PFOS Exposure Research Articles

Chronic zebrafish PFOS exposure alters sex ratio and maternal related effects in F1 offspring

Perfluorooctanesulfonic acid (PFOS) is an organic contaminant ubiquitous in the environment, wildlife, and humans. Few studies have assessed its chronic toxicity on aquatic organisms. The present study defined the effects of long-term exposure to PFOS on zebrafish development and reproduction. Specifically, zebrafish at 8 h postfertilization (hpf) were exposed to PFOS at 0, 5, 50, and 250 µg/L for five months. Growth suppression was observed in the 250 µg/L PFOS-treated group. The sex ratio was altered, with a significant female dominance in the high-dose PFOS group. Male gonad development was also impaired in a dose-dependent manner by PFOS exposure. Although female fecundity was not impacted, the F1 embryos derived from high-dose exposed females paired with males without PFOS exposure developed severe deformity at early development stages and resulted in 100% larval mortality at 7 d postfertilization (dpf). Perfluorooctanesulfonic acid quantification in embryos indicated that decreased larval survival in F1 offspring was directly correlated to the PFOS body burden, and larval lethality was attributable to maternal transfer of PFOS to the eggs. Lower-dose parental PFOS exposure did not result in decreased F1 survival; however, the offspring displayed hyperactivity of basal swimming speed in a light-to-dark behavior assessment test. These findings demonstrate that chronic exposure to PFOS adversely impacts embryonic growth, reproduction, and subsequent offspring development.

Tissue bioaccumulation patterns, xenobiotic biotransformation and steroid hormone levels in Atlantic salmon ( Salmo salar) fed a diet containing perfluoroactane sulfonic or perfluorooctane carboxylic acids

In the present study, groups of juvenile Atlantic salmon ( Salmo salar) were fed gelatine capsules containing fish-food spiked with PFOA or PFOS (0.2 mg kg −1 fish) and solvent (methanol). The capsules were given at days 0, 3 and 6. Blood, liver and whole kidney samples were collected prior to exposure (no solvent control), and at days 2, 5, 8 and 14 after exposure (Note: that day 14 after exposure is equal to 7 d recovery period). We report on the differences in the tissue bioaccumulation patterns of PFOS and PFOA, in addition to tissue and compound differences in modulation pattern of biotransformation enzyme genes. We observed that the level of PFOS and PFOA increased in the blood, liver and kidney during the exposure period. Different PFOS and PFOA bioaccumulation patterns were observed in the kidney and liver during exposure- and after the recovery periods. Particularly, after the recovery period, PFOA levels in the kidney and liver tissues were almost at the control level. On the contrary, PFOS maintained an increase with tissue-specific differences, showing a higher bioaccumulation potential (also in the blood), compared with PFOA. While PFOS and PFOA produced an apparent time-dependent increase in kidney CYP3A, CYP1A1 and GST expression, similar effects were only temporary in the liver, significantly increasing at sampling day 2. PFOA and PFOS exposure resulted in significant decreases in plasma estrone, testosterone and cortisol levels at sampling day 2, and their effects differed with 17α-methyltestostrerone showing significant decrease by PFOA (also for cholesterol) and increase by PFOS. PFOA significantly increased estrone and testosterone, and no effects were observed for cortisol, 17α-methyltestosterone and cholesterol at sampling day 5. Overall, the changes in plasma steroid hormone levels parallel changes in CYP3A mRNA levels. Given that there are no known studies that have demonstrated such tissue differences in bioaccumulation patterns with associated differences in toxicological responses in any fish species or lower vertebrate, the present findings provide some potential insights and basis for a better understanding of the possible mechanisms of PFCs toxicity that need to be studied in more detail.

