PFOS and PFOA are a class of perfluorinated chemicals that are
best known for their use in the production of Teflon and other
stain resistent materials. The interest of the FAN Pesticide Project
in this issue is due to the use of several of the PFOS and PFOA
chemicals as "inerts" in pesticides. However, most,
but not all, have been deleted from use since 2001. The so-called
"inerts" used in pesticides can account for as much
as 99%, or more, of a pesticidal formulation. US EPA's policy
is to allow the public information only on the "active substance"
and to deny the public the names of the chemicals used as "inerts"
in specific pesticide products -- even though the majority of
inerts are toxic and biologically active.
The following is a selected list of abstracts. For
more see PubMed
Environ Int. 2007 Apr 16; [Epub ahead of print]
Identification and pattern of perfluorooctane
sulfonate (PFOS) isomers in human serum and plasma.
Karrman A, Langlois I, Bavel BV, Lindstrom G, Oehme M.
Man-Technology-Environment Research Centre (MTM), Orebro University,
SE-701 82 Orebro, Sweden.
Human serum and plasma from Sweden (n=17), the United Kingdom
(the UK) (n=13) and Australia (n=40) were analyzed by high performance
liquid chromatography coupled to mass spectrometry. The objective
was to identify different perfluorooctane sulfonate (PFOS) isomers.
Similar isomer patterns typical for the electrochemical fluorination
(ECF) process were found for all samples. The
linear PFOS (L-PFOS) was the major isomer found (58-70%) followed
by the monosubstituted PFOS isomers 1/6-CF(3)-PFOS (18-22%) and
3/4/5-CF(3)-PFOS (13-18%). Disubstituted isomers were also detected.
The percentage of L-PFOS found in the serum and plasma samples
was lower compared to a standard PFOS product (76-79%). The pattern
of PFOS isomers in human serum and plasma may be suggestive concerning
potential isomeric discrimination since PFOS is only produced
by ECF. Possibilities for such isomer discrimination are discussed.
Significant higher content of L-PFOS (68%)
in Swedish samples compared to Australia and the UK (59%) was
also found, which may suggest differences in exposure sources
PMID: 17442394 [PubMed - as supplied by publisher]
Ann Epidemiol. 2007 Apr 18;
Bladder Cancer in Perfluorooctanesulfonyl
Fluoride Manufacturing Workers.
Alexander BH, Olsen GW.
From the Division of Environmental Health Sciences, School of
Public Health, University of Minnesota (B.H.A.), and
3M Company, Medical Department, Saint Paul (G.W.O.).
PURPOSE: To determine whether bladder cancer is associated with
exposure to perfluorooctane sulfonate (PFOS) in an occupational
METHODS: Incidence of bladder cancer was ascertained by postal
questionnaire to all living current and former employees of the
facility (N = 1895) and death certificates for deceased workers
(N = 188). Exposure to PFOS was estimated with work history records
and weighted with biological monitoring data. Standardized incidence
ratios (SIRs) were estimated using U.S. population-based rates
as a reference. Bladder cancer risk within the cohort was evaluated
using Poisson regression by cumulative PFOS exposure.
RESULTS: Questionnaires were returned by 1,400 of the 1895 cohort
members presumed alive. Eleven cases of primary bladder cancer
were identified from the surveys (n = 6) and death certificates
(n = 5). The SIRs were 1.28 (95% confidence interval [CI] = 0.64-2.29)
for the entire cohort and 1.74 (95% CI = 0.64-3.79) for those
ever working in a high exposed job. Compared with employees in
the lowest cumulative exposure category, the relative risk of
bladder cancer was 0.83 (95% CI = 0.15-4.65), 1.92 (95% CI = 0.30-12.06),
and 1.52 (95% CI = 0.21-10.99).
CONCLUSIONS: The results offer little support
for an association between bladder cancer and PFOS exposure, but
the limited size of the population prohibits a conclusive exposure
PMID: 17448680 [PubMed - as supplied by publisher]
Int Arch Occup Environ Health. 2007
Jan 12; [Epub ahead of print]
Transplacental exposure of neonates to
perfluorooctanesulfonate and perfluorooctanoate: a pilot study.
Midasch O, Drexler H, Hart N, Beckmann MW, Angerer J.
Institute and Outpatient Clinic of Occupational, Social and Environmental
Medicine, University of Erlangen-Nuremberg, Schillerstrasse 25,
91054, Erlangen, Germany, Angerer@asumed.med.uni-erlangen.de.
OBJECTIVES: Perfluorooctanesulfonate (PFOS) and perfluorooctanoate
(PFOA) can be released of perfluorinated compounds by biotic and/or
metabolic decomposition. Due to their ubiquitous occurrence, persistence
and bioaccumulative properties they can be found in blood of the
general population all over the world. In animal studies PFOS
and PFOA provoked cancer and showed developmental toxic potential
besides other adverse health effects. On the basis of the comparison
of maternal and umbilical cord plasma sample pairs we wanted to
examine whether infants are exposed to PFOS and PFOA via their
METHODS: We determined PFOS and PFOA in 11 plasma samples of mothers
and the 11 corresponding cord plasma samples of neonates. An analytical
method based on plasma protein precipitation followed by HPLC
with MS/MS-detection was employed. As internal standards we used
1,2,3,4-(13)C(4)-PFOS and 1,2-(13)C(2)-PFOA.
RESULTS: We found PFOS and PFOA in every plasma sample analysed.
In maternal plasma samples PFOS concentrations were consistently
higher compared to those of the related cord plasma samples (median:
13.0 mug/l vs. 7.3 mug/l). In the case of PFOA we observed only
minor differences between PFOA concentrations within the analysed
sample pairs (median: 2.6 mug/l vs. 3.4 mug/l for maternal and
cord plasma samples, respectively).
DISCUSSION: For both substances a crossing
of the placental barrier could be shown. For PFOS we observed
a decrease from maternal to cord plasma concentrations by a factor
of 0.41-0.80. To the contrary, PFOA crosses
the placental barrier obviously unhindered. These
findings show that neonates are exposed to PFOS and PFOA via their
mothers' blood. Given the current situation that only little is
known about the consequences of PFOS and PFOA exposure in the
early state of development of humans and the fact that in animal
studies both substances showed developmental toxic effects further
research regarding human health effects is indispensable.
PMID: 17219182 [PubMed - as supplied by publisher]
Toxicol Sci. 2007 Mar;96(1):133-44.
Epub 2006 Nov 28.
Gestational PFOA exposure of mice is associated
with altered mammary gland development in dams and female offspring.
White SS, Calafat AM, Kuklenyik Z, Villanueva L, Zehr RD, Helfant
L, Strynar MJ, Lindstrom AB, Thibodeaux JR, Wood C, Fenton SE.
Curriculum in Toxicology, University of North Carolina at Chapel
Hill, Chapel Hill, North Carolina 27599, USA.
Perfluorooctanoic acid (PFOA), with diverse and widespread commercial
and industrial applications, has been detected in human and wildlife
sera. Previous mouse studies linked prenatal PFOA exposure to
decreased neonatal body weights (BWs) and survival in a dose-dependent
manner. To determine whether effects were linked to gestational
time of exposure or to subsequent lactational changes, timed-pregnant
CD-1 mice were orally dosed with 5 mg PFOA/kg on gestation days
(GD) 1-17, 8-17, 12-17, or vehicle on GD 1-17. PFOA exposure had
no effect on maternal weight gain or number of live pups born.
