Line Småstuen Haug

Diet and particularly seafood are major sources of perfluorinated compounds in humans

Commercially used perfluorinated compounds (PFCs) have been widely detected in wildlife and humans, but the sources of human exposure are not fully characterized. The objectives of this study were to explore possible associations between concentrations of PFCs in serum and consumption of food with particular focus on seafood, and to compare estimated dietary intakes with determined serum PFC concentrations. Concentrations of 19 PFCs were determined in serum from 175 participants in the Norwegian Fish and Game Study and evaluated with respect to food consumption using multiple linear regression analysis. Associations between estimated individual total dietary intakes of PFCs and serum concentrations were also explored. PFC concentrations in serum were significantly associated (p<0.05) with the consumption of lean fish, fish liver, shrimps and meat, as well as age, breastfeeding history and area of residence (R(2) 0.35-0.63). The estimated dietary intakes of perfluorooctanoic acid (PFOA), perfluoroundecanoic acid (PFUnDA) and perfluorooctane sulfonic acid (PFOS) were 0.60, 0.34 and 1.5 ng/kg body weight/day, respectively. Seafood (fish and shellfish) was the major dietary source contributing 38% of the estimated dietary intakes of PFOA, 93% of PFUnDA and 81% of PFOS. The estimated dietary intakes of these three selected PFCs were significantly associated with the corresponding serum PFC concentrations (p<0.05). In conclusion, our results show that consumption of fish and shellfish is a major determinant of serum PFC concentrations. Further, significant relationships between estimated dietary intakes and serum concentrations have been demonstrated for the first time.

Prenatal Exposure to Perfluorooctanoate and Risk of Overweight at 20 Years of Age: A Prospective Cohort Study

Background: Perfluoroalkyl acids are persistent compounds used in various industrial -applications. Of these compounds, perfluorooctanoate (PFOA) is currently detected in humans worldwide. A recent study on low-dose developmental exposure to PFOA in mice reported increased weight and elevated biomarkers of adiposity in postpubertal female offspring. Objective: We examined whether the findings of increased weight in postpubertal female mice could be replicated in humans. Methods: A prospective cohort of 665 Danish pregnant women was recruited in 1988–1989 with offspring follow-up at 20 years. PFOA was measured in serum from gestational week 30. Offspring body mass index (BMI) and waist circumference were recorded at follow-up (n = 665), and biomarkers of adiposity were quantified in a subset (n = 422) of participants. Results: After adjusting for covariates, including maternal pre-pregnancy BMI, smoking, education, and birth weight, in utero exposure to PFOA was positively associated with anthropometry at 20 years in female but not male offspring. Adjusted relative risks comparing the highest with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI ≥ 25 kg/m2) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female offspring. This corresponded to estimated increases of 1.6 kg/m2 (95% CI: 0.6, 2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference, respectively. In addition, maternal PFOA concentrations were positively associated with serum insulin and leptin levels and inversely associated with adiponectin levels in female offspring. Similar associations were observed for males, although point estimates were less precise because of fewer observations. Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), and perfluorononanoate (PFNA) concentrations were not independently associated with offspring anthropometry at 20 years. Conclusions: Our findings on the effects of low-dose developmental exposures to PFOA are in line with experimental results suggesting obesogenic effects in female offspring at 20 years of age.

Levels in food and beverages and daily intake of perfluorinated compounds in Norway

Perfluorinated compounds (PFCs) have been determined in 21 samples of selected food and beverages such as meat, fish, bread, vegetables, milk, drinking water and tea from the Norwegian marked. Up to 12 different PFCs were detected in the samples. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were found in concentrations similar to or lower than what has been observed in other studies world-wide. Differences in the relative proportion of PFOA and PFOS between samples of animal origin and samples of non-animal origin were observed and support findings that PFOS has a higher bioaccumulation potential in animals than PFOA. Based on these 21 measurements and consumption data for the general Norwegian population, a rough estimate of the total dietary intake of PFCs was found to be around 100 ng d(-1). PFOA and PFOS contributed to about 50% of the total intake. When dividing the population in gender and age groups, estimated intakes were decreasing with increasing age and were higher in males than females. The estimated intakes of PFOS and PFOA in the present study are lower than what has been reported in studies from Spain, Germany, United Kingdom, Canada and Japan. This study illustrates that by improving the analytical methods for determination of PFC in food samples, a broad range of compounds can be detected, which is important when assessing dietary exposure.

