Carbon Monoxide Generation from Trihalomethane Metabolism in Rats

Abstract

Carboxyhaemoglobin (COHb) formation in rats after oral administration of trichloromethane (TCM), bromodichloromethane (BDCM), chlorodibromomethane (CDBM) and tribromomethane (TBM) increased in the order TCM < BDCM < CDBM < TBM. The trihalomethanes are substrates for cytochrome P₄₅₀ 2E1 (CYP2E1) and cytochromes P₄₅₀ 2B1/2 (CYP2B1/2) as shown by: (a) the inhibition of COHb formation due to simultaneous administration of CDBM or TBM and diethyldithiocarbamate, an inhibitor of CYP2E1, and (b) the initially higher levels of COHb after gavage of CDBM or TBM in rats pretreated with isoniazid, an inducer of CYP2E1, or pretreated with phenobarbital, an inducer of CYP2B1/2. There is an enhancement of the COHb level after daily administration of CDBM or TBM for 7 days in comparison to a single gavage, but the COHb levels were not higher due to chronic intake of CDBM with the drinking water (2.4 µmol·l^–1) in comparison to the basic levels, measured during 26 weeks.