xvEPA
United States
Environmental Protection
Agency
Health Effects Research
Laboratory
Research Triangle Park NC 27711
Research and Development
EPA-600/S1-81-037 June 1981
Project Summary
Carcinogenic Potential of
Rotenone: Subchronic
Oral and Peritoneal
Administration to Rats and
Chronic Dietary
Administration to Syrian
Golden Hamsters
R. I. Freudenthal, D. C. Thake, and R. L. Baron
Three long-term studies were per-
formed to evaluate the carcinogenic
potential of the pesticide rotenone in
hamsters and rats. Rotenone was
administered orally to Wistar rats and
by intraperitoneal injection to Sprague-
Dawley rats, which were maintained
and observed for 14 and 18 months,
respectively. Syrian golden hamsters
were maintained for 18 months on
diets containing rotenone in concen-
trations up to 1000 ppm. Following
these studies the animals were sub-
jected to extensive necropsy.
No evidence of an increased inci-
dence of mammary or any other type
of neoplasm was noted in the two rat
studies. At all dosage levels in the
hamster dietary study, no gross or
histopathological evidence was ob-
tained which suggested that rotenone
induced the formation of mammary
tumors. Three adrenal cortical carci-
nomas were observed in 65 hamsters
from the highest dosage group. While
this occurrence was suspicious, it is
questionable that it was related to
rotenone treatment. There were no
other indications of neoplastic events.
In ancillary studies there was pre-
liminary evidence that rotenone at
levels of 500 ppm in the maternal diet
was embryo-toxic and resulted in
cannibalism of the young by the ma-
ternal animals. A level of 1000 ppm
led to sterility in one or both sexes.
Hamsters fed rotenone displayed re-
duced feed consumption and dimin-
ished weight gains during the first few
months of administration.
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 doc-
umented in a separate report of the
same title (see Project Report ordering
information at back).
Introduction
This summary describes two series of
studies on the carcinogenic potential of
rotenone. In the first series, subchronic
doses of rotenone were administered to
male and female Wistar rats orally and
to Sprague-Dawley rats by intraperito-
neal injection for 42 consecutive days.
The orally treated rats were maintained
-------
for 14 months and the peritoneally
treated rats for 18 months. In the
second series, chronic dietary studies
were performed to evaluate the potential
carcinogenicity of rotenone in the Syrian
golden hamster. Several ancillary stud-
ies were carried out including a prelim-
inary reproduction experiment.
The first series included three studies.
The first study was performed to test the
palatability of rotenone in the diet of
rats. Twenty Sprague-Dawley derived
rats (10 male and 10 female rats) were
used. Body weights ranged from 125 to
145 g (females) and 150 to 175 g (males)
at the start of the feeding period. Rats
were individually housed and quaran-
tined for seven days prior to dietary
exposure to rotenone.
Five rats of each sex were assigned to
each of two dosage groups. Feeds
containing 1% corn oil were dosed with
either 500 or 1000 ppm rotenone. Feed
was presented to the rats for two weeks
followed by one week of exposure to
control diets (no rotenone or corn oil).
Individual rats and feed remaining in
feed pans were weighed weekly to
obtain body weight and feed consump-
tion values.
The second study was performed to
determine the carcinogenic potential of
rotenone delivered by intraperitoneal
injection. A group of Sprague-Dawley
rats (65 male and 65 female Charles
River rats) were used in this study. Body
weights on the first day of dosing were
67 to 156gforfemalesand110to169g
for males. Rats, housed in groups of two
per cage, were held in quarantine for 13
days prior to dose initiation. Following
quarantine, the rats were assigned to
one of three treatment groups. Rotenone
was prepared for injections by pre-
weighing amounts of the chemical
which were determined to be appropriate
for the following week. These amounts
were calculated from the mean weights
of the rats in a specific group, using the
previous week's body weights and the
weight increases estimated for the
following week from historical growth-
rate data. All samples were suspended
in corn oil on the day of dosing and
administered by intraperitoneal injec-
tion in a volume of 0.1 ml. Test groups of
25 males and 25 females each received
doses of 1.7 or 3.0 mg rotenone/kg body
weight. Control rats, 15 males and 15
females, received 0.1 ml corn oil injec-
tions. Injections were made on 42
consecutive days. Following the dosing
period, the rats were observed for a
period of 17 months, after which the
surviving animals were sacrificed and
necropsied.
