Lotti M
Università degli Studi di Padova, Istituto di Medicina del Lavoro, Italy.
Toxicol Lett. 1995 May;77(1-3):9-14. doi: 10.1016/0378-4274(95)03265-7.
Incorporating mechanistic information into the risk assessment process is necessary because proliferation of in vitro and in vivo tests of uncertain significance has led to the realisation that the quantity of toxicological information may undermine its own value. Default options in risk assessment to be used in the absence of mechanistic data are mainly derived from extrapolations. Examples from mechanistic studies on organophosphate-induced delayed polyneuropathy (OPIDP) will illustrate 3 main areas of extrapolation where mechanistic data might allow meaningful conclusions for risk assessment: (i) from animal to humans; (ii) from high to low levels of exposure; (iii) from disaggregated systems to complex systems. The continuing effort to understand the mechanisms of toxicity will reduce uncertainty in these and other areas of the extrapolation processes. It could also lead to better appreciation of the significance of biomarkers (such as lymphocyte neuropathy target esterase (NTE) for OPIDP) to be used in biomonitoring programs.
将机制信息纳入风险评估过程是必要的，因为大量意义不明确的体外和体内试验导致人们认识到，毒理学信息的数量可能会削弱其自身价值。在缺乏机制数据时用于风险评估的默认选项主要来自外推法。有机磷酸酯诱导的迟发性多神经病（OPIDP）机制研究的例子将说明外推法的3个主要领域，在这些领域中，机制数据可能为风险评估得出有意义的结论：（i）从动物到人类；（ii）从高暴露水平到低暴露水平；（iii）从分解系统到复杂系统。持续努力了解毒性机制将减少外推过程中这些及其他领域的不确定性。这也可能导致人们更好地认识生物标志物（如用于OPIDP的淋巴细胞神经病变靶酯酶（NTE））在生物监测项目中的意义。
