## 2 At this time, we have the following questions fo r the registrant based on our preliminary review

of the data:

1. For the aerobic soil metabolism study (MRID 4345578-01 and 446879-01), what U.S. soil is represented by the soil used in the study? If the soil used has no U.S. equivalent, then a new study will be required.

2. For the aerobic aquatic metabo lism study (MRID 430998-01 and 446879-02), what U.S. soil or sediment is represented by the sedime nt used in the study? If the soil or sediment used has no U.S. equivalent, a new study will be required.

3. The Terrestrial Field Dissipation (T FD) study (MRID 436468-01) appears to show much faster dissipation from soil (16-20 days) than would be indicated by the aerobic soil metabolism study (257-385 days). An explanation of the discrepancy is needed. An additional TFD study will be required if a scie ntifically reasonable, documented explanation is not possible. If the available TFD study is determined to be acceptable, an Environmental Chemistry Methods in Soil study would still be required.

In the absence of additional data, EFED request s the following environmental fate studies:

• Guideline Number: 835.2240, Study Title : Photodegradation in Water

• Guideline Number: 835.2410, Study Title : Photodegradation in Soil

• Guideline Number: 835.4100, Study Title: Aerobic Soil Metabolism

• Guideline Number 835.4200, Study Title: Anaerobic Soil Metabolism

• Guideline Number: 835.4300, Study Title: Aerobic Aquatic Metabolism

• Guideline Number: 835.4400, Study Title: Anaerobic Aquatic Metabolism

• Guideline Number: 835.6100, Study Title: Terrestrial Field Dissipation (If MRID 43646801 is determined to be acceptable, only the Environmental Chemistry Methods in Soil would be required)Guideline Number: 835.1410, Study Title: Volatility – Laboratory

• Guideline Number: 835.6200, Study Title: Aquatic Field Dissipation (only the Environmental Chemistry Methods in Water is required)

• Guideline Number: 835.7100, Study Title: Ground Water Monitoring

EFED also noted several data gaps for ecotoxi cological information and will be requesting the following studies:

• Guideline Number: 850.1400, Study Title: Freshwater Fish Early Life Stage Toxicity Test, TGAI (Rainbow Trout)

• Guideline Number: 850.1400, Study Title: Saltwater Fish Early Life Stage Toxicity Test, TGAI (sheepshead minnow)

• Guideline Number: 850.1350, Study Title: Mysid Chronic Toxicity Test (mysid shrimp, A. bahia)

• Guideline Number: 850.2100, Study Title: Ac ute Avian Oral Toxicity Test using a Passerine species, TGAI

## 3 • Guideline Number: 850.4100 Study Title: Seedling Emergence, Tier II, TEP (10 species)

• Guideline Number 850.4150 Study Title: Ve getative Vigor, Tier II, TEP (10 species)

Additionally, EFED noted several data gaps remain for ecotoxicological information of amitrole’s degradate, cyanamide, which itself is a plant growth regul ator. The 2007 problem formulation for cyanamide (PC Code 014002) re quested data for Seedling Emergence and Vegetative Vigor studies and noted data gaps, but did not request data for chronic

estuarine/marine fish and invertebrate tests. The more widespread natu re of the amitrole use pattern, versus the limited use of cyanamide on fr uit trees, makes it more likely that exposure of estuarine organisms will occur. Additionally, de spite the submitted chronic freshwater fish ELS study (MRID 44076701) for cyanamide being consider ed supplemental due to effects being observed at all concentrations, th e problem formulation did not cons ider this to be a data gap. However, scientific standards today would consider this also to be a data gap and this data is

needed to reduce uncertain ties in the risk assessment for am itrole. The supplemental fish ELS study does not fulfill the guideline requirement for a chronic freshwater fish study for cyanamide. Similar gaps and uncertainties fo r other chemicals have resulted in recent

assessments where risk to certain taxa have b een presumed due to the absence of data and reduced the opportunities to use mitiga tion measures to reduce the risk to listed species.

The requested terrestrial plant data has been submitted to the Agency and is currently in review. Since, cyanamide may be a major degradate of amitrole and the available data indicate that cyanamide may be somewhat more toxic to aq uatic organisms than parent amitrole, the

additional data on freshwater and estuarine/marine fish and estuarine/marine invertebrates is

needed to reduce uncertainties in the risk assessment. Therefor e, at this time EFED will be requesting the following studies:

• Guideline Number: 850.1350, Study Title: Mysid Chronic Toxicity Test, degradate—Cyanamide (mysid shrimp, A. bahia )

• Guideline Number: 850.1400, Study Title: Saltwater Fish Early Life Stage Toxicity Test (sheepshead minnow, using the degradate, Cyanamide).

• Guideline Number: 850.1400, Study Title: Freshwater Fish Early Life Stage Toxicity Test (rainbow trout, us ing the degradate, Cyanamide)

Without this data, risk to aquatic organisms will ha ve to be presumed. If environmental fate data is provided that shows that cyanamide is not a ma jor degradate of amitrole, than the uncertainties

in the risk assessment for amitrole would be reduced even if this data is not submitted.

## 4 

# Problem Formulation for the Ecological Risk and Drinking Water Exposure Assessments in Support of the Registration Review of Amitrole

Amitrole (CAS 61-82-5) 1H-1,2,4-triazol-3-amine

P

repared by: 

## Michael Wagman, Biologist William P. Eckel, Ph.D. Senior Science Advisor U. S. Environmental Protection Agency Office of Pesticide Programs

E nvironmental Fate and Effects Division

E nvironmental Risk Branch III 1200 Pennsylvania Ave., NW

M

ail Code 7507P Washington, DC 20460 R eviewed by: Mark Corbin, Branch Chief

D ate: May 13, 2011

## 5 Table of Contents

I. Purpose of Problem Formulation ...................................................................................... .... 6

II. Nature of Regulatory Action ................................................................................................... 6

1. Amitrole Regulatory History ............................................................................................. 6

III. Stressor ...................................................................................................................... .......... 8

1. Nature of the Chemical Stressor ..................................................................................... . 8

2. Herbicidal Mechanism of Action .............................................................................. 10

3. Overview of Pesticide Usage ........................................................................................ 10

IV. Receptors...................................................................................................................... ..... 11

1. Aquatic and Terrestrial Effects ..................................................................................... 11 2. Degradate toxicity ........................................................................................................ .... 14

3. Formulations .............................................................................................................. ...... 15 4. Ecological Incidents ...................................................................................................... ... 15 5. Ecosystems Potentially at Risk ..................................................................................... 16 VI. Conceptual Model ................................................................................................... ......... 17 1. Risk Hypothesis .................................................................................................... ........ 17 2. Conceptual Diagram ................................................................................................. .... 17 VII. Analysis Plan Options ............................................................................................. ....... 21

1. Measures of Effects and Exposure .................................................................................... 22

2. Stressors of Concern ...................................................................................................... ...... 26

VIII. Endangered Species Assessment ...................................................................................... 28

IX. Drinking Water Assessment ............................................................................................. 29

X. Clean Water Act ............................................................................................................... ..... 29

XI. Anticipated Data Needs .................................................................................................... 29

XII. Open Literature ............................................................................................................... .. 32 XIII. Bibliography ............................................................................................................ ............. 33 Appendix A: Summary of Toxicity data ....................................................................................... 34 Appendix B: Sample Inputs and Outputs from SIP ...................................................................... 51

## 6 

# I. Purpose of Problem Formulation

The purpose of this problem formulation is to provide the foundation for the ecological risk assessment being conducted for amitrole. As such, it articulates the purpose and objectives of the risk assessment, evaluates the nature of the problem, and provides a plan for analyzing the data and characterizing the risk (EPA, 1998).



# II. Nature of Regulatory Action

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

sold or distributed in the Un ited States generally must be registered by the Environmental Protection Agency (EPA). In determining whether a pesticide can be regist ered in the U.S., EPA evaluates its safety to non-target species base d on a wide range of environmental and health effects studies. 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 ( http://www.epa.gov/oppsrrd1/ registration_review/ ). 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 ov er time. Through the new registration review program, the Agency periodically reevaluates pestic ides to make sure that as change occurs, products in the marketplace can be used safely.

As part of the implementation of the new Registration Review program pursuant to Section 3(g) of the Federal Inse cticide, Fungicide, and Rodenticid e Act (FIFRA), the Agency is beginning its evaluation of amitrole to determin e whether it continues to meet the FIFRA standard for registration. This problem formulation for the envi ronmental fate, ecological risk, and endangered species assessment ch apter in support of the registra tion review will be posted in the initial docket opening the public phase of the review process.

1. Amitrole Regulatory History

Amitrole was first registered as a pestic ide in the U.S. in 1948, and EPA issued a Registration Standard March 30, 1984.

Amitrole is a terrestrial non-f ood herbicide used primarily in industrial areas (outdoors), non-agricultural rights-of-way, fencerows, hedgero ws, non-agricultural uncultivated areas, soils, ornamental and/or shade trees, and ornamental shrubs and vine s. Formulations include a

## 7 technical product, a water dispersible granule, and a product in water soluble bags (formulation not specified on label).

Amitrole is not used on food crops – there is no dietary exposure, and amitrole has no dietary tolerances. At the time of the RED, Amitrole was classified as a B2-probable human carcinogen, and confirmed adverse effects on the thyroid gland had been identified. In 2006, the HED Cancer Assessment Review Committee (CARC) re -evaluated the carci nogenic potential of

amitrole. The CARC classified amitrole as “ Not Likely To Be Carcinogenic To Humans At Doses That Do Not Alter Rat Thyroid Hormone Homeostasis. ” This decision was based on the following:

i) Treatment-related thyroid follicular cell tumors we re seen in male and female rats (multiple strains) based on evidence provided collectiv ely from several studies (Keller 1959; Johnson 1981; Steinhoff 1979; and Tsuda 1976); ii) No treatment-related tumors were seen in male or female mice (Steinhoff and Boehme 1979); iii) Amitrole is considered to be nonmutagenic and does not mediate thyroid carcinogenesis through a mutagenic mode of action; iv) The overall weight-of-the-evidence was consider ed sufficient to indicate that amitrole induced thyroid follicular tumors thr ough an antithyroidal mode of action; v) Rats are substantially more sensitive than hum ans to the development of thyroid follicular cell tumors in response to thyroid hormone imbalance.



## Therefore, the previous quantif ication of carcinogeni c potential as B2 is not applicable.

EPA was concerned about dermal exposure a nd human exposure that caused antithyroid effects in laboratory animals, and on May 15, 1984 the Agency issued a Notice of Special Review (Position Document-1) of pesticide pr oducts containing amitrole. Special Review

addressed the use of amitrole on non-crop sites (highway ri ghts-of-way, primarily), and by homeowners, and examined the carcinogenic risk to mixers, loaders and applicators. The data

indicated that amitrole induced t hyroid, pituitary and liver tumors in laboratory animals. The registrant introduced measures that reduced worker exposure to amitrole - deletion of knapsack sprayers, the adoption of a " no-glug" container design for th e liquid formulation to reduce splashing while pouring, the addition of prot ective clothing requirements to labels, and packaging of the wettable powder formulation in water soluble packets. The registrant voluntarily canceled all home owner products. The registra nt later canceled the liquid formulation product.

During the Special Review process, two Data Call-Ins (DCIs) were issued:

o 1) On February 22, 1990 requesting efficacy, usage and worker exposure monitoring data for both liquid and po wder formulations of amitrole.

o 2) On August 16, 1991 requesting product chemistry, ecological and environmental fate studies and toxicology studies.

Based on a risk and benefit assessment, the Agency issued a Notice of Final Determination (57 FR 46448) on October 8, 1992 of the Amitrole Special Review. After reviewing submitted data, the Agency continued th ese label requirements: cancer classification,

## 8 application methods limited to boom sprayers, and protective clothing. Furthermore, though EPA was initially concerned about inhalation exposure , it was determined at that time that there

is little likelihood of actual inhalation exposure from mixi ng/loading/applying amitrole.

There are three registrations: 33688-6, 33688-10 (w ater soluble granules) and 33688-5. A Reregistration Eligibility Decision (RED) document was published in August 1996, and Amitrole was found eligible for reregistration.

