk

The occupational risk assessment addresses risks to workers who may be exposed to tetramethrin when mixing, loading, or applying a pesticide (i.e., handler s), and when entering treated sites for routine tasks ( post-application). Exposure for wo rkers generally occurs via the dermal or inhalation route. However, for tetr amethrin, only inhalation ex posures were calculated

since there were no treatment rela ted systemic toxic effects at th e highest dose tested in the 21 day dermal toxicity study. The target MOE is 1,000 for occupational exposures.17 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 as sessment are derived directly from current tetramethrin labels. The occupational risk assessment is summari zed here. For further detail, see the Tetramethrin Risk Assessment for Regist ration Eligibility Decision, dated June 18, 2008, and HED Review of Evaluation of Potential Human Hea lth Risks Associated with Reside ntial Uses of Tetramethrin: Supplemental Assessment for Indoor Space Spray , dated April 27, 2009.

a. Occupational Handler Exposure and Risks

The term “handler” applies to individua ls 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 loadi ng 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 up on 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 bac kpack 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 ar e conducted by the Agency using different levels of protection. The Agency typically eval uates 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 acce ptable 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 9,000 to 50,000), and therefore, are not of concern.

T able 7. Short / Intermediate-term Inhalation MOEs for Occupational Handlers Applying General Surface and Space Sprays

Exposure Scenario Unit Exposure A
(μg/lb a.i.) Application

Rate B Amount Sprayed per Day lb a.i.

handled per day Inhalation

Dose E
(mg/kg/day) Inhalation

MOE F

M/L/A liquids with LP hand-wand or backpack

sprayer 30 40 gallons C 0.8 0.00034 10,000

L/A liquids with Triggerpump Sprayer 123 0.02 lb a.i./gallon

solution 2 gallons D 0.04 0.00007 50,00018 T able 7. Short / Intermediate-term Inhalation MOEs for Occupational Handlers Applying General Surface and Space Sprays

Exposure Scenario Unit Exposure A
(μg/lb a.i.) Application

Rate B Amount Sprayed per Day lb a.i.

handled per day Inhalation

Dose E
(mg/kg/day) Inhalation

MOE F

Aerosol can application 1300 0.35% a.i. 6 cans D 0.015 0.00039 9,000

A. Unit Exposure values are from PHED.

B. Application rates are from labels 769-939 (0.0 2 lb a.i./gallon solution) and 4822-513 (0.35%)

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 * lb 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

(lb a.i./ft 3 ) A (mg/m 3 ) B Inhalation Exposure C
(mg/day) Inhalation Dose D
(mg/kg/day) Inhalation

MOE E

0.00000001 0.218 0.0174 0.00025 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 ft 2 ] * [1 gallon/128 fl.oz.] * [8.35 lb soln/gallon] * [0.1% a.i.] /

8 ft = 0.00000001 lb a.i./ft 3

B. Application rate (mg/m 3 ) = 0.00000001 lb a.i./ft 3 * [454000 mg/lb] * [35 ft 3 /m 3 ] = 0.218 mg/m 3

C. Inhalation Exposure (mg/day) = [Application Rate (mg/m 3 ) * Breathing Rate (1 m 3 /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-applic ation” to describe exposur es to individuals that occur as a result of being in an environment that has been prev iously treated with a pesticide (also referred to as re-entry exposure). Th e Agency did not conduct a post-application risk assessment for tetramethrin for occupational ex posures. Although dermal exposure is possible and expected, no occupational pos t-application assessment was conducted because no systemic

effects were observed at the limit dose in available acceptable dermal toxicity studies in animals. Additionally, inhalation pos t-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.

8. 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 re sidues and “other substances that have a common mechanism of toxicity.”

Tetramethrin is a member of the pyrethroid cl ass of insecticides. This class also includes permethrin, cypermethrin, cyfluthrin, fluvalin ate, bifenthrin, fenpropathrin, and lambdacyhalothrin, among others. EPA developed a dr aft science policy document on the proposed19 common mechanism of toxicity for naturally-occurring pyrethri ns and synthetic pyrethroids (Proposed common mechanism grouping for the pyr ethrins and pyrethroids, draft, May 19, 2009; http://www.regulations.gov/search/R egs/home.html#documentDetail?R=09000064809a62df ). This document was supported by the FIFRA Scie ntific Advisory Panel (SAP) and EPA will finalize the policy document on th e pyrethroid common mechanism of toxicity taking into

account the SAP comments. Pe sticides with a common mechanism of toxicity are subject to

cumulative risk assessment under the FQPA. Research is on-goi ng by EPA’s Office of Research and Development (ORD) to make improvements to the Stochastic Human Exposure and Dose Simulation (SHEDS) probabilistic exposure model which are important for the cumulative risk assessment. EPA ORD is also developing phys iologically-based pharmacokinetic models for several pyrethroids. The status of both of these research modeling efforts will be reviewed by the FIFRA SAP in July, 2010. For information rega rding EPA’s efforts to evaluate the risk to pyrethroids, see http://www.epa.gov/oppsrrd1/re evaluation/pyrethroid s-pyrethrins.html.

9. Tetramethrin Human Incident Reports

The OPP Incident Data System (IDS) and Po ison 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 tetramethr in as a cause of any of the reported health effects unless supported by results from other data sources or unle ss the individual incidents are

well documented.

There were approximately 98 reported incidents in the IDS database over the five year period from 2002 to 2007 (for which the incident report was conducted) for products containing tetramethrin. Since there are no pesticide produc ts for which tetramethrin is the sole active ingredient, reported incidents ca nnot 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 docum ented health effects reported either no effects or mild effects resul ting from tetramethrin-related exposures. The majority of the symptoms included respirator y irritation, shortness of breath, blisters, welts, hives, dizziness, rashes, coughing, a nd eye irritation, which are simila r to that of other pyrethroid compounds. The PCC incidents involved a wide range of effects including cardiovascular, gastrointestinal, resp iratory, dermal, and ocular effects.

The Agency believes the number of reported inci dents is small in relation to the estimated usage of tetramethrin, which is approximate ly 15,000 to 30,000 pounds per year. Tetramethrin applications are primarily reside ntial localized or spot treatment s via aerosol or RTU sprays on an “as needed” basis (residential exposures acco unted for 98% of the reported cases involving tetramethrin); therefore, given this broa d spectrum residential use pattern, the Agency estimates the number of applications per year could range in the hundreds of thousands or greater.

In conclusion, the incident report does not garn er greater concern for the active ingredient tetramethrin solely. Furthermore, in a recent review of the pyrethroid class of chemicals and aggravated dermal and asthmatic reactions, titled “A Review of the Relationship between Pyrethrins, Pyrethroid Exposur e and Asthma and Allergies,” dated September 18, 2009, the20 Agency concluded, based on the weight of the evid ence, there is not a clear relationship between pyrethrins/pyrethroid exposure and asthma and alle rgies. Therefore, the Agency is not requiring additional warnings or label statements specific to asthmatics on pyrethroids and pyrethrins enduse product labels at this time. For more information on this revi ew, please refer to http://www.epa.gov/oppsrrd1/reev aluation/pyrethrins-pyrethroid s-asthma-allergy-9-18-09.pdf.

B. Environmental Risk Assessment

Tetramethrin is used in residential and i ndustrial/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 agricult ure or in mosquito abatement by public authorities. The use pattern is, therefore, in individual, isolated areas, and again, in small amounts. Tetramethrin also decomposes rapidl y by photolysis and hydrolysis. The localized use pattern of tetramethrin, combined with the lo w total pounds used on a national basis, and rapid degradation due to photolysis a nd hydrolysis, make it highly unlik ely 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 organism s present at the time of sprayi ng 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 w ith the localized use patterns of tetramethrin. As a result, tetramethrin’s ecologi cal 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 Ecol ogical 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 ingredie nts are more persistent than te tramethrin and provide residual activity against insects no t initially exposed. Tetramethrin decomposes rapidly by photolysis and hydrolysis in shallow, non-turbid water. Photolys is in air is expected to be rapid (half-life 30 minutes) based on reaction with ozone. Tetramethr in 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 sligh tly mobile in soil (Koc value range from 1,249- 2,939), has a vapor pressure of 7.1x10-6 mm Hg, wate r solubility of 1.83 mg/L, and an estimated Henry’s law constant of 1.7x10-6 atm-m3/mol-1.

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 the21 entire ester structure and possibly the mode of action of the parent tetramethrin. However, it too is subject to rapid hydrolysis, and therefore, expo sure to acid-NPY is unlikely. In two acceptable field dissipation studies, tetram ethrin 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, a nd tetramethrin rapidly degrades

in hours. While there are numerous outdoor uses , these applications are limited to spot treatments in localized areas and, again, the degr adation of tetramethrin to non-toxic degradates is rapid. There is potential for tetramethrin re sidues to be transported to aquatic systems from use in drainage systems, but only in acidic wa ter where hydrolysis is slower. However, the Agency believes exposure is unlikely because produc t labels prohibit direct application to water.

2. Ecological Ex posure and Risk

The possible exposure mechanisms considered following tetramethrin applications were runoff, spray drift, and direct spray. Only dire ct 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 drif t 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 te tramethrin degrades rapidly. Given that degradation of tetramethrin to non-toxic degrad ates is rapid, the primary risk will be acute exposure to tetramethrin at the time of a pplication and a brief period thereafter.

Acute toxicity data from studies submitte d 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 toxic ity 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/ ), 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 provi de insight into the dir ect 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 ch aracteristics of affected communities.

a. Terrestrial Organisms

No terrestrial modeling was conducted for te tramethrin because exposure of non-target organisms to harmful levels is unlikely based on the localized use patter ns, low total pounds used on a national basis, and rapid de gradation 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 characteri zation, 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 summarizes22 the specific measurement endpoint value selected to evaluate risk s for tetramethrin to mammals

and birds.

Table 9. Summary of Specific Measurement Endpoint Va lues Selected to Evaluate Risk for the Associated Terrestrial Animal Assessment Endpoints Selected Measurement Endpoint Values and Source

Assessment

Ends Acute

Measurement

Endpoint

(most sensitive) Species Study

Duration Toxicity

Value Most Sensitive Endpoint (MRID) Acute Toxicity

Classification

Acute oral toxicity Bobwhite quail Single oral

dose LD 50 >2250 mg/kg-bw Mortality* (416096-04/ Acceptable) Survival and Reproduction

of Birds, Reptiles and Amphibians Acute dietary toxicity Bobwhite quail and

Mallard

duck 8 days LC 50 >5620 mg/kg/-diet Mortality* (416096-05,

416096-06/ Acceptable) Practically

non-toxic

Acute oral toxicity, LD 50 Rat Single oral

dose LD 50 >5000 mg/kg-bw Mortality* (00063574/ Acceptable)

Dermal toxicity, LD 50 Rat Not

available LD 50 >5000 mg/kg-bw Mortality* (00063574/ Acceptable)

Inhalation toxicity, LC 50 Rat Not

available LC 50 >1.18 mg/L Mortality* (421464-01/ Acceptable) Survival and Reproduction

of Terrestrial

Mammals

Reproduction

NOAEL Rat Two – generation 25 mg/kg/day Mortality* (161842/ Acceptable) Practically

non-toxic

Contact LD 50 (μg/bee) Honey bee ( Apis mellifera ) 48 hours LD 50 0.155 μg/bee Mortality (416096-13/ Acceptable) Survival of

Terrestrial

Invertebrates

and Beneficial

Insects Foliar residue toxicity (honey bee) Honey bee ( Apis mellifera ) 24 hours
post

treatment < 3 hours
post

treatment Mortality (419408-01/ Acceptable) 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 practica lly non-toxic to birds and mammals on an acute exposure basis.

