  SEQ CHAPTER \h \r 1 U. S. ENVIRONMENTAL PROTECTION AGENCY

Washington, D.C. 20460

									            OFFICE OF

	PREVENTION, PESTICIDES

	AND TOXIC SUBSTANCES

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON D.C., 20460

PC Code:  036501

DP Barcode:  347376

Date: 	April 28, 2008

MEMORANDUM

Subject:	Revised Registration Review Preliminary Problem Formulation for
the Ecological Risk Assessment of Coumaphos

To:		Richard Dumas, Acting Branch Chief

Wilhelmena Livingston, Chemical Review Manager

		Mail Code: 7508P

		Special Review and Reregistration Division

From:		Fred Jenkins, Biologist

Iwona, Maher, Chemist

Nancy Andrews, Ph.D., Branch Chief

Mail Code: 7507P

		Environmental Risk Branch I

		Environmental Fate and Effects Division

Attached is EFED’s problem formulation document in support of the
coumaphos registration review docket opening.  This memorandum outlines
(1) the methods that will likely be used in the ecological risk
assessment of coumaphos, (2) data gaps, and (3) additional data needs.

Registration Review

Registration Review

Ecological Risk Assessment

Problem Formulation for:

Coumaphos

3-chloro-7-diethoxyphosphinothioyloxy-4-methylcoumarin

Prepared By:

Fred Jenkins, Biologist

Iwona Maher, Chemist

Environmental Risk Branch I

Environmental Fate and Effects Division

Office of Pesticide Programs

Approved By:

Nancy Andrews, Ph.D., Branch Chief

Environmental Risk Branch I

Environmental Fate and Effects Division

Office of Pesticide Programs

April 28, 2008

.	Problem Formulation

The problem formulation is used to establish the direction and scope of
an ecological risk assessment.  According to the Guidelines for
Ecological Risk Assessment (USEPA, 1998), a problem formulation consists
of defining the problem and purpose for the assessment, and developing a
plan for analyzing and characterizing risks.  The critical components of
the problem formulation are the selection of the assessment endpoints,
the formulation of both the risk hypotheses and the conceptual model,
and the development of an analysis plan.   The analysis plan and
supporting rationale are aimed at determining whether the coumaphos uses
pose an unreasonable adverse risk to non-target organisms including
those federally listed as threatened or endangered (hereafter referred
to as “listed”).  The registered uses of coumaphos include an
insecticide/acaricide treatment on livestock and swine bedding for
control of flies, mites, and ticks, and recently approved IR4 (DP
Barcode 315770; Dated: May 16, 2006) for use on bee hives to control
varroa mites and small hive beetles.

1.1.	Integration of Available Information

The following coumaphos risk assessment related documents are available
in the docket, and will serve as the basis for this problem formulation:

Finalization of Interim Reregistration Eligibility Decisions (IREDs) and
Interim Tolerance Reassessment and Risk Management Decisions (TREDs) for
the Organophosphate Pesticides, and Completion of the Tolerance
Reassessment and Reregistration Eligibility Process for the
Organophosphate Pesticides. Dated: July 31, 2006. EPA 738-R-00-10.

EFED Drinking Water and Ecological Risk Review for Coumaphos (036501)
IR-4 Use on Beehives DP Barcode D315770. Dated: May 16, 2006

Screening Level Aquatic Exposure Assessment for the Use of Coumaphos in
the Pacific Northwest and California to Treat Cattle via Spray and Vat
Dips for the Endangered Species (ES) Consultation Package. DP Barcode:
D303298. Dated: June 6, 2004

US EPA Reregistration Eligibility Decision (RED) for Coumaphos. Dated
August 1996. EPA 738 R-96-014.

EFED Review for Coumaphos RED.  Dated: Sep. 19, 1994. (EFED’s
environmental fate and ecological effects sections for the Coumaphos
1996 RED)

Agency Conclusions Based on Previous Coumaphos Ecological Assessments

The current ecological risk conclusions from the above mentioned
coumaphos risk assessment documents are as follows:

Avian Acute Risk

Coumaphos is expected to pose a significant acute risk to birds.  Birds
may be subject to primary exposure via ingestion of hair and skin debris
from treated cattle or secondary exposure via ingestion of birds killed
by the pesticide, and contaminated with pesticide.

Avian Chronic Risk

The Agency concluded that avian reproduction studies were not required
for coumaphos.  Such studies may be required when birds are likely to be
exposed to a pesticide repeatedly or continuously.  According to the
1996 RED document’s assessment of acute risk if there were significant
coumaphos exposure to birds, they would be killed before chronic effects
could occur.

Mammalian Acute Risk

Coumaphos is not expected to pose a risk to endangered or non-endangered
mammals because the limited use pattern of coumaphos, i.e., treatment of
cattle in confined areas, is not expected to result in significant
exposure.

Aquatic Organism Risk

Based on the Agency analysis, coumaphos usage on cattle is expected to
pose a high acute risk to aquatic invertebrates.  Coumaphos is not
expected to pose chronic or acute risks to endangered or non-endangered
fish.

EFED will utilize the information provided by the previous risk
assessment documents as a resource for conducting the ecological risk
assessment for the registration review process.  The assessment will
include risk estimates from two exposure pathways:  the application of
coumaphos to cattle via spray based on registrant submitted data on
wash-off estimates from cowhide, and from application of bioremediated
spent vat-dip solutions to land. Both exposure pathways maybe equally
important for environmental risks, and are discussed in the screening
level aquatic exposure assessment dated June 6, 2004 (D303298).

The indoor use of the coumaphos and the placement of coumaphos-treated
strips in beehives to avoid contact of bees suggest that there are no
complete routes of exposure to surface waters or to the surrounding
non-target terrestrial environment.  Therefore, without evident complete
exposure routes to aquatic and non-target terrestrial organisms, there
are no acute or chronic risk concerns and no concerns for effects to
federally listed threatened or endangered species.

1.2.	Pesticide Type, Class, and Mode of Action

Coumaphos is an insecticide/acaricide.  It belongs to the
organophosphate class of pesticides.  The toxic mode of action of
coumaphos is the inhibition of acetyl cholinesterase.

1.3.	Stressor Source and Distribution

The source of the stressor is considered to be combined residues of the
insecticide coumaphos (PC Code 036501; O,O-diethyl
O-3-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl phosphorothioate) and its
oxygen analog, coumaphoxon (O,O-diethyl
O-3-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl phosphate) from indoor
food and non-food uses.

1.4.	Overview of Pesticide Usage

Coumaphos was first registered in the United States in 1958 for use as
an insecticide. A dust formulation, the first end-use product, was
registered the following year for the control of insects on cattle.
Currently, coumaphos is registered for the control of insects, mites,
and ticks on livestock and swine bedding, and to control varroa mites,
and small hive beetles in bee hives.

The predominant use of coumaphos is as an insecticide/acaricide to
control insect pest of beef cattle.   It is also used for the same
purposes to treat dairy cattle, horses, sheep, and swine.   The targeted
insect pests include flies (face fly, horn fly), ticks, lice, mites
(scabies mite) and screw worms.  The formulation types of the registered
coumaphos products include   TC \l3 "		Overview of Pesticide Usage the
technical grade active ingredient (96% pure), manufacturing product (25%
a.i. dust), end-use products (1% a.i. dust, 11.6% a.i. and 6.15% a.i.
emulsifiable concentrates, and 42% a.i. flowable concentrate).
Coumaphos is applied directly to the livestock.   The equipment used to
apply coumaphos includes dip vats, low and high-pressure hand wands,
back rubber/oiler, mechanical dusters, dust bags and shaker cans.
Depending on animals treated and formulation type, the maximum label
application rates range from 0.005 to 0.025 lbs a.i./gallon for spray or
dip, 0.076 lbs a.i./gallon of oil for back rubbers, 0.000625 to 0.013
lbs a.i./animal for dust, and 0.042 lbs ai/1,000 sq. ft. of swine
bedding.  The coumaphos applications are primarily done during early
spring to late summer or during the fly season. Multiple applications to
livestock and livestock areas are allowed.   The use classifications for
the two liquid products, the 11.6% emulsifiable concentrate and the 42%
flowable are as Restricted Use Pesticides (RUPs).  All other products
have general use classifications.  For details on the maximum
application rates, the application equipment, and coumaphos product
names refer to an attached EFED Label Data Report dated September 13,
2007 (Attachment A:  EFED Label Data Report 036501EF).

D. Estimated Usage of Pesticide

This section summarizes the best estimates available for many of the
pesticide uses of coumaphos, based on pesticide usage information for
1990-1999 available to the Agency. A full listing of all uses of
coumaphos, with the corresponding use and usage data for each site
(cattle or other livestock), has been completed and is included in the
“Quantitative Usage Analysis for Coumaphos,” dated August 15, 2000,
which is available in the Public Docket.  The data, reported on an
aggregate and site basis, reflect annual fluctuations in use patterns as
well as the variability in using data from various information sources.
Approximately 71,000 lbs a.i. of coumaphos is used annually in the
United States.  Table 1 provides further detail regarding the annual
usage amounts of coumaphos in the US.