Retrospective Exposure Estimation for Perfluorooctanoic Acid (PFOA) for Participants in the C8 Health Project

O-30A6-2 Background/Aims: The primary source of PFOA in the environment of eastern Ohio and western West Virginia is believed to be the Washington Works facility. Percolation of deposited PFOA through the soil and pumping by industrial and municipal wells near the contaminated Ohio River is thought to explain elevated well water concentrations and human serum concentrations measured in recent years. Our objective is to estimate historical PFOA exposures and serum concentrations experienced by each of about 45,276 non-occupationally exposed participants in the C8 Health Project, based on their residential histories. Methods: We linked several environmental fate and transport models including AERMOD, PRZM3, BREZO, MODFLOW, and MT3D to simultaneously model PFOA air dispersion, transit through the unsaturated soil zone, surface water transport, and groundwater flow and transport. Annual PFOA exposure rates were estimated for each individual based on predicted calibrated water concentrations and predicted air concentrations, and default assumptions from the EPA Exposure Factors Handbook. Self-reported municipal water sources were verified using geocoded addresses and historical water distribution network maps for 6 municipal water districts. Individual exposure estimates were coupled with a one-compartment pharmacokinetic model to estimate annual serum PFOA concentrations. Results: Predicted water concentrations were within 2.3 times the observed mean water concentrations for all 6 municipal water districts. Predicted and observed median serum concentrations in 2005–2006 are 28.2 and 24.3 ppb, respectively (Spearman's rho = 0.66). Stratified by municipal water source at the time of the serum sample, Spearman rho ranges from 0.19 to 0.34. Conclusion: State-of-the-art fate and transport models provide the most defensible retrospective exposure estimates for epidemiologic studies when historical environmental measurements are lacking but source emissions rates are known. Our models predict recently observed municipal water PFOA concentrations and human serum PFOA concentrations surprisingly well, and will be used in a variety of epidemiologic studies being conducted in this region.

Effect of perfluorooctanesulfonate on osmoregulation in marine fish, Sebastesschlegeli, under different salinities

Effect of potassium salt of perfluorooctane sulfonic acid (PFOS) on the osmoregulation of marine teleost (blackrock fish), Sebastes schlegeli, was investigated under varying salinities, by monitoring serum osmolality, Na +, K +, Cl −, Ca 2+ and Mg 2+ concentrations in serum, serum glucose, and gill Na +–K + ATPase (NKA) activity. The fish was acclimatized to four salinity levels (10, 17.5, 25, and 34 psu) for 2 weeks before a 6-d exposure to 100 or 1000 μg L −1 of PFOS. Six fish from each exposure group were sampled at 24, 48, and 144 h after exposures, and serum, liver and gills were collected for analysis. NKA activity decreased by 34% and 31% relative to control at salinity levels of 25 and 34 psu, respectively, following exposure to 1000 μg L −1 PFOS. PFOS did not affect serum osmolality, Na +, Cl −, Ca 2+ and Mg 2+ concentrations; however, serum K + concentration increased during initial exposure period and then decreased after 144 h. Serum glucose levels decreased with increasing PFOS concentrations, implying high energy demand in response to exposure. Overall, PFOS exposure impaired NKA activity, altered potassium ion concentrations in serum, and reduced serum glucose levels while no other effects on serum concentrations of ionic salts were observed.

Temporal Trends of Perfluorinated Surfactants in Swedish Peregrine Falcon Eggs (Falco peregrinus), 1974−2007

Perfluorinated alkyl substances (PFAS) are today known to be globally distributed environmental contaminants. In the present study, concentrations of PFAS were analyzed in Swedish peregrine falcon eggs (Falco peregrinus), collected between 1974 and 2007. Analytes included in the study were perfluorinated carboxylates (PFCAs; carbon chain lengths C6-C15), perfluorinated sulfonates (PFSAs; C4, C6, C8, and C10), and perfluorooctane sulfonamide (PFOSA). The predominant PFAS was perfluorooctane sulfonate, PFOS (83 ng/g wet weight (w wt) mean concentration in samples from 2006), followed by perfluorotridecanoate, PFTriA (7.2 ng/g w wt) and perfluoroundecanoate, PFUnA (4.2 ng/g w wt). PFCA concentrations increased exponentially over the studied time. In contrast, concentrations of PFOS and perfluorohexane sulfonate (PFHxS) increased initially but leveled off after the mid 1980s. This is different from previously observed temporal trends in marine organisms. The present study is the first to establish temporal trends for PFAS in terrestrial biota. The results indicate potential differences between marine and terrestrial biota regarding sources of PFAS exposure and response to emission changes. The toxicological implications of PFAS exposure for the falcons are not known, but according to recent findings impaired hatching success and sublethal toxicological effects from PFOS exposure in the Swedish peregrine falcon cannot be ruled out.

