Ovary (including Estrous) - Adverse Effects
Fluorinated and Fluoride Pesticides
 
 

Function:  The ovary, or female gonad, is:
1. an exocrine gland, producing ova
2. an endocrine gland, secreting
a. the female hormones estrogen and progesterone
b. androgens, typically considered male hormones
Ref: http://www.cvm.okstate.edu/instruction/mm_curr/histology/fr/HiFRp03.htm

Estrous: A reproductive cycle in some female mammals (but not female humans, who instead have menstrual cycles). The cycle is characterised by a short period of intense sexual desire (called estrus or heat) when the animal is fertile, which often occurs only once or twice a year, and involves correlating physical changes of the reproductive tract.


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.

Bifenthrin - Acaricide, Insecticide - CAS Numbers: 82657-04-3 (Cis); 83322-02-5 (Trans)

REPRODUCTION, RAT. 50429-065 - 50429-070; 42427-42432; "Multigeneration Reproduction Study with FMC 54800 (Biphenate) Technical in Rats"; 834; FMC Toxicology Laboratory; 1/31/86; Bifenthrin technical (FMC 54800), 88.35% a.i., 98% cis, 2% trans; 100, 60, 30 and 0 ppm in the feed for 8 weeks prior to F0 mating through F2b weaning; 25/sex/dose; no fertility or reproductive effects, other effects include tremors during lactation, ovary weight reduction in adults; NOEL = 100 ppm (reproductive/fertility), NOEL = 60 ppm (tremors), NOEL = 30 ppm (ovary weight reduction); No Adverse Effects Indicated; Study Acceptable. (Martz, 1/5/87; Updated 5/8/89, Morgan)
Ref: Summary of toxicology data: Bifenthrin. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. Original date: August 26, 1987 Revised dates: 7/9/90, 9/19/94, 4/4/00.

http://www.cdpr.ca.gov/docs/toxsums/pdfs/2300.pdf

A 13-week feeding study in dogs (by capsule) of doses at nominal dose levels of 0, 2.5, 5, 10, or 20 milligram/kilogram/day (mg/kg/day) (equivalent to 2.21, 4.42, 8.84, and 17.7 mg/kg/day, based on percent active ingredient (a.i.)) for 13 weeks. There was no mortality during the study... A non-statistically significant, but possibly treatment- related reduction in body weight (bwt) gain was noted in females at 17.7 mg/kg/day (0.6 kilogram (kg)) relative to the controls (1.3 kg). None of the females at 8.84 or 17.7 mg/kg/day showed cyclic activity or signs of estrus, but cyclic activity was observed in 2, 2, and 1 female at 0, 2.21, and 4.42 mg/kg/day, respectively and \4/5\ showed signs of estrus. The lowest observed effect level (LOEL) for this 13-week study is 4.42 mg/kg/day based on the increased incidence of tremors in both sexes. The NOEL is 2.21 mg/kg/day.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule.

http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

Clodinafop-propargyl - Herbicide - CAS No. 105512-06-9

-- Top dose group males showed a higher incidence of prostate adenoma, while prostate hyperplasia was reduced. However, the total incidence of proliferative changes in the prostate remained unchanged indicating a progression from prostate hyperplasia to adenoma. Females treated at the same high dose had higher incidences of ovary tubular adenoma. The slightly enhanced incidences of these lesions are likely a consequence of the severe disturbance of the general metabolic balance due to excessive liver toxicity. In fact, male rats fed 750 ppm exhibited a marked increase in peroxisomal oxidation, and an increase in cytochrome P450 4A1/ A3 and 4A2 in their livers. Further, a decrease in cytochrome P450 isoenzymes including CYP 2A, CYP 3A, and male-specific CYP 2C11 was observed. The total oxidation rate of testosterone, aromatase (CYP 19A1) activity plasma estradiol concentration and plasma-- dihydrotestosterone are altered at this level of treatment. Clodinafop-propargyl is a potent peroxisome proliferator in the rat liver and this peroxisomal prolifering activity manifests itself by altering Cytochrome P450-dependent monooxygenses which are involved in steroid hormone homeostasis. The NOAEL of 10 ppm was equivalent to a mean daily dose of 0.32 mg/kg in males and 0.37 mg/kg in females. The EPA HIARC concluded that based on hepatocellular hypertrophy and kidney findings, the NOAEL was 1 ppm (0.031 in males and 0.034 in females.
-- Dietary treatment of rats with concentrations over 2 years resulted in initial inappetence in males and reduced body weight development in both sexes treated at 750 ppm. The main target organ of toxicity was the liver. Changes in plasma protein and lipid levels, strongly enhanced serum activities of liver enzymes, increased liver weights, and severe liver necroses were observed at dietary doses of 300 and 750 ppm in males and at 750 ppm in females. The degenerative lesions provide strong evidence that these dose levels exceeded a maximum tolerated dose (MTD). Top dose group males showed a higher incidence of prostate adenoma, while prostate hyperplasia was reduced. However, the total incidence of proliferative changes in the prostate remained unchanged indicating a progression from prostate hyperplasia to adenoma. Females treated at the same high dose had higher incidences of ovary tubular adenoma. The slightly enhanced incidences of these lesions are likely a consequence of the severe disturbance of the general metabolic balance due to excessive liver toxicity. In fact, male rats fed 750 ppm exhibited a marked increase in peroxisomal oxidation, and an increase in cytochrome P450 4A1/ A3 and 4A2 in their livers. Further, a decrease in cytochrome P450 isoenzymes including CYP 2A, CYP 3A, and male-specific CYP 2C11 was observed. The total oxidation rate of testosterone, aromatase (CYP 19A1) activity plasma estradiol concentration and plasma-- dihydrotestosterone are altered at this level of treatment. Clodinafop- propargyl is a potent peroxisome proliferator in the rat liver and this peroxisomal prolifering activity manifests itself by altering Cytochrome P450-dependent monooxygenses which are involved in steroid hormone homeostasis. The NOAEL of 10 ppm was equivalent to a mean daily dose of 0.32 mg/kg in males and 0.37 mg/kg in females. The EPA HIARC concluded that based on hepatocellular hypertrophy and kidney findings, the NOAEL was 1 ppm (0.031 in males and 0.034 in females...
8. Endocrine disruption. No special studies investigating potential estrogenic or endocrine effects of clodinafop-propargyl have been conducted. However, the standard battery of required studies has been completed. These studies include an evaluation of the potential effects on reproduction and development and an evaluation of the pathology of the endocrine organs following repeated or long-term exposure. Although prostate adenomas and ovarian adenomas were observed to be statistically increased in rats at the highest feeding level with clodinafop-propargyl, this feeding level clearly exceeded the MTD and the livers in these rats were severely compromised. These findings in the endocrine organs were considered to be secondary to the severe liver effects.
Ref: Federal Register: April 26, 2000 [Page 24471-24477]. Notice of Filing a Pesticide Petition to Establish a Tolerance for Certain Pesticide Chemicals in or on Food.