Mean pup BWs on postnatal day (PND) 1 in
all PFOA-exposed groups were significantly reduced and decrements
persisted until weaning. Mammary glands from lactating
dams and female pups on PND 10 and 20 were scored based on differentiation
or developmental stages. A significant reduction
in mammary differentiation among dams exposed GD 1-17 or 8-17
was evident on PND 10. On PND 20, delays in normal epithelial
involution and alterations in milk protein gene expression were
observed. All exposed female pups displayed stunted mammary epithelial
branching and growth at PND 10 and 20. While control litters
at PND 10 and 20 had average scores of 3.1 and 3.3, respectively,
all treated litters had scores of 1.7 or less, with no progression
of duct epithelial growth evident over time. BW was an insignificant
covariate for these effects. These findings
suggest that in addition to gestational exposure, abnormal lactational
development of dams may play a role in early growth retardation
of developmentally exposed offspring.
PMID: 17132714 [PubMed - indexed for MEDLINE]
Toxicol Sci. 2007 Feb;95(2):462-73.
Epub 2006 Nov 10.
Developmental toxicity of perfluorooctanoic
acid in the CD-1 mouse after cross-foster and restricted gestational
Wolf CJ, Fenton SE, Schmid JE, Calafat AM, Kuklenyik Z, Bryant
XA, Thibodeaux J, Das KP, White SS, Lau CS, Abbott BD.
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.
Perfluorooctanoic acid (PFOA) is a persistent pollutant and is
detectable in human serum (5 ng/ml in the general population of
the Unites States). PFOA is used in the production of fluoropolymers
which have applications in the manufacture of a variety of industrial
and commercial products (e.g., textiles, house wares, electronics).
PFOA is developmentally toxic and in mice
affects growth, development, and viability of offspring.
This study segregates the contributions of gestational and lactational
exposures and considers the impact of restricting exposure to
specific gestational periods. Pregnant CD-1 mice were dosed on
gestation days (GD) 1-17 with 0, 3, or 5 mg PFOA/kg body weight,
and pups were fostered at birth to give seven treatment groups:
unexposed controls, pups exposed in utero (3U and 5U), lactationally
(3L and 5L), or in utero + lactationally (3U + L and 5U + L).
In the restricted exposure (RE) study, pregnant mice received
5 mg PFOA/kg from GD7-17, 10-17, 13-17, or 15-17 or 20 mg on GD15-17.
In all PFOA-treated groups, dam weight gain, number of implantations,
and live litter size were not adversely affected and relative
liver weight increased. Treatment with 5 mg/kg on GD1-17 increased
the incidence of whole litter loss and pups in surviving litters
had reduced birth weights, but effects on pup survival from birth
to weaning were only affected in 5U + L litters. In utero exposure
(5U), in the absence of lactational exposure, was sufficient to
produce postnatal body weight deficits and developmental delay
in the pups. In the RE study, birth weight and survival were reduced
by 20 mg/kg on GD15-17. Birth weight was also reduced by 5 mg/kg
on GD7-17 and 10-17. Although all PFOA-exposed pups had deficits
in postnatal weight gain, only those exposed on GD7-17 and 10-17
also showed developmental delay in eye opening and hair growth.
In conclusion, the postnatal developmental effects of PFOA are
due to gestational exposure. Exposure earlier in gestation produced
stronger responses, but further study is needed to determine if
this is a function of higher total dose or if there is a developmentally
PMID: 17098816 [PubMed - indexed for MEDLINE]
Toxicol Sci. 2007 Feb;95(2):452-61.
Epub 2006 Nov 8.
Perfluorooctanoic acid and perfluorononanoic
acid in fetal and neonatal mice following in utero exposure to
8-2 fluorotelomer alcohol.
Henderson WM, Smith MA.
Interdisciplinary Toxicology Program, College of Public Health,
University of Georgia, Athens, Georgia 30602, USA. Henderson.firstname.lastname@example.org
8-2 Fluorotelomer alcohol (FTOH) and its metabolites, perfluorooctanoic
acid (PFOA) and perfluorononanoic acid (PFNA), are developmental
toxicants but metabolism and distribution during pregnancy are
not known. To examine this, timed-pregnant mice received a single
gavage dose (30 mg 8-2 FTOH/kg body weight) on gestational day
(GD) 8. Maternal and neonatal serum and liver as well as fetal
and neonatal homogenate extracts were analyzed using gas chromatography
coupled with mass spectrometry. During gestation (GD9 to GD18),
maternal serum and liver concentrations of PFOA decreased from
789 +/- 41 to 668 +/- 23 ng/ml and from 673 +/- 23 to 587 +/-
55 ng/g, respectively. PFOA was transferred to the developing
fetuses as early as 24-h posttreatment with concentrations increasing
from 45 +/- 9 ng/g (GD10) to 140 +/- 32 ng/g (GD18), while PFNA
was quantifiable only at GD18 (31 +/- 4 ng/g). Post-partum, maternal
serum PFOA concentrations decreased from 451 +/- 21 ng/ml postnatal
day (PND) 1 to 52 +/- 19 ng/ml (PND15) and PFNA concentrations,
although fivefold less, exhibited a similar trend. Immediately
after birth, pups were cross-fostered with dams that had been
treated during gestation with 8-2 FTOH (T) or vehicle (C) resulting
in four treatment groups in which the first letter represents
in utero (fetal) exposure and the second represents lactational
(neonatal) exposure: C/C, T/C, C/T, T/T. On PND1, neonatal whole-body
homogenate concentrations of PFOA from T/T and T/C groups averaged
200 +/- 26 ng/g, decreased to 149 +/- 19 ng/g at PND3 and this
decreasing trend was seen in both neonatal liver and serum from
PND3 to PND15. Based on detectible amounts
of PFOA in neonatal serum in the C/T group on PND3 (57 +/- 11
ng/ml) and on PND15 (58 +/- 3 ng/ml), we suggest that the neonates
were exposed through lactation. In conclusion, exposure of neonates
to PFOA and PFNA occurs both pre- and postnatally following maternal
8-2 FTOH exposure on GD8.
PMID: 17093205 [PubMed - indexed for MEDLINE]
Toxicol Sci. 2007 Mar
22; [Epub ahead of print]
Toxicogenomic Study of Triazole
Fungicides and Perfluoroalkyl Acids in Rat Livers Predicts Toxicity
and Categorizes Chemicals Based on Mechanisms of Toxicity.
Martin MT, Brennan R, Hu W, Ayanoglu E, Lau C,
Ren H, Wood CR, Corton JC, Kavlock RJ, Dix DJ.
Office of Research and Development, U.S.
Environmental Protection Agency, Research Triangle Park,
NC 27711, USA.
Toxicogenomic analysis of five environmental chemicals
was performed to investigate the ability of genomics to predict
toxicity, categorize chemicals and elucidate mechanisms of toxicity.
