2 

At this time, we have the following questions for 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 metabolism study (MRID 430998-01 and 446879-02), what 

U.S. soil or sediment is represented by the sediment 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 (TFD) 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 scientifically 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 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 

• 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 ecotoxicological 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: Acute 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: Vegetative 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 regulator. The 2007 problem 

formulation for cyanamide (PC Code 014002) requested 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 nature of the amitrole use 

pattern, versus the limited use of cyanamide on fruit trees, makes it more likely that exposure of 

estuarine organisms will occur. Additionally, despite the submitted chronic freshwater fish ELS 

study (MRID 44076701) for cyanamide being considered supplemental due to effects being 

observed at all concentrations, the problem formulation did not consider 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 uncertainties in the risk assessment for amitrole. The supplemental fish ELS 

study does not fulfill the guideline requirement for a chronic freshwater fish study for 

cyanamide. Similar gaps and uncertainties for other chemicals have resulted in recent 

assessments where risk to certain taxa have been presumed due to the absence of data and 

reduced the opportunities to use mitigation 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 aquatic 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. Therefore, 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, using the degradate, Cyanamide)

Without 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, 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

Prepared by:

Michael Wagman, Biologist 

William P. Eckel, Ph.D. Senior Science Advisor 

U. S. Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch III

1200 Pennsylvania Ave., NW

Mail Code 7507P

Washington, DC 20460

Reviewed by:

Mark Corbin, Branch Chief

Date:

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, and Rodenticide Act (FIFRA), all pesticides 

sold or distributed in the United States generally must be registered by the Environmental 

Protection Agency (EPA). In determining whether a pesticide can be registered in the U.S., EPA 

evaluates its safety to non-target species based 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 ability to assess risk evolves and as policies and 

practices change, all registered pesticides continue to meet the statutory standard of no 

unreasonable adverse effects to human health and the environment. Changes in science, public 

policy, and pesticide use practices will occur over time. Through the new registration review 

program, the Agency periodically reevaluates pesticides 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 Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Agency is 

beginning its evaluation of amitrole to determine whether it continues to meet the FIFRA 

standard for registration. This problem formulation for the environmental fate, ecological risk, 

and endangered species assessment chapter in support of the registration 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 pesticide in the U.S. in 1948, and EPA issued a 

Registration Standard March 30, 1984. 

Amitrole is a terrestrial non-food herbicide used primarily in industrial areas (outdoors), 

non-agricultural rights-of-way, fencerows, hedgerows, non-agricultural uncultivated areas, soils, 

ornamental and/or shade trees, and ornamental shrubs and vines. 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 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.” This decision was based on the 

following: 

i) Treatment-related thyroid follicular cell tumors were seen in male and female rats (multiple 

strains) based on evidence provided collectively 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 considered sufficient to indicate that amitrole 

induced thyroid follicular tumors through an antithyroidal mode of action; 

v) Rats are substantially more sensitive than humans to the development of thyroid follicular 

cell tumors in response to thyroid hormone imbalance. 

Therefore, the previous quantification of carcinogenic potential as B2 is not applicable. 

EPA was concerned about dermal exposure and 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 products containing amitrole. Special Review 

addressed the use of amitrole on non-crop sites (highway rights-of-way, primarily), and by 

homeowners, and examined the carcinogenic risk to mixers, loaders and applicators. The data 

indicated that amitrole induced thyroid, 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 the liquid formulation to reduce 

splashing while pouring, the addition of protective clothing requirements to labels, and 

packaging of the wettable powder formulation in water soluble packets. The registrant 

voluntarily canceled all homeowner products. The registrant 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 powder 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 these 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 mixing/loading/applying amitrole. 

 

There are three registrations: 33688-6, 33688-10 (water 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 concluded 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 and for small mammals consuming 

short grass and insects. Since there was no mortality at the highest concentration in the avian 

dietary test, amitrole was considered to represent low acute risk to birds. The RED concluded 

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

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

to mammals exceeded the chronic LOC of 1.0 for small herbivores consuming short grass, seeds 

and insects, while chronic risk to birds, fish and aquatic invertebrates was not assessed due to a 

lack of data. Based on conclusions of the potential 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 environmental fate database was complete. After 

the RED was published, a generic DCI was issued (GDCI-004401-17739) in December 1996 to 

be conducted on the active ingredient: Guidelines 17-4(a) and (b), Avian reproduction studies 

and, Guideline 72-4(b), Aquatic Invertebrate 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 Testing: Seedling Emergence only, Guideline 123-2 

Aquatic Plant Testing: All five species, and Guidelines 231 and 232 Handler exposure study to 

provide dermal and inhalation data on mixers and loaders during the use of water-soluble 

packages. The Agency also required product-specific 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-m3

/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 Kow (20°C, pH7) - 0.97 EPISuite Physical property data, 

Footprint database 

pKa/pKb 4.14, 10.7 Footprint database 

KF (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 Stable pH5 – pH9 MRID 42843801 

Aqueous 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 state 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 III.1., not all of which 

has been reviewed for acceptability. All environmental fate studies except batch equilibrium and 

hydrolysis are considered to be data gaps until review is completed. Based on the submitted 

environmental fate data, amitrole is non-volatile, very water-soluble, and mobile in soil-water 

systems. This combination of properties indicates a strong tendency to partition to water after 

terrestrial application. Its mobility in soil will be influenced by the cation exchange capacity of 

the soil, rather than organic carbon or clay content. The degradation studies show that amitrole 

is resistant to physical decay processes (hydrolysis and photolysis in water and on soil). 

Metabolism of amitrole is very slow in anaerobic water-sediment, and slow in aerobic 

soil (half-lives of about a year). Soil metabolism 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 process for amitrole, with a half-life of about 70 

to 85 days at 22°C. Interestingly, degradation was faster at 7°C (half-life 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 Scotland, 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 bodies. 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 sediment from Scotland for an assessment of 

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

Potential degradates of amitrole 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 degradation 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 triazole chemical class which are inhibitors of 

carotenoid biosynthesis. It is absorbed by foliage and roots and prevents chlorophyll 

development. 

 3. Overview of Pesticide Usage 

Amitrole is a terrestrial non-food herbicide used primarily in industrial areas (outdoors), 

non-agricultural rights-of-way, fencerows, hedgerows, and non-agricultural uncultivated areas 

and soils. The registrant requested voluntary cancellation of ornamental uses 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 product in water soluble bags (formulation not 

specified on label). It is used to control a wide range of perennial grasses 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 exposure. 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, 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 

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 toxicity study in the rabbit was high (1,500 mg/kg/day). 

IV. Receptors 

 1. Aquatic and Terrestrial Effects 

The receptor is the biological entity that is exposed to the stressor (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, which are intended to be representative of broad 

taxonomic groups, are used to extrapolate to potential effects on a variety of species (receptors) 

included under these taxonomic groupings. 

