UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, 

PESTICIDES, AND TOXIC SUBSTANCES

Environmental Fate and Ecological Risk Assessment 

for the Registration of 

Amicarbazone

4-Amino-N-tert-butyl-4,5-dihydro-3-isopropyl-5-oxo-1H-1,2,4-triazole-1-carboxamide

Prepared by:

Mohammed A. Ruhman, Ph.D.

Mike Hoffmann

United States Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch V

401 M Street, SW

Mail Code 7507C

Washington, D.C. 20460

Reviewed by:

Mah Shamim, Ph.D.

TABLE OF CONTENTS
iii

I. Executive Summary ...................................................................................................................1

A. Nature of Chemical Stressor .......................................................................................1

B. Potential Risks to Non-target Organisms......................................................................1

C. Conclusions - Exposure Characterization.....................................................................3

D. Conclusions - Effects Characterization.........................................................................4

E. Data Gaps and Uncertainties.........................................................................................5

1. Environmental Fate ............................................................................................5

2. Ecological Effects................................................................................................7

II. Problem Formulation ................................................................................................................9

A. Stressor Source and Distribution ..................................................................................9

1. Source and Intensity ..........................................................................................9

2. Physicochemical, Fate, and Transport Properties..............................................9

3. Pesticide Type, Class, and Mode of Action.....................................................10

4. Overview of Pesticide Usage...........................................................................10

B. Receptors ...................................................................................................................10

1. Ecological Effects............................................................................................10

2. Ecosystems at Risk .........................................................................................11

C. Assessment Endpoints ...............................................................................................13

D. Conceptual Model .....................................................................................................14

1. Risk Hypotheses .............................................................................................14

2. Diagram ...........................................................................................................15

E. Analysis Plan...............................................................................................................16

1. Development of Assessment Design ...............................................................16

2. Identification of Data Gaps and Methods for Conducting Assessment...........17

3. Measures to Evaluate Risk Hypotheses and Conceptual Model .....................19

a. Measures of Exposure..........................................................................19

b. Measures of Effect...............................................................................20

c. Measures of Ecosystem and Receptor Characteristics.........................20

III. Analysis .................................................................................................................................20

A. Use Characterization...................................................................................................20

B. Exposure Characterization ..........................................................................................25

1. Environmental Fate and Transport Characterization.......................................25

a. Summary of Empirical Data ...............................................................27

b. Degradation and Metabolism...............................................................28

c. Transport and Mobility ........................................................................28

d. Field Studies ....................................................................................................29

2. Measures of Aquatic Exposure........................................................................29

a. Aquatic Exposure Modeling ................................................................29

b. Aquatic Exposure Monitoring (Field Data).........................................34

3. Measures of Terrestrial Exposure....................................................................34
iv

a. Exposure Modeling for Terrestrial Animals ......................................34

b. Exposure Modeling for Non-Target Terrestrial Plants........................37

c. Terrestrial Exposure Monitoring (Field Data) ...................................38

C. Ecological Effects Characterization............................................................................38

1. Aquatic Effects ...............................................................................................39

a. Aquatic Animals ..................................................................................41

b. Aquatic Plants ....................................................................................43

2. Terrestrial Effects ...........................................................................................44

a. Terrestrial Animals .............................................................................46

b. Terrestrial Plants..................................................................................48

IV. Risk Characterization ............................................................................................................51

A. Risk Estimation - Integration of Exposure and Effects Data ....................................51

1. Non-target Aquatic Animals and Plants..........................................................51

2. Non-target Terrestrial Animals........................................................................56

3. Non-target Terrestrial Insects and Other Invertebrates ...................................61

4. Non-target Terrestrial and Semi-aquatic Plants...............................................61

B. Risk Description - Interpretation of Direct Effects.....................................................64

1. Risks to Aquatic Organisms ............................................................................64

2. Risks to Terrestrial Organisms ........................................................................67

3. Review of Incident Data ................................................................................73

4. Endocrine Effects.............................................................................................73

5. Threatened and Endangered Species Concerns...............................................74

a. Action Area ........................................................................................74

b. Taxonomic Groups Potentially at Risk................................................74

c. Indirect Effects Analysis ....................................................................77

d. Critical Habitat ...................................................................................79

e. Co-occurrence Analysis.......................................................................80

C. Description of Assumptions, Limitations, Uncertainties, Strengths, and Data Gaps .82

1. Assumptions, Limitations, Uncertainties, Strengths, and Data Gaps Related To 

Exposure For All Taxa...............................................................................82

2. Assumptions, Limitations, Uncertainties, Strengths, and Data Gaps Related To 

Exposure For Aquatic Species...................................................................82

3. Assumptions, Limitations, Uncertainties, Strengths, and Data Gaps Related To 

Exposure For Terrestrial Species...............................................................83

4. Assumptions, Limitations, Uncertainties, Strengths, and Data Gaps Related To 

Effects Assessment ...................................................................................86

5. Assumptions, Limitations, Uncertainties, Strengths, and Data Gaps Related To 

the Acute LOCs ........................................................................................90

V. Literature Cited.......................................................................................................................92

A. Environmental Fate Studies Submitted to EPA..........................................................92

B. Ecological Effects Studies Submitted to EPA ............................................................94
v

C. Open Literature and Government Reports..................................................................97
vi
vii

VI. Appendices

A. Environmental Fate and Transport Data

B. Aquatic Exposure PRZM/EXAMS Modeling

C. TERRPLANT and Results

D. T-REX Model (Version 1.1, February 24, 2005) 

E. Ecological Effects Data

F. The Risk Quotient Method and Levels of Concern

G. Detailed Risk Quotients

H. Summary of Endangered/Threatened Species

I. Data Requirement Tables

J. Incident Reports

K. Drinking Water Assessment

L. AgDRIFT Modeling Approach and Results
1

I. Executive Summary

A. Nature of Chemical Stressor 

Amicarbazone (CAS 129909-90-6) is the common name for 

4-amino-4,5-dihydro-N-(1,1-dimethylethyl)-3-(1-methylethyl)-5-oxo-1H-1,2,4-triazole-1-carbox

amide, the active ingredient in the Amicarbazone DF Herbicide (EPA Registration No. 

66330-UA). Amicarbazone DF herbicide contains 70% a.i. and is formulated as a water 

dispersible granule. Application methods for amicarbazone include ground broadcast 

spray, broadcast surface spray, broadcast surface spray/soil incorporation (1-2") by

moderate rainfall/irrigation, or soil injection. Amicarbazone is proposed for use to control 

annual broadleaf weeds in field corn and corn grown for silage. It is not intended for use on 

popcorn, sweet corn, high corn-oil hybrids or corn grown for seed. Amicarbazone can be used at 

several stages of crop development, with proposed uses for pre-plant, pre-emergence, and early 

post-emergence applications. The recommended number of applications of amicarbazone is one 

to two per year, with a maximum application rate of 0.45 lb a.i./A per year. Amicarbazone 

belongs to the triazolinone class of compounds and is a photosystem II (PS II) inhibitor with 

burn-down activity.

Available fate and transport data indicate that two major transformation products are expected to 

form in soils and be transported into the environment as a result of amicarbazone use. The two 

transformation products are Des-amino and N-methyl Des-amino. Although both were 

considered in the drinking water assessment, neither were considered in the exposure modeling for 

aquatic systems in the ecological risk assessment. Exposure modeling for aquatic systems was 

conducted with only the parent compound. Freshwater algae are the only aquatic organisms at risk 

following exposure to amicarbazone, and limited available data on the toxicity of the 

transformation products to aquatic algae and terrestrial plants suggest that they are relatively less 

toxic than the parent. Also, the parent is moderately persistent in the environment and stable to 

hydrolysis. Therefore, the transformation products will have a minimal contribution in the 

aquatic exposure assessment. 

Decarboxamide can form as a transformation product of amicarbazone by hydrolysis in alkaline

environments but was not considered in this assessment because the parent is not recommended 

for use in soils with pH >7.4. In this respect, it can be stated that this transformation product is 

expected to form when the parent is transported (by air and/or running water) into alkaline 

environments. It can also form when the parent is transported by leaching into ground water as it 

passes through alkaline layers. 

B. Potential Risks to Non-target Organisms

Risks to Aquatic Animals

This compound does not appear to pose an acute or chronic risk to aquatic animals. The 
2

risk of acute mortality is expected to be low since all acute Risk Quotients (RQs) are 

below acute risk Levels of Concern (LOCs) for freshwater fish and invertebrates, and 

estuarine/marine invertebrates. Additionally, chronic RQs for freshwater fish and 

estuarine/marine invertebrates are several orders of magnitude below the chronic LOC, 

indicating that chronic risk is low for these organisms. Estimated chronic risk to freshwater 

invertebrates is uncertain because a NOAEC was not established in the chronic toxicity study

on Daphnia magna (i.e., decreased terminal length was observed at the lowest 

concentration of amicarbazone tested). However, based on the LOAEC for freshwater 

invertebrates risk to these organisms appears to be low. Currently, there is no available data 

to assess chronic risk to estuarine/marine fish.

Risks to Terrestrial Animals

Although all calculated acute risk quotients for both birds and mammals are below acute 

risk LOCs and the risk of acute mortality to these organisms is expected to be low, 

amicarbazone appears to pose a chronic risk to both birds and mammals. Chronic avian 

toxicity studies show that exposure to amicarbazone produces adverse effects on growth 

and reproduction, with a decrease in the ratio of viable embryos per eggs set and number 

of hatchlings per eggs set in bobwhite quail and a decrease in egg shell thickness in 

mallard ducks as the most sensitive measures of effect. The chronic LOC is exceeded for 

birds exposed to amicarbazone via short grass for all application rates (RQs range from 1.36 to 

3.97), broadleaf plants/small insects for the 0.45 and 0.22 lb a.i./A application rates (RQs = 

2.23 and 1.09, respectively), and tall grass for the highest application rate (RQ = 1.82). This 

analysis indicates that birds are at chronic risk and that adverse reproductive outcomes 

may result from amicarbazone exposure. 

For mammals, results of a 2-generation reproduction study in rats show that parental 

systemic effects (decreases in body weight and body weight gain) and toxicity to offspring 

(decreases in pup weight and pup body weight gain) result from amicarbazone exposure. 

Results suggest that dietary-based chronic risk to mammals can occur through exposure 

to amicarbazone via short grass (RQ = 1.08) following only the highest suggested 

application rate. On the other hand, dose-based chronic RQsbased on exposure to 

amicarbazone via residues on short grass exceed the chronic LOC for each body weight 

class under all application rates (RQs range from 1.12 to 7.27). In addition, exposure 

to amicarbazone via residues on tall grass and broadleaf plants/small insects results in 

LOC exceedances under all application rates (RQs range from 0.51 to 3.33 and from 0.63 

to 4.09 for exposure via tall grass and broadleaf plants/small insects, respectively). No 

dose-based RQs exceeded the chronic LOC for mammals exposed to amicarbazone 

residues on fruits/pods/large insects or seeds. 

Although EFED does not currently calculate RQs for non-target insects, results of an 

acute contact study in honey bees show that the acute risk from amicarbazone exposure 

is expected to be low.
3

Risks to Aquatic and Terrestrial Plants

This screening level assessment shows that algae are the only aquatic plants at risk from 

exposure to amicarbazone as a result of runoff. RQs based on the most sensitive species, 

Skeletonema costatum, exceed the LOC for aquatic plants for the usual early pre-plant, 

pre-plant, at planting, and pre-emergence applications, and for special fall (RQ = 1.19) 

and winter applications (RQ = 1.99). Of the RQs calculated for all of the usual 

applications, only RQs for post-emergence applications for the Eastern and Western 

Corn Belt do not exceed the LOC. RQs for all of the other usual applications for the 

Eastern Corn Belt exceed the LOC (RQs range from 1.23 to 1.73). It appears that 

amicarbazone does not pose as large a risk to algae in the Western Corn Belt states; of all 

the Western Corn Belt RQs, only the RQ for the early pre-plant application exceeds the 

LOC (RQ = 1.65). 

Since amicarbazone is an herbicide that is effective at pre- and post-emergence stages, 

adverse effects on non-target terrestrial plant emergence and post-emergence survival 

and growth are a predicted outcome for the proposed uses of amicarbazone. Results of 

seedling emergence and vegetative vigor studies indicate that monocots and dicots are 

susceptible to injury and impaired growth, with dicots appearing more sensitive than 

monocots. Similar findings of this risk assessment suggest that amicarbazone poses a 

higher risk to dicots (RQs range from 0.31 to 7.62 for non-listed, and from 0.77 to 14.29 

for listed) than monocots (RQs range from 0.06 to 2.29 for non-listed, and from 0.10 to 

6.73 for listed). The RQ for non-listed dicots in adjacent terrestrial areas is the only RQ of 

all dicots (listed and non-listed) that does not exceed the LOC at the highest application 

rate, whereas for both listed and non-listed monocots, only those in semi-aquatic areas 

appear to be at risk. 

Results of this risk assessment suggest that plants are most at risk in semi-aquatic areas. 

For non-listed and listed monocots and dicots, all RQs for emergence of plants in 

semi-aquatic areas adjacent to the treatment site exceed the LOCs, except for non-listed 

monocots at the lowest application rate. The only other RQ that exceeds the LOC for

non-listed plants is for dicots exposed via spray drift at the highest application rate. For 

listed plants that are not in semi-aquatic areas, only emerging dicots in adjacent terrestrial 

areas (at the maximum application rate) and dicots exposed to amicarbazone via spray 

drift (for the maximum and middle application rates) are at risk.

Presented with the calculated RQs for terrestrial plants, it appears that the major route of 

exposure and source of risk for terrestrial plants is via runoff and soil/root uptake by 

emerging seedlings. However, given that a few RQ values did exceed LOCs for emerged 

plants exposed to drift, the AgDRIFT model (Version 2.01) was used to refine the spray drift 

exposure estimates. Downwind spray drift buffers were developed for possible use in reducing risk 

for endangered terrestrial plants that grow in close proximity to agricultural and non-agricultural 

fields that may be treated with liquid spray applications of amicarbazone. The results of the 

AgDRIFT modeling show that drift dissipation distances, based on ground boom applications at 
4

0.45 lb ai/A, range from 7 feet to 492 feet. These predicted distances provide potential spray drift 

buffer distances that can be used as a tool to protect endangered and non-endangered plants. 

Other potential spray drift prevention measures (i.e., lower release heights, wind speed 

restrictions, and specification of medium to coarse spray droplet sizes) could be based upon such 

predictions as well. 

C. Conclusions - Exposure Characterization

Amicarbazone is moderately persistent in the environment as it eventually transforms by

biotic mechanisms (t1⁄2= 87 days). Under acidic and neutral environments, 

amicarbazone is stable to hydrolysis, but transforms slowly under alkaline conditions. 

Photolysis also occurs slowly for amicarbazone in water and on soil with half-lives on the 

order of about two months, estimated for outdoor environmental conditions. The 

primary transformation products of amicarbazone are Des-amino:

N-(1,1-dimethylethyl)-4,5-dihydro-3-(1-methylethyl)-5-

oxo-1H-1,2,4-triazole-1-carboxamide; N-methyl Des-amino:

N-(1,1-dimethylethyl)-4,5-dihydro-4-methyl-3-(1-methylethyl)-5-oxo-1H-1,2,4-triazole-car

boxamide; and Decarboxamide: 

4-amino-2,4-dihydro-5-(1-methylethyl)-3H-1,2,4-triazol-3-one. 

Amicarbazone has a low vapor pressure and Henry’s Law constant. Therefore, 

volatilization, from water and soil surfaces, is not expected to be an important 

environmental fate process. The moderate persistence and high mobility of 

amicarbazone in soil make leaching of this compound to lower soil horizons and 

groundwater possible. Likewise, leaching and possible ground water contamination with 

amicarbazone’s major three transformation products are possible due to their apparent 

long persistence and high mobility. Amicarbazone is not to be applied on calcareous soils 

with pH values substantially higher than 7.4. Therefore, the fate of the chemical under 

neutral and acidic conditions only is considered in this assessment. In such 

environments, two major amicarbazone transformation products (Des-amino and 

N-methyl Des-amino) are expected to be formed. Given the moderate persistence/high 

mobility and solubility of the parent compound and the apparent high persistence/high 

mobility of the two transformation products, both amicarbazone and its first two 

transformation products are expected to dissipate slowly and at the same time be 

vulnerable to leaching/run-off. If amicarbazone is transported into alkaline ground 

water, surface water bodies and/or soils, the third transformation product 

(Decarboxamide) may be formed since this was the only major metabolite identified in the 

base-catalyzed hydrolytic transformation of amicarbazone. 

