Johnson E M
Department of Anatomy, Daniel Baugh Institute, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
Regul Toxicol Pharmacol. 1988 Mar;8(1):22-36. doi: 10.1016/0273-2300(88)90004-9.
Designations of agents as teratogenic or nonteratogenic often are inaccurate, as adverse effects are more a reflection of the timing and severity of treatment during pregnancy than agent nature. Careful consideration of both the similarities and the differences between developmental effects in animals and humans and the extent and nature of the data available are essential for protection of the human conceptus. Animal surrogates prove reliable predictors of human developmental effect levels. When the data are evaluated consistent with contemporary concepts of developmental toxicity, for example, where the effect in the embryo is only seen at maternally toxic doses and exposure is below the adult toxic level, relatively modest safety factors are sufficient for safe cross-species extrapolation. Developmental toxicity safety factor magnitude is predicated on data quality and the fact that thresholds of effect exist in mammalian pregnancy. Safety of human concepti is achieved by considering both the developmental hazard index of the chemicals in question and the severity of exposure.
将药物指定为致畸或非致畸往往并不准确，因为不良反应更多地反映了孕期治疗的时间和严重程度，而非药物的性质。仔细考虑动物和人类发育效应之间的异同以及现有数据的范围和性质，对于保护人类胚胎至关重要。动物替代物被证明是人类发育效应水平的可靠预测指标。例如，当根据当代发育毒性概念评估数据时，若仅在母体中毒剂量下才观察到胚胎效应，且暴露低于成人中毒水平，那么相对适度的安全系数就足以进行安全的跨物种推断。发育毒性安全系数的大小取决于数据质量以及哺乳动物孕期存在效应阈值这一事实。通过考虑相关化学物质的发育危害指数和暴露的严重程度，可实现人类胚胎的安全。