Acute and chronic toxicity data from studies submitted by pesticide registrants along with 

the available open literature are used to evaluate the potential direct 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 toxicity). The open literature studies will be identified through 

EPA’s ECOTOX database (http://cfpub.epa.gov/ecotox/), which employs a literature search 

engine for locating chemical toxicity 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 sensitive to the chemical and from 

changes in structure and functional characteristics of the affected 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 Amitrole measurement endpoints and values 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 LD50

Northern bobwhite 

quail 

Colinus virginianus

LD50 > 2,150 mg/kg Acceptable MRID 00160451 

(Fletcher, 1985) 

Avian subacute 5-day 

dietary LC50

Northern bobwhite 

quail C. virginianus,

Mallard duck 

Anas platyrhynchos, 

and Ring-necked 

pheasant Phasianus 

colchius 

Dietary sub-acute 

LC50 > 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 ppm1 

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) LD50

Rat 

Rattus norvegicus LD50 = 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 ppm2

or ~0.9 mg/kg/d

Acceptable MRID 44016201 

Survival of 

beneficial insect 

populations 

Honey bee 72-Hr 

acute contact LD50

Honey bee (Apis 

mellifera) acute contact 

LD50 > 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 and 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 endpoints and values for use in RQ calculations 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 

LC50

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 

EC50

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 ppm1 

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 LC50

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 LC50 

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 ppm2 NA ACR Calculation2 

Standing 

crop or 

biomass and 

growth of 

aquatic 

plants 

Freshwater 

green algae, 

cyanobacteria 

or diatom 

120-hr IC50

for biomass. 

Freshwater Diatom 

Navicula pelliculosa 

TGAI 

91.7% 1.4 ppm Acceptable 

MRID 44563102 

(Palmer & Krueger, 

1998) 

Vascular 

aquatic plants 

14-Day IC50 

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 chronic ratio (ACR) calculation value will be generated by 

examining the range of ACR values for amitrole effects to freshwater invertebrates 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 registration of amitrole. However, there were a number 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. Therefore, a new vegetative 

vigor study using TEP is needed to complete the 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 showing that surfactants and 

other inert ingredients in the formulation will disassociate rapidly from the active ingredient, 

then the requirement for a new seedling emergence study could be waived (a vegetative vigor 

study using TEP would still be required). 

The acute freshwater fish and invertebrate studies used nominal concentrations, with no data 

provided on mean-measured concentrations. However, because amitrole is very stable in water 

(in static toxicological studies that did measure concentrations, the lowest analytical recoveries 

were approximately 85% after 48—96 hours), the endpoints from these studies can be used in the 

risk assessment, although the uncertainty of using nominal concentrations will need to be 

characterized. 

Data gaps exist for amitrole’s effect on terrestrial plants, though given its mode of action and use 

as an herbicide, risk is expected to terrestrial non-target plants. There is also a lack of data on 

amitrole’s chronic effect on fish and saltwater invertebrates. 

2. Degradate toxicity 

One of the known degradates of amitrole is cyanamide, a registered plant growth regulator, PC 

code 014002. Cyanamide appears to be slightly more toxic to aquatic plants than amitrole with 

an EC50 of 0.65 ppm for Anabaena flos-aquae. Cyanamide also appears to have similar acute 

toxicity to freshwater and saltwater invertebrates, but may be significantly more toxic on a 

chronic basis with a NOAEC of 0.1 ppm for adult daphnids. Additionally, Cyanamide appears 

to be more toxic than amitrole to freshwater and saltwater fish with reported LC50 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 rainbow 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 LD50 of 173 mg/kg for bobwhite, though cyanamide does not appear to 

be toxic on a sub-acute dietary basis. Preliminary review of a chronic avian reproduction study 

(MRID 45797201) indicated that cyanamide may be less toxic to birds on a chronic basis, than 

amitrole. Like amitrole, cyanamide is practically non-toxic to bees and appears to have similar 

toxicity to terrestrial plants (most sensitive plant was onion for seedling emergence with an EC50

of 0.79 lbs a.i./acre and tomato for vegetative vigor with an EC50 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 EC25 of 0.24 lbs a.i./A and onion for 

vegetative vigor with an EC25 of 0.93 lbs a.i./acre). 

Data gaps were identified in the 2007 problem formulation for cyanamide’s effect on terrestrial 

plants, and chronic effects to estuarine/marine fish and invertebrates. However, data was only 

requested for terrestrial plants. This data has been submitted and is currently under review. 
15 

Additionally, although a data gap for chronic effects of cyanamide to freshwater fish was not 

identified in the problem formulation, the only data available is for a supplemental study on 

rainbow trout (MRID 44076701) where effects occurred 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-testing based study and does not lend itself well to 

regression analysis. It would therefore 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 invertebrates 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 degradates are identified, EFED will attempt to assess 

their toxicity using Quantitative Structural Activity Relationships (QSARs) and use a total toxic 

residue approach to assess 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 longer registered for use) had an EC50 of 2.43 ppm a.i. 

while MRID 46343713 used an 86% formulation (granular) and had an EC50 of 6.9 ppm a.i. A 

supplemental study on rainbow trout using Weedazol 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 Ecological 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), which is maintained by the American Bird 

Conservancy, indicates that no incidents associated with the use of amitrole have been reported 

to the Agency. Additionally, no incidents involving amitrole have been reported to the Agency in 

aggregated incident reports. The absence of reported incidents should not be construed as the 

absence of incidents. Incident reports for non-target organisms typically provide information 

only on mortality events and plant damage. Sublethal effects in organisms such as abnormal 

behavior, reduced growth and/or impaired reproduction are rarely reported, except for phytotoxic 

effects in terrestrial plants. EPA’s changes in the registrant reporting requirements for incidents 

in 1998 may account for a reduced number of reported incidents. Registrants are now only 

required to submit detailed information on ‘major’ fish, wildlife, and plant incidents. Minor fish, 

wildlife, and plant incidents, as well as all other non-target incidents, 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 scope, 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 receive drift or runoff. Areas adjacent to the 

treated area could include cultivated fields, fencerows and hedgerows, meadows, fallow fields or 

grasslands, woodlands, riparian habitats and other uncultivated areas. 

Aquatic ecosystems potentially at risk include water 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 environmental 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). Therefore, 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 contamination. The selection of clearly defined 

assessment endpoints is important because they provide direction and boundaries in the risk 

assessment for addressing risk management issues of concern. Changes to assessment endpoints 

are typically estimated from the available toxicity studies, which are used as the measures of 

effects to characterize potential ecological risks associated with exposure to a pesticide, such as 

amitrole. 

To estimate exposure concentrations, the ecological risk assessment considers applications at 

maximum rates. If multiple applications are allowed, the maximum amount per application and 

minimum interval between applications are used – provided that maximum total annual 

application amounts are also included in this configuration. 

Several EFED exposure models (e.g., PRZM-EXAMS, T-REX) are used 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. Toxicity tests are intended to determine effects of 

pesticide exposure on birds, mammals, fish, terrestrial and aquatic invertebrates, and plants. 

