Endocrine: Thyroid - Adverse Effects
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Thyroid Adverse Effects
PFOS - PFOA Index Page

• Due to length, we are presenting this effect as a separate section for PFOS and PFOA. The study of the adverse effects of PFOS-PFOA chemicals is in its infancy and we anticipate that more effects will be presented and published over the next several years. Most of the animal studies (as of early 2004) have been performed by the major producers of PFOS-PFOA (3M and DuPont).

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This is not an exhaustive list. The review of data was performed in 2003 to early 2004. When time allows more information will be added,

"So far, five different pathways have been identified that might explain how PFOA causes cancer and other types of toxicity. These include mitochondrial toxicity; cell membrane disruption that results in decreased cell communication; peroxisome proliferation; increased levels of estrogen and decreased levels of testosterone; and decreased thyroid hormone levels."
Ref: Environmental Working Group.
2003 report: PFCs: a family of chemicals that contaminate the planet. Part 4: PFC Health Concerns

... PFOS is persistent, bioaccumulative and toxic to mammalian species. There are species differences in the elimination half-life of PFOS; the half-life is 100 days in rats, 200 days in monkeys, and years in humans. The toxicity profile of PFOS is similar among rats and monkeys. Repeated exposure results in hepatotoxicity and mortality; the dose-response curve is very steep for mortality. This occurs in animals of all ages, although the neonate may be more sensitive. In addition, a 2-year bioassay in rats has shown that exposure to PFOS results in hepatocellular adenomas and thyroid follicular cell adenomas; the hepatocellular adenomas do not appear to be related to peroxisome proliferation. Further work to elucidate the species differences in toxicokinetics and in the mode of action of PFOS will increase our ability to predict risk to humans.
... The potential carcinogenicity of PFOS has been examined in a dietary 2-year bioassay in Sprague-Dawley rats. There was a significant increase in the incidence of hepatocellular adenomas in males and females at the highest dose of 20 ppm; the females at 20 ppm also had a significant increase in combined hepatocellular adenomas and carcinomas. In addition, there was a significant increase in thyroid follicular cell adenomas and combined thyroid follicular cell adenomas and carcinomas in the male recovery group at 20 ppm. There was no evidence of peroxisome proliferation in the livers of the treated animals.
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.

Abstract: The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15 and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were killed on GD 21, and mice on GD 18. PFOS levels in maternal serum, maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately 4-fold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver, but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.
Ref: Toxicol Sci 2003 May 28; Exposure to Perfluorooctane Sulfonate During Pregnancy in Rat and Mouse. I. Maternal and Prenatal Evaluations; by Thibodeaux JR, Hanson RG, Rogers JM, Grey BE, Barbee BD, Richards JH, Butenhoff JL, Stevenson LA, Lau C. Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

* Note from FAN:
Triiodothyronine - thyroid hormone similar to thyroxine but with one less iodine atom per molecule and produced in smaller quantity; exerts the same biological effects as thyroxine but is more potent and briefer.

Abstract: The postnatal effects of in utero exposure to perfluorooctane sulfonate (PFOS) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated with 1, 5, 10, 15 and 20 mg/kg PFOS from GD 1 to GD 18. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. In the highest dosage groups (10 mg/kg for rat and 20 mg/kg for mouse), the neonates became pale, inactive and moribund within 30-60 min, and all died soon afterward. In the 5 mg/kg (rat) and 15 mg/kg (mouse) dose groups, the neonates also became moribund but survived for a longer period of time (8-12 h). Over 95% of these animals died within 24 hr. Approximately 50% of offspring died at 3 mg/kg for rat and 10 mg/kg for mouse. Cross-fostering the PFOS-exposed rat neonates (5 mg/kg) to control nursing dams failed to improve survival. Serum concentrations of PFOS in newborn rats mirrored the maternal administered dosage and were similar to those in the maternal circulation at GD 21; PFOS levels in the surviving neonates declined in the ensuing days. Small but significant and persistent growth lags were detected in surviving rat and mouse pups exposed to PFOS prenatally, and slight delays in eye-opening were noted. Significant increases in liver weight were observed in the PFOS-exposed mouse pups. Serum thyroxine levels were suppressed in the PFOS-treated rat pups, although triiodothyronine and TSH levels were not altered. Choline acetyltransferase activity (an enzyme that is sensitive to thyroid status) in the prefrontal cortex of rat pups exposed to PFOS prenatally was slightly reduced, but activity in the hippocampus was not affected. Development of learning, determined by T-maze delayed alternation in weanling rats, was not affected by PFOS exposure. These results indicate that in utero exposure to PFOS severely compromised postnatal survival of neonatal rats and mice, and caused delays in growth and development that were accompanied by hypothyroxinemia in the surviving rat pups.
Ref: Toxicol Sci 2003 May 28. Exposure to Perfluorooctane Sulfonate During Pregnancy in Rat and Mouse. II. Postnatal Evaluation; by Lau C, Thibodeaux JR, Hanson RG, Rogers JM, Grey BE, Stanton ME, Butenhoff JL, Stevenson LA.

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