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-beta-naphthylamine and o-toluidine

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) o f 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 histori es were abstracted from company computerised records and estimates of indiv idual cumulative exposure to 2-mercaptobenzothiazole (MBT) and its derivati ves were obtained, with a job exposure matrix derived by a former factory h ygienist. Durations of employment in the aniline, phenyl-beta-naphthylamine (PBN) and o-toluidine departments were also calculated. Two analytical app roaches were used, indirect standardisation and Poisson regression. Results-Based on serial rates for the general population of England and Wal es, observed mortality for the total cohort was close to expectation for al l causes (observed (obs) deaths 1131, expected (exp) deaths 1114.5, standar dised 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% confi dence interval (95% CI) 127 to 526). This excess was dependent primarily on deaths occurring >20 years after first exposure in those who started emplo yment 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. Pn 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 dura tion 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 simultaneous analysis of all four chemical exposure variables, a significant positive trend rema ined for duration of employment with exposure to PBN (p<0.05). Further anal yses of all cases of bladder cancer (malignant and benign diagnoses) used e mployment histories lagged by 15 years; similar findings were obtained. Conclusions-It seems likely that some members of this cohort have had occup ational bladder cancer. Confident interpretation is difficult because of sm all numbers in the exposed subcohorts, relatively crude measures of exposur e assessment for the four chemicals under study, and presence of unconsider ed potential chemical confounders. The simplest interpretation of the findi ngs about bladder cancer may be that PBN (or a chemical reagent or chemical intermediate associated with its production at this factory in the 1930s a nd 1940s) is a bladder carcinogen. Priority should be given, however, to ob taining information on the cancer experience of other working populations e xposed to PBN or to o-toluidine.