Which chemicals should be grouped together for mixture risk assessments of male reproductive disorders?

Publication date: Available online 13 September 2019Source: Molecular and Cellular EndocrinologyAuthor(s): Andreas KortenkampAbstractThere is concern about cumulative exposures to compounds that disrupt male sexual differentiation in foetal life, leading to irreversible effects in adulthood, including declines in semen quality, testes non-descent, malformations of the penis and testis cancer. Traditional chemical-by-chemical risk assessment approaches cannot capture the likely cumulative health risks. Past efforts of focusing on combinations of phthalates, a subgroup of chemicals suspected of contributing to these risks, do not go far enough, as they ignore the contribution of other types of chemicals. With the aim of providing criteria for the inclusion of additional chemicals in mixture risks assessments for male reproductive health, this paper examines the mechanisms of action of various chemicals capable of disrupting male sexual differentiation. An Adverse Outcome Pathway (AOP) network for malformations of the male reproductive system is constructed that includes new findings about the role of disruptions of prostaglandin signalling. This network is used to identify pathways that converge at critical nodal points to produce down-stream adverse effects. From this knowledge, combinations of chemicals with different mechanisms of action are predicted that should result in cumulative effects. These predictions are then mapped against evidence from experimental mixture studie...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research