c/EPA
United States
Environmental Protection
Agency
Environmental Research
Laboratory
Corvallis OR 97330
Research and Development
EPA-600/3-78-082
August 1978
Study of the
Chemical and
Behavioral
Toxicology of
Substitute
Chemicals in
Microtine Rodents
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RESEARCH REPORTING SERIES
Research reports of the Office of Research and Development, U.S. Environmental
Protection Agency, have been grouped into nine series. These nine broad cate-
gories were established to facilitate further development and application of en-
vironmental technology. Elimination of traditional grouping was consciously
planned to foster technology transfer and a maximum interface in related fields.
The nine series are:
1. Environmental Health Effects Research
2. Environmental Protection Technology
3. Ecological Research
4. Environmental Monitoring
5. Socioeconomic Environmental Studies
6. Scientific and Technical Assessment Reports (STAR)
7. Interagency Energy-Environment Research and Development
8. "Special" Reports
9. Miscellaneous Reports
This report has been assigned to the ECOLOGICAL RESEARCH series. This series
describes research on the effects of pollution on humans, plant and animal spe-
cies, and materials. Problems'are assessed for their long- and short-term influ-
ences. Investigations include formation, transport, and pathway studies to deter-
mine the fate of pollutants and their effects. This work provides the technical basis
for setting standards to minimize undesirable changes in living organisms in the
aquatic, terrestrial, and atmospheric environments.
This document is available to the public through the National Technical Informa-
tion Service, Springfield, Virginia 22161.
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EPA-600/3-78-082
August 1978
STUDY OF THE CHEMICAL AND BEHAVIORAL TOXICOLOGY
OF SUBSTITUTE CHEMICALS IN MICROTINE RODENTS
By
J. M. Cholakis
L. C. K. Wong
C. C. Lee
Midwest Research Institute
Kansas City, Missouri
68-01-4915
Project Officer
Jay Gile
Terrestrial Ecology Branch
Corvallis Environmental Research Laboratory
Corvallis, Oregon 97330
CORVALLIS ENVIRONMENTAL RESEARCH LABORATORY
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CORVALLIS, OREGON 97330
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DISCLAIMER
This report has been reviewed by the Corvallis Environmental Research
Laboratory, U.S. Environmental Protection Agency, and approved for publica-
tion. Approval does not signify that the contents necessarily reflect the
views and policies of the U.S. Environmental Protection Agency, nor does
mention of trade names or commercial products constitute endorsement or
recommendation for use.
ii
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FOREWORD
Effective regulatory and enforcement actions by the Environmental Protec-
tion Agency would be virtually impossible without sound scientific data on
pollutants and their impact on environmental stability and human health. Re-
sponsibility for building this data base has been assigned to EPA's Office of
Research and Development and its 15 major field installations, one of which
is the Corvallis Environmental Research Laboratory (CERL).
The primary mission of the Corvallis Laboratory is research on the ef-
fects of environmental pollutants on terrestrial, freshwater, and marine eco-
systems; the behavior, effects and control of pollutants in lake systems; and
the development of predictive models on the movement of pollutants in the bio-
sphere.
This report provides significant new data on the toxicological response
of microtine rodents to selected agricultural chemicals.
A. F. Bartsch
Director, CERL
iii
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ABSTRACT
Ten pesticides were evaluated in acute LDso and 30-day subacute LCcQ
studies using microtine rodents (voles). The order of pesticide toxicity
based on the acute studies was: parathion > methyl parathion > dieldrin > 2,
4-D > 2,4,5-T > simazine > propanil = PCNB = HCB = trifluralin. It was
demonstrated in both the acute and the 30-day subacute studies that Microtus
canicaudus voles are approximately twice as sensitive to these pesticides as
Microtus ochrogaster. When pesticides were compared by LDc0 values in all
four species, the general order of species sensitivity was as follows: Micrc-
tus canicaudus > Microtus pennsylvanicus > Microtus ochrogaster _> Microtus
montanus.
No apparent sex differences were observed in LDen values except for
methyl parathion in Microtus canicaudus, wherein the female appears to be two-
to three-fold more'sensitive to this pesticide than the male.
Based on the 30-day subacute LCcn values, the order of pesticide toxicity
was: dieldrin > parathion > methyl parathion > HCB > 2,4,5-T > PCNB i propanil.
In the 30-day subacute feeding studies, Microtus canicaudus was more
sensitive than Microtus ochrogaster by a factor similar to that in the acute
oral studies. Toxicological signs observed throughout this study were clas-
sically similar to general pesticide intoxication observed in laboratory ani-
mals, and no gross pathology attributable to pesticide treatment was observed
in the animals.
A comparison of the LD5Q values in laboratory rodents with the most
sensitive vole species, Microtus canicaudus, revealed that the rat and mouse
are more susceptible to the lethal effects of 2,4-D, dieldrin, methyl para-
thion, parathion, propanil, and 2,4,5-T. Equal susceptibility to pesticides
for both Microtus canicaudus and laboratory rodents is evident for HCB, PCNB,
and trifluralin. The only exception noted in this study was that the Micro-
tus canicaudus appears to be more susceptible to simazine than the laboratory
rat and mouse.
This report was submitted in fulfillment of EPA Contract Number 68-01-
4195 by Midwest Research Institute under the sponsorship of the U.S. Environ-
mental Protection Agency. This report covers a period from September 16,
1976 to May 1, 1978, and work was completed as of March 10, 1978.
iv
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CONTENTS
Foreword iii
Abstract iv
Acknowledgments • vi
1. Introduction 1
2. Materials and Methods 2
Test Animals 2
Test Compounds 2
Experimental Procedures 3
Data Analysis 5
3. Results 7
2,4-D 7
Dieldrin 7
HCB. .' 9
Methyl Parathion 9
Parathion 9
PCNB 10
Propanil 10
Simazine , 11
2,4,5-T 11
Trifluralin 11
4. Discussion 12
5. Conclusions 17
References 19
Appendix
Acute and subacute oral toxicity (LD^) data 21
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ACKNOWLEDGMENTS
The research was conducted in the Biological Sciences Division under the
direction of Dr. H. M. Hubbard, Acting Director, with the assistance of
Dr. Cheng-Chun Lee, Associate Director. Dr. Paul J. Peters was the Principal
Investigator up to August 8, 1977, and technical assistance was provided by
Mr. Andrew Heinemann during the interval. Dr. Michael T. Koeferl became
Principal Investigator after August 8, 1977, with technical assistance from
Mr. Michael J. McKee. Drs. James M. Cholakis and Laurence C. K. Wong provided
administrative and technical expertise after November 15, 1977, and Mr. Jan L.
Minor assisted in computations and statistics throughout the entire project.
vi
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SECTION 1
INTRODUCTION
The large scale, worldwide use of insecticides, herbicides, and defoli-
ants has prompted the U.S. Environmental Protection Agency to undertake studies
to evaluate the global implications of general pesticide use.
As particularly toxic or persistent pesticides are identified, efforts
are made to find replacements for them. Not wishing to allow equally hazar-
dous chemicals to be used as replacements for condemned pesticides, the U.S.
Legislature passed Public Law 93-135 on October 24, 1973. This law established
the Substitute Chemicals Program which is directed at testing new pesticides
before they are adopted for wide usage.
Most toxicity testing is done with laboratory animals; however, while
these results can be used to compare the toxicity of different chemicals, as
determined in laboratories anywhere, the animal models cannot be directly ap-
plied to the actual native fauna at risk. Thus, for more reliable comparison
with the results in laboratory animals, it would be advantageous to test pes-
ticides in representative native species.
As an approach to some aspects of this problem, this study subjected four
species of vole (Microtus spp.) to toxicologic evaluation. The vole represents
a wild animal type with extensive U.S. geographic distribution; these toxico-
logic data were compared to data obtained from laboratory rodents.
The habitats of the four Microtus species chosen for toxicologic study
cover most of the United States (1). M. pennsylvanicus, the meadow vole, is
found throughout the eastern and northern United States, Canada, and Alaska.
M. ochrogaster, the prairie vole, is found throughout the Midwest and part of
central Canada. M. montanus, the montane vole, is found in the West and
Northwest, while M. canicaudus, gray-tailed vole, is found only in northwest
Oregon.
The overall objective of this work was to study the acute oral toxicity
(LD^Q) and 30-day subacute toxicity (LC^Q) of 10 selected pesticides in mi-
crotine rodents.
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SECTION 2
MATERIALS AND METHODS
TEST ANIMALS
All voles were laboratory-reared from live trapped stocks. Microtus
ochrogaster were supplied by Dr. Orin B. Mock, Associate Professor of Anatomy,
Kirkville College of Osteopathic Medicine, Kirksville, Missouri 63501. M._
canicaudus, M. montanus, and M. pennsylvanicus were supplied by Dr. Larry G.
Forslund, Assistant Professor of Biology, Oregon State University, Corvallis,
Oregon 97331. The M. pennsylvanicus originated from a colony that was lab-
reared for about 14 years by Dr. Fred Elliot, Michigan State University, East
Lansing, Michigan.
Voles were shipped to MRI when they were approximately 6 to 7 weeks of
age, and acclimated to controlled animal room environment (temperature 72°F +
5°, humidity 50% + 10% and a 16-hour light, 8-hour night cycle) for a minimum
of 1 week. Voles placed on tests were approximately 60 to 120 days of age.
Animals were handled according to standardized procedures (2-5).
