http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11879818&dopt=Abstract
2002
Chem Biol Interact Mar 20;139(3):301-16
Sex
hormone-regulated renal transport of perfluorooctanoic acid.
Kudo N, Katakura M, Sato Y, Kawashima
Y.
Faculty of Pharmaceutical Sciences, Josai University, Kayakidai
1-1, Sakado, Saitama 350-0295, Japan. naokudo@josai.ac.jp
The biological half-life (t1/2) of perfluorooctanoic
acid (PFOA) in male rats is 70 times longer than that in female
rats. The difference is mainly due to the difference
in renal clearance (CL(R)), which was significantly reduced
by probenecid, suggesting that PFOA is excreted by organic anion
transporter(s). Castration of male rats
caused a 14-fold increase in the CL(R) of PFOA, which made it
comparable with that of female rats. The elevated PFOA
CL(R) in castrated males was reduced by treating them with testosterone.
Treatment of male rats with estradiol increased the CL(R) of
PFOA. In female rats, ovariectomy caused
a significant increase in CL(R) of PFOA, which was reduced
by estradiol treatment. Treatments of female rats with testosterone
reduced the CL(R) of PFOA as observed in castrated male rats.
To identify the transporter molecules that are responsible for
PFOA transport in rat kidney, renal mRNA levels of organic anion
transporter 1 (OAT1), OAT2, OAT3, organic anion transporting
polypeptide 1 (oatp1), oatp2 and kidney specific organic anion
transporter (OAT-K) were determined in male and female rats
under various hormonal states and compared with the CL(R) of
PFOA. The level of OAT2 mRNA in male rats was only 13% that
in female rats. Castration or estradiol treatment increased
the level of OAT2 mRNA whereas treatment of castrated male rats
with testosterone reduced it. In contrast to OAT2, mRNA levels
of both oatp1 and OAT-K were significantly higher in male rats
compared with female rats. Castration or estradiol treatment
caused a reduction in the levels of mRNA of oatp1 and OAT-K
in male rats. Ovariectomy of female rats significantly increased
the level of OAT3 mRNA. Multiple regression analysis suggests
that the change in the CL(R) of PFOA is, at least in part, due
to altered expression of OAT2 and OAT3.
PMID: 11879818 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12363300&dopt=Abstract
2002
Chemosphere Oct;49(3):225-31
Concentrations
of perfluorinated acids in livers of birds from Japan and Korea.
Kannan K, Choi JW, Iseki N, Senthilkumar K, Kim DH, Giesy JP.
National Food Safety and Toxicology Center, Department of Zoology,
Institute for Environmental Toxicology, Michigan State University,
East Lansing 48824, USA. kuruntha@msu.edu
Livers of birds collected from Japan and Korea (n = 83) were
analyzed to determine the concentrations of perfluorooctanesulfonate
(PFOS), perfluorooctanesulfonamide (FOSA), perfluorooctanoic
acid (PFOA) and perfluorohexanesulfonate (PFHS). PFOS was found
in the livers of 95% of the birds analyzed at concentrations
greater than the limit of quantitation (LOQ) of 10 ng/g, wet
weight. The greatest concentration of
PFOS of 650 ng/g, wet weight, was found in the liver of a common
cormorant from the Sagami River in Kanagawa Prefecture.
Concentrations of PFOS in bird livers from Japan and Korea were
within the ranges of values reported for those from the United
States and certain European countries. PFOA and PFHS were found
in 5-10% of the samples analyzed. The greatest concentrations
of PFOA and PFHS in bird livers were 21 and 34 ng/g, wet weight,
respectively. FOSA was found in all the samples (n = 10) of
cormorants collected from the Sagami River in Japan.
The greatest concentration of FOSA in cormorant liver was 215
ng/g, wet weight. There was no significant correlation
between the concentrations of PFOS and FOSA in cormorants collected
from the Sagami River. These results suggested that the distribution
of FOSA is localized. No age- or gender-specific differences
in fluorochemical concentrations could be discerned in birds.
PMID: 12363300 [PubMed - in process]
See
full report at
http://toxsci.oupjournals.org/cgi/reprint/69/1/244.pdf
2002
Toxicol Sci Sep;69(1):244-57
Toxicity
of ammonium perfluorooctanoate in male cynomolgus monkeys after
oral dosing for 6 months.
Butenhoff J, Costa G, Elcombe C,
Farrar D, Hansen K, Iwai H, Jung R, Kennedy G Jr, Lieder P,
Olsen G, Thomford P.
3M,
St. Paul, Minnesota 55144. University of Verona, Verona 37134,
Italy. University of Dundee, Dundee DD1 95Y, Scotland. Ineos
Chlor, Runcorn, Cheshire WA7 4JE, United Kingdom. jlbutenhoff@mmm.com
Ammonium perfluorooctanoate (APFO)
is a processing aid in the production of fluoropolymers that
has been shown to have a long half-life
in human blood. To understand the potential toxicological
response of primates, groups of male cynomolgus monkeys were
given daily po (capsule) doses of either 0, 3, 10, or 30 (reduced
to 20) mg/kg/day for 26 weeks. Two monkeys from each of the
control and 10 mg/kg/day dose groups were observed for 90 days
after the last dose. Clinical observations, clinical chemistry,
determination of key hormones, gross and microscopic pathology,
cell proliferation, peroxisomal proliferation, bile-acid determination,
and serum and liver perfluorooctanoate (PFOA) concentrations
were monitored. Toxicity, including weight
loss and reduced food consumption, was noted early in
the study at the 30 mg/kg/day dose; therefore, the dose was
reduced to 20 mg/kg/day. The same signs of toxicity developed
in 3 monkeys at 20 mg/kg/day, after which treatment of these
monkeys was discontinued. One 30/20 mg/kg/day monkey developed
the signs of toxicity noted above and a possible dosing injury,
and this monkey was sacrificed in extremis on Day 29. A 3 mg/kg/day
dose-group monkey was sacrificed in extremis on Day 137 for
reasons not clearly related to APFO treatment. Dose-dependent
increases in liver weight as a result of mitochondrial proliferation
occurred in all APFO-treated groups. Histopathologic evidence
of liver injury was not observed at either 3 or 10 mg/kg/day.
Evidence of liver damage was seen
in the monkey sacrificed in moribund condition at the highest
dose. Body weights were decreased at 30/20 mg/kg. PFOA concentrations
in serum and liver were highly variable, were not linearly proportional
to dose, and cleared to background levels within 90 days after
the last dose. A no observable effect level was not established
in this study, and the low dose of 3 mg/kg/day was considered
the lowest observable effect level based on increased liver
weight and uncertainty as to the etiology leading to the moribund
sacrifice of one low-dose monkey on Day 137. Other than those
noted above, there were no APFO-related macroscopic or microscopic
changes, changes in clinical chemistry, hormones, or urinalysis,
or hematological effects. In particular, effects that have been
associated with the development of pancreatic and testicular
toxicity in rats were not observed in this study.
PMID: 12215680 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12188342&dopt=Abstract
2002
Environ Sci Technol Aug 1;36(15):3210-6
Perfluorooctanesulfonate
and related fluorinated hydrocarbons in
marine mammals, fishes, and birds from coasts of the Baltic
and the Mediterranean Seas.
Kannan K, Corsolini S, Falandysz J, Oehme
G, Focardi S, Giesy JP.
National Food Safety and Toxicology Center, Department of Zoology,
Institute for Environmental Toxicology, Michigan State University,
East Lansing 48824, USA. kuruntha@msu.edu
Perfluorooctanesulfonate (PFOS; C8F17SO3-), perfluorooctanesulfonamide
(FOSA; C8F17SO2NH2), perfluorohexanesulfonate (PFHxS; C6F13SO3-),
and perfluorooctanoate (PFOA; C7F15CO2-) were detected in 175
samples of liver and blood of bluefin tuna (Thunnus thynnus),
swordfish (Xiphias gladius), common cormorants (Phalacrocorax
carbo), bottlenose dolphins (Tursiops truncatus), striped dolphins
(Stenella coeruleoalba), common dolphins (Delphinus delphi),
fin whales (Balenoptera physalus), and long-finned pilot whales
(Globicephala melas) from the Italian coast of the Mediterranean
Sea and in livers of ringed seals (Phoca hispida), gray seals
(Halichoerus grypus), white-tailed sea eagles (Haliaeetus albicilla),
and Atlantic salmon (Salmo salar) from coastal areas of the
Baltic Sea. PFOS was detected in all of
the wildlife species analyzed. Concentrations of PFOS
in blood decreased in order of bottlenose dolphins > bluefin
tuna > swordfish. Mean PFOS concentrations
(61 ng/ g, wet wt) in cormorant livers collected from
Sardinia Island in the Mediterranean Sea were less than the
concentrations of PFOA (95 ng/g, wetwt).
PFOS concentrations in cormorant livers were significantly correlated
with those of PFOA. FOSA was found in 14 of 19 livers or blood
samples of marine mammals from the Mediterranean Sea. The
highest concentration of 878 ng FOSA/g, wet wt, was found in
the liver of a common dolphin. Livers
of ringed and gray seals from the Bothnian Bay in the Baltic
Sea contained PFOS concentrations ranging from 130 to 1,100
ng/g, wet wt. No relationships between PFOS concentrations
and ages of ringed or gray seals were observed. Concentrations
of PFOS in livers of seals were 5.5-fold greater than those
in corresponding blood. A significant positive correlation
existed between the PFOS concentrations in liver and blood,
which indicates that blood can be used for nonlethal monitoring
of PFOS. Trend analysis of PFOS concentrations in livers of
white-tailed sea eagles collected from eastern Germany and Poland
since 1979 indicated an increase in concentrations
during the 1990s. Livers of Atlantic salmons did not
contain quantifiable concentrations of any of the fluorochemicals
monitored. PFOS is a widespread contaminant in wildlife from
the Baltic and the Mediterranean Seas, while FOSA and PFOA were
detected only in certain locations indicating their sporadic
spatial distribution.