The limitation of outdoor applications to spot treatments and the non-pe rsistent nature of tetramethrin make it unlikely that exposure suffi cient 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 di et from treated feed items. The use of tetramethrin as a spot treatm ent in residential and/or commercial settings is unlikely to result in extensive tr eatment of potential feed item s. In addition, although chronic toxicity studies are not designed to determin e 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.23 Given that tetramethrin is an insecticide, it is considered highly toxic to invertebrates, including beneficial insects, such as honey bees, on an acute contac t exposure basis. Non-target invertebrates present at the time of spraying and shortly thereafter ar e 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. The Agency believes there is a low likelihood of e xposure to non-target terre strial plants because outdoor applications are limited to spot treatme nts, and therefore, is not requiring additional toxicity data at this time. The Agency, however, may reevaluate the need for this data during registration review, which is scheduled to being in 2012.

b. Aquatic Organisms

No aquatic exposure modeling was conducted for tetramethrin because exposure of nontarget organisms to harmful levels is unlikel y based on the localized use patterns, low total pounds used on a national basis, and rapid degrad ation due to photolysis and hydrolysis. Also, the aquatic exposure models assume that the chem ical 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 subm itted studies and review of the literature.

The Agency developed an effects characteri zation, 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 animal s. Table 10 summarizes the toxic effects and

reference values used to assess risks fo r tetramethrin to aquatic organisms.

Table 10. Summary of Specific Measur ement Endpoint Values Selected to Evaluate Risk for the Associated Terrestrial Animal Assessment Endpoints Selected Measurement Endpoint Values and Source

Assessment

Ends Acute

Measurement

Endpoint

(most sensitive) Species Study

Duration Toxicity

Value Most Sensitive Endpoint (MRID) Acute Toxicity

Classification

Survival and Reproduction

of Freshwater

Vertebrates (fishes, etc.) Freshwater

fish or amphibian

LC 50 Rainbow

trout ( Oncorhyn

chus mykiss) 96 hr LC 50 3.7 ppb Mortality (416096-08/ Acceptable) Very Highly

Toxic

Survival and Reproduction

of Freshwater

Invertebrates Freshwater

invertebrates Water flea ( Daphnia magna) 48 hr EC 50flowthrough 45 ppb Immobilization and mortality (416096-09/ Supplemental) Very Highly

Toxic

Freshwater and Estuarine/Mari ne Fish and Invertebrates

The acute toxicity of tetramethrin was tested in two species of fr eshwater fish (rainbow trout and bluegill sunfish) a nd one freshwater invertebrate. Based on submitted studies,24 tetramethrin is classified as very highly toxi c to fish and invertebra tes on an acute exposure basis. No chronic toxicity data were available for freshwater fi sh or invertebrates. However, the limitation of outdoor applications to spot treatments and the non-persistent nature of tetramethrin make it unlikely that exposure sufficien t to cause the chronic effects would occur. The use of tetramethrin as a spot treatment in re sidential and/or commerci al 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 toxici ty studies are not desi gned to determine how long an exposure is necessary to cause advers e chronic effects, the quick degradation of

tetramethrin would reduce the amount of time th at toxic residues are av ailable 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 estu arine/marine fish or

invertebrates because the outdoor us es of tetramethrin should not pose an acute risk to aquatic animals (fish, aquatic-phase amphibians, and in vertebrates) since exposure levels are not expected to reach thresholds where adverse effe cts would be likely for such uses. Additionally, based on the rapid photolytic and hydrolytic degrad ation of tetramethrin, and its demonstrated rapid dissipation in field studies, the exposure duration is not e xpected to be sufficient to cause reproductive effects. There are potential acute risk s to non-target aquatic organisms from direct application to drainage systems, but only in ac idic waters where hydrolys is is slower. This remains an uncertainly in the risk assessment; how ever, 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 pl ants. Runoff exposure is not expected due to very short photolysis, hydrolysis, and field di ssipation half-lives. Spray drif t exposure is expected to be minimal based on use patterns and label restrictio ns. Therefore, the Agency is not requiring additional toxicity data at this time. The Agenc y, however, may reevaluate the need for this data during registration review, which is scheduled to being in 2012.

c. Data Gaps

As stated above, the Agency does not have chro nic toxicity data for either terrestrial or aquatic organisms, acute or chronic toxicity da ta for terrestrial or a quatic plants, nor acute toxicity data for are es tuarine/marine animals. Although th ese data are guideline requirements, the available effects data, non-persistent natu re 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 In cident Information System) database for ecological incidents (run on Dec. 2, 2005) iden tified no ecological incidents involving25 tetramethrin. The number of documen ted incidents in EIIS is believ ed to be a very small fraction of total mortality caused by pesticides for a vari ety 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 a nd indirect effects to listed species resulting from the use of tetramethri n. No direct or indirect effects to endangered species are expected, except the pote ntial for direct effects for Listed insects or indirect effects to plants if they have an obligate relatio nship with a Listed insect pollinator.

Table 11. Listed Species Associated With Direct or I ndirect Effects Due to Applicat ions of Tetramethrin for

all Outdoor Uses

Listed Taxon Direct Effects Indirect Effects

Terrestrial and semi-aquatic plants – monocots None (1) Possible (2)

Terrestrial and semi-aquatic plants - dicots None (1) Possible (2)

Insects Yes (acute) None

Birds None (3) None (4)

Terrestrial phase amphibians None (3) None (4)

Reptiles None (3) None (4)

Mammals None (5) None (4)

Aquatic vascular plants None (1) None

Freshwater fish None (6) None (4)

Aquatic phase amphibians None (6) None (4)

Freshwater crustaceans None (6) None (4)

Mollusks None (6) None (4)

Marine/estuarine fish None (6) None (4)

Marine/estuarine crustacea ns None (6) 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 eval uated for the supported use of tetramethrin because risk quotients (RQs) were not calculated in this assessment. However, acute risks from tetramethrin’s outdoor uses to listed aquatic sp ecies are not expected due to low application rates, the localized and spatially fragmented us e patterns, and rapid dissipation of the chemical stressor due to photolys is and hydrolysis.26 In terrestrial environments, vertebrates such as mammals, birds, reptiles and amphibians are not expected to be at risk because tetramethrin is practical ly non-toxic to birds and mammals, and because of the localized and fragmented use pattern s. 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 expe cted to persist long enough to lead to chronic exposure.27 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 stration. The Agency has previ ously identified and required the submission of the generic (i.e., act ive ingredient-specific) data required to support reregistration of products containing the active in gredient tetramethrin. The Agency has completed its review of these generic data, and has determined that th e data are sufficient to support reregistration 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-c ontaining products are eligible for rere gistration provided that label amendments are made as outlined in Chapte r V. Appendix A summarizes the uses of the tetramethrin that are eligible for reregistra tion. Appendix B identifi es the generic data requirements that the Agency reviewed as part of its determination of rere gistration 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 la beled and used as specified in this document, would present risks inconsistent with FIFRA. Accordingly, sh ould a registrant fail to implement any of the label changes identified in this document, the Ag ency 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 cu rrent risks for tetramethrin will be adequately mitigated for the purposes of this determination under FIFRA.

B. Public Participation

Through the Agency’s public participation pr ocess, EPA worked with stakeholders and the public to reach the regulatory decisions for tetramethrin. EPA released the tetramethrin preliminary risk assessments fo r public comment on February 27, 2008, for a 60-day public comment period (Phase 3 of the public pa rticipation 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, Ki ng Company; the California Re gional Water Quality Control Board, S.F. Bay Region; the California Stormwat er Quality Associati on (CASQA); California Tri-TAC; as well as from private citizens. Th ese comments in their entirety, responses to the comments, as well as the preliminary and revise d risk assessments, are available in the public docket (OPP-2008-0014) at http:www.regulations.gov.

C. Regulatory Position

1. Regulatory Rationale28 The Agency has determined that products containing tetramethrin are eligible for reregistration provided that sp ecified label amendments are made. The following is a summary of the rationale for managing risks associated wi th the use of tetramethrin. Where labelling revisions are warranted, specific language is set forth in the summary table of Section V. Maximum application rates eligible for re registration are set forth in Appendix A.

a. Human Health Risk Management

There are no human health risks of concer n for tetramethrin, and therefore, no risk mitigation is necessary. The personal protectiv e equipment (PPE) for all occupational handlers is baseline (long-sleeve shirt, long pa nts, 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. However, although the Agency be lieves 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 reduc e the potential exposure of tetramethrin to aquatic organisms as stipulated in the Label Table, Table 12. Because outdoor uses will be limited to localized spot treatments, no additi onal mitigation measures, beyond those specified below, are required.

• Incorporation of PR Notice 2008-1, “Environmental Hazard General Labeling Statements

on Outdoor Residential Use Products” on a ppropriate outdoor non-agricultural end-use products.

• Products labeled for General Outdoor Surface and Space Sprays (except outdoor fogging devices):

“All outdoor applications must be limited to spot or crack-and-cr evice treatments only, except for the following permitted uses:

 Treatment to soil or vegetation around structures;

 Applications to building foundations up to a maximu m height of 3 feet.

Other than applications to building foundations , all outdoor applica tions to impervious surfaces such as sidewalks, driveways, patios, porches and structural surfaces (such as windows, doors, and eaves) are limited to spot treatments or crack-and-crevice applications, only.”

• Products labeled for use around or near floor dr ains must contain the following statement:

“Application is prohibited directly into sewe rs or drains, or to any area like a gutter where drainage to sewers, storm drains, water bodies, or aquatic hab itat can occur. Do not allow the product to enter any dr ain during or after application.”

• Products labeled for use in drains or sewers must c ontain the following statement:29 “Do not apply directly to sewers or drains, or to any area like a gu tter where drainage to sewers, storm drains, water bodies, or aquatic habitat can occur, except as directed by this

label.”

2. Endocrine Disruptor Screening Program

As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (inc luding pesticide active and other ingredients) may have an effect in humans or wildlife si milar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered ap proach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 scr eening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine related eff ects caused by the substance, and establish a quantitative relationship betw een the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issu ed test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was sele cted based on the potenti al for human exposure through pathways such as food and water, resi dential activity, and cer tain post-application agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors.

Tetramethrin is not among the group of 58 pestic ide active ingredients on the initial list to

be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. Accordingly, EPA anticipates i ssuing future EDSP orders/data call-ins for all registration review cases, in cluding those for which EPA ha s already opened a registration review docket for a pesticide active ingredient. The tetramethrin regist ration review docket is currently scheduled to open in 2012.

For further information on the status of the ED SP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, plea se visit our website: http://www.epa.gov/endo/.

3. Endangered Species

The Endangered Species Act required federal agen cies 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 Pr ogram to identify pesticides whose use may cause adverse impacts on federally listed endange red 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, EP A puts basic toxicity and exposure data developed30 for the REDs into context for individual list ed species and considers ecological parameters, pesticide use information, the geographic rela tionship between specific pesticide uses and species locations and biological re quirements and behavioral aspect s of the particular species. When conducted, these analyses take into cons ideration any regulatory changes recommended in this RED being implemented at th at 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 n ecessary. 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 endanger ed 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, cons titute 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 sp ecific assessment that will evaluate whether exposure may be at levels that could cause ha rm to specific listed sp ecies and their critical

habitat. That assessment refines the screen ing-level assessment to take into account the geographic area of pesticide use in relation to the listed species, th e 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 pestic ide, any geographically specific changes to the pesticide’s registration will be implemented th rough the process described in the Agency’s Federal Register Notice (54 FR 27984) regardin g implementation of the Endangered Species Protection Program.