Table 1. Coumaphos Estimated Usage for Representative Sites

Site 	Lbs. Active Ingredient Applied

(Likely Average1) 	Percent Livestock Treated

(Likely Average)

Cattle 	59,000 	5.1%

Other Livestock 	12,000 	1.3%

1 Likely averages are the EPA’s estimates of what the average uses are
likely to be sources: U.S. Census of Agriculture;       State Usage
Surveys from TX, KS, NY, WY, and NV; State use recommendations;
USDA,NASS, 2000 and EPA data. Refer to the “Quantitative Usage
Analysis for Coumaphos,” dated August 15, 2000, prepared by OPP
Biological and Economic Analysis Division.

Table 2 provides more recent summary of the estimates available for
coumaphos usage in California, based on pesticide usage information for
2004-2006 available to the Agency from the California Department of
Pesticide Regulation.

Table 2. Coumaphos use in California from 2004 to 2006

Year 	Site	Lbs AI

2004	Beehives (all or unspec.)	15.43735

2004	CHECKMITE+	47.1

2004	Honey (sugar crop)	  0.0125

2005	Beehives (all or unspec.)	  0.59993

2006	Beehives (all or unspec.)	  3.00378

By far, the largest use for this insecticide is livestock.  This is
largely due to the treatment of livestock entering the US from Mexico as
part of the USDA tick quarantine to prevent Texas cattle fever.  The
national livestock information, provided below, is the most recent
available from the USDA.  While much of the coumaphos use on livestock
along the border may be in a dip vat application, coumaphos is also used
as a body spray, dust, dust bag, pour-on, oiler scratcher, and ear tag
(USDA/NASS, 2004. Pest Management Strategic Plan for Beef Cattle and
Non-lactating Dairy Cattle - North Central Region).

Table 3. Coumaphos estimated usage on Livestock

Livestock	Year	Total Applied	Application Rate	Rate/Head/Year

 	 	(1,000 lbs)	(grams)	(grams)

All Cattle	1999	58.1	2.3	6.9

 	2006	na	na	na

Beef Cattle	1999	54.8	2.7	7.4

 	2006	na	na	na

Dairy Cattle	1999	3.3	0.7	3.1

 	2006	2.3	0.2	7.7

Sheep	2000	0.63	4	5.8

References:  USDA/NASS.  2000.  Agricultural Chemical Usage Cattle and
Cattle Facilities

                     USDA/NASS.  2007.  Agricultural Chemical Usage 2006
Dairy Cattle and Dairy Facilities Summary

                     USDA/NASS.  2001.  Agricultural Chemical Usage 2001
Sheep and Sheep Facilities

Environmental Fate Summary

Active Ingredient

Coumaphos is persistent and moderately mobile to immobile in the soil
environment.  It may reach surface water via runoff and dust drift, and
may leach into shallow ground water. The major pathway of coumaphos
degradation appears to be photodegradation in water (half-life 33
hours).  Coumaphos is stable to hydrolysis in pH 7, aerobic soil
metabolism, and field dissipation.  It appears to be immobile, with KD
values ranging from 61 to 298 for parent, and from 91 to 161 for the
degradate chlorferon.  During one field dissipation study, its mobility
appeared to be higher than expected from those KD values, which could be
attributed to higher concentrations of spent coumaphos in soil
evaporation pits.

The major coumaphos degradates identified under aerobic conditions were
chlorferon, which reached a maximum of 6.2% of the organosoluble
radioactivity, and 6-hydroxyl-3-methylbenzofuran, the oxygen analog,
which reached a maximum of 0.2% of radioactivity, both recovered at six
months.  In addition, the oxygen analog, coumaphoxon, was detected in an
aqueous photodegradation study at a maximum of 10.2% of radioactivity.

The field dissipation study results support the laboratory finding that
coumaphos is persistent.  The estimated field dissipation half-lives are
118 and 185 days.  Soil samples taken 6 to 12 inches deep contained
coumaphos, however, the soil was not sampled at sufficient depth to
define the extent of leaching.  A special retrospective field
dissipation study was conducted to characterize the depth of leaching in
disposal pits and walkways of coumaphos treatment dip vats. On-site
disposal of spent coumaphos in unlined pits was found to result in
leaching of coumaphos, chlorferon, and 40 potasan to the subsurface (72
inches in the study), and could result in ground-water contamination in
areas of shallow ground water. These compounds may reach ground water,
although there was insufficient depth of soil sampling conducted in the
study to determine if coumaphos and/or its metabolites could have
reached the deep wells that were tested during the study.

Coumaphos is nearly insoluble in water (0.05 mg/l at 25oC), and its
vapor pressure of 1x 10-7 mm Hg (20oC) suggests rather low potential for
volatility from soil and water surfaces. Depending on pH and
concentration the log Kow ranges from 3.85 to 4.04.  A supplemental
bioaccumulation in fish study suggests that total coumaphos accumulated,
with a maximum bioconcentration factor of 541X, in whole bluegill
sunfish during 30 days.  Accumulated coumaphos residues were depurated
rapidly, with 98% elimination after 1 day in untreated water.

Coumaphos Degradate

The residues of concern are coumaphos and its oxygen analog,
coumaphoxon.  Coumaphoxon is included in the Health Effects Division
tolerance expression, and was considered in the drinking water
assessment.

Fate and transport data for coumaphoxon are not available.  Using a
computer estimation program (EPI version 3.04), the coumaphoxon Koc
value was estimated to be 92.3, and water solubility 31.61 mg/l at 25oC.
 It is based on this information assumed that coumaphoxon is persistent
and mobile in the soil environment.  Subdivision N aerobic soil
metabolism and batch equilibrium studies are needed for coumaphoxon.
These data are needed to confirm the conservativeness of those
assumptions.

1.6 Incident Report

The Agency has received one bird kill that was associated with exposure
to coumaphos.  The United States Fish and Wildlife Service reported that
an unknown number of American wigeon were found dead in Washington State
in 1981.  The wigeon were in and around ponds adjacent to a feedlot.
The report states coumaphos was the causal agent but did not provide
information on how the chemical was released into the environment.

In 2003, the Minnesota Department of Agriculture submitted to the Agency
a series of eight kills of honey bees that occurred in September, 2002.
In all of these incidents, analysis of bee tissue or pollen, or both,
found residues of coumaphos present.  While the source of the coumaphos
exposure was not known, the investigators speculated that the residues
probably resulted from the beekeepers using Checkmite Bee Hive Pest
Control Strips, a coumaphos-containing product that is frequently used
on bee hives to control Vorroa mites.  Investigators identified recent
applications of other pesticides, including carbaryl and
zeta-cypermethrin, in nearby agricultural fields, but no clear pattern
emerged in the spatial or temporal pattern of these uses that would
suggest that they were the cause.  Furthermore, the residue analysis of
bee tissue and pollen did not detect any carbaryl, zeta-cypermethrin, or
other pesticides.  The investigators concluded that insufficient
evidence was available to determine if the exposure to coumaphos played
a role in these bee kills or was merely incidental.

The Agency has received no reports of adverse field effects to plants or
aquatic organisms that have been attributed to the use of coumaphos.
The Agency also has received no incident reports from pesticide
registrants concerning coumaphos contamination of ground or surface
water.

A lack of reported incidents does not necessarily mean that such
incidents have not occurred.  In addition, incident reports for
non-target plants and animals typically provide information on mortality
events only.  Reports for other adverse effects, such as reduced growth
or impaired reproduction, are rarely received (Source: US EPA Coumaphos
incident summary statement for Registration Review; Dated February 20,
2008; Author: Nicholas Mastrota).

1.7.	  TC \l2 "

	Receptors Ecological Effects Summary  TC \l3 "		Ecological Effects

Table 4 provides taxonomic groups and test species typically used to
indicate the potential for ecological effects in screening-level risk
assessments.  Within each of these very broad taxonomic groups, an acute
and/or chronic endpoint is selected from the available test data.

Table 4.  Taxonomic Groups and Most Sensitive Test Species Typically for
Ecological Effects in Screening Level Risk Assessments.

Taxonomic group	Example(s) of representative species	Endpoint Used

Birdsa

Bobwhite quail (Colinus virginianus)

Mallard duck (Anas platyrhynchos)

Acute, LD50/LC50

Chronic, NOAEC

Mammals	Laboratory rat (Rattus norvegicus)	Acute LD50

NOAEC

Terrestrial insects	Honeybees (Apis mellifera)	Acute Oral LD50

Freshwater fishb	Rainbow trout (Oncorhynchus mykiss)

Fathead minnow (Pimephales promelas)	Acute LC50

Chronic NOAEC

Freshwater invertebrates	Water flea (carinata)

Water flea (Daphnia magna)

 	Acute LC50

 NOAEC

Estuarine/marine fish	Sheepshead minnow (Cyprinodon variegatus)	Acute
LC50

Estuarine/marine invertebrates	Mysid shrimp (Mysidopsis bahia)

Eastern oyster (Crassostrea virginica)	Acute LC50

Acute EC50

Terrestrial plants	Monocots – N/A

Dicots – N/A	Seedling Emergence (Tier I or Tier II no EC25 estimated)

Vegetative Vigor

(Tier I or Tier II no EC25

estimated)

Freshwater vascular aquatic plants and algae	Duckweed (Lemna gibba)
Acute EC25

NOAEC

Freshwater non-vascular aquatic plants 	Diatom (Navicula pelliculosa)
Acute EC25

EC05

Estuarine/marine non-vascular aquatic plants 	Diatom (Skeletonema
costatum)	Acute EC50

EC05

aBirds are used as surrogates for terrestrial phase amphibians and
reptiles (US EPA, 2004).

bFreshwater fish are used as surrogates for aquatic phase amphibians (US
EPA, 2004).

