Accession Number : ADA299028

Title :   Evaluation of In Vitro Alternatives to the Dog Cardiac Sensitization Assay.

Descriptive Note : Final rept. Apr-Jul 94,

Corporate Author : MANTECH ENVIRONMENTAL TECHNOLOGY INC DAYTON OH

Personal Author(s) : Frazier, J. M.

PDF Url : ADA299028

Report Date : OCT 1994

Pagination or Media Count : 23

Abstract : Many halogenated hydrocarbons have been shown to be cardiac sensitizers, i.e., chemicals that alter the sensitivity of the heart to endogenous chemical signals such that under conditions of stress cardiac failure may occur. The best known examples of these agents are solvents and propellants used in aerosol dispensers that have led to the death of "glue sniffers" as a result of cardiac arrest. The standard toxicological test for cardiac sensitization involves the exposure of dogs to the test agent and the recording of the EKG to determine the cardiac response to a systemic injection of epinephrine. In some cases the experimental procedure is lethal. It would be useful, both from a practical as well as a humane point of view, to have non-whole animal test procedures, possibly in vitro tests, that would provide quantitative evaluation of the risk for cardiac sensitization of candidate chemicals for Department of Defense applications. This report reviews various i7i vitro models that potentially could be developed for such purposes, including primary cell cultures, cell lines, and isolated organ cultures. At this time, none of the models have been developed for this application. It is apparent that a better understanding of the mechanism of cardiac sensitization would allow for the more rapid development and validation of non-whole animals test systems.

Descriptors :   *IN VITRO ANALYSIS, *HALOGENATED HYDROCARBONS, *CARDIAC ARREST, TEST AND EVALUATION, STRESSES, INJECTION, DEPARTMENT OF DEFENSE, AEROSOLS, RISK, VALIDATION, CHEMICALS, FAILURE, TEST METHODS, PROPELLANTS, RESPONSE, SOLVENTS, RECORDING SYSTEMS, CELLS(BIOLOGY), ASSAYING, HEART, CULTURES(BIOLOGY), DOGS, DISPENSERS, ELECTROCARDIOGRAPHY, SENSITIZING, EPINEPHRINE.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE