# Environmental Fate, Ecological Risk and Endangered Species Assessment in Support of the Registration Review of Nithiazine (PC 441300)

Chemical Name(s): Nithiazine (2H-1,3- thiazine, tetrahydro-2-(nitromethylene))

Chemical Abstracts Serv ice (CAS) Number: 58842-20-9
Chemical Family: Nitromethylene hete rocycle; Neonicotinoid insecticide
Pesticidal Mode of Action (M oA): Acts selectively on an insect’s cholinergic central nervous system as an agonist of the post-synaptic nicoti nic acetylcholine receptors ( n AChRs), its molecular target site . In order to be effective, it must be ingested.
Empirical Formula: C 5 

### H 8 

### N 2 

### O 2 

### S (molecular mass 160.19 g/mol)
End-use Product: Sandoz 9023 Fly Ba it Station (EPA Reg. # 2724-461)
Target Pest(s): House fly ( Musca domestica ), Lesser house fly ( Fannia canicularis )

Prepared by: 

### James K. Wolf, Environmental Scientist Tanja Crk, Biologist

Reviewed by: 

### Mark Corbin, Senior Fate Scientist Stephanie Syslo, RAPL

Through: Dana Spatz, Branch Chief U. S. Environmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division

Environmental Risk Branch III 1200 Pennsylvania Ave., NW

Mail Code 7507P Washington, DC 20460



### February 23, 2010

## 1.0 Executive Summary

1.1 Nature of Stressor

Nithiazine is an insecticide us ed to target and kill house flie s and the lesser house flies. In the single registered end-use product, nithiazi ne is formulated into a sugar matrix which is applied as solid coating to a sheet, or strip, of moistu re-free non-absorptive material. The strip containing the nithiazi ne is then set into a protec tive pouch. A container of a fly attractant with a pungent odor is crushed at the time of application. Th e label states that the bait strip should be placed low to th e ground, and out of reach of children and animals. The bait is less effective at heights greater than 4 ft above ground, in moist areas or in direct sunlight. Nithi azine is in a class of chem icals called the neonicotinoids. Nithiazine, like other neonicotinoids, acts sele ctively on the insect’s cholinergic central nervous system as an agonist of the post- synaptic nicotinic acetylcholine receptors ( n AChRs), its molecular target site.

The label notes that effectiveness is likely to diminish within 8 weeks (56 days). Nithiazine is subject to rapid photodegra dation (photolysis half-life of 0.6 hours). Nithiazine is stable to hydrolysis at environmentally relevant pHs ( i.e., pH 7), with a halflife of greater than 90 days. However, hydrol ysis rates increase w ith both decreasing and increasing pH conditions. Volatilization is also not a significant route of dissipation with a vapor pressure value of 4.6 x 10 -7 

### mm Hg. The acute toxicity data indicate that technical grade nithiazine is practically non-toxic to birds, mammals, and fish, and slightly toxic to aquatic invertebrates. No environmental fate or ecological effects information is available on degrad ation products or formulations.

One of the ingredients of the fly attractan t is (Z)-9-tricosene (also known as cis-9- tricosene, muscalure, and muscamone), a re gistered active ingredient (PC 103201). (Z)-9-

Tricosene is classified as a biochemical pesticide because, even though chemically synthesized, it is identical to the se x pheromone of the female house fly Musca

domestica . It is used as an insect attractant with a "non-toxic" mode of action. (Z)-9-

tricosene is included in this assessment becau se of its specific attraction to flies.

The risk conclusions for (Z)-9-tricosene ar e presented in the Registration Eligibility Decision (RED) (USEPA, 1994a, 1994b). In the RED, the Agency had concerns about potential risks to avian species because the (Z )-9-tricosene was formulated as a granular. However, in this case, because the attractant (Z)-9-tricosene is formulated as a liquid instead of a granular, the expected exposure to birds should be minimal.

In addition, the submitted ecologi cal effects studies indicated that (Z)-9-tricosene is highly toxic to aquatic inve rtebrates but practically non-toxic to freshwater fish. However, risk to aquatic organisms was e xpected to be minimal from the uses of products specified in the RED because of lo w exposure potential. The Agency believes

2

### that the exposure of non-target animals to (Z)-9-tricosene, wh en used as fly attractant for

the nithiazin e bait strip, will be also be mini mal and potential risk to listed and non-listed non-target species is expected to be low.

1.2 Potential Risk

Chemical Properties Likely as a result of its rapid degradation when exposed to sunli ght, the label language recommends that the bait be protected from mo isture and direct sunl ight. Because the bait is to be placed above the ground and protec ted from moisture, the likelihood of exposure to non-target animals is reduced as is the poten tial to be transporte d to a non-target site.

Ecological Risk Conclusions The bait is most likely to impact target insect s (flies) at the point of treatment. Given its environmental fate properties and the method of application, it is less likely that nontarget insects will be impacted at the point of treatment.

Other than flies, one could assume that honey bees might be exposed to nithiazine. However, there are no toxicological effects da ta for beneficial insects (i.e., pollinators such as honey bees) to estimate risk. Gene rally in the absence of data, the Agency assumes risk. However, a study by Iwasa et al., (2004) suggests that the occurrence of differential toxicity of honey bees to neonico tinoid insecticides is based upon chemical structure. Nithiazine is a nitromethylen e, a less toxic structural class of the nitroguanidine class of neonicotinoids. In addition, the solid sugar matrix does not represent a desirable feeding medium for honey bees and the bait pheromone attractant is highly specific to flies (USEPA, 1994a). Hence, exposure to honey bees should be

minimal.

If the baits are located close to the ground, small mammals (and birds) could be exposed

to the nithiazine. The label doe s not specify a minimum height , only that the bait not be placed higher than 4 feet. However, if used as directed on th e product label, the likelihood of exposure to non-ta rget wildlife is minimal. Similarly, the likelihood of exposure to aquatic and terrest rial plants is minimal.

In conclusion, beyond the point of treatment, direct or indirect exposure to ecological receptors is not expected. If used as di rected on the product label, the likelihood of exposure to non-target wildlife and flora is minimal. Therefore, ecological exposure and effects are not expected from this use.

1.3 Endangered Species Assessment

Environmental exposure to nithia zine is expected to be neglig ible to non-target terrestrial and aquatic organisms. This is based on the regi stered use of nithiazi ne as a bait station that is required to be out of sunlight and moisture to be effective. Therefore, the use directions, product placement, and product construction will minimize or prevent movement and exposure to non-target organisms or their food sources. The point of use is

3

### the only place where direct exposure coul d occur. Therefore, the anticipated

environm ental concentrations for nithiazine ar e expected to be below levels which could be of toxicological significance to non-targ et terrestrial and a quatic organisms.

In addition, the submitted toxicity data indicate that nithiazine is practically non-toxic to slightly toxic to freshwater aquatic orga nisms and terrestrial birds and mammals. The reported toxicity values for a quatic invertebrates also suggest low toxicity from exposure to nithiazine. Overall, nithiazine is not expe cted to have direct adverse effects to nonlisted and listed terrestrial mammals, birds, or reptiles and land-phase amphibians,

terrestrial beneficial and listed insects or terre strial plants. Nithiazine is not expected to

cause direct adverse effects to non-listed and listed fish, aqua tic invertebrates or aquatic plants. Since direct effects are not expected for any taxa, indirect effects are also not expected. No adverse modification of criti cal habitat is expected fr om use of nithiazine.

The following table lists the potential direct and indirect effects to listed species from use

of nithiazine.

4

### 5 Table 1. Potential Risks to Non-target Non-liste d and Listed Species Associated with Direct or Indirect Effects from the Propos ed Application of Nithiazine.

Direct Effects 2 Indirect Effects to Listed Species

Taxonomic Group Effects Endpoint 1

Non-listed Listed Potential Indirect Effects Due

to Direct Effect to: 3

Aquatic vascular plants Measures of biomass-NA No No No Not applicable

Dicot terrestrial plants Measures of biomass-NA No No No Not applicable

Monocot terrestrial plants Measures of biomass-NA No No No Not applicable

Freshwater

Vertebrates Acute: mortality LC 50 Chronic: growth & reproduction– NA No No No Not applicable

Estuarine/Marine

Vertebrates Acute: mortality- NA Chronic: growth & reproduction-NA No No No Not applicable

Freshwater

invertebrates Acute: mortality EC 50 Chronic: growth & reproduction-NA No No No Not applicable

Estuarine/Marine

Invertebrates Acute: mortality –NA Chronic: growth & reproduction –NA No No No Not applicable

Mammals Acute oral dose: mortality

LD 50 Chronic: growth and reproduction-NA No No No Not applicable

Birds Acute oral dose: mortality

LD 50 Sub-Acute dietary: mortality and growth

LC 50 Chronic: growth and reproduction- NA No No No Not applicable

Terrestrial

invertebrates Acute contact and oral: mortality-NA No No No Not applicable

1 Abbreviations: NA = toxic ity data not available

2 Negligible exposures to non-target organisms due to nithiazine use as a bait (no spray drif t, runoff, or spillage). Only possible exposure at point of use. Th erefore adverse effects not expected.

3 Due to bait use specifications, a nd method of application of nithiazine, exposure is not expected.



### Therefore, a No-Effect determination was concluded regarding th e potential for the registered use of nithiazine to affect federally listed species.