TEST COMPOUNDS
All pesticides were supplied by the USEPA. Most were either obtained in
analytical grade from the manufacturer, or were recrystallized in the labora-
tories of the EPA:
1. 2,4-D acid damp (2,4-dichlorophenoxyacetic acid), lot No. 093826,
Dow Chemical Company, Midland, Michigan;
2. HCB (hexachlorobenzene), lot No. HX160P2719, Matheson, Coleman and
Bell, Norwood, Ohio;
3. Simazine (2-chloro-4,6-bis-ethylamino-S-triazine), lot No. FL-750033
and FL-751091, CIBA-GEIGY, Agricultural Division, Mclntosh, Alabama;
4. Methyl parathion (0,0-dimethyl 0-p_-nitrophenyl phosphorothioate),
no lot number, Monsanto Agricultural Products, St. Louis, Missouri;
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5. Parathion (0,0-diethyl 0-p_-nitrophenyl phosphorothioate), no lot
number, Monsanto Agricultural Products, St. Louis, Missouri;
6. PCNB (pentachloronitrobenzene), lot No. 2J-13-76, Olin Corporation,
Industrial Products and Service Division, Mclntosh, Alabama;
7. Propanil (3*,4'-dichloropropionanilide), no lot No., Rohm and Haas
Company, Philadelphia, Pennsylvania;
8. 2,4,5-T (2,4,5-trichlorophenoxyacetic acid, iso-octyl ester), lot No.
LF-5362, Thompson-Hayward Company, Kansas City, Missouri;
9. Trifluralin (a,a,a-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine),
no lot No., Eli Lilly and Company, Tippecanoe Laboratories, Lafayette, Indiana;
and
10. Dieldrin (1,2,3,4,10,10-hexachloro-exo-6,7-epoxy-l,4,4a,5,6,7,8,8a-
octahydro-l,4-endo, exo-5,8-dimethanonaphthalene), lot No. 12 PCD-38, Shell
Chemical Company, Houston, Texas.
EXPERIMENTAL PROCEDURES
Acute LD5Q
The LDijQ or medium lethal dose is defined as the statistical estimate of
the dosage of a pesticide (in mg/kg body weight) which kills 50% of the voles
within 14 days after a single oral administration of the compound.
Pesticides were administered by gavage to voles which had been food-
deprived overnight. Most pesticides were pulverized and then sifted through
a 300 jii screen prior to weighing. All pesticides were administered at dosing
volumes of either 10 ml/kg or 20 ml/kg body weight. After experimentation
with various vegetable oils, agars, etc., we found that an aqueous solution
of 1% methyl cellulose (Methocel, lot No. 7412X, grade 60HG, Dow Chemical
Company) with or without 0.4% Tween 80 was a very satisfactory suspending
agent. All drug suspensions were agitated for uniformity using a Polytron,
Model No. PT 10/35, Brinkman Instruments Company, Westbury, Connecticut. Both
untreated and treated control animals were maintained throughout the study.
Dose-range (DR) studies were initially performed with five voles/dose
group and later changed to three voles/dose group. Animals were housed five
per cage while on test. The DR study was run for 3 to 7 days. Once limits
of mortality were established in the DR study for each chemical, then appro-
priate log dosage intervals were selected for the full scale study (0.2, 0.1,
or 0.05 log units depending on the defined limits). The full-scale studies
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for acute 1059 evaluation utilized 10 voles/dosage level with a minimum of
five test groups. More test groups were added, as needed, in order to more
accurately define mathematically the acute 1&5Q or subacute LC50. If the DR
study revealed that less than one-half of the animals would die at 5,000 mg/kg,
then only 10 voles were dosed at 5,000 mg/kg. No attempt was made to define
any mortality above 5,000 mg/kg for the acute study or 50,000 ppm for the
subacute studies.
Animals were observed immediately after dosing and daily for 28 days for
toxicologic and other behavioral signs. Daily observations of clinical signs
were of a semi-quantitative nature (i.e., severe depression, moderate exo-
phthalmos, etc.).
After 28 days, a gross necropsy was performed on a representative number
of surviving animals (.= 50% from each dosage group). Necropsy of animals that
died while on study was not successful because the dead animal was usually
cannibalized by its cage-mates.
30-Day Subacute LC5Q
The LCijQ (median lethal concentration) is defined as that concentration
(in parts per million or ppm) of pesticide which kills 50% of the animals
within 30 days when the compound is administered daily in the diet.
Thirty-day subacute feeding studies were performed after an initial 7-
day DR study was performed with 3 to 5 voles/group utilizing 3 to 5 groups/
pesticide. The full-scale study was accomplished with 10 voles/group and
five groups/test compound utilizing appropriate log dosage intervals. The
pesticide was divided into small portions and mixed with equal parts of the
feed (lab chow and alfalfa) in a mortar and pestle and then added to the bulk
feed in a cement mixer and/or ball mill. Lower dietary concentrations were
made by dilution of the main stock.
To determine the amount of pesticide to be incorporated into the feed
mixture, control body weights and food consumption were determined in 10 voles
in each of four groups: M. ochrogaster, male; M. ochrogaster, female; M.
canicaudus, male; and M._ canicaudus, female. This allowed the conversion of
parts per million (ppm) in diet to mg/kg/day and vice-versa:
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Body weight
46.0
35.3
37.9
27.7
Food consumption
per day, gfL/
5.62
4.62
7.01
6.70
1 ppra in Diet
equals, in
mg /kg /day Jl/
0.122
0.131
0.185
0.242
1 rag/kg/day
equals, in
ppm of diet!!/
8.2
7.6
5.4
4.1
Animal
M._ ochrogaster, Male
M._ ochrogaster, Female
M. canicaudus, Male
M. canicaudus, Female
aj Recorded data.
b/ Computed data.
Animals were observed daily for 30 days for toxicologic and other be-
havioral signs. Daily observations of clinical signs were of a semiquantita-
tive basis (i.e., severe depression, moderate ataxia, etc.).
After 30 days of observations, a gross necropsy was performed on a repre-
sentative number of surviving animals (£50% from each dosage group). Necropsy
of animals that died while on study was not successful because the dead animal
was usually cannibalized by its cage-mates.
Feed Preparation
The control and stock vole diet consisted of a mixture of rat chow mash
and alfalfa: Wayne Lab-Blox Mash, lot No. 8600-00, Allied Mills, Inc., Chicago,
Illinois; 17% dehydrated alfalfa meal, Western Alfalfa Corporation, Shawnee
Mission, Kansas. After mixing three parts Wayne Mash to two parts alfalfa
meal in a cement mixer (Sears, Roebuck and Company), the mixture was further
formulated with 1 liter of tap water to 10 kg of mixture and pelleted. A
model No. 2298-4A pellet mill, California Pellet Mill Company, San Francisco,
California, was used for this purpose.
Special Procedures
Cross inhalation contamination or room pesticide odor was avoided by a
unique holding system: special holding racks capable of housing 30 large
cages (five voles/cage) were utilized for the 30-day subacute feeding studies.
Each set of two cages had its own reverse flow-exhaust system such that no
pesticide odors could enter the room or other cages within this holding rack.
DATA ANALYSIS
All data from both the acute and subacute studies were evaluated by a
computer technique using the probit analysis method of Finney (6). The per-
cent mortality, the dosage, and the number of animals dosed were used for
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computation. The program generated the 1^50 (LC^Q), the LD]_Q CLC^0), the
LDgQ (LCgg), the slope, the standard errors, and the 95% confidence limits
(see Appendix II for computer printouts). If Finney's g factor ^ 1, the 95%
confidence limits are not validly computed. Only one 100% mortality and only
one 0% mortality dosage groups were entered into the probit program, even
though in some situations more than one 100% or 0% mortality group was obtained.
The acute oral LD5Q was computed based on a 14-day observation period,
even through observation continued through day 28, and the subacute dietary
LC5Q was computer based on a 30-day feeding period.
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SECTION 3
RESULTS
The results of the acute and subacute studies in microtine voles are
presented by pesticide. Table 1 is a summary tabulation of all LD5Q and LCc
(95% confidence limits) determinations performed in this study. Appendix I
contains detailed tables of every study performed and includes dosage group,
% mortality, day of death of each animal, mean day of death/dosage group,
LD^Q, and 95% confidence limits. Appendix II contains computer sheets for
each study with results as described in the Materials and Methods section.
2,4-D
The acute oral LD^Q'S in male and female M. ochrogaster voles were 2,106
and 2,104 mg/kg, respectively; and in the male and female M. canicaudus voles
were 1,205 and 1,314 mg/kg, respectively. In M.. ochrogaster no remarkable
toxicologic signs were noted at lower dosages; however, some lethargy, pal-
pebral closure, and convulsion before death were noted at high dosages of
2,4-D. Most deaths were noted within 72 hours of dosing. In M. canicaudus
some loss of righting reflex was noted with hind-limb paralysis, and labored
breathing at high doses. Most deaths occurred within 24 hours of dosing.
DIELDRIN
The acute oral LD5Q's in male and female M. ochrogaster were 201 and
216 mg/kg, respectively; for male and female M. canicaudus were 94 and 101
mg/kg, respectively; for male and female M. montanus were 229 and 182 mg/kg,
respectively; and for male and female M._ pennsylvanicus were 179 and 173 mg/
kg, respectively. No toxic signs were observed at low doses; however, tremor,
hind-limb paralysis, depression, and convulsions in some animals were noted
at high doses of dieldrin. Most deaths occurred within 72 hours post dosing.