PFCs and Cholesterol: A Sticky Connection

Vol. 118, No. 2 NewsOpen AccessPFCs and Cholesterol: A Sticky Connection Tanya TillettMA Tanya Tillett Search for more papers by this author Published:1 February 2010https://doi.org/10.1289/ehp.118-a81bCited by:2AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Polyfluoroalkyl chemicals (PFCs), highly stable compounds used in consumer items such as food packaging, textiles, and paper products, are known to migrate throughout and persist in the environment. Animal studies have described the development of adverse health effects such as tumors and developmental delays with exposure to the PFCs perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). A new study now suggests these and other PFCs may affect serum cholesterol levels in humans [EHP118:197–202; Nelson et al.].Elevated cholesterol levels are associated with an increased risk of cardiovascular disease, and are one of the conditions that define metabolic syndrome. Risk factors for high cholesterol include diet, low physical activity, and a family history of the condition, but increasing evidence indicates some environmental chemicals also may contribute. With estimated half-lives of up to 8.5 years, PFCs are classified as persistent organic pollutants (POPs). However, unlike most POPs, which are stored primarily in fat tissue, PFCs persist by forming chemical bonds to proteins in the liver and serum.Previous studies in humans have reported positive associations between PFOS and PFOA exposures and higher cholesterol levels. The research team in the current study investigated the relationship between insulin resistance, cholesterol levels, body size, and exposure to two less studied PFCs, perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) in addition to PFOS and PFOA. The study used data from the 2003–2004 National Health and Nutrition Examination Survey.The authors found a positive association between total cholesterol (TC) and serum concentrations of PFOS, PFOA, and PFNA. TC is the sum of low-density and very low-density lipoproteins (“bad” cholesterol) and high-density lipoproteins (“good” cholesterol). The findings appeared driven by an increase in the non–high-density lipoprotein fraction of TC, and the association was most pronounced for PFNA. In contrast, PFHxS concentrations were inversely related to TC: samples reflecting the highest PFHxS exposure had the lowest TC levels.The authors observed little evidence of associations between body size, insulin resistance, and PFC concentrations. They note several limitations in this study, including the fact they could not rule out the possibility of reverse causality—that is, that having higher cholesterol levels could lead to increased PFC concentrations in the blood. Nevertheless, the results support previous epidemiologic research indicating that environmentally relevant exposures to PFCs may affect human cholesterol metabolism or homeostasis.Certain environmental chemicals may be a risk factor for high cholesterol.FiguresReferencesRelatedDetailsCited by Kim S, Shin H, Lee Y and Cho H (2017) Sex-specific risk assessment of PFHxS using a physiologically based pharmacokinetic model, Archives of Toxicology, 10.1007/s00204-017-2116-5, 92:3, (1113-1131), Online publication date: 1-Mar-2018. Kim S, Heo S, Lee D, Hwang I, Lee Y and Cho H (2016) Gender differences in pharmacokinetics and tissue distribution of 3 perfluoroalkyl and polyfluoroalkyl substances in rats, Food and Chemical Toxicology, 10.1016/j.fct.2016.09.017, 97, (243-255), Online publication date: 1-Nov-2016. Vol. 118, No. 2 February 2010Metrics About Article Metrics Publication History Originally published1 February 2010Published in print1 February 2010 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Exposure to Polyfluoroalkyl Chemicals and Cholesterol, Body Weight, and Insulin Resistance in the General U.S. Population

