xvEPA
United States
Environmental Protection
Agencv
Health Effects Research
Laboratory
Research Triangle Park NC 27711
Research and Development
EPA-600/S1-81-048 Aug. 1981
Project Summary
Effects of Post-Implantation
Exposure to Selected
Pesticides on
Reproductivity in Rats
Fitzgerald Spencer
The post-implantational effects of
dinoseb. PCB's (Aroclor 1254),
rotenone and zineb on reproductive
systems were examined using de-
cidualized pseudopregnant rat as a
model. Uterine protein, uterine
glycogen, uterine water, and ovarian
protein were studied in day-10 de-
cidualized pseudopregnant rats fed
the toxicants from days 6 through 9 of
pseudopregnancy. Dinoseb reduced
uterine protein and uterine glycogen in
rats fed 25 ppm and higher concentra-
tions. Uterine water and uterine
weight were reduced at the highest
dosage of 750 ppm. Ovarian protein
was diminished at 150 ppm and
higher concentrations. PCB's lowered
uterine glycogen, but uterine protein
content was not reduced in a dose-
related manner. Ovarian protein con-
tent was diminished at 50 ppm and
higher concentrations. Uterine weight
and uterine water were not changed in
rats fed up to 1000 ppm of the PCB's.
Rotenone reduced uterine protein in
rats fed 200 ppm and higher con-
centrations. Uterine glycogen was
diminished at 10 ppm and higher
concentrations. In day-16 pregnant
rats fed rotenone (100, 200,400, and
600 ppms) from days 6-16 of preg-
nancy, placenta! protein, placenta!
glycogen, ovarian protein, and mater-
nal body weight were reduced. Addi-
tionally, these dosing regimens re-
duced fetal survival rate. Fetal weight
of fetus delivered from rotenone-fed
dams was not affected. The decid-
ualized pseudopregnant uterine, and
placenta! functions and fetal survival
rate of rats were not affected by zineb
up to 2500 ppm.
This Project Summary was devel-
oped by EPA's Health Effects Re-
search Laboratory, Research Triangle
Park. NC, to announce key findings of
the research project that is fully
documented in a separate report of the
same title (see Project Report ordering
information at back).
Introduction
The talidomide episode caused great
public concern and left no doubt on the
necessity of testing possible teratogenic
and fetotoxic effects of compounds that
may be encountered by pregnant
women.
Since the presence of many classes of
pesticides in the environment offers
numerous opportunities for these
toxicants to enter the physiological
systems of various species of animals
including man, there has been an
increased interest in studying the
teratogenic effects of certain pesticides
on mammalian reproduction.
Pesticides such as DDT have been
shown to reduce estradiol liter in blood
of ringdoves, Streptopelia risoria. On
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the basis of experiments, the eggshell
thinning action of chlorinated hydro-
carbons has been attributed to direct
estrogenic action of DDT and its analogs
(RGB's).
Because pseudopregnant and preg-
nant rats have identical mechanisms for
controlling the onset and loss of uterine
sensitivity, the deciduomal response in
decidualized pseudopregnant rats was
used to study possible reproductive
disruption as caused by various pesticides
in pregnant uteri.
Results and Discussion
Uterine weight and uterine water
content of decidualized pseudopregnant
rats exposed to dinoseb were only
reduced at the highest dosage of 750
ppm. In comparison with the control,
uterine protein and uterine glycogen
contents were reduced at 25 ppm and
higher concentrations. Ovarian protein
content of the rats exposed to dinoseb
for 4 days was not affected up to 500
ppm. The difference in susceptibility to
dinoseb, between uterine protein con-
tent and ovarian protein content might
be attributed to a differential distribution
of dinoseb within the reproductive
system. In pregnant rats, exposed to
dinoseb for 10 days, ovarian protein
content was reduced at 200 ppm and
higher concentrations.
Ovarian protein of the decidualized
pseudopregnant (OCR PSPG) rats ex-
posed to the PCB, Aroclor 1254, was
reduced to 50 ppm and higher con-
centrations. Uterine protein content
was reduced at 25 ppm and higher
concentrations. This reduction was not
dose-dependent, and the difference
was attributed to abnormal control
value. Uterine glycogen content of the
rats was reduced at 150 ppm and higher
concentrations. Uterine weight and
uterine water content, regardless of the
dose of the PCB's being tested, were not
affected.
In OCR PSPG rats exposed to rotenone,
uterine weight was reduced at 100 ppm
and higher concentrations, but uterine
water content was not affected. Ovarian
protein content was not reduced up to
750 ppm. Uterine protein content was
reduced at 200 ppm, in comparison with
the control. Uterine glycogen content
was decreased at 10 ppm and higher
concentrations. Placental protein con-
tent and placental glycogen content of
pregnant rats exposed to rotenone were
reduced. Ovarian protein content of rats
was diminished. Rotenone did not affect
the developing embryos. Fetal survivial
rate of the fetuses was decreased at 100
ppm and higher concentrations. Fetuses
delivered from dams exposed to rotenone
during the post-implantational stage of
pregnancy did not exhibit any reduction
in body weight. The levels of zineb
tested in the intrauterine environment,
i.e. uterine protein, uterine glycogen
and uterine water contents of the rats,
were not affected. Ovarian protein in
both the pseudopregnant and pregnant
rats exposed to zineb for 4 days and 10
days, respectively, was not affected.
Placental protein was not affected by
zineb. In comparison with the control,
placental glycogen content was in-
creased. This increase was not dose-
dependent. Development of implantation
sites in pregnant rats after 7 days of
exposure to zineb was not affected. The
fetal survival rate was not affected.
Fetal weight was reduced but this
decrease was not regarded to be
compound-related since it was not
dose-dependent.
Conclusions
Dinoseb, PCB's (Aroclor 1254), and
rotenone are uterotoxic, causing dis-
ruption on the integrity of decidualized
pseudopregnant uterus. Since the
intrauterine environment is maintained
by sex hormones, namely, estrogen and
progesterone, anti-estrogenic, and anti-
progrestogenic properties of these
toxicants could be inferred.
Rotenone interferes with fetal de-
velopment. Because development of the
placenta corresponds with that of the
fetus, any interference imposed on the
placenta by rotenone may be viewed as
essentially disruptive to the fetal
development process. In addition,
rotenone is fetotoxic. The fetotoxic
potential of rotenone is designated by a
decrease in fetal survival rate.
This study shows that zineb has low
toxic effects on the maternal repro-
ductive system and the fetus. This could
be attributed to the fact that zineb does
not accumulate to a large extent in
mammalian tissues and could be
metabolized readily.
Recommendation
Further studies on the toxicological
effects of pesticides upon the repro-
ductive system should be correlated
with the adrenal functions.
Consideration should be given to
dietary intake of the animal during any
toxicological studies in reproduction.
Fitzgerald Spencer is with the Department of Biological Sciences and Health
Research, Southern University, Baton Rouge, LA 70813.
August Curley is the EPA Project Officer (see below).
The complete report, entitled "Effects of Post-Implantation Exposure to
Selected Pesticides on Reproductivity in Rats," (Order No. PB 81-213 209;
Cost: $6.50, subject to change) will be available only from:
National Technical Information Service
5285 Port Royal Road
Springfield, VA 22161
Telephone: 703-487-4650
The EPA Project Officer can be contacted at:
Health Effects Research Laboratory
U.S. Environmental Protection Agency
Research Triangle Park. NC 27711
i US GOVERNMENT PRINTING OFFICE 1981 -757-012/7304
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Environmental Protection
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Information
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