Document ID: EPA-HQ-OPP-2006-1002-0010
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-01-17T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

	WASHINGTON, D.C.  20460

OFFICE OF

PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES

September 27, 2006

Memorandum

SUBJECT:	Antimycin A:  Health Effects Division (HED) Considerations for
the Reregistration Eligibility Decision (RED) Document.  Phase I.  	 

		Barcode: DP# 310734 

FROM:	Deborah Smegal, MPH, Toxicologist/Risk Assessor

		Re-Registration Branch 1 

		Health Effects Division (HED) (7509P)

	

THRU:		Michael Metzger, Branch Chief 

		And

		Christine Olinger, Senior Scientist

		Reregistration Branch I

		Health Effects Division (HED), (7509P) 

TO:		Lance Wormell, Chemical Review Manager 

Reregistration Branch 2		

Special Review and Reregistration Division (SRRD) (7508P)

Background:

with certain species being more sensitive to the compound than others. 
Unlike other registered piscicides, fish are reportedly not able to
detect and thus avoid antimycin A in treatment areas.  Antimycin A is
used in fish management because low treatment concentrations are
required to achieve management objectives and the compound is reported
to degrade rapidly making it possible to restock treated areas within a
short time after treatment.  The chemical structure of antimycin A is
shown in Figure 1.

Figure 1:  Chemical Structure of Antimycin A

There is currently one active Antimycin A registration (Section 3). 
There is currently no emergency exemption (Section 18) use or special
local need (Section 24c) use.  No tolerance exists for commodities
treated with antimycin A although food fish (aquaculture) ponds can be
treated with antimycin A to remove undesirable scaled fish.  Because
treatments generally occur before stocking with fingerling catfish and
roughly 9 months elapse before those fish are ready for harvest, the
potential for antimycin residues in harvested fish is considered
unlikely.

SUMMARY AND CONCLUSIONS 

	HED believes that there are insufficient data available at this time to
conduct a quantitative human health risk assessment for Antimycin A. 
Currently, HED lacks reliable information on the hazard of Antimycin A
with regard to developmental, reproductive, neurological, dermal,
inhalation and chronic toxicity.  However, Antimycin A is a restricted
use pesticide used only by trained and/or certified applicators that is
used in quantities of less than 100 lbs per year in the U.S.   There is
currently only one registered product that is used at low application
rates resulting in water concentrations of less than 25 ppb, and
according to SRRD the Agency will require additional label language to
preclude human exposure.  

	Based on discussions with the SRRD risk management team, in lieu of
calling in additional data to perform a risk assessment, the SRRD
intends to implement mitigation measures though product labels, a use
manual, and proper training to address the following issues identified
below.  If the following mitigation measures are not adopted, HED will
require the submission of data to support a human health risk
assessment.  

For the stream/lake use, mitigation measures are necessary to prevent
food exposure, drinking water, swimming and/or recreational exposures
(i.e. the dead fish must not be eaten; drinking water must be treated
with a deactivation agent; the area must be posted to keep swimmers out
of the area; hikers must be warned not to consume fish, drink the water
or swim in the treated areas).  

For the catfish farm use, mitigation measures must be put in place to
prevent food exposure (i.e. a 12 month, or greater, harvest prohibition
following application)

.   

	HED believes that improvements in label language, in addition to other
measures required by SRRD as part of the Re-Registration Eligibility
Decision (RED), will ensure there will be negligible human exposure from
food, swimming and drinking water, and minimal exposure to workers with
the addition of PPE.  Thus, HED believes the resulting risks would also
be negligible when the product is used by trained applicators according
to the label instructions.  

USE INFORMATION 

 and rivers.  Deeper water bodies may require the use of a pump
mechanism (to ensure adequate mixing throughout the water column) where
Antimycin A is dispensed through a perforated hose stretching the length
of the water column or is delivered through the propeller wash.

.  

There are two broad uses for Antimycin A as a piscicide:  Complete kill
and selective kill. In a complete kill, the water body is treated at 5
to 25 ppb of Antimycin A to eliminate all fish in the treatment area.  A
common objective of a complete kill is to eliminate invasive or
non-native species in an area to restore threatened or indigenous
species.