BackgroundPolyfluoroalkyl chemicals (PFCs) are used commonly in commercial applications and are detected in humans and the environment worldwide. Concern has been raised that they may disrupt lipid and weight regulation.ObjectivesWe investigated the relationship between PFC serum concentrations and lipid and weight outcomes in a large publicly available data set.MethodsWe analyzed data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES) for participants 12–80 years of age. Using linear regression to control for covariates, we studied the association between serum concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) and measures of cholesterol, body size, and insulin resistance.ResultsWe observed a positive association between concentrations of PFOS, PFOA, and PFNA and total and non-high-density cholesterol. We found the opposite for PFHxS. Those in the highest quartile of PFOS exposure had total cholesterol levels 13.4 mg/dL [95% confidence interval (CI), 3.8–23.0] higher than those in the lowest quartile. For PFOA, PFNA, and PFHxS, effect estimates were 9.8 (95% CI, −0.2 to 19.7), 13.9 (95% CI, 1.9–25.9), and −7.0 (95% CI, −13.2 to −0.8), respectively. A similar pattern emerged when exposures were modeled continuously. We saw little evidence of a consistent association with body size or insulin resistance.ConclusionsThis exploratory cross-sectional study is consistent with other epidemiologic studies in finding a positive association between PFOS and PFOA and cholesterol, despite much lower exposures in NHANES. Results for PFNA and PFHxS are novel, emphasizing the need to study PFCs other than PFOS and PFOA.

Combined effects of polyfluorinated and perfluorinated compounds on primary cultured hepatocytes from rare minnow ( Gobiocypris rarus) using toxicogenomic analysis

Polyfluorinated and perfluorinated compounds (PFCs) are used in numerous commercial products and have been ubiquitously detected in the environment as well as in the blood of humans and wildlife. To assess the combined effects caused by PFCs in mixtures, gene expression profiles were generated using a custom cDNA microarray to detect changes in primary cultured hepatocytes of rare minnows exposed to six individual PFCs (perfluorooctanoic acid, perfluorononanoic acid, perfluorodecanoic acid, perfluorododecanoic acid, perfluorooctane sulfonate, and 8:2 fluorotelomer alcohol) and four formulations of the PFCs mixtures. Mixtures as well as individual compounds consistently regulated a particular gene set, which suggests that these conserved genes may play a central role in the toxicity mediated by PFCs. Specifically, a number of genes regulated by the mixtures were identified in this study, which were not affected by exposure to any single component. These genes are implicated in multiple biological functions and processes, including fatty acid metabolism and transport, xenobiotic metabolism, immune responses, and oxidative stress. More than 80% of the altered genes in the PFOA- and PFOS-dominant mixture groups were of the same gene set, while the gene expression profiles from single PFOA and PFOS exposures were not as similar. This work contributes to the development of toxicogenomic approaches in combined toxicity assessment and allows for comprehensive insights into the combined action of PFCs mixtures in multiple environmental matrices.

Perfluoroalkyl Contaminants in an Arctic Marine Food Web: Trophic Magnification and Wildlife Exposure

