M. Valentovic, Bethany A. Rogers, M.Kathleen Meadows
Mar 14, 1997
Citations
0
Influential Citations
16
Citations
Quality indicators
Journal
Toxicology
Abstract
3,5-Dichloroaniline is an intermediate in the production of certain fungicides. This study characterized the capacity of 3,5-dichloroaniline and two putative metabolites to induce methemoglobin formation. In vivo intraperitoneal (i.p.) administration of 0.8 mmol/kg 3,5-dichloroaniline resulted in elevated (P < 0.05) methemoglobin levels at 2 and 4 h after injection and returned to control values within 8 h. In vitro methemoglobin generation was monitored in washed erythrocytes incubated for 60 min at 37 degrees C with 4 and 8 mM 3,5-dichloroaniline. Methemoglobin generation in vitro was higher (P < 0.05) than control values in erythrocytes incubated for 30 min with 0.2-0.6 mM 4-amino-2,6-dichlorophenol or 5-100 microM 3,5-dichlorophenylhydroxylamine. The in vitro methemoglobin generating capacity in decreasing order was: 3,5-dichlorophenylhydroxylamine > 4-amino-2,6-dichlorophenol > > 3,5-dichloroaniline. The results of the in vitro studies further indicated that none of the compounds tested induced lipid peroxidation. Erythrocytes incubated with 5-100 microM 3,5-dichlorophenylhydroxylamine in vitro were associated with depletion of glutathione. These results indicated that: (a) 3,5-dichloroaniline and its metabolites can induce methemoglobin formation; (b) the N-hydroxy metabolite was the most potent inducer of hemoglobin oxidation and (c) glutathione depletion was associated with methemoglobin formation by 3,5-dichlorophenylhydroxylamine.