Effect of route of administration on the disposition of acrylonitrile: quantitative whole-body autoradiographic study in rats.

摘要

Previous studies on the effect of route of administration on acrylonitrile (VCN) toxicity in animal models indicated high rates of metabolism in rats that received an oral dose than those received an i.p. VCN dose. To evaluate the role of route of administration on the distribution of VCN, a quantitative whole-body autoradiography (QWBA) and elimination studies were conducted. Equimolar doses of 2-[14C]-VCN were administered i.v. or p.o. to male Fischer (F-344) rats. Time course of QWBA indicated a higher retention and covalent interaction of radioactivity in the liver, spleen and bone marrow of rats received an i.v. dose of 2-14C-VCN than those received a p.o. dose. Unlike rats that received an i.v. dose of VCN, the animals received an oral dose showed a high retention of 14C in blood, stomach and gastric mucosa. Differences were also reflected in 14C elimination in urine, feces and expired air. Animals treated orally with 2-[14C]-VCN excreted 61% of the administered radioactive dose (4% in expired air, 4% in urine and 53% in feces). Rats that received an i.v. dose of 2-[14C]-VCN, however, eliminated only 30% of the total radioactive dose (expired air 2%, urine 8% and feces 21%). The results indicate that metabolism, detoxication and elimination of VCN are more pronounced following oral administration as compared to i.v. route of administration. The study also demonstrates that the systemic administration of VCN enhances its covalent interaction and retention in the tissues thus cause more toxicity in these organs.