BackgroundMunicipal drinking water contaminated with perfluorinated alkyl acids had been distributed to one-third of households in Ronneby, Sweden. The source was firefighting foam used in a nearby ...airfield since the mid-1980s. Clean water was provided from 16 December 2013.ObjectiveTo determine the rates of decline in serum perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), and their corresponding half-lives.MethodsUp to seven blood samples were collected between June 2014 and September 2016 from 106 participants (age 4–84 years, 53% female).ResultsMedian initial serum concentrations were PFHxS, 277 ng/mL (range 12–1660); PFOS, 345 ng/mL (range 24–1500); and PFOA, 18 ng/mL (range 2.4–92). The covariate-adjusted average rates of decrease in serum were PFHxS, 13% per year (95% CI 12% to 15%); PFOS, 20% per year (95% CI 19% to 22%); and PFOA, 26% per year (95% CI 24% to 28%). The observed data are consistent with a first-order elimination model. The mean estimated half-life was 5.3 years (95% CI 4.6 to 6.0) for PFHxS, 3.4 years (95% CI 3.1 to 3.7) for PFOS and 2.7 years (95% CI 2.5 to 2.9) for PFOA. The interindividual variation of half-life was around threefold when comparing the 5th and 95th percentiles. There was a marked sex difference with more rapid elimination in women for PFHxS and PFOS, but only marginally for PFOA.ConclusionsThe estimated half-life for PFHxS was considerably longer than for PFOS and PFOA. For PFHxS and PFOS, the average half-life is shorter than the previously published estimates. For PFOA the half-life is in line with the range of published estimates.
Objective and sources: We reviewed the epidemiologic literature for PFOA. Data synthesis: Perfluorooctanoic acid (PFOA) does not occur naturally but is present in the serum of most residents of ...industrialized countries (U.S. median, 4 ng/mL). Drinking water is the primary route of exposure in some populations, but exposure sources are not well understood. PFOA has been used to manufacture such products as Gore-Tex and Teflon. PFOA does not break down in the environment; the human half-life is estimated at about 3 years. PFOA is not metabolized in the body; it is not lipophilic. PFOA is not directly genotoxic; animal data indicate that it can cause several types of tumors and neonatal death and may have toxic effects on the immune, liver, and endocrine systems. Data on the human health effects of PFOA are sparse. There is relatively consistent evidence of modest positive associations with cholesterol and uric acid, although the magnitude of the cholesterol effect is inconsistent across different exposure levels. There is some but much less consistent evidence of a modest positive correlation with liver enzymes. Most findings come from cross-sectional studies, limiting conclusions. Two occupational cohort studies do not provide consistent evidence for chronic disease; both are limited by sample size and reliance on mortality data. Reproductive data have increased recently but are inconsistent, and any observed adverse effects are modest. Conclusions: Epidemiologic evidence remains limited, and to date data are insufficient to draw firm conclusions regarding the role of PFOA for any of the diseases of concern.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Thyroid hormones (THs) are especially important for brain maturation and development during the fetal period and childhood. Several epidemiological studies have assessed the possible association ...between exposure to perfluoroalkyl substances (PFAS) and thyroid outcomes during the early stages of life. We aimed to review this evidence.
We conducted a systematic review in compliance with the PRISMA Statement (search conducted in PubMed and Embase, as well as in the citations of the selected articles). We chose studies if they dealt with thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxin (T4), or thyroid dysfunctions, and perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) or perfluorononanoic acid (PFNA) measured in the blood of pregnant women and/or children up to 19years old.
We included in this review three cross-sectional, one case-control, and six cohort studies (publication: 2011–2015), focusing on prenatal life (n=7), childhood (n=2) or both periods (n=1). We observed a high degree of heterogeneity across studies in terms of sampling time (different gestational weeks, at birth, or childhood), outcomes, adjustment for potential confounders, and statistical approach. We found some evidence of a positive association between PFHxS and PFOS exposure and TSH levels measured in maternal blood, and PFNA and TSH levels measured in the blood of boys aged ≥11years.
Although there is a small number of studies with comparable data, we found some consistency of a positive association between maternal or teenage male exposure to some PFAS and TSH levels based on the current literature. However, further studies are required to confirm these possible relationships.
