Boxenbaum H, Neafsey P J, Fournier D J
Drug Metabolism Department, Merrell Dow Research Institute, Cincinnati, Ohio 45215-6300.
Drug Metab Rev. 1988;19(2):195-229. doi: 10.3109/03602538809049623.
A historical survey of the literature indicates that benefits derived from low doses of toxic substances have been reported over many centuries. Hippocrates, Paracelsus, Arndt, Schulz, and Hahnemann (founder of homeopathy) have all reported that low doses of toxic substances may be "stimulatory" or otherwise beneficial. Assessment of mortality data from modern-day bioassay studies indicates that low-dose animal exposure to a variety of toxic agents can, through an unknown mechanism, also induce beneficial changes which promote health and prolong life (longevity hormesis). This nonspecific and apparently reversible phenomenon has been modeled kinetically through use of age-specific mortality rate and a generalized Gompertz function; the basic assumption is that mortality in an interval is a function of the weighted sum of intensities of physiologic injury during that interval. It was assumed that longevity-enhancing hormetic reduction in population injury may be decremented from life-shortening injury produced through the aging process and concomitant toxicity. At low exposure levels, a net reduction in age-specific mortality rate can sometimes be observed. The implications for risk assessment are significant. It is tacitly assumed in generating virtually all estimates of risk that toxic manifestations observed at higher doses are the sole effects elicited at lower doses. This appears to be qualitatively incorrect.
对文献的历史调查表明，几个世纪以来都有关于低剂量有毒物质益处的报道。希波克拉底、帕拉塞尔苏斯、阿恩特、舒尔茨以及顺势疗法创始人哈内曼都曾报道，低剂量有毒物质可能具有“刺激作用”或其他益处。对现代生物测定研究中的死亡率数据评估表明，低剂量动物接触多种有毒物质，通过一种未知机制，也能引发促进健康和延长寿命的有益变化（长寿兴奋效应）。这种非特异性且明显可逆的现象已通过使用特定年龄死亡率和广义冈珀茨函数进行动力学建模；基本假设是，某一时间段内的死亡率是该时间段内生理损伤强度加权总和的函数。据推测，群体损伤中增强寿命的兴奋效应减少量可能源于衰老过程和伴随毒性导致的缩短寿命的损伤。在低暴露水平下，有时可以观察到特定年龄死亡率的净降低。这对风险评估具有重要意义。在几乎所有风险评估中都默认，高剂量下观察到的毒性表现是低剂量下引发的唯一效应。但这在定性上似乎是不正确的。