http://www.fluoridealert.org/pesticides/Clodinafop-prop.Apr26.2000.htm

Cyfluthrin - Insecticide - CAS No. 68359-37-5

-- Rats Four groups of 30 male and 24 female Mura:SPRA (SPF 68 Han) rats received 14C radiolabelled cyfluthrin as either oral doses of 0.5 or 10 mg/kg bw or intravenous or intraduodenal doses of 0.5 mg/kg bw. Another group received unlabelled cyfluthrin orally once a day for 14 consecutive days, followed by a single oral dose of 0.5 mg/kg bw 14C-cyfluthrin... The residues found in the organs and tissues were influenced by the route of administration, as the mean relative concentration of cyfluthrin in the bodies of males and females at sacrifice was lower after oral administration (0.013) than after intravenous injection (0.06). Female rats had higher plasma concentrations after oral administration of the single high or low dose; 48 h after administration, lower concentrations were detected in the bone and muscle of animals of each sex and in the testes of males rats. The sciatic nerve showed a similar relative concentration value, which may explain the toxic effects observed on the peripheral nervous system. Higher concentrations were detected in the spleen, adrenal glands, liver, and plasma of both males and females and in the ovaries. The renal fatty tissue concentration was about seven times higher after either oral or intravenous administration, whereas the mean concentration in brain was significantly lower ( p = 0.0006-0.006) (Klein et al., 1983).
-- Groups of 28 male and 28 female Sprague-Dawley rats received diets containing 0, 100, 300, or 1000 mg/kg cyfluthrin (purity, 95%) incorporated into the powdered diet on a 0.4% maximum clay carrier, daily for three months... The food consumption and body-weight gains of females and males at the highest dose were significantly lower than those of the control group. The body-weight gain depression in females appeared to recover after cessation of treatment, while that of the males remained significantly low... The absolute weights of the liver, heart, and lung were decreased in male rats at the high dose, and females at this dose had depressed liver, kidney, adrenal, and ovarian weights. In both males and females at the high dose, the relative weight of the submaxillary gland was increased...
Ref: Cyfluthrin. Toxicological evaluation of certain veterinary drug residues in food. WHO FOOD ADDITIVES SERIES 39 Prepared by: The forty-eighth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). World Health Organization, Geneva 1997.
http://www.fluoridealert.org/pesticides/Cyfluthrin.WHO.Tox.Eval.97.htm

Dichlofluanid - Wood Preservative, Antifoulant, Fungicide, Acaricide - CAS No. 1085-98-9

-- Two-year Study. The following study is considered to be flawed due to the lack of histopathological evaluation and it was not GLP compliant. Beagles (4/sex/group) received dietary administration of either 0, 100, 300, 1000 or 3000 ppm dichlofluanid (90 % purity); equivalent to 3.6, 10.5, 34 and 107 mg kg -1 d -1 (males) and 3.4, 11, 34 and 101.4 mg kg -1 d -1 (females) respectively, for a two year study period... Absolute organ weights in males of the liver, lung, spleen, kidneys, adrenals, pancreas and heart were all decreased at 3000 ppm; the greatest being a 35 % decrease in testes weight. Decreases in relative organ weights were reported in males in the thyroid, heart, spleen and testes (20 % at 3000 ppm) at the top dose. The relative kidney and liver weights were elevated at both 1000 (21 and 3.4 %) and 3000 ppm (18 and 10 %). In females absolute organ weights were reduced : the thyroid in all treatment groups, by 32-36 %; ovaries 31-55 % from 100 ppm; and heart by 14-27 % at 1000 and 3000 ppm. The absolute spleen weights were raised in females at 1000 ppm and above by 18-20 %. In females there was a slight increase in the relative organ weights of the pancreas above 1000 ppm and spleen weight was elevated by 25 and 60 % at 1000 and 3000 ppm. A decrease in ovary weight was reported at all doses (55 % at 3000 ppm). The changes in organ weight in females preclude the setting of a NOEL. [Unpublished, 1969]
Ref: January 2003 - Evaluation on: Booster biocides in antifouling products. Full review of Dichlofluanid. No. 206. Evaluation of Fully Approved or Provisionally Approved Products. Prepared by : The Health and Safety Executive Biocides & Pesticides Assessment Unit, Magdalen House, Stanley Precinct Bootle Merseyside L20 3QZ Available from: Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX, UK. Also available at:
http://www.pesticides.gov.uk/citizen/Evaluations/206_dichlofluanid.pdf

