Critical assessment of epidemiological studies on the carcinogenicity of 1,3-butadiene and styrene

1,3-Butadiene. The consistent finding in five epidemiological studies of workers occupationally exposed to butadiene is excess mortality from lymphohaematopoietic malignancy. This highly reproducible finding is noted despite methodological limitations in each of the published studies that tend to diminish the likelihood of observing an etiological association: (i) lack of detailed data on individual exposures to butadiene; and (ii) increasing longevity of many patients with lymphohaematopoietic malignancies, owing to treatment with modern therapeutic regimens, which results in their not being included in analysis of mortality. The observed excess in cancer mortality is most clearly evident in subpopulations heavily exposed to butadiene: production and maintenance workers as well as African-American workers. These epidemiological data strongly suggest an etiological association between exposure to butadiene and human cancer. The data amply fulfil all of Bradford Hill's criteria for causality. It is reasonable to conclude that there now exists convincing evidence for the carcinogenicity of butadiene to humans. Styrene. Epidemiological data on styrene suggest the possibility of an association with lymphohaematopoietic malignancy, although the finding has not been consistent. The most recent epidemiological study, an analysis of 35,000 European workers, suggests, however, an association between these malignancies and time elapsed since first occupational exposure to styrene. Preliminary data from a nested case-control study within the cohort also suggest an association with cumulative exposure to styrene. Although the current classification of the human carcinogenicity of styrene within the IARC Monographs programme appears to be reasonable, if the new findings are confirmed it may become necessary in the near future to revise the classification. Downgrading of the IARC classification is clearly contraindicated in light of current epidemiological and toxicological data.