D. Labeling Requirements

In order to be eligible for reregistration, various use and safety information will be included in the labeling of all e nd-use products containing tetramethr in. For the specific labeling statements, refer to Section V of this RED document.31 V. What Registrants Need to Do

The Agency has determined that products containing tetramethrin are eligible for reregistration provided that th e required label amendments are made. The Agency intends to issue Data Call-In Notices (DCIs) requiring pr oduct-specific data. Generally, registrants will have 90 days from receipt of a DCI to comp lete 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 tetram ethrin to be eligible for reregistration.

A. Manufacturing Use Products

1. Additional Generic Data Requirements

The generic data base supporting the reregistration of tetramet hrin for currently registered

uses has been reviewed and determined to be su bstantially complete. However, a few data gaps remain, and these are listed below.

Product Chemistry All product chemistry data requireme nts will be required for the te chnical grade active ingredient (see Appendix B).

Toxicology 830.7050 UV / Visible Absorption

870.1300 Acute Inhalation

870.2500 Acute Dermal Irritation

870.2600 Skin Sensitization 870.3700a Developmental Toxicity (rodent) 870.6200a Acute Neurotoxicity 870.6200b Subchronic Neurotoxicity study 870.6300 Developmental Neurotoxicity study 2
870.7800 Immunotoxicity

2. Labeling for Manufacturing-Use Products

2 Based on the Agency’s review of existing pyrethroid data, EPA has come to the conclusion that the DNT is not a particularly sensitive study for comparing the sensitivity of young and adult animals to pyrethroids. EPA has recently determined that, as an a lternative to the generation and submissi on of a new DNT study, pyrethroid registrants may instead choose to cite the six previously submitted DNT studies for pyrethroid pesticides. The Agency is also investigating the need for additional experimentation, specific to the mode of action and pharmacokinetic characteristics of pyrethroids, to evalua te the potential for increased susceptibility of young organisms. These conclusions and determinations were communicated to registrants of some pyrethroid activeingredients in a letter from EPA dated September 4, 2009 (available from the public docket EPA-HQ-OPP2008-0331-0027). Further details are also available from the website http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html

.32 To ensure compliance with FIFRA, manufact uring-use product (MUP) labeling should be revised to comply with all current EPA regulatio ns, PR Notices, and applicable policies. The MUP labeling should bear the label st atements contained in Table 12.

B. End-Use Products

1. Additional Product-Sp ecific Data Requirements

Section 4(g)(2)(B) of FIFRA calls for the Ag ency 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 curren t EPA acceptance criteria, and if not, commit to conduct new studies. If a regi strant 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 Re gistrant’s Response Form provided for each product. The Agency intends to issue a separate product-specific data call-in (PDCI), outlining specific data requirements. For any questions re garding the PDCI, please contact Karen Jones at (703) 308-8047.

In addition to the standard product-specifi c data requirements, efficacy data for all applications that target public health pests must be submitted. Additional information on the efficacy data can be found in the Series 810 Product Performance Test Guidelines on the Agency’s website ( http://www.epa.gov/opptsfrs/publications/OPPTS_Harmonized/ 810_Product_Performance_Test_Guidelines/index. html).

Efficacy Data 810.3000 General considerations for efficacy of invertebrate control agents 810.3100 Soil treatments for imported fire ants 810.3200 Livestock, poultry, fur- and w oo-bearing animal treatment 810.3300 Treatments to control pests of humans and pets 810.3400 Mosquito, black fly, and biting midge (sand fly) treatments

810.3500 Premises treatments SS Special study for arthropods

The Agency is also requiring a compan ion animal study (870.7200) for tetramethrin products used on domestic animals. The study is to ensure that pesticid e formulations for the treatment of external pe sts on domestic animals have an adequate margin of safety for the treated companion animal. In addition, data from compani on animal safety studies also serve as a basis for product labeling.

