Page 1 of 44 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

PC Code: 006314

DP Barcode: D426678 September 8

, 2015 MEMORANDUM

SUBJECT: Registration Review: Combined Problem Formulation for Preliminary

Environmental Fate and Ecological Risk Assessment for Antimycin A

TO: Christina Scheltema , Chemical Review Manager

Avivah Jakob, Team Leader Risk Management and Implementation Branch III Pesticide Re

- Evaluation Division (7508P)

Will Donovan, Residue Chemist Alexandra LaMay, Risk Assessor & ORE Health Effects Division (750 9 P )

FROM: Cheryl Sutton, Ph.D., Environmental Scientist

Thomas Steeger, Ph.D., Senior Science Advisor Environmental Risk Branch IV Environmental Fate and Effects Division (7507P)

REVIEWED BY: Catherine Aubee, Senior Scientist

James Carleton, Ph.D., Senior Fate Scientist Katrina White, Ph.D., R isk A ssessment P roject L eader Environmental Risk Branch IV Environmental Fate and Effects Division (7507P)

THROUGH: Jean Holmes, D.V.M., M.P.H., Branch Chief

Environmental Risk Branch IV Environmental Fate and Effects Division (7507P)

The Environmenta l Fate and Effects Division (EFED) has completed a combined problem formulation and preliminary environmental fate and ecolo gical risk assessment in support of the Registration Review of the nitrosalicylanilide piscicide antimycin A (also referred as Fintr ol ® Concentrate; PC Code 006314; CAS No: 1397

- 94

- 0)

. Antimycin A is classified as a “Restricted Use” p esticide.- Page 2 of 44

-

EFED examin ed the most recent environmental fate and ecological risk assessment written in support of the May, 2007 Reregistration Eligibility Decision ( RED ) for antimycin A in association with updated toxicity, exposure, and usage information to determine if additional data are needed t o support the Registration Review of antimycin A. In addition, EFED considered the latest Agency science polic ies and risk assessment methodologies

. Because the database was determined to be sufficient to assess the ecological risk for use of antimycin A, the preliminary risk assessment has been combined with the problem formulation for registration review

. Since the underlying fate and effects data have not changed since the earlier assessment in 2007 and no additional data are required at this time , this preliminary risk assessment does not differ substantially from the previous and the reader is referred to the earlier document for a more detailed discussion of the available data. The previous assessment provides much greater detail on the use of a ntimycin A to restore native fish populations and information on the toxicity of potassium permanganate, which is u sed to deactive the Fintrol ® and prevent its movement outside of targeted treatment areas. S ubsequent to the 2007 ecological risk assessment, the US National Park Service finalized their standard operating procedure (SOP) for the use of

a ntimycin A to res tore fish populations, and this SOP is now referenced on the Fintrol ® product l abel. The SOP provides detailed instructions on the use of and deactication of antimycin A with potassium permanganate

. These procedures help to further ensure that antimycin A will not move outside of the targeted treatment area.

Risk Conclusions

Antimycin A is registered for use as a piscicide for use in fish management and aquaculture
programs . T he single registered end

- use product is Fintrol ® Concentrate. A ntimycin A appears to sorb to sediment (potentially at a high level) and to degrade primarily by hydrolysis . It appears
not to volatilize, does not readily dissolve in water, n or does it bioaccumulate

. However,

a ntimycin A is rapidly degraded by the deactivation pro cess required in the SOP linked to the Fintrol ® Concentrate label.

On an acute exposure basis

, a ntimycin A is moderately toxic to mammals, highly to very highly toxic to birds

, and very highly toxic to aquatic animals

. There are no data to evaluate the c hronic toxicity of antimycin to animals

, and there are no data to evaluate the toxicity of antimycin to either terrestrial or aquatic plants.

Like many of the chemicals used for killing fish ( i.e ., piscicides), for fishery management purposes, antimycin A has very detailed standard operating procedures (SOPs) developed by the US National Park Service in collaboration with the New Mexico Department of Game and Fish

. T hese SOPs are considered part of the federal label and ensure that relatively rigorous meth ods are routinely used to greatly reduce the likelihood of exposure and adverse effects to non

- target organisms outside of the desired treatment area. Although these SOPs do not apply to Fintrol ®

use in catfish production ponds, the chemical’s use in aqua culture is accompa nied by long holding periods (> 1 yr) during which time the compound is expected to degrade to negligible levels.

The results of this screening

- level risk assessment are similar to those identified in the environmental fate and ecological risk assessment written in support of the R ED for A ntimycin- Page 3 of 44

-

A in 2007

. Exposure to the compound resulting from the maximum treatment concentration is expected to kill all fish and aquatic invertebrates in the immediate treatment area

. However, in lotic (flowing water) environments

, after a specified treatment period, the compound is deactivated (detoxified) through the use of a strong oxidizing agent (potassium permanganate ; KMnO 4 ) into degradates that are no longer toxic . The oxidizing agent is applied at a deactivation station a t the perimeter of the Fintrol ® treatment area to ensure that it does not move outside of the intended treatment area

. Detoxification is typically verified using caged fish (bioassays) located downstream of the permanganate re lease sites. While there is uncertainty as to the extent to which active compound may be able to move outside of the treatment area, available data based on downstream bioassays indicate that antimycin residues are no longer at a concentrata t ion s suffici ent to kill fish

. The effect of potassium permangante on non

- target organism has been reviewed in previous
assessments (USEPA, 2006 a ) and the exte nt of its effects depend on the amount of organic material in the water treated; however, as a strong oxidizing agent, the compound can be highly toxic to aquatic organims . Riparian habitat on the margins of treated water typically contribute s sufficient organic matter to rapidly deplete permanganate close to the detoxification stations

. Within the targe ted treatment area and b ased on the most sensitive species and at the maximum treatment concentration, risk quotient (RQ) values for a ntimycin A exceed acute risk levels of concern (LOCs) by several orders of magnitude for direc t adverse effects to Federal ly listed threatened and endangered (hereafter referred to as “listed”) and non

- listed fish and invertebrates

. Because the SOP, which is part of the Federal label, requires that antimycin A be deactivated to prevent its movement outside of the treatment a rea, and given that treatment concentrations/durations are intended to result in 100% kill of the target species when a ntimycin A is used to restore fish populations, the likelihood of chronic exposure and/or effects is considered low. While both birds (a nd by extension reptiles and terrestrial

- phase amphibians) may be exposed through consumption of prey impaired by antimycin A , the likelihood of adverse effects to these taxa from secondary exposure is considered low.

Although antimycin A is used in catfi sh production ponds, its use is limited to clearing fingerling production ponds of scaled fish

, which can compete with catfish and carry disease. For use in aquaculture, antimycin is not typically deactivated as it is when used in lotic environmental. Ho wever, catfish production ponds are not typically drained ( if at all ) until after catfish have been harvested , at least one year after treatment. Based on available data, antimycin A would likely degrade during the holding period and is clearly not toxic to the catfish for which it was initially used to protect from comp eti tion with other species.

Uncertainties

There is a high degree of uncertainty surrounding the quantitative estimation of the environmental properties of antimycin A

. Only two environmental fate studies (hydrolysis and aerobic aquatic metabolism) were submitted for the compound, and results of the two are partially contradictory

. Additionally, n o quantitative information regarding the relative concentrations of the transformatio n products is available. However, uncertainty associated with the lack of environmental fate data is somewhat mitigated by the fact that the compound is- Page 4 of 44

-

deactivated with a strong oxidizing agent following its use in flowing water, and that relatively detai led standard operating procedures are in place as part of the label

. Bioassays (caged fish) are used concurrently with treatments to confirm that antimycin A does not move outside of the desired treatment area.

No data are available on the chronic toxicity of antimycin A to terrestrial or aquatic animals; however, the likelihood of chronic exposure is considered low for aquatic organisms in the treatment area since treatment concentration of up to 25 μg/L are exp ected to result in 100% mortality of both fish (and by extension aquatic

- phase amphibians) and aquatic invertebrates.

No data are available on the toxicity of antimycin A to benthic invertebrates. Although antimycin may partition to benthic sediments, the treatment concentrations used in fishery management are considered sufficient to result in complete mortality of both fish and invertebrates in the water column. If residues move into sediment, a similar situation is considered likely, i.e ., complete mortality. Available data indicate though that long

- term effects to macroinvertebrate populations in treated streams were minimal and that recovery occurred within several months of treatment.

No data are available for either aquatic or terrestrial plant s ; the use of the compound by resource management agencies such as the National Park Service and state fishery management agencies have not reported any incidents involving plants

. Also, for fishery management purposes, the compound is added directly to w ater and while backpack sprayers may be used to treat shallow waters along shorelines, the spray is not applied to terrestrial plants but rather to the water. Similarly, the use of antimycin A in catfish production ponds is a direct application to water a nd production ponds do not typically contain terrestrial and/or emergent aquatic plants since they would interfere with catfish harvest and serve as possible habitat for snails which vector diseases.

Provided that use of Fintrol ® and/or the current formul ation of antimycin as currently specified on the label does not change, no additional data are recommended at this time.

## Environmental Fate and Ecological Problem Formulation and Preliminary Risk Assessment for the Registration Review of Antimycin A

CAS 1397

- 94

- 0 PC Code 006314

September 8 , 2015

Prepared b

y Cheryl Sutton , Ph.D., Environmental Scientist Thomas Steeger, Ph.D., Senior Science Advisor U.S. Environmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division (EFED) Environmental Risk Branch IV 1200 Pennsylvania Ave., NW Mail Code 7507P Washington, DC 20460 Reviewed by Catherine Aubee, Senior Scientist James Carleton, Ph.D., Senior Fate Scientist Katrina White, Ph.D., RAPL Jean Holmes, D.V.M., M.P.H., Branch Chief- Page 6 of 44

- 

## Table of Contents

1. Executive Summary

................................ ................................ ................................ .............. 8 2. Problem Formulation

................................ ................................ ................................ ....... 10 2.1. Conclusions from Previous Risk Assessments

................................ .............................. 10 2.1.1. Ecological Risk Assessment

................................ ................................ .................... 10 2.1.2. Drinking Water Exposure Assessments

................................ ................................ 11 2.1.3 Clean Water Act Programs

................................ ................................ ........................ 11 2.2. Nature of Regulatory Action

................................ ................................ ...................... 12 2.3. Stressor Source and Distribution

................................ ................................ .............. 12 2.3.1. Nature of the Che mical Stressor

................................ ................................ ............. 12 2.3.2. Overview of Pesticide Usage

................................ ................................ ................ 14 2.4. R eceptors

................................ ................................ ................................ ................... 15 2.4.1. Aquatic and Terrestrial Effects

................................ ................................ ........... 15 2.4.2. Ecosystems Potentially at Risk

................................ ................................ ......... 16 2.5. Assessment Endpoints

................................ ................................ ................................ 16 2.6. Risk Hypotheses

................................ ................................ ................................ ......... 16 2.6.2. Potential Exposure Pathways and Effects

................................ .......................... 17 2.7. Analysis Plan

................................ ................................ ................................ .............. 18 2.7.1. Measures of Exposure

................................ ................................ ........................ 18 2.7.1.1 Measures of Aquatic Exposure

................................ ................................ ................................ 18 2.7.1.2. Measures of Terrestrial Exposure

................................ ................................ ............................ 18 2.7.2. Measures of Effect

................................ ................................ .............................. 19 2.7.3. Integration of Exposure and E ffects

................................ ................................ 20 2.8. Preliminary Identification of Data Gaps

................................ ............................ 21 3. Analysis

................................ ................................ ................................ .............................. 21 3.1. Use Characterization

................................ ................................ ................................ .. 21 3.2. Exposure Characterization

................................ ................................ ........................ 22 3.2.1. Environmental Fate and Transport Characterization

................................ ...... 22 3.2.1.1. Transport and Mobility

................................ ................................ ................................ ............ 24 3.2.1.3. Field Studies

................................ ................................ ................................ ............................ 25 3.2.1.4. Bioaccumulation

................................ ................................ ................................ ...................... 25 3.2.1.5. Transformation Products

................................ ................................ ................................ .......... 25 3.2.2. Measures of Aquatic Exposure

................................ ................................ ............ 26 3.2.2.1. Estimated Environmental Concentrations in Surface

................................ ............................... 26 3.2.2.2. Monitoring Data

................................ ................................ ................................ ....................... 26 3.2.3. Measures of Terrestrial Exposure

................................ ................................ ....... 26 3.3. Ecological Effects Characterization

................................ ................................ .......... 27 3.3.3. Review of Incident Data

................................ ................................ ....................... 31 4. Risk Characterization

................................ ................................ ................................ ......... 32 4.1. Screening

- Level Risk Quotient (R Q) Values

................................ ............................ 32 4.1.1. RQ Values for Aquatic Organisms

................................ ................................ ...... 32 4.1.2. RQ Val ues for Terrestrial Organisms

................................ ................................ . 33 4.2. Risk Description

................................ ................................ ................................ .......... 33 4.2.1. Risks to Aquatic Organisms

................................ ................................ ................. 34 4.2.1.1. Freshwater Fish, Amphibians, and Invertebrates

................................ ................................ ..... 34 4.2.2. Risks to Terrestrial Organisms

................................ ................................ ............ 36 4.2.2.1. Birds, Reptiles, and Terrestrial

- phase Amphibians

................................ ................................ .. 36- Page 7 of 44

- 4.2.2.2. Mammals

................................ ................................ ................................ ................................ . 38 4.2.2.3. Terrestr ial Invertebrates

................................ ................................ ................................ ........... 39 4.2.2.4. Terrestrial Plants

................................ ................................ ................................ ...................... 39 5. Endocrine Disruptor Screening Program (EDSP)

................................ ........................... 39 6. Federally Threatened and Endangered (Listed) Species of Concern

............................ 39 7. Conclusions

................................ ................................ ................................ .......................... 40 8. References

................................ ................................ ................................ ............................ 41 9

. Appendix A. SIP Results

................................ ................................ ................................ .... 44

List of Tables

T ABLE 1. C HEMICAL P ROFILE OF A NTIMYCIN A.

