Serum Levels Of Perfluorooctane Sulfonate Research Articles

Serum perfluorooctane sulfonate and perfluorooctanoate and risk of postmenopausal breast cancer according to hormone receptor status: An analysis in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Per- and polyfluoroalkyl substances (PFAS) are highly persistent endocrine-disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case-control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultraperformance liquid chromatography-tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype-specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs lowest quartile of serum PFOS (ORs [95% CIs]=1.59 [1.01-2.50], 2.34 [1.29-4.23], and 2.19 [1.21-3.98], respectively) and elevated but nonstatistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER-, PR-, ER+/PR-, and ER-/PR- tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor-positive tumors, and possibly between PFOA and receptor-negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology.

Effect of Plasma and Blood Donations on Levels of Perfluoroalkyl and Polyfluoroalkyl Substances in Firefighters in Australia

Elevated levels of blood perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been associated with a range of adverse health outcomes. Firefighters have been exposed to PFASs in firefighting foams and have previously been shown to have higher PFAS levels in blood samples than the general population. No interventions have been shown to reduce PFAS levels. To examine the effect of blood or plasma donations on PFAS levels in firefighters in Australia. This 52-week, open-label, randomized clinical trial enrolled participants from May 23 to August 23, 2019. Participants were 285 Fire Rescue Victoria staff or contractors with serum levels of perfluorooctane sulfonate (PFOS) of 5 ng/mL or more who were eligible to donate blood, had not donated blood in the 3 months prior to randomization, and were able to provide written informed consent. Analysis was performed on an intention-to-treat basis from May to July 2021. Firefighters with baseline PFOS levels of 5 ng/mL or more were randomly assigned to donate plasma every 6 weeks for 12 months, donate blood every 12 weeks for 12 months, or be observed only. The primary end points were changes in the serum PFOS and perfluorohexane sulfonic acid (PFHxS) levels after 12 months of plasma or blood donations or after observation only. Secondary end points included changes in serum PFAS levels from week 52 to week 64, changes in other PFASs, and changes in complete blood count, biochemistry, thyroid function, and lipid profile from screening to week 52. A total of 285 firefighters (279 men [97.9%]; mean [SD] age, 53.0 [8.4] years) were enrolled; 95 were randomly assigned to donate plasma, 95 were randomly assigned to donate blood, and 95 were randomly assigned to be observed. The mean level of PFOS at 12 months was significantly reduced by plasma donation (-2.9 ng/mL; 95% CI, -3.6 to -2.3 ng/mL; P < .001) and blood donation (-1.1 ng/mL; 95% CI, -1.5 to -0.7 ng/mL; P < .001) but was unchanged in the observation group. The mean level of PFHxS was significantly reduced by plasma donation (-1.1 ng/mL; 95% CI, -1.6 to -0.7 ng/mL; P < .001), but no significant change was observed in the blood donation or observation groups. Analysis between groups indicated that plasma donation had a larger treatment effect than blood donation, but both were significantly more efficacious than observation in reducing PFAS levels. Plasma and blood donations caused greater reductions in serum PFAS levels than observation alone over a 12-month period. Further research is needed to evaluate the clinical implications of these findings. anzctr.org.au Identifier: ACTRN12619000204145.

Intrauterine exposure to perfluorinated compounds and overweight at age 4: A case-control study.

The aims were to investigate the association between maternal serum levels of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS) and perfluorononanoic acid (PFNA) in early pregnancy and overweight in the child at 4 years and to assess potential heterogeneity in exposure effect between strata with different levels of other risk factors for overweight. We used a case-control design and included 354 cases (ISO-BMI ≥ 18 kg/m2) and 2 controls per case (ISO-BMI ≤17 kg/m2) from child health care centers in Malmö, Sweden. Controls were selected stratified on risk scores for overweight in a propensity score framework. Maternal serum levels were analyzed in biobanked samples collected by routine around gestational week 14. Logistic regression was used to estimate odds ratios between quartiles of maternal serum levels and child overweight at age 4. There were no consistent monotonic exposure-response relationships. We found some significant odds ratios in specific quartiles but these were regarded as spurious findings. The absence of an effect was consistent over risk strata. We did not find evidence of an association between maternal serum levels of PFOS, PFOA, PFHxS and PFNA in early pregnancy and child overweight at age 4. The level of other risk factors for overweight did not affect children's susceptibility to prenatal PFAS exposure.