These tests include short-term acute, sub-acute, and reproduction studies and are typically 

arranged in a hierarchical or tiered system that progresses from basic laboratory tests to applied 

field studies. The toxicity studies are used to evaluate the potential of a pesticide to cause 
17 

adverse effects, to determine whether further testing is required, and to determine the need for 

precautionary label statements to minimize the potential 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 concentrations. An exposure pathway is the means by which a pesticide 

moves in the environment from a source to an ecological 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 receptors, and a feasible route of exposure. 

A conceptual model for amitrole provides a written description and visual representation 

of the predicted relationships between 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 risk 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 basis for the risk hypothesis and conceptual model 

developed for current registered uses of amitrole. 

 1. Risk Hypothesis 

 For amitrole, the following ecological risk hypothesis 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 threatened and endangered species. 

 

 2. Conceptual Diagram 

The potential exposure pathways and effects 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 likely routes of exposure and effects; 

dashed lines depict potential routes of exposure not considered likely 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 aquatic (water) and terrestrial (soil) habitats. The 

movement away from the site of application represents 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, growth, and reproduction in the receptors. 
18 

The environmental fate properties of amitrole and its degradates of concern indicate that 

leaching, runoff and spray drift represent potential transport mechanisms of amitrole and its 

major degradates to aquatic and terrestrial organisms. 

For amitrole, spray drift exposure to terrestrial and aquatic ecosystems potentially occurs through 

off site drift from non-crop land use sites. Exposure 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 Figures 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 survival, growth and reproduction, 

that may occur in the receptors due to exposure 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 conducted with amitrole, however with a log Kow of 

-0.97, amitrole bioaccumulation through 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 Kd is < 

50 and the Koc is < 1,000. The 1996 RED described low Kds ranging from 0.152 to 0.922 ml/g 

and Kocs ranging from 11.6—51.2. Assuming the review of the existing fate data or submission 

of additional data confirm these low values, then exposure through sediment will not be viewed 

as a significant pathway. Atmospheric deposition due to volatilization is unlikely due to 

amitrole’s low vapor pressure of 4.4 x 10-7 mmHg. 
19 

Figure 1: Conceptual model depicting 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 Kd is < 50 and the Koc is < 1,000.
20 

Figure 2: Conceptual model depicting stressors, generic exposure pathways, and potential effects to 

terrestrial organisms (terrestrial plants, terrestrial invertebrates, and dietary routes of exposure for 

terrestrial vertebrates) from the use of amitrole to amitrole non-food crop use sites. Dotted lines indicate 

exposure pathways that have a low likelihood of contributing to ecological risk. 
21 

Figure 3: Conceptual model 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 likelihood of contributing to ecological risk. 

VII. Analysis Plan Options 

In order to address the risk hypothesis, the potential for adverse effects on the environment is 

estimated. The use, environmental fate, and ecological effects of amitrole are characterized and 

integrated to assess the risks. Integration of exposure and effects 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 ecological 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 organisms from particular uses of amitrole, 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 opening 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 terrestrial environments, all 

exposure modeling and resulting risk conclusions 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 crops 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 minimum 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) EECs 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 Pesticide 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 generate daily exposures and calculated l-in10 

year acute and chronic EECs of amitrole that may occur in surface water bodies adjacent to 

application sites receiving amitrole through runoff and spray drift. PRZM simulates pesticide 

application, movement, and transformation on an agricultural field and the resultant pesticide 

loadings to a receiving water body via runoff, erosion and spray drift. PRZM scenarios have also 

been adapted to address non-agricultural applications. EXAMS simulates the fate of the pesticide 

in the water body and estimates resulting concentrations 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 outlet. The measure of exposure for aquatic species is the 1in10 year return peak or rolling mean concentration. 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-phase amphibians. The 1-in-10 year 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 animals assumed to be in the target area or in an area exposed 

to spray drift are derived using the T-REX model (version 1.4.1, 10/09/2008). This model 

incorporates the Kenega nomograph, 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 field 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, including information on 118 species of plants, 121 

pesticides, and 17 chemical classes. 
23 

EECs for terrestrial plants inhabiting dry and riparian/wetland areas adjacent to the target area 

are derived using TerrPlant (version 1.2.2, 12/26/2006). This model uses estimates of pesticides 

in runoff and in spray drift to calculate EECs. EECs are based upon solubility, 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 terrestrial 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 deposition at distances that exceed 1000 feet, AGDisp (version 

8.13; dated 12/14/2004) (Teske and Curbishley 2003) is used, which simulates aerial and ground 

applications using a Gaussian 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 toxicity endpoints (bobwhite LD50 > 2150 mg/kg and mallard NOAEC 

= 100 ppm) and the most sensitive acute and chronic mammalian toxicity endpoints (rat with 

LD50 = 4008 mg/kg and NOAEL = 0.9 mg/kg). Drinking 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 amitrole did not pass this Tier I screen, this concern 

is based more on the solubility 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/science/modelspg.htm#terrestrial

 1.4. Inhalation Exposure 

The Screening Tool for Inhalation Risk (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 application rate and method of application for 

spray drift. STIR incorporates results from several toxicity studies including acute oral and 

inhalation rat toxicity endpoints obtained 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 formulated 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 inhalation study, was not available. Therefore, EFED 

cannot evaluate the risk posed by inhalation exposure. Without additional information, EFED 

cannot preclude inhalation exposure as a significant pathway for exposure to amitrole. However, 

the chemical vapor pressure is very low (4.4E-07) and so amitrole is unlikely to volatize in 

appreciable concentrations. HED 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 wildlife inhalation risk from amitrole. 

 1.5. Measures of Effect 

Ecological effect data are used as measures of direct and indirect effects to biological receptors. 

Data will be obtained from registrant-submitted studies or from literature studies identified by 

ECOTOX. The ECOTOXicology database (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 mixture 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 upon the information submitted by the public in 

response to the opening of the Registration Review docket for amitrole. Additionally, the effects 

data may be revised as the quality and scientific soundness of those ECOTOX studies with 

amitrole or its degradates that were identified as potentially fulfilling a data gap, or as more 

sensitive than current values, are reviewed. When guideline or open literature studies are not 

available, a quantitative structure-activity relationship (QSAR) model 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 included behavioral changes (e.g., 

lethargy, changes in coloration and effects olfaction). Quantitative assessments of risks, though, 

are limited to those endpoints that can be directly 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 birds 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 this screening-level assessment are the LD50 (Lethal Dose), 

LC50 (Lethal Concentration) and ECx or ICx (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 chronic 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 IC05 or EC05 is 

used. The use of this endpoint in place of the NOAEC can introduce a large degree of uncertainty 

due to the need to extrapolate this endpoint in some cases and the high degree of variability in 

the plant metrics as compared to a 5% inhibition. 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 Pesticide Programs” (USEPA, 2004). 