PubMed Abstract: Two types of reactions were observed on the alteration of Drosophila vitellogenesis [established biomarker for estrogen action] by the four fungicides used in this study. Dithane M45 resulted in stimulation associated with egg retention. However, the other three fungicides (Benlate, Bouillie bordelaise and Euparene) resulted in inhibition to a varying degree. Although the inhibition was comparatively limited due to Benlate it induced an egg retention. The inhibition was very high due to Bouillie bordelaise and Euparene [dichlofluanid]. With Bouillie bordelaise an egg retention occured together with the reduction of vitellogenesis and caused an increase in the rate of the follicle resorption. The latter depended on the duration of treatment. With Euparene [dichlofluanid], no egg retention was observed and the toxicity was only noticed on vitellogenesis.
Ref: J Environ Sci Health B 1997 May;32(3):411-28. [Ovarian activity of Drosophila melanogaster Meigen (Diptera), during a chronic intoxication with four fungicides: anatomical and cytological study] [Article in French] by Marchal-Segault D, Lauge G.

Dichlofluanide has been reported as a hormonal active substance in the environment in a review of the German Umweltbundesambt (Schramm et al., 1996). However, a concentration range for which this "hormonal activity" was found, was not reported (page 44). [Schramm K.-w., thumm W. * Kettrup A. (1996). Hormonal active substances in the environment: exposition, impact and detection. Expert Round. Endocrinically active chemicals in the environment. UBA Texte 3/96. Umweltbundesamt, Germay.]
Ref: RIVM report 601506005. BIOCIDES (II). Refined aquatic environmental risk assessment of 28 priority biocides. B.J.W.G. Mensink. November 2000. RIVM = Rijksinstituut voor Volksgezondheid en Milieu. National Institute of Public Health and the Environment.

http://www.rivm.nl/bibliotheek/rapporten/601506005.pdf

Dithiopyr - 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)
-- Thirteen-week Feeding Study in Mice. Dithiopyr was administered via the diet to groups of 12 male and 12 female CD-1 mice for 13 weeks at concentrations of 0, 10, 100, 1000 and 5000 ppm... Other findings included [no concentrations listed]: multiple organ weight effects, adrenal cortical hypertrophy and ovarian atrophy. The subchronic NOEL in mice is considered to be 10 ppm. (The Institute of Environmental Toxicology, 1989)
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

http://wwwsoc.nii.ac.jp/pssj2/tec_info/dithiopy.pdf

Epoxiconazole - Fungicide - CAS No. 135319-73-2 (formerly 106325-08-0)

Endocrine disruption. A series of mechanistic studies were performed to elucidate and define the aromatase enzyme inhibition properties of epoxiconazole. The following conclusions can be drawn from the in vivo data: The effects on the ovaries are assessed to be the result of the following: Decreasing aromatase enzyme activity which is responsible for converting both testosterone and adrostendione (male sex-steroids) into female sex steroids (e.g., estradiol). This action would result in decreased estradiol (i.e., estrogen) and increased androgen. As a consequence of reduced estradiol levels, measured LH and FSH concentrations are slightly altered. The increased incidences of neoplasms in the ovaries are considered to be the result of a continuous cell proliferation by these stimulating [[Page 57342]] hormones of the regulating hormones of the pituitary-gonadal axis (LH and FSH). The changes adrenals are assessed to be the result of the following: Decreasing adrenal-cortical enzyme activity. This action would result in decreased adrenal hormones such as corticosterone levels. As a consequence of reduced corticosterone levels, pronounce ACTH concentrations are found. The increased incidences of neoplasms in the adrenals are considered to be the result of a continuos cell proliferation by these stimulating hormones of the pituitary-adrenal axis ACTH.
Ref: Federal Register: September 22, 2000 [Page 57338-57344]. Notice of Filing Pesticide Petitions to Establish Tolerances for Certain Pesticide Chemicals in or on Food.
http://www.fluoridealert.org/pesticides/Epoxiconazole.FR.Sept.2000.htm

"Epoxyconazole 106325-08-0 Banned. Low degradability, toxic to water-living organisms and endocrine effects. 1997."
Definition: "Banned. A substance which for health or environmental reasons by an authority decision is either no longer approved for any area of application, or for which an approval or registration has been denied from the first instance."

Ref: Euopean Commission. Appendix 5. Substances which may not be included as active ingredients in approved pesticide products, Chapter 15, Section 2, subsection one.

http://www.kemi.se/lagar_eng/pdf/app5_8.pdf

Ethalfluralin - Herbicide - CAS No. 55283-68-6

-- In vitro mammalian chromosome aberration test: In Chinese hamster ovary cells, ethalfluralin was negative without S9 activation, but it was clastogenic with activation.
Ref: Federal Register: January 17, 2002. Ethalfluralin; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Ethalfluralin.FR.Jan17.2002.htm

Flonicamid - Insecticide - CAS No. 158062-67-0

-- In the multi-generation rat reproduction study, the NOAEL was 300 ppm for both parental animals (13.5-32.8 and 16.3-67.0 mg/kg/day, respectively, for males and females) and their offspring. The effects at the highest dose of 1,800 ppm included the following: increased kidney weights and gross and histopathological alterations in the kidney. Findings noted in the top dose females included delayed vaginal opening and increased liver, kidney and spleen weights in the F1 generation and reduced ovary and adrenal weights in the parental generation and decreased uterine weights in the F1 female weanlings. There was an increase in the FSH and LH levels in F1 females tested for these endpoints. These findings did not affect the reproductive performance or survival of offspring in the study.
-- Endocrine disruption. No special studies investigating potential estrogenic or other endocrine effects of flonicamid have been conducted. Some suggestions of possible endocrine effects were reported at the highest dose tested (1,800 ppm) in the multi-generation reproduction study which showed increased FSH and LH levels, a delay in the time to vaginal opening in the F1 generation, and reduced ovary and adrenal weights in the parental generation. However, there were no effects on reproductive performance or survival of the offspring in the study. At levels that are expected to be found in the environment, flonicamid will not cause any endocrine-related effects.
Ref: Federal Register: May 23, 2003 (Volume 68, Number 100)] [Notices] [Page 28218-28222]. Flonicamid; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/Flonicamid.FR.May23.2003.htm

