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Carbon Monoxide Generation from Trihalomethane Metabolism in Rats

Martin Luther University, Institute of Environmental Toxicology, Halle (Saale), Germany

Britt Damme

Martin Luther University, Institute of Environmental Toxicology, Halle (Saale), Germany

Carboxyhaemoglobin (COHb) formation in rats after oral administration of trichloromethane (TCM), bromodi chloromethane (BDCM), chlorodibromomethane (CDBM) and tribromomethane (TBM) increased in the order TCM < BDCM < CDBM < TBM. The trihalomethanes are sub strates for cytochrome P₄₅₀ 2E1 (CYP2E1) and cyto chromes P₄₅₀ 2B1/2 (CYP2B1/2) as shown by: (a) the inhibi tion of COHb formation due to simultaneous administra tion 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 CYP281/2. There is an en hancement of the COHb level after daily administration of CDBM or TBM for 7 days in comparison to a single gav age, 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.

Key Words: Carboxyhaemoglobin • Trihalomethanes • Oxidative metabolism • CYP2E1

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