A little background information:
The uterus is located in the lower abdomen between the bladder
and the rectum. The uterus is also called the womb. It is
pear-shaped, and the lower, narrow end of the uterus is
the cervix. When a woman is pregnant, the baby grows in
the uterus until he or she is born. On each side of the
uterus at the top are the fallopian tubes and ovaries.
Together, the uterus, vagina, ovaries, and fallopian tubes
make up the reproductive system.
In women who have not gone through menopause ("the
change" or "change of life"), the ovaries
produce the hormone estrogen at the beginning of the menstrual
cycle. Estrogen helps to prepare the lining of the uterus
(called the endometrium) for possible pregnancy. When the
uterus is ready, one of the ovaries releases an egg. The
egg travels down the fallopian tube where it waits for possible
fertilization. If the woman becomes pregnant, the fertilized
egg travels to the uterus where it attaches to the endometrium.
If she does not, the endometrium and the unfertilized egg
are discharged through the vagina during the woman's next
The Endocrine System:
Illustration by K. Born in Our Stolen Future
by Theo Colborn, Dianne Dumanoski and JP Myers
use of high doses increases the likelihood that potentially
significant toxic effects will be identified. Findings of
adverse effects in any one species do not necessarily indicate
such effects might be generated in humans. From a conservative
risk assessment perspective however, adverse findings in
animal species are assumed to represent potential effects
in humans, unless convincing evidence of species specificity
Food and Agricultural Organization of the United Nations
This is not an exhaustive list.
When time allows more information will be added.
- Fungicide -
In a chronic/oncogenicity study Fisher rats
received 0, 50, 200, 5,000, or 10,000 ppm of benthiavalicarb-
isopropyl for up to 104 weeks. The NOAEL was 200 ppm (9.9 mg/kg/day
and 12.5 mg/kg/day in males and females respectively), based
on a variety of toxic effects, primarily in the liver and kidney,
and adenocarcinomas of the uterus
at 5,000 ppm.
Ref: March 9, 2005. Petition
for the establishment of Tolerances on Imported Grapes and Tomatoes.
Federal Register: March 9, 2005.
Acaracide, Insecticide - CAS No. 122453-73-0
of Carcinogenicity, but Not Sufficient to Assess Human
Carcinogenic Potential'' based on significant
trends in liver tumors (adenomas and combined adenomas/ carcinomas),
malignant histiocytic sarcomas, and testicular cell tumors in
male rats and uterine polyps in female
rats seen at the highest dose.
Federal Register: September 26, 2003. Chlorfenapyr; Pesticide
Tolerance. Final Rule.
11, 2003, comments submitted to US EPA by FAN's Pesticide
Project on the pesticide petition from BASF Corporation
to establish a tolerance for residues of chlorfenapyr
on all food items in food handling establishments where
food products are held, processed, and/or prepared at
0.01 parts per million (ppm).
- Also Online
at US EPA Docket OPP-2003-0205.
Endocrine Disruption. In the petition, BASF states: ...
There is no information available which suggests that
chlorfenapyr would be associated with endocrine effects.
5.1 However, US EPA noted endocrine effects in the following
study: In the rat chronic toxicity/carcinogenicity study
(MRID 43492837), there were increased trends in the incidence
of hepatocellular adenomas, hepatocellular adenomas and/or
carcinomas combined, malignant histiocytic sarcomas and
testicular interstitial cell tumors in males rats. In
female rats there were significant increasing trends in
endometrial stromal polyps. Significant difference in
pair-wise comparison of fibroadenomas at the low dose
and carcinomas at the mid-dose existed for female rats.
There was no evidence of tumorigenic potential in mice....
Ref: US EPA OPPT. February 12, 1998.
SUBJECT: Chlorfenapyr - 129093: Health Effects Division
Risk Characterization for Use of the Chemical Chlorfenapyr
(Alert, EPA File Symbol 5905-GAI) in/on Citrus (6F04623).
Case: 287132. Barcode: D221320- http://www.epa.gov/opprd001/chlorfenapyr/memohed2.pdf
17, 2003, reply to comments from FAN's Pesticide Project,
from Daniel J. O’Byrne, Product Registrations Manager, BASF
at US EPA Docket OPP-2003-0205.