## 2.0 Problem Formulation

The problem formulation for this risk assessment and effects determination was provided in the following document: USEPA Registra tion Review Problem Formulation for Nithiazine, dated January 28, 2009. Based on the label use of nithiazine, this assessment focuses on the most relevant chemical prope rties, exposure routes, and endpoints as well as the assumptions and risk hypothesis in the Problem Formulation document.

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), all pesticides

distributed or sold in the Un ited States generally must be registered by the United States Environmental Protection Agency (U.S. EPA). To determine whether a pesticide can be registered, the U.S. EPA evaluates its safety to non-target species based on a wide range

of environmental and health effects studi es. In 1996, FIFRA was amended by the Food Quality Protection Act (FQPA), and EPA was mandated to implement a new program for the periodic review of pesticides, i.e ., registration review 1 

### . The registration review program is intended to ensure that, as the abili ty to assess risk evolves and as policies and practices change, all registered pesticides co ntinue to meet the st atutory standard of no

unreasonable adverse effects to human health and the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the new registration review program, the Agency periodically reevaluate s pesticides to make sure that as change occurs, products in the market place can be used safely. Nithiazine, which was first registered by the EPA in 1995, is undergoing just such a reevaluation.

2.1 Stressor Description

Nithiazine ( Figure 1 ) is an insecticide used to target and kill house flies ( Musca domestica) and the lesser house fly ( Fannia canicularis ). The Sandoz 9023 Fly Bait Station (EPA Reg. # 2724-461) co ntains the active ingredient in a sugar-based matrix (solid) on a (non-absorptive) strip set in a protective plastic pouc h (bait station) ( Figure

2 ). The label indicates that the bait strip contai ns 1% nithiazine (active ingredient (a.i.)) (114-120 mg nithiazine per strip 2 

### ) and 99% other ingredients. The active ingredient is contained in a sugar-based matrix which is attractive to flies and potentially non-target insects. An ampoule containing a fly attractan t with a pungent odor is crushed at the time of application. The insect attr actant, which includes (Z)-9-t ricosene, is contained in a glass ampoule that is attached to each bait st rip. (Z)-9-tricosene is a pheromone that is released into the air by cr ushing the ampoule onto an absorbent pad, which slowly

releases the attractan t into the air.

The label states that the ba it station should be placed low to the ground, and out of reach

of children and animals. The bait station is less effective at heights gr eater than 4 ft above ground, in rafters, if mobile (i.e., blows in th e wind or is placed on moving objects), in

moist areas or in direct s unlight. Nithiazine is subj ect to rapid photodegradation

1 http://www.epa.gov/oppsrrd1/registration_review/

2 From: S.R. Spaulding, Senior Director, Regulatory Affairs, Central Life Sciences, Wellmark
International. To: Jill Bloom, PRD, USEPA. Date: 11/18/09.



### 6

### (photolysis half-life of 0.6 hours). D ue to a low vapor pressure, vol atilization is not a significant route of dissipation for nithiazine. Excessive moisture will reduce the residual life of the fly bait station. The product labe l states that the fly bait station should be protected from moisture and di rect sunlight, when possible.

Figure 1. Chemical structure of nithiazine.

Figure 2. Picture of Quikstrike Baitstrip.

Also known as cis-9-tricosene, muscalure, or muscamone, (Z)-9-Tricosene (CAS # 27519-02-4) is classified as a biochemical pesticide because, even though chemically synthesized, it is identical to the sex pheromone of the female house fly. As an insect

attractant it has a "non-toxic" mode of action. A Reregistration Eligibility Decision (RED) was completed by the Agency on the active ingredient (Z)-9 -tricosene in 1994 (USEPA, 1994a). The risk assessment conduc ted for the RED was based upon a granular

7

### for mulation of (Z)-9-tricosene, rather than a li quid formulation as is used with nithiazine in the fly bait station.

2.2 Environmental Fate Summary

The major route of nithiazine dissipation ap pears to be photolysis. The photolysis halflife is 0.6 hours. Hydrolysis appears to play a less significant role at expected pH conditions (around pH 7) where the hydrolysis half-life is > 90 days. Metabolism should be minimal due to anticipated use pattern (isolated from micr obes found in soil and water). The vapor pressure (4.6 x 10 -7 

### mm Hg) indicates that vol atilization will not be an important route of dissipation. The directions on the label suggest that the bait strip limits the potential for offsite transpor t to terrestrial areas and wa ter bodies. Transport from the use site by runoff and drift will be negligible due to use practices (covered and off the ground) and formulation (solid). There is no in formation as to what degradation products are formed and the relevant environmental fate properties.

Based upon the labeled use, no additional enviro nmental fate studies per 40 CFR Part 158 were required by the Agency (USEPA, 1994c). Data were extracted from submitted

studies and the Pesticide Fact Sheet (USEPA, 1994c); see Table 2 which is a summary of

the available environmental fate properties of nithiazine.

.
Table 2. Environmental Fate Properties of Nithiazine

Property Value (units) MRID or Data Source

Vapor pressure 4.6 x 10 -7 mm Hg at 25 o C 41397701

Solubility in water 40% at 23 o C 40661301

K

ow 0.4 00065944

pK

a 10.4 41650002

Hydrolysis half-life (T 1/2 ) pH 1: 0.125 days

pH 7: >90.0 days

pH 9: 13.0 days 00065944

Photolysis half-life (T 1/2 ) 0.6 hours Pesticid e Fact Sheet (1994)

.



### 2.3 Mode of Action

Nithiazine, like other neonicotinoids, acts sele ctively on an insect’s cholinergic central nervous system as an agonist of the post- synaptic nicotinic acetylcholine receptors ( n AChRs), its molecular target site. In order to be effective, nithiazine must be ingested.

8

### 2.4 Use Characterization

Nithiazine is an insecticide used to target and kill house flies and the lesser house fly.

The nithiazine is lo cated in a bait strip whic h contains 1% nithiazine (a.i.) and 99% other ingredients. The mass of nithiazine in a bait strip is not specified on the label, but the registrant has indicated that each strip contains 114-120 mg nithiazine 3 

### , or 2.65 x 10 -4 

### lbs a.i. per strip. The use rate is 1 station per 300 ft 2 

### (8.82 x 10 -7 

### lb a.i./ft 2 

### ) for enclosed areas where fly populations are low and 1 station per 100-150 ft 2 

### (2.65 x 10 -6 

### lb a.i./ft 2 

### ) in open areas where fly populations are hi gh. The bait is less e ffective at heights greater than 4 ft above ground, in rafters, if mobile (i.e ., blows in the wind or is placed on moving objects), in moist areas or in direct sun light. Based upon information submitted by the registrant approximately 100 lbs a.i. are sold per year 4



### .

Suggested use sites include: garbage chutes , dumpsters, loading docks, waste containers, grease pits, rest areas, outdoor restroom fac ilities, in and around stables, dairy barns, milking parlors, loafing sheds, kennels, poultr y houses, aviaries, sw ine houses, feedlots, refuse and recycling facilities, around comme rcial food-handling faci lities, restaurants, bars, groceries, stores, and other facilities where hous e flies are a nuisance.

Current nithiazine registrations are summarized in Table 3

.

Table 3. Current Nithiazine Registrations

Product Name

(Registrant) EPA Registration

Number (latest label date) Active Ingredients (% w/w) USE

Section 3 End Use Products

Sandoz 9023 Fly Bait

Station 2724-461 (09/06/05) 1.0 The Sandoz 9023 fly

bait station can be used in a variety of areas.

Technical 2724-472

Technical A0159

Insecticide 2724-472 97.0 An insecticide for formulating use only



### 2.5 Assessment Endpoints

This assessment considers the potential for adverse effects as a result of nithiazine use per label specifications. As described in the Ag ency’s Overview Document (U.S. USEPA, 2004), the most sensitive endpoint for each ta xon is evaluated. Assessment endpoints are selected based on ecosystems typically at risk from pesticide use and include direct toxic effects on the survival, reproduction, and gr owth of terrestrial and aquatic life.

3 From: S.R. Spaulding, Senior Director, Regulatory Affairs, Central Life Sciences, Wellmark
International. To: Jill Bloom, PRD, USEPA. Date 11/18/09.

4 Based upon information submitted by the Registrant (dated 10-07-08) provided by Jill Bloom, PRD,

USEPA on 09-25-09.



### 9

### Toxicity d ata for nithiazine are available fr om three bird studies, two freshwater fish studies, and one freshwat er invertebrate study. Table 4 summarizes the available registrant-submitted, ecological toxicity studie s for nithiazine including endpoint toxicity

values.

