Page 2 of 11 The 1995 risk assessment addressed exposures and risks associated with occupational and residential uses of starlicide. The assessment recommended numerous risk mitigation and labeling measures. Given implementation of th e recommended label restrictions and personal protective equipment (PPE) requi rements for workers, the 1995 assessment determined that exposures to starlicide from re gistered uses would not pr esent risks of concern.

HED’s problem formulation conc lusions are as follows.

1) A dietary exposure assessment was not c onducted for the 1995 assessment because starlicide was determined to be a non-food use pesticide. However, HED has determined that under current labels uses in livestock and poultry feed lots constitute a food use. Therefore, EPA is working with the registrants to revise the la bels to include language that is sufficiently restrictive to preclude exposure to livestock. Consequently, a dietary assessment will not be required for Registration Review. 2) A drinking water exposure assessment is no t required for Registration Review based on use

patterns. 3) A quantitative residential exposure assessment was not conducted for the 1995 assessment. However, use in accordance with current labels could result in post-ap plication exposure to children. Therefore, EPA is working with the registrants to revise the labels to include language that is sufficiently re strictive to preclude resident ial postapplication exposure. Consequently, a residential exposure asse ssment will not be required for Registration

Review. 4) The occupational exposure a ssessment needs to be revised for Registration Review to include a quantitative assessment of exposures to o ccupational handlers and workers re-entering

treated sites. 5) An aggregate risk assessment is not require d for Registration Review on the presumption that labels will be adequately revised to precl ude dietary or residential exposures. 6) A subchronic dermal toxicity study is required for Registration Review based on the registered uses and application methods. 7) Developmental toxicity studi es in the rat and rabbit are requ ired for Registration Review for non-food use pesticides under 40 CFR Part 158. 8) A reproduction toxicity study in rats is re quired for Registration Review for non-food use pesticides under 40 CFR Part 158. 9) An immunotoxicity study and acute and subc hronic neurotoxicity st udies are required for Registration Review under 40 CFR Part 158 as a part of the new data requirements for registration of a pesticide (food and non-food uses).Page 3 of 11 Introduction

HED has evaluated the existing human health risk assessments for starlicide to determine

whether sufficient data are available and whether a new human health risk assessment is needed to support Registration Review. HED has consid ered the most recent risk assessments for starlicide, updates to its toxicity, exposure a nd usage databases, and current Agency science policies and risk assessment methods.

Use Profile

Starlicide is an avicide used for control of predatory birds i.e., birds preying on newborn livestock, Federally-designated Threatened or Endangered Species, and ot her species designated to be in need of special protecti on. It is also used to control birds causing health, nuisance, or economic problems. Use sites vary by species but include livestock and poultry feedlots, buildings, non-crop areas, Federal and State protected areas, coasta l areas, and bird staging and roosting sites. Starlicide is sl ow-acting and highly toxic to target species, with death occurring 1-3 days after ingestion. Starlicide is a restri cted use pesticide to be sold to and used only certified applicators or persons under their direct supervision. Starlicide is applied by manual or mechanical broadcast of treated bait (e.g., grain, corn, bread crumbs) and by placement of treated bait in feeding stations (i.e., sma ll piles or bait containe rs). Starlicide is not available for use by homeowners. However, there may be potential for post-application exposure to residents entering treated areas.

Chemical Identity

Table 2.1. Starlicide Nomenclature

Chemical structure

Common name Starlicide

IUPAC name 3-Chloro-4-methylaniline

CAS name 3-Chloro-4-methylbenzenamine hydrochloride

CAS registry number 7745-89-3

Hazard Identification/Toxicology

Starlicide was determined to be a low volume, minor use pesticide for the 1995 risk assessment. HED waived the guideline requireme nts for repeat dose oral and dermal toxicity studies for non-food use pesticides due to low us e and low exposure expected from uses actively registered in 1995. Consequently, there are very few toxicological studies available for starlicide. Developmental and reproduction toxicity studies are not available for starlicide. Newly required neurotoxicity and immunotoxicity studies are not available for starlicide. A non-Page 4 of 11 guideline chronic cancer study conducted by the National Cancer Institut e (NCI) with mice and

rats indicates that starlicide is not a carcinogen. Available mu tagenicity tests indicate that starlicide is not mutagenic.

Based on available acute toxicity data, starlicide is moderate ly acutely toxic via the oral route (Category II), minimally toxic via the de rmal route (Category IV ) and moderately to severely irritating, both dermally and ocularly (Category I). OPP di d not require an acute inhalation study for starlici de citing the fact that the technical material is incorporated into viscous bait. However, starlicide was placed in to xicity Category I for acute inhalation based on the severely irritating properties observed in the ocular and dermal irritation studies.

