Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Thyroid Hormone during Pregnancy

BACKGROUND: Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy. OBJECTIVES: Our goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women. METHODS: We measured the concentration of 10 PBDE congeners, free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation. RESULTS: Serum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (ΣPBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), -20.6 to 0.0] and 18.7% (95% CI, -29.2 to -4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T4) were also significantly elevated in participants in the highest quartile of ΣPBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T4 were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ΣPBDEs. CONCLUSIONS: Results suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development

Importance of Passive Diffusion in the Uptake of Polychlorinated Biphenyls by Phagotrophic Protozoa

Unicellular protozoan grazers represent a size class of organisms where a transition in the mechanism of chlorobiphenyl (CB) introduction, from diffusion through surface membranes to ingestion of contaminated prey, could occur. This study compares the relative importance of these two processes in the overall uptake of polychlorinated biphenyls by protists. Uptake rates and steady-state concentrations were compared in laboratory cultures of grazing and nongrazing protozoa. These experiments were conducted with a 10-μm marine scuticociliate (Uronema sp.), bacterial prey (Halomonas halodurans), and a suite of 21 CB congeners spanning a range of aqueous solubilities. The dominant pathway of CB uptake by both grazing and nongrazing protozoa was diffusion. Organic-carbon-normalized CB concentrations (in the protozoan cell) were equivalent in grazing and nongrazing protozoa for all congeners studied. Rate constants for uptake into and loss from the protozoan cell were independently determined by using [3,3′,4,4′-(14)C]tetrachlorobiphenyl (IUPAC no. 77), 0.38 ± 0.03 min(−1) and (1.1 ± 0.1) × 10(−5) (g of organic carbon)(−1) min(−1), respectively. Magnitudes of the uptake and loss processes were calculated and compared by using a numerical model. The model result was consistent with data from the bioaccumulation experiment and supported the hypothesis that diffusive uptake is faster than ingestive uptake in phagotrophic unicellular protozoa

Physiologically Based Pharmacokinetic (PBPK) Models for Lifetime Exposure to PCB 153 in Male and Female Harbor Porpoises (Phocoena phocoena): Model Development and Evaluation

Physiologically based pharmacokinetic (PBPK) models were developed for the most persistent polychlorinated biphenyl (PCB 153) in male and female harbor porpoises (Phocoena phocoena) to elucidate processes such as uptake, distribution, and elimination. Due to its limited metabolic capacities, long life span, and top position in marine food chains, this species is highly sensitive to pollution. The models consist of 5 compartments, liver, blubber, kidney, brain, and a compartment which accounts for the rest of the body, all connected through blood. All physiological and biochemical parameters were extracted from the literature, except for the brain/blood partition coefficient and rate of excretion, which were both fitted to data sets used for validation of the models. These data sets were compiled from our own analyses performed with GCMS on tissue samples of harbor porpoises. The intake of PCB 153 was from milk from birth to 4 months, and after weaning fish was the main food source. Overall, these models reveal that concentrations of PCB 153 in males increase with age but suggest that,asthe animalsgrowolder, metabolic transformation can be a possible pathway for elimination as well. In contrast, the model for females confirms that gestation and lactation are key processes for eliminating PCB 153 as body burdens decrease with age. These PBPK models are capable of simulating the bioaccumulation of PCB 153 during the entire life span of approximately 20 years of the harbor porpoises