Elucidating the differences in metal toxicity by quantitative adverse outcome pathways

Yang, L; Zeng, J; Gao, N; Zhu, L; Feng, J

HERO ID

10618602

Reference Type

Journal Article

Year

2022

Language

English

PMID

36083827

HERO ID 10618602
In Press No
Year 2022
Title Elucidating the differences in metal toxicity by quantitative adverse outcome pathways
Authors Yang, L; Zeng, J; Gao, N; Zhu, L; Feng, J
Journal Environmental Science & Technology
Volume 56
Issue 18
Page Numbers 13233-13244
Abstract Numerous studies have reported that the toxicity differences among metals are widespread; however, little is known about the mechanism of differences in metal toxicity to aquatic organisms due to the lack of quantitative understanding of their adverse outcome pathway. Here, we investigated the effects of Cd and Cu on bioaccumulation, gene expression, physiological responses, and apical effects in zebrafish larvae. RNA sequencing was conducted to provide supplementary mechanistic information for the effects of Cd and Cu exposure. On this basis, we proposed a quantitative adverse outcome pathway (qAOP) suitable for metal risk assessment of aquatic organisms. Our work provides a mechanistic explanation for the differences in metal toxicity where the strong bioaccumulation of Cu enables the newly accumulated Cu to reach the threshold that causes different adverse effects faster than Cd in zebrafish larvae, resulting in a higher toxicity of Cu than that of Cd. Furthermore, we proposed a parameter CIT/BCF (the ratio of internal threshold concentration and bioaccumulation factor) that helps to understand the toxicity differences by combining the information of bioaccumulation and internal threshold of adverse effects. This work demonstrated that qAOP is an effective quantitative tool for understanding the toxicity mechanism and highlight the importance of toxicokinetics and toxicodynamics at different biological levels in determining the metal toxicity.
Doi 10.1021/acs.est.2c03828
Pmid 36083827
Wosid WOS:000854962900001
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword quantitative adverse outcome pathway, zebrafish larvae, metals, toxicokinetic, toxicodynamic, toxicity difference