In the 30-day subacute feeding studies, the LCgg's in male and female M.
ochrogaster were 129 and 82 ppm, respectively; and in the male and female M.
canicaudus were 43 and 39 ppm, respectively. No toxic signs were noted at
low doses; however, sporadic breathing, piloerection, increased spontaneous
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TABLE 1. THK LD50 ANI) !,CW VALUES OF PESTICIDES TN VOLES
OO
Pesticide
2,4-D
Dieldrin
1KB
Methyl-
parathion
Para th ion
PCNB
Propauil
Slmazine
2,4,5-T
(ester)
Trifluralin
H. ochrogaater
J-DSO teg/kg)
"'- 2,106(1,803-2,572)
* -' 2,104(1,895-2,388)
«* 201(163-261)
? 216(177-294)
•* > 5,000
* >5,000
96(61-151)
•* >5,000
* >5,000
«* >5,000
* >5,000
•* 3,925(3,437-4,568)
* 3,251(2,636-3,979)
o* 4.963(4,227-5,940)
* 3,889(3,298-4,623)
«* >5,000
? "5,000
Acute Studies
M. canicaudus M. roontauus
LD50 (mg/kg) W5Q (rag/kg)
1,205(955-1,513)
1,314(1,013-1,791)
94(73-124) 229(177-616)
101(64-201) 182(159-219)
>5,000
"5,000
137(104-183)
57(40-79) 379(325-512)
55(49-67)
49(43-57)
"5,000 4,194(2,870-17,110)
"5,000 3,717(2,981-5,048)
2,758(2,258-3,366)
2,527(2,070-3,095)
2,014(1,401-2,896)
2,363(2,090-2,686)
2,071(1,653-2,682)
2,123(1,097-4,109) 2,057(1,645-2,860)
> 5,000
"5,000
Subaru Ce
JJ. pciingylvaiiicuB H. ochrogaster
LDsn (mg/kg) LC50 (ppm)
179(118-271) 129(36-459)
173(145-213) 82(58-102)
3,553(2,654-5,007)
3,450(g i 1)
371(304-426) 912(345-1,136)
699(605-787)
"5,000 42,840(32,790-82,830)
"5,000 37,270(28,250-65,400)
" 50,000
"32,000 <50,000
2.066(1,382-3,501)
19,670(17,100-22,750)
Studies
M. canicaudus
LC50 (ppm)
43(36-50>
39(15-101)
1,280(857-1,919)
1,047(533-1,940)
613(g » 1)
192(170-228)
11.290(5,728-15,750)
23,780(18,660-30,140)
15,660(g $ 1)
20,250(g •=• 1)
10,810(9,605-11,920)
. — —
Values are expressed as die LDcQ or
a/ a" = male.
b/ 9 = female.
(95% confidence limits); If g jj I, confidence limits noi computed.
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activity, decreased activity with slight tremors, convulsions and hind-limb
extension at death were noted in higher dosage groups. No gross pathology
attributable to the compound was seen in the animals.
HCB
The acute oral 11*50 in the male and female of both M^ ochrogaster and M^_
canicaudus were greater than 5,000 mg/kg. Some animals at 5,000 rag/kg ex-
hibited depression, decreased spontaneous activity, and palpebral closure;
however, all animals recovered within 24 hours after dosing.
In the 30-day subacute feeding studies, the LC^Qis in male and female
M. ochrogaster were 3,553 and 3,450 ppm, respectively; and in the male and
female M. canicaudus were 1,280 and 1,047 ppm, respectively. Toxicological
signs noted at high doses of HCB were: shivering, lethargy, body tremors,
and hind-limb extension at death for one animal. Necropsy performed on sur-
viving animals after 30 days revealed no significant findings attributable to
compound administration.
METHYL PARATHION
The acute oral LD^g's in male and female M^_ ochrogaster were 311 and
253 mg/kg, respectively; for male and female frL_ canicaudus were 137 and 57 mg/
kg, respectively; and for female M. montanus and female M._ pennsylvanicus were
379 and 371 mg/kg, respectively. After dosing with methyl parathion, the fol-
lowing toxic signs were common to most voles: ataxia, lacrimation, body
tremors, muscle fasciculations, depression, labored breathing, palpebral clo-
sure, piloerection, hind-limb extension, complete paralysis, convulsions, and
death within 15 minutes in some voles at the higher dosage levels.
In the 30-day subacute feeding studies, the LX^Q'S in the female species
of both M. ochrogaster and M. canicaudus were 912 and 613 ppm, respectively.
At low concentrations of methyl parathion, some labored breathing and body
tremors were noted. At higher concentrations of pesticide piloerection,
lethargy, lacrimation, piloerection, body tremors, palpebral closure, and
hunched or arched back were noted in some voles.
PARATHION
The acute oral LDgg's in male and female M. ochrogaster were 87 and 96
mg/kg, respectively; and for male and female M. canicaudus were 55 and 49 mg/
kg, respectively. Animals treated at high dosages exhibited ataxia, tremors,
piloerection, palpebral closure, hind-limb extension, and convulsions prior
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to death. Most voles died within 24 hours of dosing with several dying within
1 or 2 hours after dosing with, parathlon.
In the 30-day subacute feeding studies, the IX^g's in both female species
of M. ochrogaster and M. canicaudus were 699 and 192 ppm, respectively. Toxi-
cological observations were piloerection, ataxia, depression, body tremors,
loss of forearm coordination, and abdominal muscle contractions or fascicu-
lations. The death pattern was variable, but most animals died after about
7 to 14 days on test. No gross pathology attributable to pesticide treatment
was noted at the 30-day necropsy.
PCNB
The acute oral LI>50 was greater than 5,000 mg/kg in both sexes of M.
ochrogaster, M. canicaudus and M. pennsylvanicus . No toxico logical signs were
noted except for some piloerection, loss of righting reflex, lacrimation, and
decreased activity in a few voles. Most of these signs disappeared after 24
hours of dosing. The acute oral LD^Q'S in male and female M. montanus were
4,194 and 3,717 mg/kg, respectively. Most deaths occurred between 2 and 6
days of dosing. No other toxic signs were noted in this study.
In the 30-day subacute studies, the IX^g' s in male and female M. ochro-
gaster were 42,840 and 37,270 ppm, respectively; and for male and female M.
canicaudus were 11,290 and 23,780 ppm, respectively. Animals exhibited toxi-
cological signs of lacrimation, piloerection, irregular breathing, lethargy,
and body tremors at high concentrations of PCNB. Alopecia was noted, but
this was not considered to be drug-related. No gross pathology attributable
to pesticide treatment was seen in the animals at the 30-day necropsy.
PROPANIL
The acute oral LD50's in both male and female M._ ochrogaster were greater
than 5,000 mg/kg. The acute oral lino's in male and female M. canicaudus
were 2,758 and 2,527 mg/kg, respectively. The toxic signs observed at high
doses were difficulty in breathing, lethargy, loss of righting reflexes and
paralysis. Most animals died within 48 hours of dosing.
In the 30-day subacute studies, the LC5Q in male and female M._ ochrogaster
was greater than 50,000 ppm in the male and greater than 32,000 ppm, but less
than 50,000 ppm for the female. The U^Q'S in male and female M._ canicaudus
were 15,660 and 20,250 ppm, respectively. The toxic signs were piloerection,
palpebral closure, depression and loss of motor control in one vole. No gross
pathology attributable to pesticide treatment was seen in the animals at the
30-day necropsy.
10
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SIMAZINE
The acute oral LDc^'s in male and female M. ochrogaster were 3,925 and
3,251 rag/kg, respectively; and for male and female M. canicaudus were 2,014 and
2,363 mg/kg, respectively. The toxic signs noted were hind-limb extension,
piloerection, loss of anal sphinter control, lethargy, muscle spasms, lacrima-
tion, and depression. Most animals died after 4 to 5 days of dosing with
simazine.
2,4,5-T
The acute oral LD5Qfs in male and female M. ochrogaster were 4,963 and
3,889. mg/kg, respectively; for male and female M. canicaudus were 2,071 and
2,123 mg/kg, respectively; for female M. montanus the LI>5o was 2,057 mg/kg, and
for male M. pennsylvanicus was 2,066 mg/kg. The toxic signs noted were lethargy,
palpebral closure, ataxia, and decreased spontaneous activity.
In the 30-day subacute studies, the IX^g's in female M. ochrogaster and
female M. canicaudus were 19,670 and 10,810 ppm, respectively. The toxic signs
noted were piloerection, palpebral closure, lethargy, decreased spontaneous
activity, and depression. Most animals died after 10 days on test. No gross
pathology attributable to pesticide treatment was seen in the animals.
TRIFLURALIN
The acute oral t-D^Q was greater than 5,000 mg/kg for both sexes of M.
ochrogaster and M. canicaudus. No toxic signs were noted except for some voles
with depression, which disappeared within 24 hours of dosing.
11
-------
SECTION 4
DISCUSSION
In the acute oral studies, voles were treated with the vehicle (1% methyl
cellulose) in the same dosing volume as the experimental test group. A high
incidence of deaths in the vehicle-treated group of the M._ pennsyIvanicus male
(14.7%) was attributed to rupturing of the esophagus during intubation. This
problem was encountered early in the study and corrected after some experimen-
tation with dosing needles and different dosing techniques.
In the acute oral toxicity studies, M. canicaudus was generally more sus-
ceptible to 2,4-D, dieldrin, parathion, propanil, simazine, 2,4,5-T and methyl
parathion (male) than M. ochrogaster, M. montanus and M. pennsyIvanicus by a
factor of about 2:1. Since the LD5Q was greater than 5,000 mg/kg for PCNB, HCB
and trifluralin in both sexes of these species, no conclusion could be made
with regard to species sensitivity. In the acute oral 11)50 study. tne female
M. canicaudus was four to five times more susceptible to methyl parathion than
the female M. ochrogaster.
In the feeding studies, early experimentation with a closed feeder food
system revealed that the voles on the subacute studies could not adapt to this
feeding method. Thereafter, an open jar feeder was used in all subacute stud-
ies, a system which proved more satisfactory. However, one problem with this
technique was a slightly higher food consumption than reported in the litera-
ture (literature: 3.0-3.5 gm/day/vole (2); this study: 5.6-7.0 gm/day/vole).
