Dataset Information

Zebrafish Embryonic Exposure to BPAP and Its Relatively Weak Thyroid Hormone-Disrupting Effects.

ABSTRACT: Safe endocrine-disrupting alternatives for bisphenol A (BPA) are needed because its adverse health effects have become a public concern. Some bisphenol analogues (bisphenol F and S) have been applied, but their endocrine-disrupting potential is either not negligible or weaker than that of BPA. However, the endocrine-disrupting potential of bisphenol AP (BPAP), another BPA alternative, has not yet been fully assessed. Hence, we evaluated the thyroid hormone (TH)-disrupting potency of BPAP because THs are essential endocrine hormones. Zebrafish embryos were exposed to BPAP (0, 18.2, 43.4, or 105.9 ?g/L) for 120 h, and TH levels, the transcription of 16 TH-related genes, the transcriptome, development, and behavior were evaluated. In our study, a decrease in T4 level was observed only at the maximum nonlethal concentration, but significant changes in the T3 and TSH? levels were not detected. BPAP did not cause significant changes in transcription and gene ontology enrichment related to the TH system. Developmental and behavioral changes were not observed. Despite T4 level reduction, other markers were not significantly affected by BPAP. These might indicate that BPAP has weak or negligible potency regarding TH disruption as a BPA alternative. This study might provide novel information on the TH-disrupting potential of BPAP.

SUBMITTER: Lee S

PROVIDER: S-EPMC7712898 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Zebrafish Embryonic Exposure to BPAP and Its Relatively Weak Thyroid Hormone-Disrupting Effects.

Lee Sangwoo S Eghan Kojo K Lee Jieon J Yoo Donggon D Yoon Seokjoo S Kim Woo-Keun WK

Toxics 20201113 4

Safe endocrine-disrupting alternatives for bisphenol A (BPA) are needed because its adverse health effects have become a public concern. Some bisphenol analogues (bisphenol F and S) have been applied, but their endocrine-disrupting potential is either not negligible or weaker than that of BPA. However, the endocrine-disrupting potential of bisphenol AP (BPAP), another BPA alternative, has not yet been fully assessed. Hence, we evaluated the thyroid hormone (TH)-disrupting potency of BPAP because ...[more]

PMID: 33202880

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Project description:Endocrine disruption from environmental contaminants has been linked to a broad spectrum of adverse outcomes. One concern about endocrine-disrupting xenobiotics is the potential for additive or synergistic (i.e., greater-than-additive) effects of mixtures. A short-term dosing model to examine the effects of environmental mixtures on thyroid homeostasis has been developed. Prototypic thyroid-disrupting chemicals (TDCs) such as dioxins, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers have been shown to alter thyroid hormone homeostasis in this model primarily by up-regulating hepatic catabolism of thyroid hormones via at least two mechanisms. Our present effort tested the hypothesis that a mixture of TDCs will affect serum total thyroxine (T4) concentrations in a dose-additive manner. Young female Long-Evans rats were dosed via gavage with 18 different polyhalogenated aromatic hydrocarbons [2 dioxins, 4 dibenzofurans, and 12 PCBs, including dioxin-like and non-dioxin-like PCBs] for 4 consecutive days. Serum total T4 was measured via radioimmunoassay in samples collected 24 hr after the last dose. Extensive dose-response functions (based on seven to nine doses per chemical) were determined for individual chemicals. A mixture was custom synthesized with the ratio of chemicals based on environmental concentrations. Serial dilutions of this mixture ranged from approximately background levels to 100-fold greater than background human daily intakes. Six serial dilutions of the mixture were tested in the same 4-day assay. Doses of individual chemicals that were associated with a 30% TH decrease from control (ED30), as well as predicted mixture outcomes were calculated using a flexible single-chemical-required method applicable to chemicals with differing dose thresholds and maximum-effect asymptotes. The single-chemical data were modeled without and with the mixture data to determine, respectively, the expected mixture response (the additivity model) and the experimentally observed mixture response (the empirical model). A likelihood-ratio test revealed statistically significant departure from dose additivity. There was no deviation from additivity at the lowest doses of the mixture, but there was a greater-than-additive effect at the three highest mixtures doses. At high doses the additivity model underpredicted the empirical effects by 2- to 3-fold. These are the first results to suggest dose-dependent additivity and synergism in TDCs that may act via different mechanisms in a complex mixture. The results imply that cumulative risk approaches be considered when assessing the risk of exposure to chemical mixtures that contain TDCs.

Dataset Information

Zebrafish Embryonic Exposure to BPAP and Its Relatively Weak Thyroid Hormone-Disrupting Effects.

Publications

Zebrafish Embryonic Exposure to BPAP and Its Relatively Weak Thyroid Hormone-Disrupting Effects.

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