Information on the potential effects of amitrole on non-target animals is also collected from the 

Ecological Incident Information System (EllS). The EllS is a database containing adverse effect 
25 

(typically mortality) reports on non-target organisms where such effects have been associated 

with the use of pesticides. This document describes the lack of currently known incidents with 

historic registered amitrole uses. This description will be updated for any new incidents that 

occur between now and the conduct of the risk assessment and effects determination. 

 1.6 Integration of Exposure and Effect 

The exposure and toxicity effects data are integrated in order to evaluate the risks of 

adverse ecological effects on non-target species. For the risk assessment of amitrole, the risk 

quotient (RQ) method is used to compare estimated exposure and measured toxicity values. The 

RQ method involves dividing estimated 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 used to indicate when 

applications of amitrole, as directed on the label, have the potential to cause adverse effects to 

non-target animals. In the absence of data for either acute or chronic effects, 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/LC501

0.5 

Acute 

Restricted Use 

Potential for effects to animals from acute exposures 

Risks may be mitigated through restricted use classification

Peak EEC/LC501

0.1 

Acute Listed 

Species 

Listed species may be potentially affected by acute 

exposures 

Peak EEC/LC501

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/EC50 1 

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

EC052 1 

Terrestrial Animals (mammals and birds) 

Acute Potential for effects to non-listed animals from acute 

exposures 

EEC/LC50 (Dietary) 0.5 

EEC/LD50 (Dose) 

Acute 

Restricted Use 

Potential for effects to animals from acute exposures 

Risks may be mitigated through restricted use classification

EEC/LC50 (Dietary) 0.2 

EEC/LD50 (Dose) 

Acute Listed 

Species 

Listed species may be potentially affected by acute 

exposures 

EEC/LC50 (Dietary) 0.1 

EEC/LD50 (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/LD50 0.05 

Terrestrial and Semi-Aquatic Plants 

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

exposures 

EEC/ EC25 1 

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

exposures 

EEC/ NOAEC or 

EC052 1 

1 LC50 or EC50. 2 An EC05 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 aquatic ecotoxicological studies on 
27 

fish and terrestrial plant seedling emergence and vegetative vigor studies. 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 gaps of Tier II vegetative vigor and seedling 

emergence studies on terrestrial plants and chronic effects on estuarine/marine fish and 

invertebrates. However, the Final Work Plan for the Registration Review 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 chronic effects of cyanamide on estuarine/marine fish 

and invertebrates and an additional data gap has been identified for the chronic effect of 

cyanamide on freshwater fish. Submission of these data would reduce uncertainties in the risk 

assessment. Cyanamide’s risk assessment for registration 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 formulation are significantly 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 could potentially be a concern. Using conservative 

assumptions of a maximum labeled use rate of 4.0 lbs ai/A, very-fine to fine droplet size, and a 

high boom, the 90th percentile concentration of the EPA-defined pond at the edge of field due to 

spray drift is 0.0138 ppm. The LC50 of the most sensitive species, Americamysis bahia was 2.8 

ppm. Because the estimated drift EEC is lower than the acute LC50, formulated product testing 

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

freshwater invertebrate studies with 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 numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

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

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

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

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of the 1994 RED decision, EPA reviewed these data and selected the 

most sensitive endpoints for relevant risk assessment scenarios from the existing hazard 

database. However, as required by FFDCA section 408(p), amitrole is subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP). 

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

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

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

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 
28 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

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

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 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 issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for amitrole. For further information on 

the status of the EDSP, the policies and procedures, the list 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 threatened and/or endangered (listed) species from 

uses of amitrole. This assessment will be conducted 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 registrations of amitrole is based on an action 

area. The action area is considered the area directly or indirectly 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 understanding that exposures below the 

Agency’s defined LOCs constitute a no-effect threshold. For the 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 potential exposure that exceeds the Agency’s LOCs. 

Specific measures of ecological effect that define the action area for listed species include any 

direct and indirect effects and/or potential modification of its critical habitat, including reduction 

in survival, growth, and reproduction as well as the full suite of sublethal effects available in the 

effects literature. Therefore, the action area extends 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 cellular level of organization. In situations 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 registration 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/attains_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 Water Body and Other Water Quality Data in OPP’s 

Registration Review Risk Assessment and Management Process (see: 

http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-sop.pdf) in order to ensure 

they can be used quantitatively or qualitatively 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, uncertainties 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 for 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 data, 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 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 

 The registrant is asked for clarification on three studies. For aerobic soil metabolism 

studies, what U.S. soil is represented by the foreign soil used? For aerobic aquatic metabolism 

studies, what U.S. soil is represented by the foreign soil used? What is the explanation for the 

apparent discrepancy between the behavior of amitrole in laboratory studies (long half-life) and 

terrestrial field dissipation studies (short half-life)? Additional studies will be required if these 

studies are not found to be acceptable. 

 

 2. Ecological Effects 

Several toxicity studies with technical amitrole are 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 amitrole to freshwater and 

estuarine/marine fish and estuarine/marine invertebrates. 40 CFR 158 requires an 

estuarine/marine fish early life stage study and an estuarine/marine invertebrate full life cycle 

because amitrole may enter the environment 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/marine acute invertebrate endpoint. Additionally, 

information is needed on amitrole’s degradate’s (cyanamide) chronic toxicity to freshwater and 

estuarine/marine fish and estuarine/marine invertebrates. Without 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, than 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: Acute 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 (rainbow 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. ECOTOX 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 review and evaluation of 

the EPA food-chain (Kenaga) nomagram, an instrument for estimating pesticide 

residues on plants. Environ. Toxicol. Chern., 13, 1383-1391. 

Hoerger, F. and E. E. Kenaga, 1972. Pesticide Residues on Plants: Correlation of Representative 

Data as a Basis for Estimation of their Magnitude 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 Division, Washington 

D.C. 

U.S. Environmental Protection Agency. 1998. Guidelines for Ecological Risk Assessment. 

Risk Assessment Forum, Office of Research 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 Agency, Washington, D.C. 20460. EPA 100-B00-002. December 2000. 

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

Process in the Office of Pesticide Programs, U.S. Environmental Protection Agency. 

Endangered and Threatened Species Effects 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: Procedures for Conducting Consultation 

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

March 1998. 
34 

Appendix A: Summary of Toxicity data 

Table 1. Summary of Submitted Aquatic Toxicity Data for Amitrole that May be Used Quantitatively. 

Study 

Type 

Test Species Genus 

Species

Study Type 

TGAI

/ TEP 

% ai 

Toxicity Endpoint (95% 

C.I.) 

Slope 

Measured/ 

Nominal 

Expressed in terms of 

a.i. 

