Docket Number EPA-HQ-OPP-2008-0847 

www.regulations.gov 

Nithiazine 

Interim Registration Review Decision 

Case Number 7415 

March 2016 

Approved 

Yu-Ting Guilara:PE. 

by: ~ Director 

Pesticide Re-evaluation Division 

Date: -3/to/!b 

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Table of Contents 

I. INTRODUCTlON .......................................................................................................................................... l 

II. USE AND USAGE ........................................................................................................................................ 2 

A. Nithiazine General Background ..... ....... ... .. .. ... .......... ... ... .. ....... ........... ............................................... 2 

Ill. SCIENTIFIC ASSESSMENTS .................................................................................................................. 3 

A. HUMAN HEALTH ASSESSMENT ..... .... .. .. .. .. .... ........ ...................... .............. .................................... 3 

1. Hazard Identification ............................................... ........ ...... ....... ........... .... .......... .. .. ........... ........... ...... 3 

2. Dietary Exposure ............................................................ .......................................... ..................... .......... 3 

3. Residential and Occupational Exposure ........... ............. ...................................... .. .................. .. ....... ...... 3 

4. Aggregate Risk .......................................... ... ... ....... .. ............ ........ ................... .. ......... .. ... .... ........... ......... 3 

5. Cumulative Risk .......................... ...................................................... ................................ .. .................... 3 

B. ENVIRONMENTAL ASSESSMENT ......... .. .. ................................. ... ................................................. 3 

1. Environmental Fate and Exposure ................................................................. ........................................ 4 

2. Ecological Risks Characteristics .................. .... .......................... ....... .. .................................................... 4 

C. INCIDENT REPORTS ................................. .. .. .. .. .. .. ......................... .................................................... 4 

1. Human Incidents .......... .... .. .... ........ .. ........................... .. .......................... .................................... ......... 4 

2. Ecological Incidents ................... .. ... ................... ...................... .. ...................... .... .. ......... .. ............ ...... 4 

D. ENDOCRINE DISRUPTOR SCREENING PROGRAM .................................................................. 4 

IV. INTERIM REGISTRATION REVIEW DECISION ............................................................................. 5 

V. NEXT STEPS ........................................................................................................................................... 6 

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Nithiazine References 

I. Registration Review Proposed Decisions: Busan 74 (HPMTS) and Nithiazine. Joan 

Harrigan-Farrelly. December 15, 2010. 

2. Registration Review: Pesticide Dockets Opened for Review and Comment. Richard P. 

Keigwin, Jr., March 11, 2009 

3. Nithiazine Summary Document Registration Review: Initial Docket March 2009. 

Richard P. Keigwin, Jr., February 27, 2009 

4. Appendix A: Food/Feed & Non-Food/Non-Feed Uses Considered in Registration 

Review Work Planning. March 18, 2009 

5. Reader's Guide to Nithiazine. Jill Bloom. March 25, 2009 

6. Nithiazine : Revised Registration Review Scoping Document for Human Health 

Assessments. Shalu Shelat, Shanna Recore, Dr. Steve Dapson and Felecia Fort, 

November 25, 2008 

7. Registration Review-Problem Formulation for Nithiazine. Tanja Crk, Jim Goodyear, 

Keara Moore, Mark Corbin, and Dana Spatz. January 28, 2009. 

8. Nithiazine Final Work Plan Registration Review August 2009. Richard P. Keigwin, Jr. 

August 20, 2009. 

9. New Chemical Registration: The Unconditional Registration of the New Chemical A0-

1 59 for Use in Agricultural Buildings for Housefly Control. Stephen L. Johnson. 

February 15, 1995. 

10. EEB Review (DP I 58953). P. Hutton. August 20, 1991. 

ll. Updated Review ofThiazine (441300) Incident Reports. Monica Hawkins, Jessie 

Cordova, and Mary Manibusan. February 26, 2009. 

12. Nithiazine Summary Document Registration Review: Initial Docket March 2009. 

Richard P. Keigwin, Jr. February 27, 2009 

13. Nithiazine: Environmental Fate, Ecological Risk and Endangered Species Assessment 

in Support of the Registration Review ofNithiazine (PC 441300). James K. Wolf, 

Tanja Crk, and Dana Spatz. February 23, 2010. 

14. Nithiazine Proposed Registration Review Final Decision Case 7415. Richard P. 

Keigwin, Jr. December 3, 2010. 

15. Pesticide Fact Sheet, Name of Chemical: A0-159. RobertS. Brennis. December 1994. 

16. Review Studies ofTechnical IN AOI 59-26 DP. Douglas J. Urban. March 18, 2009. 

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I. Introduction 

This document is the Environmental Protection Agency's (EPA or the Agency) Interim 

Registration Review Decision for nithiazine and is being issued pursuant to 40 CFR §§ 

155.56 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). The Agency may issue, when it determines it to be 

appropriate, an Interim Registration Review Decision before completing a registration review. 

Among other things, the Interim Registration Review Decision may: 1) require new risk 

mitigation measures; 2) impose interim risk mitigation measures; 3) identify additional data or 

other information required to complete the review; and 4) include schedules for submitting the 

required data, conducting the new risk assessment and completing the registration review. For 

further information on nithiazine, additional documents can be found in EPA's public docket 

(EPA-HQ-OPP-2008-0847) at www.regulations.gov. 

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 

generally must be registered by the 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 and reduce risk evolves and as policies and practices change, all registered pesticides 

continue to meet the statutory standard of no unreasonable adverse effects. Changes in 

science, public policy, and pesticide use practices will occur over time. Through the 

registration review program, the Agency periodically re-evaluates pesticides to make sure that 

as these changes occur, products in the marketplace can continue to be used safely. 