In a selective kill, the water body is treated at 0.5 to 1.0 ppb of
Antimycin A to eliminate only small, scaled fish.  A common objective of
a selective kill is to eliminate smaller fish to free up food and other
resources for larger fish.  Selective kills at higher concentrations are
also used in catfish farming to eliminate scaled fish that commonly
reduce the catfish yields of commercial catfish farmers.  According to
the Fintrol® label, scaled fish in catfish farms succumb to treatment
at 5 to 10 ppb of Antimycin A whereas catfish generally tolerate up to
20 ppb.

According to the Fintrol® label, in complete and selective kills, dead
fish may be collected and disposed of or left to biodegrade.  Areas
downstream of the treatment area may or may not be neutralized with an
oxidizing agent such as potassium permanganate to intentionally
inactivate Antimycin A.

Detoxification:

.  Potassium permanganate is a strong oxidizing agent commonly used to
purify drinking water and kill pond algae.  According to the product
label, water may be considered detoxified when fingerling rainbow trout
or fingerling bluegills survive for at least 48 hours in livecars placed
100 yards downstream from the site of potassium permanganate
introduction.  

Usage and Use Rates:

According to the registrant, less than 100 lbs. of Antimycin A are used
annually in the US.  EPA’s Screening Level Usage Analysis returned no
data on agricultural or non-agricultural uses of Antimycin A.  Antimycin
A is available as a soluble concentrate/liquid.  Retreatment and reentry
intervals are not specified on the current label.  

3.0	HAZARD CHARACTERIZATION tc \l1 "HAZARD CHARACTERIZATION 

.    Table 1 presents the acute toxicity data for Antimycin A. 

Table 1.  Summary of AcuteToxicity Data for Antimycin A

Test	

Species	

Results	

Reference

Oral LD50 	

Rat	Toxicity Category I

(technical)	1993 EPA Review

D189202

286 mg/kg (males)

361 mg/kg/ (females)

316 mg/kg  (combined)

 (Toxicity Category II) for 23% 	

MRID 45937201 (Acceptable)

Dermal LD50 	

Ratt	>5000 mg/kg

(Toxicity Category IV) for 23%	MRID 46762604 (Acceptable)

 Inhalation LC50	

Rat	<0.166 mg/L 

(Toxicity Category II)

(technical)	1993 EPA Review

D189202

>2.59 mg/L

MMAD-2.8 um; GSD-4.1

 (Toxicity Category IV) for 23%	MRID 46762605

(Acceptable)

Dermal Irritation	

Rabbit	Not a dermal irritant	MRID 46762602

(Acceptable

Eye Irritation	Rabbit	Irritation resolved within 48 hours for a 0.5%
solution	1993 EPA Review

D189202

Opacity: Non washed; at 1 hr, 2/3 scattered diffuse areas of opacity,
1/3 easily discernible translucent areas of opacity.  At 24 hrs, 1/3
scattered diffuse areas of opacity.  Form 48 to 72 hrs, 2/3 scattered
diffuse areas of opacity.  Washed:  at 1 hr, 1/3 scattered diffuse areas
of opacity, 2/3 easily discernible translucent areas of opacity, 1/3
scattered diffuse areas of opacity.

(Toxicity Category II) for 23%	MRID 46762603

(Acceptable)

(a) Contains 23% Antimycin A

	The toxicological database is inadequate to conduct a quantitative risk
assessment.  The Agency lacks information regarding developmental,
reproductive, neurological, dermal, inhalation and chronic toxicity of
Antimycin A.  Only one oral subchronic toxicity study is available which
is discussed below.  

	Subhronic Toxicity.  In a subchronic study, rats exposed to the end use
product containing Antimycin A (23% ai) exhibited an increased incidence
of diarrhea or soft feces at the lowest dose tested of 0.5 mg/kg/day.  A
NOAEL was not established.  A detailed summary of the study is provided
below.  

