title: Potential thresholds for genotoxic effects by micronucleus scoring.
abstract: The concept of thresholds in genotoxicity has been open for debate in the last decades. The micronucleus (MN) test contributed to a large extent in understanding the dose-response relationship for aneugens and clastogens. The threshold concept for aneuploidy is well accepted by the scientific community based on the data and for mechanistic reasons. The concept of threshold for clastogens is still challenging. Acceptance is based on a case-by-case basis together with thorough mechanistic understanding of the different steps from the mutagen-target interactions to MN formation for this class of genotoxicants. This review summarises the significant achievements in the assessment of threshold for genotoxins using the MN test and concludes with an overview of knowledge gaps and recommendations.
authors.affiliation: Novartis Institutes for Biomedical Research, Translational Sciences, Preclinical Safety, Genetic Toxicology and Safety Pharmacology, Klybeckstrasse 141, CH-4057 Basel, Switzerland. azeddine.elhajouji@novartis.com
authors.forename: Azeddine
authors.initials: A
authors.lastname: Elhajouji
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lukamowicz
authors.forename: Zoryana
authors.initials: Z
authors.lastname: Cammerer
authors.forename: Micheline
authors.initials: M
authors.lastname: Kirsch-Volders
mesh_terms: D024422:Aneugens / Q000633:toxicity*; D000782:Aneuploidy; D004249:DNA Damage; D004351:Drug Resistance; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D012680:Sensitivity and Specificity
chemical_list: D024422:Aneugens; D009153:Mutagens