Occup Environ
Med. 2003 Oct;60(10):722-9.
Mortality
of employees of a perfluorooctanesulphonyl fluoride manufacturing
facility.
Alexander
BH, Olsen GW, Burris JM, Mandel JH, Mandel JS.
University of Minnesota,
School of Public Health, Division of Environmental and Occupational
Health, MMC 807 Mayo Building, 420 Delaware St, SE Minneapolis,
MN 55409, USA. balex@umn.edu AIM:
To evaluate the mortality
experience of a cohort of employees of a perfluorooctanesulphonyl
fluoride (POSF) based fluorochemical
production facility.
METHODS: A retrospective cohort mortality study followed all
workers with at least one year of cumulative employment at the
facility. The jobs held by cohort members were assigned to one
of three exposure subgroups; high exposed, low exposed, and
non-exposed, based on biological monitoring data for perfluorooctane
sulphonate (PFOS).
RESULTS: A total of 145 deaths were identified in the 2083 cohort
members. Sixty five deaths occurred among workers ever employed
in high exposed jobs. The overall mortality rates for the cohort
and the exposure subcohorts were lower than expected in the
general population. Two deaths from liver cancer were observed
in the workers with at least one year of high or low exposure
(standardised mortality ratio (SMR) 3.08, 95% CI 0.37 to 11.10).
The risk of death from bladder cancer was increased for the
entire cohort (three observed, SMR 4.81, 95% CI 0.99 to 14.06).
All three bladder cancers occurred among workers who held a
high exposure job (SMR 12.77, 95% CI 2.63 to 37.35). The bladder
cancer cases primarily worked in non-production jobs, including
maintenance and incinerator and wastewater treatment plant operations.
CONCLUSION: Workers employed in high exposure
jobs had an increased number of deaths from bladder cancer;
however it is not clear whether these three cases can be attributed
to fluorochemical exposure, an unknown bladder carcinogen encountered
during the course of maintenance work, and/or non-occupational
exposures. With only three observed cases the possibility of
a chance finding cannot be ruled out.
PMID: 14504359
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14587845&dopt=Abstract
J Environ
Monit. 2003 Oct;5(5):753-7.
Concentrations
of perfluorooctane sulfonate (PFOS)
and perfluorooctanoic acid (PFOA)
in vacuum cleaner dust collected in Japanese homes.
Moriwaki
H, Takatah Y, Arakawa R.
Osaka City Institute
of Public Health & Environmental Sciences, 8-34 Tojo-cho, Tennoji-ku,
Osaka 543-0026, Japan. hiroshi.moriwaki@iphes.city.osaka.jp
Perfluorooctane sulfonate
(PFOS) and perfluorooctanoic acid
(PFOA) are shown to be
globally distributed, environmentally persistent and bioaccumulative.
Although there is evidence that these compounds exist in the
serum of non-occupationally exposed humans, the pathways leading
to the presence of PFOS and PFOA are not well characterized.
The concentrations of PFOS and PFOA in the vacuum cleaner dust
collected in Japanese homes were measured. The
compounds were detected in all the dust samples and the
ranges were 11-2500 ng g(-1) for PFOS and 69-3700 ng g(-1) for
PFOA. It was ascertained that PFOS and PFOA were present in
the dust in homes, and that the absorption of the dust could
be one of the exposure pathways of the PFOS and PFOA to humans.
With regard to risk management, it is important to consider
the usage of PFOS and PFOA in the indoor environment in order
to avoid further pollution.
PMID:
14587845 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14565571&dopt=Abstract
Arch Environ
Contam Toxicol. 2003 Aug;45(2):149-58.
Perfluorooctane
sulfonate concentrations in surface water in Japan.
Saito
N, Sasaki K, Nakatome K, Harada K, Yoshinaga T, Koizumi A.
Research Institute
for Environmental Sciences and Public Health of Iwate Prefecture,
Morioka Iwate, Japan.
Perfluorooctane
sulfonate (PFOS) is a class of specialty chemicals used in a
variety of applications, and has been found to be globally distributed
in many living organisms including humans. Several analytical
methods have been developed for determination of PFOS in environmental
samples and biological matrices. However, these methods employ
liquid chromatography/tandem mass spectrometry (LC/MS/MS), an
instrumentation which has limited accessibility because it is
expensive to use and maintain. In the present study we present
the development of a robust analytical method using liquid chromatography/mass
spectrometry (LC/MS) in combination with solid phase extraction.
The high yield and concentration of the
present method enabled us to quantify PFOS as low as 0.1 ng/L.
This method was applied to the determination of PFOS in 142
surface water samples collected from various geographic locations
around Japan. The geometric mean (geometric standard deviation)
(ng/L) for river samples (n = 126) was 2.37 (4.13), with a median
of 1.68 and a range of 0.3-157 ng/L, and for coastal sea water
samples (n = 16) was 1.52 (4.14), with a median of 1.21 and
a range of 0.2-25.2 ng/L. However, the
concentrations in most of the samples were much lower than the
values reported in the US, except for those from the Jinzu (135.0
ng/L) and Tama (157 ng/L) Rivers. Because
surface waters in the Ara (13.0-38.5 ng/L), Tama (0.7-157.0
ng/L), and Yodo (0.9-27.3 ng/L) Rivers, sources of drinking
water for more than eight million people, were moderately contaminated
with PFOS, more work is needed to assess exposure to PFOS.
PMID: 14565571
[PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14521435&dopt=Abstract
AIHA J
(Fairfax, Va). 2003 Sep-Oct;64(5):651-9.