PMID: 12188342 [PubMed - in process]
From
TOXNET
2002
- Source: Crisp Data Base National Institutes of Health
Epidemiologic
Evaluation of Perfluorooctyl Compounds
RAYMER
JH
JRAYMER@RTI.ORG,
RESEARCH TRIANGLE INSTITUTE, 3040 CORNWALLIS RD PO BOX 12194,
RESEARCH TRIANGLE PARK, NC 27709
DESCRIPTION: This
epidemiologic study will evaluate the potential endocrine and
reproductive ramifications in human males of exposures to environmental
concentrations of perfluourinated chemicals, including perfluourooctylsulfonate
(PFOS) and perfluoroocatanoate (PFOA). Products containing these
chemicals were recently withdrawn from the market by a major
manufacturer amid concerns of persistence, toxicity, and widespread
population exposures to these chemicals. The proposed study
will focus on the semen quality and endocrine status of a potentially
susceptible subpopulation, i.e., men of couples who present
at a fertility clinic. It will use a case-control design in
that the study population will include a high prevalence of
men experiencing reproductive problems ("cases") as well as
men with a normal fertility status ("controls"). By using a
case-control design (the approach of choice for investigating
rare outcomes), the study will be able to efficiently detect
any important exposure-related reproductive problems. If exposure
levels are associated with male reproductive problems, the study
participants are expected to represent a range of exposure to
PFOA and PFOS, which will be measured in samples of blood and
semen; concentrations in these biological media will reflect
the multi-route exposures to these chemicals experienced by
virtually all people in our society. Semen quality will be assessed
using both routine measures and a test designed to more accurately
and reproducibly assess normal, motile, and fertile sperm. Measurements
of Follicle Stimulating Hormone, Luteinizing Hormone, Prolactin,
Estradiol and free and total Testosterone will reflect the hormonal
status of the males and will provide evidence of perturbed endocrine
function. If the exposure effect is limited to a sensitive subset
of the general population, our study is more likely to detect
an association compared to studies that sample on PFOA/PFOS
exposure status in an occupational setting. Keywords: blood
test endocrine gland /system endocrine disorder hormone regulation
/control mechanism semen fluorohydrocarbon human subject exotoxin
questionnaire statistics /biometry epidemiology male reproductive
system male reproductive system disorder male environmental
toxicology toxin metabolism clinical research liquid chromatography
mass spectrometry environmental exposure
Language: English
Publication Types:
Research
Supporting
Agency: U.S. DEPT. OF HEALTH AND HUMAN SERVICES; PUBLIC HEALTH
SERVICE; NATIONAL INSTITUTES OF HEALTH, NATIONAL INSTITUTE OF
ENVIRONMENTAL HEALTH SCIENCES
Country or State:
NORTH CAROLINA
Zip
Code: 27709
Year of Publication:
2002
Secondary Source
ID: CRISP/2002/ES11683-02
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12151638&dopt=Abstract
2002
Toxicol Sci Aug;68(2):429-36
Inhibition
of gap junctional intercellular communication
by perfluorinated compounds in rat liver and dolphin kidney
epithelial cell lines in vitro and Sprague-Dawley rats in vivo.
Hu W, Jones PD, Upham BL, Trosko JE, Lau
C, Giesy JP.
Aquatic Toxicology Laboratory, Department of Zoology, National
Food Safety and Toxicology Center and Institute of Environmental
Toxicology, Michigan State University, East Lansing, Michigan
48824, USA.
Gap junctional intercellular communication
(GJIC) is the major pathway of intercellular signal transduction,
and is thus important for normal cell growth and function. Recent
studies have revealed a global distribution of some perfluorinated
organic compounds, especially perfluorooctane sulfonic acid
(PFOS) in the environment. Because other perfluoroalkanes had
been shown to inhibit GJIC, the effects of PFOS and related
sulfonated fluorochemicals on GJIC were studied using a rat
liver epithelial cell line (WB-F344) and a dolphin kidney epithelial
cell line (CDK). In vivo effects on GJIC were studied in Sprague-Dawley
rats orally exposed to PFOS for 3 days or 3 weeks. Effects on
GJIC were measured using the scrape loading dye technique. PFOS,
perfluorooctane sulfonamide (PFOSA), and perfluorohexane sulfonic
acid (PFHA) were found to inhibit GJIC in a dose-dependent fashion,
and this inhibition occurred rapidly and was reversible. Perfluorobutane
sulfonic acid (PFBS) showed no significant effects on GJIC within
the concentration range tested. A structure activity relationship
was established among all 4 tested compounds, indicating that
the inhibitory effect was determined by the length of fluorinated
tail and not by the nature of the functional group. The results
of the studies of the 2 cell lines and the in vivo exposure
were comparable, suggesting that the inhibitory effects of the
selected perfluorinated compounds on GJIC were neither species-
nor tissue-specific and can occur both in vitro and in vivo.
PMID: 12151638 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12109751&dopt=Abstract
2002
Environ Toxicol Chem Jul;21(7):1490-6
Ecological
impact and environmental fate of perfluorooctane sulfonate on
the zooplankton community in indoor microcosms.
Sanderson H, Boudreau TM, Mabury SA, Cheong
WJ, Solomon KR.
Department of Environment, Technology and Social Studies, University
of Roskilde, Denmark. Hanss@ruc.dk
There is presently a substantial amount of information being
gathered concerning the environmental risk associated with the
perfluorooctane sulfonate (PFOS) compound. The U.S. Environmental
Protection Agency (U.S. EPA) is requiring that more research
be completed before making definitive decisions concerning the
regulatory issues covered in the significant new use rule (18/10-2000)
under the Toxic Substance Control Act. However, there are no
risk assessment requirements under seminatural conditions in
microcosms. The PFOS can enter, and has
been found in, the aquatic environment through different pathways,
including spills associated with use of fire-fighting foams
containing PFOS, leaching from washing Scotchgard-treated clothes
with the wastewater, leaching from various coatings, discharges
as residual waste from fluorochemical production, or volatilization
and transportation atmospherically. The
biota is the sink of PFOS rather than the sediment or soil.
The aim of this article is to determine a 35-d community
no-observable-effect concentration (NOECcommunity) for freshwater
zooplankton and the fate of PFOS during the course of study.
The PFOS persisted in the water phase with only slight reductions
over the study; only the decrease from 33.9 mg/L at day 1 to
29.8 mg/L at day 35 was significant. A
90 to 100% reduction (p < 0.01) of the total zooplankton
population was found after one week of exposure to 30 mg PFOS/L
and a similar reduction after two weeks at 10 mg PFOS/L.
The Daphnia magna 21-d NOECsurvival of 12 mg/L has previously
been found in a standard laboratory bioassay by 3M. The rank
order of susceptibility for the test community was Copepoda
> Cladocera > Rotifera, assuming all adverse direct effects.
PMID: 12109751 [PubMed - in process]
From
TOXNET
Toxicologist
2002 Mar;66(1-S):26
Perfluorooctanesulfonate-induced
perinatal mortality in rat pups is not a result of reduced serum
lipids.
Luebker
D York R Seacat A Butenhoff J
3M
Medical Department,
Corporate Toxicology, 3M, St. Paul, MN. Source:
This study was designed
to test the hypothesis that hypolipidemia causes perfluorooctanesulfonate
(PFOS)-induced perinatal mortality in rats. Female rats were
supplemented with either 500 mg/kg of mevalonic acid lactone
(MAL) twice daily or 500 mg/kg cholesterol (CHOL) once daily
and compared to non-supplemented controls. Dose groups consisted
of Tween 80 vehicle control, CHOL/vehicle control, MAL/vehicle
control, 1.6 mg/kg/d PFOS, 1.6 mg/kg/d PFOS + MAL, 1.6 mg/kg/d
PFOS + CHOL, 2.0 mg/kg/d PFOS, 2.0 mg/kg/d PFOS + CHOL, and
2.0 mg/kg/d PFOS + MAL. Female rats were dosed for 42 days prior
to mating to untreated males, during mating and through the
end of gestation or four days of lactation. Fetuses from eight
litters per dose group were taken by cesarean section on day
21 of gestation. All remaining dams were allowed to litter,
and were sacrificed with litters on day 5 of lactation. For
all or some of the groups, PFOS sera levels and serum lipids,
glucose, and mevalonic acid were measured at both time points.
For fetuses and gestation day 21 dams, all clinical chemistry
parameters remained at or above control levels with the exception
of triglycerides (TRIG), which were decreased in fetuses in
the MAL-supplemented 2 mg/kg dose group. On lactation day 5,
dams had decreased CHOL in all PFOS-treated groups and decreased
TRIG in the PFOS-only and CHOL-supplemented PFOS groups. Pups
in the CHOL-supplemented 2 mg/kg/d group had decreased TRIG.
MAL or CHOL supplementation was unable to prevent or mitigate
the perinatal mortality. Viability indices for the Tween 80
vehicle control, CHOL/vehicle control, MAL/vehicle control,
1.6 mg/kg/d PFOS, 1.6 mg/kg/d PFOS + MAL, 1.6 mg/kg/d PFOS +
CHOL, 2.0 mg/kg/d PFOS, 2.0 mg/kg/d PFOS + MAL, and 2.0 mg/kg/d
PFOS + CHOL were 97, 99, 98, 49, 41, 42, 17, 1, and 14 percent,
respectively. Results suggest that the observed perinatal mortality
is not a result of hypolipidemia in the perinatal period.
International Standard
Serial Number: 0731-9193
Publication Types:
MEETING ABSTRACT
From
TOXNET
Toxicologist
2002 Mar;66(1-S):25
Maternal
and developmental toxicity of perfluorooctane sulfonate (PFOS)
in the rat.
Lau
C Rogers JM Thibodeaux JR Hanson RG Grey BE Barbee BD Richards
J Butenoff JL
Reprod. Toxicology
Div., USEPA, Research Triangle
Park, NC.
The maternal and
developmental toxicity of PFOS, an environmentally persistent
compound used as surfactants and insecticides, were evaluated.
Timed-pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or
10 mg/kg/day PFOS/K+ by gavage on GD 2 through term. Controls
received 0.5% Tween-20 vehicle (1 mL/kg). Some rats were killed
on GD 21 for teratological examination, others were allowed
to deliver, and postnatal growth and development were monitored.
PFOS levels in serum and liver were determined. Maternal weight
gain was suppressed by PFOS, likely due to reduced food and
water intake. Serum cholesterol, triglycerides, thyroxine (T4)
and triiodothyronine (T3) in PFOS-treated dams were lower than
those in controls, but TSH was not affected. PFOS did not alter
the number of implantations or live fetuses at term, although
small deficits in fetal weight were noted in the high dose groups.
Cleft palate, anasarca, cardiac ventricular septal defect, and
small/hemorrhagic lung were detected, primarily in the 10 mg/kg
group. Live birth was observed in all groups; however, neonates
in the 10 mg/kg group were moribund and died within 4-6 h. While
newborns in the 5 mg/kg group appeared viable, greater than
95% were found dead within 24 h; postnatal growth was retarded
in the survivors. Cross-fostering of pups to control dams at
birth did not improve the survival rate, nor adverse effect
seen in control pups nursed by PFOS-exposed dams. Postnatal
viability was greater in the lower dose groups and surviving
neonates appeared to thrive, but mild hypothyroidism (only T4
reduction) and delays in eye opening were noted. These dose-dependent
adverse effects will be compared to the body burdens of PFOS.
Our results indicate both maternal and
developmental toxicity of PFOS in the rat; while PFOS altered
the thyroid status, this hormonal imbalance is not likely the
sole contributor to neonatal mortality.
International Standard
Serial Number: 0731-9193
Publication Types:
MEETING ABSTRACT
From
TOXNET
Toxicologist
2002 Mar;66(1-S):25
Critical
period for increased neonatal mortality induced by perfluorooctane
sulfonate (PFOS) in the rat.
Grasty
RC Grey BE Thibodeaux J Lau C Rogers JM
Reproductive Toxicology
Division, NHEERL, ORD, EPA, Research
Triangle Park, NC.
