Uterus - Adverse Effects
Fluorinated and Fluoride Pesticides

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 period (menstruation).
Ref: http://womenshealth.about.com/cs/uterinehealth/a/abouttheuterus.htm

The Endocrine System:

Illustration by K. Born in Our Stolen Future (1996)
by Theo Colborn, Dianne Dumanoski and JP Myers

The 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 is available.

-- Food and Agricultural Organization of the United Nations

Note: This is not an exhaustive list.
When time allows more information will be added.

Benthiavalicarb-isopropyl - Fungicide - CAS No. 177406-68-7

.• 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.

Chlorfenapyr - Acaracide, Insecticide - CAS No. 122453-73-0

-- Classification: ``Suggestive Evidence 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.
Ref: Federal Register: September 26, 2003. Chlorfenapyr; Pesticide Tolerance. Final Rule.

August 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). http://www.fluorideaction.org/pesticides/chlorfenapyr.comments.aug03.htm - Also Online at US EPA Docket OPP-2003-0205.

5. 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-

September 17, 2003, reply to comments from FAN's Pesticide Project, from Daniel J. O’Byrne, Product Registrations Manager, BASF Corporation. http://www.fluorideaction.org/pesticides/chlorfenapyr.basf.sept.2003.pdf - Also online at US EPA Docket OPP-2003-0205.

Regarding Point 5: Endocrine Effects This comment addresses findings of endometrial stromal polyps and testicular interstitial cell tumours

The 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... Overall, 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, spleen, seminal vesicles, ovaries and uterus were noted on gross post-mortem examination... (The Institute of Environmental Toxicology, 1987)
Ref: Summary 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


Ethylene fluorohydrin - Rodenticide - CAS No. 371-62-0

REPRODUCTIVE HAZARDS: 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 Data Base.


Fluazifop-butyl - 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]
Ref: TOXNET profile from Hazardous Substances Data Bank for FLUAZIFOP-BUTYL.

Fluazifop-P-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).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003

Fluazinam - Fungicide - CAS No. 79622-59-6

-- In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain...
Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.

-- 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.


Flubendiamide - Insecticide - CAS No. 272451-65-7

Results 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"
•• This 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.
•• This 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 PA 15205

Flucarbazone-sodium - Herbicide - 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.

Flucythrinate - 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).

Ref: 1985 World Health Organization Review for Flucythrinate.

Flufenacet - 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 1998.


Fluoxastrobin - Fungicide - CAS No. 193740-76-0

Combined 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.


The incidence of uterus adenocarcinomas was statistically significantly increased. 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 2).
European Food Safety Authority.

Fluthiacet-methyl - Herbicide - CAS No. 117337-19-6

-- Carcinogenicity 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.


Hydramethylnon - Insecticide - 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.


Norflurazon - 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 ovaries, the increased absolute and relative liver weight, and the increased incidence of pyelonephritis (guideline §83-2; MRID 00111649).
-- 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).


Noviflumuron - 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
Ref: August 2005 - Summary of toxicological data. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.

PFOS - 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.

Prosulfuron - 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.

Sodium fluoride - 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.

1996 Abstract: 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. Relationship between fluoride concentration in drinking water and mortality rate from uterine cancer in Okinawa prefecture, Japan; by Tohyama E.
Erratum in: * J Epidemiol 1997 Sep;7(3):184.

Tefluthrin - 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 liver necrosis 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.

Tetraconazole - Fungicide - CAS No. 112281-77-3

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)
Ref: August 2005 - Evaluation of Tetraconazole in the product Domark 40ME Fungicide. Australian Pesticides and Veterinary Medicines Authority.

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