1.8.	Ecosystems at Risk  TC \l3 "		Ecosystems at Risk

The ecosystems that are predicted to be potentially at risk due to the
use and potentially disposal of coumaphos include: 1) aquatic habitats
in which coumaphos may enter via runoff after a direct application of
bioremendiated vat-dip solution on land and via wash-off from the cattle
hide that may wade in these habitats,   and 2) terrestrial ecosystems
where terrestrial animals may come in contact with coumaphos via direct
contact with treated cows, exposure to cow hair with coumaphos residues,
exposure to soil or feed in and around treatment areas, and exposure to
soil on which bioremendiated vat-dip solution was disposed on.

Receptors

The aquatic receptors likely to be exposed to coumaphos include fish,
aquatic invertebrates, and aquatic stages of amphibians and plants
inhabiting water bodies that may contain coumaphos washed from treated
cattle wading in these habitats.   The sole terrestrial receptors likely
to be exposed to coumaphos are terrestrial animals that may come in
contact with coumaphos via direct contact with treated cows, exposure to
cow hair with coumaphos residues, and exposure to soil or feed in and
around treatment areas.

1.8.2.	Assessment Endpoints  TC \l2 "	Assessment Endpoints

Assessment endpoints are defined as “explicit expressions of the
actual environmental values that are to be protected.”  Operationally,
the environmental value is represented by an ecological entity and
associated attributes or characteristics.  The assessment endpoints for
this ecological risk assessment will be survival, growth, and
reproduction of aquatic organisms and terrestrial animals that may be
exposed to coumaphos.

Assessment endpoints and toxicity data used to evaluate the assessment
endpoints are identified in Tables 4 and 5.

1.9.	Conceptual Model

The conceptual model depicts the potential ecological risks associated
with coumaphos uses.  The model is generic and assumes that coumaphos
can affect terrestrial and aquatic organisms if environmental
concentrations are sufficiently elevated as a result of coumaphos label
uses and coumaphos disposal.  Coumaphos is an insecticide/acaricide used
for external use on animals and animal premises applied as a direct
whole animal or wound treatment to control pests.  It can enter the
outdoor environment either as excess material lost during outdoor
application, as material shed, wash off from animals, and during
disposal.  A diagram of the conceptual model is presented in Figure 1.
The exposure pathway from disposal of bioremediated vat-dip solution
onto land was not assessed in 1994 EFED’s RED Chapter.  The disposal
of coumaphos bioremediated dip-vat solution on land maybe equally
important for aquatic and terrestrial exposure as coumaphos washoff into
the water body.

A review of the label provided revealed the following application
restrictions and disposal requirements:

“Do not treat areas such as drinking cups, mangers, or troughs where
livestock feed.  Do not contaminate water, food, feedstuff, food or feed
handling equipment, or milk or meat handling equipment.”

“The Agency requires that spent dip-vat solution be bioremediated, and
recommends the bioremediation method developed by the USDA.  The treated
solution must be transferred to shallow, concrete-lined evaporation
ponds for further degradation.  The evaporation ponds must be
constructed to prevent overflow or flooding during wet seasons and must
be lined with reinforced concrete. Dried sludge generated in the
evaporation ponds must not be applied agricultural land and should be
disposed according to solid waste disposal regulations established by
your Local and/or State Environmental Control Agency.”

The extent of the exposure can be better understood upon availability of
current coumaphos disposal procedures.  There was no mention of the
method of disposal for solution contained within the bioremediation
“evaporation ponds”.  Two assumptions can be made with regard to the
handling of spent solution. Once in the bioremediation ponds, the level
of solution within the pond is maintained by evaporation and removal and
proper disposal of solids.  Alternatively, the liquid is discharged to
water under an NPDES permit or applied to land. Under an NPDES permit,
OPP assumes that precautions have been taken to adequately protect
aquatic life.  Because application to agricultural land of a pesticide
product is generally assessed by OPP, therefore, application of
bioremediated coumaphos to agricultural land would be assessed as a
potential exposure pathway.

Figure 1. Conceptual model of the fate/transport and effects of
coumaphos in the environment.

1.10.	Risk Hypotheses  TC \l3 "		Risk Hypotheses

Hypothesis:  Non-target terrestrial and aquatic animals and plants are
at risk of direct and indirect effects resulting from labeled uses
or/and disposal of coumaphos.

1.11.	Analysis Plan  TC \l2 "	Analysis Plan

The analysis plan is the final step in the Problem Formulation.  During
this step measures of exposure and measures of effect are used to
evaluate the risk hypotheses and are listed in Tables 4 and 5 for a
specific assessment endpoint.  The RQ is obtained by dividing the
measures of exposure for a particular assessment endpoint by the
measures of effect for that endpoint.

	1.11.1.	Measures of Exposure  TC \l4 "			Measures of Exposure

In order to assess exposure to non-target organisms, it is necessary to
have information on the concentration of active ingredient on the hides
of treated cattle, and information on the potential of coumaphos to
wash-off into water when cattle wade into bodies of water. The
registrant has

submitted two studies that address these issues (MRIDs: 42512601 and
42512602). Those studies have been reviewed and found to be acceptable
for use in a risk assessment.  Information from those studies will be
incorporated in the registration review risk assessment for both
terrestrial and aquatic non-target organisms.

In addition, current guidance, procedure, or protocols on the
application of the bioremediated vat-dip solution on land are needed.
In previous EFED assessment (D303298), a potential exposure pathway to
bioremediated coumaphos applied to agricultural land was based on
guidance from proposed USDA land farming methods (D230394; D239676,
6/4/98).  At that time, uncertainties were associated with the estimated
maximum application rate per acre.

	1.11.2.	Measures of Effect

Registrant Submitted Ecotoxicity

Below is a summary of the ecotoxicity studies submitted by the
registrant.

Avian Toxicity

There are nine acceptable avian acute toxicity studies (MRID’s
00022923, 112842, and 00160000) and one supplemental simulated field
study (Gdln. 71-5; MRID 425126-04).  The species tested in the avian
acute toxicity studies include Mallard duck (Anas platyrhynchos),
Bobwhite quail (Colinus virginianus), Ring-necked pheasant (Phasianus
colchicus), and Japanese quail (Coturnix japonica).  There were 34
species of wild birds tested in the simulated field study.

The avian acute toxicity studies demonstrated that coumaphos’s acute
toxicity to birds ranged from highly to very highly toxic on an acute
oral toxicity basis (acute oral LD50 toxicity values ranged from 7.94
ppm - 29.8 ppm), and moderately to very highly toxic on an acute dietary
toxicity basis (acute dietary toxicity values ranged from 85 ppm - 401
ppm).

Based on the Coumaphos 1996 RED document, the Agency concluded that
avian reproduction studies were not required for coumaphos.  Such
studies may be required when birds are likely to be exposed to a
pesticide repeatedly or continuously.  According to the 1996 RED
document’s assessment of acute risk if there were significant
coumaphos exposure to birds, they would be killed before chronic effects
could occur.  Currently, there are no available reproductive toxicity
studies.

The purpose of the field simulation study was to evaluate the exposure
of wild birds to coumaphos treated cows in an open pen.  The field
simulation study was deemed as scientifically sound but did not meet the
requirements for a simulated (pen) field test.  The study was classified
as supplemental, because only one study site was used and only 8 cows
were treated.  The results indicate that potential pathways of exposure
to birds include direct contact with treated cows, exposure to cow hair,
and exposure to soil or feed in and around treatment areas.

Mammalian Toxicity

The registrant submitted mammalian ecotoxicity studies testing coumaphos
include a rat acute oral LD50 study (MRID 00110597) and a rat two-year
generational reproduction study (MRID 43061701).

The rat acute LD50 study demonstrated that coumaphos is highly toxic to
mammals (LD50 value of 17 mg/kg).  The rat two-year generation
reproduction study demonstrated that cholinesterase inhibition, observed
at 5 and 25 ppm was manifested as dose-related decreases in erythrocyte
(RBC) and plasma cholinesterase (ChE).  The RBC ChE was inhibited
31-70%, relative to concurrent controls, at 5 ppm and 53%-95% at 25 ppm.
 Generally, no differences were noted between Day 47 (or 56) and Day 91
ChE levels.  Brain levels were biologically significantly inhibited (
30%) in FO and F1 females.  In pups, plasma and RBC ChE levels were
inhibited (31%-44%) at 25 ppm on lactation day 21 but not on lactation
day 4.  Based on these results, the NOEL and LEL for ChE inhibition were
1 and 5 ppm, respectively.  There were no other signs of systemic
toxicity.  The NOEL and LEL for systemic toxicity was equal to or
greater than 25 ppm.  Reproductive toxicity was not observed in this
study.  Consequently, the NOEL for reproductive toxicity was 25 ppm and
the LEL for reproductive toxicity was greater than 25 ppm.

Insect toxicity

According to the 1996 RED document for coumaphos, the Agency deemed that
the data requirements for non-target insects testing are not applicable
for the coumaphos use patterns, and no studies were required or
submitted.