An occupational
exposure assessment of a perfluorooctanesulfonyl fluoride production
site: biomonitoring.
Olsen
GW, Logan PW, Hansen KJ, Simpson CA, Burris JM, Burlew MM, Vorarath
PP, Venkateswarlu P, Schumpert JC, Mandel JH.
Medical
Department, 3M Co.,
St. Paul, MN 55144, USA.
This investigation
randomly sampled a fluorochemical manufacturing employee population
to determine the distribution of serum fluorochemical levels
according to employees' jobs and work areas. Previous analyses
of medical surveillance data have not shown significant associations
between fluorochemical production employees' clinical chemistry
and hematology tests and their serum PFOS and perfluorooctanoate
(PFOA, C(7)F(15)COO(-)) concentrations, but may have been subject
to nonparticipation bias. A random sample of the on-site film
plant employee population, where fluorochemicals are not produced,
determined their serum concentrations also. Of the 232 employees
randomly selected for serum sampling, 186 (80%) employees participated
(n=126 chemical plant; n=60 film plant). Sera samples were extracted
using an ion-pairing extraction procedure and were quantitatively
analyzed for seven fluorochemicals using high-pressure liquid
chromatography electrospray tandem mass spectrometry methods.
Geometric means (in parts per million) and 95% confidence intervals
(in parentheses) of the random sample of 126 chemical plant
employees were: PFOS 0.941 (0.787-1.126); PFOA 0.899 (0.722-1.120);
perfluorohexanesulfonate 0.180 (0.145-0.223); N-ethyl perfluorooctanesulfonamidoacetate
0.008 (0.006-0.011); N-methyl perfluorooctanesulfonamidoacetate
0.081 (0.067-0.098); perfluorooctanesulfonamide 0.013 (0.009-0.018);
and perfluorooctanesulfonamidoacetate 0.022 (0.018-0.029). These
geometric means were approximately one order of magnitude higher
than those observed for the film plant employees.
PMID: 14521435
[PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14587916&dopt=Abstract
Environ
Toxicol Chem. 2003 Nov;22(11):2739-45.
Response
of the zooplankton community and environmental fate of perfluorooctane
sulfonic acid in aquatic microcosms.
Boudreau
TM, Wilson CJ, Cheong WJ, Sibley PK, Mabury SA, Muir DC, Solomon
KR.
Centre for Toxicology,
Department of Environmental Biology, Bovey Building, University
of Guelph, Guelph, Ontario, Canada N1G 2W1. tboudreau@esg.net
Little is known regarding
perfluorooctane sulfonic acid (PFOS)
toxicity to freshwater organisms. This field evaluation aims
to assess the toxicological risk associated with exposure to
PFOS across levels of biological organization. The analysis
of variance study was conducted in replicate (n = 3) 12,000
L outdoor microcosms. Multivariate techniques were used to assess
the response of zooplankton community structure and dynamics,
as well as a floating macrophyte, Lemna gibba. The
zooplankton community was significantly affected (p <
0.05) by the treatment regime given by the Monte Carlo permutations
for all sampling times. A community-level no-observable-effect
concentration ([NOEC]community) of 3.0 mg/L was determined for
the 35-day study, however, longer term studies are recommended.
The most sensitive taxonomic groups, Cladocera
and Copepoda, were virtually eliminated in 30 mg/L treatments
after 7 d. The 42-d 50% inhibition concentration (IC50)
for L. gibba frond number was 19.1 mg/L and the NOEC was 0.2
mg/L. Furthermore, we investigated the persistence of PFOS over
285 d in microcosms under natural conditions. Perfluorooctane
sulfonic acid concentration showed no drastic reduction in any
treatment microcosm over the entire study period, confirming
that this compound undergoes little degradation in aquatic systems.
Presently, there appears to be little
hazard to these freshwater organisms at reported environmental
concentrations.
PMID:
14587916 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12959528&dopt=Abstract
Environ
Toxicol Chem. 2003 Sep;22(9):2037-41.
Exposure
patterns of perfluorooctane sulfonate in aquatic invertebrates
from the Western Scheldt estuary and the southern North Sea.
Van
de Vijver KI, Hoff PT, Van Dongen W, Esmans EL, Blust R, De
Coen WM.
Over the past decades
little research has been conducted on the environmental behavior
and effects of fluorinated organochemicals (FOCs). Recently
it has been reported that perfluorooctane sulfonic acid (PFOS)
is occurring worldwide. Little is known about the PFOS levels
in organisms originating from the southern North Sea and the
Western Scheldt estuary. In this study, we determined, for the
first time, the PFOS-exposure levels in Crangon crangon, Carcinus
maenas, and Asterias rubens from these ecosystems. Concentrations
on a wet-weight basis in soft tissues of shrimp, crab, and starfish
ranged from 19 to 520 ng/g, from 24 to 877 ng/g, and from 9
to 176 ng/g, respectively. These results show the existence
of a PFOS pollution gradient in organisms along the Western
Scheldt estuary, with the highest concentrations near Antwerp.
The range of PFOS levels in shrimp and
crab are slightly higher in coastal regions compared with sampling
sites in open water. This study shows widespread distribution
of PFOS in the Belgian and Dutch marine and estuarine environment
at rather high concentrations.
PMID:
12959528 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12948855&dopt=Abstract
Biochem
Pharmacol. 2003 Sep 1;66(5):749-56.
