Time-course studies of the distribution of [1-14C]acrylonitrile in rats after intravenous administration.
Intravenous injection of acrylonitrile (ACN) causes adrenal hemorrhagic necrosis. ACN and its metabolites react with glutathione and bind covalently with macromolecules. Hence the purpose of this investigation was to measure the distribution and covalent binding of radiolabel derived from [1-14C]ACN in order to determine whether binding of ACN or its metabolites may be implicated in the pathogenesis of ACN-induced adrenal injury. Following intravenous injections of ACN, concentrations of total radiolabel were highest in the blood, liver, duodenum, kidneys, and adrenals. Except for blood, there was a time-dependent decrease in total radiolabel in these tissues. Compared with other major organ systems, the levels of covalently bound radiolabel were lower in the adrenal glands. These results do not support a role of covalent binding of ACN or its metabolites in the adrenal toxicity of ACN, but suggest that the initial high concentrations of total radiolabelled compounds derived from ACN could play a role in the action of ACN on the adrenal glands.
Silver
E H
EH
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
Szabo
S
S
Cahill
M
M
Jaeger
R J
RJ
D000181:Acrylonitrile / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D005260:Female; D007275:Injections, Intravenous; D009570:Nitriles / Q000493:pharmacokinetics*; D010277:Parasympathomimetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014018:Tissue Distribution
D009570:Nitriles; D010277:Parasympathomimetics; D000181:Acrylonitrile