PFOS belongs to a
class of fluorinated organic chemicals with broad industrial
use. Despite a reduction in the manufacturing of products containing
PFOS and many of its metabolic precursors, levels of accumulated
PFOS in the environment warrant evaluation of its potential
for toxicity. The present study investigated the critical period
for increased neonatal mortality caused by PFOS. Timed-pregnant
Sprague-Dawley rats were treated by oral gavage with 25 mg/kg
PFOS (potassium salt in 0.5% Tween-20) for four consecutive
days during either GD 2-5, 6-9, 10-13, 14-17 or 17-20. Controls
were given vehicle daily throughout GD 2-20. Blood samples were
taken the day after the last day of dosing to determine maternal
PFOS levels. Dams were allowed to continue normal pregnancy
through birth. Maternal weight gain was reduced in treated animals
during dosing and returned to near control levels by term. Similar
patterns were seen in food and water consumption. Average litter
size was normal in all groups compared to controls with no significant
difference in average pup weight on the day of birth. PFOS induced
decreases in neonatal survival were seen for each group while
controls remained at about 100% survival. Mortality increased
as the dosing period fell later during gestation with the latest
group (GD 17-20) approaching 100% mortality. All deaths occurred
before PD 4 with most taking place during the first 24 hours.
Growth retardation was observed in surviving pups of treated
dams and gross dissection suggested underdeveloped lungs. A
second study compared postnatal survival between dams treated
with 100 mg/kg PFOS on GD 17 or 20. Both groups had a high rate
of neonatal death with no significant difference between the
two. Analysis of maternal PFOS levels are in underway. These
results demonstrate that the critical period for PFOS induced
neonatal mortality in the rat occurs near birth.
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=12083418&dopt=Abstract
2002
Inflammation Jun;26(3):121-7
Peroxisome
proliferator-activated receptor agonists inhibit inflammatory
edema and hyperalgesia.
Taylor BK, Dadia N, Yang CB, Krishnan
S, Badr M.
Division of Pharmacology, School of Pharmacy, University of
Missouri-Kansas City, 64108, USA.
Previous studies have produced conflicting data on the contribution
of the peroxisome proliferator-activated receptors (PPARs) to
the inflammatory process. This study investigated the effects
of several PPARalpha and PPARgamma subtype-specific agonists
on the inflammation and hyperalgesia produced by intraplantar
carrageenan injection in unanesthetized male Sprague-Dawley
rats. Intraperitoneal administration of PPARalpha agonists reduced
edema in parallel to their potencies determined in vitro. Perfluorooctanoic
acid (PFOA) inhibited carrageenan-induced edema in a dose-dependent
manner, and also reduced thermal hypersensitivity. Furthermore,
PFOA produced much more robust effects when administered 0.5-24
hrs before carrageenan, as compared to when it was administered
1.5 hrs after carrageenan. Intraperitoneal administration of
similar doses of the PPARgamma agonist rosiglitazone, but not
the less potent agonist, troglitazone, reduced edema when administered
before but not after carrageenan. We conclude that systemic
administration of potent PPARalpha and PPARgamma agonists exert
anti-hyperalgesic and/or antiinflammatory actions in vivo, possibly
by interfering with the initiation of inflammation.
PMID: 12083418 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12099451&dopt=Abstract
2002
Environ Sci Technol Jun 15;36(12):2566-71
Perfluorooctanesulfonate
and related fluorinated hydrocarbons in
mink and river otters from the United States.
Kannan K, Newsted J, Halbrook RS, Giesy
JP.
National Food Safety and Toxicology Center, Department of Zoology,
Institute of Environmental Toxicology, Michigan State University,
East Lansing 48824, USA. kuruntha@msu.edu
Mink and otters are good integrators of their aquatic environments
and useful sentinel species for determining exposure to environmental
contaminants. In this study, perfluorooctanesulfonate (PFOS;
C8F17SO3-), perfluorooctanesulfonamide (FOSA; C8F17SO2NH2),
perfluorohexanesulfonate (PFHxS; C6F13SO3-), and perfluorooctanoate
(PFOA; C7F15CO2-) were measured in livers of mink and river
otters collected from various locations in the United States.
PFOS was found in all mink livers analyzed. Frequencies of occurrence
of FOSA, PFHxS, and PFOA were less. The
greatest concentration of PFOS measured in liver of mink was
5140 ng/g, wet weight. Maximum concentrations of FOSA, PFHxS,
and PFOA in mink livers were 590, 39, and 27 ng/g, wet weight,
respectively. There were no significant positive relationships
between concentrations of PFOS and PFHxS or PFOA in mink livers.
Concentrations of PFOS were positively correlated with those
of FOSA in mink livers from Illinois. There was no significant
correlation between concentrations of PFOS and lipid content
in mink livers. There were no age- or sex-related differences
in the concentrations of fluorochemicals in mink livers. Greater
concentrations are associated with those individuals collected
near urbanized and/or industrialized areas.
PFOS was detected in livers of all
river otters collected from Washington and Oregon at concentrations
ranging from 25 to 994 ng/g, wet wt.
PMID: 12099451 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12093614&dopt=Abstract
2002
Toxicology Jul 15;176(3):175-85
Interactions
of fluorochemicals with rat liver fatty acid-binding protein.
Luebker DJ, Hansen KJ, Bass NM, Butenhoff
JL, Seacat AM.
3M Medical Department, Corporate
Toxicology, 3M Center Building 220-2E-02, Saint Paul,
MN 55144, USA. djluebker@mmm.com
Liver-fatty acid binding protein (L-FABP) is an abundant intracellular
lipid-carrier protein. The hypothesis that perfluorooctanesulfonate
(PFOS), perfluorooctanoate (PFOA), and certain related perfluorooctanesulfonamide-based
fluorochemicals (PFOSAs) can interfere with the binding affinity
of L-FABP for fatty acids was tested. The relative effectiveness
of PFOA, PFOS, N-ethylperfluorooctanesulfonamide (N-EtFOSA),
N-ethylperfluorooctanesulfonamido ethanol (N-EtFOSE), and of
the strong peroxisome proliferator Wyeth-14643 (WY) to inhibit
11-(5-dimethylaminonapthalenesulphonyl)-undecanoic acid (DAUDA)
binding to-L-FABP was determined. The dissociation constant
(Kd) of the DAUDA-L-FABP complex was 0.47 nM. PFOS
exhibited the highest level of inhibition of DAUDA-L-FABP binding
in the competitive binding assays, followed by N-EtFOSA,
WY, and, with equal IC(50)s, N-EtFOSE and PFOA. The in vitro
data presented in this study support the hypothesis that these
fluorochemicals may interfere with the binding of fatty acids
or other endogenous ligands to L-FABP. Furthermore, this
work provides evidence to support the hypothesis that displacement
of endogenous ligands from L-FABP may contribute to toxicity
in rodents fed these fluorochemicals.
PMID: 12093614 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12075127&dopt=Abstract
2002
Toxicol Sci Jul;68(1):249-64
Subchronic
toxicity studies on perfluorooctanesulfonate potassium salt
in cynomolgus monkeys.
Seacat AM, Thomford PJ, Hansen
KJ, Olsen GW, Case MT, Butenhoff JL.
3M Medical
Department, Saint Paul, Minnesota 55133. Covance,
Madison, Wisconsin 53704. 3M Environmental Laboratory, Saint
Paul, Minnesota 55133.
This study was conducted to determine the earliest measurable
response of primates to low-level perfluorooctanesulfonate (PFOS)
exposure and to provide information to reduce uncertainty in
human health risk assessment. Groups of male and female monkeys
received 0, 0.03, 0.15, or 0.75 mg/kg/day potassium PFOS orally
for 182 days. Recovery animals from each group, except the 0.03
mg/kg/day dose group, were monitored for one year after treatment.
Significant adverse effects occurred only
in the 0.75 mg/kg/day dose group and included compound-related
mortality in 2 of 6 male monkeys, decreased body weights, increased
liver weights, lowered serum total cholesterol, lowered triiodothyronine
concentrations (without evidence of hypothyroidism), and lowered
estradiol levels. Decreased serum total cholesterol occurred
in the 0.75 mg/kg/day dose group at serum PFOS levels > 100
ppm. Hepatocellular hypertrophy and lipid
vacuolation were present at term in the 0.75 mg/kg/day dose
group. No peroxisomal (palmitoyl CoA oxidase) or cell
proliferation (proliferating cell nuclear antigen immunohistochemistry)
was detected. Complete reversal of clinical and hepatic effects
and significant decreases in serum and liver PFOS occurred within
211 days posttreatment. Liver-to-serum PFOS ratios were comparable
in all dose groups, with a range of 1:1 to 2:1. Serum concentrations
associated with no adverse effects (0.15 mg/kg/day) were 82.6
+/- 25.2 ppm for males and 66.8 +/- 10.8 ppm for females.
Comparison of serum PFOS concentrations associated with no adverse
effect in this study to those reported in human blood samples
(0.028 +/- 0.014 ppm) indicated an adequate margin of safety.
PMID: 12075127 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11993863&dopt=Abstract
2002
Environ Sci Technol Apr 15;36(8):1681-5
Quantitative
characterization of trace levels of PFOS and PFOA in the Tennessee
River.
Hansen KJ, Johnson HO, Eldridge JS, Butenhoff
JL, Dick LA.
3M Environmental
Laboratory and 3M Medical Department,
St. Paul, Minnesota 55133-3331, USA. kjhansen@mmm.com
Although there is evidence of widespread distribution of organic
fluorochemicals such as perfluorooctane sulfonate and perfluorooctanoate,
in the environment, the versatility of these compounds in industrial
and commercial applications complicates characterization of
pathways into the environment. A solid-phase extraction method
coupled with HPLC-negative-ion electrospray tandem mass spectrometry
was developed to quantitatively measure trace levels of organic
fluorochemicals in drinking water and surface water. Using this
method, certain fluorochemicals can be quantitatively measured
in water samples down to 25 ppt,
a level well below calculated drinking water advisory levels.
To assess fluorochemical distribution in a localized geography
and to ascertain whether fluorochemical manufacturing facilities
contribute to environmental levels of fluorochemicals, 40 water
samples were collected on an 80-mi stretch of the Tennessee
River, near a fluorochemical manufacturing
site in Decatur, AL. Low levels (ppt) of perfluorooctane
sulfonate were determined throughout the stretch of river sampled.
Concentrations of the measured fluorochemicals increased downstream
of the fluorochemical manufacturing facility, indicating that
effluent from manufacturing is one likely source of organic
fluorochemicals into the river.
PMID: 11993863 [PubMed - in process]
From
TOXNET
Source: EPA/OTS;
Doc #000811838T
Order Number: NTIS/OTS020492913
2002
- SUPPORT: SELECTED FLUOROCHEMICALS
IN THE DECATUR, ALABAMA AREA, WITH COVER LETTER DATED 10-24-01
Corporate Name: ENTRIX
INC
Keywords:
3M CO
PERFLUOROOCTANESULFONATE
ENVIRONMENTAL FATE
MONITORING
CAS Registry Numbers:
335-67-1
355-46-4
754-91-6
1763-23-1
Classification Code: TSCA Sect. 8E Rec 01/09/02
Year of Publication: 2002
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11883418&dopt=Abstract
2002
Environ Sci Technol Feb 15;36(4):545-51
Monitoring
perfluorinated surfactants in biota and surface water samples
following an accidental release of fire-fighting
foam into Etobicoke Creek.
