• 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).