870.7200 Companion animal study

2. Labeling for End-Use Products

To be eligible for reregistration, 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 dist ribution and sale of products bearing old33 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 la bel changes, and other factors.34C. Labeling Changes Summary TableIn order to be eligible for reregistration, amend all product labels to comply withthe following table. Table 12 describes howlanguage on the labels should be amended.Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on LabelManufacturing Use ProductsMaximum application rates eligible for reregistration are set forth in Appendix A.For Manufacturing Use Products thatwill be formulated into total releasefogger end-use products that containdirections for use indoorsIf information is available that justifies a duration longer than 2 hoursfor the waiting period before beginning ventilation following anapplication or a duration longer than 2 hours as the length of theventilation period, submit that information to the Agency.Directions for useFor all Manufacturing Use Products “Only for formulation into aninsecticidefor the following use(s) [fillblank only with those uses that are being supported by MP registrant].”Directions for useOne of these statements may be addedto a label to allow reformulation of theproduct for a specific use or alladditional uses supported by aformulator or user group“This product may be used to formulate products for specific use(s) notlisted on the MP label if the formulator, user group, or grower hascomplied with U.S. EPA submission requirements regarding support ofsuch use(s).”“This product may be used to formulate products for any additional use(s)not listed on the MP label if the formulator, user group, or grower hascomplied with U.S. EPA submission requirements regarding support ofsuch use(s).”Directions for UseEnvironmental Hazards Statements“ENVIRONMENTAL HAZARDS”“This pesticide is highly toxic to aquatic organisms, including fish andaquatic invertebrates. Do not discharge effluent containing this productinto lakes, streams, ponds, estuaries, oceans, or other waters unless inaccordance with the requirements of a National Pollutant DischargeEliminations System (NPDES) permit and the permitting authority hasbeen notified in writing prior to discharge. Do not discharge effluentcontaining this product to sewer systems without previously notifying thelocal sewage treatment plant authority. For guidance, contact your StatePrecautionary Statements:Environmental Hazards35Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on LabelWater Board or Regional Office of the Environmental Protection Agency.”End-Use Products Intended for Occupational Use (WPS and Non-WPS)Maximum application rates eligible for reregistration are set forth in Appendix A.PPE Requirements for Ready To Use(RTU) Formulations (RTU Liquids andPressurized Liquids)“Personal Protective Equipment (PPE)”“Some materials that are chemical-resistant to this product are [registrantinserts correct material(s)].” For more options, follow the instructions forcategory [insert A, B, C, D, E, F,G or H] on the chemical-resistancecategory selection chart.“Applicators and other handlers must wear:> Long-sleeve shirt and long pants, and> Shoes plus socks.”Immediately following/belowPrecautionary Statements: Hazardsto Humans and Domestic AnimalsPPE Requirements for LiquidConcentrates including EmulsifiableConcentrates“Personal Protective Equipment (PPE)”“Some materials that are chemical-resistant to this product are [registrantinserts correct material(s)].” For more options, follow the instructions forcategory [insert A, B, C, D, E, F,G or H] on the chemical-resistancecategory selection chart.“Mixers, Loaders, Applicatorsand other handlers must wear:> Long-sleeve shirt and long pants, and> Shoes plus socks.”Immediately following/belowPrecautionary Statements: Hazardsto Humans and Domestic AnimalsUser Safety Requirements“Follow manufacturer’s instructionsfor cleaning/maintaining PPE. If nosuch instructions for washables exist, use detergent and hot water. Keepand wash PPE separately from other laundry.”Precautionary Statements: Hazardsto Humans and Domestic Animalsimmediately following the PPErequirementsUser Safety Recommendations “User Safety Recommendations”“Users should wash hands before eating, drinking, chewing gum, usingtobacco, or using the toilet.”“Users should remove clothing/ PPE immediately if pesticide gets inside,Precautionary Statements under:Hazards to Humans and DomesticAnimals(Must be placed in a box.)36Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Labelthen wash thoroughly and put on clean clothing.”“Users should remove PPE immediately after handling this product. Washthe outside of gloves before removing. As soon as possible, washthoroughly and change into clean clothing.”Environmental Hazards Statements forOutdoor Aerosols and FoggersANDOutdoor Products RegisteredOnlyforCommercial Use Sites (eg. golfcourses).“ENVIRONMENTAL HAZARDS”“This pesticide is extremely toxic to aquatic organisms, including fish andaquatic invertebrates. Do not apply directly to water, or to areas wheresurface water is present, or to inter-tidal areas below the mean high watermark. Do not contaminate water when cleaning equipment or disposing ofequipment washwater or rinsate.”“This product is highly toxic to bees exposed to direct treatment onblooming crops or weeds.Do not apply this product or allow it to drift toblooming crops or weeds while beesare actively visiting the area.”Precautionary Statements: Hazards toHumans and Domestic AnimalsEnvironmental Hazard Statements onLiquid Concentrateconsumeroutdoorproducts (e.g., liquids mixed with waterby the user for a tank sprayer or hoseend attachment)“This pesticide is extremely toxic to aquatic organisms, including fish andinvertebrates.To protect the environment, do not allow pesticide to enter or run off intostorm drains, drainage ditches, guttersor surface waters. Applying thisproduct in calm weather when rain is not predicted for the next 24 hourswill help to ensure that wind or rain does not blow or wash pesticide offthe treatment area. Rinsing application equipment over the treated areawill help avoid run off to water bodies or drainage systems.This pesticide is highly toxic to bees exposed to direct treatment onblooming crops or weeds. Do not apply this product or allow it to drift toblooming crops or weeds while bees are actively visiting the treatmentarea.”Environmental Hazard StatementEnvironmental Hazard Statements onLiquid Ready-to-Use (except aerosolsand foggers)consumeroutdoorproducts“This pesticide is extremely toxic to aquatic organisms, including fish andinvertebrates.To protect the environment, do not allow pesticide to enter or run off intostorm drains, drainage ditches, guttersor surface waters. Applying thisEnvironmental Hazard Statement37Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Labelproduct in calm weather when rain is not predicted for the next 24 hourswill help to ensure that wind or rain does not blow or wash pesticide offthe treatment area.This pesticide is highly toxic to bees exposed to direct treatment onblooming crops or weeds. Do not apply this product or allow it to drift toblooming crops or weeds while bees are actively visiting the treatmentarea.”Environmental Hazards Statements forProducts Labeled for Indoor Uses Only“ENVIRONMENTAL HAZARDS”“This pesticide is extremely toxic to aquatic organisms, including fish andaquatic invertebrates. Do not contaminate water when disposing ofequipment, washwater, or rinsate.See Directions for Use for additionalprecautions and requirements.”For indoor commercial, industrial orinstitutional products packagedin containers equal to or greater than 5 gallons or 50 lbs add thefollowing statement:“Do not discharge effluent containing this product into lakes, streams,ponds, estuaries, oceans, or otherwaters unless in accordance with therequirements of a National Pollution Discharge Elimination System(NPDES) permit and the permitting authority has been notified in writingprior to discharge. Do not discharge effluent containing this product tosewer systems without previously notifying the local sewage treatmentplant authority. For guidance contact your State Water Board or RegionalOffice of the EPA."Precautionary Statements: Hazards toHumans and Domestic Animals38Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on LabelEnvironmental Hazards Statements forProducts Labeled for Both Indoor andOutdoor Uses Only“ENVIRONMENTAL HAZARDS for TERRESTRIALAPPLICATIONS”Refer to appropriate consumer outdoor environmentalhazard statementsabove.“ENVIRONMENTAL HAZARDS for INDOOR USE”“This pesticide is extremely toxic to aquatic organisms, including fish andaquatic invertebrates. Do not contaminate water when disposing ofequipment, washwater, or rinsate.See Directions for Use for additionalprecautions and requirements.”For indoor commercial, industrial orinstitutional products packagedin containers equal to or greater than 5 gallons or 50 lbs add thefollowing statement:“Do not discharge effluent containing this product into lakes, streams,ponds, estuaries, oceans, or otherwaters unless in accordance with therequirements of a National Pollution Discharge Elimination System(NPDES) permit and the permitting authority has been notified in writingprior to discharge. Do not discharge effluent containing this product tosewer systems without previously notifying the local sewage treatmentplant authority. For guidance contact your State Water Board or RegionalOffice of the EPA."Precautionary Statements: Hazards toHumans and Domestic AnimalsRestricted-Entry Interval for Productswith Directions for use within thescope of the Worker ProtectionStandard for Agricultural Pesticides(WPS)For Products Subject to WPS asrequired by Supplement 3 of PR Notice93-7“Do not enter or allow worker entry into treated areas during the restrictedentry interval (REI) of 12 hours.”Directions for Use, in theAgricultural Use Requirements Box39Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on LabelEarly Entry Personal ProtectiveEquipmentFor Products Subject to WPS asrequired by Supplement 3 of PR Notice93-7“PPE required for early entry to treated areas that is permitted under theWorker Protection Standard and that involves contact with anything thathas been treated, such as plants, soil, or water is coveralls, shoes andsocks, and waterproof gloves.”Directions for Use, in AgriculturalUse Requirements BoxGeneral Application Restrictions “Do not apply thisproduct in a way that will contact workers or otherpersons, either directly or through drift. Only protected handlers may be inthe area during application.”“Do not apply when food is present.”“Do not use in food areas of food handling establishments, restaurants, orother areas where food is commercially prepared or processed. Do not usein serving areas while food is exposedor facility is in operation. Servingareas are areas where prepared foods are served, such as dining rooms, butexcluding areas where foods may be prepared or held. In the home, allfood processing surfaces and utensilsshould be covered during treatmentor thoroughly washed before use. Exposed food should be covered orremoved.”Place in the Directions for Usedirectly above the Agricultural UseBoxEntry Restrictions for NonWPS UsesFor products that do not contain directions for use that allow peopleto be present during application:“Do not enter or allow others to enter treated area until sprays have dried.”For products that contain directionsfor use that allow people to bepresent 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 bepresent during application), do not enter or allow others to enter treatedarea until sprays have dried.”For products that contain directionsfor use that allow people to bepresent during application AND are labeled for use as a space spray:If no WPS uses on the product label,place the appropriate statement in theDirections for Use Under GeneralPrecautions and Restrictions. If theproduct also contains WPS uses, thencreate a Non-Agricultural UseRequirements box as directed in PRNotice 93-7 and place the appropriatestatement inside that box.40Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Label“Except when (insert application method or site that allows people to bepresent during application), do not enter or allow others to enter untilvapors, mists, and aerosols have dispersed, and the treated area has beenthoroughly ventilated.”For total release foggers (TRF) labeled for indoor use (see additionalrequirements in TRF section below):“Wait at least two (2) hours after application, then open windows, ventsand doors for two more hours. If an odor is still detected additionalventilation isrequired.”General Application Restrictions for allproducts that do not contain directionsfor use in drains or sewersProducts labeled for use around or near floor drains must contain thefollowing statement.“Application is prohibited directly into sewers or drains, or to any arealike a gutter where drainage to sewers, storm drains, water bodies, oraquatic habitat can occur. Do notallow the product to enter any drainduring or after application.”Directions for UseGeneral Application Restrictions for allproducts that contain directions for usein drains or sewers“Do not apply directly to sewers or drains, or to any area like a gutterwhere drainage to sewers, storm drains, water bodies, or aquatic habitatcan occur, except as directed by this label.”Directions for UseGeneral Application Restrictions forTotal Release Foggers (TRF) labeledfor indoor useNote to registrants: The following labeling was sent to pyrethrins andpyrethroid registrants on March 23, 2010. The following labelstatements are required to appear on TRF EUPs, except wheremanufacturers can satisfactorily explain to the Agency that analternative approach would be adequate to address the causes of bugbomb exposure incidents.Use simple terms to express the volume of space treated in terms oflinear dimensions, with an assumed ceiling height, rather than in termsof cubic feet. Update the current statements to follow this model in theDirections for Use:Example: “One canister of foggerwill treat a room up to x feetby y feet with an 8 foot ceiling.”Directions for Use41Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on LabelAll current restrictions and requirements regarding the size of thetreated area remain unchanged.At a minimum include pictograms, where applicable, to illustrate thefollowing list of restrictions and directions for use:•do not use multiple canisters in a room•do not use in small confined areas•turn off ignition sources•remove or cover exposed food•air out the room before enteringInclude the following directions that prohibit use in closed, confinedspaces:•“Do not use in small, enclosed spaces such as closets, cabinets orunder counters or tables. Use of a fogger in an enclosed spacemay cause the product to explode, resulting in injury to people ordamage to property.”Include prominent headings using different font size or style (e.g., bold) inthe directions, such as:•To Use This Product Correctly[before the standard languageabout small spaces and ignition sources]•Before you fog [cover food, remove pets, etc]•To Start Fogging [how to set up and activate]•Airing Out [how long]Include the following phrase in a prominent place in the directions and inboldface type:•“Vacate the treated house, individual apartment unit, or otherstructure immediately”In addition to the standard Precautionary Statements, add the followinglanguage to the Precautionary Statements section of the label:•“Breathing spray mist may be harmful.”42Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on LabelInclude the following statement in bold font in the Directions for Use:•“Does not control bed bugs”Include the phrase “Do Not Re-enterfor X Hours” in aprominent place inthe directions and in boldface type. Include a clock face pictogram shadingthe entry restriction immediately above or below this direction.Example:Provide door knob hang tags atthe point-of-salewith a space forcustomers to write-in when the entry restricted time has expired.•For example, the text on the hangtag could state: “Do not enteruntil [space for time] on [space for date].”Add the following statement to tell others of the treatment:•“Fill out and place hang-tag on thedoor to the treated area to alertfamily and others with access to the treated area not to enter for Xhours.”Include label statements in both English and Spanish on all indoor totalrelease fogger product labels. Verify that the Spanish language text is atrue and accurate translation of the English text and submit verification43Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Labelstatement to EPA. Include both language versions of the labeling on theproduct container.Note: EPA is working to develop more general guidance for non-Englishpesticide labeling. If companies are interested in substituting a differentlanguage on product labels, in placeof Spanish, please submit a rationalefor such substitution along with the alternate label language.Additional Application Restrictions ForOutdoor Residential UseProducts labeled for General Outdoor Surface and Space Sprays(except outdoor fogging devices):“All outdoor applications must be limited to spot or crack-and-crevicetreatments only, except for the following permitted uses:(1) Treatment to soil or vegetation around structures;(2) Applications to building foundations, up to a maximum height of 3feet.Other than applications to building foundations, all outdoor applications toimpervious surfaces such as sidewalks, driveways, patios, porches andstructural surfaces (such as windows,doors, and eaves) are limited to spotand crack-and-creviceapplications, only.”Note to registrant: If the end use product does not contain directions foruse consistent with the exceptions above the exceptions may be eliminatedfrom the label.Requirements for Granular Formulations labeled or intended foroutdoor residential uses:“Apply this product directly to the lawnor garden area. Water treated areaas directed on this label. Donot water to the point of run-off.”“Do not make applications during rain.”Requirements for Liquid, Dust, and Ready to Use Formulationsproducts labeled or intended for outdoor residential uses:Directions for Use under GeneralPrecautions and Restrictions44Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Label“Do not water the treated areato the point of run-off.”“Do not make applications during rain.”End Use Products Primarily Used by Consumers/HomeownersMaximum application rates eligible for reregistration are set forth in Appendix A.Environmental Hazards Statements forOutdoor Aerosols (including TRF)ANDOutdoor Products RegisteredOnlyforCommercial Use Sites (eg. golfcourses).“ENVIRONMENTAL HAZARDS”“This pesticide is extremely toxic to aquatic organisms, including fish andaquatic invertebrates. Do not apply directly to water, or to areas wheresurface water is present, or to inter-tidal areas below the mean high watermark. Do not contaminate water when cleaning equipment or disposing ofequipment washwater or rinsate.”“This product is highly toxic to bees exposed to direct treatment onblooming crops or weeds.Do not apply this product or allow it to drift toblooming crops or weeds while beesare actively visiting the area.”Precautionary Statements: Hazards toHumans and Domestic AnimalsEnvironmental Hazard Statements onLiquid Concentrateconsumeroutdoorproducts (e.g., liquids mixed with waterby the user for a tank sprayer or hoseend attachment)“This pesticide is extremely toxic to aquatic organisms, including fish andinvertebrates. To protect the environment, do not allow pesticide to enteror run off into storm drains, drainageditches, gutters or surface waters.Applying this product in calm weather when rain is not predicted for thenext 24 hours will help to ensure that wind or rain does not blow or washpesticide off the treatment area. Rinsing application equipment over thetreated area will help avoid run off towater bodies or drainage systems.This pesticide is highly toxic to bees exposed to direct treatment onblooming crops or weeds. Do not apply this product or allow it to drift toblooming crops or weeds while bees are actively visiting the treatmentarea.”Environmental Hazard StatementEnvironmental Hazard Statements onLiquid Ready-to-Use (except aerosols,including TRF)consumeroutdoorproducts“This pesticide is extremely toxic to aquatic organisms, including fish andinvertebrates. To protect the environment, do not allow pesticide to enteror run off into storm drains, drainageditches, gutters or surface waters.Applying this product in calm weather when rain is not predicted for theEnvironmental Hazard Statement45Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Labelnext 24 hours will help to ensure that wind or rain does not blow or washpesticide off the treatment area.This pesticide is highly toxic to bees exposed to direct treatment onblooming crops or weeds. Do not apply this product or allow it to drift toblooming crops or weeds while bees are actively visiting the treatmentarea.”Environmental Hazards Statements forProducts Labeled for Indoor Uses Only“ENVIRONMENTAL HAZARDS”“This pesticide is extremely toxic to aquatic organisms, including fish andaquatic invertebrates. Do not contaminate water when disposing ofequipment, washwater, or rinsate.See Directions for Use for additionalprecautions and requirements.”For indoor commercial, industrial orinstitutional products packagedin containers equal to or greater than 5 gallons or 50 lbs add thefollowing statement:“Do not discharge effluent containing this product into lakes, streams,ponds, estuaries, oceans, or otherwaters unless in accordance with therequirements of a National Pollution Discharge Elimination System(NPDES) permit and the permitting authority has been notified in writingprior to discharge. Do not discharge effluent containing this product tosewer systems without previously notifying the local sewage treatmentplant authority. For guidance contact your State Water Board or RegionalOffice of the EPA."Precautionary Statements: Hazards toHumans and Domestic AnimalsEnvironmental Hazards Statements forProducts Labeled for Both Indoor andOutdoor Uses Only“ENVIRONMENTAL HAZARDS for TERRESTRIALAPPLICATIONS”Refer to appropriate consumer outdoor environmentalhazard statementsabove.“ENVIRONMENTAL HAZARDS for INDOOR USE”“This pesticide is extremely toxic to aquatic organisms, including fish andPrecautionary Statements: Hazards toHumans and Domestic Animals46Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Labelaquatic invertebrates. Do not contaminate water when disposing ofequipment, washwater, or rinsate.See Directions for Use for additionalprecautions and requirements.”For indoor commercial, industrial orinstitutional products packagedin containers equal to or greater than 5 gallons or 50 lbs add thefollowing statement:“Do not discharge effluent containing this product into lakes, streams,ponds, estuaries, oceans, or otherwaters unless in accordance with therequirements of a National Pollution Discharge Elimination System(NPDES) permit and the permitting authority has been notified in writingprior to discharge. Do not discharge effluent containing this product tosewer systems without previously notifying the local sewage treatmentplant authority. For guidance contact your State Water Board or RegionalOffice of the EPA."Entry Restrictions for Non-WPS UsesFor products that do not contain directions for use that allow peopleto be present during application:“Do not enter or allow others to enter treated area until sprays have dried.”For products that contain directionsfor use that allow people to bepresent 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 bepresent during application), do not enter or allow others to enter treatedarea until sprays have dried.”For products that contain directionsfor use that allow people to bepresent during application AND are labeled for use as a space spray:“Except when (insert application method or site that allows people to bepresent during application), do not enter or allow others to enter untilIf no WPS uses on the product label,place the appropriate statement in theDirections for Use Under GeneralPrecautions and Restrictions. If theproduct also contains WPS uses, thencreate a Non-Agricultural UseRequirements box as directed in PRNotice 93-7 and place the appropriatestatement inside that box.47Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Labelvapors, mists, and aerosols have dispersed, and the treated area has beenthoroughly ventilated.”For total release foggers labeledfor indoor use (see additionalrequirements in TRF section below):“Wait at least two (2) hours after application, then open windows, ventsand doors for two more hours. If an odor is still detected additionalventilation isrequired.”General Application Restrictions “Do not apply this product in a way that will contact adults, children, orpets, either directly or through drift.”Place at the beginning of theDirection for UseGeneral Application Restrictions for allproducts that do not contain directionsfor use in drains or sewersProducts labeled for use around or near floor drains must contain thefollowing statement.“Application is prohibited directly into sewers or drains, or to any arealike a gutter where drainage to sewers, storm drains, water bodies, oraquatic habitat can occur. Do notallow the product to enter any drainduring or after application.”Directions for UseGeneral Application Restrictions for allproducts that contain directions for usein drains or sewers“Do not apply directly to sewers or drains, or to any area like a gutterwhere drainage to sewers, storm drains, water bodies, or aquatic habitatcan occur, except as directed by this label.”Directions for UseAdditional Application Restrictions ForOutdoor Residential UseProducts labeled for General Outdoor Surface and Space Sprays(except outdoor fogging devices:“All outdoor applications must be limited to spot or crack-and-crevicetreatments only, except for the following permitted uses:(1) Treatment to soil or vegetation around structures; and,(2) Applications to building foundations, up to a maximum height of 3feet.Other than applications to building foundations, all outdoor applications toimpervious surfaces such as sidewalks, driveways, patios, porches andstructural surfaces (such as windows,doors, and eaves) are limited to spotand crack-and-creviceapplications, only.”Note to registrant: If the end use product does not contain directions foruse consistent with the exceptions above the exceptions may be eliminatedDirections for Use under GeneralPrecautions and Restrictions48Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Labelfrom the label.Requirements for Granular Formulations labeled or intended foroutdoor residential uses:“Apply this product directly to the lawnor garden area. Water treated areaas directed on this label. Donot water to the point of run-off.”“Do not make applications during rain.”Requirements for Liquid, Dust, and Ready to Use Formulationsproducts labeled or intended for outdoor residential uses:“Do not water the treated areato the point of run-off.”“Do not make applications during rain.”Application Restrictions for End UseProducts containing directions forindoor use“Do not apply when food is present. Exposed food should be covered orremoved. All food preparation surfaces and utensils should be coveredduring treatment or thoroughly washed before use.”Directions for use, within theapplication restrictions areaGeneral Application Restrictions forTotal Release Foggers (TRF) labeledfor indoor useNote to registrants: The following labeling was sent to pyrethrins andpyrethroid registrants on March 23, 2010. The following labelstatements are required to appear on TRF EUPs, except wheremanufacturers can satisfactorily explain to the Agency that analternative approach would be adequate to address the causes of bugbomb exposure incidents.Use simple terms to express the volume of space treated in terms oflinear dimensions, with an assumed ceiling height, rather than in termsof cubic feet. Update the current statements to follow this model in theDirections for Use:Example: “One canister of foggerwill treat a room up to x feetby y feet with an 8 foot ceiling.”All current restrictions and requirements regarding the size of theDirections for Use49Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Labeltreated area remain unchanged.At a minimum include pictograms, where applicable, to illustrate thefollowing list of restrictions and directions for use:•do not use multiple canisters in a room•do not use in small confined areas•turn off ignition sources•remove or cover exposed food•air out the room before enteringInclude the following directions that prohibit use in closed, confinedspaces:•“Do not use in small, enclosed spaces such as closets, cabinets orunder counters or tables. Use of a fogger in an enclosed spacemay cause the product to explode, resulting in injury to people ordamage to property.”Include prominent headings using different font size or style (e.g., bold) inthe directions, such as:•To Use This Product Correctly[before the standard languageabout small spaces and ignition sources]•Before you fog [cover food, remove pets, etc]•To Start Fogging [how to set up and activate]•Airing Out [how long]Include the following phrase in a prominent place in the directions and inboldface type:•“Vacate the treated house, individual apartment unit, or otherstructure immediately”In addition to the standard Precautionary Statements, add the followinglanguage to the Precautionary Statements section of the label:•“Breathing spray mist may be harmful.”50Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on LabelInclude the following statement in bold font in the Directions for Use:•“Does not control bed bugs”Include the phrase “Do Not Re-enterfor X Hours” in aprominent place inthe directions and in boldface type. Include a clock face pictogram shadingthe entry restriction immediately above or below this direction.Example:Provide door knob hang tags atthe point-of-salewith a space forcustomers to write-in when the entry restricted time has expired.•For example, the text on the hangtag could state: “Do not enteruntil [space for time] on [space for date].”Add the following statement to tell others of the treatment:•“Fill out and place hang-tag on thedoor to the treated area to alertfamily and others with access to the treated area not to enter for Xhours.”Include label statements in both English and Spanish on all indoor totalrelease fogger product labels. Verify that the Spanish language text is atrue and accurate translation of the English text and submit verificationstatement to EPA. Include both language versions of the labeling on the51Table 12. Summary of Labeling Changes for TetramethrinDescription Amended Labeling Language Placement on Labelproduct container.Note: EPA is working to develop more general guidance for non-Englishpesticide labeling. If companies are interested in substituting a differentlanguage on product labels, in placeof Spanish, please submit a rationalefor such substitution along with the alternate label language.52Appendix A.Non-Food and Non-Feed Use Patterns Subjectto the Reregistration of TetramethrinMaximum Application RateUse Profile(Application Method)% ActiveIngredient (% a.i.)Volume-basedArea-basedSpace-basedGeneral IndoorAand Outdoor SprayB(Trigger Pump Sprays, Low Pressure Hand Wand,Back Pack Sprayer)0.20 0.02 lb ai/galsolution0.00002 lb ai/ft20.000002 lb ai/ft3Aerosol Cans (Indoor & Outdoor Spray)0.35 0.035 lb ai/galsolution0.000035 lb ai/ft20.0000035 lb ai/ft3Indoor Total Release FoggerA0.54 n/a n/a 6 oz can / 4,600 ft3Animal Treatment(Aerosol Can)0.063 n/a n/a n/aOutdoor Jet Sprays (intended for wasp andhornet use only)0.20 1-2 sec burst n/a n/aOutdoor Fogging DevicesBC0.10 n/a 0.0000001 lb ai/ft21.25E-08 lb ai/ft3AUse sites include but are not limited to: commercial, industrial, institutional, and residential locations; agricultural structures and equipment;eating establishments; animal kennels andsleeping quarters; empty greenhouses; hospitals.BUse sites include but are not limited to: commercial, industrial, institutional, and residential locations; compost piles; ornamental plants; patios;paths.CExcludes RTU fogging devices.53 Appendix B. Data Supporting Guidelin e Requirements for Tetramethrin