Moody CA, Martin JW, Kwan WC, Muir DC,
Mabury SA.
Department of Chemistry, University of Toronto, Ontario, Canada.
Perfluorinated surfactants have emerged
as priority environmental contaminants due to recent
reports of their detection in environmental and biological matrices
as well as concerns regarding their persistence and toxicity.
In June 2000, 22000 L of fire retardant foam containing
perfluorinated surfactants was accidentally released at L. B.
Pearson International Airport, Toronto, ON, and subsequently
entered into Etobicoke Creek, a tributary to Lake Ontario. A
suite of analytical tools that include liquid chromatography/tandem
mass spectrometry (LC/MS/MS) and 19F NMR were employed to characterize
fish (common shiner, Notropus cornutus) and surface water samples
collected following the discharge of the perfluorinated material.
Total perfluoroalkanesulfonate (4, 6, and 8 carbons) concentrations
in fish liver samples ranged from 2.00 to 72.9 microg/g, and
total perfluorocarboxylate (5-14 carbons) concentrations ranged
from 0.07 to 1.02 microg/g. In addition to fish samples, total
perfluoroalkanesulfonate (6 and 8 carbons) concentrations were
detected in creek water samples by LC/MS/MS over a 153 day sampling
period with concentrations ranging from <0.017 to 2260 microg/L;
perfluorooctanoate concentrations (<0.009-11.3 microg/L)
were lower than those observed for the perfluoroalkane-sulfonates.
By 19F NMR, the total perfluorinated surfactant concentrations
in surface water samples ranged from < 10 to 17000 microg/L.
A bioaccumulation factor range of 6300-125000 was calculated
for perfluorooctanesulfonate, based on concentrations in fish
liver and surface water. The residence time of perfluorooctanesulfonate
in Etobicoke Creek as well as the high bioaccumulation in fish
liver suggests that perfluorinated surfactants
will persist and bioaccumulate following release into
the aquatic environment.
PMID: 11883418 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11910459&dopt=Abstract
2002
Arch Environ Contam Toxicol Apr;42(3):313-8
Perfluorooctane
sulfonate in oysters, Crassostrea virginica, from the Gulf
of Mexico and the Chesapeake Bay, USA.
Kannan K, Hansen KJ, Wade TL, Giesy JP.
National Food Safety and Toxicology Center, Department of Zoology,
Institute for Environmental Toxicology, Michigan State University,
East Lansing, Michigan 48824, USA.
Concentrations of perfluorooctane sulfonate (PFOS), a metabolite
of several sulfonated perfluoroorganic compounds, were measured
in oysters collected from 77 locations in the Gulf of Mexico
and Chesapeake Bay of the United States. PFOS
was detected in oysters collected from 51 of the 77 locations
at concentrations ranging from < 42 to 1,225 ng/g on a dry
weight basis. This study provides baseline data for future
monitoring programs to examine long-term trends in concentrations
of PFOS.
PMID: 11910459 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11896291&dopt=Abstract
2002
Toxicol Sci Apr;66(2):244-52
Structural determinants of
fluorochemical-induced mitochondrial dysfunction.
Starkov AA, Wallace KB.
Department of Biochemistry and Molecular Biology, University
of Minnesota School of Medicine, 10 University Drive, Duluth,
Minnesota, USA.
Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS)
are thought to induce peroxisome proliferation and interfere
with mitochondrial metabolic pathways. Direct measurements revealed
that PFOA and the unsubstituted sulfonamide of perfluorooctane
(FOSA) uncouple mitochondrial respiration by increasing proton
conductance. The purpose of this investigation was to characterize
structural determinants responsible for the mitochondrial uncoupling
effect of several structurally related fluorochemicals. Included
in the study were PFOA, PFOS, FOSA, the N-acetate of FOSA (perfluorooctanesulfonamidoacetate,
FOSAA), N-ethylperfluorooctanesulfonamide (N-EtFOSA), and the
N-ethyl alcohol [2-(N-ethylperfluorooctanesulfonamido)ethyl
alcohol, N-EtFOSE] and N-acetic acid (N-ethylperfluorooctanesulfonamidoacetate,
N-EtFOSAA) of N-EtFOSA. Each test compound was dissolved in
ethanol and added directly to an incubation medium containing
substrate-energized rat liver mitochondria. Mitochondrial respiration
and membrane potential were measured concurrently using an oxygen
electrode and a TPP+ -selective electrode, respectively. All
of the compounds tested, at sufficiently high concentrations,
had the capacity to interfere with mitochondrial respiration,
albeit via different mechanisms and with varying potencies.
At sufficiently high concentrations, the free acids PFOA and
PFOS caused a slight increase in the intrinsic proton leak of
the mitochondrial inner membrane, which resembled a surfactant-like
change in membrane fluidity. Similar effects were observed with
the sulfonamide N-EtFOSE. Another fully
substituted sulfonamide, N-EtFOSAA, at high concentrations caused
inhibition of respiration, the release of cytochrome c, and
high-amplitude swelling of mitochondria. The swelling
was prevented by cyclosporin A or by EGTA, indicating that this
compound induced the mitochondrial permeability transition.
The unsubstituted and mono-substituted
amides FOSA, N-EtFOSA, and FOSAA all exerted a strong uncoupling
effect on mitochondria resembling that of protonophoric uncouplers.
Among these compounds, FOSA was a very potent uncoupler of
oxidative phosphorylation, with an IC50 of approximately
1 microM. These data suggest that the protonated nitrogen atom
with a favorable pKa is essential for the uncoupling action
of perfluorooctane sulfonamides in mitochondria, which may be
critical to the mechanism by which these compounds interfere
with mitochondrial metabolism to induce peroxisome proliferation
in vivo.
PMID: 11896291 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11879971&dopt=Abstract
2002
Toxicol Lett Mar 24;129(1-2):23-32
Perfluorooctanoate,
perflourooctanesulfonate, and N-ethyl perfluorooctanesulfonamido
ethanol; peroxisome proliferation and mitochondrial biogenesis.
Berthiaume J, Wallace KB.
Department of Biochemistry and Molecular Biology, Toxicology
Graduate Program, University of Minnesota School of Medicine,
10 University Drive, Duluth, MN 55812-2496, USA.
Compounds that cause peroxisome proliferation in rats and mice
have been reported to interfere with mitochondrial (mt) bioenergetics
and possibly biogenesis. The purpose of this investigation was
to establish whether proliferation of peroxisomes and mitochondria
are necessarily related. Perfluorooctanesulfonate (PFOS) and
N-ethyl perfluorooctanesulfonamido ethanol (N-EtFOSE) were investigated
as peroxisome proliferators in comparison to perfluorooctanoic
acid (PFOA). Three parameters were chosen to assess peroxisome
proliferation, stimulation of lauroyl CoA oxidase activity,
reduction of serum cholesterol concentration, and hepatomegaly.
mt Biogenesis was assessed through cytochrome oxidase activity,
cytochrome content and mitochondrial DNA (mtDNA) copy number.
PFOA, PFOS, or N-EtFOSE was administered via a single i.p. injection
at 100 mg/kg in male rats, and measurements were made 3 days
later. In this model,
PFOS and PFOA share similar potencies as peroxisome proliferators,
whereas N-EtFOSE showed no activity. mt Endpoints were
altered only in the PFOA treatment group, which consisted of
a decrease cytochrome oxidase activity in liver tissue and an
increase in the mtDNA copy number. None of the perfluorooctanoates
significantly altered mt cytochrome content following acute
in vivo treatment. These data demonstrate
that acute administration of PFOS or PFOA causes hepatic peroxisome
proliferation in rats. However, stimulation of mt biogenesis
is not a characteristic response of all peroxisome proliferators.
PMID: 11879971 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11811941&dopt=Abstract
2002
Int Immunopharmacol Feb;2(2-3):389-97
Potent
suppression of the adaptive immune response
in mice upon dietary exposure to the potent peroxisome proliferator,
perfluorooctanoic acid.
Yang Q, Abedi-Valugerdi M, Xie Y, Zhao
XY, Moller G, Nelson BD, DePierre JW.
Department of Biochemistry and Biophysics, Wallenberg Laboratory,
Stockholm University, Sweden. qian@dbb.su.se
In a previous investigation, we demonstrated that severe thymus
and spleen atrophy occurs in mice upon dietary exposure to several
potent peroxisome proliferators (PPs). In the present investigation,
the effects of the potent PP perfluorooctanoic acid (PFOA)
on the adaptive immunity of mice was evaluated both in vivo
and ex vivo. The in vivo immune response examined involved immunization
of mice with horse red blood cells (HRBCs), displaying T-cell-dependent
antigens after pre-treatment with a PFOA-containing diet for
10 days. Subsequent quantitation of the primary humoral response
was performed employing both the plaque-forming cell (PFC) assay
and determination of the antibody titer by ELISA. The results
clearly demonstrate that oral administration of PFOA prevents
both the increases in plaque formations by anti-IgM and -IgG
and in serum levels of IgM and IgG normally evoked by such immunization.
Ex vivo spleen cells proliferation (assayed as incorporation
of 3H-thymidine) in response to both T- and B-cell activators
was attenuated by dietary treatment with PFOA, although the
analogous in vitro treatment of mouse spleen cells with this
same compound had no such effects. Thus,
the relatively metabolically inert PP PFOA may exert adaptive
immunosuppression in mice by an indirect mechanism. The possible
relevance of this immunosuppression to the alterations in plasma
lipids caused by PPs is discussed.
PMID: 11811941 [PubMed - indexed for MEDLINE]
From
TOXNET
Toxicologist
2002 Mar;66(1-S):25
Perfluorooctanesulfonate-induced
perinatal mortality in rat pups is associated with a steep dose-response.
Butenhoff
J York R Seacat A Luebker D
3M
Medical Department,
Corporate Toxicology, 3M, St. Paul, MN.
To better define
the dose-response of perinatal mortality observed in prior reproduction
studies with perfluorooctanesulfonate (PFOS), female rats were
administered potassium PFOS by oral intubation at dose levels
of 0, 0.4, 0.8, 1.0, 1.2, 1.6, and 2.0 mg/kg/d for 42 days prior
to mating to untreated males, during mating and through the
end of gestation (cesarean section) or four days of lactation
(natural delivery). At day 21 of gestation, fetuses from eight
litters in the 0, 1.6, and 2.0 mg/kg/d dose groups were taken
by cesarean section. All remaining dams were allowed to litter,
and were sacrificed with litters on day 5 of lactation. For
all or some of the groups, PFOS sera levels, serum lipids, glucose
and thyroid hormones were measured at both time points. Milk
cholesterol and liver PFOS were also measured on lactation day
5. Significant decreases in cholesterol and increases in LDL
were observed in all fetuses from the 1.6 and 2.0 mg/kg/d PFOS
dose groups on day 21 of gestation. On day 5 of lactation, dams
had significantly decreased serum cholesterol at all dose levels,
significantly decreased serum triglycerides in the 1.6 and 2.0
mg/kg/d dose groups, and significantly increased serum glucose
in the 2.0 mg/kg/d dose group. Although T4 (free and total)
appeared to be decreased when measured by RIA, free T4 was normal
across all dose groups (dams) when measured using equilibrium
dialysis. T3 was low at 1.2 mg/kg/d and above in dams but not
fetuses and pups. TSH was not elevated and thyroid histology
was normal. Dams in the 0.8 mg/kg/d and higher dose groups showed
an increase in relative liver weight, a decrease in body weight
gain, a decrease in feed consumption, and a slight decrease
in the duration of gestation. Pup growth was decreased at 1.2
mg/kg/d and higher. Viability indices for pups from the 0, 0.4,
0.8, 1.0, 1.2, 1.6, and 2.0 mg/kg/d groups were 97, 98, 93,
89, and 82, 49, and 17 percent, respectively.