•First review on PFAS exposure and thyroid outcomes during pregnancy and childhood•Scarce comparable studies due to great heterogeneity across them•Some evidence of a positive association between maternal PFHxS and PFOS exposure and TSH levels•Some evidence of a positive association between TSH and PFNA levels in boys ≥11years•No evidence of other thyroid dysfunction or hormones related to PFAS
•Probenecid is associated with modest or nil increase in serum PFAS.•Inhibition of OAT1 and OAT3 appears to have little effect on serum PFAS.•Cholestyramine significantly lowers serum PFAS ...concentrations.
Longer serum half-lives of perfluoroalkyl substances (PFAS) in humans compared to other species has been attributed to differences in the activity of organic anion transporters (OAT).
Among 56,175 adult participants in the community-based C8 Health Project, 23 subjects were taking the uricosuric OAT-inhibitor probenecid, and 36 subjects were taking the bile acid sequestrant cholestyramine. In regression models of log transformed serum PFAS, medication effects were estimated in terms of mean ratios, adjusting for age, gender, BMI, estimated glomerular filtration rate (eGFR) and water-district of residence.
Probenecid was associated with modest, but not statistically significant increases in serum PFAS concentrations. In contrast, cholestyramine significantly lowered serum PFAS concentrations, notably for perfluorooctane sulfonic acid (PFOS).
The effectiveness of cholestyramine in a community setting supports the importance of gastrointestinal physiology for PFAS excretion kinetics, especially for PFOS. We did not find clear evidence that probenecid, an inhibitor of OAT, affects PFAS clearance.
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•This study provides refined estimates of the half-life of eight PFAS, especially including the branched PFOS-isomers.•The determinants leading to shorter half-life were young age; ...better kidney function; female gender in fertile age; and possibly gut inflammation and lower gut permeability.•The result also suggested a time-dependent PFAS elimination process, with more rapid elimination in the first year after the end of exposure, than later.
Per- and polyfluoroalkyl substances (PFAS) are persistent substances with surfactant and repellent properties. Municipal drinking water contaminated with PFAS had been distributed for decades to one third of households in Ronneby, Sweden. The source was firefighting foam used in a nearby airfield since the mid-1980s. Clean water was provided from December 16, 2013.
The purpose was to estimate serum half-lives and their determinants in the study population for different PFAS.
Up to ten blood samples were collected between 2014 and 2018 from 114 participants (age 4–84 years at entry, 53% female). 19 PFAS were analysed. Linear mixed models were used to estimate the half-lives.
Eight PFAS were increased in Ronneby: perfluorooctanoic acid (PFOA), perfluoropentane sulfonate (PFPeS), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), linear perfluorooctane sulfonate (L-PFOS) and three branched perfluorooctane sulfonates (1 m-PFOS, 3/4/5m-PFOS and 2/6m-PFOS). The mean estimated half-lives (in years) were 0.94 (95 %CI 0.86–1.02) for PFPeS, 2.47 (2.27–2.7) for PFOA, 2.67 (2.51–2.85) for 2/6m-PFOS, 2.73 (2.55–2.92) for L-PFOS, 3.43 (3.19–3.71) for 3/4/5m-PFOS, 4.52 (4.14–4.99) for PFHxS, 4.55 (4.14–5.06) for PFHpS, and 5.01 (4.56–5.55) for 1 m-PFOS.
The most important determinants of a shorter half-life were young age, and better kidney function measured by estimated glomerular filtration rate and ratio of paired urine and serum PFAS levels, followed by female sex during their fertile period aged 15–50. Markers of gut inflammation and reduced permeability i.e. zonulin and calprotectin were also possibly associated with shorter half-life. The results also suggested a time-dependent PFAS elimination process, with more rapid elimination in the first year after the end of exposure.
The half-life estimates are in line with past estimates for some PFAS such as PFOA, and the novel results for different PFOS isomers. These results provide observational support for elimination routes – renal, fecal and maternal.
Exposures to perfluoroalkyl substances (PFAS) have shown positive associations with serum lipids in previous studies. While many studies on lipids investigated associations with perfluorooctane ...sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), there are only a few studies regarding other PFAS, such as perfluorohexane sulfonic acid (PFHxS). The purpose of the current study is to investigate if associations with serum lipids were present, not only for serum PFOS and PFOA, but also for PFHxS, and if the associations with PFAS remained also in a comparison based only on residency in areas with contrasting exposure to PFAS.
1945 adults aged 20-60 were included from Ronneby, Sweden, a municipality where one out of two waterworks had been heavily contaminated from aqueous fire-fighting foams, and from a nearby control area. The exposure was categorized based on either been living in areas with contrasting PFAS exposure or based on the actual serum PFAS measurements. Regression analyses of serum lipids were fitted against serum PFAS levels, percentile groups, smooth splines and between exposed and reference areas, adjusting for age, sex and BMI.