Effect 

MRID 

(Year) 

Classificatio

n Date of 

DER 

Comm

Acute Freshwater Fish

Acute Emerald Shiner 

Notropis 

atherinoides 

TEP 

%ai 

not 

provid

ed 

96-Hr LC50 = 420 ppm 

Nominal Concentrations 

Mortality 00025435 

(1963) 

Supplemental 

07/08/1982 

No % active ingredient giv

as amitrol-T. Emerald shine

organism. No dose mor

presented. An insufficient 

statistical analysis us

Acute Rainbow Trout 

Oncorhynchus 

mykiss 

Static 

TGAI 

96.5% 

96-Hr LC50 > 1000 ppm 

Mean-Measured 

 00160454 

(1985) 

Acceptable 

09/24/1986 

Acute Bluegill sunfish 

Lepomis 

macrochirus

Static 

TGAI 

96.5% 

96-Hr LC50 > 1000 ppm 

Nominal Concentrations 

 00160453 

(1985) 

Acceptable 

09/24/1986 

Acute Bluegill sunfish 

Lepomis 

macrochirus

Static 

TGAI 

90% 

96-Hr LC50 > 180 ppm 

Nominal 

 43923702 

(1976) 

Acceptable 

07/15/1982 

No data (dose-respons

concentrations) pro

Acute Rainbow trout 

Oncorhynchus 

mykiss 

Static 

TGAI 

90% 

96-Hr LC50 > 180 ppm 

Nominal 

 43923701 

(1976) 

Acceptable 

07/15/1982 

No data (dose-respons

concentrations) pro

Acute Channel Catfish 

Ictalurus punctatus 

TGAI 

90% 

96-Hr LC50 > 160 ppm 40094602 

(1982) 
35 

Study 

Type 

Test Species Genus 

Species

Study Type 

TGAI

/ TEP 

% ai 

Toxicity Endpoint (95% 

C.I.) 

Slope 

Measured/ 

Nominal 

Expressed in terms of 

a.i. 

Effect 

MRID 

(Year) 

Classificatio

n Date of 

DER 

Comm

Acceptable 

07/15/1982 

Acute Fathead Minnow 

Pimephales 

promelas 

TGAI 

90% 

96-Hr LC50 > 100 ppm 40094602 

(1982) 

Acceptable 

07/15/1982 

Acute Rainbow Trout 

Oncorhynchus 

mykiss

Static 

TEP 

23.6% 

96-hr LC50 > 20.05 ppm 

(mean measured) 

 46467105 

(1995) 

Supplemental 

01/09/2006 

Supplemental due to being u

while not testing up to 100 pWeedazol TL with a listed p(240 mg/L CaCO3) was high

Number of fish/treatment levrequirements, but was less threcommended 10 fish/treatm

Chronic Freshwater Fish—No quantitative studies available Acute Estuarine/Marine Fish Acute Sheepshead minnow 

Cyprinodon 

variegates 

Static-Renewal

TGAI 

98.2% 

96-hr LC50 > 1000 ppm 

(mean measured) 

NOEAC > 1000 ppm 

No effect 42817801 

(1993) 

11/10/1993 

Acceptable 

Chronic Estuarine/Marine Fish-no quantitative studies available Acute Freshwater Invertebrates

Acute Water Flea Daphnia 

magna 

Static 

TGAI 

% a.i. 

not 

given 

26-hr LC50 = 23 ppb 

(15.3-44.4 ppm) 

Mortality 00017800 

(1966) 

Supplemental 

07/01/1982 

Test was only conducted for the percent active of the techdose-mortality data was pub

Acute Water Flea Daphnia 

magna 

Static 

TGAI 

91.8% 

48-hr LC50 = 18 ppm 

(16-21 ppm) 

Slope = 7.8 (4.5-11.1) 

nominal concentration 

Mortality 00160455 

(1985) 

Acceptable 

09/24/1986 
36 

Study 

Type 

Test Species Genus 

Species

Study Type 

TGAI

/ TEP 

% ai 

Toxicity Endpoint (95% 

C.I.) 

Slope 

Measured/ 

Nominal 

Expressed in terms of 

a.i. 

Effect 

MRID 

(Year) 

Classificatio

n Date of 

DER 

Comm

Acute Water Flea Daphnia 

magna

Static 

TEP 

23.6% 

48-hr EC50 = 2.43 ppm 

(1.99—3.10 ppm) 

Slope: N/A 

mean measured 

Immobilization/

mortality 

46467106 

(1995) 

Acceptable 

02/08/2006 

Test material was Weedazol 236 g/L. Hardness (224-230 

than recommended. Not conGLP. 

Acute Scud 

Gammarus fasciatus 

Static 

TEP 

21.6% 

> 100 ppm 05001497 

(1970) 

Supplemental 

09/17/1979 

Acute Glass shrimp 

Palaemonetes 

kadiakensis 

Static

TEP 

21.6% 

> 100 ppm 05001497 

(1970) 

Supplemental 

09/17/1979 

Acute Sowbug 

Asellus brevicaudus 

Static

TEP 

21.6% 

> 100 ppm 05001497 

(1970) 

Supplemental 

09/17/1979 

Acute Daphnia 

Daphnia magna 

Static

TEP 

21.6% 

30.0 ppm 05001497 

(1970) 

Supplemental 

09/17/1979 

Acute Seed shrimp 

Cypridopsis vidua 

Static

TEP 

21.6% 

32.0 ppm 05001497 

(1970) 

Supplemental 

09/17/1979 

Acute Waterflea 

Daphnia magna 

Static 

TEP 

21.6% 

26-Hr LC50 = 40 ppm Mortality 05001465 

(1966) 

Supplemental 

08/31/1979 

Test was only 26 hours. Amalso present in the formulati2nd compound was not provi

Acute Waterflea 

Daphnia magna 

Static 

TEP 

86% 

EC50 = 6.9 ppm 

(4.67-10.24) 

Slope: N/A 

Mean-Measured 

Mortality/ 

Immobilization 

46343713 

(1997) 

Acceptable 

04/28/2005 

Not reported whether aeratiowater hardness (242-244 mg

recommended. Formulation 

Chronic Freshwater Invertebrates
37 

Study 

Type 

Test Species Genus 

Species

Study Type 

TGAI

/ TEP 

% ai 

Toxicity Endpoint (95% 

C.I.) 

Slope 

Measured/ 

Nominal 

Expressed in terms of 

a.i. 

Effect 

MRID 

(Year) 

Classificatio

n Date of 

DER 

Comm

Chronic Water Flea Daphnia 

magna 

21-day Renewal 

TGAI 

96.5% 

21-day NOAEC = 0.32 

ppm 

LOAEC = 0.56 ppm 

Nominal 

Growth 

Egg production, 

larval survival 

affected at 

higher 

treatment levels 

44342301 

(1994) 

Supplemental 

06/03/2002 

Only 10 daphnids tested/levrecommended 3 test chambesurvival testing. Presence oreported. Dry weight not m

Acute Estuarine/Marine Invertebrates Acute Shell Deposition 

Eastern Oyster 

Crassostrea 

virgninica 

Flow-Through 

TGAI 

98.2% 

96-hr EC50 > 110 ppm 

NOEC = 110 ppm 

 42837401 

(1993) 

Acceptable 

11/05/1993 

Acute Mysid Shrimp 

Americamysis bahia 

Static 

TGAI 

98.2% 

96-hr LC50 = 2.8 ppm 

(2.5-3.3 ppm) 

Slope = 9.8 (5.7-14.0) 

Mean-measured 

Mortality 42818201 

(1993) 

Acceptable 

11/05/1993 

Chronic Esturarine/Marine Invertebrates– no quantitative studies available Aquatic Plants 

Tier II Green Algae 

Psuedokirchneriella 

subspicatum 

TEP 

23.6

% 

72 hr EC50/IC50 = 23 ppm 

(20-27 ppm) 

4.63 

Mean-measured 

Biomass 46467113 

(1995) 

Supplemental 

1/4/2006 

Test duration was only 72 hrequirement of 96 hours. Thconsidered for Tier I screenimaterial was Weedazol TL wg/L. 