Circulating levels of perfluoroalkylated compounds and breast cancer risk: Evidence from a nested case-control study

Introduction The incidence of breast cancer is continuing to rise in Western countries, and there has been increasing interest in understanding the contribution of exposure to endocrine disrupting chemicals (EDCs) to this increase. A large group of EDCs, for which the long-term health effects remain uncharacterized with regards to breast cancer, are perfluoroalkyated compounds (PFAS). PFAS are a group of synthetic compounds that are stable, persistent and bioaccumulative. Among PFAS, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the most frequent compounds found in food and are ubiquitously present in the blood of Western populations. The objective of this study was to investigate the associations between serum levels of PFOS and PFOA and the risk of breast cancer in a nested case-control study. Methods E3 N (“Etude Epidemiologique aupres de femmes de l’Education Nationale”) is a French prospective cohort that enrolled 98,995 women aged 40–65 years at inclusion in 1990. After inclusion, women were followed-up every 2–3 years through self-administered questionnaires. We identified 198 cases of incident invasive breast cancer with available blood samples, collected between 1994 and 1999. For each case, one control was randomly sampled from women in the cohort who were free of breast cancer at the time of diagnosis of the corresponding case. Controls were matched to cases by age and menopausal status at blood collection, study center, and year of blood collection. Serum levels of PFOS and PFOA were measured for each woman included in the study (n = 396) by liquid chromatography coupled to tandem mass spectrometry. Women were divided into quintiles based on serum levels of PFOS and PFOA separately. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). After running univariate models, all models were adjusted for total serum lipids, body mass index, smoking status, physical activity, education level, family history of breast cancer, history of benign breast disease, parity/age at first full-term pregnancy, total breastfeeding duration, age at menarche, age at menopause, current use of menopausal hormone therapy, use of hormonal contraceptives, adherence to a Western dietary pattern and adherence to a Mediterranean dietary pattern. Results The average serum levels of PFOS and PFOA were 19.08 ng/mL (Standard deviation [SD] 8.19) and 7.32 ng/mL (SD 3.49), respectively. Since serum levels were right skewed, all values were log-transformed in order to achieve a normal distribution. In univariate analyses, no statistically significant association was found between PFOS or PFOA serum levels and breast cancer risk. After adjustment, PFOS serum levels were positively and linearly associated with breast cancer risk (highest quintile: OR 3.46, 95% CI 1.40–8.52, compared with the lowest; Ptrend = 0.006). In contrast, when considering PFOA levels, only women in the 2nd quintile group had a significantly increased risk of breast cancer (OR 2.41, 95% CI 1.08–5.35), suggesting a non-monotonic dose-response pattern. Conclusions This study provides evidence of an association between circulating levels of PFAS and breast cancer risk. In particular, PFOS was linearly associated with breast cancer risk starting from internal values equal to 13.3 ng/mL, while only a low dose effect was highlighted for PFOA, with a increased risk for values between 4.7 and 5.8 ng/mL. This study reflects real-life exposure of a non-professionally exposed population of women in France. Our results highlight the importance of focusing on low-dose effects when studying EDCs, as well as the importance of considering exposure to EDCs, and in particular to PFAS, as a relevant risk factor for breast cancer, thus as a serious public health issue.