Drinking water contamination caused high serum levels of PFOS (median 157 ng/ml) and PFHxS (median 136 ng/ml) and PFOA (median 8.6 ng/ml). These serum PFAS levels in the exposed groups were 5 to 100-fold higher than in the controls. In this population with mixed PFAS exposure, predominantly PFOS and PFHxS, PFAS exposure were positively associated with serum lipids. This was observed both when quantifying exposure as contrast between exposed and controls, and in terms of serum PFAS. Due to high correlations between each PFAS, we cannot separate them.
In conclusion, the present study provides further evidence of a causal association between PFAS and serum lipids, especially for PFHxS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Evidence supports an association between PFOA and kidney and testicular cancer.•Consistent evidence for a link with cholesterol, but not with heart disease.•Suggestive evidence for a link between ...PFOA and ulcerative colitis.•A link with liver and immune function but little link for liver or infectious disease.•A possible link with low birthweight may be due to reverse causality or confounding.
The C8 Science Panel was composed of three epidemiologists charged with studying the possible health effects of PFOA in a highly exposed population in the mid-Ohio Valley. The Panel determined in 2012 there was a ‘probable link’ (i.e., more probable than not based on the weight of the available scientific evidence) between PFOA and high cholesterol, thyroid disease, kidney and testicular cancer, pregnancy-induced hypertension, and ulcerative colitis.
Here, former C8 Science Panel members and collaborators comment on the PFOA literature regarding thyroid disorders, cancer, immune and auto-immune disorders, liver disease, hypercholesterolemia, reproductive outcomes, neurotoxicity, and kidney disease. We also discuss developments regarding fate and transport, and pharmacokinetic models, and discuss causality assessment in cross-sectional associations among low-exposed populations.
For cancer, the epidemiologic evidence remains supportive but not definitive for kidney and testicular cancers. There is consistent evidence of a positive association between PFOA and cholesterol, but no evidence of an association with heart disease. There is evidence for an association with ulcerative colitis, but not for other auto-immune diseases. There is good evidence that PFOA is associated with immune response, but uneven evidence for an association with infectious disease. The evidence for an association between PFOA and thyroid and kidney disease is suggestive but uneven. There is evidence of an association with liver enzymes, but not with liver disease. There is little evidence of an association with neurotoxicity. Suggested reductions in birthweight may be due to reverse causality and/or confounding. Fate and transport models and pharmacokinetic models remain central to estimating past exposure for new cohorts, but are difficult to develop without good historical data on emissions of PFOA into the environment.
Overall, the epidemiologic evidence remains limited. For a few outcomes there has been some replication of our earlier findings. More longitudinal research is needed in large populations with large exposure contrasts. Additional cross-sectional studies of low exposed populations may be less informative.
Exposure to some perfluoroalkyl substances (PFAS), such as perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA), may alter ...levels of sex hormones and insulin-like growth factor-1 (IGF-1) in animals. Human studies on this topic are scarce, and none have been conducted in young children.
We investigated the relationship between levels of PFAS and estradiol, total testosterone, and IGF-1 in 2,292 children (6-9 years of age) from the C8 Health Project who lived near a chemical plant in the Mid-Ohio Valley (USA) with local contamination from PFOA.
Serum samples were collected in 2005-2006 and analyzed for PFAS, sex hormones, and IGF-1. Results from regression models were expressed as the adjusted percentage difference (95% CI) per sex-specific interquartile range (IQR) increment of each PFAS serum concentration. Analyses by PFAS quartiles were also conducted.
Median concentrations of PFHxS, PFOA, PFOS, and PFNA were 8, 35, 22, and 1.7 ng/mL in boys and 7, 30, 21, and 1.7 ng/mL in girls. In boys, PFOA concentrations were significantly associated with testosterone levels (-4.9%; 95% CI: -8.7, -0.8%); PFOS with estradiol (-4.0%; 95% CI: -7.7, -0.1%), testosterone (-5.8%; 95% CI: -9.4, -2.0%), and IGF-1 (-5.9%; 95% CI: -8.3, -3.3%); and PFNA with IGF-1 (-3.5%; 95% CI: -6.0, -1.0%). In girls, significant associations were found between PFOS and testosterone (-6.6%; 95% CI: -10.1, -2.8%) and IGF-1 (-5.6%; -8.2, -2.9%); and PFNA and IGF-1 (-3.8%; 95% CI: -6.4, -1.2%). In both sexes, the magnitudes of the associations decreased monotonically across quartiles for both testosterone and IGF-1 in relation to PFOS, and for IGF-1 and PFNA in girls.
