Hazard assessment of beta-lactams: Integrating in silico and QSTR approaches with in vivo zebrafish embryo toxicity testing

Ying Han; Yuanyuan Ma; Bo Chen; Jingpu Zhang; Changqin Hu

doi:10.1016/j.ecoenv.2021.113106

Hazard assessment of beta-lactams: Integrating in silico and QSTR approaches with in vivo zebrafish embryo toxicity testing

Ecotoxicol Environ Saf. 2022 Jan 1:229:113106. doi: 10.1016/j.ecoenv.2021.113106. Epub 2021 Dec 21.

Authors

Ying Han¹, Yuanyuan Ma², Bo Chen², Jingpu Zhang³, Changqin Hu⁴

Affiliations

¹ Department of Pharmacology, NHC Key Laboratory of Biotechnology of Antibiotics, Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Institute for Chemical Drug Control, National Institutes for Food and Drug Control, Beijing 102629, China.
² Department of Pharmacology, NHC Key Laboratory of Biotechnology of Antibiotics, Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
³ Department of Pharmacology, NHC Key Laboratory of Biotechnology of Antibiotics, Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: zhangjingpu@imb.pumc.edu.cn.
⁴ Institute for Chemical Drug Control, National Institutes for Food and Drug Control, Beijing 102629, China. Electronic address: hucq@nifdc.org.cn.

PMID: 34942418
DOI: 10.1016/j.ecoenv.2021.113106

Abstract

Antibiotics have emerged as a well-known representative of pharmaceuticals and personal care products (PPCPs) by causing public health and environmental problems due to their potential toxicity. β-lactams are the most commonly used antibiotics in the world. This study used zebrafish embryos to evaluate the toxicity of β-lactams. The results showed that 23 β-lactam compounds induced malformation and death in a concentration-response manner. Moreover, this study established and validated quantitative structure-toxicity relationship (QSTR) models for the toxicity of β-lactams in zebrafish. These models performed well and fast in the prediction of the acute toxicity of β-lactams. Structural interpretation indicated that the β-lactam ring, the thiazolidine/dihydrothiazine rings, the side chains, and spatial configuration are the main factors responsible for the toxicity of β-lactams. The results from our previous studies and this study also revealed that the potential biological risks caused by β-lactams and their degradation products could not be ignored. This study provided important data for further environmental risk assessment of β-lactams and regulatory purposes.

Keywords: Environmental hazard assessment; In silico; QSTR; Zebrafish; β-lactams.

MeSH terms

Animals
Anti-Bacterial Agents / toxicity
Cosmetics*
Toxicity Tests
Zebrafish
beta-Lactams* / toxicity

Substances

Anti-Bacterial Agents
Cosmetics
beta-Lactams