Kanno J
Cellular & Molecular Toxicology Division, Biological Safety Research Center, National Institute of Health Sciences.
Nihon Rinsho. 2000 Dec;58(12):2495-501.
The Endocrine Disruptor Issue has been brought up widely to the public by a book titled "Our stolen future"(Theo Colborn et al., 1996), in which the reproductive impairment of a variety of wild life was documented in relation to chemical exposures. The fear that the similar adverse effects could have been observed in humans is based on the understandings that estrogens and androgens are highly conserved signaling molecules among species. In addition, the estrogen receptors are known to have abilities to bind a variety of chemicals. Although such chemicals bind weakly to the receptor, it is also known that, at least in some assay systems, high concentration of these chemicals can elicit effects that are quite similar to those of the natural hormones. Thus, such "hermonally active agents, HAAs" can be ligands to the hormone receptors in an organism, and may cause adverse effects, namely the "receptor-mediated toxicity", which is a relatively new concept in the field of toxicology. This new aspects of toxicology is briefly discussed in relation to the reversible/irreversible effects in developing organisms and the shape of dose-response curves, both especially in the low-dose ranges, now often referred to as "low-dose effects".
《我们被偷走的未来》(西奥·科尔伯恩等人,1996年)这本书将内分泌干扰物问题广泛地呈现给了公众。书中记录了各种野生动物因接触化学物质而出现的生殖功能受损情况。人们担心在人类身上也可能观察到类似的不良影响,这是基于这样的认识:雌激素和雄激素是物种间高度保守的信号分子。此外,已知雌激素受体能够结合多种化学物质。尽管这些化学物质与受体的结合力较弱,但至少在某些检测系统中,高浓度的这些化学物质能够引发与天然激素非常相似的效应。因此,这类“具有激素活性的物质,HAAs”可以作为生物体中激素受体的配体,并可能导致不良反应,即“受体介导的毒性”,这在毒理学领域是一个相对较新的概念。本文简要讨论了毒理学的这一新方面,涉及发育生物体中的可逆/不可逆效应以及剂量-反应曲线的形状,特别是在低剂量范围内,现在通常称为“低剂量效应”。