Point 5: Endocrine Effects This comment addresses findings
of endometrial stromal polyps and testicular interstitial
occurrence of endometrial stromal
polyps in the uterus was slightly increased in
high-dose females, as compared to controls. Although the
incidence of endometrial stromal
polyps in high-dose females (5/65 or 7.7%) is statistically
different from the concurrent control females (0/65)
by the Fisher Exact Test (p< 0.05), the incidences are
not statistically different using the exact prevalence
method. This is the more appropriate method to compare
two groups with heterogeneous survival rates (survival
was significantly increased in high-dose females). All
five females with stromal polyps were sacrificed at termination.
Furthermore, the incidence (0/65) of these benign polyps
in the control females was unusually low for this commonly
occurring proliferative lesion that may represent an aging,
hormonal-type response. Moreover, the incidence in high-dose
females is only slightly above the overall total mean
historical rate (35/727 or 4.8%), and well below the maximal
spontaneous incidence (8/60 or 13.3%). Therefore, the
occurrence of this benign proliferative lesion in females
of the high-dose group is not considered treatment related...
there is no indication of an endocrine effect of chlorphenapyr
in any of the studies, including the two-generation study
in rats and the oncogenicity studies in rats and mice.
Herbicide - CAS No. 97886-45-8
The following results
were presented by a Monsanto scientist.
-- Four-week Feeding Study in Mice. Dithiopyr was administered
via the diet to groups of 6 male and 6 female CD-1 mice for 4
weeks at concentrations of 0, 300, 1000, 3000, 10,000 and 30,000
ppm... [No concentrations listed for the
following effects:]-- Liver enlargement and discoloration,
adrenal enlargement, and atrophy
of the thymus,
vesicles, ovaries and
uterus were noted on gross post-mortem
examination... (The Institute of Environmental
of Toxicology Studies With Dithiopyr. Dennis P. WARD. Toxicology
Department, The Agricultural Grop, A Unit of Monsanto
Company (Received February 20, 1993). Also available at
- Rodenticide - CAS No. 371-62-0
An increase in sternebral ossification defects,
hydronephrosis, runting (pup weight less than 2.7 g), variant
rib ossifications, extra vertebral ossification centers, cardiac
septal defects, and intrauterine
growth retardation were noted in rats.
Ref: TOXNET profile from Hazardous Substances
- Herbicide - CAS No. 69806-50-4
Fluazifop butyl was evaluated for developmental toxicity in adult
virgin Sprague-Dawley CD rats (160/group) administered oral doses
of 0, 1, 5, 10 and 200 mg/kg/day during gestation days 6-20. No
increased maternal mortality or overt toxicity was attributed to
treatment. At gestation Day 21 sacrifice of the dams, a slight but
significantly depressed mean bodyweight gain among those of a 200
mg/kg/day dosage was indicative of dose-related and significant
(p < 0.05; Student's t-test) reduction in
gravid uterus weights... [ICI
AMERS INC; Teratology Study with Fluazifop Butyl in Rats; 06/03/81;
EPA Doc No. 88-920007020; Fiche No. OTS0545395]
-- Fluazifop butyl (CAS # 69806-50-4) was evaluated for developmental
toxicity in the progeny of Sprague-Dawley CD rats administered oral
doses of 0 (corn oil vehicle control), 10, 50 and 200 mg/kg/day
by gavage on gestation days 6-20. The general condition of treated
rats was comparable to controls. Treatment did not alter food consumption
and usage efficiency, although terminal mean bodyweights were significantly
(p < 0.05; multiple t-test) depressed in the high-dose (200 mg/kg/day)
group. Gravid uterus weights were also
significantly (p < 0.01) elevated in
association with the high dosage... [ICI AMERS
INC; Butyl 2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy) propionate
butyl: Effects of Oral Administration Upon Pregnancy in Rats; 05/23/80;
EPA Doc No. 88-920006839; Fiche No. OTS0543844]
TOXNET profile from Hazardous Substances Data Bank for FLUAZIFOP-BUTYL.