The ecological risk assessment in the RED c oncluded that maximum labeled use rates of amitrole for registered uses at that time exceeded acute endangered levels of concern (LOCs) for birds feeding on short and tall grass and broadleaf plants an d for small mammals consuming short grass and insects. Since there was no mort ality at the highest conc entration in the avian dietary test, amitrole was considered to represen t low acute risk to bird s. The RED concluded

that no acute LOCs were exceeded for freshwat er fish or invertebrates, but risk to

estuarine/marine invertebrates exceeded the acu te endangered species LOC of 0.05. Chronic risk

to mammals exceeded the chronic LOC of 1.0 for sm all herbivores consuming short grass, seeds and insects, while chronic risk to birds, fish a nd aquatic invertebrates wa s not assessed due to a lack of data. Based on conclusions of the poten tial for human health and environmental risks, the RED contains the Agency's decisions and conditions under which these uses and products will be eligible for reregistration.

During the RED process, EPA determined that exposure risks were mitigated by the requirement of water soluble bags, and that the e nvironmental fate database was complete. After the RED was published, a generic DCI was i ssued (GDCI-004401-17739) in December 1996 to be conducted on the active ingred ient: Guidelines 17-4(a) and (b), Avian reproduction studies and, Guideline 72-4(b), Aquatic In vertebrate Life Cycle with Daphnia magna . Confirmatory studies were required in order to complete the Agency's risk assessment and conclusions: Guideline 123-1(a), Terrestrial Plant Testin g: Seedling Emergence only, Guideline 123-2 Aquatic Plant Testing: All five species, a nd Guidelines 231 and 232 Handler exposure study to provide dermal and inhalation data on mixers and loaders du ring the use of water-soluble packages. The Agency also required product-spec ific data including product chemistry and acute toxicity studies, revised Confidential Statements of Formula (CSFs), and revised labeling for reregistration. A PDCI (PDCI-004401-0160) was also issued in December 1996.



# III. Stressor Source and Distribution

1. Nature of the Chemical Stressor

Table III.1. Nature of the Chemical Stressor Reference / Comment

Common name amitrole

Chemical name (CAS/IUPAC) 1H-1,2,4-triazol-3-

amine Footprint database accessed 02/01/2011:
http://sitem.herts.ac.uk/aeru/footprint/en/Reports/31.htm 

## Pesticide type Herbicide Footprint database Chemical class triazole Footprint database CAS number 61-82-5 Footprint database Empirical formula C2H4N4 Footprint database

## 9 Molecular mass (g/mol) 84.08 Footprint database Vapor pressure 4.4 E-7 mmHg Footprint database Henry’s Law Constant (atm-m 3 

## /mol) 1.74 E-13 Calculated as vapor pressure/ solubility

Solubility in water (g/L) 280,000 mg/L 264,000 mg/L (20°C) EPISuite physical property data

Footprint database Log K
ow 

## (20°C, pH7) - 0.97 EPISuite Physical property data, Footprint database pK
a 

## /pK b 

## 4.14, 10.7 Footprint database

K F 

## (Freundlich adsorption coefficient, Batch Equilibrium) 0.714 silty clay soil 0.223 sandy loam

soil 0.152 sand soil

0.922 silt soil MRID 42676601 Sorption correlated to Cation Exchange Capacity (CEC) but not to organic carbon or clay content Hydrolysis half-life St able pH5 – pH9 MRID 42843801Aqueous Photolysis halflife 937 days (pH7, dark-corrected) MRID 42943201 (note 1)

Soil Photolysis half-life 158 days (darkcorrected) MRID 42676601 (note 1)

Aerobic Soil Metabolism

half-life 385 days (7°C) 257 days (22°C) MRID 43457801, 44687901 (note 1) Half-lives based on CO2 evolved due to high

unextracted residues Aerobic Aquatic

Metabolism half-life 69.3 days (22°C, dark) 84.5 days (22°C, light/dark) 31.7 days (7°C, light/dark) MRID 43099801, 44687902 (note 1)

Anaerobic Aquatic

Metabolism half-life Stable (7 - 22°C) MRID 43570301 (note 1)

Anaerobic Soil

Metabolism No data

Terrestrial Field Dissipation 16 to 20 days MRID 43646801 (note 1) Oregon and Washington st ate bare soil study Volatility - Laboratory No data

Ground Water Monitoring No data

Bioconcentration factor No data submitted Not expected to bioconcentrate based on low log Kow (-0.97) Notes: (1) No Data Evaluation Record (DER) available. Data is currently in review. Unreviewed results presented.

Environmental Fate/Exposure Summary:

## 10 This problem formulation is based on the data presented in Table I II.1., not all of which has been reviewed for acceptabili ty. All environmental fate studi es except batch equilibrium and hydrolysis are considered to be data gaps unt il review is completed. Based on the submitted environmental fate data, amitrole is non-volatile, very water-soluble, and m obile in soil-water systems. This combination of properties indica tes a strong tendency to pa rtition to water after terrestrial application. It s mobility in soil will be influenced by the cation exchange capacity of the soil, rather than organic car bon or clay content. The degrad ation studies show that amitrole is resistant to physical decay processes (hydr olysis and photolysis in water and on soil).

Metabolism of amitrole is very slow in an aerobic water-sediment, and slow in aerobic soil (half-lives of about a year). Soil metabo lism studies showed a large amount of unextracted residue, so half-lives were calculated based on carbon dioxide evolved. Aerobic aquatic metabolism appears to be the fastest degradation pr ocess for amitrole, with a half-life of about 70 to 85 days at 22°C. Interestingly, degradation wa s faster at 7°C (half-lif e 32 days) than at 22°C, which is counter-intuitive. This discrepancy may be explained by the fact that the water and sediment used in the experiment were from Sc otland, so the microbes may have been adapted to

a cold climate.

Based on the available data, it appears that terrestrially-applied amitrole will be transported by runoff and spray drift to water bodi es. Once transported to water, amitrole’s exact

rate of metabolization is unclear given the counter-intuitive data provided in the aerobic aquatic metabolism study and the relevance of using se diment from Scotland for an assessment of

amitrole’s fate and environmental effects in sediment typical of the United States.

Potential degradates of amitr ole with recognized effects include cyanamide (itself a registered plant growth regulator, PC code 014002) which was detected in the TFD study, and 1,2,4-triazole. Due to the stability of amitrole to many degradati on processes, it is unlikely that additional degradates of concern will be identified upon review of the data.

2. Herbicidal Mechanism of Action

Amitrole is an herbicide that belongs to the tr iazole chemical class wh ich are inhibitors of carotenoid biosynthesis. It is absorbed by foliage and r oots and prevents chlorophyll development.

3. Overview of Pesticide Usage

Amitrole is a terrestrial non-f ood herbicide used primarily in industrial areas (outdoors), non-agricultural rights-of-way, fencerows, hedge rows, and non-agricultural uncultivated areas and soils. The registrant requested voluntary can cellation of ornamental us es and/or shade trees,

and ornamental shrubs and vines at the time of the RED. Current labels include a technical product, a water dispersible granule, and a pr oduct in water soluble bags (formulation not specified on label). It is used to control a wi de range of perennial gr asses and broad-leaved weeds. Amitrole is applied at a rate of 4 lb product per acre, or 3.4 to 3.5 pounds active ingredient per acre.

## 11 Amitrole is not used on food crops – there is no human dietary e xposure. A drinking

water assessment will be conducted for amitrole as part of the registration review process. Amitrole has no dietary tolerances. At the time of the RED, Am itrole was classified as a B2- probable human carcinogen, and confirmed advers e effects on the thyroid gland had been identified. In 2006, the HED Cancer Assessmen t Review Committee (CARC) re-evaluated the carcinogenic potential of amitrole. The CARC classified amitrole as “ Not Likely To Be Carcinogenic To Humans At Doses That Do Not Alter Rat Thyroid Hormone Homeostasis”. A dermal exposure assessment was not conducted as part of the 1996 RED. The dermal NOAEL selected from the dermal developmental toxic ity study in the rabbit wa s high (1,500 mg/kg/day).



# IV. Receptors

1. Aquatic and Terrestrial Effects

The receptor is the biological entity that is exposed to the stresso r (EPA, 1998). Given its use as an industrial herbicide, many types of biological receptors (birds, mammals, terrestrial plants, freshwater fish, etc.) are expected to be potentially exposed to amitrole.

Consistent with the process described in the Overview Document (EPA, 2004), the risk assessment will use a surrogate species approach in its evaluation of amitrole. Toxicological data generated from surrogate test species, wh ich are intended to be representative of broad taxonomic groups, are used to extrapolate to poten tial effects on a variety of species (receptors)

included under these ta xonomic groupings.

Acute and chronic toxicity da ta from studies submitted by pesticide registrants along with the available open literature are us ed to evaluate the potential di rect effects of amitrole to the aquatic and terrestrial receptors identified in this section. This includes toxicity data on the technical grade active ingredient, degradates, and when available, formulated products (e.g. “SixPack” studies of mammalian toxic ity). The open literature studie s will be identified through EPA’s ECOTOX database (http://cfpub.epa.gov/ecotox/ ), which employs a literature search engine for locating chemical toxic ity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide insight into the direct and indirect effects of

amitrole on biotic communities from loss of species that are sensit ive to the chemical and from changes in structure and functional characte ristics of the affect ed communities.

Table IV.1a and Table IV.1b summarize the most sensitive ecological toxicity endpoints for terrestrial and aquatic organisms respectively based on an evaluation of both submitted studies and the open literature.

## 12 Table IV.1a: Applicable Terrestrial Am itrole measurement endpoints and va lues for use in RQ calculations

for the terrestrial effects determination

Assessment Endpoint Measures of Effect Species Toxicity Value Study

classification (Selection basis) Reference

Abundance (i.e., survival, reproduction, and growth) of

individuals and populations of birds Avian (single dose) acute oral 21-day LD 50 Northern bobwhite quail Colinus virginianus LD 50 > 2,150 mg/kg Acceptable MRID 00160451 (Fletcher, 1985)

Avian subacute 5-day dietary LC 50 Northern bobwhite quail C. virginianus,

Mallard duck Anas platyrhynchos,

and Ring-necked pheasant Phasianus

colchius Dietary sub-acute

LC 50 > 5,000 ppm Acceptable (Most sensitive) MRIDs 00160452, 00160476 (Fletcher, 1985) & 00022923 (Hill et al., 1975)

Avian reproduction

NOAEC Mallard duck Anas platyrhynchos Reproductive study NOAEC = 100 ppm 1 Acceptable (Most sensitive) MRID 45015402 (Gallagher et al., 1999)

Abundance (i.e., survival, reproduction, and growth) of

individuals and populations of

mammals Mammalian acute oral (single dose) LD 50 Rat Rattus norvegicus LD 50 = 4,080 mg/kg Acceptable (Most sensitive) No MRID number available (Gaines et al., 1997)

Mammalian 2- generation rat reproduction

NOAEL Rat Rattus norvegicus NOAEL = 15 ppm 2
or ~0.9 mg/kg/d Acceptable MRID 44016201

Survival of

beneficial insect populations Honey bee 72-Hr

acute contact LD 50 Honey bee ( Apis mellifera ) acute contact

LD 50 > 200 ug/bee Acceptable MRID 454571114 (Candolfi, 1996)

Survival and growth of terrestrial plants Seedling Emergence Monocot—No

Data NA NA NA

Dicot—No Data NA NA NA Vegetative Vigor Monocot –No Data NA NA NA

Dicot—No Data NA NA NA

1 

### Based on reduced mean adult male body weight, egg production and feed consumption observed at 350 ppm.

2 

### Based on clinical signs of toxicity, mortality, and decreases in body weight, body weight gained, food consumption, food efficiency, decreases in mating and fertility indices, implantation sites/litter and mean pup male/female ratio and selected absolute and relative organ weights, increases in thyroid weight and activity, slightly longer gestation interval, follicular cell hypertrophy, and hyperplasia an d nodular hyperplasia and/or adenoma, hepatocellular hypertrophy and other microscopic changes in the adrenals liver, pituitary, mammary gland and kidney, and a high incidence of pseudopregnancy observed at 112.5 ppm.