To better understand the bioaccumulation behavior of perfluoroalkyl contaminants (PFCs), we conducted a comparative analysis of PFCs and lipophilic organohalogens in a Canadian Arctic marine food web. Concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctansulfoamide (PFOSA), and C7-C14 perfluorocarboxylic acids (PFCAs) ranged between 0.01 and 0.1 ng x g(-1) dry wt in sediments and 0.1 and 40 ng x g(-1) wet wt in biota, which was equivalent to or higher than levels of PCBs, PBDEs, and organochlorine pesticides. In beluga whales, PFOS and PFCA concentrations were higher (P < 0.05) in protein-rich compartments (liver and blood), compared to other tissues/fluids (milk, blubber, muscle, and fetus). In the marine mammalian food web, concentrations of PFOSA and lipophilic organochlorines (ng x g(-1) lipid equivalent) and proteinophilic substances (i.e., PFOS and C8-C14 PFCAs, ng x g(-1) protein) increased significantly (P < 0.05) with trophic level. Trophic magnification factors (TMFs) of organochlorines ranged between 5 and 14 and exhibited significant curvilinear relationships (P < 0.05) with octanol-water and octanol-air partition coefficients (KOW, KOA). TMFs of perfluorinated acids (PFAs) ranged between 2 and 11 and exhibited similar correlation (P < 0.05) with protein-water and protein-air partition coefficients (KPW, KPA). PFAs did not biomagnify in the aquatic piscivorous food web (TMF range: 0.3-2). This food web specific biomagnification behavior was attributed to the high aqueous solubility and low volatility of PFAs. Specifically, the anticipated phase-partitioning of these proteinophilic substances, represented by their protein-water (KPW) and protein-air (KPA) partition coefficients, likely results in efficient respiratory elimination in water-respiring organisms but very slow elimination and biomagnification in air-breathing animals. Lastly, the results indicate that PFOS exposure in nursing Hudson Bay beluga whale calves (CI95 range = 2.7 x 10(-5) to 1.8 x 10(-4) mg x kg bw(-1) x d(-1)), exceedsthe oral reference dose for PFOS (7.5 x 10(-5) mg x kg bw(-1) x d(-1)), which raises concern for potential biological effects in these and other sensitive Arctic marine wildlife species.

Consequences of prenatal PFOA exposure on mouse mammary gland growth and development in F1 and F2 offspring

Consequences of prenatal PFOA exposure on mouse mammary gland growth and development in F1 and F2 offspring

Perfluorooctane sulfonate-induced changes in fetal rat liver gene expression

In utero exposure of laboratory rats to perfluorooctane sulfonate (PFOS, C 8F 17SO 3 −), a chemically stable surfactant that is widely disseminated in the environment and present in serum samples from wildlife and humans, is associated with decreased neonatal survival, and growth deficits as well as hepatomegaly. This hepatomegaly in newborn rats exposed to PFOS in utero resembles that observed in adults and is characterized by peroxisome proliferation and decreased liver triglycerides, both of which are suspected to be manifested through PPARα-mediated transcriptional regulation. The purpose of the present investigation was to determine whether these changes in metabolic status are a reflection of transcriptional changes in fetal rat liver using global gene expression array analyses. Gravid Sprague–Dawley rats were administered 3 mg/kg PFOS by gavage daily from gestational day 2–20 and terminated on day 21. Although there was no treatment-related frank terata, there was a substantial effect of PFOS on the perinatal hepatic transcriptome—225 unique transcripts were identified as statistically increased and 220 decreased by PFOS exposure; few transcripts were changed by more than two-fold. Although the PPARα transcript (Ppara) itself was not affected, there was a significant increase in expression of gene transcripts associated with hepatic peroxisomal proliferation as well as those responsible for fatty acid activation, transport and oxidation pathways (both mitochondrial and peroxisomal). Additional metabolic pathways altered by in utero PFOS exposure were a stimulation of fetal hepatic fatty acid biosynthesis and a net reduction of Cyp7a1 transcript, which is required for bile acid synthesis. There were minimal effects on the expression of thyroid-related gene transcripts. In conclusion, gene expression analysis provides strong evidence indicating transcriptional control of the altered metabolic status of neonates following PFOS exposure in utero, much of which appears to be under the influence of a functional perinatal PPARα regulatory pathway.

Transcriptional effects of PFOS in isolated hepatocytes from Atlantic salmon Salmo salar L.