Data Supporting Guideline Requirements for the Reregistration of Tetramethrin

Guideline

Number Study Description Citation(s)

PRODUCT CHEMISTRY
830.1550 Product Identity and Composition Required
830.1600 Description of Materials Used Required
830.1620 Description of Production Process Required
830.1670 Discussion of Formation of Impurities Required
830.1700 Preliminary Analysis Required
830.1750 Certified Limits Required
830.1800 Enforcement Analytical Method Required
830.6302 Color Required
830.6303 Physical State Required
830.6304 Odor Required
830.6313 Stability Required
830.7000 pH Required
830.7050 UV/Visible Absorption Required
830.7200 Melting Point Required
830.7220 Boiling Point Required
830.7300 Density Required
830.7370 Dissociation Constant Required

830.7550

830.7570 Octanol / Water Partition Coefficient Required

830.7840

830.7860 Solubility Required

830.7950 Vapor Pressure Required

ECOLOGICAL EFFECTS
850.1010 Aquatic Inverteb rate Acute 41609609
850.1025 Oyster Acute Toxicity Test Data gap
850.1035 Mysid Acute Toxicity Test Data gap
850.1045 Penaeid Acute Toxicity Test Data gap
850.1055 Bivalve Acute Toxicity Test Data gap
850.1075 Fish Acute Toxicity

Freshwater 41609608, 41609607
Estuarine / Marine Data gap
850.1300 Aquatic Invertebrate Life Cycle (Freshwater) Data gap
850.1350 Aquatic Invertebrate Li fe Cycle (Marine) Data gap

850.1400 Fish Early Life-Stage (Freshwater and Marine) Data gap

850.1500 Fish Full Life-Cycle (Freshwater and Marine) Data gap

850.1710 Oyster BCF Data gap54 Data Supporting Guideline Requirements for the Reregistration of Tetramethrin

Guideline

Number Study Description Citation(s)

850.1730 Fish BCF Data gap
850.1850 Aquatic Food Chain Transfer Data gap
850.2100 Avian Acute Oral Toxicity 41609604
850.2200 Avian Subacute Dietary Toxicity 41609605, 41609606
850.2300 Avian Reproduction Toxicity Data gap
850.2400 Wild Mammal Toxicity 00063574, 00161842
850.3020 Honey Bee Acute Contact Toxicity 41609613
850.3030 Residues on Foliage Honeybee Toxicity 41940801
850.3040 Honeybee Feeding Toxicity Test Data gap
850.4100 Seedling Emergence and Growth Data gap
850.4150 Vegetative Vigor Data gap
850.4400 Aquatic Plant Growth Data gap
850.4500 Algal Plant Toxicity Data gap
850.4550 Algal Plant Toxicity Data gap

TOXICOLOGY
870.1100 Acute Oral Toxicity 42146405
870.1200 Acute Dermal Toxicity 00063574, 40276101
870.1300 Acute Inhalation Toxicity Required
870.2400 Acute Eye Irritation 41609611
870.2500 Acute Dermal Irritation Required
870.2600 Skin Sensitization Required
870.3100 90-Day Oral Toxicity in Rodents 42146404
870.3150 90-Day Oral Toxicity in Non-rodents 42146403, 41698902
870.3200 21/28 -Day Dermal Toxicity 41995004
870.3465 90-Day Inhalation Toxicity 42012101, 41995003

870.3700 Prenatal Developmental Toxicity Required 42189202, 41995005, 00114369, 00114370

870.3800 Reproduction and Fertility Effects, 2- Generation Reproduction 00114371, 00137656, 00137658, 00161842

870.4100 Chronic Toxicity 41723301, 40009401, 40280401, 00156488, 40007501, 41723302, 42189301, 44083501

870.4200 Carcinogenicity 41723301, 40009401, 40280401, 00156488, 40007501, 41723302 870.4300 Combined Chronic Toxicity/Carcinogenicity 00158951, 40276301, 44096001
870.5265 Gene Mutation (Ames assay) 40276001, 40275801

870.5385 Bone Marrow Chromosomal Aberration Test 40275901, 42414401, 42414402, 42414403

870.5550 Unscheduled DNA Synthesis in mammalian

cells in culture 40778401, 40275801

870.6200 Neurotoxicity Screening battery

(a) Acute Neurotoxicity Required 42601501, 42601502, 43152701 (b) Subchronic Neurotoxicity Required55 Data Supporting Guideline Requirements for the Reregistration of Tetramethrin

Guideline

Number Study Description Citation(s)

870.6300 Developmental Neur otoxicity Study Required

870.7485 Metabolism and Pharmacokinetics 42448901, 42448902 Special Study – motor activity in male and female mice post-natally exposed by

inhalation 44222801

ENVIRONMENTAL FATE
835.1230 Leaching and Adsorption / Desorption 41995007, 42212901
835.1410 Laboratory Volatility Data gap
835.2120 Hydrolysis 41995006
835.2240 Photodegradation in Water 00164634, 43773401
835.2370 Photodegradation in Air Data gap
835.2410 Photodegradation on Soil Data gap

835.4100 Aerobic Soil Metabolism 42563301

835.4200 Anaerobic Soil Metabolism Data gap
835.4300 Aerobic Aquatic Metabolism Data gap
835.4400 Anaerobic Aquatic Metabolism Data gap
835.6100 Terrestrial Field Dissipation 42622401, 42622402
835.6200 Aquatic (Sediment) Dissipation Data gap
835.6400 Combination and Tank Mixes Dissipation Data gap
835.7100 Ground Water Monitoring Data gap
835.8100 Field Volatility Data gap56 Appendix C. Technical Support Documents

Additional documentation in support of the Te tramethrin 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 Di vision’s Risk Assessment for Reregistration Eligibility Decision. June 18, 2008.

