Unit ad Ststtt
Environ man tal Protection
Agancy
Offica of Partictd« and Toxic Subctancoa
Offica of Pastidda Program (TS-7S6C1
Washington, DC 20460
540/FS-88-107
vvEPA Pesticide
Fact Sheet

Name of Chemical: ethoprop
Reason for Issuance: Registration Standard
Date Issued:	June 30, 1988
Fact Sheet Number: 3:2
1.	DESCRIPTION OF CHEMICAL
Generic Name: 0-ethyl S,S - dipropyl phosphorodithioate
Common Name: Ethoprop
Empirical Formula: CgHjg O2PS2
Trade Names: Mocap*, VC 9-104
EPA Pesticide Chemical
(Shaughnessy) Number: 041101
Chemical Abstract Service Number (CAS): 13194-48-4
Pesticide Type: Insecticide, Nematocide, and Fungicide
Chemical Class: Organophosphate
O.S. Registrant: Rhone - Poulenc, Inc.
2.	USE PATTERNS AND FORMULATIONS
Application Sites:
Food crop application of ethoprop: bananas,
broccoli (EUP), cabbage, califlower (EUP),
corn grain, corn fodder and forage, cucumbers,
mushrooms, okra, fresh corn including sweet
corn (kernals plus cob with husk removed),
lima beans, lima bean foage, snap beans, snap
bean forage, peanuts, peanut hay, pineapples,
pineapple fodder and forage, potatoes, soybeans,
soybean forage and hay, sugarcane, sugarcane
fodder and forage, and sweet potatoes (40 CFR
$180.31 and $180,262). There are no internat-
ional tolerances or Codex Maximum Residue Limits
for residues of ethoprop. The ethoprop toler-
ance (40 CFR $180,262) should be revised to read,
"pineapples, pineapple fodder and forage,"
instead of "Pineapple fodder and forage.¦

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3. SCIENCE FINDINGS
Summary Science Statement
Ethoprop is an organophosphate insecticide whose primacy
mechanism of toxicity is cholinesterase inhibition. Animal
studies have shown that ethoprop inhibits plasma, erythrocyte,
and brain cholinesterase activity. Technical ethoprop is
highly toxic (Toxicity Category I to mammals when acutely
administered orally, dermally, or via inhalation). Applica-
tion of 0.1 ill of undiluted ethoprop (technical) into rabbit
eyes for the eye irritation test produced 100% mortality
within one hour post exposure (Toxicity Categroy I). No
delayed neurotoxicity was observed in hens administered
approximately 70% ethoprop.
Treatment-related inhibition of brain, erythrocyte, and
plasma cholinesterase activities were observed in a rat sub-
chronic feeding study (90 days). The pattern of cholinesterase
inhibition suggested that the no observable effect level
(NOEL) for cholinesterase depression was approximately 0.3 ppm
(0.015 mg/kg/day). Cholinesterase inhibition (plasma and
erythrocyte) was also judged to have occurred at the lowest
dose tested (1.0 ppm).
The potential chronic toxicity, oncogenicity, teratology,
and reproductive toxicity of ethoprop could not be fully eval-
uated with the available data (see pages 4,5,6 for the details)
Additional information is required.
An acceptable battery of mutagenicty tests (gene mutation,
chromosomal abberation, and DNA damage) was submitted. In
the presence of a metabolic activation system, ethoprop was
determined to be a genotoxic agent in vitro in two types of
chromosomal aberration studies. Ethoprop was not determined
to be a mutagen in two gene mutations studies. For DNA
damage, an assay determined ethoprop to be inactive (negative).
Four special studies are required to address certain
questions which arose in the assessment of the ethoprop data-
base. The first is designed to determine a NOEL for cholin-
esterase inhibition in the rat, the second to resolve issues
in the dog chronic feeding study (including the determination
of a NOEL for cholinesterase inhibition in the dog), the third
to confirm in vitro genotoxic findings with an in vivo cyto-
genic assay, and the fourth to resolve the issue of eye lesions
noted in the mouse oncogenicity study.

