Urine mutagenicity and biochemical effects of the drinking water mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), following repeated oral administration to mice and rats.
Mutagenicity analysis of urine from rats treated by oral gavage with MX at a dose of 64 mg/kg for 14 days revealed that only 0.3% of the administered compound was excreted in a genotoxically active form. At lower doses, mutagenicity was not detectable. No evidence of micronucleus induction in peripheral blood erythrocytes was observed in mice treated similarly. These findings indicate that MX is extensively detoxified in vivo and is unlikely to cause genetic damage in systemic tissues except at relatively high doses where detoxification pathways become saturated. In a separate experiment, significant depressions were observed in D-glucaric acid and thioether excretion and in levels of several liver enzymes involved in xenobiotic metabolism. The mechanism for these metabolic alterations and their relevance to the in vivo metabolism of the compound require further investigation.
Meier
J R
JR
U.S. Environmental Protection Agency, Cincinnati, Ohio 45268, USA.
Monarca
S
S
Patterson
K S
KS
Villarini
M
M
Daniel
F B
FB
Moretti
M
M
Pasquini
R
R
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001711:Biotransformation; D004326:Drinking; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D005260:Female; D005618:Fresh Water; D005663:Furans / Q000008:administration & dosage / Q000633:toxicity*; D005937:Glucaric Acid / Q000378:metabolism; D005966:Glucuronidase / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008830:Microbodies / Q000737:chemistry; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013440:Sulfides / Q000378:metabolism; D014556:Urine / Q000737:chemistry*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D005663:Furans; D009153:Mutagens; D013440:Sulfides; D014874:Water Pollutants, Chemical; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; D005966:Glucuronidase; D005937:Glucaric Acid