In Vitro Toxicology Testing: It’s Time to Report the Sex of Cells

In light of evidence taken from numerous fields indicating that males are routinely used more than females as test subjects,1-3 and the resulting poor outcomes of such practice,4,5 a conversation on balancing the sex of sample sets is not a new one. In a 2014 meta-analysis of nearly 300 studies, Prendergast and colleagues discovered that females have erroneously been considered more variable owing to their estrous cycle; instead, males were found to be more inconsistent under some experimental conditions.6 These results were subsequently confirmed by meta-analysis of microarray datasets.7 If we are to agree that sex of the subject (be it animal or human) is important to disclose, then the lack of representation to this day is troubling – and it is furthermore troubling that many studies fail even to report the sex of tissues or cells, meaning we have no idea as to the relevance of sex to measured outcomes. There have been several calls to action on this point in the biomedical field,3 yet we as a toxicology community have not yet been fully persuaded of our failure.