The Dow Chemical Company, Toxicology & Environmental Research and Consulting, 1803 Building, Midland, MI, 48674, USA.
Applied Pharmacology and Toxicology, Inc., C.E.H.T. Dept. Physiological Sciences, University of FL College of Veterinary Medicine, 2250 NW 24th Avenue, Gainesville, FL, 32605, USA.
Regul Toxicol Pharmacol. 2018 Nov;99:142-158. doi: 10.1016/j.yrtph.2018.09.002. Epub 2018 Sep 12.
The endocrine system is responsible for growth, development, maintaining homeostasis and for the control of many physiological processes. Due to the integral nature of its signaling pathways, it can be difficult to distinguish endocrine-mediated adverse effects from transient fluctuations, adaptive/compensatory responses, or adverse effects on the endocrine system that are caused by mechanisms outside the endocrine system. This is particularly true in toxicological studies that require generation of effects through the use of Maximum Tolerated Doses (or Concentrations). Endocrine-mediated adverse effects are those that occur as a consequence of the interaction of a chemical with a specific molecular component of the endocrine system, for example, a hormone receptor. Non-endocrine-mediated adverse effects on the endocrine system are those that occur by other mechanisms. For example, systemic toxicity, which perturbs homeostasis and affects the general well-being of an organism, can affect endocrine signaling. Some organs/tissues can be affected by both endocrine and non-endocrine signals, which must be distinguished. This paper examines in vitro and in vivo endocrine endpoints that can be altered by non-endocrine processes. It recommends an evaluation of these issues in the assessment of effects for the determination of endocrine disrupting properties of chemicals. This underscores the importance of using a formal weight of evidence (WoE) process to evaluate potential endocrine activity.
内分泌系统负责生长、发育、维持内环境稳定以及控制许多生理过程。由于其信号通路的整体性，很难将内分泌介导的不良影响与短暂波动、适应性/代偿性反应或由内分泌系统以外的机制引起的内分泌系统不良影响区分开来。在需要通过使用最大耐受剂量（或浓度）来产生效应的毒理学研究中尤其如此。内分泌介导的不良影响是指化学物质与内分泌系统的特定分子成分（例如激素受体）相互作用而发生的那些不良影响。对内分泌系统的非内分泌介导的不良影响是通过其他机制发生的。例如，全身性毒性会扰乱内环境稳定并影响生物体的整体健康状况，从而影响内分泌信号。一些器官/组织可能同时受到内分泌和非内分泌信号的影响，必须加以区分。本文研究了体外和体内的内分泌终点，这些终点可能会受到非内分泌过程的影响。它建议在评估化学物质的内分泌干扰特性的影响时，评估这些问题。这强调了使用正式的证据权重（WoE）过程来评估潜在的内分泌活性的重要性。
