Acetone potentiation of acute acetonitrile toxicity in rats

Journal Article · Tue Jan 01 04:00:00 EST 1985 · J. Toxicol. Environ. Health; (United States)

DOI:https://doi.org/10.1080/15287398509530690· OSTI ID:6430387

Freeman, J J; Hayes, E P

The purpose of these studies was to investigate the nature and mechanism of a toxicologic interaction between acetonitrile and acetone. Results of oral doe-response studies utilizing 1:1 (w/w) mixture of acetonitrile and acetone, or varying doses of acetonitrile administered together with a constant dose of acetone, indicated that acetone potentiated acute acetonitrile toxicity three- to fourfold in rats. The onset of severe toxicity (manifested by tremors and convulsions) was delayed in the groups dosed with both solvents compared to the groups that received acetonitrile or acetone alone. Blood cyanide (a metabolite of acetonitrile) and serum acetonitrile and acetone concentrations were measured after oral administration of 25% aqueous solutions of acetonitrile, acetone, or acetonitrile plus acetone. Concentrations of cyanide in the blood of rats given acetonitrile plus acetone remained near baseline, in contrast to the high concentrations found in rats dosed with acetonitrile alone. At 34-36 h, high blood cyanide concentrations were found in rats dosed with both of the solvents. This delayed onset of elevation of blood cyanide coincided with the occurrence of clinical signs and with the disappearance of serum acetone. In further pharmacokinetic studies, blood cyanide concentrations were measured after similar dosage regimens of acetone and acetonitrile. Peak cyanide concentrations were found to be significantly greater in rats dosed with both solvents than in rats given only acetonitrile. Administration of either sodium thiosulfate or a second dose of acetone prevented the toxicity associated with exposure to both solvents.

• Research Organization: Rutgers Univ., Joint Graduate Program in Toxicology, Piscataway, NJ
• OSTI ID: 6430387
• Journal Information: J. Toxicol. Environ. Health; (United States), Journal Name: J. Toxicol. Environ. Health; (United States) Vol. 15:5; ISSN JTEHD
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETONE
ACETONITRILE
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BODY FLUIDS
CYANIDES
DISPERSIONS
DOSE-RESPONSE RELATIONSHIPS
KETONES
MAMMALS
MATERIALS
METABOLISM
MIXTURES
NITRILES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RATS
RESPONSE MODIFYING FACTORS
RODENTS
THIOSULFATES
TOXICITY
VERTEBRATES