Document ID: EPA-HQ-OPP-2011-0641-0009
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-01-27T05:00Z

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

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
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
C.  Open Literature and Government Reports	97

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

      

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-carboxamide, 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 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.

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 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 (t(1/2)= 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-carboxamide; 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, 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 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 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.

(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.  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 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-carboxamide, 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 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)
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).

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.

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 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 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 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.
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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 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 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.
      
      
 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).

      ·	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.  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.
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Figure 2.	Regional distribution of field corn and corn for silage acreage in the United States in 2002 (USDA/NASS county level data).

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
Surface spray and shallow incorporation;

                                     0.450

                                     0.450

Pre-plant

29 days before planting

                                     0.450

                                    0.21873

At planting

At planting

Open furrow, seed, close furrow-surface apply- incorporate 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 herbicides

Early Post- 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 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.

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

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

137.5C

451215-01

Boiling point

Decompose above 180C

451215-01

Vapor pressure (VP)

1.3x10[-6] Pa ( 9.8x10[-9] mm Hg) at 20C
3.0x10[-6] Pa (2.2x10[-8] mm Hg) at 25C["]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 (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)

451218-03

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

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 (t(1/2)= 73 days) and by photolysis on soil surfaces subjected to sunlight (t(1/2)= 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

                         N-methyl Des-amino Degradate

                                 Decarboxamide

      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).  [14]C-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 [14]C-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 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 ug 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 

            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 t(1/2)x2: 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. 
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).

                                       
                              Application Window

                                    Chosen 
                                   Run Date

                                       
                                   Location

                                Representative
                                   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
                                       R
                                    16-Nov.
                                    Note  2
                                    TX 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
                                       A
                                       N
                                       T
                                    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
                                    Note  3
                                    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
                                                                               
                                    22-Feb.
                                                                               
                                    IL 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).

                                       
                              Application 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
                                       G
                                       E
                                       C
                                      E*
                                       
                                       

                                    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

                                    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 90[th] 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. 

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.

Buffer

Drift [1]

Initial 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 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

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./A[b]

short grass

                                     107.6

                                     38.11
                                       

tall grass

                                     49.32

                                     16.14
                                       

broadleaf plants and small insects

                                     60.53

                                     20.18
                                       

fruits/pods/large insects

                                     6.73

                                     3.14

                                       
                               0.22 lb a.i./A[c]

short grass

                                     52.51

                                     18.60
                                       

tall grass

                                     24.07

                                     7.88
                                       

broadleaf plants and small insects

                                     29.54

                                     9.85
                                       

fruits/pods/large insects

                                     3.28

                                     1.53

                               0.15 lb a.i./A[d]
                                       
                                       
                                       

short grass

                                     36.74

                                     13.01
                                       

tall grass

                                     16.84

                                     5.51
                                       

broadleaf plants and small insects

                                     20.67

                                     6.89
                                       

fruits/pods/large insects

                                     2.30

                                     1.07

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 applications.

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.  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 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 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 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 

                               Exposure 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)

                                                                               
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

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.

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 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 ug a.i./L, while the LOAEC is 80.5 ug 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 ug 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.

Table 13. Amicarbazone toxicity reference values (TRVs) for terrestrial organisms.

                               Exposure Scenario

                                   Species 

                               Exposure Duration

                           Toxicity Reference Value
                                       

                                   Endpoint

                                   Reference
                               (Classification)

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-generation reproductive 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 platyrhynchos)

                                 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 platyrhynchos) and 
                                bobwhite quail
                             (Colinus virginiamus)

                  Avian reproduction study (dietary exposure)
                                       
                            Mallard Duck: 20 weeks
                                       
                           Bobwhite Quail: 21 weeks

NOAEC = 27.1 ppm a.i. [a] 
(for both mallard duck and bobwhite quail)

LOAEC =149 ppm a.i.  [a] 
(for both mallard duck and bobwhite quail)

Reduction in number of viable embryos and hatchlings per eggs set for bobwhite quail

Decreased eggshell thickness for mallard duck

                                 MRID 45121814
                              (Duck: Acceptable)
                                       
                       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 (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 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(R)) 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 25[o]C) 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 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. 

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. 

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. 

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 

                           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