• 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.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf
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.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf
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).
Ref: 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.
Ref: http://cholesterol.about.com/cs/hypolipidemia/