Metabolism of bromodichloroacetate in B6C3F1 mice.
Trichloroacetate (TCA), dichloroacetate (DCA), and bromodichloroacetate (BDCA) are byproducts of the chlorination of drinking water. TCA acts primarily as a peroxisome proliferator, but DCA produces tumors at doses less than required for peroxisome proliferation. BDCA does not induce peroxisome proliferation even at high doses. This study attempts to determine whether differences in the metabolism of the trihaloacetates (THAs) may contribute to their differing toxicological properties. Studies were performed in male B6C3F1 mice given [14C1,2]TCA, [14C1]BDCA, and [14C1,2]DCA by gavage. The replacement of a Cl by a Br greatly enhances THA metabolism. Much less radiolabel from BDCA is retained in the carcass after 24 hr than from TCA. Radiolabel from BDCA is largely found in the urine, with oxalate being the major metabolite. TCA is largely eliminated unchanged in the urine. There are dose-related changes in the rate of CO2 production from BDCA. The initial rate of CO2 production is reduced from 4.1 +/- 0.3 hr-1 at 5 and 20 mg/kg to 2.7 +/- 0.6 hr-1 at 100 mg/kg, but the net conversion to CO2 in 24 hr is greater at the highest dose. As would be predicted, substitution Br for Cl on TCA greatly increased its metabolism.
Xu
G
G
Pharmacology/Toxicology Graduate Program, Washington State University, USA.
Stevens
D K
DK
Bull
R J
RJ
D000085:Acetates / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D000818:Animals; D001711:Biotransformation; D003999:Dichloroacetic Acid / Q000493:pharmacokinetics / Q000652:urine; D005243:Feces / Q000737:chemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014018:Tissue Distribution; D014238:Trichloroacetic Acid / Q000493:pharmacokinetics / Q000652:urine
D000085:Acetates; D014238:Trichloroacetic Acid; D003999:Dichloroacetic Acid; C100580:bromodichloroacetic acid