Table of Content

I. INTRODUCTION............................................................................................................... .............................4

A. N ITHIAZINE G ENERAL B ACKGROUND ....................................................................................................5

II. SCIENTIFIC ASSESSMENTS .................................................................................................... .................5

A. H UMAN H EALTH

............................................................................................................................... .......5 1. Hazard Identification ..............................................................................................................................5 2. Dietary Exposure and Risk .....................................................................................................................5 3. Residential Exposure and Risk ...............................................................................................................5 4. Aggregate Risk

............................................................................................................................... .........6 5. Occupational Risk

............................................................................................................................... ....6

6. Cumulative Risk

............................................................................................................................... .......6 7. Endocrine Disruptor Screening Program ..............................................................................................6

B. E COLOGICAL R ISK

............................................................................................................................... ...7 1. Environmental Fate and Exposure ........................................................................................................7 2. Ecological Risks Characterizations ........................................................................................................7 3. State Water Quality Concerns [Clean Water Act] ..................................................................................7

C. I NCIDENTS R EPORTS

............................................................................................................................... 8

1. Human Incidents

............................................................................................................................... ......8 2. Ecological Incidents

............................................................................................................................... .8

III. PROPOSED RI SK MITIGATION ................................................................................................. ............8

IV. PUBLIC COMMENTS........................................................................................................... ......................8

V. TRADE IRRITANTS ............................................................................................................ .........................8

VI. ENVIRONMEN TAL JUST ICE ..................................................................................................................8

VII. PROPOSED REGISTRATION REVIEW FINAL DECISION..............................................................9

VIII. NEXT STEPS .............................................................................................................. ...............................9

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### Nithiazine Registration Review Team

Office of Pesticide Programs:

Biological and Economic Analysis Division

Rafael Prieto

Don Atwood

Dave Donaldson

Environmental Fate and Effects Division

James K. Wolf Tanja Crk Dana Spatz

Health Effects Division

Shalu Shelat

Shanna Recore Steve Dapson

Registration Division

Richard Gebken

Mark Suarez

Pesticide Re-evaluation Division

Yan Donovan

Office of General Counsel

Philip Ross, Esq.

3I. Introduction

This document is the Environmental Pr otection Agency’s (EPA or the Agency) Proposed Registration Review Final Decision for Nithiazine and is being issued pursuant to 40 CFR §§ 155.57 and 155.58. A registration review decision is the Agency's determination whether a pesticide meets, or does not meet, the standard for registration in the Federal Insecticide, Fungicide, and R odenticide Act (FIFRA). FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, manda ted the continuous review of existing pesticides. All pesticides distri buted or sold in the United States must generally be registered by EPA, 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 cha nge, all registered pesticides contin ue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide us e practices will occur over time. Through the registration review program, the Agency periodically reevalua tes pesticides to make sure that as change occurs, products in the marketplace can be us ed safely. Information on this program is provided at: http://www.epa.gov/oppsrr d1/registration_review/

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In 2006, the Agency implemented the Registration Review program pursuant to FIFRA section 3(g) and will review each regist ered pesticide every 15 years to determine

whether it continues to meet the FI FRA standard for registration.

Pursuant to 40 CFR § 155.50, the Agency fo rmally initiated regi stration review for nithiazine (Case 7415). The following timeline highlights significant events that have occurred during the registrati on review of nithiazine:

 March 18, 2009 – Publication of the Nithiazine Summary Document in the docket (EPA-HQ-OPP-2008-0847) for a 60-day pub lic comment period. The Summary Document also included the preliminary wo rk plan (PWP). During that time, EPA received no comments during the public comment period for the nithiazine Preliminary Work Plan.

 August 11, 2009 – Publication of the Nithia zine Final Work Plan (FWP), which

stated that the Agency will conduct a qualitative ecological risk assessment for listed species, which will include a finding on the eff ect of nithiazine use on federally listed threatened or endangered species and their de signated critical habitats. The FWP also stated that Agency does not anticipate requiring any additional studies through the data call-in process for nithiazine.

Additional information on nithiazine can be found in EPA’s public docket (EPA-HQOPP-2008-0847) at www.regulations.gov

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4A. Nithiaz ine General Background

Nithiazine, or 2H-1,3-Thiazine, tetrahydro-2-(nitromethylene), (c ase # 7415) is an insecticide belonging to the neonicotinoid cl ass of pesticides, which has been synthesized based on the structure of the naturally occurring pesticide ni cotine (present in toba cco). Nithiazine was first registered by EPA in 1995. It is register ed for use for house fly control in animal housing facilities (especially poultry facilities; also feed lots , dairy barns, loafing sheds, and stables), and in industrial and other locations (such as garb age chutes, dumpsters, loading docks, grease pits, rest areas, and outdoor restrooms).

