Biological and biological-effect monitoring of workers exposed to 4,4'-methylene-bis(2-chloroaniline).

ABSTRACT

4,4'-Methylene-bis(2-chloroaniline) (MOCA), a curing agent used in polyurethane manufacture, is a genotoxic and carcinogenic amine. This study aimed to assess occupational exposure to MOCA using as indices (1) the post-work urinary output of MOCA; (2) urinary thioethers, assuming that conjugation with glutathione might be a significant pathway for the elimination of putative electrophilic metabolites of MOCA; and (3) sister-chromatid exchange (SCE) frequency in peripheral lymphocytes as an indicator of genetic damage. Process workers at a polyurethane production unit were found to have up to 38 mumol MOCA mol-1 creatinine in their urine at the end of a work shift. Smaller quantities were found in the urine of laboratory and supervisory staff, but none was detected in the urine of a group of office and sales staff from an unrelated industry, who served as unexposed controls. There was no evidence of MOCA-related urinary thioether output. There was a graded increase in SCE frequency from controls to process workers, consistent with their apparent exposure to MOCA. Administration of MOCA to rats (5 daily i.p. injections of 125 or 250 mg kg-1 resulted in dose-related increases in MOCA excretion and in lymphocyte SCE frequency, but there was no change in thioether output. These results indicate that urinary thioether excretion is inappropriate for monitoring MOCA exposure, but that where MOCA exposure can be demonstrated, by the presence of MOCA in urine, this is associated with genetic damage in both man and in the rat.