Dietert R R, Etzel R A, Chen D, Halonen M, Holladay S D, Jarabek A M, Landreth K, Peden D B, Pinkerton K, Smialowicz R J, Zoetis T
Department of Microbiology and Immunology and Institute of Comparative and Environmental Toxicology, Cornell University, Ithaca, New York, USA.
Environ Health Perspect. 2000 Jun;108 Suppl 3(Suppl 3):483-90. doi: 10.1289/ehp.00108s3483.
Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment.
在毒理学风险方面,胎儿、婴儿和青少年(成年前个体)不应被简单地视为“小成年人”。我们列举了一些发育毒性物质的具体例子,这些物质对儿童的毒性比对成年人更大,重点关注对免疫和呼吸系统的影响。我们描述了发育中的免疫和呼吸系统在药代动力学方面的差异以及靶器官对毒性物质敏感性的变化。在现有动物模型的背景下,确定了发育过程中不同的易损窗口。我们提供了直接研究易损窗口差异的具体方法。这些方法基于基础发育生物学以及免疫和呼吸系统内离散发育过程的存在。这些过程可能会影响对毒性物质的发育易感性差异,导致终生的毒理学变化。我们还提供了一个比较研究的模板。最后,我们讨论了这些数据在风险评估中的应用。