Nielsen Gunnar Damgård, Ovrebø Steinar
National Research Centre for the Working Environment, Section of Airway Irritation and Allergy, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark.
Regul Toxicol Pharmacol. 2008 Aug;51(3):253-69. doi: 10.1016/j.yrtph.2008.04.002. Epub 2008 Apr 14.
The setting of occupational exposure limits (OELs) are founded in occupational medicine and the predictive toxicological testing, resulting in exposure-response relationships. For compounds where a No-Observed-Adverse-Effect-Level (NOAEL) can be established, health-based OELs are set by dividing the NOAEL of the critical effect by an overall uncertainty factor. Possibly, the approach may also be used for carcinogens if the mechanism is epigenetic or the genetic effect is secondary to effect from reactions with proteins such as topoisomerase inhibitors, and mitotic and meiotic spindle poisons. Additionally, the NOAEL approach may also be used for compounds with weak genotoxic effect, playing no or only a minor role in the development of tumours. No health-based OEL can be set for direct-acting genotoxic compounds where the life-time risks may be estimated from the low-dose linear non-threshold extrapolation, allowing a politically based exposure level to be set. OELs are set by several agencies in the US and Europe, but also in-house in major chemical and pharmaceutical companies. The benchmark dose approach may in the future be used where it has advantage over the NOAEL approach. Also, more attention should be devoted to sensitive groups, toxicological mechanisms and interactions as most workplace exposures are mixtures.
职业接触限值（OELs）的设定基于职业医学和预测性毒理学测试，由此得出接触-反应关系。对于能够确定未观察到有害作用水平（NOAEL）的化合物，基于健康的OELs是通过将关键效应的NOAEL除以一个总体不确定性系数来设定的。如果致癌物质的作用机制是表观遗传的，或者遗传效应是由与拓扑异构酶抑制剂、有丝分裂和减数分裂纺锤体毒物等蛋白质反应产生的效应继发而来的，那么这种方法也可能适用于致癌物质。此外，NOAEL方法也可用于遗传毒性作用较弱、在肿瘤发生过程中不起作用或仅起次要作用的化合物。对于直接作用的遗传毒性化合物，无法设定基于健康的OELs，其终身风险可通过低剂量线性无阈值外推法估算，从而设定基于政策的接触水平。美国和欧洲的多个机构都设定OELs，大型化学和制药公司也在内部设定。未来在比NOAEL方法更具优势的情况下，可能会采用基准剂量法。此外，由于大多数工作场所的接触都是混合物，因此应更多地关注敏感人群、毒理学机制和相互作用。