D. Conclusions - Effects Characterization

Results of acute toxicity studies indicate that technical grade amicarbazone 

(amicarbazone TGAI) is practically non-toxic to honey bees, slightly toxic to mammals, 
5

and slightly toxic to practically non-toxic to birds. However, results of chronic toxicity 

studies show that longer-term exposure to amicarbazone TGAI results in adverse effects 

on growth and reproductive parameters in birds and toxicity to parents and offspring in 

mammals. Chronic exposure of bobwhite quail and mallard ducks resulted in 

exposure-related reproductive effects, including decreased number of viable embryos per 

eggs set, number of hatchlings per egg set, and eggshell thickness as the most sensitive 

endpoints. In mammals, chronic exposure of rats resulted in decreased body weight and 

body weight gain in parents and offspring, but no adverse effects on reproductive 

outcome. No data are available to characterize the effects of amicarbazone metabolites 

in mammals, birds, or insects. 

Results of Tier 2 seedling emergence and vegetative vigor terrestrial plant studies with 

the amicarbazone formulated product MKH 3586 70 WG show that both monocots and 

dicots are sensitive to exposure, with dicots appearing more sensitive. Tier 2 seedling 

emergence and vegetative vigor studies with the amicarbazone metabolite MKH 3594 

(Des-amino) indicate that the metabolite is less toxic than the parent compound for the 

four species tested, except for onion. Based on the results of the seedling emergence 

test, Des-amino appears to be more toxic to onion than the parent.

Toxicity studies demonstrate that amicarbazone is practically non-toxic on an acute basis 

to freshwater and estuarine/marine fish, slightly toxic to freshwater invertebrates, and 

slightly toxic to practically non-toxic to estuarine/marine invertebrates. Longer-term 

exposure of aquatic animals to amicarbazone produces adverse effects on growth 

parameters in freshwater fish and on growth and reproductive parameters in freshwater 

and estuarine/marine invertebrates. Data are not available to characterize the effects of 

longer-term exposure of estuarine/marine fish to amicarbazone. No data are available to 

characterize the effects of amicarbazone metabolites in aquatic animals. 

In the aquatic environment, amicarbazone appears to be particularly toxic to algae, but 

produces adverse effects on survival and growth in both algae and vascular plants. The 

results of a single study assessing the toxicity of the amicarbazone metabolite Des-amino 

in Selenastrum capricornutum (a freshwater green algae), indicate that Des-amino is less 

toxic than the parent compound.

E. Data Gaps and Uncertainties

1. Environmental Fate 

The screening level risk assessment for amicarbazone has been conducted despite 

unfulfilled guideline requirements and existing data gaps. Table I-1 (Appendix I 

attached to the new chemical registration review) lists the status of the fate and transport 

data requirements for amicarbazone. In order to meet data requirements and reduce 
6

uncertainty, the registrant is requested to conduct:

(1) New aerobic soil metabolism studies for additional US soils chosen to represent 

important use areas with varied texture and organic matter content. In this respect, It is 

advised to consider one or more of the soils used in the submitted adsorption/desorption 

studies; especially if these soils can represent one or more major proposed use areas; 

and

(2) Two aerobic water/sediment metabolism studies representing a water/sediment 

system in the proposed use area (pond water and river water/sediment systems).

No anaerobic metabolism studies are requested at this time because available data from 

the submitted anaerobic water/sediment system suggest amicarbazone is stable in 

anaerobic systems. In case other non-submitted data suggest different conclusion, the 

registrant is requested to submit such data or conduct new studies. It is important to 

note that prospective ground water studies for amicarbazone are underway. 

Complete characterization of the fate of amicarbazone requires physicochemical (i.e. 

solubility and vapor pressure) and fate data on its three major metabolites: Des-amino, 

N-methyl Des-amino and Decarboxamide. In obtaining the data, the test material for the 

requested studies should be the individual metabolites. At this time, the following 

studies are requested for only Des-amino, N-methyl Des-amino:

(1) Hydrolysis; and

(2) Aerobic soil metabolism.

The objectives for these studies are to obtain data on transformation kinetics of the 

transformation products and possible transformation pathway(s) from parent and among 

metabolites. Data will be valuable in the establishment of degradation pathway(s) for

amicarbazone in important environmental systems and in identifying the terminal 

degradate(s) of the chemical in these systems. For the degradate Decarboxamide, the 

registrant is requested to submit a map showing soils with pH >7.4 where amicarbazone 

is not recommended for use. An indication of published measured pH of the major water 

bodies would also be helpful. Unless label changes are made to include restrictions (as 

opposed to recommendations) against the use of amicarbazone on alkaline soils, future 

requests for additional studies on the Decarboxamide degradate will be based on the 

submitted map and are currently in reserve.

In this risk assessment, the following uncertainties are identified:

(1) Exposure modeling for aquatic systems was conducted with only the parent 

compound, amicarbazone, and transformation products were not included in the 
7

exposure assessment. Freshwater algae are the only aquatic organisms at risk following 

exposure to amicarbazone, and limited available data on the toxicity of the transformation 

products to aquatic algae and terrestrial plants suggest that they are relatively less toxic 

than the parent.

(2) In absence of replicates for selected abiotic and biotic fate studies, degradation rates were 

multiplied by safety factors to account for inherent variability and uncertainty in the aquatic 

exposure assessment. EFED requires a minimum of three studies to secure such variability. 

(3) Assignment of the time-line of exposure to the transformation products of 

amicarbazone: Uncertainty was a result of the limited data available on the transformation 

products of amicarbazone and therefore, it was difficult determine which transformation 

product(s) would be the terminal. 

(4) Assignment of Des-amino and N-methyl Des-amino as the only terminal 

transformation products: In this assessment, only two of the major three transformation 

products of amicarbazone were considered; Des-amino and N-methyl Des-amino. This 

was based on data suggesting that these two transformation products are the terminal 

transformation products in the environment where the chemical is proposed to be applied; 

to non-calcareous soils (pH <7.4). Submitted data suggest that the third major 

degradate, Decarboxamide forms as a result of hydrolysis at pH 9 (i.e. in alkaline 

environments) and indirect aqueous photolysis (i.e. shallow surface water). Uncertainty 

exists on the importance of this degradate in areas where the parent is proposed to be 

applied. This assessment did not cover the possibility of finding this degradate in 

shallow surface water where the parent is applied or transported by drift and/or running 

water nor it covers the possibility of finding this degradate in ground water resulting from 

alkaline hydrolysis of the parent in soil sub surface layers or calcareous aquifers.

2. Ecological Effects

The screening level risk assessment for amicarbazone has been conducted despite 

unfulfilled guideline requirements and existing data gaps. Table I-2 (Appendix I 

attached to the new chemical registration review) lists the status of the ecological effects 

data requirements for amicarbazone. In order to meet data requirements and reduce 

uncertainty in this risk assessment, we are requesting that the registrant submits the 

following:

(1) Guideline 71-2: Acute Avian Dietary (Quail); the submitted study does not satisfy the 

guideline. The submitted study was classified as invalid because of poor husbandry and because 

it failed to establish a valid LC50 value with corresponding 95% confidence limits. Therefore, it 

cannot be comfortably stated that the LC50 is likely to be greater than 5000 ppm. An acceptable 

study will improve the certainty of the risk assessment.
8

(2) Guideline 71-4: Avian Reproduction (Mallard and Quail) using the Amicarbazone 

degradates. Currently, there are no available data to assess the chronic toxicity of each of 

the degradates to birds. Based on the half-lives from the one aerobic soil metabolism study, the 

metabolites are highly persistent and there is the potential for exposure of birds to these chemicals.

In addition, there is evidence that the parent and its degradates accumulate in potential 

forage items for birds. At this time, these data are being requested for only Des-amino 

and N-methyl Des-amino. The value of this additional information is high. Unless label 

changes are made to include restrictions (as opposed to recommendations) against the use of 

amicarbazone on alkaline soils, an additional study on the chronic toxicity of the degradate, 

Decarboxamide, is in reserve pending the submission of the requested soils map showing

where amicarbazone is not recommended for use on alkaline soils.

(3) Guideline 72-4: Fish Early Life Stage - Estuarine/Marine; no chronic 

estuarine/marine fish toxicity data were submitted or located in the open literature for

amicarbazone. Based on the usage patterns of amicarbazone concentrated heavily in 

the Midwest and low risk to freshwater fish, chronic risk to estuarine/marine fish appears 

to be low. However, low risk to freshwater fish does not necessarily indicate that risk to 

estuarine/marine fish is also low. Amicarbazone is intended for use such that its 

presence in water is likely to be continuous or recurrent and quantifiable taxonomic 

sensitivity factors between freshwater and estuarine/marine fish do not exist. Therefore, 

chronic risks associated with estuarine/marine fish exposure to amicarbazone are 

unknown and a fish early life stage for estuarine/marine fish is being requested.

(4) Guideline 72-4: Aquatic Invertebrate Life Cycle (Freshwater Invertebrates); estimated 

chronic effects for freshwater invertebrates are uncertain because the study submitted by the 

registrant shows a statistically significant decrease in terminal lengths, the most sensitive 

endpoint, at all test concentrations. Although the study is scientifically sound, it does not satisfy

the guideline because a NOAEC was not experimentally determined for all endpoints. The 

uncertainties associated with predicted risks to freshwater invertebrates could be 

reduced if chronic toxicity data on amicarbazone were provided to the Agency. 

(5) Guideline 72-4: Aquatic Invertebrate Life-Cycle (Marine Invertebrates); the available 

chronic estuarine/marine invertebrate toxicity study is classified as supplemental and 

does not meet guideline requirements because several endpoints were not examined. 

Daily survival of the first-generation mysids, the number of reproductive females, 

second-generation mysid survival, development, and behavior, and gender-specific 

terminal growth measurements were not reported. The uncertainties associated with 

predicted chronic risk to estuarine/marine invertebrates can be reduced if the applicable 

raw data are provided to the Agency. 

(6) Guideline 123-1: Tier II Vegetative Vigor; the available vegetative vigor study using 

amicarbazone is classified as invalid for sugarbeet and tomato only. Data collected for these 

species are classified as invalid due to overcrowded conditions and heightened competition. 
9

Acceptable data submitted for these species will improve the certainty of the risk 

assessment. Because sugarbeet appears to be a very sensitive species, the risk to 

non-target plants may be underestimated until we have additional data. Therefore, the 

value of this additional information is very high.

(7) Guideline 123-1: Tier II Seedling Emergence and Vegetative Vigor using the 

Amicarbazone Degradates; Des-amino and N-methyl Des-amino. There is uncertainty

regarding terrestrial plant risk associated with exposure to amicarbazone degradates. 

The current submitted seedling emergence and vegetative vigor studies using Des-amino 

each only test the toxicity to three species of terrestrial non-target plants. Also, the 

available vegetative vigor data for sugarbeet is classified as invalid due to overcrowded 

conditions and heightened competition. Because sugarbeet appears to be a very 

sensitive species, the risk to non-target plants may be underestimated until we have 

additional data. The seedling emergence study also indicates that Des-amino is more 

toxic than the parent compound for one of the three species tested. A NOAEC and an 

EC05 were determined for onion emergence in this study that were lower than the NOAEC 

and EC05 determined for the most sensitive endpoint for onion in the Tier II seedling 

emergence test with the parent. This indicates that, at least for this species, there could 

be a greater risk associated with Des-amino than with the parent. In addition, while all 

EC25's and NOAECs for the other species were greater than the highest concentration 

tested (0.028 lb a.i./A), the applied concentrations were less than the maximum 

application rate. Based on the half-lives from the one aerobic soil metabolism study, the 

metabolites are highly persistent and there is the potential for exposure of plants to these 

chemicals. At this time, these data are being requested for only Des-amino and N-methyl 

Des-amino and value of this additional information is high. Unless label changes are made to 

include restrictions (as opposed to recommendations) against the use of amicarbazone on alkaline 

soils, a seedling emergence and vegetative vigor study on the toxicity of the degradate, 

Decarboxamide, is in reserve pending the submission of the requested soils map 

showing where amicarbazone is not recommended for use on alkaline soils.

Remaining uncertainties in this risk assessment include:

(1) A NOAEC was not established for freshwater invertebrates in the chronic toxicity study 

on Daphnia magna (i.e., decreased terminal length was observed at the lowest 

concentration of amicarbazone tested). Therefore, measures of effect were estimated based 

on the LOAEC in order to complete the screening-level assessment of potential risk, and there is 

uncertainty associated with the predicted risk to freshwater invertebrates.

(2) Amicarbazone exhibits systemic toxicity to plants, transport through run-off or 

leaching and subsequent uptake by plants is likely, and herbicides that are photosystem II 

inhibitors like amicarbazone have a tendency to be metabolized into non-phytotoxic 

chemicals by plants that are resistant to their adverse effects. In addition, confined 

rotational crop studies suggest that amicarbazone and its degradates can accumulate in 

plants. Therefore, there is great uncertainty concerning the amount of this chemical and 
10

its degradates in plants and the magnitude of exposure to animals that forage on those 

plants. 

II. Problem Formulation

A. Stressor Source and Distribution

1. Source and Intensity

Amicarbazone parent and its transformation products Des-amino (32-34%) and N-methyl 

Des-amino (11%) are considered to be the stressors that would result from application of 

amicarbazone to field corn and/or silage corn. Most of the applied chemical will reach 

the soil (planted with field or silage corn) while only a small fraction is expected to reach 

nearby terrestrial and/or aquatic environments by drift. Following application of 

formulated products of amicarbazone to non-calcareous soils (pH 7), bio-transformation 

is expected to result in the formation of its two major transformation products Des-amino 

and N-methyl Des-amino. Aquatic systems and ground water are expected to potentially 

receive additional contamination with the parent and the transformation products as a 

result of the moderate persistence/high mobility of the parent and the apparent high 

persistence/high mobility of the transformation products. Although the level of 

contamination of the parent in an aquatic system may increase over that received from 

initial drift (as a result of run-off/erosion), the level of contamination of an aquatic system 

with the degradation products will be dependent, with one exception, on the quantity of 

run-off/erosion of the parent into the aquatic system since the parent is stable to 

hydrolysis. The exception is shallow/clear water bodies in which the parent degrades 

slowly via photolysis into one of its metabolites, Des-amino. 

2. Physicochemical, Fate, and Transport Properties

Amicarbazone and its degradation products are characterized by their high mobility in soil 

and moderate to long persistence time. The relatively low log Kow and high water 

solubility of the parent suggest bio-concentration in aquatic species such as fish will be 

low. The low vapor pressure and low Henry’s Law constant suggest volatilization from 

soil and water will not be an important environmental fate process.

3. Pesticide Type, Class, and Mode of Action

Amicarbazone is the common name for 

4-amino-4,5-dihydro-N-(1,1-dimethylethyl)-3-(1-methylethyl)-5-oxo-1H-1,2,4-triazole-1-c

arboxamide, which is the active ingredient in Amicarbazone DF Herbicide. The active 

ingredient is formulated as a water dispersible granule (70% amicarbazone and 30% inert 

ingredients, EPA Registration No. 66330-UA). Amicarbazone belongs to the triazolinone 
11

class of compounds and is a photosystem II (PS II) inhibitor with burn-down activity. This 

portion of the photosynthesis cycle uses light energy to drive two chemical reactions: the 

oxidation of water and the reduction of plastoquinone. Over twenty polypeptides and 

several different redox components (chlorophyll, pheophytin, plastoquinone, tyrosine, 

Mn, Fe, cytochrome b559, carotenoid, and histidine) have been shown to participate in 

light-induced electron transfer during this process (North Dakota State University 

Extension Service, 2003). No specific information is available on the mechanism of 

action of amicarbazone which affects the PS II process. 

4. Overview of Pesticide Usage

The amicarbazone herbicide formulation was developed and patented by Bayer AG of 

Leverkusen Germany. In 2002, Arvesta (San Francisco) acquired the worldwide rights 

to the product which is approved for use in Brazil (as Dinamic) and is under review for 

registration by the U.S. EPA Office of Pesticide Programs for its proposed use as a 

selective ground-spray herbicide to control important annual broadleaf weeds in field and 

silage corn in the United States. It can be used at several stages of crop development, 

with proposed uses for pre-plant, pre-emergence, and early post-emergence 

applications. Targeted as a competitor for atrazine, amicarbazone provides control of 

broadleaf weeds at lower application rates. Amicarbazone is not intended for use on 

popcorn, sweet corn, high corn oil hybrids or corn grown for seed. 

B. Receptors 

1. Ecological Effects

Table 1 gives examples of taxonomic groups and test species evaluated for ecological 

effects in screening-level risk assessments. Within each of these very broad taxonomic 

groups, an acute and/or chronic measure of effect is selected from the available test data. 

Additional ecological effects data for amicarbazone are available for honey bees (Apis 

mellifera) and have been incorporated into the risk characterization as an additional line 

of evidence. In addition to studies on the parent compound, ecological effects data for 

amicarbazone the Des-amino metabolite are available for terrestrial plants and algae. 

No studies on amicarbazone TGAI were submitted for chronic exposure of 

estuarine/marine fish.

Table 1. Taxonomic groups and test species evaluated for ecological effects in 

screening-level risk assessments.

Taxonomic group Example(s) of representative species

Birds a Mallard duck (Anas platyrhynchos)

Bobwhite quail (Colinus virginianus)
12

Table 1. Taxonomic groups and test species evaluated for ecological effects in 

screening-level risk assessments.

