ABSTRACT

Carbon monoxide (CO) was first discovered as a metabolite of a xeno-biotic in the 1970s. CO formation caused by exposure to dichloromethane (DCM) was suggested as the result of the chance observation that a physician had much higher than expected levels of carboxyhemoglobin on each of two mornings following his use of varnish remover the evening before. Animal experiments showed the metabolic CO formation: In order to estimate combined effects of CO and DCM, rats were exposed to 100 ppm CO and 1000 ppm DCM. The chapter reviews factors influencing the CO formation due to metabolism of xenobiotics, mainly of DCM, to show differences between CO hypoxia caused by CO or DCM exposure, and to characterize the possible CO risk due to DCM exposure. The perfused liver of rats was used as an experimental model to investigate the interaction of DCM-derived CO with cytochrome P-450: Monitoring was done of the spectral change following DCM in perfused liver.