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.
Exposure to methylmercury was shown to decrease neural stem cell populations, whereas aerobic fitness has beneficial effects on the adult brain that relies on improved neurogenesis in the hippocampus.
To examine the association between aerobic fitness and neurocognitive outcomes at young adult age, along with the potential moderating effect of prenatal exposure to methylmercury.
At age 22 years, 262 members of a Faroese birth cohort, established in 1986-1987, underwent a graded exercise test of aerobic fitness to measure maximal oxygen uptake (VO2Max). Their prenatal methylmercury exposure had been assessed from the mercury concentration in cord blood. We estimated cross-sectional associations between VO2Max and multiple measures of neurocognitive function. In addition, we compared groups with low and high prenatal methylmercury exposure.
A one standard deviation (SD) increase in VO2Max was associated with better scores on short-term memory and cognitive processing speed by 0.21 SD (95% CI: -0.04, 0.46) and 0.28 SD (95% CI: 0.02, 0.54), respectively. In the group with lower prenatal methylmercury exposure, a one SD increase in VO2Max was associated with increased scores on cognitive processing speed by 0.45 SD (95% CI: 0.08, 0.81) and with a slightly lesser benefit in short-term memory. No such association was observed in the group with high prenatal methylmercury exposure.
Higher aerobic capacity was associated with better performance in short-term memory and processing speed. However, prenatal methylmercury exposure seemed to attenuate these positive associations.
Background: Breast-feeding may affect the risk of developing allergy during childhood and may also cause exposure to immunotoxicants, such as polychlorinated biphenyls (PCBs), which are of concern as marine pollutants in the Faroe Islands and the Arctic region. Objectives: The objective was to assess whether sensitization and development of allergic disease was associated with duration of breast-feeding and prenatal or postnatal exposures to PCBs and methylmercury. Methods: A cohort of 656 singleton births was formed in the Faroe Islands during 1999-2001. Duration of breast-feeding and history of asthma and atopic dermatitis were recorded at clinical examinations at ages 5 and 7 years. PCB and mercury concentrations were determined in blood samples obtained at parturition and at follow-up. Serum from 464 children (71%) at age 7 years was analyzed for total IgE and grass-specific IgE. Results: The total IgE concentration in serum at age 7 years was positively associated both with the concomitant serum PCB concentration and with the duration of breastfeeding. However, the effect only of the latter was substantially attenuated in a multivariate analysis. A raised grass-specific IgE concentration compatible with sensitization was positively associated with the duration of breast-feeding and inversely associated with prenatal methylmercury exposure. However, a history of asthma or atopic dermatitis was not associated with the duration of breast-feeding, but children with atopic dermatitis had lower prenatal PCB exposures than non-allergic children. Conclusions: These findings suggest that developmental exposure to immunotoxicants may both increase and decrease the risk of allergic disease, and that associations between breast-feeding and subsequent allergic disease in children may, at least in part, reflect lactational exposure to immunotoxic food contaminants.
As a model of high trophic level carnivores, sledge dogs were fed from 2 to 18 months of age with minke whale blubber containing organohalogen compounds (OHC) corresponding to 128 µg PCB/day. Controls were fed uncontaminated porcine fat. Thyroid hormone levels were assessed in 7 exposed and 7 control sister bitches (sampled at age 6-18 months) and 4 exposed and 4 control pups, fed the same diet as their mothers (sampled age 3-12 months). Lower free and total T3 and T4 were seen in exposed vs. control bitches beyond 10 months of age, and total T3 was lower through 3-12 months of age in exposed pups. A negative correlation with thyroid gland weight was significant for SDDT, as was a positive association with total T3 for dieldrin. This study therefore supports observational data that OHCs may adversely affect thyroid functions, and it suggests that OHC exposure duration of 10 months or more may be required for current OHC contamination levels to result in detectable adverse effects on thyroid hormone dynamics.
Quality assurance of exposure biomarkers usually focuses on laboratory performance only. Using data from a prospective birth cohort study in the Faroe Islands, we have assessed the total imprecision of exposure biomarkers. As biomarkers of prenatal methylmercury exposure, mercury concentrations were determined in cord blood, cord tissue, and maternal hair. We determined their mutual correlations and their associations with the child's neurobehavioral effect variables at age 7 years. The exposure biomarkers correlated well with one another, but the cord blood mercury concentration showed the best associations with neurobehavioral deficits. Because at least three exposure parameters were available, factor analysis and structural equation modeling could be applied to determine the total imprecision of each biomarker. For the cord-blood parameter, the total imprecision was 25-30%, and almost twice as much for maternal hair. The total imprecision of these biomarkers much exceeded the normal laboratory variability of less than 5%. Such imprecision can cause underestimation of dose-related toxicity, and data analysis should therefore include sensitivity analyses that take this factor into account. Ignoring preanalytical imprecision may cause serious bias.