The relationship
between liver peroxisome proliferation and adipose tissue atrophy
induced by peroxisome proliferator exposure and withdrawal in
mice.
Xie
Y, Yang Q, Nelson BD, DePierre JW.
Unit for Biochemical
Toxicology, Wallenberg Laboratory, Department of Biochemistry
and Biophysics, Stockholm University, S-106 91, Stockholm, Sweden
We have previously
demonstrated that severe adipose tissue atrophy occurs upon
dietary treatment of mice with potent peroxisome proliferators
(PPs). This atrophy occurs subsequent to peroxisome proliferation
in the liver and may represent a novel addition to the pleiotropic
effects exerted by PPs. In the present study we have characterized
the recovery of mice from such atrophy following cessation of
exposure. Following termination of treatment with perfluorooctanoic
acid (PFOA) for 7 days, the adipose
tissue atrophy was rapidly reversed, beginning on 2-5 days of
recovery and being complete within 10 days. In contrast, hepatic
peroxisome proliferation recovered much more slowly, indicating
that these processes are not strictly coordinated. Analysis
of lipoprotein lipase and hormone-sensitive lipase activities
in adipose tissue revealed that the decrease and increase in
these activities, respectively, caused by PFOA were both reversed
within 10 days of recovery. Overall, these data provide further
support for our previous conclusion that the adipose tissue
atrophy induced by PFOA is caused, at least in part, by changes
in the activities of lipoprotein lipase and hormone-sensitive
lipase. The serum level of cholesterol, which increased after
termination of PFOA treatment, returned to normal with a time-course
similar to the recovery of adipose tissue weight, although hepatic
peroxisome proliferation was still present. The possible relationship
between the reduction in serum cholesterol and/or in its availability
to peripheral tissues and the associated atrophy of adipose
tissues caused by PPs is discussed.
PMID: 12948855
[PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12854699&dopt=Abstract
Environ
Sci Technol. 2003 Jun 15;37(12):2634-9.
A survey
of perfluorooctane sulfonate and related perfluorinated organic
compounds in water, fish, birds, and humans from Japan.
Taniyasu
S, Kannan K, Horii Y, Hanari N, Yamashita N.
National Institute
of Advanced Industrial Science and Technology (AIST), 16-1 Onogawa,
Tsukuba, Ibaraki 305-8569, Japan.
Occurrence of perfluorooctane
sulfonate (PFOS) in the tissues of humans and wildlife is well
documented. In this study, concentrations and distribution of
PFOS, perfluorohexane sulfonate (PFHS), and perfluorobutane
sulfonate (PFBS) were determined in samples of surface water,
fish and bird blood and livers, and human blood collected in
Japan. Notable concentrations of PFOS
were found in surface water and fish from Tokyo Bay. PFOS was
found in all of the 78 samples of fish blood and liver analyzed.
Based on the concentrations of PFOS in water and in fish livers,
bioconcentration factors were calculated to range from 274 to
41 600. Concentrations of PFOS in the blood of Japanese human
volunteers ranged from 2.4 to 14 ng/mL. PFHS was detected
in 33% of the fishes analyzed, at concentrations severalfold
less than those of PFOS.
PMID: 12854699
[PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12820537&dopt=Abstract
J Toxicol
Sci. 2003 May;28(2):49-57. R
Toxicity
and toxicokinetics of perfluorooctanoic acid in humans and animals.
Kudo
N, Kawashima Y.
Department of Toxicology
and Applied Pharmacology, Faculty of Pharmaceutical Sciences,
Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
Perfluorooctanoic
acid (PFOA) is an octanoic acid derivative to which all aliphatic
hydrocarbons are substituted by fluorine. PFOA and its salts
are commercially used in various industrial processes.
The chemical is persistent in the environment and does not undergo
biotransformation. It was reported that PFOA is found
not only in the serum of occupationally exposed workers but
also general populations. Recent studies have suggested that
the biological half-life of PFOA in humans is 4.37 years based
on study of occupationally exposed workers. It is increasingly
suspect that PFOA accumulates and affects human health, although
the toxicokinetics of PFOA in humans remain unclear. In experimental
animals, PFOA seems low in toxicity. PFOA is well-absorbed following
oral and inhalation exposure, and to a lesser extent following
dermal exposure. Once absorbed in the body, it distributes predominantly
to the liver and plasma, and to a lesser extent the kidney and
lungs. PFOA is excreted in both urine and feces. Biological
half-life of PFOA is quite different between species and sexes
and the difference is due mainly to the difference in renal
clearance. In rats, renal clearance of PFOA is regulated by
sex hormones, especially testosterone. PFOA is excreted
into urine by active tubular secretion, and certain organic
anion transporters are though to be responsible for the secretion.
Fecal excretion is also important in the elimination of PFOA.
There is evidence that PFOA undergoes enterohepatic circulation
resulting in reduced amounts of fecal excretion. Elucidation
of the mechanisms of transport in biological systems leads to
elimination and detoxification of this chemical in the human
body.
PMID: 12820537
[PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12807361&dopt=Abstract
Chem Res
Toxicol. 2003 Jun;16(6):775-81.
Binding
of perfluorooctanoic Acid to rat and human plasma proteins.
Han
X, Snow TA, Kemper RA, Jepson GW.
DuPont
Haskell Laboratory for Health and Environmental Sciences, P.O.
Box 50, Newark, Delaware 19714.
