An evaluation of the utility of blood concentration of somatic mutagens to inform germ cell mutagenic hazard

The Globally Harmonized System (GHS) for classification and labeling of chemicals ensures consistent communication of chemical hazards. Within this framework, germ cell mutagenicity data holds unique importance due to the potential for heritable mutations. However, germ cell mutagenicity testing is rarely conducted, prompting the need for alternative strategies. The aim of this study by the Health and Environmental Sciences Institute’s Genetic Toxicology Technical Committee was to investigate whether germ cell mutagenicity can be predicted from blood concentrations of substances that are genotoxic in somatic tissues. If feasible, such an approach would avoid further testing in germ cells. We identified 11 and 30 substances with blood concentration data together with dominant lethal test (DLT) and transgenic rodent (TGR) gene mutation data in male germ cells. We observed significant correlations between doses with positive genotoxic responses in somatic tissues (e.g., micronuclei or mutant frequencies) and positive results in the DLT or the TGR assay in testis. However, considerable variation was noted in genotoxic outcomes that could not be explained by blood concentrations. For instance, blood concentrations of genotoxic substances that were positive in somatic tissues and/or germ cells were not significantly different from those of substances positive for somatic cell genotoxicity and negative in germ cells. We conclude that the concentration of a somatic genotoxic substance in blood alone is insufficient to predict germ cell mutagenicity.

GODSCHALK Roger;  BRAUWERS Bente;  CHEN Connie;  CORVI Raffaella;  DEARFIELD Kerry;  DOUGLAS George;  HONARVAR Naveed;  KIRKLAND David;  LE CURIEUX Frank;  OLSEN Ann-Karin;  PFUHLER Stefan;  STANKOWSKI Leon;  WHITE Paul A;  VAN BENTHEM Jan;  MARCHETTI Francesco; 

2025-12-01

ACADEMIC PRESS INC ELSEVIER SCIENCE

JRC141653

1096-0295 (online),    0273-2300 (print),   

https://www.sciencedirect.com/science/article/pii/S0273230025002211,    https://publications.jrc.ec.europa.eu/repository/handle/JRC141653,   

10.1016/j.yrtph.2025.105989 (online),