Mammals Laboratory rat (Rattus norvegicus)

Insects Honey bee (Apis mellifera L.)

Freshwater fish b Bluegill sunfish (Lepomis macrochirus)

Rainbow trout (Oncorhynchus mykiss)

Freshwater invertebrates Water flea (Daphnia magna)

Estuarine/marine fish Sheepshead minnow (Cyprinodon variegatus)

Estuarine/marine invertebrates Eastern oyster (Crassostrea virginica) 

Mysid shrimp (Americamysis bahia)

Terrestrial plants c Monocots – corn (Zea mays)

Dicots – soybean (Glycine max)

Aquatic plants and algae Duckweed (Lemna gibba) 

Green algae (Selenastrum capricornutum)

a

Birds represent surrogates for amphibians (terrestrial phase) and reptiles.

b

Freshwater fish may be surrogates for amphibians (aquatic phase).

c

Four species of two families of monocots, of which one is corn; six species of at least four dicot families, of which 

one is soybeans.

A complete discussion of all toxicity data available for this risk assessment and the 

resulting measurements of effect selected for each taxonomic group are included in 

Appendix E.

2. Ecosystems at Risk 

Ecosystems potentially at risk are expressed in terms of the selected assessment 

endpoints. The typical assessment endpoints for screening-level pesticide ecological risk 

assessments are reduced survival and reproductive and growth impairment for both 

aquatic and terrestrial animal species. Aquatic animal species of potential concern 

include freshwater fish and invertebrates, estuarine/marine fish and invertebrates, and 

amphibians. Terrestrial animal species of potential concern include birds, mammals, 

beneficial insects, and earthworms. For both aquatic and terrestrial animal species, 

direct acute and direct chronic exposures are considered. The measures of effect 

selected to characterize potential ecological risks associated with exposure to 

amicarbazone are summarized in Table 2. 

Table 2. Summary of assessment endpoints and measures of effect for 

amicarbazone (TGAI).
13

Table 2. Summary of assessment endpoints and measures of effect for 

amicarbazone (TGAI).

Assessment Endpoint Measures of Effect

1. Abundance (i.e., survival, reproduction, and 

growth) of individuals and populations of birds.

1a. Bobwhite quail acute oral LD50.

1b. Mallard duck subacute dietary LC50.

1c. Bobwhite quail and mallard duck chronic 

reproduction NOAEC and LOAEC.

2. Abundance (i.e., survival, reproduction, and 

growth) of individuals and populations of 

mammals.

2a. Laboratory rat acute oral LD50.

2b. Laboratory rat 2-generation reproduction 

chronic NOAEC and LOAEC.

3. Survival and reproduction of individuals and 

communities of freshwater fish and invertebrates.

3a. Rainbow trout and bluegill sunfish acute LC50.

3b. Fathead minnow chronic (early-life) NOAEC 

and LOAEC.

3c. Water flea acute EC50.

3d. Water flea chronic (life-cycle) LOAEC

4. Survival and reproduction of individuals and 

communities of estuarine/marine fish and 

invertebrates.

4a. Sheepshead minnow acute LC50.

4b. Eastern oyster and mysid shrimp acute LC50.

4c. Mysid shrimp chronic (life-cycle) NOAEC and 

LOAEC.

5. Survival of beneficial insect populations. 5a. Honeybee acute contact LD50.

5b. Honeybee acute oral LD50.

6. Perpetuation of individuals and populations of 

non-target terrestrial and semi-aquatic species 

(crops and non-crop plant species).

6a. Monocot and dicot seedling emergence and 

vegetative vigor EC25 values.

7. Maintenance and growth of individuals and 

populations of aquatic plants from standing crop 

or biomass.

7a. Algal and vascular plant (i.e., duckweed) EC50

values for growth rate and biomass measurements. 

LD50 = Lethal dose to 50% of the test population.

NOAEC = No-observed-adverse-effect concentration.

LOAEC = Lowest-observed-adverse-effect concentration.

LC50 (EC50) = Lethal (effective) concentration to 50% of the test population.

LC25 (EC25) = Lethal (effective) concentration to 25% of the test population.

For terrestrial and semi-aquatic plants, the screening assessment endpoint is the 

perpetuation of populations of non-target species (crops and non-crop plant species). 

Existing testing requirements have the capacity to evaluate emergence of seedlings and 

vegetative vigor. Although it is recognized that the endpoints of seedling emergence 

and vegetative vigor may not address all terrestrial and semi-aquatic plant life cycle 

components, it is assumed that impacts at emergence and in active growth have the 

potential to impact individual competitive ability and reproductive success.
14

For aquatic plants, the assessment endpoint is the maintenance and growth of standing 

crop or biomass. Measures of effect for this assessment endpoint focus on algal and 

vascular plant (i.e., duckweed) growth rates and biomass measurements.

In order to protect threatened and endangered species, all assessment endpoints are 

measured at the individual level. Although all endpoints are measured at the individual 

level, they provide insight about risks at higher levels of biological organization (e.g. 

populations and communities). For example, pesticide effects on individual survivorship 

have important implications for both population rates of increase and habitat carrying 

capacity.

The ecological relevance of selecting the above-mentioned assessment endpoints is as 

follows: 1) complete exposure pathways exist for these receptors; 2) the receptors may 

be potentially sensitive to pesticides in affected media and in residues on plants, seeds, 

and insects; and 3) the receptors could potentially inhabit areas where pesticides are 

applied, or areas where runoff and/or spray drift may impact the sites.

C. 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. Assessment endpoints are ultimately 

selected from the available toxicity studies, and are used as the measures of effects to 

characterize potential ecological risks associated with exposure to amicarbazone.

This ecological risk assessment considers single applications of maximum application 

rates of amicarbazone to fields that have vulnerable soils to estimate exposure 

concentrations. In addition, this assessment is not intended to represent a site- or 

time-specific analysis. Instead, this assessment is intended to represent high-end 

exposures at a national level. Likewise, the most sensitive toxicity endpoints are used 

from surrogate test species to estimate treatment-related direct effects on acute mortality 

and 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, subacute, 

and reproduction studies and are typically arranged in a hierarchical or tiered system that 
15

progresses form basic laboratory tests to applied field studies. The toxicity studies are 

used to evaluate the potential of a pesticide to cause 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 

(CFR 40 §158.202, 2002). A summary of measurements of effect selected to 

characterize potential ecological risks associated with exposure to amicarbazone is 

provided in Table 2.

D. Conceptual Model 

1. Risk Hypotheses 

Risk hypotheses are specific assumptions about potential adverse effects (i.e., changes 

in assessment endpoints) and may be based on theory and logic, empirical data, 

mathematical models, or probability models (US EPA 2004). For this assessment, the 

risk is stressor-initiated, where the stressor is the release of amicarbazone to the 

environment. The following risk hypothesis is presumed for this screening level 

assessment:

Based on the mobility and persistence of amicarbazone and its transformation products, 

the mode of action, and the food-web of the non-target and target aquatic and terrestrial 

ecosystems, amicarbazone and its transformation products have the potential to cause 

reduced survival and reproductive and growth impairment of terrestrial and aquatic 

animals, and terrestrial plants. The parent compound, amicarbazone, has the 

potential to impair growth and survival of aquatic plants.

In order for a chemical 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 exposure 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. In addition, the potential mechanisms of 

transformation (i.e., which transformation products may form in the environment, in which 

media, and how much) must be understood, especially for a chemical whose 

metabolites/transformation products are of greater toxicological concern than the parent 

compound. The assessment of ecological exposure pathways, therefore, includes an 

examination of the source and potential migration pathways for constituents, and the 

determination of potential exposure routes (e.g., ingestion, inhalation, dermal 

absorption).

Application methods for amicarbazone include ground broadcast spray, broadcast 

surface spray, broadcast surface spray/soil incorporation (1-2") by moderate 

rainfall/irrigation, or soil injection. Ecological receptors that may potentially be exposed 
16

to amicarbazone and its transformation products include terrestrial and semi-aquatic 

wildlife (i.e., mammals, birds, amphibians, and reptiles), terrestrial and semi-aquatic 

plants, and soil invertebrates. In addition, aquatic receptors (e.g., freshwater and 

estuarine/marine fish and invertebrates, and amphibians) may also be exposed as a 

result of potential migration of amicarbazone via spray drift and/or runoff/erosion from the 

site of application to various watersheds and other aquatic environments. These data 

formed the basis for identifying potential endpoints, stressors, and ecological effects 

associated with uses of amicarbazone.

Acute and chronic toxicity data were identified and used for quantifying risks to mammals 

and birds. For aquatic ecosystems, acute toxicity data were available to select toxicity 

reference values for fish, aquatic invertebrates, macrophytes, and algae. Based on the 

available data, the Agency determined the measures of effect that can be quantitatively 

assessed for amicarbazone. The terrestrial toxicity data can be used to quantify 

reductions in populations of mammals and birds due to lethality as well as sub-lethal 

effects associated with chronic exposures. The aquatic toxicity data can be used to 

quantify risks in reductions of aquatic invertebrates and fish, and indirect effects on 

aquatic communities due to loss of species that are sensitive to amicarbazone, and 

corresponding changes in structure and functional characteristics of the affected 

communities.

2. Diagram

The conceptual model used to depict the potential ecological risk associated with 

amicarbazone is fairly generic and assumes that as an herbicide, amicarbazone is 

capable of affecting terrestrial and aquatic organisms provided that environmental 

concentrations are sufficiently elevated as a result of proposed label uses. However, 

through a preliminary iterative process of examining fate and effects data, the conceptual 

model, i.e., the risk hypothesis, has been refined to reflect the likely exposure pathways 

and the organisms that are most relevant and applicable to this assessment (Figure 1).

Since preliminary review of the available ecological effects data suggests that 

amicarbazone is slightly toxic to practically non-toxic to terrestrial animals on an acute 

exposure basis, acute effects to terrestrial animals are not expected. However, chronic 

exposure studies indicate that mammals and birds may be at chronic risk. Currently 

EFED does not calculate RQs for non-target beneficial insects; however, since results of 

laboratory studies suggest that amicarbazone is practically non-toxic to honey bees on an 

acute exposure basis, acute effects to non-target insects are not expected. Since 

amicarbazone is an herbicide, adverse effects on growth and survival of non-target plants 

is expected. Furthermore, results of Tier 2 toxicity studies in terrestrial plants show that 

non-target terrestrial plants may be at risk due to exposure to amicarbazone and its 

transformation products. Exposure to aquatic organisms is expected from a combination 

of direct spray-drift and runoff. Results of acute toxicity studies indicate that 
17

amicarbazone is practically non-toxic to estuarine/marine and freshwater fish, slightly 

toxic to freshwater invertebrates, and slightly toxic to practically non-toxic to 

estuarine/marine invertebrates; thus, acute effects to aquatic animals are expected to be 

minimal. Based on the results of chronic toxicity studies, freshwater invertebrates may

be at risk due to chronic exposure. However, estimated chronic effects for freshwater 

invertebrates and estuarine/marine fish are uncertain because a NOAEC was not established for 

freshwater invertebrates in the chronic toxicity study on Daphnia magna (i.e., decreased 

terminal length was observed at the lowest concentration of amicarbazone tested) and no 

chronic data were submitted by the registrant for estuarine/marine fish. However, based on the 

LOAEC for freshwater invertebrates, risk to these organisms appears to be low. Results of 

toxicity studies in aquatic plants indicate that aquatic algae may also be at risk due to 

amicarbazone exposure.

Figure 1. General Conceptual Model for Amicarbazone Screening Level Ecological Risk Assessment.
18

E. Analysis Plan

1. Development of Assessment Design

This document characterizes the environmental fate of amicarbazone to assess whether its 

proposed label uses will result in levels of exposure in aquatic and terrestrial environments that 

pose significant ecological risks. Residues in potential dietary sources for mammals and birds 

(e.g., vegetation and insects) were estimated using the conceptual approach given in the model 

T-REX. Risks to terrestrial plants were based on estimated environmental concentrations (EECs) 

calculated using TERRPLANT. For aquatic receptors (animals and plants), the main pathway of 
19

exposure is through direct contact with surface water contaminated by drift and/or runoff/erosion 

from agricultural fields. Risks to aquatic species were based on EECs of amicarbazone in surface 

water which were calculated using the Tier 2 model PRZM/EXAMS. Integration of effects and 

potential exposure provides an estimate of the risk to non-target endangered/threatened and 

non-endangered animals and plants that could potentially impact the registration decision of 

amicarbazone under the Federal Insecticide, Fungicide and Rodenticide Act, the Food Quality 

Protection Act, and the Endangered Species Act.

2. Identification of Data Gaps and Methods for Conducting Assessment

The adequacy of the submitted data was evaluated relative to Agency guidelines. The following 

identified data gaps result in a degree of uncertainty in evaluating the ecological risk of 

amicarbazone.

· Although the degradation products of amicarbazone appear to be persistent, no 

reliable data are available that adequately quantify the rates of their degradation nor 

the possible transformation within these products.

· There is uncertainty regarding terrestrial plant risk associated with 

exposure to amicarbazone degradates. The current submitted seedling 

emergence and vegetative vigor studies using Des-amino each only test 

the toxicity to three species of terrestrial non-target plants. Also, the 

available vegetative vigor data for sugarbeet is classified as invalid due to 

overcrowded conditions and heightened competition. Because sugarbeet 

appears to be a very sensitive species, the risk to non-target plants may be 

underestimated until we have additional data. The seedling emergence 

study also indicates that Des-amino is more toxic than the parent 

compound for one of the three species tested. A NOAEC and an EC05

were determined for onion emergence in this study that were lower than the 

NOAEC and EC05 determined for the most sensitive endpoint for onion in 

the Tier II seedling emergence test with the parent. This indicates that, at 

least for this species, there could be a greater risk associated with 

Des-amino than with the parent. In addition, while all EC25's and NOAECs 

for the other species were greater than the highest concentration tested 

(0.028 lb a.i./A), the applied concentrations were less than the maximum 

application rate. Based on the half-lives from the one aerobic soil metabolism 

study, the metabolites are highly persistent and there is the potential for exposure of 

plants to these chemicals. Therefore, additional seedling emergence and 

vegetative vigor data are needed to reduce the uncertainty regarding the 

toxicity of amicarbazone degradates to plants.

· No reliable data are available that adequately depict the toxicity of the 

degradation products of amicarbazone to aquatic animals. Based on the 
20

aerobic soil metabolism half-lives, the Koc, and water solubility, the metabolites are 

highly persistent and mobile and there is the potential for exposure to these 

chemicals. 

· Currently, there are no available data to assess the chronic toxicity of each of the 

degradates to birds. Based on the aerobic soil metabolism half-lives, the 

metabolites are highly persistent in the terrestrial environment and there is the 

potential for exposure of birds to these chemicals. In addition, there is evidence 

that the parent and its degradates accumulate in potential forage items for 

birds. Therefore, there is uncertainty surrounding chronic risk to birds, and the 

value of this additional information is high.

· No bioconcentration/bioaccumulation studies were submitted. Risks to 

top-level carnivores via consumption of pesticide-contaminated small 

mammals and birds were not evaluated due to a lack of data for these 

receptors. In addition, food chain exposures for aquatic and semiaquatic 

wildlife receptors (e.g., via consumption of contaminated aquatic plants, 

aquatic invertebrates and/or fish) were also not considered. However, 

based on the low log Kow and high water solubility, 

bioconcentration/bioaccumulation of amicarbazone is not expected to be of 

concern.

· Exposure and associated risks to amicarbazone in sediment were not 

evaluated for aquatic receptors and/or semiaquatic wildlife. Amicarbazone 

and its degradation products do not adsorb strongly to soil and are unlikely 

to partition significantly to sediment in the water column.

· Based on the usage patterns of amicarbazone concentrated heavily in the Midwest 

and low risk to freshwater fish, chronic risk to estuarine/marine fish appears to be 

low. However, low risk to freshwater fish does not necessarily indicate that risk to 

estuarine/marine fish is also low. Amicarbazone is intended for use such that its 

presence in water is likely to be continuous or recurrent and quantifiable taxonomic 

sensitivity factors between freshwater and estuarine/marine fish do not exist. 

Therefore, chronic risks associated with estuarine/marine fish exposure to

amicarbazone are unknown and a fish early life stage for estuarine/marine fish is 

being requested.

· A NOAEC was not established for freshwater invertebrates in the chronic 

toxicity study on Daphnia magna (i.e., decreased terminal length was 

observed at the lowest concentration of amicarbazone tested). Therefore, 

measures of effect were estimated based on the LOAEC in order to complete the 

screening-level assessment of potential risk, and there is uncertainty associated 

with the predicted risk to freshwater invertebrates.
21

· The available chronic estuarine/marine invertebrate toxicity study does not 

examine several endpoints. Daily survival of the first-generation mysids, the 

number of reproductive females, second-generation mysid survival, development, 

and behavior, and gender-specific terminal growth measurements were not 

reported. Therefore, there are uncertainties associated with predicted chronic risk to 

estuarine/marine invertebrates.