Fish Toxicity

Freshwater fish acute toxicity

There are nine acceptable registrant submitted freshwater fish acute
toxicity studies testing coumaphos, TGAI, (MRID’s 40098001, and
112840).  The species tested include

Cutthroat trout	(Oncorhynchus clarki), Rainbow trout (Oncorhynchus
mykiss), Lake trout (Salvelinus namaycush), Channel catfish (Ictalurus
punctatus), Bluegill sunfish (Lepomis macrochirus), Largemouth bass
(Micropterus salmoides), and Walleye (Stizostedion vitreum v.).

Based on the results of these studies coumaphos was classified as
moderately toxic to highly toxic to freshwater fish (LC50’s range from
0.340 ppm to 5.9 ppm).

Freshwater fish chronic toxicity

There is one available freshwater fish early-life stage study using
rainbow trout (Oncorhynchus mykiss).  The results of this study
demonstrated that chronically exposing the early life-stage of rainbow
trout caused significant effects to growth at a NOEC, and a LOEC of
0.0117 ppm, and 0.0246 ppm, respectively (MRID 43066301).

Marine estuarine fish acute toxicity

There is one registrant submitted marine estuarine fish acute toxicity
test (MRID 40228401)  using sheepshead minnow (Cyprinodon variegates).
Based on the results of this study, coumaphos is classified as highly
toxic to marine/estuarine fish (LC50 = 0.280 ppm).

Marine/ estuarine fish chronic toxicity

Currently, no data have been submitted to the Agency on the chronic
effects of coumaphos to marine/estuarine fish.

Aquatic Invertebrate Toxicity

Freshwater invertebrate acute toxicity

There are six registrant submitted freshwater invertebrate acute
toxicity studies testing coumaphos (MRID’s 40098001, 05009242,
05017538, 41778503, and 41778504).  These studies test species of water
flea and scud including Daphnia magna, Simocephalus serrulatus, and
Gammarus lacustris.  Based on the Agency’s review of the studies,
three of these studies were deemed acceptable and three were deemed
supplemental.  The results of these studies showed that coumaphos is
very highly toxic to freshwater invertebrates (EC50’s range from
0.000074 ppm to 0.000224 ppm).

Freshwater invertebrate chronic toxicity

There is one registrant submitted freshwater invertebrate chronic
toxicity study (MRID 431166-01).  This study is a Daphnia magna chronic
toxicity study (Gdln 72-4).  Based upon the Agency’s review of the
study, the study was deemed as acceptable.  This test shows survival as
the most sensitive endpoint.  The NOEAC for survival is 0.000037 ppm.

Marine/estuarine invertebrate acute toxicity

There are two registrant submitted marine/estuarine invertebrate acute
toxicity studies testing comaphos’s acute toxicity to the pink shrimp
(Penaeus duorarum) and eastern oyster (Crassostrea virginica).  Based on
the Agency’s review of these studies, both are deemed as acceptable.
The results of these studies indicate that coumaphos is highly toxic to
very highly toxic to marine estuarine invertebrates (EC50 values are
0.002 ppm and 0.290 ppm for the pink shrimp and eastern oyster
respectively).

Marine/estuarine invertebrate chronic toxicity

Currently, there are no marine/estuarine invertebrate chronic toxicity
study data available to the Agency.

Non-target Plant Toxicity

Currently no non-target plant toxicity data have been submitted to the
Agency.

Based on the 1996 RED document for coumaphos, the Agency concluded that
data requirements for non-target plant testing are not applicable for
the coumaphos use patterns, and no studies were required.  However the
Agency has currently concluded in this problem formulation that because
cattle with coumaphos treated hides may wade in aquatic water bodies,
the aquatic plants in these water bodies may be exposed to coumaphos
that washes off the hides of these wading cattle.  Aquatic plant
toxicity data is needed to evaluate the potential effects that aquatic
plants may experience upon being exposed to coumaphos.  The Agency also
presumes that there is a potential that terrestrial plants will be
exposed to coumaphos via the disposal of the dip vat solution.  As
mentioned in the Conceptual Model section more information is needed
about the method of disposal of the vat dip solution in order to
adequately access the potential exposure to non-target organisms such as
terrestrial plants.

 Most Sensitive Endpoints of Effects Data

The following tables 5 and 6 demonstrate the most sensitive endpoints of
all the registrant submitted terrestrial toxicity studies and aquatic
organism toxicity studies respectively.   These endpoints will be the
proposed measures of effects that will be used to calculate risk
quotients for the registration review screening level risk assessment of
coumaphos.  The proposed measures of effects are however subject to
change based on the results of the Agency’s review of coumaphos data
available in the open literature via the ECOTOX database.

Table 5. Summary of terrestrial assessment endpoints and proposed
measures of effects for the screening level risk assessment of
Coumaphos.

Assessment Endpoint

 Measurement Endpoint

Avian Acute Effects to Survival	Acute oral LD50 = 29.8 mg/kg (MRID
00160000)

Acute dietary LC50 = 85 ppm  (MRID 112842)

Avian Chronic Effects to Reproduction, Survival, and/or Growth  ADVANCE
\d6 	No data available *

Mammalian Acute Effects to Survival	Acute oral LD50  17 mg/kg (MRID
00110597)

Mammalian Chronic Effects to Reproduction, Survival, and/or Growth	NOEAL
= 1 ppm (MRID 43061701)

Non-target Beneficial Insect Acute Effects to Survival  ADVANCE \d6 	No
data available **

Terrestrial Plants Survival and Growth	No data available ***

* Note: Based on the Coumaphos 1996 RED document, the Agency concluded
that avian reproduction studies were not required for coumaphos.  Such
studies may be required when birds are likely to be exposed to a
pesticide repeatedly or continuously. The assessment of acute risk
(§A.2.b) indicates that if there were significant exposure to birds,
they would be killed before chronic effects can occur.

** Note:  According to the 1996 RED document for coumaphos, the Agency
deemed that the data requirements for non-target insects testing are not
applicable for the coumaphos use patterns, and no studies were required
or submitted.  However, because of the recently approved IR4
registration to use coumaphos in honey bee hives to control varroa mites
and small hive beetles, the Agency will need this data to evaluate the
potential toxic effects of coumaphos to honey bees.  This data is needed
especially since coumaphos’s targeted mode of action is to control
insect pests.  In addition, according to the Agency’s incident report
for coumaphos, there was a bee kill incident in which an analysis
revealed that the bee’s tissue and pollen in this incident contained
residues of coumaphos.  Consequently, the Agency needs to determine
whether the toxic mode of action will adversely affect bees.

*** Note: Currently no non-target plant toxicity data have been
submitted to the Agency.

Based on the 1996 RED document for coumaphos, the Agency concluded that
data requirements for non-target plant testing are not applicable for
the coumaphos use patterns, and no studies were required.

Table 6. Summary of aquatic assessment endpoints and proposed measures
of effects for the screening level risk assessment of Coumaphos.

Assessment Endpoint

 Measurement Endpoint

Freshwater Fish Acute Effects to Survival	LC50 = 280 ppb (MRID 40098001)

Freshwater Fish Chronic Effects to Reproduction, Survival, and/or Growth
 ADVANCE \d6 	NOEAL = 11.7 ppb (MRID 43066301)

Freshwater Invertebrate Acute Effects to Survival	LC50 = 0.074 ppb (MRID
40098001)

Freshwater Invertebrate  Chronic Effects to Reproduction, Survival,
and/or Growth  ADVANCE \d6 	NOEAL = 0.0337 ppb (MRID 431166-01)

Marine/Estuarine Fish Acute Effects to Survival	LC50 = 280 ppb (MRID
40228401)

Marine/Estuarine Fish Reproduction and/or Survival	No data available

Marine/Estuarine Invertebrate Survival	LC50 = 2 ppb (MRID 40228401)

Marine/Estuarine Invertebrate Reproduction and/or Survival	No data
available

Aquatic Vascular and Non-vascular Plant Survival and Growth	No data
available *

* Note: Currently no non-target plant toxicity data have been submitted
to the Agency.

Based on the 1996 RED document for coumaphos, the Agency concluded that
data requirements for non-target plant testing are not applicable for
the coumaphos use patterns, and no studies were required.  However the
Agency has currently concluded in this problem formulation that because
cattle with coumaphos treated hides may wade in aquatic water bodies,
the aquatic plants in these water bodies will be exposed to coumaphos
that washes off the hides of these wading cattle.  Aquatic plant
toxicity data is needed to evaluate the potential effects that aquatic
plants may experience upon being exposed to coumaphos.

1.11.3.	Preliminary Identification of Data Gaps for Fate and Ecological
Assessment

Environmental fate and transport data for coumaphos are mostly
supplemental; however, support a qualitative characterization of the
properties of coumaphos in the environment.  The only missing laboratory
studies are anaerobic soil metabolism study (162-2), aerobic and
anaerobic aquatic metabolism studies (162-3, 162-4).  The missing
laboratory studies would be beneficial for a better characterization of
the potential for coumaphos leaching to ground water or remaining in
surface water at concentrations of ecological or human health concern;
however they will not adversely effect the risk conclusions as presented
in the 2004 Screening Level Aquatic Exposure Assessment for the Use of
Coumaphos in the Pacific Northwest and California, nor in the 1996 RED.