## 13 Table IV.1b: Applicable Amitrole en dpoints and values for use in RQ ca lculations for the aquatic effects

determination

Assessment Endpoint Measures of

Effect Species % Test

Material (TGAI) Toxicity

Value Study

classification (Selection basis) Reference

Survival and reproduction

of

individuals

and

communities

of freshwater

fish Freshwater fish

acute 96-hr

LC 50 Fathead Minnow Promephales promelas

& Channel catfish Ictalurus punctatus TGAI

90% > 100 ppm Acceptable (most sensitive) MRID 40094602 (Johnson & Finley, 1980)

Freshwater fish early life-stage

NOAEC No Data

NA NA NA NA

Survival and reproduction

of

individuals

and

communities

of freshwater

invertebrates Freshwater

invertebrate

acute 48-hr

EC 50 Water flea ( Daphnia magna ) TGAI

91.8% 18.0 ppm Acceptable (most sensitive) MRID 00160455 (Forbis, 1985)

Freshwater

invertebrate reproductive

NOAEC Water flea ( Daphnia magna ) TGAI

96.5% 0.32 ppm 1 Supplemental (most sensitive) MRID 44342301 (Heimbach., 1994)

Survival and reproduction

of

individuals

and

communities

of estuarine

and marine

fish Estuarine and

marine acute

96-h LC 50 Sheepshead minnow Cyprinodon variegats TGAI

94.3% > 1000 ppm Acceptable MRID 42817801 (Collins, 1993)

Estuarine and

marine reproductive

NOAEC No Data

NA NA NA NA

Survival and reproduction

of

individuals

and

communities

of estuarine

and marine

invertebrates Estuarine and

marine

invertebrate

acute
96-hr LC 50 Mysid Shrimp Americamysis bahia TGAI

98.2% 2.8 ppm Acceptable (most sensitive) MRID 42818201 (Collins, 1993b)

Estuarine and

marine

invertebrate reproductive

NOAEC Mysid Shrimp Americamysis bahia NA 0.050 ppm 2 NA ACR Calculation 2

Standing

crop or biomass and growth of aquatic plants Freshwater green algae, cyanobacteria

or diatom

120-hr IC 50 for biomass. Freshwater Diatom Navicula pelliculosa

TGAI

91.7% 1.4 ppm Acceptable MRID 44563102 (Palmer & Krueger, 1998)

Vascular aquatic plants 14-Day IC 50 Duckweed Lemna gibba TGAI

91.7% 2.5 ppm Acceptable MRID 44548803 (Palmer & Krueger, 1998)

1 

### Based on reduced adult length observed at 0.56 ppm. Decreased reproduction was observed at 1.0 ppm.

2 

### In the absence of acceptable data, an acute to ch ronic ratio (ACR) calculation value will be generated by examining the range of ACR va lues for amitrole effects to freshwater in vertebrates and applying it to the acute saltwater value to obtain a chronic estuarine/marine invertebrate endpoint. This results in a freshwater invertebrate

ACR of 56.25.



## Previously, the supplemental study, MRID 42813702, had been used to provide data on vegetative vigor to support the re gistration of amitrole. However, there were a num ber of issues associated with this study including the use of TGAI in place of a typical end-use product (TEP),

## 14 use of calcium sulfate as a diluent, and a lack of negative controls. Th erefore, a new vegetative vigor study using TEP is needed to complete th e risk assessment on amitrole. Similarly, the previously acceptable seedling emergence study (MRID 44540101) has been downgraded to supplemental based on the use of TGAI instead of TEP. A new seedling emergence study using TEP is needed to complete the risk assessment. If data is provided show ing that surfactants and other inert ingredients in the formulation will disassociate rapidly from the active ingredient, then the requirement for a new seedling emergen ce study could be waived (a vegetative vigor study using TEP would still be required).

The acute freshwater fish and invertebrate stud ies used nominal concentrations, with no data provided on mean-measured concentrations. Howeve r, because amitrole is very stable in water (in static toxicological studies th at did measure concentrations, th e lowest analytical recoveries were approximately 85% after 48—9 6 hours), the endpoints from these studies can be used in the risk assessment, although the uncertainty of us ing nominal concentrations will need to be

characterized.

Data gaps exist for amitrole’s effect on terrestria l plants, though given its mode of action and use as an herbicide, risk is expected to terrestrial non-target plants. There is al so a lack of data on

amitrole’s chronic effect on fish and saltwater invertebrates.

2. Degradate toxicity

One of the known degradates of am itrole is cyanamide, a registered plant growth regulator, PC code 014002. Cyanamide appears to be slightly more toxic to aquatic plants than amitrole with

an EC 50 

## of 0.65 ppm for Anabaena flos-aquae . Cyanamide also appears to have similar acute toxicity to freshwater and saltwater invertebra tes, but may be significantly more toxic on a chronic basis with a NOAEC of 0.1 ppm for adult daphnids. Additiona lly, Cyanamide appears

to be more toxic than amitrole to freshwa ter and saltwater fish with reported LC 50 

## values ranging from 46 ppm for rainbow trout (MRID 073728) to 88 ppm for bluegill (ACC. No. 073728). Chronic effects of cyanamide also occurred on rai nbow trout at the lowest concentration tested, 0.507 ppm (MRID 44076701).

For terrestrial effects, cyanamide appears to be significantly more acutely toxic than amitrole to birds, with an acute oral LD 50 

## of 173 mg/kg for bobwhite, though cyanamide does not appear to be toxic on a sub-acute dietary ba sis. Preliminary review of a chronic avian reproduction study (MRID 45797201) indicated that cyanamide may be le ss toxic to birds on a chronic basis, than amitrole. Like amitrole, cyanamide is practically non-toxic to bees and ap pears to have similar toxicity to terrestrial plants (most sensitive plant was onion for seedling emergence with an EC 50 

## of 0.79 lbs a.i./acre and tomato for vegetative vigor with an EC 50 

## of 3.1 lbs a.i./acre. In the supplemental seedling emergence and vegetative vigor data for amitrole, the most sensitive endpoints were cabbage for seedling emergence with an EC 25 

## of 0.24 lbs a.i./A and onion for vegetative vigor with an EC 25 

## of 0.93 lbs a.i./acre).

Data gaps were identified in the 2007 problem fo rmulation for cyanamide’s effect on terrestrial plants, and chronic effects to estuarine/marine fi sh and invertebrates. However, data was only requested for terrestrial plants. This data ha s been submitted and is currently under review.

## 15 Additionally, although a data gap fo r chronic effects of cyanamide to freshwater fish was not identified in the problem formulation, the onl y data available is fo r a supplemental study on rainbow trout (MRID 44076701) where effects occu rred at all concentrations. The problem

formulation stated that a NOAEC value would be estimated for use in the risk assessment; however the Fish ELS study is a hypothesis-tes ting based study and does not lend itself well to regression analysis. It would th erefore be inappropriate to use an estimated NOAEC in the risk assessment. Therefore, EFED will request chronic data for cyanamide on freshwater and

estuarine/marine fish and estuarine/marine inve rtebrates as part of this risk assessment.

There is currently some uncertainty over whether other degradates of amitrole occur and at what rates do they appear. As more information on amitrole’s degradation becomes available (through review of the existing fate data, submission of additional data, or review of the open literature), additional metabolites, such as 1,2,4-triazole, may need to be evaluated in the risk assessment. Other than cyanamide, if additional major degrad ates are identified, EFED will attempt to assess their toxicity using Quantitative Structural Acti vity Relationships (QSARs) and use a total toxic residue approach to asse ss exposures to amitrole.

3. Formulations

Two acceptable studies using TEP on daphnids were submitted that indicate that formulations may potentially be more toxic to aquatic animals than the TGAI. MRID 46467106 using Weedazol TL (a 23.6% formulation, no longe r registered for use) had an EC 50 

## of 2.43 ppm a.i.

while MRID 46343713 used an 86% form ulation (granular) and had an EC 50 

## of 6.9 ppm a.i. A supplemental study on rainbow trout using W eedazol TL (MRID 46467105) found no effects at the limit dose treatment level of 20.05 ppm a.i. (95 ppm formulation). Where exposure to the formulation would occur in the environment, these data will be used for assessing both direct and indirect risks rather than the TGAI. Both of these formulations were significantly less acutely

toxic to rats than the TGAI.

4. Ecological Incidents

A preliminary review on April 19, 2011, of the Ec ological Incident Information System (EIIS, version 2.1), which is maintained by the Agency ’s Office of Pesticide Programs, and the Avian Monitoring Information System (AIMS), whic h is maintained by the American Bird Conservancy, indicates that no inci dents associated with the use of amitrole have been reported to the Agency. Additionally, no inci dents involving amitrole have b een reported to the Agency in aggregated incident reports. The absence of re ported incidents should not be construed as the absence of incidents. Incident reports for non- target organisms typica lly provide information only on mortality events and plant damage. Subl ethal effects in organisms such as abnormal behavior, reduced growth and/or impaired repr oduction are rarely reported, except for phytotoxic effects in terrestrial plants. EPA’s changes in the registrant reporting re quirements for incidents in 1998 may account for a reduced number of re ported incidents. Registrants are now only required to submit detailed information on ‘major’ fi sh, wildlife, and plant in cidents. Minor fish, wildlife, and plant incidents, as well as all other non-target in cidents, are generally reported

## 16 aggregately and are not included in EIIS. In addition, there have been changes in state monitoring efforts due to a lack of resources.

5. Ecosystems Potentially at Risk

The ecosystems at risk are often extensive in scop e, and as a result it may not be possible to identify specific ecosystems during the development of a baseline risk assessment. However, in general terms, terrestrial ecosystems potentially at risk could include the treated area and areas immediately adjacent to the treated area that may r eceive drift or runoff. Areas adjacent to the treated area could include cultivated fields, fenc erows and hedgerows, meadows, fallow fields or grasslands, woodlands, riparian habita ts and other uncultivated areas.

Aquatic ecosystems potentially at risk include wa ter bodies adjacent to or downstream from, the treated area and might include impounded bodies such as ponds, lakes and reservoirs, or flowing waterways such as streams or rivers. For uses in coastal areas, aquatic habitat also includes marine ecosystems, including estuaries.



# V. Assessment Endpoints

Assessment endpoints are defined as "explicit expressions of the actual environmen tal value that is to be protected." Defining an assessment endpoint involves two steps: 1) identifying the valued

attributes of the environment that are considered to be at risk; and 2) operationally defining the assessment endpoint in terms of an ecological entity (i.e., a community of fish and aquatic invertebrates) and its attributes (i.e., survival and reproduction). Th erefore, selection of the assessment endpoints is based on valued entities (i.e., ecological receptors), the ecosystems potentially at risk, the migration pathways of pesticides, and the routes by which ecological receptors are exposed to pesticide-related c ontamination. The selection of clearly defined assessment endpoints is important because they provide direction and bou ndaries in the risk assessment for addressing risk management issu es of concern. Changes to assessment endpoints are typically estimated from the available toxici ty studies, which are used as the measures of effects to characterize potential ec ological risks associated with e xposure to a pesticide, such as

amitrole.

To estimate exposure concentratio ns, the ecological risk assessmen t considers applications at maximum rates. If multiple applications are a llowed, the maximum amount per application and minimum interval between applications are used – provided that maximum total annual application amounts are also incl uded in this configuration.

Several EFED exposure models (e.g., PRZM-EXAMS, T-REX) are us ed to estimate high-end exposure to amitrole. The most sensitive toxicity endpoints are used from surrogate test species

to estimate treatment-related direct effects on acute mortality and 15 chronic reproductive, growth and survival assessment endpoints. Toxic ity tests are intended to determine effects of pesticide exposure on birds, mammals, fish, terrest rial and aquatic invert ebrates, and plants. These tests include short-term acute, sub-acu te, and reproduction studies and are typically arranged in a hierarchical or tie red system that progresses from ba sic laboratory tests to applied field studies. The toxicity studi es are used to evaluate the pot ential of a pesticide to cause

## 17 adverse effects, to determine whether further tes ting is required, and to determine the need for precautionary label statements to minimize the pot ential adverse effects to non-target animals and plants.