· No valid data are available on the acute dietary toxicity of amicarbazone to 

the northern bobwhite quail (Colinus virginianus). However, acceptable 

data were submitted for the mallard duck (Anas platyrhynchos) and risks 

from acute dietary exposure to birds was assessed using these data for this 

risk assessment.

· No Tier II vegetative vigor data are available to assess amicarbazone 

toxicity to sugar beet and tomato. However, acceptable vegetative vigor data were 

submitted for other plant species and acute risk to terrestrial plants was assessed 

using these data for this risk assessment.

· Amicarbazone exhibits systemic toxicity to plants, transport through run-off 

or leaching and subsequent uptake by plants is likely, and herbicides that 

are photosystem II inhibitors like amicarbazone have a tendency to be 

metabolized into non-phytotoxic chemicals by plants that are resistant to 

their adverse effects. In addition, confined rotational crop studies suggest 

that amicarbazone and its degradates can accumulate in plants. 

Therefore, there is great uncertainty concerning the amount of this chemical 

and its degradates in plants and the magnitude of exposure to animals that 

forage on those plants. 

· Inhalation and dermal exposure routes for amicarbazone in terrestrial 

mammals and birds were not evaluated in this assessment. 

Amicarbazone is directed for use as a ground spray and has a low vapor 

pressure and Henry’s Law constant. Therefore, volatilization from water 

and soil surfaces (and thus inhalation exposure) is not expected to be 

significant. However, the degree to which dermal exposure may be 

important compared to exposure from dietary ingestion is an uncertainty. 

Even though the dermal route of exposure may be important to the overall 

risk assessment, it requires analyses and data that are beyond the scope of 

a screening-level assessment. Consideration of inhalation and dermal 

routes of exposure is done more routinely in higher level (Tier II) 

assessments. Uncertainties associated with exposure pathways for

terrestrial animals are discussed in Section IV(C).
22

· Surrogates were used to predict potential risks for species with no data (i.e., 

reptiles and amphibians). It was assumed that the use of surrogate effects 

data is sufficiently conservative to apply to the broad range of species within 

taxonomic groups. If other species are more or less sensitive to 

amicarbazone and associated transformation products than the surrogates, 

risks may be under- or overestimated, respectively.

3. Measures to Evaluate Risk Hypotheses and Conceptual Model

a. Measures of Exposure

Aquatic exposure concentrations for this assessment were modeled using the Tier II 

linked, Pesticide Root Zone Model version 3.1.2 beta (Carsel and others, 1997) and 

Exposure Analysis Modeling System version 2.98.04 (Burns, 1997); referred to as 

PRZM/EXAMS. The linked PRZM and EXAMS model is typically used by EFED in 

estimating pesticide concentrations in aquatic systems. PRZM is employed to evaluate 

run-off loading from a ten-hectare agricultural field to a receiving surface water body

(one-hectare-by-two-meter-deep “standard” pond). Residues in potential dietary 

sources for mammals and birds (e.g., vegetation, insects) were estimated using the 

conceptual approach given in the model T-REX Version 1.12 (T-REX, 2004). For 

terrestrial plants, exposure was estimated using the model TERRPLANT, Version 1.0 

(TERRPLANT, 2001).

b. Measures of Effect

Measures of effect are generally based on the results of a toxicity study, although 

monitoring data may also be used to provide supporting lines of evidence for the risk 

characterization. However, there is no currently available monitoring data because this 

is a new chemical. A complete summary of the measures of effect based on toxicity 

studies for different ecological receptors and effect endpoints (acute/chronic) is given in 

Table 2. Examples of measures of acute effects (e.g., lethality) include an oral LD50 for 

birds and mammals, an LC50 for fish and invertebrates, and an EC50 for plants based on 

biomass and growth rate measurements. Examples of measures of chronic effects 

include NOAEL values for birds and mammals based on reproduction or developmental 

endpoints.

c. Measures of Ecosystem and Receptor Characteristics

Selected models are: Tier 2 PRZM/EXAMS (for aquatic exposure assessment), Tier 1 

T-REX (for terrestrial animal dietary exposure assessment), and Tier 1 TERRPLANT (for 

terrestrial plant exposure assessment). Selected ecosystems used in exposure 

modeling are intended to be generally representative of any aquatic or terrestrial 

ecosystem associated with areas where amicarbazone is used. The receptors 

addressed by the aquatic and terrestrial risk assessments are summarized in Figure 1. 
23

For aquatic assessments, generally fish and aquatic invertebrates in both freshwater and 

estuarine/marine environments are represented. For terrestrial assessments, three 

different size classes of small mammals are represented, along with five potential 

foraging categories (short grass, tall grass, broadleaf plants/small insects, 

fruits/pods/seeds/large insects, and seeds). For birds, four potential foraging categories 

are considered (short grass, tall grass, broadleaf plants/small insects, and 

fruits/pods/seeds/large insects). For terrestrial plants, both dicots and monocots are 

represented. Detailed information regarding the toxicity data available for these various 

classes of aquatic and terrestrial receptors is provided in Appendix E.

III. Analysis

A. Use Characterization

Amicarbazone is a new selective herbicide being registered for use in the control of 

annual broadleaf weeds for corn crops; therefore, no statistics regarding the amount of 

product used and location of its use in the United States are available. Since 

amicarbazone is being proposed for use on field corn and silage corn, its use can be 

anticipated to occur anywhere in the U.S., but predominantly in Midwestern states. Corn 

is the largest crop grown in the United States, in terms of both volume and value. The 

states of Iowa, Illinois, Nebraska, and Minnesota account for more than 50 percent of U.S. 

corn production. Other major corn-producing states include Indiana, Wisconsin, South 

Dakota, Michigan, Missouri, Kansas, Ohio and Kentucky. Regional distribution of field 

corn and corn for silage acreage in the U.S. in 2002 is depicted in Figure 2, and reflects 

the anticipated regions for amicarbazone use throughout the U.S.
24

Figure 2. Regional distribution of field corn and corn for silage acreage in the 

United States in 2002 (USDA/NASS county level data).
25

This herbicide is not recommended for use in coarse-textured soils (sand, loamy sand 

and sandy loam soils), or in soils with pH >7.4, such as calcareous soils. Amicarbazone is 

proposed to be applied as broadcast ground spray, broadcast surface spray, broadcast 

surface spray/soil incorporated 1 to 2 inches, injected or irrigated in at a maximum rate of 

10.25 oz formulated product/acre/year (0.45 lb a.i/acre/year) (Table 3). The maximum 

annual label rate is usually applied at a single application, but can be applied as a split 

application under certain conditions. The chemical is proposed to be applied to 

conventional/till or conservation/no till crop systems: early pre-plant (30 days before 

planting), pre-plant (29 days before planting), during planting, pre-emergence (after 

planting/prior to weed or crop emergence), and early post emergence (up to 10-leaf collar 

stage V-10). The proposed label also permits special fall applications following harvest 

of a previous crop. fall application should take place after October 15, before the ground 

freezes, with or without the spring planting application (up to within 30-days of planting 

corn in the spring). Amicarbazone can be used as part of specified tank-mixes to control 

emerged weeds, and is most effective when surface applied (prior to weed germination) and 

subsequently distributed into the top 1-2" by moderate rainfall/irrigation, mechanical shallow 

incorporation, or injection.

The recommended use rates for Amicarbazone DF Herbicide depend upon the timing of 

the application and the characteristics of the soil to which the product is applied (Table 3). 

The maximum use rate of 10.25 ounces formulation/acre (0.45 lb a.i./acre) is 

recommended only for early pre-plant applications conducted in the states comprising the 

Eastern corn belt (i.e., MN, MO, AR, LA, and IA east of the US Hwy 71 and points east). 

Lesser rates of 5.0-7.5 ounce formulation/acre (0.22-0.33 lb a.i./acre) or 5.0-10.25 

ounces formulation/acre (0.22-0.45 lb a.i./acre) are recommended for pre-plant and 

pre-emergence applications in the Eastern corn belt states (depending on the organic 

matter content of the soil), and for early pre-plant applications in the states comprising the 

Western corn belt (i.e., ND, SD, NE, KS, OK, TX, and IA west of US Hwy 71 and points 

west). For pre-plant and pre-emergence applications in the Western corn belt states, the 

recommended use rate is 5.0 ounces formulation/acre (0.22 lb a.i./acre). For early 

post-emergence applications, the recommended use rate is 2.25 to 3.5 oz

formulation/acre (0.10 to 0.15 lb a.i./A). 

Table 3. Label application parameters recommended for amicarbazone (Ground spray only).

Application Windows Application 

Procedure

(All Ground Spray)

Rate (lb a.i./Acre)*: Maximum per 

Year

Plant Stage Date of Application

Eastern 

Corn Belt 1

Western Corn Belt 2

I. Usual Applications

Early 

Pre-plant

 30 days before planting Surface spray; 

Or

0.450 0.450
26

Application Windows Application 

Procedure

(All Ground Spray)

Rate (lb a.i./Acre)*: Maximum per 

Year

Plant Stage Date of Application

Eastern 

Corn Belt 1

Western Corn Belt 2

Pre-plant 29 days before planting Surface spray and shallow 

incorporation; 0.450 0.21873

At planting At planting Open furrow, seed, close 

furrow-surface applyincorporate or/irrigate in

Pre-emergence From planting to prior to 

emergence 

Surface applied when weeds are 

small and actively growing 

mostly in tank-mix with other 

Early Post- herbicides

emergence

From emergence to the 10-leaf 

collar stage

0.15

II. Special Applications

Fall 

Applications

After October 15 before 

ground is frozen

Surface applied into stubble: till 

then apply 

Or

Apply then till (incorporation)

One application= 0.45

2 applications= 0.22 + 0.22

Locations 3

Spring application Usual types of application stated 

above

Winter Weed 

Control

Following fall harvest of 

previous crops

(from November to within 30 

days of planting)

Surface applied into stubble: till 

then apply 

Or

Apply then till (incorporation

One application= 0.45

2 applications= 0.22 + 0.22

Locations 4

Spring application Usual types of application stated 

above

Pre-plant

& 

Pre-emergence 

Burn down

This application is recommended when weeds are present at the time of treatment and amicarbazone is 

recommended to be used in tank- mix with other herbicides. No rate was stated in the label, however, the 

rate is expected to be lower than the maximum annual rate (0.45 lb a.i./acre).

*

Rates: 0.45 lb a.i/Acre= 0.50 Kg/Hac; 0.22 lb a.i/Acre= 0.25 Kg/Hac; 0.22 lb a.i/Acre= 0.25 Kg/Hac; and 0.15 lb 

a.i/Acre= 0.17 Kg/Hac.

1

Eastern corn belt states: MN, MO, AR, LA and IA (east of US Hwy 71 and points east).

2 Western corn belt states: ND, SD, NE, KS, OK, TX, and IA (west of US Hwy 71 and points west). 

3

IA, MN, ND, SD, WI, NE (north of Route 20), IL (north of route 136), and OH (north of Interstate 70).

4 KS, OK and TX.

Amicarbazone label designates areas for various application procedures and rates. A

map showing these areas is included in Figure 3. Locations of various highways stated 
27

in the label were used to designate the western corn belt, eastern corn belt, and the areas 

for winter weed and fall application on the map. Additionally, the map includes 

representative corn scenarios used in modeling to calculate aquatic EECs for the 

ecological risk assessment.
28

Figure 3. A map showing designated areas for the proposed various types of 

applications of amicarbazone.
29

B. Exposure Characterization

1. Environmental Fate and Transport Characterization

Arvesta Corporation is seeking registration for the use of amicarbazone, a new selective 

herbicide to be used for control of annual broadleaf weeds in field corn and corn grown for

silage. Since this is a relatively new compound, information on the environmental fate of 

amicarbazone comes primarily from registrant-submitted data. The important 

physicochemical and environmental fate properties of amicarbazone are provided in 

Table 4.

Table 4. Physicochemical and Fate Properties of Amicarbazone and Mobility of 

its Major Transformation Products.

Property Value Reference 

(MRID)

I. Physicochemical Properties of Parent Amicarbazone

Molecular Weight 241 451215-01

SMILES Notation NN(C(C(C)C)=NN1C(NC(C)(C)C)=O)C1=O

CAS number 129909-90-6 451215-01

Water solubility 4.6 g/L 451215-01

Melting point 137.5C 451215-01

Boiling point Decompose above 180C 451215-01

Vapor pressure (VP) 1.3x10-6

Pa ( 9.8x10-9 mm Hg) at 20C

3.0x10-6Pa (2.2x10-8 mm Hg) at 25C

"C 451215-01

Kow 14 unbuffered;

15 at pH 4;

17 at pH 7 and 9

451215-01

Henry’s law constant 1.5x10-12 atm m3 mol

-1

(from VP and solubility) 451215-01

Calculated 

II. Fate Properties of Parent Amicarbazone

Hydrolysis half-lives pH 4= stable

pH 7= stable

pH 9= 66 days

Major Degradation products: Decarboxamide (Max 29% @30 

days)

451217-30

Aqueous photolysis 

half-lives

Direct photolysis: Stable in sterile pH 7 buffer

Indirect photolysis: 73 days of natural sunlight equivalent 

451218-03
30

Property Value Reference 

(MRID)

(NSE) in pond water pH 8.4

Major Degradation products: Des-amino (Max 16% @35 days 

of NSE) and Decarboxamide (Max 9% @35 days of NSE with 

2% in the dark control)

Soil photolysis half-life 54.4 days of NSE (18.6 days artificial light)

Major Degradation products: Des-amino (Max 15% @34 days 

of NSE)

4512171-4

Aerobic soil metabolism 

half-life

87 days (clay loam soil, NE)

Major Degradation products: Des-amino (Max 34-32% 

@180-360 days) and N-methyl Des-amino (Max 11% @360 

days)

451217-31

Anaerobic soil half-life No data submitted

Aerobic aquatic half-life No data submitted

Anaerobic aquatic 

half-lives (water/silt loam 

sediment system)

Stable (>4 years) in the total system and

533 days in water column.

451217-24

Adsorption coefficient Koc= 24.2 (clay soil)

Koc= 16.7 (sandy clay soil)

Koc= 19.0 (sandy clay loam soil)

451217-19

Koc= 35.9 (silt loam soil, NE)

Koc= 32.0 (silt loam soil, LA)

Koc= 37.0 (silt loam soil, NE)

Koc= 22.9 (silt loam soil, WI)

451217-32

Mobility in soil (aged= the 

parent and its 

transformation products)

Koc= 16.2-42.6 (loamy soil, NE)

Note: 74% of the applied was collected in the leachate as 

parent)

451217-17

Terrestrial Field half-lives 29 days (NE silty clay loam soil cropped with pre-emergent 

corn)

Major Degradation products: Des-amino (Max 26% @59 days) 

451217-18

19 days (WI silt loam soil cropped with pre-emergent corn)

Major Degradation products: Des-amino (Max 27% @ 61 

days)

451217-27

Bio-concentration factor No data submitted

III. Mobility of the Major Three Transformation products of Amicarbazone

Adsorption coefficient 

(Koc) for: Des-amino

26.4-42.3 (the same four silt loam soils used for the parent 

study collected from NE, LA, NE and WI)

451218-01
31

Property Value Reference 

(MRID)

Adsorption coefficient 

(Koc) for: N-methyl 

Des-amino

34.3-56.4 (the same four silt loam soils used for the parent 

study collected from NE, LA, NE and WI)

451217-33

Adsorption coefficient 

(Koc) For: 

Decarboxamide

09.4-13.8 (the same four silt loam soils used for the parent 

study collected from NE, LA, NE and WI)

451218-02

a. Summary of Empirical Data 

Laboratory studies indicated that amicarbazone is moderately persistent and very mobile 

in soils. Bio-degradation appears to be the main route for its environmental dissipation in 

soils with a half-live of nearly two or three months. Degradation of amicarbazone is 

expected to occur faster under alkaline conditions due to possible additional contribution 

of hydrolysis; however, amicarbazone is intended to be used in soils having slightly acidic 

to neutral pH. Limited data suggest that the degradation products of amicarbazone are 

also highly persistent and mobile under most environmental conditions. It is noted that 

amicarbazone was shown to degrade by indirect aqueous photolysis (t1⁄2= 73 days) and 

by photolysis on soil surfaces subjected to sunlight (t1⁄2= 54 days). Indirect aqueous 

photolysis may have limited contribution to amicarbazone dissipation in clear/shallow 

surface water; however, photolysis on soil is expected to be unimportant because of label 

recommended incorporation of the pesticide just after application. The chemical 

structures of amicarbazone and its primary degradation products Des-amino, N-methyl 

des-amino, and Decarboxamide are shown in Figure 4.

Figure 4. Amicarbazone and its primary degradation products.