	90-Day Oral Toxicity Study in Rat.  In a subchronic oral toxicity study
(MRID 45533301, 46762601), Fintrol® Concentrate (23% a.i., Batch #
1977) was administered to 10 Sprague-Dawley rats/sex/dose in the diet at
active ingredient dose levels of 0, 0.5, 5 and 10 mg/kg/day from Day 0
until Day 41 and  0, 0.5, 10 and 20 mg/kg/day from Day 42 until study
termination.

	The following parameters were examined: clinical signs, body weight,
food consumption, functional observational battery, hematology, clinical
chemistry, gross lesions, selected organ weights, and histopathology of
selected tissues and organs.

	No adverse neurological effects were observed in any groups as assessed
by the functional observational battery (FOB) conducted at 3 months. 
Also, survival,  gross lesions, and microscopic pathology findings were
not affected by treatment with the test material and no eye
abnormalities were observed during ophthalmoscopic examinations.  

	No treatment-related hematology findings were observed except for
neutrophils in the Group IV females.  The neutrophil in the females was
significantly higher (145%)  than that of the control group.  But this
finding was not corroborated by gross or microscopic pathology and was
not considered toxicologically significant.

	No treatment-related clinical chemistry findings were observed except
for two parameters.  Total protein in the Group III males and Group IV
females and calcium in the Group IV females  were significantly less
(15-18%)  than those of the control group.  But these findings were not
corroborated by gross or microscopic pathology and was not considered
toxicologically significant.

	In Group II (0.5 mg/kg) animals, diarrhea in one male on days 31 and 32
and soft feces in 3 females on eight days (Days 33, 40, 41, 86-90) were
observed.  In both Groups III and IV (5 and 10 mg/kg) animals,
increasing incidence of diarrhea or soft feces were observed when
compared to the control or Group II animals. 

	Group IV male and female rats gained 21% less weight than the control
animals, however, no treatment-related effects were observed on absolute
body weights and food consumption at all doses.  Increased incidence of
diarrhea and soft stool was considered as treatment related effects due
to Antimycin effect on the intestinal flora leading to  diarrhea and
soft feces.

	The LOAEL was 0.5 mg/kg/day based on occurrence of increased incidence
of diarrhea or soft feces.  The NOAEL was not established. 

	This study is classified as acceptable/guideline and satisfies the
guideline requirements (OPPTS 870.3100a; OECD 408) for a subchronic oral
toxicity study in the rat.  Although there was a change in dosage from 5
and 10 to 10 and 20 mg/kg on day 42 onward, the effect of the chemical
on the intestinal flora occurred prior to the changes in dosages.

4.0  EXPOSURE ASSESSMENT AND CHARACTERIZATION

	There are insufficient data available at this time to conduct a
quantitative human health risk assessment for Antimycin A.  Currently,
HED lacks reliable information on the hazard of Antimycin A with regard
to developmental, reproductive, neurological, dermal, inhalation and
chronic toxicity.  However, Antimycin A is a restricted use pesticide
used only by trained and/or certified applicators that is used in
quantities of less than 100 lbs per year in the U.S.   There is
currently only one registered product that is used at low application
rates resulting in water concentrations of less than 25 ppb, and SRRD
will require additional label language to preclude human exposure.  

Based on its use pattern there are potential exposures for workers
during application, children or adult recreational users of treated
lakes/streams via swimming, anglers harvesting fish after treatment, and
dietary exposures from the catfish farm use, and potential drinking
water exposures from the treatment of lakes/streams/reservoirs that
could be used as a drinking water source.  Each is briefly discussed
below.    

.  Currently, the label indicates that one container of product can be
applied in five gallons of water, which is equivalent to a solution
strength of 2900 ppm.  The aerosol exposures could also be reduced by
specifying the application of coarse spray droplets.

 in animals was transient.  

	Residential/Recreational Exposure.  HED believes that exposure to
Antimycin A can be prevented through improved label language.   The
label needs to clearly state that dead fish must not be eaten, drinking
water must be treated with a deactivation agent; the area must be posted
to keep swimmers out of the area; hikers/fisherman must be warned not to
consume fish, drink the water or swim in the treated areas for a period
of time (time to be specified later but at least 1 week after treatment
and possibly longer).  