Table 4. Summary of Assessment Endpoints and Measures of Ecological Effect

Assessment Endpoint Measures of Ecological Effect 1

Aquatic Environments

Survival and reproduction of individuals and

communities of freshwater fish 96-hr Fish acute toxicity 2 LC 50 :
Rainbow Trout ( Oncorhynchus mykiss )

Bluegill Sunfish ( Lepomis macrochirus )

Survival and reproduction of individuals and

communities of freshwater invertebrates 48-hr Aquatic Invertebrate toxicity 2 EC 50 :
Water Flea ( Daphnia magna )

Terrestrial Environments

Avian acute oral toxicity 2 LD 50 : Northern Bobwhite Quail ( Colinus virginianus) Abundance (i.e. survival, reproduction, and growth) of individuals and populations of birds and mammals) Avian dietary toxicity 2 LC 50 :
Northern Bobwhite Quail ( Colinus virginianus)

Mallard Duck ( Anas platyrhynchos)

Acute oral toxicity 2 LD 50 :

Rat

Acute Dermal toxicity 2 LD 50 :

Rabbit

1 All studies used technical grade IN A0159-26 (pur ity >99%) except when otherwise stated (see table footnote #2)

2 Acute study also exists for (Z)-9-tricosene (See ( Z)-9-tricosene RED (USEPA 1994a)).



### Non-target Insects Effects

Nithiazine belongs to a class of pesticid es called neonicotinoids, which have been synthesized based on the structure of the natu rally occurring pesticide nicotine (Jeschke and Nauen, 2008). Neonicotinoids are divide d into the nitro-substituted and cyanosubstituted subclasses. Accordi ng to Iwasa, et al., (2004), thes e substitutions are essential for insecticidal activity. The nitro-substituted compounds ( Figure 3 ) are further divided into nitromethylenes and nitroguanidines ( Table 5 ). Nithiazine is a nitromethylene neonicotinoid. Generally, the nitroguanidine ne onicotinoids are the more toxic subclass. While there are no guideline studies on the toxici ty of nithiazine to pollinators, a search of the literature yielded a re port documenting the relative toxi city of neonicotinoids to honeybees. In a laboratory bioassay reported by Iwasa et al. (2004), imidacloprid and the other nitroguanidine neonicotinoids were more acutely toxic to honeybees than the only tested nitromethylene pesticide (nitenpyram) and the several tested cyano-substituted neonicotinoids (Table 5).

10

### Nitro-substituted Cyano-substituted

Nitromethylenes (nithiazine) Nitroguanidines (e.g., imidacloprid)

Neonicotinoids

Figure 3. S tructural Relationshi p between Neonicotinoid Classes.

Iwasa et al. (2004) suggest that typically the narrow spectru m insecticides like imidacloprid are more toxic than the broad sp ectrum chemicals like thiacloprid (Table 5).

Nithiazine was not commercia lized for broad agricultural use (Jeschke and Nauen, 2008) because of its rapid degradation due to photolysis. Jeschke and Nauen (2008) present information showing that nithiazine is 125 and 25 times less toxic (based upon LC 90 

### ’s) than imidacloprid and thiamethoxam, respectively. The honey bee ( Apis mellifera) LD 50 

### for nitenpyram, which is in the same functional group as nithi azine (Table 5) is 7 times

less toxic to bees than imid acloprid (Iwasa et al., 2004).

Table 5. Functional groups, chemical product, relative b ee toxicity, and spectrum of nithiazine and several other neonicotinoids based on open literature studies. Functional Group 2 Chemical Name Relative Bees Toxicity Spectrum Bee LD 50 1

Nitro-substitution Nitromethylenes/nitroeamines Nithiazine NC 2 NC 2 ND 4
Nitenpyram NC 2 Fleas 3 0.138

Toxic to bees 1,5
N-Nitro-guanidines/N-Nitro-imines Imidacloprid Toxic Narrow 1 0.0179

Thiamethoxam Toxic NC 0.0299

Clothianidin Toxic NC 0.0218

Less toxic to bees 1

Cyano-substitution N-Cyano-amidines/N-Cyno-imines Thiacloprid Safe Broad 1 14.6 Acetamiprid Safe Broad 1 7.07

1 Iwasa et al., 2004

2 NC - not classified (Jeschke and Nauen, 2008)

3 Flea control orally taken by dogs and cats

4 ND no data

5 Jeschke and Nauen, 2008



### 11

### 2.5.1 Ecosystems Potentia lly at Risk

Given the label prescribed use of nithiazine, ecosystems are not expect ed to be at risk. The bait is most likely to impact target insects (flies) at the point of treatment. It is less likely that non-target insect s will be impacted at the poi nt of treatment. Beyond this, direct or indirect exposure to ecological recepto rs is not expected. If used as directed on the product label, the likelihood of exposure to non-target wildlif e and plants is minimal.

2.5.2 Ecological Effects

Ecological effects evaluations traditionally focus on direct effects to the groups of organisms residing in the ecosystems at risk a nd are based on ratios (risk quotients) of the estimated environmental concentration (EEC) to a designated toxicity endpoint for a surrogate test organism. Given the use of this product, direct or i ndirect exposure to nontarget ecological receptors, except potentially at the point of treatment, is not expected. Therefore, no risk quotient s are calculated for birds, fish, mammals, or plants.

There is no toxicity data for beneficial inse cts (e.g., pollinators) so risk quotients could not be determined. However, information is av ailable to compare the relative toxicities of

nithiazine to other neonic otinoids (see section 2.5 Non-target Insects Effects)

.

2.5.2.1 Direct

Direct effects of an organism from exposure to a pesticide are assessed based on impacts to the survival, growth, and re production of various taxa. The ba it is most likely to impact target insects (flies) at the point of treatment . It is less likely that non-target insects will be impacted at the point of treatment. Be yond this, direct or indirect exposure to ecological receptors is not expected. If used as directed on the pr oduct label, then the likelihood of exposure to non-targ et wildlife and plants is mi nimal. Therefore, ecological exposure and direct effects are not expected from this use

2.5.2.2 Indirect

Transport to terrestria l areas and water bodies from the use site by runoff and drift should be negligible and indirect e ffects should be non-existent give n label-dictated use practices (covered and off the ground), the formulati on (solid on a paper strip), and rapid degradation due to photolysis.

2.6 Risk Hypothesis

The amount of active ingredient sold in nithi azine bait stations each year is small (< 100

lbs a.i. 5 

### ) relative to amounts of insecticides marketed in non-bait station formulations.

5 Based upon information submitted by the Registra nt (dated 10-07-08) provided by Jill Bloom, RPD,

USEPA on 09-25-09.



### 12

### Nithiazine is used in a fly bait whereby the ac tive ingredient is mi xed with a sugar-based matrix and placed (as a solid) on a nonabsorbe nt strip. The product is used in selfcontained units applied in discrete locations with a spatial extent limited to building size areas with negligible potentia l for offsite transport. The a pplication method does not lead

to drift to terrestria l areas or to water bodi es. The units are not intended for moist areas and do not contain amounts of active ingredient sufficient for runoff to be a concern.

The bait is most likely to impact target insects (flies) at the point of treatment. It is less likely that non-target insect s will be impacted at the poi nt of treatment. Beyond this, direct or indirect exposure to ecological recepto rs is not expected. If used as directed on the product label, then the lik elihood of exposure to non-targ et wildlife and flora is minimal. Therefore, ecological exposure and effects are not expected from this use.

2.7 Results of Previous Assessments

The documents available in the Office of Pesticide Programs Regulatory Docket and which serve as the basis for this assessment include the following:

 January 1995 New Chemical Registrati on Decision Memorandum (From: S.L. Johnson; Director Registration Division; To: D. M. Barolo ; Director Office Pesticide Programs. February 15. 1995)

 December 1994 Pesticide Fact Sheet: (USEPA, 1994c)

 January 2009 Ecological Problem Formul ation for Nithiazine (USEPA, 2009 )

The new chemical registration determined th at the likelihood of exposure to non-target wildlife was minimal (Johnston, 1995). No new studies have been submitted since the initial registration decision. Ther efore, results of the latest assessment do not differ from conclusions outlined here. The only exception is a fuller explanation of the active ingredient (Z)-9-tricosene (PC Code: 103201), a volatile, chemically synthesized pheromone present in glass ampoules in the ou ter shell of the bait station. Low doses of the pheromone have had reproductive effects on waterfowl and have been shown to be highly toxic to freshwater invertebrates. For additiona l information concerning the toxicity and ecotoxicity s ee the (Z)-9-tricosene RED (USEPA, 1994a). However, when product containing the pheromone is used corr ectly, and given the use pattern of the fly bait station, the risk to the envir onment is expected to be low.

13

### 2.8 Analysis P lan

This assessment was conducted in accordance with the m ethods and procedures described in the Overview Document (USEPA, 2004).

2.8.1. Measures of Exposure

Measures of exposure are norm ally based on aq uatic and terrestrial models that estimate

environmental concentrations of the chemi cal being assessed usi ng labeled application

rates and methods.

The measure of exposure concentrations for aquatic species in water bodies receiving runoff and/or spray drift are typically estimat ed with the Tier I GENEEC model and the

Tier II PRZM/EXAMS model. The measure of exposure for aquatic species in water bodies receiving base flow from ground wate r leachate originating at the site of application are usually estimated with SCI-GROW.

The measures of terrestrial e xposure for vertebrate and inve rtebrate animals are typically estimated with the T-REX model. Exposure for terrestrial plants is normally estimated

with the TerrPlant model.

However, due to use of the bait strip, it is un likely that the nithiazine will reach aquatic or

terrestrial environments. Ther efore, aquatic and terrestrial exposure concentrations were

not estimated.

2.8.2. Measures of Effect

Measure s of effect are obtained from a suite of registrant-submitted guideline studies that

are conducted with a limited number of surrogate test species.

The acute measures of effect used in th is baseline-level assessment are the LD 50 

### (median Lethal Dose), LC 50 

### (median Lethal Concentration) or EC 50 

### (median Effects Concentration). The endpoints for chronic measures of exposure are the NOAEC and the NOAEL. Acute toxicity studies were submitted for birds (3 studies), freshwater fish (2 studies), freshwater invert ebrates (1 study), and mammals (2 studies). The endpoints

used for risk characterization were derived fr om studies that underwent review and were classified as “acceptable” (conducted under guide line conditions and considered to be scientifically valid) or “supplemental” (c onditions deviated from guidelines but the results are considered to be scientifically valid).

