Anesthetic Metabolism - Toxic Effects in OR Personnel.
Stanford University, Terminal Progress Report :6 pages
Studies were conducted on the binding of halothane (151677) metabolites to human liver and gonads. Possible metabolism of nitrous-oxide (10024972) was also studied using isotope ratio mass spectrometry and a method of electron paramagnetic resonance spin trapping. A gas chromatograph/mass spectrometry technique was developed to identify and quantify the volatile metabolites of halothane produced in patients and in-vitro incubations. The most toxic metabolite was formed in the patient's breathing circuit, mainly from contact of halothane with hot, wet soda lime. Toxicity and mutagenicity studies, making use of a new log growth mutagenic assay particularly appropriate for assessing potentially mutagenic halocarbons, indicated that some of the reductive metabolites were moderately mutagenic. Efforts were undertaken to develop a synthetic system in which drug metabolism can be studied using highly purified single forms of cytochrome-P-450 proteins in a membrane environment of exactly defined composition and physical properties. An aim in the development of this reconstitution technique was the ability to use human liver cytochromes in this system and ultimately develop a system in which drug toxicity could be tested in human liver cell components without exposing humans to harmful drugs.
NIOSH-Grant; Pulmonary-system-disorders; Pharmacodynamics; Metabolic-study; Anesthetics; Anesthesiology; Chromatographic-analysis; Mutagens; Liver-damage;
Anesthesia Stanford University 300 Pasteur Drive Stanford, Calif 94305
NTIS Accession No.
Stanford University, Terminal Progress Report
Stanford University, Stanford, California