Nithiazine is formulated into a bait station in which ot her components serve to attract flies. This use limits opportunities for exposure of non- target organisms in several ways. The user is instructed through the product label to depl oy the bait station off the ground in an area out of the sun and where it is protected from rai n. The construction of the bait station acts to preclude direct exposure to larger flying species such as birds.

II. Scientific Assessments

A. Human Health

1. Hazard Identification The toxicity database for the active ingredient , nithiazine, is considered sufficient for the purpose of human health risk assessment. The acute toxicity categories for oral, dermal, eye irritation, and dermal irritation ar e II, III, I, and IV, respectivel y. Data waivers were granted for the acute inhalation toxicity and dermal sensitization stud ies based on limited exposure due to the bait station design of the end-use product.

2. Dietary Exposure and Risk Nithiazine currently has no established tolera nces on food or animal commodities. The low vapor pressure (4.6x10 -7 ) of nithiazine indicates that re sidues from vaporization of the bait station depositing on food are not likely; therefore, a diet ary risk assessment was not required.

Nithiazine is not administered into the envi ronment and thus nithiazine residues are not expected to reach surface wate r or ground water. Therefore, a drinking water assessment was not required.

3. Residential Exposure and Risk The end-use product contains 1% n ithiazine and is formulated as a ready-to-use bait station where the pesticide is contained within a pl astic shell. Therefore, handler and postapplication exposures are expected to be neg ligible. A residential risk assessment was not required.

54. Aggregate Risk Since there are no dietary exposure (food or water) or residential exposure from the registered use of nithiazine, an a ggregate assessment was not required.

5. Occupational Risk The active ingredient is contained within a r eady-to-use welded plastic shell with small feeding holes. This construction reduces the potential for skin contact with the active ingredient. Therefore, any a pplicator and post-application e xposures are expected to be negligible. An occupational ri sk assessment was not required.

6. Cumulative Risk EPA has not made a common mode of toxicity finding as to nithiazine and any other substances, and nithiazine does not appear to produce a toxic metabolite produced by other substances. Therefore, a cumulative risk as sessment was not applicable at this time.

7. Endocrine Disruptor Screening Program As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (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 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 cons ists of a battery of 11 screening assays to identify the potential of a chemical substan ce to interact with th e estrogen, 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 in teract with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determ ine 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 substanc e, and establish a qua ntitative relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticid e active ingredients and 9 inert ingredients.

This list of chemicals was selected based on the potential for human exposure through pathways such as food and water, reside ntial activity, and cert ain post-application agricultural scenarios. Th is list should not be construed as a list of known or likely endocrine disruptors.

Nithiazine is not among the group of 58 pesticid e active ingredients on th e initial list to be

screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. Accordingly, EPA anticipates issuing EDSP orders/data call-ins for all Registration Review cases, including those for which EPA has already opened a Registration Review docket for a pes ticide active ingredient.

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

6B. Ecological Risk

As stated in the Final Work Plan, the Agency conducted a qualitative eco logical risk

assessment on nithiazine. Below are the summar y findings from the latest ecological risk assessment. Please see the Agency memo “Nithiazine: Environmental Fate, Ecological Risk and Endangered Species Assessment in Support of the Registration Review of Nithiazine,” dated 02/23/2010, for more details.

1. Environmental Fate and Exposure The major route of nithiazine dissipation appear s to be photolysis. The vapor pressure (4.6 x

10 -7 mm Hg) indicates that volati lization will not be an important route of dissipation. Based on the registered use of nithiazine as a bait station that is requir ed by label instructions to be deployed out of sunlight and moisture to be effective, the likeli hood of exposure to nontarget wildlife is minimal. Similarly, the li kelihood of exposure to aquatic and terrestrial plants is minimal. Therefore, ecological exposure and effects are not expected from this use.

2. Ecological Risks Characterizations If used as directed on the pr oduct label, the likelihood of expos ure to non-target wildlife is minimal. Similarly, the likelihood of exposure to aquatic and terrestrial plants is minimal. Overall, nithiazine is not expected to have direct advers e effects to non-listed and listed terrestrial mammals, birds, or reptiles and land-phase amphibians, terrestrial beneficial and listed insects or terrestrial plants . Nithiazine is not expected to cause direct adverse effects to non-listed and listed fish, aquatic in vertebrates or aquatic plants. Since direct effects are not expected for any taxa, indirect effects are al so not expected. No a dverse modification of critical habitat is expected from use of nithiazine.