# VI. Conceptual Model

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically significant c oncentrations. An exposure pathway is the means by which a pesticide

moves in the environment from a source to an eco logical receptor. For an ecological pathway to be complete, it must have a source, a release mechanism, an environmental transport medium, a point of exposure for ecological receptor s, and a feasible route of exposure.

A conceptual model for amitrole provides a wr itten description and visual representation of the predicted relationships be tween amitrole, potential routes of exposure, and the predicted effects for the assessment endpoint. A conceptual model consists of two major components: risk hypothesis and a conceptual diagram (EPA, 1998).

As discussed previously, an ecological ri sk assessments was conducted by EFED for

amitrole in the national level risk assessment supporting the RED (USEPA 1996) This previous

assessment and more recent data serve as a basi s for the risk hypothesis and conceptual model developed for current registered uses of amitrole.

1. Risk Hypothesis

For amitrole, the following ecological risk hypo thesis is being employed for this baseline

risk assessment:

Amitrole, when used in accordance with the label, results in potential adverse effects upon the survival, growth, and reproduction of non-target terrestrial and aquatic organisms. Given the degree of persistence of amitrole and its degree of mobility, there is a likelihood of exposure to terrestrial and/or aquatic organisms These nontarget organisms include Federally-listed th reatened and endangered species.

2. Conceptual Diagram

The potential exposure pathways and effect s of the non-crop uses of amitrole as an herbicide are depicted in Figure 1 for Aquatic Organisms/Plants, and in Figures 2-3 for

Terrestrial Animals/Plants . Solid arrows depict the most likel y routes of exposure and effects; dashed lines depict potential rout es of exposure not considered likel y for amitrole. As depicted in these figures, transport mechanisms ( e.g . sources) for amitrole applied on non-crop use sites may result in the movement of the pesticide into aqua tic (water) and terrestrial (soil) habitats. The movement away from the site of application repr esents exposure pathways for a broad range of biological receptors of concern (non-target animals) and the potential attribute changes, i.e.

, effects such as reduced survivals, gr owth, and reproduction in the receptors.

## 18 The environmental fate properties of amitrole an d its degradates of concern indicate that leaching, runoff and spray drift represent poten tial transport mechanisms of amitrole and its major degradates to aquatic and terrestrial organisms.

For amitrole, spray drift exposure to terrestrial and a quatic ecosystems potentially occurs through off site drift from non-crop land use sites. Exposur e to terrestrial and aquatic ecosystems through runoff and erosion occurs as a result of amitrole’s mobility and its persistence. These transport mechanisms and resulting movement of amitrole into aquatic habitats (water) and terrestrial habitats (soil and foliage) are depicted in Fi gures 1-3. These figures also depict exposure pathways for a broad range of biological receptors of concern (nontarget animals and plants) and the potential attribute changes, i.e., effects such as reduced surv ival, growth and reproduction, that may occur in the receptors due to e xposure to amitrole and its major degradates.

2.1. Non-Significant Pathways

Non-significant pathways are represented with a dashed line in the conceptual diagram. No

bioconcentration studies have been conducte d with amitrole, however with a log K

ow 

## of -0.97, amitrole bioaccumulation th rough the aquatic food chain does not appear to be a significant pathway.

Exposure through aquatic sediment may not be a pathway of concern provided amitrole’s K d 

## is <

50 and the K

oc 

## is < 1,000. The 1996 RED described low K d 

## s ranging from 0.152 to 0.922 ml/g

and K

oc 

## s ranging from 11.6—51.2. Assuming the review of the existing fate data or submission

of additional data confirm thes e low values, then exposure thr ough sediment will not be viewed as a significant pathway. Atmospheric depos ition due to volatiliza tion is unlikely due to amitrole’s low vapor pressure of 4.4 x 10 -7 

## mmHg.

## 19 Figure 1: Conceptual model depict ing stressors, exposure pathways, and potential effects to aquatic organisms from the use of amitrole to non-food crop use sites. Dotted lines indicate exposure pathways that have a low likelihood of contributing to ecological risk. 

## Stressor

Source

Receptors

Attribute Change Amitrole and its Resulting Degradates Applied to Non-Food Crop Use Sites

Spray drift

Aquatic animals

Invertebrates

Vertebrates

Individual org anisms

Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae and

vascular plants Reduction in prey

Modification of PCEs

related to prey availability Habitat integrity Reduction in primary productivity

Reduced cover Community change

Modification of PCEs related to

habitat Surface water/

Sediment 1 Runoff

Aquatic Animals
Invertebrates

Vertebrates 

## Exposure

Media

Uptake/gills or integument

Ingestion Ingestion Atmospheric transport

Wet/dry deposition Soil Leaching to

Groundwater

Uptake/gills or integument

Aquatic Plants

Non-vascular
Vascular Uptake/cell,
roots, leaves Riparian p lan ts

terrestrial

exposure pathways (see Figure 3)

1 Exposure through sediment may not be a pathway of concern pr ovided a review of the fate data show that amitrole’s K d is < 50 and the K oc is < 1,000.

## 20 Figure 2: Conceptual mode l depicting stressors, generic exposure pathways, and potential effects to terrestrial organisms (terrestrial plants, terrestrial in vertebrates, and dietary routes of exposure for terrestrial vertebrates) from the use of amitrole to amit role non-food crop use sites. Dotted lines indicate exposure pathways that have a low likelihoo d of contributing to ecological risk.

## 21 Figure 3: Conceptual mode l depicting stressors, drinking water and inhalation exposure pathways, and potential effects to terrestrial animals from the use of amitrole to non-food crop use sites. Dotted lines indicate exposure pathways that have a low like lihood of contributing to ecological risk.



# VII. Analysis Plan Options

In order to address the risk hypot hesis, the potential for adverse effects on the environment is estimated. The use, environmental fate, and ecolo gical effects of amitrol e are characterized and integrated to assess the risks. Integration of exposure and eff ects is accomplished using a risk quotient (RQ: ratio of exposure concentration to effects concentration) approach. Although risk

is often defined as the likelihood and magnitude of adverse ecologi cal effects, the risk quotientbased approach does not provide a quantitative estimate of likelihood and/or magnitude of an adverse effect. However, as outlined in the Overview Document (USEPA 2004b), the likelihood of effects to individual organi sms from particular uses of am itrole, if exposure occurs, is estimated using the probit dose-response slope and either the LOC or the actual calculated RQ value. This analysis plan will be revisited and may be revised depending upon the information submitted by the public in response to the openi ng of the Registration Review docket for

amitrole.

## 22 1. Measures of Effects and Exposure

1.1 Measures of Aquatic Exposure

In order to estimate risks of amitrole exposures in aquatic and terres trial environments, all exposure modeling and resulting risk conclusi ons will at a minimum be based on maximum application rates and methods, and will be estimated for each use of amitrole. Uses with the same application rates and intervals applied to the crop s grown in similar areas will be grouped for this analysis. Additional modeling may be performed where refinement of application rates other

than maximum or intervals other than minimu m will aid in informing risk decision options.

Because of amitrole’s non-agricultural use pattern, the Tier 1 exposure model, GENEEC (GENeric Estimated Environmental Concentration) will be used in the initial risk screen to predict aquatic (surface water) EEC s and sediment pore water concentrations using the soil/water partition coefficient and degradation kinetic data to estimate runoff from a ten hectare field into a one hectare by two meter deep "standard" pond. Should any taxa exceed the level of concern, the Tier II models, the Pesticid e Root Zone Model coupled with the Exposure Analysis Model System (PRZM/EXAMS) will be used with non-agricultural scenarios. PRZM (v3.l2.2, May 2005) and EXAMS (v2.98.4.6, April 2005) are simulation models coupled with the input shell pe5.pl (Aug 2007). The models gene rate daily exposures and calculated l-in10 year acute and chronic EECs of amitrole that may occur in surface water bodies adjacent to application sites receiv ing amitrole through runoff and spray drift. PRZM simulates pesticide application, movement, and transformation on an agricultural field and th e resultant pesticide loadings to a receiving water body via runoff, eros ion and spray drift. PRZM scenarios have also been adapted to address non-agricu ltural applications. EXAMS simula tes the fate of the pesticide in the water body and estimates resulting concentr ations in surface water and sediment. The standard scenarios used for ecological pesticide assessments for crop land assume application to a 10-hectare agricultural field that drains into an adjacent l-hectare water body that is 2 meters deep (20,000 m3 volume) with no ou tlet. The measure of exposure fo r aquatic species is the 1in10 year return peak or rolling mean concentratio n. The 1-in-10 year peak is used for estimating acute exposure to aquatic organisms. The l-in- 10-year 60-day mean is used for assessing chronic exposure to fish and aquatic-pha se amphibians. The 1-in-10 y ear 21-day mean is used for assessing chronic exposure to aquatic invertebrates. Surrogate scenarios will be used to simulate the dominant non-ag uses ( e.g. right-of-way, ornamentals, etc.).

1.2. Measures of Terrestrial Exposure

Exposure estimates for terrestrial an imals assumed to be in the target area or in an area exposed to spray drift are derived using the T-RE X model (version 1.4.1, 10/09/2008). This model incorporates the Kenega nomogr aph, as modified by Fletcher et al. (1994)

, which is based on a large set of field residue data . The upper limit values from the nomograph represent the 95th percentile of residue values from actual fiel d measurements (Hoerger and Kenega 1972). The

Fletcher et al. (1994) modifications to the Kenega nomograph are based on measured field residues from 249 published research papers, incl uding information on 118 species of plants, 121 pesticides, and 17 chemical classes.

## 23 EECs for terrestrial plants inhabi ting dry and riparian/wetland areas adjacent to the target area are derived using TerrPlant (v ersion 1.2.2, 12/26/2006). This model us es estimates of pesticides in runoff and in spray drift to calculate EECs. EECs are based upon solubi lity, application rate and minimum incorporation depth.

Two spray drift models, AgDisp and AgDRIFT are used to assess the distance from the edge of the target area needed for spray drift residue levels to drop below LOCs for terrestrial plants, dietary items for wildlife, and effects to te rrestrial insects. AgDRIFT (version 2.01; dated 5/24/2001) (Teske et a12001) is used to simulate ground, aerial, and spray blast applications. To estimate potential spray drift de position at distances that ex ceed 1000 feet, AGDisp (version 8.13; dated 12/14/2004) (Teske and Curbishley 2003) is used, whic h simulates aerial and ground applications using a Gaussi an far-field extension.

1.3. Terrestrial Animal Drinking Water Exposure

The Screening Imbibition program (SIP v.l.O, Released June 15, 2010) was used to calculate an upper bound estimate of exposure using amitrole's solubility (28,000 ppm), the most sensitive

acute and chronic avian toxi city endpoints (bobwhite LD 50 

## > 2150 mg/kg and mallard NOAEC = 100 ppm) and the most sensitive acute and ch ronic mammalian toxicity endpoints (rat with

LD 50 

## = 4008 mg/kg and NOAEL = 0.9 mg/kg). Drinki ng water exposure alone was determined to be a potential pathway of concern for avian and mammalian species on an acute and chronic

basis.

However, at least on an acute basis, although amitrol e did not pass this Tier I screen, this concern

is based more on the solubili ty of the chemical, rather than its actual toxicity.

This pathway will be explored further with the development of SIP v.2.0 in the Ecological Risk Assessment for amitrole. For a sample of the output generated by SIP v.l.O, please see Appendix B. Detailed information about the SIP v.l.O, as well as the tool, can be found on the EPA's

website at http://www.epa.gov/pesticides/s cience/modelspg.htm#terrestrial

1.4. Inhalation Exposure

The S creening T ool for I nhalation R isk (STIR v.1.0, November 19, 2010) is used to calculate an upper bound estimate of exposure using a pesticide’ s vapor pressure and molecular weight for vapor phase exposure as well as the maximum a pplication rate and method of application for spray drift. STIR incorporates results from several toxicity studies including acute oral and inhalation rat toxicity endpoints obt ained from the “six-pack” of core studies, which are a series of six guideline studies that are submitted to the Registration Division of the Office of Pesticide Programs for technical and formulat ed products of a pesticide as well as the most sensitive acute oral avian toxicity endpoint. STIR could not be used to screen amitrole’s risk through inhalation exposure since a needed input, the rat inhalati on study, was not available. Therefore, EFED cannot evaluate the risk posed by inhalation expos ure. Without additional information, EFED cannot preclude inhalation exposure as a significan t pathway for exposure to amitrole. However, the chemical vapor pressure is very low (4.4E-07) a nd so amitrole is unlik ely to volatize in appreciable concentrations. HE D is requesting a rat inhalation study in their scoping document.

