Person:

Nielsen, Flemming

Passage of environmental chemicals across the placenta has important toxicological consequences, as well as for choosing samples for analysis and for interpreting the results. To obtain systematic data, we collected in 2000 maternal and cord blood, cord tissue, placenta, and milk in connection with births in the Faroe Islands, where exposures to marine contaminants is increased. In 15 sample sets, we measured a total of 87 environmental chemicals, almost all of which were detected both in maternal and fetal tissues. The maternal serum lipid-based concentrations of organohalogen compounds averaged 1.7 times those of cord serum, 2.8 times those of cord tissue and placenta, and 0.7those of milk. For organohalogen compounds detectable in all matrices, a high degree of correlation between concentrations in maternal serum and the other tissues investigated was generally observed (r 2 > 0.5). Greater degree of chlorination resulted in lower transfer from maternal serum into milk. Concentrations of pentachlorbenzene,γ-hexachlorocyclohexane, and several polychlorinated biphenyl congeners with low chlorination were higher in fetal samples and showed poor correlation with maternal levels. Perfluorinated compounds occurred in lower concentrations in cord serum than in maternal serum. Cadmium, lead, mercury, and selenium were all detected in fetal samples, but only mercury showed close correlations among concentrations in different matrices. Although the environmental chemicals examined pass through the placenta and are excreted into milk, partitions between maternal and fetal samples are not uniform.

Background: Some persistent environmental chemicals are suspected of causing an increased risk of type 2 diabetes mellitus, a disease particularly common after the age of 70. This concern was examined in a cross-sectional study of elderly subjects from a fishing population with elevated contaminant exposures from seafood species high in the food chain. Methods: Clinical examinations of 713 Faroese residents aged 70 –74 years (64% of eligible population) included fasting plasma concentrations of glucose and insulin, and glycosylated hemoglobin. Lifetime exposure to persistent environmental chemicals from pilot whale and other traditional food was estimated from a dietary questionnaire and by analysis of blood samples for polychlorinated biphenyls (PCBs) and related food contaminants. Results: Septuagenarians with type 2 diabetes or impaired fasting glycemia tended to have higher PCB concentrations and higher past intake of traditional foods, especially during childhood and adolescence. In nondiabetic subjects, the fasting insulin concentration decreased by 7% (95% CI 12% to 2%) for each doubling of the PCB concentration after adjustment for sex and body mass index at age 20. Conversely, the fasting glucose concentration increased by 6% (1% to 13%) for each doubling in PCB. Similar associations were seen in subjects without impaired fasting glycemia, while further adjustment for current body mass index and lipid metabolism parameters attenuated some of the associations. Conclusions: Impaired insulin secretion appears to constitute an important part of the type 2 diabetes pathogenesis associated with exposure to persistent lipophilic food contaminants.

Background

Endocrine disrupting industrial chemicals, such as polychlorinated biphenyls (PCBs), are suspected to adversely affect male reproductive functions.

Objectives

The Faroe Islands community exhibits an unusually wide range of exposures to dietary contaminants, and in this setting we examined the possible association between PCB exposure and semen quality and reproductive hormones in fertile Faroese men.

Methods

Participants in this cross-sectional study include 266 proven fertile men residing in the Faroe Islands. PCB levels and hormone profiles were measured in serum samples taken at the clinical examination that included semen quality parameters.

Results

A significant positive association was seen between serum-PCB and the testosterone/estradiol ratio (p=0.04). In the unadjusted analyses, elevated PCB exposure was associated with increased serum concentrations of SHBG (p=0.01) and FSH (p=0.05). We found no association between the serum PCB concentration and the semen quality variables.

Conclusion

In this population of highly exposed fertile men, the current serum-PCB concentration was associated with higher androgen/estrogen ratio. Further studies are needed to establish the findings and further document PCB-associated hormonal effects, any time windows of increased susceptibility, and the role of PCB in sub-fecundity.

Background

Several persistent organochlorine pollutants (POPs) possess endocrine disrupting abilities, thereby potentially leading to an increased risk of obesity and metabolic diseases, especially if the exposure occurs during prenatal life. We have previously found associations between prenatal POP exposures and increased BMI, waist circumference and change in BMI from 5 to 7 years of age, though only among girls with overweight mothers.

Objectives

In the same birth cohort, we investigated whether prenatal POP exposure was associated with serum concentrations of insulin and leptin among 5-year-old children, thus possibly mediating the association with overweight and obesity at 7 years of age.

Methods

The analyses were based on a prospective Faroese Birth Cohort (n=656), recruited between 1997 and 2000. Major POPs, polychlorinated biphenyls (PCBs), p,p’-dichlorodiphenyldichloroethylene (DDE) and hexachlorobenzene (HCB), were measured in maternal pregnancy serum and breast milk. Children were followed-up at the age of 5 years where a non-fasting blood sample was drawn; 520 children (273 boys and 247 girls) had adequate serum amounts available for biomarker analyses by Luminex® technology. Insulin and leptin concentrations were transformed from continuous to binary variables, using the 75th percentile as a cut-off point. Multiple logistic regression was used to investigate associations between prenatal POP exposures and non-fasting serum concentrations of insulin and leptin at age 5 while taking into account confounders.