................................ ................................ ...................... 13 T ABLE 2. A GENCY R ISK Q UOTIENT (RQ) M ETRICS AND L EVELS OF C ONCERN (LOC) P ER R ISK C LASS

. . 20 T ABLE 3. C HEMICAL P ROPERTIES AND E NVIRONMENTAL F ATE P ARAMETERS OF A NTIMYCIN A.

........... 22 T ABLE 4. H YDROLYSIS R ATES FOR A NTIMYCIN A FROM S UBMITTED D ATA AND P UBLISHED L ITERATURE

. ................................ ................................ ................................ ................................ ...... 25 T ABLE 5

. A QUATIC A NIMAL A CUTE AND C HRONIC T OXICITY E STIMATES FOR A NTIMYCIN A.

................ 28 T ABLE 6

. T ERRESTRIAL A NIMAL A CUTE T OXICITY E STIMATES FOR A NTIMYCIN A.

................................ 30 T ABLE 7

. A CUTE RISK QUOTIENTS FOR FRESHWATER FISH AND INVERTEBRATES BA SED ON A TARGETED
ANTIMYCIN A TREATMENT RATE OF 25 μG /L.

................................ ................................ .................... 32 T ABLE 8

. A CUTE RISK QUOTIENTS FOR ESTUARINE / MARINE FISH AND INVE RTEBRATES BASED ON A
TARGETED ANTIMYCIN A TREATMENT RATE OF 25 μG /L.

................................ ................................ .. 33 T ABLE 9

. A CUTE DOSE

- BASED RISK QUOTIENTS FOR PISCIVOROUS BIRD S BASED ON POTENTIAL RESIDUES
IN DEAD OR DYING FIS H

. ................................ ................................ ................................ ..................... 37 T ABLE 10

. A CUTE DOSE

- BASED RISK QUOTIENTS FOR PISCIVOROUS MAMM ALS BASED ON POTENTI AL
RESIDUES IN DEAD OR DYING FISH

. ................................ ................................ ................................ .... 39- Page 8 of 44

-

1

. Executive Summary

Antimycin A ( CAS 1397

- 94

- 0, under the tradename Fintrol ® )

, is a restricted use nitrosalicylanilide pesticide derived as a fermentation product from Streptomyces mold and is registered for use as a means to kill fish, i.e ., a piscicide

. The chemical is primarily used to renovate recreational fish populations by removing unwanted fish species from streams

, impoundments and small lakes (<50 ha) for subsequent reestablishment of native aquatic communities; and to remove scaled fish from catfish fingerling fish production ponds. The chemical acts by uncoupling oxidative phosphorylation by blocking the electron transport pathway to Complex II I within mitochondria.

The residues of concern for this assessment were determined to be antimycin A parent only

. Antimycin A is applied directly to water via means ( e.g ., drip stations) , thereby avoiding spray d rift, and is maintained at a targeted treatment concentration for specified periods of time prior to deactivation of the compound with a strong oxidizing agent (potassium permanganate) in treated
streams

. Although environmental fate data are limited, the p rimary route of degradation appears to be base hydrolysis

, because under alkaline conditions the compound can degrade with a half

li fe of approximately 30 minutes

. However, in a submitted aquatic metabolism study (pH 6.5)

, the compound persisted in an aquatic environment with a half

- life of from 2 3 to 47 days

, although the se results were uncertain since the half

- life in that study exceeded the expected half

life from hydrolysis alone at the study pH

. Adsorption to sediment in that study may have limited the availability of the compound to degrade via hydrolysis. Field studies on downstream movement also show that the compound

, when introduced to flowing waters

, can persist and remain toxic to aquatic animals for distances of 1.75 km or more beyond the in tended treatment

zone when no effort is made to deactivate (chemically degrade) the compound

. There are no direct measurements of antimycin sorption to soils or sediments ; however, indirect evidence suggests that antimycin will partition significantly to s oil and sediments

, which may reduce potential exposure s outside of the immediate treatment area.

On an acute exposure basis antimycin is moderately toxic to mammals, highly to very highly toxic to birds and very highly toxic to aquatic animals resulting i n mortality

. There are no data to evaluate the chronic toxicity of antimycin to animals and there are no data to evaluate the toxicity of antimycin to either terrestrial or aquatic plants. However, given that all aquatic animals are likely to be killed by acute exposure to the compound and that other than for use in aquaculture the compound is deactivated to prevent movement of the compound outside of the desired treatment area, the potential for chronic exposure is considered low

. With respect to plants, the compound is applied directly to water

, and

, based on multiple years of use by the National Park Service and state fishery management agencies, there are no reports of adverse effects to either terrestrial or aquatic plants in the treatment area. Aquatic plants in aquaculture operations are minimized as they would interfere with catfish harvest and serve as habitat for snails which can vector parasites/diseases of catfish.

Based on the most sensitive species and the maximum tr eatment concentrations of 25 μg/L, acute risk levels of concern are exceeded for aquatic animals by factors of roughly 6,000X. Even for the least sensitive fish and aquatic invertebrates tested, treatment concentrations of 25 μg/L- Page 9 of 44

-

would exceed acute risk levels of concern

. These risk conclusions extend to amphibians using aquatic habitat treated with antimycin A

. Although antimycin is moderately to very highly toxic to terrestrial animals on an acute oral exposure basis, the target concentration in water of 25 μg/L or less is expected to present a low risk of acute mortality for birds , reptiles, and mammals through ingestion of antimycin

- treated water or ingestion of dead/dying fish

, based on an analysis of residues in fish

.

Because there are no chronic toxicity data, it is not possible to estimate potential chronic risk to aquatic or terrestrial animals. However, i n situations where antimycin is applied to flowing water, the chemical is deactivated (detoxified) with a strong oxidizing agent ( e.g ., potas sium permanganate ) at de activation stations a t the perimeter of the treatment area, as described in the US Park Service SOP (USDOI, 2012) , which are part of the technical label

. Additionally, in flowing water, antimycin A would eventually be flushed through the system and would also be diluted by inflow from untreated tributaries. Bioassays are required below the treatment area to ensure that the antimycin A is no longer active ; the extent to which this deactivation process is effective is uncertain . H owever, bioassays downstream of t he detoxification stations indicate that the compound is no longer at levels which affect the fish used in the bioassay

. Also, in both lentic and lotic environments

, because of the relatively extensive logistics involved in preparing for and conducting antimycin treatments , antimycin is typically only applied once per year

. Thus, the likelihood of chronic exposure in a lotic environment is low; however, in the absence of data, risk to nontarget organisms cannot be precluded. In situations where antimycin is not deactivated with potassium permanganate and there is not rapid dilution by untreated water, such as in many lentic (static water) environments, the chronic risk to non

- target aquatic orga nisms is uncertain. However according to the SOP, the use of antimycin in restoring fish populations is for a complete kill; therefore, the likelihood that any aquatic animals would survive is considered low.

Where antimycin is used to remove scaled fish from catfish fingerling production ponds,
treatment concentrations are considerably lower than 25 μg/L in order to not impair the health/survival of catfish

. Furthermore , the likelihood of either acute or chronic effects in non

target animals from the use of antimycin in aquaculture is low since the treated water is typically retained within the aquaculture facility for a year or longer until the catfish are of marketable size . To the extent that treated water is not retained but rather released into surro unding streams/rivers, the risk to non

- target aquatic animals is uncertain.

Based on laboratory data, aquatic invertebrates appear to be as sensitive to antimycin as fish; however, field studies of antimycin in high

- gradient mountain streams, where the c ompound was deactivated with potassium permanganate after the desired treatment time, suggests that aquatic invertebrates are not affected or are at worst temporarily affected as they repopulated these areas through immigration . Sampling conducted several months to up to a year after treatment indicate that aquatic invertebrate abundance and diversity were similar to pretreatment levels. Even in first

- order streams where antimycin was not deactivated with p e rmanganate, invertebrate drift and survival did no t appear to be significantly affected during or immediately after 8

- hr treatments at 10 μg/L

. Whether these studies are indicative of aquatic invertebrate communities in all antimycin use areas is uncertain.- Page 10 of 44

-

Effects on listed species may be an important consideration for site

- specific applications

. However, a ntimycin A is an important chemical control measure used by federal and state fishery management agencies to restore fish habitat by eliminating invasive species.

2

. Pr oblem Formulation

The purpose of problem formulation is to provide the foundation for the environmental fate and ecological risk assessment being conducted for the labeled uses of 3

- methylbutanoic acid 3[[3

- (formylamino)

- 2

- hydroxylbenzoyl]amino]

- 8

- hexyl

- 2,6

- dimethyl

- 4,9

- dioxo

- 1,5

- dioxonan

- 7

- yl
ester (antimycin A, also referred to as Fintrol ® Concentrate; PC Code 006314; CAS No: 1397

- 94

- 0)

. The problem formulation sets the obje ctives for the risk assessment and provides a plan for analyzing the data and characterizing the risk ( USEPA 1998 a )

. As part of the Registration Review process, a Problem Formulation (PF) for this risk assessment has been developed simultaneously with the conduct of the Registration Review Preliminary Risk Assessment (PRA) itself, as it was determined that available data a re sufficient to conduct the risk assessment at this time

. A separate Problem Formulation document will not be issued for antimycin A

.

2.1. Conclusions from Previous Risk Assessments

The ecological risk assessment written in support of the 2007 Reregistration Eligbility Decision ( RED ; USEPA 2007 1 ) document for antimycin A was issued in September 2006 (USEPA 2006 a 2 ) and finalized in March 2007 following the comment period

. Based on the previous analysis of the environmental fate, ecotoxicity, and registered uses of antimycin A, exposure to the compound resulting from the maximum treatment concentration is expected to kill fish and aquatic invertebrates in the immediate treatment area

. Ho wever, in lotic environments

, the compound is deactivated to ensure that it does not move outside of the intended treatment area

. B ioassays are conducted downstream of the treatment area to e nsure that antimycin is no longer toxic. Based on the most sensit ive species and at the maximum treatment concentration, risk quotient (RQ) values exceed acute risk levels of concern (LOCs) by several orders of magnitude

.

2.1.1. Ecological Risk Assessment

The major environmental fate and ecological risk conclusions presente d in the RED were as follows:

 Antimycin is applied directly to water and is maintained at a targeted treatment concentration for specified periods of time

. Although environmental fate data are limited,

1 USEPA. 2007. Reregistration Eligibility Decision for Antiycin A. List D. Case No. 4121. Available on line at: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2006

- 1002

- 0029 2 USEPA. 2006. Revised Environmental Fate and Ecological Risk Assessment Chapter (DP Barcode D310730) in Support of Phase III o f the Reregistration Eligibility Decision on Antimycin A (PC Code 006314). Available on line at: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2006

- 1002

- 0004- Page 11 of 44

-

the primary route of degradation is base hydrolysis

, by which

, under alkaline conditions (pH 8

- 9)

, the compound can degrade with a half

- life of approximately 3 hours

. H alf

- lives at environmentally relevant pH values (pH 5 to 8) ranged from less than 1 hour to 10 hours

. A more complete discussion of hydrolysis was included in Appendix G of the ecological risk assessment written in support of the 2007 RED 2

.

 Based on the most sensitive species and typical treatment concentrations of 25 μg/L, acute risk levels of concern ar e exceeded for aquatic anim als by several orders of magnitude

. Even for the least sensitive fish and aquatic invertebrates tested, treatment concentrations of 25 μg/L would exceed acute risk levels of concern

. Although antimycin is moderately to very highl y toxic to terrestrial animals on an acute oral exposure basis, treatment rates to water of 25 μg/L or less are expected to present a low risk of acute mortality for birds and mammals through ingestion of dead/dying fish or direct ingestion of antimycin

- tr eated
water.

Since the underlying environmental fate and ecological effects (toxicity) data have not changed since the earlier assessment in 2007 3 , this preliminary risk assessment does not differ substantially from the previous one , and the reader should refer to the earlier document for a more detailed discussion of the available data. The previous assessment also provides much greater detail on the use of antimycin to restore native fishes and on the toxicity of potassium permanganate, which is used to deactive the compound and prevent its movement outside of targeted treatment areas.

2.1.2. Drinking Water Exposure Assessments

EFED conducted a drinking water assessment (DWA) of antimycin A 4 in 2006 to evaluate potential risks to humans

. The highest environmental concentration was considered the maximum treatment concentration of 25 μg/L

. Chronic exposure values were estimated using a range of hydrolysis degradation rates and the most conservative degradation rate (using the longest reported hydrolysi s half

- life) which yielded a 1

- yr average chronic concentration of 4.6 μg/L

. Details may be found in the 2006 assessment. At the time of the previously

- conducted DWA, deactivation of the compound was not required for streams, as it now is in the current S OP for antimycin A use , precluding the need for a DWA

.

2.1.3 Clean Water Act Programs

Antimycin A is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. No Total Maximum Daily Load s (TMDL s ) or water quality criteria have been developed for antimycin A

. 5

3 Ibid USEPA 2007. 4 USEPA. 2007 a . Antimycin A Drinking Water Characterization. DP Barcode D310732. Dated June 21, 2006. Available on line at: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2006

- 1002

- 0011
5 USEPA. 2015. Watershed Assessment, Tracking and Environmental Results. Specific State Causes of Impairment that Make Up th e National Pesticides Cause of Impairment Group. http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885 \- Page 12 of 44

-

2. 2. Nature of Regulatory Action

The preliminary risk assessment is con ducted as part of the Agency’s Registration R eview
process for pesticide active ingredients

. In 1996, FIFRA was amended by the Food Quality Protection Act (FQPA), and the Agency was mandated to implement a new program for the periodic review of pesticides, i.e ., Registration Review 6 . The Registration Review program is intended to ensure that, as the ability to asse ss risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health and the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the new Registration Review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely.

