Aneuploidy: a report of an ECETOC task force

Area of Science:

• Toxicology
• Genetics
• Risk Assessment

Background:

• Aneuploidy is implicated in birth defects, pregnancy loss, and cancer.
• Chemically induced aneuploidy is a concern, but human data are limited.
• Existing toxicological tests may not adequately detect aneugenic chemicals.

Purpose of the Study:

• To evaluate the aneugenic potential of chemicals using standard genotoxicity assays.
• To assess the reliability of current methods for detecting chemically induced aneuploidy.
• To propose recommendations for improved safety assessment strategies.

Main Methods:

• Critical review of data from standard genotoxicity assays for 16 known or suspected aneugens.
• Analysis of in vitro and in vivo mammalian cell assays.
• Examination of subcellular, fungal, plant, and Drosophila test systems.

Main Results:

• Only nine chemicals are definitive aneugens based on in vivo rodent assays.
• Most aneugens are negative in bacterial mutation assays but positive for polyploidy in vitro.
• Definitive aneugens induce micronuclei in vivo; some also induce structural aberrations.
• No chemical identified as exclusively inducing germ cell aneuploidy.

Conclusions:

• A standard genotoxicity battery, including in vitro cytogenetics, is recommended for screening.
• In vitro polyploidy induction warrants further in vivo somatic cell micronucleus testing.
• Thresholds for aneuploidy induction not involving DNA interaction should be considered in risk assessment.