Three triazole antifungals (myclobutanil, propiconazole and triadimefon)
and two perfluorinated chemicals (perfluorooctanoic acid (PFOA)
and perfluorooctane sulfonate (PFOS))
were administered daily via oral gavage for 1, 3, or 5 consecutive
days to male Sprague-Dawley rats at single doses of 300, 300,
175, 20, or 10 mg/kg/d, respectively. Clinical chemistry, hematology
and histopathology were measured at all time points. Gene expression
profiling of livers from 3 rats per treatment group at all time
points was performed on the CodeLink RU1 rat array. Data were
analyzed in the context of a large reference toxicogenomic database
containing gene expression profiles for over 630 chemicals. Genomic
signatures predicting hepatomegaly and hepatic injury preceded
those results for all five chemicals and further analysis segregated
chemicals into two distinct classes. The triazoles caused similar
gene expression changes as other azole antifungals, particularly
the induction of PXR (pregnane X receptor)-regulated xenobiotic
metabolism and oxidative stress genes. In contrast,
PFOA and PFOS exhibited PPARalpha (peroxisome proliferator-activated
receptor alpha) agonist-like effects on genes associated with
fatty-acid homeostasis. PFOA and PFOS also resulted in downregulation
of cholesterol biosynthesis genes, matching an in vivo decrease
in serum cholesterol, and perturbation of thyroid hormone metabolism
genes matched by serum thyroid hormone depletion in vivo.
The concordance of in vivo observations and gene expression findings
demonstrated the ability of genomics to accurately categorize
chemicals, identify toxic mechanisms of action, and predict subsequent
PMID: 17383973 [PubMed - as supplied
Int J Mol Med. 2007 May;19(5):733-9.
influences feeding behavior and gut motility via the hypothalamus.
Asakawa A, Toyoshima M, Fujimiya M, Harada K, Ataka
K, Inoue K, Koizumi A.
Department of Health and Environmental Sciences,
Kyoto University Graduate School of Medicine, Kyoto 606-8501,
Perfluorinated compounds (PFCs) have been employed
as surface treatment agents in a variety of products. Perfluorooctane
sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the two
most commonly found PFCs in the environment and human blood. We
investigated the effects of PFOS and PFOA on feeding behavior.
PFOS or PFOA was administered intracerebroventricularly in mice
or rats. Following administration, food intake, gastroduodenal
motility, gastric emptying, gene expression of hypothalamic neuropeptides,
and c-Fos expression along with immunoreaction for urocortin 2
in the paraventricular nucleus (PVN) were determined. Centrally
administered PFOS and PFOA decreased food intake. Administration
of PFOS decreased gastric emptying and disrupted the fasted motor
activity in the antrum and duodenum. The gene expression of urocortin
2 in the hypothalamus and c-Fos expression and immunoreaction
for urocortin 2 in the PVN were increased by the action of PFOS.
A centrally administered corticotropin-releasing factor type 2
receptor (CRFR2) antagonist blocked PFOS-induced anorexia. These
findings indicate that PFOS and PFOA influence feeding behavior.
This effect is mediated via the activation of hypothalamic
urocortin 2 and CRFR2, and the suppression of gastroduodenal motor
activity. These observations indicate that
PFCs may act centrally to influence behavior and physiological
functions in humans.
PMID: 17390077 [PubMed - in process]
Environ Res. 2007 Feb;103(2):176-84.
Epub 2006 Aug 8.
Comparison of human whole blood, plasma,
and serum matrices for the determination of perfluorooctanesulfonate
(PFOS), perfluorooctanoate (PFOA), and other fluorochemicals.
Ehresman DJ, Froehlich JW, Olsen GW, Chang SC, Butenhoff JL.
Medical Department, 3M Company,
Mail Stop 220-6W-08, St. Paul, MN 55144-1000, USA.
Interest in human exposure to perfluorinated acids, including
perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHS),
perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA)
has led to their measurement in whole blood, plasma and serum.
Comparison of measurements in these different blood-based matrices,
however, has not been rigorously investigated to allow for across-matrix
comparisons. This research evaluated concentrations of PFBS, PFHS,
PFOS, and PFOA in whole blood collected in heparin (lithium) and
ethylenediamine tetraacetic acid (EDTA), plasma samples collected
in heparin and EDTA, and serum (from whole blood allowed to clot).
Blood samples were collected from 18 voluntary participants employed
at 3M Company. Solid phase extraction methods were used for all
analytical sample preparations, and analyses were completed using
high-pressure liquid chromatography/tandem mass spectrometry methods.
Serum concentrations ranged from: limit of quantitation (LOQ,
5 ng/mL) to 25 ng/mL for PFBS; LOQ (5 ng/mL) to 75 ng/mL for PFHS;
LOQ (5 ng/mL) to 880 ng/mL for PFOS; and LOQ (5 or 10 ng/mL) to
7320 ng/mL for PFOA. Values less than the LOQ were not included
in the statistical analyses of the mean of the ratios of individual
values for the matrices. PFBS was not quantifiable in most samples.
Serum to plasma ratios for PFHS, PFOS, and PFOA were 1:1 and this
ratio was independent of the level of concentrations measured.
Serum or plasma to whole blood ratios, regardless of the anticoagulant
used, approximated 2:1. The difference between
plasma and serum and whole blood corresponded to volume displacement
by red blood cells, suggesting that the fluorochemicals are not
found intracellularly or attached to the red blood cells.
PMID: 16893538 [PubMed - indexed for MEDLINE]
J Agric Food Chem. 2007
Apr 18;55(8):3203-10. Epub 2007 Mar 24.
Dietary Exposure of Canadians
to Perfluorinated Carboxylates and Perfluorooctane Sulfonate via
Consumption of Meat, Fish, Fast Foods, and Food Items Prepared
in Their Packaging.
Tittlemier SA, Pepper K, Seymour C, Moisey J, Bronson
R, Cao XL, Dabeka RW.
Food Research Division, Banting Research Centre
2203D, and Chemical Health Hazard Assessment Division, Banting
Research Centre 2204D, Health Canada, Ottawa, Ontario K1A 0L2,
Human exposure to perfluorinated compounds is a
worldwide phenomenon; however, routes of human exposure to these
compounds have not been well-characterized. Fifty-four solid food
composite samples collected as part of the Canadian Total Diet
Study (TDS) were analyzed for perfluorocarboxylates and perfluorooctanesulfonate
(PFOS) using a methanol extraction liquid chromatography tandem
mass spectrometry method. Foods analyzed included fish and seafood,
meat, poultry, frozen entrees, fast food, and microwave popcorn
collected from 1992 to 2004 and prepared as for consumption. Nine
composites contained detectable levels of perfluorinated compounds-four
meat-containing, three fish and shellfish, one fast food, and
one microwave popcorn. PFOS and perfluorooctanoate (PFOA) were
detected the most frequently; concentrations ranged from 0.5 to
4.5 ng/g. The average dietary intake of
total perfluorocarboxylates and PFOS for Canadians was estimated
to be 250 ng/day, using results from the 2004 TDS composites.
A comparison with intakes of perfluorocarboxylates and PFOS via
other routes (air, water, dust, treated carpeting, and apparel)
suggested that diet is an important source
of these compounds. There was a substantial margin of exposure
between the toxicological points of reference and the magnitude
of dietary intake of perfluorinated compounds for Canadians >/=
12 years old. Keywords: PFOS; PFOA; diet; food; exposure estimate.
PMID: 17381114 [PubMed - in process]
Environ Health Perspect. 2007
Feb;115(2):226-30. Epub 2006 Nov 28.
Exposure of perfluorinated
chemicals through lactation: levels of matched human milk and
serum and a temporal trend, 1996-2004, in Sweden.
Karrman A, Ericson I, van Bavel B, Darnerud PO,
Aune M, Glynn A, Lignell S, Lindstrom G.
