Docket Number EPA-HQ-OPP-2011-0907 www.regulations.gov



## Tetramethrin Summary Document Registration Review: Initial Docket

December 20113 

### 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 su mmarize 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 Revi ew: 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 te tramethrin 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 Stat es (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The registration review program is intended to ma ke 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 unreasonabl e 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 prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided at: http://www. epa.gov/oppsrrd1/registration_review/.

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e 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 belie ves are needed to make a registration review decision. After reviewing and responding to co mments and data received in the docket during this initial comment period, the Agency will de velop and commit to a final work plan and schedule for the registration review of tetramethrin.

Tetramethrin is a broad-spectrum, first-generation s ynthetic pyrethroid insect icide. It is a rapid knockdown agent registered for use against flying a nd crawling insects, such as wasps, hornets, roaches, ants, fleas, and mosquitoes. At this ti me, there are no register ed food or agricultural uses of tetramethrin. It is used primarily in residential, commercial, in stitutional, and industrial

areas and can be used both i ndoors, including applications to pets, and outdoors. Some tetramethrin end-use products are labeled fo r use by pest control operators only although tetramethrin products are not classified as re stricted 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 fo r the pyrethroids and pyrethrins was recently published on November 9, 2011 and is availa ble 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 endangere d species assessment, for all uses of tetramethrin. For human health, EPA anticipates the need to conduct revise d residential and occupa tional risk assessments during registration review. If t oxicological endpoints or points of departure are revised based on the data that are anticipated to be required for re gistration review, they will be considered in the5 new assessment, as well as any changes to the st andard operating procedures or default exposure assumptions. Below is a summary of the issu es 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 modeli ng methodologies, updated toxicological endpoints, and data submitted under the antici pated 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 en closed 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 a ssessment, standard expected environmental concentrations (EECs) cannot be directly calculated (without majo r assumptions) using the tools on which EPA typically relies. Th e difficulty in calculating standard EECs is

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

a.i./ft 3” ) 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 anti cipated 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,” retreat ment intervals, or maximum annual application rates. In the absen ce of clear label information, EPA must approximate these parameters in order to conduct a quantitative assessment for tetramethrin. The Agency encourages clear a nd consistent label langu age 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 eco logical risk assessment planned during registration review will allow the Agency to determine whether tetramethrin’s use has “no effect” or “may affect” federally liste d threatened or endangered species (listed species) or their designated critical habita ts. 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.6  On January 19, 2011, the Center for Biologi cal Diversity and the Pesticide Action

Network North America filed a lawsuit in th e United States District Court for the Northern District of California, against EP A for allegedly failing to undergo consultation with the Services regarding the effects of over 350 pesticides, incl uding tetramethrin, on over 200 endangered and threatened species throughout the United States (Center for Biological Diversity, et al. v. EP A, et al., No. C 11-00293 (N.D.Cal.)

.

 Data gaps exist in the ecological database fo r tetramethrin. EPA anticipates requiring the following studies for use in conducting a comp lete ecological risk assessment, including an endangered species assessment, for th e registration review of tetramethrin.

835.6100 – Terrestrial field dissipation study 1
835.6200 – Aquatic field dissipation study 1
850.1020 – Gammarid acute toxicity (using TGAI and TEP) 850.1025 – Acute toxicity estuar ine and marine organism s (oyster shell growth) 850.1035 – Acute toxicity es tuarine and marine organisms (mysid) 850.1075 – Acute toxicity estu arine and marine organisms (using TGAI for

estuarine/marine fish and us ing TEP for freshwater fish) 850.2100 – Avian oral toxicity (passerine species) 850.4100 – Terrestrial plant toxicity, seedling emergence, Tier II 850.4150 – Terrestrial plant toxic ity, vegetative vigor, Tier II