2. 3

. Stressor Source and Distribution

2. 3

. 1

. Nature of the Chemical Stressor

Antimycin A (3

- methylbutanoic acid 3[[3

- (formylamino)

- 2

- hydroxylbenzoyl]amino]

- 8

- hexyl

2,6

- dimethyl

- 4,9

- dioxo

- 1,5

- dioxonan

- 7

- yl ester) is a R estricted U se nitrosalicylanilide pesticide derived as a fermentation product from Streptomyces mold and is registered for use to kill fish, i.e
., a piscicide

. Antimycin A consists of four major components which in turn consist of a pair of compounds, for a total of eight significant homologues

— four “major” and four “minor”

— that are dis tinguished by their chemical substituents (USDOI, 2012)

. A ntimycin A uncouples oxidative phosphorylation by blocking the electron transport pathway to C omplex I II within the mitochondria. 7

Based on preliminary analyses using liquid chromatography/mass s pectroscopy of an antimycin sample from the OPP Biological and Economic Assessment Division repository, a ntimycin is composed of eight components that group into two major categories: ones that have a butyl chain and the others that have a hexyl chain. W ithin each of these groups, four different structures exist based upon differences in the acyloxy side chain (butyl and propyl structural isomers) as depicted in Figure 1.

6 http://www.epa.gov/oppsrrd1/registration_review/ 7 B ittermann, A.D., J.M. Lazorchak and J.C. Dorofi. 1996. Profile of toxic response to sediments using whole

- animal and in vitro submitochondrial particle (SMP) assays. Journal of Environment al Toxicology and Chemistry 15(3): 319

– 324.- Page 13 of 44

-

The chemical profile of antimycin A is provided in Table 1

. As described in Section 3.2.1.4 , this screening

- level ecological risk assessment focuses on antimycin A parent only

.

Table 1

. Chemical Profile of Antimycin A. Common name Antimycin A Registered Product Name Fintrol ® Concentrate (EPA Registration No. 39096

- 2) Chemical name 3

- methylbutanoic acid 3[[3

- (formylamino)

- 2

- hydroxylbenzoyl]amino]

- 8

- hexyl

- 2,6

- dimethyl

- 4,9

- dioxo

- 1,5

- dioxonan

- 7

- yl ester Structure (A3 form of the molecule, the most toxic of the 8 homologues) Figure 1 . Chemical constituents of antimycin A.- Page 14 of 44

-

SMILES Notation O1C(=O)C(NC(=O)Cc2c(O)c(NC(=O))ccc2)C(C)OC(=O)C(CCCCCC) C(OC(=O)CC(C)C)C1 Pesticide type Restricted U se piscicide Chemical class N itrosalicylanilide CAS number 1397

- 94

- 0 Empirical formula C 28 H 40 N 2 O 9 Molecular mass 548.6 g mol - 1

2. 3 .2

. Overview of Pesticide Usage

Antimycin is a relatively minor

- use piscicide used primarily for direct applications to mountain streams, lakes, ponds and fishery operations. As part of a fish management program, antimycin A is used primarily by Federal and state agencie s to eliminate invasive or non

- native species in an area where threatened or indigenous species are intended later to be re estabilished (USDOI 2012) 8

. Based on the single registered end

- use product (Fintrol ® Concentrate ), antimycin A is applied directly to water ( streams, lakes, and ponds ) to achieve a maximum single treatment concentration of 25 μg active ingredient (a.i.) per liter of water (25 μg a.i./L ; maintained for a maximum 8

- hr treatment

. period)

. Actual treatment levels are species and goal specific

. Fo r use in aquaculture, the label recommends between 7 and 10 μg a.i./L and specifies that for “selective kill” use in aquaculture, not to apply the product in a way that will result in a treatment concentration greater than 10 .0 μg a.i./L

. For “ complete kill” use, the label specifies no t to apply the product in a way that will result in treatment concentrations greater than 25 .0 μg a.i./L . The maximum annual number of treatments in an area is 3 (with a minimum retreatment interval of 1 day), and the maximum annual cummulative treatment concentration is 50 .0 μg a.i./L (USDOI, 2012 9 )

.

Based on the SOP for the use of Fintrol ® for fish habitat restoration (USDOI, 2012 10 )

, it may be used in streams, ponds, and small lakes or impoundments (<50 ha) to remove ce rt ain fish species for subsequent reestablishment of native aquatic communities by fishery/natural resource

8 USDOI. 2012. National Park Service Standard Operating Practices for the Use of Fintrol (Antimycin A) for Restoration of Nati ve Fish Populations. U.S. Department of Interior, National Park Service Natural R esource Repoft NPS/NRSS/WRD/NRR

— 2012/594.
9 Ibid USDOI. 2012.
10 Ibid USDOI. 2012.- Page 15 of 44

-

managers

. The compound is applied to water by a drip

- feed device which is part of a drip station, or by backpack sprayer, boat bailer, or other hand

- held sprayer

. None of these methods are expected to result in spray drift. According to the SOP, the compound is applied at levels intended to result in a lethal concentration for 100%, i.e ., LC 100 , for the non

- native fish targeted by the treatment. Deeper water bodies may require the use of a pump mechanism (to ensure adequate mixing throughout the water column) using a perforated hose or delivery through the boat’s propeller wash

. Spray drift from anitmycin A applications is not conside red likely even when applied by backpack sprayers since hand

- held wands are used to dispense the spray relatively close to the surface of the water. Prior to application, the active ingredient is mixed with a diluent (which contains a surfactant) to incre ase solubility

. Together

, these materials ( i.e
., the active ingredient and the diluent) comprise the product Fintrol ®

. Similar to other piscicides, antimycin A is a R estricted U se product (RUP) and the chemical has relatively detailed SOPs developed by t he National Park Service associated with its use to renovate fish populations (USDOI, 2012 11 )

. Since the SOPs are linked to the Federal label, they are considered part of the label and must be followed by the end user

. Current SOPs require deactivation of the compound with potassium permanganate following its use in all streams. T he Fintrol ® label provides instructions for de activating antimycin A with potassium permanganate (KMnO 4 ) at a treatment concentration of 1 m g/ L (part per million) . Potassium permanganate (CAS No. 7722

- 64

- 7) is a strong oxidizing agent commonly used to purify drinking water and kill pond algae. According to the product label, antimycin may be considered de activated when fingerling rainbow trout ( Oncorhynchus mykiss ) or juvenile bluegill sunfish ( Lepomis macrochirus ) survive for at least 48 hours in holding tanks ( live

- cars ) placed 91 meters (100 yards) downstream from the site of potassium permanganate application. Depending on environmental c onditions ( e.g . total organic carbon) higher KMnO 4 treatment rates ( e.g . 3

– 4 mg/L) may be required to deactivate antimycin A 12

.

2. 4

. Receptors

2. 4 .1

. Aquatic and Terrestrial Effects

A receptor is a biological entity that is exposed to a stressor (USEPA 199 8 13 )

. Consistent with the process described in the O verview of the Ecological Risk Assessment Process in the Office of Pesticide Programs (USEPA 2004 14 ), this risk assessment uses a surrogate species approach in its evaluation of antimycin A

. T oxic ity data generated from surrogate test species, which are intended to be representative of broad taxonomic groups, are used to extrapolate potential effects on a variety of species (receptors) included under these taxonomic groupings.

A cute and c hronic toxicity data from studies submitted by pesticide registrants along with data from the available open literature are used to evaluate potential direct effects of antimycin A to

11 Ibid USDOI. 2012.
12 Ibid USDOI. 2012.
13 USEPA. 1998. Guidelines for Ecological Risk Assessment. EPA/630/R

- 95/002F. Published in 63 FR 26846; May 14, 1998. U.S. Environmental Protection Agency, Washington, DC. April, 1998.
14 USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. Environmental Prote ction Agency. Endangered and Threatened Species Effects Determinati ons. Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington, D.C. Available online at http://www.epa.gov/oppfead1/endanger/consu ltation/ecorisk

- overview.pdf

.- Page 16 of 44

-

aquatic and terrestrial receptors

. The open literature studies are locat ed through EPA’s database ECOTOX ( http://cfpub.epa.gov/ecotox/ ), which provides a source for locating single chemical toxicity data for aquatic life, terrestrial plants, and wildlife

.

2. 4 .2

. Ecosystems Potentially at Risk

E cosystems at potential risk are often extensive in scope; therefore, it is not possible to identify such ecosystems in other than general terms in a screening

- level assessment

. In general terms, terrestrial ecosyste ms potentially at risk are areas immediately adjacent to tre ated s urface water,
e.g ., riparian habitats

. Aquatic ecosystems potentially at risk i nclude water bodies adjacent to or down stream from treated area s and may include natural or impounded lentic systems , i.e.
, ponds, lakes

, and reservoirs

, and lotic ( flowing ) waterways , i.e.
, streams and rivers

. Within water bod ies, the water column, sediment , and pore water are all compartments of potential concern

.

2. 5

. Assessment Endpoints

Assessment endpoints represent the actual environmental value s that are to be protected, defined by ecological entitities (species, community, etc. ) and their attr ibute s or characteristics (USEPA 1998 )

. For antimycin A , the ecological entities assessed include the following: birds , amphibians, reptiles, mammals, freshwater fish , terrestrial and aquatic invertebrates, and terrestrial and aquatic plants

. The assessed attributes for any of these entities may include growth, survival, and /or reproduction

. (Se e Table 2 i n Section 2.7.3 , the Analysi s Plan, for further discussion).

The assessment endpoints are intended to reflect population sustainability and community structure within ecosystems

, and hence relate to ecosystem risk

. If risks are identified for given specie s/taxa based on a screening

- level assessment, then such risks might be expected to translate to higher levels of biological organization.

2. 6

. Risk Hypotheses

For antimycin A , the following risk hypothesis is employed for the ecological risk assessment:

The use of antimycin A in accordance with the label results in adverse effects on survival and/or fecundity to non

- target aquatic plants and animals

. To the extent that terrestrial animals may feed o n dead or dying fish in the treatment area a nd/ or ingest antimycin

treated water, terrestrial animals may experience adverse effects as well.- Page 17 of 44

- 2. 6 .2

. Potential Exposure Pathways and Effects

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically significant concentrations

. An exposure pathway is the means by which a pesticide moves in the environment from a source to an ecological receptor

. For an ecological pathway to be complete, it must include a source, a release mechanism, an environmental transport medium, a point of exposure for ecological receptors, and a feasible route of exposure. The potential exposure pathways and effects of the registered uses of antimycin A are mediated by the fact that the compound is deactivated foll owing use

. Consequently, most of the normally assessed routes of exposure are not considered likely for antimycin A

. The sole appl ication type is direct application to water as a pis cicide via methods not expected to result in spray drift

. Organisms that m ay be exposed to antimycin A for short periods following application (prior to deactivation) include aquatic receptors ( e.g ., freshwater and estuarine/marine fish and invertebrates, aquatic

- phase amphibians, and plants)

. Exposure s to terrestrial and semi

- aquatic wildlife ( i.e. , mammals, birds, terrestrial

- phase amphibians, terrestrial invertebrates, and reptiles) and plants could occur, but are expected to be limited both temporally and spatially

. Ingestion of treated moribund fish by avian and mammalian s cavengers is potential route of evaluation which is evaluated in the risk characterization section of this document.

When used as a piscicide, antimycin A is deposited directly into a receiving water, which may be a stream, pond, lake or reservoir

. Once i n the water column, non

- target aquatic organisms may be exposed to antimycin A vi a three main exposure pathways and two minor pathways.

1. Antimycin A will initially be distributed in the water column of the receiving water , and

o rganisms in the water column (aquatic invertebrates, fish, amphibians and plants) may be directly exposed through contact

. Antimycin A is applied in conjunction with a diluent that increases its solubility

. Organisms can take up soluble antimycin A through the gills or integument

. If sufficient concentrations exist, then individual toxic effects in aquatic invertebrates, fish, aquatic

- phase amphibians and /or plants can result

. This may result in reductions in population size s of species within these taxa. T his is expected to be the main route of exposure for antimycin A

.

2. Anti mycin A released into water will likely sorb to sediment and suspended solids

. Receptors such as aquatic invertebrates, fish, and aquatic

- phase amphibians may be exposed to sorbed antim ycin A through incidental ingestion of sediment and/or suspended solids. This can result in changes in populations based on reduced survival, growth and reproduction.

3. Antimycin A may also sorb to plant surfaces

. Ingestion of plant materials with sorbed

an timycin A can result in a similar exposure pathway as described for sediment and suspended solids

. No nvascular or vascular plants may also be exposed to antimycin A through direct contact or root uptake

. This could result in changes in plant populations du e to direct toxicity

. However, s ince no plant toxicity data are availab le for antimycin A, risks to aquatic plants cannot be evaluated

.- Page 18 of 44

-

4. Antimycin A residues may accumulate in target and non

- target organisms , although this is not considered likely given t he low estimated bioconcentration factor

. Other organisms that live in or around the treatment area may be exposed to antimycin A by consuming treated organisms.

5. Direct exposure of terrestrial animals/plants to antimycin is not likely since the chemical i s only applied to water bodies

. Indirect exposure to both mammals and birds is possible through the consumption of dead and dying fish and larger invertebrates and through ingestion of antimycin

- treated water

. Exposure via residues on foliage adjacent to t he water body is not expected because the application methods will not result in spray drift.