Fluazifop-butyl - Herbicide - CAS No. 69806-50-4

-- Fluazifop butyl was evaluated for reproductive and developmental effects in 2 successive generations of Charles River Wistar strain rats (30/sex/group) exposed continuously to 0, 10, 80 and 250 ppm in the diet. Each respective parent generation had received treatment for a minimum of 100 days (F0) and 120 days (F1) prior to mating. F0 and F1 dams weaned their progeny for 25 days postpartum to time of offspring selection for mating and continued study (F1) or sacrifice (F1, F2). Thirty days after sacrifice of their offspring, the surviving F1 females and select F1 males were sacrificed and with representative F1 and F2 offspring were examined histologically... Necropsy of F0 parents revealed no gross pathology and, although testes and epididymis of F0 males of a 250 ppm exposure were reduced, histological review identified no treatment-related changes. Conversely, F1 parents were found with gross indications of toxicity.. . Testis and epididymis weights in the males (80, 250 ppm), and pituitary gland (80, 250 ppm), uterus (80, 250 ppm), brain (250 ppm) and lung weights (250 ppm) in females were significantly reduced. Female F1 ovarian weights were increased relative to controls in association with a 250 ppm dietary exposure. Upon histological investigation, increased incidence geriatric nephropathy [kidney](both sexes, 80 and 250 ppm), distension of mesenteric and/or cervical lymph nodes (250 ppm) and increased severity of nephrocalcinosis (females, 80 and 250 ppm), and an increased slight testicular tubular atrophy in males (250 ppm) were noted... [ICI AMERS INC; Fluazifop butyl: Effects Upon Reproductive Performance of Rats Treated Continuously Through 2 Generations (Final Report); 03/17/81; EPA Doc No. 88-920006849; Fiche No. OTS05543854]
Ref: TOXNET profile from Hazardous Substances Data Bank for FLUAZIFOP-BUTYL.
http://www.fluoridealert.org/pesticides/Fluazifop-butyl.TOXNET.HSDB.htm

Fluazifop-P-butyl - Herbicide - CAS No. 79241-46-6

ONCOGENICITY, MOUSE [OR HAMSTER] 411-125 180756 Rattray, N. J., “Fluazifop-p-butyl: 80 week carcinogenicity study in hamsters,” Central Toxicology Laboratory (CTL), Alderley Park Macclesfield, 2/1/01. Lab Study ID: Syngenta No.1606-01. Golden Syrian hamsters, 51/sex/group, were dosed in diet with 0, 0, 200, 750, or 3000 ppm fluazifop-p-butyl (91.6%) for 81-83 weeks. The dual control groups were treated identically. An additional 12/sex/group (same doses) were allocated for 1-yr sacrifice (for hematology only). Estimated achieved doses were 12.5, 47, and 194 mg/kg/day (M) and 12.1, 46, and 181 mg/kg/day (F). No NOEL was established... Findings at the higher two dose levels only included decreased testes weights, reduced spermatozoa counts in epididymides and increased cataract development in males. Stromal cell/sex cord hyperplasia was elevated in high dose females. Benign stromal cell/sex cord tumors were slightly but significantly elevated in 3000 ppm females (incidences of 1, 1, 3, 4, and 5 in controls through high dose groups, respectively). Study is not acceptable, but presumed upgradeable (there is a need to explain why this species was selected for this study, and individual data for hamsters should be provided). The ovarian tumor findings, in addition to the several noted histopathology findings without NOEL’s, are possible adverse effects. Contemporary historical control data are needed if the registrant desires to re-visit DPR conclusions about findings of this study. The DPR review briefly discusses some ramifications of ovarian and testicular findings. Aldous, 5/20/02.
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/Fluazifop-P-butyl.CAepa.02.pdf

Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.
http://www.fluoridealert.org/pesticides/Fluazifop-P-Butyl.MSDS.pdf

Fludioxonil - Fungicide - CAS No. 131341-86-1

-- Gene mutation and other genotoxic effects were studied using fludioxonil technical: ... iii. Chromosome aberrations assay (in vitro) in Chinese hamster ovary (CHO) cells with and without S9 activation provided convincing evidence that [[Page 53823]] fludioxonil is a clastogen and polyploidy inducer.
Ref: Federal Register. October 7, 1998. Fludioxonil; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Fludioxonil.FR.Oct.1998.htm

-- In vitro Chromosome aberration. Chinese hamster ovary cells were tested with and without metabolic activation from 1.37 to 700 g/mL. Positive for nondisjunction of chromosomes both in the presence and absence of activation.
-- Fludioxonil was not mutagenic in the tests for gene mutations. However, because of the powerful induction of polyploidy in the in vitro Chinese hamster ovary cell cytogenetic assay and the suggestive evidence of micronuclei induction in rat hepatocytes in vivo, additional mutagenicity testing was performed in an in vivo study specifically designed for aneuploidy analysis.
Ref: Federal Register: December 29, 2000. Fludioxonil; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fludioxonil.FR.Dec.2000.htm