Toxicity points of departure (PODs) were not selected for the 1995 risk assessment. PODs for dietary exposure were no t required because the registered uses were determined to be non-food. Quantitative occupational and residentia l exposure assessments were not required for starlicide because the Agency determined that there was lo w potential for exposure both to occupational handlers during use and to persons entering treated sites after application is complete.

Data Requirements

Carcinogenicity and subchronic and chronic oral toxicity st udies are not required for nonfood use pesticides. However, based on HED’s ev aluation of existing labe ls, registered use of

starlicide in livestock an d poultry feed lots is considered a food use. EPA is working with the registrants to revise the labels to include language that is suffi ciently restrictive to preclude exposure to livestock. If these labeling change s were not made, Subchronic Oral Toxicity (870.3100, 870.3150), Chronic Oral T oxicity (870.4100) and Carc inogenity (870.4200) studies would be required for Registrati on Review. As noted, an NCI cancer study with mice and rats has previously been submitted. This study was not required for registration of starlicide in 1995 and has not been officially reviewed to de termine its adequacy based on OCSPP Harmonized Test Guidelines Series 870. If carcinogenicity studies are required for registration review, the available NCI cancer study will be evaluated to determine whethe r it is an acceptable guideline study that can be used for risk assessment.

HED’s label and use evaluation al so indicates the potential fo r repeated exposures to both occupational handlers and worker s who re-enter treated sites. Consequently, the following guideline toxicity studies are required for Registration Review of starlicide; Acute Inhalation Toxicity (870.1300), Subchronic Dermal Toxicity (870.3250), Prenatal Developmental Toxicity (870.3700), Reproduction And Fertility Effect s (870.3800), Neurotoxicity Battery (870.6200), and Immunotoxicity (870.7800). A neurotoxicity battery and an immu notoxicity study are required for food and non-food use pesticides in accordance with the re vised 40 CFR Part 158 Toxicology Data Requirements.

Conclusions

The HED Registration Review team has re-eva luated the toxicity analysis conducted for the starlicide occupational and residential e xposure assessment conducted in 1995. Based on thisPage 5 of 11 evaluation, all of the toxicologica l data requirements for non-food use pesticides are applicable and the required studies need to be submitted by the registrant for Registration Review. In addition, dermal and inhalation PODs for use in a quantitative occupational exposure assessment

need to be identified based on the required toxicity data.

Dietary and Drinking Water Exposure

The risk assessment conducted for the RED in 1995 designated registered uses of

starlicide as nonfood with the stipulation that uses allowing application to ar eas where food or feed crops are grown be removed from existing labels and that la bels be revised to include a 365 day prohibition on grazing animals and growing cr ops on lands treated with starlicide baits. Under these conditions, a dietary exposure asse ssment was not required for the RED. A quantitative drinking water assessment was also not required for the RED based on limited use patterns and restrictions against placement of treated baits within 50 feet of water bodies.

Data Requirements

Since the Agency considered the uses of starlicide to be non-food in 1995, residue chemistry data were not required. However, HED has determined that existing broadcast use of

starlicide in livestock and poultry feed lots is considered a food use under current criteria for

determination what constitutes a food use. Theref ore, EPA is working with starlicide registrants to revise the labels to include language that is sufficiently restrictiv e to preclude dietary exposure. Therefore, data applicable to food use pesticides are not re quired for Registration

Review.

Conclusions

While a dietary exposure assessment was not required for the 1995 assessment based on a non-food use determination, current product labe ls and several Special Local Needs (SLN) registrations issued since completion of the 1995 assessment provide for br oadcast application of treated bait (e.g., grain, corn, br eadcrumbs) to feed lots for livestock and poultry. These

broadcast feedlot uses have been evaluated a nd are considered to be food uses under current

criteria. In order for starlicide to be designated a non-food use pest icide, the feed lot use must be modified to practically and adequa tely ensure that livestock will not be exposed to treated bait. As previously noted, EPA is working with the re gistrants to revise the labels as needed to preclude a food use determination.

Residential Exposure

Starlicide is a restricted use pesticide limite d to use by certified professional applicators. It cannot be purchased or appl ied by homeowners. Therefore, a residential handler exposure assessment was not required for the 1995 assessment. While the RED assessment indicated that there was potential exposure to residents ente ring treated sites after application, the Agency concluded that post-treatment residential exposur es would be minimal based on use restrictions, and a residential post-app lication exposure assessment was not required.Page 6 of 11 Conclusions

Based on a review of currently registered labe ls and use patterns, HE D believes that there may be potential for post-application exposure to residents entering treate d areas. HED’s review

indicates that label restrictions are clearly intended to prevent such exposure. However, current label restrictions are inadequa te to limit exposure sufficiently to preclude the need for a residential post-application exposure assessment. Therefore, the starli cide registrants are working with EPA to revise existing labels w ith language that is suffi ciently restrictive to preclude exposure to children.