	Dietary.   No tolerance exists for commodities treated with antimycin A
although food fish (aquaculture) ponds can be treated with antimycin A
to remove undesirable scaled fish.  Because treatments generally occur
before stocking with fingerling catfish and roughly 9 months elapse
before those fish are ready for harvest, the potential for antimycin
residues in harvested fish is considered unlikely.  Residues in catfish
are expected to be low based on the low application rate (less than 25
ppb) and label restrictions not to harvest fish for 1 yr following
treatment.  Based on discussions with the risk management team, SRRD
also intends to improve the label language regarding timeframe required
for sport fishing in water bodies treated with Antimycin A.  

	Estimates of Water Concentrations for Drinking Water.  The Agency
estimated drinking water concentrations from the use of Antimycin A. 
Details of this assessment are provided in the Environmental Fate and
Effects Division (EFED) memo from D. Young, June 21, 2006, D310732.  A
brief summary is provided in this section.   When antimycin is applied
to a water body (whether a lake, pond, or stream) the most conservative
acute concentration that could be used for drinking water assessments is
the application concentration.  The maximum application concentration is
ambiguous but is “roughly” 25 ppb.  However, because of the
significant uncertainties regarding the persistence and sorption
properties of Antimycin A, temporal concentrations trends and chronic
concentrations prediction are also full of uncertainty.  With this
regard, ranges of estimates of chronic concentrations can be made by
using the full range of possible degradation rates.  The Agency (EFED)
provided a range of chronic concentrations that may result following a
25 ppb application of Antimycin to a water body and shows that chronic
concentrations vary considerably depending on the half life assumed for
Antimycin A, with a value of 4.6 ppb the most conservative based on the
longest reported half life (47 days).  A chronic concentration of 0.0013
ppb was estimated based on a half-life of 20 minutes.   

For human drinking water, Antimycin may move downstream from the point
of application (outflow from a lake or a stream) and could enter a
drinking water reservoir.  Because of the uncertainties surrounding the
degradation of Antimycin and the great variability in potential travel
times from the point of application to a reservoir, only first
approximations of Antimycin concentrations in human drinking water can
be made.  The worst possible case would be the concentration of
Antimycin at the point of application—an acute concentration of
“roughly” 25 ppb.  The worst possible case for a chronic
concentration would be the concentration derived using the longest
reported aquatic half life—“roughly” 4.6 ppb, depending on actual
application rate.  These “rough” estimates of 25 ppb and 4.6 ppb
chronic are the EFED-recommended acute and chronic concentrations for
use in human drinking water exposure assessments.   

The above recommended concentrations apply to both surface water and
groundwater. While applications of Antimycin are made only to surface
waters, it is possible that Antimycin could migrate to groundwater
(e.g., by leaching beneath a pond or stream); however, the resulting
groundwater concentrations would be no higher than the source surface
water concentration.  Thus, the above recommendations are also
conservative estimates of groundwater concentrations.  

	Based on discussions with the risk management team, the Agency intends
to require that drinking water must be treated with a deactivation agent
to preclude human exposure to Antimycin A.  

5.0	DATA NEEDS:  

	Environmental fate data gaps have been identified, and efforts are
underway by the U. S. Geological Survey, the EPA Office of Research and
Development and the Office of Pesticide Programs’ Biologic and
Economic Assessment Division laboratories to address some of the
uncertainties regarding analytical method development and potential
routes of degradation.

.  

	(2)  Although hydrolysis data are available on Antimycin, there is
considerable variability in the data and degradation half-lives range
from 30 minutes to 47 days.  Additional information on Antimycin A
degradation would be helpful.  

	(3) Additionally, while there are anecdotal data suggesting that
Antimycin A is inactivated through the use of an oxidant, e.g. potassium
permanganate, there are no data to identify the reaction products.    
SEQ CHAPTER \h \r 1  

6.0  RECOMMENDED LABEL REVISIONS:  

The label should more clearly state the maximum application rates, as
the current label provides “rough estimates”. 

