Löf A, Johanson G
Department of Occupational Medicine, National Institute for Working Life, Solna, Sweden.
Crit Rev Toxicol. 1998 Nov;28(6):571-650. doi: 10.1080/10408449891344272.
This article reviews, with an emphasis on human experimental data, factors known or suspected to cause changes in the toxicokinetics of organic solvents. Such changes in the toxicokinetic pattern alters the relation between external exposure and target dose and thus may explain some of the observed individual variability in susceptibility to toxic effects. Factors shown to modify the uptake, distribution, biotransformation, or excretion of solvent include physical activity (work load), body composition, age, sex, genetic polymorphism of the biotransformation, ethnicity, diet, smoking, drug treatment, and coexposure to ethanol and other solvents. A better understanding of modifying factors is needed for several reasons. First, it may help in identifying important potential confounders and eliminating negligible ones. Second, the risk assessment process may be improved if different sources of variability between external exposures and target doses can be quantitatively assessed. Third, biological exposure monitoring may be also improved for the same reason.
本文着重依据人体实验数据,综述了已知或疑似会导致有机溶剂毒代动力学发生变化的因素。毒代动力学模式的此类变化会改变外部暴露与靶剂量之间的关系,因而可能解释所观察到的个体对毒性作用易感性的一些差异。已表明会改变溶剂吸收、分布、生物转化或排泄的因素包括体力活动(工作量)、身体组成、年龄、性别、生物转化的基因多态性、种族、饮食、吸烟、药物治疗以及与乙醇和其他溶剂的共同暴露。出于若干原因,需要更好地了解这些调节因素。首先,这可能有助于识别重要的潜在混杂因素并排除可忽略的因素。其次,如果能够定量评估外部暴露与靶剂量之间不同的变异性来源,风险评估过程可能会得到改进。出于同样的原因,生物暴露监测也可能会得到改善。