- Herbicide - CAS No. 79241-46-6
The chronic dietary (all populations), intermediate-term dermal
and inhalation, and intermediateterm incidental oral endpoints
were selected from the 2-generation reproduction study in rats
based on decreased spleen, testes
and epididymal weights in males, and decreased
uterine and pituitary weights in females (page 5). ...
The uterine weight decrement seen in the
reproduction study showed a good dose-response and was
supported by a dose-response in the pituitary weight decrement
at the same doses. In addition, in the hamster, hyperplasia in
the ovary was seen at high dose levels. One of the subchronic
studies in the rat with fluazifop-P-butyl showed testicular weight
decrement, while the other one with fluazifop-butyl did not at
approximately the same doses as in the reproduction study; at
the highest dose tested in the subchronic study with fluazifop-butyl
absolute testes weights were increased 30%. The reason is unknown,
but may be due to animal variation or other unknown factors such
as edema. The testes and epididymal weight decrement and uterine
and ovarian effects suggest possible endocrine
related effects. However, negative in vitro studies suggest
estrogen and androgen hormones were not involved. Agonistic and
antagonistic studies with fluazifop-butyl, fluazifop-P-butyl and
the fluazifop acid metabolite were conducted in yeast cells containing
human estrogen and androgen receptors. No receptor activity was
found with any of the test materials over a sufficiently wide
concentration range (page 19).
December 10, 2004. US
EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance
Reassessment Eligibility Decision (TRED) Document. EPA Docket
-- In subchronic and
chronic toxicity studies, fluazinam targeted
the following organs: liver, lung, uterus,
testes, pancreas, thymus, thyroid, stomach, eyes and brain...
Note REG2003-12. Fluazinam. Pest
Management Regulatory Agency. Health Canada. Ottawa. October 27,
-- 90-Day oral toxicity
rats NOAEL: Males = 3.8 mg/kg/day; Females = 4.3 mg/kg/day [[Page
46731]] LOAEL Males = 38 mg/kg/day; Females = 44 mg/kg/day based
on increased liver weights and liver histopathology
in males, and increased lung and uterus
weights in females.
Ref: Federal Register. September 7, 2001.
Fluazinam; Pesticide Tolerance. Final Rule.
- Insecticide - CAS No. 272451-65-7
of a reproductive toxicity study in rats (exposure route not stated):
Thyroid, liver, uterine, thymus,
and spleen weight changes in 2000
and 20000 ppm F1 and F2 pups.
Ref: TSCA Health & Safety Study
Cover Sheet "Public Display Copy"
document was cited at EPA's
site: "TSCA 8(e) and FYI Submissions Received from 11-15-04-11-26-04".
It is important to note this as the document itself does not identify
flubendiamide or its CAS No.
study was conducted in the laboratory of The Institute of Environmental
Toxicology - Japan
•• Source of Data/Study
Sponsor: Bayer Material Science Corporation, 100 Bayer Road, Pittsburg
- CAS No. 181274-17-9
-- Study # 870.3800.
Reproduction and fertility effects in rats Parental/Systemic NOAEL
= 287 mg/kg/day for males and 340 mg/kg/day for females with a
slight, increased incidence of moderate cecal enlargement occurring
as an adaptive response to treatment. LOAEL = 800 mg/kg/day for
males based decreased liver weight
and 991 mg/kg/day for females based on decreased
uterine weight and increased incidence of severe
cecal enlargement. Reproductive/Offspring NOAEL = 287 mg/kg/day
for males and 340 mg/kg/day for females LOAEL = 800 mg/kg/day
for males and 991 mg/kg/day for females based on reduced pup weights,
decreased liver weight
in male pups, marbled liver, air filled stomach
Ref: US EPA Pesticide Fact Sheet for Flucarbazone-sodium.
September 29, 2000.
