Docket Number EPA-HQ-OPP-2011-0907 

www.regulations.gov 

Tetramethrin Summary Document 

Registration Review: Initial Docket 

December 2011 

 

3

TABLE OF CONTENTS 

I. Preliminary Work Plan (PWP) 4 

II. Fact Sheet 12 

III. Summary of Data Gaps 18 

__________________________________________________________________ 

Please Note 

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency's 

current position based on the following documents: 

1. Registration Review – Preliminary Problem Formulation for the Ecological Risk 

Assessment for Tetramethrin. E. Gelmann. December 5, 2011. 

2. Tetramethrin: Human Health Risk Scoping Document in Support of Registration Review. 

B. Daiss. December 13, 2011. 

3. BEAD Chemical Profile for Registration Review: Tetramethrin (Chemical Code 069003). 

N. Mallampalli. September 20, 2011. 

4. Tetramethrin: Review of Human Incidents. K. Oo. August 11, 2011. 

These and other supporting documents for the tetramethrin registration review case may be 

found in the docket EPA-HQ-OPP-2011-0907 at http://www.regulations.gov.
4

I. PRELIMINARY WORK PLAN – TETRAMETHRIN

Introduction: 

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. The registration review program is intended to make sure that, as the ability 

to assess risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided at: http://www.epa.gov/oppsrrd1/registration_review/. 

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The Agency will consider benefits information and data as required by FIFRA. The 

public phase of registration review begins when the initial docket is opened for each case. The 

docket is the Agency’s opportunity to state what it knows about the pesticide and what additional 

risk analyses and data or information it believes are needed to make a registration review 

decision. After reviewing and responding to comments and data received in the docket during 

this initial comment period, the Agency will develop and commit to a final work plan and 

schedule for the registration review of tetramethrin. 

Tetramethrin is a broad-spectrum, first-generation synthetic pyrethroid insecticide. It is a rapid 

knockdown agent registered for use against flying and crawling insects, such as wasps, hornets, 

roaches, ants, fleas, and mosquitoes. At this time, there are no registered food or agricultural 

uses of tetramethrin. It is used primarily in residential, commercial, institutional, and industrial 

areas and can be used both indoors, including applications to pets, and outdoors. Some 

tetramethrin end-use products are labeled for use by pest control operators only although 

tetramethrin products are not classified as restricted use pesticides. Products containing 

tetramethrin were first registered in 1968. The Reregistration Eligibility Decision (RED) for 

Tetramethrin was completed in June 2008 and revised in April 2010. Tetramethrin, like other 

members of the pyrethroid class of insecticides, affects the peripheral and central nervous 

systems. The cumulative risk assessment for the pyrethroids and pyrethrins was recently 

published on November 9, 2011 and is available in the public docket EPA-HQ-OPP-2011-0746. 

Anticipated Risk Assessment and Data Needs:

The Agency anticipates the need to require data and to conduct a comprehensive ecological risk 

assessment, including an endangered species assessment, for all uses of tetramethrin. For human 

health, EPA anticipates the need to conduct revised residential and occupational risk assessments 

during registration review. If toxicological endpoints or points of departure are revised based on 

the data that are anticipated to be required for registration review, they will be considered in the 
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new assessment, as well as any changes to the standard operating procedures or default exposure 

assumptions. Below is a summary of the issues relevant to the registration review of 

tetramethrin. 

Ecological Risk: 

 The most recent comprehensive ecological risk assessment for tetramethrin was 

completed in February 2008 in support of the tetramethrin RED. 

 An updated comprehensive ecological risk assessment of all registered uses of 

tetramethrin will be conducted during registration review. The new assessment will 

incorporate the most up-to-date modeling methodologies, updated toxicological 

endpoints, and data submitted under the anticipated registration review data call-in. 

 Because tetramethrin uses to be considered in the ecological risk assessment are limited 

to spot treatments (e.g., spraying a wasp hive), space treatments (e.g., spraying of an 

aerosol can in a storage room or other enclosed space), and ornamental applications 

against crawling and flying insects (e.g., spraying hedges), a standard risk assessment 

using risk quotients (RQs) compared to levels of concern (LOCs) is not applicable for 

these kinds of uses. For the anticipated assessment, standard expected environmental 

concentrations (EECs) cannot be directly calculated (without major assumptions) using 

the tools on which EPA typically relies. The difficulty in calculating standard EECs is 

due to a number of factors including non-standard use rates (e.g., “1-2 second burst,” “lbs 

a.i./ft3”) and estimations of the magnitude of use in a given area (e.g., a neighborhood or 

campsite) at a given time. For the tetramethrin risk assessment, the Agency will use 

available tools and information and the anticipated required ecological data to help 

quantitatively characterize the potential for risk instead of the more typical approach of 

comparing RQs to LOCs. 