 Studies conducted with freshw ater invertebrates and fish are expected to be required using a typical end-use product (TEP) containi ng tetramethrin and th e synergist piperonyl butoxide in addition to a pr oduct 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 ingr edient ratios, selection of the TEPs for the anticipated testing requirement would incl ude those with the highest sy nergist-to-active ingredient ratio and that are regi stered 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 de tailed 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.7  The Food Quality Protection Act (FQPA) require s the Agency to consider the cumulative risks of chemicals sharing a common mechanism of toxicity. Tetramethrin is a member of the pyrethroid/pyrethri ns common mechanism group ( http://www.regulations.gov ; EPA-HQ-OPP-2008-0489-0006). The members of this group share the ab ility to interact with voltage-gated sodium channels ultimatel y leading to neurotoxicity. The cumulative risk assessment for the pyrethroids/pyreth rins 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, a llowing the Agency to consid er new uses for pyrethroid active ingredients. For information regardi ng EPA’s efforts to evaluate the risk of exposure to pyrethroids, refe r to the Agency’s website 2

.

 A dietary (food) exposure assessm ent is not anticipated to be needed during registration review because there are currently no regist ered food or feed uses for tetramethrin. Dietary exposure is not expect ed based on registered uses.

 A drinking water dietary assessment for tetramet hrin is not anticipat ed during registration review given the limited extent of potential exposures based on curre ntly registered use sites and the environmental fate properties of tetramethrin that limit its mobility.

 A revised residential exposure assessment is anticipated during re gistration review to reflect current standard operating procedur es and revised toxi cological endpoints.

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

reflect current standard operating procedures.

 During registration review, EPA will consid er 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 F actsheet for further details regarding the previously-issued DCI. No additional human h ealth 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 th e FQPA Safety Factor to 1X for adults, including women of child-bearing age, and ch ildren greater than 6 years of age. However, the Agency is retaining a 3X FQPA Safety Factor for chil dren from birth to 6 years of age. The 3X is based on age- dependent-pharmacokinetics and is further supported by physiologically-based pharmacokine tic (PK) model predictions of a 3-fold increase of pyrethroid concentr ation in juvenile target tissu e compared to adults. As more data for individual pyrethr oids become available and prev iously 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.html8 (EPA-HQ-OPP-2011-0907) for a detailed discussi on of the anticipated risk assessments

and data needs.

Endocrine Disruptor Screening Program :

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its reregistration decision for tetramethrin, EPA reviewed these data and selected the most sensitive endpoints fo r relevant risk assessment scenarios from the existing hazard database. However, as requi red by FFDCA section 408(p ), tetramethrin is subject to the endocrine screeni ng part of the Endocrine Disrup tor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 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 pest icide active ingredients and 9 inert ingredients. Tetramethrin is not among the group of 58 pesticide active ingred ients on the initial list to be screened under the EDSP. Accordingly, as part of registrati on review, EPA will issue future EDSP orders/data call-ins, requiring the submission of EDSP scr eening assays for tetramethrin. For further information on the status of the EDSP, the polic ies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, pl ease visit our website: http://www.epa.gov/endo/

.

Timeline :

EPA has created the following estimated timeline for the completion of tetramethrin’s registration review.9 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 wo rk plan for the tetramethrin case.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any tr ade 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 na ture of the concern. Because tetramethrin is not regi stered 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) pursu ant 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 thr ee water body impairments with th e individual pyrethroid active ingredients bifenthrin, lambda c yhalothrin, esfenvalerate/fenvalera te, and permethrin identified as the cause of impairment. More informa tion on California’s addi tional impaired water body listings can be found at EPA’s website 4

.

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.html10 No water bodies have been designated as impair ed specifically for tetramethrin, nor have any TMDLs been developed fo r this active ingredient 5 . More information on impaired water bodies and TMDLs can be found at the Agency’s website 6 . 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 Procedur e: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Regist ration Review Risk Assessment and Management Process 7 in order to ensure they can be us ed quantitatively or qualitatively in pesticide risk assessments.

