Disposition and metabolism of 1,2-dimethylnaphthalene in rats.

The aim of this study was to investigate the distribution, excretion and metabolism of 1,2-dimethylnaphthalene-[ring-U-3H] in rats. The experiments were performed on 54 male outbred IMP:Wist rats with body weight of 200 g +/- 20%. The compound was given i.p. in olive oil in a single dose of 28 mg/kg (about 6.2 MBq per animal). 3H radioactivity was traced in selected organs and tissues, blood, urine and faeces, 1-72 h following the administration. The main metabolites were isolated from urine and identified by the GC-MS method. Faeces and urine proved to be the main route of tritium elimination. Over 93% of the given compound was excreted during the first 72 h. Maximum level of tritium in plasma was observed during the 4th h after the compound administration. The accretion of 3H proceeded with kinetic constant of 0.7 h, followed by monophasic decline with the half-life of about 19h. In organs and tissue, the highest concentration during the first hours after administration were detected in the fat, adrenals, liver, spleen and kidneys. Then gradual decline of tritium was noticed in all examined tissues. The following urinary metabolites were identified: 1. 1,2-dimethylthionaphthalene, 2. 1,2-dimethylnaphthol, 3. 1-methylnaphthalene-2-methanol, 4. 1-methyl-2-naphthoic acid and 5. 1,2-dimethylmethylthionaphthalene. In conclusion, 1,2-dimethylnaphthalene has a relatively rapid turnover rate in the rat organism and does not form deposits in the tissue. The metabolism encompasses ring hydroxylation and glutathione conjugation leading to thionaphthol and oxygenation, and then to naphthoic acid.