## 24 If rat inhalation data is submitted, EFED will use the models that are available at the time of the

risk assessment to assess avian and wild life inhalation risk from amitrole.

1.5. Measures of Effect

Ecological effect data are used as measures of di rect and indirect effect s to biological receptors. Data will be obtained from registrant-submitted st udies or from literature studies identified by ECOTOX. The ECOTOXicology databa se (ECOTOX) was searched in order to provide more ecological effects data to bridge existing data gaps. ECOTOX is a source for locating single chemical toxicity data and potential chemical mi xture toxicity data for aquatic life, terrestrial plants, and wildlife. ECOTOX was created and is maintained by the USEPA, Office of Research and Development, and the National Health and Environmental Effects Research Laboratory's Mid-Continent Ecology Division ( http://cfpub.epa.gov/ecot020 ). The effects data for amitrole and its degradates may be revised depending upo n the information submitted by the public in response to the opening of the Re gistration Review docket for amitr ole. Additionally, the effects data may be revised as the quality and scie ntific soundness of thos e ECOTOX studies with amitrole or its degradates that were identified as potentially fulfilling a data gap, or as more sensitive than current values, ar e reviewed. When guideline or open literature studies are not available, a quantitative structur e-activity relationship (QSAR) m odel may be used as a surrogate

to estimate the effects.

Where available, sublethal effects observed in both registrant-submitted and open literature studies will be evaluated qualitatively. Such effects have include d behavioral changes (e.g., lethargy, changes in coloration a nd effects olfaction). Quantitati ve assessments of risks, though, are limited to those endpoints that can be direc tly linked to the Agency's assessment endpoints of impaired survival, growth, and reproduction.

The assessment of risk for direct effects to non-target organisms makes the assumption that toxicity of amitrole and its degradates to bird s is similar to terrestrial-phase amphibians and reptiles. The same assumption is made for fish and aquatic-phase amphibians.

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

## (Lethal Dose),

LC 50 

## (Lethal Concentration) and EC

x 

## or IC

x 

## (Effects Concentration or Inhibition Concentration).These measures of acute toxicity result in 50% or x% of the respective effect in tested organisms. The endpoints for chroni c measures of exposure are the NOAEC (No Observed Adverse Effects Concentration) and the NOAEL (No Observed Adverse Effects Level). For plant species, in the case where a NOAEC cannot be determined, the IC 05 

## or EC 05 

## is used. The use of this endpoint in place of th e NOAEC can introduce a large degree of uncertainty

due to the need to extr apolate this endpoint in some cases and the high de gree of variability in the plant metrics as compared to a 5% inhibiti on. The methods used to assess the risk are

consistent with those outlined in the document “Overview of the Ecological Risk Assessment

Process in the Office of Pes ticide Programs” (USEPA, 2004).

Information on the potential effects of amitrole on non-target animals is al so collected from the Ecological Incident Information System (EllS). Th e EllS is a database containing adverse effect

## 25 (typically mortality) reports on non-target organism s where such effects have been associated with the use of pesticid es. This document describes the lack of currently known incidents with historic registered amitrole uses. This descript ion will be updated for any new incidents that

occur between now and the c onduct of the risk assessment and effects determination.

1.6 Integration of Exposure and Effect

The exposure and toxicity effects data are inte grated in order to ev aluate the risks of adverse ecological effects on non-targ et species. For the risk a ssessment of amitrole, the risk quotient (RQ) method is used to compare estimate d exposure and measured toxicity values. The RQ method involves dividing es timated environmental concentrations (EEC) by acute and chronic toxicity values. The resulting RQs are then compared to the Agency’s Levels of Concern (LOC) (USEPA, 2004) ( Table VII.1 ). These criteria are us ed to indicate when applications of amitrole, as directed on the labe l, have the potential to cause adverse effects to non-target animals. In the absence of data for ei ther acute or chronic e ffects, the conservative assumption will be to presume that adverse risk effects cannot be precluded for amitrole and its degradates.

## 26 Table VII.1 - Agency Risk Quotient (RQ) Metrics and Levels 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

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

Aquatic Plants

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

### 1

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

EC 05 2 

### 1

Terrestrial Animals (mammals and birds)

Acute Potential for effects to non-listed animals from acute

exposures EEC/LC 50 

### (Dietary) 0.5 EEC/LD 50 

### (Dose)

Acute

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

### (Dietary) 0.2 EEC/LD 50 

### (Dose)

Acute Listed Species Listed species may be potentially affected by acute

exposures EEC/LC 50 

### (Dietary) 0.1 EEC/LD 50 

### (Dose)

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

Terrestrial Invertebrates

Acute Listed Species Listed species may be potentially affected by acute

exposures EEC/LD 50 

### 0.05

Terrestrial and Semi-Aquatic Plants

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

exposures EEC/ EC 25 

### 1

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

exposures EEC/ NOAEC or

EC 05 2 

### 1

1 

### LC 50 

### or EC 50



### . 2 

### An EC 05 

### is used when a NOAEC is not available



## 2. Stressors of Concern

2.1. Amitrole and its Degradates

The stressors of concern for this assessment include amitrole and its degradate, cyanamide. Other degradates of concern may be identified upon review of the environmental fate data which will be completed prior to initiation of the risk assessment, and may include 1,2,4-triazole. Due to a lack of data on parent amitrole, EFED is requesting chronic a quatic ecotoxicological studies on

## 27 fish and terrestrial plant seedli ng emergence and vegetative vigor st udies. Additionally, data is needed for an avian acute oral study conducted with a passerine species. In the 2007 problem formulation on cyanamide, EFED cited data ga ps of Tier II vegetative vigor and seedling emergence studies on terrestrial plants and ch ronic effects on estuarine/marine fish and invertebrates. However, the Final Work Plan for the Registration Re view of cyanamide only requested terrestrial plant data. This data will be reviewed and included as part of the amitrole risk assessment. Data gaps remain for the chr onic effects of cyanamide on estuarine/marine fish

and invertebrates and an additi onal data gap has been identifie d for the chronic effect of cyanamide on freshwater fish. Submission of thes e data would reduce uncertainties in the risk assessment. Cyanamide’s risk assessment for regi stration review is scheduled for 2012 and if the requested data is available it can be used in both risk assessments

2.2. Formulations

The available data indicate that Weedazol TL (a no longer registered formulation) and an unnamed (water soluble) granular formul ation are significantl y more toxic to Daphnia magna than the technical ingredient. AgDrift 2.01 was used as a screen to determine whether exposure of aquatic ecosystems due to spray drift coul d potentially be a concern. Using conservative assumptions of a maximum labeled use rate of 4.0 lbs ai/A, very-fine to fi ne droplet size, and a high boom, the 90 th 

## percentile concentration of the EPA-de fined pond at the edge of field due to spray drift is 0.0138 ppm. The LC 50 

## of the most sensitive species, Americamysis bahia was 2.8 ppm. Because the estimated drift EEC is lower than the acute LC 50 

## , formulated product testing

on fish or estuarine/marine invertebrates is not required. However, the available data from the

freshwater invertebrate studies wi th TEP will be used in the risk assessment to determine risk to aquatic animals due to spray drift.

2.3. Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of the 1994 RED decisi on, EPA reviewed these data and selected the most sensitive endpoints for relevant risk as sessment scenarios from the existing hazard database. However, as required by FFDCA secti on 408(p), amitrole is subj ect to the endocrine screening part of the Endocrine Di sruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a

## 28 chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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. Amitrole is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issu e future EDSP orders/data callins, requiring the submission of EDSP screening assays for amitrole. For further information on the status of the EDSP, the policie s and procedures, the lis t of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

.



# VIII. Endangered Species Assessment

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), EPA will evaluate risks to Federally-listed threat ened and/or endangered (listed) species from

uses of amitrole. This assessment will be condu cted in accordance with the Overview Document (USEPA 2004), provisions of the ESA, and the Services’ Endangered Species Consultation

Handbook (USFWS/NMFS 1998)

.

The assessment of effects associated with regi strations of amitrole is based on an action

area. The action area is consider ed the area directly or indirec tly affected by the federal action, as indicated by the exceedance of Agency Levels of Concern (LOCs) used to evaluate direct and indirect effects. The Agency’s approach to defining the action area under the provisions of the Overview Document (USEPA 2004) considers the results of the risk assessment process to

establish boundaries for that action area with the understandi ng that exposures below the Agency’s defined LOCs constitute a no-effect threshold. For th e purposes of this assessment,

attention will be focused on the footprint of the action ( i.e. , the area where amitrole application occurs), plus all areas where offsite transport ( i.e. , runoff, volatilization and long-range atmospheric transport, etc.) may result in potent ial exposure that exceeds the Agency’s LOCs. Specific measures of ecological effect that defi ne the action area for listed species include any

direct and indirect effects and/or potential modification of its cri tical habitat, including reduction in survival, growth, and reproductio n as well as the full suite of s ublethal effects available in the effects literature. Therefore, the action area ex tends to a point where environmental exposures are below any measured lethal or sublethal effect threshold for any biological entity at the whole organism, organ, tissue, and cellula r level of organization. In situ ations where it is not possible to determine the threshold for an observed effect, the action area is not spatially limited and is

assumed the entire United States.

## 29 

# IX. Drinking Water Assessment

The Health Effects Division is currently completing a Scoping Document for the registration review of amitrole. Given amitrole’s mobility and persistence, it may have the potential to contaminate ground water, although there is no evidence of groundwater contamination from amitrole residues. A drinking water assessment will be conducted for amitrole as part of the re gistration review process



# X. Clean Water Act

Amitrole is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at http://iaspub.epa.gov/waters10/at tains_nation_cy.control#causes (accessed 04/26/2011)

.

The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Wa ter Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process (see: http://www.epa.gov/oppfead1/cb/p pdc/2006/november06/session1-sop.pdf ) in order to ensure they can be used quantitatively or qual itatively in pesticide risk assessments.



# XI. Anticipated Data Needs

The Agency does foresee requiring additional fate and ecological effects studies prior to conducting the planned assessments. Data gaps, un certainties and potential paths forward for the

assessment of amitrole are described below.

1. Environmental Fate

The existing database of environmental fate studies for amitrole will be reviewed prior to the completion of the risk assessment, and Data Evaluation Records will be produced. The existing data was used in the 1996 RED, but standards fo r some studies have evolved and some studies may no longer be acceptable.

All environmental fate studies are considered data gaps at this time, except for batch equilibrium and hydrolysis. In the absence of additional da ta, EFED requests the following environmental

fate studies:

• Guideline Number: 835.2240, Study Title : Photodegradation in Water

• Guideline Number: 835.2410, Study Title : Photodegradation in Soil

• Guideline Number: 835.4100, Study Title: Aerobic Soil Metabolism

• Guideline Number 835.4200, Study Title: Anaerobic Soil Metabolism

• Guideline Number: 835.4300, Study Title: Aerobic Aquatic Metabolism

• Guideline Number: 835.4400, Study Title: Anaerobic Aquatic Metabolism

## 30 • Guideline Number: 835.6100, Study Title: Terrestrial Field Dissipation (If the currently unreviewed TFD study, MRID 43646801, is determined to be acceptable, only the Environmental Chemistr y Methods in Soil would be required)

• Guideline Number: 835.1410, Study Title: Volatility – Laboratory

• Guideline Number: 835.6200, Study Title: Aquatic Field Dissipation (only the Environmental Chemistry Methods in Water is required)

• Guideline Number: 835.7100, Study Title: Ground Water Monitoring

The registrant is asked for clarificati on on three studies. For aerobic soil metabolism studies, what U.S. soil is represented by the fo reign soil used? For aerobic aquatic metabolism studies, what U.S. soil is represented by the fore ign soil used? What is the explanation for the apparent discrepancy between the behavior of am itrole in laboratory stud ies (long half-life) and terrestrial field dissipation studies (short half-life)? A dditional studies will be required if these studies are not found to be acceptable.

2. Ecological Effects

Several toxicity studies with technical amitrole ar e needed to better assess the potential risk of amitrole exposure to non-target organisms. On the terrestrial side, no acceptable data are

available for the acute oral risk of amitrole to passerine bird species or effects to terrestrial plants.

For aquatic organisms, no data is available for the chronic risk of amitr ole to freshwater and

estuarine/marine fish and estuarine/mari ne invertebrates. 40 CFR 158 requires an estuarine/marine fish early life stage study and an estuarine/marine invert ebrate full life cycle because amitrole may enter the envi ronment in significant concentrations because of its expected use patterns ( i.e. rights-of-way uses), studies of other organisms (invertebrates) indicate that reproductive physiology of fish and/or invertebrates may be affected (MRID 44342301 showed reduction in egg production and larval survival of daphnids), and because amitrole is stable in water (MRIDs 42843801, 42943201, 43099801, & 44687902). For estuarine/marine fish, in the absence of an estuarine/marine fish early life stage study, freshwater fish data will be used instead. For estuarine/marine invertebrates, in the absence of estuarine/marine invertebrate life cycle study, an ACR will be generated from the available freshwater invertebrate acute and chronic data and applied to the estuarine/mari ne acute invertebrate endpoint. Additionally, information is needed on amitrole’s degradate’s (cyanamide) chronic toxic ity to freshwater and

estuarine/marine fish and estuar ine/marine invertebrates. Wit hout this data, risk to aquatic organisms will have to be presumed. If environmental fate data is provided that shows that cyanamide is not a major degradate of amitrole, th an the uncertainties in the risk assessment for

amitrole would be reduced even if this data is not submitted.

## 31 40 CFR part

158 Test

Guideline (OPPTS) Requirement Description Test Species Are Data Available

for Risk Assessment? MRID Study

Classification

Birds and Mammals

71-1 (850.2100) Avian oral toxicity Northern bobwhite (TGAI) Yes MRID

00160451 Acceptable

Passerine study (TGAI) No Data Gap Data Gap

71-2 (850.2200) Avian dietary toxicity Northern bobwhite (TGAI) Yes 00160452 Acceptable

Mallard duck (TGAI) Yes 00160476 Acceptable

71-3 (850.2400) Wild mammal -- Not Required -- --

71-4 (850.2300) Avian reproduction Northern bobwhite (TGAI) Yes 45015401 Acceptable

Mallard (TGAI) Yes 45015402 Acceptable

Beneficial Insects

141-1 (850.3020) Honeybee acute contact toxicity Honeybee Yes 454571114 Acceptable

Fish

72-1 (850.1075) Freshwater fish acute toxicity Fathead

minnow/channel catfish (TGAI) Yes 40094602 Acceptable

Rainbow trout (TGAI) Yes 43923701 Acceptable

72-3 (850.1075) Marine/estuarine fish acute toxicity Sheepshead minnow (TGAI) Yes 42817801 Acceptable

72-4 (850.1400) Fish early life-stage (freshwater) Rainbow Trout (TGAI) No Data Gap Data Gap

Rainbow Trout (Degradate)

72-4 (850.1400) Fish early life-stage (saltwater) Sheepshead minnow (TGAI) No Data Gap Data Gap

Sheepshead minnow (Degradate) No Data Gap Data Gap

Aquatic Invertebrates

72-2 (850-1010) Freshwater invertebrate acute toxicity Water flea (TGAI) Yes 00160455 Acceptable

72-3 (850.1025) Bivalve acute toxicity (Shell deposition) Eastern oyster (TGAI) Yes 42837401 Acceptable

72-3 (850.1035) Crustacean acute toxicity Mysid (TGAI) Yes 42818201 Acceptable

72-4 (850.1300) Aquatic invertebrate life cycle (freshwater) Water flea (TGAI) Yes 44342301 Supplemental

72-4 (850.1350) Aquatic invertebrate life cycle (saltwater) Mysid (TGAI) No Data Gap Data Gap

Mysid (Degradate) No Data Gap Data Gap

Phytotoxicity

(850.4100) Tier II Seedling emergence 10 species (TEP) No Data Gap Data Gap

(850.4150) Tier II Vegetative vigor 10 species (TEP) No Data Gap Data Gap

123-2

850.4400

850.5400 Tier II aquatic plant growth (algal and aquatic vascular plant toxicity) with

TGAI . Duckweed (vascular) Yes 44548803 Acceptable

Freshwater diatom Yes 44563102 Acceptable

## 32 40 CFR part

158 Test

Guideline (OPPTS) Requirement Description Test Species Are Data Available

for Risk Assessment? MRID Study

Classification

Marine diatom Yes 44563101 Acceptable

Blue-green algae Yes 44548802 Acceptable

Green Algae Yes 44548801 Acceptable



## Ecotoxicological Studies Requested

Parent Amitrole

• Guideline Number: 850.1350, Study Title: Mysid Chronic Toxicity Test, TGAI (mysid shrimp, A. bahia)

• Guideline Number: 850.1400, Study Title: Freshwater Fish Early Life Stage Toxicity Test, TGAI (Rainbow Trout)

• Guideline Number: 850.1400, Study Title: Saltwater Fish Early Life Stage Toxicity Test, TGAI (sheepshead minnow)

• Guideline Number: 850.2100, Study Title: Ac ute Avian Oral Toxicity Test using a Passerine species, TGAI

• Guideline Number: 850.4100 Study Title: Seedling Emergence, Tier II, TEP (10 species)

• Guideline Number 850.4150, Study Title: Vegetative Vigor, Tier II, TEP (10 species)

Degradate Cyanamide

• Guideline Number: 850.1350, Study Title: Mysid Chronic Toxicity Test, degradate—Cyanamide (mysid shrimp, A. bahia )

• Guideline Number: 850.1400, Study Title: Saltwater Fish Early Life Stage Toxicity Test (sheepshead minnow, using the degradate, Cyanamide).

• Guideline Number: 850.1400, Study Title: Freshwater Fish Early Life Stage Toxicity Test, degradate—Cyanamide (ra inbow trout is the preferred species)



# XII. Open Literature

The Agency will conduct a search of the open literature to determine if any ecotoxicity data relevant to amitrole are available. If so, an evaluation will be made as to whether or not the data are adequate for use in a risk assessment. The Agency uses the ECOTOX database as its mechanism for searching the open literature. EC OTOX integrates three previously independent databases - AQUIRE, PHYTOTOX, and TERRETOX - into a system, which includes toxicity data derived predominately from the peer-reviewed literature for aquatic life, terrestrial plants,

## 33 and terrestrial wildlife, respectively.



# XIII. Bibliography

Fletcher, J.S, Nellessen, lE. & Pfleeger, T.G. (1994) Literature revi ew and evaluation of the EPA food-chain (Kenaga) nomagram, an instrument for estimating pesticide residues on plants. Envir on. Toxicol. Chern., 13, 1383-1391.

Hoerger, F. and E. E. Kenaga, 1972. Pesticide Resi dues on Plants: Correlation of Representative Data as a Basis for Estimation of their Magnit ude in the Environment. In F. Coulston and F. Korte, eds., Environmental Quality and Safety: Chemistry, Toxicology, and Technology, Georg Thieme Publ., Stuttgart, West Germany, pp. 9-28.

Teske M.E., and T.B. Curbishley. 2003. "AGDISP Version 8.07 User Manual." Technical Note No. 02-06. Continuum Dynamics, Inc., Ewing, NJ.

U.S. Environmental Protection Agency. 1996. Amitrole Reregistration Eligibility Decision. Office of Pesticide Programs, Special Review and Reregistration Di vision, Washington

D.C.

U.S. Environmental Protection Agency. 1998. Guidelines for Ecological Risk Assessment. Risk Assessment Forum, Office of Resear ch and Development, Washington, D.C. EPA/630/R-95/002F. April 1998.

U.S. Environmental Protection Agency. 2000. Risk Characterization Handbook. Science Policy Council, U.S. Environmental Protection Agen cy, Washington, D.C. 20460. EPA 100-B00-002. December 2000.

U.S. Environmental Protection Agency. 2004. Ov erview of the Ecological Risk Assessment

Process in the Office of Pes ticide Programs, U.S. Environmental Protection Agency. Endangered and Threatened Species Effect s Determinations. Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington, D.C. January 23, 2004.

U.S. Fish and Wildlife Service (USFWS) and National Marine Fisheries Service (NMFS). 1998. Endangered Species Consultation Handbook: Pr ocedures for Conducting Consultation

and Conference Activities Under Section 7 of the Endangered Species Act. Final Draft.