In addition, there are no environmental fate data for the coumaphoxon.
Coumaphoxon, oxygen analog of coumaphos, was detected in an aqueous
photodegradation study at a maximum of 10.2% of applied radioactivity.
Coumaphoxon is coumaphos’ degradate of concern due to its toxicity
being greater than the toxicity of parent.  Therefore, Subdivision N
aerobic soil metabolism and batch equilibrium studies are proposed to be
requested for coumaphoxon.

Table 7, below, identifies fate and ecological studies, which are
missing or are not acceptable, and may be requested to assess risk to
the environment.  Coumaphos is an insecticide/acaricide used for
external use on animals and animal premises applied as a direct whole
animal or wound treatment to control pests.  It can enter the outdoor
environment either as excess material lost during outdoor application,
as material shed, washoff from animals, and during disposal.  The extent
of exposure from bioremediated spent vat-dip solution can be better
understood upon availability of current coumaphos disposal
procedure/techniques.  If proven that these routes of expose are minimal
or none, the fate studies for coumaphoxon would be waived.

Table 7.  Preliminary Identification of Data Gaps for Fate and
Ecological Assessment.

Fate and Ecological Taxa studies 	Description of studies	Projected
status of data gaps	Basis for decision

Aquatic  plant toxicity studies for guideline 850.4400 and 850.5400
Parent – Study was not submitted	Proposed to request the study	Refer
to information provided below

Anaerobic soil  metabolism study 	Parent - Study was not submitted	Study
not requested

	Aerobic aquatic metabolism study 	Parent - Study was not submitted
Study not requested

	Anaerobic aquatic metabolism study 	Parent - Study was not submitted
Study not requested Registrant requested a waiver.  Waiver was granted
under the condition that disposed spent vat-dip on land will not exceed
concentration of 0.01 ppm in the top 6” soil.	It will characterize the
potential for coumaphos leaching to ground water or remaining in surface
water.  If current disposal protocol fulfills the waiver requirement the
study is not needed.

Aerobic soil metabolism study 	Oxon analog - Study was not submitted
Proposed to request the study	To confirm the computer estimated (EPI v.
3.04) DW modeling parameter.

Batch equilibrium study 	Oxon analog - Study was not submitted	Proposed
to request the study	To confirm the computer estimated (EPI v. 3.04) DW
modeling parameter.

Fate Data Gaps

Guideline Number:  835.4100

Study Title: Aerobic Soil Metabolism (Oxygen Analog)

Guideline Number: 835.1220

Study Title: Batch Equilibrium (Oxygen Analog)

Rationale for Requiring the Environmental Fate Studies Performed in the
Laboratory

Depending on how quickly and to what extent coumaphoxon degrades in
soil, and to what extent it is mobile; coumaphoxon may or may not
contribute to ground water and surface water contamination from cattle
washoff and/or disposal of bioremediated spent vat-dip onto land.

EPA requires a series of individual laboratory studies as well as field
studies to assess the behavior and fate of a pesticide in the
environment. Controlled environmental fate and transport laboratory
studies are used to determine the persistence, mobility, and
bioconcentration potential of a pesticide active ingredient and its
major degradates. Coumaphoxon, coumaphos’ oxygen analog, is a
degradate of concern, and therefore one metabolism study and one
mobility study are requested to provide the minimum information on fate
and transport of this degradate.  The studies offer information on how,
or by what mechanism, the pesticide degrades, the rate at which it
degradates, where it goes, and what transformation products are formed.
Data from these studies are used as inputs to exposure models. These
models estimate the expected environmental concentrations of the
pesticide and the pesticide’s degradates under various environmental
and use conditions. The laboratory studies also help to focus field
study design by providing information on which transformation products
are likely to be produced, and thus need to be tracked, and the
environmental media (e.g., soil, sediment, water, air) that should be
sampled, including the depth to which soil/sediment samples should be
collected.

The soil microbial metabolism study determines the persistence of the
pesticide, in this case its oxygen analog, when it interacts with soil
microorganisms under aerobic conditions.  These studies also identify
the significant degradates that result from biological degradation.

The batch equilibrium study determines the mobility of the pesticide or
degradate in soil, the potential to leach into the shallow groundwater
or its availability to surface runoff following rainfall events.

Practical Utility of the Data

How will the data be used?

The soil metabolism studies would facilitate a better understanding of
coumaphos’ oxygen analog degradation under aerobic (oxygen-rich)
conditions in the laboratory, and as an input parameter for drinking
water modeling and aquatic modeling.

The batch equilibrium study would facilitate a better understanding of
coumaphos’ oxygen analog mobility in soil in the laboratory, and as an
input parameter for drinking water modeling and aquatic modeling.

The soil metabolism studies help to determine how fast the oxygen analog
(coumaphoxon) degrades in the presence of microorganisms in different
natural soils.  They also determine what metabolites are formed.

How could the data change the Agency’s decision, or impact the
Agency’s future decision-making?

If data indicate that coumaphoxon degrades slowly in soil, and is
mobile, then coumaphos usage on cattle and/or disposal of bioremediated
cattle dip solution may pose risk to aquatic organisms, and additional
use/disposal precautions and/or restrictions may be necessary.

Ecological Toxicity Data Gaps

Guideline Number:  850.4400 (Aquatic Plant Toxicity Test, Tier 1)

Guideline Number: 850.5400 (Study Title: Algal Toxicity, Tier I)

Rationale for Requiring the Aquatic Plant and Algal Toxicity Studies

Cattle often wade in aquatic water bodies that are located in and around
their pastures.  Thus, if cattle with coumaphos treated hides wade in
these water bodies, the aquatic plant and algal inhabitants of these
ecosystems may be exposed to coumaphos that washes off the hides of
these cattle.  Currently, there are no aquatic plant or algal toxicity
data testing coumaphos that have either been submitted by the registrant
or are available in the open literature.  Thus, in accordance with the
40 Code of Federal Regulations Part 158 aquatic plant and algal toxicity
data for coumaphos are required.  In addition based on the Agency’s
TOXDATA database, very little data are available which evaluate the
toxic effects of other organophosphate pesticides on aquatic plants and
algae.  Consequently, the Agency is very uncertain of the effects that
coumaphos may have on aquatic plants and algae.  However, based on
available organophosphate aquatic plant and algal toxicity data, naled,
an organophosphate insecticide such as coumaphos, demonstrates
significant acute toxicity to algae and aquatic plants at EC50 values as
low as 12 ppb (MRID 42529603).  Moreover according to an assessment
("Coumaphos Analysis of Risks to Endangered and Threatened Salmon and
Steelhead", August 1, 2004 by Jennifer Leyhe) presenting a crude
estimation of level of exposure from loss of coumaphos applied to cattle
wading into surface water, the estimated environmental concentration
(EEC) from one cow was estimated at 0.15 ppb, assuming 50% was wash-off.
 Thus assuming that 100 cows would wade in the same water, the EEC would
be 15 ppb.  This level of exposure is within the range at which naled
caused significant acute toxic effects to aquatic plants and algae.
Therefore, in order to address the uncertainty regarding the toxic
effects of coumaphos to aquatic plants and algae, the Agency must obtain
aquatic plant and algal toxicity data.  This is especially important
considering that 1) aquatic plants and algae may potentially be exposed
to coumaphos concentrations that are within the range of naled
concentrations that cause significant aquatic plant and algal toxicity,
2) coumaphos may possibly have similar aquatic plant and algal toxicity
to naled because the two chemicals are in the same chemical class, and
3) aquatic plants and algae are a critical element of healthy aquatic
ecosystem, and thus it is very important to evaluate the potential
impact that coumaphos may have on them.

How did the Agency make their decision without the data?

According to the Coumaphos 2006 RED document, the Agency initially
presumed that the registered uses would result in minimal coumaphos
exposure to plants.  Consequently, the Agency concluded that no plant or
algal toxicity data were required for coumaphos.  The Agency also
presumed in the 2006 RED document that the primary non-target organisms
that would be exposed to coumaphos would include 1) aquatic
invertebrates and fish inhabiting water bodies that may encounter wading
cattle with coumaphos treated hides and 2) birds that may be exposed to
coumaphos via direct contact with the hides of coumaphos treated cattle.
 However, based upon the Agency’s current review of the registered
uses of coumaphos, the Agency has determined that coumaphos treated
cattle that wade in aquatic habitat will also result in aquatic plant
and algal exposure to coumaphos.

How will the data be used?

The Agency will use the data to calculate risk quotient calculations
that will determine whether or not aquatic plants or algae exposed to
the estimated environmental concentrations of coumaphos are at risk
above the Agency’s level of concern.   If the risk quotient
calculations from this data demonstrate risk to aquatic plants or algae
that exceed the Agency’s level of concern, this data may also be used
to help the Agency to determine a means of mitigating this risk.

How could the data change the Agency’s decision, or impact the
Agency’s future decision-making?

If the data reveals that coumaphos poses adverse risks to aquatic plants
or algae that exceed the Agency’s level of concern, the Agency may
make a decision to mitigate the usage of coumaphos to alleviate the
risks posed to aquatic plants or algae.