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=11871713&dopt=Abstract
2002
J Environ Monit Feb;4(1):90-5
Method for the determination of sub-ppm concentrations
of perfluoroalkylsulfonate anions in water.
Hebert GN, Odom MA, Craig PS, Dick DL,
Strauss SH.
Department of Chemistry, Colorado State University, Fort Collins
80523, USA.
The determination of sub-ppm concentrations of aqueous perfluoroalkylsulfonate
(PFSt) anions, including perfluorooctylsulfonate (PFOS), has
been accomplished with a relatively simple mass spectrometric
procedure that does not require extraction of the analytes into
an organic solvent or a chromatographic separation prior to
injection into the negative-ion electrospray ionization mass
spectrometer. Sample pretreatment was minimized and consisted
of dilution of the aqueous samples of groundwater, surface water,
tap water, and distilled water with acetonitrile, addition of
dodecylsulfate (DDS) as an internal standard, and, in some cases,
addition of known amounts of perfluorobutylsulfonate (PFBS)
or PFOS for standard-addition experiments. The linear-response
range for PFOS is 25.0 microg L(-1) to 2.5 mg L(-1). The lower
limit of this range is three orders of magnitude lower than
an equally straightforward chromatographic method. The relative
errors for standard aqueous solutions containing only 25.0 microg
L(-1) and 2.5 mg L(-1) PFOS are +/- 14% and +/- 7%, respectively,
with 133 microg L(-1) DDS as the internal standard. The detection
limit and quantification limit for PFOS in these standards are
5.0 microg L(-1) and 25.0 microg L(-1), respectively. Six different
PFS anions, containing three to eight carbon atoms, were identified
and quantified in an aqueous film-forming foam (AFFF) formulation
using the method of standard additions. Two alkylsulfate anions
and two perfluoroalkylcarboxylate anions were also identified
in the AFFF formulation.
PMID: 11871713 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11842814&dopt=Abstract
2002
Anal
Chem Feb 1;74(3):584-90
Collection
of airborne fluorinated organics and analysis by gas chromatography/chemical
ionization mass spectrometry.
Martin JW, Muir DC, Moody CA, Ellis DA,
Kwan WC, Solomon KR, Mabury SA.
Department of Environmental Biology, University of Guelph, Ontario.
The
ubiquitous detection of perfluorooctane sulfonate (PFOS) in
humans and animals
has produced a need for sensitive and compound-specific analytical
methods to determine the environmental distribution of fluorinated
organic contaminants. A suite of potential PFOS precursors (sulfonamides)
and fluorotelomer alcohols (FTOHs) were separated by gas chromatography
and detected by chemical ionization mass spectrometry (GC/CI-MS).
Full-scan spectra were collected in both positive and negative
chemical ionization (PCI and NCI, respectively) mode to determine
retention time windows and fragmentation patterns. In selected
ion monitoring (SIM) mode, instrumental detection limits ranged
from 0.2 to 20 pg for individual analytes, depending on ionization
mode. PCI mode was preferred for routine analysis because of
the simple mass spectra produced, typified by the presence of
a major molecular ion [M + H]+. High-volume air samplers collected
gaseous and particle-bound fluoroorganics on composite media
consisting of XAD-2, polyurethane foam (PUF), and quartz-fiber
filters. The combined collection efficiency for individual analytes
was 87 to 136% in breakthrough experiments. Application
of the method to the analysis of ambient air from urban and
rural sites confirmed the presence of six novel fluorinated
atmospheric contaminants at picogram per meter3 concentrations.
Low concentrations of fluoroorganics were consistently detected
in blanks (<4 pg m(-3)); however, this did not prevent confirmation
or quantification of environmental concentrations.
PMID: 11842814 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11908906&dopt=Abstract
2002
Lipids Feb;37(2):139-46
Characterization
of the adipose tissue atrophy induced
by peroxisome proliferators in mice.
Xie Y, Yang Q, Nelson BD, DePierre
JW.
Unit for Biochemical Toxicology, Department of Biochemistry
and Biophysics, Stockholm University, Sweden. yi@dbb.su.se
In the present study, we characterized the effects of peroxisome
proliferators (PP) on adipose tissue in mice. Treatment with
potent PP, such as perfluorooctanoic acid
(PFOA), 2-methyl-2-(p(1,2,3,4-tetrahydroxy-naphthyl)-phenoxy)propionic
acid, (4-chloro-6-(2,3-xylidino)2-pyrimidinylthio) acetic acid,
and di(2-ethylhexyl)phthalate, caused dramatic decreases in
adipose tissue weight, whereas the moderately potent PP, acetylsalicylic
acid, had a relatively weak effect. This decrease in weight
reflects a loss of fat from adipocytes rather than a loss of
cells, as demonstrated by constant DNA content. The dose-dependency
and time-course experiments indicate that peroxisome proliferation
occurs simultaneously with or prior to adipose tissue atrophy.
Thus, hepatic peroxisome proliferation might result in the increased
mobilization of lipids and lipid utilization in liver. The enhanced
adipose tissue hormone-sensitive lipase (HSL) activity and down-regulated
lipoprotein lipase (LPL) activity observed upon PP treatment
might, at least in part, explain the loss of fat via increased
FA release from adipocytes and/or decreased FA uptake from the
circulation, respectively. In addition, the possible involvement
of the increased tumor necrosis factor alpha expression found
upon PFOA treatment in reducing
the insulin sensitivity of adipose tissue and thereby altering
LPL and HSL activities is discussed.
PMID: 11908906 [PubMed - indexed for MEDLINE]
From
TOXNET
2001
Teratology
Jun;63(6):290
Developmental
toxicity of perfluorooctane sulfonate (PFOS) in the rat and
mouse.
Lau
C Rogers JM Hanson RG Barbee BD Narotsky MG Schmid JE Richards
JH
Reproductive Toxicology
Division, NHEERL, USEPA, Research
Triangle Park, NC.
PFOS, a compound
in a class of organic fluorochemicals that is widely used as
surfactants and to a lesser extent, insecticides, was evaluated
for developmental toxicity in laboratory rodents. Timed-pregnant
Sprague-Dawley rats and CD-1 mice were given either 1, 5, or
10 mg/kg PFOS (potassium salt) by gavage daily beginning on
GD 2 until term. Controls received 0.5% Tween-20 vehicle (1
mL/kg). Half of the animals were sacrificed on GD 21 (rat) or
GD 17 (mouse) for teratological examination, the remaining dams
were allowed to deliver and postnatal growth and viability were
monitored. In rats, significant deficits of maternal weight
gain were seen in the 5 and 10 mg/kg PFOS groups. Lower maternal
serum cholesterol and triglycerides were noted at 10 mg/kg,
but liver weights were unaffected. Lower fetal weight, cleft
palate and anasarca were detected in the 10 mg/kg group. Live
birth was observed in all treatment groups; however, neonates
in the 10 mg/kg group were moribund and all died within 46 h.
While pups in the 5 mg/kg group were born alive and appeared
lively, greater than 95% were found dead within 24 h. Among
the few survivors, marked growth retardation (30%) was seen
in the first week of life. In mice, PFOS did not alter the maternal
weight gain appreciably, although liver weight of the dams were
markedly elevated in the 5 and 10 mg/kg groups (127% and 174%
of controls, respectively). In contrast to the rats, only serum
triglycerides were reduced in the 5 and 10 mg/kg groups in the
mice. PFOS did not significantly affect the mouse fetal weight,
although the incidence of fetal mortality was slightly increased
in the 10 mg/kg group. PFOS also did not significantly alter
the litter size, but a persistent reduction of neonatal body
weight (15-20%) was found in the 10 mg/kg group in the first
three days of life. These results indicate both maternal and
developmental toxicity of PFOS in rats and mice, although the
response sensitivity differs between these two species.
International Standard
Serial Number: 0040-3709
Publication Types:
MEETING ABSTRACT
No Abstract
available
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11348100&dopt=Abstract
2001
Environ Sci Technol Apr 1;35(7):154A-160A
Growing
concern over perfluorinated chemicals.
Renner R.
PMID: 11348100 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11597582&dopt=Abstract
2001
Biochem Pharmacol Oct 15;62(8):1133-40
Further
evidence for the involvement of inhibition of cell proliferation
and development in thymic and splenic
atrophy induced by the peroxisome proliferator perfluoroctanoic
acid in mice.
Yang Q, Xie Y, Eriksson AM, Nelson BD,
DePierre JW.
Unit for Biochemical Toxicology, Department of Biochemistry
& Biophysics, Wallenberg Laboratory, Stockholm University,
S-106 91, Stockholm, Sweden. Qian@dbb.su.se
We recently demonstrated that severe thymic and splenic atrophy
occur upon dietary treatment of mice with potent peroxisome
proliferators (PPs), e.g. perfluorooctanoic acid (PFOA), WY-14,643,
nafenopin, and di(2-ethylhexyl)phthalate (DEHP). In the present
study, we investigated this phenomenon further employing a relative
inert PP, PFOA. Comparison of the dose-dependencies and time-courses
indicated that the peroxisome proliferative effect occurred
prior to atrophy of both the thymus and spleen. However, following
withdrawal of PFOA from the diet, the weight of the thymus and
spleen rapidly returned to normal within 10 and 5 days, respectively,
in contrast to the more persistent peroxisome proliferation.
Furthermore, the changes in thymus and spleen weight upon PFOA
treatment and the following withdrawal from diet paralleled
the changes in total thymocyte and splenocyte counts, respectively.
It was found previously that the decreases in the thymocyte
populations present in the S and G2/M phases, as well as in
the number of CD4+CD8+ cells upon PFOA treatment, were the most
dramatic, perhaps reflecting inhibition of thymocyte proliferation
in connection with thymocyte development. Here, the recovery
of thymocytes began with increases in the populations in these
same phases of the cell cycle, with CD4+CD8+ cells recovering
most rapidly, lending further support to our previous hypothesis.
The possible relationship of these immunotoxic effects of PPs
to the changes they cause in fatty acid metabolism is discussed.
PMID: 11597582 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11505980&dopt=Abstract
2001
Environ
Sci Technol Aug 1;35(15):3065-70
Perfluorooctane
sulfonate in fish-eating water birds including bald eagles and
albatrosses.