High Levels of Perfluorooctane Sulfonate in Children at the Onset of Diabetes

Background. Impairments of endocrine system may be associated with exposure to perfluorinated compounds that are able to bind nuclear receptors, including the peroxisome proliferator-activating receptors. Aim of this study was to assess perfluorooctane sulfonate and perfluorooctanoic acid concentrations in children and adolescents at the onset of type 1 diabetes compared to healthy controls. Methods. Forty-four children and adolescents were recruited and subdivided into two groups: (A) 25 subjects with type 1 diabetes and (B) 19 healthy controls. Perfluorinated compounds were measured using high performance liquid chromatography with electrospray ionization tandem mass spectrometry. Nonparametric statistical analysis was performed. Results. Perfluorooctane sulfonate concentrations were significantly higher in patients with type 1 diabetes compared to controls (1.53 ± 1.50 versus 0.55 ± 0.15 ng/mL, resp.; p < 0.001). Multivariate linear regression analysis identified lipid levels as significant predictive factors for perfluorooctane sulfonate levels. Conclusions. Our data suggests that higher serum levels of perfluorooctane sulfonate may be considered a biomarker of exposure and susceptibility to develop type 1 diabetes.

Human serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in Uyghurs from Sinkiang-Uighur Autonomous Region, China: background levels study.

Perfluorinated compounds (PFCs), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), are a family of commonly used industrial chemicals whose persistence and ubiquity in blood samples of humans and wildlife have become a growing concern. Despite PFOS and PFOA having been found in human blood and tissue samples from occupationally exposed workers and the general worldwide population, little systematic knowledge has accrued with respect to exposure levels in Uyghurs in the Sinkiang-Uighur Autonomous Region of China, which is predominantly agricultural and pastoral. Our goal was to provide background data for biological monitoring in the general population of this region. In this study, 110 self-reported healthy human serum samples were collected from nonoccupationally exposed Uyghurs volunteers and analyzed by microbore HPLC-electrospray tandem mass spectrometry. Among the 110 blood specimens, PFOS was detected in 102 samples (93%) and ranged from the lower limit of quantification of 0.01 to 22.63 μg/L with a median of 1.93 μg/L (interquartile range 1.00-3.43 μg/L). The median was higher among males (2.39 μg/L; interquartile range 1.23-4.40 μg/L) than that among females (1.20 μg/L; interquartile range 0.83-2.77 μg/L). No significant difference was observed with respect to age. The concentration of PFOA was lower than that of PFOS and was found only in seven samples (6%) at concentrations above the limit of quantification. This study is the first investigation to reveal serum PFOS and PFOA levels in the general population of Uyghurs. PFOS and PFOA concentrations found in the present investigation were lower than those found in recent studies consisting of subjects from different geographic locations (PFOS 5.0-44.7 μg/L, PFOA 1.5-10 μg/L).

PFOA and PFOS are associated with reduced expression of the parathyroid hormone 2 receptor (PTH2R) gene in women

Little is known about interactions between environmental and genetic risk factors for osteoarthritis (OA). Genetic factors include variation or mutation in genes involved in parathyroid hormone signalling. Exposure to the endocrine disrupting chemicals perfluoro-octanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) have been suggested as potential environmental contributors, although evidence to support this association is conflicting. Here we test the hypothesis that PFOA and PFOS may alter the mRNA expression of genes in the parathyroid signalling cascade to provide evidence on possible pathways between these chemicals and OA. We measured the relationship between PFOA or PFOS serum levels and the in vivo expression of the Parathyroid hormone 1 and 2 genes (PTH, PTH2), Parathyroid hormone 1 and 2 receptor genes (PTH1R, PTH2R) and the parathyroid hormone-like (PTHLH) gene in peripheral blood from a cross-sectional population study designed to assess the potential health effects of these chemicals. We used multivariate linear regression models and found that PFOA or PFOS was inversely correlated with parathyroid hormone 2 receptor (PTH2R) expression (coefficients=−0.43 and −0.32, p=p=0.017 and 0.006 for PFOA and PFOS respectively) in 189 female subjects. The levels of PTH2 transcripts encoding the ligand of PTH2r, were also found to be lower in women with OA (median 2.08) compared with controls (median 3.41, p=0.046). As the parathyroid signalling cascade is a known candidate for osteoarthritis risk and our findings raise the possibility that exposure to these chemicals may contribute to the pathogenesis of OA in some individuals.

PFOA and PFOS serum levels and miscarriage risk.