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The Agency is unable to provide a quantitative esti-
mate of the ethoprop potential for groundwater contamination.
Ethoprop was found to be very mobile in columns of loam soil
types. Additional studies are required to assess the potent-
ial for groundwater contamination including hydrolysis,
photolysis in water and soils, leaching of soil degradates,
and field dissipation.
Chemical/Physical Characteristics Of Ethoprop (Technical)
"Clear yellow tinted liquid with a strong mercaptan
odor.
"Boiling point 86-9l°C at 0.2 mm Hg.
"Solubility in water to 843 ppm at 21°C and soluble
in most organic solvents.
°No corrosion observed on SAE type 1020 steel or
aluminum foil of the type used to line a bag of
granular formulation 332 hours at 21°C.
Toxicological Characteristics
Acute Oral Toxicity: Toxicity Category I [LD50 (mg/kg;
rats): males, 61.03 (49.19-75.01)J;females, 32.8 (25.41-
42.44).
Acute Dermal Toxicity: Toxicity Category I [ LD50 (mg/kg;
rabbits): 25.7 (14.44-45.83) mg/kg].
Acute Inhalation: Toxicity Category I [LC50 (mg/1;
rats): 0.12 (0.08-0.17)].
Primary Dermal Irritation: Toxicity Category I. All
rabbits died within 8 hours post exposure. No primary irrit-
ation index was obtainable.
Primary Eye Irritation: Toxicity Categroy I. All rab-
bits died within one hour post exposure.
Skin Sensitization: Data was not submitted, and not
required because of the early onset of death observed in
the other acute tests.
Delayed Neurotoxicity: No acute delayed neurotoxicity
was observed in the hen. The oral LD50 (hens) of Mocap EC
is 9.9 (8.8-12.1) mg/kg

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Subchronic Dermal Toxicity: The study reviewed was con-
sidered supplementary because large variations exhisted in
plasma and erythrocyte cholinesterase levels observed among
the animals on test. An acceptable study is required.
Subchronic Feeding Studies: (Non-rodent) - An acceptable
13-week study was conducted using the beagle dog. Ethoprop
(technical) was tested using dietary dose levels of 1.0, 3.0,
and 100 ppm. Cholinesterase inhibition was the only treatment
related effect noted. No toxicological significant inhibition
of plasma or erythrocyte cholinesterase was judged to have
occurred at the lowest dose tested (1.0 ppm; 0.075 mg/kg/day).
The lowest effect level for cholinesterase depression was 3.0
ppm (0.225 mg/kg/day).
(Rodent) - The subchronic feeding study (rats; Charles River)
is considered supplemental, and has been used to establish a
provisional acceptable daily intake (PADI). Three groups of
25 albino rats per sex were fed ethoprop technical in the daily
diet at doses of 0, 0.3, 1.0 or 100 ppm for 90 days. The
pattern of cholinesterase inhibition suggests that the NOEL
is approximately 0.3 ppm (0.015 mg/kg/day). A new subchronic
rat study is not required provided an acceptable rat chronic
feeding study is conducted. The data obtained from the chronic
study will suffice in this case for the information needed for
a subchronic oral toxicity study.
Chronic Toxicity
Due to various deficiences, the available studies for
nonrodent and rodent chronic toxicity do not fulfill current
requirements. Adequate data are needed. Beagle dogs were
fed ethoprop in their diets at 0, 0.025, 1.0 and 10 mg/kg/day
for 52 weeks. Plasma cholinesterase (ChE) was inhibited in
females at all dose levels. Whereas, the mid- and high dose
levels are effect levels for erythrocyte ChE inhibition, and
the high-dose is an effect level for brain ChE inhibition.
Also, all male dogs at all dose levels exhibited less weight
gain than the control group. No NOEL could be determined
from the study.
In order to determine a NOEL for plasma erythrocyte and
and the issue of decreased male body weight gain in all test
groups, the Agency is requiring an abbreviated study of 17
weeks.
In the chronic feeding study, Fisher 344 rats were fed
0, 4.5, 9.0 and 18 ppm of ethroprop for 12 weeks, and then
placed on diets of 0, 49, 98 or 196 ppms for the remaining
52 weeks. Cholinesterase inhibition was observed at all
the dose levels and a N0E1 could not be determined. The
MTD was considered to be the highest dose tested. The study
is considered supplemental, and additional information is
requi red.
The one year dog chronic feeding study is evaluated to
be inadequate, but does not need to be repeated. The Agency

