Vaginal - Adverse Effects
Fluorinated and Fluoride Pesticides

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.

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.

Haloxyfop-etotyl - Herbicide - CAS No. 87237-48-7

Reproductive Effects: In rats, oral doses of 10 and 50 mg/kg/day of haloxyfop-ethoxyethyl from days 6 to 16 of pregnancy reduced the number of live offspring per litter and caused vaginal bleeding in the mother (5). Teratogenic Effects: Oral doses of 50 mg/kg/day of haloxyfop-ethoxyethyl in rats between days 6 and 16 of pregnancy caused developmental abnormalities in the offspring's urogenital system and death to the fetus (5). Oral doses of 7.5 mg/kg/day of haloxyfop-methyl given to rats from days 6 to 15 of pregnancy caused delayed bone formation in the offspring (6).
Ref: EXTOXNET Pesticide Information Profile

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

Abstract: The purpose was to discover whether fluoride (F) accumulates in the pineal gland and thereby affects pineal physiology during early development. The [F] of 11 aged human pineals and corresponding muscle were determined using the F-electrode following HMDS/acid diffusion. The mean [F] of pineal was significantly higher (p<0.001) than muscle: 296 ± 257 vs. 0.5 ± 0.4 mg/kg respectively. Secondly, a controlled longitudinal experimental study was carried out to discover whether F affects the biosynthesis of melatonin, (MT), during pubertal development using the excretion rate of urinary 6-sulphatoxymelatonin, (aMT6s), as the index of pineal MT synthesis. Urine was collected at 3-hourly intervals over 48 hours from two groups of gerbils (Meriones unguiculatus), low-F (LF) and high-F (HF) (12 f, 12 m/group): under LD: 12 12, from prepubescence to reproductive maturity (at 9-12 weeks) to adulthood, i.e., at 7, 9, 11 1/2 and 16 weeks. The HF pups received 2.3 ug F/g BW/day from birth until 24 days whereafter HF and LF groups received food containing 37 and 7 mg F/kg respectively and distilled water. Urinary aMT6s levels were measured by radioimmunoassay. The HF group excreted significantly less aMT6s than the F group until the age of sexual maturation. At 11 1/2 weeks, the circadian profile of aMT6s by the HF males was significantly dimished but, by 16 weeks, was equivalent to the LF males. In conclusion, F inhibits pineal MT synthesis in gerbils up until the time of sexual maturation. Finally, F was associated with a significant acceleration of pubertal development in female gerbils using body weights, age of vaginal opening and accelerated development of the ventral gland. At 16 weeks, the mean testes weight of HF males was significantly less (p<0.002) than that of the LF males. The results suggest that F is associated with low circulating levels of MT and this leads to an accelerated sexual maturation in female gerbils. The results strengthen the hypothesis that the pineal has a role in pubertal development.
Ref: The effect of fluoride on the physiology of the pinal gland; by Jennifer Anne Luke.
A dissertation submitted to the School of Biological Sciences, University of Surrey, in fulfilment of the requirements for the Degree of Doctor of Philosophy. Guildford 1997.

Sulfentrazone - Herbicide - CAS No. 122836-35-5

Reproduction and fertility effects (rat) Nonguideline - [870.3800] Parental/Systemic NOAEL = 20 mg/kg/day LOAEL = 51 mg/kg/ day (F1 females) based on decrease in pre-mating body weight gain (10%) Offspring and Reproductive NOAEL = 16 mg/kg/ day LOAEL = 40 mg/kg/ day based on reduced gestation day 20 fetal weights; decreased postnatal day 0, 4 and 7 pup weights; decreased pup survival; delayed vaginal patency; reduced epididymal, prostate, and testicular weights Additional information supports the conclusions reached in the 2- generation reproduction study in rats
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.

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

-- Reproductive toxicity study-- Rats. In the 2-generation reproductive toxicity study in rats, the maternal (systemic) NOAEL was 0.7 mg/kg/day, based on dystocia, delayed vaginal opening, and increased liver weight at the LOAEL of 5.9 mg/kg/day. The developmental (pup) NOAEL was 0.7 mg/kg/day, based on increased time to observation of balanopreputial skin fold [foreskin] and liver weight at the LOAEL of 5.9 mg/ kg/day. At the high dose of 35.5 mg/kg/day, there was a decrease in the mean number of live pups per litter on lactation days 0 and 4 (precull) in the presence of significant maternal toxicity.
Ref: Federal Register: December 6, 1999. Tetraconazole; Pesticide Tolerances for Emergency Exemptions. Final Rule.

Reproduction Study Rats received 0, 10, 70 or 490 ppm of tetraconazole in the diet for two generations. Offspring at 70 and 490 ppm had a slight retardation of growth and sexual maturation (delayed vaginal opening and balanopreputial cleavage). Increased liver weights were seen in F1 and F2 pups at 490 ppm as well as female pups at 70 ppm at weaning. No external and internal abnormalities were found for both F1 and F2 pups. The NOEL was 10 ppm (0.4 mg/kg bw/day) for reproduction and postnatal toxicity. (page 5-6)
Ref: August 2005 - Evaluation of Tetraconazole in the product Domark 40ME Fungicide. Australian Pesticides and Veterinary Medicines Authority.

Note from EC:
"Dystocia. Literally, it means difficult labor and practically means abnormally slow progress of labor. The word comes from the Greek 'dys' meaning 'difficult, painful, disordered, abnormal' and 'tokos' meaning 'birth'. Four potential factors may cause difficult labor characterized by abnormally slow progress. They may occur separately or together.
1) Uterine contractions may be either too weak or too uncoordinated to open up the cervix. There may also be inadequate pushing with voluntary muscles during the second stage of labor.
2) The baby may be lined up wrong to easily pass through the birth canal. Alternatively, there may be other problems with the baby that also retard passage of the baby through the birth canal.
3) The maternal bony pelvis may be too narrow to allow the baby to pass through the birth canal.
4) Abnormalities of the birth canal other than those of the bony pelvis may obstruct fetal descent.
The most common cause of dystocia is a small bony pelvis and/or insufficiently strong and coordinated uterine contractions. [drnathan/sitedex.htm]."
-- Balanopreputial skin fold- see:

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

-- 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).

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