14

### 2.8.3. Integration of Exposure and Effects

The exposure and toxicity effects data are inte grated in order to ev aluate the risks of adverse ecological effects on non-target spec ies. Generally, the risk quotient (RQ)

m ethod is used to compare estimated exposur e and measured toxici ty values. The RQ method involves dividing EECs by acute and ch ronic toxicity values. The resulting RQs are then compared to the Agency’s Le vels of Concern (LOC) (USEPA, 2004) ( Appendix

A ). These criteria are generally used to indi cate when applications of pesticides, as directed on the label, have the potential to cause adverse effects to listed and non-listed non-target organisms.

This method was not applied for nithiazine due to low toxicity valu es on an acute basis and, based upon the labeled use and applica tion method, low potential for transport via runoff and drift to a non-target site. In addi tion, the rapid dissipation due to photolysis contributes to the assumption th at chronic risk to terrestria l and aquatic organisms would

be minimal.



## 3.0 Exposure Assessment

EFED concludes that based upon the labeled use of nithiazine, exposure is expected to be minimal. The product is used in self-contained units applied in discrete locations with a spatial extent limited to building-size areas with negligible potential for offsite transport. The application method does not allow for drift or runoff to terrestrial areas or to water bodies. The bait strips are not intended for moist areas and do not contain amounts of active ingredient sufficient for runoff to be a concern. The bait is most likely to impact target insects (flies) at the point of treatment . It is less likely that non-target insects will be impacted at the point of treatment. Be yond this, direct or indirect exposure to ecological receptors is not expected. If used as directed on the pr oduct label, then the likelihood of exposure to non-targ et wildlife and flora is mini mal. Therefore, ecological exposure and effects are not expected from this use.

3.1 Label Application Rates

The mass of nithiazine in a bait strip is not specified on the label, but the registrant has indicated that each strip c ontains 114-120 mg nithiazine 6 

### , or 2.65 x 10 -4 

### lbs a.i. per strip.

The label use rate is 1 station /300 ft 2 

### for enclosed areas where fly populations are low

and 1 station /100-150 ft 2 

### in open areas where fly populations are high. The number of strips allowed per year, how often a strip ma y be used, and the minimum number of days between strips is not stated on the label. The label indicates that a strip is effective for about 56 days (8 weeks).

3.2 Aquatic Exposure

6 From: S.R. Spaulding, Senior Director, Regula tory Affairs, Central Life Sciences, Wellmark International. To: Jill Bloom, PRD, USEPA. Date: 11/18/09.



### 15

### Given the use of the bait stri p and application m ethod, exposure to aquatic animals and plants is not expected.

3.3 Terrestrial Exposure

Given the current labeled use and the fate ch aracteristics of nithi azine, the likelihood of nithiazine residues being transp orted offsite to adjacent water bodies or soil (terrestrial environment) is minimal. Any residues tran sported away from th e use site would be expected to degrade in the environment primar ily by photolysis. Theref ore, direct contact of terrestrial mammals, birds, and invertebrates to the nithiazine in the bait is the most likely means of exposure. Animals and insect s may potentially be attracted to the bait because the active ingredient ha s been formulated into a sugar matrix and affixed to a strip. However, the label in structs users to keep the bait off the ground which will minimize exposure to small animals. Meanwhile , non-target insects ma y not be attracted to (Z)-9-tricosene as it is a pheromone speci fic for flies. Also, non- target insects may not be able to uptake the solid matrix. Sim ilarly, given the labeled use and application method, terrestrial plant e xposure is not expected.

3.4 Soil Accumulation

Soil accumulation is not expected given the use and rapid photolysis of nithiazine.



## 4.0 Effects Assessment

This assessment evaluates the potential for advers e affects as a result of nithiazine use. Assessment endpoints include direct toxic effects on the survival, reproduction, and growth of terrestrial and aqua tic life. Toxicity endpoints are established based on data generated from guideline studies submitted by the registrant, and from open literature

studies that meet the criteria for inclusi on into the ECOTOX database maintained by EPA/ORD. As described in the Agency’s Overview Document (U.S. USEPA, 2004) and according to EFED policy, the most sensitive endpoint for each taxon is evaluated. In aquatic systems, taxa evaluated include aquati c plants, invertebrates, and fish. Fish serve as a surrogate for aquatic-phase amphibian s when amphibian data are unavailable or unacceptable for quantitative use. Where data ar e available, respective endpoints are used for freshwater and estuarine/marine organism s. In terrestrial systems, taxa evaluated include birds and mammals; data for terrestria l plants were not avai lable. Bird endpoints are generally derived from guideline studies on bobwhite quail and/or mallard duck. Bird data are used as a surrogate for reptiles a nd terrestrial-phase amphibians when data for these taxa are unavailable or unacceptable fo r quantitative use. Mamm al data are derived from guideline studies conducted on laboratory rats, mice, or rabbits.

For this assessment, evaluated taxa include bi rds (3 studies), freshwater fish (2 studies),

freshwater invertebrate s (1 study), and mammals (2 studies). Table 6 summarizes the available registrant-submitted, ecological t oxicity studies for nithiazine including

16

### endpoint toxicity values. All ecotoxicity da ta for (Z)-9-tricosene are available in the RED (USEPA, 1994a).

Table 6. Ecological Eff ects Data Summary for Nith iazine and (Z)-9-Tricosene 1

Assessment Endpoint Measures of

Effect 2 Species Toxicity

Value Toxicity

Classification Data Available for

Risk Assessment MRID

Avian acute oral toxicity

LD 50 Northern Bobwhite Quail ( Colinus virginianus ) 2290 mg ai/kg bw Practically

nontoxic Yes (Acceptable) 41650008

Northern Bobwhite Quail ( Colinus virginianus ) >4364 mg ai/kg

diet Slightly toxic Yes (Acceptable) 41650009 Abundance (i.e. survival, reproduction, and growth) of

individuals and populations of

birds Avian dietary toxicity LC 50

Mallard Duck ( Anas platyrhynchos ) >4573 mg ai/kg

diet Slightly toxic Yes (Acceptable) 41650010

Rainbow Trout ( Oncorhynchus mykiss ) 117 ppm (ai) Practically

nontoxic Yes (Acceptable) 41650011 Survival and reproduction of

individuals and

communities of

freshwater fish 96-hr Fish acute toxicity

LC 50 Bluegill Sunfish ( Lepomis

macrochirus ) 142 ppm (ai) Practically

nontoxic Yes (Acceptable) 41650012

Survival and reproduction of

individuals and

communities of

freshwater

invertebrates 48-hr Aquatic

Invertebrate toxicity EC 50 Water Flea ( Daphnia magna ) 33.85 ppm (ai) Slightly toxic Yes (Acceptable) 41650013

Acute Oral toxicity LD 50 Rat

Male

Female 285 mg ai/kg bw

314 mg ai/kg

bw Yes (Acceptable)

Guideline series 81-1 41127501 Abundance (i.e. survival, reproduction, and growth) of

individuals and populations of

mammals Acute Dermal toxicity LD 50 Rabbit Male; Female >5000 mg ai/kg

bw Tox Category

III Yes (Acceptable)

Guideline series 81-2 41127502

(Z)-9-tricosene

Acute Oral toxicity LD 50 Rat Male; Female >10,000

mg a.i./kg

bw Tox Category

IV Yes (Acceptable)

Guideline series 81-1 240209603 Abundance (i.e. survival, reproduction, and growth) of

individuals and populations of

mammals Acute Dermal toxicity LD 50 Rabbit Male; Female >20,000

mg a.i./kg

bw Tox Category

IV Yes (Acceptable)

Guideline series 81-2 240209605

1 Only the mammalian data are presented here for comparison, but additional data are available in the (Z)-9-tricosene RED (USEPA 1994a).

2 All studies used technical grade IN A0159-26 (purity >99%) except when otherwise stated



### 17

### 4.1 Aquatic Effects Characterization

Nithiazine was originally registered for us e in 1995. Guideline studies f rom that time were available for freshwater aquatic invertebra tes and fish. Overall, nithiazine is slightly

toxic to invertebrates an d practically non-toxic to fish on an acute basis. No chronic tests

were conducted.

96-Hour Freshwater Fish Acute Toxicity. Nithiazine is practically nontoxic to rainbow trout ( Oncorhynchus mykiss ) and bluegill sunfish ( Lepomis macrochirus ) with LC 50 

### values of 117 ppm and 142 ppm, respectively.

48-Hour Aquatic Inver tebrate Toxicity. Nithiazine is slightly toxic to the water flea ( Daphnia magna ) with an EC 50 

### value of 33.85 ppm.

4.2 Terrestrial Effects Characterization

Guideline studies evaluating effects on birds and mammals (rat and rabbit) are available

for nithiazine. On an acute oral basis nith iazine is practically nontoxic to northern bobwhite quail. On a dietary basis nithiazine is slightly toxic to northern bobwhite quail and mallard duck. Nithiazine is moderately to xic to rats based on an acute oral study and is practically nontoxic to rabbits on an acute dermal basis.