Acaricide, Insecticide - CAS No. 70124-77-5
-- Groups of 50 male
and 50 female CD (Sprague-Dawley derived) rats received technical
flucythrinate (80% pure) in the diet at 0, 30, 60 or 120 ppm daily
for 24 months... At autopsy, high-dose females exhibited an increased
incidence of cystic uterus... The
uterine cysts found at autopsy in
the high-dose females were characterized as
endometrial cysts. In the high-dose females, further slight
increases in uterine pathology were
described histologically, namely etritis/endometritis,
cystic endometrial hyperplasia and uterine fibrovascular polyps.
Mammary fibroadenomas occurred at
similar incidences in all female groups. The incidence of
mammary adenomas in treated females exceeded that of controls,
but not in a dose-related manner...
-- -- Groups of 50 male and 50 female CD (Sprague-Dawley derived)
rats received technical flucythrinate (80% pure) in the diet at
0, 30, 60 or 120 ppm daily for 24 months... At autopsy, high-dose
females exhibited an increased incidence of cystic
uterus... ((Brewer et al., 1981).
1985 World Health Organization Review for Flucythrinate.
- Herbicide - CAS No. 142459-58-3
-- In the rat chronic
feeding / carcinogenicity study the NOEL was less than 1.2 mg/kg/day
in males and less than 1.5 mg/kg/day in females and the LOEL was
1.2 mg/kg/day in males and 1.5 mg/kg/day in females based on
methemoglobinemia and multi-organ effects
in blood, kidney, spleen, heart, and uterus.
Under experimental conditions the treatment did not alter the
spontaneous tumor profile. In the mouse carcinogenicity study
the NOEL was less than 7.4 mg/kg/day in males and was 9.4 mg/kg/day
for females and the LOEL was 7.4 mg/kg/day for males and was 38.4
mg/kg/day for females based on cataract
incidence and severity. There was no evidence of carcinogenicity
for flufenacet in this study.
-- Chronic Feeding/ Carcinogenicity (rat): NOEL < 25 ppm [1.2
mg/kg/day in males and 1.5 mg/kg/day in females]. LOEL = 25 ppm
[1.2 mg/kg/day in males and 1.5 mg/kg/day in females] based
on methemoglobinemia and
multi-organ effects in blood, kidney, spleen,
heart, and uterus.
Under experimental conditions the treatment did not alter the
spontaneous tumor profile.
Ref: US EPA. Pesticide Fact Sheet. Flufenacet
Reason for Issuance: Conditional Registration Date Issued: April
- Fungicide - CAS No. 193740-76-0
chronic toxicity / carcinogenicity--rats. decreased
body weight, decreased body weight gain, and decreased food efficiency
in both sexes; decreased
spleen weight in males; and
microscopic lesions in the uterus of females. The
apparent increase in tumors in the uterus and thyroid were addressed
and resolved by an Agency committee, which
concluded that no carcinogenic concern exists for fluoxastrobin.
Ref: Federal Register. September 16, 2005.
Fluoxastrobin; Pesticide Tolerances. Final Rule.
incidence of uterus adenocarcinomas was statistically significantly
The RMS concluded that this was not a substance-related carcinogenic
effect. However, the range of the historical control is not the
only criterion for the biological relevance of an increased tumor
incidence. The incidence of the adenocarcinomas
in the uterus is significantly increased from 3/50 animals in
the control group to 10/49 animals in the highest dose and furthermore,
the incidence of uterine glandular hyperplasia is also clearly
increased from 1/50 to 6/49. A common (e.g. endocrine) mechanism
of both findings can not be excluded (page
Ref: PEER REVIEW REPORT ON FLUOXASTROBIN.
August 15, 2005. European
Food Safety Authority.
- Herbicide - CAS No. 117337-19-6
rats. NOAEL in males = 2.1 mg/kg/day LOAEL in males = 130 mg/kg/day
NOAEL in females = 2.5 mg/kg/day LOAEL in females = 154 mg/kg/dayIn
males there were decreased body weight,
liver toxicity, pancreatic toxicity and microcytic anemia. In
females there were liver toxicity, uterine
toxicity and slight microcytic anemia.
In males only at 130 and 219 mg/kg/day there was respectively,
an increase in the trend toward pancreatic
exocrine adenomas and pancreatic islet cell adenomas.
