• 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).