A sensitive method for determination of a broad range of perfluorinated compounds in serum suitable for large-scale human biomonitoring

A sensitive and reliable method based on column switching liquid chromatography (LC) coupled to a triple quadrupole mass spectrometer (MS) has been developed for quantification of 19 perfluorinated compounds (PFCs) in serum. A volume of only 150microl serum is used and protein precipitation by methanol is the only sample preparation necessary prior to injection into the column switching system. Pseudo-MRM is used as a detection mode for determination of PFCs, resulting in reduced background noise and considerably increased sensitivity for the perfluorinated alkyl sulfonates and the perfluorinated alkyl sulfonamides. The estimated limits of detection for the method were as low as 0.0020-0.050ngPFCs/ml serum. The accuracy determined from spiking experiments, reported as recovery of added amount, was between 85 and 121% in the range 0.20-50ngPFC/ml serum, except for perfluorodecylsulfonate for which the accuracy was 146% at 0.20ngPFC/ml serum. The low sample volume needed, the limited manual handling and the broad range of analytes which are included, make this method advantageous for large-scale epidemiological studies. This column-switching technique can easily be set up on standard LC-MS/MS instruments and is thus available to a wide range of laboratories.

Investigation on Per- and Polyfluorinated Compounds in Paired Samples of House Dust and Indoor Air from Norwegian Homes

Per- and polyfluorinated compounds (PFCs) have been found to be ubiquitously distributed in human populations, however the sources of human exposure are not fully characterized. A wide range of PFCs were determined in paired samples of indoor air and dust from 41 Norwegian households. Up to 18 ionic and 9 neutral PFCs were detected. The concentrations found are comparable to or lower than what has previously been reported in North America, Europe, and Asia. The highest median concentrations in dust were observed for perfluorohexanoic acid (28 ng/g), perfluorononanoic acid (23 ng/g), perfluorododecanoic acid (19 ng/g), and perfluorooctanoic acid (18 ng/g). However, perfluoroalkyl sulfonic acids (PFSAs) were also frequently detected. Fluortelomer alcohols were the most prominent compounds found in indoor air, with median concentrations for 8:2 fluortelomer alcohol, 10:2 fluortelomer alcohol, and 6:2 fluortelomer alcohol of 5173, 2822, and 933 pg/m(3) air, respectively. All perfluoroalkyl sulfonamides and sulfonamidoethanols (FOSA/FOSEs) were detected in more than 40% of the air samples. For the first time, significant positive correlations (p < 0.05) between PFSAs in house dust and FOSA/FOSEs in the indoor air have been shown, supporting the hypothesis that FOSA/FOSEs may be transformed to PFSAs. Further, we found the age of the residence to be a predictor of PFC concentrations in both indoor air and house dust. These results are important for estimating the exposure to PFCs from the indoor environment and for characterization of exposure pathways.

Pre-natal exposure to perfluoroalkyl substances may be associated with altered vaccine antibody levels and immune-related health outcomes in early childhood

Abstract Perfluoroalkyl substances (PFAS) are suggested to have immunosuppressive effects; exposure in utero and in the first years of life is of special concern as fetuses and small children are highly vulnerable to toxicant exposure. The objective of this study was to investigate the effect of pre-natal exposure to PFAS on responses to pediatric vaccines and immune-related health outcomes in children up to 3 years of age. In the prospective birth-cohort BraMat, a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), pregnant women from Oslo and Akershus, Norway, were recruited during 2007–2008. Three annual questionnaire-based follow-ups were performed. Blood samples were collected from the mothers at the time of delivery and from the children at the age of 3 years. As a measure of pre-natal exposure to PFAS, the concentrations of perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) were determined in maternal blood from 99 BraMat participants. Main outcome measures were anti-vaccine antibody levels, common infectious diseases and allergy- and asthma-related health outcomes in the children up to the age of 3 years. There was an inverse association between the level of anti-rubella antibodies in the children’s serum at age 3 years and the concentrations of the four PFAS. Furthermore, there was a positive association between the maternal concentrations of PFOA and PFNA and the number of episodes of common cold for the children, and between PFOA and PFHxS and the number of episodes of gastroenteritis. No associations were found between maternal PFAS concentrations and the allergy- and asthma-related health outcomes investigated. The results indicate that pre-natal exposure to PFAS may be associated with immunosuppression in early childhood.

Perfluorinated compounds and subfecundity in pregnant women

Background: Perfluorinated compounds are ubiquitous pollutants; epidemiologic data suggest they may be associated with adverse health outcomes, including subfecundity. We examined subfecundity in relation to 2 perfluorinated compounds—perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Methods: This case-control analysis included 910 women enrolled in the Norwegian Mother and Child Cohort Study in 2003 and 2004. Around gestational week 17, women reported their time to pregnancy and provided blood samples. Cases consisted of 416 women with a time to pregnancy greater than 12 months, considered subfecund. Plasma concentrations of perfluorinated compounds were analyzed using liquid chromatography–mass spectrometry. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for each pollutant quartile using logistic regression. Estimates were further stratified by parity. Results: The median plasma concentration of PFOS was 13.0 ng/mL (interquartile range [IQR] = 10.3–16.6 ng/mL) and of PFOA was 2.2 ng/mL (IQR = 1.7–3.0 ng/mL). The relative odds of subfecundity among parous women was 2.1 (95% CI = 1.2–3.8) for the highest PFOS quartile and 2.1 (1.0–4.0) for the highest PFOA quartile. Among nulliparous women, the respective relative odds were 0.7 (0.4–1.3) and 0.5 (0.2–1.2). Conclusion: Previous studies suggest that the body burden of perfluorinated compounds decreases during pregnancy and lactation through transfer to the fetus and to breast milk. Afterward, the body burden may increase again. Among parous women, increased body burden may be due to a long interpregnancy interval rather than the cause of a long time to pregnancy. Therefore, data from nulliparous women may be more informative regarding toxic effects of perfluorinated compounds. Our results among nulliparous women did not support an association with subfecundity.