Amicarbazone Parent Des-amino Degradate
32

N-methyl Des-amino Degradate Decarboxamide
33

b. Degradation and Metabolism

Under acidic and neutral conditions amicarbazone was stable and did not hydrolyze 

significantly over the course of a 30-day incubation period (MRID 45121730). A half-life 

of 66 days was observed for amicarbazone in sterile pH 9 buffer solution, with 

Decarboxamide identified as the only major transformation product. Amicarbazone was 

stable when irradiated with an artificial light source in sterile pH 7 buffer solution (i.e. 

direct photolysis), but a half-life of approximately 73 days was observed when 

amicarbazone was irradiated in pond water at pH 8.4 (indirect photolysis) (MRID 

45121803). It is noted that in the indirect photolysis study, the pH of the pond water was 

alkaline and hydrolysis may have enhanced its degradation. 

Amicarbazone applied to a silt loam soil from Nebraska at a rate of 3.4 mg a.i./kg ( label 

rate of 0.45 lb a.i./acre, depth of 0.4"), dissipated from irradiated samples with a 

reviewer-calculated half-life of 54.4 days of natural sunlight (MRID 45121714). 

Following an application of 0.26 mg a.i./kg soil ( label rate of 0.45 lb a.i./acre, depth of 

5.1") to a clay loam from Nebraska, amicarbazone dissipated with a half-life of about 87 

days under aerobic conditions. Two major transformation products were identified in this 

aerobic soil biodegradation study: Des-amino and N-methyl Des-amino (MRID 

45121731). 14C-labeled amicarbazone was almost stable in an anaerobic water/silt 

loam sediment system (half-life >4 years in the entire mesocosm and 533 days in water) 

(MRID 45121724).

No data are available to quantify the biodegradation kinetics of the transformation 

products of amicarbazone; however, based on the apparent stability of Des-amino and 

N-methyl Des-amino in soils (MRID 45121731), it is assumed that these degradation 

products are highly persistent. In a single aerobic soil metabolism study that monitored 

the dissipation of 14C-labeled amicarbazone in a clay loam soil (pH 6.8; organic matter 

2.06%) from Nebraska, N-methyl Des-amino shows no decline within a period of one year

while Des-amino shows only slight decline as it reached a maximum of 33.5-33.9% of the 

total applied radioactivity at 180-270 days post-application and slowly decreased to 

32.1% at 360 days post-application. 

c. Transport and Mobility

Based upon Koc values in the range of 19 to 37 measured in several soils, amicarbazone 

is classified as highly mobile in soil and leaching to lower soil horizons and groundwater is 

expected (MRID 45121719). Furthermore, the adsorption/desorption characteristics of 

the major transformation of amicarbazone suggest that the transformation products of 

amicarbazone are also highly mobile in soils and possess the potential to leach into 

groundwater (MRID 45121732).

Volatilization is not expected to be an important environmental fate process for 
34

amicarbazone based upon the relatively low Henry’s Law constant and vapor pressure of 

the parent compound (MRID 45121714). 

d. Field Studies

Amicarbazone was surface applied at a nominal rate of 0.56 kg a.i./ha (0.5 lb a.i./acre), 

dissipated from the top soil (0-15 cm) of a Nebraska silty clay loam cropped with 

pre-emergent corn (10.8% sand, 62% silt, 27.2% clay, pH 6.1, organic matter 3.04%) with 

a field calculated half-life of 29 days, with Des-amino identified as the major degradation 

product (MRID 45121718). Amicarbazone was only detected once in the 15-30 cm 

depth, at 0.011 μg a.i./g at 9 days post application, and was not detected below that 

depth. However, Des-amino was detected at depths of 45-60 cm at a sampling date 540 

days after the application of amicarbazone. At the completion of the 540-day study 

period, the total carryover of residues of amicarbazone and its transformation products 

were 0% and 26.8% of the nominal application rate, respectively.

In another study, amicarbazone was surface applied at a rate of 0.56 kg a.i./ha (0.5 lb 

a.i./acre), to a Wisconsin silt loam cropped with pre-emergent corn (8.3% sand, 65.5%, 

26.2%, pH 6.7, 4.0% organic matter) dissipated from the top soil (0-15 cm) with a half-life 

of 19 days (MRID 45121727). Amicarbazone was only detected in the 15-30 cm soil 

cores on sampling days 19 and 28; however, Des amino was the major degradate and 

was detected in the 30-45 cm soil core up to 528 days post application. The degradation 

profile of amicarbazone was considered bi-phasic, with an initial degradation rate that 

was much greater in the first several days of the study than for the remainder of the study. 

At the completion of the 528-day study period, the total carryover of residues of 

amicarbazone and its degradation products were 0% and 19.4% of the nominal 

application rate, respectively.

The field dissipation half-lives were significantly lower than those obtained from 

laboratory studies and a number of factors could account for these differences. 

Volatilization, plant uptake and runoff were not accounted for in either field study and a 

mass balance was not determined. Although volatilization losses are not expected to be 

major environmental fate processes, plant uptake may occur and losses due to runoff and 

erosion over the course of 500 days may be significant. In addition to the normal amount 

of rainfall occurring at these sites, 1.5-2.0 inches of water was applied to the fields during 

each of nine supplemental irrigations. These supplemental irrigations along with the 

normal amount of rainfall received during the course of these field studies are likely to 

result in leaching as well as erosion and runoff losses from the soils. Other losses may 

include plant uptake.

2. Measures of Aquatic Exposure
35

a. Aquatic Exposure Modeling

Amicarbazone is a new herbicide and, as a result, no surface water monitoring data are 

available. For this reason, the Agency modeled the EECs using the Tier 2 model 

PRZM-EXAMS. 

Background information on PRZM/EXAMS and selected model runs are provided in 

Appendix B. Input values are summarized in Table 5.

Table 5. Summary of input parameters for PRZM/EXAMS

Input Parameter Value Reference

Molecular Weight (grams) 241.3 Product chemistry submission (MRID 451218-03)

Vapor Pressure (torr) 9.75x10-9 Registrant data (MRID 451217-14)

Aerobic Soil Metabolism Half-life (days) 261 One value of 87 days multiplied by 3 (MRID 451217-31)

Water column Half-life (days)

(Aerobic Aquatic Metabolism half-life)

522 Aerobic soil t1⁄2x2: No aerobic aquatic metabolism study/No 

significant hydrolysis (Guidance) 1

Benthic sediment Half-life (days) 

(Anaerobic Aquatic Metabolism half-life)

Stable Half-life for the total system >4 years (MRID 451217-24)

Application Rate (Kg a.i./ha) and

(Application Efficiency)

0.503

(0.99)

Maximum label rate for field/silage corn (Bayer Corporation 

Product Label, no data) 2

Appl. Number (Method of Application) One 

(Ground 

spray)

Product Label

Depth of Incorporation (inches) None Product Label 3

Spray Drift (fraction) 0.01 The default value (Guidance) 1

Solubility (mg/L or ppm) 4,600 Product chemistry submission (451217-14)

Koc (L Kg-1) 26.8 Average for seven soils (MRIDs 451217-19 and 451217-32)

Hydrolysis Half-life @ pH 7 (days) Stable MRID 451217-30

Direct Aqueous Photolysis Half-life(days) Stable Note: indirect photolysis half-life reported for amicarbazone is 73 

days (MRID 451218-03)

1 Selection as per Guidance for Selecting Input Parameters in Modeling the Environmental Fate and 

Transport of Pesticides; Version II (US EPA, 2002).

2

 Parent rate (kg/ha)= parent rate (0.45 lbs a.i./a) x 1.121.

3

Label calls for incorporation of the pesticide to a depth of 1-2" after or along with spraying. However, no 

incorporation is also possible; therefore, No incorporation was used for all runs because EECs were more 

conservative with no incorporation (CAM 1 except for post emergence= CAM 2) compared to incorporation 

(CAM 4 with 2.54 cm depth) in two runs at planting dates. 
36

Nozzle height, droplet size and spray quality were chosen to be: fine-medium, high boom, and fine, 

respectively (EFED default).

Exposure modeling for aquatic systems was conducted with only the parent compound, 

amicarbazone; transformation products were not included in the exposure assessment. 

Based on the limited available toxicity data, the transformation products appear to be 

relatively less toxic to aquatic algae than the parent. Also, the parent is persistent in the 

environment and stable to hydrolysis. Therefore, the transformation products are 

expected to have a minimal contribution in the aquatic exposure assessment and 

modeling of the total residue (parent + transformation products) will probably be less 

conservative. Fate data for the transformation products were not complete and the 

default aerobic soil half-life value for the parent was used (half-life multiplied by three in 

modeling). Results of the PRZM/EXAMS farm pond simulations (EECs for amicarbazone 

in aquatic systems resulting from application to corn) are summarized in Table 6..

Table 6. PRZM/EXAMS farm pond modeling results for amicarbazone (EECs in ppb).

Applicatio

n Window

Chosen 

Run Date Location

Representati

ve

Scenario Peak 96 hrs 21 Days 60 Days 90 Days

Yearly

Average

F

A

L

L

30-Oct

Note 1

IL corn 20.18 20.16 20.11 19.97 19.10 17.55

30-Oct. ND corn 13.66 13.65 13.62 13.57 13.49 11.25

30-Oct. OH corn 10.56 10.54 10.53 10.40 10.21 9.39

The above runs were for one application at date specified. Two-application scenario runs were not 

possible because of the long time intervals between applications (173-178 days)

W

I

N

T

E

16-Nov. Note 2TX corn 33.78 33.73 33.53 29.14 27.31 24.10

The above run was for one application at the date specified. A two-application scenario run was not 

possible because of the long time interval between applications (108 days).

E

A

R

L

Y

P

R

E

P

L

05-Jan.

East

Note 3

MS corn 22.72 22.70 22.60 22.43 22.26 19.59

05-Jan. NC-W corn 20.68 20.66 20.61 20.48 20.37 18.40

15-Jan. PA corn 16.96 16.95 16.92 16.81 16.72 15.04

09-Jan. NC-E corn 14.93 14.92 14.86 14.77 14.67 13.12

23-Jan. OH corn 14.69 14.68 14.64 14.57 14.49 13.00

23-Jan. IL corn 12.98 12.97 12.94 12.87 12.79 11.69

04-Dec.

West

Note 4

TX corn 25.84 25.79 25.57 20.14 19.61 17.30

01-Jan. CA corn 10.49 10.48 10.44 10.32 10.23 9.13

28-Jan. ND corn 8.87 8.86 8.82 8.72 8.63 7.93

22-Feb.

East

OH corn 21.28 21.25 21.15 20.89 20.69 17.69

04-Feb. NC-W corn 21.08 21.06 21.01 20.86 20.70 18.37

04-Feb. MS corn 19.76 19.73 19.65 19.41 19.22 16.86
37

Applicatio

n Window

Chosen 

Run Date Location

Representati

ve

Scenario Peak 96 hrs 21 Days 60 Days 90 Days

Yearly

Average

A

N

T

22-Feb. Note 3IL corn 18.30 18.28 18.25 18.06 17.86 15.40

14-Feb. PA corn 8.45 8.44 8.42 8.35 8.29 7.39

08-Feb. NC-E corn 6.75 6.75 6.73 6.67 6.62 5.97

31-Jan.

West

Note 4

CA corn 14.77 14.75 14.70 14.63 14.57 13.30

27-Feb. ND corn 10.64 10.63 10.59 10.49 10.39 9.57

03-Jan. TX corn 9.12 9.10 9.04 8.93 8.83 7.41

19-Feb.

East

Note 3

MS corn 25.80 25.77 25.67 25.43 25.15 21.32

09-Mar. OH corn 18.93 18.92 18.88 18.80 18.77 17.30

09-Mar. IL corn 14.47 14.46 14.42 14.34 14.27 13.27

23-Feb. NC-E corn 11.03 11.03 10.99 10.91 10.81 9.76

19-Feb. NC-W corn 11.02 11.00 10.95 10.82 10.70 9.65

01-Mar. PA corn 9.60 9.58 9.55 9.44 9.34 7.82

18-Jan.

West

Note 4

TX corn 28.00 27.96 27.82 27.52 27.36 23.77

15-Feb. CA corn 14.20 14.19 14.13 13.98 13.87 12.39

14-Mar. ND corn 13.44 13.43 13.40 13.33 13.24 12.27

1

IA, MN, ND, SD, WI, NE (north of Route 20), IL (north of route 136), and OH (north of Interstate 70)

2

KS, OK and TX

3

Eastern corn belt states: MN, MO, AR, LA and IA (east of US Hwy 71 and points east)

4 Western corn belt states: ND, SD, NE, KS, OK, TX, and IA (west of US Hwy 71 and points west). 

Table 6 (Continued). PRZM/EXAMS farm pond modeling results for amicarbazone (EECs 

in ppb).

Applicatio

n Window

Chosen 

Run Date Location Representative

Scenario Peak 96 hrs 21 Days 60 Days 90 Days

Yearly

Average

P

R

E

E

M

E

R

21-Mar.

East 

Note 3

MS corn 23.36 23.33 23.18 22.79 22.40 18.02

21-Mar. NC-W corn 19.65 19.63 19.51 19.25 19.01 16.68

31-Mar. PA corn 18.06 18.04 17.95 17.71 17.47 14.87

08-Apr. IL corn 15.96 15.95 15.89 15.64 15.49 14.26

08-Apr. OH corn 9.26 9.24 9.20 9.09 8.98 7.61

25-Mar. NC-E corn 5.78 5.77 5.73 5.63 5.55 4.71

17-Feb.

West

Note 4

TX corn 7.79 7.78 7.72 7.59 7.48 6.16

13-Apr. ND corn 7.65 7.64 7.61 7.48 7.37 6.62

17-Mar. CA corn 3.92 3.91 3.89 3.82 3.77 3.29

05-Apr.

East 

Note 3

MS corn 20.84 20.80 20.65 20.17 19.77 16.58

23-Apr. IL corn 18.98 18.95 18.86 18.57 18.29 15.87

05-Apr. NC-W corn 13.34 13.32 13.24 13.06 12.88 11.19

15-Apr. PA corn 12.93 12.91 12.84 12.63 12.44 11.31

23-Apr. OH corn 12.22 12.20 12.14 11.93 11.75 9.95

09-Apr. NC-E corn 6.20 6.19 6.15 6.05 5.95 5.11
38

Applicatio

n Window

Chosen 

Run Date Location Representative

Scenario Peak 96 hrs 21 Days 60 Days 90 Days

Yearly

Average

G

E

C

E*

28-Apr.

West

Note 4

ND corn 9.22 9.22 9.20 9.15 9.11 8.50

04-Mar. TX corn 4.16 4.15 4.12 4.08 4.04 3.23

01-Apr. CA corn 1.79 1.79 1.78 1.75 1.73 1.49

09-Apr.

East 

Note 3

MS corn 29.416 29.358 29.089 28.41 27.828 22.838

19-Apr. PA corn 13.804 13.792 13.754 13.676 13.611 10.8429

27-Apr. IL corn 13.038 13.017 12.913 12.701 12.5 11.024

09-Apr. NC-E corn 11.721 11.71 11.665 11.498 11.3176 10.0456

13-Apr. NC-W corn 11.273 11.253 11.179 11.018 10.864 9.6685

27-Apr. OH corn 7.8654 7.853 7.7948 7.6482 7.5266 6.7827

02-May

West

Note 4

ND corn 9.3632 9.3581 9.3362 9.2854 9.2442 8.5594

08-Mar. TX corn 3.7275 3.7188 3.6845 3.5995 3.5293 3.0708

05-Apr. CA corn 2.3674 2.3635 2.347 2.3068 2.2745 1.9402

P

O

S

T

E

M

E

R

G.

23-May

East 

Note 3

OH corn 8.4404 8.4364 8.4161 8.3714 8.3336 6.35

23-May IL corn 7.8143 7.8019 7.7475 7.5864 7.4552 6.8117

18-May NC-W corn 6.7491 6.7458 6.7339 6.7046 6.675 6.213

03-May MS corn 6.4757 6.4553 6.3897 6.2776 6.2151 5.3709

12-May PA corn 4.8232 4.82 4.8061 4.7743 4.7486 4.2067

03-May NC-E corn 3.0488 3.0414 3.02 2.9823 2.9655 2.737

02-Apr.

West

Note 4

ND corn 5.2056 5.1947 5.1531 5.0641 4.9997 4.542

27-May TX corn 4.3101 4.3007 4.2648 4.203 4.1294 3.6375

30-April CA corn 1.2689 1.2668 1.2576 1.2358 1.0735 0.9639

3

Eastern corn belt states: MN, MO, AR, LA and IA (east of US Hwy 71 and points east)

4 Western corn belt states: ND, SD, NE, KS, OK, TX, and IA (west of US Hwy 71 and points west).

* Runs included under this category (Pre-emergence) are: first 9 rows for mid way within the pre-plant 

window; second 9 rows for at planting and third 9 rows for 4 days after planting.

In all PRZM/EXAMS modeling, the default value of 1% was used to represent the contribution of 

drift to resultant aquatic EECs. To determine if a 1% drift assumption is reasonable for 

amicarbazone, AgDRIFT modeling was used to determine the 90th percentile drift profile 

assuming ground spray swath width of 45 ft. along with the most conservative application 

procedure: ASAE of very fine to fine with high boom (50"). Figure 5 shows the spray profile as 

predicted by the AgDRIFT model.

