Department of Environmental Medicine, Institute of Public Health (C.A.G.T., L.I.R., C.D., P.G., F.N., T.K.J.), and Institute of Sports Science and Clinical Biomechanics (A.G., M.R.-L., L.B.A.), University of Southern Denmark, 5000 Odense C, Denmark; and Department of Biostatistics (K.D.S., T.S.), University of Copenhagen, 1353 Copenhagen, Denmark.
Our objective was to explore whether childhood exposure to perfluorinated and polyfluorinated compounds (PFCs), widely used stain- and grease-repellent chemicals, is associated with adiposity and markers of glycemic control.
Body mass index, skinfold thickness, waist circumference, leptin, adiponectin, insulin, glucose, and triglyceride concentrations were assessed in 8- to 10-year-old children in 1997 in a subset of the European Youth Heart Study, Danish component. Plasma PFC concentrations were available from 499 children. Linear regression models were performed to determine the association between PFC exposure and indicators of adiposity and markers of glycemic control.
There was no association between PFC exposures and adiposity or markers of glycemic control in normal-weight children. Among overweight children, an increase of 10 ng perfluorooctane sulfonic acid/mL plasma was associated with 16.2% (95% confidence interval [CI], 5.2%-28.3%) higher insulin concentration, 12.0% (95% CI, 2.4%-22.4%) higher ß-cell activity, 17.6% (95% CI, 5.8%-30.8%) higher insulin resistance, and 8.6% (95% CI, 1.2%-16.5%) higher triglyceride concentrations, and an increase of 10 ng perfluorooctanoic acid/mL plasma was associated with 71.6% (95% CI, 2.4%-187.5%) higher insulin concentration, 67.5% (95% CI, 5.5%-166.0%) higher ß-cell function, 73.9% (95% CI, 0.2%-202.0%) higher insulin resistance, and 76.2% (95% CI, 22.8%-153.0%) higher triglyceride concentrations.
Increased PFC exposure in overweight 8- to 10-year-old children was associated with higher insulin and triglyceride concentrations. Chance findings may explain some of our results, and due to the cross-sectional design, reverse causation cannot be excluded. The findings therefore need to be confirmed in longitudinal studies.
Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are used in a variety of consumer products and have been detected worldwide in human blood. Recent studies mainly of highly exposed populations have indicated that PFOA and PFOS may affect serum cholesterol levels, but the magnitude of the effect may be inconsistent across exposure levels. The aim of the present cross-sectional study was to investigate the association between plasma PFOA and PFOS and total cholesterol in a general, middle-aged Danish population. The study population comprised 753 individuals (663 men and 90 women), 50-65 years of age, nested within a Danish cohort of 57,053 participants. Blood samples were taken from all cohort members at enrolment (1993-1997) and stored in a biobank at -150°C. Plasma levels of PFOA and PFOS and serum levels of total cholesterol were measured. The associations between plasma PFOA and PFOS levels and total cholesterol levels were analysed by generalized linear models, both crude and adjusted for potential confounders. We observed statistically significant positive associations between both perfluorinated compounds and total cholesterol, e.g. a 4.4 [95% CI ?=? 1.1-7.8] higher concentration of total cholesterol (mg/dL) per interquartile range of PFOA plasma level. Sex and prevalent diabetes appeared to modify the association between PFOA and PFOS, respectively, and cholesterol. In conclusion, this study indicated positive associations between plasma PFOA and PFOS levels and total cholesterol in a middle-aged Danish population, although whether the observed pattern of results reflects a causal association is unclear.
Cites: Drug Chem Toxicol. 2000 Nov;23(4):603-2011071397
Cites: Environ Sci Technol. 2011 Oct 1;45(19):8137-4320939531
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.
We investigated whether in utero exposure to PFOA and PFOS affects semen quality, testicular volume, and reproductive hormone levels.
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.
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.
The results suggest that in utero exposure to PFOA may affect adult human male semen quality and reproductive hormone levels.
Cites: Environ Sci Technol. 2004 Sep 1;38(17):4489-9515461154
Cites: Environ Health Perspect. 2004 Aug;112(11):1204-715289168
Perfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited.
We investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children.
Among 83,389 mother-child pairs enrolled in the Danish National Birth Cohort during 1996-2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child's sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights.
Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in = 90% of the samples. We did not find consistent evidence of associations between mother's PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise.
In this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children.
Cites: Environ Sci Technol. 2011 Oct 1;45(19):8151-921682250
Cites: J Autism Dev Disord. 2010 Feb;40(2):139-4819728067
Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are used in a variety of industrial and consumer products and have been detected worldwide in human blood. The sources for human exposure are not well described, but dietary intake is suggested as an important source. In this study of 652 Danish men from the Diet, Cancer and Health cohort, we examined intake of 10 major dietary groups, tap water drinks, alcohol consumption, cooking method, geographical area, age, smoking status, and BMI as potential determinants of PFOA and PFOS plasma levels. Living in the Aarhus area was associated with higher PFOA and PFOS plasma levels compared with living in the Copenhagen area, and never smokers had higher levels than current smokers. Frying as compared with other cooking methods was a determinant of PFOA and PFOS levels. BMI and alcohol consumption were inversely associated with both compounds. Among the dietary groups, only intake of eggs was significantly positively associated with PFOS plasma levels. In future studies, PFOA and PFOS levels in air, dust and water samples should be measured to elucidate further the sources of exposure; exposure through diet needs to be studied in greater detail. Our finding of a higher body burden of PFOA and PFOS among never smokers also warrants further evaluation.
