Exposure assessment of workers in the production of cyclophosphamide

Cyclophosphamide (CP) is an experimentally well documented mutagen and carcinogen both in vitro and in vivo test systems, and also in humans. It is biotransformed to alkylating metabolites, but also at its manufacture stages includes potent alkylating intermediates. The highest potential exposure during manufacture, detected by chemical analysis of air samples, was found to occur during specific operations at the end of the process, when airborne concentrations of CP may rise up to several hundred micrograms/m3. Mutagenicity measurements of air samples at the beginning of the process revealed direct mutagenicity similar to the CP intermediates. The workers were using supplied air masks, gloves and protective clothing, and no responses in urinary mutagenicity were detected when after-work and after-holiday samples were compared. Also, the cytogenetic parameters such as chromosomal aberrations and sister chromatid exchanges (SCE), did not differ in frequency between the group of workers in the CP production unit and the control group from other units of the same factory.