 Certain tetramethrin labels are unclear with respect to application parameters like the size 

of the treated area, the extent of a treated “spot,” retreatment intervals, or maximum 

annual application rates. In the absence of clear label information, EPA must 

approximate these parameters in order to conduct a quantitative assessment for 

tetramethrin. The Agency encourages clear and consistent label language for the sake of 

all stakeholders and encourages registrants to review tetramethrin product labels for 

clarity. 

 A risk assessment that supports a complete endangered species determination has not 

been conducted for tetramethrin. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether tetramethrin’s use has 

“no effect” or “may affect” federally listed threatened or endangered species (listed 

species) or their designated critical habitats. When an assessment concludes that a 

pesticide’s use “may affect” a listed species or its designated critical habitat, the Agency 

will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries 

Service (the Services), as appropriate. 
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 On January 19, 2011, the Center for Biological Diversity and the Pesticide Action 

Network North America filed a lawsuit in the United States District Court for the 

Northern District of California, against EPA for allegedly failing to undergo consultation 

with the Services regarding the effects of over 350 pesticides, including tetramethrin, on 

over 200 endangered and threatened species throughout the United States (Center for 

Biological Diversity, et al. v. EPA, et al., No. C 11-00293 (N.D.Cal.).

 Data gaps exist in the ecological database for tetramethrin. EPA anticipates requiring the 

following studies for use in conducting a complete ecological risk assessment, including 

an endangered species assessment, for the registration review of tetramethrin. 

835.6100 – Terrestrial field dissipation study1

835.6200 – Aquatic field dissipation study1

850.1020 – Gammarid acute toxicity (using TGAI and TEP) 

850.1025 – Acute toxicity estuarine and marine organisms (oyster shell growth) 

850.1035 – Acute toxicity estuarine and marine organisms (mysid) 

850.1075 – Acute toxicity estuarine and marine organisms (using TGAI for 

estuarine/marine fish and using TEP for freshwater fish) 

850.2100 – Avian oral toxicity (passerine species)

850.4100 – Terrestrial plant toxicity, seedling emergence, Tier II 

850.4150 – Terrestrial plant toxicity, vegetative vigor, Tier II 

 Studies conducted with freshwater invertebrates and fish are expected to be required 

using a typical end-use product (TEP) containing tetramethrin and the synergist piperonyl 

butoxide in addition to a product containing tetramethrin and the synergist MGK-264. 

Tetramethrin may be co-formulated with either or both synergists in numerous products. 

Because available information indicates that greater toxicity enhancement can occur at 

higher synergist-to-active ingredient ratios, selection of the TEPs for the anticipated 

testing requirement would include those with the highest synergist-to-active ingredient 

ratio and that are registered for outdoor uses. 

 Please refer to the December 5, 2011 document Registration Review – Preliminary 

Problem Formulation for the Ecological Risk Assessment for Tetramethrin in the 

registration review docket (EPA-HQ-OPP-2011-0907) for a detailed discussion of the 

anticipated risk assessment and data needs. 

Human Health Risk:

 The most recent comprehensive human health risk assessment for tetramethrin was 

conducted in June 2008 in support of the tetramethrin RED. The occupational and 

residential exposure assessments were revised in 2009 and 2010. 

 

1

 See footnote 7 of 40 CFR 150.1300. EPA anticipates requiring only the environmental chemistry analytical 

methods and independent laboratory validation (ILV) portions of this guideline for soil and water, rather than the 

full field dissipation study. 
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 The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative 

risks of chemicals sharing a common mechanism of toxicity. Tetramethrin is a member 

of the pyrethroid/pyrethrins common mechanism group (http://www.regulations.gov; 

EPA-HQ-OPP-2008-0489-0006). The members of this group share the ability to interact 

with voltage-gated sodium channels ultimately leading to neurotoxicity. The cumulative 

risk assessment for the pyrethroids/pyrethrins was published on November 9, 2011 and is 

available at http://www.regulations.gov; EPA-HQ-OPP-2011-0746. No cumulative risks 

of concern were identified, allowing the Agency to consider new uses for pyrethroid 

active ingredients. For information regarding EPA’s efforts to evaluate the risk of 

exposure to pyrethroids, refer to the Agency’s website2

.