Results

Girls with highest prenatal POP exposure were more likely to have high non-fasting insulin levels (PCBs 4th quartile: OR=3.71; 95% CI: 1.36, 10.01. DDE 4th quartile: OR=2.75; 95% CI: 1.09, 6.90. HCB 4th quartile: OR=1.98; 95% CI: 1.06, 3.69) compared to girls in the lowest quartile. No significant associations were observed with leptin, or among boys. A mediating effect of insulin or leptin on later obesity was not observed.

Conclusion

These findings suggest, that for girls, prenatal exposure to POPs may play a role for later development of metabolic diseases by affecting the level of insulin.

To learn the extent of human exposure to polyfluoroalkyl compounds (PFCs) in a remote fishing population, we measured, in Faroese children and pregnant women, the serum concentrations of nine PFCs, including perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA), by using on-line solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry. The serum samples analyzed had been collected between 1993 and 2005 from 103 children 7 years of age, 79 of these children at 14 years of age, and from 12 pregnant women and their children 5 years later. PFOS was detected in all samples analyzed, and both PFOA and PFNA in all but one of the samples. The concentrations found are comparable to those reported elsewhere. Correlations between paired concentrations were poor. However, PFOS and PFNA concentrations correlated well with the frequency of pilot whale dinners and with concentrations of mercury and polychlorinated biphenyls. One whale meal every two weeks increased the PFOS concentration in 14-year olds by about 25% and PFNA by 50%. The high frequency of detection of most PFCs suggests widespread exposure in the Faroe Islands already by the early 1990s, with whale meat being an important source.

Synopsis: Pilot whale meat may have been an important source of dietary exposure to PFOS and PFNA among Faroe Islands residents since the 1990s

Reliable and standardized methods are necessary to determine the expression of antioxidative enzymes and their role in maintaining health. In addition, the variability of the enzyme activities within the general population caused by age, gender, and life-style factors must be described. This study describes methodological conditions that are suitable for analyzing copper–zinc superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione reductase (GR) in human erythrocytes with a high degree of reproducibility. Intervals for the enzyme activities have been established in a randomly selected population of 220 individuals between 20 and 89 years of age. An age-related decrease was observed in CuZn-SOD and GR activities, whereas no age-related changes were demonstrated for GSH-Px and CAT. The GSH-Px activity was positively associated with the intake of dietary supplements and negatively correlated with tobacco consumption. These factors probably account for the fact that women tended to have higher GSH-Px activity.

Recent studies suggest that exposure to perfluorinated alkylate substances (PFASs) may induce immunosuppression in humans and animal models. In this exploratory study, twelve healthy adult volunteers were recruited. With each subject, serum-PFAS concentrations were measured and their antibody responses prospectively followed for 30 days after a booster vaccination with diphtheria and tetanus. The results indicated that serum-PFAS concentrations were positively correlated, and positively associated, with age and male sex. The specific antibody concentrations in serum were increased from Day 4 to Day 10 post-booster, after which a constant concentration was reached. Serum PFAS concentrations showed significant negative associations with the rate of increase in the antibody responses. Interestingly, this effect was particularly strong for the longer-chain PFASs. All significant associations remained significant after adjustment for sex and age. Although the study involved a small number of subjects, these findings of a PFAS-associated reduction of the early humoral immune response to booster vaccination in healthy adults supported previous findings of PFAS immunosuppression in larger cohorts. Furthermore, the results suggested to us that cellular mechanisms right after antigen exposure should be investigated more closely to identify possible mechanisms of immunosuppression from PFAS.

Background

Most epidemiologic studies of methylmercury (MeHg) health effects rely on a single measurement of a MeHg biomarker to assess long-term exposures. Long-term reproducibility data are, therefore, needed to assess the reliability of a single measure to reflect long-term exposures. In this study we assessed within-person reproducibility of red blood cell (RBC) mercury (Hg), a marker of methyl-mercury, over 10–15-years in a sample of 57 women.

Methods

Fifty-seven women from the Nurses’ Health Study II provided two blood samples 10–15-years apart (median:12 years), which were analyzed for mercury levels in the red blood cells (B-Hg*). To characterize within-person reproducibility we estimated correlation and intraclass correlation coefficients (r and ICC) across the two samples. Further, we compared different prediction models, including variables on fish and seafood consumption, for B-Hg* at the first sample using leave-one-out cross-validation to assess predictive ability.

Results

Overall, we observed strong correlations over 10–15 years (r=0.69), as well as a high ICC (0.67; 95%CI: 0.49, 0.79). Fish and seafood consumption reported concurrently with the first B-Hg* sample accounted for 26.8% of the variability in that B-Hg*, giving a correlation of r=0.52.

Conclusions

Despite decreasing B-Hg* levels over time, we observed strong correlations and high ICC estimates across B-Hg* measured 10–15 years apart, suggesting good relative within-person stability over time. Our results indicate that a single measurement of B-Hg* likely is adequate to represent long-term exposures.