Association of In Utero Persistent Organic Pollutant Exposure With Placental Thyroid Hormones.

In utero exposure to persistent organic pollutants (POPs) can result in thyroid function disorder, leading to concerns about their impact on fetal and neonatal development. The associations between placental levels of various POPs and thyroid hormones (THs) were investigated. In a prospective Danish study initially established for assessing congenital cryptorchidism, 58 placenta samples were collected from mothers of boys born with (n = 28) and without (n = 30) cryptorchidism. The concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), organotin chemicals (OTCs), organochlorine pesticides (OCPs), T4, T3, and rT3 were measured. The associations between placental THs and various POPs were analyzed using multiple linear regression. Five PBDEs, 35 PCBs, 14 PCDD/Fs, 3 OTCs, 25 OCPs, T4, T3, and rT3 were measured. No correlation between THs and the odds of cryptorchidism was found. Several POPs were significantly associated with THs: (1) T4 was inversely associated with BDEs 99, 100, ΣPBDE, and 2378-TeCDD, and positively associated with 1234678-HpCDF; (2) T3 was positively associated with 2378-TeCDF and 12378-PeCDF; and (3) rT3 was positively associated with PCB 81, 12378-PeCDF, and 234678-HxCDF, and inversely associated with tributyltin, ΣOTC, and methoxychlor. These results revealed that POP exposures were associated with TH levels in placenta, which may be a possible mechanism for the impacts of POP exposures on children's growth and development. This study provides new insight into the complexity of thyroid-disrupting properties of POPs. More research is needed to elucidate the biological consequences of POP exposures.

Do flame retardant chemicals increase the risk for thyroid dysregulation and cancer?

PURPOSE OF REVIEW: Flame retardant chemicals are added to consumer products to reduce fire incidence and severity; approximately 1.5 million tons of these chemicals are used annually. However, their widespread use has led to their ubiquitous presence in the environment and chronic accumulation in human tissues. We summarize current trends in human flame retardant chemical exposure, and review recent data highlighting concerns for thyroid dysregulation and cancer risk in human populations. RECENT FINDINGS: Polybrominated diphenyl ethers were once commonly used as flame retardant chemicals, but recently were phased out. Exposure is associated with thyroid dysregulation (mainly T4 reductions) in animals, with new work focusing on specific mechanisms of action. Polybrominated diphenyl ethers also impact human thyroid regulation and are related to clinical thyroid disease, but associations appear both dose and life-stage dependent. Emerging data suggest that common alternate flame retardant chemicals may be more potent thyroid disruptors than their predecessors, which is particularly concerning given increasing levels of exposure. SUMMARY: Potential health impacts of flame retardant chemicals are only beginning to be understood for 'legacy flame retardant chemicals' (i.e., polybrominated diphenyl ethers), and are largely unevaluated for newer-use chemicals. Cumulatively, current data suggest impact on thyroid regulation is likely, potentially implicating flame retardant chemicals in thyroid disease and cancers for which thyroid dysregulation impacts risk or prognosis.

AQUATOX coupled foodweb model for ecosystem risk assessment of Polybrominated diphenyl ethers (PBDEs) in lake ecosystems.

The AQUATOX model considers the direct toxic effects of chemicals and their indirect effects through foodwebs. For this study, the AQUATOX model was applied to evaluating the ecological risk of Polybrominated diphenyl ethers (PBDEs) in a highly anthropogenically disturbed lake-Baiyangdian Lake. Calibration and validation results indicated that the model can adequately describe the dynamics of 18 biological populations. Sensitivity analysis results suggested that the model is highly sensitive to temperature limitation. PBDEs risk estimate results demonstrate that estimated risk for natural ecosystems cannot be fully explained by single species toxicity data alone. The AQUATOX model could provide a good basis in ascertaining ecological protection levels of "chemicals of concern" for aquatic ecosystems. Therefore, AQUATOX can potentially be used to provide necessary information corresponding to early warning and rapid forecasting of pollutant transport and fate in the management of chemicals that put aquatic ecosystems at risk.

Identification of differentially expressed genes in the digestive gland of manila clam Ruditapes philippinarum exposed to BDE-47.

Suppression subtractive hybridization (SSH) was used to identify alterations in gene transcription of the manila clam Ruditapes philippinarum after exposure to 5µg/L 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) for 15days. The ability to accumulate BDE-47 in digestive gland and gill was also evaluated in order to provide information for food safety. Analysis of tissue extracts indicated that digestive gland had the higher BDE-47 levels (12,463.1±1334.8 ng/g d.w.) compared to gill (6368.6±738.7ng/g d.w.) after a 15-day exposure period. Forward and reverse SSH libraries were made from pooled digestive glands of R. philippinarum, from which 75 high quality sequences were obtained by BLAST analysis. The expression of 39 genes with significant homology (E-value<10(-5)) out of the 75 sequences was investigated by quantitative RT-PCR. Among the 39 genes, 27 genes were found up-regulated while 12 genes were found down-regulated after the BDE-47 exposure. The 39 genes were involved in cellular cycle, cytoskeleton, substance and energy metabolism, stress response, innate immunity and cell signaling and transport which were extensively discussed. This study provides a preliminary basis for studying the response of marine bivalves upon exposure to PBDEs in terms of regulated gene expression.

Facing the challenge of data transfer from animal models to humans: the case of persistent organohalogens.

A well-documented fact for a group of persistent, bioaccumulating organohalogens contaminants, namely polychlorinated biphenyls (PCBs), is that appropriate regulation was delayed, on average, up to 50 years. Some of the delay may be attributed to the fact that the science of toxicology was in its infancy when PCBs were introduced in 1920's. Nevertheless, even following the development of modern toxicology this story repeats itself 45 years later with polybrominated diphenyl ethers (PBDEs) another compound of concern for public health. The question is why? One possible explanation may be the low coherence between experimental studies of toxic effects in animal models and human studies. To explore this further, we reviewed a total of 807 PubMed abstracts and full texts reporting studies of toxic effects of PCB and PBDE in animal models. Our analysis documents that human epidemiological studies of PBDE stand to gain little from animal studies due to the following: 1) the significant delay between the commercialisation of a substance and studies with animal models; 2) experimental exposure levels in animals are several orders of magnitude higher than exposures in the general human population; 3) the limited set of evidence-based endocrine endpoints; 4) the traditional testing sequence (adult animals--neonates--foetuses) postpones investigation of the critical developmental stages; 5) limited number of animal species with human-like toxicokinetics, physiology of development and pregnancy; 6) lack of suitable experimental outcomes for the purpose of epidemiological studies. Our comparison of published PCB and PBDE studies underscore an important shortcoming: history has, unfortunately, repeated itself. Broadening the crosstalk between the various branches of toxicology should therefore accelerate accumulation of data to enable timely and appropriate regulatory action.