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is requiring specified special studies to resolve the defic-
iencies noted in the one-year dog chronic feeding study. The
Agency review for chronic and oncogenic potential in rats
(MRID 00138636) indicated that for the chronic feeding portion
of this study the classification was core - supplemental. It
cannot be upgraded since no NOEL for cholinesterase inhibition
was observed. At all doses of ethoprop tested, cholinesterase
inhibition of >20% was observed. Additional information must
be submitted. In addition, the Agency is requiring summary
incidence tables for clinical observations.
Oncogenicity
The requirements for oncognicity testing (two species)
are not fulfilled, and data must be submitted. B6C3F1 mice
were fed 0, 15, 30, and 60 ppm of ethoprop in their diet
for 78 weeks. The study did not demonstrate oncoginic effects
under the conditions of this study. However, the highest dose
tested <60 ppm) is considered to be at least two times under
the maximum tolerated dose. This study is considered supple-
mental.
Fisher 344 rats were fed 0. 4.5, 9.0, and 18 ppm of
ethoprop for 12 weeks, and then placed on diets containing 0,
49, 98, or 196 ppm of ethoprop for the remaining 52 weeks.
Under the conditions of this study, there was an increase in
the number of C-cell adenomas of the thyroid in males re-
ceiving the high-dose when compared to controls, and there
was a dose-felated increase in the number of endometrial
polyps in females. However, the total number of individual
tissues examined histologically per group was not presented.
Consequently, the incidence of these lesions cannot be deter-
mined or analyzed statistically, and an evaluation of the
oncogenic potential of ethoprop cannot be performed from
the reported study. This study is considered by the Agency
to be supplementary. Additional data are required.
Teratology
Ethoprop technical was adminstered by oral intubation
to groups of Sprague-Dawley rats at doses of 0. 0.16, 1.6,
and 16.0 mg/kg/day (MRID 00104532). However, based on the
data presented and the current guidelines for examining
teratology studies, the potential of the test material to
cause developmental toxicity cannot be fully evaluated.
More specifically, certain deficienceis were noted in the
rat study at the time the initial registration standard
was prepared (although occurrances of compound-related terata
were not). At that time, a request was made for historical
control data with regard to parameters such as delayed
ossification. Apparently, these data were not submitted.
Since then, new Agency guidelines have stressed that obser-
vations be made for all aspects of developmental toxicity,
and not just occurrances of terata. For these reasons.

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complete historical control data for all measured fetal
and maternal parameters (details in MRID 00104532) and
individual litter data for all measured fetal parameters
are now required. The issue of potential developmental
toxicity in the rat needs to be addressed before the status
of the study (now supplemental) can be upgraded.
A teratology study in New Zealand White rabbits was
submitted in which ethoprop technical was administered by
gavage to groups of animals at doses of 0, 0.125, 0.500,
and 2.00 mg/kg. Since the data submitted in the study
were not sufficient to fully evaluate such things as
whether test material adminstration resulted in maternal
toxicity or resulted in an increase in skeletal variations,
a NOEL and LEL for maternal and developmental toxicity
could not be determined. Additional data, including his-
torical control data for fetal and maternal parameters, are
needed for the resolution of these issues (MRID 00161619).
Reproduction
A three-generation study in Fisher 344 rats in which
ethoprop technical was administered at dose levels of 0,
60.5, 131, and 262 ppm was not sufficient to satisfy the data
requirements for reproductive toxicity (MRID 00162164). The
data presented was considered insufficient to determine a NOEL
and LEL for maternal and developmenal toxicity, because question^
were raised with regard to such things as culling procedures anc*
the appropriateness of other parts of the protocol, animal ill-
ness, lack of food consumption and diet analysis data, inadeqate
data presentation, and descrepancies in data reporting.
Mutagenicity; An acceptable battery of mutagenic tests
(gene mutation, negative; chromosomal abberation, positive;
and DNA damage, inactive) were evaluated. An acceptable
bone marrow cytogenetic analysis in rats is needed to provide
in vitro confirmation of in vitro findings in the chromosomal
abberation studies submitted.