On October 28, 2011, the California Department of Pesticide Regulation (DPR) announced proposed restrictions to 17 pyrethroid pesticid es, including tetramethri n, used by pest control applicators and maintena nce gardeners in urban areas to pr otect water quality. Restrictions would include: 1) prohibiting a pplications during rain, when puddl es are present, 2) prohibiting use over drains or natural drainage areas, a nd 3) restricting app lication methods around structures. More information about the propos ed regulations are available on DPR’s website 8

.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, 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 thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to tetramethr in compared to the general population. Please comment if you are aware of any sub-populatio ns that may have atypical, unusually high exposure compared to th e general population.

Other Information:

Stakeholders are also specifically asked to prov ide 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, applicati on 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/legb ills/rulepkgs/11-004/11-004.htm11 2. use or potential use distribution ( e.g. , acreage and geographical di stribution of relevant use sites)

3. use history

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

5. application timing (date of firs t application and application in tervals) – 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 da ta (not derived from state level data)

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

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

c. total pounds per year – county

d. the year the pesticide was last us ed 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 alr eady 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 i ssue a Final Work Plan for the registration

review of tetramethrin.12 

### 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 Bi osciences Corporati on are the technical registrants of tetramethrin. There are appr oximately 160 Section 3 product registrations.

 Because there are no food or feed uses of tetr amethrin, there are no to lerances established

for this chemical.

 Pesticide Re-evaluation Di vision, 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-generatio n synthetic pyrethroid in secticide. It is a rapid knockdown agent registered for use agai nst flying and crawling insects, including wasps, hornets, roaches, ants, fleas, and mosquitoes.

 Tetramethrin is nearly always co-formula ted with synergists, other pyrethroid active ingredients, or growth inhi bitors for greater effectiven ess and to control a broader spectrum of insect pests. These other ac tive ingredients are more persistent than tetramethrin and provide re sidual activity against inse cts not exposed initially.

 Use sites include commercial, residential, a nd horticultural applica tions 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 pr oducts are labeled for use by pest control operators only although tetramethrin products are not cla ssified as restricted use pesticides.

 Products are formulated as pressurized liquids, ready-to -use liquids, emulsifiable concentrates, and liquid concentrates. Tetr amethrin products can be applied by aerosol cans, handheld sprayers, foggers , and mechanical sprayers.

 The Agency has very limited usage data for te tramethrin due to its non-agricultural and diffuse types of use patterns. In 2005, the most recent year for which EPA has data,13 approximately 310,000 pounds of tetramethrin were used for indoor residential

treatments. Data for earlier or more recen t 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 recen tly 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 describe d in a RED by ensuring that pe sticide 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 Pr oblem 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 th e localized use patter n of tetramethrin, combined with low total pounds used on a natio nal basis, and rapid degradation due to photolysis and hydrolysis, made it highly unlik ely that non-target organisms would be exposed at harmful levels.

 The RED found that, based on the available ecoto xicity data, the most acutely sensitive organisms to tetramethrin were fish, aquatic i nvertebrates, 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.14 Human Health Risk Assessment Status :

Please refer to Tetramethrin: Human Health Risk Scopi ng 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 “Gr oup 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. Tetr amethrin 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 labe ling restrictions, exposure to food was considered likely to be negligible. For these reasons, a quantitati ve assessment of dietar y risk for residential

uses was not conducted.

Residential (Non-occupational):

 The residential exposure assessment conducte d in July 2008 included handler and postapplication residentia l exposure scenarios. Residen tial handler exposure and risk estimates were conducted using EPA’s stan dard deterministic modeling methodology and default assumptions for most exposure scenario s. Residential post- application exposure

and risk to tetramethrin was assessed using probabilistic modeling approaches.

 Residential scenarios were assessed for expos ure 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, a ssessed using standard deterministic risk assessment methodology, showed that estimated risks were not of concern.