Kannan K, Franson JC, Bowerman WW, Hansen
KJ, Jones PD, Giesy JP.
Department of Zoology, Institute of Environmental Toxicology,
Michigan State University, East Lansing 48824, USA. kuruntha@msu.edu
Perfluorooctane sulfonate (PFOS) was measured in 161 samples
of liver, kidney, blood, or egg yolk from 21 species of fish-eating
water birds collected in the United States including albatrosses
from Sand Island, Midway Atoll, in the central North Pacific
Ocean. Concentrations of PFOS in the blood
plasma of bald eagles collected fromthe midwestern United States
ranged from 13 to 2,220 ng/mL (mean: 330 ng/mL), except
one sample that did not contain quantifiable concentrations
of PFOS. Concentrations of PFOS were greater in blood plasma
than in whole blood. Among 82 livers from various species of
birds from inland or coastal U.S. locations, Brandt's
cormorant from San Diego, CA, contained the greatest concentration
of PFOS (1,780 ng/g, wet wt). PFOS was also found in
the sera of albatrosses from the central North Pacific Ocean
at concentrations ranging from 3 to 34 ng/mL. Occurrence
of PFOS in birds from remote marine locations suggests widespread
distribution of PFOS and related fluorochemicals in the environment.
PMID: 11505980 [PubMed - indexed for MEDLINE]
From
TOXNET
Source: EPA/OTS;
Doc #000811833O
Order Number: NTIS/OTS020492913
2001:
SUPPORT: ACCUMULATION OF PERFLUOROOCTANESULFONATE AND
RELATED FLUOROCHEMICALS IN FISH TISSUES, WITH COVER LETTER DATED
09-05-01
Corporate Name: NATL
FOOD SFTY & TOX CTR
Keywords:
3M CO
PERFLUOROOCTANE SULFONATE
ENVIRONMENTAL EFFECTS
TISSUE CONCENTRATION
FISH-FRESHWATER
FISH-MARINE
CAS Registry Numbers:
335-67-1
355-46-4
754-91-6
1763-23-1
Classification Code: TSCA Sect. 8E Rec 09/10/01
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11350215&dopt=Abstract
2001
Toxicol Appl Pharmacol May 15;173(1):56-64
Reactive
oxygen species and mitochondria mediate the induction of apoptosis
in human hepatoma HepG2 cells by the rodent peroxisome proliferator
and hepatocarcinogen, perfluorooctanoic acid.
Panaretakis T, Shabalina IG, Grander D,
Shoshan MC, DePierre JW.
Unit of Biochemical Toxicology, Department of Biochemistry,
Wallenberg Laboratory, Stockholm University, S-106 91 Stockholm,
Sweden. theoharis.panaretakis@cck.ki.se
We have previously shown that one of the most potent rodent
hepatocarcinogens, perfluorooctanoic acid
(PFOA), induces apoptosis in human HepG2 cells in a dose- and
time-dependent manner. In this study we have investigated
the involvement of reactive oxygen species (ROS), mitochondria,
and caspase-9 in PFOA-induced apoptosis. Treatment with 200
and 400 microM PFOA was found to cause a
dramatic increase in the cellular content of superoxide anions
and hydrogen peroxide after 3 h. Measurement of the mitochondrial
transmembrane potential (Delta Psi(m)) after PFOA treatment
showed a dissipation of Delta Psi(m) at 3 h. Caspase-9 activation
was seen at 5 h after treatment with 200 microM PFOA. In order
to evaluate the importance of these events in PFOA-induced apoptosis,
cells were cotreated with PFOA and N-acetylcysteine (NAC), a
precursor of glutathione, or Cyclosporin A (CsA), an inhibitor
of mitochondrial permeability transition pore (MPT pore). NAC
reduced Delta Psi(m) dissipation, caspase 9 activation, and
apoptosis, indicating a role for PFOA-induced ROS. In addition,
CsA also reduced Delta Psi(m) dissipation, caspase 9 activation,
and apoptosis, indicating a role for PFOA-induced opening of
the MPT pore. In summary, we have delineated a ROS and mitochondria-mediated
pathway for induction of apoptosis by PFOA. Copyright 2001 Academic
Press.
PMID: 11350215 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11311214&dopt=Abstract
2001
Chem Biol Interact Apr 16;134(2):203-16
Comparison
of the elimination between perfluorinated fatty acids with different
carbon chain length in rats.
Kudo N, Suzuki E, Katakura M, Ohmori K,
Noshiro R, Kawashima Y.
Faculty of Pharmaceutical Sciences, Josai University, Keyakidai
1-1, Sakado, 350-0295, Saitama, Japan. naokudo@josai.ac.jp
Elimination in urine and feces was compared between four perfluorinated
fatty acids (PFCAs) with different
carbon chain length. In male rats, perfluoroheptanoic acid (PFHA)
was rapidly eliminated in urine with the proportion of 92% of
the dose being eliminated within 120 h after an intraperitoneal
injection. Perfluorooctanoic acid (PFOA), perfluorononanoic
acid (PFNA) and perfluorodecanoic acid (PFDA) was eliminated
in urine with the proportions of 55, 2.0 and 0.2% of the dose,
respectively. By contrast, four PFCAs were eliminated in feces
with the proportion of less than 5% of the dose within 120 h
after an injection. In female rats, the
proportions of PFOA and PFNA eliminated in urine within 120
h were 80% and 51% of the dose, respectively, which were significantly
higher compared with those in male rats. There
was the tendency that PFCA with longer carbon chain length is
less eliminated in urine in both male and female rats.
Fecal elimination of PFCAs was not different between PFCAs in
female rats and comparable to those in male rats. The rates
of biliary excretion of PFCAs in male rats were slower than
those in female rats. Sex-related difference
in urinary elimination of PFOA was abolished when male rats
had been castrated. On the contrary, treatment with testosterone
suppressed the elimination of PFOA in urine in both castrated
male rats and female rats.
The effect of testosterone was in a
time- and dose-dependent manner. These results suggest that
PFCAs are distinguished by their carbon chain length by a renal
excretion system, which is regulated by testosterone.
PMID: 11311214 [PubMed - indexed for MEDLINE]
| http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12805763&dopt=Abstract
ScientificWorldJournal.
2001 Nov 6;1(11):627-9.
Global
biomonitoring of perfluorinated organics.
Giesy
JP, Kannan K, Jones PD.
The
environmental distribution of fluorinated
organic compounds (FOCs) has been less well described
than the other halogenated hydrocarbons such as chlorinated
and brominated compounds. This is despite the fact that
FOCs have been used in a wide variety of products and
applications for more than 50 years. FOCs
are resistant to hydrolysis, photolysis, microbial degradation,
or metabolism by vertebrates due to the high energy
of carbon-fluorine bond. In particular, perfluorinated
(fully fluorinated) compounds (PFCs) have the potential
to persist in the environment. But, until recently,
the extent and magnitude of environmental distribution
of PFCs was unknown. Recent development of an analytical
technique for PFCs using high performance liquid chromatography-negative
ion electrospray tandem mass spectrometry (HPLC-ESMSMS)[1]
permitted the survey of PFCs in livers and blood plasma
of wildlife on a global scale[2].
PMID:
12805763 [PubMed - in process]
|
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11348064&dopt=Abstract
2001
Environ
Sci Technol Apr 1;35(7):1339-42
Global
distribution of perfluorooctane sulfonate in wildlife.
Giesy JP, Kannan K.
Department of Zoology, National Food Safety and Toxicology Center,
Institute for Environmental Toxicology, Michigan State University,
East Lansing 48824, USA. jgiesy@aol.com
Here we report, for the first time, on the global distribution
of perfluorooctanesulfonate (PFOS), a fluorinated organic contaminant.
PFOS was measured in the tissues of wildlife, including, fish,
birds, and marine mammals. Some of the species studied include
bald eagles, polar bears, albatrosses, and various species of
seals. Samples were collected from urbanized areas in North
America, especially the Great Lakes region and coastal marine
areas and rivers, and Europe. Samples were also collected from
a number of more remote, less urbanized locations such as the
Arctic and the North Pacific Oceans. The
results demonstrated that PFOS is widespread in the environment.
Concentrations of PFOS in animals from
relatively more populated and industrialized regions, such as
the North American Great Lakes, Baltic Sea, and Mediterranean
Sea,were greater than those in animals from remote marine locations.
Fish-eating, predatory animals such as
mink and bald eagles contained concentrations of PFOS that were
greater than the concentrations in their diets. This suggests
that PFOS can bioaccumulate to higher trophic levels of the
food chain. Currently available data indicate that
the concentrations of PFOS in wildlife are less than those required
to cause adverse effects in laboratory animals.
PMID: 11348064 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11329707&dopt=Abstract
2001
Environ
Sci Technol Apr 15;35(8):1593-8
Accumulation
of perfluorooctane sulfonate in marine
mammals.
Kannan K, Koistinen J, Beckmen K, Evans
T, Gorzelany JF, Hansen KJ, Jones PD, Helle E, Nyman M, Giesy
JP.
National Food Safety and Toxicology Center, Department of Zoology,
Institute of Environmental Toxicology, Michigan State University,
East Lansing, Michigan 48824, USA. kuruntha@msu.edu
Perfluorooctane sulfonate (PFOS) is a perfluorinated molecule
that has recently been identified in the sera of nonindustrially
exposed humans. In this study, 247 tissue samples from 15 species
of marine mammals collected from Florida, California, and Alaskan
coastal waters; and northern Baltic Sea; the Arctic (Spitsbergen);
and Sable Island in Canada were analyzed for PFOS. PFOS was
detected in liver and blood of marine mammals from most locations
including those from Arctic waters. The
greatest concentrations of PFOS found in liver and blood were
1520 ng/g wet wt in a bottlenose dolphin from Sarasota Bay,
FL, and 475 ng/mL in a ringed seal from the northern Baltic
Sea (Bothnian Sea), respectively. No age-dependent increase
in PFOS concentrations in marine mammals was observed in the
samples analyzed. The occurrence of PFOS in marine mammals from
the Arctic waters suggests widespread global distribution of
PFOS including remote locations.
PMID: 11329707 [PubMed - indexed for MEDLINE]
From
TOXNET
2000
Int J Toxicol 2000
Nov-Dec;19(6):35
Rat and
rabbit developmental toxicology studies with two perfluorinated
compounds administered orally.
York
RG Case MT Christian MS
Primedica Argus Research
Lab., Inc., Horsham, PA.
Developmental toxicology
(teratology) studies were done on two perfluorinated compounds--perfluorooctanesulfonate
(PFOS) and 2-(N-ethyl perfluoroctanesulfonamido)-ethyl alcohol
(N-EtFOSE). Dose selection for these oral developmental toxicity
studies were based upon dose-range study results. Dose levels
of 0, 1, 5, 10 and 20 mg/kg/day were used for the rat N-EtFOSE
study, and dose levels of 0, 0.1, 1.0, 2.5 and 3.75 mg/kg/day
were used for both the PFOS and the N-EtFOSE rabbit studies.