This higher food consumption was generally due to spillage. Other sources of
problem areas in collecting food consumption data were: voles had a tendency
to fill the feeder jars with bedding material and the voles would deposit fecal
material in the feeders.
In the 30-day subacute studies, M. canicaudus was more susceptible to
pesticides (dieldrin, parathion, methyl parathion, HCB, 2,4,5-T, PCNB and
propanil) than the M. ochrogaster by a factor of about 2:1. This is the
similar relationship seen in the acute studies, i.e., 2:1 relationship. How-
ever, if we examine the relationship developed in the subacute study between
ppm in diet and convert this to mg/kg/day of pesticide consumed, the 2:1 rela-
tionship between the M. ochrogaster and M. canicaudus is not nearly so evident:
12
-------
1 ppm in Diet Equals
Animal in mg/kg/day3/
M. ochrogaster, male 0.122
M. ochrogaster, female 0.131
M. canicaudus, male 0.185
M. canicaudus, female 0.242
a/ See Materials and Methods section.
It appears that M. canicaudus consume about twice as much food as the M.
ochrogaster. Table 2 presents the LC5Q data as ppm recomputed to mg/kg/day
from the control food consumption-body weight data (see Methods section). An
examination of this recomputed data now reveals clear species differences of
LC5Q values only with parathion and PCNB (male only). Comparison of data on the
basis of mg/kg/day minimizes the differences in species susceptibility for di-
eldrin, HCB, propanil, 2,4,5-T and even methyl parathion. Even though M. cani-
caudus voles consume about twice as much food as the M. ochrogaster, parathion
and PCNB (male) are still twice as toxic to the M._ canicaudus as to the M.
ochrogaster species.
The overall rank order of pesticide toxicity based on the 30-day subacute
(1050) values (ppm) is as follows: dieldrin > parathion > methyl parathion >
HCB > 2,4,5-T > PCNB > propanil (simazine, 2,4-D and trifluralin were not
studied). In the acute oral studies (LD5Q), the order of toxicity of the first
three pesticides was parathion > methyl parathion > dieldrin, etc.
Some tentative explanations of these differences are as follows:
1. Parathion, methyl parathion but not dieldrin, could have stimulated
(induced) the liver drug metabolizing enzyme systems to increase the detoxica-
tion of these pesticides (7,8).
2. Dieldrin could have been acting in a cumulative manner (9,10). It
can be shown that the dieldrin acute LD50 values are approximately equal to
the subacute LC values (on a mg/kg/day basis):
M. canicaudus
Dieldrin
LC^n
9
9
X
X
X
Mean Day of Death =
10
12
"Total"
LC50
90
108
LD50
94
101
Ratio
1
1
13
-------
TABLE 2. THE LC5Q VALUES OF PESTICIDES IN VOLES (SUBACUTE).
(ppm vs. mg/kg/day)
Dieldrin
HCB
Methyl
parathion
Parathion
PCNB
Propanil
2,4,5-T
(ester)
M. ochrogaster
LC50 (ppm)
b/
o»- 129(36-459)
? - 82(58-102)
a* 3,553(2,654-5,007)
* 3,450(g > 1)
? 912(345-1,136)
* 699(605-787)
o* 42,840(32,790-82,830)
f 37,270(28,250-65,400)
«* > 50, 000
? > 32, 000 < 50, 000
? 19,670(17,100-22,750)
M. canicaudus
LC5Q (ppm)
43(36-50)
39(15-101)
1,280(857-1,919)
1,047(533-1,940)
613(g > 1)
192(170-228)
11,290(5,728-15,750)
23,780(18,660-30,140)
15, 669 (g 5 1)
20,250(g y 1)
10,810(9,605-11,920)
M. ochrogaster
LC50 (mg/kg/day)^
16(4-56)
11(8-13)
433(324-611)
452(g S 1)
119(45-149)
92(79-103)
5,226(4,000-10,105)
4,882(3,700-8,567)
> 6,100
>4,192 <6,550
2,577(2,240-2,980)
M. canicaudus
LC5() (mg/kg/day)£/
9(8-10)
9(4-24)
268(179-401)
253(129-469)
148(g § 1)
46(41-55)
2,360(1,197-3,292)
5,755(4,516-7,294)
3,273(g S 1)
4,900(g * 1)
2,259(2,007-2,491)
Values are expressed as LC5Q (95% confidence limits); if Finney's g = 1, confidence limits not validly computed.
a/ LC5Q in mg/kg/day (computed from control food consumption data - see Material and Methods and Discussion section)
b/ «*=» male
c/ ^ = female
-------
"Total"
LC50
Ratio LD5Q
Parathion
LC50
46
x Mean Day of Death =
x 6.2
"Total"
LC50
285
LD50
57
This data interpretation suggests that dieldrin is cumulative in its
effects and that parathion can be tolerated by M^_ canicaudus in amounts much
higher than the single lethal dose. However, more detailed studies should be
performed before final conclusions can be made about these differences (i.e.,
bioavailability, distribution, excretion experiments, etc.).
To determine if the vole represents a more or less sensitive species than
the laboratory rat or mouse, an extensive review of the literature was under-
taken to tabulate rat and mice LD^Q'S. Table 3 provides a comparison of the
acute LD5Qfs of M. ochrogaster, M. canicaudus, the laboratory rat and the mouse.
Generally, it appears that both the laboratory rat and mouse are more sensitive
than (2:1) or about equal to M. canicaudus with respect to acute toxicity of
these pesticides. However, species variability, strain differences among rats
and mice, laboratory condition, dosing techniques, vehicle variables, chemical
formulation variations, etc., make any strict comparative evaluation subject
to reasonable criticism. Some outstanding exceptions should be noted: (1) the
four- to ten-fold difference between the laboratory animal and vole LD5Q values
with 2,4,5-T (i.e., LD5Q £ 300-551 mg/kg for laboratory animals (12,16,17) vs.
LD50 = 2,000-5,000 mg/kg for voles). A reasonable explanation of this finding
is that earlier study with 2,4,5-T showed that it was contaminated with high
concentrations of TCDD or 2,3,7,8-tetrachlorodibenzodioxin. These earlier
studies probably reflected TCDD toxicity and not necessarily 2,4,5-T ester
formulations studies (20,21); however, more careful manufacturing processes
have decreased this dioxin product to less than 0.1 ppm. (2) Similarly large
order of magnitude differences between the laboratory species and voles with
respect to parathion, methyl parathion, and dieldrin. It would appear that the
laboratory animal is more sensitive to these three pesticides than the vole.
(3) The only example in this entire report that suggests the vole is more
sensitive than the laboratory rat or mice is with simazine, i.e., LD5Q >
5,000 mg/kg for lab animals vs. LD5Q ^ 2,000 mg/kg for M._ canicaudus.
The overall order of pesticide toxicity for the laboratory rat and mouse
is as follows: parathion > methyl parathion > dieldrin > 2,4,5-T^ 2,4-D^
propanil > PCNB > HCB > trifluralin ^ simazine (see Table 3). This order is
quite similar to that established in the voles, and except for the sensitivity
difference between voles and laboratory rodents, the similar pesticide toxicity
order suggests a common mechanism of pesticide action.
15
-------
TABLE 3. COMPARISON OF THE LD5Q VALUES OF TEN PESTICIDES IN VOLES, RATS, AND MICE.
2,4-D
Dieldrin
HCB
Methyl
parathion
Parathion
PCNB
Propanil
Simazine
2,4,5-T
(ester)
Trlfluralin
M. ochrogaster
L»50 (mg/kg)
Jr-l 2,106(1,803-2,572)
%±' 2,104(1,895-2,388)
o» 201(163-261)
j 216(177-294)
0* >5,000
$ >5,000
& 311(223-480)
j 253(75-974)
o* 87(76-102)
$ 96(61-151)
o* >5,000
% >5,000
o» >5,000
$ >5,000
^ 3,925(3,437-4,568)
$ 3,251(2,636-3,979)
^r 4,963(4,227-5,940)
$ 3,889(3,298-4,623)
a* 5,000
$ 5,000
M. canicaudus
LD50 (rag/kg)
1,205(955-1,513)
1,314(1,013-1,791)
94(73-124)
101(64-201)
>5,000
>5,000
137(104-183)
57(40-79)
55(49-67)
49(43-57)
>5,000
>5,000
2,758(2,258-3,366)
2,527(2,070-3,095)
2,014(1,401-2,896)
2,363(2,090-2,686)
2,071(1,653-2,682)
2,123(1,097-4,109)
>5,000
>5,000
Laboratory Rat
LD50 Ranges^.'
300 to 666
46 to 87
3,500 to 10,000
14 0*
24 %
7.6 to 13 **
3.6 %
1,650 to 12,000
560 to 1,400
>5,000
300 to 495
3,700 to 10,000
Laboratory Mouse
LD50 Ranges3/
368 to 375
114
4,000
23
6 to 25
LD5Q
not found
LD5Q
not found
5,000
551
5,000
Values are expressed as LD5Q or LC5Q (95% confidence limits).
a./ LD5Q values (mg/kg) tabulated from literature. See references 11 to 19.
b_/ tf = male
c £ = female
-------
SECTION 5
CONCLUSIONS
The acute oral toxicity (LDso) and 30-day feeding effects (LC5Q) were per-
formed in adult microtus voles with selected pesticides. Conclusions are as
follows: (1) Based on the acute oral toxicity (U^Q) studies, the overall
order of pesticide toxicity is as follows: parathion > methyl parathion >
dieldrin > 2,4-D > 2,4,5-T > simazine > propanil = PCNB = HCB = trifluralin;
(2) the general order of species sensitivity to pesticides is as follows: M.
canicaudus > M. pennsylvanicus > M. ochrogaster > M^_ montanus; (3) M. canicau-
dus are approximately twice as sensitive to pesticide treatment as M. ochro-
gaster in both the acute and 30-day subacute studies (on a ppm basis); (4) No
apparent sex differences were observed in 11)50 values except for methyl para-
thion in M. canicaudus (female twice as sensitive as male); (5) Based on the
30-day subacute toxicity (LC5g) study, the overall order of pesticide toxicity
is as follows: dieldrin > parathion > methyl parathion > HCB > 2,4,5-T >PCNB>
propanil (simazine, 2,4-D and trifluralin not tested); (6) No apparent sex
difference was observed in LC5Q values except for PCNB in M. canicaudus (male
twice as sensitive as female); and (7) Laboratory rodents are generally more
sensitive to pesticides than the most sensitive vole species, M. canicaudus.