Environmental fate data suggest (but have not clearly demonstrated) that antimycin A has a low potential to volatilize

. Additionally, t he compound is applied directly to water . Therefore, the likelihood of inhalation exposure in wildlife is considered low.

2. 7

. Analysis Plan

2. 7 .1

. Measures of Exposure

2. 7 .1.1 Measures of Aquatic Exposure

For antimycin A, the registered uses of the compound as a piscicide require the direct application of the compound to water to maintain specific water treatment concentrations for defined durations of time

. Therefore, aquatic exposure values are specific to meet the management objective of the treat ment , i.e ., to result in 100% mortality of the target species

. As such, exposure modeling per se is not needed for antimycin A within the treatment site , as actual label maximum treatment levels will be used

. Becau se the compound is deactivated with a stro ng oxidizing agent ( e.g ., potassium permanganate ) and deactivation is verified using fish bioassays downstream of the deactivation stations following use in streams, only acute EECs for the target site will be used in risk estimation

.

2. 7 .1.2

. Measures of Terrestrial Exposure

Antimycin A is applied directly to water via methods that will not result in spray drift, and exposure to terrestrial environments is expected to be low; therefore, exposure estimates will not be calculated for determining residues on terrestrial animal forage items

. Since antimycin A is applied directly to water, exposure of terrestrial plants to the compound is expect to be low; therefore, exposure estimates for terrestrial plants will not be calculated.

The S creeni ng I mbibition P rogram (SIP v.1.0, r eleased June 15, 2010) was used to calculate an
upper

- bound estimate of exposure using the maximum treatment concentration for antimycin ( i.e ., 25 μg/L)

, that was in turn compared to the most sensitive acute avian and mam malian toxicity endpoints (see Table 6 )

. Although a ntimcyin A is classified as very highly toxic to birds ( LD 50 =2.9 mg/ kg body weight ) and the compound is moderately toxic to mammals ( LD 50 =286 mg/kg body weight) on an acute oral exposure basis , model output indicates that drinking water- Page 19 of 44

-

alone is not a potential concern for either birds or mammals

. For a sample of the output generated by SIP v.1.0, please see Appendix B

. Since no data are available to assess the potential chronic risks of antimy cin A to birds and mammasls, SIP indicates that the risk is uncertain

. However, as discussed in this assessment, the likelihood of chronic exposure to antimycin is considered low.

Although EPA typically evaluates potential exposure to non

- target organis ms via exposure using the Screening Tool for Inhalation Risk (STIR), for fishery management purposes

, antimycin A is applied directly to water using metering metering devices (drip stations). Although shorelines may be spot treated using a back

- pack sprayer, there is a low likelihood that either mammals or birds would be in close proximity to the applica tors during such applications as applicators walk along the shorelines with the hand

- held wands typically maintained within a short distance (< 2 feet) of the water to ensure the delivery of the material to the targeted area. Therefore, the Agency did not evaluate potential exposure to non

- target organisms using the STIR model.

While the potential for bioaccumulation of antimycin A is considered low based on measured residues in bioconcentration studies

, given that treatment concentrations used in fish re storataion efforts are intended to result in 100% mortality, the KABAM model [K ow (based) Aquatic BioAccu mulation Model, Version 1.0] is typically used as a screen to estimate potential bioaccumulation of hydrophobic organic pesticides in freshwater aquati c food webs and subsequent risks to mammals and birds via consumption of aquatic prey contaminated with antimycin

. The bioaccumulation portion of KABAM relies on a pesticide’s octanol

- water partition coefficient (K ow ) to estimate uptake and elimination con stants through respiration and diet of aquatic organisms in different trophic levels. Pesticide tissue concentrations in aquatic organisms are calculated for different trophic levels of a food web through diet and respiration and are used to estimate dose

- and dietary

- based exposures and associated risk quotients for mammals and birds consuming aquatic organisms

. While t he log K ow for antimycin is estimated to be 4.21

, other model input values, e.g. , organic carbon partition coefficient (K oc ), are not avail able for antimycin A; therefore, the model was not run

. However, the risk description section of the document discusses potential risks to birds and mammals which may forage of fish killed by antimycin A treatments

. This analysis indicate s that the risk to birds and mammals that
consume aqu a tic prey contaminated by antimycin is low.

2

. 7 .2

. Measures of Effect

Measures of effect are obtained from a suite of registrant

- submitted guideline studies which were conducted with a limited number of surrogate test species

. The test species are not intended to be representative of the most sensitive species but rather wer e selected based on their ability to thrive under laboratory conditions

. Toxicity testing reported in this risk assessment utilizes surrogate species to represent all freshwater fish (2000+) and bird (680+) species in the U.S

. T he ECOTOXicology database (E COTOX), was searched in June 2015 to determine whether additional, more sensitive ecological effects data were available for antimycin A ; however, no such data were identified

. The acute measures of effect used in this screening

- level assessment are the L D 50 (Lethal Dose), LC 50 (Lethal Concentration)

, EC 50 (Effects Concentration) , and IC 50 (Inhibition Concentration)

.- Page 20 of 44

-

These are measures of acute toxicity which result in 50% of the respective effect in tested organisms

. The endpoints for chronic measures of exposure are the NOAEC (No Observed Adverse Effect Concentration) and the NOAEL (No Observed Adverse Effect Level)

. Toxicity studies were submitted for freshwater fish and invertebrates

, estuarine/marine fish and invertebrates

, birds an d mammals

. The endpo ints used for risk characterization were derived from studies which underwent review and were classified as “acceptable” (conducted under guideline conditions and considered to be scientifically valid) or “supplemental” (conditions deviated from guidelines but the results we re considered to be scientifically valid).

2. 7 .3

. Integration of Exposure and Effects

The exposure and toxicity effects data are integrated in order to evaluate the risks of adverse ecological effects on nontarget species

. For the risk assessment of antimycin A , the risk quotient (RQ) method is used to compare estimated exposure with measured toxicity endpoint s

. The RQ method involves dividing EEC s by the most sensitive acute and chronic toxicity endpoint s available

. The resulti ng RQs are then compared to the Agency’s Levels of Concern (LOC) (USEPA 2004) ( Table 2 ). Any LOC exceedences are used to indicate use s of antimycin A that have the potential to cause adverse e ffects to non

- target organisms.

Table 2

. Agency Risk Quotient (RQ) Metrics and Levels of Concern (LOC) Per Risk Class.
R isk C lass R isk D escription RQ LOC Aquatic Animals (fish and invertebrates)

Acute Potential for effects to non

- listed animals from acute
exposures Peak EEC/LC 50 1 0.5

Acute Restricted Use Potential for effects to animals from acute exposures

Risks may be mitigated through restricted use classification Peak EEC/LC 50 1 0.1

Acute Listed Species Listed species may be potentially affected by acute
exposures Peak EEC/LC 50 1 0.05

Chronic Potential for effects to non

- listed and listed animals from chronic exposures 60

- day EEC/NOAEC (fish) 1 21

- day EEC/NOAEC (invertebrates) Aquatic Plants
Non

- Listed Potential for effects to non

- listed plants from exposures Peak EEC/LC 50 1 1
Listed Potential for effects to listed plants from exposures Peak EEC/NOAEC 1
EEC/ EC 05
1 LC 50 or EC 50 . 2 EEC based on upper bound Kenaga nomogram values for foliar exposure.- Page 21 of 44

- 2.8

. Preliminary Identification of Data Gaps

The database on the environmental fate and transport properties of antimycin is incomplete

. Since the compound is used exclusively as a piscicide, the terrestrial fate properties are relatively undocumented

. The database on the ecological effects of antimycin is incomplete

. There are no chronic toxicity data for either terrestrial or aquatic animals; however, the likelihood of chronic exposure to antimycin following application to flowing water is likely low due to a combination of degradation, advective removal (assuming t hat exposed animals stay relatively fixed in space and do not move with the concentration pulse) , deactivation

, and dilution

. While the chemical is expected to partition to sediments and will likely do so in lentic environments ( e.g ., ponds and lakes), the intent of the treatments is to achieve 100% mortality of the target species. Given that invertebrates exhibit roughly similar sensitivity as fish to antimycin, the effects to benthic invertebrates is expected to be similar. Additionally, there are no da ta for terrestrial or aquatic plants ; however, the use of this product in National Parks to restore native fish has not resulted in any incident reports for adverse effects to either terrestrial or aquatic plants

. The likelihood of exposure to terrestrial plants is considered low; how ever, aquatic plants will be exposed and the potential risk to these plants is uncertain.

No toxicity data are available to assess the effects of antimycin A on terrestrial invertebrates such as honey bees (

Apis mellifera ); ho wever, given that the compound is used to treat water directly and that these treatments typically occur in high altitude lakes and high gradient streams (USDOI 2012) , the likelihood of exposure for terrestrial invertebrates is considered low.

3

. A nalysis

3.1

. Use Characterization

Antimycin A is a piscicide used for selective ( e.g ., scaled fish removal from aquaculture facilities) or complete fish kills ( e.g ., fish restoration efforts)

. Based on the single registered end

use product (Fintrol ® Concentrate ), antimycin A is applied directly to water ( e.g. , streams, lakes, ponds ) , using methods described previously, to achieve a maximum single treatment concentration of 25 μg active ingredient (a.i.) per liter of water (25 μg a.i./L ) and maintained at this concentration for a maximum 8

- hr treatment period)

. The maximum annual number of treatments in an area is 3 (with a minimum retreatment interval of 1 day), and the maximum annual treatment concentration is 50 μg a.i./L (USDOI, 2012)

. For fish rest oration efforts, t arget treatment concentrations vary with the type of fish targeted and treatment goals, as described in the SOP (USDOI, 2012).

Based on the standard operating procedures (SOP) for the use of Fintrol ® , it may be used in streams, ponds, a nd small lakes or impoundments (<50 ha) to remove non

- native fish species for subsequent reestablishment of native aquatic communities (USDOI 2012)

. The compound must be deactiva ted using potassium permanganate foll owing its use in all streams to prevent its movement out of the targeted treatment area

.- Page 22 of 44

-

3.2

. Exposure Characterization

3.2. 1. Environmental Fate and Transport Characterization

Antimycin A (3

- methylbutanoic acid 3[[3

- (formylamino)

- 2

- hydroxylbenzoyl]amino]

- 8

- hexyl

2,6

- dimethyl

- 4,9

- dioxo

- 1,5

- dioxonan

- 7

- yl ester) consists of four major components which in turn consist of a pair of compounds, for a total of eight significant homologues (i.e., structural isomers)

— four “major” and four “minor”

— that are distinguished by their chemical substituents

. The environmental fate data set submitted for antimycin A is limited , consisting of only an hydrolysis and an aerobic aquatic metabolism study

. Preliminary estimates of the phy sical and chemical properties that determine the fate and transport of a ntimycin A are detailed in Table 3

. These values were estimated using a quantitative structure activity

- based calculator, open literature, and registrant

- submitted studies

. There is a high degree of uncertainty surrounding the quantitative estimation of the environmental properties of antimycin, as well as the submitted data

. However, antimycin A can partition to sediment and appeaers to degrade primarily by hydrolysis . It a p pears n ot to volatilize, does not readily dissolve in water, n or does it bioaccumulate

. Additionally, the environmental fate of antimycin A will be significantly affected by the deactivation process required in the SOP linked to the Fintrol ® Concentrate label.

Othe r than the parent compound, no additional residues of concern have been identified

.

Table 3

. Chemical Properties and Environmental Fate Parameters of Antimycin A.
Chemical/Fate Parameter Value Description/Comments Source (MRID) Selected Physical/Chemical Parameters

Chemical name 3

- methylbutanoic acid 3[[3

- (formylamino)

- 2

- hydroxylbenzoyl]amino]

- 8

- hexyl

- 2,6

- dimethyl

- 4,9

- dioxo

1,5

- dioxonan

- 7

- yl ester ˗ ˗

Molecular mass 548.6 g mol - 1

˗ ˗
Vapor pressure ( 25  C ) 3.08 x 10 - 22 Torr Estimated value. Not volatile. EPISuiteTM v4.11

Water solubility ( 25  C ) 0.089 mg/L Limited solubility in water. EPISuiteTM v4.11

Octanol

- water partition coefficient ( Log K OW ) 4.21 Estimated value. EPISuiteTM v4.11

Henry’s Law Constant (25°C) 1.82 x 1 0 - 21 atm

- m 3 /mole Estimated value. Not volatile from water or moist soil. EPISuiteTM v4.11

Persistence- Page 23 of 44

-

Chemical/Fate Parameter Value Description/Comments Source (MRID)

Hydrolysis half

- life (d) pH 5, 25  C pH 7, 25  C pH 9, 25  C Submitted Data pH 5: 15 days pH 7: 3 days pH 9: 3 hrs

Scientific Literature Minutes (higher pHs) to hours (below pH 9). U ncertain. Non

- guideline

,

literature data indicate faster base

- catalyzed hydrolysis at

> pH 8. Likely the main degradation route at > pH 8. 46023101 ; USEPA 200 6 a

Aqueous photolysis half

- life

(25  C) No data. Data were waived in 2001 ( DP Barcode D276036 ). ˗
Soil photolysis half

- life (25  C) No data. These d ata are not required for a n aquatic use

. ˗

Aerobic soil metabolism half

- life (25°C) No data.

˗ ˗

Anaerobic soil metabolism half

- life (25°C) No data. These data are not required for an aquatic use. ˗ Aerobic aquatic metabolism half

- life ( 25°C ) 2 3

- 47 days (water pH 6.5) Highly uncertain value since it is longer than hydrolytic half

- life at that pH

. Adsorption to sediment may have limited hydrolysis. 45895901

Anaerobic aquatic metabolism half

- life ( 25°C ) No data. Data were waived in 2001 ( DP Barcode D276036 ). ˗

Mobility

Freundlich soil

- water partition coefficients (K F ); No data.

