Intestinal transformation of 2,6-dinitrotoluene in male Wistar rats.
1. Metabolites formed by anaerobic incubation of 2,6-dinitrotoluene (2,6-DNT) with intestinal microflora of male Wistar rats were examined. Intestinal transformation of 2,4-dinitrotoluene (2,4-DNT) was also studied to determine whether azoxy compounds are produced in the anaerobic incubation. 2. 2,6-DNT was transformed by the intestinal microflora into 2-nitroso-, 2-hydroxylamino- and 2-amino-6-nitrotoluene, and 2,6-diaminotoluene. A time course study showed that 2-nitroso-, 2-hydroxylamino-, and 2-amino-6-nitrotoluene reached peaks at 2, 5 and 6 h of the anaerobic incubation; 2,6-diaminotoluene appeared at 12 h of the incubation. The formation of 2,6-diaminotoluene from 2-amino-6-nitrotoluene in the incubation was confirmed. 3. Two nitroazoxy compounds, namely, 2,2'-dimethyl-5,5'-dinitroazoxybenzene and 4,4'-dimethyl-3,3'-dinitroazoxybenzene, in addition to known metabolites (nitrosonitrotoluenes, hydroxylaminonitrotoluenes, aminonitrotoluenes and diaminotoluene), were detected in the incubation of 2,4-DNT with intestinal microflora. The formation of the two nitroazoxy compounds (2% dose in 24 h) was non-enzymic and merely involved mixing 2-hydroxylamino-4-nitrotoluene with 2-nitroso-4-nitrotoluene or 4-hydroxylamino-2-nitrotoluene with 4-nitroso-2-nitrotoluene in methanol, respectively.
Faculty of Engineering, Toyama University, Japan.
M
M
Sayama
M A
MA
Mori
Y
Y
Maruyama
M
M
Inoue
H
H
Kozuka
D000818:Animals; D001391:Azo Compounds / Q000378:metabolism; D001673:Biodegradation, Environmental; D002273:Carcinogens / Q000493:pharmacokinetics; D004136:Dinitrobenzenes / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology; D008297:Male; D009578:Nitrobenzenes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001391:Azo Compounds; D002273:Carcinogens; D004136:Dinitrobenzenes; D009578:Nitrobenzenes; C016403:2,4-dinitrotoluene; C023514:2,6-dinitrotoluene