The final study was performed to
determine the carcinogenic potential of
rotenone delivered by oral gavage. A
group of 150 Charles River Wistar rats
(75 of each sex) were used in this study.
Body weights on the first day of dosing
ranges from 75 to 145 g for females and
from 81 to 156 g for males. Animals
were caged in pairs and quarantined as
above. Following quarantine, rotenone
was administered by gavage with a
stainless steel feeding needle. The
rotenone suspension was prepared as
described above for the 18-month study.
The rotenone-corn oil mixture was
given in a volume of 0.25 ml daily for 42
consecutive days. Doses of 0,1.7, or 3.0
mg rotenone/kg body weight were
administered to groups of 25 males and
25 females. Following 42-day adminis-
tration period, the rats were observed
for 13 months, after which the rats were
sacrificed and necropsied.
In both long-term rat studies, growth
was recorded weekly for three months
and biweekly for the remainder of the
study. At the conclusion of the studies,
gross and microscopic pathology was
performed.
The second series of studies concerned
the effects of rotenone on Syrian golden
hamsters. In a preliminary subchronic
trial a group of 10 hamsters were given
oral intubations of 80 mg rotenone/kg
body weight, suspended in 1.0 ml corn
oil, daily for nine days.
Two four-week preliminary dietary
studies were conducted to provide in-
formation on the palatability of rotenone-
containing feeds and to evaluate gross
toxicity in the treated animals. Rotenone
was blended with Purina Hamster Chow
Meal to yield concentrations of 0, 63,
125, 250, 500, and 1000 ppm for the
subacute studies. Hamster weights
ranged from 50 to 70 g at the beginning
of the study. Animals were given access
to control feed for one week prior to
dosing.
In the preliminary trials, hamsters in
groups of 10 animals (5 males and 5
females) were fed rotenone-containing
feeds for 14 days followed by 14 days of
control feed. Animal body weights and
feed consumption were determined
weekly. Gross necropsies were performed
at the end of the 14-day control diet
feeding period.
A long-term (18-month) study to
evaluate the potential carcinogenicity of
rotenone in hamsters was performei
Rotenone was incorporated in the fee
of the test animals for the duration <
the study. Groups of 50 male and 5
female hamsters were fed diets cor
taining rotenone at concentrations of (
125, 250, 500, or 1000 ppm for 1
months. All diets contained 1% corn o
to aid the uniform dispersal of rotenon*
Animals were weighed weekly for th
first six months and bi- or tri-weekl
thereafter. Feed consumptions wer
measured weekly throughout the studi
Daily observations were made for moi
tality, behavior, and appearance. Ham
sters were subjected to complete ne
cropsy and examined for evidence c
tumors at the time of sppntaneou
death or, following sacrifice, at th
termination of the study.
Tissues examined and removed a
necropsy were placed in buffered, neu
tral 10% formalin. Tissues from animal:
in the 0, 125, and 1000 ppm group:
were processed, sectioned at 5 microns
and stained with hematoxylin and eosir
for histologic evaluation. The groups fee
250 and 500 ppm rotenone were ex
eluded from initial histopathologica
examination since these data would be
superfluous if either of two situation:
existed: (1) chemical -related tumor;
were found in the 125 ppm (low-dosage
group or (2) no chemical-related tumors
were found in the 125 ppm (low-dosage
or the 1000 ppm (high-dosage) groups
In the first situation, the tumor-inducing
threshold dosage would be below 125
ppm, and data from the 250 and 50C
ppm groups would not add to the ques-
tion of the carcinogenic nature of rote-
none. In the second circumstance, lack
of tumors in the high- and low-dosage
groups would suggest that the tumor-
inducing threshold for rotenone is
above 1000 ppm and that formation of
tumors by intermediate dosages would
be extremely unlikely. If tumors were
found in the 1000 ppm rotenone group,
but none in the 125 ppm group, the
preserved tissues could have been
processed and examined for the estab-
lishment of a dietary threshold.
The following tissues were removed
at necropsy: skin (thoracic and abdomi-
nal), mammary gland, trachea, lung,
heart, abdominal aorta, bronchial, man-
dibular and mesenteric lymph nodes,
spleen, thymus, kidney, ureter, bladder,
ovary, uterus, testicle, epididymis, pros-
tate, seminal vesicle, salivary gland,
tongue, esophagus, stomach, duodenurd|
jejunum, ileum, cecum, colon, recturrff
-------
pancreas, liver, gall bladder, thyroid,
parathyroid, adrenal, rib, femur, muscle,
brain (cerebrum, cerebellum and medulla),
pituitary, spinal cord, sciatic nerve, and
eyes. Selected sections of kidney, spleen,
liver, adrenal, and thyroid were stained
by the Bennhold Congo red method for
amyloid detection. Other selected sam-
ples of adrenal were stained by the
Gomori chromaffin staining technique
for chromaffin granule detection. Micro-
scopic examination of tissues was
performed by board-certified or board-
eligible pathologists.
In an ancillary study, an effort was
made to evaluate the effects of rotenone
on reproduction. Male and female ani-
mals were fed diets containing rotenone
at 0, 500, or 1000 ppm for three months
and then mated twice at appropriate
times to evaluate the effects of rotenone
on reproduction. Groups of 50 females
and 25 males (50 males in the controls)
were used in this effort.
Results
Mean body weight gains were sup-
pressed in both male and female rats fed
either 500 or 1000 ppm rotenone in the
diet. Females appeared to be moresensi-
ive to rotenone than male rats in this
•espect. Male rats fed 1000 ppm rotenone
experienced smaller weight gains than
hose on 500 ppm diets.
Feed consumption was slightly higher
or rats fed 500 ppm rotenone compared
o those fed 1000 ppm (days 7-14).
t/Vhen rats were returned to normal
diets (days 14-21), feed consumption
doubled. It is concluded that feed con-
aining rotenone at a concentration of
500 ppm is less palatable to rats than
normal feed and dietary ingestion at this
concentration leads to depressed body
weight gains in immature rats. The use
of rats for dietary carcinogenicity bio-
assays may be limited by the dosage
levels that can be used in long-term
studies.
The intent of the next phase of the
project was to duplicate, in a different
strain of rats, an earlier study in which
mammary tumors were found in rats
following intraperitoneal administration
of rotenone. Male rats which received
3.0 mg/kg rotenone exhibited up to 25%
lower body weights than controls during
the 18-month study, while the 1.7
mg/kg group maintained body weights
intermediate to those of controls and
the 3.0 mg/kg animals. The most highly
dosed female rats also experienced
duced body wieghts which were on
average not less than 87% of those of
the controls.
Table 1 presents the rat survival data
for this study. No increases in death
resulted from rotenone exposure. Con-
trol, low dose, and high dose groups
experienced 23,16, and 30% mortalities,
respectively, within the 18-month study
period. No substantial sex difference in
mortality was noted.
There were numerous mammary
gland neoplasms observed both macro-
scopically and microscopically in ani-
mals from the control group and both
treatment groups. These were for the
most part fibroadenomas and they
occurred with similar frequency among
control and treatment groups. In addition
to the fibroadenomas, one adenoma
occurred in females given 3.0 mg/kg
and three in females given 1.7 mg/kg;
the latter occurred in conjunction with
fibroadenomas. Mammary carcinoma
was present in one female given 3.0
mg/kg.
Several fibroadenomas were also present
in males from the control and 1.7 mg/kg
groups. Fibroadenomas occurred in
control rats with a frequency equal to or
greater than that of treated groups, and
the incidence of all female animals
bearing mammary neoplasms was 60,
72, and 43% for the control, low- and
high-dosage groups, respectively. The
highest incidence of mammary neo-
plasms in male rats occurred in the
control group. Two lymphosarcomas
occurred in females given 3.0 mg/kg; all
other neoplasms occurred in only one
animal for any given dosage group with
the exception of chromophobe adenomas
of the pituitary gland and adrenal cortical
adenomas, which occurred with similar
frequency among control and treatment
groups.
The only non-neoplastic lesions which
occurred with substantially greater
frequencies in rotenone-treated animals
compared to controls included myo-
cardial fibrosis and/or lymphoreticular
myocarditis in both the 1.7 and 3.0
mg/kg groups and cystic ductular dila-
tations in mammary glands of females
given 3.0 mg/kg. Complete summaries
of all neoplastic and non-neoplastic
lesions observed in the animals ne-
cropsied in this study are given in the
full Project Report.
In the second long-term study, where
rotenone was administered by oral
gavage to Wistar rats, no appreciable
differences were seen in body weights
between the different groups throughout
the study. Although this study was not
as lengthy nor did it use the same route
of administration as that described
previously, the Wistar strain appears to
display lower sensitivity to rotenone
administration as measured by body
weights.
