Abstract

Administration of dihalomethanes to rats resulted in the formation of carbon monoxide as evidenced by elevated levels of carboxyhemoglobin. An intraperitoneal dose of 3.0 mmoles of dichloromethane per kg yielded a maximum carboxyhemoglobin level of about 8% at 2 hr. Corresponding values for dibromomethane were 14% saturation at 4-5 hr, whereas diiodomethane produced a maximal carboxyhemoglobin level of 8% at about 3 hr. Bromochloromethane gave a maximum saturation of about 5% occurring at 4 hr. No other one-carbon compound studied resulted in elevated carboxyhemoglobin levels. Prior administration of phenobarbital or 3-methylcholanthrene produced no appreciable alterations in carboxyhemoglobin levels; SKF 525-A also failed to alter carboxyhemoglobin levels. However, the repeated administration of dichloromethane, but not dibromomethane, resulted in a substantial increase in carboxyhemoglobin levels over those seen in rats given a single dose. In order to determine the source of the carbon monoxide, ¹³C-dichloromethane (60 atom % ¹³C) was administered to rats, and ¹³C-carbon monoxide was found to be formed, which proves that dichloromethane is metabolized to carbon monoxide.