Although no compound-related deaths occurred in the dosed pregnant
females on the developmental toxicity studies, maternal toxicity
(reduced body weight gain and feed consumption) was present
at higher dose levels in all three studies. At high maternally
toxic doses, associated effects occurred in the conceptuses-increased
abortions in PFOS and N-EtFOSE rabbits, reduced fetal weights
in N-EtFOSE rats and PFOS rabbits, and increased late resorptions
in N-EtFOSE rabbits. Detailed external gross, soft tissue, and
skeletal fetal examinations failed to reveal any malformations
in either species. Similar results, i.e., only effects associated
with maternal toxicity, had been found in previously conducted
PFOS rat developmental toxicity studies. It was concluded that
these perfluorinated compounds were not selective developmental
toxicants in either rats or rabbits.
International Standard
Serial Number: 1091-5818
Publication Types:
MEETING ABSTRACT
From
TOXNET
2001
Toxicologist Mar;60(1):221-2
Oral
(gavage) cross-fostering study of potassium perfluorooctanesulfonate
(PFOS) in rats.
Case
MT, York RG, Butenhoff JL
3M,
Medical Department,
Corporate Toxicology, Saint Paul, MN.
Abstract: This study
was done to explore the cause of neonatal mortality in a prior
multi-generation reproduction/developmental study in rats. Groups
of female rats (25/group) were administered Potassium Perfluorooctanesulfonate
(PFOS) by daily oral intubation at dose levels of 0 or 1.6 mg/kg/day.
The female rats were dosed for 42 days prior to mating to untreated
males. After mating, dosing continued in the females throughout
gestation and the 21 days of lactation. At parturition, cross-fostering
was done by transferring each litter to another dam which had
delivered - no dam was allowed to raise its own litter. On day
of lactation 4, litters were culled to 10, with equal numbers
per sex where possible. Mean body weights were reduced in the
treated (1.6 mg/kg/day) females during the premating and gestation
periods. These body weight effects correlated with reduced food
consumption. Reduced pup survival occurred in two of the four
sub-groups as shown by the following data. Control dams X Control
pups had 3/191 (1.6%) pup deaths (single death in three litters).
Treated dams X Treated pups had 34/177 (19.2%) pup deaths (deaths
in 8 of 12 litters). Control dams X Treated pups had 16/166
(9.6%) pup deaths (deaths in 10 of 11 litters). Treated dams
X Control pups had 2/181 (1.1%) pup deaths (single death in
two litters). These data indicate that the reduced pup survival
observed in a prior PFOS rat multi-generation reproduction/developmental
study was a result of pup exposure in utero and not a result
of effects on the dam from exposure.
From
TOXNET
2001
- SUPPORT:
PERFLUOROOCTANESULFONATE
POTASSIUM SALT (PFOS): AN ACUTE ORAL TOXICITY STUDY WITH THE
HONEY BEE, W/ATTACHMENTS & COVER LETTER DATED
05/01/01
Corporate Name: CENTRAL
SCIENCE LAB
Source: EPA/OTS;
Doc #000811816P
CAS Registry Numbers:
2795-39-3
Order Number: NTIS/OTS020492912
Classification Code:
TSCA Sect. 8E Rec 05/04/01
Year of Publication:
2001
Secondary Source
ID: TSCATS/454358
From
TOXNET
2001
- SUPPORT:
LTR FR
3M TO USEPA W/TABULAR SUMMARY OF
DRAFT REPORT FROM A 2-YR DIETARY STDY OF POTASSIUM PERFLUOROOCTANESULFONATE
(PFOS) IN RATS, DATED 05-24-01
Corporate Name: COVANCE
LABS INC Source:
EPA/OTS; Doc
#000811819S
CAS Registry Numbers:
2795-39-3
Order Number: NTIS/OTS020492913
Classification Code:
TSCA Sect. 8E Rec 05/25/01
Year of Publication:
2001
Secondary Source
ID: TSCATS/454669
From
TOXNET
2001
- SUPPORT:
DETERMINATION
OF THE PRESENCE & CONCENTRATION OF POTASSIUM PERFLUOROOCTANESULFONATE
IN THE SERUM & LIVER OF SD RATS EXPOSED TO PFOS VIA GAVAGE,
W/CVR LTR DATED 09-05-01
Source: EPA/OTS;
Doc #000811826Q
CAS Registry Numbers:
2795-39-3
Order Number: NTIS/OTS020492913
Classification Code:
TSCA Sect. 8E Rec 09/10/01
Year of Publication:
2001
Secondary Source
ID: TSCATS/454672
From
TOXNET
2001
- SUPPORT:
REPORT
AMENDMENT 1: COMBINED ORAL FERTILITY, DEVELOPMENTAL, & PERINATAL/POSTNATAL
REPRODUCTION TOXICITY STUDY OF PFOS IN RATS, WITH COVER LETTER
DATED 09-05-01
Corporate Name: ARGUS
RES LABS
Source: EPA/OTS;
Doc #000811827R
CAS Registry Numbers:
2795-39-3
Order Number: NTIS/OTS020492913
Classification Code:
TSCA Sect. 8E Rec 09/10/01
Year of Publication:
2001
Secondary Source
ID: TSCATS/454673
From
TOXNET
2001
- SUPPORT:
DETERMINATION
OF PRESENCE & CONC OF PFOS, PFOSA, PFOSAA, & EtFOSE-OH IN SERA
& LIVER OF RATS EXPOSED TO N-EtFOSE W/COVER LETTER
DATED 09-05-01
Corporate Name: 3M
CO
Source: EPA/OTS;
Doc #000811829T
CAS Registry Numbers:
1691-99-2
Order Number: NTIS/OTS020492913
Classification Code:
TSCA Sect. 8E Rec 09/05/01
Year of Publication:
2001
Secondary Source
ID: TSCATS/454675
From
TOXNET
2001
- SUPPORT:
DETERMINATION
OF PRESENCE & CONC OF PFOS OR ANOTHER METABOLITE OF N-EtFOSE
IN SERA & LIVER SAMPLES, WITH COVER LETTER DATED
09-05-01
Source: EPA/OTS;
Doc #000811830L
CAS Registry Numbers:
1691-99-2
Order Number: NTIS/OTS020492913
Classification Code:
TSCA Sect. 8E Rec 09/10/01
Year of Publication:
2001
Secondary Source
ID: TSCATS/454676
From
TOXNET
2001
- SUPPORT:
DETERMINATION
OF THE PRESENCE & CONCENTRATION OF PFOS, PFOSA, M556, & M570
IN LIVER & SERA SAMPLES, WITH COVER LETTER DATED
09-05-01
Corporate Name: 3M
CO; PACE ANALYTICAL LAB INC
Source: EPA/OTS;
Doc #000811828S
CAS Registry Numbers:
24448-09-7
Order Number: NTIS/OTS020492913
Classification Code:
TSCA Sect. 8E Rec 09/05/01
Year of Publication:
2001
Secondary Source
ID: TSCATS/454674
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10779693&dopt=Abstract
2000
Biochim Biophys Acta May 1;1474(3):397-409
Presence
and inducibility of peroxisomes in a human glioblastoma cell
line.
Cimini A, Cristiano L, Bernardo A, Farioli-Vecchioli
S, Stefanini S, Ceru MP.
Department of Basic and Applied Biology, University of L'Aquila,
via Vetoio n. 10, 67010 Coppito (AQ), Italy.
We investigated the effect of the peroxisomal proliferator (PP)
perfluorodecanoic acid (PFDA),
alone or in combination with 9-cis-retinoic acid (RX) on the
human glioblastoma cell line Lipari (LI). Cell proliferation,
apoptotic rate, peroxisome morphology and morphometry, peroxisomal
enzyme activities and the presence of peroxisome proliferator-activated
receptors (PPARs) were examined. We show
that PFDA alone produces pleiotropic effects on LI cells
and that RX enhances some of these effects. Peroxisomal number
and relative volume, as well as palmitoyl-CoA oxidase activity
and protein, are increased by PFDA treatment, with a synergistic
effect by RX. The latter, alone or in association with PFDA,
induces catalase activity and protein, increases apoptosis and
decreases cell proliferation. PPAR isotypes alpha and gamma
were detected in LI cells. While the former is apparently unaffected
by either treatment, the latter increases in response to PFDA,
independent of the presence of RX. The results of this study
are discussed in terms of PPARalpha activation and PPARgamma
induction by PFDA, by either a direct or an indirect mechanism.
PMID: 10779693 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10965884&dopt=Abstract
2000
Endocrinology Sep;141(9):3137-48
The
peroxisome proliferator perfluorodecanoic acid inhibits the
peripheral-type benzodiazepine receptor (PBR) expression and
hormone-stimulated mitochondrial cholesterol transport and steroid
formation in Leydig cells.
Boujrad N, Vidic B, Gazouli M, Culty M,
Papadopoulos V.
Department of Cell Biology, Georgetown University Medical Center,
Washington, DC 20007, USA.
The peroxisome proliferator perfluordecanoic
acid (PFDA) has been shown to exert an antiandrogenic
effect in vivo by acting directly on the interstitial Leydig
cells of the testis. The objective of this study
was to examine the in vitro effects of PFDA and identify its
site of action in steroidogenesis using as model systems the
mouse tumor MA-10 and isolated rat Leydig cells. PFDA inhibited
in a time- and dose-dependent manner the hCG-stimulated Leydig
cell steroidogenesis. This effect was localized at the level
of cholesterol transport into the mitochondria. PFDA did not
affect either the total cell protein synthesis or the mitochondrial
integrity. Moreover, it did not induce any DNA damage. Morphological
studies indicated that PFDA induced lipid accumulation in the
cells, probably due to the fact that cholesterol mobilized by
hCG did not enter the mitochondria to be used for steroidogenesis.
In search of the target of PFDA, we examined its effect on key
regulatory mechanisms of steroidogenesis. PFDA did not affect
the hCG-induced steroidogenic acute regulatory protein (StAR)
levels. However, it was found to inhibit the mitochondrial peripheral-type
benzodiazepine receptor (PBR) ligand binding capacity, 18-kDa
protein, and messenger RNA (mRNA) levels. Further studies indicated
that PFDA did not affect PBR transcription, but it rather accelerated
PBR mRNA decay. Taken together, these
data suggest that PFDA inhibits the Leydig cell steroidogenesis
by affecting PBR mRNA stability, thus inhibiting PBR expression,
cholesterol transport into the mitochondria, and the subsequent
steroid formation. Moreover, this action of PFDA on PBR
mRNA stability indicates a new mechanism of action of peroxisome
proliferators distinct from the classic transcription-mediated
regulation of target genes.
PMID: 10965884 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11091278&dopt=Abstract
2000
Clin Exp Immunol Nov;122(2):219-26
Effects
of peroxisome proliferators on the thymus
and spleen of mice.
Yang Q, Xie Y, Depierre JW.