Genotoxicity. Mutagenicity potential of fludioxonil was tested in several studies. In the Chinese hamster ovary (CHO) cell assay, some clastogenic and polyploidogenic effects were seen at or near the precipitating concentration of the test substance. However, results were negative in the Ames assay, CHO V79 cell assay, hepatocyte DNA repair assay, rat hepatocyte micronucleus test, mouse bone marrow test, and Chinese hamster bone marrow test. A dominant lethal test conducted in the mouse was also negative.
Ref: Federal Register. March 29, 2000. [Page 16602-16608]. Notice of Filing a Pesticide Petition to Establish a Tolerance for Certain Pesticide Chemicals in or on Food.

http://www.fluoridealert.org/pesticides/Fludioxonil.FR.March29.2000.htm

Flufenoxuron - Acaricide, Insecticide, Herbicide - CAS No. 101463-69-8

-- Abstract: Flufenoxuron (Benzoylphenylurea derivative)-an environmental antimoulting insecticide-is recently used for controlling insect production in cultivated areas. In the present work, the insecticide was administered intragastrically by stomach tube at a dose of 20 mg/kg b.wt. to the Juvenile female and male albino rats (Rattus norvegicus) every other day for three weeks. Histological examination of ovaries revealed that the flufenoxuron induced massive degeneration of ovarian follicles with much cellular debris in the antrum and pyknotic granulosa cells. On the other hand, the testis of flufenoxuron-treated animals exhibited marked decrease of the thickness of tunica albuginea and atrophy of the seminiferous tubules. There was a marked increase of desquamated spermatogenic cells within the lumina of seminiferous tubules. Multinucleated giant cells and vanishing of sperms were observed in the majority of tubules of flufenoxuron-treated animals in comparison with control. Epididymides sperm of experimental group exhibited the presence of increased number of spermatic precursors as well as varieties of sperm anomalies. The hepatic tissues toxicated with the insecticide showed nuclear disintegration, massive breakdown of hepatocytes and internal haemorrhage. The observed gonadal dysfunction may be attributed to hepatic damage or decline of gonadal hormone involved in either processes.
Ref: J. Egypt. Ger. Soc. Zool., Vol. 25(B), 45-64, 1998.
EFFECTS OF FLUFENOXURON-AN ENVIRONMENTAL ANTIMOULTING INSECTICIDE ON GONAD FUNCTION OF ALBINO RATS; by EL-Sayyad, H.I. and Karim, S.A. http://www.egsz.org/BiologicalCurrentContent/Zoology/Comparative%20Physiology/TOXICOLOGY.htm

Fluorouracil - Former insect Chemosterilant; now used as a pharmaceutical - CAS No. 51-21-8

Fluorouracil has not been adequately studied in animals to determine its effects on fertility and general reproductive performance. Following intraperitoneal administration of 125 or 250 mg/kg in rats, chromosomal aberrations and changes in chromosomal organization of spermatogonia were induced; spermatogonial differentiation was also inhibited, resulting in transient infertility. In a strain of mouse that is sensitive to the induction of sperm head abnormalities after exposure to a number of chemical mutagens and carcinogens, no abnormalities were produced at oral dosages of up to 80 mg/kg daily. Following intraperitoneal administration at weekly doses of 25 or 50 mg/kg weekly for 3 weeks during the preovulatory phases of oogenesis in female rat, the incidence of fertile matings was substantially reduced, development of preimplantation and postimplantation embryos was delayed, and the incidence of preimplantation lethality and chromosomal anomalies in the embryos was increased. In a limited study in rabbits, a single 25 mg/kg dose or daily doses of 5 mg/kg for 5 days had no effect on ovulation, appeared not to affect implantation, and had only a limited effect in producing zygote destruction. Drugs that inhibit DNA, RNA, and protein synthesis like fluorouracil might be expected to have adverse effects on gametogenesis. [McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 93. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1993 (Plus Supplements, 1993). 576]
Ref: TOXNET profile from Hazardous Substances Data Base for FLUOROURACIL.

http://www.fluoridealert.org/pesticides/Fluorouracil.TOXNET.HSDB.htm
Definition
Gametogenesis: The meiotic process by which mature gametes (ova and sperm) are formed.
Oogenesis refers specifically to the production of ova and spermatogenesis to the production of sperm. [Definition from: GeneTests from the University of Washington and Children's Health System, Seattle]

Flurprimidol - Plant Growth Regulator - CAS No. 56425-91-3

-- Subchronic Studies. A 90-day feeding study in rats treated to 0, 1.68, 6.04, 20.39, 68.34 mg/kg/day (males) and 0, 1.98, 7.13, 24.37, 78.47 mg/kg/day (females) of flurprimidol. The systemic No-Observable- Effect-Level (NOEL) was 1.68 mg/kg/day and the Lowest-Effect- Level (LEL) was 6.04 mg/kg/day based on increased hepatic enzyme induction in males (significant and dose increases in p- nitroanisol O-demthylase activity). At 24.37 mg/kg/day there was increased relative and absolute ovarian (female) and relative liver (male) weight. At 68.34 mg/kg/day, there was increased absolute liver weight (males).
Ref: EPA Pesticide Fact Sheet for Flurprimidol. Reason for Issuance: New Chemical Registration. Date Issued: FEB 22 1989. Fact Sheet Number: 202.
http://www.fluoridealert.org/pesticides/Flurprimidol.EPA.Facts.1989.htm

-- Reproduction Study A 2 generation reproduction study in the rat treated with (time weighted average) 0, 1.8, 7.3, and 74 mg/kg/day of flurprimidol had a Parental Systemic Toxicity NOEL of 1.8 mg/kg/day and a LEL of 7.3 mg/kg/day based on increased incidence of non-neoplastic hepatocellular alterations including fatty change and vacuolation (males) and increased susceptibility to stress factors. The Reproductive NOEL was 7.3 mg/kg/ and the LEL was 74 mg/kg/day based on decreased mating, fertility, fetal survival (stillbirths), neonatal survival and neonatal body weight in both sexes and in both generations. There was an increased incidence of persistent vaginal estrous and no corpora lutea. Additional parental signs of toxicity at 74 mg/kg/day included increased susceptibility to stress (pregnant females) resulting in death, increased relative liver weight (males and females), depressed body weight, weight gain and food consumption (males and females)...
Ref: EPA Pesticide Fact Sheet for Flurprimidol. Reason for Issuance: New Chemical Registration. Date Issued: FEB 22 1989. Fact Sheet Number: 202.