Ref: Federal Register: December 21, 2001.
Fluthiacet-methyl; Pesticide Tolerance. Final Rule.
- CAS No. 67485-29-4
- On May 28, 1998,
the Agency’s Cancer Peer Review Committee concluded that the dose
levels of 100 ppm in males, and 50 ppm in females were adequate
to assess the carcinogenic potential of hydramethylnon in rats....
The statistically significant increases
in tumors observed in the uterus
(adenomatous polyps) and adrenals
(medullary adenomas) were not considered to be biologically
significant since they were seen at excessive doses (i.e., at
200 ppm). Under the conditions of this study, the NOAEL was 50
ppm (2.4 mg/kg/day in males, 3.0 mg/kg/day in females), and the
LOAEL was 100 ppm (4.9 mg/kg/day in males, 6.2 mg/kg/day in females)
based on small, soft testes, decreased testicular
weights, and testicular atrophy in males; and decreased
body weight gain in females. This study is classified as acceptable
and satisfies guideline requirement 83-5 for a chronic feeding/carcinogenicity
study in rodents.
Ref: US EPA. Reregistration Eligibility
Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.
- Herbicide - CAS No. 27314-13-2
-- A two-year carcinogenicity
study was conducted in male and female CD-1 HaM/ICR Swiss mice
in which 125 mice/sex/dose were administered technical norflurazon
in the diet at dose levels of 0, 85, 340, or 1360 ppm (0, 12.8,
58.7, or 218.8 mg/kg/day) for 100-104 weeks...
Increased incidences of enlarged spleen, nephritis, swollen/enlarged
liver, and nodular enlargement of the liver were observed in high
dose male mice, while increased incidences of pyelonephritis,
enlarged liver, and
cystic ovaries were observed in high dose female mice.
Carcinogenic potential was evidenced by an increased incidence
of hepatic adenoma and combined adenoma/carcinoma
in high dose male mice. The systemic NOEL was determined
to be 12.8 mg/kg/day (85 ppm) for male mice, and 58.7 mg/kg/day
(340 ppm) for female mice. The systemic LEL was determined to
be 58.7 mg/kg/day (340 ppm) for male mice, based on the increased
incidence of enlarged spleen, increased
absolute and relative liver weight, and increased incidence of
nephritis. The systemic LEL was determined to be 218.8
mg/kg/day (1360 ppm) for female mice, based on the increased incidence
of enlarged liver and cystic
increased absolute and relative liver weight,
and the increased incidence of pyelonephritis (guideline §83-2;
-- A chronic toxicity and carcinogenicity study was conducted
in Sprague-Dawley rats. In this study, technical norflurazon was
administered in the diet at dose levels of 0, 125, 375, or 1025
ppm (0, 6.25, 18.75, or 51.25 mg/kg/day) for 104 weeks... Other
microscopic alterations observed at the high dose included an
increased incidence of parathyroid hyperplasia
(both sexes), hemosiderin pigment deposition in the spleen
(males only) and liver (both sexes), and endometritis
and squamous metaplasia of the uterus (females). The
systemic NOEL was determined to be 375 ppm (18.75 mg/kg/day) for
both sexes. The systemic LEL was determined to be 1025 ppm (51.25
mg/kg/day) in both sexes, based on the increased kidney
weight and accompanying microscopic pathologic changes, as well
as the increase in liver weight in male and female rats
and the increase in thyroid weight in males.
There was no evidence of carcinogenicity for norflurazon (guideline
83-5; MRIDs 00111617 and 00082019). As a result of the July 18,
1990 meeting of the OPP/Health Effects Division Carcinogenicity
Peer Review Committee, norflurazon was classified as a non quantifiable
Group C - possible human carcinogen - based
upon statistically significant pair-wise comparisons of the incidence
of liver adenomas and combined liver adenomas/ carcinomas as well
as statistically positive trends for these lesions in male CD-1
mice receiving 218.8 mg/kg/day norflurazon technical in
the diet for up to 104 weeks (MRID 00111649).
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION
NORFLURAZON. LIST A. CASE 0229.
