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PFOS - PFOA
(Perfluorinated chemicals)
 
 

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• 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.

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... 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.

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...
-- Title: Rat Teratology Study T-3351 Final Report – Project No. 154-160
TEST SUBSTANCE Identity: Potassium Perfluorooctylsulfonate, CAS No. 2795-39-3
. Dosing regimen (list all with units): Four groups of 25 pregnant Sprague-Dawley rats were administered Potassium Perfluorooctylsulfonate in corn oil by gavage on gestation days 6-15. Doses were adjusted according to the most recent recorded body weight. Doses: 0, 1, 5, and 10 mg/kg/day .. Statistically significant increases in incomplete closure of the skull were observed in the low- and high-dose groups but not in the mid-dose group. Statistically significant increases in the incidences in the number of litters containing fetuses with visceral anomalies, delayed ossification, and skeletal variations were observed in the high dose group of 10 mg/kg/day. These included external and visceral anomalies of the cleft palate, subcutaneous edema, and cryptorchsm as well as delays in skeletal ossification of the skull, pectoral girdle, rib cage, vertebral column, pelvic girdle and limbs. Skeletal variations in the ribs and sternebrae were also observed at this dose level.
-- Title: ORAL (STOMACH TUBE) DEVELOPMENTAL TOXICITY STUDY OF PFOS IN RABBITS. 3M T-6295.10, ARGUS RESEARCH LABORATORIES STUDY NUMBER: 6295.10, 1999. TEST SUBSTANCE. Identity: Potassium Perfluorooctylsulfonate (PFOS), CAS No. 2795-39-3. Year study performed: 1999. Species/Strain: New Zealand White rabbits. Number of animals per dose: 22 (additional total of 19 rabbits, 3-5 per dose, were included in a satellite study to determine the concentrations of PFOS in maternal liver and serum.). Route of administration: Gavage. Dosing regimen (list all with units): Four groups of 22 pregnant New Zealand White rabbits were administered Potassium Perfluorooctylsulfonate (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... There was also a significant reduction in the ossification of the sternum (litter averages) in the 2.5 and 3.75 mg/kg/day groups, and a significant reduction in the ossification of the hyoid (litter averages), metacarpals (litter averages) and pubis (litter and fetal averages) in the 3.75 mg/kg/day group.
-- 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. Statistically significant increases in incomplete closure of the skull were observed in the low- and high-dose groups but not in the mid-dose group. Statistically significant increases in the incidences in the number of litters containing fetuses with visceral anomalies, delayed ossification, and skeletal variations were observed in the high dose group of 10 mg/kg/day. These included external and visceral anomalies of the cleft palate, subcutaneous edema, and cryptorchism as well as delays in skeletal ossification of the skull, pectoral
girdle, rib cage, vertebral column, pelvic girdle, and limbs. Skeletal variations in the ribs and sternebrae were also observed.
Under the conditions of the study, a NOAEL of 1 mg/kg/day and a LOAEL of 5 mg/kg/day for developmental 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

-- Lau et al. (2001) administered Sprague-Dawley rats and CD-1 mice doses of 0, 1, 5 or 10 mg/kg/day PFOS in 0.5% Tween-20 by gavage beginning on gestation day 2 and continuing until term. Half of the dams were sacrificed on gestation day 21 (rats) or gestation day 17 (mice) and the remaining dams were allowed to deliver. Preliminary results are available. In rats, there was a significant reduction in maternal body weight gain at 5 and 10 mg/kg/day. Maternal serum cholesterol and triglycerides were reduced at 10 mg/kg/day, but liver weights were comparable to control. At 10 mg/kg/day, there was a reduction in fetal body weight and an increase in cleft palate and anasarca. All pups were born alive, but within 4-6 hours after birth all the pups in the 10 mg/kg/day group died, and 95% of the pups in the 5 mg/kg/day group died within 24 hours...
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... Developmental toxicity was evident at doses of 2.5 mg/kg/day and above. The number of corpora lutea,
resorptions, live/dead fetuses, litter size and sex ratio were comparable among treated and control groups. Mean fetal body weight (male, female and sexes combined) was significantly reduced in the 2.5 and 3.75 mg/kg/day groups. There was also a significant reduction in the ossification of the sternum (litter averages) in the 2.5 and 3.75 mg/kg/day groups, and a significant reduction in the ossification of the hyoid (litter averages), metacarpals (litter averages) and pubis (litter and fetal averages) in the 3.75 mg/kg/day group. The LOAEL for developmental toxicity was 2.5 mg/kg/day and the NOAEL was 1.0 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

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....

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...
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.

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... All rats in the 30 ppm group survived until the end of the study... Histologic examination also showed lesions in all treated groups. Centrilobular to midzonal cytoplasmic hypertrophy of hepatocytes and focal necrosis was observed in the liver; the incidence and relative severity were greater in the males. In addition, especially among rats in the 300, 1000 and 3000 ppm groups, treatment related histologic lesions were noted in the primary (thymus, bone marrow) and secondary (spleen, mesenteric lymph nodes) lymphoid organs, stomach, intestines, muscle and skin. In the thymus, this consisted of depletion in the number and size of the lymphoid follicles and in the bone marrow hypocellularity was noted. The spleen was slightly atrophied with a corresponding decrease in the size and number of lymphoid follicles and cells and a similar depletion was noted in the mesenteric lymph nodes.
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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