17
-------
REFERENCES
1. The Mammals of North America. E. R. Hall and K. R. Kelson, eds. The
Ronald Press Company, New York, Vol. II, 1959.
2. Kruckenberg, S. M., G. T. Hartke, H. W. Leipold, and J. E. Cook. The
Prairie Vole as a Laboratory Animal. Lab. Animal, 5:19-20 (1976).
3. Lee, C., and D. J. Horvath. Management of the Meadow Vole (Microtus
pennsylvanicus). Laboratory Animal Care, 19OL):88-91 (1969).
4. Richmond, M., and C. H. Conaway. Management, Breeding and Reproductive
Performance of the Vole, Microtus Ochrogaster, in a Laboratory Colony.
Laboratory Animal Care, 19(1):80-87 (1969).
5. Dewsburg, D. A. The Use Muroid Rodents in the Psychology Laboratory.
Behav. Res. Meth. Instr., 6(3):301-308 (1974).
6. Statistical Methods in Biological Assay. D. J. Finney, ed. Griffin,
London, 1971.
7. DuBois, K. P., J. Doull, P. R. Salerno, and J. M. Coon. Studies on the
Toxicity and Mechanisms of Action of p-Nitrophenyl Diethyl Thiono Phos-
phate (Parathion). J. Pharmacol. Exp. Therap., 95:70-91 (1949).
8. DuBois, K. P- Low Level Organophosphorus Residues in the Diet. Arch.
Environ. Health. 10:837-841 (1965).
9. Hodge, H. C., A. M. Boyce, W. B. Deichmann, and H. F. Kraybill. Toxicology
and No-Effect Levels of Aldrin and Dieldrin. Toxicol. Appl. Pharmacol.,
10:613-675 (1967).
10. Hutterer, F., F. Schaffner, F. M. Klion, and H. Popper. Hypertrophic,
Hypoactive Smooth Endoplasmic Reticulum: A Sensitive Indicator of
Hepatotoxicity Exemplified by Dieldrin. Science, 161:1017-1019 (1968).
11. Ben-Dyke, R., D. M. Sanderson, and D. N. Noafces. Acute Toxicity Data for
Pesticides. World Review of Pest Control, 9:119-127 (1970).
19
-------
12. Registry of Toxic Effects of Chemical Substances. H. E. Christensen, ed.
NIOSH, 1976 Edition.
13. Finnegan, J. K., P. S. Larson, R. B. Smith, Jr., H. B. Haag, and G. R.
Hennigar. Acute and Chronic Toxicity Studies on Pentachloronitro-
benzene. Arch. Int. Pharmacodyn., CXIV(l):38-52 (1958).
14. U.S. Environmental Protection Agency: Criteria Document for Aldrin/
Dieldrin. USEPA, GPO, 1976.
15. Hill, E. V., and H. Carlisle. Toxicity of 2,4-Dichlorophenoxyacetic Acid
for Experimental Animals. J. Indust. Hygiene and Tox., 29(2):85-95
(1947).
16. Rowe, V. K., and T. A. Hymas. Summary of Toxicological Information on
2,4,-D and 2,4,5-T Type Herbicides and an Evaluation of the Hazards to
Livestock Associated with Their Use. Am. J. Vet. Res., 15:622-629
(1954).
17. Gaines, T. B. Acute Toxicity of Pesticides. Toxicol. Appl. Pharmacol.,
14:515-534 (1969).
18. Handbook of Toxicity of Pesticides to Wildlife. R. K. Tucker and D. G.
Crabtree, eds. GPO, 1970.
19. Ecological Effects of Pesticides on Non-Target Species. D. Pimental, ed.
GPO, 1971.
20. Panel on Herbicides: Report on 2,4,5-T, A Report of the Panel on Herbi-
cides of the President's Science Advisory Committee. Executive Office
of the President, Office of Science and Technology, U.S. Government
Printing Office, Washington, D.C. (1971).
21. Moore, J. A., and K. D. Courtney. Teratology Studies With the Trichloro-
phenoxy Acid Herbicides, 2,4,5-T and Silvex. Teratology, 4:236 (1971).
20
-------
APPENDIX A
ACUTE AND SUBACUTE ORAL TOXICITY
(LD5Q) DATA
21
-------
TABLE A-l. ACUTE ORAL W5Q OF 2,4-D IN M.. OCHROGASTER
Dose
(mg/kg)
Mortality
Time of death
(days)
Mean
(days
4,000
2,500
1,995
1,585
1,260
1,000
790
10/10
10/15
1/10
5/15
2/10
1/10
0/10
Male
1,1,1,1,1,3,3,3,3,3
1,1,1,1,1,2,3,3,6,7
3
1,1,1,3,3
3,3
4
2.0
2.6
1.8
3.0
4,000
2,500
1,995
1,585
1,260
1,000
Female
10/10 1,1,1,1,2,3,3,3,3,3 2.1
13/15 1,1,1,1,1,2,2,2,3,3,3,3,6 2.2
2/10 1,6,(27) 3.5
1/15 3
1/10 1
0/10 (26)
LD5Q (95% confidence limits) Male: 2,106 (1,803-2,572) mg/kg
Female: 2,104 (1,895-2,388) mg/kg
23
-------
TABLE A-2. ACUTE ORAL LD5Q OF 2,4-D IN M.. CANICAUDUS
Dose
(mg/kg)
Mortality
Time of death
(days)
Mean
(days)
2,500
1,585
1,000
630
10/10
6/10
5/10
0/10
Male
1,1,1,1,1,4,4,4,4,4
1,1,1,1,4,4
1,1,4,4,4
2.5
2.0
2.8
2,500
1,585
1,000
630
400
10/10
4/10
3/10
2/10
0/10
Female
1,1,1,1,1,1,1,4,4,4
1,1,1,4,(19)
4,4,4,(19)
1,11
1.9
1.8
4.0
6.0
LD50 (95% confidence limits) Male:
Female:
1,205 (955-1,513) mg/kg
1,314 (1,013-1,791) mg/kg
24
-------
TABLE A-3. ACUTE ORAL LD50 OF DIELDRIN IN M.. OCHROGASTER
Dose Mortality Time of death Mean
(mg/kg) d.(l-14) (day3) (days)
Male
398 9/10 2,2,2,2,2,2,4,4,7 3.0
320 9/10 1,1,1,2,5,5,5,5,6 3.4
250 4/10 2,3,3,3 2.8
200 5/10 1,1,1,5,5 2.6
150 3/10 3,7,8 6.0
126 1/10 1
100 2/7 7,8 7.5
79 1/10 1
63 1/10 1
Female
315 8/10 2,2,3,3,7,7,7,8 4.9
250 6/10 3,4,4,4,4,7,(25) 4.3
200 4/10 5,5,5,6 5.3
150 2/10 3,3 3.0
126 1/10 5
100 2/5 3,8 5.5
79 0/10 (28)
LD5Q (95% confidence limits) Male: 201 (163-261) mg/kg
Female: 216 (177-294) mg/kg
25
-------
TABLE A-4., ACUTE ORAL LD5Q OF DIELDRIN IN M.. CANICAUDUS
Dose Mortality Time of death Mean
(mg/kg) d.(l-14) (days) (days)
Male
240 10/10 1,1,4,4,4,4,4,4,4,4 3.4
150 8/10 1,1,4,4,5 3.0
96 4/10 1,4,4,4 3.3
60 1/10 4
40 2/10 4,4 - 4.0
25 0/10
Female
250 6/10 1,2,3,3,4,4 2.8
150 8/10 1,4,4 3.0
96 5/10 1,1,4,4,4 2.8
60 3/10 4
40 4/10 4,4,5,5 4.5
25 0/10
LD5Q (95% confidence limits) Male: 94 (73-124) mg/kg
Female: 101 (64-201) mg/kg
26
-------
TABLE A-5. ACUTE ORAL LD5Q OF HCB IN M.. OCHROGASIER
Dose Mortality Time of death Mean
(mg/kg) d.(l-14) (days) (days)
Male
5,000 0/10
Female
5,000 0/10
LD5Q (95% confidence limits) Male: >5,000 mg/kg
Female: >5,000 mg/kg
TABLE A-6. ACUTE ORAL LDCA OF HCB IN M. CANICAUDUS
Dose
(mg/kg)
5,000
3,160
1,995
5,000
3,160
1,995
Mortality Time of death
d.(l-14) (days)
Male
0/10
0/5
0/5
Female
0/9
1/5 1
0/5
Mean
(days)
(95% confidence limits) Male: >5,000 mg/kg
Female: >5,000 mg/kg
27
-------
TABLE A-7. ACUTE ORAL LD50 OF METHYL PARATHION IN M.. OCHROGASTER
Dose Mortality Time of death Mean
(mg/kg) d.(l-14) (days) (dayg)
Male
790 7/10 1,1,3,3,3,3,4 2.6
500 7/10 1,1,1,3,3,3,3 2.1
355 7/10 1,1,1,1,1,1,8,(22) 2.0