Changes in Concentrations of Perfluorinated Compounds, Polybrominated Diphenyl Ethers, and Polychlorinated Biphenyls in Norwegian Breast-Milk during Twelve Months of Lactation

At present, scientific knowledge on depuration rates of persistent organic pollutants (POPs) is limited and the previous assumptions of considerable reduction of body burdens through breast-feeding have recently been challenged. We therefore studied elimination rates of important POPs in nine Norwegian primiparous mothers and one mother breast-feeding her second child by collecting breast-milk samples (n = 70) monthly from about two weeks to up to twelve months after birth. Perfluorinated compounds (PFCs), polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), and polychlorinated biphenyls (PCBs) were determined in the breast-milk samples. Linear mixed effect models were established for selected compounds, and significant decreases in the range of 1.2-4.7% in breast-milk concentrations per month were observed for a wide range of PCBs and PBDEs. For the first time, depuration rates for perfluorooctylsulfonate (PFOS) and perfluorooctanoic acid (PFOA) are presented, being 3.8 and 7.8% per month, respectively (p < 0.05). The relative amount of the branched PFOS isomers in the breast-milk samples was 18% on average (range 6-36%, RSD 30%). There were no significant differences in isomer pattern between the mothers, or changes during the lactation period. After a year of nursing the breast-milk concentrations of PFCs, PBDEs, and PCBs were reduced by 15-94%.

Placental transfer of perfluorinated compounds is selective--a Norwegian Mother and Child sub-cohort study.

Perfluorinated compounds (PFCs) comprise a large group of man-made fluorinated chemicals used in a number of consumer products and industrial applications. PFCs have shown to be persistent, bio-accumulative and widespread in the environment. Animal studies have demonstrated hepatotoxicity, immunotoxicity, developmental toxicity as well as hormonal effects. We investigated prenatal exposure to several PFCs and detected up to seven different PFCs in 123 paired samples of human maternal and cord blood, from a subcohort of the Norwegian Mother and Child Cohort Study (MoBa). The maternal and foetal levels were significantly correlated for all PFCs tested with median PFC concentrations in cord blood ranging between 30 and 79% of the maternal concentrations, demonstrating placental passage. The composition of the different PFCs varied between cord and maternal blood, with a higher proportion of shorter chained PFCs together with a higher amount of the branched isomers of perfluorooctane sulfonate (PFOS) in cord blood. Additionally, the sulfonate group seems to impede transfer efficiency. This indicates a selective placental passage of the different PFCs and hence a specific foetal exposure.

Associations of in utero exposure to perfluorinated alkyl acids with human semen quality and reproductive hormones in adult men.

Background: Perfluorinated alkyl acids (PFAAs), persistent chemicals with unique water-, dirt-, and oil-repellent properties, are suspected of having endocrine-disrupting activity. The PFAA compounds perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are found globally in humans; because they readily cross the placental barrier, in utero exposure may be a cause for concern. Objectives: We investigated whether in utero exposure to PFOA and PFOS affects semen quality, testicular volume, and reproductive hormone levels. Methods: We recruited 169 male offspring (19–21 years of age) from a pregnancy cohort established in Aarhus, Denmark, in 1988–1989, corresponding to 37.6% of the eligible sons. Each man provided a semen sample and a blood sample. Semen samples were analyzed for sperm concentration, total sperm count, motility, and morphology, and blood samples were used to measure reproductive hormones. As a proxy for in utero exposure, PFOA and PFOS were measured in maternal blood samples from pregnancy week 30. Results: Multivariable linear regression analysis suggested that in utero exposure to PFOA was associated with lower adjusted sperm concentration (ptrend = 0.01) and total sperm count (ptrend = 0.001) and with higher adjusted levels of luteinizing hormone (ptrend = 0.03) and follicle-stimulating hormone (ptrend = 0.01). PFOS did not appear to be associated with any of the outcomes assessed, before or after adjustment. Conclusions: The results suggest that in utero exposure to PFOA may affect adult human male semen quality and reproductive hormone levels.