To our knowledge, this is the first study suggesting that PFAS are associated with lower levels of IGF-1 and sex hormones in young children.
Lopez-Espinosa MJ, Mondal D, Armstrong BG, Eskenazi B, Fletcher T. 2016. Perfluoroalkyl substances, sex hormones, and insulin-like growth factor-1 at 6-9 years of age: a cross-sectional analysis within the C8 Health Project. Environ Health Perspect 124:1269-1275; http://dx.doi.org/10.1289/ehp.1509869.
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Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
•Serum PFAS levels for an exposed Swedish community are presented.•PFAS originated from AFFF result in different exposure profile.•Serum PFHxS and PFOS levels were hundredfold higher than general ...population.•Serum PFOA was higher, but to a less extent, than general population.•Shorter chain PFAS were presented in contaminated drinking water and in exposed population.
In December 2013, it was discovered that drinking water supplied to one third of the households in Ronneby, southern Sweden, was highly contaminated by PFAS (sum level >10,000 ng/L) originated from firefighting foams used at a nearby military airport.
To report serum PFAS levels of Ronneby residents participating in a biomonitoring program, and to describe the variation by age, sex and calendar period for residential exposure. In addition, a reference group living in a neighboring municipality without PFAS contaminated drinking water was examined.
Blood samples and demographic data were collected for 3297 Ronneby residents and 226 individuals from the reference group. Yearly residence addresses were available for 3086 Ronneby residents from the national population registry. Serum concentrations of PFHxS, PFOS and PFOA were determined in all participants, with additional PFHpA, PFNA and PFDA in subsets of the participants.
The population geometric means for serum PFHxS, PFOS and PFOA were 114, 135 and 6.8 ng/mL for all Ronneby residents, i.e.135, 35 and 4.5 times higher than for the reference group. Ronneby residents who resided in the area with contaminated water supply during 2005–2013 showed much higher PFAS levels in 2014 than those exposed only before 2005. Ronneby residents who never resided in the area with contaminated water supply also had higher serum PFAS levels than the reference group. All three PFAS were highly correlated (rs > 0.9 for each pair). Serum PFAS levels were lowest in teenage years and then increased with age. Adult females had lower PFAS levels on average than males under the age of 60 but higher above 60.
The results reveal high serum PFAS levels dominated by PFHxS and PFOS in the Ronneby residents highly exposed to PFAS originated from firefighting foams. The PFAS exposure in Ronneby permits studies of associations to a range of health parameters, as well as studies of the toxicokinetics of PFAS exposure.
Background: Animal studies suggest that some perfluoroalkyl acids (PFAAs), including perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic add (PFNA) may impair thyroid ...function. Epidemiological findings, mostly related to adults, are inconsistent. Objectives: We investigated whether concentrations of PFAAs were associated with thyroid function among 10,725 children (1-17 years of age) living near a Teflon manufacturing facility in the Mid-Ohio Valley (USA). Methods: Serum levels of thyroid-stimulating hormone (TSH), total thyroxine (TT₄), and PFAAs were measured during 2005-2006, and information on diagnosed thyroid disease was collected by questionnaire. Modeled in utero PFOA concentrations were based on historical information on PFOA releases, environmental distribution, pharmacokinetic modeling, and residential histories. We performed multivariate regression analyses. Results: Median concentrations of modeled in utero PFOA and measured serum PFOA, PFOS, and PFNA were 12, 29, 20, and 1.5 ng/mL, respectively. The odds ratio for hypothyroidism (n = 39) was 1.54 95% confidence interval (CI): 1.00, 2.37 for an interquartile range (IQR) contrast of 13 to 68 ng/mL in serum PFOA measured in 2005-2006. However, an IQR shift in serum PFOA was not associated with TSH or TT₄ levels in all children combined. IQR shifts in serum PFOS (15 to 28 ng/mL) and serum PFNA (1.2 to 2.0 ng/mL) were both associated with a 1.1% increase in TT₄ in children 1-17 years old (95% CIs: 0.6, 1.5 and 0.7, 1.5 respectively). Conclusions: This is the first large-scale report in children suggesting associations of serum PFOS and PFNA with thyroid hormone levels and of serum PFOA and hypothyroidism.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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