Perfluorooctanoic
acid (PFOA) is a commercially important organic fluorochemical
and is considered to have a long half-life in human blood. In
this paper, PFOA binding to rat and human plasma proteins was
investigated. On the basis of results from size-exclusion chromatography
and ligand blotting, most PFOA was in protein-bound form in
male and female rat plasma, and the primary PFOA binding protein
in plasma was serum albumin. PFOA binding to rat serum albumin
(RSA) in the gas phase was observed by electrospray ionization
MS. (19)F NMR experiments revealed that binding to RSA caused
peak broadening and chemical shift changes of PFOA resonances,
and on the basis of this observation, the dissociation constant
was determined to be approximately 0.3 mM. The dissociation
constants for PFOA binding to RSA and human serum albumin (HSA)
and the numbers of PFOA binding sites on RSA and HSA were also
determined by a separation method using microdesalting columns.
No significant difference was found between PFOA binding to
RSA and PFOA binding to HSA. The dissociation constants for
binding of PFOA to RSA or HSA and the numbers of PFOA binding
sites were in the range of 0.3-0.4 mM and 6-9, respectively.
On the basis of these binding parameters and the estimated plasma
concentration of serum albumin, greater than 90% of PFOA would
be bound to serum albumin in both rat and human blood.
PMID: 12807361
[PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12781843&dopt=Abstract
Comp Biochem
Physiol C Toxicol Pharmacol. 2003 May;135(1):77-88.
Alterations
in cell membrane properties caused by perfluorinated compounds.
Hu
W, Jones PD, DeCoen W, King L, Fraker P, Newsted J, Giesy JP.
National Food Safety
and Toxicology Center, Institute for Environmental Toxicology
and Department of Zoology, Michigan State University, MI 48824,
East Lansing, USA
The recent detection
of perfluorinated compounds (PFCs) in wildlife from even remote
locations has spurred interest in the environmental occurrence
and effects of these chemicals. While the global distribution
of PFCs is increasingly understood, there is still little information
available on their effects on wildlife. The
amphiphillic nature of PFCs suggests that their effects could
be primarily on cell membranes. In this study we measured
the effects of PFCs on membrane fluidity and mitochondrial membrane
potential using flow cytometry and effects on membrane permeability
using cell bioassay procedures (H4IIE, MCF-7, PLHC-1). Of the
PFCs tested, only perfluorooctane sulfonic acid (PFOS) increased
the permeability of cell membranes to the hydrophobic ligands
used. Three PFCs were tested in the membrane fluidity assay:
PFOS, perfluorohexane sulfonic acid (PFHS), and perfluorobutane
sulfonic acid (PFBS). PFOS increased membrane fluidity in fish
leukocytes in a dose-dependent fashion, while PFHS and PFBS
had no effect in the concentration range tested. The lowest
effective concentrations for the membrane fluidity effects of
PFOS were 5-15 mg/l. Effects on mitochondrial membrane potential
occurred in the same concentration range as effects on membrane
fluidity. This suggests that PFOS effects
membrane properties at concentrations below those associated
with other adverse effects.
PMID: 12781843
[PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12773773&dopt=Abstract
Toxicol
Sci 2003 May 28; [epub ahead of
print]
Exposure
to Perfluorooctane Sulfonate During Pregnancy in Rat and Mouse.
I. Maternal and Prenatal Evaluations.
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, NC.
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.
PMID: 12773773
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12773772&dopt=Abstract
Toxicol
Sci 2003 May 28; [epub ahead of
print]
Exposure
to Perfluorooctane Sulfonate During Pregnancy in Rat and Mouse.
II. Postnatal Evaluation.
Lau
C, Thibodeaux JR, Hanson RG, Rogers JM, Grey BE, Stanton ME,
Butenhoff JL, Stevenson LA.
Reproductive Toxicology
Division, National Health and Environmental Effects Research
Laboratory, Office of Research and Development, U.S. Environmental
Protection Agency, Research Triangle Park, NC.
The postnatal effects
of in utero exposure to perfluorooctane sulfonate (PFOS) were
evaluated in the rat and mouse. Pregnant Sprague-Dawley rats
were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from
gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated
with 1, 5, 10, 15 and 20 mg/kg PFOS from GD 1 to GD 18. Controls
received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg
for mice). At parturition, newborns were observed for clinical
signs and survival. All animals were born alive and initially
appeared to be active. In the highest dosage groups (10 mg/kg
for rat and 20 mg/kg for mouse), the neonates became pale, inactive
and moribund within 30-60 min, and all died soon afterward.
In the 5 mg/kg (rat) and 15 mg/kg (mouse) dose groups, the neonates
also became moribund but survived for a longer period of time
(8-12 h). Over 95% of these animals died
within 24 hr. Approximately 50%
of offspring died at 3 mg/kg for rat and 10 mg/kg for mouse.
Cross-fostering the PFOS-exposed rat neonates (5 mg/kg) to control
nursing dams failed to improve survival. Serum concentrations
of PFOS in newborn rats mirrored the maternal administered dosage
and were similar to those in the maternal circulation at GD
21; PFOS levels in the surviving neonates declined in the ensuing
days. Small but significant and persistent
growth lags were detected in surviving rat and mouse pups exposed
to PFOS prenatally, and slight delays in eye-opening were noted.
Significant increases in liver weight
were observed in the PFOS-exposed mouse pups. Serum
thyroxine levels were suppressed in the PFOS-treated
rat pups, although triiodothyronine and TSH levels were not
altered. Choline acetyltransferase activity
(an enzyme that is sensitive to thyroid status) in the prefrontal
cortex of rat pups exposed to PFOS prenatally was slightly reduced,
but activity in the hippocampus was not affected. Development
of learning, determined by T-maze delayed alternation in weanling
rats, was not affected by PFOS exposure. These
results indicate that in utero exposure to PFOS severely compromised
postnatal survival of neonatal rats and mice, and caused delays
in growth and development that were accompanied by hypothyroxinemia
in the surviving rat pups.
