Determination of potential thresholds for N-ethyl-N-nitrosourea and ethyl methanesulfonate based on a multi-endpoint genotoxicity assessment platform in rats.

Autor: Zhu X; Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.; West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China., Huo J; Department of Nutrition and Food Safety, Chongqing Center for Disease Control and Prevention, Chongqing, China.; Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China., Zeng Z; Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.; Chengdu Fifth People's Hospital, Chengdu, Sichuan, China., Liu Y; Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, Sichuan, China., Li R; Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, Sichuan, China., Chen Y; Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, Sichuan, China., Zhang L; Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, Sichuan, China., Chen J; Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu, Sichuan, China. umbrellayy@163.com.; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, Sichuan, China. umbrellayy@163.com.
Jazyk: angličtina
Zdroj: Environmental science and pollution research international [Environ Sci Pollut Res Int] 2022 Dec; Vol. 29 (56), pp. 85128-85142. Date of Electronic Publication: 2022 Jul 06.
DOI: 10.1007/s11356-022-21605-z
Abstrakt: The main goal of the study was to investigate the genotoxic response of N-ethyl-N-nitrosourea (ENU) and ethyl methanesulfonate (EMS) at low doses in a multi-endpoint genotoxicity assessment platform in rats and to derive potential thresholds and related metrics. Male Sprague-Dawley rats were treated by daily oral gavage for 28 consecutive days with ENU (0.25 ~ 8 mg/kg bw) and EMS (5 ~ 160 mg/kg bw), both with six closely spaced dose levels. Pig-a gene mutation assay, micronucleus test, and comet assay were performed in several timepoints. Then, the dose-response relationships were analyzed for possible points of departure (PoD) using the no observed genotoxic effect level and benchmark dose (BMD) protocols with different critical effect sizes (CES, 0.05, 0.1, 0.5, and 1SD). Overall, dose-dependent increases in all investigated endpoints were found for ENU and EMS. PoDs varied across genetic endpoints, timepoints, and statistical methods, and selecting an appropriate lower 95% confidence limit of BMD needs a comprehensive consideration of the mode of action of chemicals, the characteristics of tests, and the model fitting methods. Under the experimental conditions, the PoDs of ENU and EMS were 0.0036 mg/kg bw and 1.7 mg/kg bw, respectively.
(© 2022. The Author(s).)
Databáze: MEDLINE
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