Nithiazine belongs to a class of pesticid es called neonicotinoids, which have been synthesized based on the structur e of the naturally occurring pe sticide nicotine (present in tobacco). Neonicotinoids are divided into the nitro-substituted and cyano-substituted subclasses, and the nitro-substi tuted compounds are further divi ded into nitromethylenes and nitroguanidines. Imidacloprid, a nitroguanidine neonicotinoid, is acutely toxic to honeybees, and it has been suggested as a factor in the de cline of honey bee populations. Nithiazine is a nitromethylene neonicotinoid. While there are no guideline studies on the toxicity of nithiazine to pollinators, a search of the li terature yielded a report documenting the relative toxicity of neonicotinoids to honeybees. The lite rature findings indicate that Nithiazine is less toxic to honey bees than imidicloprid. In addition, nithiazine is formulated into a solid sugar matrix, that does not repr esent a desirable feeding medium for honey bees and the bait pheromone attractant that is applied to the matrix is highly specific to fl ies. Hence, exposure to honey bees should be minimal.

3. State Water Quality Concerns [Clean Water Act]

Nithiazine has not been identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information from http://oaspub.epa.gov/tmdl/waters_list.im pairments?p_impid=3 . The Agency invites submission of water quality data for this pesticid e, including that which could lead to a listing

7of an im paired water body under the Clean Water Act. 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 Assessmen t and Management Process (see: http://www.epa.gov/pesticides/ ppdc/2006/november06/session1-sop.pdf ), in order to ensure they can be used quantitatively or qualitativel y in pesticide risk assessments. Absent the submission of any such data, the Agency does no t anticipate that nithiazine use will impact water quality or result in water body impairment.

C. Incidents Reports

1. Human Incidents A search of the OPP Incident Data System (IDS) from 2002 to the present identified only one incident for nithiazine. The symptoms app eared generic and were not confirmed to be related to nithiazine exposure.

2. Ecological Incidents No Ecological incident is exp ected based on the use where the active ingredient is contained

in a bait station.

III. Proposed Risk Mitigation

Since there are no risks of concern to either humans or the environment, no additional risk mitigation is needed for the use of nithiazine.

IV. Public Comments

This proposed registration review final decisi on along with the Agency’s new ecological risk assessment are available for a 60-day public comme nt period from the date these document are posted. The public is invi ted to comment on EPA’s proposed registration review final decision and rationales. The Agency will carefu lly consider all comments, and any additional information that is provided in a timely ma nner, prior to issuing a final decision for the nithiazine registration review case.

V. Trade Irritants

No tolerances have been estab lished for nithiazine residues si nce it is a non food/feed use.

There are no Codex MRLs for nithia zine and its transformation products.

VI. Environmental Justice

EPA seeks to achieve environmental justice—th e fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income—in the development, implementation, and enforcement of environmenta l laws, regulations, and policies. To help address potential environmental justice issues, the Agency sought information, as explained in the Summary Document, on groups or segments of the population who, as a result of their

89 location, cultural practices, or other factors, may have atypical, unus ually high exposure to the registered pesticide products containing n ithiazine compared to the general population. The Agency did not receive any comments to that effect. At this time, EPA does not believe that use of the registered pesticide products co ntaining nithiazine will cause harm to or a disproportionate impact on at-risk communities.

For additional information regarding environmen tal justice issues, please visit EPA’s website

at: http://www.epa.gov/compliance/e nvironm entaljustice/index.html

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VII. Proposed Registrati on Review Final Decision

The Agency has determined that no additional data are required at this time to support the continuing registrations of nith iazine products. The Agency has considered nithiazine in light of the standard for regist ration and safety factors in the FIFRA and FFDCA, as amended by FQPA. EPA has found that th ere are not likely to be any unreasonable adverse effects to the U.S. population in general, and to infants and children in particul ar, or to non-target organisms or the environment from the use of registered pesticide n ithiazine products when currently required label instructions are follo wed. In addition, EPA has concluded that nithiazine is not expected to have direct or indirect advers e effects to non-listed and listed species. No adverse modification of critical habitat is expected fr om use of nithiazine.

Therefore, in accordance with 40 CFR Section 155.57 and 40 CFR Section 155.58, the Agency’s proposed registration review final d ecision is that the sta ndards for Registration

Review have been met and that the re gistration of nithiazine products may be maintained.

VIII. Next Steps

Pursuant to 40 CFR § 155.58, the Agency is issu ing this proposed registration review final decision and placing it in the nithiazine re gistration review dock et (EPA-HQ-OPP-2008- 0847). A Federal Register Notice will announce its availability and allow a 60-day public comment period. If there are no significant comments or additional information submitted to the docket during that comment pe riod that lead the Agency to change its proposed decision,

EPA will issue a final decision for nithiazine. The Agency anticipates the final decision will be issued in early 2011.