Man-Technology-Environment (MTM) Research Centre,
Orebro University, Orebro, Sweden. email@example.com
BACKGROUND: Only limited data exist on lactation
as an exposure source of persistent perfluorinated chemicals (PFCs)
OBJECTIVES: We studied occurrence and levels of PFCs in human
milk in relation to maternal serum together with the temporal
trend in milk levels between 1996 and 2004 in Sweden. Matched,
individual human milk and serum samples from 12 primiparous women
in Sweden were analyzed together with composite milk samples (25-90
women/year) from 1996 to 2004.
RESULTS: Eight PFCs were detected in the serum samples, and five
of them were also above the detection limits in the milk samples.
Perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonate (PFHxS)
were detected in all milk samples at mean concentrations of 0.201
ng/mL and 0.085 ng/mL, respectively. Perfluorooctanesulfonamide
(PFOSA), perfluorooctanoic acid (PFOA), and perfluorononanoic
acid (PFNA) were detected less frequently.
DISCUSSION: The total PFC concentration in maternal serum was
32 ng/mL, and the corresponding milk concentration was 0.34 ng/mL.
The PFOS milk level was on average 1% of the corresponding serum
level. There was a strong association between increasing serum
concentration and increasing milk concentration for PFOS (r(2)
= 0.7) and PFHxS (r(2) = 0.8). PFOS and PFHxS levels in composite
milk samples were relatively unchanged between 1996 and 2004,
with a total variation of 20 and 32% coefficient of variation,
CONCLUSION: The calculated total amount
of PFCs transferred by lactation to a breast-fed infant in this
study was approximately 200 ng/day. Lactation is a considerable
source of exposure for infants, and reference concentrations for
hazard assessments are needed.
PMID: 17384769 [PubMed - in process]
Environ Sci Technol. 2007
Serum concentrations of 11
polyfluoroalkyl compounds in the U.S. population: data from the
national health and nutrition examination survey (NHANES).
Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP,
Tully JS, Needham LL.
Division of Laboratory Sciences, National Center
for Environmental Health, Centers for Disease Control and Prevention,
Atlanta, Georgia 30341, USA. Acalafat@cdc.gov
We measured the concentrations of 11 polyfluoroalkyl
compounds (PFCs), including perfluorooctane sulfonic acid (PFOS),
perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid
(PFHxS) in 1562 serum samples collected from a representative
U.S. population 12 years of age and older in the 1999-2000 National
Health and Nutrition Examination Survey. Participants represented
both sexes, three race/ethnicities (non-Hispanic blacks, non-Hispanic
whites, and Mexican-Americans), and four age categories (12-19
years, 20-39 years, 40-59 years, and 60 years and older). PFCs
were extracted from 100 microL of serum using on-line solid-phase
extraction coupled to isotope dilution-high performance liquid
chromatography-tandem mass spectrometry; limits of detection ranged
from 0.05 to 0.2 ng/ mL. PFOS, PFOA, PFHxS, and perfluorooctane
sulfonamide were detected in all samples analyzed; 2-(N-ethyl-perfluorooctane
sulfonamido) acetic acid, 2-(N-methyl-perfluorooctane sulfonamido)
acetic acid, and perfluorononanoic acid were detected in more
than 90% of samples, which suggests prevalent exposures to several
PFCs in the U.S. population. The concentrations
of most PFCs were similar regardless of the participants' ages
but were higher in males than in females. Mexican Americans
had lower concentrations than non-Hispanic blacks and non-Hispanic
whites, whose concentrations were similar. Higher
education was associated with higher concentrations of PFOS and
PFOA. These data will serve as a nationally representative
baseline of the U.S. population's exposure to PFCs to which other
populations can be compared, and will play an important role in
public health by helping set research priorities, ranging from
health effects studies to defining sources and pathways of exposure.
PMID: 17438769 [PubMed - in process]
Environ Int. 2007 Feb 5; [Epub ahead
Perfluorinated chemicals in blood of residents
in Catalonia (Spain) in relation to age and gender: A pilot study.
Ericson I, Gomez M, Nadal M, van Bavel B, Lindstrom G, Domingo
Man-Technology-Environment (MTM) Research Center, Department
of Natural Sciences, Orebro University, SE-701 82 Orebro, Sweden.
Fluorinated organic compounds (FOCs) are a group of chemicals
widely used as surfactants, lubricants, polymers, and fire-fighting
foams. Recent studies have shown the ubiquitous distribution of
FOCs in the environment, wildlife, and humans. We here report
the results of a pilot study conducted to provide preliminary
data on the levels of 13 FOCs in the blood of
48 residents in Catalonia, Spain, in relation to gender
and age (25+/-5 and 55+/-5 years). The highest mean concentration
was obtained for perfluorooctane sulfonate (PFOS, 7.64 ng/ml),
followed by perfluorohexane sulfonate (PFHxS, 3.56 ng/ml) and
perfluorooctanoic acid (PFOA, 1.80 ng/ml). Four other FOCs showed
mean levels between 0.30 and 0.44 ng/ml, whereas those of the
remaining 6 compounds were below the detection limit.
Regarding gender, the blood levels of PFHxS and PFOA were significantly
higher (p<0.05) in men than in women, while differences according
to age were only noted for PFHxS (p<0.05) and perfluorooctane
sulfonamide (PFOSA) (p<0.001), for which the levels were higher
in the younger (25+/-5 years) group of subjects. A significant
correlation between PFOS levels and those of the remaining detected
FOCs (except PFDA) was found. In general terms, the current FOC
concentrations were lower than those found in recent studies concerning
levels of these chemicals in human blood and serum of subjects
from different countries.
PMID: 17289145 [PubMed - as supplied by publisher]
Chemosphere. 2007 May;68(1):105-11.
Epub 2007 Jan 30.
Preliminary evidence of a decline in perfluorooctanesulfonate
(PFOS) and perfluorooctanoate (PFOA) concentrations in American
Red Cross blood donors.
Olsen GW, Mair DC, Reagen WK, Ellefson ME, Ehresman DJ, Butenhoff
JL, Zobel LR.
3M Company, Medical Department,
St. Paul, MN 55144, United States.
The purpose of this pilot study was to determine whether perfluorooctanesulfonate
(PFOS,C(8)F(17)SO(3)(-)) and perfluorooctanoate (PFOA,C(7)F(15)CO(2)(-))
concentrations in American Red Cross blood donors from Minneapolis-St.
Paul, Minnesota have declined after the 2000-2002 phase-out of
perfluorooctanesulfonyl-fluoride (POSF, C(8)F(17)SO(2)F)-based
materials by the primary global manufacturer, 3M Company. Forty
donor plasma samples, categorized by age and sex, were collected
in 2005, and PFOS and PFOA concentrations were compared to 100
(non-paired) donor serum samples collected in 2000 from the same
general population that were analyzed at the time using ion-pair
extraction methods with tetrahydroperfluorooctanesulfonate as
an internal standard. Eleven of the 100 samples originally collected
were reanalyzed with present study methods that involved (13)C-
labeled PFOA spiked into the donor samples, original samples,
control human plasma, and the calibration curve prior to extraction,
and was used as a surrogate to monitor extraction efficiency.
