In vitro models for gonadal and placental toxicity: A review and industry survey

In recent years, there has been a significant push towards the development of animal-free methods in toxicology. Despite this progress, the adoption of such methods in safety assessment practices remains limited, particularly in the context of gonadal and placental toxicity. This paper reviews current in vitro models relevant to gonadal (gametogenesis and steroidogenesis) and placental biology, and potentially applicable in developmental and reproductive toxicology (DART). Additionally, we present the results of a survey conducted among DART experts (n = 16), examining current practices and perceptions in industry regarding these in vitro methodologies. The findings indicate a predominant reliance on animal models, largely driven by regulatory requirements, despite concerns about their ability to reliably predict human outcomes. Respondents reported limited familiarity with and confidence in available in vitro models for gonadal and placental toxicity, yet expressed optimism about their future integration. These findings underscore the need for increased awareness of gonadal and placental in vitro models, particularly among DART risk assessors, to facilitate a shift toward more reliable and human relevant risk assessments.