http://www.fluoridealert.org/pesticides/Flurprimidol.EPA.Facts.1989.htm

Lactofen - Herbicide - CAS No. 77501-63-4

-- Subchronic feeding-- Mice-- 3-month. Groups of Male and female mice were fed diets containing Lactofen Technical at concentrations of 0, 40, 200, 1,000, 5,000, and 10,000 for 13-weeks. At week 5, the dosage of the 40 ppm groups was increased to 2,000 ppm. Treatment related mortality occurred at dosages above 1,000 ppm. The LOEL was 200 ppm based on: increased WBC; decreased hematocrit, hemoglobin and RBC; increased alkaline phosphatase, SGOT, SGPT, cholesterol and total serum protein levels; increased weights or enlargement of the spleen, liver, adrenals, heart and kidney; histopathological changes of the liver, kidney, thymus, spleen, ovaries and testes. In general, effects were slight in the 200 ppm groups, and moderate to severe in the 1,000 ppm groups.
Ref: Federal Register: February 25, 1998 [Page 9532-9540]. Notice of Filing of Pesticide Petition.

http://www.fluoridealert.org/pesticides/Lactofen.FR.Feb.1998.htm

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).
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION NORFLURAZON. LIST A. CASE 0229.

http://www.fluoridealert.org/PESTICIDES/Norflurazon.RED.EPA.pdf

-- A nine-month oral toxicity study (MRID 00091056) was conducted using the F generation of rats from a two-year carcinogenicity study (MRID 00082019). In this study, rats were given technical norflurazon in the diet at dose levels of 0, 125, 250, or 500 ppm (0, 6.25, 12.5, and 25 mg/kg/day) for 39 weeks... At 500 ppm... Thyroid weight was decreased in males by approximately 30% vs control, while thyroid weight was increased in females between 11-47% vs control. Gonadal weight (left gonad) was increased in female rats by 30%. At 250 ppm, thyroid weight was decreased by 30% in male rats, but was increased by 11-29% in female rats. However, there were no reported microscopic alterations in this organ at any dose level tested. Gonadal weight in female rats was increased by 17% vs. control. The systemic NOEL was determined to be 250 ppm (12.5 mg/kg/day) in both sexes. The systemic LEL was determined to be 500 ppm (25 mg/kg/day) in both sexes, based on the dose-related increase in liver weight in male and female rats at 39 weeks, the increase in gonad weight of females, and the microscopic changes observed in kidneys of both sexes. Although dramatic effects on thyroid weight were observed at 250 ppm in both sexes, there were no data indicating any alteration in histology of this organ. Thus, the weight change, while indicative of an effect of norflurazon, is not supported as a toxic effect based on available data (guideline: non-guideline study; classified as core supplementary; MRID 00091056).
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION NORFLURAZON. LIST A. CASE 0229.

http://www.fluoridealert.org/PESTICIDES/Norflurazon.RED.EPA.pdf

PFOA - Insecticide, US EPA List 3 Inert

Perfluorooctane sulfonate (PFOS) is a degradation product of sulfonyl-based fluorochemicals that are used extensively in industrial and household applications. Humans and wildlife are exposed to this class of compounds from several sources. Toxicity tests in rodents have raised concerns about potential developmental, reproductive, and systemic effects of PFOS. However, the effect of PFOS on the neuroendocrine system has not been investigated thus far. In this study, adult female rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg body weight (BW) for 2 weeks. Food and water intake, BW, and estrous cycles were monitored daily. At the end of treatment, PFOS levels in tissues were measured by high-performance liquid chromatography (HPLC) interfaced with electrospray mass spectrometry. Changes in brain monoamines were measured by HPLC with electrochemical detection, and serum corticosterone and leptin were monitored using radioimmunoassay. Treatment with PFOS produced a dose-dependent accumulation of this chemical in various body tissues, including the brain. PFOS exposure decreased food intake and BW in a dose-dependent manner. Treatment with PFOS affected estrous cyclicity and increased serum corticosterone levels while decreasing serum leptin concentrations. PFOS treatment also increased norepinephrine concentrations in the paraventricular nucleus of the hypothalamus. These results indicate that exposure to PFOS can affect the neuroendocrine system in rats.
Ref: Environ Health Perspect. 2003 Sep;111(12):1485-9. Neuroendocrine effects of perfluorooctane sulfonate in rats; by Austin ME, Kasturi BS, Barber M, Kannan K, MohanKumar PS, MohanKumar SM.