 A dietary (food) exposure assessment is not anticipated to be needed during registration 

review because there are currently no registered food or feed uses for tetramethrin. 

Dietary exposure is not expected based on registered uses.

 A drinking water dietary assessment for tetramethrin is not anticipated during registration 

review given the limited extent of potential exposures based on currently registered use 

sites and the environmental fate properties of tetramethrin that limit its mobility.

 A revised residential exposure assessment is anticipated during registration review to 

reflect current standard operating procedures and revised toxicological endpoints. 

 During registration review, a revised occupational exposure assessment is anticipated to 

reflect current standard operating procedures. 

 During registration review, EPA will consider data submitted under the 2010 RED data 

call-in (DCI) (GDCI-069003-28621) and revise toxicological endpoints as needed. See 

the “Data Call-In Status” section of the Factsheet for further details regarding the 

previously-issued DCI. No additional human health data are anticipated to be needed for 

this registration review case. 

 EPA recently re-evaluated the need of a 10X FQPA Safety Factor for human health risk 

assessments for pyrethroid pesticides. Based on a review of the available guideline and 

literature studies, the Agency is reducing the FQPA Safety Factor to 1X for adults, 

including women of child-bearing age, and children greater than 6 years of age. 

However, the Agency is retaining a 3X FQPA Safety Factor for children from birth to 6 

years of age. The 3X is based on age-dependent-pharmacokinetics and is further 

supported by physiologically-based pharmacokinetic (PK) model predictions of a 3-fold 

increase of pyrethroid concentration in juvenile target tissue compared to adults. As 

more data for individual pyrethroids become available and previously required data (June 

2010 RED DCI) are submitted, the Agency will determine whether re-evaluation of the 

age-related sensitivity of pyrethroids is appropriate. 

 Please refer to the December 13, 2011 document Tetramethrin: Human Health Risk 

Scoping Document in Support of Registration Review in the registration review docket 

 

2 http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html
8

(EPA-HQ-OPP-2011-0907) for a detailed discussion of the anticipated risk assessments 

and data needs. 

Endocrine Disruptor Screening Program: 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its reregistration decision for tetramethrin, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p), tetramethrin is 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar 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 approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Tetramethrin 

is not among the group of 58 pesticide active ingredients on the initial list to be screened under 

the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data 

call-ins, requiring the submission of EDSP screening assays for tetramethrin. For further 

information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, 

future lists, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/. 

Timeline:

EPA has created the following estimated timeline for the completion of tetramethrin’s 

registration review. 
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Registration Review for Tetramethrin – Projected Registration Review Timeline

Activities Estimated Date 

Opening the Docket 

Open Docket and Public Comment Period 2011 – December 

Close Public Comment 2012 – February 

Case Development 

Final Work Plan 2012 – May 

Issue DCI 2013 – Jan. – March 

Data Submission 2014 – Jan. – March 

Open Public Comment Period for Draft Risk Assessments 2015 – July – Sept. 

Close Public Comment Period 2015 – Oct. – Dec. 

Registration Review Decision 

Open Public Comment Period for Proposed Registration Review 

Decision 

 2016 – Jan. – March 

Close Public Comment Period 2016 – April – June 

Registration Review Decision and Begin Post-Decision Follow-up 2016 

Total (years)3 5 

Guidance for Commenters: 

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the tetramethrin case. 

Trade Irritants: 

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Limits (MRLs) or disparities between U.S. tolerances and MRLs in key 

export markets, providing as much specificity as possible regarding the nature of the concern. 

Because tetramethrin is not registered for food/feed uses in the U.S., it has no U.S. tolerances. 

Water Quality: 

On October 11, 2011, EPA approved California's 2008 - 2010 list of impaired water bodies that 

require total maximum daily loads (TMDLs) pursuant to the Clean Water Act, section 303(d), 

and 40 CFR 130.7(d)(2). This list includes 11 water body impairments due to pyrethroid 

pesticides as a group, and three water body impairments with the individual pyrethroid active 

ingredients bifenthrin, lambda cyhalothrin, esfenvalerate/fenvalerate, and permethrin identified 

as the cause of impairment. More information on California’s additional impaired water body 

listings can be found at EPA’s website4. 