Tier II Marine diatom 

Skeletonema 

costatum

TGAI 

91.7

% 

120 hr EC50 = 3.0 ppm 

(2.5 – 3.5 ppm) 

Slope N/A 

Mean-measured 

Cell density 44563101 

(1998) 

Acceptable 

11/5/1998 

Study was conducted using cycle. 

Tier II Freshwater diatom 

Navicula 

pelliculosa 

TGAI 

91.7

% 

120 hr EC50 = 1.4 ppm 

(0.98 – 2.0 ppm) 

Mean-Measured 

Cell density 44563102 

(1998) 

Acceptable 

Only 3 replicates were utiliz
38 

Study 

Type 

Test Species Genus 

Species

Study Type 

TGAI

/ TEP 

% ai 

Toxicity Endpoint (95% 

C.I.) 

Slope 

Measured/ 

Nominal 

Expressed in terms of 

a.i. 

Effect 

MRID 

(Year) 

Classificatio

n Date of 

DER 

Comm

11/5/1998 

Tier II Green Algae 

Selenastrum 

capricornutum 

TGAI 

91.7

% 

120 hr EC50 = 2.3 ppm 

(1.9-2.7 ppm) 

Slope N/A 

Mean-Measured 

Cell density 44548801 

(1998) 

Acceptable 

2/7/2000 

Tier II Blue-green Algae 

Anabaena flosaquae 

TGAI 

91.7

% 

120 hr EC50 = 3.4 ppm 

(3.2 – 3.8 ppm) 

Slope N/A 

Mean-measured 

Cell density 44548802 

(1998) 

Acceptable 

5/17/1999 

Tier II Duckweed Lemna 

gibba

TGAI 

91.7

% 

14-day EC50 = 2.5 ppm 

(2.1 – 3.0 ppm) 

Slope N/A 

Mean-measured 

Average Frond 

Density 

44548803 

(1998) 

Acceptable 

5/7/2002 

Tier II Green Algae 

Pseudokirchneriella 

subcapitata

TGAI 

86% 

72-hr EC50 = 18.0 ppm 

(14 – 22 ppm) 

4.39 

Mean-measured 

Cell Density 46343714 

(1997) 

Supplemental 

4/28/2005 

Test duration was only 72 h

requirement of 96 hour

considered for Tier I sc

Abbreviations: TGAI = technical grade active ingredient; TEP=typical end use product; conc.=concentration; C.I. = confidence intervaTable 2. Summary of Submitted Aquatic Toxicity Data for Amitrole That May be Used Qualitatively, We

Studies, or are Unacceptable. 

Study 

Type 

Test Species 

Genus Species

Study Type 

TGAI/ 

TEP 

% ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ 

Nominal 

Expressed in terms of 

a.i. 

Effect 

MRID (Year) 

Classification 

Date of DER 

Comme

Acute Freshwater Fish

Acute Common carp 

Cyprinus 

No Data 00075203 

(1971) 

No details previded on %a.i., tesdose-mortality response. Uniden
39 

Study 

Type 

Test Species 

Genus Species

Study Type 

TGAI/ 

TEP 

% ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ 

Nominal 

Expressed in terms of 

a.i. 

Effect 

MRID (Year) 

Classification 

Date of DER 

Comme

carpio Invalid 

07/12/1982 

Acute Tench 

Tinca rulgaris

No Data 00075203 

(1971) 

Invalid 

07/12/1982 

No details previded on %a.i., tesdose-mortality response. Uniden

Acute Freshwater Invertebrates 

Acute Waterflea 

Daphnia 

magna 

TEP 

% ai not 

provided 

 Mortality 05020721 

 (1966) 

Invalid 

07/09/1982 

Major inadequacies in this study chambers and the lack of discrete 

Acute Waterflea 

Daphnia 

magna 

static 

TEP 

%ai not 

provided 

 05001497 

(1982) 

Supplemental 

No dose mortality data presented

Acute Phantom 

Midge 

Chaoborus 

punctipennis 

TEP 

50% 

No LD50 value could be 

generated 

96-Hr LOAEC = 5.6 

ppm 

mortality 

 No emergence of adults occurred 

56 ppm. There was no control d

Acute Crayfish 

Orconectes 

nais 

TEP 

21.6% 

 05001497 

(1970) 

Invalid 

09/17/1979 

Acute Hard clam 

Mercenaria 

mercenaria

Unclear if 

TEP or 

TGAI used 

 05002007 

(1969) 

Invalid 

09/11/1979 

Unclear whether technical grade 

were used. Also missing data 

control and wa

Acute American 

Oyster 

Crassostrea 

virginica 

Unclear if 

TEP or 

TGAI used 

 05002007 

(1969) 

Invalid 

09/11/1979 

Unclear whether technical grade 

were used. Also missing data 

control and wa
40 

Study 

Type 

Test Species 

Genus Species

Study Type 

TGAI/ 

TEP 

% ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ 

Nominal 

Expressed in terms of 

a.i. 

Effect 

MRID (Year) 

Classification 

Date of DER 

Comme

Acute Scud 

Gammarus 

fasciatus

TGAI 

90% 

96-Hr LC50 > 10 ppm 40094602 

(1982) 

Acceptable 

07/15/1982 

Organisms were mature in

requirement of early 

Aquatic Plants 

Green Algae 

Selenastrum 

capricornutum 

 42813701 

(1993) 

Supplemental 

12/21/1994 

Supplemental due to contaminatireplicates. Other issues with inoMultiple counts of each replicate 

sampling times. Inadequate growcell counting methods were inadconducted for 72 hours. Amitrolconcentration inhibited algal gro

Abbreviations: TGAI = technical grade active ingredient; TEP=typical end use product; conc.=concentration; C.I. = confidence intervaTable 3. Summary of Terrestrial Toxicity Data Submitted for Amitrole That May be Used Quantitatively

Study Type Test Species TGAI/TEP % ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ nominal 

Effect 

MRID 

(Year) 

Classificatio

n, DER date 

or source 

Mammals 

Acute Oral Laboratory 

Rat 

Rattus 

norvegicus 

TGAI LD50 > 24,000 mg/kg 00063601 

Acute Oral Laboratory 

Rat 

TGAI LD50 = 4,080 mg/kg Gaines et al., 

1997 
41 

Study Type Test Species TGAI/TEP % ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ nominal 

Effect 

MRID 

(Year) 

Classificatio

n, DER date 

or source 

Rattus 

norvegicus 

2-Generation 

Chronic 

Laboratory 

Rat 

Rattus 

norvegicus

TGAI 

97-98% 

NOEL = 15 ppm (0.90 

mg/kg/day in males, 

1.23 mg/kg/day in 

females. 