The main aim of the current in vitro experiment was to search for makers for PFOS exposure in isolated hepatocytes from Atlantic salmon Salmo salar, based on genes responding to PFOS exposure in other animals. Primary cell cultures of hepatocytes were exposed to four concentrations of PFOS (2.1–6.2–15.1–25.0 mg/L) for 24 and 48 h and the transcriptional levels of 12 genes encoding proteins known to respond to PFOS were quantified with real-time RT-PCR. The 12 examined genes were caspase 3B (apoptosis), GSH-Px and HSP70 (cellular stress), CYP1A, CYP3A, GST and UGT (P450 and phase II enzymes), acyl-CoA oxidase, PPARα, PPARβ and PPARγ (lipid metabolism) and Na +–K +-ATPase (ion regulation). Most of the studied genes responded in a dose-dependent manner to PFOS exposure, although the transcriptional differences in general where small with regard to fold change. Our results clearly suggest that PFOS exposure enhanced cellular stress in the examined cells, even though the exact mechanisms behind this stress remain unknown. The results from this in vitro experiment showed that genes known to be affected by PFOS exposure in other species also were induced in hepatocytes of Atlantic salmon, giving us the rationale to expand to testing the actual in vivo magnitude of effect in Atlantic salmon exposed to PFOS at doses usually seen in nature/diets.

Perfluorooctanoic Acid–Induced Immunomodulation in Adult C57BL/6J or C57BL/6N Female Mice

BackgroundPerfluorooctanoic acid (PFOA), an environmentally persistent compound of regulatory concern, has been reported to reduce antibody responses in mice at a single dose.ObjectiveThe aim of this study was to evaluate PFOA effects on humoral and cellular immunity using standard assays for assessing immune function, and to derive dose–response data.MethodsC57BL/6J mice received 0 or 30 mg PFOA/kg/day for 10 days; half of the exposed groups were switched to vehicle and half continued on PFOA for five days. C57BL/6N mice received 0–30 mg/kg/day of PFOA in drinking water for 15 days. Mice were immunized with sheep red blood cells or sensitized to bovine serum albumin in Freund’s complete adjuvant on day 10 of exposure; immune responses were determined 1 day post-exposure.ResultsWe found that 30 mg PFOA/kg/day given for 10 or 15 days reduced IgM synthesis; serum collected 1 day postexposure contained 8.4 × 104 or 2.7 × 105 ng PFOA/mL, respectively. IgM synthesis was suppressed at exposures ≥ 3.75 mg PFOA/kg/day in a dose-dependent manner, and IgG titers were elevated at 3.75 and 7.5 mg PFOA/kg/day. Serum PFOA at 3.75 mg/kg/day was 7.4 × 104 ng/mL 1 day postexposure, or 150-fold greater than the levels reported in individuals living near a PFOA production site. Using a second-degree polynomial model, we calculated a benchmark dose of 3 mg/kg/day, with a lower bound (95% confidence limit) of 1.75 mg/kg/day. Cell-mediated function was not affected.ConclusionsIgM antibodies were suppressed after PFOA exposure. The margin of exposure for reduced IgM antibody synthesis was approximately 150 for highly exposed human populations.

Community Exposure to Perfluorooctanoate: Relationships Between Serum Concentrations and Exposure Sources

The objective of this study was to determine serum (perfluorooctanoate [PFOA]) in residents near a fluoropolymer production facility: the contributions from air, water, and occupational exposures, personal and dietary habits, and relationships to age and gender. The authors conducted questionnaire and serum PFOA measurements in a stratified random sample and volunteers residing in locations with the same residential water supply but with higher and lower potential air PFOA exposure. Serum (PFOA) greatly exceeded general population medians. Occupational exposure from production processes using PFOA and residential water had additive effects; no other occupations contributed. Serum (PFOA) depended on the source of residential drinking water, and not potential air exposure. For public water users, the best-fit model included age, tap water drinks per day, servings of home-grown fruit and vegetables, and carbon filter use. Residential water source was the primary determinant of serum (PFOA).