Avian Oral Toxicity. Nithiazine is practically no ntoxic to norther n bobwhite quail ( Colinus virginianus ), producing an LD 50 

### of 2290 mg/kg-bw.

Avian Dietary Toxicity. Nithiazine is slightly toxi c to northern bobwhite quail ( Colinus virginianus ) and mallard duck ( Anas platyrhynchos ) with LC 50 

### values of >4364 mg/kgdiet and >4573 mg/kg-diet, re spectively, based on mean meas ured dietary concentrations of four replicate samples of the highest reported dose taken on the fifth and final day of dosing. The study authors reported the nominal LC 50 

### values as 5620 ppm, which was the highest nominal concentration tested. Guidelin es recommend that, in lieu of establishing a precise LC 50 

### (as the case is here), it may instead be shown that the LC 50 

### >5000 ppm. If

in the future it becomes evident that actual use of the technical grade approaches or surpasses the measured LC 50 

### values of the avian studies , these studies may be reevaluated and additional testing or information may be required.

Mammal Oral Toxicity . Nithiazine is moderately toxic to rats with LD 50 

### s of 285 mg/kg for males and 314 mg/kg for females. The attractant, (Z)-9-tricosene, is practically nontoxic to rats on an acute oral basis (LD 50 

### >10,000 mg/kg).

Mammal Dermal Toxicity. Nithiazine is practically nontoxi c to rabbits with an acute dermal toxicity of > 5000 mg/kg for males. (Z)-9-tricosene is pr actically nontoxic to rabbits on an acute dermal basis (LD 50 

### >20,000 mg/kg).

18

### 4.2.1 Terrestrial Plant Data

There are no registrant submitted data on pl ant toxicity. However, based upon the labeled use, there should be no terrestrial plant exposure to nithiazine.

4.2.2 Terrestrial Invertebrate Data

Registrant submitted data on terrestrial invertebrates, including honeybees, is not available. However, based upon the labeled use and components of the bait strip product, there should be no exposure beyond the point of treatment.

4.2.3 ECOTOX Data

Terrestrial data search in the public ECOTOX database ( http://cfpub.epa.gov/eco tox/quick_query.htm ) yielded ten house fly studies. Qualitative information concerning honey bee toxicity wa s obtained from Iwasa et al. (2004).



## 5.0 Risk Estimation and Risk Description

Risk is typically estimated by calculating the ratio of the expected environmental concentration and the appropriate toxicity endpoint. This va lue is the risk quotient (RQ), which is then compared to pre-establishe d levels of concern (LOC) for each category

evaluated. However due to the labeled use of the nithiazine baits and the application method, limited or no exposure is expected to aquatic or terrestri al organisms beyond the point of treatment. Therefore RQs were not determined for the nithiazine baits.

5.1 Aquatic Risk Summary

Based on currently available data, nithiazine app ears to be of relatively low toxicity on an acute basis to aquatic fish and inverteb rates in freshwater systems. Based upon the labeled use, there is low potenti al for transport via runoff and drift to a non-target site. In addition, dissipation due to hydr olysis and rapid dissipation du e to photolysis contributes to the assumption that chronic risk to aquatic organisms (a nimals and plants) would be minimal. Nithiazine appears to pose very lo w risk to aquatic ecosystems based on the data currently available.

5.2 Terrestrial Risk Summary

Based on currently available data, nithiazine app ears to be of relatively low toxicity on an acute basis to mammals and birds. Based upon the labeled use, ther e is low potential for transport via runoff and drift to a non-target site. In additi on, the rapid dissipation due to photolysis contributes to the assumption that chronic risk to terrestrial organisms (animals and plants) would be minimal. Ri sk to terrestrial invertebrates (including

19

### honeybees) is not expected since the attractant pherom one, (Z)-9-tricose ne, is specific for flies, and the solid sugar matrix does not re present a desirable feeding medium for bees.

20

### Citations

Iwasa, T., N. Motoyam a, J.T. Ambrose, R. M. Roe. 2004. Mechanism for the differential toxicity of neonicotinoid insecticides in the honey bee, Apis mellifera . Crop

Protection: 371-378.

Jeschke, P. and R. Nauen. 2008. Review Neonicotinoids – from zero to hero in insecticide chemistry. Pest. Manag. Sci. 64:1084-1098.

USEPA. 1994a. (Z)-9-Tricosene. Regi stration Eligibility Decision (RED) U.S. Environmental Protection Agenc y. EPA 738-R-94-028. Washington, DC.

USEPA. 1994b. (Z)-9-Tricosene. R.E.D. FACTS. U.S. Environmental Protection Agency. EPA 738-R-94-025. Washington, DC.

USEPA. 1994c. Pesticide Fact Sheet: Name of Chemical: AO-159. New Chemical Registration. December 1994. U.S. Environmental Protection Agency. OPP/OPPTS. Washington, DC.

USEPA. 2009. Registration Re view – Problem Formulation for Nithiazine. DP Barcode

D360687. 01/28/09. U.S. Environmental Protection Agency, OPP/OPPTS/

Environmental Fate and Eff ects Division, Washington, DC.

21

## APPENDIX A. RQ methodology and LOCs

RQ Tables for screening level ecological assessments.

Risk characterization integrates the results of the exposure and ecotoxicity data to

evaluate the likelihood of advers e ecological effects. The m eans of this integration is called the quotient method. Risk quotients (RQs) are calculated by dividing exposure estimates by acute and chronic ecotoxicity values.

RQ = EXPOSURE/TOXICITY

RQs are then compared to OPP's levels of concern (LOCs). These LOCs are used by OPP to analyze potential ri sk to nontarget organisms and the need to consider regulatory action. The criteria indicate that a pesticide used as directed has the potential

to cause adverse effects on nont arget organisms. LOCs currently address the following risk presumption catego ries: 1) acute - poten tial for acute risk is high; regulatory action may be warranted in addition to restricted use classification, 2) acute restricted use - the potential for acute risk is hi gh, but may be mitigated through restricted use classification, 3) acute endangered species - endangered sp ecies may be adversel y affected, and 4) chronic risk - if the potential for chronic risk is high regula tory action may be warranted. Currently, EFED does not perform assessments for chronic risk to plants, acute or chronic risks to nontarget insects, or chronic risk from granul ar/bait formulations to birds

or mammals.

The ecotoxicity values (measurement endpoi nts) used in the acute and chronic risk quotients are derived from required studies . Examples of ecotoxicity values derived from short-term laboratory studies th at assess acute effects are: 1) LC 50 

### (fish and birds), 2) LD 50 

### (birds and mammals), 3) EC 50 

### (aquatic plants and aquatic invertebrates), and 4) EC25 (terrestrial plants). Exam ples of toxicity effect levels derived from the results of long-term laboratory studies that assess chronic effects are: 1) LOAEC (birds, fish, and aquatic invertebrates), 2) NOAEC (birds, fish and aquatic invertebra tes), and 3) MATC (fish and aquatic invertebrates). For bird s and mammals, the NOAEC generally is used as the ecotoxicity test value in assessing chronic effects, although other values may be used when justified. Generally, the MATC (defined as the geometric mean of the NOAEC and LOAEC) is used as the ecotoxicity test value in assessi ng chronic effects to fish and aquatic invertebrates. However, the NOAEC is used if the measurement end point is production of offspring or survival.

Risk presumptions and the corresponding RQs and LOCs are tabulated below.

22Agency Risk Quotient (RQ) Metrics and Le vels of Concern (LOC ) Per Risk Class.

RISK CLASS RISK DESCRIPTION RQ LOC

Aquatic Animals (fish and invertebrates)

Acute Potential for effects to non-listed animals from acute

exposures Peak EEC/LC 50 1 0.5

Acute

Restricted Use Potential for effects to an imals from acute exposures Risks may be mitigated through restricted use classification Peak EEC/LC 50 1 0.1

Acute Listed Species Listed species may be potentially affected by acute

exposures Peak EEC/LC 50 1 0.05

60-day EEC/NOAEC (fish) Chronic Potential for effects to non-listed and listed animals from chronic exposures 21-day EEC/NOAEC (invertebrates) 1

Aquatic Plants

Non-Listed Potential for effects to non-listed plants from exposures Peak EEC/LC 50 1 1

Listed Potential for effects to listed plants from exposures Peak EEC/NOAEC 1

Terrestrial Animals (mammals and birds)

EEC 2 /LC 50 (Dietary) Acute Potential for effects to non-listed animals from acute

exposures EEC/LD 50 (Dose) 0.5

EEC 2 /LC 50 (Dietary) Acute

Restricted Use Potential for effects to an imals from acute exposures Risks may be mitigated through restricted use classification EEC/LD 50 (Dose) 0.2

EEC 2 /LC 50 (Dietary) Acute Listed Species Listed species may be potentially affected by acute

exposures EEC/LD 50 (Dose) 0.1

Chronic Potential for effects to non-listed and listed animals from chronic exposures EEC 2 /NOAEC 1

Terrestrial and Semi-Aquatic Plants

Non-Listed Potential for effects to non-target, non-listed plants from

exposures EEC/ EC 25 1

EEC/ NOAEC Listed Plant Potential for effects to non-target, listed plants from

exposures EEC/ EC 05 1

1 LC 50 or EC 50

. 2 Based on upper bound Kenega values for foliar exposure.



### 23

### APPENDI X B Studies Submitted to the Agency.

Guideline: 61-1 Chemical Identity

------------------------------------------------------------------------------------- MRID: 40661301 Powell, J. (1988) DuPont Fly Trap SD35651 (AO159): Product Identity and Composition: Laboratory Project ID: PC/1-AO159. Unpublished compilation prepared by E. I. du Pont de Nemours and Co., Inc. 94

p.