Aggregate Exposure

The aggregate risk assessment integrates the assessments conducted for dietary/drinking water and residential exposure. An aggregat e assessment was not conducted for the 1995 RED

since starlicide uses were determined to be non-food and residential exposures were qualitatively determined to be minimal and not of concern.

Conclusions

Given the registrants’ ongoing work to revise labels to adequately limit exposure to livestock and children, and aggregate assessment is not required for Re gistration Review.

Occupational Exposure

The Agency determined in 1995 that a quant itative assessment of occupational handler and post-application exposure was not required based label restrictions that limit use to certified applicators or persons under thei r direct supervision, use patterns that result in limited exposure, and requirements for use of pers onal protective equipment. The Agency expressed concerns for inhalation exposure to occupational handlers wh o mix and load large volumes of starlicide

concentrate. To address thos e concerns, EPA imposed label re strictions requiring respiratory protection for workers handling one pound or more of starlicide concentrate. The Agency concluded in 1995 that handling small volumes of starlicide would result in minimal exposure and that when large volumes are needed, the resp irator requirements woul d sufficiently minimize the risk of inhalation exposure to workers. Ba sed on these considerations , a risk assessment was not required for occupational exposures.

Conclusions

A quantitative occupational exposure assessmen t is required for Registration Review of

starlicide. A review of activel y registered products and SLN la bels indicates that there is potential for repeat exposure to occupational handlers and to work ers who reenter treated sites. Labels provide for repeated manual and mechanic al broadcast applicati on of treated bait (e.g., grain, corn, bread crumbs) to large areas. U nder current SOPs, a quant itative assessment of dermal and inhalation exposure and risk to occupational handlers is required based on application methods that are antici pated to result in occupational exposures. A qualitative review of potential post-applica tion exposure scenarios is also re quired. Based on that review, aPage 7 of 11 quantitative assessment of post-application expos ure to workers may also be required. The occupational assessment needs to incorporate PODs selected based toxicity data required for Registration Review.

Incident Report

An updated incident report was conducted for starlicide for Registration Review. From 2006 to 2011, there were no incident cases reported fo r starlicide in either the main or aggregate Incident Data Systems. Based on the lack of repo rted incident cases, ther e does not appear to be

a concern at this time that would warrant furthe r investigation. The Agency will continue to

monitor the incident information and if a con cern is triggered, additional analysis will be

included in the risk assessment.

Endocrine Disruption

As required by FIFRA and FFDCA, EPA review s numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute,

subchronic and chronic toxici ty, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or syst emic toxicity. These studies include endpoints which may be susceptible to endocrine influenc e, including effects on endocrine target organ histopathology, organ weights, es trus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard asse ssments, EPA evaluates

acute tests and chronic studies that assess growth, developmen tal and reproductive effects in different taxonomic groups. As part of its reregistration decision

, EPA reviewed these data and selected the most sensitive endpoi nts for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), starlicide is subject to the endocrine screening part of the Endocrine Disruptor Screenin g Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredie nts) may have an effect in hu mans or wildlife similar to an effect produced by a “naturally occurring estr ogen, or other such endocrine effects as the Administrator may designate.” The EDSP em ploys 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 w ith 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 th e next stage of the EDSP where EPA will determine which, if any, of the Ti er 2 tests are necessary based on the available data. Tier 2 testing is designe d to identify any adverse endocr ine-related effects caused by the substance, and establish a dose-re sponse relationship between the dos e and the E, A, or T effect.

Under FFDCA section 408(p), the Agency mu st 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. Starlicide is not among the group of 58 pesticide active ingredient s on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issu e future EDSP orders/data callins, requiring the submission of EDSP screening assays for starlicide. For further information onPage 8 of 11 the status of the EDSP, the policie s and procedures, the lis t of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

.

Cumulative

EPA does not have, at this time, available data to determine whether starlicide has a common mechanism of toxicity w ith other substances. EPA has not made a common mechanism of toxicity finding for starlicide and any other substances and, starlicide does not appear to produce a toxic metabolite produced by other substances which have tolerances in the U. S. Therefore, EPA has not assumed that starlicide has a common mechanism of toxicity with other

substances.