- Insecticide - CAS No. 121451-02-3
-- “XDE-007: Two-year Dietary Chronic
Toxicity/Oncogenicity and Chronic Neurotoxicity Study in Fischer
344 Rats,” (Yano, B.L., Dryzga, M.D., Thomas, J.;
Toxicology & Environmental Research and Consulting, The Dow
Chemical Company, Midland, MI; Laboratory Project Study ID: 011168;
4.22.05). Noviflumuron ((N-[3,5-dichloro-2-fluoro-4(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea;
XDE-007, 97.9% pure) was fed in diet to Fischer 344 rats (75/sex/dose)
for 90 days, 1 or 2 years at 0, 0.1, 1.0, 75 or 300 mg/kg/day.
Subchronic toxicity was assessed after 90 days of treatment on
10/sex/dose at 0 and 1.0 mg/kg/day doses only. At 1 year,10/sex/dose
(chronic toxicity group), and 5/sex/dose (chronic neurotoxicity
group) were necropsied. The remaining 50/sex/dose were necropsied
after 2 years (oncogenicity group). Chronic NOEL = 1.0 mg/kg/day
(At > 75 mg/kg/day there were decreased body weights and body
weight gains along with increases or decreases
in absolute and/or relative organ weights (liver, kidney,
brain, heart, adrenal, testes, spleen, epididymides
were affected) at 12 and/or 24 months. Skin/tail papules and pustules
were observed in males (300 mg/kg/day) and females (> 75 mg/kg/day)
in the second year. Females showed an increase in phthisis bulbi
at 300 mg/kg/day. Prothrombin time in males and cholesterol levels
in females were increased at > 75 mg/kg/day at 24 months. ALP
activities were increased in both sexes at > 75 mg/kg/day at
24 months. Urine specific gravity was decreased (both sexes at
> 75 mg/kg/day) and urine volume was increased (M 300 mg/kg/day
and F > 75 mg/kg/day) at 24 months. Lung inflammation, hepatocytic
hypertrophy (both sexes > 75 mg/kg/day), mineralization of
renal pelvic epithelium (M > 75 mg/kg/day), epididymal aspermia
(M > 75 mg/kg/day), atrophy of seminiferous tubules (300 mg/kg/day),
tail hyperkeratosis +/- inflammation (both sexes 300 mg/kg/day),
tail tip necrosis (M 300 mg/kg/day) and hyperplasia of renal pelvic
epithelium (M 300 mg/kg/day) were observed at 24 months. Leukemia
was decreased in both sexes at > 75 mg/kg/day at 24 months.)
Possible adverse effect: Hepatocellular adenomas (benign, M 300
mg/kg/day), uterine stromal polyps (F >
75 mg/kg/day), and liver foci (M > 75 mg/kg/day) were increased
at 24 months. Acceptable. Silva, 8/19/05
August 2005 - Summary of toxicological data. California EPA, Department
of Pesticide Regulation, Medical Toxicology Branch.
- Insecticide, US EPA List 3 Inert
In a second prenatal
developmental toxicity study, groups of 25 pregnant Sprague-Dawley
rats were administered 0, 1, 5, and 10 mg/kg/day PFOS in corn
oil by gavage on gestation days (GD) 6-15 (Wetzel, 1983). Sexually
mature Sprague-Dawley rats, one per sex per cage, were paired
until confirmation of mating or until two weeks had elapsed. Mating
was confirmed by daily vaginal examinations for the presence and
viability of sperm or the presence of a copulatory plug. The day
of confirmation of mating was designated as day 0 of gestation.
Doses were adjusted according to the most recently recorded body
weight measurements. Dams were observed twice daily for signs
of mortality and moribundity and once daily for clinical signs
of toxicity. Individual body weights and food consumption were
recorded on GD 6, 8, 12, 16, and 20. Animals were sacrificed on
GD 20 by CO2 asphyxiation and the fetuses were delivered by cesarean
section on GD 20. A gross necropsy was performed on all dams...