Quantification was performed by high performance liquid chromatography
tandem mass spectrometry methods. Among the 100 serum samples
analyzed for PFOS, the geometric mean was 33.1ngml(-1) (95% CI
29.8-36.7) in 2000 compared to 15.1ngml(-1) (95% CI 13.3-17.1)
in 2005 (p<0.0001) for the 40 donor plasma samples. The
geometric mean concentration for PFOA was 4.5ngml(-1) (95% CI
4.1-5.0) in 2000 compared to 2.2ngml(-1) (95% CI 1.9-2.6) in 2005
(p<0.0001). The decrease was consistent across donors' age
and sex. To confirm these preliminary findings, additional sub-sets
of year 2000 samples will be analyzed, and a much larger biomonitoring
study of other locations is planned.
PMID: 17267015 [PubMed - in process]
J Chromatogr A. 2007
Mar 28; [Epub ahead of print]
Trace analysis of total fluorine
in human blood using combustion ion chromatography for fluorine:
A mass balance approach for the determination of known and unknown
Miyake Y, Yamashita N, So MK, Rostkowski P, Taniyasu
S, Lam PK, Kannan K.
National Institute of Advanced Industrial Science
and Technology (AIST), 16-1 Onogawa, Tsukuba, Ibaraki 305-8569,
The number of perfluorochemicals (PFCs) that have
been found in biological and environmental matrices is increasing
as analytical standards and methods evolve. Perfluorooctanesulfonate
(PFOS) and perfluorooctanoate (PFOA) constitute only a fraction
of the total suite of PFCs found in environmental and biological
matrices. A robust method and approach is needed to evaluate
the mass of fluorinated compounds in biological matrices. In this
study, we developed a method to measure total fluorine (TF) and
organic fluorine (TOF) in human blood matrices using combustion
ion chromatography (CIC). Blood matrices (whole blood, serum,
and plasma) were analyzed in bulk to determine TF. An aliquot
of the blood was also extracted with organic solvents such as
methyl-tert-butyl ether (MTBE) and hexane, and organic and aqueous
extracts were separated, to fractionate organofluorines from inorganic
fluorine. The organic layer was analyzed for TF by CIC, and for
known PFCs by high performance liquid chromatography-tandem mass
spectrometry (HPLC-MS/MS). PFCs measured by HPLC-MS/MS accounted
for >80% of the TF in the organic fraction. The aqueous fraction
contained inorganic fluorine and other non-extractable organofluorines.
However, in the bulk sample, fluoride and non-extractable organofluorines
accounted for >70% of the TF in blood samples from the general
population. In occupationally exposed individuals, known organofluorines
accounted for a major proportion of the TF. These
results suggest the existence of yet uncharacterized fluorine
fraction in human blood. Further studies are needed to
characterize the aqueous fraction that contains inorganic fluorine
and non-extractable forms of fluorine.
PMID: 17416376 [PubMed - as supplied
Toxicol Sci. 2007 Mar
15; [Epub ahead of print]
Exposure to the Immunosuppresant,
Perfluorooctanoic Acid, Enhances the Murine Ige and Airway Hyperreactivity
Response to Ovalbumin: PFOA Enhances OVA Induced Allergic Response.
Fairley K, Purdy R, Kearns S, Anderson S, Meade
National Institute for Occupational Safety and Health,
Morgantown, WV 26505, B.J. Meade's email: firstname.lastname@example.org.
These studies were conducted to investigate the
role of dermal exposure to Perfluorooctanoic acid (PFOA), a known
immunosuppressant, on the hypersensitivity response to ovalbumin
in a murine model of asthma. PFOA has had widespread use as a
carpet and fabric protectant. BALB/c mice were exposed dermally,
on the dorsal surface of each ear, to concentrations of PFOA ranging
from 0.01-1.5% (applied dose 0.25-50 mg/kg) for 4 days. In hypersensitivity
studies, mice were also intraperitoneally injected with 7.5 mug
ovalbumin and 2 mg alum on days 1 and 10 and in some studies,
challenged with 250 mug ovalbumin by pharyngeal aspiration on
days 17 and 26. Following exposure to PFOA, an increase in liver
weights and a decrease in thymus and spleen weights and cellularities
were observed. Similar immunomodulatory trends were demonstrated
in mice co-administered PFOA and ovalbumin (OVA). Compared to
the OVA alone exposed animals, an increase in total IgE was demonstrated
when mice were co-exposed to OVA and concentrations of PFOA ranging
from 0.75-1.5%, while the OVA-specific IgE response peaked with
0.75% PFOA co-exposure (p </= 0.05). OVA-specific airway hyperreactivity
was increased in the 1.0% PFOA co-exposed group (p </= 0.05),
with an increased pleiotropic cell response characterized by eosinophilia
and mucin production, in animals co-exposed to concentrations
of PFOA up to 1.0%, as compared to the ovalbumin alone exposed
animals. In a murine model, PFOA was demonstrated
to be immunotoxic following dermal exposure, with an enhancement
of the hypersensitivity response to ovalbumin, suggesting that
PFOA exposure may augment the IgE response to environmental allergens.
PMID: 17369199 [PubMed - as supplied
Toxicol Sci. 2007 Jan;95(1):108-17.
Epub 2006 Oct 17.
Activation of mouse and human peroxisome
proliferator-activated receptors (alpha, beta/delta, gamma) by
perfluorooctanoic acid and perfluorooctane sulfonate.
Takacs ML, Abbott BD.
Reproductive Toxicology Division, National Health and Environmental
Effects Research Laboratory, Office of Research and Development,
US Environmental Protection Agency,
Research Triangle Park, North Carolina 27711, USA.
This study evaluates the potential for perfluorooctanoic acid
(PFOA) and perfluorooctane sulfonate (PFOS) to activate peroxisome
proliferator-activated receptors (PPARs), using a transient transfection
cell assay. Cos-1 cells were cultured in Dulbecco's Minimal Essential
Medium (DMEM) with fetal bovine serum in 96-well plates and transfected
with mouse or human PPARalpha, beta/delta, or gamma reporter plasmids.
Transfected cells were exposed to PFOA (0.5-100 microM), PFOS
(1-250 microM), positive controls (i.e., known agonists and antagonists),
and negative controls (i.e., DMEM, 0.1% water, and 0.1% dimethyl
sulfoxide). Following treatment for 24 h, activity was measured
using the Luciferase reporter assay. In this assay, PFOA had more
transactivity than PFOS with both the mouse and human PPAR isoforms.
PFOA significantly increased mouse and human PPARalpha and mouse
PPARbeta/delta activity relative to vehicle. PFOS significantly
increased activation of mouse PPARalpha and PPARbeta/delta isoforms.
No significant activation of mouse or human PPARgamma was observed
with PFOA or PFOS. The PPARalpha antagonist, MK-886, significantly
suppressed PFOA and PFOS activity of mouse and human PPARalpha.
The PPARgamma antagonist, GW9662, significantly suppressed PFOA
activity on the human isoform. In conclusion, this study characterized
the dose response and differential activation of mouse and human
PPARalpha, beta/delta, gamma by PFOA and PFOS. While this model
allows opportunities to compare potential activation by perfluoroalkyl
acids, it only evaluates the interaction and activation of the
PPAR reporter constructs and is not necessarily predictive of
a toxicological response in vivo.
PMID: 17047030 [PubMed - indexed for MEDLINE]
Environ Sci Technol. 2007
Spatial distribution of perfluoroalkyl
contaminants in lake trout from the Great Lakes.