Information on this program is provided at http://www2.epa.gov/pesticidereevaluation/registration-review-process. 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. 

EPA is issuing an interim registration review for nithiazine so that it can move forward with 

aspects of the registration review that are complete. The Environmental Protection Agency 

had previously issued a Proposed Decision for nithiazine. However, because EPA has not 

made a determination under the Endocrine Disruption Screening Program (EDSP) Federal 

Food Drug and Cosmetic Act (FFDCA) section 408(p), the Agency is issuing an Interim 

Decision at this time. The Agency will complete endocrine screening for nithiazine, pursuant 

to the Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(p), before completing this 

registration review. 

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). 

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This document is organized in five sections: the Introduction, a summary of public comments 

and EPA's response; Use and Usage, which describes how and why nithiazine is used and 

summarizes data on its use; Scientific Assessments, which summarizes EPA's risk 

assessment, any revisions, and risk conclusions; Interim Registration Review Decision, which 

describes the regulatory rationale for EPA's registration review decision; and, last, the Next 

Steps and Time line for completion of this registration review. 

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 ofthe 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. 

• December 22, 20 I 0 - Publication of the Nithiazine Proposed Registration Review 

Final Decision for a 60-day public comment period. No comments were received 

during the public comment period. The proposed decision determined that no 

addition data or labeling changes were required to support the continued registration 

of nithiazine products. Due to the nature of the bait station, nithiazine is not likely to 

result in a risk to human health. Also, nithiazine was not expected to have direct or 

indirect adverse effects to non-listed and listed species. 

Additional information on nithiazine can be found in EPA's public docket (EPA-HQ- OPP2008-0847) at www.regulations.gov. 

II. Use and Usage 

A. Nithiazine General Background 

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. 

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III. Scientific Assessments 

A. Human Health Assessment 

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 

Nithiazine currently has no established tolerances on food or animal commodities. The low 

vapor pressure ( 4.6x 1 o-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 and Occupational Exposure 

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

where the pesticide is contained within a plastic shell. This construction reduces the potential 

for skin contact with the active ingredient. Therefore, residential and occupational handler and 

post- application exposures are expected to be negligible. A residential and occupational risk 

assessment was not required. 

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. 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. 

B. Environmental Assessment 

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 ofNithiazine," 

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 

3 
I o-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 imidacloprid. 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. 

C. Incident Reports 

I. 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. A query of Aggregate IDS from OI /Ol/20IO to today (1211611 5) found 

5 minor severity incidents. 

2. Ecological Incidents 

No Ecological incidents have been reported in Ecological Incident Information System (EllS) 

or Incident Data System (IDS). Since the active ingredient is contained in a bait station no 

incidents are expected. 

D. Endocrine Disruptor Screening Program 

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

adverse outcomes from exposure to chemicals. Collectively, these studies assess potential 

adverse outcomes from exposure to chemicals. These studies include acute, sub-chronic and 

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

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

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

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA 

evaluates acute tests and chronic studies that assess growth, developmental and reproductive 

effects in different taxonomic groups. As part of its most recent registration decision for 

nithiazine, EPA reviewed these data and selected the most sensitive endpoints for relevant 

risk assessment scenarios from the existing hazard database. However, as required by 

FFDCA section 408(p ), nithiazine is subject to the endocrine screening part of the Endocrine 

Disruptor Screening Program (EDSP). 

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

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a "naturally occurring estrogen, or other such endocrine effects as the 

Administrator may designate." The EDSP employs a two-tiered approach to making the 

statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to 

identify the potential of a chemical substance to interact with the estrogen, androgen, or 

thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are 

found to have the potential to interact with E, A, or T hormonal systems will proceed to the 

next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are 

necessary based on the available data. Tier 2 testing is designed to identify any adverse 

endocrine-related effects caused by the substance, and establish a dose-response relationship 

between the dose and the E, A, or T effect. 

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

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

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

second list of chemicals identified for EDSP screening was published on June 14, 2013 and 

includes some pesticides scheduled for Registration Review and chemicals found in water. 

Neither of these lists should be construed as a list of known or likely endocrine disruptors. 

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

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

website. Nithiazine is not included on List 1 or List 2 of the EDSP screening program. 

Nithiazine will be reviewed by the EDSP screening program later in the process. 

In this interim decision, EPA is making no human health or environmental safety findings 

associated with the EDSP screening of nithiazine. Before completing this Registration 

Review, the Agency will make an EDSP FFDCA section 408(p) determination. 

IV. Interim Registration Review Decision 

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Interim 

Registration Review Decision. Except for the EDSP component of this case, the Agency has 

made the following Interim Registration Review Decision: ( 1) no additional data are required at 

this time; (2) changes to the affected registrations and their labeling are not needed at this time. 

No changes were made to the Agency's decision for nithiazine since the publication of the 

Nithiazine Proposed Registration Review Decision. 

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In this interim registration review decision, EPA is making no human health or environmental 

safety finding associated with the EDSP screening ofnithiazine. The Agency's final 

registration review decision for nithiazine will depend upon an EDSP FFDCA section 408(p) 

determination. 

V. Next Steps 

A Federal Register Notice will announce the availability of this Interim Registration Review 

Decision. The Interim Decision will be published in the nithiazine registration review docket 

(EPA-HQ-OPP-2008-0847). As indicated above, this Interim Registration Review Decision 

for nithiazine concludes that no additional data are required at this time. A final decision on 

the nithiazine registration review case will occur after a determination under EDSP FFDCA 

section 408(p) has been made. 

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