2. Crowley, M. Tetramethrin: Phase IV Re vised Occupational and Residential Exposure

Assessment and Recommendations for the Rere gistration Eligibilit y Decision. June 13,

2008.

3. Eckel, W. et al. Revised Environmental Fate and Ecological Risk Assessment for the Reregistration Eligibility Decision on Tetramethrin. February 5, 2008.

4. Abdel-Saheb, I. Revised Drinking Water Asse ssment for Tetramethrin Use as a Rapid Knockdown Agent Against Flying and Cr awling Insects. February 5, 2008.

5. Crowley, M. HED Review of “Evaluation of Potential Human Health Risks Associated

with Residential Uses of Tetramethrin: Supplemental Assessment for Indoor Space Spray” (EPA MRID 47713101). April 27, 2009.

6. Daiss, B. Tetramethrin: Benchmark Dose An alysis of Toxicity Endpoint for Incidental Oral Exposure. January 6, 2010.

7. Crowley, M. HED Review of “Evaluation of Potential Human Health Risks Associated

with Residential Uses of Tetramethrin: Revised Supplemental – Short-Term Oral Benchmark Dose Analysis” (EPA MRID 47921601). February 25, 2010.57 Appendix D. Bibliography

In addition to the studies listed in Appendi x B, this bibliograp hy contains additional citations considered to be part of the data base supporting the rere gistration 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 reregistration de cision for Tetramethrin.

MRID Citation Reference

63574 Miyamoto, J.; Kadota, T.; Kohda, H. (1977) Acute Oral and Dermal Toxicities of Neopynamin in Mice and Rats. (Unpublis hed 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) Reproducti on Test of Neopynamin: Part 2. Teratology Study in Rats: Doc. Code IT-01-0076. (Tra nsla- tion; unpublished study received Sep 20, 1982 under 10308-1; prepared by Sum itomo Chemical Co., Ltd., Japan, submitted by Sumitomo Chemical Co., Ltd., Baltimore, MD; CDL:248342-B) 114370 Sato, T.; Narama, K. (1982) Reproducti on Test of Neopynamin: Part 3. Teratology Study in Rabbits: Doc. Code IT-01-0077. (Tra nsla- tion; unpublishe d study received Sep 20, 1982 under 10308-1; prepared by Su mitomo 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 unde r 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 Biosear ch, 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 Reproduc tion 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 Toxi city and Oncogenicity Study in Mice: Neopynamin: Final Report: Project No. 343-136. Unpublish- ed study prepared by Hazleton Laboratories America, Inc. 4980 p.58 MRID Citation Reference

161842 Pence, D.; Wolfe, G.; Kulwich, B. (1986) Two-generation Reproduction Study in Rats: Neopynamin Forte: Final Repo rt: Project No. 343-147. Unpublished study prepared by Hazleton Labo- ra tories America, Inc. 418 p. 164634 Chen, Y.; Casida, J. (1970) Photodecompos ition 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. 343-117. Unpublished study prepared by Hazleton Laboratories America, Inc. 7 p. 40009401 Cox, R. (1986) Two-year Dietary Admi nistration 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) Mutageni city 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 14(1):1-4. 40275901 Kogiso, S.; Hara, M.; Yoshitake, A.; et al. (1986) In vivo Chro mo- 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.; Hara, M.; et al. (1987) Reverse Mutation Test of Neopynamin in Salmonella typhimurium and Escherichia coli: Lab Project No.: IT70-0205. 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 Toxi city 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 C ontrol Data for Liver Adenoma Incidence among Mice, and Supporting Informa tion: Hazleton Product No. 343-107. Unpublished study prepared by Hazleton Laboratories America, Inc. 53 p. 40778401 Kogiso, S. (1988) In vitro Unsche duled 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-01-0008): Final Report: Lab Project Number: IW/01/0008. 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: La b Project Number: 166/133. U npublished study prepared by Sumitomo Chemical Company. 54 p.59 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 T oxicity of Neo-Pynamin to Bluegill: (Lepomis-macrochirus): Lab Projec t Number: IW/01/0010. Unpublished study prepared by Analytical Bio-Chemis try Labora- tories, Inc. 188 p. 41609608 Bowman, J. ; Gormley, M. (1990) Acute Flow-Through Toxicity of Neo- Pynamin to Rainbow Trout (Oncorhynchus myki ss): Lab Project Number: IW/01/0011. Unpublished study prepared by Analytical Bio-Chemistry Laboratories, Inc., 189 p. 41609609 Burgess, D. (1990) Acute Flow-thro ugh Toxicity of Neo-Pynamin to Daphnia magna: Lab Project Number: IW/01/ 0009. Unpublished Study Prepared by Analytical Bio-Chemistry Laboratories, Inc., 176 p. 41609611 Nakanishi, T. (1990) Primary Eye and Sk in Irritation Tests with Neo-Pynamin in Rabbits: Lab Project Number: IT/00/ 0217. Unpublished study prepared by Biochemistry and Toxicology Laboratory. 20 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 pr epared by Hazleton Laboratories America, Inc. 398 p. 41723301 Cox, R. (1974) Two-Year Dietary Administra tion 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 To xicity Study in Rats: Neo-Pynamin Technical: Lab Projec t 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 Inhala tion Toxicity Study of Neo- Pynamin in Rats (Determination of the no Observed Effect Level): Lab Project Number: 2279. Unpublished study prepared by Sumitomo Chem ical Co., Ltd, Environmental Health Science Lab. 938 p. 41995004 Osheroff, M. (1991) 21-Day Dermal Toxic ity 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 NeoPynamin 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.60 MRID Citation Reference

41995007 Yoshimura, J.; Mikami, N.; Matsuo, M.; et al. (1991) Adsorption and Desorption of Tetramethrin in Water-Soil Suspensi on 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 Inhala tion 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 S ub- 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. 42146403 Hosokowa, S.; Hiromori, T.; Seki, T.; et al. (1981) Six-month Subchronic Toxicity Study of Neo-Pynamin Forte in Rats: La b Project Number: IT-00-0139. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 97 p. 42146404 Hosokowa, S. (1982) One Month Oral Subacute Toxicity Study with Neo-Pynamin Forte in Rats: Lab Project Number: IT-20-0188. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 65 p. 42146405 Kohda, H.; Misaki, Y.; Suzuki, T. (1981) Ac ute Oral Subcutan- eous, Intraperitoneal and Dermal Neo-Pynamin Forte in Rats and Mice: Lab Project Number: IT-00-0086. Unpublished study pre- pared by Sumitomo Chemical Co., Ltd. 38 p. 42189202 Robinson, K.; Washer, G.; Noveroske, J. (1991) An Oral Range- Finding Teratology Study of Neo-Pynamin in the Rat: Lab Project Number: 95219. Unpublished study prepared by Bio-Research Labs., Ltd. 520 p. 42189301 Dalgard, D. (1991) Chronic Toxicity Study in Dogs with Neo- Pynamin: IT-11-0242: Lab Project Number: 343-235. Unpublished stud y prepared by Sumitomo Chemical Co., Ltd. 406 p. 42212901 Yoshimura, J.; Mikami, N.; Matsuo, M.; et al. (1992) Aged Column Leaching Study of ?carbon 14|-Tetramethrin in Soil: Lab Project Number: LEA91001. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 81 p. 42414401 Murli, H. (1992) Single Acute Exposure Dose Selection Study on Neo-Pynamin: Final Report: Lab Project Number: 1 2400-0-59IP. Unpublished study prepared by Hazleton Washington, Inc. 20 p. 42414402 Murli, H. (1992) Bone Marrow Toxicity Study for In vivo Murine Bone Marrow Cytogenetics Assay with Neo-Pynamin: Final Report: Lab Project Number: 12400-1- 459IP: IT-21-0253. Unpublished study prepar ed by Hazleton Washington, Inc. 21 p. 42414403 Murli, H. (1992) Mutagenicity Test on Neo-Pynamin Measuring Chromosomal

Aberrations In vivo in Mouse Bone Ma rrow Cells: Final Report: Lab Project Number: 12400-0-451IP: IT-21-0254. Unpub lished study prepared by Hazleton Washington, Inc. 35 p. 42448901 Shiba, K. (1992) Metabolism of (1RS, tr ans)-Tetramethrin in Rats: Lab Project Number: 2556: IM-20-0015. Unpublished st udy prepared by Sumitomo Chemical Co., Ltd. 393 p.61 MRID Citation Reference

42448902 Shiba, K. (1992) Metabolism of (1RS,cis)-Tetramethrin in Rats: Lab Project Number: 2557: IM-20-0016. Unpublished st udy prepared by Sumitomo Chemical Co., Ltd. 382 p. 42563301 Yoshimura, J.; Mikami, N.; Matsuo, M. (1992) Aerobic Soil Metabolism Study of (Carbon 14)-(1RS)-trans-Tetramethrin: Lab Project Number: SOI90001. Unpublished study prepared by Sumitomo Chemical Co., Ltd. 209 p. 42601501 Robinson, K.; Benjamin, W.; Noveroske, J. (1992) An Acute Study of the Potential Effects of Orally Administered Neo-P ynamin on Behavior and Neuromorphology in Rats: Lab Project Number: 97137. Unpublis hed study prepared by Bio-Research Labs, Inc. 609 p. 42601502 Robinson, K.; Benjamin, W.; Noveroske, J. (1992) A Time of Peak Behavioral Effects Study of a Single Oral Administrati on of Neo-Pynamin in Rats: Lab Project Number: 97139. Unpublished study prepared by Bio-Research Labs, Inc. 69 p. 42622401 Ver Hey, M. (1992) A Terrestrial Field Dissipation Study with Tetramethrin (NeoPynamin) Applied for Control of Insects in Plants (California Field Study): Lab Project Number: SUMITOMO-1150. Unpub lished study prepared by Colorado Analytical Research & Development Corp. 397 p. 42622402 Ver Hey, M. (1992) A Terrestrial Field Dissipation Study with Tetramethrin (NeoPynamin) Applied for Control of Insects in Plants (Florida Field Study): Lab Project Number: SUMITOMO-1150. Unpublished study prepared by Colorado Analytical Research & Development Corp. 450 p. 43152701 Robinson, K.; Benjamin, W.; Noveroske, J. (1993) An Acute Study of the Potential Effects of Orally Administered Neop ynamin on Behavior and Neuromorphology in Rats: Supplemental Volume: Lab Project Number: 97137: IT/21/0258. Unpublished study prepared by Bio-Research Lab., Ltd. 6 p. 43261603 Woollen, B.; Marsh, J.; Thornley, K. (1992) Cypermethrin: Pharmacokinetics in Man Following A Single Dermal Dose: Lab Project Number: CTL/R/1077. Unpublished study prepared by Zeneca Central Toxicology Lab. 40 p. 43773401 Chen, Y.; Casida, J. (1969) Photodegradat ion of pyrethrin I, allethrin, phthalthrin,

and dimethrin: Modifications in the acid moiety. J. Agr. Food Chem. 17(2):208-215. 44083501 Walker, M. (1996) 52-Week Toxicity St udy in Dogs with Neo-Pynamin: Final Report: Lab Project Number: CHV 343- 249: IT-0276: 343-249. Unpublished study prepared by Corning Hazleton Inc. 456 p. 44096001 Moore, M. (1995) Dietary Oncogenicity Study in Mice with Neo-Pynamin: Final Report: Lab Project Number: HWA 3 43-242: IT-51-0272: 343-242. Unpublished study prepared by Hazleton Washington, Inc. 1332 p. 44222801 Ivens, I.; Pauluhn, J.; Schmuck, G. (1996) Tetramethrin: Motor Activity