PMID: 12773772
[PubMed - as supplied by publisher]
From
TOXNET
Toxicologist
2003 Mar;72(S-1):342
Maternal
and developmental toxicity of perfluorooctane sulfonate (PFOS)
in the mouse.
Thibodeaux
J Hanson RG Grey BE Barbee BD Richards JH Butenhoff JL Rogers
JM Lau C
RTD, USEPA,
Research Triangle Park, NC.
Abstract: The maternal
and developmental toxicity of PFOS, an environmentally persistent
compound that has been used in the manufacture of surfactants
and insecticides, were evaluated. Timed-pregnant CD1 mice were
gavaged with 1, 5, 10, 15, or 20 mg/kg/day PFOS/K+ from GD 2
to term. Controls received an equivalent volume of 0.5% Tween-20
vehicle (10 mL/kg). Some dams were killed on GD 18 for teratological
examination, while those remaining were allowed to deliver to
monitor the postnatal growth and development of their offspring.
PFOS levels in maternal serum and liver were determined at term.
Maternal weight gain was suppressed by 20 mg/kg PFOS, indicating
the general maternal toxicity of the chemical. Serum triglycerides
and thyroxine in dams treated with greater than 5 mg/kg PFOS
were significantly lower than controls. Dose-dependent maternal
liver weight increases were observed at term. PFOS did not alter
the number of implantations, live fetuses, or fetal weight at
term. Cleft palate, sternal defects, cardiac ventricular septal
defect, and enlargement of the right atrium were detected, primarily
in the 20 mg/kg group. Live birth was observed in all groups;
however, neonates in the 20 mg/kg group were moribund and died
within 4-6 h. While newborns in the 15 mg/kg group appeared
viable, all were found dead within 24 h. Postnatal viability
was greater in the lower dose groups and surviving neonates
appeared to thrive, but significant delays in eye opening were
observed. These dose-dependent adverse effects will be compared
to the body burdens of PFOS. These results are similar to the
maternal and developmental toxicity of PFOS previously described
in the rat, although the mouse appears to be a less sensitive
species.
International Standard
Serial Number: 0731-9193
Publication
Types: MEETING ABSTRACT
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12729279&dopt=Abstract
J Environ
Monit 2003 Apr;5(2):341-5
Occurrence
and persistence of perfluorooctanesulfonate and other perfluorinated
surfactants in groundwater at a fire-training
area at Wurtsmith Air Force Base, Michigan, USA.
Moody CA, Hebert GN, Strauss SH, Field
JA.
Department of Chemistry, Oregon State University, Corvallis,
Oregon 97331, USA.
Various formulations of fire-extinguishing materials, including
aqueous film-forming foams (AFFFs), were used as part of fire-training
exercises conducted at Wurtsmith Air Force Base (WAFB) in northeastern
Michigan from the 1950s until the base was decommissioned in
1993. As a result of past fire-training exercises, AFFF-laden
wastewater containing fuels, solvents, and other materials directly
entered groundwater without prior treatment. Perfluorinated
surfactants are key components in some AFFF formulations. In
this study, groundwater was analyzed for perfluoroalkanesulfonates
and perfluorocarboxylates. Perfluoroalkanesulfonates were directly
detected using negative-ion electrospray ionization mass spectrometry.
Derivatized perfluorocarboxylates were detected using electron
impact gas chromatography-mass spectrometry. Groundwater from
wells around fire-training area FTA-02 at WAFB contained four
perfluorinated surfactants ranging in concentration from 3 to
120 microg L(-1): perfluorooctanesulfonate (PFOS); perfluorohexanesulfonate;
perfluorooctanoate; and perfluorohexanoate. This
is the first report demonstrating that PFOS, recently shown
to be toxic to organisms ranging from zooplankton to primates,
is still present in groundwater in measurable quantities five
or more years after its last known use.
PMID: 12729279 [PubMed - in process]
From
TOXNET
Toxicologist
2003 Mar;72(S-1):76
Multi-generation
reproduction study of ammonium perfluorooctanoate in rats.
Butenhoff
JL, Kennedy GL, O'Connor JC, York RG
3M, Saint Paul, MN.
