As part of the 7th International Workshops on Genotoxicity Testing held in Tokyo, Japan in November 2017, a workgroup of experts reviewed and assessed the risk of
aneugens for human health. The present manuscript is one of three manuscripts from the workgroup and reports on the unanimous consensus reached on the evidence for
aneugens affecting germ cells, their mechanisms of action and role in
hereditary diseases. There are 24 chemicals with strong or sufficient evidence for germ cell aneugenicity providing robust support for the ability of chemicals to induce germ cell
aneuploidy. Interference with microtubule dynamics or inhibition of
topoisomerase II function are clear characteristics of germ cell
aneugens. Although there are mechanisms of chromosome segregation that are unique to germ cells, there is currently no evidence for germ cell-specific
aneugens. However, the available data are heavily skewed toward chemicals that are aneugenic in somatic cells. Development of high-throughput screening assays in suitable animal models for exploring additional targets for
aneuploidy induction, such as meiosis-specific
proteins, and to prioritize chemicals for the potential to be germ cell
aneugens is encouraged. Evidence in animal models support that: oocytes are more sensitive than spermatocytes and somatic cells to
aneugens; exposure to
aneugens leads to
aneuploid conceptuses; and, the frequencies of
aneuploidy are similar in germ cells and zygotes. Although
aneuploidy in germ cells is a significant cause of
infertility and pregnancy loss in humans, there is currently limited evidence that
aneugens induce
hereditary diseases in human populations because the great majority of
aneuploid conceptuses die in utero. Overall, the present work underscores the importance of protecting the human population from exposure to chemicals that can induce
aneuploidy in germ cells that, in contrast to carcinogenicity, is directly linked to an adverse outcome.