Survival data are presented in Table
2. Again, no significant number of
deaths can be attributed to rotenone
treatment in this study. Because of the
different rates of lesions observed in the
control groups, it is difficult to make
comparisons on the lethality of rotenone
in Wistar and Sprague-Dawley rats.
Neoplasms were observed in mam-
mary glands of three female rats from
this study. Multiple adenomas (two)
were present in two animals, one from
the control group and one from the 1.7
mg/kg dosage group. There were other
small masses observed grossly in which
mammary cysts, ductal or glandular
ectasias, or mild hyperplasias were
observed microscopically. Ductal or
glandular ectasias and cysts were
slightly more prevalent in females from
the 1.7 or 3.0 mg/kg dosage groups as
compared to the control group.
Adrenal cortical adenomas occurred
in greater numbers in both the 1.7 and
Table 1.
Rat Survival Following Rotenone Intraperitoneal Injections
Dosage Group
3.0 mg/kg
1.7 mg/kg
Control
Month
0
11
12
13
14
15
16
17
18
Male
25
21
21
21
20
18
18
17
17
Female
25
21
21
21
21
20
19
19
18
Male
25
24
24
24
24
24
23
23
22
Female
25
25
24
24
23
23
23
23
20
Male
15
15
15
14
12
12
12
11
11
Female
15
15
15
14
14
13
13
12
12
-------
Table 2.
Month
Rat Survival Following Rotenone Oral Gavage
Dosage Group
3.0 mg/kg
1.7 mg/kg
Control
Male
Female
Male
Female
Male
Female
0
7
8
9
JO
11
12
13
14
25
25
25
25
24
24
23
23
23
25
24
24
24
24
24
24
24
24
25
25
25
25
25
25
25
24
24
25
24
24
24
24
24
24
24
24
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
3.0 mg/kg dosage groups compared to
the controls. This was especially notice-
able in the females and occurred with
similar frequency among females from
both the high- and low-dosage groups.
Fibrosarcomas occurred in subcuta-
neous sites in three males from the 3.0
mg/kg dosage group and one fibroma
was observed in a male rat from the 1.7
mg/kg dosage groups. Neitherfibromas
nor fibrosarcomas were observed in
control groups in this study.
Bile duct hyperplasias were observed
in three females and one male from the
high-dose group and one male from the
control group. These were extremely
mild changes. All other neoplastic
lesions, and other non-neoplastic
changes, occurred with similar or
greater frequencies in the control groups.
There was a striking difference be-
tween the incidence of mammary neo-
plasia among Wistar rats, treated orally,
compared to Sprague-Dawley rats ex-
posed by intraperitoneal administration
(Table 3). The incidence of mammary
fibroadenomas in the intraperitoneal
treatment group was as high in the
control animals as in those given 1.7
mg/kg and higher than the group given
3.0 mg/kg. The incidence of animals
from the intraperitoneal study with
mammary neoplasms was similar for
rats in the 1.7 mg/kg and control groups
since the three adenomas occurred in
animals which also had fibroadenomas.
The lowest incidence was recorded in
those rats given 3.0 mg/kg. These data
were interpreted as showing no evidence
that rotenone enhanced or induced
mammary neoplasia in animals under
the condition of either the intraperito-
neal or the oral treatment study.
The significantly higher incidence of
mammary neoplasia in animals treated
intraperitoneally compared to the oral
treatment group may reflect a different
incidence of spontaneous mammary
neoplasms in Wistar and Sprague-
Dawley rats. The large number of spon-
taneous fibroadenomas commonly pre-
sent in Sprague-Dawley rats was
evident in this study and was in sharp
contrast to the absence of this tumor
type in the Wistar rats.
Observations were made of hamsters
administered rotenone orally on a sub-
acute basis for nine days. The animals
became lethargic soon after the initial
dose. Three animals died during the first
two days of the study and exhibited an
oily substance in the peritoneal cavity
although no stomach punctures were
found. Other animals displayed signs of
diarrhea, eye discharge, lameness,
shaggy coats, and mouth ulcerations.
The lungs, liver and G.I. tract were
congested and redness was observed in
the lungs and pleura. Intussusceptions
of the small intestine and rectal pro-
lapses were commonly seen. Hamsters
treated only with corn oil exhibited mild
diarrhea which subsided after four days.