250 5/10 1,1,1,1,1,(29) . 1.0
178 2/10 1,1 1.0
126 2/10 1,1 1.0
89 1/10 1
50 0/5
Female
790 7/10 1,2,3,3,3,3,3 2.6
500 8/9 1,1,1,1,3,3,3,3 2.0
355 7/10 1,1,1,1,1,1,1 1.0
250 8/10 1,1,1,1,1,1,1,1 1.0
178 4/10 1,1,1,1 1.0
126 1/10 1
89 0/10
LD50 (95% confidence limits) Male: 311 (223-480) mg/kg
Female: 253 (75-974) mg/kg
28
-------
TABLE A-8. ACUTE ORAL LD50 OF METHYL PARATHION IN M.. CANICAUDUS
Dose
(mg/kg)
Mortality
Time of death
(days)
Mean
(days)
Male
400
250
160
100
63
40
10/10
8/10
5/10
3/10
2/10
0/10
1,1,1,1,1,1,1,1,1,1
1,1,1,1,1,1,1,1
1,1,1,1,2
1,1,1
1,1
(27)
1.0
1.0
1.2
1.0
1.0
250
160
100
63
40
25
16
Female
10/10 1,1,1,1,1,1,1,1,1,5
9/10 1,1,1,1,1,1,1,2,2
6/10 1,1,1,1,1,1
5/10 1,1,1,1,2
3/10 1,1,1
4/10 1,1,1,1
0/10 (18,18,18)
1.4
1.2
1.0
1.0
LD5Q (95% confidence limits) Male:
Female:
137 (104-183) mg/kg
57 (40-79) mg/kg
29
-------
TABLE A-9. ACUTE ORAL LDCrt OF PARATHION IN M. OCHROGASTER
50
Dose
(mg/kg)
Mortality
Time of death
(days)
Mean
(days)
126
100
80
63
50
40
10/10
5/10
4/10
1/10
1/10
0/10
Male
1,1,1,1,1,1,1,1,1,1
1,1,1,1,2
1,1,1,1
3
2
1.0
1.2
1.0
Female
160
126
100
80
63
50
10/10
9/10
7/10
7/10
2/10
0/10
1,1,1,1,1,3,3,3,3,3
1,1,1,1,1,1,1,1,1
1,1,1,1,1,1,1
1,1,1,1,1,1,1
1,1
2.0
1.0
1.0
1.0
1.0
LD5Q (95% confidence limits) Male:
Female:
87 (76-102) mg/kg
96 (61-151) mg/kg
30
-------
TABLE A-10. ACUTE ORAL ID OF PARATHION IN M.. CANICAUDUS
Dose Mortality Time of death Mean
(me/kg) d.(l-14) (days) (days)
Male
100 10/10 1,1,1,1,1,1,1,1,1,2 1.1
60 4/10 1,1,5,6 3.2
50 6/10 1,1,1,1,1,3 1.3
40 1/10 6
32 0/10
25 0/10
Female
60
50
40
32
25
8/10
5/10
3/10
0/10
0/10
1,1, 1,1,1,1,.!, 2
1,1,1,1,1
2,11,14
1.1
1.0
9.0
LD5Q (95% confidence limits) Male: 55 (49-67) mg/kg
Female: 49 (43-57) mg/kg
TABLE A-11. ACUTE ORAL LD5Q OF PCNB IN M^ OCHROGASTER
Dose Mortality Time of death Mean
(mg/kg) d.(l-14) (days) (days)
Male
5,000 0/10
Female
5,000 0/10
LD50 (957. confidence limits) Male: > 5,000 mg/kg
31 Female: > 5,000 mg/kg
-------
TABLE A-12. ACUTE ORAL LD50 OF PCNB IN M.. CANICAUDUS
Dose Mortality Time of death Mean
Cms/kg) d.(l-14) (days) (days)
Male
5,000 2/10 1,3 2.0
Female
5,000 3/10 2,3,8 4.3
LD5Q (957. confidence limits) Male: > 5,000 mg/kg
Female: >5,000 mg/kg
TABLE A-13. ACUTE ORAL LD50 OF PROPANIL IN Mj. OCHROGASTER
Dose
(mg/kg)
5,000
2,510
1,260
5,000
2,510
1,260
Mortality
d.(l-14)
6/20
0/10
1/10
8/20
6/10
1/10
Time of death
(days)
Male
1,3,4,4,4,7
3
Female
1,1,1,1,3,3,4,7
1,1,7,7,9,10
4, (17, 25)
Mean
(days)
3.8
2.6
5.8
LD5Q (95% confidence limits) Male: >5,000 mg/kg
Fema le: >5,000 mg/kg
32
-------
TABLE A-14.
Dose
60 1 f\
, J1U
5,010
4,000
3,160
2,510
1,995
1,585
1,230
630
6,310
5,010
4,000
3,160
2,510
1,995
1,585
1,230
1,000
ACUTE ORA1
Mortality
Q / 1 A
y/ JLU
8/10
7/10
8/10
4/10
3/10
1/10
1/10
0/5
10/10
7/9
7/10
6/10
5/10
5/10
3/10
1/10
0/10
,11150 OF PROPANIL IN M. CA
Time of death
(days)
Male
1,1,1,1,1,1,2,4
2,2,3,3,3,4,4
2,2,2,2,2,3,3,3
2,2,2,4
2,2,2
2, (21)
12
Female
1,1,1,1,1,1,1,1,1,2
1,1,1,2,2,2,3
2,2,2,2,2,3,5
2,2,2,2,2,2
2,2,2,2,3
2,2,2,2,3
2,2,5
1
NICAUDUS
Mean
(days)
i i
1.1
1.5
3.0
2.4
2.5
2.0
1.1
1.7
2.6
2.0
2.2
2.2
3.0
LD5Q (957. confidence limits) Male:
Female:
2,758 (2,258-3,366) rag/kg
2,527 (2,070-3,095) tng/kg
33
-------
TABLE A-15. ACUTE ORAL LD5() OF SIMAZINE IN M^ OCHROGASTER
Dose
(mg/kg)
Mortality
Time of death
(days)
Mean
(days)
6,310
5,000
4,000
3,160
2,820
2,500
8/10
8/10
11/20
4/10
2/10
0/10
Male
3,3,3,3,3,6,6,6 4.1
3,3,3,3,4,4,10,10 5.0
2,3,3,3,3,3,5,6,7,10,14 5.4
3,3,4,4 . 3.5
3,3 3.0
Female
6,310
5,000
4,000
3,160
2,500
1,995
1,585
9/10
9/10
11/20
5/10
2/10
1/10
3/10
3,3,3,3,3,3,3,6,7 3.8
3,3,4,4,7,7,7,10,10 5.0
1,1,3,3,6,6,7,7,7,9,12 5.6
1,3,3,3,7 3.4
3,7
4
3,3,12 6.0
LD50 (95% confidence limits) Male:
Female:
3,925 (3,437-4,568) mg/kg
3,251 (2,636-3,979) mg/kg
34
-------
TABLE A-16. ACUTE ORAL LD5Q OF SIMAZINE IN M. CANICAUDUS
Dose Mortality Time of death Mean
(mg/kg) d.(l-14) (days) (days)
Male
3,548 8/10 2,2,2,4,4,4,5,6 3.6
2,818 6/10 2,2,2,4,4,4 3.0
2,240 4/10 2,4,4,10 5.0
1,780 5/10 1,1,1,2,5 2.0
1,412 4/10 1,1,1,10 3.2
Female
3,548 9/10 1,2,2,2,2,2,4,5,5 2.8
2,818 8/10 1,1,2,2,4,4,4,4 2.8
2,240 5/10 1,1,2,2,4 2.0
1,780 1/10 1
1,412 0/10
LDc0 (957. confidence limits) Male: 2,014 (1,401-2,896) mg/kg
Female: 2,363 (2,090-2,686) mg/kg
35
-------
TABLE A-17. ACUTE ORAL TOXICITY (H>50) OF 2,4,5-T IN M. OCHROGASTER
Dose Mortality
(mg/kg) d.(l-14)
Time of death
(days)
Mean
(days)
7,433
5,935
4,688
3,724
2,960
9/10
5/10
6/10
3/10
0/10
Male
1,1,2,2,2,4,4,4,4
1,2,2,4,4
2,2,2,4,4,4
5,5,5
2.7
2.6
3.0
5.0
7,433
5,935
4,688
3,724
2,960
2,352
2,255
1,484
Female
10/10 1,3,3,3,3,3,3,4,4,4 3.1
13/15 3,3,3,3,3,4,4,4,5,6,6,6,7 4.4
5/10 3,3,3,4,4 3.4
3/14 4,4,5 4.3
3/10 3,3,11 5.7
1/5 6
4/10 3,4,11,12 7.5
0/15
LD
50
confidence limits) Male:
Female:
4,963 (4,227-5,940) mg/kg
3,889 (3,298-4,623) mg/kg
36
-------
TABLE A-18. ACUTE ORAL LD5Q OF 2,4,5-T IN M.. CANICAUDUS
Dose Mortality Time of death Mean
(mg/kg) d.(l-14) (days) (days)
Male
3,160
2 510
£- y J **\J
1,995
1,585
1,260
2,510
1,995
1,585
1,260
1,000
7/10
7/10
/ / J-^J
5/10
5/10
0/10
6/10
5/9
2/9
3/10
4/10
1,1,2,2,2,2,2
1,1,1,1,1
1,1,1,1,9
Fema le
2,2,2,2,2,2
2,2,2,2,5,5
2,2
939
*• ) J> *
2225
*.,£,£, j
1.7
1 0
JB • W
1.0
2.6
2.0
3.0
2.0
4.7
2.7
LD5Q (95% confidence limits) Male: 2,071 (1,653-2,682) mg/kg
Female: 2,123 (1,097-4,109) mg/kg
TABLE A-19. ACUTE ORAL U>50 OF TRIFLURALIN IN M.. OCHROGASTER
Dose Mortality Time of death Mean
(mg/kg) d. (1-14) (days) (days)
Male
5,000 0/10
Female
5,000 1/10 1
LD5Q (95% confidence limits) Male: >5,000 mg/kg
Female: >5,000 mg/kg
37
-------
TABLE A-20. ACUTE ORAL LDcr. OF TRIFLURALIN IN M. CANICAUDUS
~~~~~~^^^^~
Dose
(mg/kg)
5,000
5,000
Mortality Time of death
d.(l-14) (days)
Male
1/10 2
Female
2/10 3,9,(>14)
Mean
(days)
5.5
(95% confidence limits) Male: >5,000 mg/kg
Female: >5,000 mg/kg