Serum concentrations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were assessed in relation to miscarriage in a population of mid-Ohio River Valley residents highly exposed to PFOA through contaminated drinking water. Serum PFOA and PFOS concentrations were measured in 1129 women in 2005-2006 who reported pregnancy outcomes in follow-up interviews between 2008 and 2011. In the analysis, we included 1438 reported live births, stillbirths, and miscarriages with estimated conception dates after the serum measurements. Preconception serum levels of PFOA and PFOS were analyzed in relation to miscarriage using logistic regression and generalized estimating equations. There was little evidence of association between PFOA and miscarriage. For PFOS, when including all reported prospective pregnancies, the odds ratio of miscarriage per log ng/ml increase was 1.21 (95% confidence interval = 0.94-1.55); in subanalyses restricted to each woman's first pregnancy conceived after the serum measurement, the odds ratio was 1.34 (1.02-1.76). Categorical analyses showed elevated odds ratios for the top 4 quintiles relative to the first quintile, without a monotonic trend. Positive associations between PFOS and miscarriage were strongest among nulligravid pregnancies. In this prospective study of miscarriage in a population exposed to high levels of PFOA and background levels of PFOS, we found little evidence of association with serum levels of PFOA and limited evidence of association with serum levels of PFOS.

Polymorphisms in Phase I and Phase II genes and breast cancer risk and relations to persistent organic pollutant exposure: a case–control study in Inuit women

BackgroundWe have previously reported that chemicals belonging to the persistent organic pollutants (POPs) such as perfluorinated compounds (PFAS) and polychlorinated biphenyls (PCBs) are risk factors in Breast Cancer (BC) development in Greenlandic Inuit women. The present case–control study aimed to investigate the main effect of polymorphisms in genes involved in xenobiotic metabolism and estrogen biosynthesis, CYP1A1, CYP1B1, COMT and CYP17, CYP19 and the BRCA1 founder mutation in relation to BC risk and to explore possible interactions between the gene polymorphisms and serum POP levels on BC risk in Greenlandic Inuit women.MethodsThe study population consisted of 31 BC cases and 115 matched controls, with information on serum levels of POPs. Genotyping was conducted for CYP1A1 (Ile462Val; rs1048943), CYP1B1 (Leu432Val; rs1056836), COMT (Val158Met; rs4680), CYP17A1 (A1> A2; rs743572); CYP19A1 (C> T; rs10046) and CYP19A1 ((TTTA)n repeats) polymorphisms and BRCA1 founder mutation using TaqMan allelic discrimination method and polymerase chain reaction based restriction fragment length polymorphism. The χ2 –test was used to compare categorical variables between cases and controls and the odds ratios were estimated by unconditional logistic regression models.ResultsWe found an independent association of CYP1A1 (Val) and CYP17 (A1) with BC risk.Furthermore, an increased BC risk was observed for women with high serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) and carriers of at least: one CYP1A1 variant Val allele; one variant COMT Met allele; or the common CYP17 A1 allele. No combined effects were seen between PFAS exposure and CYP1B1 and CYP19 polymorphisms. The risk of BC was not found significantly associated with exposure to PCBs and OCPs, regardless of genotype for all investigated SNPs. The frequency of the Greenlandic founder mutation in BRCA1 was as expected higher in cases than in controls.ConclusionsThe BRCA1 founder mutation and polymorphisms in CYP1A1 (Val) and CYP17 (A1) can increase the BC risk among Inuit women and the risk increases with higher serum levels of PFOS and PFOA. Serum PFAS levels were a consistent risk factor of BC, but inter-individual polymorphic differences might cause variations in sensitivity to the PFAS/POP exposure.