 

3

 Any changes in the cumulative risk from the pyrethroid class of insecticides may impact this time estimate. 

4 http://www.epa.gov/region9/water/tmdl/california.html
10

No water bodies have been designated as impaired specifically for tetramethrin, nor have any 

TMDLs been developed for this active ingredient5. More information on impaired water bodies 

and TMDLs can be found at the Agency’s website6. The Agency invites submission of water 

quality data for this pesticide. To the extent possible, data should conform to the quality 

standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired 

Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and 

Management Process7 in order to ensure they can be used quantitatively or qualitatively in 

pesticide risk assessments. 

On October 28, 2011, the California Department of Pesticide Regulation (DPR) announced 

proposed restrictions to 17 pyrethroid pesticides, including tetramethrin, used by pest control 

applicators and maintenance gardeners in urban areas to protect water quality. Restrictions 

would include: 1) prohibiting applications during rain, when puddles are present, 2) prohibiting 

use over drains or natural drainage areas, and 3) restricting application methods around 

structures. More information about the proposed regulations are available on DPR’s website8. 

Environmental Justice: 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to tetramethrin compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population. 

Other Information: 

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining the risk assessments, including any species-specific ecological 

determinations. The Agency is interested in obtaining the following information: 

1. confirmation on the following label information 

a. sites of application 

b. formulations 

c. application methods and equipment 

d. maximum application rates 

e. frequency of application, application intervals, and maximum number of 

applications per season 

f. geographic limitations on use 

 

5

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

6 http://www.epa.gov/owow/tmdl/

7 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm

8 http://www.cdpr.ca.gov/docs/legbills/rulepkgs/11-004/11-004.htm
11

2. use or potential use distribution (e.g., acreage and geographical distribution of relevant 

use sites) 

3. use history 

4. median and 90th percentile reported use rates (lbs ai/1000 sq ft) from usage data – 

national, state, and county 

5. application timing (date of first application and application intervals) – national, state, 

and county 

6. sub-county use site location data 

7. usage/use information for non-agricultural uses 

8. directly acquired county-level usage data (not derived from state level data) 

a. maximum reported use rate (lbs ai/acre) from usage data – county 

b. median and 90th percentile number of applications – county 

c. total pounds per year – county 

d. the year the pesticide was last used in the county/sub-county area 

e. the years in which the pesticide was applied in the county/sub-county area 

9. typical application interval (days) 

10. state or local use restrictions 

11. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency 

12. monitoring data 

Next Steps: 

After the 60-day public comment period closes, the Agency will review and respond to any 

comments received in a timely manner and then issue a Final Work Plan for the registration 

review of tetramethrin. 
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II. FACT SHEET 

 

Background Information: 

 Tetramethrin’s registration review case number: 2660. 

 Tetramethrin’s PC code: 069003. 

 Tetramethrin’s CAS No.: 7696-12-0. 

 Tetramethrin was first registered for use in the United States in 1968.

 The Tetramethrin RED was completed in June 2008 and revised in April 2010.

 Sumitomo Chemical Company and Valent Biosciences Corporation are the technical 

registrants of tetramethrin. There are approximately 160 Section 3 product registrations. 

 Because there are no food or feed uses of tetramethrin, there are no tolerances established 

for this chemical. 

 Pesticide Re-evaluation Division, Chemical Review Manager: Monica Wait, 

wait.monica@epa.gov 

 Registration Division, Product Manager: Richard Gebken, gebken.richard@epa.gov

Use & Usage Information: (For additional details, refer to the BEAD Chemical Profile for 

Registration Review: Tetramethrin in the registration review docket EPA-HQ-OPP-2011-0907.) 

 Tetramethrin is a broad-spectrum, first-generation synthetic pyrethroid insecticide. It is a 

rapid knockdown agent registered for use against flying and crawling insects, including 

wasps, hornets, roaches, ants, fleas, and mosquitoes. 

 Tetramethrin is nearly always co-formulated with synergists, other pyrethroid active 

ingredients, or growth inhibitors for greater effectiveness and to control a broader 

spectrum of insect pests. These other active ingredients are more persistent than 

tetramethrin and provide residual activity against insects not exposed initially. 