Human Studies

The risk assessment for starlicid e did not rely on data from studies in which adult human subjects were intentionally exposed to a pest icide or other chemical. However, future occupational and/or residential assessments conducte d for registration review of starlicide will use data contained in HED’s ge neric pesticide exposure database s such as Pesticide Handlers Exposure Database (PHED), the Agricultural Re entry Task Force (ARTF) Database and the Outdoor Residential Exposure Task Force (OR ETF) Database). Recommended unit exposures for occupational handler assessments have genera lly been derived only from PHED. However, recently both the ORETF and AHETF have produced pesticide handler e xposure monitoring data that the Agency is using in place of PHED ( http://www.epa.gov/pesticides/science/handlerexposure-data.html ). As more reliable data become available, the Agency will continue to replace existing data and new exposure monitori ng data will be incorporated into HED’s Registration Review assessments as necessary.

EPA has reviewed all the studies suppor ting the multi-pesticide generic exposure databases used to derive recommended unit expo sures for occupational and residential exposure assessments and has found no clear and convincing ev idence that the conduct of any of them was either fundamentally unethical or significantly deficient relati ve 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 c ontinued reliance on these studies.

Environmental Justice

Potential areas of environmental justice concer ns, to the extent possi ble, were considered in this human health risk assessment, in acco rdance with U.S. Executive Order 12898, "Federal

Actions to Address Environmental Justice in Minority Populations and Low-Income Populations," http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf ).

As a part of every pesticide risk assessment , OPP considers a large variety of consumer subgroups according to well-esta blished procedures. In line with OPP policy, HED estimates risks to population subgroups fr om pesticide exposures that ar e based on patterns of that subgroup’s food and water consumption, and activ ities in and around the home that involvePage 9 of 11 pesticide use in a residential setting. Whenever appropriate , non-dietary exposures based on home use of pesticide products and associated ri sks for adult applicators and for toddlers, youths, and adults entering or playing on treated ar eas postapplication are evaluated. Further considerations are currently in development, as OPP has committed resources and expertise to the development of specialized software and mode ls that consider expo sure to bystanders and farm workers as well as lifestyle and traditiona l dietary patterns among specific subgroups.

Conclusions/Future Actions Needed

The actions needed in the future Registrati on Review for starlicide are listed below.

Hazard Identification an d Endpoint Selection The following toxicity studies required for non-food us e pesticides are not available for starlicide and need to be submitted for Registration Review : acute inhalation, subchronic dermal, prenatal developmental, reproduction, ne urotoxicity, and immunotoxicit y. Based on current OPP standards, PODs for dermal and inhalation expo sure endpoints, selected based on the required toxicity data, are needed fo r adequate assessment of occupational exposure and risk.

Dietary and Drinking Wa ter Exposure and Risk USDA has agreed to revise the labels as needed to preclude a food use determination. Therefore, dietary and drinking water exposure as sessments will not be required for Registration

Review.

Residential Exposure and Risk USDA has agreed to revise existi ng labels to more practically and adequately restrict residential post-application exposure. Therefore, a quant itative residential exposu re assessment is not required for Registration Review.

Aggregate Exposure and Risk Given USDA’s agreement to revise existing la bels to preclude expos ure to livestock and children, an aggregate assessment is not required for Registration Review.

Occupational Exposure and Risk A quantitative assessment of dermal and inhalati on exposure and risk to occupational handlers is required as starlicide application me thods are likely to result in e xposures to applicators. A more detailed review of potential post-ap plication exposure scenarios associ ated with registered uses is needed. Based on that review, a quantitative assessment of worker re-entering treated sites may also be required. The occupational assessment needs to incorporate PODs selected based on toxicity data required for Registration Review.

Incident Report Based on the incident report conducted for Registra tion Review, there does not appear to be a concern at this time. The Agency will continue to monitor the incident information and if a concern is triggered, additional analysis wi ll be included in the risk assessment.

Data RequirementsPage 10 of 11 Toxicological Data - Acute Inhalation Toxicity (GLN 870.1300), - Subchronic Dermal Toxicity (GLN 870.3250) - Prenatal Developmenta l Toxicity (GLN 870.3700) - Reproduction and Fertility Effects (GLN 870.3800) - Neurotoxicity Battery (GLN 870.6200) - Immunotoxicity study (GLN (870.7800)Page 11 of 11 References

The HED Chapter of the Reregistration Eligibility Decision Document for Starlicide, T. Myers, (7/13/95, TXR 0011608)

Occupational and Residential Exposure Assessmen t and Recommendations for the Reregistration Eligibility Document for Starli cide, J. Leahy (5/3/95, D208849)

Starlicide: Toxicology Chapter for the Reregistra tion Eligibility Document, I. Mauer, (4/17/95, D208850)

Starlicide: Review of Human Inci dents. S. Recore, (5/17/11, D389683)