Ammonium perfluorooctanoate (APFO) is a surfactant used primarily
as an aid in processing various fluoropolymers, and perfluorooctanoate
has been identified in human sera from the US at very low concentrations
(mean 6 ppb). The potential reproductive toxicity of APFO was
studied using current EPA OPPTS 870.3800 guidelines. Male and
female Sprague-Dawley rats were dosed orally with 0, 1, 3, 10,
or 30 mg/kg/day APFO. P rats (approximately 6 weeks old) were
dosed at least 70 days prior to mating and until sacrificed
(after mating for males; after weaning for females). F1 rats
were dosed similarly, beginning at weaning. The F2 pups were
maintained through 22 days of lactation. Reproductive parameters
evaluated in P and F1 rats included estrous cycling, sperm number
and quality, mating, fertility, natural delivery, and litter
viability and growth. Day of sexual maturation (F1) and anogenital
distance (F2) were also determined. Feed consumption, body weight
gain, selected organ weight, gross pathology and appropriate
histopathology were collected. No effects on mating or fertility
were discovered. P and F1 males experienced significant toxicity
(decreased body weight and organ weight changes) even at the
lowest dose tested, P females had reduced body weights and organ
weight changes at 30 mg/kg/day, and F1 females had reduced body
weight gains at 30 mg/kg/day and reduced pituitary weights at
3 mg/kg/day and higher. The 30 mg/kg/day F1 pups had decreased
birth weight and viability; however, F2 pups at 30 mg/kg/day
did not show a loss in viability. Sexual maturation was delayed
in F1 (both sexes). Estrous periods per 21 days were increased
in F1 females; however, this is likely an artifact of the evaluation
method, as an evaluation of raw estrous cycling data did not
indicate significant abnormalities. At the doses tested. APFO
did not cause specific effects on reproductive capacity, but
did produce toxicity and delayed sexual maturation. The NOAEL
for reproduction was greater than 30 mg/kg (P and F1) based
on lack of effect on mating, fertility, and natural delivery.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12560171&dopt=Abstract
Aquat Toxicol.
2003 Feb 12;62(3):227-34.
Impact
of perfluorooctanoic acid on the structure of the zooplankton
community in indoor microcosms.
Sanderson
H, Boudreau TM, Mabury SA, Solomon KR.
Department of Environment,
Technology & Social Studies, University of Roskilde, PO-Box
260, DK 4000 Roskilde, Denmark. hanss@ruc.dk
There is presently,
a substantial amount of information being gathered concerning
the environmental risk associated with the perfluorooctanoic
acid (PFOA) compound. The aim of this paper was to determine
a 35 day community no observable effect concentration (NOEC(community))
or lowest observable effect concentration (LOEC) for freshwater
zooplankton exposed to PFOA during a study in 30 l indoor aquatic
microcosms. Some significant (P < 0.01)
temporal fluctuations in zooplankton abundance were observed,
however, a NOEC(community) could not be calculated. LOEC for
various species varied between 10 and 70 mg l(-1). According
to LOEC values, the tentative order of descriptors sensitivity
was as follows: Daphnia magna > richness > or = Cyclops canthocamptus
staphylinus > Cyclops diaptomus>total zooplankton > or = Rotifera
sp. The long term ecological significance of these temporal
fluctuations could not be determined in this study, however,
the overall study cessation analysis showed that the structure
of the ecosystem was changed from a more diverse community dominated
by larger species towards a less diverse community dominated
by smaller more and robust species (P < 0.05). Additional
chronic toxicity testing should also be addressed since these
compounds are so persistent and recalcitrant.
PMID: 12560171
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12712289&dopt=Abstract
Arch Environ
Contam Toxicol 2003 Apr;44(3):307-13
Laboratory evaluation of the toxicity of Perfluorooctane
Sulfonate (PFOS) on Selenastrum capricornutum, Chlorella vulgaris,
Lemna gibba, Daphnia magna, and Daphnia pulicaria.
Boudreau TM, Sibley PK, Mabury SA, Muir
DG, Solomon KR.
Centre for Toxicology, Department of Environmental Biology,
Bovey Building, University of Guelph, Guelph, Ontario, N1G 2W1
Canada. tboudrea@evb.uoguelph.ca
Perfluorooctane sulfonate (PFOS) is an anthropogenic compound
found in trace amounts in many environmental compartments far
from areas of production. This, along with the highly persistent
nature of PFOS, presents a concern for possible effects in aquatic
ecosystems. The objective of this study was to determine the
toxicity of PFOS in representative freshwater organisms. Toxicity
testing using standard laboratory protocols was performed on
the green algae Selenastrum capricornutum and Chlorella vulgaris,
the floating macrophyte Lemna gibba, and the invertebrates Daphnia
magna and Daphnia pulicaria. No observable effect concentration
(NOEC) values were generated from the most sensitive endpoints
for all organisms. Autotroph inhibition of growth NOEC values
were 5.3, 8.2, and 6.6 mg/L for S. capricornutum, C. vulgaris,
and L. gibba, respectively. The 48-h immobility NOEC values
for D. magna and D. pulicaria were 0.8 and 13.6 mg/L, respectively.
In comparison to immobility, the 21-day lethality NOEC for D.
magna was 5.3 mg/L. Based on effect (immobility) values, the
most sensitive of all test organisms was D. magna. The most
sensitive organism based on 50% inhibition of growth (IC(50))
was L. gibba, with an IC(50) value of 31.1 mg/L determined from
wet weight. This is 4.3 times less than the LC(50) for D. pulicaria,
which was 134 mg/L. Significant adverse effects (p < or = 0.05)
were observed for all organisms in concentrations >134 mg/L.
The results indicate that under laboratory
conditions PFOS is acutely toxic to freshwater organisms at
concentrations at or near 100 mg/L. Based on known environmental
concentrations of PFOS, which occur in the low ng/L to low microg/L
range, there is no apparent risk to freshwater systems. However,
further work is required to investigate long-term effects in
these and other freshwater organisms.
PMID: 12712289 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12666917&dopt=Abstract
Environ
Sci Technol 2003 Mar 1;37(5):888-91
Human
donor liver and serum concentrations of perfluorooctanesulfonate
and other perfluorochemicals.
Olsen GW, Hansen KJ, Stevenson
LA, Burris JM, Mandel JH.