Figure 5. Spray drift distribution as a function of distance from the aquatic farm pond. 
39

Data indicate that the spray drift value of 1% (default value used in PRZM/EXAMS modeling) 

corresponds to a buffer distance of 150 ft. buffer, 1.3% drift value to 100 ft. buffer, and 6.16% 

drift value to no buffer as calculated by AgDRIFT. Due to the fact that no buffer is specified in 

the label, new PRZM/EXAMS modeling was executed for the most conservative scenario 

TX-corn with winter application using spray drift values of 1.3% and 6.16%. The results for this 

exercise are included in Table 7 along with the contribution of drift to modeled EECs. Data 

indicate very low drift contribution to EECs even with no buffer; the concentration increased by

about 3% of the total contribution of drift plus run-off/erosion. Therefore, it appears that a buffer 

is not an effective tool for reducing the risk to aquatic systems for this chemical and that the 1% 

spray drift default value used in PRZM/EXAMS modeling is a reasonable assumption. 

Table 7. Predicted farm pond 

EECs due to drift alone “AgDRIFT 

model” compared to those 

attributed to drift plus run-off/erosion 

“PRZM/EXAMS 

model”at varied buffer distances.
40

Buffer Drift 1Initial EEC (ppb): AgDRIFT 

2

Acute EEC (ppb):PRZM/EXAMS 3 Drift Contribution to EEC

0 ft. 6.16% 1.55 37.89 4%

100 ft. 1.30% 0.33 34.03 1%

150 ft. 0.98% 0.25 33.78 <1%

1

“AgDRIFT model” predicted value for spray drift, note: value for the 100 ft. buffer equals to 

0.98% which similar to the 1% default value used in PRZM/EXAMS modeling, therefore no new 

run was executed and values entered are for the 1% drift.

2

“AgDRIFT model” predicted initial EECs: attributed to drift alone

3

“PRZM/EXAMS model” predicted acute EECs: attributed to drift plus run-off/erosion 

b. Aquatic Exposure Monitoring (Field Data)

No data were identified to provide information on aquatic monitoring.

3. Measures of Terrestrial Exposure

a. Exposure Modeling for Terrestrial Animals 

The EFED terrestrial exposure model, T-REX (Version 1.1, dated February 24, 2005), is 

used to estimate exposures and risks to avian and mammalian species. Input values on 

avian and mammalian toxicity as well as chemical application and foliar dissipation 

half-life data are required to run the model. The model generates both estimated 

exposure concentrations (EECs) and risk quotients (RQs). Specifically, the model 

provides estimates of concentrations (upper bound and mean) of chemical residues on 

the surfaces of different types of foliage that may be sources of dietary exposure to avian, 

mammalian, reptilian, or terrestrial-phase amphibian receptors. The surface residue 

concentration (ppm) is estimated by multiplying the application rate (pounds active 

ingredient per acre) by a value specific to each food item. These values (termed the 

Hoerger-Kenaga estimates) along with a more detailed discussion of the methodology 

implemented by T-REX, are presented in Appendix D (T-REX Model). 

T-REX was run for corn crops using the inputs provided in Table 8 for single applications 

of each of the three maximum proposed application rates for amicarbazone. Three 

different application rates were recommended for varying application scenarios as 

follows: 

(1) A maximum rate of 0.45 lb a.i./A was recommended for: (a) Early 

Pre-plant, Pre-plant, At planting, and Pre-emergence applications in 

the Eastern Corn-belt; (b) Early Pre-plant applications in Western 
41

Corn Belt; (c) Special fall applications; and (d) Winter applications.

(2) A maximum rate of 0.22 lb a.i./A was recommended for Pre-plant, 

At planting, and Pre-emergence applications in the Western Corn 

Belt.

(3) A maximum rate of 0.15 lb a.i./A was recommended for all 

Early Post-emergence applications.

Uncertainties in the terrestrial EECs are associated with a lack of data on dissipation from foliar 

surfaces. When data are absent, as in this case, EFED assumes a 35-day foliar dissipation 

half-life, based on the work of Willis and McDowell (1987). However, it should be noted that 

because the EEC represents the concentration immediately following a direct application, 

the foliar dissipation half-life variable is only influential for scenarios involving multiple 

applications. 

Amicarbazone exhibits systemic toxicity to plants, transport through run-off or leaching 

and subsequent uptake by plants is likely, and herbicides that are photosystem II 

inhibitors like amicarbazone have a tendency to be metabolized into non-phytotoxic 

chemicals by plants that are resistant to their adverse effects. In addition, confined 

rotational crop studies suggest that amicarbazone and its degradates can accumulate in 

plants. Therefore, there is great uncertainty concerning the amount of this chemical and 

its degradates in plants and the magnitude of exposure to animals that forage on those 

plants. 

No reliable data are available that adequately depict the toxicity of the transformation 

products of amicarbazone to terrestrial animals, and exposure modeling for terrestrial 

animals was only performed using the parent. Based on the half-lives from the one aerobic 

soil metabolism study, the metabolites are highly persistent and there is the potential for exposure 

of terrestrial animals to these chemicals. Subsequently, there is uncertainty about the risk that 

these metabolites pose to terrestrial animals.

Table 8. Input parameters used in T-REX v1.1 to determine terrestrial EECs for 

amicarbazone.

Input Variable Parameter Value Source

Maximum application rates 0.45, 0.22, or 0.15 lb a.i./A Product Label

Maximum number of applications per 

year

1 Product Label

Frequency of application NA NA
42

Table 8. Input parameters used in T-REX v1.1 to determine terrestrial EECs for 

amicarbazone.

Input Variable Parameter Value Source

Foliar dissipation half-life 35 days T-REX Default Value

The EECs on food items may be compared directly with dietary toxicity data or converted to an

oral dose, as is done for small mammals. For mammals, the residue concentration is converted to 

daily oral dose based on the fraction of body weight consumed daily as estimated through 

mammalian allometric relationships. The screening-level risk assessment for amicarbazone uses 

upper bound predicted residues as the measure of exposure. A summary of the predicted upper 

bound and mean residues of amicarbazone that may be expected to occur on selected avian or 

mammalian food items immediately following application is presented in Table 9 for each 

scenario. More detailed summaries of the T-REX output are presented in Appendix D. 

Amicarbazone residues ranged from 107.6 to 2.30 ppm for upper bound residues and 

38.11 to 1.07 ppm for mean residues. Amicarbazone residues were highest on the 

surfaces of short grass and lowest on the surfaces of fruits, pods, and large insects.

Table 9. Upper bound (24-hour) terrestrial upper bound and mean EECs found 

on selected avian and mammalian food items as calculated using T-REX.a

Application 

Rate

Forage Type Upper Bound 

EECs

(ppm)

Mean EECs 

(ppm)

0.45 lb a.i./Ab

short grass 107.6 38.11

tall grass 49.32 16.14

broadleaf plants and small 60.53 20.18

fruits/pods/large insects 6.73 3.14

0.22 lb a.i./Ac

short grass 52.51 18.60

tall grass 24.07 7.88

broadleaf plants and small 29.54 9.85

fruits/pods/large insects 3.28 1.53

0.15 lb a.i./Adshort grass 36.74 13.01

tall grass 16.84 5.51

broadleaf plants and small 20.67 6.89

fruits/pods/large insects 2.30 1.07
43

a EEC equivalent dose = Upper bound Kenega value * (%BW consumed/100). %BW consumed = 114%, 65%, and 

29% for small, medium, and large birds, respectively.

b Maximum recommended label application rate for amicarbazone for the following:

(1) Early Pre-plant, Pre-plant, At planting, and Pre-emergence applications in the Eastern Corn Belt; (2) 

Early Pre-plant applications in Western Corn Belt; (3) Special Fall applications; and (4) Winter 

applications.

c Maximum recommended label application rate for amicarbazone for Pre-plant, At planting, and 

Pre-emergence applications in the Western Corn Belt.

d Maximum recommended label application rate for amicarbazone for all Early Post-emergence 

b. Exposure Modeling for Non-Target Terrestrial Plants

TERRPLANT (TERRPLANT, Version 1.0, dated August 8, 2001) was used to estimate exposures 

and risks to terrestrial plant species (see Appendix C for a more detailed discussion of the 

TERRPLANT Model and results). Input parameters for the model included: (1) toxicity values 

for monocots and dicots (EC25 values and EC05 or NOAEC values); (2) application rate; (3) 

run-off, based on chemical solubility; and (4) soil incorporation depth. The model provides 

estimates of exposure concentrations and risk quotients (RQs) for plant species that are not 

federally endangered or threatened (non-listed), and for those that are federally 

endangered or threatened (listed). Input values used for estimating terrestrial plant exposure 

risks to amicarbazone are summarized in Table 10. 

Table 10. Input parameters used in TERRPLANT v1.0 to determine terrestrial EECs for 

plants exposed to amicarbazone.

Input Variable Parameter Value Source

Maximum application rates 0.45, 0.22, or 0.15 lb a.i./A Product Label

Runoff Value (0.01, 0.02, or 0.05 if 

chemical solubility <10, 10-100, or 

>100 ppm, respectively)

0.05 a TERRPLANT 2001

Minimum incorporation depth 

(inches)

1 Product Label

a

Based on the water solubility of 4,600 mg a.i./L.

TERRPLANT was run for single applications of each of the three maximum proposed 

application rates (0.45, 0.22, and 0.15 lb a.i./A) of amicarbazone for the varying 

application scenarios. Amicarbazone can be applied at early stages of crop 

development as a ground spray that is unincorporated, incorporated at a minimum depth 

of one inch or irrigated in. For pesticide applications with a minimum incorporation depth 

of one inch or less, the total loading EECs derived for the incorporation method will be 

same as the unincorporated method. Therefore, only one set of EECs are calculated for 

each maximum application rate in this assessment. EECs are estimated for total loading 
44

to terrestrial areas of concern, total loading to semi aquatic areas, and spray drift for 

each maximum application rate (Table 11). 

Exposure modeling for terrestrial plants was only performed using the parent, 

amicarbazone, due in part to the limited available data on the toxicity of amicarbazone’s 

degradates to terrestrial and semi-aquatic plants. Based on the half-lives from the one 

aerobic soil metabolism study, the metabolites are highly persistent and there is the potential for 

exposure of plants to these chemicals. Subsequently, there is uncertainty about the risk that 

these metabolites pose to terrestrial plants.

Table 11. Summary output EECS from TERRPLANT for amicarbazone.

Application Rate

(lb a.i./A)

EECs for plants 

inhabiting areas adjacent 

to 

treatment site

(lb a.i./A)

EECs for semi-aquatic 

plants inhabiting areas 

adjacent to treatment site

(lb a.i./A)

Drift EEC

(lb a.i./A)

0.45 0.0269 0.2287 0.0045

0.22 0.0131 0.1116 0.0022

0.15 0.0092 0.0781 0.0015

c. Terrestrial Exposure Monitoring (Field Data) 

No data were identified to provide information on terrestrial monitoring.

C. Ecological Effects Characterization

In screening-level ecological risk assessments, effects characterization describes the 

types of effects a pesticide has on aquatic or terrestrial organisms. This characterization 

is based on registrant-submitted studies that describe information regarding acute and 

chronic effects toxicity for various aquatic and terrestrial animals and plants, and not open 

literature, because this is a new active ingredient registration. Appendix E summarizes 

the results of the registrant-submitted toxicity studies used to characterize effects for this 

risk assessment. Toxicity testing reported in this section does not represent all species 

of birds, mammals, or aquatic organisms. Only a few surrogate species for both 

freshwater fish and birds are used to represent all freshwater fish (2000+) and bird (680+) 

species in the United States. For mammals, acute studies are usually limited to the 

Norway rat or the house mouse. Estuarine/marine testing is usually limited to a 

crustacean, a mollusk, and a fish. Also, testing for reptiles and amphibians is not 

required. The risk assessment assumes that avian, reptilian, and terrestrial phase 

amphibian toxicities are similar. The same assumption is used for fish and aquatic 
45

phase amphibians.

In general, categories of acute toxicity ranging from “practically nontoxic” to “very highly 

toxic” have been established for aquatic organisms (based on LD50, LC50, and EC50 

values), terrestrial mammals (based on LD50 values), avian species (based on LC50 and 

LD50 values), and non-target insects (based on LD50 values for honey bees) (U.S. EPA 

2001). These categories are presented in Appendix E.

Presently, there is a dearth of reliable data that adequately depict the toxicity of all of the 

transformation products of amicarbazone to aquatic and terrestrial plants and animals. 

Subsequently, there is uncertainty surrounding the toxicity of these chemicals to the taxonomic 

groups under consideration. Only limited data on the toxicity of Des-amino to aquatic algae and 

terrestrial plants are available. These data are discussed further in Sections 1b and 2b of the 

Ecological Effects Characterization.

Results of toxicity studies indicate that technical grade amicarbazone is practically

non-toxic to honey bees, slightly toxic to practically non-toxic to birds, and slightly toxic to 

mammals on an acute basis. However, results of chronic toxicity studies show that 

longer-term exposure to amicarbazone TGAI results in adverse effects on reproductive 

parameters in birds, and toxicity to parents and offspring in mammals. Toxicity studies 

demonstrate that amicarbazone is practically non-toxic on an acute basis to 

estuarine/marine and freshwater fish, slightly toxic to freshwater invertebrates, and 

slightly toxic to practically non-toxic to estuarine/marine invertebrates. Chronic exposure 

of aquatic animals to amicarbazone produces adverse effects on growth parameters in 

freshwater fish and on growth and reproductive parameters in freshwater and 

estuarine/marine invertebrates. Data are not available to characterize the effects of 

chronic exposure of estuarine/marine fish to amicarbazone. In aquatic plants, 

amicarbazone produces adverse effects in both algae and vascular plants. In a single test 

with Des-amino, the degradate was less toxic to algae than the parent. Results of Tier 2 

terrestrial plant studies with the amicarbazone formulated product MKH 3586 70 WG

show that both monocots and dicots are sensitive to exposure in both seedling 

emergence and vegetative vigor studies. In both studies, dicots appear more sensitive

than monocots. Tier 2 seedling emergence and vegetative vigor studies with the 

amicarbazone metabolite MKH 3594 (Des-amino) indicate that the metabolite is less toxic 

than the parent compound for the four species tested, except onion.

1. Aquatic Effects

The acute and chronic toxicity reference values associated with freshwater and 

estuarine/marine species exposure to amicarbazone are summarized in Table 12. All 

toxicity reference values used to assess the potential risks of amicarbazone exposure are 

obtained from studies using technical amicarbazone. A more detailed summary of the 

aquatic toxicity data available to characterize risks associated with amicarbazone 
46

applications is given in Appendix E, Tables E-1 through E-7 and Table E-13.

Table 12. Amicarbazone toxicity reference values (TRVs) (mg of active 

ingredient/L) for aquatic organisms.

Exposure 

Scenario Species 

Exposur

e 

Duration

Toxicity Reference 

Value

(mg a.i./L) Endpoint

Reference

(Classification)

Freshwater Fish

Acute Rainbow Trout

Oncorhynchus 

mykiss

96 hours LC50 > 120.4 mg a.i./L No 

endpoints 

affected

MRID 45121807

(Supplemental)

Chronic Fathead 

minnow

Pimephales 

promelas

33 days NOAEC = 7.3

LOAEC = 13.0

Dry weight MRID 45121602

(Acceptable)

Freshwater Invertebrates

Acute Water flea

Daphnia magna

48 hours EC50 = 40.8 Mortality & 

sub-lethal 

effects a 

effectaa

MRID45121808

(Acceptable)

Chronic Water flea

Daphnia magna

21 days NOAEC  0.252

LOAEC = 0.252

Terminal 

length

MRID45121822

(Supplemental)

Estuarine/Marine Fish

Acute Sheepshead

minnow

Cyprinodon 

variegatus

96 hours LC50 >118.0 No 

endpoints 

affected

MRID 45121806

(Acceptable)

Chronic

No data submitted

Estuarine/Marine Invertebrates

Acute Saltwater mysid

Mysidopsis 

bahia

96 hours LC50 = 109.7 Mortality

MRID 45121810

(Acceptable)

Chronic

Saltwater mysid

Mysidopsis 

bahia

28 days NOAEC = 5.0

LOAEC = 10.0

Terminal 

dry weight MRID 45121601

(Supplemental)
47

Aquatic Plants

Algae Acute Marine diatom

Skeletonema 

costatum

96 hours EC50 = 0.017

NOAEC = 0.0057 

Cell 

density

MRID 45121818

(Acceptable)

Macrophytes

Acute

Duckweed

Lemna gibba

14 days EC50 = 0.210

NOAEC = 0.0406 

Frond dry 

weight

MRID 45121805

(Acceptable)

a

Sub-lethal effects include erratic movements, floating at surface, and abnormal position on tank bottom.

a. Aquatic Animals

Freshwater Fish

The acute toxicity of amicarbazone (TGAI) was evaluated in rainbow trout (Oncorhynchus 

mykiss; MRID 45121807) and bluegill sunfish (Lepomis macrochirus; MRID 45121804). 