MRID: 42730301 McDaniel, J. (1993) Beginning Materials/Manufacturing Procedure: Zoecon 9023 Flybait Station. Unpublished study prepared by Zoecon Corp. 58 p.

Guideline: 61-2 Description of Be ginning Materials and Manufacturing Process

------------------------------------------------------------------------------------- MRID: 40661301 Powell, J. (1988) DuPont Fly Trap SD35651 (AO159): Product Identity and Composition: Laboratory Project ID: PC/1-AO159. Unpublished compilation prepared by E. I. du Pont de Nemours and Co., Inc. 94

p.

MRID: 42730301 McDaniel, J. (1993) Beginning Materials/Manufacturing Procedure: Zoecon 9023 Flybait Station. Unpublished study prepared by Zoecon Corp. 58 p.

MRID: 44456803 McDaniel, J. (1996) Sandoz 9023 Fly Bait Station: Description of Beginning Materials and Manufacturing Procedure: Final Report: Lab Project Number: 2331. Unpublished study prepared by Sandoz Agro, Inc. 8

p.

Guideline: 61-3 Discussion of Formation of Impurities

------------------------------------------------------------------------------------- MRID: 40661301 Powell, J. (1988) DuPont Fly Trap SD35651 (AO159): Product Identity and Composition: Laboratory Project ID: PC/1-AO159. Unpublished compilation prepared by E. I. du Pont de Nemours and Co., Inc. 94

p.

MRID: 41650001 Silveria, E. (1990) Determinati on of Nitrosamines in Technical A0159: Lab Project Number: AMR-1890- 90. Unpublished study pre- pared by Battelle. 21 p.

Guideline: 62-1 Preliminary Analysis

------------------------------------------------------------------------------------- MRID: 40661302



### 24Silveira, E. (1988) Technical AO159 Product Chemistry: Analysis and Certification of Product Ingredients: Laboratory Project ID: PC/2-AO159. Unpublished compilation prepared by E. I. du Pont de Nemours and Co., Inc. 39 p.

MRID: 42379801 Waeghe, T. (1992) Technical Grad e DPX-A0159: Analysis and Certif ication of Product Ingredients ?Product Chemistry Data|: Lab Project Number: AMR 2243-91. Unpublished study prepared by E. I. du Pont de Nemours and Co. 31 p.

MRID: 44456802 Spoonemore, H. (1996) Method Validation for the Analysis of Sandoz 9023.005: Final Report: Lab Project Number: 9023ZOE00515RB: 2330. Unpublished study prepared by Sandoz Agro, Inc. 40 p.

Guideline: 62-2 Certification of limits

------------------------------------------------------------------------------------- MRID: 40661302 Silveira, E. (1988) Technical AO159 Product Chemistry: Analysis and Certification of Product Ingredients: Laboratory Project ID: PC/2-AO159. Unpublished compilation prepared by E. I. du Pont de Nemours and Co., Inc. 39 p.

Guideline: 62-3 Analytical Method

------------------------------------------------------------------------------------- MRID: 44456802 Spoonemore, H. (1996) Method Validation for the Analysis of Sandoz 9023.005: Final Report: Lab Project Number: 9023ZOE00515RB: 2330. Unpublished study prepared by Sandoz Agro, Inc. 40 p.

Guideline: 63-0 Reports of Multiple phys/chem Characteristics

------------------------------------------------------------------------------------- MRID: 48675 Shell Development Company (19??) SD 35651--Chemical Identity and Physical Properties. (Unpublished study received Jan 22, 1976 under un known admin. no.; CDL:226468-A)

MRID: 48679 Shell Development Company (1976) Summary: ?SD 35651|. Includes two undated methods entitled: Determination of SD 35651 in air; Determination of SD 35651 in a fly trap--liquid chromatographic method. (Compilation; unpublishe d study received Jan 22, 1976 under unknown admin. no.; CDL:226468- E)

MRID: 49363 Shell Development Company (1972) SD 35651--Chemical Identity and Physical Properties. (Unpublished study received on unknown date un der 201-EX-54; CDL:226504-A)

MRID: 55128 Shell Development Company (1972) SD 35651--Chemical Identity and Physical Properties. (Unpublished study received Apr 6, 1976 under 201-EX-52; CDL:229058-A)



### 25MRID: 56516 Shell Development Company (19??) SD 35651--Chemical Identity and Physical Properties. (Unpublished study received Apr 6, 1976 under 201-EX-51; CDL:230448-A)

MRID: 56517 Shell Development Company (1972) Vapor Pressure of 35651 and Mus- calure. (Unpublished study received Apr 6, 1976 under 201-EX- 51; CDL:230448-B)

MRID: 65944 Shell Development Company (1972?) ?Chemical Characteristics of SD 35651|. (Compilation; unpublished study received Apr 6, 1976 under 201-EX-51; CDL:229057-A)

MRID: 44456801 Moorman, R.; Witte, J. (1997) The Characterization, Density, pH, Color, Odor, and Physical State of Sandoz 9023.005: Final Report: Lab Project Number: N650: SANDOZ 9023: 2262. Unpublished study prepared by Sandoz Agro, Inc. 19 p.

Guideline: 63-7 Density

------------------------------------------------------------------------------------- MRID: 41650002 Silveria, E. (1990) Technical A0159: Physical and Chemical Chara- cteristics: Lab Project Number: AMR1888-90. Unpublished study prepared by E. I. du Pont de Nemours and Co. 9 p.

Guideline: 63-10 Dissociation Constant

------------------------------------------------------------------------------------- MRID: 41650002 Silveria, E. (1990) Technical A0159: Physical and Chemical Chara- cteristics: Lab Project Number: AMR1888-90. Unpublished study prepared by E. I. du Pont de Nemours and Co. 9 p.

Guideline: 63-12 pH

------------------------------------------------------------------------------------- MRID: 41650002 Silveria, E. (1990) Technical A0159: Physical and Chemical Chara- cteristics: Lab Project Number: AMR1888-90. Unpublished study prepared by E. I. du Pont de Nemours and Co. 9 p.

Guideline: 63-17 Storage stability

------------------------------------------------------------------------------------- MRID: 49368 Shell Development Company (19??) Fly Trap--Estimate of Lifetime: ?SD 35651|. (Unpublished study received on unknown date under 201-EX-54; CDL:226504-H)

MRID: 55130



### 26Shell Development Company (19??) Fly Trap--Air Conc entration of Ac- tive Ingredients. (Unpublished study received Apr 6, 1976 under 201-EX-52; CDL:229058-F)

MRID: 56358 Shell Development Company (19??) Fly Trap--Estimate of Lifetime. (Unpublished study received on unknown date under 201-EX-55; CDL:226509-G)

MRID: 65945 Shell Development Compan y (1976) Summary: ?SD 35651 |. (Compila- tion; unpublished study received Apr 6, 1976 under 201-EX-51; CDL:229057-F)

Guideline: 71-1 Avian Single Dose Oral Toxicity

------------------------------------------------------------------------------------- MRID: 41650008 Culotta, J. (1990) H 18,253: An Acute Oral Toxi city Study with the Northern Bobwhite Wildlife International Ltd: Lab Project Num- ber: 112-235: 290-90. Unpublished study prepared by E. I. du Pont de Nemours and Co. 18 p.

Guideline: 71-2 Avian Dietary Toxicity

------------------------------------------------------------------------------------- MRID: 41650009 Driscoll, C.; Hoxter, K.; Smith, G. (1990) H 18,253: A Dietary LC50 Study with the Northern Bobwhite: Lab Project Number: 112-233: 291-90. Unpublished study prepared by Wildlife International Ltd. 26 p.

MRID: 41650010 Driscoll, C.; Hoxter, K.; Smith, G. (1990) H 18,253: A Dietary LC50 Study with the Mallard: Lab Project Number: 112-234: 292-90. Unpublished study prepared by Wildlife International Ltd. 26 p.

Guideline: 72-1 Acute Toxicity to Freshwater Fish

------------------------------------------------------------------------------------- MRID: 41650011 Baer, K. (1990) Static Acute 96-Hour LC50 of IN A0159-26 to Rainbow Trout, Oncorhynchus mykiss: Lab Project Number: HLR 201-90: MR- 4581-805. Unpublished study prepared by E. I. du Pont de Nemours and Co., Inc. 20 p.

MRID: 41650012 Baer, K. (1990) Static Acute 96-Hour LC50 of IN A0159-26 to Blue- gill Sunfish, Lepomis Macrochirus: Lab Project Number: HLR 200- 90: MR-4581-805. Unpublished study prepared by E. I. du Pont de Nemours and Co., Inc. 20 p.

Guideline: 72-2 Acute Toxi city to Freshwater Invertebrates

------------------------------------------------------------------------------------- MRID: 41650013



### 27Baer, K. (1990) Static Acute 48-Hour EC50 of IN A0159-26 to Daphnia magna: Lab Project Number: HLR 199-90: MR-4581-805. Unpublished study prepared by E. I. du Pont de Nemours and Co., Inc. 22 p.

