Table of Content 

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

A. NITHIAZINE GENERAL BACKGROUND....................................................................................................5

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

A. HUMAN HEALTH......................................................................................................................................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. ECOLOGICAL RISK..................................................................................................................................7

1. Environmental Fate and Exposure ........................................................................................................7

2. Ecological Risks Characterizations........................................................................................................7

3. State Water Quality Concerns [Clean Water Act]..................................................................................7

C. INCIDENTS REPORTS ...............................................................................................................................8

1. Human Incidents.....................................................................................................................................8

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

III. PROPOSED RISK MITIGATION .............................................................................................................8

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

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

VI. ENVIRONMENTAL JUSTICE ..................................................................................................................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. 

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I. Introduction

 This document is the Environmental Protection 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 Rodenticide Act (FIFRA). FIFRA, as amended by the Food 

Quality Protection Act (FQPA) of 1996, mandated the continuous review of existing 

pesticides. All pesticides distributed 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 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/. 

 In 2006, the Agency implemented the Registration Review program pursuant to 

FIFRA section 3(g) and will review each registered pesticide every 15 years to determine 

whether it continues to meet the FIFRA standard for registration. 

 Pursuant to 40 CFR § 155.50, the Agency formally initiated registration review for 

nithiazine (Case 7415). The following timeline highlights significant events that have 

occurred during the registration review of nithiazine: 

 March 18, 2009 – Publication of the Nithiazine Summary Document in the docket 

(EPA-HQ-OPP-2008-0847) for a 60-day public comment period. The Summary 

Document also included the preliminary work 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 Nithiazine 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 effect of nithiazine use on federally listed 

threatened or endangered species and their designated 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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A. Nithiazine General Background 

Nithiazine, or 2H-1,3-Thiazine, tetrahydro-2-(nitromethylene), (case # 7415) is an insecticide 

belonging to the neonicotinoid class of pesticides, which has been synthesized based on the 

structure of the naturally occurring pesticide nicotine (present in tobacco). Nithiazine was 

first registered by EPA in 1995. It is registered 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 garbage chutes, dumpsters, loading 

docks, grease pits, rest areas, and outdoor restrooms). 

Nithiazine is formulated into a bait station in which other 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 deploy the bait station off the ground in an area out 

of the sun and where it is protected from rain. 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 are II, III, I, and IV, respectively. Data waivers were granted 

for the acute inhalation toxicity and dermal sensitization studies 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 tolerances on food or animal commodities. The low 

vapor pressure (4.6x10-7) of nithiazine indicates that residues from vaporization of the bait 

station depositing on food are not likely; therefore, a dietary risk assessment was not 

required. 

Nithiazine is not administered into the environment and thus nithiazine residues are not 

expected to reach surface water or ground water. Therefore, a drinking water assessment was 

not required. 

 3. Residential Exposure and Risk 

The end-use product contains 1% nithiazine and is formulated as a ready-to-use bait station 

where the pesticide is contained within a plastic shell. Therefore, handler and postapplication exposures are expected to be negligible. A residential risk assessment was not 

required. 

 

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4. Aggregate Risk 

Since there are no dietary exposure (food or water) or residential exposure from the 

registered use of nithiazine, an aggregate assessment was not required. 

 

 5. Occupational Risk 

The active ingredient is contained within a ready-to-use welded plastic shell with small 

feeding holes. This construction reduces the potential for skin contact with the active 

ingredient. Therefore, any applicator and post-application exposures are expected to be 

negligible. An occupational risk 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 assessment was not applicable at this time. 

 7. Endocrine Disruptor Screening Program 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (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 quantitative 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 pesticide 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, residential activity, and certain post-application 

agricultural scenarios. This list should not be construed as a list of known or likely endocrine 

disruptors. 

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

screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide 

chemicals. Accordingly, EPA anticipates 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 pesticide active ingredient. 

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

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

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

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B. Ecological Risk 

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

assessment on nithiazine. Below are the summary 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 appears to be photolysis. The vapor pressure (4.6 x 

10-7 mm Hg) indicates that volatilization will not be an important route of dissipation. Based 

on the registered use of nithiazine as a bait station that is required by label instructions to be 

deployed out of sunlight and moisture to be effective, the likelihood of exposure to nontarget wildlife is minimal. Similarly, the likelihood 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 product label, the likelihood of exposure 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 adverse 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 invertebrates or aquatic plants. Since direct effects are not 

expected for any taxa, indirect effects are also not expected. No adverse modification of 

critical habitat is expected from use of nithiazine. 

Nithiazine belongs to a class of pesticides called neonicotinoids, which have been 

synthesized based on the structure of the naturally occurring pesticide nicotine (present in 

tobacco). Neonicotinoids are divided into the nitro-substituted and cyano-substituted 

subclasses, and the nitro-substituted compounds are further divided into nitromethylenes and 

nitroguanidines. Imidacloprid, a nitroguanidine neonicotinoid, is acutely toxic to honeybees, 

and it has been suggested as a factor in the decline 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 literature yielded a report documenting the relative 

toxicity of neonicotinoids to honeybees. The literature 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 represent a desirable feeding medium for honey bees and the bait 

pheromone attractant that is applied to the matrix is highly specific to flies. 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.impairments?p_impid=3. The Agency invites 

submission of water quality data for this pesticide, including that which could lead to a listing 

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of an impaired 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 Assessment 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 qualitatively in pesticide risk assessments. Absent the 

submission of any such data, the Agency does not 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 appeared generic and were not confirmed to be 

related to nithiazine exposure. 

 2. Ecological Incidents 

No Ecological incident is expected 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 decision along with the Agency’s new ecological risk 

assessment are available for a 60-day public comment period from the date these document 

are posted. The public is invited to comment on EPA’s proposed registration review final 

decision and rationales. The Agency will carefully consider all comments, and any additional 

information that is provided in a timely manner, prior to issuing a final decision for the 

nithiazine registration review case. 

V. Trade Irritants 

No tolerances have been established for nithiazine residues since it is a non food/feed use. 

There are no Codex MRLs for nithiazine and its transformation products.

VI. 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 sought information, as explained 

in the Summary Document, on groups or segments of the population who, as a result of their 

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location, cultural practices, or other factors, may have atypical, unusually high exposure to 

the registered pesticide products containing nithiazine 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 containing nithiazine will cause harm to or a 

disproportionate impact on at-risk communities.

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

at: http://www.epa.gov/compliance/environmentaljustice/index.html. 

VII. Proposed Registration Review Final Decision

The Agency has determined that no additional data are required at this time to support the 

continuing registrations of nithiazine products. The Agency has considered nithiazine in 

light of the standard for registration and safety factors in the FIFRA and FFDCA, as amended 

by FQPA. EPA has found that there are not likely to be any unreasonable adverse effects to 

the U.S. population in general, and to infants and children in particular, or to non-target 

organisms or the environment from the use of registered pesticide nithiazine products when 

currently required label instructions are followed. In addition, EPA has concluded that 

nithiazine is not expected to have direct or indirect adverse effects to non-listed and listed 

species. No adverse modification of critical habitat is expected from 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 decision is that the standards for Registration 

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

VIII. Next Steps 

Pursuant to 40 CFR § 155.58, the Agency is issuing this proposed registration review final 

decision and placing it in the nithiazine registration review docket (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 period 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.