Ikeda M
Department of Public Health, Kyoto University Faculty of Medicine, Japan.
Toxicol Lett. 1995 May;77(1-3):85-91. doi: 10.1016/0378-4274(95)03276-2.
It is well recognized in industrial and environmental health that man is exposed simultaneously to more than one chemical. Interaction may take place in the metabolism of chemicals absorbed in combination or in sequence, especially when the chemicals share similar chemical structures. It is further conceivable that the extent of possible metabolic interaction will depend on the intensity of exposure. Moreover, the metabolism of chemicals may be modified by social habits, especially smoking. No systemic and comprehensive studies however have been reported in literature, possibly because the combinations of the chemicals are various and the exposure intensities vary greatly. In a survey of factories where workers were exposed to either benzene alone (20 ppm as GM and 86 ppm as max.), toluene alone (38 and 86 ppm) or a combination of both, the urinary levels of phenol (a metabolite of benzene) and hippuric acid (that of toluene) were significantly lower among the co-exposed workers as compared with the levels in workers who were exposed to either benzene or toluene alone (Inoue et al. (1988) Int. Arch. Occup. Environ. Health 60, 15-20). In contrast, a similar factory survey on the workers exposed to a mixture of toluene (3 ppm as GM) and xylenes (3 ppm for the sum of the 3 isomers) revealed that increments in urinary hippuric acid and methylhippuric acid levels were equal to the values after individual exposure (Huang et al. (1994) Occup. Environ. Med. 51, 42-46). Furthermore, the hippuric acid levels in the urine of workers exposed to toluene (18 ppm as GM) were not reduced by the co-exposure to MEK (16 ppm) or IPA (7 ppm) (Ukai et al. (1994) Occup. Environ. Med. 51, 523-529). In a human volunteer study with repeated exposures, metabolic interaction took place when the subjects were exposed to a combination of 95 ppm toluene and 80 ppm xylenes (mostly m-isomer), whereas no interaction was detected after the exposure to a combination of 50 ppm toluene and 40 ppm xylenes (Tardif et al. (1991) Int. Arch. Occup. Environ. Health 63, 279-284). From the observation it appears likely that due caution should be exercised when the intensity of the combined exposure is high but not necessarily so when the exposure is low. The threshold remains yet to be established.
在工业与环境卫生领域，人们早已认识到人类会同时接触多种化学物质。化学物质在被同时或先后吸收时，其代谢过程中可能会发生相互作用，尤其是当这些化学物质具有相似的化学结构时。进一步可以想象，可能的代谢相互作用程度将取决于接触强度。此外，化学物质的代谢可能会受到社会习惯的影响，尤其是吸烟。然而，文献中尚未报道过系统全面的研究，这可能是因为化学物质的组合多种多样，且接触强度差异极大。在一项针对工人的工厂调查中，这些工人要么单独接触苯（平均20 ppm，最高86 ppm），要么单独接触甲苯（38 ppm和86 ppm），要么同时接触两者。结果发现，与单独接触苯或甲苯的工人相比，同时接触两种物质的工人尿液中苯酚（苯的代谢产物）和马尿酸（甲苯的代谢产物）的水平显著降低（井上等人（1988年）《国际职业与环境卫生档案》60卷，第15 - 20页）。相比之下，另一项针对接触甲苯（平均3 ppm）和二甲苯（三种异构体总和为3 ppm）混合物的工人的类似工厂调查显示，尿液中马尿酸和甲基马尿酸水平的增加与单独接触后的数值相当（黄等人（1994年）《职业与环境医学》51卷，第42 - 46页）。此外，接触甲苯（平均18 ppm）的工人尿液中马尿酸水平，在同时接触甲乙酮（16 ppm）或异丙醇（7 ppm）时并未降低（乌凯等人（1994年）《职业与环境医学》51卷，第523 - 529页）。在一项针对人类志愿者的重复接触研究中，当受试者接触95 ppm甲苯和80 ppm二甲苯（主要是间位异构体）的组合时发生了代谢相互作用，而接触50 ppm甲苯和40 ppm二甲苯的组合后未检测到相互作用（塔尔迪夫等人（1991年）《国际职业与环境卫生档案》63卷，第279 - 284页）。从这些观察结果来看，当联合接触强度较高时似乎应格外谨慎，但接触强度较低时不一定如此。阈值仍有待确定。
