ArticleEnvironmental science and pollution research international2022
Determination of potential thresholds for N-ethyl-N-nitrosourea and ethyl methanesulfonate based on a multi-endpoint genotoxicity assessment platform in rats.
Article in Environmental science and pollution research international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 4 citations in OpenAlex.
- Advancing genotoxicity assessment with transcriptomic biomarkers: from 2D to 3D HepaRG spheroid models.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- In vitro and in vivo antimutagenic activity of Echinops spinosus crude extract and its aqueous fraction in mouse bone marrow and spleen.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025Article
- Chitosan Nanoparticles Loaded withPharmaceutics · 2023Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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