TABLE A-21. ACUTE ORAL LD5Q OF DIELDRIN IN M.. PENNSYLVANICUS
Dose
(mg/kg)
Mortality
Time of death
(days)
Mean
(days)
Male
250
200
150
126
100
63
10/100
2/10
6/10
1/10
1/12
0/5
1,1,1,1,1,1,2,4,4,9 2.3
2,13,(25,25)
1,1,2,3,3,3
2
3
7.5
2.2
Female
400
250
200
150
126
100
63
5/5
9/10
5/10
4/10
0/10
3/10
0/5
1,1,1,1,2
1,1,1,2,3,3,7,7,8
1,3,3,6,9,(> 14)
1,1,1,3
(20)
3,3,3
1.2
3.7
4.4
1.5
3.0
LD (957. confidence limits) Male:
50 3® Female:
179 (118-271) mg/kg
173 (145-213) mg/kg
-------
TABLE A-22. ACUTE ORAL LD5Q OF DIELDRIN IN M._ MONTANUS
Dose Mortality Time of Death Mean
(mg/kg) d.q-14) (days) (days)
Male
316 5/5 1,2,2,5,5 3.0
250 6/10 1,1,1,3,4,5 2.5
200 2/15 1,5,(16) 3.0
150 6/15 1,2,6,11,11,13 7.3
125 3/14 1,1,13 5.0
100 3/14 1,4,6 3.7
Female
250 10/10 1,1,1,1,2,2,2,3,3,4 2.0
200 6/15 1,1,1,2,2,5,(16) 2.0
150 5/15 1,2,6,8,11 5.6
125 2/14 8,8 8.0
100 1/10 1
LD50 (957. confidence limits) Male: 229 (177-616) mg/kg
Female: 182 (159-219) mg/kg
39
-------
TABLE A-23. ACUTE ORAL LD5Q OF METHYL PARATHION IN M. PENNSYLVANICUS
Dose
(mg/kg)
793
ton
OJU
397
250
Mortality
10/10
Wi r\
1U
o / 1 n
y/ iu
5/10
1/10
Time of Death Mean
(days) (days)
Female
1,1,1,1,1 . i.o
LDrn (95% confidence limits) Female: 371 (304-426) mg/kg
'50
TABLE A-24. ACUTE ORAL LD50 OF METHYL PARATHION IN M. MONTANUS
Dose
(mg/kg)
562
355
316
280
250
224
Mortality
d.(l-14)
9/10
3/10
3/10
2/10
2/10
2/10
Time of Death
(days)
Female
1,1,1,1,1,1,1,2,2
1,1,2
1,2,2
1,2
2,2
1,1, (21, 23)
Mean
(days)
1.2
1.3
1.7
1.5
2.0
1.0
LD50 (95% confidence limits) Female: 379 (325-512) mg/kg
40
-------
TABLE A-25. ACUTE ORAL LD50 OF PCNB IN M._ PENNSYLVANICUS
Dose Mortality Time of death Mean
(mg/kg) d.(l-14) (days) (days)
Male
5,000 1/15 2,(23,23)
Female
5,000 1/15 4
LD50 (95% confidence limits) Male: > 5,000 mg/kg
Female: > 5,000 mg/kg
TABLE A-26. ACUTE ORAL LD50 OF PCNB IN M. MONTANUS
Dose
(mg/kg)
5,000
3,160
2,000
1,585
5,000
3,160
2,000
1,585
Mortality Time of death Mean
d.(l-14) (days) (days)
8/15
3/5
2/10
1/10
11/15
4/10
0/10
1/10
Male
1,2, 2, 5, 6, 6, 6, 6, (26)
5, 5, 5, (20)
1,1
2
Female
2,2,2,2,5,5,6,6,6,6,14
1,5,5,6
(< 14)
4.3
5.0
1.0
5.1.
4.3
LD5Q (95% confidence limits) Male: 4,194 (2,870-17,110) mg/kg
Female: 3,717 (2,981-5,048) mg/kg
41
-------
TABLE A-27. ACUTE ORAL LD5Q OF 2,4,5-T IN M^ PENNSYLVANICUS
Dose
(me/kg)
3,162
2,512
1,995
1,585
1,260
Mortality
d.a-14)
9/10
4/10
5/10
2/10
4/10
Time of Death
(days)
Male
1,1,
1,1,
1,1,
2,3
2,2,
1,2,2,3,3,4,13
1,2
1,2,14
2,3
Mean
(days)
3.3
1.3
3.8
2.5
2.3
LD50 (95% confidence limits) Male: 2,066 (1,382-3,501) mg/kg
TABLE A-28. ACUTE ORAL TOXICITY (LD50) OF 2,4,5-T IN M. MONTANUS
Dose
(mg/kg)
3,722
2,352
1,869
1,484
1,178
935
Mortality
d.(l-14)
10/10
4/10
3/10
3/10
2/10
2/10
Time of Death
(days)
Female
1,1,1,1,1,1,1,1,1,2
2,3,3,5
1,2,3
1,2,9
1,1, (29)
3, 3, (29, 29)
Mean
(days)
1.1
3.3
2.0
4.0
1.0
3.0
LD5Q (95% confidence limits) Female: 2,057 (1,645-2,860) mg/kg
42
-------
TABLE A-29. SUBACUTE DIETARY LC50 OF DIELDRIN IN M._ OCHROGASTER
Concentration
(ppm)
Mortality
d.(l-30)
Time of Death
(days)
Mean
(days)
400
250
160
126
100
63
Male
10/10 7,7,7,8,8,8,9,9,11,13 8.7
10/10 3,7,7,7,8,9,11,13,13,14 9.2
10/10 8,8,9,13,13,14,15,18,19,20 13.7
1/10 13
2/10 17,19 18.0
2/11 11,15 13.0
400
250
160
100
63
Female
10/10 3,4,8,8,8,9,9,11,13,15 8.8
10/10 7,7,9,9,9,10,11,13,13,13 10.1
10/10 8,8,9,10,11,13,14,14,18,18 12.3
6/10 10,11,13,13,19,20 14.3
3/10 13,13,14 13.3
LC50 (95% confidence limits) Male: 129 (36-459) ppm
Female: 82 (58-102) ppm
43
-------
TABLE A-30. SUBACUTE DIETARY LC5Q OF DIELDRIN IN M. CANICAUDUS
Concentration
(prm)
Mortality
d.(l-30)
Time of Death
(days)
Mean
(days)
Male
100
63
40
25
16
10/10
10/10
3/10
0/10
0/10
2,3,3,3,4,7,7,7,7,10
4,4,7,7,7,8,8,9,10,14
2,21,22
5.3
7.8
15.0
160
63
40
25
16
10
10/10
9/10
0/10
3/9
3/10
1/10
Female
7,7,7,7,7,7,8,8,9,10
7,7,7,7,7,8,10,13,17
16,17,17
2,17,17
23
7.0
9.2
16.7
12.0
LC5Q (95% confidence limits) Male: 43 (36-50) ppm
Female: 39 (15-101) ppm
44
-------
TABLE A-31. SUBACUTE DIETARY LC OF HCB IN M._ OCHROGASTER
ju •
Concentration
(ppm)
5,000
2,500
1,250
625
313
5,000
3,890
2,500
1,250
625
313
Mortality Time of Death
d.(l-30) (days)
Male
8/10 9,19,21,25,27,29,29,30
2/10 22,29
0/10
0/10
0/10
Female
9/10 10,19,20,20,21,23,25,25,26
9/10 18,20,21,21,24,25,25,28,29
0/10
0/10
0/10
1/10 29
Mean
(days)
23.6
25.5
21.0
23.4
LC5Q (95% confidence limits) Male: 3,553 (2,654-5,007) ppm
Female: 3,450 (g 2 1) ppm
-------
TABLE A-32. SUBACUTE DIETARY LC5Q OF HCB IN M. CANICAUDUS
Concentration Mortality Time of Death Mean
d.(l-30) (days) (days)
Male
5,000 9/10 10,11,11,11,13,16,26,29,29 17.3
2,500 8/10 19,21,22,23,23,24,27,29 23.5
1,250 6/10 5,9,27,27,29,29 21.0
625 2/10 10,10 10.0
313 0/10
Female
5,000 5/5 17,17,20,20,22 19.2
2,500 3/5 12,14,29 18.3
1,250 5/5 16,16,27,30,30 23.8
625 1/5 3
313 0/5
LC50 (95% confidence limits) Male: 1,280 (857-1,919) ppm
Female: 1,047 (533-1,940) ppm
46
-------
TABLE A-33. SUBACUTE DIETARY LC5Q OF METHYL PARATHION IN >L_ OCHROGASTER
ConcentrationMortalityTime of DeathMean
(ppm) d.q-30) (days) (days)
Female
2,000
1,780
1,585
1,412
1,259
891
10/10
9/10
9/10
6/10
8/9
5/10
8,11,11,11,11,12,13,14,15,15
6,8,8,9,11,12,14,15,22
11,12,12,14,14,15,16,18,22
12,15,16,25,26,27
5,5,7,15,16,16,17,20
5,8,10,14,18
12.1
11.7
14.9
20.2
12.6
11.0
LC5Q (95% confidence limits) Female: 912 (345-1,136) ppm
TABLE A-34. SUBACUTE DIETARY LC50 OF METHYL PARATHION IN M._ CANICAUDUS
Concentration Mortality Time of Death Meln~
d.(l-30) (days)
. \
Female
1,096
875
692
550
436
7/10
8/10
2/9
2/10
7/10
5,5,7,9,9,15,16
5,5,7,8,9,11,13
5,19
11,13
9,9,11,11,12,22,25
9.4
7.3
12.0
12.0
14.1
LC50 (957. confidence limits) Female: 613 (g > 1) ppm
-------
TABLE A-35. SUBACUTE DIETARY LC5Q OF PARATHION IN M. OCHROGASTER
Concentration
(ppm)
1,750
1,380
1,096
871
692
500
Mortality
d.Cl-30)
10/10
10/10
10/10
7/10
7/10
0/10
Time of Death
