Towards a non-animal risk assessment for anti-androgenic effects in humans.

摘要: Toxicology testing is undergoing a transformation from system based on high-dose studies in laboratory animals to one founded primarily vitro methods that evaluate changes normal cellular signalling pathways using human-relevant cells or tissues. We review the tools and approaches could be used develop non-animal safety assessment for anti-androgenic effects humans, with focus molecular initiating events (MIEs) human disorders indicate critical functioning of hypothalamus-pituitary-testicular (HPT) axis. In test systems exist which can characterize chemicals some MIEs such as androgen receptor antagonism, inhibition steroidogenic enzymes 5α-reductase inhibition. When alongside information describing pharmacokinetics specific chemical exposure, these inform pathways-based assessment. However, parts HPT axis occurring hypothalamus pituitary are not well represented by accepted methods. perturbations need developed before fully integrated model described. Knowledge gaps also prevent us data predict type severity vivo effect(s) arise given level activity. This means more work needed reliably link an MIE adverse outcome. especially low activity, exposure put mode action into context risk-based decision-making.