˗ ˗

Or ganic carbon

- normalized soil partition coefficients (K FOC ) Adsorption

1030

- 1.658E+004 L/kg

Desorption No data. Estimated values. No data available. Indicates compound will be slightly mobile to hardly mobile in

s ediment

. Pesticide is applied with diluent that may alter mobility by increasing solubility. EPISuiteTM v4.11

Field Dissipation
Aquatic field dissipation half

- life No data Data were waived (1993).

˗

Fish Bioconcentration

Fish bioconcentration factors (steady

- state); depuration
rate 277

- 350X No data available. Estimated values. EPISuiteTM v4.11; PBT Profiler.- Page 24 of 44

- 3 .2.1.1

. Transport and Mobility

Although the registrant did not provide sorption studies for antimycin A, aerobic aquatic metabolism study data indicate that antimycin A partitioned to the sediment phase (MRID 45895901 )

. Rough estimates of sorption were made from the aerobic aquatic study by considering the relative distribution of antimycin in the water and the sediment as measured in that study

. If equilibrium between the water and the sediment were assumed throughout the aerobic aquatic study

, then K d values would range from about 1 to 88 ml/g or K oc in the range of 84 to 10

, 000 ml/g (USEPA 2006 a )

. While this is a wide range with respect to mobility in sediment, it is unclear how it would relate to actual adsorption in the environment, given that the compound is applied in conjuction with a diluent to greatly increase its solubility in water. Estimates of adsorption using a quantitative structural analysis approach yielded an estimated K oc range of 1030

- 1.6 6 x 10 4 L/kg , indicating that the compound would be be slightly mobile to hardly mobile in sediment

.

3.2.1.2

. Degradatio n

A ntimycin A is degraded abiotically through hydrolysis, with much more rapid degration observed at higher pH levels in multiple studies (Hussain, 1969; Walker et al ., 19 64; Lee et al

. 1971)

. Submitted data indicate that antimycin hydrolyzes with a half

- life of 15 days at a pH of 5, 3 days at pH 7, and 3 hours at pH 9 (MRID 46023101)

. However, a more recent study by Kenneke (2006), which suggests that hydrolysis is an impo rtant mechanism of degradation, does not clearly show a correlation between degradation rate and pH

. That study estimated half lives of approximately 4

- 10 hours in unmixed systems , and half lives of 1

- 10 hours in mixed systems

. Hydrolysis rates from the li terature are summarized in Table 4

. In all cases hydrolysis half lives are on the order of minutes to hours. A more complete discussion of available hydrolysis data for antimycin A was presented in the ecological risk assessment (USEPA 2006 a ) conducted in support of the 2007 RED. Antimycin A is also expected to degrade via photolysis (Ott)

, although guideline data have not been submitted.

Transformation products were not identified in the registrant

- submitted study 15

, Lee et al

. 16 or Kenneke 17

. In an anecdo tal report, Walker et al

. 18 claimed that antimycin degrades by base hydrolysis and produced a diagram showing the mechanism of degradation along with assumed breakdown products. Hussain 19 made similar claims as to the degradation products. Thes e products are blastmycic acid, antimyc in lactone, and antimycic acid. Further degradation via hydrolysis yields antimycic acid, formic acid, aminosalicylic acid, and an amino acid (Hubert &

15 Heim D. 2003. Hydrolysis Determination for Antimycin A Complex. Project Number 47132. Unpublished study prepared by Analytical Bio

Chemistry Labs, Inc. 63 p. (MRID 460231

- 01)

. 16 Lee T.H., Derse, P.H., and Morton, S. 197 1

. Effects of Physical and Chemical Conditions on the Detoxification of Antimycin. Transactions of the American Fisheries Society 1971; 100: 13

– 17 17 Kenneke , J. 2006 Memo from John Kenneke to Thomas Steeger and “ Summary of Antimycin Hydrolysis Research by John F. Kenneke ” Appendix G of USEPA 2006

. 18 Walker C.R., R.E. Lennon, and B.L. Berger. 1964. Preliminary observations on the toxicity of antimycin A to fish and other aq uatic animals. U.S. Bureau of Sport Fisheries and Wildlife, Investigations in Fish Co ntrol No. 2 (Circular No. 186). 18 pp.
19 Hussain , A. 1969. 1969. Kinetics and mechanisms of hydrolysis of antimyc i n A in solution. Journal of Pharmaceutical Sciences 58: 316

- 320

.- Page 25 of 44

-

Schmidt, 2001). No quantitative information regarding the relativ e concentrations of the transformation products is available.

The only other registrant submitted environmental fate study is an aerobic aquatic transformation study which indicated that antimycin A degrades with a half

- life of 23

- 47 days in pH 6.5 wate r (MRID 45895901 ) . This half

- life is substantially longer than the expected half

- life due to hydroly sis alone at this pH, which adds some uncertainty to the half

- lives reported in this study as well as the hydrolysis studies

. However, since the aerobic aquatic study was conducted with sediment present, it is possible that the longer half

- life could be due to sorption of antimycin A to sediment in the still system, which may shield the compound from hydrolytic degradation.

Table 4

. Hydrolysis Rates for Antimycin A from Submitted Data and Published Literature.

Property Value Source Hydrolysis pH 3 9 hours Kenneke (2006) Hydrolysis pH 4 8.3 hours Kenneke (2006) Hydrolysis pH 5 10.5 hours Kenneke (2006) Hydrolysis pH 6 11 hours Kenneke (2006) Hydrolysis pH 7 7.1 hours Kenneke (2006) Hydrolysis pH 8 10 hours Kenneke (2006) Hydrolysis pH 9 3.4 hours Kenneke (2006) Hydrolysis pH 5 15 days MRID 46023101 Hydrolysis pH 7 3 days MRID 46023101 Hydrolysis pH 9 3 hours MRID 46023101 Hydrolysis pH 4.5

– 5.5 >7 hours Lee et al . (1971) Hydrolysis pH 7

– 8 5.5 hours Lee et al . (1971) Hydrolysis pH 8.5 40 minutes Lee et al . (1971) Hydrolysis pH 9.5 20 minutes Lee et al . (1971) Hydrolysis pH 10 6 minutes Lee et al . (1971) Hydrolysis pH 7.55(A1 only) 46 hours Hussain (1969) Hydrolysis pH 9 (A1 only) 2.2 hours Hussain (1969) Hydrolysis pH 10.1 (A1 only) 1 minute Hussain (1969)

3.2.1.3

. Field Studies

A quatic field dissipation data have not been submitted for antimycin A

.

3.2.1.4

. Bioaccumulation

Bioconcentration in fish data have not been submitted

. Based on BCF estimates using EPI Suite

, the chemical has a relatively low potential for bioconcentrating in aquatic organisms (estimated BCF = 270

- 350X)

. However, as antimycin A is us ed as a pisicide, such data would be of limited

use.

3.2.1.5. Transformation Products

Submitted studies did not characterize transformation products, although published literature has tentatively identified hydrolysis products. These products are blastmy cic acid, antimycin lactone, and antimycic acid ( Hussain, 1969; Walker et al ., 1964; Lee et al . 1971)

. Blastmycic acid further- Page 26 of 44

-

hydrolyses to antimycic acid and formic acid; the antimycic acid may further hydrol ize to aminosalicylic acid, a relative of aspi rin, and an amino acid (Hubert & Schmidt, 2001). No quantitative information regarding the relative concentrations of the transformation products is available. However, antimycin A must be deactivated following use with a high oxidizing compound (potassi um permanganate). The byproducts of permanganate treatment are highly insoluble manganese oxides ( Ott ). The exact nature and extent of these deactivation products is uncertain; however, fish bioassays downstream of permanganate deactivation stations indic ate that remaining antimy c in A residues are not at levels sufficient to result in adverse effects to the fish used in the assays.

3.2.2

. Measures of Aquatic Exposure

3.2.2. 1. Estimated Environmental Concentrations in Surface

Water

Standard exposure modeling was not conducted for antimycin A

. The registered uses of antimycin A as a piscicide require the direct application of the compound to water to maintain specific water concentrations for defined durations of time

. Therefore, aquatic exposure value s are specific to meet the management objective of the treatment

. When antimycin is applied to a water body

, the most conservative acute concentration that could be used for ecological aquatic exposure assessment is the treatment concentration

. Thus,

s c reening

- level acute E E Cs of antimycin A (parent only) in surface water are the maximum labeled use or target rate of 25 μg/L (parts per billion; ppb ) as stated on the label and in the document (incorporated by reference) “ Standard Operating Procedures for the Use of Fintrol ® (Antimycin A) for Restoration of Native Fish Populations ” ( USDOI , 2012)

.

3.2.2. 2

. Monitoring Data

No monitoring data are available for antimycin A

. EFED conducted a search (April 2015) of the United States Geological Services (USGS) National Water Quality Assessment (NAWQA) Program database ( http://cida.usgs.gov/nawqa_queries_public/ ) and the California Department of Pesticide Regulation (CDPR) surface water and sediment data base ( http://cdpr.ca.gov/docs/emon/surfwtr/surfcont.htm )

. For use in fishery restoration efforts, m onitoring for antimycin A within the treatment area is typically conducted via bioassay, i.e ., caged live fish , typically using the species targeted by the
treatment

.

3.2.3. Measures of Terrestrial Exposure

Exposure of t errestrial plants and wildlife to a ntimycin A is not estimated in this assessment because the chemical is applied directl y to aquatic systems and is not expected to move to terrestrial environments

. Although not considered a major exposure pathway, potential exposure of terrestrial animals to antimycin by ingestiong of prey (fish) containing residues of the compound is con sidered in the risk description section of the document- Page 27 of 44

-

3.3

. Ecological Effects Characterization

The ecological effects characterization for a ntimycin A is primarily based up on f ederal laboratory data for the TGAI and for specified formulations

. The large majority of available toxicity data for a ntimycin A are for aquatic animals ( i.e. , fish and aquatic invertebrates)

. Additional data were submitted by the registrant and represented a compendium of unpublished studies 20 ; however, information on t he toxicity of antimycin A contained in many of these additional submissions was not of sufficient quality to use quantitatively in this ecological risk
assessment.

Acute toxicity data are available for 16 species of fish ( Table 5 ) , including 15 freshwate r species and one estuarine/marine species . All of the studies are classified as supplemental since they were not conducted according to current standards; however, these data are considered of sufficient quality for use in risk assessment . Studies were c onducted with either technic al grade (>95% a ntimycin A ) or with formulations containing either 1% or 10% a ctive ingredient (a.i.)

. The freshwater p addlefish ( Polyodon spathula ) is the most sensitive (LC 50 =0.001 μ g/L) species tested. Although the paddlefis h is the most sensitive species

, the raw data used to support this endpoint could not be evaluated ; therefore

, this value cannot be used to quantitatively assess risk. The most sensitive species for which raw data could be reviewed is coho salmon ( Oncorhynchus kisutch ); therefore, the freshwater fish acute toxicity endpoint (96

- hr LC 50 ) is 0.009 μ g/L. Based on the sensitivity of freshwater fish to antimycin, the chemical is classified as very highly toxic to fish on an acute exposure basis.

Based o n the available data, f ish in the family Ictaluridae (catfish), like black bullhead ( Ictalurus melas ) and channel catfish ( Ictalurus punctatus ), are the least sensitive species tested

, which accounts for how antimycin A can be used to selectively remove sc aled fish from catfish aquaculture ponds. Although paddlefish (sometimes referred to as a spoonbill catfish) do not have a pronounced number of scales and yet are the most sensitive species to antimycin, this phylogenic ally primitive fish species is not re lated to the catfish but is instead distantly related to sturgeon and similar to the sturgeon has a limited amount of scales

. Toxicity testing of formulated product (1 to 10% active ingredient) indicates that formulated products of antimycin A are less to xic than the technical grade active ingredient; the 96

- hr LC 50 , for bluegill sunfish ( Lepomis macrochirus ) is 1.18 μ g/L for the formulated product ( Table 5 ) ; whereas the technical grade active ingredient has a 96

- hr LC 50 of 0.034 μ g/L. Similarly, rainbow
trout ( Oncorhynchus mykiss ) ha s LC 50 values ranging from 0. 0 63 to 0. 185 μ g/L for formulated product while technical grade antimycin ha s an LC 50 averaging 0.01 1 μg/ L.

No chronic toxicity data are available on antimycin A for freshwater fish

. A search of th e open literature did not identify any additional data on the chronic toxicity of antimycin A to fish.

Although an acute toxicity test measuring effects of technical grade antimycin A to waterfleas ( D. magna ) was submitted (MRID 400980

- 01), the study fail ed to establish a definitive EC 50

20 Ayerst Laboratories. 1964. Efficacy of Antimycin. (Compilation: unpublished study received in 1994 under 8991

- 5l CDL: 005666

- A (Accession No. l 00135924))- Page 28 of 44

-

value ( Table 5 ) since greater than 50% mortality was observed in all of the treatment groups

. However, a 96

- hr EC 50 value is available for the scud, Gammarus fasciatus (EC 50 =0.008 μg/L)

. Based on the sensitivity of Gammarus to antimycin A, the compound is classified as very highly toxic to freshwater invertebrates on an acute exposure basis.

A search of the open literature did not identify other studies that would provide additional information concerning the acute toxicity of freshwater invertebrates exposed to antimycin A.

No chronic toxicity data on antimycin A are available for freshwater invertebrates

. A search of the open literature did not identify other studies that would provide additional information

conc erning the chronic toxicity of antimycin A to freshwater invertebrates.