Guideline: 81-1 Acute oral toxicity in rats

------------------------------------------------------------------------------------- MRID: 48677 Lukes, T.H.; Paa, H. (1974) Report to Shell Develo pment Company: Acute Toxic ity Studies with Technical SD 35651: IBT No. 601- 05907. (Unpublished study received Jan 22, 1976 under unknown admin. no.; prepared by Industrial Bio-Test Laboratories, Inc. , submitted by Shell Chemical Co., Washington, D.C.; CDL:226468-C)

MRID: 119122 Lukes, T.; Paa, H. (1974) Report to Shell Developm ent Company: Acute Toxicity Studies with Technical SD 35651: IBT No. 601- 05907. (Unpublished study received Jan 22, 1976 under unknown admin. no.; prepared by Industrial Bio-Test Laboratories, Inc. , submitted by Shell Chemical Co., Washington, DC; CDL:225926-A)

MRID: 41127501 Sarver, J. (1989) Acute Oral Toxic ity Study with DPX-A0159-24 in Male and Female Rats: Haskell Lab. Rept. No. 221-89. Unpublish- ed study prepared by E.I. du Pont de Nemours and Co., Inc. 36 p.

Guideline: 81-2 Acute dermal toxicity in rabbits or rats

------------------------------------------------------------------------------------- MRID: 48677 Lukes, T.H.; Paa, H. (1974) Report to Shell Develo pment Company: Acute Toxic ity Studies with Technical SD 35651: IBT No. 601- 05907. (Unpublished study received Jan 22, 1976 under unknown admin. no.; prepared by Industrial Bio-Test Laboratories, Inc. , submitted by Shell Chemical Co., Washington, D.C.; CDL:226468-C)

MRID: 119122 Lukes, T.; Paa, H. (1974) Report to Shell Developm ent Company: Acute Toxicity Studies with Technical SD 35651: IBT No. 601- 05907. (Unpublished study received Jan 22, 1976 under unknown admin. no.; prepared by Industrial Bio-Test Laboratories, Inc. , submitted by Shell Chemical Co., Washington, DC; CDL:225926-A)

MRID: 41127502 Sarver, J. (1989) Acute Dermal Toxicity Study of DPX-A0159-24 in Rabbits: Haskell Lab. Rept. No. 180- 89. Unpublished study pre- pared by E.I. du Pont de Nemours and Co., Inc. 13 p.

Guideline: 81-4 Prim ary eye irritation in rabbits

------------------------------------------------------------------------------------- MRID: 48677 Lukes, T.H.; Paa, H. (1974) Report to Shell Develo pment Company: Acute Toxic ity Studies with Technical SD 35651: IBT No. 601- 05907. (Unpublished study received Jan 22, 1976 under unknown admin. no.; prepared by Industrial Bio-Test Laboratories, Inc. , submitted by Shell Chemical Co., Washington, D.C.; CDL:226468-C)



### 28MRID: 49711 Levenstein, I. (1976) To Determine If the Test Mate rial Produces Any Irritation When Instilled into Rabbits' Eyes Employing the Reference Method Described: Assay No. 65448. (Unpublished study received Sep 14, 1976 under 201-EX- 51; prepared by Leberco Labo- rato ries, submitted by Shell Chemical Co., Washington, D.C.; CDL:229061-A)

MRID: 49712 Levenstein, I. (1976) To Determine If the Test Mate rial Produces Any Irritation When Instilled into Rabbits' Eyes Employing the Reference Method Described: Assay No. 65447. (Unpublished study received Sep 14, 1976 under 201-EX- 55; prepared by Leberco Labo- rato ries, submitted by Shell Chemical Co., Washington, D.C.; CDL:229060-A)

MRID: 119122 Lukes, T.; Paa, H. (1974) Report to Shell Developm ent Company: Acute Toxicity Studies with Technical SD 35651: IBT No. 601- 05907. (Unpublished study received Jan 22, 1976 under unknown admin. no.; prepared by Industrial Bio-Test Laboratories, Inc. , submitted by Shell Chemical Co., Washington, DC; CDL:225926-A)

MRID: 41127503 Brock, W. (1989) Primary Eye Irritation Study with DPX-A0159-24 in Rabbits: Haskell Lab. Rept. No. 192-89. Unpublished study pre- pared by E.I. du Pont de Nemours and Co., Inc. 19 p.

MRID: 43003802 Blaszcak, D. (1993) Pr imary Eye Irritation Study of Zoecon 9023 Flybait in Rabbits: Final Report: Lab Project Number: 1948: 92-0747: 9023. Unpublished study prepared by Pharmaco LSR, Inc. 21 p.

Guideline: 81-5 Primary dermal irritation

------------------------------------------------------------------------------------- MRID: 48677 Lukes, T.H.; Paa, H. (1974) Report to Shell Develo pment Company: Acute Toxic ity Studies with Technical SD 35651: IBT No. 601- 05907. (Unpublished study received Jan 22, 1976 under unknown admin. no.; prepared by Industrial Bio-Test Laboratories, Inc. , submitted by Shell Chemical Co., Washington, D.C.; CDL:226468-C)

MRID: 41127504 Sarver, J. (1989) Primary Dermal Irritation Study with DPX-A0159-24 in Rabbits: Haskell Lab. Rept. No. 168-89. Unpublished study prepared by E.I. du Pont de Nemours and Co., Inc. 12 p.

MRID: 43003801 Blaszcak, D. (1993) Primary Dermal Irritation Study of Zoeco n 9023 Flybait in Rabbits: Final Report: Lab Project Number: 1950: 92-0746: 9023. Unpublished study prepared by Pharmaco LSR, Inc. 16 p.

Guideline: 81-8 Acute ne urotoxicity screen study in rats

-------------------------------------------------------------------------------------



### 29MRID: 42672101 Foss, J. (1993) Acute Neurotoxicity Study of DPX-A0159-31 Administered Orally via Gavage to Crl:CDBR VAF/Plus Rats: Lab Project Number: 9427-001: 104-014: HLO 381-92. Unpublished study prepared by Argus Research Labs, Inc. 952 p.

Guideline: 84-2 Interaction with Gonadal DNA

------------------------------------------------------------------------------------- MRID: 41650003 Reynolds, V. (1990) Mutagenicity Testing of IN A0159-26 in the Sal- monella Tymphimurium Plate Incorporation Assay: Lab Project Num- ber: HLR 250-90: 4581-801: 500. Unpublished study prepared by E. I. du Pont de Nemours and Co., Inc. 27 p.

MRID: 41650004 Bentley, K. (1990) Mutagenicity Evaluation of IN A0159-26 in the CHO/HPRT Assay: Lab Project Number: HLR 231-90: 4581-801. Un- published study prepared by E. I. du Pont de Nemours and Co., Inc. 20 p.

MRID: 41650005 Stahl, R. (1990) In Vitro Evaluation of IN A0159-26 for Chromosome Aberrations in Human Lymphocytes: Lab Project Number: HLR 258- 90: 4581-801: 545. Unpublished study prepared by E. I. du Pont de Nemours and Co., Inc. 22 p.

MRID: 41650006 Reynolds, V. (1990) Mouse Bone Marrow Micronucleus Assay of IN A0159-26: Lab Project Number: 329- 90: 4581-801: 572. Unpub- lished by prepared by E. I. du Pont de Nemours and Co., Inc. 17 p.

MRID: 41650007 Bentley, K. (1990) Assessment of IN A0159-26 in the In Vitro Un- scheduled DNA Synthesis Assay in Primary Rat Hepatocytes: Lab Project Number: HLR 230-90: 4581-801. Unpublished study prepar- ed by E. I. du Pont de Nemours and Co., Inc. 17 p.

Guideline: 151-16 Analyt ical Methods for Certified Limits

------------------------------------------------------------------------------------- MRID: 42978902 Nguyen, K. (1993) Method Validation for the Analys is of AO159 Technical, Fly Bait Premix and Fly Bait Station: Lab Project Number: 1908: 9023 ZOE 005 1 5 RB. Unpublished study prepared by Zoecon Corporation. 65 p.

Guideline: 151-17 Physical and Chemical Properties

------------------------------------------------------------------------------------- MRID: 42978903 Nguyen, K. (1993) Product Chemistry of ZOECON 9023 Flybait Premix Containing Approximately 5% AO159: Lab Project Number: 1965: 9023 ZOE005 15 RB. Unpublished study prepared by Zoecon Corporation. 15 p.



### 30Guideline: 152-15 Hypersensitivity Study

------------------------------------------------------------------------------------- MRID: 42978901 Blaszcak, D. (1993) Closed-Patch Re peated Insult Dermal Sensitization Study of ZOECON 90 23 Flybait in Guinea Pigs (Buehler Method): Final Report: Lab Project Number: 1949: 92-0748: 9023. Unpublished study prepared by Pharmaco LSR, Inc., Toxi cology Services North America. 26 p.