 Based on comments submitted to the Agency fo r the residential post-application exposure assessment, EPA conducted a refined proba bilistic assessment of risks using the Cumulative and Aggregate Risk Evaluation Sy stem (CARES) for those scenarios that presented risks of concern based on the determ inistic assessment. Probabilistic exposure assessment is recognized as a refinement over deterministic assessment because it incorporates the full range of exposures and their associated probabi lities. Based on the probabilistic exposure assessment, EPA concl uded 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 incide ntal oral exposure was conduc ted, and a new endpoint was

selected. EPA revised the CARES assessment in February 2010 in order to incorporate the new endpoint and to evalua te products with a higher percent active ingredient than

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

estimated risks were belo w the level of concern.

Aggregate:

 An aggregate risk assessment typically ev aluates the combined risk from dietary exposure (food plus drinking wa ter) 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 e xposures were below the level of concern.

Occupational:

 In the most recent tetramethr in risk assessment, risks to occupational handlers were evaluated based on registered uses and were found to be be low EPA’s level of concern.

 Occupational post-application scenarios were not assessed because there was no dermal endpoint, and post-application inhalation exposures were no t 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 su ch studies, involving exposure to many different pesticides, comprise generi c pesticide exposure da tabases such as the Pesticide Handlers Exposure Database (PHE D) and the Outdoor Residential Exposure Task Force (ORETF) Database. EPA has revi ewed 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 eith er fundamentally uneth ical or significantly

deficient relative to the ethical standard s prevailing at the time the research was conducted. All applicable re quirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfie d, and there is no regulatory

barrier to continued re liance on these studies.

Cumulative:

 The Food Quality Protection Act (FQPA) require s the Agency to consider the cumulative risks of chemicals sharing a common mechanism of toxicity. Tetramethrin is a member of the pyrethroid/pyrethri ns common mechanism group ( http://www.regulations.gov ; EPA-HQ-OPP-2008-0489-0006). The members of this group share the ab ility to interact with voltage-gated sodium channels ultimatel y leading to neurotoxicity. The cumulative risk assessment for the pyrethroids/pyreth rins was published on November 9, 2011 and is

available at http://www.regulations.gov ; EPA-HQ-OPP-2011-0746. No cumulative risks16 of concern were identified, a llowing the Agency to consid er new uses for pyrethroid active ingredients. For information regardi ng EPA’s efforts to evaluate the risk of exposure to pyrethroids, refe r to the Agency’s website 9

.

Incidents :

 A review of the Ecological Incident Informa tion System (EIIS), the ‘Aggregate Incident Reports’ (v. 1.0) database, and the Avian M onitoring Information System (AIMS) for ecological incidents involving tetramet hrin was completed on July 11, 2011. The

searches of EIIS and AIMS identified no ecological incide nts 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 qu arter. For tetramethrin, registrants have reported one minor fish and wildlife incident and nine minor plant

incidents between 1998 and 2009. Unless additi onal 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 al ways co-formulated with other pesticide active ingredients, there are no cases reporte d 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), wh ich 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 uniqu e 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 a bout the nature of the incident, reported 416 cases involving tetramethrin as one of the active ingr edients 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.html17 870.3700 – Prenatal developmenta l toxicity (due 6/2012) 870.6200 – Neurotoxicity battery, acut e and subchronic (due 6/2012) 870.6300 – Developmental neurot oxicity (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 toxici ty 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 tetram ethrin products can be obtained from the Pesticide Product Label System (PPLS) website 10

.

10 http://oaspub.epa.gov/pestlabl/ppls.home18 

### 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 requi red 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 study 11 TGAI 12

835.6200 Aquatic field dissipation study 11 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 estuari ne 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

II 12 TEP 12

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

The studies below were previously required thro ugh 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 neurotoxi city battery TGAI due 6/2012
870.6300 Developmental neurotoxicity 13 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 observ ed by the Tier I study would necessitate conduct and submission of a Tier II study as well.

13 The June 2010 DCI included the statem ent, “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.”