CYTOTOXIC AND NONCYTOTOXIC EFFECTS OF THE MEIC REFERENCE CHEMICALS ONSPONTANEOUSLY CONTRACTING PRIMARY CULTURED RAT SKELETAL-MUSCLE CELLS

This study was designed to evaluate the suitability of a multi-endpoin t test system using primary cultured spontaneously contracting rat ske letal muscle cells to indicate an acute neuro- and/or cardiotoxic pote ntial of chemicals. The concentration-dependent effects of the 50 MEIC (Multicenter Evaluation of In Vitro Cytotoxicity) reference chemicals on contractility, indicative of the functional integrity of the elect rically active muscle cell membrane, were determined. Additionally, ef fects on two other endpoints, glucose consumption and viability, were monitored to reveal whether alterations in contractility were associat ed with cytotoxicity. In total, 30 of the tested compounds inhibited c ontractility at non-cytotoxic concentrations. The contractility-inhibi ting and cytotoxic potencies differed by factors of more than 10 in th e case of diazepam, phenol, propranolol, phenobarbital, mercuric chlor ide, thioridazine, verapamil, chloroquine, quinidine, phenytoin and at ropine, of more than 100 in the case of amitriptyline, dextropropoxyph ene, orphenadrine and amphetamine, and even more than 1000 for nicotin e. On the basis of the available knowledge of the acute toxic effects and modes of acute toxic action of the test compounds, this characteri stic response pattern is shown to be highly predictive for compounds r eported to be cardio- and/or neurotoxic owing to interference with exc itable membrane functions and/or neurotransmission. Copyright (C) 1996 Elsevier Science Ltd.