 Use sites include commercial, residential, and horticultural applications as space sprays, 

broadcast surface treatments, crack and crevice treatments, outdoors as localized space 

and contact sprays on ornamental plants, perimeter treatments (e.g., sidewalks, 

entranceways, outside surfaces of buildings). Tetramethrin products can also be used to 

treat pet premises and as direct applications to pets. 

 There are no registered food use applications for tetramethrin. 

 Some tetramethrin end-use products are labeled for use by pest control operators only 

although tetramethrin products are not classified as restricted use pesticides. 

 Products are formulated as pressurized liquids, ready-to-use liquids, emulsifiable 

concentrates, and liquid concentrates. Tetramethrin products can be applied by aerosol 

cans, handheld sprayers, foggers, and mechanical sprayers. 

 The Agency has very limited usage data for tetramethrin due to its non-agricultural and 

diffuse types of use patterns. In 2005, the most recent year for which EPA has data, 
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approximately 310,000 pounds of tetramethrin were used for indoor residential 

treatments. Data for earlier or more recent years were not available. Usage was not 

reported in the available reports for food handling establishments; however, usage may 

be occurring below the reporting threshold. 

Recent Actions:

 The revised RED for tetramethrin was recently completed in June 2010, and the product 

reregistration process, which starts after completion of a RED, is still ongoing for many 

tetramethrin products. Product reregistration is EPA's program for implementing all risk 

reduction measures as described in a RED by ensuring that pesticide product labels are 

amended accordingly. To initiate the product reregistration process, EPA sends pesticide 

registrants a data call-in notice requiring product-specific acute toxicity and product 

chemistry data and revised labeling. This information is needed to complete the 

reregistration of each pesticide product covered by the RED. As part of product 

reregistration, approximately 100 tetramethrin products have been voluntarily cancelled 

by registrants, and 160 remain to be reregistered. 

Ecological Risk Assessment Status:

Please refer to the Registration Review – Preliminary Problem Formulation for the Ecological 

Risk Assessment of Tetramethrin, December 5, 2011 for a detailed discussion of the key findings 

of the most recent ecological risk assessments. A summary follows: 

 

Summary of Risks: 

 The most recent comprehensive ecological risk assessment for tetramethrin was 

completed in February 2008 in support of the 2008 RED. 

 In the RED, ecological exposures were not quantified because of tetramethrin’s limited 

use patterns. The RED concluded that the localized use pattern of tetramethrin, 

combined with low total pounds used on a national basis, and rapid degradation due to 

photolysis and hydrolysis, made it highly unlikely that non-target organisms would be 

exposed at harmful levels. 

 The RED found that, based on the available ecotoxicity data, the most acutely sensitive 

organisms to tetramethrin were fish, aquatic invertebrates, and insects. Tetramethrin was 

practically non-toxic to birds and mammals on an acute basis. The only chronic 

(reproductive) data submitted was for the rat. The no-adverse-effect-concentration 

(NOAEC) was relatively low (25 mg/kg/day); however, quick degradation of 

tetramethrin was expected to reduce the amount of time that exposure potential would 

reach this level. 

 The only taxa considered at risk in the RED were terrestrial invertebrates present at the 

time and place of localized spraying. 
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Human Health Risk Assessment Status: 

Please refer to Tetramethrin: Human Health Risk Scoping Document in Support of Registration 

Review, December 13, 2011 for a detailed discussion of the key findings of the most recent 

human health risk assessment. A summary follows: 

Hazard Characterization:

 Tetramethrin was classified as a “Group C, possible human carcinogen without 

quantification” by the Cancer Peer Review Committee in 1989. This classification 

corresponds to a classification of “Suggestive Evidence of Carcinogenic Potential,” under 

EPA’s 2005 Guidelines for Carcinogen Risk Assessment. 

Dietary (Food and Drinking Water):

 At the time of the RED, tetramethrin had no registered food uses and no tolerances for 

specific raw agricultural commodities. Tetramethrin was not registered for direct 

application to agricultural crops, livestock animals, or livestock premises, where 

livestock are used for food. There were uses in the home where food could be exposed 

(e.g., kitchen), but due to labeling restrictions, exposure to food was considered likely to 

be negligible. For these reasons, a quantitative assessment of dietary risk for residential 

uses was not conducted. 