Evidence of maternal toxicity, that was observed at the 5 and
10 mg/kg/day dose groups both during and following treatment and
considered to be treatment-related, consisted of hunched posture,
anorexia, bloody vaginal discharge, uterine stains, alopecia,
rough haircoat, and bloody crust. Significant decreases in mean
body weight gains during GD 6-8, 6-16, and 0-20 were also observed
at the 5 and 10 mg/kg/day dose groups. These reductions were considered
to be treatment-related since mean body weight gains were greater
than controls during the post-exposure period (GD 16-20). Significant
decreases in mean total food consumption were observed on GD 17-20
in the10 mg/kg/day dose group, and on GD 7-16 and 0-20 in both
the 5 and 10 mg/kg/day dose groups. The
mean gravid uterine weight in the 10 mg/kg/day dose group was
significantly lower when compared with controls. The mean
terminal body weights minus the gravid uterine weights were lower
in all treated groups, with significant decreases at 5 and 10
mg/kg/day. High-dose animals also exhibited an increased incidence
in gastrointestinal lesions. No significant differences were observed
in pregnancy rates, number of corpora lutea, and number and placement
of implantation sites among treated and control groups. Two dams
in the 10 mg/kg/day dose group were found dead on GD 17. Under
the conditions of the study, a NOAEL of 1 mg/kg/day and a LOAEL
of 5 mg/kg/day for maternal toxicity were indicated.
Ref: November 21, 2002 report:
Hazard Assessment of Perfluorooctane sulfonate
(PFOS) and its salts.
Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
- Herbicide - CAS No. 94125-34-5
-- Long term toxicity
and carcinogenicity Target / critical effect:
Liver (hepatocellular hypertrophy in mice), indication
of hormonal disruption (uterus and mammalian
gland in rats) at high dose levels. Lowest relevant
NOAEL: NOAEL = 1,7 mg/kg bw/day (18 month, mouse) Carcinogenicity:
No carcinogenic potential
Ref: July 2, 2002 - Review
report for the active substance prosulfuron. European Commission
Health & Consumer Protection Directorate-General.
- Wood preservative, US EPA List 4B Inert
- CAS No. 7681-49-4
1998 Abstract: SUMMARY: Sodium fluoride
(5 mg/kg body weight) was effective from the 45th day of treatment
in causing a significant decline in DNA
and RNA levels of mice ovary and uterus, indicating alterations
in nucleic acid and protein metabolism in these organs. The oestrus
cycle was irregular with prolonged duration of the diestrus stage
which in turn severely affected the fertility rate in treated
mice. The administration of amino acids glycine and glutamine,
individually and in combination along with NaF, helped in maintaining
the status quo of all parameters as compared to control, thus
elucidating their ameliorative role.
Ref: Fluoride 1998; 31(3):143-148. Ameliorative role of amino
acids on fluoride-induced alterations in mice (Part II): ovarian
and uterine nucleic acid metabolism; by D Patel and NJ Chinoy.
This study is Part II of the earlier experiment reported in Fluoride
1996; 29(4):217-226. Full report at
1996 Abstract: Summary: The effects
on female mice of sodium fluoride (NaF)
administration, at a dose of 5 mg/kg body weight for varied
durations (7, 15, 30, 45 and 60 days), were investigated in order
to evaluate time-related changes in uterine carbohydrate metabolism.
The therapeutic effects of simultaneous glycine and/or glutamine
administration along with NaF, for 45 and 60 days, were also investigated.
The results revealed that the NaF was effective from the 45th
day of treatment, and was much more effective after 60 days. A
significant decline in body weight and uterine weight was observed.
Accumulation of glycogen in the uterus with a concomitant
decrease in blood glucose could be correlated with inhibition
of phosphorylase activity affecting uterine
carbohydrate metabolism. The serum catecholamine concentrations
were significantly enhanced, possibly due to stress induced by
administration of fluoride. The elevated catecholamine levels
may be one of the causative factors affecting carbohydrate metabolism,
and would influence the hypothalamus
gonadal axis. Decreased levels of protein
in serum and uterus indicated altered uterine metabolsm in the
presence of fluoride. Administration of the amino acids
glycine and gluthamine, individually and in combination, along
with NaF, helped to maintain the status quo of all parameters
compared with controls. The results demonstrate that the amino
acids glycine and glutamine have an ameliorative effect on NaF-treated
animals. Hence it is suggested that a protein rich diet could
mitigate the fluoride-induced health hazards in endemic areas
the world over.