In preliminary dietary studies, the
mean body weight data showed a sub-
stantial reduction in growth of males
during the first week of being fed 1000
ppm rotenone. This effect was reversed,
with observed weight gains greater
than normal, after return to the control
diet. During the course of this prelimi-
nary study, no abnormal behavior or
symptoms were observed and none of
the hamsters died.
Gross observations at necropsy
showed the lungs of several 1000 ppm
hamsters to be congested and colored
cherry red. Several small petechial
hemorrhagic areas were present on the
lung surface. Also seen were congestion
of the duodenal mucosa, dilation of
meningeal vessels, and hemorrhagic
enteritis in the small intestines. Similar
but less extensive lesions were present
in animals given 500 ppm. No lesions
were found in the 250 ppm or lower
dosage groups. Preliminary study sug-
gested that 1000 ppm in the diet would
be an appropriately high dosage level for
the chronic study.
Mortality was evident in the long-
term carcinogenesis study. Substantial
spontaneous death losses were en-
countered in all groups of hamsters
from this study during the first 12
months of exposure. The deaths were
apparently not related to rotenone
administration since the losses were as
Table 3. Comparison of Incidence of Mammary Gland Neoplasia in Rats
Administered Rotenone Orally and Intraperitoneally
Species
and
Route
Wistar
(oral
gavage)
Sprague-
Dawley
(intra-
peri-
toneal
injection)
Type
of
Neoplasm
Adenoma
Adenoma
Carcinoma*
Adenocar-
cinoma*
Fibroadenoma
Fibroadenoma
Fibroadenoma
Fibroadenoma
Fibroadenoma
Adenoma^
Adenoma
Adenoma
Carcinoma
Treatment Level
No. (mg/kg)
1
1
1
1
8
3
13
1
7
3
1
1
1
Control
1.7
1.7
1.7
Control
Control
1.7
1.7
3.0
1.7
3.0
Control
3.0
No.
in
Group
25
24
24
24
15
14
25
24
21
25
21
15
21
Sex
F
F
F
F
F
M
F
M
F
F
F
F
f
Incidence
%
4
4
4
4
53
21
52
4
33
12
5
7
5
*0ccurred in same animal.
\AH three adenomas in this group occurred in animals which also had fibroadenomas.
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high or higher in controls than in the
treatment groups. A pathogenic strain
of E. coll was isolated from several
animals dying during this period and
preliminarily suggested that a heat-
labile enterotoxin of E. coli may have
been responsible for early mortality.
These observations were not investi-
gated further.
Survival data for the hamsters studied
are presented in Table 4. Spontaneous
deaths were not dose-related for rotenone
nor were there sex-related differences
for mortalities in the test groups. Female
control animals experienced a high
death rate during the final five months
of the study, which may have been
related to the enteric infections which
were prevalent in this group early in the
study.
Change in body weight was used as a
measure of hamster growth. Both 50
and 1000 ppm groups exhibited depres-
sed body weights relative to other test
groups, particularly males fed the higher
dosage. This trend may have resulted in
part from the decreased feed consump-
tion for these groups during the first six
months of the study, as noted with rats.
Gross visible lesions encountered at
necropsy of hamsters dying spontane-
ously and of animals sacrificed at study
termination are presented in the full
Project Report. Notable lesions en-
countered in animals dying spontane-
ously were nephrosis due to apparent
amyloid deposition, centrilobular con-
gestion and necrosis of the liver, vege-
tative thrombosis generally in the left
atrium of the heart, pulmonary conges-
tion, hemorrhage, and pneumonia as
well as atrophy or hypoplasia of the
testicles.
Several tumors were also apparent at
necropsy. Ovarian tumors were noted in
one female of the 1000 ppm group and
in one of the control group. Masses
involving leg muscles were found in one
female of the 1000 ppm group and in
one female of the control group. A renal
tumor was suspected in one male of the
500 ppm group, and a cystic adenoma
was found in one female of the 125 ppm
group; possible thyroid tumors were
found in one female hamster of the 125
ppm group and two females of the
control group. An adrenal tumor was
suspected in one female of the 1000
ppm group, and a lymphoid neoplasm
was present in several tissues from one
female of the 250 ppm group. Several
other lesions and alterations were also
found.
