Exposure to complex mixtures: implications for biological monitoring

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.