• 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 excerpt: "...
one of the most potent rodent hepatocarcinogens,
perfluorooctanoic acid (PFOA), induces apoptosis in human HepG2
cells in a dose- and time-dependent manner... In summary,
we have delineated a ROS [reactive oxygen species] and mitochondria-mediated
pathway for induction of apoptosis by PFOA."
Ref: 2001. Toxicol Appl Pharmacol May 15;173(1):56-64.
Reactive oxygen species and mitochondria mediate the induction
of apoptosis in human hepatoma HepG2 cells by the rodent peroxisome
proliferator and hepatocarcinogen, perfluorooctanoic acid;
by Panaretakis T, Shabalina IG, Grander D, Shoshan MC, DePierre
Abstract excerpt: "...
it is concluded that PFOA is a true liver
cancer promoter that may not require extensive initial DNA damage
for its promoting activity."
Ref: 2003-2004. Dis Markers;19(1):19-25.
enzymes and 8-hydroxydeoxyguanosine in rat liver treated with
perfluorooctanoic acid; by Abdellatif A, Al-Tonsy AH, Awad
ME, Roberfroid M, Khan MN.
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.
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.
-- Numerous repeat-dose oral toxicity studies on PFOS have been
conducted in rats and primates. In general, exposure to PFOS results
in hepatotoxicity and mortality; the dose-response curve for mortality
is very steep for rats and primates. Adverse signs of toxicity
observed in 90-day rat studies included increases
in liver enzymes, hepatic vacuolization and hepatocellular hypertrophy,
gastrointestinal effects, hematological
abnormalities, weight loss, convulsions, and death. These effects
were reported at doses of 2 mg/kg/day and above. In a dietary
2-year bioassay in Sprague-Dawley rats, hepatotoxicity,
characterized by centrilobular hypertrophy, centrilobular eosinophilic
hepatocytic granules, centrilobular hepatocytic pigment, or centrilobular
hepatocytic vacuolation was noted in male and/or female
rats given 5 or 20 ppm. Hepatocellular centrilobular
hypertrophy was also observed in mid-dose (2 ppm) male
rats. Significant increases in the incidence
of cystic hepatocellular degeneration were found in all the male
treated groups (0.5, 2, 5, or 20 ppm). Based on the pathological
findings in the liver, the LOAEL was 5 ppm and the NOAEL was 2
ppm in female rats. In males, the LOAEL was 0.5 ppm, and a NOAEL
was not established...
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.
Inductions by perfluoro-octanoic acid (PFOA) of
hepatomegaly, peroxisomal beta-oxidation, microsomal 1-acylglycerophosphocholine
acyltransferase and cytosolic long-chain acyl-CoA hydrolase were
compared in liver between male and female rats. Marked
inductions of these four parameters were seen concurrently in
liver of male rats, whereas the inductions in liver of female
rats were far less pronounced. The sex-related difference
in the response of rat liver to PFOA was much more marked than
that seen with p-chlorophenoxyisobutyric acid (clofibric acid)
or 2,2'-(decamethylenedithio)diethanol (tiadenol). Hormonal
manipulations revealed that this sex-related difference in the
inductions is strongly dependent on sex hormones, namely that
testosterone is necessary for the inductions, whereas oestradiol
prevented the inductions by PFOA.
1989. Biochem J Jul 15;261(2):595-600. Sex-related
difference in the inductions by perfluoro-octanoic acid of peroxisomal
beta-oxidation, microsomal 1-acylglycerophosphocholine acyltransferase
and cytosolic long-chain acyl-CoA hydrolase in rat liver;
by Kawashima Y, Uy-Yu N, Kozuka H.