(days)
Female
7,7,7,8,9,9,11,12,17,19
4,5,7,7,8,9,11,15,16,19
4,5,7,8,9,12,12,12,13,16
6,8,11,11,14,14,21
6,11,17,17,20,26
Mean
(days )
10.5
10.1
9.8
12.1
13.8
LC5Q (957. confidence limits) Female: 699 (605-787) ppm
CANICAUDUS
Concentration
(ppm)
251
200
158
141
112
Mortality
d.(l-30)
9/10
3/10
5/10
1/10
0/10
Time of Death
(days)
Female
3,3,4,4,5,5,6,7,8
4,5,5
5,5,6,6,9
9
Mean
(days)
5.0
4.7
6.2
LC_0 (957. confidence limits) Female: 192 (170-228)
48
-------
TABLE A-37. SUBACUTE DIETARY LC5Q OF PCNB IN M._ OCHROGASTER
Concentration Mortality Time of Death Mean
(ppm) d.(l-30) (days) (days)
Male
50,000 6/10 12,12,17,18,18,20 16.2
32,000 3/10 17,22,30 23.0
20,000 1/10 30
12,600 0/10
7,900 0/10
Female
50,000 6/9 9,11,12,17,21,30 16.7
32,000 4/10 12,19,20,25 19.0
20,000 2/10 14,14 14.0
12,600 0/10
7,900 0/10
LC5Q (957= confidence limits) Male: 42,840 (32,790-82,830) ppm
Female: 37,270 (28,250-65,400) ppm
49
-------
TABLE A-38. SUBACUTE DIETARY LC50 OF PCNB IN M._ CANICAUDUS
Concentration
(ppm)
Mortality
d.(1-303
Time of Death
(days)
Mean
(days')
50,000
32,000
20,000
12,600
7,900
Male
10/10 2,2,4,4,4,5,6,11,11,14
9/10 2,3,4,4,6,6,19,20,29
7/10 6,6,6,6,8,22,22
5/10 2,3,5,6,6
4/10 6,8,8,9
6.3
10.3
10.9
4.4
4.8
Female
50,000
32,000
20,000
12,600
7,900
9/9
6/9
4/8
0/10
0/10
4,5,5,6,6,8,11,11,14
5,6,6,13,14,29
3,3,17,30
7.8
12.2
13.3
LC50 (95% confidence limits) Male:
Female:
11,290 (5,728-15,750) ppm
23,780 (18,660-30,140>ppm
50
-------
TABLE A-39. SUBACUTE DIETARY LC5Q OF PROPANIL IN M^ OCHROGASTER
ConcentrationMortalityTime of DeathMean
(ppm) d.(l-30) (days) (days)
Male
50,000 2/11 15,15 15.0
32,000 0/10
20,000 0/10
12,600 1/10 2
7,900 1/10 3
Female
50,000 6/9 3,4,10,15,16,30 13.0
32,000 0/10
20,000 0/10
12,600 0/10
7,900 1/10 30
LC50 (95% confidence limits) Male: > 50,000 ppm
Female: > 32,000 < 50,000 ppm
51
-------
TABLE A-40. SUBACUTE DIETARY LC50 OF PROPANIL IN M. CANICAUDUS
ConcentrationMortalityTime of DeathMean
(ppm) d.(l-30) (days) (days)
Male
20,000 9/10 2,2,4,5,5,10,12,13,27- 8.9
12,600 0/10
7,900 1/10 3 3.5
5,000 4/10 1,3,4,6
3,160 0/10
Female
20,000 4/10 2,3,3,5 3.3
12,600 4/10 6,6,16,24 13.0
7,900 0/10
5,000 0/10
3,160 1/10 3
LC5Q (95% confidence limits) Male: 15,660 (g £ 1) ppm
Female: 20,250 (g •« 1) ppm
52
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TABLE A-41. SUBACUTE DIETARY LC50 OF 2,4,5-T IN M. OCHROGASTER
Concentration
(pom)
Mortality
d.(l-30)
Time of Death
(days)
Mean
(days)
Female
29,674
23,739
14,837
13,220
11,780
9,362
10/10
7/10
2/10
0/10
1/10
0/10
4,5,5,6,7,9,10,11,11,14
13,18,18,22,24,26,30
15,27
27
8.2
21.6
21.0
LC5Q (95% confidence limits) Female: 19,670 (17,100-22,750) ppm
TABLE A-42. SUBACUTE DIETARY LC5Q OF 2,4,5-T IN M. CANICAUDUS
Concentration Mortality
(ppm) d.(l-30)
Time of Death
(days)
Mean
(days)
Female
14,837
13,220
11,780
9,362
7,418
10/10
7/10
6/10
4/10
0/10
2,4,5,6,6,6,12,14,17,20
2,2,3,6,7,11,29
3,4,5,7,11,27
2,3,6,9
9.2
8.6
9.5
5.0
LC50 (95% confidence limits) Female: 10,810 (9,605-11,920) ppm
53
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
EPA-600/5-78-082
2.
3. RECIPIENT'S ACCESSION NO.
4. TITLE AND SUBTITLE
STUDY OF THE CHEMICAL AND BEHAVIORAL TOXICOLOGY OF
SUBSTITUTE CHEMICALS IN MICROTINE RODENTS
5. REPORT DATE
August 1978
6. PERF9RMING ORGANIZATION CODE
7. AUTHOR(S)
James M. Cholakis, Laurence C. K. Wong, and Cheng-Chun
Lee
8. PERFORMING ORGANIZATION REPORT NO.
MRI 4298-B
. PERFORMING ORGANIZATION NAME AND ADDRESS
Midwest Research Institute
A25 Volker Boulevard
Kansas City, Missouri 64110
10. PROGRAM ELEMENT NO.
1EA714
11. CONTRACT/GRANT NO.
68-01-4195
12. SPONSORING AGENCY NAME AND ADDRESS
Corvallis Environmental Research Laboratory
U.S. Environmental Protection Agency
200 S.W. 35th Street
13. TYPE OF REPORT AND PERIOD COVERED
Final
* •* 1 -t
5. SUPPLEIV
14. SPONSORING AGENCY CODE
EPA/600/02
EPA-ORD
15. SUPPLEMETMTAR
TES
is. ABSTRACT Acute oral U>50 and 30-day dietary subacute LC5Q studies or 10 selected pest-
icides were evaluated in microtine rodents. As a means to developing new animal model
systems, four species of microtine rodents including Microtus ochrogaster (MO), Microtus
canicaudus (MC), Microtus pennsylvanicus (MP) and Microtus montanus (MM) voles were used
The acute LDcQ (median lethal dose in mg/kg) in all four species and the subacute LC5Q
(median lethal concentration in ppm) in MO and MC voles were computed using probit an-
alysis. The data from both the acute and the 30-day subacute studies revealed that MC
voles were approximately twice as sensitive to these pesticides as MO voles. Based on
the acute studies, the overall order of pesticide toxicity was as follows: parathion >
methyl parathion>dieldrin>2,4-D >2,4,5-T>simazine propanil = PCNB = HCB = triflura-
lin. The general order of species sensitivity was as follows: MC>MP>MO>MM. No ap-
parent sex differences were observed in MP, MO or MM voles. In MC voles, the female ap-
peared to be two- to threefolds more sensitive to methyl parathion than the male. Based
on the 30-day subacute LC5Q studies, the overall order of pesticide toxicity is as fol-
lows: dieldrin>parathion> methyl parathion >HCB >2,4,5-T >PCNB> propanil. Based on
jO values the laboratory rodents appear to be more susceptible to 2,4-D, dieldrin,
methyl parathion, parathion, propanil, and 2,4,5-T, equally susceptible to HCB, PCNB, and
trifluralin. and less susceptible to simazine than the MC voles.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COSATI l:icld/Group
Animals
*Pesticides
*Toxicology
Acute LD5Q
Subacute LC5Q
6T
13. DISTRIBUTION STATEMENT
RELEASE TO PUBLIC
19. SECURITY CLASS (This Report)
UNCLASSIFIED
1. NO. OF PAGES
60
20. SECURITY CLASS (This page)
UNCLASSIFIED
22. PRICE
EPA Form 2220-1 (9-73)
54
4 U.S. GOVERNMENT PRINTING OFFICE: 1978-797-800/238 REGION 10
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