	<IP_ADDRESS>	Other Informational Needs

There is specific information that will assist the Agency in refining
the ecological risk assessment, including any species-specific effects
determinations.  The Agency is very much interested in obtaining the
following information:

any current information pertaining to disposal of bioremediated cattle
dip spent solution (i.e. dried sludge generated in the evaporation
ponds)

confirmation on the following label information

sites of application

formulations

application methods and equipment

maximum application rates

frequency of application, application intervals, and maximum number of
applications per season

geographic limitations on use

use or potential use distribution (e.g., acreage and geographical
distribution of relevant crops)

use history

median and 90th percentile reported use rates (lbs. a.i./acre) from
usage data – national, state, and county

application timing (date of first application and application intervals)
by crop – national, state, and county

sub-county crop location data

usage/use information for non-agricultural uses (e.g., forestry,
residential, rights-of-way)

directly acquired county-level usage data (not derived from state level
data)

maximum reported use rate (lbs. a.i./acre) from usage data – county

percent crop treated – county

median and 90th percentile number of applications – county

total pounds per year – county

the year the pesticide was last used in the county/sub-county area

the years in which the pesticide was applied in the county/sub-county
area

typical interval (days)

state or local use restrictions

ecological incidents (non-target plant damage and avian, fish,
reptilian, amphibian and mammalian mortalities) not already reported to
the Agency

monitoring data

The analysis plan will be revisited and potentially revised depending
upon the data available in the open literature and the information
submitted by the public in response to the opening of the Registration
Review docket.

	1.12.	Open Literature

No open literature fate studies have been found that might provide
useful information in the areas of previously discussed data gaps.

In regards to ecotoxicity data, the Agency uses the ECOTOX database as
its mechanism for searching the open literature for ecological effects
information.  ECOTOX integrates three previously independent databases -
AQUIRE, PHYTOTOX, and TERRETOX - into a system which includes toxicity
data derived predominately from the peer-reviewed literature, for
aquatic life, terrestrial plants, and terrestrial wildlife,
respectively.  Endpoints from ECOTOX are used to calculate risk
quotients for non-target organisms only if these endpoints are
acceptable and are more sensitive than the most sensitive endpoints
produced by the registrant submitted studies.  Currently, the Agency’s
ECOTOX database search for coumaphos open literature data is pending
completion.

Residues of Coumaphos and Coumaphos Degradates in Water

Submitted fate and transport data suggest that coumaphos is persistent
and moderately mobile to immobile.  If applied to soil coumaphos may
potentially drift off or runoff into surface water, and leach into
shallow ground water.  Although, no data were submitted for coumaphoxon,
it is assumed that this degradate of coumaphos is also persistent and
mobile, thus, may potentially runoff into surface water and leach into
ground water resources.  In shallow clear waters with good light
penetration, coumaphos will rapidly form coumaphoxon.

Coumaphos waste product, after being bioremediated, could be applied
directly to soils where it would be available for leaching into ground
water, or for direct runoff following a runoff producing rainfall event.
 In addition, there is a potential environmental exposure from spray
applications to cattle that subsequently wade into surface water where
material is washed off from direct contact with water, and during rain
events.

On June 6, 2000 EFED provided an estimate of the potential coumaphos and
coumaphoxon environmental exposures from the disposal of bioremediated
vat-dip solution for an FQPA assessment (DP266513).  At that time, the
exposure pathway associated with the application of coumaphos to cattle
via spray, that may be equally as important for drinking water
assessment, was not assessed.

No drinking water concerns exist for coumaphos used in beehives within
the honeybee colony in accordance with the coumaphos product label.  The
use of coumaphos impregnated strips, CheckMite+® Pest Control Strip,
within a beehive structure effectively eliminates pathways of exposure
to surface and ground water.

Mammals (via contact with soil and vegetation

Upland Soil and Foliage (via direct application from diposal of vat
solution and washoff from treated cows)

 Cattle

  hide

Altered Aquatic Community Assemblages:

Effects to riparian habitat availability

Effects to food supply

Altered Terrestrial Community Assemblages:

Reduced food supply and edge habitat availability

Indirect

Effects

Aquatic Animals

Effects to survival, growth, and

Reproduction

Other adverse sublethal effects

Non-Target Terrestrial or Riparian/Wetland Plants

Plant growth abnormalities

Lethality

Developmental/reproductive

Effects

 Reduced Population growth

Terrestrial Animal

Lethality

Reproductive/

developmental

Effects

Other adverse sublethal effects

Direct Effects

Aquatic Invert.and

Vertebrates

Aquatic Plants

Riparian/

Wetland

Plants

Terrestrial Upland

Plants

Birds (with soil and cattle)

Receptors

Gill/Integument Uptake

Uptake/Adsorption

Direct Contact/

Root Uptake

Direct Contact

And Ingestion

Exposure Point

Surface Water

Sediment (vat-dip runoff and washoff

from treated cows)

Riparian/Wetland

Foliage/Soil (via runoff and washoff

from treated cows)

Source:

Exposure

Media

Stressor

Roaming cattle with coumaphos treated hides and

disposal of bioremediated vat-dip solution.


[Federal Register Volume 88, Number 151 (Tuesday, August 8, 2023)]
[Notices]
[Page 53479]
[FR Doc No: 2023-16937]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. EF14-1-006]

Southwestern Power Administration; Notice of Filing

    Take notice that on July 7, 2023, Southwestern Power Administration
submits tariff filing: 013 IS Power Rate schedule Amendment P-13B to be
effective 7/15/2023.
    Any person desiring to intervene or to protest this filing must
file in accordance with Rules 211 and 214 of the Commission's Rules of
Practice and Procedure (18 CFR 385.211, 385.214). Protests will be
considered by the Commission in determining the appropriate action to
be taken, but will not serve to make protestants parties to the
proceeding. Any person wishing to become a party must file a notice of
intervention or motion to intervene, as appropriate. Such notices,
motions, or protests must be filed on or before the comment date. On or
before the comment date, it is not necessary to serve motions to
intervene or protests on persons other than the Applicant.
    The Commission strongly encourages electronic filings of comments,
protests and interventions in lieu of paper using the ``eFiling'' link
at http://www.ferc.gov. Persons unable to file electronically may mail
similar pleadings to the Federal Energy Regulatory Commission, 888
First Street NE, Washington, DC 20426. Hand delivered submissions in
docketed proceedings should be delivered to Health and Human Services,
12225 Wilkins Avenue, Rockville, Maryland 20852.
    In addition to publishing the full text of this document in the
Federal Register, the Commission provides all interested persons an
opportunity to view and/or print the contents of this document via the
internet through the Commission's Home Page (http://ferc.gov) using the
``eLibrary'' link. Enter the docket number excluding the last three
digits in the docket number field to access the document. At this time,
the Commission has suspended access to the Commission's Public
Reference Room, due to the proclamation declaring a National Emergency
concerning the Novel Coronavirus Disease (COVID-19), issued by the
President on March 13, 2020. For assistance, contact the Federal Energy
Regulatory Commission at [email protected] or call toll-free,
(886) 208-3676 or TYY,<PHONE_NUMBER>.
    The Commission's Office of Public Participation (OPP) supports
meaningful public engagement and participation in Commission
proceedings. OPP can help members of the public, including landowners,
environmental justice communities, Tribal members and others, access
publicly available information and navigate Commission processes. For
public inquiries and assistance with making filings such as
interventions, comments, or requests for rehearing, the public is
encouraged to contact OPP at<PHONE_NUMBER> or [email protected].
    Comment Date: 5:00 p.m. Eastern Time on August 7, 2023.

    Dated: August 2, 2023.
Debbie-Anne A. Reese,
Deputy Secretary.
[FR Doc. 2023-16937 Filed 8-7-23; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register: November 2, 2009 (Volume 74, Number 210)]
[Notices]
[Page 56677-56679]
[DOCID:fr02no09-89]

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SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-60880; File No. SR-NASDAQ-2009-090]

Self-Regulatory Organizations; The NASDAQ Stock Market LLC;
Notice of Filing and Immediate Effectiveness of a Proposed Rule Change
To Permit Listing Option Series That Are Restricted to Closing
Transactions if Such Series Are Listed and Restricted to Closing
Transactions on Another National Securities Exchange

October 26, 2009.
    Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934
(``Act'') \1\, and Rule 19b-4 \2\ thereunder, notice is hereby given
that on October 16, 2009, The NASDAQ Stock Market LLC (``Nasdaq'')
filed with the Securities and Exchange Commission (``SEC'' or
``Commission'') the proposed rule change as described in Items I and
II, below, which Items have been prepared by Nasdaq. Nasdaq filed the
proposal as

a ``non-controversial'' proposed rule change pursuant to Section
19(b)(3)(A)(iii) of the Act \3\ and Rule 19b-4(f)(6) thereunder.\4\ The
Commission is publishing this notice to solicit comments on the
proposed rule change from interested persons.
---------------------------------------------------------------------------

    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
    \3\ 15 U.S.C. 78s(b)(3)(A)(iii).
    \4\ 17 CFR 240.19b-4(f)(6).
---------------------------------------------------------------------------

I. Self-Regulatory Organization's Statement of the Terms of Substance
of the Proposed Rule Change

    NASDAQ is filing a proposal for the NASDAQ Options Market (``NOM''
or ``Exchange'') to amend its Chapter IV, Section 4 (Withdrawal of
Approval of Underlying Securities) to permit the Exchange to list
option series that are restricted to closing transactions if such
series are listed and restricted to closing transactions on another
exchange. The Exchange requests that the Commission waive the 30-day
operative delay period contained in Exchange Act Rule 19b-
4(f)(6)(iii).\5\
---------------------------------------------------------------------------

    \5\ 17 CFR 240.19b-4(f)(6)(iii).
---------------------------------------------------------------------------

    The text of the proposed rule change is available from Nasdaq's Web
site at http://nasdaq.cchwallstreet.com, at Nasdaq's principal office,
and at the Commission's Public Reference Room.

II. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

    In its filing with the Commission, Nasdaq included statements
concerning the purpose of and basis for the proposed rule change and
discussed any comments it received on the proposed rule change. The
text of these statements may be examined at the places specified in
Item IV below. Nasdaq has prepared summaries, set forth in sections A,
B, and C below, of the most significant aspects of such statements.

A. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

1. Purpose
    The purpose of the proposed rule change is to amend NOM Chapter IV,
Section 4 to permit the Exchange to list option series that are
restricted to closing transactions if such series are listed and
restricted to closing transactions on another exchange.
    This filing is based on a similar immediately effective filing
recently filed by another options exchange, Chicago Board Options
Exchange (``CBOE'').\6\ In that filing, it was noted that the impetus
for the filing was a customer request for it to list a series of
options that was previously delisted by the filing exchange but listed
on another exchange and restricted to closing transactions, a situation
that may equally occur on NOM as well as other options exchanges.
---------------------------------------------------------------------------

    \6\ See Securities Exchange Act Release No. 60625 (September 4,
2009), 74 FR 46825 (September 11, 2009) (SR-CBOE-2009-066) (notice
of filing and immediate effectiveness).
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    Chapter IV, Section 3 (Criteria for Underlying Securities) sets
forth the requirements or criteria that underlying securities must meet
before the Exchange may initially list options on such securities.
Chapter IV, Section 4 sets forth listing maintenance and delisting
criteria in respect of securities underlying options listed on the
Exchange that are used by the Exchange to determine whether such
listing status should be continued. These rules do not have provisions
for listing option series that are restricted to closing transactions
where such series are listed on another exchange.
    The Exchange proposes to add new subsection (m) to Chapter IV,
Section 4 to provide that if an option series is listed but restricted
to closing transactions on another national securities exchange, the
Exchange may list such series (even if such series would not otherwise
be eligible for listing under the Exchange's rules), which shall also
be restricted to closing transactions on the Exchange.\7\ No
restrictions will be in place with respect to the exercise of any
restricted series.
---------------------------------------------------------------------------

    \7\ The parenthetical text is being proposed to eliminate
ambiguity about the Exchange's ability to list a restricted series
pursuant to proposed subsection (m) to Chapter IV, Section 4 in the
event other Exchange rules would otherwise prohibit the listing of
that series.
---------------------------------------------------------------------------

    The Exchange believes that the proposed rule change should
encourage competition and be beneficial to traders and market
participants by providing them with a means to trade on the Exchange
securities that are listed and traded on other exchanges.
2. Statutory Basis
    The Exchange believes that its proposal is consistent with Section
6(b) of the Act \8\ in general, and furthers the objectives of Section
6(b)(5) of the Act \9\ in particular, in that it is designed to prevent
fraudulent and manipulative acts and practices, to promote just and
equitable principles of trade, to foster cooperation and coordination
with persons engaged in facilitating transactions in securities, and to
remove impediments to and perfect the mechanisms of a free and open
market and a national market system. Permitting the Exchange to
accommodate possible customer requests and allow execution of trades on
the Exchange will encourage competition and not harm investors or the
public interest.
---------------------------------------------------------------------------

    \8\ 15 U.S.C. 78f(b).
    \9\ 15 U.S.C. 78f(b)(5).
---------------------------------------------------------------------------

B. Self-Regulatory Organization's Statement on Burden on Competition

    Nasdaq does not believe that the proposed rule change will result
in any burden on competition that is not necessary or appropriate in
furtherance of the purposes of the Act.

C. Self-Regulatory Organization's Statement on Comments on the Proposed
Rule Change Received From Members, Participants, or Others

    Written comments were neither solicited nor received.

III. Date of Effectiveness of the Proposed Rule Change and Timing for
Commission Action

    The Exchange believes that the foregoing proposed rule change may
take effect upon filing with the Commission pursuant to Section
19(b)(3)(A) \10\ of the Act and Rule 19b-4(f)(6)(iii) thereunder \11\
because the foregoing proposed rule change does not: (i) Significantly
affect the protection of investors or the public interest; (ii) impose
any significant burden on competition; and (iii) become operative for
30 days from the date on which it was filed, or such shorter time as
the Commission may designate, if consistent with the protection of
investors and the public interest.\12\
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    \10\ 15 U.S.C. 78s(b)(3)(A).
    \11\ 17 CFR 240.19b-4(f)(6)(iii).
    \12\ In addition, Rule 19b-4(f)(6)(iii) requires the self-
regulatory organization to submit to the Commission written notice
of its intent to file the proposed rule change, along with a brief
description and text of the proposed rule change, at least five
business days prior to the date of filing of the proposed rule
change, or such shorter time as designated by the Commission. Nasdaq
has satisfied this requirement.
---------------------------------------------------------------------------

    A proposed rule change filed under Rule 19b-4(f)(6) normally may
not become operative prior to 30 days after the date of filing.
However, Rule 19b-4(f)(6)(iii) \13\ permits the Commission to designate
a shorter time if such action is consistent with the protection of
investors and the public interest. The Exchange has requested that the
Commission waive the 30-day operative delay period. The Commission
believes that waiver of the 30-day operative delay period is consistent
with the protection of investors and the public interest. In
particular, the Exchange would be permitted to list the restricted

series solely for the purpose of closing transactions as long as the
restricted series is listed on another national securities exchange. In
addition, the proposed rule change is substantially similar to the
rules of CBOE.\14\ The Commission therefore designates the proposal
operative upon filing.\15\
---------------------------------------------------------------------------

    \13\ 17 CFR 240.19b-4(f)(6)(iii).
    \14\ See CBOE Rule 5.4.12(b).
    \15\ For purposes only of waiving the operative delay for this
proposal, the Commission has considered the proposed rule's impact
on efficiency, competition, and capital formation. See 15 U.S.C.
78c(f).
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    At any time within 60 days of the filing of the proposed rule
change, the Commission may summarily abrogate such proposed rule change
if it appears to the Commission that such action is necessary or
appropriate in the public interest, for the protection of investors, or
otherwise in furtherance of the purposes of the Act.\16\
---------------------------------------------------------------------------

    \16\ 15 U.S.C. 78s(b)(3)(C).
---------------------------------------------------------------------------

IV. Solicitation of Comments

    Interested persons are invited to submit written data, views, and
arguments concerning the foregoing, including whether the proposed rule
change is consistent with the Act. Comments may be submitted by any of
the following methods:

Electronic Comments

     Use the Commission's Internet comment form (http://
www.sec.gov/rules/sro.shtml); or
     Send an e-mail to<EMAIL_ADDRESS>Please include
File Number SR-NASDAQ-2009-090 on the subject line.

Paper Comments

     Send paper comments in triplicate to Elizabeth M. Murphy,
Secretary, Securities and Exchange Commission, 100 F Street, NE.,
Washington, DC 20549-1090.

All submissions should refer to File Number SR-NASDAQ-2009-090. This
file number should be included on the subject line if e-mail is used.
To help the Commission process and review your comments more
efficiently, please use only one method. The Commission will post all
comments on the Commission's Internet Web site (http://www.sec.gov/
rules/sro.shtml). Copies of the submission, all subsequent amendments,
all written statements with respect to the proposed rule change that
are filed with the Commission, and all written communications relating
to the proposed rule change between the Commission and any person,
other than those that may be withheld from the public in accordance
with the provisions of 5 U.S.C. 552, will be available for inspection
and copying in the Commission's Public Reference Room, 100 F Street,
NE., Washington, DC 20549, on official business days between the hours
of 10 a.m. and 3 p.m. Copies of such filing also will be available for
inspection and copying at the principal office of Nasdaq. All comments
received will be posted without change; the Commission does not edit
personal identifying information from submissions. You should submit
only information that you wish to make available publicly. All
submissions should refer to File Number SR-NASDAQ-2009-090 and should
be submitted on or before November 23, 2009.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\17\
---------------------------------------------------------------------------

    \17\ 17 CFR 200.30-3(a)(12).
---------------------------------------------------------------------------

Florence E. Harmon,
Deputy Secretary.
[FR Doc. E9-26255 Filed 10-30-09; 8:45 am]

BILLING CODE 8011-01-P


[Federal Register Volume 87, Number 204 (Monday, October 24, 2022)]
[Notices]
[Pages 64227-64229]
[FR Doc No: 2022-23034]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-N-2391]

Miles Laboratories Inc.; Proposal To Withdraw Approval of an
Abbreviated New Drug Application for Alcohol and Dextrose Injection; 5
Milliliters/100 Milliliters, 5 Grams/100 Milliliters; Opportunity for a
Hearing

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration's (FDA or Agency) Center for
Drug Evaluation and Research (CDER) is proposing to withdraw approval
of an abbreviated new drug application (ANDA) for Alcohol and Dextrose
Injection, 5 milliliters (mL)/100 mL, 5 grams (g)/100 mL, and is
announcing an opportunity for the ANDA holder to request a hearing on
this proposal: Miles Laboratories Inc., P.O. Box 1986, 4th and Parker
St., Berkeley, CA 94701, is the last holder of record. The bases for
the proposal are that the ANDA holder has repeatedly failed to file
required annual reports for this ANDA and that the Agency has
scientific data and experience to show that the drug product under this
ANDA is unsafe for use under the conditions of use for which the
product was approved.