A single estuarine/marine fish acute toxicity study of technical grade antimycin A with the spot ( Leiostomus xanthurus ) resulted in a 48

- hr LC 50 of 0.23 μg/L; therefore, antimycin A i s classified as very highly toxic to estuarine/marine fish on an acute exposure basis

. No chronic estuarine/marine fish toxicity data were submitted and no useable data were located in the open literature for antimycin A; therefore, chronic risks associa ted with estuarine/marine fish exposure to antimycin A are unknown

. Antimycin A is very high ly toxic to estuarine/marine invertebrates on an acute exposure basis with a 96

- hr LC 50 =24 μg/L for pink shrimp ( Panaeus duorarum ; Table 5 )

. Acute toxicity data were also available on the Eastern oyster, Crassostrea virginica

, showing that antimycin is very highly toxic (LC 50 =62 μg/L ) to mollusks as well.

No chronic estuarine/marine invertebrate toxicity data were submitted and no useable data were located in the open literature for antim ycin A; therefore, chronic toxicity associated with estuarine/marine inverteb rate exposure to antimycin A is un certain

. No data are available to assess the toxicity of antimycin A to vascular or nonvascular aq uatic plants or to sediment

- dwelling (benthic) invertebrates

.

Table 5

. Aquatic Animal Acute and Chronic Toxicity Estimates for Antimycin A.

Taxonomic Group Surrogate

Species Type of

Risk Type of

Endpoint (% ai) Endpoint MRID Acute Toxicity Classification
Aquatic

Freshwater Fish Bluegill Sunfish

Lepomis macrochirus Acute 96

- hr LC 50 (95.5%) 0.034 μg a

. i

. /L 40098001 Very Highly Toxic (Supplemental) 96

- hr LC 50 (10%) 1.18 μg a.i. /L TN901 006314 Very Highly Toxic

(Supplemental) 48

- hr LC 50 (1%) 29.5 μg a.i. /L TN1533 Highly Toxic (Supplemental) 48

- hr LC 50 (1%) 29.5 μg a.i. /L TN153 Very Highly Toxic (Supplemental) Green Sunfish Lepomis cyanellus Acute 96

- hr LC 50 (95.5%) 0.22 μg a.i. /L 40098001 Highly Toxic (Supplemental)- Page 29 of 44

-

Taxonomic Group Surrogate

Species Type of

Risk Type of

Endpoint (% ai) Endpoint MRID Acute Toxicity Classification

Rainbow Trout ( Oncorhynchus mykiss ) Acute 96

- hr LC 50 (95.5%) 0.012 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)

Acute 96

- hr LC 50

(95.5%) 0.010 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)

Acute 96

- hr LC 50

(10%) 0.185 μg a.i. /L TN944 006314 Very Highly Toxic

(Supplemental)

Acute 48

- hr LC 50

(1%) 0.063 μg a.i. /L TN35 Very Highly Toxic (Supplemental) Cutthroat Trout Oncorhynchus clarki Acute 96

- hr LC 50 (95.5%) 0.057 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)

Coho Salmon Oncorhynchus kisutch Acute 96

- hr LC 50 (95.5%) 0.009 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)

Lake Trout Salvelinus namaycush \ h Acute 96

- hr LC 50 (95.5%) 0.053 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)

Goldfish (Carassius auratus) Acute 96

- hr LC 50 (95.5%) 0.180 μg a.i. /L 40098001 Highly Toxic (Supplemental)

Fathead Minnow (Pimephales promelas) Acute 96

- hr LC 50 (95.5%) 0.025 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)

Black Bullhead Ictalurus melas Acute 96

- hr LC 50 (95.5%) 4.8 μg a.i. /L 40098001 Highly Toxic (Supplemental) Channel Catfish Ictalurus punctatus Acute 96

- hr LC 50 (95.5%) 1.36 μg a.i. /L 40098001 Highly Toxic (Supplemental)
Mosquitofish Gambusia affinis Acute 96

- hr LC 50 (95.5%) 0.19 μg a.i. /L 40098001 Highly Toxic (Supplemental)
Largemouth Bass Micropterus salmoides Acute 96

- hr LC 50 (95.5%) 0.24 μg a.i. /L 40098001 Highly Toxic (Supplemental)

Yellow Perch Perca Flavescens Acute 96

- hr LC 50 (95.5%) 0.04 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)

White Crappie Pomoxis annularis Acute 96

- hr LC 50 (95.5%) 0.34 μg a.i. /L 40098001 Highly Toxic (Supplemental)

Paddlefish Polyodon spathula Acute 96

- hr LC 50 (95.5%) 0.001 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)

Estuarine/ Marine Fish Spot

Leistomus xanthurus Acute 48

- hr LC 50 (95.5%) 0.23 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)

Freshwater Invertebrates Water Flea

Daphnia magna Acute 48

- hr EC 50 (95.5%) <10 μg a.i. /L 40098001 Very Highly Toxic (Supplemental) Scud Gammarus Acute 96

- hr EC 50 (95.5%) 0.008 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)- Page 3 0 of 44

-

Taxonomic Group Surrogate

Species Type of

Risk Type of

Endpoint (% ai) Endpoint MRID Acute Toxicity Classification
fasciatus Isopod Asellus brevicaudus Acute EC 50 (95.5%) >1.0 μg a.i. /L 40098001 Very Highly Toxic (Supplemental)

Estuarine/ Marine Invertebrates Pink Shrimp

Panaeus duorarum Acute 96

- hr EC 50 (95.5%) 24 μg a.i. /L 40228401 Very Highly Toxic (Supplemental)

Blue Crab Callinectes sapidus Acute 48

- hr LC 50 (95.5%) >100 μg a.i. /L 40228401 Very Highly Toxic (Supplemental)
Eastern Oyster Crassostrea virginica Acute LC 50 (95.5%) 62 μg a.i. /L 40228401 Very Highly Toxic (Supplemental)

No avian toxicity data are available for technical grade antimycin

. However, based on acute oral (14

- day) toxicity studies using formulated product of unspe cified strength (MRID 135924),

a ntimycin is classified as very highly toxic to water fowl (mallard duck LD 50 =2.9 mg/kg bw) and highly toxic to upland game birds ( b obwhite quail LD 50 =39 mg/kg bw; Table 6 )

. No data are available to evaluate the subacute dietary t oxicity of antimycin A to birds nor are data avail able to evaluate the chronic toxicity of antimycin A to birds.

No acute oral rat t oxicity data are available on technical grade antimcyin A; however, the acute oral LD 50 for Fintrol ® Concentrate (20% solution) is 286 mg/kg for male and 361 mg/kg for femal e rats 21 (MRID 455279

- 01). Based on these data, the formulated endproduct is classified as moderately toxic to mammals on an acute oral exposure basis

. No chronic toxicity data are available for mammals.

No data are available to assess the toxicity of anti mycin A to terrestrial invertebrates

. EPA has identified a process for evaluating the risk of pesticides to bees ( Apis mellifera ) that relies on a suite of laboratory

- based studies examining the acute and chronic toxicity of pesticides to individual adult and larval bees

. Depending on the outcome of the laboratory

- based studies and risk estimates, higher

- tier studies of bee colonies may be required

. This risk assessment process and the need for effects data on bees are dependent on whether exposure to bees from the use of the compound is considered likely

. Given that antimycin is applied directly to water and is typically used in high altitude lakes and high gradient streams, the likelihood of exposure for bees is considered low

.

Table 6

. Terrestrial Animal Acute Toxicity Estimates for Antimycin A.

Taxonomic Group Surrogate

Species Type of

Risk Type of

Endpoint (% a

. i

. ) Endpoint MRID Acute Toxicity Classification

Terrestrial

21 Kuhn, J.O. 2001. Fintrol ® Concentrate (Antimycin) Final Report Acute Oral Toxicity in Rats. Stillmeadow, Inc. Report No. 6025

- 00. Submitted to Aquabiotics Cor poration, Bainbridge Island, WA. (MRID 455279

- 01).- Page 31 of 44

-

Taxonomic Group Surrogate

Species Type of

Risk Type of

Endpoint (% a

. i

. ) Endpoint MRID Acute Toxicity Classification

Birds Mallard duck

Anas platyrhynchos Acute

Oral 14

- day LD 50

(Not Reported) 2.9 mg/kg 135924 Very Highly Toxic (Supplemental) Bobwhite quail Colinus virginianus Acute

Oral 14

- day LD 50

(Not Reported) 39 mg/kg 135924 Highly Toxic (Supplemental)

Mammals Rat Acute Oral LD 50

(20%) 1 286 mg/kg

(male) 361 mg/kg (female) 45527901 Highly Toxic (Supplemental)

3.3.3. Review of Incident Data

The Ecological Incident Information System (EIIS) is an internal OPP database that houses ecological incidents that have been reported to the Agency

. When available, EIIS includes date and location of an incident, type and magnitude of effects observed in various species, use(s) of pesticides known or suspected of contributing to the incident, and results of any chemical residue analysis or other analyses conducted during incident investigat ion

. EIIS incidents are categorized according to the certainty that the incident resulted from pesticide exposure

. A search of the EIIS for ecological incidents run on February 10, 2015, identified no incident reports for antimycin A

. However, i ncidents may have occurred due to antimycin A exposures but may not have been reported due to various factors, including lack of reporting or a lack of o bservation of effects. Although the lack of incident reports does not necessarily indicate the absence of incidents , the restricted use of the compound c oupled with its detailed SOPs is expected to l imit the extent of unintended exposure

. No plant or wildlife incidents have been reported through OPP’s aggregate incident report database and no avian incide nts have been captured in the Avian Incident Monitoring System (AIMS; American Bird Conservancy 20 13 ) 22 as of February 10, 2015

. The AIMS database contains publicly available reports on pesticide

- related avian incidents through 2005.

22 Available at: http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/index.cfm- Page 32 of 44

-

4

. Risk Characterizati on

4.1. Screening

- Level Risk Quotient (RQ) Values

This screening

- level ass essment of the labeled use s of antimycin A relies on the deterministic RQ method to provide a metric of potential risks

. The RQ provides a comparison of exposure estimates to toxicity endpoints ( i.e. , estimated exposure s divided by acute and /or chronic toxicity endpoint s expressed in the same units as exposures , respectively )

. The resulting unitless RQ values are compared to the Agency’s Levels of Concern ( LOCs ) , as shown in Ta ble 3

. EPA uses LOCs to indicate when the use of a pesticide, as directed by the label, has the potential to cause adverse effects to nontarget organisms

. In this approach , RQ s that exceed non

- listed species LOC s necessarily also exceed the corresponding l isted species LOC s

. A discussion of the RQ values for antimycin A and of other information that provides context for the interpretation of potential risk to various taxa is presented in the Risk Description in Section 4.2

.

4.1.1. RQ Values for Aquatic Organisms

At the maximum treatment concentration of 25 μg/L, the acute estimated environmental concentration (EEC) of antimycin is expected to be equivalent to the treatment rate

. At this exposure concentration, RQ values (RQ=EEC/LC 50 ) for freshwater fish and invertebrates are 2,778 and 3,125

, respectively

. The a cut e risk to non

- listed species levels of concern (RQ≥0.5) for fish and invertebrates are exceeded by factors of 5,556 and 6,250X for fish and invertebrates, respectively ( Table 7 )

. Even if RQ val ues were based on the least sensitive fish, i.e ., black bullhead 96

- hr LC 50 =4.8 μg/L, the RQ (5.6) would exceed the acute high risk LOC by a factor of 11X

. Additionally, at the lower treatment concentration (5 μg/L) 23 recommended to remove scaled fish from aquaculture ponds, the RQ is 1.04 and exceed s the acute risk to non

- listed species LOC.

Table 7

. Acute risk quotients for freshwater fish and invertebrates based on a targeted antimycin A treatment rate of 25 μg/L.

Species Estimated Exposure Concentration (μg/L) Toxicity

LC 50 (μg/L) Acute RQ Value

Coho Salmon ( Oncorhynchus kisutch ) 25 0.009 2,778 a

Scud ( Gammarus fasciatus ) 25 0.008 3

, 125 a

a Exceeds acute risk (RQ≥0.5), restricted use (RQ≥0.1), and endangered species (RQ≥0.05) levels of concern.
No acceptable toxicity data are available with which to evaluate the chronic risk to aquatic animals associated with the use of antimycin; however, given that the treatment concentrations at intended to result in 100% morgality of the target fish species and exceed acute median lethal concentrations by several orders of magnitude of both fish and invertebrates , it is reasonable to believe that most fish and aquatic invertebrates will be killed at the maximu m treatment

23 Avery, J.L. 2006. Use of Fintrol ® to remove scaled fish in catfish ponds. The Catfish Journal. April 2006- Page 33 of 44

-

concentrations and durations of antimycin A

. In situations where antimycin is applied to flowing water, it is deactivated with a strong oxidizing agent

, potassium permanganate

. The co mbination of advective removal , dilution with untreated water and deactivation with potassium permanganate makes chronic exposure to antimycin at toxic levels unlikely

. While the efficacy of deactivation is an uncertainty, fish bioassays positioned downst ream of the K M nO 4 release stations indicate that antimycin is no longer at levels that result in acute toxicity to the fish used in the bioassay. Additionally, the acute toxicity of antimycin makes it likely that few biological receptors w ill be present to exhibit effects of chronic exposure

. However, if/when treated water is not deactivated using permanganate nor substantially diluted by untreated water ( e.g ., in lentic environments such as high alpine lakes) , the potential for chronic risks is uncertain.

At the maximum application rate, the acute RQ value s for estuarine/marine fish and invertebrates are 109 and 1.0, respectively ( Table 8 )

. Both fish and invertebrate RQ values exceed the acute risk to non listed species LOC by factors of 218X and 2X, respec tively

. Although the toxicity value for estuarine/marine mollusks (62 μg/L) is higher ( less sensitive ) than that of pink shrimp, the RQ value for mollusks (RQ=0.40) exceeds the acute risk to listed species LOC (RQ≥0 .05 ).