Dietary intake, age, gender, and body mass index were investigated as possible predictors of perfluorinated compounds in a study population from northern Norway (44 women and 16 men). In addition to donating a blood sample, the participants answered a detailed questionnaire about diet and lifestyle. Perfluorooctane sulfonate (PFOS) (29 ng/mL), perfluorooctanoate (PFOA) (3.9 ng/mL), perfluorohexane sulfonate (PFHxS) (0.5 ng/mL), perfluorononanoate (PFNA) (0.8 ng/mL), and perfluoroheptane sulfonate (PFHpS) (1.1 ng/mL) were detected in more than 95% of all samples. Of the dietary items investigated, fruit and vegetables significantly reduced the concentrations of PFOS and PFHpS, whereas fatty fish to a smaller extent significantly increased the levels of the same compounds. Men had significantly higher concentrations of PFOS, PFOA, PFHxS, and PFHpS than women. There were significant differences in PFOS isomer pattern between genders, with women having the largest proportion of linear PFOS. PFOS, PFHxS, and PFHpS concentrations also increased with age.
Cites: Int Arch Occup Environ Health. 2007 Jul;80(7):643-817219182
Perfluorinated compounds (PFCs) are man-made chemicals that are heat stable, non-flammable and able to repel both water and oils. Biomonitoring research shows global distribution in human, animal and aquatic environments of these chemicals. PFCs have been shown to activate the peroxisome proliferator-activated receptors which play a large role in metabolism and the regulation of energy homeostasis. Previous epidemiological research has also suggested a potential role of PFCs on lipid and glucose metabolism.
The objectives of this study were to examine the association between the levels of perfluorinated compounds perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) in plasma and metabolic function and plasma lipid levels.
Using cross-sectional data from the Canadian Health Measures Survey (Cycle 1 2007-2009) we examined the association in adults between plasma levels of PFOA, PFOS and PFHxS (n=2700) on cholesterol outcomes, metabolic syndrome and glucose homeostasis using multivariate linear and logistic regression models.
We found some evidence of a significant association between perfluoroalkyl substances, notably PFHxS, with total cholesterol (TC), low-density lipoprotein cholesterol (LDL), total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL) and non-HDL cholesterol as well as an elevated odds of high cholesterol. We found some associations with PFOA and PFOS in our unweighted models but these results did not remain significant after weighting for sampling strategy. We found no association with metabolic syndrome, or glucose homeostasis parameters.
This study showed lower levels of PFOA and PFOS and slightly higher levels of PFHxS than other published population studies. Our results did not give significant evidence to support the association with cholesterol outcomes with PFOS and PFOA. However, we did observe several significant associations with the PFHxS and cholesterol outcomes (LDL, TC, NON-HDL, TC/HDL ratio).
Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have consistently been associated with higher cholesterol levels in cross sectional studies. Concerns have, however, been raised about potential confounding by diet and clinical relevance.
To examine the association between concentrations of PFOS and PFOA and total cholesterol in serum during pregnancy taking into considerations confounding by diet.
854 Danish women who gave birth in 1988-89 and provided a blood sample and reported their diet in week 30 of gestation.
Mean serum PFOS, PFOA and total cholesterol concentrations were 22.3 ng/mL, 4.1 ng/mL and 7.3 mmol/L, respectively. Maternal diet was a significant predictor of serum PFOS and PFOA concentrations. In particular intake of meat and meat products was positively associated while intake of vegetables was inversely associated (P for trend
Municipal 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.
To determine the rates of decline in serum perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), and their corresponding half-lives.
Up to seven blood samples were collected between June 2014 and September 2016 from 106 participants (age 4-84 years, 53% female).
Median 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.
The 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.
Immune suppression may be a critical effect associated with exposure to perfluorinated compounds (PFCs), as indicated by recent data on vaccine antibody responses in children. Therefore, this information may be crucial when deciding on exposure limits.
Results obtained from follow-up of a Faroese birth cohort were used. Serum-PFC concentrations were measured at age 5 years, and serum antibody concentrations against tetanus and diphtheria toxoids were obtained at age 7 years. Benchmark dose results were calculated in terms of serum concentrations for 431 children with complete data using linear and logarithmic curves, and sensitivity analyses were included to explore the impact of the low-dose curve shape.
Under different linear assumptions regarding dose-dependence of the effects, benchmark dose levels were about 1.3 ng/mL serum for perfluorooctane sulfonic acid and 0.3 ng/mL serum for perfluorooctanoic acid at a benchmark response of 5%. These results are below average serum concentrations reported in recent population studies. Even lower results were obtained using logarithmic dose-response curves. Assumption of no effect below the lowest observed dose resulted in higher benchmark dose results, as did a benchmark response of 10%.
The benchmark dose results obtained are in accordance with recent data on toxicity in experimental models. When the results are converted to approximate exposure limits for drinking water, current limits appear to be several hundred fold too high. Current drinking water limits therefore need to be reconsidered.