March 1998.34Appendix A: Summary of Toxicity dataTable 1. Summary of Submitted Aquatic Toxicity Datafor Amitrole that May be Used Quantitatively.StudyTypeTest SpeciesGenusSpeciesStudy TypeTGAI/ TEP% aiToxicity Endpoint (95%C.I.)SlopeMeasured/NominalExpressed in terms ofa.i.EffectMRID(Year)Classification Date ofDERCommentsAcute Freshwater FishAcute Emerald ShinerNotropisatherinoidesTEP%ainotprovided96-Hr LC50= 420 ppmNominal ConcentrationsMortality 00025435(1963)Supplemental07/08/1982No % active ingredient given. Formulation was listedas amitrol-T. Emerald shineris not a recommended testorganism. No dose mortality curve or data werepresented. An insufficient sample size was used. Thestatistical analysis used was not provided.Acute Rainbow TroutOncorhynchusmykissStaticTGAI96.5%96-Hr LC50> 1000 ppmMean-Measured00160454(1985)Acceptable09/24/1986Acute Bluegill sunfishLepomismacrochirusStaticTGAI96.5%96-Hr LC50> 1000 ppmNominal Concentrations00160453(1985)Acceptable09/24/1986Acute Bluegill sunfishLepomismacrochirusStaticTGAI90%96-Hr LC50> 180 ppmNominal43923702(1976)Acceptable07/15/1982No data (dose-response mortality, analyticalconcentrations) provided in the report.Acute Rainbow troutOncorhynchusmykissStaticTGAI90%96-Hr LC50> 180 ppmNominal43923701(1976)Acceptable07/15/1982No data (dose-response mortality, analyticalconcentrations) provided in the report.Acute Channel CatfishIctalurus punctatusTGAI90%96-Hr LC50> 160 ppm40094602(1982)35StudyTypeTest SpeciesGenusSpeciesStudy TypeTGAI/ TEP% aiToxicity Endpoint (95%C.I.)SlopeMeasured/NominalExpressed in terms ofa.i.EffectMRID(Year)Classification Date ofDERCommentsAcceptable07/15/1982Acute Fathead MinnowPimephalespromelasTGAI90%96-Hr LC50> 100 ppm40094602(1982)Acceptable07/15/1982Acute Rainbow TroutOncorhynchusmykissStaticTEP23.6%96-hr LC50> 20.05 ppm(mean measured)46467105(1995)Supplemental01/09/2006Supplemental due to being unable to calculate an LD50while not testing up to 100 ppm. Test material wasWeedazol TL with a listed purity of 236 g/L. Hardness(240 mg/L CaCO3) was higher than recommended.Number of fish/treatment level (7) met OECDrequirements, but was less than the 850.1075 guidelinerecommended 10 fish/treatment levelChronic Freshwater Fish—No quantitative studies availableAcute Estuarine/Marine FishAcute Sheepshead minnowCyprinodonvariegatesStatic-RenewalTGAI98.2%96-hr LC50> 1000 ppm(mean measured)NOEAC > 1000 ppmNo effect 42817801(1993)11/10/1993AcceptableChronic Estuarine/Marine Fish-no quantitative studies availableAcute Freshwater InvertebratesAcute Water FleaDaphniamagnaStaticTGAI% a.i.notgiven26-hr LC50= 23 ppb(15.3-44.4 ppm)Mortality 00017800(1966)Supplemental07/01/1982Test was only conducted for 26 hours, no indication ofthe percent active of the technical ingredient, and nodose-mortality data was published in this paper.Acute Water FleaDaphniamagnaStaticTGAI91.8%48-hr LC50= 18 ppm(16-21 ppm)Slope = 7.8 (4.5-11.1)nominal concentrationMortality 00160455(1985)Acceptable09/24/198636StudyTypeTest SpeciesGenusSpeciesStudy TypeTGAI/ TEP% aiToxicity Endpoint (95%C.I.)SlopeMeasured/NominalExpressed in terms ofa.i.EffectMRID(Year)Classification Date ofDERCommentsAcute Water FleaDaphniamagnaStaticTEP23.6%48-hr EC50= 2.43 ppm(1.99—3.10 ppm)Slope: N/Amean measuredImmobilization/mortality46467106(1995)Acceptable02/08/2006Test material was Weedazol TL with a listed purity of236 g/L. Hardness (224-230 mg/L CaCO3) was higherthan recommended. Not conducted in accordance withGLP.Acute ScudGammarus fasciatusStaticTEP21.6%> 100 ppm 05001497(1970)Supplemental09/17/1979Acute Glass shrimpPalaemoneteskadiakensisStaticTEP21.6%> 100 ppm 05001497(1970)Supplemental09/17/1979Acute SowbugAsellus brevicaudusStaticTEP21.6%> 100 ppm 05001497(1970)Supplemental09/17/1979Acute DaphniaDaphnia magnaStaticTEP21.6%30.0 ppm 05001497(1970)Supplemental09/17/1979Acute Seed shrimpCypridopsis viduaStaticTEP21.6%32.0 ppm 05001497(1970)Supplemental09/17/1979Acute WaterfleaDaphnia magnaStaticTEP21.6%26-Hr LC50= 40 ppm Mortality 05001465(1966)Supplemental08/31/1979Test was only 26 hours.Ammonium thiocyanate wasalso present in the formulation used and the %a.i. of this2ndcompound was not provided.Acute WaterfleaDaphnia magnaStaticTEP86%EC50= 6.9 ppm(4.67-10.24)Slope: N/AMean-MeasuredMortality/Immobilization46343713(1997)Acceptable04/28/2005Not reported whether aeration was used or not and thewater hardness (242-244 mg/L CaCO3) was higher thanrecommended. Formulation was water soluble granules.Chronic Freshwater Invertebrates37StudyTypeTest SpeciesGenusSpeciesStudy TypeTGAI/ TEP% aiToxicity Endpoint (95%C.I.)SlopeMeasured/NominalExpressed in terms ofa.i.EffectMRID(Year)Classification Date ofDERCommentsChronic Water FleaDaphniamagna21-day RenewalTGAI96.5%21-day NOAEC = 0.32ppmLOAEC = 0.56 ppmNominalGrowthEgg production,larval survivalaffected athighertreatment levels44342301(1994)Supplemental06/03/2002Only 10 daphnids tested/level. Did not includerecommended 3 test chambers with 5 daphnids each forsurvival testing. Presenceor absence of ephippia notreported. Dry weight not measured.Acute Estuarine/Marine InvertebratesAcuteShellDepositionEastern OysterCrassostreavirgninicaFlow-ThroughTGAI98.2%96-hr EC50> 110 ppmNOEC = 110 ppm42837401(1993)Acceptable11/05/1993Acute Mysid ShrimpAmericamysis bahiaStaticTGAI98.2%96-hr LC50= 2.8 ppm(2.5-3.3 ppm)Slope = 9.8 (5.7-14.0)Mean-measuredMortality 42818201(1993)Acceptable11/05/1993Chronic Esturarine/Marine Invertebrates– no quantitative studies availableAquatic PlantsTier II Green AlgaePsuedokirchneriellasubspicatumTEP23.6%72 hr EC50/IC50= 23 ppm(20-27 ppm)4.63Mean-measuredBiomass 46467113(1995)Supplemental1/4/2006Test duration was only 72 hours; less than the guidelinerequirement of 96 hours. The study should beconsidered for Tier I screening purposes only. Testmaterial was Weedazol TL with a listed purity of 236g/L.Tier II Marine diatomSkeletonemacostatumTGAI91.7%120 hr EC50= 3.0 ppm(2.5 – 3.5 ppm)Slope N/AMean-measuredCell density 44563101(1998)Acceptable11/5/1998Study was conducted using a 16-hour light/10-hour darkcycle.Tier IIFreshwater diatomNaviculapelliculosaTGAI91.7%120 hr EC50= 1.4 ppm(0.98 – 2.0 ppm)Mean-MeasuredCell density 44563102(1998)AcceptableOnly 3 replicates were utilized.38StudyTypeTest SpeciesGenusSpeciesStudy TypeTGAI/ TEP% aiToxicity Endpoint (95%C.I.)SlopeMeasured/NominalExpressed in terms ofa.i.EffectMRID(Year)Classification Date ofDERComments11/5/1998Tier II Green AlgaeSelenastrumcapricornutumTGAI91.7%120 hr EC50= 2.3 ppm(1.9-2.7 ppm)Slope N/AMean-MeasuredCell density 44548801(1998)Acceptable2/7/2000Tier II Blue-green AlgaeAnabaena flosaquaeTGAI91.7%120 hr EC50= 3.4 ppm(3.2 – 3.8 ppm)Slope N/AMean-measuredCell density 44548802(1998)Acceptable5/17/1999Tier II DuckweedLemnagibbaTGAI91.7%14-day EC50= 2.5 ppm(2.1 – 3.0 ppm)Slope N/AMean-measuredAverage FrondDensity44548803(1998)Acceptable5/7/2002Tier II Green AlgaePseudokirchneriellasubcapitataTGAI86%72-hr EC50= 18.0 ppm(14 – 22 ppm)4.39Mean-measuredCell Density 46343714(1997)Supplemental4/28/2005Test duration was only 72 hours; less than the guidelinerequirement of 96 hours. The study should beconsidered for Tier I screening purposes only.Abbreviations: TGAI = technical grade active ingredient; TEP=typical end use product; conc.=concentration; C.I. = confidence intervalTable 2. Summary of Submitted Aquatic Toxicity Data for Amitrole That May be Used Qualitatively, Were Open LiteratureStudies, or are Unacceptable.StudyTypeTest SpeciesGenus SpeciesStudy TypeTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/NominalExpressed in terms ofa.i.EffectMRID (Year)ClassificationDate of DERCommentsAcute Freshwater FishAcute Common carpCyprinusNo Data 00075203(1971)No details previded on %a.i., test water parameters or adose-mortality response. Unidentified formulation.39StudyTypeTest SpeciesGenus SpeciesStudy TypeTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/NominalExpressed in terms ofa.i.EffectMRID (Year)ClassificationDate of DERCommentscarpioInvalid07/12/1982Acute TenchTinca rulgarisNo Data 00075203(1971)Invalid07/12/1982No details previded on %a.i., test water parameters or adose-mortality response. Unidentified formulation.Acute Freshwater InvertebratesAcute WaterfleaDaphniamagnaTEP% ai notprovidedMortality 05020721(1966)Invalid07/09/1982Major inadequacies in this study were the use of aerated testchambers and the lack of discrete dose-mortality data.Acute WaterfleaDaphniamagnastaticTEP%ai notprovided05001497(1982)SupplementalNo dose mortality data presented.Acute PhantomMidgeChaoboruspunctipennisTEP50%No LD50value could begenerated96-Hr LOAEC = 5.6ppmmortalityNo emergence of adults occurred at concentrations above56 ppm. There was no control data provided.Acute CrayfishOrconectesnaisTEP21.6%05001497(1970)Invalid09/17/1979Acute Hard clamMercenariamercenariaUnclear ifTEP orTGAI used05002007(1969)Invalid09/11/1979Unclear whether technical grade and/or formulated productwere used. Also missing data on temperature, solventcontrol and water qualityAcute AmericanOysterCrassostreavirginicaUnclear ifTEP orTGAI used05002007(1969)Invalid09/11/1979Unclear whether technical grade and/or formulated productwere used. Also missing data on temperature, solventcontrol and water quality40StudyTypeTest SpeciesGenus SpeciesStudy TypeTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/NominalExpressed in terms ofa.i.EffectMRID (Year)ClassificationDate of DERCommentsAcute ScudGammarusfasciatusTGAI90%96-Hr LC50> 10 ppm40094602(1982)Acceptable07/15/1982Organisms were mature instead of the guidelinerequirement of early instar stages.Aquatic PlantsGreen AlgaeSelenastrumcapricornutum42813701(1993)Supplemental12/21/1994Supplemental due to contamination of three of nine controlreplicates. Other issues with inoculation occurred.Multiple counts of each replicate were not performed at allsampling times. Inadequate growth conditions occurred orcell counting methods were inadequate. Study was onlyconducted for 72 hours.Amitrole at the highestconcentration inhibited algal growth by more than 50%.Abbreviations: TGAI = technical grade active ingredient; TEP=typical end use product; conc.=concentration; C.I. = confidence intervalTable 3. Summary of Terrestrial Toxicity Data Submitted for Amitrole That May be Used Quantitatively.Study TypeTest SpeciesTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/ nominalEffectMRID(Year)Classification, DER dateor sourceCommentsMammalsAcute Oral LaboratoryRatRattusnorvegicusTGAI LD50> 24,000 mg/kg00063601Acute Oral LaboratoryRatTGAI LD50= 4,080 mg/kg Gaines et al.,1997From: Gaines, T.B.;Kimbrough, R.D.;41Study TypeTest SpeciesTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/ nominalEffectMRID(Year)Classification, DER dateor sourceCommentsRattusnorvegicusLinder, R.E.; (1973) TheToxicity of Amitrole inthe Rat: Toxicol. Appl.Pharmacol. 26:118-129.2-GenerationChronicLaboratoryRatRattusnorvegicusTGAI97-98%NOEL = 15 ppm (0.90mg/kg/day in males,1.23 mg/kg/day infemales.LOEL = 112.5 ppm(5.88 mg/kg/day inmales, 7.83 mg/kg/dayin females.Clinical signs of toxicity, mortality, anddecreases in body weight, body weightgained, food consumption, foodefficiency and selected absolute andrelative organ weights, increase in thyroidweight and activity, follicular cellhypertrophy and hyperplasia and nodularhyperplasia and/or adenoma,hepatocellular hypertrophy and othermicroscopic changes in the adrenals,liver, pituitary, mammary gland andkidney, a high incidence ofpseudopregnancy, decreases in matingand fertility indices, implantationsites/litter and mean pup male/femaleratio and a slightly higher gestationinterval.44016201BirdsAcute Oral BobwhitequailColinusvirginianusTGAI91.83%21-D LD50> 2,150mg/kg00160451(1985)Acceptable09/24/1986No sublethal effects ormortality observed.AcuteDietaryMallard DuckAnasplatyrhynchosTGAI91.83%8-D LC50> 5,000 ppm 00160476(1985)Acceptable09/24/1986AcuteDietaryBobwhitequailColinusvirginianusTGAI91.83%8-D LC50> 5,000 ppm 00160452(1985)Acceptable09/24/1986No mortality or sublethaleffects were observed.42Study TypeTest SpeciesTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/ nominalEffectMRID(Year)Classification, DER dateor sourceCommentsAcuteDietaryMallard duckAnasplatyrhynchosTGAI90%5-D LC50>5000mg/kg-bw00022923(1975)Acceptable07/15/1982AcuteDietaryRing-neckedpheasantPhasianuscolchicusTGAI90%5-D LC50>5000mg/kg-bw00022923(1975)Acceptable07/15/1982Nine birdsused/concentrationAcuteDietaryJapanesequailCoturnixjaponicaTGAI90%5-D LC50>5000mg/kg-bw00022923(1975)Supplemental07/15/1982Determined to besupplemental due to theuse of a non-guidelinespecies, Japanese quailAvianReproductionMallard DuckAnasplatyrhynchosTGAI91.7%22-Wk NOAEC = 100ppm22-Wk LOAEC = 350ppmReduced mean adult male body weight,reduced egg production, reduced feedconsumption45015402(1999)Acceptable03/18/2002The duration of the egglaying period withtreated diet was only 3weeks for both the 350and 1225 ppm treatmentgroups. However, theegg laying exposure inthe control and 100 ppmtreatment level was 11weeks. No treatmentrelated effects wereobserved in the 100 ppmtreatment level comparedto the control.AvianReproductionBobwhitequailColinusvirginianusTGAI91.7%22-Wk NOAEC = 450ppm22-Wk LOAEC = 2025ppmReduced % normal hatchlings, eggs set,live 3-wk embryos, 14-d hatchlings,weight of 14-d hatchlings45015401(1999)Acceptable03/18/2002Most sensitive endpoints:normal hatchlings/eggslaid, normalhatchlings/eggs set,normal hatchlings/live 3-wk embryos, 14-dsurvivors/eggs set, # and43Study TypeTest SpeciesTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/ nominalEffectMRID(Year)Classification, DER dateor sourceCommentsweight of 14-d oldsurvivorsTerrestrial InvertebratesAcutecontactHoneybeeApis melliferaTEP23.6% 72-hr LD50>200μg/beeNOEL = 200 μg/bee454571114(1992)Acceptable01/08/2006Test material wasWeedazol TL with alisted purity of 236 g/L.Acute Oral HoneybeeApis melliferaTEP23.6%72-hr LD50>200μg/beeNOEL = 100 μg/bee454571114(1992)Acceptable01/08/2006Mortality was 50% in thehighest treatment groupof 200 μg/bee. Testmaterial was WeedazolTL with a listed purity of236 g/L.AcuteContactHoneybeeApis melliferaTEP%ai notprovidedLD50> 10 μg/bee 00001999(1967)Acceptable12/3/1979TEP was described asamitrol AT.AcuteContactHoneybeeApis melliferaTEP%ai notprovided00036935(1975)Acceptable12/02/1981At 12.09 μg/bee,mortality was 4.1%.TEP used includedWeedazol, Cytrol, ATA.Terrestrial PlantsTier IISeedlingEmergenceBeanPhaseolusvulgarisTGAI91.7%EC25= 3.13 lbs ai/A(2.7—3.4)NOAEL = 0.63 lbsai/ANominalShoot Height 44540101(1998)Supplemental03/22/2002Amended04/30/2011TGAI used in place ofTEP. The organic mattercontent of the soil (2.8%)was greater thanrecommended (1.0%)Tier IISeedlingEmergenceCabbageBrassicaoleraceaTGAI91.7%EC25= 0.24 lbs ai/A(0.12—0.47)NOAEL = 0.10 lbsai/ANominalShoot Dry Weight 44540101(1998)Supplemental03/22/2002Amended04/30/2011TGAI used in place ofTEP. The organic mattercontent of the soil (2.8%)was greater thanrecommended (1.0%)Tier II Carrot TGAI EC25= 1.22 lbs ai/A Phytotoxicity44540101 TGAI used in place of44Study TypeTest SpeciesTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/ nominalEffectMRID(Year)Classification, DER dateor sourceCommentsSeedlingEmergenceDaucuscarota91.7%NOAEL = 0.63 lbsai/ANominal(1998)Supplemental03/22/2002Amended04/30/2011TEP. The organic mattercontent of the soil (2.8%)was greater thanrecommended (1.0%)Tier IISeedlingEmergenceLettuceLactucasativaTGAI91.7%EC25= 0.59 lbs ai/A(0.13—1.9)EC05= 0.06 lbs ai/ANominalShoot Dry Weight 44540101(1998)Supplemental03/22/2002Amended04/30/2011TGAI used in place ofTEP. The organic mattercontent of the soil (2.8%)was greater thanrecommended (1.0%)Tier IISeedlingEmergenceSoybeanGlycine maxTGAI91.7%EC25= 2.59 lbs ai/ANOAEL = 0.63 lbsai/ANominalShoot Height 44540101(1998)Supplemental03/22/2002Amended04/30/2011TGAI used in place ofTEP. The organic mattercontent of the soil (2.8%)was greater thanrecommended (1.0%)Tier IISeedlingEmergenceTomatoSolanumlycopersicumTGAI91.7%EC25= 0.81 lbs ai/ANOAEL = 0.25 lbsai/ANominalPhytotoxicity 44540101(1998)Supplemental03/22/2002Amended04/30/2011TGAI used in place ofTEP. The organic mattercontent of the soil (2.8%)was greater thanrecommended (1.0%)Tier IISeedlingEmergenceCornZea maysTGAI91.7%EC25> 3.9 lbs ai/ANOAEL = 1.6 lbs ai/ANominalPhytotoxicity 44540101(1998)Supplemental03/22/2002Amended04/30/2011TGAI used in place ofTEP. The organic mattercontent of the soil (2.8%)was greater thanrecommended (1.0%)Tier IISeedlingEmergenceOnionAllium cepaTGAI91.7%EC25= 0.93 lbs ai/ANOAEL = 0.25 lbsai/ANominalShoot Height 44540101(1998)Supplemental03/22/2002Amended04/30/2011TGAI used in place ofTEP. The organic mattercontent of the soil (2.8%)was greater thanrecommended (1.0%)45Study TypeTest SpeciesTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/ nominalEffectMRID(Year)Classification, DER dateor sourceCommentsTier IISeedlingEmergenceRyegrassLoliumperenneTGAI91.7%EC25= 1.79 lbs ai/ANOAEL = 0.63 lbsai/ANominalPhytotoxicity 44540101(1998)Supplemental03/22/2002Amended04/30/2011TGAI used in place ofTEP. The organic mattercontent of the soil (2.8%)was greater thanrecommended (1.0%)Tier IISeedlingEmergenceWheatTriticumaestivumTGAI91.7%EC25= 3.06 lbs ai/ANOAEL = 0.63 lbsai/ANominalPhytotoxicity 44540101(1998)Supplemental03/22/2002Amended04/30/2011TGAI used in place ofTEP. The organic mattercontent of the soil (2.8%)was greater thanrecommended (1.0%)Tier IIVegetativeVigorMaizeZea maysTGAI98.22%EC25= 0.57 lbs ai/A(0.35—0.90)NOAEL = 0.25 lbsai/ANominalPhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control wasnot included in the studydesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorPerrenial RyeLoliumperenneTGAI98.22%EC25= 0.17 lbs ai/A(0.01—2.00)NOAEL = 0.031 lbsai/ANominalPhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control wasnot included in the studydesign. TGAI used46Study TypeTest SpeciesTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/ nominalEffectMRID(Year)Classification, DER dateor sourceCommentsinstead of TEP.Tier IIVegetativeVigorOatsAvena sativaTGAI98.22%EC25= 0.84 lbs ai/A(0.61—1.15)NOAEL = 0.50 lbsai/ANominalPhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control wasnot included in the studydesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorWheatTriticumaestivumTGAI98.22%EC25= 0.13 lbs ai/A(0.10—0.16)NOAEL = 0.031 lbsai/ANominalPhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control wasnot included in the studydesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorBush BeanPhaseolusvulgarisTGAI98.22%EC25= 0.25 lbs ai/A(0.21—0.29)NOAEL = 0.031 lbsai/ANominalPhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control wasnot included in the study47Study TypeTest SpeciesTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/ nominalEffectMRID(Year)Classification, DER dateor sourceCommentsdesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorCucumberCucumissativusTGAI98.22%EC25= 0.31 lbs ai/A(0.25—0.39)NOAEL = 0.13 lbsai/ANominalPhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control wasnot included in the studydesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorLettuceLactucasativaTGAI98.22%EC25= 0.24 lbs ai/A(0.15—0.39)NOAEL = 0.016 lbsai/ANominalPhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control wasnot included in the studydesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorRed PepperCapsicumanuumTGAI98.22%EC25= 0.17 lbs ai/A(0.15—0.20)NOAEL = 0.031 lbsai/ANominalPhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control was48Study TypeTest SpeciesTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/ nominalEffectMRID(Year)Classification, DER dateor sourceCommentsnot included in the studydesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorPepperCapsicumanuumTGAI98.22%EC25= 0.20 lbs ai/A(0.09—0.44)NOAEL = 0.031lbsai/ANominalPhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control wasnot included in the studydesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorSoybeanGlycine maxTGAI98.22%EC25= 0.32 lbs ai/A(0.05—2.27)NOAEL = 0.031 lbsai/APhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control wasnot included in the studydesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorSunflowerHelianthusannuusTGAI98.22%EC25= 0.026 lbs ai/A(0.023—0.029)NOAEL = 0.016NominalPhytotoxicity 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, than49Study TypeTest SpeciesTGAI/TEP% aiToxicity Endpoint(95% C.I.)SlopeMeasured/ nominalEffectMRID(Year)Classification, DER dateor sourceCommentsa negative control wasnot included in the studydesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorRadishRaphanussativusTGAI98.22%EC25= 0.19 lbs ai/A(0.13—0.27)NOAEL = 0.13 lbsai/ANominalShoot Dry Weight 42813702(1993)Supplemental11/02/1993EC25and NOAEL valuesfor shoot height and dryweight were notdetermined.Calciumsulfate was used as adiluent during seedlinggermination. If this wasused for the control, thana negative control wasnot included in the studydesign. TGAI usedinstead of TEP.Tier IIVegetativeVigorLeekAlliumTGAI98.22%EC25= 1.05 lbs ai/A(0.70—1.57)NOAEL = 1.0 lbs ai/ANominal42813702(1993)Supplemental11/02/1993Amended09/11/1994Leek seeds demonstratedpoor control germination(< 60%). Calciumsulfate was used as adiluent. If this was usedfor the control, than anegative control was notincluded in the studydesign. TGAI usedinstead of TEP50Table 4. Summary of Terrestrial ToxicityData Submitted for Amitrole that MayOnly be Used Qualitatively or areUnacceptable/Invalid.Study TypeTest SpeciesTGAI orTEP% aiToxicityEndpoint(95% C.I.)SlopeMeasured/nominalEffectMRID (Year)Classification,DER date orsourceCommentsBirdsAcute Oral Mallard DuckAnasplatyrhynchosTEP23.6%NOEC forsublethal effects= 670 mg/kg-bw46467104(1995)Invalid01/03/2006Invalid due to regurgitation in thehighest dose of 2000 mg/kg-bw.Fasting period not specified. Nomortality or regurgitation was observedin any concentration up to andincluding 670 mg/kg-bw. Test materialwas Weedazol TL with a listed purityof 236 g/L.