Department of Biochemistry, Stockholm University, Sweden. Qian@tuborg.biokemi.su.se
The effects of peroxisome proliferators on the immune system
of male C57B1/6 mice have been investigated. Significant
atrophy of the thymus and spleen was observed in animals treated
with potent peroxisome proliferators (e.g. perfluorooctanoic
acid (PFOA), di(2-ethylhexyl)phthalate (DEHP), Wy-14643
and nafenopin), whereas the effects of a moderate peroxisome
proliferator (i.e. acetylsalicylic acid (ASA)) were relatively
weak. The time course of thymic and splenic
atrophy caused by PFOA was found to resemble the time course
of the increase in liver weight and of peroxisome proliferation.
Analysis of the numbers and phenotypes of thymocytes and splenocytes
from PFOA-treated mice revealed the following:
(i) the numbers of thymocytes and splenocytes were decreased
> 90% and about 50%, respectively, by PFOA treatment;
(ii) although all populations of thymocytes were decreased,
the immature CD4+CD8+ population was decreased most dramatically;
(iii) the numbers of both T and B cells in the spleen were decreased
by PFOA treatment.
Analysis of the cell cycle of thymocytes indicated that the
thymic atrophy caused by PFOA in mice results, at least in part,
from inhibition of thymocyte proliferation. Interestingly, in
vitro exposure to PFOA for up to 24 h did not produce analogous
effects in either thymocytes or splenocytes. Thus, the thymic
and splenic atrophy caused by PFOA appears to involve an indirect
pathway.
PMID: 11091278 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11071397&dopt=Abstract
2000
Drug Chem Toxicol Nov;23(4):603-20
Plasma
cholecystokinin and hepatic enzymes, cholesterol and lipoproteins
in ammonium perfluorooctanoate production workers.
Olsen GW, Burris JM, Burlew MM, Mandel
JH.
Medical Department,
3M Company, St. Paul, MN 55144-1000, USA.
Ammonium perfluorooctanoate is a potent synthetic surfactant
used in industrial applications. It rapidly dissociates in biologic
media to perfluorooctanoate [CF3(CF2)6CO2-], which is the anion
of perfluorooctanoic acid [PFOA, CF3(CF2)6COOH].
PFOA is a peroxisome proliferator known to increase the incidence
of hepatic, pancreas and Leydig cell adenomas in rats.
The pancreas acinar cell adenomas may be the consequence of
a mild but sustained increase of cholecystokinin as a result
of hepatic cholestasis. Although no significant clinical hepatic
toxicity was observed, PFOA was reported to have modulated hepatic
responses to obesity and alcohol consumption among production
workers. To further assess these hypotheses, we examined medical
surveillance data of male workers involved in ammonium perfluorooctanoate
production in 1993 (n=111), 1995 (n=80) and 1997 (n=74). Serum
PFOA was measured by high-performance liquid chromatography
mass spectrometry methods. Plasma cholecystokinin was measured
(only in 1997) by the use of direct radioimmunoassay. Serum
biochemical tests included hepatic enzymes, cholesterol and
lipoproteins. Serum PFOA levels, by year, were: 1993 (mean 5.0
ppm, SD 12.2, median 1.1 ppm, range 0.0-80.0 ppm); 1995 (mean
6.8 ppm, SD 16.0, median 1.2 ppm, range 0.0-114.1 ppm); and
1997 (mean 6.4 ppm, SD 14.3, median 1.3 ppm, range 0.1-81.3
ppm). Cholecystokinin values (mean 28.5 pg/ml, SD 17.1, median
22.7 pg/ml, range 8.8-86.7 pg/ml) approximated the assay's reference
range (up to 80 pg/ml) for a 12 hour fast and were negatively,
not positively, associated with employees' serum PFOA levels.
Our findings continue to suggest there is no significant clinical
hepatic toxicity associated with PFOA levels as measured in
this workforce. Unlike a previously reported observation, PFOA
did not appear to modulate hepatic responses to either obesity
or alcohol consumption. Limitations of these findings include:
1) the cross-sectional design as only 17 subjects were common
for the three surveillance years;
2) the voluntary participation that ranged between 50 and 70
percent; and
3) the few subjects with serum levels > or = 10 ppm.
PMID: 11071397 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10670823&dopt=Abstract
2000
Chem Biol Interact Jan 15;124(2):119-32
Induction
by perfluorinated fatty acids with different carbon chain length
of peroxisomal beta-oxidation in the liver of rats.
Kudo N, Bandai N, Suzuki E, Katakura M,
Kawashima Y.
Faculty of Pharmaceutical Sciences, Josai University, Sakado,
Saitama, Japan.
The potency of the induction of peroxisomal beta-oxidation was
compared between perfluorinated fatty acids (PFCAs)
with different carbon chain lengths in the liver of male and
female rats. In male rats, perfluoroheptanoic acid (PFHA) has
little effect, although perfluorooctanoic acid (PFOA), perfluorononanoic
acid (PFNA) and perfluorodecanoic acid (PFDA) potentially induced
the activity. By contrast, PFHA and PFOA did not induce the
activity of peroxisomal beta-oxidation in the liver of female
rats while PFNA and PFDA effectively induced the activity. The
induction of the activity by these PFCAs was in a dose-dependent
manner, and there is a highly significant correlation between
the induction and hepatic concentrations of PFCAs in the liver
regardless of their carbon chain lengths. These results strongly
suggest that the difference in their chemical structure is not
the cause of the difference in the potency of the induction.
Hepatic concentrations of PFOA and PFNA was markedly higher
in male compared with female rats. Castration of male rats reduced
the concentration of PFNA in the liver and treatment with testosterone
entirely restored the reduction. In contrast to the results
obtained from the in vivo experiments, the activity of peroxisomal
beta-oxidation was induced by PFDA and PFOA to the same extent
in cultured hepatocytes prepared from both male and female rats.
These results, taken together, indicate that difference in accumulation
between PFCAs in the liver was responsible for the different
potency of the induction of peroxisomal beta-oxidation between
PFCAs with different carbon chain lengths and between sexes.
PMID: 10670823 [PubMed - indexed for MEDLINE]
From
TOXNET
2000
SUPPORT:
PFOS:
A DIETARY LC50 STUDY WITH THE NORTHERN BOBWHITE WITH COVER LETTER
DATED 04-25-00
Corporate Name: WILDLIFE
INTL, LTD
Source: EPA/OTS;
Doc
#8EHQ-0800-0373
CAS Registry Numbers:
1763-23-1
Order Number: NTIS/OTS020492910
Classification Code:
TSCA Sect. 8E Rec 08/21/00
Year of Publication:
2000
Secondary Source
ID: TSCATS/454171
From
TOXNET
2000
- SUPPORT:
PROTOCOL
& REPORT OF DATA FOR EXPLORATORY 28-DAY ORAL TOXICITY STUDY
IN RATS: TELOMER ALCOHOL, TELOMER ACRYLATE, [ ], PFHS, PFOS,
W/ ATTACHMENTS, CVR LTR
DATED 05-04-00
Corporate Name: 3M
ENVIRONMENTAL LAB
Source:
EPA/OTS; Doc #8EHQ-0800-0373
Registry Numbers:
355-46-4
1763-23-1
Order Number: NTIS/OTS020492910
Classification Code:
TSCA Sect. 8E Rec 08/21/00
Year of Publication:
2000
Secondary Source
ID: TSCATS/454192
From
TOXNET
2001
- SUPPORT:
DETERMINATION
OF PRESENCE & CONC OF PFOS, M556, PFOSAA, & PFOSA IN LIVERS
& PFOS, M556, PFOSAA, PFOSA, & EtFOSE-OH IN SERA OF EtFOSE-OH
EXPOSED RATS, W/CVR LTR DATED 09-10-01
Corporate Name: 3M
CO & BATTELLE COLUMBUS LABS
Source:
EPA/OTS; Doc #000811825P
CAS Registry Numbers:
754-91-6
1691-99-2
1869-77-8
2795-39-3
Order Number: NTIS/OTS020492913
Classification Code:
TSCA Sect. 8E Rec 09/10/01
Year of Publication:
2001
Secondary Source
ID: TSCATS/454671
From
TOXNET
2000
- SUPPORT:
LETTER
FROM 3M TO USEPA RE SUPPL REPORTS RELATED TO PREV SUBMS 8EHQ-0998-373,
374, & 394 PFOS 2-GEN REPROD STUDY, W/ATTCHMTS (INCLD'G AMENDED
FINAL REPORT) DATED 04-20-00
Source: EPA/OTS;
Doc #000811782R
CAS Registry Numbers:
1691-99-2
2795-39-3
Order Number: NTIS/OTS0204929-9
Classification Code:
TSCA Sect. 8E Rec 04/26/00
Year of Publication:
2000
Secondary Source
ID: TSCATS/44
From
TOXNET
2000
- SUPPORT:
ORAL
(STOMACH TUBE) DEVELOPMENTAL TOXICITY STUDY OF PFOS IN RABBITS
WITH ATTACHMENTS & COVER LETTER DATED
04-25-00
Corporate Name: ARGUS
RES LABS
Source: EPA/OTS;
Doc #8EHQ-0800-0373
CAS Registry Numbers:
1763-23-1
Order Number: NTIS/OTS020492910
Classification Code:
TSCA Sect. 8E Rec 08/21/00
Year of Publication:
2000
Secondary Source
ID: TSCATS/454168
From
TOXNET
2000
- SUPPORT:
SUMMARY
REPORT: 104-WK DIETARY CHRONIC TOX & CARCINOGENICITY STUDY W/PERFLUOROOCTANE
SULFONIC ACID POTASSIUM SALT (PFOS: T-6295) IN RATS WITH CVR
LTR
DATED 05-04-00
Corporate
Name: COVANCE
Source: EPA/OTS;
Doc #8EHQ-0800-0373
CAS Registry Numbers:
2795-39-3
Order Number: NTIS/OTS020492910
Classification Code:
TSCA Sect. 8E Rec 08/21/00
Year of Publication:
2000
Secondary Source
ID: TSCATS/454174
From
TOXNET
2000
- SUPPORT:
26-WK
CAPSULE TOXICITY STUDY W/PERFLUOROOCTANE SULFONIC ACID POTASSIUM
SALT (PFOS; T-6295) IN CYNOMOLGOUS MONKEYS WITH COVER LETTER
DATED 05-04-00
Corporate Name: COVANCE
LABS
Source: EPA/OTS;
Doc #8EHQ-0800-0373
CAS Registry Numbers:
1763-23-1
Order Number: NTIS/OTS020492910
Classification Code:
TSCA Sect. 8E Rec 08/21/00
Year of Publication:
2000 Secondary Source ID: TSCATS/454175
From
TOXNET
2000
- SUPPORT:
FLUOROCHEMICALS
IN NAIVE RATS: INVESTIGATING THE BACKGROUND SERUM & LIVER PFOS
LEVELS IN NAIVE RATS FR DIFFERENT SOURCES, WITH COVER LETTER
DATED 05-04-00
Source: EPA/OTS;
Doc #8EHQ-0800-0373
CAS Registry Numbers:
1763-23-1
Order Number: NTIS/OTS020492910
Classification Code:
TSCA Sect. 8E Rec 08/21/00
Year of Publication:
2000
Secondary Source
ID: TSCATS/454178
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