3M Medical Department, 220-3W-05,
St. Paul, Minnesota 55144, USA. gwolsen@mmm.com
Perfluorooctanesulfonate (PFOS, CaF17SO3-) has been identified
in the serum of nonoccupationally exposed humans and in serum
and liver tissue in wildlife. The purpose of this investigation
was to determine whether PFOS liver concentrations in humans
are comparable to the approximate 30 ng/mL average serum concentrations
reported in nonoccupationally exposed subjects. Thirty-one donors
(16 male and 15 female, age range 5-74) provided serum and/or
liver samples for analysis of PFOS and three other fluorochemicals:
perfluorosulfonamide (PFOSA, C8F17SO2NH2), perfluorooctanoate
(PFOA, C7F15CO2-), and perfluorohexanesulfonate (PFHxS, C6F13SO3-).
Both sera and liver samples were extracted by ion-pair extraction
and quantitatively assayed using high-performance liquid chromatography
electrospray tandem mass spectrometry.
Liver PFOS concentrations ranged from <4.5 ng/g (limit of quantitation,
LOQ) to 57.0 ng/g. Serum PFOS concentrations ranged from <6.1
ng/mL (LOQ) to 58.3 ng/mL. Among the 23 paired samples,
the mean liver to serum ratio was 1.3:1 (95% confidence interval
0.9:1-1.7:1). This liver to serum ratio
is comparable to that reported in a toxicological study of cynomolgus
monkeys, which had liver and serum concentrations 2-3 orders
of magnitude higher than observed in these human donors. This
information may be useful in human risk characterization for
PFOS. Liver to serum ratios were not estimated for PFOA, PFHxS,
and PFOSA as 90% of the human donor liver samples were determined
to be less than the LOQ.
PMID: 12666917 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12661183&dopt=Abstract
J Occup
Environ Med 2003 Mar;45(3):260-70
Epidemiologic
assessment of worker serum perfluorooctanesulfonate
(PFOS) and perfluorooctanoate (PFOA) concentrations
and medical surveillance examinations.
Olsen GW, Burris JM, Burlew MM, Mandel
JH.
Medical Dept., 3M Company, Mail
Stop 220-3W-05, St. Paul, MN 55144, USA. gwolsen@mmm.com
Perfluorooctanesulfonyl fluoride (POSF, C8F17SO2F) is used to
create applications for surfactants and paper, packaging, and
surface (e.g., carpets, textiles) protectants. Such POSF-based
products or their residuals may degrade or metabolize to PFOS
(C8F17SO3-). PFOS concentrates in liver and serum and results
in hypolipidemia as an early effect of cumulative dosages.
Male and female employees of two perfluorooctanyl-manufacturing
locations (Antwerp, Belgium and Decatur, Alabama) participated
in a periodic medical surveillance program that included hematology,
clinical chemistry, thyroid hormone, and urinalysis testing.
Serum concentrations of PFOS and perfluorooctanoate (PFOA, C7F15CO2-,
used as a fluoropolymer emulsifier) were measured via mass spectrometry
methods. The mean serum PFOS and PFOA
concentrations for 263 Decatur employees were 1.32 parts per
million (ppm; geometric mean 0.91, range 0.06-10.06 ppm)
and 1.78 ppm (geometric mean 1.13, range 0.04-12.70 ppm), respectively.
Mean concentrations were approximately
50% lower among 255 Antwerp workers. Adjusting for potential
confounding factors, there were no substantial changes in hematological,
lipid, hepatic, thyroid, or urinary parameters consistent with
the known toxicological effects of PFOS or PFOA in cross-sectional
or longitudinal analyses of the workers' measured serum fluorochemical
concentrations.
PMID: 12661183 [PubMed - in
process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12627649&dopt=Abstract
Environ
Toxicol Chem 2003 Mar;22(3):608-14
Perfluorooctane
sulfonic acid in bib (Trisopterus
luscus) and plaice (Pleuronectes
platessa) from the Western Scheldt and the Belgian North Sea:
distribution and biochemical effects.
Hoff PT, Van de Vijver K, Van Dongen W,
Esmans EL, Blust R, De Coen WM.
Department of Biology, Research Unit Ecophysiology, Biochemistry
and Toxicology, Antwerp University, Groenenborgerlaan 171, B-2020
Antwerp, Belgium. phoff@ruca.ua.ac.be
A biomonitoring campaign was conducted in the Belgian North
Sea and in the Western Scheldt (The Netherlands) with the primary
goal to assess perfluorooctane sulfonic acid (PFOS) contamination
and distribution in different biota. This study covers the results
obtained for bib (Trisopterus luscus) and plaice (Pleuronectes
platessa) and includes the assessment of some stress-related
biochemical endpoints. Analysis of liver and muscle PFOS concentrations
of both species provided evidence for the existence of a PFOS
pollution gradient along the Western Scheldt with higher levels
at the upstream locations and a lower degree of PFOS pollution
at the marine locations. Cellular necrosis was studied by measuring
aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) levels in the serum. Serum ALT but
not serum AST was shown to correlate positively with the PFOS
liver concentration in bib (r = 0.44, p < 0.05), indicating
that PFOS might contribute to the induction of hepatic damage
in bib in the area of study. Analysis of total carbohydrate,
lipid, and protein content of bib liver tissue revealed a positive
correlation between the protein content and the PFOS liver concentration
(r = 0.55, p < 0.01). Whether this is due to induction of compensatory
mechanisms, detoxification, or repair processes remains unclear.
PMID: 12627649 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12595174&dopt=Abstract
Aquat Toxicol
2003 Feb 26;62(4):349-59
Evaluation
of the toxicological effects of perfluorooctane sulfonic acid
in the common carp (Cyprinus carpio).
