### DocketNumber EPA-HQ-OPP- 2008-0847 www. regulation s .gov



# Nithiazine Interim Registration Review Decision Case Number 7415

March 2016



## Approved by:

# ~ Yu-Ting Guilara:PE. Director Pesticide Re-evaluation Division Date: 

# -3/to/!b

0

### 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

1

### 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 B loom. 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 Formulationfor 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- 159 for Use in Agricultural Buildings for Housefly Control
. Stephen L. Johnson. February 15, 1995. 10. 

### EEB Review (DP I58953). 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 7 415. Richard P
. Keigwin , Jr. December 3, 2010
. 15. 

### Pesticide Fact Sheet , Name of Chemical: A0-159. RobertS. Brennis. December 1994. 16. 

### Review Studies ofTechnical INAOI59-26 DP. Douglas J. Urban
. March 18 , 2009
.

0I. 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 ofno 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/regi stration-review-proces s . 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 ofthe 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 ofpesticides, which has been synthesized based on the structure ofthe naturally occurring pesticide nicotine (present in tobacco). Nithiazine was first regi stered 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). 1This document is organized in five sections: the Introduction, a summary ofpublic 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 Timeline for completion ofthi s 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 ofthe 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 ofnithiazine 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 I0

- Publication ofthe 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 ofnithiazine 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 ofnon-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.

2III. Scientific Assessments A. Human Health Assessment 1. Hazard Identification The toxicity database for the active ingredient, nithiazine, is considered sufficient for the purpose ofhuman 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 establi shed tolerances on food or animal commodities. The low vapor pressure (4.6x 1 

# o- 7 ) of nithiazine indicates that residues from vaporization ofthe 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 oftoxicity 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 eco logical risk assessment on nithiazine
. Below are the summary findings from the latest eco logical 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 ofnithiazine dissipation appears to be photolysis. The vapor pressure (4.6 x 3I

## o- 7 mm Hg) indicates that volatilization will not be an important route ofdissipation. Based on the registered use ofnithiazine as a bait station that is required by label instructions to be deployed out of sunlight and moisture to be effective , the likelihood ofexposure 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 ofexposure to non-target wildlife is minimal. Similarly, the likelihood of expo sure 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 fi sh, 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 ofnithiazine. Nithiazine belongs to a class ofpesticides called neonicotinoids, which have been synthesi zed 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 ofthe literature yielded a report documenting the relative toxi city 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 4chronic toxicity, including assessments ofcarcinogenicity, 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 ofchemicals 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 ofthe 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 Regi stration 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. 5In 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 avai lability ofthis 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
.

6