Cholesterol - Adverse Effects
(Perfluorinated chemicals)

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Adverse Effects

Cholesterol Adverse Effects
PFOS - PFOA Index Page

• Due to length, we are presenting this effect as a separate section. The study of the adverse effects of PFOS 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 3M, its major producer.

• 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.

In a 6-month study of Cynomolgus monkeys, low food consumption, excessive salivation, labored breathing, hypoactivity, ataxia, hepatic vacuolization and hepatocellular hypertrophy, significant reductions in serum cholesterol levels, and death were observed at 0.75 mg/kg/day. No effects were observed at doses of 0.15 or 0.03 mg/kg/day. No effects were noted in animals at any dose level following a 52-week recovery period...
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.

Another study reported an increase in estradiol levels in workers with the highest PFOA serum
levels;however,none of the other hormone levels analyzed indicated any adverse effects. Some
of the same employees who participated in the hormone study also were included in a study of
cholecystokinin (CCK)levels in employees. No positive association was noted between CCK
values and PFOA. The other available study examined cholesterol and other serum components
in workers. There did not appear to be any significant differences among workers of different
exposure levels. At plants where the serum PFOA levels were lower, cross-sectional and
longitudinal studies found positive significant associations between PFOA and cholesterol and
triglyceride levels
. In addition,a positive,significant association was reported between PFOA
and T3 hormone and a negative association with HDL in the cross-sectional study. There are
many limitations to the studies conducted to date, and therefore, all of these results must be
interpreted carefully.
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.

28-Day Range-Finding, Oral Capsule-Dosing Study in Cynomolgus Monkeys: Male and female cynomolgus monkeys weighing 2.1 to 2.4 kg were given capsules placed directly in the stomach that contained PFOS at either 0.0 mg/kg/day (two males and two females), 0.02 mg PFOS/kdday (three males and three females), or 2.0 mg/kg/day (one male and one female) for 28 days in a range-finding study to determine doses for a six- month chronic oral capsule-dosing study (Thornford, PJ, 1998). Blood was collected for clinical chemistry on study days - 7 (baseline values) ,2 , 7, 14 and 29. In addition to standard hematologic parmeters and serum chemistry determinations, sex and thyroid hormones, cholecystokinin (CCK) and pancreatic amylase were measured. At the same time points and on day 3, blood was also obtained for determination of serum PFOS concentration. Tissues were obtained at necropsy, weighed, fixed and prepared for histopathologic analysis. In addition to histopathologic samples, liver specimens were obtained for analysis for proliferating cell nuclear antigen (PCNA), determination of PFOS concentration, and determination of palmitoyl CoA oxidase activity. Serum PFOS
concentrations increased with a high degree of linearity at both dose levels, with no difference between males and females and at a linear rate of 5.3 ppm serum PFOS per mg/kg (for details please see subsection on toxicokinetics). At the end of the 28-day dosing period, serum PFOS concentration in the 0.02 mg/kg/day dose group reached approximately 3 ppm and in the 2.0 mg/kg/day dose group, serum concentrations reached approximately 300 ppm. The only treatment-related effect observed in the study was a dramatic reduction in serum cholesterol in the male and female that received a dose of 2.0 mg/kg/day. Serum cholesterol dropped fiom baseline values of 150 and 14 1 mg/dl for the male and female, respectively, to 91 and 62 mg/dl at termination on day 29. The first evidence of a significant decrease occurred between day 2 and day 7 for the female, with a day 2 value of 136 mg/dl and a day 7 value of 117 mg/dl. The male cholesterol value fell from to 15l mg/dl on day 2 to 137 on day 7. The day 7 values for the male and female corresponded to a serum PFOS concentration of 72 ppm. This cholesterol data and corresponding cumulative dose and serum PFOS concentrations are summarized in Table IV.7. There were no other significant findings.
Ref: Perfluorooctane Sulfonate: Current Summary of Human Sera, Health and Toxicology Data. 3M. January 21,1999.

Hypolipidemia: The mechanism of the hypolipidemic effect of PFOS has been studied. Rats were fed 12 mg/kg/day for 7 - 14 days (0.02% in diet). Decreased body weight, increased liver weight, increased liver triacylglycerol, increased liver free cholesterol, decreased liver cholesterol ester, decreased serum cholesterol and triacylglycerols were observed. Hepatocytes isolated from treated rats showed reduced synthesis of cholesterol from acetate, pyruvate and hydroxymethylglutarate but not from mevalonate, increased oxidation of palmitate and reduced fatty acid synthesis. Activities of liver hydroxymethyl glutaric acid-CoA reductase and acyl-CoA:cholesterol acyltransferase were reduced. These results suggest that the hypolipemic effect of PFOS may be due to impaired production of lipoprotein particles due to reduced synthesis and esterification of cholesterol together with enhanced oxidation of fatty acids in the liver (Haughom and 0ystein, 1992).
Perfluorooctane Sulfonate: Current Summary of Human Sera, Health and Toxicology Data. 3M. January 21,1999.

Note from FAN:
Hypolipidemia, or hypolipoproteinemia, is a disorder in lipid metabolism where there is too little cholesterol and/or triglyceride present in the blood.
Hypolipoproteinemia is a general term used for individuals who do not produce enough cholesterol and/or triglyceride in their bodies. Although relatively rare, these disorders can be just as detrimental as having too many lipids in the blood.

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