McLean A E
Proc R Soc Lond B Biol Sci. 1979 Jul 18;205(1158):179-97. doi: 10.1098/rspb.1979.0059.
All substances are toxic when the dose is large enough. In order to regulate the use of chemicals, we need to measure the level at which toxic effects are found. Epidemiological evidence suggests that present levels of chemical use do not lead to widespread harmful contamination of the human environment. For chemicals, most of the problems of toxicity are found in the workplace, while the population at large gets most of its toxic effects from voluntary exposure to substances such as tobacco smoke and ethanol. The prevention and control of toxic effects depends on a series of steps. This begins with measurement of toxicity in model systems, such as laboratory animals, and the estimation of the likely exposure of workers or consumers. Reliable extrapolation of information gathered from animals to the diverse and biochemically differing human population depends on understanding mechanisms of toxic effects. The toxic effect and mechanisms of action of substances such as carbon tetrachloride or paracetamol have been extensively investigated, and our ability to predict toxicity or develop antidotes to poisoning has had some success, but epidemiology is still an essential part of assessment of toxic effects of new chemicals. The example of phenobarbitone shows how animal experiments may well lead to conclusions which do not apply to man. After measurement of toxicity and assessment of likely hazards in use comes the final evaluation of the use of a chemical. This depends not only on its toxicity, but also on its usefulness. The direct effects on health may be small in comparison with the indirect advantageous effects which a useful substance such as vinyl chloride may bring. The assessment of risks and benefits of new chemicals can be partly removed from a political style of discourse, but the evaluation of the relative weight to be attached to these risks and benefits is inescapably political. The scientific contribution must be to allow the debate to take place in the light of maximum clarity of information about the consequences of use of chemicals.
所有物质，只要剂量足够大，都会有毒性。为了规范化学品的使用，我们需要测定发现毒性作用的剂量水平。流行病学证据表明，目前化学品的使用水平不会导致对人类环境的广泛有害污染。对于化学品而言，大多数毒性问题出现在工作场所，而普通人群大多是因自愿接触烟草烟雾和乙醇等物质而受到毒性影响。毒性作用的预防和控制取决于一系列步骤。这首先要在模型系统（如实验动物）中测定毒性，并估计工人或消费者可能的接触情况。要将从动物身上收集到的信息可靠地外推到多样化且生化特征不同的人类群体，就依赖于对毒性作用机制的理解。四氯化碳或对乙酰氨基酚等物质的毒性作用及作用机制已得到广泛研究，我们在预测毒性或开发中毒解毒剂方面取得了一些成功，但流行病学仍是评估新化学品毒性作用的重要组成部分。苯巴比妥的例子表明动物实验可能得出不适用于人类的结论。在测定毒性并评估使用中可能的危害之后，就要对化学品的使用进行最终评估。这不仅取决于其毒性，还取决于其用途。与氯乙烯等有用物质可能带来的间接有利影响相比，其对健康的直接影响可能较小。新化学品风险和益处的评估在一定程度上可以脱离政治化的讨论方式，但对这些风险和益处相对权重的评估不可避免地带有政治性。科学的贡献必须是让关于化学品使用后果的信息尽可能清晰，从而使辩论得以进行。