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Metabolism: Available studies do not fulfil the re-
quirement for metabolism data. However in one study the
metabolites O-ethyl-S-propylphosphorothioic acid and O-
ethyl-phosphoric acid, as well as ethoprop, were detected
in the urine. An acceptable study is required.
Special Studies: The following special studies are
required to address questions generated from the evalu-
ation of the submitted data:
A special study is required in rats for the purpose
of determining a definitive NOEL for plasma, erythrocyte,
and brain cholinesterase inhibition. A protocol must be
submitted to the Agency for approval prior to commencement'
of this study.
A subchronic feeding study in dogs is required to
address issues of decrease in animal body weight gain and
the lack of a NOEL for cholinesterase inhibition in the
present 1-year study. This study is required for purposes
of determining a most sensitive species for cholinesterase
inhibition. A protocol must be submitted to the Agency
prior to initiation of this study.
An acceptable rat bone marrow cytogenetic analysis
study is required for in vivo confirmation of in vitro
cytogenetic findings observed in the chromosomal aberration
studies.
Two 60-day mouse studies are required in order to
resolve the question of whether eye lesions observed in
the 78-week mouse oncogeniciy study were systemic effects
of the test material administration. One test must be by
oral g*vage in the B6C3F1 mouse, and the other one must
be a dietary study in another mouse strain.
Environmental Characteristics
Data on the metabolism of ethoprop in plants are not
considered adequate. These data identified several metabo-
lites of ethoprop, but did not quantitate them. Given the
nature of this chemical, unusual or exceptionally toxic
metabolites are not expected. Quantitation of known and/or
supposed metabolites will allow a more complete toxicological
evaluation. Additional data form 14 C-radiolableled exper-
iments on corn, potatoes, and cabbage are needed. Although
not required previously, metabolism studies on ruminants and
poultry are now needed to elucidate the pathway for metabolism
of ethoprop in animals. Tolerances for ethoprop are currently
expressed in terms of parent compound per se, and will be
reassessed when the additional required studies are submitted
and reviewed.

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The Agency is unable to provide a quantitative estimation
of the ethoprop potential for groundwater contamination.
Ithoprop was found to be very mobile in columns of loamy
sand and loam soil types. Additional studies are required to
assess the potential for ground water contamination including
hydrolysis, photolysis in water and soils, leaching of soil
degradates, and field dissipation.
Ecological Characteristics
Birds
Ethoprop technical is highly toxic to bird species on
acute oral, dietary, and dermal bases. Acceptable acute and
subchronic dietary toxicity studies are available. Field
dissipation studies which will more accurately define acute
hazards to bird species inhabiting treated areas are required.
Avian reproduction studies may be needed if it is found that
ethoprop residues remain at significant levels in the field
for an extended period of time. Acute and simulated field
studies show sufficient hazard to wildlife to require the
following field studies: 1) One study with the emulsifiable
concentrate on pineapples. 2) One study with the granular
product (G) on corn or potatoes.
-Ring-neck pheasants; 95% a.i.j oral LD50 «= 118 (103-
134 mg/kg).
-Bobwhite quail; 95% a.i.; oral LD50 - 33
(27-40 mg/kg).
-Mallards; *LC50 - 287 (215-382 mg/kg).
Aquatic Studies
Technical ethoprop is very highly toxic to aquatic
invertebrates. It is moderately to highly toxic to rainbow
trout and highly toxic to bluegills, crustaceans, and marine
fish species. Ethoprop is slightly toxic to embryo larvae of
oyster species. Further assessment to the potential hazards
to aquatic organisms cannot be made until certain environ-
mental fate data are submitted and reviewed. At that time an
estimated environmental concentration (EEC) will be developed.
Further aquatic data requirements will be reserved until the
EEC and environmental fate data are available.
-	Rainbow trout; 95% a.i.; LC50 = 1.02 (0.56-2.10) mg/1.
-	Bluegills; 95% a.i.; LC50 = 0.30 (0.23-0.40 mg/1).
-	Mysidopsis bahai (shrimp); LC50 = 23 ppb.
-	Callinectes sapidus (blue crabs); 100% mortality at
24 hours when exposed to 1 ppm.
-	Cyprinidon varieatus (sheepshead minnows); LC50 (static
tank; 96 hours testing) = 748.3 ppb.
-	Leiostomus xanthurus (spot); LC50 (static tank; 96 hours
testing) » 32 ppb.
-	Cyprinidon varieatus (sheepshead minnows); flow thru

