Toxicogenomic assessment of 6-OH-BDE47 induced developmental toxicity in chicken embryo
Citation:
Peng, Y., P. Xia, J. Zhang, Dan Villeneuve, J. Zhang, Z. Wang, S. Wei, H. Yu, AND X. Zhang. Toxicogenomic assessment of 6-OH-BDE47 induced developmental toxicity in chicken embryo. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 50(22):12493-12503, (2016).
Impact/Purpose:
An adverse outcome pathway (AOP) linking activation of the aryl hydrocarbon receptor (AhR) to embryolethality in birds has been developed and submitted to the AOP-wiki. However, to date, most of the support from that AOP is based on studies with a limited number of classic, dioxin-like AhR agonists. The present study is one of the first to test these AOP-based predictions for a hydroxylated polybrominated diphenyl ether which has been previously shown to activate the AhR in vitro, but had not been previously tested in birds, in vivo. Thus, the experiment provides a real-world test of the AOP and the ability to predict hazard using that AOP. While not every key event described in the AOP was observed, likely due to lack of temporal resolution in the study, overall the results were largely consistent with the proposed AOP. Consequently, they help increase confidence in its use for various regulatory applications and help to expand the established domain of chemical initiators for which the AOP has relevance. Given that AhR agonism is one of the activities frequently detected through effects-based monitoring of environmental samples, this AOP, and others related to the molecular initiating event of AhR activation are likely to be highly relevant for risk assessment purposes. This research supports activities and goals under CSS Project 17.01, adverse outcome pathway discovery and development, and was the result of EPA’s collaboration with the Chinese Ministry of Science and Technology (MOST), project 3.1 Emerging Contaminants, subtask 3.1A collaborative AOP development.
Description:
Hydroxylated and methoxylated polybrominated diphenyl ethers (OH-/MeO-PBDEs) are analogs of PBDEs with hundreds of possible structures and many of them can activate aryl hydrocarbon receptor (AhR), however, the in vivo evidence on the toxicity of OH-/MeO-PBDEs are still very limited. 6-OH-BDE47 is a relatively potent AhR activator and a predominant congener of OH-PBDEs detected in the environment. Here the developmental toxicity of 6-OH-BDE47 in chicken embryos was assessed using a toxicogenomic approach. Fertilized chicken eggs were dosed via in ovo administration of 0.006 to 0.474 nmol 6-OH-BDE47/g egg followed by 18-days incubation. Significant embryo mortality (LD50=0.294 pmol/g egg) and increased hepatic somatic index (HSI) were caused by 6-OH-BDE47 exposure. The functional enrichment of differentially expressed genes (DEGs) associated with oxidative phosphorylation, generation of precursor metabolites and energy, and electron transport chain suggest that 6-OH-BDE47 exposure may disrupt the embryo development by altering the function of energy production in mitochondrion. Moreover, AhR mediated responses including up-regulation of CYP1A4 was observed in the livers of embryos exposed to 6-OH-BDE47. Overall, this study confirmed the prediction of embryo lethality by 6-OH-BDE47 consistent with an adverse outcome pathway (AOP) linking AhR activation to embryo lethality. The results provide an example of application of AOP in the hazard and ecological risk assessment of environmental emerging chemicals.