Following an official recommendation in the Faroe Islands that women should abstain from eating mercury-contaminated pilot whale meat, a survey was carried out to obtain information on dietary habits and hair samples for mercury analysis. A letter was sent to all 1180 women aged 26-30 years who resided within the Faroes, and the women were contacted again 1 year later. A total of 415 women responded to the first letter; the second letter resulted in 145 repeat hair samples and 125 new responses. Questionnaire results showed that Faroese women, on average, consumed whale meat for dinner only once every second month, but the frequency and meal size depended on the availability of whale in the community. The geometric mean hair-mercury concentration at the first survey was higher in districts with available whale than in those without (3.03 vs. 1.88 microg/g; P=0.001). The mercury concentration also depended on the frequency of whale meat dinners and on the consumption of dried whale meat. The 36 women who did not eat whale meat at all had a geometric mean hair-mercury concentration of 1.28 microg/g. At the time of the second survey, the geometric mean had decreased to 1.77 microg/g (P
Seafood consumption is the primary route of methylmercury (MeHg) exposure for most populations. Inherent uncertainties in dietary survey data point to the need for an empirical tool to confirm exposure sources. We therefore explore the utility of Hg stable isotope ratios in human hair as a new method for discerning MeHg exposure sources. We characterized Hg isotope fractionation between humans and their diets using hair samples from Faroese whalers exposed to MeHg predominantly from pilot whales. We observed an increase of 1.75‰ in d(202)Hg values between pilot whale muscle tissue and Faroese whalers' hair but no mass-independent fractionation. We found a similar offset in d(202)Hg between consumed seafood and hair samples from Gulf of Mexico recreational anglers who are exposed to lower levels of MeHg from a variety of seafood sources. An isotope mixing model was used to estimate individual MeHg exposure sources and confirmed that both ?(199)Hg and d(202)Hg values in human hair can help identify dietary MeHg sources. Variability in isotopic signatures among coastal fish consumers in the Gulf of Mexico likely reflects both differences in environmental sources of MeHg to coastal fish and uncertainty in dietary recall data. Additional data are needed to fully refine this approach for individuals with complex seafood consumption patterns.
BACKGROUND: Epidemiological documentation of endocrine disruption is complicated by imprecise exposure assessment, especially when exposures are mixed. Even if the estrogenic activity of all compounds were known, the combined effect of possible additive and/or inhibiting interaction of xenoestrogens in a biological sample may be difficult to predict from chemical analysis of single compounds alone. Thus, analysis of mixtures allows evaluation of combined effects of chemicals each present at low concentrations. METHODS: We have developed an optimized in vitro E-Screen test to assess the combined functional estrogenic response of human serum. The xenoestrogens in serum were separated from endogenous steroids and pharmaceuticals by solid-phase extraction followed by fractionation by high-performance liquid chromatography. After dissolution of the isolated fraction in ethanol-DMSO, the reconstituted extract was added with estrogen-depleted fetal calf serum to MCF-7 cells, the growth of which is stimulated by estrogen. After a 6-day incubation on a microwell plate, cell proliferation was assessed and compared with the effect of a 17-beta-estradiol standard. RESULTS AND CONCLUSIONS: To determine the applicability of this approach, we assessed the estrogenicity of serum samples from 30 pregnant and 60 non-pregnant Danish women thought to be exposed only to low levels of endocrine disruptors. We also studied 211 serum samples from pregnant Faroese women, whose marine diet included whale blubber that contain a high concentration of persistent halogenated pollutants. The estrogenicity of the serum from Danish controls exceeded the background in 22.7 % of the cases, while the same was true for 68.1 % of the Faroese samples. The increased estrogenicity response did not correlate with the lipid-based concentrations of individual suspected endocrine disruptors in the Faroese samples. When added along with the estradiol standard, an indication of an enhanced estrogenic response was found in most cases. Thus, the in vitro estrogenicity response offers a promising and feasible approach for an aggregated exposure assessment for xenoestrogens in serum.
Perfluorinated alkylated substances (PFAS) have been extensively used in consumer products and humans are widely exposed to these persistent compounds. A recent study found no association between exposure to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) and miscarriage, but no studies have examined adverse effect of the more recently introduced PFASs. We therefore conducted a case-control study within a population-based, prospective cohort during 2010-2012. Newly pregnant women residing in the Municipality of Odense, Denmark were invited to enroll in the Odense Child Cohort at their first antenatal visit before pregnancy week 12. Among a total of 2,874 participating women, 88 suffered a miscarriage and 59 had stored serum samples, of which 56 occurred before gestational week 12. They were compared to a random sample (N=336) of delivering women, who had also donated serum samples before week 12. Using a case-control design, 51 of the women suffering a miscarriage were matched on parity and gestational day of serum sampling with 204 delivering women. In a multiple logistic regression with adjustment for age, BMI, parity and gestational age at serum sampling, women with the highest tertile of exposure to perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in pregnancy had odds ratios for miscarriage of 16.5 (95% CI 7.4-36.6-36.5) and 2.67 (1.31-5.44), respectively, as compared to the lowest tertile. In the matched data set, the OR were 37.9 (9.9-145.2) and 3.71 (1.60-8.60), respectively. The association with perfluorohexane sulfonic acid (PFHxS) was in the same direction, but not statistically significant, while no association was found with PFOA and PFOS. Our findings require confirmation due to the possible public health importance, given that all pregnant women are exposed to these widely used compounds.
Perfluorinated chemicals (PFCs) have been widely used and have emerged as important food contaminants. A recent study on pregnant women suggested that PFC exposure was associated with a longer time to pregnancy (TTP). We examined the association between serum concentrations of PFCs in females and TTP in 222 Danish first-time pregnancy planners during the years 1992-1995.
The couples were enrolled in the study when discontinuing birth control and followed for six menstrual cycles or until a clinically recognized pregnancy occurred. Fecundability ratio (FR) was calculated using discrete-time survival models. In addition, odds ratio (OR) for TTP >6 cycles was calculated.
OR for TTP >6 cycles for those with PFC concentrations above the median were 0.96 [95% confidence interval (CI): 0.54-1.64] for perfluorooctane sulfonic acid (PFOS), the major PFC, compared with those below the median. FRs for those with PFOS concentrations above the median were 1.05 (95% CI: 0.74-1.48) compared with those below the median. Other PFCs showed the same lack of association with TTP. The results were not affected by adjustment for covariates. PFOS and perfluorooctanoic acid concentrations were similar to those observed in a previous Danish study.
These findings suggest that exposure to PFCs affects TTP only to a small extent, if at all.