## 51 

# Appendix B: Sample Inputs and Outputs from SIP

Table 1. Inputs

Parameter Value

Chemical name Amitrole
Solubility (in water at 25 o 

### C; mg/L) 28000

Mammalian LD 50 

### (mg/kg-bw) 4008 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg-bw) 0.9 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 

### (mg/kg-bw) 2150 Avian test species mallard duck Body weight (g) of "other" avian species Mineau scaling factor 1.15

Mallard NOAEC (mg/kg-diet) 100 Bobwhite quail NOAEC (mg/kg-diet) NOAEC (mg/kg-diet) for other bird species Body weight (g) of other avian species NOAEC (mg/kg-diet) for 2nd other bird species Body weight (g) of 2nd other avian species

Table 2. Mammalian Results

Parameter Acute Chronic Upper bound exposure (mg/kg-bw) 4816.0000 4816.0000 Adjusted toxicity value (mg/kg-bw) 3082.7956 0.6922 Ratio of exposure to toxicity 1.5622 6957.0794

Conclusion* Exposure through drinking water alone is a

potential concern for

mammals Exposure through drinking water alone is a

potential concern for

mammals

## 52 Table 3. Avian Results

Parameter Acute Chronic Upper bound exposure (mg/kg-bw) 22680.0000 22680.0000 Adjusted toxicity value (mg/kg-bw) 1116.3346 4.9613 Ratio of exposure to acute toxicity 20.3165 4571.4228

Conclusion* Exposure through drinking water alone is a

potential concern for
birds Exposure through drinking water alone is a

potential concern for
birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential for effects to non-target animals.