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tank; 96 hours testing; LC50 ¦ 232.67 ppb.
~ Laqodon rhomboides (pinfish); flow thru tank? 96 hours
testing; LC50 - 7,2 ppb.
- Oyster species (embryo larvae)95% a.i.; EC50 - 11.0
5.6-32 ppm).
Tolerance Assessment
Tolerances for residues of ethoprop in or On food commod-
ities are published in 40 CFR S180.262 and §180.31. The tol-
erances are set at 0.02 ppm for all the listed commodities.
A conclusive tolerance reassessment was not made at this time
due to lack of data for the following; a) The metabolism of
ethoprop in plants and animals, b) Storage stability, c) Re-
sidue and toxicity studies. Additional data are required.
A final reevaluation of the tolerances and ADI will be made
as soon as the requested data concerning storage stability,
metabolism* residue, and toxicitiy are reevaluated. No
new tolerances for ethoprop will be granted in the interim.
Data on the metabolism of ethoprop in plants are not
considered adequate. These data indentified several plant
metabolites of ethoprop, but did not quantitate them. Given
the nature of this chemical, unusual or exceptionally toxic
metabolites are not expected. Quantitation of known and/
or supposed metabolites will allow a more complete toxic-
ological evaluation. Additional data from ^C-radiolabled
experiments on corn, potatoes, and cabbage are needed.
Although not required previously, metabolsim studies on
ruminants and poultry are now needed to eludidate the path-
way for metabolism of ethoprop in animals. Tolerances for
ethoprop are currently expressed in terms of parent compound
per se, and will be reassessed when the additional required
studies are submitted and reviewed.
Adequate analytical methodologies are available for en
forcement of the present tolerances in terms of ethoprop per
se. Ethoprop is completely recovered by the multiresidue
procedures in the Pesticide Analytical Manual (vol. 1, proto-
cols II and III), and partially recovered by protocol I. No
data are available for protocol IV. These data are required.
If any metabolites of toxicological concern are identified in
the metabolism studies required, additional validated analy-
tical methodologies may be needed.
4. SUMMARY OF REGULATORY POSITIONS AND RATONALES
Ethoprop meets the criteria for resticted use classi-
fication.
- Ethoprop is not a candiate for Special Review at this
time.
The Agency will not grant any new tolerances or new
uses for ethoprop until data required under this
Standard have been received and tolerances reassessed.

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- The Agency is unable to provide a quantitative esti-
mation of the ethoprop potential for groundwater
contamination. Additional studies required are hydro-
lyis, photolysis in water and soil, leaching of soil
degradates, and field dissipation.
In order to remain in compliance, updated label precau-
tions are required to address the hazard to fish and
wildlife.
The Agency will reevaluate reentry protection for
ethoprop when the requested data are received and
evaluated. In the interim, 24 hours is the establish-
ed reentry interval for all crops.
5. SUMMARY OF REQOIRED LABEL MODIFICATION
An updated Environmental Hazard Statement is required.
6- SUMMARY OF OUTSTANDING DATA REQUIREMENTS
Data Gaps
The Agency has identified missing data required to
fully evaluate the human and environmental risks associated
wih the use of ethoprop.
Toxicology	Time Frame for
Data Submission
(Months)	
*21 day dermal toxicity (rabbit)	12
"90 day feeding (rodent? not required	.........15
if a chronic rat feeding study is performed).
"Chronic toxicity (rodent and nonrodent)	50
"Oncogenicity (mouse, rat)			..50
'Teratogenicity (rat, rabbit) — 		15
"Reproduction (2-generation rat)	39
"Mutagenicity testing (cytogenetic analysis)	14
"Metabolism	24
"Other Special testing
rat	14
subchronic	18
subchronic (2)	......24
Environmental Fate/Exposure
"Hydrolysis			 9
"Leaching and adsorption/desorption	12
"Soil dissipation	27
"Soil dissipation, long term	....50
"Spray drift					27

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°Photogegradation in air, soil, and water	 9
"Volatility (lab)	12
•Volatility (field)	15
•Rotational crops (confined; accumulation)	39
•Rotational crops (field; accumulation)	50
•Accumulation: fish	12
Fish & Wildlife
"Actual field testing with birds	48
Residue Chemistry
•Nature of residue (metabolism, plants,
and livestock)	18
•Residue analytical methods	15
"Storage stability data	18
•Magnitude of residue in meat, milk, poultry,
and eggs	15
•Residue data	15-30
Product Chemistry
•All purity and composition	 6
"Analysis and certification of product	12
•Physical and chemical characteristics; i.e.
color, physical state, odor, boiling point,
dissociation constant, stability	 6
•All analysis and certification of product
ingredients	12
*
7. CONTACT PERSON AT EPA
William H. Miller
Product Manager (16)
Insecticide-Rodenticide Branch
Registration Division (TS-767C)
Environmental Protection Agency
Washington, D.C. 20460
Telephone No. (703) 557-2600
DISCLAIMER: The information presented in this Pesticide
Fact Sheet is for informational purposes only and may not be
used to fulfill data requirements for pesticide registration
and reregistration.

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