A further cohort study of workers employed at a factory manufacturing chemicals for the rubber industry, with special reference to the chemicals 2-mercaptobenzothiazole (MBT), aniline, phenyl-β-naphthylamine and o-toluidine

Abstract

Objectives - To investigate mortality and cancer morbidity in workers from a factory manufacturing chemicals for the rubber industry. Methods - The mortality (1955-96) and cancer morbidity experience (1971- 92) of a cohort of 2160 male production workers from a chemical factory in north Wales were investigated. All subjects had at least 6 months employment at the factory and some employment in the period 1955-84. Detailed job histories were abstracted from company computerised records and estimates of individual cumulative exposure to 2-mercaptobenzothiazole (MBT) and its derivatives were obtained, with a job exposure matrix derived by a former factory hygienist. Durations of employment in the aniline, phenyl-β-naphthylamine (PBN) and o-toluidine departments were also calculated. Two analytical approaches were used, indirect standardisation and Poisson regression. Results - Based on serial rates for the general population of England and Wales, observed mortality for the total cohort was close to expectation for all causes (observed (obs) deaths 1131, expected (exp) deaths 1114.5, standardised mortality ratio (SMR) 101), and for all cancers (obs 305, exp 300.2, SMR 102). There was a significant (p<0.05) excess mortality from cancer of the bladder in the 605 study subjects potentially exposed to one or more of the four chemicals being investigated (obs 9, exp 3.25, SMR 277, 95% confidence interval (95% CI) 127 to 526). This excess was dependent primarily on deaths occuring >20 years after first exposure in those who started employment before 1955 (obs 7, exp 1.25, SMR 560, 95% CI 225 to 1154, p<0.001). There were 30 subjects in the total study cohort who, on the basis of death certificates or cancer registration particulars, had had malignant bladder cancer. In separate analyses of the four exposure history variables (after adjustment for age), Poisson regression showed significant positive trends for risk of notification of bladder cancer increasing with cumulative duration of employment in the PBN (p<0.001) and o-toluidine departments (p<0.01); similar findings were not obtained for cumulative exposure to MBT or for duration of employment in the aniline department. In a simultaneous analysis of all four chemical exposure variables, a significant positive trend remained for duration of employment with exposure to PBN (p<0.05). Further analyses of all cases of bladder cancer (malignant and benign diagnoses) used employment histories lagged by 15 years; similar findings were obtained. Conclusions - It seems likely that some members of this cohort have had occupational bladder cancer. Confident interpretation is difficult because of small numbers in the exposed subcohorts, relatively crude measures of exposure assessment for the four chemicals under study, and presence of unconsidered potential chemical confounders. The simplest interpretation of the findings about bladder cancer may be that PBN (or a chemical reagent or chemical intermediate associated with its production at this factory in the 1930s and 1940s) is a bladder carcinogen. Priority should be given, however, to obtaining information on the cancer experience of other working populations exposed to PBN or to o-toluidine.