Measurements in Male and Female Mice Postnatally Exposed to Tetramethrin by Inhalation (Including Measuremenets of Mus carinic Acetylcholine Receptors in the Brain): Lab Project Number: IT -0277: T3059027: 25749. Unpublished study prepared by Bayer AG. 219 p.62 MRID Citation Reference

45485501 McKeown, K. (2001) Determination of th e Dislodgeability of Tetrachlorvinphos (TCVP) from the Fur of Dogs Following th e Application of an Insecticide Powder, Pump Spray of Aerosol: Lab Projec t Number: 2001-3: 1555. Unpublished study prepared by Hartz Mountain Corp. 137 p. 46099001 Jacobs, L.; Driver, J.; Pandian, M. ( 2003) Residential Exposure Joint Venture National Pesticide Use Survey - Design, Implementation, Analysis Methods and Results. Project Number: 03/REJV/12M/002. Unpublished study prepared by NFO Worldgroup and Infoscientific.com, Inc. 155 p. 46188602 Non-Dietary Exposure Task Force (ND ETF) Study Volume 2. Post-Application Deposition Measurements for Pyrethrins & Piperonyl Butoxide Following Use of a Total Release Indoor Fogger.

46188613 NDETF Volume 13. Measurement of Transf er of Pyrethrin and Piperonyl Butoxide Residues from Vinyl and Carpet Flooring Tr eated with a Fogger Formulation to DSS Wetted Hands Following a Single Hand Press.

46188618 NDEFT Volume 18. Measurement of Ai r Concentration, Dermal Exposure, and Deposition of Pyrethrin and Piperonyl But oxide Following the Use of an Aerosol Spray. 46188623 NDETF Volume 23. Post-Application De position Measurements for Permethrin & Piperonyl Butoxide Following Use of a Total Release Indoor Fogger. 46188629 Selim, S. (2003) Measurement of Transfer of Permethrin and Piperonyl Butoxide Residues from Vinyl and Carpet Flooring Tr eated with a Fogger Formulation to DSS Wetted Hands Following a Single Hand Pr ess: Final Report. Project Number: 01/031/PY01, 02/0014. Unpublished study prepared by Toxcon Health Sciences Research Centre, En-Cas Analytical La boratories and Selim and Associates. 161 p. 46382501 Selim, S. (2004) A Single Dose, Open Labe l Study to Investigate the Absorption and Excretion of Orally Administrated or Dermally Applied (Carbon 14)-Labeled Pyrethrin I (PI) to Healthy Male Volunteers. Project Number: SEL/0204, BTAZ/103, PBR/013911. Unpublished study prepared by Ch arles River Laboratories and Bayer Ag Institute of Biological Monitoring and Pharma Bio-Research Clinics, B.V. 433 p. 46493701 Holden, L., and Thomas Osimitz. A Statistical Assessment of Generic Transferability Relationships for Pyrethri ns, the Synthetic Py rethroids, and the Synergists Piperonyl Butoxide and M GK-264. Prepared for the Non-Dietary Exposure Task Force. March 1, 2005. 47713101 Driver, J.; Ross, J.; Pandian, M.; et. al.; (2009) Evaluation of Po tential Human Health

Risks Associated with Residential Uses of Tetramethrin: Supplemental Assessment for Indoor Space Spray. Project Number: VBC/001/09. Unpublished study prepared by Infoscientific.Com. 14 p. 47921601 Driver, J.; Ross, J.; Pandian, M.; et al. (2009) Evaluation of Potential Human Health

Risks Associated with Residential Uses of Tetramethrin: Revised Supplemental -

Short-Term Oral Benchmark Dose Analysis. Project Number: VBC/003/09. Unpublished study prepared by Infoscientific.com. 215 p. Cremlyn, R. 1978. Pesticides: Preparation and Mode of Action , John Wiley and Sons, Chichester, UK.63 MRID Citation Reference

Crofton, K.M., Kehn, L.S., and Gilbert, M.E. (1995) Vehicle and route dependent effects of a pyrethroid insecticide, delta methrin, on motor function in the rat. Neurotoxicology and Teratology 17:489-495 Fletcher, J. S., J. E. Nellessen, and T. G. Pleeger, 1994. Literature review and evaluation of the EPA Food-chain ( ) nom ogram, an instrument for estimating pesticide residues on plants. Environmenta l Toxicology and Chemistry 3 (9): 1383-

11391. Hill, I.R. 1985. Effects on non-target organisms in terrestrial and aquatic environments. In: J.P. Leahey, Editor, The Pyrethroid Insecticides , Taylor and Francis, London, UK. Hoerger, F., and E.E. Kenaga. 1972. Pes ticide residues on plants: Correlation of representative data as a basi s for estimation of their magnitu de in the environment. In F. Coulston and F. Korte, eds., E nvironmental Quality and Safety: Chemistry, Toxicology, and Technology, Georg Thieme Publ, Stuttgart, West Germany. Pp. 9-

28

. Kohda, H. (1985). Acute toxicity of S-1844 in rates. IH178505. Sumitomo

Chemical Co. Ltd. Takarazuka Research Center, Hyogo, Japan. Unpublished report (LLT-50-0002). Lloyd .J. et al. 1963. Further studies on a pyrethrum-resist ant strain of the grain weevil, Sitolhilus franarius (L.). J. Sci. Food Agric . 655-663. Pesticide Handlers Exposure Database (PHED) Surrogate Exposure Guide Tulve, N.S., J.C. Suggs, T. McCurdy, E.A. Cohen Hubal and J. Moya. 2002. J. Exp Anal Environ Epid. 12:259-264. Wolansky, M. J., Gennings, C., nd Croft on, K.M. (2006). Relative potencies for acute effects of pyrethroids on motor f unction in rats. Toxicol. Sci. 89, 271-27764 Appendix E. Tetramethrin Acute Mammalian Toxicity Batching

UNITED STATES ENVIRONM ENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

December 3, 2008

MEMORANDUM

SUBJECT: Tetramethrin [PC Codes 069003], Ac ute Mammalian Toxicity Batching Appendix for Tetramethrin RED Document.

FROM: Marianne Lewis, Biologist [sign. M.Lewis 12/3/08] Product Reregistration Branch Special Review and Reregi stration Division (7508P)

TO: Monica Wait, CRM Reregistration Branch III Special Review and Reregistrati on Division (7508P)

Attached is the batching appendix for Tetram ethrin. Please let me know if you have any questions regarding this document.65 EPA'S BATCHING OF TETRAM ETHRIN PRODUCTS FOR MEETING ACUTE TOXICITY DATA REQUIREMENTS FOR REREGISTRATION

In an effort to reduce the time, resources and number of animals needed to fulfill the acute toxicity data requirement s for reregistration of products containing TETRAMETHRIN as the active ingredient, the Agency has batched pr oducts which can be considered similar for purposes of acute toxicity. Factor s considered in the sorting pro cess include each product's active and inert ingredients (identity, percent composition and biological activity), type of formulation (e.g., emulsifiable concentrate, aerosol, wetta ble powder, granular, et c.), and labeling (e.g., signal word, use classification, precautionary labe ling, etc.). Note that the Agency is not describing batched products as "s ubstantially similar" since so me products within a batch may not be considered chemically simila r or have identical use patterns.

Using available information, batching has b een accomplished by the process described in the preceding paragraph. Notwith-standing the batching process, the Agency reserves the right to require, at any time, acute toxicity data for an individual product s hould the need arise.

Registrants of products within a batch may choose to cooperatively generate, submit or cite a single battery of six acute toxicological studies to re present all the products within that batch. It is the registrants' option to participate in the process with all other registrants, only some of the other registrants, or only their own products within a batch, or to generate all the required acute toxicological studies for each of their own pr oducts. If a registrant chooses to generate the data for a batch, he/she must use one of the produc ts within the batch as the test material. If a registrant chooses to rely upon previously subm itted acute toxicity data, he/she may do so provided that the data base is complete and va lid by today's standards (see acceptance criteria attached), the formulation tested is considered by EPA to be similar for acute toxicity, and the formulation has not been significantly altere d since submission and acceptance of the acute toxicity data. Regardless of whether new data is generated or existing data is referenced, registrants must clearly identify the test materi al by EPA Registration Numb er. If more than one confidential statement of formula (CSF) exists fo r a product, the registrant must indicate the formulation actually tested by id entifying the corresponding CSF.

In deciding how to meet the product specific data requirements, re gistrants must follow the directions given in the Data Call-In Notice and its attachments appended to the RED. The DCI Notice contains two response forms which are to be completed and submitted to the Agency within 90 days of receipt. The first form, "Dat a Call-In Response," asks whether the registrant will meet the data requirements for each product. The second form, "Requirements Status and Registrant's Response," lists the product specif ic data required for each product, including the standard six acute toxicity tests. A registrant who wishes to pa rticipate in a batch must decide whether he/she will provide the data or depend on someone else to do so. If a registrant supplies the data to support a batch of products, he/she must select one of the following options: Developing Data (Option 1), Submitting an Exis ting Study (Option 4), Upgrading an Existing Study (Option 5) or Citing an Existing Study (Op tion 6). If a registrant depends on another's data, he/she must choose among: Co st Sharing (Option 2), Offers to Cost Share (Option 3) or Citing an Existing Study (Option 6) . If a registrant does not want to participate in a batch, the choices are Options 1, 4, 5 or 6. However, a registrant shou ld know that choosing not to66 participate in a batch does not pr eclude other registrants in the batch from citing his/her studies and offering to cost share (Option 3) those studies.

Many products containing TETRAMETHRIN have been previously batched in the PBO, Pyrethrins, & MGK 264 REDs. If a TETRAMETHR IN product registration number cannot be found in the following tables, pl ease refer to the batching appe ndices for PBO, Pyrethrins, & MGK 264. One hundred and thirty eight pr oducts have been found which contain TETRAMETHRIN as the active ingredient, and have not been previously batched in the PBO, Pyrethrins, & MGK 264 REDs. These products have been placed into seventeen batches and a No Batch group in accordance with the active and inert ingredients and type of formulation.

Batching Instructions :

No Batch : Each product in this Batch should generate their own data.

NOTE: The technical acute toxicity values incl uded in this document are for informational purposes only. The data supporting these values may or may not meet the current acceptance

criteria.