Furdui VI, Stock NL, Ellis DA, Butt CM, Whittle
DM, Crozier PW, Reiner EJ, Muir DC, Mabury SA
Department of Chemistry, University of Toronto,
80 St. George Street, Toronto, Ontario, M5S 3H6.
Individual whole body homogenates of 4 year old
lake trout (Salvelinus namaycush) samples collected in 2001 from
each of the Great Lakes were extracted using a novel fluorophilicity
cleanup step and analyzed for perfluoroalkyl compounds (PFCs).
Standard addition and internal standardization were used for quantification.
Results were reported (+/- SE) for perfluorinated carboxylates
(PFCAs), perfluorinated sulfonates (PFSAs), and unsaturated fluorotelomer
carboxylates (8:2 and 10:2 FTUCA). The lowest average concentration
of sigmaPFC was found in samples from Lake Superior (13+/-1 ng
g(-1)), while the highest average concentration
was found in samples from Lake Erie (152+/-14 ng g(-1)).
Samples from Lake Ontario (60+/-5 ng g(-1)) and Lake Huron (58
+/-10 ng g(-1)) showed similar average sigmaPFC concentrations,
although the perfluorinated sulfonate/carboxylate ratios were
different. The major perfluoroalkyl contaminant
observed was perfluorooctane sulfonate (PFOS) with the highest
concentration found in samples from Lake Erie (121+/-14
ng g(-1)), followed by samples from Lake Ontario (46+/-5 ng g(-1)),
Lake Huron (39 +/-10 ng g(-1)), Lake Michigan (16+/-3 ng g(-1)),
and Lake Superior (5+/-1 ng g(-1)). Perfluorodecane
sulfonate (PFDS) was detected in 89% of the samples, with the
highest concentration in Lake Erie samples (9.8+/-1.6 ng g(-1)),
and lowest concentration in samples from Lake Superior (0.7 +/-
0.1 ng g(-1)). Statistically significant
correlations were observed between PFOS and PFDS concentrations,
and PFOS concentration and body weight, respectively. The
PFCAs were detected in all samples, with the highest total average
concentration in samples from Lake Erie (19 ng g(-1)), followed
by samples from Lake Huron (16 ng g(-1)), Lake Ontario (10 ng
g(-1)), Lake Michigan (9 ng g(-1)) and Lake Superior (7 ng g(-1)).
The compounds with significant contributions to the sigmaPFCA
concentrations were PFOA and C9-C13-PFCAs. The 8:2 FTUCA
was detected at concentrations ranging between 0.1 and 0.2 ng
g-1, with the highest level in samples showing also elevated concentrations
of PFOA (4.4 ng g(-1) for Lake Michigan vs 1.5 ng g(-1) for all
other samples). The 10:2 FTUCA was detected only in 9% of all
samples (nd, 45 pg g(-1)). For those PFCs where we determined
lake water concentrations, the highest log BAFs were calculated
for PFOS (4.1), PFDA (3.9), and PFOSA (3.8).
PMID: 17396640 [PubMed - in process]
Anal Bioanal Chem. 2007 Feb;387(4):1469-78.
Epub 2007 Jan 3.
Polar herbicides, pharmaceutical products,
perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and
nonylphenol and its carboxylates and ethoxylates in surface and
tap waters around Lake Maggiore in Northern Italy.
Loos R, Wollgast J, Huber T, Hanke G.
European Commission - DG Joint Research Centre, Institute for
Environment and Sustainability, Via Enrico Fermi, TP 290, 21020
Ispra, Italy. Robert.Loos@jrc.it
A survey of contamination of surface and drinking waters around
Lake Maggiore in Northern Italy with polar anthropogenic environmental
pollutants has been conducted. The target analytes were polar
herbicides, pharmaceuticals (including antibiotics), steroid estrogens,
perfluorooctanesulfonate (PFOS), perfluoroalkyl carboxylates (including
perfluorooctanoate PFOA), nonylphenol and its carboxylates and
ethoxylates (NPEO surfactants), and triclosan, a bactericide used
in personal-care products. Analysis of water samples was performed
by solid-phase extraction (SPE) then liquid chromatography-triple-quadrupole
(tandem) mass spectrometry (LC-MS-MS). By extraction of 1-L water
samples and concentration of the extract to 100 microL, method
detection limits (MDLs) as low as 0.05-0.1 ng L(-1) were achieved
for most compounds. Lake-water samples from seven different locations
in the Southern part of Lake Maggiore and eleven samples from
different tributary rivers and creeks were investigated. Rain
water was also analyzed to investigate atmospheric input of the
contaminants. Compounds regularly detected at very low
concentrations in the lake water included: caffeine (max. concentration
124 ng L(-1)), the herbicides terbutylazine (7 ng L(-1)), atrazine
(5 ng L(-1)), simazine (16 ng L(-1)), diuron (11 ng L(-1)), and
atrazine-desethyl (11 ng L(-1)), the pharmaceuticals carbamazepine
(9 ng L(-1)), sulfamethoxazole (10 ng L(-1)), gemfibrozil (1.7
ng L(-1)), and benzafibrate (1.2 ng L(-1)), the surfactant metabolite
nonylphenol (15 ng L(-1)), its carboxylates (NPE(1)C 120 ng L(-1),
NPE(2)C 7 ng L(-1), NPE(3)C 15 ng L(-1)) and ethoxylates (NPE(
n )Os, n = 3-17; 300 ng L(-1)), perfluorinated surfactants (PFOS
9 ng L(-1), PFOA 3 ng L(-1)), and estrone (0.4 ng L(-1)).
Levels of these compounds in drinking water produced from Lake
Maggiore were almost identical with those found in the lake itself,
revealing the poor performance of sand filtration and chlorination
applied by the local waterworks.
PMID: 17200857 [PubMed - in process]
J Toxicol Environ Health A. 2007
A methodology for estimating human exposure
to perfluorooctanoic acid (PFOA): a retrospective exposure assessment
of a community (1951-2003)
Paustenbach DJ, Panko JM, Scott PK, Unice KM.
ChemRisk, Inc., San Francisco, California
94105, USA. email@example.com
Perfluorooctanoic acid (PFOA) is a persistent chemical that was
recently shown to be widely distributed in the ambient environment.
Because of concerns about the possible adverse health effects
on persons exposed to PFOA, a retrospective exposure assessment
was conducted for a population of about 50,000 persons who reside
near one of the facilities where this chemical was used. No similar
study of any chemical with the properties of PFOA had ever been
performed; thus, several novel methods were developed and applied
in this analysis. Historical records of the emissions from the
facility were the basis for the estimates of the potential intake
of (PFOA) by residents over the past 53 yr. Various well-accepted
environmental models were dynamically combined in order to estimate
the concentrations in all relevant environmental media including
ambient air, surface soil, drinking water, and homegrown vegetables.
Following considerable analyses, particulate deposition from facility
air emissions to soil and the subsequent transfer of the chemical
through the soil was determined to be the most likely source of
PFOA that was detected in groundwater. The highest off-site environmental
concentrations were predicted to occur about 1 mile away. For
this approximately square mile area, during the time period 1951-2003,
the model-estimated average air concentration was 0.2 microg/m3,
the estimated surface soil concentration was 11 microg/kg, and
the estimated drinking water concentration was 4 microg/L. Similar
data were generated for 20 additional geographical areas around
the facility. Comparison of measured PFOA concentrations in groundwater
in the various water districts indicated that the models appeared
to overpredict recent groundwater concentrations by a factor of
3 to 5. The predicted historical lifetime and average daily estimates
of PFOA intake by persons who lived within 5 miles of the plant
over the past 50 yr were about 10,000-fold less than the intake
of the chemical not considered as a health risk by an independent
panel of scientists who recently studied PFOA.