LOEL = 112.5 ppm 

(5.88 mg/kg/day in 

males, 7.83 mg/kg/day 

in females. 

Clinical signs of toxicity, mortality, and 

decreases in body weight, body weight 

gained, food consumption, food 

efficiency and selected absolute and 

relative organ weights, increase in thyroid 

weight and activity, follicular cell 

hypertrophy and hyperplasia and nodular 

hyperplasia and/or adenoma, 

hepatocellular hypertrophy and other 

microscopic changes in the adrenals, 

liver, pituitary, mammary gland and 

kidney, a high incidence of 

pseudopregnancy, decreases in mating 

and fertility indices, implantation 

sites/litter and mean pup male/female 

ratio and a slightly higher gestation 

interval. 

44016201 

Birds 

Acute Oral Bobwhite 

quail 

Colinus 

virginianus 

TGAI 

91.83% 

21-D LD50 > 2,150 

mg/kg 

 00160451 

(1985) 

Acceptable 

09/24/1986 

Acute 

Dietary 

Mallard Duck 

Anas 

platyrhynchos

TGAI 

91.83% 

8-D LC50 > 5,000 ppm 00160476 

(1985) 

Acceptable 

09/24/1986 

Acute 

Dietary 

Bobwhite 

quail 

Colinus 

virginianus

TGAI 

91.83% 

8-D LC50 > 5,000 ppm 00160452 

(1985) 

Acceptable 

09/24/1986 
42 

Study Type Test Species TGAI/TEP % ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ nominal 

Effect 

MRID 

(Year) 

Classificatio

n, DER date 

or source 

Acute 

Dietary 

Mallard duck 

Anas 

platyrhynchos 

TGAI 

90% 

5-D LC50 >5000 

mg/kg-bw 

 00022923 

(1975) 

Acceptable 

07/15/1982 

Acute 

Dietary 

Ring-necked 

pheasant 

Phasianus 

colchicus

TGAI 

90% 

5-D LC50 >5000 

mg/kg-bw 

 00022923 

(1975) 

Acceptable 

07/15/1982 

Acute 

Dietary 

Japanese 

quail 

Coturnix 

japonica

TGAI 

90% 

5-D LC50 >5000 

mg/kg-bw 

 00022923 

(1975) 

Supplemental 

07/15/1982 

Avian 

Reproduction 

Mallard Duck 

Anas 

platyrhynchos

TGAI 

91.7% 

22-Wk NOAEC = 100 

ppm 

22-Wk LOAEC = 350 

ppm 

Reduced mean adult male body weight, 

reduced egg production, reduced feed 

consumption 

45015402 

(1999) 

Acceptable 

03/18/2002 

Avian 

Reproduction 

Bobwhite 

quail 

Colinus 

virginianus

TGAI 

91.7% 

22-Wk NOAEC = 450 

ppm 

22-Wk LOAEC = 2025 

ppm 

Reduced % normal hatchlings, eggs set, 

live 3-wk embryos, 14-d hatchlings, 

weight of 14-d hatchlings 

45015401 

(1999) 

Acceptable 

03/18/2002 
43 

Study Type Test Species TGAI/TEP % ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ nominal 

Effect 

MRID 

(Year) 

Classificatio

n, DER date 

or source 

Terrestrial Invertebrates 

Acute 

contact 

Honeybee 

Apis mellifera

TEP23.6% 72-hr LD50 >200 

μg/bee 

NOEL = 200 μg/bee 

 454571114 

(1992) 

Acceptable 

01/08/2006 

Acute Oral Honeybee 

Apis mellifera

TEP 

23.6% 

72-hr LD50 >200 

μg/bee 

NOEL = 100 μg/bee 

 454571114 

(1992) 

Acceptable 

01/08/2006 

Acute 

Contact 

Honeybee 

Apis mellifera

TEP 

%ai not 

provided 

LD50 > 10 μg/bee 00001999 

(1967) 

Acceptable 

12/3/1979 

Acute 

Contact 

Honeybee 

Apis mellifera

TEP 

%ai not 

provided 

 00036935 

(1975) 

Acceptable 

12/02/1981 

Terrestrial Plants 

Tier II 

Seedling 

Emergence 

Bean 

Phaseolus 

vulgaris 

TGAI 

91.7% 

EC25 = 3.13 lbs ai/A 

(2.7—3.4) 

NOAEL = 0.63 lbs 

ai/A 

Nominal 

Shoot Height 44540101 

(1998) 

Supplemental 

03/22/2002 

Amended 

04/30/2011 

Tier II 

Seedling 

Emergence 

Cabbage 

Brassica 

oleracea 

TGAI 

91.7% 

EC25 = 0.24 lbs ai/A 

(0.12—0.47) 

NOAEL = 0.10 lbs 

ai/A 

Nominal 

Shoot Dry Weight 44540101 

(1998) 

Supplemental

03/22/2002 

Amended 

04/30/2011 

Tier II Carrot TGAI EC25 = 1.22 lbs ai/A Phytotoxicity 44540101 
44 

Study Type Test Species TGAI/TEP % ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ nominal 

Effect 

MRID 

(Year) 

Classificatio

n, DER date 

or source 

Seedling 

Emergence 

Daucus 

carota 

91.7% 

NOAEL = 0.63 lbs 

ai/A 

Nominal 

(1998) 

Supplemental

03/22/2002 

Amended 

04/30/2011 

Tier II 

Seedling 

Emergence 

Lettuce 

Lactuca 

sativa 

TGAI 

91.7% 

EC25 = 0.59 lbs ai/A 

(0.13—1.9) 

EC05 = 0.06 lbs ai/A 

Nominal 

Shoot Dry Weight 44540101 

(1998) 

Supplemental

03/22/2002 

Amended 

04/30/2011 

Tier II 

Seedling 

Emergence 

Soybean 

Glycine max 

TGAI 

91.7% 

EC25 = 2.59 lbs ai/A 

NOAEL = 0.63 lbs 

ai/A 

Nominal 

Shoot Height 44540101 

(1998) 

Supplemental

03/22/2002 

Amended 

04/30/2011 

Tier II 

Seedling 

Emergence 

Tomato 

Solanum 

lycopersicum 

TGAI 

91.7% 

EC25 = 0.81 lbs ai/A 

NOAEL = 0.25 lbs 

ai/A 

Nominal 

Phytotoxicity 44540101 

(1998) 