Disposal methods for unused pesticide need to be clearly stated.  

The label should restrict aerial applications.  

.   Mitigation measures are necessary to prevent food exposure, drinking
water, swimming and/or recreational exposures.  The label needs to
clearly state that dead fish must not be eaten, drinking water must be
treated with a deactivation agent; the area must be posted to keep
swimmers out of the area; hikers/fisherman must be warned not to consume
fish, drink the water or swim in the treated areas.  

	For workers proper personal protective equipment (PPE) should be
required to prevent dermal exposure.  For example, additional label
language should specify that workers wear long-sleeved shirt and long
pants to preclude dermal exposure during application.   It is
recommended that the applicators should be certified.  

	Retreatment and reentry intervals are not specified on the current
label.  The language for re-entry of treated areas or fishing of treated
lakes/streams needs to be improved to more clearly specify a time limit
(time to be specified later but at least 1 week after treatment and
possibly longer),  or concentration level (< 1 ppb) in addition to the
current criteria of survival of sensitive species for 48 hours.  

	The label should be improved to provide more guidance on when the
deactivation agent is required. 

	Catfish farm use.   Mitigation measures must be put in place to prevent
food exposure (i.e. a 12 month, or greater, harvest prohibition
following application).  The use rate should be reduced to 10 ppb as a
maximum concentration since catfish are sensitive to 20 ppb, and this
use is meant to control undesirable scaled fish.  

7.0  REFERENCES:

Kuhn, J (2001)   Fintrol Concentrate (Antimycin): 90-day oral toxicity
study in rat (diet). Stillmeadow, Inc.,  Sugar Land, TX.  Laboratory
Study No. 6024-00, August 28, 2001.  Submitted by Aquabiotics Corp. MRID
45533301.  Unpublished.

USEPA 2005.  Antimycin A Use Closure Memo.  Case No. 4121.  Memo from
L.Wormell (SRRD) to Antimycin A RED Team.  October 26, 2005.

USEPA 2006.  Antimycin A Drinking Water Characterization  Memo from D.
Young Environmental Fate and Effects Division (EFED), to L. Wormell/T.
Myers (SRRD) and C. Olinger (HED).  June 21, 2006, D310732

 PAGE  10 

BR:should be Streptomyces mold

BR: Again, throughout the document it needs to be clear if the
discussion is about ppb/mg/l of Fintrol or antimycin A, since Fintrol is
not 100% antimycin A.

BR: Overall, a) and c) recommendations are geing followed in most areas
now where Fintrol is being applied.

BR: Also lakes and reservoirs.

BR: Although Fintrol is more effective in warm water, the statement as
written is misleading for all applications.  However, it is true for
applications to standing bodies of water with identical pH’s.

BR: Is antimycin A/Fintrol broken down by oxidation or hydrolysis? 
Should it be both?  The other EPA documents use hydrolysis. 

BR: Up to 4 ppm is often required to neutralize, with the amount to be
determined by bioassay.

BR:  If Fintrol is 23% ai antimycin, that should be stated at the start
of each document, and after that, Fintrol should be used for all
references to applications.  

BR: Although antimycin A may not be an eye irritant, Fintrol is.

BR: I agree that the label should define a specific concentration for
tank mixes for backpack sprayers.  This would also help field
applications, since high concentrations in tank mixes often do not
result in good distribution within the target area.

BR: Although antimycin may not be an eye irritant, Fintrol causes eye
irritation.  The label should state that Fintrol causes severe eye
irritation, and add that applicators should not wear contact lenses,
since the lens can hold Fintrol against the eye.  Fintrol can melt a
soft contact lens onto the cornea of applicators if eye protection is
not used.

BR: Should read, “Fintrol will dissipate due to natural oxidation,
hydrolysis, dilution, or application of potassium permanganate.”

BR: being developed in 2006 by USGS, Lacrosse.

BR: These seem to be ok, with many already used.