Table 8

. Acute risk quotients for estuarine/marine fish and invertebrates based on a targeted antimycin A treatment rate of 25 μg/L.

Species Estimated Exposure Concentration (μg/L) Toxicity

LC 50 (μg/L) Acute RQ Value

Spot ( Leiostomus xanthurus ) 25 0.23 109 a
Pink Shrimp (Panaeus duorarum) 25 24 1.0 a

a Exceeds ac ute risk to non

- listed species LOC (RQ≥0.5) and acute risk to listed species LOC (RQ≥0.05).

4.1.2. RQ Values for Terrestrial Organisms

The use of antimycin A to achieve fishery management objectives, i.e
, where in the compound is applied directly to water, is not likely to repres ent a route of exposure to birds via consumption of antimycin A residues on terrestrial forage items since the compound is applied directly to
water

. Therefore, RQ values are not calcu lated for terrestrial organisms; however, the risk discussion se c tion provide s a brief analysis of potential secondary risks to birds and mammals from the consumption of prey items containing antimycin A.

4. 2

. Risk Description

Antimycin A (Fintrol ® ) is applied directly to water and is maintained at a targeted treatment concentration f

or periods of time specified in the SOP to achieve 100% mortality for the targeted species

. Based on available data, t he primary route of degradation appears to be base hydr olysis

, where under alkaline conditions

, the compound can degrade with half

- lives of roughly 30 minutes

. While t here are no direct measurements of antimycin A sorption

, indirect evidence suggests that a ntimycin A will sorb to sediments and may reduce poten tial exposure outside of- Page 34 of 44

-

the immediate treatment area

. The extent to which non

- target organisms will be exposed is also mitigated by the fact that where the compound is applied to flowing water, antimycin A is intentionally detoxified through the use of a strong oxidizing agent

, potassium permanganate

. Where the compound is used to remove scaled fish from aquaculture facilities, such facilities hold water for many months because of the expense of replacing water and the potential to lose fish in the process . Therefore, the compound is likely to degrade during the protracted holding periods and

, based on the fact that fingerling catfish are stocked in the ponds after antimycin treatment, there is no indication that antimycin A residues are at levels which ad verse ly affect the catfish

.

4. 2 .1. Risks to Aquatic Organisms

4. 2 .1.1. Freshwater Fish , Amphibians, and Invertebrates

Antimycin A is applied directly to water and as a piscicide

, it is intended to kill fish

. Antimycin’s high toxicity to fish accounts for the low treatment concentrations (typically 25 μg/L or less) needed to kill fish

. With fish LC 50 values as low as 1 nanogram (n) per liter (part per trillion (ppt r )) and treatment rates 25 hundred times higher than this LC 50 value, the direct applicat ion of antimycin to flowing and static water to eliminate undesirable fish species is likely to kill many of the fish species present

. Since fish serve as surrogates for aquatic phase amphibians, risk is presumed for aquatic

- phase amphibians as well.

Anti mycin’s use in aquaculture to remove scaled fish from catfish production ponds does not typically involve subsequent deactivation with potassium permanganate; rather, the antimycin is allowed to degrade naturally in the production pond water

. F ingerling ca tfish would not be harvested as food fish for roughly 1

– 1.5 years post

- treatment

. Since the intent of these treatments is to remove scaled fish and since fingerlings are introduced after treatment, there have been no adverse effects repo r ted on the finge rling catfish as a result of this treatment.

The available laboratory data indicate that freshwater invertebrates have roughly similar sensitivities as fish to antimycin A on an acute exposure basis

, and many of these species may die at treatment concentrations of 25 μg/L

. Although there are anecdotal reports 24 suggesting that plants and invertebrates are relatively unaffected by antimycin treatments, no laboratory data have been reviewed by EPA that can substantiate these claims

. To the extent that application rates are less than 25 μg/L and less sensitive animals are in the treatment areas, aquatic invertebrate mortality could be substantially reduced. Although invertebrates are less conspicuous members of the aquatic communit y, they are a major component of aquatic ecosystems and food webs

. Any significant effects on invertebrates would most likely influence other components of the ecosystem

. Effects may not be limited to merely a change in total biomass as a result of widespr ead mortality but any changes associated with differential sensitivity could bring about significant changes in the community structure, which could alter system function.

24 Wisconsin Alumni Research Foundation. 1965. Antimycin as a Fish Toxicant: a resume of information and data pertaining to t he use of antimycin in fish management procedure s in ponds and lakes. (Accession No. 00135924)- Page 35 of 44

-

Estuarine/marine invertebrate data on Eastern oysters indicate that they are less s ensitive to antimycin than other invertebrates

, although risk quotients based on mollusk toxicity data exceed the acu te risk to listed species levels of concern.

In addition to acute risks, there is a potential for chronic effects to freshw ater invertebra tes when antimycin is applied directly to water . T he limited data on freshwater invertebrates suggest that
t hey are as sensitive to antimycin as fish, and it is possible that many inv ertebrates will not survive antimycin treatment concentrations in the tar geted area at the typical application rate; therefore, chronic effects will be limited by a lack of receptors

. Additionally, at the maximum recommended treatment rate, a single application of antimycin directly to water is intended to kill all fish in the treated area; therefore, it is unlikely that repeated applications of antimycin will occur withi n the same year

. Also, hydrolysis data indicate that antimycin degrades rapidly in the environment, parti cularly at warmer temperatures in alkaline waters and can be deactivated with potassium permanganate to prevent its movement to non

- target areas , thus further reducing the likelihood of chronic exposure.

Based on the available information it is reasonable to believe that one component of the initial risk hypothesis discussed in the problem formulation cannot be rejected, i.e ., t he use of antimycin A in accordance with the label will likely result in adverse effe cts, such as acute mortality, to aquatic anim als when the chemical is used at maximum target concentration of 25 μg/L

. The e xtent of mortality to nontarget organisms is uncertain; field studies suggest that while aquatic invertebrate populations are immediately affected in terms of decreased numbers, invertebrate communities can recover to pretreatment levels in terms of both abundance and diversity within several months 25 . Monitoring conducted by the National Park Service in the Great Smoky Mountains National Park during efforts to remove non

- native rainbow trout and to restore a viable population of native brook trout ( Salvelinus fontinalis ) indicated that negative effects to the macroinvertebrate community in streams ranging between 1

– 4 th order treated with Fintrol ® at 8 μg/L for 8 consecutive hrs were short

- lived and the invertebrate community recovered within two months post

- treatment

. 26 The monitoring data indicated that there was greater abundance and species richness after treatment amo ng the major stream

- dwellin g benthic marcroinvvertebrate orders. The rapid recolonization of treatment areas by invertebrates (via upstream drift/immigration) from untreated areas was attributed to the the initial abse nce of fish ( i.e ., reduced predation on invertebrates) which in turn facilitated the restocking of insectivorous native brook trout shortly thereafter. 27 While the initial risk hypothesis included potential risk to terrestrial animals feeding on dead or dying fish or through the ingestion of antimycin

- treated water, th e likelihood of adverse effects on these taxa is considered low based on available data ; further analysis of this is provided in the risk description

.

25 Moore, S.E., M.A. Kulp, J. Hammonds, and B. Rosenlund. 2005. Restoration of Sams Creek and an Assessment of Brook Trout Res toration Methods, Great Smoky Mountain National Park. National Park Service, U. S. Department of the Interior. Technical Report NPS/NRWRD/NRTR

- 2005.
26 Gibbs, W. K. 2013 . Effects of Fintrol (Antimycin A) Application on Benthic macroinvertebrate communities in the Lynn Camp Prong Watershed, Great Smokey Mountains National Park. Dissertatiaon Presented to the Faculty of the Graduat e School Tennessee Technological University in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Environmental Science

. May 2013.
27 Ibid Gibbs, W. K. 2013.- Page 36 of 44

- 4. 2 .2. Risks to Terrestrial Organisms

4. 2 .2.1. Birds , Reptiles, and Terrestrial

- phase Amphibians

No RQ values were calculated for birds since antimycin is applied directly to water and the likelihood of residues on terrestrial animal forage items on land is considered low; however, on the chance that birds forage on dead or dying fish, it is possible to estimate the potential amount of antimycin A in their diet

. For example, the weight of food ingested (FI) by a great blue heron Ardea herodias (body weight=2.576 kg) is given by taking the antilog of the value estimate using formula ( EQ1 ) recommended by the Wildlife Exposure Factors Handbook 28

.

Log 10 (FI) = 0.966 log 10 (body weight in grams)

– 0.640 (EQ 1)

Based on this relationship, a blue heron will consume 452 g of fish per day

. Piscivorous birds are likely to consume small to medium

- sized fish and therefore rainbow trout are used as a surrogate

. Fish tissue residue data for fish killed with antimycin indicate that rainbo w trout contained as much as 172 μg antimycin/ k g 29

. Therefore, a heron eating 0.45 kg would consume 77 μg (0.45 kg/day x 172 μg/kg) of antimycin.

Extrapolations from one bird to another need to consider differences in the scaling of toxicity for differences in body weight. The LD 50 can be adjusted for body weight based on the formula ( EQ 2 ) recommended by Mineau et

. A l 30 :
Adjusted LD 50 = LD 50 (AW/TW) (a

- 1) (EQ 2)

W here adjusted LD 50 is the median 50% lethal dose for the species being assessed, LD 50 is the median lethal dose in the test organism, AW is the body weight of the assessed organism, TW is the body weight for the test organ ism, and a is the slope of the regression line for estimating the assessed species LD 50 from the test species LD 50 (EFED default value of 1.15). In the case of assessing a blue heron, 2576 g is a suitable value (adult bird) for AW

. The test organism is a

m allard duck

, which weighs about 1230 g

. With a test LD 50 of 2.9 mg kg - 1 , the adjusted LD 50 is 3.2 mg kg - 1

. The actual dose is then the LD 50 times the weight of the heron (2.576 kg) which equals 8.246 mg

. Therefore, the amount of antimycin potentially consumed by herons is several orders of magnitude less than the acute median lethal dose; the dose

- based RQ value is less than 0.01 and is below acute risk levels of concern for non

- listed and listed species ( Table 9 ).

Based on the Wildlife Exposure Factors Handbook 31 the mean food ingestion rate for a bald eagle ( Haliaeetus leucocephalus ) is 0.12 kg/kg bw day. A bald eagle weighing 5 .089 kg 32 would

28 ORD 1993. Wildlife Exposure Factors Handbook. Office of Health a nd Environmental Assessment, Office of Research and Development. EPA/600/R

- 93/187. http://www.epa.gov/ncea/pdfs/birds.pdf
29 Ritter, P.O. and F.M. Strong. 1966. Residues in tissues of fish killed by antimycin. Journal of Agricultural Food Chemistry 14(4): 403

– 407 (MRID 461534

- 01) 30 Mineau, P

. , B.T. Collins, and A. Baril

. 1996. On the use of scaling factors to improve interspecies extrapolation of acute toxicity in birds. Regulatory Toxicology and Pharmacology. 24: 24

- 29. 31 Ibid ORD 1993.

32 According to the USFWS, male and female bald eagles can weigh as much as 14 (6.4 kg) and 10 lbs (4.5 kg), respectively.- Page 37 of 44

-

consume 610 g of fish per day representing a po tential antimyc in exposure of 105 μg (0.610 kg/day x 172 μg/kg)

. The adjusted LD 50 for bald eagles is 3.6 mg kg - 1 and the equivalent dose for a 5.089

- kg bird is 18.32 mg ; therefore, the dose

- based RQ value is less than acute risk LOCs ( Table 9 ).

Similarly, the mean for food ingestion rate for a belted kingfisher ( Ceryle alcyon ) is 0.11 g/g

day 33

. Based on this rate, an adult kingfisher weighing 148 g would consume 16 g of fish per day representing a potential antimycin exposure of 2.8 μg (0.016 kg/day x 172 μg/kg)

. The adjusted LD 50 for kingfishers is 2.1 mg kg - 1 and once again, the estimated exposure is well below the effects threshold.

Table 9

. Acute dose

- based risk quotients for piscivorous birds based on potential residues in dead or dying fish.
Species Estimated Daily Dose (μg) Adjusted LD 50 (μg) Acute RQ Value

Blue Heron ( Ardea Herodias) 77 8246 <0.01
Bald Eagle (Haliaeetus leucocephalus) 105 18,320 <0.01
Belted Kingfisher ( Ceryle alcyon ) 2.8 311 <0.01

Only acute oral toxicity data are available for birds and these indicate that antimcyin is highly to very highly toxic to birds on an acute exposure basis

. Risk quotients calculated using the dose

based acute toxicity values resulted in values below acute risk LOCs

. The dose

- based approach considers the uptake and absorption kinetics of a gavage toxicity study to approximate exposure associated with uptake from a dietary matrix

. Toxic response is a function of duration and intensity of exposure

. For many co mpounds, a gavage dose represents a very short

- term, high intensity exposure

. Although the dose

- based estimates may not reflect reality in that animals do not receive a bolus dose while feeding, it is possible that a short

- duration, high

- intensity exposure could occur associated with feeding alongside treated surface waters since many birds may gorge themselve s when food items are available; this would be particular true as birds

o pportunistically feed on dead and dying fish

.