Supplemental

03/22/2002 

Amended 

04/30/2011 

Tier II 

Seedling 

Emergence 

Corn 

Zea mays 

TGAI 

91.7% 

EC25 > 3.9 lbs ai/A 

NOAEL = 1.6 lbs ai/A 

Nominal 

Phytotoxicity 44540101 

(1998) 

Supplemental

03/22/2002 

Amended 

04/30/2011 

Tier II 

Seedling 

Emergence 

Onion 

Allium cepa 

TGAI 

91.7% 

EC25 = 0.93 lbs ai/A 

NOAEL = 0.25 lbs 

ai/A 

Nominal 

Shoot Height 44540101 

(1998) 

Supplemental

03/22/2002 

Amended 

04/30/2011 
45 

Study Type Test Species TGAI/TEP % ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ nominal 

Effect 

MRID 

(Year) 

Classificatio

n, DER date 

or source 

Tier II 

Seedling 

Emergence 

Ryegrass 

Lolium 

perenne 

TGAI 

91.7% 

EC25 = 1.79 lbs ai/A 

NOAEL = 0.63 lbs 

ai/A 

Nominal 

Phytotoxicity 44540101 

(1998) 

Supplemental

03/22/2002 

Amended 

04/30/2011 

Tier II 

Seedling 

Emergence 

Wheat 

Triticum 

aestivum 

TGAI 

91.7% 

EC25 = 3.06 lbs ai/A 

NOAEL = 0.63 lbs 

ai/A 

Nominal 

Phytotoxicity 44540101 

(1998) 

Supplemental

03/22/2002 

Amended 

04/30/2011 

Tier II 

Vegetative 

Vigor 

Maize 

Zea mays 

TGAI 

98.22% 

EC25 = 0.57 lbs ai/A 

(0.35—0.90) 

NOAEL = 0.25 lbs 

ai/A 

Nominal 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 

Tier II 

Vegetative 

Vigor 

Perrenial Rye 

Lolium 

perenne 

TGAI 

98.22% 

EC25 = 0.17 lbs ai/A 

(0.01—2.00) 

NOAEL = 0.031 lbs 

ai/A 

Nominal 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 
46 

Study Type Test Species TGAI/TEP % ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ nominal 

Effect 

MRID 

(Year) 

Classificatio

n, DER date 

or source 

Tier II 

Vegetative 

Vigor 

Oats 

Avena sativa 

TGAI 

98.22% 

EC25 = 0.84 lbs ai/A 

(0.61—1.15) 

NOAEL = 0.50 lbs 

ai/A 

Nominal 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 

Tier II 

Vegetative 

Vigor 

Wheat 

Triticum 

aestivum

TGAI 

98.22% 

EC25 = 0.13 lbs ai/A 

(0.10—0.16) 

NOAEL = 0.031 lbs 

ai/A 

Nominal 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 

Tier II 

Vegetative 

Vigor 

Bush Bean 

Phaseolus 

vulgaris 

TGAI 

98.22% 

EC25 = 0.25 lbs ai/A 

(0.21—0.29) 

NOAEL = 0.031 lbs 

ai/A 

Nominal 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 
47 

Study Type Test Species TGAI/TEP % ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ nominal 

Effect 

MRID 

(Year) 

Classificatio

n, DER date 

or source 

Tier II 

Vegetative 

Vigor 

Cucumber 

Cucumis 

sativus 

TGAI 

98.22% 

EC25 = 0.31 lbs ai/A 

(0.25—0.39) 

NOAEL = 0.13 lbs 

ai/A 

Nominal 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 

Tier II 

Vegetative 

Vigor 

Lettuce 

Lactuca 

sativa 

TGAI 

98.22% 

EC25 = 0.24 lbs ai/A 

(0.15—0.39) 

NOAEL = 0.016 lbs 

ai/A 

Nominal 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 

Tier II 

Vegetative 

Vigor 

Red Pepper 

Capsicum 

anuum 

TGAI 

98.22% 

EC25 = 0.17 lbs ai/A 

(0.15—0.20) 

NOAEL = 0.031 lbs 

ai/A 

Nominal 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 
48 

Study Type Test Species TGAI/TEP % ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ nominal 

Effect 

MRID 

(Year) 

Classificatio

n, DER date 

or source 

Tier II 

Vegetative 

Vigor 

Pepper 

Capsicum 

anuum 

TGAI 

98.22% 

EC25 = 0.20 lbs ai/A 

(0.09—0.44) 

NOAEL = 0.031lbs 

ai/A 

Nominal 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 

Tier II 

Vegetative 

Vigor 

Soybean 

Glycine max 

TGAI 

98.22% 

EC25 = 0.32 lbs ai/A 

(0.05—2.27) 

NOAEL = 0.031 lbs 

ai/A 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 

Tier II 

Vegetative 

Vigor 

Sunflower 

Helianthus 

annuus 

TGAI 

98.22% 

EC25 = 0.026 lbs ai/A 

(0.023—0.029) 

NOAEL = 0.016 

Nominal 

Phytotoxicity 42813702 

(1993) 

Supplemental 

11/02/1993 
49 

Study Type Test Species TGAI/TEP % ai 

Toxicity Endpoint 

(95% C.I.) 

Slope 

Measured/ nominal 

Effect 

MRID 

(Year) 

Classificatio

n, DER date 

or source 

Tier II 

Vegetative 

Vigor 

Radish 

Raphanus 

sativus 

TGAI 

98.22% 

EC25 = 0.19 lbs ai/A 

(0.13—0.27) 

NOAEL = 0.13 lbs 

ai/A 

Nominal 

Shoot Dry Weight 42813702 

(1993) 

Supplemental 

11/02/1993 

Tier II 

Vegetative 

Vigor 

Leek 

Allium 

TGAI 

98.22% 

EC25 = 1.05 lbs ai/A 

(0.70—1.57) 

NOAEL = 1.0 lbs ai/A 

Nominal 

 42813702 

(1993) 

Supplemental 

11/02/1993 

Amended 

09/11/1994 
50 

Table 4. Summary of Terrestrial Toxicity Data Submitted for Amitrole that May Only be Used Qualitativ

Unacceptable/Invalid. 

Study Type Test Species TGAI or TEP 

% ai 

Toxicity 

Endpoint 

(95% C.I.) 

Slope 

Measured/ 

nominal 

Effect 

MRID (Year) 

Classification, 

DER date or 

source 

Co

Birds 

Acute Oral Mallard Duck 

Anas 

platyrhynchos

TEP 

23.6% 

NOEC for 

sublethal effects 

= 670 mg/kg-bw 

 46467104 

(1995) 

Invalid 

01/03/2006 

Invalid due to 

highest dose 

Fasting perio

mortality or regu

in any conce

including 670 mg

was Weedazol T

of 
51 

Appendix B: Sample Inputs and Outputs from SIP 

 

 Table 1. Inputs 

 Parameter Value 

 Chemical name Amitrole 

 Solubility (in water at 25oC; mg/L) 28000 

 

 Mammalian LD50 (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 LD50 (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.