Residential (Non-occupational): 

 

 The residential exposure assessment conducted in July 2008 included handler and postapplication residential exposure scenarios. Residential handler exposure and risk 

estimates were conducted using EPA’s standard deterministic modeling methodology and 

default assumptions for most exposure scenarios. Residential post-application exposure 

and risk to tetramethrin was assessed using probabilistic modeling approaches. 

 Residential scenarios were assessed for exposure via inhalation and incidental ingestion 

pathways. Dermal exposure was not assessed based on absence of adverse effects in 

dermal toxicity studies. 

 Residential handler exposure scenarios, assessed using standard deterministic risk 

assessment methodology, showed that estimated risks were not of concern. 

 Based on comments submitted to the Agency for the residential post-application exposure 

assessment, EPA conducted a refined probabilistic assessment of risks using the 

Cumulative and Aggregate Risk Evaluation System (CARES) for those scenarios that 

presented risks of concern based on the deterministic assessment. Probabilistic exposure 

assessment is recognized as a refinement over deterministic assessment because it 

incorporates the full range of exposures and their associated probabilities. Based on the 

probabilistic exposure assessment, EPA concluded that uses of tetramethrin do not 

indicate risks of concern. 
15

 Based on additional comments submitted to EPA, a benchmark dose analysis of the 

toxicity endpoint for incidental oral exposure was conducted, and a new endpoint was 

selected. EPA revised the CARES assessment in February 2010 in order to incorporate 

the new endpoint and to evaluate products with a higher percent active ingredient than 

those that were included in the 2008 assessment. Based on the revised assessment, 

estimated risks were below the level of concern. 

Aggregate: 

 An aggregate risk assessment typically evaluates the combined risk from dietary 

exposure (food plus drinking water) and any residential uses. An aggregate assessment 

was not conducted for the previous risk assessment since tetramethrin uses were 

determined to be non-food, and residential exposures were below the level of concern. 

Occupational:

 In the most recent tetramethrin risk assessment, risks to occupational handlers were 

evaluated based on registered uses and were found to be below EPA’s level of concern. 

 Occupational post-application scenarios were not assessed because there was no dermal 

endpoint, and post-application inhalation exposures were not expected for non-volatile 

compounds such as tetramethrin. 

Human Studies: 

 Past tetramethrin occupational and residential risk assessments rely in part on data from 

studies in which adult human subjects were intentionally exposed to a pesticide to 

determine their dermal and inhalation exposure. Many such studies, involving exposure 

to many different pesticides, comprise generic pesticide exposure databases such as the 

Pesticide Handlers Exposure Database (PHED) and the Outdoor Residential Exposure 

Task Force (ORETF) Database. EPA has reviewed all the studies supporting these multipesticide generic exposure databases, and has found no clear and convincing evidence 

that the conduct of any of them was either fundamentally unethical or significantly 

deficient relative to the ethical standards prevailing at the time the research was 

conducted. All applicable requirements of EPA’s Rule for the Protection of Human 

Subjects of Research (40 CFR Part 26) have been satisfied, and there is no regulatory 

barrier to continued reliance on these studies. 

Cumulative: 

 The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative 

risks of chemicals sharing a common mechanism of toxicity. Tetramethrin is a member 

of the pyrethroid/pyrethrins common mechanism group (http://www.regulations.gov; 

EPA-HQ-OPP-2008-0489-0006). The members of this group share the ability to interact 

with voltage-gated sodium channels ultimately leading to neurotoxicity. The cumulative 

risk assessment for the pyrethroids/pyrethrins was published on November 9, 2011 and is 

available at http://www.regulations.gov; EPA-HQ-OPP-2011-0746. No cumulative risks 
16

of concern were identified, allowing the Agency to consider new uses for pyrethroid 

active ingredients. For information regarding EPA’s efforts to evaluate the risk of 

exposure to pyrethroids, refer to the Agency’s website9. 

Incidents: 

 A review of the Ecological Incident Information System (EIIS), the ‘Aggregate Incident 

Reports’ (v. 1.0) database, and the Avian Monitoring Information System (AIMS) for 

ecological incidents involving tetramethrin was completed on July 11, 2011. The 

searches of EIIS and AIMS identified no ecological incidents involving tetramethrin. 

However, for a variety of reasons, a lack of reported incidents does not necessarily mean 

that no incidents have occurred. 