Batch 1 EPA Reg. No. Percen tage Active Ingredient

10308-1 95.0

73049-145 95.0

73049-258 100.0

Batch 2 EPA Reg. No. Percen tage Active Ingredient

270-356 Tetramethrin: 0.400

Phenothrin: 0.300 Pyriproxyfen: 0.015

1021-177 Tetramethrin: 0.400

Phenothrin: 0.300 Pyriproxyfen: 0.015

2517-76 Tetramethrin: 0.400

Phenothrin: 0.300 Pyriproxyfen: 0.015

9444-165 Tetramethrin: 0.400

Phenothrin: 0.300 Pyriproxyfen: 0.015

28293-215 Tetramethrin: 0.400

Phenothrin: 0.300 Pyriproxyfen: 0.015

Batch 3 EPA Reg. No. Percen tage Active Ingredient

192-196 Tetramethrin: 0.400

Phenothrin: 0.30067 Pyriproxyfen: 0.015

1021-1622 Tetramethrin: 0.400

Phenothrin: 0.300 Pyriproxyfen: 0.015

2724-663 Tetramethrin: 0.400

Phenothrin: 0.300 Pyriproxyfen: 0.015

40849-55 Tetramethrin: 0.400

Phenothrin: 0.300 Pyriproxyfen: 0.015

68543-23 Tetramethrin: 0.400

Phenothrin: 0.300 Pyriproxyfen: 0.015

Batch 4 EPA Reg. No. Percen tage Active Ingredient

4822-436 Tetramethrin: 0.50 Cypermethrin: 0.15

9688-254 Tetramethrin: 0.10 Cypermethrin: 0.60

Batch 5 EPA Reg. No. Percen tage Active Ingredient

769-584 Tetramethrin: 0.20

Esfenvalerate: 0.10

9444-145 Tetramethrin: 0.20

Esfenvalerate: 0.10

Batch 6 EPA Reg. No. Percen tage Active Ingredient

1021-1715 Tetramethrin: 0.20

Permethrin: 0.20

8848-83 Tetramethrin: 0.20

Permethrin: 0.20

Batch 7 EPA Reg. No. Percen tage Active Ingredient

73049-313 Tetramethrin: 0.20

Permethrin: 0.50

73049-314 Tetramethrin: 0.10

Permethrin: 0.25

73049-328 Tetramethrin: 0.20

Permethrin: 0.50

Batch 8 EPA Reg. No. Percen tage Active Ingredient68 73049-436 Tetramethrin: 0.10

Permethrin: 0.10

73049-437 Tetramethrin: 0.20

Permethrin: 0.20

Batch 9 EPA Reg. No. Percen tage Active Ingredient

2724-533 Tetramethrin: 0.40

Permethrin: 0.30

8845-67 Tetramethrin: 0.40

Permethrin: 0.30

Batch 10 EPA Reg. No. Percen tage Active Ingredient

192-153 Tetramethrin: 0.286

Permethrin: 0.572

239-2535 Tetramethrin: 0.050

Permethrin: 0.100

2724-541 Tetramethrin: 0.050

Permethrin: 0.100

2724-547 Tetramethrin: 0.050

Permethrin: 0.100

8845-84 Tetramethrin: 0.050

Permethrin: 0.100

46515-21 Tetramethrin: 0.029

Permethrin: 0.057

46515-30 Tetramethrin: 0.029

Permethrin: 0.057

Tetramethrin: 0.40

Permethrin: 0.30

Batch 11 EPA Reg. No. Percen tage Active Ingredient

4822-271 Tetramethrin: 0.200

Permethrin: 0.200

4822-423 Tetramethrin: 0.119

Permethrin: 0.124

4822-533 Tetramethrin: 0.200

Permethrin: 0.200

Batch 12 EPA Reg. No. Percen tage Active Ingredient

1021-1780 Tetramethrin: 0.20

Phenothrin: 0.20

1021-1806 Tetramethrin: 0.15

Permethrin: 0.1569 Batch 13 EPA Reg. No. Percen tage Active Ingredient

478-101 Tetramethrin: 0.20

Phenothrin: 0.20

498-160 Tetramethrin: 0.20

Phenothrin: 0.20

8845-68 Tetramethrin: 0.20

Phenothrin: 0.20

46813-10 Tetramethrin: 0.20

Phenothrin: 0.20

Batch 14 EPA Reg. No. Percen tage Active Ingredient

1021-1775 Tetramethrin: 0.2000

Phenothrin: 0.2000

1021-1808 Tetramethrin: 0.2000

Phenothrin: 0.2000

2724-540 Tetramethrin: 0.0500

Phenothrin: 0.1000

2724-542 Tetramethrin: 0.0286

Phenothrin: 0.0572

2724-543 Tetramethrin: 0.05

Phenothrin: 0.10

8845-83 Tetramethrin: 0.05

Phenothrin: 0.10

Batch 15 EPA Reg. No. Percen tage Active Ingredient

2724-536 Tetramethrin: 0.2

Phenothrin: 0.4

5887-118 Tetramethrin: 0.2

Phenothrin: 0.4

Batch 16 EPA Reg. No. Percen tage Active Ingredient

192-184 Tetramethrin: 0.200

Phenothrin: 0.125

498-156 Tetramethrin: 0.200

Phenothrin: 0.125

506-140 Tetramethrin: 0.200

Phenothrin: 0.125

1021-1649 Tetramethrin: 0.200

Phenothrin: 0.125

3862-127 Tetramethrin: 0.200

Phenothrin: 0.12570 4313-87 Tetramethrin: 0.200

Phenothrin: 0.125

5887-158 Tetramethrin: 0.200

Phenothrin: 0.125

7405-71 Tetramethrin: 0.200

Phenothrin: 0.125

7754-44 Tetramethrin: 0.200

Phenothrin: 0.125

9444-181 Tetramethrin: 0.200

Phenothrin: 0.125

10806-105 Tetramethrin: 0.200

Phenothrin: 0.125

11623-38 Tetramethrin: 0.200

Phenothrin: 0.125

40849-52 Tetramethrin: 0.200

Phenothrin: 0.125

44446-54 Tetramethrin: 0.200

Phenothrin: 0.125

46515-44 Tetramethrin: 0.200

Phenothrin: 0.125

55809-3 Tetramethrin: 0.200

Phenothrin: 0.125

68543-8 Tetramethrin: 0.200

Phenothrin: 0.125

Batch 17 EPA Reg. No. Percen tage Active Ingredient

192-189 Tetramethrin: 0.20

Phenothrin: 0.20

239-2523 Tetramethrin: 0.05

Phenothrin: 0.10

239-2524 Tetramethrin: 0.20

Phenothrin: 0.20

239-2525 Tetramethrin: 0.25

Phenothrin: 0.15

478-93 Tetramethrin: 0.25

Phenothrin: 0.15

498-114 Tetramethrin: 0.20

Phenothrin: 0.19

499-355 Tetramethrin: 0.40

Phenothrin: 0.30

506-157 Tetramethrin: 0.20

Phenothrin: 0.20

706-83 Tetramethrin: 0.20

Phenothrin: 0.20

769-609 Tetramethrin: 0.2571 Phenothrin: 0.15

1021-1587 Tetramethrin: 0.25

Phenothrin: 0.15

1021-1588 Tetramethrin: 0.20

Phenothrin: 0.20

1021-1667 Tetramethrin: 0.20

Phenothrin: 0.20

1021-1862 Tetramethrin: 0.10

Phenothrin: 0.10

2724-529 Tetramethrin: 0.25

Phenothrin: 0.20

2724-530 Tetramethrin: 0.25

Phenothrin: 0.15

2724-537 Tetramethrin: 0.20

Phenothrin: 0.20

2724-545 Tetramethrin: 0.20

Phenothrin: 0.20

2724-597 Tetramethrin: 0.25

Phenothrin: 0.15

2724-604 Tetramethrin: 0.20

Phenothrin: 0.20

2724-615 Tetramethrin: 0.20

Phenothrin: 0.40

2915-59 Tetramethrin: 0.20

Phenothrin: 0.20

5887-123 Tetramethrin: 0.20

Phenothrin: 0.19

5887-159 Tetramethrin: 0.25

Phenothrin: 0.15

7056-99 Tetramethrin: 0.25

Phenothrin: 0.15

8845-63 Tetramethrin: 0.25

Phenothrin: 0.15

8848-38 Tetramethrin: 0.20

Phenothrin: 0.20

8848-42 Tetramethrin: 0.40

Phenothrin: 0.30

9688-54 Tetramethrin: 0.20

Phenothrin: 0.40

10088-116 Tetramethrin: 0.25

Phenothrin: 0.15

10806-41 Tetramethrin: 0.25

Phenothrin: 0.14

10807-61 Tetramethrin: 0.20

Phenothrin: 0.20

10807-182 Tetramethrin: 0.2572 Phenothrin: 0.15

11623-11 Tetramethrin: 0.20

Phenothrin: 0.20

11715-82 Tetramethrin: 0.20

Phenothrin: 0.20

28293-160 Tetramethrin: 0.40

Phenothrin: 0.30

40849-4 Tetramethrin: 0.20

Phenothrin: 0.20

40859-46 Tetramethrin: 0.20

Phenothrin: 0.40

46515-40 Tetramethrin: 0.25

Phenothrin: 0.15

46515-43 Tetramethrin: 0.20

Phenothrin: 0.20

64240-23 Tetramethrin: 0.25

Phenothrin: 0.15

No Batch EPA Reg. No. Per centage Active Ingredient

478-126 Tetramethrin: 0.2

Permethrin: 0.4

706-109 Tetramethrin: 0.200

Phenothrin: 0.125

769-931 Tetramethrin: 0.25

Phenothrin: 0.15

769-938 Tetramethrin: 0.284

Resmethrin: 0.120

769-939 Tetramethrin: 2.84

Resmethrin: 2.96

1021-1384 80.0

1021-1386 Tetramethrin: 8.9

Phenothrin: 8.9

1021-1387 Tetramethrin: 12.5

Phenothrin: 7.5

1021-1437 Tetramethrin: 8.0

Phenothrin: 16.0

1021-1505 Tetramethrin: 12.30

Phenothrin: 9.23

1021-1613 Tetramethrin: 0.20

Esfenvalerate: 0.03

1021-1640 Tetramethrin: 10.00

Phenothrin: 6.26

1021-1652 Tetramethrin: 10.01

Esfenvalerate: 1.57

1021-1659 Tetramethrin: 8.8973 Permethrin: 8.90

1021-1856 Tetramethrin: 0.05 Cypermethrin: 0.05

2724-538 Tetramethrin: 12.0

Phenothrin: 3.83

2724-599 Tetramethrin: 0.40

Phenothrin: 0.23 Butoxypolypropylene glycol: 51.92

4822-513 Tetramethrin: 0.35

Permethrin: 0.10

Allethrin: 0.10

4822-514 Tetramethrin: 0.3

Permethrin: 0.1

7056-185 Tetramethrin: 0.2

Permethrin: 0.2

10807-191 Tetramethrin: 0.2

Esfenvalerate: 0.1

73049-233 Tetramethrin: 25.0

Resmethrin: 10.6

73049-255 Tetramethrin: 0.250

Resmethrin: 0.106

73049-260 Tetramethrin: 26.64

Resmethrin: 5.85

73049-262 Tetramethrin: 0.25

Resmethrin: 0.25

73049-264 Tetramethrin: 16.67

Resmethrin: 7.06

73049-265 Tetramethrin: 20.84

Resmethrin: 20.84

73049-315 Tetramethrin: 16.0

Resmethrin: 40.0

73049-434 Tetramethrin: 10.0

Permethrin: 10.0