Details of these studies are provided in Table E-1. Results of acute exposure studies 

yield 96-hour LC50 values in bluegill sunfish and rainbow trout of >128.5 and >120.4 mg 

a.i./L, respectively, indicating that amicarbazone is practically non-toxic to freshwater fish 

on an acute basis. Only one fish displayed sub-lethal effects (abnormal position at 

bottom of test chamber in 66.4 mg a.i./L treatment group) in the testing with bluegill 

sunfish, and no sub-lethal effects were found in the study on rainbow trout. These studies 

do not fulfill guideline requirements for an acute toxicity study with the rainbow trout 

[§72-1(c)] or bluegill sunfish [§72-1(a)] and are classified as supplemental because the 

mean fish weight determined from control fish at test termination was less than the 

required initial weight range of 0.5 to 5g (0.36g and 0.43g, respectively for each study).

This ecological risk assessment uses the lowest acute toxicity value (LC50 >120.4 mg 

a.i./L in rainbow trout) to evaluate risk of acute exposure of freshwater fish to 

amicarbazone.

The effects of chronic exposure of freshwater fish to amicarbazone (TGAI) were 

evaluated in an early life-stage study in fathead minnow (Pimephales promelas; MRID 

45121602). Study details are provided in Table E-2. No treatment-related adverse 

effects were observed for reproductive parameters. Treatment-related effects were 

observed on terminal dry weight in the 13, 26, and 48 mg a.i./L treatment groups (33-day 

LOAEC = 13 mg a.i./L, NOAEC = 7.3 mg a.i./L), and terminal wet weight in the 48 mg 

a.i./L treatment group (33-day LOAEC = 48 mg a.i./L, NOAEC = 26 mg a.i./L). This study 

fulfills the guideline requirements for an early life-stage toxicity study with freshwater fish 

[§72-4(a)] and is classified as acceptable. The NOAEC of 7.3 mg a.i./L was used to 

assess the risk of chronic exposure of freshwater fish to amicarbazone.

Freshwater Invertebrates
48

The acute toxicity of amicarbazone TGAI was evaluated in Daphnia magna under static 

conditions (MRID 45121808). Study details are provided in Table E-3. After 48 hours, 

mortality was 0% in the control, 15.0, and 25.2 mg a.i./L test groups, 10% in the 40.8 and 

69.5 mg a.i./L test groups, and 15% in the 119 mg a.i./L test group. The 48-hour LC50

value was >119 mg a.i./L. Treatment-related sub-lethal effects included erratic 

movements, floating at the surface, and abnormal positions on the tank bottom. The 

48-hour NOAEC value is 25.2 mg a.i./L. After 48 hours, sublethal effects were seen in 0% 

of the control, 15.0, and 25.2 mg a.i./L test groups, 50% of the 40.8 mg a.i./L test group, 

100% of the 69.5 mg a.i./L test group, and 75% of the 119 mg a.i./L test group. Based on 

the 48-hour EC50 value of 40.8 mg a.i./L, amicarbazone is classified as slightly toxic to 

freshwater invertebrates. This study satisfies the guideline requirements for an acute 

toxicity study with freshwater invertebrates (§72-2) and is classified as acceptable. This 

ecological risk assessment uses the EC50 value of 40.8 mg a.i./L to evaluate the risk of 

acute exposure of freshwater invertebrates to amicarbazone.

The chronic toxicity of amicarbazone TGAI to freshwater invertebrates has been 

assessed in a 21-day life-cycle toxicity test using Daphnia magna (MRID 45121822). 

Study details are summarized in Table E-4. No treatment-related effects on adult 

survival, time to first brood release, or terminal dry weights were observed. 

Treatment-related effects observed in this study included a decrease in the number of 

young/adult/reproductive day in the two highest treatment groups of 4.72 and 9.51 mg 

a.i./L (21-day LOAEC = 4.72, NOAEC = 2.31 mg a.i./L), and decreased terminal length in 

all treatment groups (21-day LOAEC = 0.252, NOAEC <0.252 mg a.i./L). Since this 

life-cycle chronic toxicity study did not experimentally determine a NOAEC, it does not 

satisfy the guideline requirements for a chronic toxicity study with freshwater 

invertebrates [§72-4(b)] and is classified as supplemental. However, the animals in the 

lowest test concentration (0.252 mg a.i./L) had an average terminal length of 5.05mm, 

only about a two percent reduction in length as compared to the control organisms 

(average length = 5.17 mm). The LOAEC of 0.252 mg a.i./L was used in this risk 

assessment for the most sensitive effect (terminal length) to assess the risk of chronic 

exposure of freshwater invertebrates to amicarbazone. Thus, there is some uncertainty 

regarding the characterization of chronic risk.

Estuarine/Marine Fish

The acute toxicity of amicarbazone TGAI was evaluated in sheepshead minnow 

(Cyprinodon variegatus; MRID 45121806). Study details are summarized in Table E-5. 

No mortalities or signs of toxicity were observed, yielding a 96-hour LC50 value of >118 

mg a.i./L, indicating that amicarbazone is practically non-toxic to estuarine/marine fish on 

an acute basis. This study satisfies the guideline requirements for a 96-hour acute toxicity 

study for estuarine/marine fish [§72-3(a)] and is classified as acceptable. This ecological 

risk assessment uses the LC50 value of >118 mg a.i./L to evaluate the risk of acute 

exposure of estuarine/marine fish to amicarbazone.
49

Chronic toxicity studies in estuarine/marine fish were not submitted, and therefore, the 

chronic effects of amicarbazone on estuarine/marine fish could not be assessed.

Estuarine/Marine Invertebrates

The acute toxicity of amicarbazone TGAI to estuarine/marine invertebrates was 

evaluated in Eastern oyster (Crassostrea virginica; MRID 45121809) and saltwater mysid 

(Mysidopsis bahia; MRID 45121810). In Eastern oyster, no mortalities or statistically 

significant reductions in shell growth were observed at the highest concentration of 

amicarbazone tested (63 mg a.i./L). Based on the LC50 of >63 mg a.i./L, amicarbazone 

is classified as slightly toxic to practically non-toxic to the Eastern oyster. Since this 

study was conducted at one concentration that was significantly less than the required 

limit concentration, it does not satisfy the requirements of an acute toxicity test with an 

estuarine/marine mollusk [§72-3(b)] and is classified as supplemental. Based on a 

calculated 96-hour LC50 value of 109.7 mg a.i./L, amicarbazone TGAI is classified as 

practically non-toxic to mysid shrimp on an acute basis. At 96 hours, mortality was 0% in 

the control and 47 mg a.i./L test groups, 5% in the 82 mg a.i./L test group, and 90% in 

the 140 mg a.i./L test group. Treatment-related sub-lethal effects (erratic swimming and 

lethargy) were also observed, with a 96-hour NOAEC value of 47 mg a.i./L based on 

mortality and sublethal effects. This study fulfills the requirements of an acute LC50 test 

with an estuarine/marine organism [§72-3(c)] and is classified as acceptable. Study 

details are provided in Table E-6. The calculated LC50 value of 109.7 mg a.i./L in mysid 

shrimp was used to evaluate risk of acute exposure of estuarine/marine invertebrates to 

amicarbazone.

The chronic toxicity of amicarbazone TGAI to estuarine/marine invertebrates was 

determined in a 28-day life-cycle test with mysid shrimp (Mysidopsis bahia; MRID 

45121601). Study details are provided in Table E-7. Treatment-related adverse effects 

were observed for terminal dry weight in the 10 and 20 mg a.i./L treatment groups 

(LOAEC = 10 mg a.i./L, NOAEC=5.0 mg a.i./L), and this was the most sensitive endpoint. 

Terminal length (LOAEC = 20 mg a.i./L, NOAEC=10 mg a.i./L) and number of 

young/reproductive day (LOAEC = 20 mg a.i./L, NOAEC=10 mg a.i./L) were also 

decreased in the 20 mg a.i./L treatment group, while juvenile survival (LOAEC = 20 mg 

a.i./L, NOAEC = 10 mg a.i./L) was decreased in the 20 and 41 mg a.i./L treatment groups. 

The 41 mg a.i./L treatment group was excluded from all statistical analyses other than for 

juvenile survival because there was only one replicate. This study does not fulfill the 

guideline requirements for an aquatic invertebrate life-cycle toxicity test using Mysidopsis 

bahia [§72-4(c)] and is classified as supplemental due to the following: survival data were 

not reported daily or in terms of each gender (following pairing); the number of 

reproductive females and the number of offspring produced per female were not 

provided; second-generation mysids were not monitored daily for at least 4 days for 

survival, development, and behavior; and terminal growth measurements were not 

provided in terms of each gender. This study could be upgraded to acceptable if the 
50

required raw data were submitted. To assess chronic risk in estuarine/marine 

invertebrates, the 28-day NOAEC value of 5.0 mg a.i./L for decreased terminal dry weight 

was used.

b. Aquatic Plants 

Acute toxicity studies on technical grade amicarbazone were conducted with duckweed 

(Lemna gibba; MRID 45121805), green algae (Selenastrum capricornutum; MRID 

45121820), a marine diatom (Skeletonema costatum; MRID 45121818), blue-green alga 

(Anabaena flos-aquae; MRID 45121825), and a freshwater diatom (Navicula pelliculosa) 

(MRID 45121812). Study details are provided in Table E-13. Exposure of duckweed to 

amicarbazone resulted in decreased number of fronds (14-day EC50 value of 220 μg 

a.i./L) and decreased frond dry weight (most sensitive effect, 14-day EC50 value of 210 μg 

a.i./L). The NOAEC reported for decreased frond dry weight is 40.6 μg a.i./L, while the 

LOAEC is 80.5 μg a.i./L. This toxicity study satisfies the guideline requirements for an 

aquatic vascular plant study with Lemna gibba [§123-2] and is classified as acceptable. 

For macrophytes, the L. gibba 14-day EC50 value of 210 μg a.i./L for decreased frond dry 

weight was used to assess risk to non-listed aquatic macrophytes, while the NOAEC of 

40.6 μg a.i./L for decreased frond dry weight was used to assess risk to listed aquatic 

macrophytes. 

In all species of algae tested, amicarbazone TGAI resulted in decreased cell density and 

biomass. Decreased growth rate was exhibited by all species of algae except 

Selenastrum capricornutum. EC50 values range from 17 μg a.i./L for decreased cell 

density in Skeletonema costatum to >490 μg a.i./L for decreased growth rate in 

Anabaena flos-aquae. For algae, the lowest 96-hour EC50 value of 17 μg a.i./L for 

decreased cell density in the marine diatom, Skeletonema costatum, was used to assess 

acute risk to non-listed algae, while the NOAEC of 5.67 μg a.i./L for decreased cell density 

was used to assess risk to listed aquatic algae. This study satisfies the guideline 

requirements for an aquatic nonvascular plant study with Skeletonema costatum [§123-2] 

and is classified as acceptable. 

The effects of acute exposure of the amicarbazone metabolite Des-amino were evaluated 

in the green algae S. capricornutum (MRID 45121827, Table E-13). Results of this study 

show that the Des-amino metabolite is much less toxic than its parent compound, with no 

adverse effects on cell density, growth rate, or biomass at concentrations up to 1353 μg 

metabolite/L.

2. Terrestrial Effects 

The toxicity measures of effect used to characterize risks of amicarbazone exposure to 

birds and mammals are summarized in Table 13. Results of all studies in terrestrial 

animal species are summarized in Appendix E, Tables E-9 to E-11.
51

Table 13. Amicarbazone toxicity reference values (TRVs) for terrestrial 

organisms.

Exposur

e 

Scenario Species 

Exposure 

Duration

Toxicity Reference 

Value

Endpoint

Reference

(Classificatio

n)

Mammals

Acute rat

(Rattus 

norvegicus)

Single oral 

dose

LD50 = 1087 mg a.i./kg 

body wt 

Mortality MRID 

45121605

(Acceptable)

Chronic rat

(Rattus 

norvegicus)

2-generatio

n 

reproductiv

e study

(dietary 

exposure)

NOAEC = 100 ppm a.i. 

LOAEC = 500 ppm a.i 

a

[NOAEC in ppm 

equivalent to dose of 

6.4 mg a.i./kg body 

wt/day in males and 7.3 

mg a.i./kg body wt/day 

in females; LOAEC in 

ppm equivalent to dose 

of 33.9 mg a.i./kg body 

wt/day in males and 

38.7 mg a.i./kg body 

wt/day in females] b

Decreased body 

weight and 

weight gain for 

male and female 

pups and 

parents

MRID 

45121625

(Acceptable)

Birds

Acute bobwhite 

quail (Colinus 

virginianus)

single oral 

dose

LD50 = 1965 mg a.i./kg 

body wt

NOAEL = 250 mg a.i./kg 

body wt

LOAEL = 500 mg a.i./kg 

body wt 

Mortality

Decreased male 

food 

consumption 

and male body 

weight gain

MRID 

45121811 

(Supplemental

)

Acute mallard duck

(Anas 

platyrhyncho

s)

5-day 

dietary

LC50 >10,536 ppm a.i. 

a

NOAEC = 627 ppm a.i.

LOAEC = 1222 ppm a.i.

Mortality

Body weight and 

food 

consumption

MRID 

45121815 

(Acceptable)

Chronic mallard duck

(Anas 

platyrhyncho

s) and 

Avian 

reproductio

n study 

NOAEC = 27.1 ppm a.i. 

a

(for both mallard duck 

and bobwhite quail)

Reduction in 

number of viable 

embryos and 

hatchlings per 

MRID 

45121814

(Duck: 

Acceptable)
52

bobwhite 

quail

(Colinus 

virginiamus)

(dietary 

exposure)

Mallard 

Duck: 20 

weeks

Bobwhite 

Quail: 21 

weeks

LOAEC =149 ppm a.i. 

a

(for both mallard duck 

and bobwhite quail)

eggs set for 

bobwhite quail

Decreased 

eggshell 

thickness for 

mallard duck

MRID 

45121819 

(Quail: 

Acceptable)

Terrestrial Insects

Acute honeybee

(Apis 

mellifera)

48 hour 

acute 

contact 

study

LD50 >200 μg a.i./bee Mortality MRID 

45121816 

(Supplemental

)

Acute honeybee

(Apis 

mellifera)

48 hour 

acute oral 

study

LD50 = 24.4 μg a.i./bee

NOAEL =9.9 μg a.i./bee

LOAEL =19.8 μg a.i./bee

Mortality

Mortality, 

uncoordinated 

movements, and 

lethargy

MRID 

45121816 

(Supplemental

)

Plants - Tier II seedling emergence

Monocot onion single 

application

EC25 = 0.10 lb a.i./A

EC05 = 0.034 lb a.i./A c

Dry weight MRID 

45121821

(Acceptable)

Dicot sugar beet single 

application

EC25 = 0.030 lb a.i./A

NOAEC = 0.016 lb a.i./A

Dry weight MRID 

45121821

(Acceptable)

Plants - Tier II vegetative vigor

Monocot onion single 

application

EC25 = 0.026 lb a.i./A

NOAEC = 0.016 lb a.i./A

Dry weight MRID 

45121821

(Acceptable)

Dicot buckwheat single 

application

EC25 = 0.0037 lb a.i./A

NOAEC = 0.002 lb a.i./A

Dry weight MRID 

45121821

(Acceptable)

a Results are expressed in terms of dietary concentration (ppm a.i. or mg a.i./kg diet)

b

Dose-based equivalent was calculated by study authors based on food consumption during the study.

c

In the absence of a valid NOAEC value, the EC05 value was used to characterize risk to listed 

monocots. 

a. Terrestrial Animals 

Mammals

Results of an acute oral toxicity study in rats (Rattus norvegicus) show that administered 

single doses of amicarbazone TGAI yield an LD50 value of 1087 mg a.i./kg body weight 
53

(MRID 45121605). Based on these results, amicarbazone TGAI is classified as slightly 

toxic to mammals. The oral LD50 of 1087 mg a.i./kg body weight will be used to assess 

acute risk in mammals. Results of a 2-generation reproductive study in rats show that no 

treatment-related adverse effects on reproductive parameters resulted from long-term 

exposure to amicarbazone (MRID 45121625). Due to the lack of reproductive toxicity, 

the NOAEC for reproductive effects was 1000 ppm a.i. However, chronic amicarbazone 

exposure resulted in parental systemic toxicity (decreases in weight and weight gain) and 

toxicity to offspring (decreases in body weight and body weight gain) at the two highest 

test concentrations of 500 and 1000 ppm a.i.. The LOAEC and NOAEC for the affected 

endpoints for both pups and parents were 500 ppm a.i. and 100 ppm a.i., respectively. 