Hoff PT, Van Dongen W, Esmans EL, Blust
R, De Coen WM.
Department of Biology, Research Unit Ecophysiology, Biochemistry
and Toxicology, Antwerp University, Groenenborgerlaan 171, Belgium.
phoff@ruca.ua.ac.be
In the present study we evaluated the toxicological effects
of a scarcely documented environmental pollutant, perfluorooctane
sulfonic acid (PFOS), on selected biochemical endpoints in the
common carp, Cyprinus carpio. Juvenile organisms were exposed
to PFOS through a single intraperitoneal injection (liver concentrations
ranging from 16 to 864 ng/g after 5 days of exposure) and after
1 and 5 days effects were assessed in liver and serum of the
exposed organisms. The investigation of the hepatotoxicity of
PFOS included the determination of the peroxisome proliferating
potential (peroxisomal palmitoyl CoA oxidase and catalase activity)
and the compounds influence on the average DNA basepair length
(ABPL) by agarose gel electrophoresis. Total antioxidant activity
(TAA), cholesterol and triglyceride levels were monitored in
the serum. After 1 day of exposure the ABPL was significantly
increased in the 270 and 864 ng/g treatment groups. After 5
days of exposure significant increases relative to the control
were observed for the 16, 270 and 864 ng/g treatment groups.
Enzyme leakage from the liver was investigated by measurement
of alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) activities in the serum. At 561, 670 and 864 ng/g PFOS
a significant increase in serum ALT activity became apparent
after 5 days of exposure with values ranging from 159 to 407%
relative to the control. For serum AST activity a significant
increase for the 864 ng/g treatment group was observed with
a value of 112% relative to the control. Determination of the
polymorphonuclear leukocyte migration into liver tissue as assessed
through myeloperoxidase (MPO) activity in liver, was used as
an indicator for inflammation. It appeared that inflammation
was not involved in the observed membranous enzyme leakage for
the 561, 670 and 864 ng/g PFOS treatment groups. The
results of this study suggest that PFOS induces inflammation-independent
enzyme leakage through liver cell membranes that might be related
to cell necrosis. Furthermore, results show that PFOS
does not significantly affects serum antioxidant levels nor
does it clearly induce peroxisome proliferation in carp. This
study also points out that PFOS might interfere with homeostasis
of the DNA metabolism. The results of these biochemical
analyses were used to perform an initial hazard assessment study
indicating that PFOS levels observed in tissues of wildlife
populations could induce a clear rise in serum transaminase
levels indicative for disruption of hepatocyte membrane integrity.
PMID: 12595174 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12504346&dopt=Abstract
Toxicology
2003 Feb 1;183(1-3):117-31
Sub-chronic
dietary toxicity of potassium perfluorooctanesulfonate in rats.
Seacat AM, Thomford PJ, Hansen KJ, Clemen
LA, Eldridge SR, Elcombe CR, Butenhoff JL.
3M Medical Department, Corporate
Toxicology, 3M Center 220-2E-02, Saint Paul, MN 55133, USA.
Perfluorooctanesulfonate
(PFOS) is a widely disseminated persistent compound found at
low (part-per-billion) concentrations in serum and liver samples
from humans and fish-eating wildlife. This study investigated
the hypotheses that early hepatocellular peroxisomal proliferation
and hepatic cellular proliferation are factors in chronic liver
response to dietary dosing, that lowering of serum total cholesterol
is an early clinical measure of response to treatment, and that
liver and serum PFOS concentrations are proportional to dose
and cumulative dose after sub-chronic treatment. PFOS was administered
in diet as the potassium salt at 0, 0.5, 2.0, 5.0, and 20 parts
per million (ppm) to Sprague Dawley rats for 4 or 14 weeks.
At 4 weeks, effects included decreased serum glucose and an
equivocal (<twofold) increase in hepatic palmitoyl CoA oxidase
(PCoAO) activity in 20 ppm dose-group males and elevation of
alanine aminotransferase (ALT) in 20 ppm dose-group females.
At 14 weeks, the 20 ppm males had increased liver weight, decreased
serum cholesterol, increased non-segmented neutrophils, and
increased ALT. Relative liver weights and urea nitrogen were
increased in both sexes at 14 weeks. Hepatocytic
hypertrophy and cytoplasmic vacuolation were observed in the
5 or 20 ppm male and the 20 ppm female dose groups. An
increase in hepatic PCoAO activity was not observed at 14 weeks,
and the average hepatocyte proliferation index was not increased,
although, individual animals had mild increases. Serum and liver
PFOS concentrations were proportional to dose and cumulative
dose. Serum concentrations were generally
higher in females than in males. The liver-to-serum PFOS
ratios ranged from approximately 3:1 to 12:1. After 14 weeks,
the no-observed-adverse effect level (NOAEL) in males and females
was 5 ppm. The NOAEL corresponded to mean serum PFOS concentrations
of 44 ppm (microg/ml) in males and 64 ppm in females and mean
liver PFOS concentrations of 358 ppm in males and 370 ppm in
females. Results for this study:
(1) did not provide strong evidence for hepatocellular peroxisomal
or cellular proliferation at the doses tested;
(2) suggested that lowering of serum total cholesterol may not
be the earliest clinically-measurable response to treatment
in the rat; and
(3) confirmed that serum and liver PFOS concentrations on repeated
dosing are proportional to dose and cumulative dose.
PMID: 12504346
[PubMed - indexed for MEDLINE]
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