Non-Guideline Study

------------------------------------------------------------------------------------- MRID: 48676 Citation: Shell Chemical Company (1974?) Summar y: ?Technical SD 35651|. Sum- mary of study 226468-C. (Unpublished study received Jan 22, 1976 under u nknown admin. no.; CDL:226468-B)

MRID: 48678 Citation: Shell Development Company (19??) Poten tial Hazard of the SD 35651/ Muscalure Fly Trap. (Unpublished study received Jan 22, 1976 un der unknown admin. no .; CDL:226468-D)

MRID: 49364 Citation: Shell Development Comp any (1974?) Summary: ?S D 35651|. (Unpu b- lished study received on unknown date under 201-EX-54; CDL: 226504-B)

MRID: 49366 Citation: Shell Chemical Company (1976?) Summary: ?SD 35651|. Summary of studies 226504-G,

226504-H and 226504-M. (Unpublished study receive d on unknown date under 201-EX-54; CDL:226504- F)

MRID: 49367 Citation: Shell Development Company (19??) Fly Tr ap--Air Concentration of Active Ingredients: ?SD 35651|. (Unpublished study r eceived on unknown date under 201-EX-54; CDL:226504-G)

MRID: 49370 Citation: Shell Development Company (1975) Determination of SD 35651 in Air: Tentative Method. (Unpublished study received on unknown da te under 201-EX-54; CDL:226504-J)

MRID: 49372 Citation: Shell Development Company (1975) Determination of SD 35651 in a Fly Trap--Liquid Chromatographic Method (Tentative) . (Unpublished study received on unknown date under 201-EX-54; CDL:226504-L)

MRID: 49373 Citation: Shell Development Co mpany (1976) ?Efficacy Studies w ith SD 35651-- Houseflies and Mosquitoes|. (Unpublished study received on un- known date un der 201-EX-54; CDL:226504-M)

MRID: 55129 Citation: Shell Chemical Company (1974?) Summary: ?SD 35651|. Summary of study 229058-C. (Unpublished study received Apr 6, 19 76 under 201-EX-52; CDL:229058-B)

MRID: 55132 Citation: Shell Development Company (1975) Determination of SD 35651 in Air: Tentative Method. (Unpublished study received Apr 6, 19 76 under 201-EX-52; CDL:229058-H)

MRID: 55133 Citation: Shell Development Company (1976) Insecticide Screening--SD 35651. (Unpublished study received Apr 6, 1976 under 20 1-EX-52; CDL: 229058-K)



### 31MRID: 56359 Citation: Shell Development Company (1975) Determination of SD 35651 in Air: Tentative Method. (Unpublished study received on unknown da te under 201-EX-55; CDL:226509-H)

MRID: 56518 Citation: Shell Chemical Company (19??) Summary: ?SD 35651|. Summary of studies 230448-H,

230448-I and 230448-N thr ough 230448-R. (Un- publis hed study received Apr 6, 1976 under 201-EX-51; CDL: 230448-G)

MRID: 56520 Citation: Shell Development Company (1975) Determination of SD 35651 in Air: Tentative Method. (Unpublished study received Apr 6, 19 76 under 201-EX-51; CDL:230448-K)

MRID: 56521 Citation: Shell Development Company (1973) Insecticide Screening--SD 35651. (Unpublished study received Apr 6, 1976 under 20 1-EX-51; CDL: 230448-N)

MRID: 56522 Citation: Shell Development Comp any (1974) Fly Toxicity of Dry SD 35651. (Unpublished study received Apr 6, 1976 under 201-EX-51; CDL: 230448-O)

MRID: 56523 Citation: Shell Development Company (1974) Fly Toxicity of SD 35651 in a Water Trap. (Unpublished study received Apr 6, 1976 under 201- EX-51; CDL:230448-P)

MRID: 56524 Citation: Shell Development Company (1974) Room Studies with an SD 35651/ Water Fly Trap. (Unpublished study received Apr 6, 19 76 under 201-EX-51; CDL:230448-Q)

MRID: 56525 Citation: Shell Development Compan y (1976) ?Efficacy of SD 35651|. (Compi- lati on; unpublished study received Apr 6, 1976 under 201-EX-51; CDL:230448-R)

MRID: 65947 Citation: Shell Development Company (1975) Determination of SD 35651 in Air: Tentative Method. (Unpublished study received Apr 6, 19 76 under 201-EX-51; CDL:229057-H)

MRID: 73595 Citation: Shell Development Company (19??) Poten tial Hazard of the SD 35651/ Muscalure Fly Trap. (Unpublished study received Apr 6, 1976 un- der 201-EX-51; CDL:230448-F)

MRID: 73701 Citation: Shell Development Company (19??) Poten tial Hazard of the SD 35651/ Muscalure Fly Trap. (Unpublished study received Apr 6, 1976 un- der 201-EX-52; CDL:229058-E)

MRID: 79559 Citation: Shell Development Company (19??) Poten tial Hazard of the SD 35651/ Muscalure Fly Trap. (Unpublished study received Apr 6, 19 76 under 201-EX-51; CDL:229057-E)

MRID: 119123 Citation: Shell Chemical Co. (1976) Efficacy Data Demo nstrating the Usefull- ness ?sic| of the Product for the Purpose Proposed. (Compila- tion; unpublished study received Jan 22, 1976 under unknown ad- min. no.; CDL:225926-D)



### 32MRID: 40661300 Citation: E. I. du Pont de Nemours and Co., Inc. (1988?) Submission of Chem- istry Data in Support of Du Pont Fly Trap--SD 35651(AO159). Transmittal of 2 studies.

MRID: 41127500 Citation: E.I. du Pont de Nemours & Co., Inc. (1989) Submission of Toxicology Data to Dupport the Application for Du Pont Fly Trap - SD35651 for an Ex perimental Use Permit. Transmittal of 4 studies.

MRID: 41397700 Citation: E. I. du Pont de Nemours and Co. (1990) Submission of Environmental Fate Data in Support of A0159 Experimental Use Permit and Regis- tration. Transmittal of 1 study.

MRID: 41397701 Citation: Foster, J. (1975) Transport Potential of A0159: Lab Project Number: 1588-90. Unpublished study prepared by Shell Development Co. 45 p.

MRID: 41650000 Citation: E. I. du Pont de Nemours and Co., Inc. (1990) Submission of Chemistry and Toxicity Data in support of an application for registration for Du Pont Technical A0159 Insecticide. Transmittal of 13

studies.

MRID: 42379800 Citation: E.I. du Pont de Nemours & Co., Inc. (1992) Submission of Data in Fulfillment of the Requirement for Analysis and Certification of Product Ingredients for Du Pont Technical A0159: Product Chemistry Study. Transmittal of 1 study.

MRID: 42654400 Citation: Du Pont (1993) Submission of toxicity data in support of the FIFRA 6(a)2 requirement for Du

Pont Technical AO159 Insecticid e. Transmittal of 1 study.

MRID: 42654401 Citation: Lin, W. (1993) Letter Sent to U.S. EPA Office of Pesticide Programs dated Feb. 1, 1993: Regarding preliminary toxicology information of Du Pont Technical AO159 Insecticide on rats. Prepared by Du Pont. 3 p.

MRID: 42672100 Citation: DuPont (1993) Submission of toxicity data in support of FIFRA 6(a)(2) requirements for DuPont

Technical A0159 Insecticide. Transmittal of 1 study.

MRID: 42730300 Citation: Zoecon Corp. (1993) Submission of product chemistry data in support of the Zoecon 9023 Flybait Station registration. Transmittal of 1 study.

MRID: 42978900 Citation: Zoecon Corporation (1993) Submission of Efficacy Data, Product Chemistry and Toxicology Data for Zoecon 9023 Flybait Station in Support of Registration. Transmittal of 4 Studies.

MRID: 42978904 Citation: Cocke, J.; Nolan, M.; H ogsette, J. (1993) ZOECON 9023 Flybait Station Housefly Efficacy Field Trials: Interim Report: Lab Project Number: 1484: 9023ZOE005I5RB. Unpublished study prepared by Ag Ventures, Inc.; Tarleton State University and Local Producers in Stephenville, TX Area. 111 p.

MRID: 43003800 Citation: Zoecon Corp. (1993) Submission of Acute Toxicology Data in Support of Registration of Zoecon 9023 Flybait Station. Transmittal of 2 Studies.



### 33

### 34 MRID: 43856800 Citation: Sandoz Agro, Inc. (1995 ) Submission of Efficacy Data in Support of the Amended Registration of Sandoz 9023 Fly Bait Station. Transmittal of 1 Study.

MRID: 43856801 Citation: Barton, W. (1995) Paper vs. Plastic Nith iazine Fly Bait Station Efficacy: Interim Report: Lab Project Number: 2265: 311-95-51: N650. Unpublished study prepared by CAVL, Inc. 11 p.

MRID: 44011700 Citation: Sandoz Agro, Inc. (1996) Submission of Pes ticide Use Data in Support of the Registration of Sandoz 9023 Fly Bait Station. Transmittal of 2 Studies.

MRID: 44011701 Citation: Barton, W. (1995) Paper vs. Plastic Nith iazine Fly Bait Station Efficacy: Final Report: Lab Project Number: 2265: 311-95-51: N650. Unpublishe d study prepared by CAVL , Inc. and Barry Miller Poultry Farm. 17 p.

MRID: 44011702 Citation: Ahrens, E. (1995) Paper vs. Plastic Nith iazine Fly Bait Station Efficacy: Final Report: Lab Project Number: 2264: N650. Unpublished study prepared by Randy Miller Dairy. 14 p.

MRID: 44456800 Citation: Wellmark International (1997) Submission of Product Chemistry Data in Support of the Registration for Sandoz 9023 Fly Bait Station. Transmittal of 3 Studies.

MRID: 47040600 Citation: Wellmark International (2007) Submission of Toxicity Data in Support of the FIFRA 6(a)(2) Data Requirements for Technical AO159 In secticide. Transmittal of 1 Study.

MRID: 47040601 Citation: Beck, M. (2006) A 28-Day Oral (Gavage) Toxicity Study of RF2043 in Rats: Final Report. Project Number: 3101, WIL/551005, RF2043. Unpublished study prepared by WIL Research Laboratories, Inc. 358 p.