To assess chronic exposure risk in mammals, the NOAEC value of 100 ppm a.i. for 

parental systemic toxicity and toxicity in offspring will be used. Results of this study are 

expressed in terms of both dietary concentration (NOAEC = 100 ppm a.i.) and the 

equivalent daily dose (NOAEL = 6.4 mg a.i./kg body wt/day in males); both of these 

values will be used to assess the chronic risk of amicarbazone in mammals. Additional 

details pertaining to acute and chronic toxicity studies in mammals are presented in Table 

E-11.

Birds

Acute toxicity studies on technical grade amicarbazone have been conducted with 

bobwhite quail (Colinus virginianus) and mallard ducks (Anas platyrhynchos); results are 

summarized in Tables E-8 and E-9. For the acute single-dose toxicity study with 

bobwhite quail, 0% mortality occurred in the 0, 63, 125, 250, and 500 mg a.i./kg body 

weight test groups, while 40% mortality was observed in the 1000 and 2000 mg a.i./kg bw 

test groups. Although 50% mortality was not observed in any test group, results of probit 

analysis yielded an LD50 value of 1965 mg a.i./kg body weight (95% C.I.: 1260 to 

11254)(MRID 45121811), classifying amicarbazone as slightly toxic to birds on an acute 

oral basis. An LD50 was calculated despite 50% mortality not actually being observed 

because statistically it cannot be stated with much certainty that the LD50 is above 2000 

mg a.i./kg bw. Based on reductions in male body weight gain, the LOAEL and NOAEL for 

the study were 500 and 250 mg a.i./kg body weight, respectively. Reductions in female 

body weight gain were also evident in the 1000 and 2000 mg a.i./kg body weight 

treatment groups. Since this study fails to establish a precise LD50 value, or establish 

with certainty that the LD50 is above 2000 mg a.i./kg body weight, it does not satisfy the 

guideline requirements for acute oral toxicity studies with the bobwhite quail (§71-1) and 

is classified as supplemental. To assess acute oral risk of amicarbazone to birds, the 

acute oral LD50 value of 1965 mg a.i./kg body weight was used. 

Results of an acute dietary exposure study in mallard ducks (MRID 45121815) yielded an 

acute LC50 value of >10, 536 ppm a.i. Based on these results, amicarbazone is 

classified as practically non-toxic to birds on an acute dietary basis. Although no 

treatment-related mortality or signs of pathology were observed at the highest test 

concentration, sub-lethal effects were observed at 1222 ppm a.i. Body weight and feed 
54

consumption were the endpoints affected. Based on reduced terminal body weight, a 

NOAEC of 627 ppm a.i. was reported. This toxicity study satisfies the guideline 

requirements for avian dietary studies with mallards (§71-2(b)) and is classified as 

acceptable. To assess acute dietary risk of amicarbazone to birds, the acute dietary 

LC50 value of >10,536 ppm a.i. was used.

Results of avian reproduction studies of bobwhite quail (MRID 45121819) and mallard 

ducks (MRID 45121814) exposed to amicarbazone are detailed in Table E-10. In 

bobwhite quail, a reduction in the number of viable embryos per eggs set and a decrease 

in the number of hatchlings per eggs set were observed at 149 ppm a.i., with a dietary 

NOAEC value of 27.1 ppm a.i. Similarly, in mallard ducks, LOAEC and NOAEC values 

of 149 and 27.1 ppm a.i., respectively, were reported for decreased egg shell thickness. 

Male weight gain was also affected in the bobwhite quail (LOAEC = 722, NOAEC = 149 

ppm a.i.), while the number of eggs laid, eggs cracked, eggs not cracked of eggs laid, 

eggs set, eggs set of eggs laid, viable embryos of eggs set, live embryos, hatchling 

weight, and survivor weight were all endpoints that were affected in mallard ducks 

(LOAEC = 722 and NOAEC = 149 ppm a.i. for all). These studies satisfy the guideline 

requirements for avian reproduction studies with bobwhite quail and mallard ducks 

(§71-4) and are classified as acceptable. To assess chronic risk in birds, the dietary 

NOAEC of 27.1 ppm a.i. was used. 

Non-target Insects

Results of an acute contact study in honey bees (Apis mellifera L.) using technical grade 

amicarbazone yield an LD50 value of >200 μg a.i./bee (MRID 45121816), indicating that 

amicarbazone is practically non-toxic to honey bees. This study is classified as 

supplemental because the solvent used is not an EPA-recommended solvent (Adhäsit®) 

and therefore, the study does not meet guideline requirements for a contact toxicity test 

with honey bees (§141-1). In an acute oral exposure study in honey bees, an LD50 value 

of 24.4 μg a.i./bee was reported (MRID 45121816). In this same study, sub-lethal effects 

(uncoordinated movements and lethargy) were reported during the first 4 hours after oral 

exposure, with an NOAEL value of 9.9 μg a.i./bee. At 24 and 48 hours, no sub-lethal 

effects were observed. The acute oral study is classified as supplemental because it is a 

non-guideline study. The results of these tests are summarized in Table E-12

b. Terrestrial Plants

Terrestrial plant testing (seedling emergence and vegetative vigor) is required for herbicides that 

have terrestrial non-residential outdoor use patterns and that may move off the application site 

through either volatilization (vapor pressure > 1.0 x 10-5 mm Hg at 25oC) or drift (aerial or 

irrigation), and/or that may have listed species associated with the application site. In addition, 

terrestrial Tier II studies are required for all low dose herbicides (those with the maximum use rate 

of 0.5 lbs ai/A or less) and any pesticide showing a negative response equal to or greater than 25% 

in Tier I tests. Tier II terrestrial plant testing is required for amicarbazone because it is a low dose 

herbicide with the potential for widespread use. Tier II tests measure the responses of plants at five 
55

or more test chemical concentrations relative to a control. For seedling emergence and vegetative 

vigor testing, the following plant species and groups should be tested: (1) six species of at least 

four dicotyledonous families, one species of which is soybean (Glycine max) and the second crop 

is a root crop; and (2) four species of at least two monocotyledonous families, one of which is corn 

(Zea mays).

Tier 2 studies were conducted using the amicarbazone formulated product MKH 3586 70 

WG (MRID 45121821) and the amicarbazone metabolite MKH 3586 70 WG (MRID 

45121826). Seedling emergence and vegetative vigor were studied on a combination of eleven 

non-target crops (including soybean, buckwheat, sugarbeet, carrot, canola, lettuce, tomato, oat, 

ryegrass, corn, and onion) following application of amicarbazone formulated product MKH 

3586 70 WG. Details of these studies are summarized in Tables E-14 (for most sensitive 

species), Table E-15 (most sensitive parameter for all species tested for seedling emergence), and 

Table E-16 (most sensitive parameter for all species tested for vegetative vigor). Based on the 

results of these tests, it appears that emerging seedlings are less sensitive to amicarbazone via 

soil/root uptake exposure than emerged plants via foliar routes of exposure. All tested plants 

exhibited adverse effects in the vegetative vigor toxicity tests following exposure to amicarbazone, 

while four of the ten species tested (corn, oat, ryegrass, and soybean) were not adversely 

affected in the seedling emergence study. For both seedling emergence and vegetative 

vigor, dicots appear more sensitive than monocots. These data also suggest that 

grasses (family Poaceae) are generally more tolerant than other plant families, and that 

amicarbazone appears to be a little more selective and not a broad spectrum herbicide 

based on the distribution of toxicity among the species tested. For example, while the 

grasses (oat, corn, and ryegrass) and soybean (a legume) are basically resistant to 

amicarbazone and tomato appears to have some tolerance, the rest of the species 

appear to be sensitive to this chemical.

Overall, the results of studies using the amicarbazone formulated product MKH 3586 70 

WG show that both monocots and dicots are sensitive to exposure for both seedling 

emergence and vegetative vigor parameters and that dry weight was the most sensitive 

parameter in both studies. Results of seedling emergence studies identify onion as the 

most sensitive monocot (EC25 = 0.10 lb a.i./A; EC05 = 0.034 lb a.i./A, NOAEC = 0.126 lb 

a.i./A) and sugarbeet as the most sensitive dicot (EC25 = 0.030 lb a.i./A; NOAEC = 0.016 

lb a.i./A). Results of vegetative vigor studies show that onion is the most sensitive 

monocot (EC25 = 0.026 lb a.i./A; NOAEC = 0.016 lb a.i./A) and buckwheat is the most 

sensitive dicot (EC25 = 0.0037 lb a.i./A; NOAEC = 0.002 lb a.i./A). EC25 values were used 

to assess risk in non-listed species, while NOAEC values were used to assess risk in 

listed species. However, since the seedling emergence NOAEC for onion is greater than 

the EC25 value, the NOAEC value may not represent a valid toxicity value for use in 

characterization of risk. Therefore, in the absence of a valid seedling emergence 

NOAEC value in monocots, the EC05 value of 0.034 lb a.i./A for onion was used to assess 

risk to listed monocot species. 
56

The seedling emergence study using amicarbazone is classified as acceptable and fulfills the 

guideline requirements for seedling emergence studies (Subdivision J, §123-1 (a; TIER II)). The 

vegetative vigor study using amicarbazone is classified as acceptable for buckwheat, canola, 

lettuce, soybean, oat, onion, corn, and ryegrass, and fulfills the guidance requirements for 

vegetative vigor studies for these species (Subdivision J, §123-1(b; Tier II)). However, 

vegetative vigor data collected for sugar beet and tomato are classified as invalid due to 

overcrowded conditions and heightened competition, and are not used in this assessment. EPA 

protocol allows a maximum of 2 and 3 plants per six inch pot for tomato and sugar beet, 

respectively. The vegetative vigor study deviated from this acceptable protocol for these species 

by exceeding these recommendations and having 5 plants per 3.5 inch pot.

Results of Tier 2 seedling emergence and vegetative vigor studies with the amicarbazone 

metabolite MKH 3594 (Des-amino) indicate that the metabolite is less toxic than the 

parent compound for three of the four species tested (sugarbeet, lettuce, 

buckwheat)(MRID 45121826). Only the seedling emergence study determined a NOAEC 

for any species; onion emergence and onion dry weight each had a NOAEC of 0.013 lb 

a.i./A. A NOAEC could not be determined for any other species in either test; all other 

NOAECs were greater than the highest concentration tested (0.028 lb a.i./A). These 

tests applied concentrations of Des-amino at levels found to be toxic for the parent. 

Thus, the tests were conducted at concentrations less than the maximum application 

rate. Although an EC25 could not be calculated for any endpoint because a 25% effect 

was not elicited, a NOAEC and an EC05 were determined to be 0.013 and 0.014 lb a.i./A, 

respectively, for onion emergence. This NOAEC and EC05 are less than the values 

determined for onion in the emergence study with the parent, suggesting that Des-amino is 

more toxic than amicarbazone to onion. These tests do not fulfill the US EPA guideline 

requirements for seedling emergence and vegetative vigor studies (§123-1, TIER II)) because they 

were conducted with MKH 3594 (Des-amino), a metabolite of MKH 3586. Vegetative vigor data 

collected for sugar beet using Des-amino are classified as invalid due to overcrowded conditions 

and heightened competition, and are not used in this assessment. Details of this study are 

provided in Table E-14. 
57

IV. Risk Characterization

Risk characterization is the integration of exposure and ecological effects 

characterization to determine the ecological risk from the use of amicarbazone, and the 

likelihood of effects on aquatic and terrestrial organisms based on varying pesticide-use 

scenarios. The risk characterization provides an estimation and a description of the risk; 

articulates risk assessment assumptions, limitations, and uncertainties; synthesizes an 

overall conclusion; and provides the risk managers with information to make regulatory 

decisions.

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

adverse ecological effects on non-target species. For the assessment of amicarbazone 

risks, the risk quotient (RQ) method was used to compare exposure and measured 

toxicity values (see Appendix F). Estimated environmental concentrations (EECs) were 

divided by acute and chronic toxicity values. The resulting RQs were then compared to 

the Agency’s levels of concern (LOCs). These LOCs, which are summarized in 

Appendix F, are the Agency’s interpretive policy used to analyze potential risk to 

non-target organisms and the need to consider regulatory action. These criteria are 

used to indicate when a pesticide’s use as directed on the label has the potential to cause 

adverse effects on non-target organisms. Details of the RQs derived for all aquatic and 

terrestrial organisms are provided in Appendix G.

A. Risk Estimation - Integration of Exposure and Effects Data 

1. Non-target Aquatic Animals and Plants

To assess risk of amicarbazone to non-target aquatic animals (i.e., fish and invertebrates) 

and plants (i.e., macrophytes and algae), surface water EECs for amicarbazone (parent 

only) were obtained from the Tier 2 model PRZM/EXAMS based on the 

label-recommended usage scenarios (Table 6) and a 1% drift assumption for ground 

sprays. This risk assessment uses the highest peak 24-hour concentration (winter weed control on 

Texas corn) in surface water generated from the PRZM/EXAMS model to represent acute 

exposure to fish, aquatic invertebrates, algae, and macrophytes, and the highest 21-day

concentration of all scenarios (winter weed control on Texas corn) to represent chronic exposure to 

aquatic invertebrates and fish. No RQs calculated using these concentrations exceeded any 

LOC for any aquatic animal or macrophyte. Therefore, further calculations of additional 

RQs based on lower EECs for other usage scenarios were not performed for any aquatic 

animal or aquatic vascular plant in this assessment. However, there were exceedances 

for aquatic algae, and multiple RQs were calculated for this organism based on the 

various label-recommended usage scenarios. 
58

Toxicity reference values for aquatic organisms exposed to technical grade 

amicarbazone are summarized in Table 12. Toxicity data are either inadequate or 

unavailable to calculate RQs based on the following measures of effect (e.g., acute or 

chronic toxicity reference values) and receptors:

· chronic NOAEC toxicity data for estuarine/marine fish

Acute RQs for fish and aquatic invertebrates are summarized in Table 14. Chronic RQs 

for fish and aquatic invertebrates are summarized in Table 15. Risk quotients for 

non-listed and listed aquatic plants are summarized in Table 16 and Table 17, 

respectively. Risk quotients for aquatic algae for the multiple scenarios generated by

PRZM/EXAMS are listed in Table 18.

Table 14. Acute RQs for fish and invertebrates exposed to amicarbazone.

Species Category Organism

LC50 or EC50 

a

(mg a.i./L)

Peak 24-hour EEC b

(mg a.i./L)

Acute RQ c

(EEC/LC50)

freshwater fish rainbow trout >120.4 0.03378 No acute risk

freshwater 

invertebrates water flea 40.8 0.03378 0.0008

estuarine/marine 

fish

sheepshead 

minnow >118.0 0.03378 No acute risk

estuarine/marine 

invertebrates saltwater mysid 109.7 0.03378 0.0003

a

 RQs are based on the following toxicity data: for freshwater fish, the rainbow trout (Oncorhynchus 

mykiss) 96 -hr LC50 >120.4 mg a.i./L; for freshwater invertebrates, the water flea (Daphnia magna) 48-hr 

EC50 =40.8 mg a.i./L; for estuarine/marine fish, the sheepshead minnow (Cyprinodon variegatus) 96-hr 

LC50 >118 mg a.i./L; and for estuarine/marine invertebrates, the saltwater mysid (Mysidopsis bahia) 96-hr 

LC50 = 109.7 mg a.i./L.

b

 EEC value (mg/L) reported is the highest peak 24-hour concentration in surface water of all scenarios 

generated from PRZM/EXAMS 2.

c

 RQs are below the LOC for acute risk (LOC 0.5), acute restricted use (LOC 0.1), and acute 

endangered species risk (LOC 0.05).

Table 15. Chronic RQs for fish and invertebrates exposed to amicarbazone.

Species Category Organism NOAEC a

(mg a.i./L)

EEC b

(mg a.i./L)

Chronic RQ c

(EEC/NOAEC)

freshwater fish fathead minnow 7.3 0.03353 0.005 
59

Table 15. Chronic RQs for fish and invertebrates exposed to amicarbazone.

Species Category Organism NOAEC a

(mg a.i./L)

EEC b

(mg a.i./L)

Chronic RQ c

(EEC/NOAEC)

freshwater 

invertebrates

water flea 0.252 0.03353 0.133 

estuarine/marine 

fish No data submitted

estuarine/marine 

invertebrates saltwater mysid 5.0 0.03353 0.007 

a

 RQ values are based on the following toxicity data: fathead minnow (Pimephales promelas) 33-day

NOAEC = 7.3 mg a.i./L; water flea (Daphnia magna) 21-day LOAEC = 0.252 mg a.i./L; and saltwater 

mysid (Mysidopsis bahia) 28-day NOAEC = 5.0 mg a.i./L.

b

 EEC values (mg a.i./L) used for fish and invertebrates are the highest 21-day average concentration in 

surface water of all scenarios generated from PRZM/EXAMS.

c

 RQs are below the LOC for chronic risk (LOC 1).

Table 16. Acute RQs for non-listed aquatic plants exposed to amicarbazone.

Organism EC50

a

(mg a.i./L)

Peak 24-hour EEC b

(mg a.i./L)

Acute RQ 

(EEC/EC50)

S. costatum 0.017 0.03378