Microcosm Evaluation of the Toxicity and Risk to Aquatic Macrophytes from Perfluorooctane Sulfonic Acid

Perfluorooctane sulfonic acid (PFOS) is an anthropogenic contaminant detected in various environmental and biologic matrices. This compound is a fluorinated surfactant, a class of molecules renowned for their persistence and their global distribution but for which few ecotoxicological data are currently available, especially under field conditions. The toxicity of PFOS to the aquatic macrophytes Myriophyllum sibiricum and M. spicatum was investigated using 12,000 L outdoor microcosms. Replicate microcosms (n = 3) were treated with 0.3, 3, 10, and 30 mg/L PFOS as the potassium salt and assessed at regular intervals during a period of 42 days. M. sibiricum was more sensitive to PFOS under these simulated field conditions than M. spicatum. Toxicity was observed in the evaluated end points at > 3 mg/L PFOS for EC10s and > 12 mg/L PFOS for EC50s for M. spicatum and in M. sibiricum at > 0.1 mg/L PFOS for EC10s and > 1.6 mg/L PFOS for EC50s. The no observed-effect concentration (NOEC) for M. spicatum was consistently > or = 11.4 mg/L PFOS, whereas the NOEC for M. sibiricum was > or = 0.3 mg/L PFOS. A risk assessment for these plants estimated a negligible probability of toxicity being observed in these plants from PFOS exposure at current environmental concentrations.

Identification of genes responsive to PFOS using gene expression profiling

Perfluorooctane sulfonic acid (PFOS) is widely distributed in the environment including in the tissues of wildlife and humans, however, its mechanism of action remains unclear. Here, the Affymetrix rat genome U34A genechip was used to identify alterations in gene expression due to PFOS exposure. Rat hepatoma cells were treated with PFOS at 2–50 mg/L (4–100 μM) for 96 h. Sprague-Dawley rats were orally dosed with PFOS at 5 mg/kg/day for 3 days or 3 weeks. Genes that were significantly ( P <0.0025) induced were primarily genes for fatty acid metabolizing enzymes, cytochrome P450s, or genes involved in hormone regulation. Consistent expression profiles were obtained for replicate exposures, for short-term and long-term in vivo exposures, and for acute and chronic exposures. One major pathway affected by PFOS was peroxisomal fatty acid β-oxidation, which could be explained by the structural similarity between PFOS and endogenous fatty acids.

Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. II: postnatal evaluation.

The postnatal effects of in utero exposure to perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 18. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. In the highest dosage groups (10 mg/kg for rat and 20 mg/kg for mouse), the neonates became pale, inactive, and moribund within 30-60 min, and all died soon afterward. In the 5 mg/kg (rat) and 15 mg/kg (mouse) dosage groups, the neonates also became moribund but survived for a longer period of time (8-12 h). Over 95% of these animals died within 24 h. Approximately 50% of offspring died at 3 mg/kg for rat and 10 mg/kg for mouse. Cross-fostering the PFOS-exposed rat neonates (5 mg/kg) to control nursing dams failed to improve survival. Serum concentrations of PFOS in newborn rats mirrored the maternal administered dosage and were similar to those in the maternal circulation at GD 21; PFOS levels in the surviving neonates declined in the ensuing days. Small but significant and persistent growth lags were detected in surviving rat and mouse pups exposed to PFOS prenatally, and slight delays in eye opening were noted. Significant increases in liver weight were observed in the PFOS-exposed mouse pups. Serum thyroxine levels were suppressed in the PFOS-treated rat pups, although triiodothyronine and thyroid-stimulating hormone [TSH] levels were not altered. Choline acetyltransferase activity (an enzyme that is sensitive to thyroid status) in the prefrontal cortex of rat pups exposed to PFOS prenatally was slightly reduced, but activity in the hippocampus was not affected. Development of learning, determined by T-maze delayed alternation in weanling rats, was not affected by PFOS exposure. These results indicate that in utero exposure to PFOS severely compromised postnatal survival of neonatal rats and mice, and caused delays in growth and development that were accompanied by hypothyroxinemia in the surviving rat pups.