Pyridalyl - Insecticide - CAS No. 179101-81-6

Subchronic toxicity.
-- Pyridalyl technical was tested in rats in a 3-month feeding study. Effects included decreased body weight gain, altered blood biochemistry, increased relative liver weight and
histopathological changes in the liver, ovary, adrenal and lung. The NOAEL is 100 ppm (5.56 mg/kg/day in males and 6.45 mg/kg/day in females).
-- A 13-week feeding study in mice was conducted. Effects included decreased body weight gain, hematological and blood biochemical effects,increased liver weight, decreased kidney and ovary weights and histopathological changes in liver, kidney, ovary and adrenal. The NOAEL is 70 ppm in males (8.169 mg/kg/day) and 700 ppm in females (86.78 mg/kg/day)
Ref: Federal Register: December 5, 2003. Pyridalyl; Notice of Filing a Pesticide Petition.

http://www.fluorideaction.org/pesticides/pyridalyl.fr.dec.5.2003.htm

Tembotrione - Herbicide - CAS No. 335104-84-2

90-day Oral Yoxicity - Mouse study: NOAEL =M/F: 64/75.6 mg/kg/day. LOAEL =M/F: 631/783 mg/kg/day based on decreased uterine weights and increased corpora lutea in the ovary in females... (page 47)
90-Day Oral Toxicity - Rat study : In females, the following microscopic changes were observed at an increased incidence: multifocal corticotubular basal vacuolation (slight) in the kidneys occurred in a dose-dependent manner 1-6/10 in all treated groups compared to 0/10 in controls; diffuse hypertrophy of the interstitial gland in the ovaries was observed in the 1500 ppm and 7000 ppm groups (3/10) compared to 0/10 in controls. These effects were considered treatment-related. (page 56)
• Certain changes in multiple organs seen in the subchronic, chronic, dermal, and reproduction studies (e.g., microscopic changes in the thyroid gland, adrenal gland, and pancreas; increased number of corpora lutea in the ovary, and delayed preputial separation) may be due to various mechanisms including possible liver-pituitary-thyroid homeostatic disruption or inhibition of steroid synthesis (Page 6)... When additional appropriate screening and/or testing protocols being considered under the Agency’s EDSP have been developed, tembotrione may be subjected to further screening and/or testing to better characterize effects related to endocrine disruption (page 29).
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.

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

-- The class of compounds (triazoles) to which tetraconazole belongs is known to induce liver microsomal enzymes. The follicular cell hypertrophy and cystic follicular hyperplasia of the thyroid seen in male rats at 1,280 ppm are also likely to be linked to the hepatic changes. Compounds such as phenobarbital are also known to induce thyroid changes in rats due to increased hepatic clearance of thyroxin, mediated by hepatic enzyme induction.
-- A chronic feeding/carcinogenicity study was conducted with tetraconazole in Crl:CD-l (ICR)BR mice at dietary levels of 10, 90, 800, and 1,250 ppm for 80 weeks. Treatment-related non-neoplastic changes were also seen at 1,250 ppm in the lungs, kidneys,
testes, epididymides, ovaries and bone, particularly the cranium; a compression of the brain was noted in a number of mice reflecting the extent of cranial bone changes and an increased thymic involution was seen in male mice that died on test. The 1,250 ppm dietary level for tetraconazole, because of the substantial bwt gain changes and increased mortality (more in males), appeared to be above the maximum tolerated dose (MTD). At 800 ppm, there were increases in non neoplastic changes in lungs, kidneys, testes, epididymides, ovaries and bone. In addition, there was substantial reduction in weight gain as compared with zero-dose control animals, but the mortality rate was unaffected. Eight hundred ppm appeared to be a reasonable estimate of the MTD for mouse.
Ref: Federal Register: October 14, 1999. Notice of Filing Pesticide Petitions to Establish a Tolerance for Certain Pesticide Chemicals in or on Food. PP 9F5066, 9F6023, and 7E4830.
http://www.fluoridealert.org/pesticides/Tetraconazole.FR.Oct14.1999.htm

Sodium fluoride - Wood preservative, EPA List 4B Inert - CAS No. 7681-49-4

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
http://www.fluoride-journal.com/98-31-3/313-143.htm

Abstract: Summary. Forty-eight albino rabbits were administered fluorde as sodium fluoride subcutaneously in daily doses of 5, 10, 20, and 50 mg/kg body weight for three and a half months. Twelve controls received 1 cc distilled water/kg body weight/day for the same period. Ovaries from the control and fluoridated animals were analysed for DNA and RNA content. The experimental animals showed significant depletion (P < 0.001) of ovarian DNA and RNA compared to the controls. The data indicate that fluoride inhibits nucleic acid synthesis in the ovary. The findings also suggest that fluoride acts directly on DNA to produce structural changes in ovarian tissue which were subsequently confirmed by histopathological examination of control and treated animals. Further studies are desirable to define the possible role of fluoride in causing deleterious effects on reproduction such as delayed oestrus, repeated failure to conceive, and lowered viability detected earlier in experimental animals.
Ref: Fluoride 1994; 27(2):76-80. Preliminary observations on alterations in rabbit ovary DNA and RNA content in experimental fluorosis; by A Shashi

Abstract: Summary. A study was made of the effects on ovary and uterus of adminis-tering sodium fluoride (10 mg/kg body weight) or aluminium chloride (200 mg/kg body weight) alone and in combination to female albino mice (Mus musculus) for 30 days. The reversibility of the induced effects by withdrawal of NaF + AlCl3 treatment and by administering ascorbic acid (AA), calcium (Ca), or vitamin E alone and in combination were also investigated. All treat-ments (NaF, AlCl3, and NaF + AlCl3) resulted in a significant decline of ovarian protein and 3 • - and 17 • -hydroxysteroid dehydrogenase activities which could be related to increased cholesterol levels in the ovary suggesting altered steroidogenesis. The treatment also caused a hypercholesterolemic effect in serum. Accumulation of glycogen in uterus could be related to inhibition of phosphorylase activity affecting carbohydrate metabolism. The withdrawal of combined treatment for 30 days brought about an incomplete recovery. However, AA, Ca, or vitamin E supplementation alone and in combination produced an additive effect for recovery of most of the parameters almost to control levels. Hence the effects of NaF and/or AlCl3 are transient and reversible.
Ref: Fluoride 2001; 34(1):9-20. Effects of sodium fluoride and aluminum chloride on ovary and uterus of mice and their reversal by some antidotes; by NJ Chinoy and TN Patel. Full report available at
http://www.fluoride-journal.com/01-34-1/341-9.pdf