DATES: The ANDA holder may submit a request for a hearing by November
23, 2022. Submit all data, information, and analyses upon which the
request for a hearing relies by December 23, 2022. Submit electronic or
written comments by December 23, 2022.

ADDRESSES: The request for a hearing may be submitted by the ANDA
holder by either of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments to submit your request
for a hearing. Comments submitted electronically to https://www.regulations.gov, including any attachments to the request for a
hearing, will be posted to the docket unchanged.

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     Because your request for a hearing will be made public,
you are solely responsible for ensuring that your request does not
include any confidential information that you or a third party may not
wish to be posted, such as medical information, your or anyone else's
Social Security number, or confidential business information, such as a
manufacturing process. The request for a hearing must include the
Docket No. FDA-2022-N-2391 for ``Miles Laboratories Inc.; Proposal To
Withdraw Approval of an Abbreviated New Drug Application for Alcohol
and Dextrose Injection, 5 Milliliters/100 Milliliters, 5 Grams/100
Milliliters; Opportunity for a Hearing.'' The request for a hearing
will be placed in the docket and publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday,<PHONE_NUMBER>.
    The ANDA holder may submit all data and analyses upon which the
request for a hearing relies in the same manner as the request for a
hearing except as follows:
     Confidential Submissions--To submit any data analyses with
confidential information that you do not wish to be made publicly
available, submit your data and analyses only as a written/paper
submission. You should submit two copies total of all data and
analyses. One copy will include the information you claim to be
confidential with a heading or cover note that states ``THIS DOCUMENT
CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy,
including the claimed confidential information, in its consideration of
any decisions on this matter. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov
or available at the Dockets Management Staff between 9 a.m. and 4 p.m.,
Monday through Friday,<PHONE_NUMBER>. Submit both copies to the Dockets
Management Staff. Any information marked as ``confidential'' will not
be disclosed except in accordance with Sec.  10.20 (21 CFR 10.20) and
other applicable disclosure law.
    Comments Submitted by Other Interested Parties: For all comments
submitted by other interested parties, submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that

identifies you in the body of your comments, that information will be
posted on https://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2022-N-2391 for ``Miles Laboratories Inc.; Proposal To Withdraw
Approval of an Abbreviated New Drug Application for Alcohol and
Dextrose Injection, 5 Milliliters/100 Milliliters, 5 Grams/100
Milliliters; Opportunity for a Hearing.'' Received comments, those
filed in a timely manner (see ADDRESSES), will be placed in the docket
and, except for those submitted as ``Confidential Submissions,''
publicly viewable at https://www.regulations.gov or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with Sec.  10.20 and other applicable
disclosure law. For more information about FDA's posting of comments to
public dockets, see 80 FR 56469, September 18, 2015, or access the
information at https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852,<PHONE_NUMBER>.

FOR FURTHER INFORMATION CONTACT: Kaetochi Okemgbo, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6224, Silver Spring, MD 20993-0002, 301-
796-1546.

SUPPLEMENTARY INFORMATION: On November 22, 1974, FDA approved ANDA
083483 for Alcohol and Dextrose Injection. In a letter dated June 23,
1999, Bayer Corporation, which had at least partially acquired Miles
Laboratories Inc., notified FDA that Alcohol and Dextrose Injection, 5
mL/100 mL, 5 g/100 mL, the subject of ANDA 083483, was no longer
marketed, and FDA moved the drug product to the ``Discontinued Drug
Product List'' section of the ``Approved Drug Products With Therapeutic
Equivalence Evaluations,'' which is known generally as the ``Orange
Book.'' FDA has not received information specified in 21 CFR 314.72 to
change the ownership of ANDA 083483, although Miles Laboratories Inc.
does not appear to be separately manufacturing drug products. The
Agency is therefore identifying Miles Laboratories Inc. as the ANDA
holder of record in this Federal Register notice, but in the event that
another entity holds ANDA 083483, the Agency is also providing notice
to that entity.
    The holder of an approved ANDA to market a new drug for human use
is required to submit annual reports to FDA concerning its approved
ANDA under Sec. Sec.  314.81 and 314.98 (21 CFR 314.81 and 314.98).
Because the holder of ANDA 083483 for Alcohol and Dextrose Injection, 5
mL/100 mL, 5 g/100 mL, has repeatedly failed to submit the required
annual reports, FDA proposes to withdraw approval of ANDA 083483 under
Sec.  314.150(b)(1) (21 CFR 314.150(b)(1)).
    Additionally, under 21 CFR 314.161, FDA has determined that Alcohol
and Dextrose Injection, 5 mL/100 mL, 5 g/100 mL, approved under ANDA
083483 was withdrawn from sale for safety and effectiveness reasons
(see 86 FR 72606 (December 22, 2021)) (this determination also applied
to other applications and to the 10 mL/100 mL, 5 g/100 mL strength of
Alcohol and Dextrose Injection approved under NDA 004589). In light of
our determination, FDA proposes to withdraw approval of ANDA 083483
under Sec.  314.150(a)(2)(i) because the Agency has scientific data and
experience to show that Alcohol and Dextrose Injection, 5 mL/100 mL, 5
g/100 mL, is unsafe for use under the conditions of use for which the
product was approved.
    As explained in our Federal Register notice determining that
Alcohol and Dextrose was withdrawn for safety and effectiveness
reasons, Alcohol and Dextrose Injection is indicated to provide
increased caloric intake. The use of Alcohol and Dextrose raises
several safety concerns because there are many risks associated with
the exposure to alcohol. Today, alcohol is contraindicated for use in
patients with neurologic disorders, such as seizures, who have current
or past substance abuse problems or who are pregnant. It can cause
intoxication, respiratory depression, and disturbances in serum glucose
levels. FDA-approved alternatives for intravenous calorie
supplementation that do not include alcohol were approved after these
Alcohol and Dextrose products and are available today.
    Therefore, notice is given to the ANDA holder and to all other
interested persons that the Director of CDER proposes to issue an
order, under section 505(e)(2) of the Federal Food, Drug, and Cosmetic
Act (FD&C Act) (21 U.S.C. 355(e)(2)), withdrawing approval of ANDA
083483 and all amendments and supplements thereto on the grounds that:
(1) the ANDA holder has failed to submit reports required under
Sec. Sec.  314.81 and 314.98 and section 505(k) of the FD&C Act, and
(2) the Agency has scientific data and experience to show that Alcohol
and Dextrose Injection, 5 mL/100 mL, 5 g/100 mL, is unsafe for use
under the conditions of use for which the product was approved.
    In accordance with section 505(e) of the FD&C Act and Sec. Sec.
314.150(a)(2)(i) and (b)(1) and Sec.  314.200 (21 CFR 314.200), the
ANDA holder is hereby provided an opportunity for a hearing to show why
the approval of ANDA 083483 should not be withdrawn and an opportunity
to raise, for administrative determination, all issues relating to the

legal status of the drug product covered by ANDA 083483.
    An ANDA holder who decides to seek a hearing must file the
following: (1) a written notice of participation and request for a
hearing (see DATES and ADDRESSES) and (2) the data, information, and
analyses relied on to demonstrate that there is a genuine and
substantial issue of fact that requires a hearing (see DATES and
ADDRESSES). Any other interested person may also submit comments on
this notice. The procedures and requirements governing this notice of
opportunity for a hearing, notice of participation and request for a
hearing, the information and analyses to justify a hearing, other
comments, and a grant or denial of a hearing are contained in Sec.
314.200 and in 21 CFR part 12.
    The failure of an ANDA holder to file a timely written notice of
participation and request for a hearing, as required by Sec.  314.200,
constitutes an election by that ANDA holder not to avail itself of the
opportunity for a hearing concerning CDER's proposal to withdraw
approval of the ANDA and constitutes a waiver of any contentions
concerning the legal status of the drug product. FDA will then withdraw
approval of the ANDA, and the drug product may not thereafter be
lawfully introduced or delivered for introduction into interstate
commerce. Any new drug product introduced or delivered for introduction
into interstate commerce without an approved ANDA is subject to
regulatory action at any time.
    A request for a hearing may not rest upon mere allegations or
denials but must present specific facts showing that there is a genuine
and substantial issue of fact that requires a hearing (Sec.
314.200(g)). If a request for a hearing is not complete or is not
supported, the Commissioner of Food and Drugs will enter summary
judgment against the person who requests the hearing, making findings
and conclusions, and denying a hearing (Sec.  314.200(g)(1)).
    All submissions under this notice of opportunity for a hearing must
be filed in two copies. Except for data and information prohibited from
public disclosure under 21 U.S.C. 331(j) or 18 U.S.C. 1905, the
submissions may be seen at the Dockets Management Staff (see ADDRESSES)
between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to
the docket at https://www.regulations.gov.
    This notice is issued under section 505(e) of the FD&C Act and
under authority delegated to the Director of CDER by the Commissioner
of Food and Drugs.

    Dated: October 14, 2022.
Patrizia Cavazzoni,
Acting Director, Center for Drug Evaluation and Research.
[FR Doc. 2022-23034 Filed 10-21-22; 8:45 am]
BILLING CODE 4164-01-P