Study of Hydrazine Metabolism and Toxicity
Abstract
The research project studying hydrazine in rats has revealed the following: 1) The uptake of hydrazine into the liver may be a saturable process; 2) After a hepatotoxic dose of hydrazine the concentration in the liver is about 0.2mM; 3) Some hydrazine remains in the liver 24 hours after a single dose at a level higher than the plasma level; 4) At the highest dose level (81mg/kg) rats lost weight over the following 4 days and liver weight was decreased. At a dose of 27mg/kg, the liver weight was elevated 4 days after the single dose; 5) The rats given the highest dose still showed fatty liver 4 days after dosing. Rats given lower doses also showed some vacuolation in hepatocytes; 6) Determination of hydrazine and acetylhydrazine in urine after various single doses showed a dose dependent decrease in acetylation; 7) NMR revealed a number of metabolites: unchanged hydrazine, acetyl and diacetylhydrazine, hydrazones with pyruvate and 2-oxogltarate, urea and ammonia; 8) Studies in hepatocytes have shown that hydrazine is cytotoxic at concentrations of 16mM and above; 9) Hepatocyte studies have also shown that 8mM hydrazine depletes ATP and glutathione; and 10) Preliminary studies in microsomes have shown that hydrazine is metabolised by a cytochrome P450 dependent system. Chemical breakdown and other enzymic breakdown are also involved however.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 13, 1989
- Accession Number
- ADA217103
Entities
People
- J. A. Timbrell
Organizations
- University of London