Ref: Fluoride 1996; 29(4):217-226. Ameliorative
role of amino acids on fluorde-induced alterations in uterine
carbohydrate metabolism in mice; by NJ Chinoy and D Patel.
The Okinawa Islands located in the southern-most part of Japan
were under U.S. administration from 1945 to 1972. During that
time, fluoride was added to the drinking water supplies in most
regions. The relationship between fluoride concentration in drinking
water and uterine cancer mortality rate
was studied in 20 municipalities of Okinawa and the data were
analyzed using correlation and multivariate statistics. The main
findings were as follows.
(1) A significant positive correlation was
found between fluoride concentration in drinking water and uterine
cancer mortality in 20 municipalities (r = 0.626, p < 0.005).
(2) Even after adjusting for the potential confounding variables,
such as tap water diffusion rate, primary industry population
ratio, income gap, stillbirth rate, divorce rate, this association
was considerably significant.
(3) Furthermore, the time trends in the uterine cancer mortality
rate appear to be related to changes in water fluoridation practices.
Ref: J Epidemiol. 1996 Dec;6(4):184-91.
between fluoride concentration in drinking water and mortality
rate from uterine cancer in Okinawa prefecture, Japan; by
Erratum in: * J Epidemiol 1997 Sep;7(3):184.
- Insecticide - CAS No. 79538-32-2
-- In a chronic/oncogenicity
study, mice were dosed at 0, 25, 100, or 400 ppm (actual dose
levels were equivalent to 3.4, 13.5, or 54.4 mg/kg/day) for 104
weeks. The chronic LOEL is 13.5 mg/kg based on hemangiomatous
changes of the uterus and
observed in the mid- and high-dose females. The chronic
NOEL is 3.4 mg/kg. Under the conditions of this study, there was
no evidence of carcinogenic potential.
-- In a developmental toxicity study, rats were dosed at 0, 1,
3, or 5 mg/kg/day from days 7 through 16 of gestation. The maternal
LOEL is 3 mg/kg/day, based on treatment-related decrease body
weight gains during dosing. The maternal NOEL is 1 mg/kg/day.
Developmental toxicity was demonstrated at 5 mg/kg/day as an increase
in the fetal incidence of bilaterally unossified
calcanea (92.9% vs. 87.5% in controls, p<0.05; litter incidence
was not shown) and a slight increase in the pes score (3.05 vs.
2.96 in controls) indicating slight inhibition of ossification
at these sites. There were no treatment-related effects
on the number, growth, and survival of the young in utero. In
addition, the inter-group differences in the mean numbers of corpora
lutea, implantations, pre- and post- implantation deaths,
live fetuses, proportion of male fetuses,
and fetal weights were not remarkable. The developmental LOEL
is 5 mg/kg/day, based on inhibited ossification.
The developmental NOEL is 3 mg/kg/day.
Ref: Federal Register: November 26, 1997.
Tefluthrin; Pesticide Tolerance. Final Rule.
- Fungicide - CAS
Chronic & Carcinogenicity Studies.
Rats received 0, 10, 80, 640 or 1280 ppm (the last dose to males
only) of tetraconazole in the diet for 2 years... At interim sacrifice,
female rats showed an absence of corpora lutea in the ovaries
and a decrease in the incidence of epithelial mucification in
cervix and vagina in all treated groups, and squamous
metaplasia in the endometrial glands of the uterus at 80 and 640
ppm. At the end of the study, females showed thickened uterus
at 640 ppm and males showed a higher incidence of enlarged
cervical lymph nodes at 640 and 1280 ppm, along with cystic sinuses
at 1280 ppm. (page 5)
2005 - Evaluation of Tetraconazole in the product Domark 40ME
Fungicide. Australian Pesticides and Veterinary Medicines Authority.