PMID: 17162497 [PubMed - indexed for MEDLINE]
Int Arch Occup Environ Health. 2007
Feb;80(4):313-9. Epub 2006 Aug 17.
Occurrence of perfluorinated substances
in an adult German population in southern Bavaria.
Fromme H, Midasch O, Twardella D, Angerer J, Boehmer S, Liebl
Bavarian Health and Food Safety Authority, Department of Environmental
Health, Veterinaerstrasse 2, 85764, Oberschleissheim, Germany,
OBJECTIVES: Perfluorinated compounds (PFCs) are a large group
of chemicals produced for several decades and widely used for
many industrial and consumer applications. Because of their global
occurrence in different environmental media, their persistence,
and their potential to bioaccumulate in organisms they are of
toxicological and public concern.
METHODS: In the present study, the internal exposure to perfluorooctane
sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in 356 human
plasma samples collected from an adult population in Germany in
2005 is quantified.
RESULTS: We were able to detect the target analytes in all plasma
samples and observed a significant correlation between the PFOS
and PFOA concentrations. In female participants, the levels of
PFOS and PFOA ranged between 2.5-30.7 (median: 10.9 mug/l) and
1.5-16.2 mug/l (median: 4.8 mug/l), respectively. In males we
observed concentrations from 2.1 to 55.0 mug/l (median: 13.7 mug/l)
for PFOS and from 0.5 to 19.1 mug/l (median: 5.7 mug/l) for PFOA.
A significant correlation between both PFOS and PFOA concentrations
and gender was observed. We also found increased levels of the
PFCs with increasing age of the participants, but this association
reached statistical significance among females only.
CONCLUSIONS: Our data agree well with results of other recent
studies in Europe and suggest that the current
exposure of the adult German population is lower than the exposure
of the US and Canadian population. The sources of human
exposure are currently not well understood. Toxicological implications
are restricted to animal studies and occupational investigations
not adequate for quantitative risk assessment in humans. Overall,
more scientific research is necessary to characterize the body
burden of PFCs (especially for relevant subsets of the population)
and the main sources and routes, which are responsible for human
exposure and possible health implications of these compounds.
PMID: 16915390 [PubMed - in process]
Chemosphere. 2007 Mar 16; [Epub
ahead of print]
Perfluorinated compounds in the Pearl
River and Yangtze River of China.
So MK, Miyake Y, Yeung WY, Ho YM, Taniyasu S, Rostkowski P,
Yamashita N, Zhou BS, Shi XJ, Wang JX, Giesy JP, Yu H, Lam PK.
Centre for Coastal Pollution and Conservation, Department of
Biology and Chemistry, City University of Hong Kong, Tat Chee
Avenue, Kowloon, Hong Kong SAR, People's Republic of China; National
Institute of Advanced Industrial Science and Technology (AIST),
16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan.
A total of 14 perfluorinated compounds (PFCs) were quantified
in river water samples collected from tributaries of the Pearl
River (Guangzhou Province, south China) and the Yangtze River
(central China). Among the PFCs analyzed,
perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA)
were the two compounds with the highest concentrations. PFOS concentrations
ranged from 0.90 to 99ng/l and <0.01-14ng/l in samples from
the Pearl River and Yangtze River, respectively; whereas those
for PFOA ranged from 0.85 to 13ng/l and 2.0-260ng/l. Lower
concentrations were measured for perfluorobutane sulfonate (PFBS),
perfluorohexane sulfonate (PFHxS), perfluorooctanesulfoamide (PFOSA),
perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA),
perfluorononaoic acid (PFNA), perfluorodecanoic acid (PFDA), and
perfluoroundecanoic acid (PFUnDA). Concentrations of several perfluorocarboxylic
acids, including perfluorododecanoic acid (PFDoDA), perfluorotetradecanoic
acid (PFTeDA), perfluorohexadecanoic acid (PFHxDA) and perfluorooctadecanoic
acid (PFOcDA) were lower than the limits of quantification in
all the samples analyzed. The highest concentrations
of most PFCs were observed in water samples from the Yangtze River
near Shanghai, the major industrial and financial centre in China.
In addition, sampling locations in the lower reaches of the Yangtze
River with a reduced flow rate might serve as a final sink for
contaminants from the upstream river runoffs. Generally,
PFOS was the dominant PFC found in samples from the Pearl River,
while PFOA was the predominant PFC in water from the Yangtze River.
Specifically, a considerable amount of PFBS (22.9-26.1% of total
PFC analyzed) was measured in water collected near Nanjing, which
indicates the presence of potential sources of PFBS in this part
of China. Completely different PFC composition profiles were observed
for samples from the Pearl River and the Yangtze River. This indicates
the presence of dissimilar sources in these two regions.
PMID: 17368725 [PubMed - as supplied by publisher]
Aquat Toxicol. 2007
May 1;82(2):135-43. Epub 2007 Feb 15.
Induction of oxidative stress
and apoptosis by PFOS and PFOA in primary cultured hepatocytes
of freshwater tilapia (Oreochromis niloticus).
Liu C, Yu K, Shi X, Wang J, Lam PK, Wu RS, Zhou
State Key Laboratory of Freshwater Ecology and Biotechnology,
Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan
430072, PR China; Graduate School of the Chinese Academy of Sciences,
Beijing 100039, PR China.
Perfluorinated organic compounds (PFOCs) are emerging
persistent organic pollutants (POPs) widely present in the environment,
wildlife and human. We studied the cellular toxicology of perfluorooctane
sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on oxidative
stress and induction of apoptosis in primary cultured hepatocytes
of freshwater tilapia (Oreochromis niloticus). Cultured hepatocytes
were exposed to PFOS or PFOA (0, 1, 5, 15 and 30mgL(-1)) for 24h,
and a dose-dependent decrease in cell viability was determined
using trypan blue exclusion method. Significant induction of reactive
oxygen species (ROS) accompanied by increases in activities of
superoxide dismutase (SOD), catalase (CAT) and glutathione reductase
(GR) were found, while activities of glutathione peroxidase (GPx)
and glutathione-S-transferase (GST) were decreased. Glutathione
(GSH) content was reduced following treatment of PFOA and PFOS.
A dose-dependent increase in the lipid peroxidation (LPO) level
(measured as maleic dialdehyde, MDA) was observed only in the
PFOA exposure groups, whereas LPO remained unchanged in the PFOS
exposure groups. Furthermore, a significant activation of caspase-3,
-8, -9 activities was evident in both PFOS and PFOA exposure groups.
Typical DNA fragmentation (DNA laddering) was further characterized
by agarose gel electrophoresis. The overall
results demonstrated that PFOS and PFOA are able to produce oxidative
stress and induce apoptosis with involvement of caspases in primary
cultured tilapia hepatocytes.
PMID: 17374408 [PubMed - in process]
Biochim Biophys Acta. 2007 May;1768(5):1299-308.
Epub 2007 Feb 9.
Effect of potassium perfluorooctanesulfonate,
perfluorooctanoate and octanesulfonate on the phase transition
of dipalmitoylphosphatidylcholine (DPPC) bilayers.
Xie W, Kania-Korwel I, Bummer PM, Lehmler HJ.