No chronic avian toxicity data were submitted or located in the open literature for antimycin; therefore, chronic risks associated with avian exposure to antimycin are unknown

. However, the likelihood of chronic exposure is considered low since dead fish would soon sink to the bottom of treated water

. While exposure is possible through ingestion of antimycin A residues in drinking water during treatments when water is maintained at a specific concentration for specified duration , the likelihood of acute risk is c onsidered low given the results of the initial screen using the S creening I mbibition P rogram tool

.

http://www.fws.gov/midwest/eagle/recovery/biologue.html 33 Ibid ORD 1993- Page 38 of 44

- 4. 2 .2.2. Mammals

Similarly, the use of antimycin A as a piscicide is not likely to represent a means of exposure to wild mammals via consumption of antimycin residues on terrestrial forage items (plants, seeds, insects) since the compound is applied directly to water

. Based on the chance that different ly

sized mammals forage on dead or dying fish, it is possible to estimate the potential amount of antimycin in their diet

. Using daily food intake as estimated by Nagy 34 ( EQ3 ), a 350 g mammal will consume about 68 g of food based on the allometric equation:

F=0.621*BW 0.564 /(1

- W) (EQ3)

where F is the daily food intake in grams of fresh weight, BW is the body mass of the organism in grams, and W is the mass fraction of water in the food. For this assessment W is assumed to be 0.75 35

. Piscivorous mammals are not confined to eating small fis h and may feed opportunistically on any sized fish that may succumb to antimycin; therefore, common carp ( Cyprinus carpio ) are used as surrogates

. Based on the data on antimycin tissue residues in common carp with a body weight of 99 grams, a small mammal would only consume 68% (68/99) of the total carp body mass

. According to the data for common carp, maximum total body residues of antimycin in carp tissue amounted to 261 μg/kg 36

. A 350

- g mammal consuming 68 grams represents an equivalent dose of 18 mg of a ntimycin; this value is below the median lethal dose of antimycin (286 mg/kg*0.350 kg=100 mg) for similarly sized mammals.

Similar to birds, extrapolations from one size of mammal to another must consider differences in the scaling of toxicity for differ ence in body weight

. The LD 50 can be adjusted for body weight based on the formula recommended by Mineau et al. 37 ( EQ4 ):

Adjusted LD 50 = LD 50 (TW/AW) (0.25) (EQ4)

where adjusted LD 50 is the median 50% lethal dose for the species being assessed, LD 50 i s the median lethal dose in the test organism, AW is the body weight of the assessed organism and TW is the body weight for the test organism. Since we are assessing a large mammal, 1000 g is a suitable value for AW

. The test organism is a rat weighing abo ut 350 g

. With a test LD 50 of 286 mg/kg, the adjusted LD 50 is 220 mg/kg

. Using the daily intake equation, a 1000

- g mammal will consume about 122 g of food

. If the animal fed exclusively on carp killed by antimycin, the equivalent dose would be 0.122 kg *26 1 μg/kg or 32 μg of antimycin

. Once again, this value is well below the estimated median lethal equivalent dose adjusted for body weight (220 mg/kg * 1 kg=220 mg) and the RQ value is less than 0.01 ( Table 1 0 )

. Therefore, even if fish are available for consumption by mammals scavenging along the shoreline for dead or dying fish, it is not likely that the mammals would consume sufficient quantities of antimycin to result in acute toxicity.

34 Nagy, K.A. 1987. Field metabolic rate and food requirement scaling in mammals and birds. Ecological Monographs 57: 111

- 128. 35 Ibid Nagy 1987. 36 Ibid Ritter and Strong. 1966.
37 Ibid Mineau et al. 1996

.- Page 39 of 44

-

Table 10

. Acute dose

- based risk quotients for piscivorous mammal s based on potential residues in dead or dying fish.
Species Estimated Daily Dose (μg) Adjusted LD50 (μg) Acute RQ Value
Large Mammal (1000 g) 8.9 220,000 <0.01

4. 2 .2.3. Terrestrial Invertebrates

RQs for terrestrial invertebrates were not calculated as no toxicity data are available

. Given that antimycin A is applied directly to water and is typically used in high altitude lakes and high gradient streams, the likelihood of exposure to terrestrial invertebrates such as pollinator insects is considered low.

4. 2 .2.4. Terrestrial Plants

No toxicity data are availale for terrestrial plants; however, given that antimycin A is applied direct ly to water, the likelihood of exposure to terrestrial plants is considered low

.

5. Endocrine Disruptor Screening Program (EDSP)

Antimycin A was not included in the first group of chemicals for which orders to conduct Tier 1 EDSP testing were issued

. For additional information the EDSP program, visit http://www.epa.gov/endo/

.

6

. Federally Threatened and Endangered (Listed) Species of Concern

In November 2013, the EPA, along with the U.S. Fish & Wildlife Service (USFWS), the National Marine Fisheries Service (NMFS) (collectively, the Services) , and the U.S. D epartment of Agric ulture (USDA) released a summary of their joint Interim Approaches for assessing risks to listed species from pesticides

. The Interim Approaches were developed jointly by the a g encies in response to the N ational A cademy of S ciences’ (NAS) recommendations and reflect a common approach to risk assessment shared by the a gencies as a way of addressing scientific differences between the EPA and the Services

. The NAS report outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the Endangered Species Act (ESA) and FIFRA

. The joint I nterim Approaches were released prior to a stakeholder workshop held on November 15, 2013

. In addition, the EPA presented the joint Interim Approaches at the December 2013 P esticide P rogram D ialogue C ommittee (PPDC) and S tate

- FIFRA Issues Research and Eval uation Group ( SFIREG ) meetings, and held a stakeholder workshop in April 2014, allowing additional opportunities for stakeholders to comment on the Interim Approaches

. As part of a phased, iterative process for developing the Interim Approaches, the agenci es will also consider public comments on the Interim Approaches in connection with the development of upcoming- Page 40 of 44

-

Registration Review decisions

. The details of the joint Interim Approaches are contained in the white paper “ Interim Approaches for National

- Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report ,” dated November 1, 2013

. Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, this preliminary risk assessment for antimycin d oes not contain a complete ESA analysis that includes effects determinations for specific listed species or designated critical habitat. Although EPA has not yet completed effects determinations for specific species or habitats, for this preliminary assess ment EPA conducted a screening

- level assessment for all taxa of non

- target wildlife and plants that assumes for the sake of the assessment that listed species and designated critical habitats may be present in the vicinity of the application of antimycin

. This screening level assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists once the scientific methods being developed by the agencies have been fully vetted. This screening

- level risk

ass essment for antimycin indicates potential risks of direct effects to listed freshwater and estuarine/marine fish and invertebrates

. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk assessments for end angered and threatened (listed) species and their designated critical habitats, these methods will be applied to subsequent analyses for antimycin as part of completing this registration review

.

7

. Conclusions

The results of this screening

- level risk assessment are similar to those identified in the environmental fate and ecological risk assessment written in support of the Reregistration Eligibility Decision for antimycin A in 2007

. Exposure to the compound resulting from the maximum treatment concent ration is expected to kill fish and aquatic invertebrates in the immediate treatment area ; acute risk LOCs are exceeded and the compound is intended to kill fish

. However, in lotic environments

, a ntimycin A is degraded (deactivated) through the use of a
st rong oxidizing agent ( e.g ., potassium permanganate) into fragments that are no longer toxic, to ensure that it does not move outside of the intended treatment area

. While the extent to which the deactivation process is effective is uncertain, fish bioassays downstream of the deactivation stations are used to demonstrate whether residues are at levels acutely toxic to the test species. Given the expense and logistical constraints of treating large lakes with antimycin, t he extent of this use is expected to be low; however, no data are available with which to evaluate the extent of use in lentic environments where the compound would not be deactivated

. Based on the most sensitive species and at the maximum treatment conce ntration, risk quotient (RQ) values excee d acute risk LOCs by several orders of magnitude for direc t adverse effects to listed and non

- listed fish and invertebrates ; however, whether listed species are actually at risk requires a more detailed assessment t han what is contained in this preliminary risk assessment . The risk hypothesis presented in the problem formulation states that the use of antimycin A in accordance with the label results in adverse effects on survival and/or fecundity to non

- target aquati c plants and animals. Based on the current assessment, there is a likelihood of direct effects ( i.e ., acute mortality) on fish and invertebrates from the use of antimycin A as a piscicide. Although no data- Page 41 of 44

-

are available to assess the potential for advers e effect s to aquatic plants , there are no reported incidents of such effects by either the National Park Service or state fishery management agencies which have employed antimycin A

. Monitoring of macroinvertebrate communities in treated streams indicate t hat adverse effects are short

- lived; invertebrate communities recovered within several months and species richness and abundance especially for benthic macroinvertrates increased relative to pretreatment conditions. While the potential risk to terrestrial animals was hypothesized, the current analysis does not support that component of the risk hypothesis. There are no data with which to evaluate the potential effects of antimycin on terrestrial plants and terrestrial invertebrates; however, given the dire ct application of the material to water, the likelihood of exposure to these taxa is considered low.

8

. References

Abidi, S.L. and B.R. Adams. 1987. 1H and 13C resonance designation of antimycin A1 by two

dimensional NMR spectroscopy. Magn. Reson. C hem. 25: 1078

- 1080.

Abidi, S.L. 1988. High

- performance liquid chromatographic separation of subcomponents of antimycin A. J. Chromatogr. 447: 65

- 79.

Fletcher, J.S., J.E. Nellessen, and T.G. Pfleeger

. 1994

. Literature review and evaluation of the EPA food

- chain (Kenaga) nomogram, and instrument for estimating pesticide residues on plants

. Environmental Toxicology and Chemistry 13 (9):1383

- 1391.

Hoerger, F., and E.E. Kenaga

. 1972

. Pesticide residues on plants: Correlation of representative data as a ba sis for estimation of their magnitude in the environment

. In F. Coulston and F. Korte, eds., Environmental Quality and Safety: Chemistry, Toxicology, and Technology, Georg Thieme Publ, Stuttgart, West Germany, pp. 9

- 28.

Hubert, T.D. and L. J. Schmidt, “An timycin A Use in Fisheries: Issues Concerning EPA Registration”, USGS, Upper Midwest Environmental Sciences Center, La Crosse, WI, 2001.

Hussain, A. 1969. Kinetics and mechanisms of hydrolysis of antimycin A in solution. Journal of Pharmaceutical Sciences 58: 316

- 320.

Kenneke, J.F. Summary of Antimycin Hydrolysis Research, US EPA, unpublished report

. ( See USEPA 2006b .)

Lee, T.H., Derse, P.H., and Morton, S. 1971. Effects of Physical and Chemical Conditions on the Detoxification of Antimycin. Tran sactions of the American Fisheries Society 1971; 100: 13

– 17

. Ott, Kevin C. Antimycin. A Brief Review of Its Chemistry, Environmental Fate, and Toxicology. http://www.newmexicotu.org/Anti mycin%20Summary.pdf- Page 42 of 44

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U.S. Department of the Interior (US DOI )

. 2012

. Standard Operating Procedures for the Use of Fintrol ® (Antimycin A) for Restoration of Native Fish Populations

. U.S. Dept. of the Interior, National Park Service, Natural Resource Stewardship and Science, Ft. Collins CO. Nov. 2012.

U.S. Environmental Protection Agency (USEPA)

. 2015

. Ecological Inci dent Information System, v. 2.1

. Accessed on February 10, 2015

. Description online at : http://www.epa.gov/pesticides/science/models_db.htm

.

USEPA. 2014

. Estimation Program Interface (EPI) Suite TM

. http://www.epa.gov/opptintr/exposure/pubs/episuite.htm

USEPA. 2009 a

. Water models. Available online at http://www.epa.gov/oppefed1/models/water/

.

USEPA. 2009 b

. ECOTOXicology Database, v. 4.0

. Accessed on 12 April 2012

. Available online
at http://cfpub.epa.gov/ecotox/

.

USEPA. 2009 c . Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of Pesticides, Version 2.1

. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, O ffice of Pesticide Programs, Environmental Fate and Effects Division, October 22, 2009. Online at: http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm

USEPA. 2007

. Reregistration Eligibility Decision for Antiycin A

. List D. Case No. 4121

. Available on line at: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

2006

- 1002

- 0029

USEPA. 2006 a . Revised Environmental Fate and Ecological Risk Assessment Chapter (DP Barcode D310730) in Support of Phase III of the Reregistration Eligibility D ecision on Antimycin A (PC Code 006314)

. Available on line at: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2006

- 1002

- 0004

USEPA. 2006 b

. Antimycin A Drinking Water Characterization (Revision 1) (DP Barcode D333893)

. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Environm ental Fate and Effects Division. November 29, 2006.

USEPA. 2006 c , TerrPlant v. 1.2.2 User’s Guide

. Office of Pesticide Pro grams, Environmental Fate and Effects Division, Washington, D.C

. December 26, 2006.

USEPA. 2004

. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. Environmental Protection Agency

. Endangered and Threatened Specie s Effects Determinations

. Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washington, D.C

. Available online at http://www.epa.gov/op

pfead1/endanger/consultation/ecorisk

- overview.pdf

.- Page 43 of 44

-

USEPA. 1998. Guidelines for Ecological Risk Assessment

. EPA/630/R

- 95/002F

. Published in 63 FR 26846; May 14, 1998

. U.S. Environmental Protection Agency, Washington, DC

. April, 1998.

USEPA. 1993 b

. Wildlife Exposure Factors Handbook

. EPA/600/R

- 13/187a

. Office of Research and Development, Washington, D.C.

USEPA. 1992. Pesticides in Ground Water Database: A Compilation of Monitoring Studies: 1971

- 1991: National Summary. U.S. Environmental Protection A gency, Washington, DC.

Walker, C.R., R.E. Lennon, and B.L. Berger. 1964. Preliminary observations on the toxicity of antimycin A to fish and other aquatic animals. U.S. Bureau of Sport Fisheries and Wildlife, Investigations in Fish Control No. 2 (Circular No. 186). 18 pp.

Willis, G.H. and L.L. McDowell

. 1987

. Pesticide persistence on foliage

. Reviews of Environmental Contamination and Toxicology 100: 23

- 73.- Page 44 of 44

-

9

. Appendix A

. S creening I mbibition P rogram ( SIP ) Results