Tembotrione - Herbicide - CAS No. 335104-84-2

90-day Oral Yoxicity - Mouse study: NOAEL =M/F: 64/75.6 mg/kg/day. LOAEL =M/F: 631/783 mg/kg/day based on decreased uterine weights and increased corpora lutea in the ovary in females... (page 47)
90-Day Oral Toxicity - Rat study : In females, the following microscopic changes were observed at an increased incidence: multifocal corticotubular basal vacuolation (slight) in the kidneys occurred in a dose-dependent manner 1-6/10 in all treated groups compared to 0/10 in controls; diffuse hypertrophy of the interstitial gland in the ovaries was observed in the 1500 ppm and 7000 ppm groups (3/10) compared to 0/10 in controls. These effects were considered treatment-related. (page 56)
• Certain changes in multiple organs seen in the subchronic, chronic, dermal, and reproduction studies (e.g., microscopic changes in the thyroid gland, adrenal gland, and pancreas; increased number of corpora lutea in the ovary, and delayed preputial separation) may be due to various mechanisms including possible liver-pituitary-thyroid homeostatic disruption or inhibition of steroid synthesis (Page 6)... When additional appropriate screening and/or testing protocols being considered under the Agency’s EDSP have been developed, tembotrione may be subjected to further screening and/or testing to better characterize effects related to endocrine disruption (page 29).
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.

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

A chronic feeding/carcinogenicity study was conducted with tetraconazole in Crl:CD-l (ICR)BR mice at dietary levels of 10, 90, 800, and 1,250 ppm for 80 weeks. Treatment-related non-neoplastic changes were also seen at 1,250 ppm in the lungs, kidneys, testes, epididymides, ovaries and bone, particularly the cranium; a compression of the brain was noted in a number of mice reflecting the extent of cranial bone changes and an increased thymic involution was seen in male mice that died on test. The 1,250 ppm dietary level for tetraconazole, because of the substantial bwt gain changes and increased mortality (more in males), appeared to be above the maximum tolerated dose (MTD). At 800 ppm, there were increases in non neoplastic changes in lungs, kidneys, testes, epididymides, ovaries and bone. In addition, there was substantial reduction in weight gain as compared with zero-dose control animals, but the mortality rate was unaffected. Eight hundred ppm appeared to be a reasonable estimate of the MTD for mouse.
Ref: Federal Register: October 14, 1999. Notice of Filing Pesticide Petitions to Establish a Tolerance for Certain Pesticide Chemicals in or on Food. PP 9F5066, 9F6023, and 7E4830.

http://www.fluoridealert.org/pesticides/Tetraconazole.FR.Oct14.1999.htm

• Metbolism nd Toxicokinetics. Tetraconazole was broadly distributed to all organs and tissues tested, with the highest level detected in the liver, followed by kidneys, gonads, brain and bones. Low residual levels were still detected in the liver and gastrointestinal tract (sometimes bones) at 72 hr.
Chronic & Carcinogenicity Studies. An absence of corpora lutea in ovaries and thin uterus in females were seen at 800 and 1250 ppm. ... 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.
http://www.fluorideaction.org/pesticides/tetraconazole.2005.report.australia.pdf

Triflumizole - Fungicide - CAS No. 68694-11-1

-- Chronic feeding/oncogenicity studies were conducted in both the rat and mouse. The chronic feeding study in the rat suggests that the liver is the main target organ with the ovary and kidney as secondary target organs. Although there was an accompanying increase in organ weights, no carcinogenic effects were seen...
-- A 2-year feeding/oncogenicity study with Sprague-Dawley rats was conducted. Rats were fed 0, 5, 20 or 80 mg/kg/day doses of triflumizole equivalent to 0, 100, 400 and 1600 ppm triflumizole for 104 weeks with an interim sacrifice at 52 weeks. Numerous organ weights, clinical chemistry and hematology parameters and microscopic changes indicate the main target organ is the liver, with fatty vacuolization and periacinar hepatic hypertrophy seen at all dose levels tested. Ovarian organ weights as well as well-developed follicles indicate the ovary as a target...
-- In a 3-generation rat reproduction study, dose levels of 0, 70, 170 and 420 ppm in feed resulted in a NOEL greater than 70 ppm (LDT) based on increased gestation length. At 170 ppm there was pup mortality. At 420 ppm, there was reduced body weight gain, increased length of estrous cycles, reduced vaginal cornification, extended gestation length and high pup mortality.
Ref: EPA Pesticide Fact Sheet September 1991. Triflumizole (Terraguard, Procure).

http://pmep.cce.cornell.edu/profiles/fung-nemat/tcmtb-ziram/triflumizole/fung-prof-triflumizole.html

-- Endocrine disruption. In the rat reproduction study there was an increase in placental weight in females at the high dose level of 170 ppm. There was also a biologically significant increase in gestation length in high dose F0 and F2 females (F1a and F3a intervals). The NOAEL for endocrine effects is 70 ppm (3.5 mg/kg/day).
Ref: [Federal Register: July 6, 2001 [Notices] [Page 35623-35628]. Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluoridealert.org/pesticides/Triflumizole.FR.July6.2001.htm

-- Two three-generation reproduction studies in rats (when considered together) with a reproductive toxicity NOEL of 30 ppm (1.5 mg/kg/day) and a reproductive toxicity LEL of 70 ppm (3.5 mg/kg/day). Triflumizole is considered a reproductive toxicant.
Ref: Federal Register: November 16, 1994. Pesticide Tolerances and Feed Additive Regulations for Triflumizole. Final Rule.
http://www.fluoridealert.org/pesticides/Triflumizole.FR.Nov.16.1994.htm

 
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