The University of Iowa, Department of Occupational and Environmental
Health, 100 Oakdale Campus #221 IREH, Iowa City, IA 52242-5000,
Perfluorooctanesulfonic acid (PFOS) is a persistent environmental
pollutant that may cause adverse effects by inhibiting pulmonary
surfactant. To gain further insights in this potential mechanism
of toxicity, we investigated the interaction of PFOS potassium
salt with dipalmitoylphosphatidylcholine (DPPC) - the major component
of pulmonary surfactant - using steady-state fluorescence anisotropy
spectroscopy and DSC (differential scanning calorimetry). In addition,
we investigated the interactions of two structurally related compounds,
perfluorooctanoic acid (PFOA) and octanesulfonic acid (OS) potassium
salt, with DPPC. In the fluorescence experiments a linear depression
of the main phase transition temperature of DPPC (T(m)) and an
increased peak width was observed with increasing concentration
of all three compounds, both using 1,6-diphenyl-1,3,5-hexatriene
(DPH) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene
p-toluenesulfonate (TMA-DPH) as fluorescent probes. PFOS caused
an effect on T(m) and peak width at much lower concentrations
because of its increased tendency to partition onto DPPC bilayers,
i.e., the partition coefficients decrease in the K(PFOS)>K(PFOA)>>K(OS).
Similar to the fluorescence anisotropy measurements, all three
compounds caused a linear depression in the onset of the main
phase transition temperature and a significant peak broadening
in the DSC experiments, with PFOS having the most pronounced effect
of the peak width. The effect of PFOS and other fluorinated surfactants
on DPPC in both mono- and bilayers may be one mechanism by which
these compounds cause adverse biological effects.
PMID: 17349969 [PubMed - in process]
Biochim Biophys Acta. 2007 Apr;1771(4):506-13.
Epub 2007 Jan 9.
Defect in fatty acid esterification of
dolichol in Niemann-Pick type C1 mouse livers in vivo.
Turunen M, Schedin-Weiss S.
Department of Biochemistry and Biophysics, Stockholm University,
Fatty acid esterification of dolichol and cholesterol in Niemann-Pick
type C1 mouse (Balb/c NIH npc1(-/-)) livers was investigated in
response to treatment with peroxisomal proliferators. These inducers
have hypolipidemic properties and influence the mevalonate pathway
and the intracellular transport of the final products of this
biosynthetic route. Such inducers are consequently interesting
to use in a disease model with defective intracellular transport
of lipids. In wild-type mice, the levels of dolichol and cholesterol
found as free alcohols were not changed to any great extent upon
treatment with the peroxisomal inducers dehydroepiandrosterone,
clofibrate and diethylhexylphtalate. In contrast, the amounts
of dolichyl esters increased whereas cholesteryl esters decreased
by the same treatments. The rate of enzymatic esterification of
dolichol in isolated microsomes was accordingly elevated after
5- to 7-day treatments with the efficient peroxisomal
proliferators DEHP and PFOA, while the corresponding esterification
of cholesterol was decreased. Upon peroxisomal induction in npc1(-/-)
mice, the enzymatic dolichol esterification in vitro increased
whereas the low concentration of dolichyl esters remained unchanged.
The results thus demonstrate that the induction of fatty acid
esterification of dolichol in vivo is impaired in npc1(-/-) mouse
liver. It is therefore proposed that the intracellular lipid transport
defect in npc1(-/-) mouse liver disables either dolichol and/or
the fatty acid from reaching the site of esterification in vivo.
This proposal was strengthened by the finding that the amount
of dolichol was decreased in an isolated Golgi fraction from npc1(-/-)
PMID: 17292665 [PubMed - in process]
J Chromatogr A. 2007 Mar 2;1143(1-2):98-104.
Epub 2006 Dec 23.
Determination of trace levels of total
fluorine in water using combustion ion chromatography for fluorine:
a mass balance approach to determine individual perfluorinated
chemicals in water.
Miyake Y, Yamashita N, Rostkowski P, So MK, Taniyasu S, Lam
PK, Kannan K.
National Institute of Advanced Industrial Science and Technology,
16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan.
Perfluorinated compounds (PFCs) such as perfluorooctanesulfonate
(PFOS) and perfluorooctanoate (PFOA) have received worldwide attention
because of their environmental persistence and widespread distribution.
Because of the lack of robust analytical methods and standards
to detect all of the PFCs, and their precursors and metabolic
intermediates, a mass balance approach involving the determination
of total fluorine (TF), followed by fractionation of samples to
separately determine inorganic and organic fluorine, is needed.
In this study, we have developed a method to determine low microg/L
levels of total fluorine (TF) in seawater samples. Further, seawater
samples were fractionated into organic and inorganic fractions
by extraction with organic solvents, which were then analyzed
for TF, extractable organic fluorine (EOF) and inorganic fluorine
(IF; i.e., fluoride). Concentrations of known perfluorinated compounds
(PFCs) including PFOS and PFOA were also determined in water samples
by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to
enable calculation of the fraction of fluorine that is contributed
by PFCs to TF. A major proportion of fluorine in seawater was
in the form of fluoride (>90% in locations not affected by
direct discharges). Nevertheless, within
the organofluorine fraction, a major percentage (60-90%) of fluorine
still remains unknown in water samples, suggesting the occurrence
of other fluorinated acids in addition to known perfluorinated
acids. Further studies are needed to identify and quantify the
unidentified organofluorines in seawater. Mass balance analysis
of total organic fluorine (TOF) and EOF is important, if we are
to understand transport and fate of fluorinated compounds in the
environment, and if we are to identify the sources of unidentified
PMID: 17229428 [PubMed - in process]
Int J Hyg Environ Health. 2007
Mar 16; [Epub ahead of print]
The Environmental Specimen
Bank for Human Tissues as part of the German Environmental Specimen
Wiesmuller GA, Eckard R, Dobler L, Gunsel A, Oganowski
M, Schroter-Kermani C, Schluter C, Gies A, Kemper FH.
Environmental Specimen Bank for Human Tissues, University
Hospital Munster, Domagkstrasse 11, 48149 Munster, Germany.
The German Environmental Specimen Bank for Human
Tissues (ESBHum) as part of the German Environmental Specimen
Bank (ESB) focuses on documenting and assessing trends of human
exposure via real-time monitoring of body burden and long-term
storage of samples under stable deep freezing conditions (-150
degrees C) for later retrospective analyses. Real-time monitoring
is performed after completing sampling processes of one year and
covers actually 20 inorganic and 5 organic substances. While concentrations
of several substances, e.g., arsenic, cadmium and mercury, are
remained unchanged over time, other substances, e.g., lead and
pentachlorophenol (PCP), show a clearly perceptible decrease.
Substances which are not routinely analyzed in real-time monitoring
are retrospectively measured by indication in the stored human
specimens. Indications of retrospective monitoring are availability
of valid analytical methods, e.g., in case of PCDF and PCDD, or
assessment of concentration trends of substances with actual interest
of toxicology and/or environmental medicine, e.g., polybrominated
diphenyl ethers (PBDE), perfluorooctane
sulfonate (PFOS) and perfluorooctanoic acid (PFOA). While
over time the body burden of dioxins as well as PFOS and PFOA
decreased, the PBDE concentrations in human blood increase. The
observed decrease of blood lead and PCP levels over time is a
consequence of legal prohibition and restriction. The time-dependent
concentrations of the aforementioned substances agree with results
of other national studies. So it can be concluded that the German
ESBHum is an important instrument for health-related environmental
observation and protection in Germany.
PMID: 17369091 [PubMed - as supplied