Inverse association of colorectal cancer prevalence to serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in a large Appalachian population

BackgroundPerfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC). However, the link between these compounds and CRC remains unknown. In this cross-sectional study, we investigated the association of CRC diagnosis to PFOA and PFOS blood levels in a large Appalachian population.MethodsParticipants were 47,359 adults ≥ 21 years of age and residing in six PFOA-contaminated water districts in the mid-Ohio Valley (N = 47,151 cancer-free adults, 208 cases of primary CRC). All participants completed a comprehensive health survey between 2005 and 2006; serum levels of PFOA, PFOS, and a range of other blood markers were also measured. Medical history was assessed via self report and cancer diagnosis confirmed via chart review.ResultsCRC showed a strong inverse, dose–response association with PFOS serum levels (odds ratio (OR) adjusted for potential confounders = 0.2, 95% confidence interval (CI) 0.2,0.3) for highest vs. lowest quartile of PFOS, P-trend < 0.00001) and a significant, but more modest inverse association with PFOA (adjusted OR = 0.6 (CI 0.4, 0.9) for highest vs. lowest quartile, P-trend = 0.001). These inverse associations were stronger in those diagnosed within the previous 6 years and resident in the same water district for a minimum of 10–15 years preceding assessment. The relationship between PFOA and CRC was also more pronounced in men and leaner adults, and showed a stronger linear trend at lower exposure levels.ConclusionsIn this large cross-sectional study, we found a strong, inverse association between PFOS and likelihood of CRC diagnosis and a significant, although more modest inverse association between PFOA and CRC. If confirmed in prospective investigations, these findings may aid in identifying new strategies for CRC prevention and treatment and inform future studies regarding mechanisms underlying CRC pathogenesis.

Estimation of Reference Values for PFOS and PFOA in Human Biomonitoring and Relevance of Exposure among Family Members in China

The reference values of serum perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations were evaluated based on the human blood samples collected from Kashi, Xinjiang. And human serum samples of family members from Liaoning were evaluated for levels of PFOS and PFOA with the purpose to compare exposure pathways for family members. Among the 110 blood specimens from Kashi, the detection frequency of PFOS and PFOA was 93% and 6%, respectively. Reference values of serum PFOS, evaluated as the 90th percentiles of the concentrations, were determined to be 6.44 ug/L. Significant positive correlations were observed for serum levels of PFOS and PFOA among family members in Liaoning. Specially, stronger correlation between mother and offspring was observed than that between father and offspring. And stronger correlation of serum PFOS and PFOA levels was observed among fam- ily members in rural areas than those in big and small-medium cities. Difference in the association of serum PFOS and PFOA level among family members suggested that exposure in the outdoor and working environment of different oc- cupations should be evaluated. Present study provides reference values for exposure assessment in China and potential pathways of human exposure to PFOS and PFOA.

Serum levels of perfluoroalkyl compounds in human maternal and umbilical cord blood samples

Perfluoroalkyl compounds (PFCs) are end-stage metabolic products from industrial flourochemicals used in the manufacture of plastics, textiles, and electronics that are widely distributed in the environment. The objective of the present study was to quantify exposure to perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonate (PFHxS), perfluoroheptanoic acid (PFHpA), and perfluorononanoic acid (PFNA) in serum samples collected from pregnant women and the umbilical cord at delivery. Pregnant women ( n=101) presenting for second trimester ultrasound were recruited and PFC residue levels were quantified in maternal serum at 24–28 weeks of pregnancy, at delivery, and in umbilical cord blood (UCB; n=105) by liquid chromatography–mass spectrometry. Paired t-test and multiple regression analysis were performed to determine the relationship between the concentrations of each analyte at different sample collection time points. PFOA and PFOS were detectable in all serum samples analyzed including the UCB. PFOS serum levels (mean±S.D.) were significantly higher ( p<0.001) in second trimester maternal serum (18.1±10.9 ng/mL) than maternal serum levels at delivery (16.2±10.4 ng/mL), which were higher than the levels found in UCB (7.3±5.8 ng/mL; p<0.001). PFHxS was quantifiable in 46/101 (45.5%) maternal and 21/105 (20%) UCB samples with a mean concentration of 4.05±12.3 and 5.05±12.9 ng/mL, respectively. There was no association between serum PFCs at any time point studied and birth weight. Taken together our data demonstrate that although there is widespread exposure to PFCs during development, these exposures do not affect birth weight.