Body Weight Decrease - Adverse Effects
PFOS - PFOA
(Perfluorinated chemicals)
 
 

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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).

• Click here to return to the same section for fluorine & organofluorine pesticides.

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.



Adverse signs of toxicity observed in Rhesus monkey studies included anorexia, emesis, diarrhea, hypoactivity, prostration, convulsions, atrophy of the salivary glands and the pancreas, marked decreases in serum cholesterol, and lipid depletion in the adrenals. The dose range for these effects was reported between 1.5-300 mg/kg/day. No monkeys survived beyond 3 weeks into treatment at 10 mg/kg/day or beyond 7 weeks into treatment at doses as low as 4.5 mg/kg/day.
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.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

-- 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... Significant decreases in mean fetal weights for both males and females were observed in the 5 and 10 mg/kg/day dose groups. The percent of male fetuses was 52%, 54%, and 60% for 1, 5, and 10 mg/kg/day, respectively, compared to 44% in controls...
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.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

Christian et al. (1999a) administered pregnant New Zealand White rabbits, 22 per group, doses of 0, 0.1, 1.0, 2.5 or 3.75 mg/kg/day PFOS in 0.5% Tween-80 by gavage on gestation days 7-20. A dose volume of 5 mL/kg was administered, adjusted daily on the basis of individual body weights... Mean fetal body weight (male, female and sexes combined) was significantly reduced in the 2.5 and 3.75 mg/kg/day groups...
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.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

Postnatal deaths and other developmental effects were reported at low doses in offspring in a 2-generation reproductive toxicity study in rats. At the two highest doses of 1.6 and 3.2 mg/kg/day, pup survival in the first generation was significantly decreased. All first generation offspring (F1 pups) at the highest dose died within a day after birth while close to 30% of the F1 pups in the 1.6 mg/kg/day dose group died within 4 days after birth. As a result of the pup mortality in the two top dose groups, only the two lowest dose groups, 0.1 and 0.4 mg/kg/day, were continued into the second generation. The NOAEL and LOAEL for the second generation offspring (F2 pups) were 0.1 mg/kg/day and 0.4 mg/kg/day, respectively, based on reductions in pup body weight.
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.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

Developmental effects were also reported in prenatal developmental toxicity studies in the rat and rabbit, although at slightly higher dose levels. Signs of developmental toxicity in the offspring were evident at doses of 5 mg/kg/day and above in rats administered PFOS during gestation. Significant decreases in fetal body weight and significant increases in external and visceral anomalies, delayed ossification, and skeletal variations were observed. A NOAEL of 1 mg/kg/day and a LOAEL of 5 mg/kg/day for developmental toxicity were indicated. In the same study, evidence of treatment-related signs of maternal toxicity were also observed at doses of 5 mg/kg/day and above and mainly consisted of hunched posture, anorexia, bloody vaginal discharge, uterine stains, alopecia, rough hair coat, and bloody crust, as well as decreases in body weight gains and food consumption. Reductions in the mean terminal body weights minus the gravid uterine weights were also observed at doses > 5 mg/kg/day. A NOAEL of 1 mg/kg/day and a LOAEL of 5 mg/kg/day for maternal toxicity were indicated. In rabbits, significant reductions in fetal body weight and significant increases in delayed ossification were observed in the offspring of pregnant females administered PFOS during gestation at doses of 2.5 mg/kg/day and above. A NOAEL of 1.0 mg/kg/day and a LOAEL of 2.5 mg/kg/day for developmental toxicity were indicated. Maternal toxicity in the does was evident at doses of 1.0 mg/kg/day and above, and consisted of an increase incidence of abortions and scant feces, as well as significant reductions in mean maternal body weight gains and food consumption. A NOAEL of 0.1 mg/kg/day and a LOAEL of 1.0 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.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

3.5 Reproductive Toxicity Studies in Animals
York (2002) conducted an oral two-generation reproductive toxicity study of APFO, which is summarized below. Although this preliminary risk assessment focuses on developmental toxicity, the summary below of the two generation reproductive toxicity study includes all endpoints. Five groups of 30 Sprague-Dawley rats per sex per dose group were administered APFO by gavage at doses of 0,1,3,10, and 30 mg/kg/day six weeks prior to and during mating. Treatment of the F0 male rats continued until mating was confirmed,and treatment of the F0 female rats continued throughout gestation, parturition, and lactation....
Parental Males (F0)... At necropsy, statistically significant reductions in terminal body weights were seen at 3,10,and 30 mg/kg/day...
F1 Males ...
Statistically significant increases in clinical signs of toxicity were also observed in F1 males during most of entire postweaning period.These signs included an increased incidence of annular constriction of the tail at all doses ,with statistical significance at the 1,10,and 30 mg/kg/day; a significant increase at 10 and 30 mg/kg/day in the
number of male rats that were emaciated; and a significant increase in the incidence of urine-stained abdominal fur, decreased motor activity,and abdominal distention at 30 mg/kg/day. Body weights and body weight gains were statistically significantly reduced prior to and during cohabitation and during the entire dosing period in all treated groups. Statistically significant reductions in body weights were observed at 10 and 30 mg/kg/day during days 8-15, 22-29, 29- 36, 43-50, and 50-57 postweaning. Body weight gains were also significantly reduced in the 30 mg/kg/day group on days 1-8,15-22, 36-43, 57-64, and 64-70 postweaning. Statistically significant, dose-related reductions in body weight gains were observed for the entire dosage period (days 1-113 postweaning). Absolute food consumption values were significantly reduced
at 10 and 30 mg/kg/day during the entire precohabitation period (days 1-70 postweaning), while relative food consumption values were significantly increased... Statistically significant, dose-related decreases in terminal body weights of parental F1 males were observed in the 1,3,10,and 30 mg/kg/day dose groups...
Ref:
April 10, 2003: Preliminary Risk Assessment of the Developmental Toxicity associated with Exposure to Perfluorooctanoic Acid and its Salts. US EPA Office of Pollution Prevention and Toxics. 63 pages.

Abstract: 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.

In the rat subchronic study, Goldenthal et al. (1978b) administered CD rats, 5/sex/group, dietary levels of 0, 30, 100, 300, 1000 or 3000 ppm PFOS (FC-95) for 90 days. The males weighed 196- 232 g and the females weighed 165-206 g at study initiation. The dietary levels were equivalent to doses of 0, 2, 6, 18, 60 and 200 mg/kg/day... The rats were sacrificed after 90 days of treatment and a gross necrospy was conducted... All of the rats in the 300, 1000 and 3000 ppm groups died. Death occurred between days 13-25 and days 18-28 for the males and females, respectively, in the 300 ppm group...
The rats in all groups showed signs of toxicity including emaciation, convulsions following handling, hunched back, red material around the eyes, yellow material around the anogenital region, increased sensitivity to external stimuli, reduced activity and moist red material around the mouth or nose. Three males and two females in the 100 ppm group died prior to scheduled sacrifice. Two of the males and the two females died during week 5 and the third male died during week 11 of the study...
Ref: August 31, 2000. MEMORANDUM. SUBJECT: Hazard Assessment of PFOS. FROM: Jennifer Seed Branch Chief, Existing Chemical Assessment Branch, Risk Assessment Division (7403). THRU: Oscar Hernandez , Division Director, Risk Assessment Division (7403). TO: Charlie Auer, Division Director, Chemical Control Division (7405).

 
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