The disposition and metabolism of 1,3,5-[U-14C]trioxane in male Wistar albino rats.
The present study was designed to investigate 1,3,5-[U-14C]trioxane (TOX) distribution, excretion and metabolism. The experiments were performed on male Wistar albino rats after a single administration of TOX at doses of 40 mg/kg and 400 mg/kg. The exhaled air proved to be the main route of 14C elimination, mainly as 14CO2. During the first 12 h following the administration of 40 mg/kg of TOX the exhalation of 14CO2 was monophasic, with a half-life of 3.5 h. After the administration of 400 mg/kg, TOX was eliminated mainly as 14CO2 with the exhaled air (77%) and unchanged TOX (8%). About 3% of 14C was excreted in the urine as unchanged 1,3,5-trioxane. With regards to TOX elimination from blood plasma for the lower dose, a biphasic process was observed, with half-lives of 4.5 and 72 h. The amount of 14C bound by the erythrocytes was minute compared with the amount in blood plasma. When the higher dose of TOX was administered the efficiency of 14C binding to the erythrocytes was found to be 10 times higher than the respective value for blood plasma. Among the examined tissues the highest concentration of TOX-derived radioactivity was detected in the liver while the lowest was in fat tissue and brain. A subsequent decay of radioactivity occurred in the tissues. The results of the present study indicate that TOX belongs to the group of compounds, which are rapidly eliminated from the organism; hence TOX should not be expected to accumulate within the tissues. The data obtained confirm the assumed pattern of metabolic transformation, according to which 1,3,5-trioxane undergoes enzymatic transformation to formaldehyde, with carbon dioxide and water being the final products.
Ligocka
D
D
Toxicokinetics Laboratory, Institute of Occupational Medicine, Lodz, Poland.
Sapota
A
A
Jakubowski
M
M
D000818:Animals; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D007509:Irritants / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D007509:Irritants