 Ecological incidents are also reported to the Agency by pesticide registrants in 

aggregated incident reports. Registrants report certain types of incidents to the Agency as 

aggregate counts of incidents occurring per product per quarter. For tetramethrin, 

registrants have reported one minor fish and wildlife incident and nine minor plant 

incidents between 1998 and 2009. Unless additional information on these aggregated 

incidents becomes available, they will be assumed to be representative of registered uses 

of tetramethrin for the ecological risk assessment. 

 An updated human health incident report was conducted for tetramethrin for registration 

review. In general, a relatively large number of incidents have been reported. However, 

because tetramethrin products are almost always co-formulated with other pesticide 

active ingredients, there are no cases reported for products containing tetramethrin as a 

single chemical only. Human incident data may warrant further analysis during the 

registration review risk assessment. 

 The Aggregate Incident Data System (IDS), which reports less severe human incidents as 

counts, showed 3,772 incidents involving tetramethrin from January 1, 2006 to June 8, 

2011. Aggregate IDS does not provide a unique report or additional details about the 

incidents, and single chemical incidents are not distinguished from multiple chemical 

incidents. From January 1, 2006 to June 8, 2011, the Main IDS, which stores data for 

more severe incidents, including details about the nature of the incident, reported 416 

cases involving tetramethrin as one of the active ingredients in the product. 

Tolerances and International Harmonization: 

 Because there are no registered food or feed uses for tetramethrin, no tolerances are 

currently established. 

Data Call-In Status: 

 A generic data call-in (GDCI-069003-28621) was issued in June 2010 for the following 

studies based the 2010 revised RED. 

 

9 http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html
17

870.3700 – Prenatal developmental toxicity (due 6/2012) 

870.6200 – Neurotoxicity battery, acute and subchronic (due 6/2012) 

870.6300 – Developmental neurotoxicity (DNT) (registrant intends to cite six 

previously submitted DNT studies for pyrethroid pesticides) 

870.7800 – Immunotoxicity (submitted 8/2011 and in review) 

 Product-specific acute toxicity and product chemistry data associated with product 

reregistration were required by product data call-ins issued in June 2010 (PDCI-069003-

28170). 

Labels: 

 

 Registration numbers and labels for tetramethrin products can be obtained from the 

Pesticide Product Label System (PPLS) website10. 

 

10 http://oaspub.epa.gov/pestlabl/ppls.home 
18

III. SUMMARY OF DATA GAPS – TETRAMETHRIN 

The table below summarizes anticipated data needs for tetramethrin listed in Section I of this 

document and outstanding data previously required through EPA’s data call-in process. 

Guideline 

Number Anticipated Data Need Test Material 

Estimated 

Timeframe 

(Months from 

receipt of DCI) 

835.6100 Terrestrial field dissipation study11 TGAI 12 

835.6200 Aquatic field dissipation study11 TGAI 12 

850.1020 Gammarid acute toxicity TGAI & TEP 12 

850.1025 Acute toxicity estuarine and marine organisms 

(oyster shell growth) TGAI 12 

850.1035 Acute toxicity estuarine and marine organisms 

(mysid) TGAI 12 

850.1075 Acute toxicity estuarine and marine organisms 

TGAI for 

estuarine / 

marine fish. 

TEP for 

freshwater fish. 

12 

850.2100 Avian oral toxicity (passerine species) TGAI 12 

850.4100 Terrestrial plant toxicity, seedling emergence, Tier 

II12 TEP 12 

850.4150 Terrestrial plant toxicity, vegetative vigor, Tier II12 TEP 12 

The studies below were previously required through a generic data call-in (GDCI-069003-28621), 

issued in June 2010. The studies are listed for reference although they will NOT be included in the 

anticipated registration review DCI. 

870.3700 Prenatal developmental toxicity TGAI due 6/2012 

870.6200 Acute and subchronic neurotoxicity battery TGAI due 6/2012 

870.6300 Developmental neurotoxicity13 TGAI due 6/2014 

870.7800 Immunotoxicity TGAI in review 

 

11 See footnote 7 of 40 CFR 150.1300. EPA anticipates requiring only the environmental chemistry analytical 

methods and ILV portions of this guideline for soil and water, rather than the full field dissipation study. 12 The DCI expected to be issued will provide that a Tier I plant study may be conducted in lieu of a Tier II study 

with the understanding that any adverse effects observed by the Tier I study would necessitate conduct and 

submission of a Tier II study as well. 13 The June 2010 DCI included the statement, “EPA has 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.”