In this study no substantial histopath-
ological differences were seen between
treatment groups. Males in this study
had less amyloid depositions in the liver,
spleen, adrenals, and thyroid than
females. No profound differences in the
incidence of non-neoplastic pathologic
lesions were observed between rotenone-
treated animals at various dose levels
and the control group. No pathologic
alterations of note were seen in any
dose group relative to mammary gland
changes. Under the conditions of this
bioassay, rotenone is not carcinogenic
to the Syrian golden hamster. However,
the occurrence of increased levels of
adrenal cortical tumors in hamsters as
well as in rats should be noted.
Two groups of hamsters (50 males
and 50 females) were maintained on a
control diet throughout the modified
reproduction study. Each female was
caged with one male for mating. Preg-
Table 4. Hamster Survival During the Rotenone Dietary Study
Dosage Group
1000 ppm
500 ppm
250 ppm
125 ppm
Control
Month Male Female Male Female Male Female Male Female Male Female
0
12
13
14
15
16
17
18
19
(until
50
33
32
29
27
26
25
25
24
50
34
33
30
28
27
24
19
19
50
35
34
33
32
31
29
26
25
50
30
28
26
26
23
21
20
18
50
33
31
27
27
25
24
20
19
50
37
34
30
30
28
27
24
20
50
35
32
27
26
25
24
24
21
50
28
26
25
24
22
19
14
9
50
30
30
30
29
28
25
22
22
50
28
27
23
20
14
11
6
2
necropsy)
nancies occurred, offspring were deliv-
ered, weaned, and discarded. The
process was repeated to produce a
second litter.
The Fia generation all appeared
healthy through weaning. Forty-three
litters were delivered from 50 females.
Litter sizes ranged from 2 to 10 pups,
with an average of 7. One to three pups
were retained from each litter and
observed for tumor formation over an
extended period. The second group of
offspring (F,b) also appeared to be
healthy through weaning. There was an
average of 12 pups per litter which
ranged in size from 9 to 17 pups.
A group of animals (50 females and
25 males, with mean body weights of 45
g for both sexes) were maintained on a
1000 ppm rotenone diet containing 1 %
corn oil for three months and mated.
The parental hamsters continued to
increase in body weight for the first five
weeks of the study, after which time
feed consumption decreased. Fifteen (3
males and 12 females) of the 75 animals
studied died during the first two months.
The physical conditions deteriorated
and body weights decreased in the
survivors. After eight to nine weeks the
downward trend in body weights re-
versed, the animals became more alert,
their coats developed a sheen and food
consumption returned to normal.
Females were observed daily accord-
ing to the Orsini technique to monitor
estrus cycles. During the fourth month
of the study, mating was initiated by
housing one male with two females at
the end of the first day of the estrus
cycle, which is normally four days in
duration. Although several vaginal
plugs were observed, it was soon de-
termined that one or both sexes were
infertile since no pregnancies occurred.
Males were observed to have smaller
than normal testicles. This group was
discontinued when pregnancies failed
to occur.
Another group of hamsters (25 males
and 50 females) were maintained on a
500 ppm rotenone diet for three months
prior to and during the mating periods.
Mating was carried out as described
above.
The first generation of offspring (Fia)
consisted of 45 litters from 50 females.
Only seven litters survived through
weaning as the dam often cannibalized
or totally neglected her young. The pups
were all smaller than normal. The
average litter size was 9 pups and
ranged from 4 to 15 offspring. The
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second mating of the 500 ppm group
yielded 21 litters, ranging in size from 7
to 16 pups with an average of 12. The
dams again refused to nurse their young
and often cannibalized them.
Six months after the beginning of the
500 ppm rotenone feeding study, and
10 months for the control group, the
studies were terminated because of
high toxicity at the 500 ppm level,
exhibited by large numbers of fetal
deaths, maternal deaths, cannibalism of
offspring pups, and offspring death
which resulted in a small number of
hamsters surviving weaning. While
rotenone at 500 ppm did not substan-
tially affect parental reproduction, sur-
vival of offspring was severely affected
in hamsters. As these studies were not
carried further, more data are needed to
evaluate fully the effects of rotenone on
hamster reproduction.
R. I. Freudenthal is with Stauffer Chemical Co., Farmington, CT 06032; D. C.
7hake is with Battelle Memorial Institute. Columbus, OH 43201.
R. L. Baron is the EPA Project Officer (see below).
The complete report, entitled "Carcinogenic Potential of Rotenone: Subchronic
Oral and Peritoneal Administration to Rats and Chronic Dietary Administra-
tion to Syrian Golden Hamsters," (Order No. PB 81-190 936; 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 -757-012/7128
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