MEMBRANE BURDENS OF CHLORINATED BENZENES LOWER THE MAIN PHASE-TRANSITION TEMPERATURE IN DIPALMITOYL-PHOSPHATIDYLCHOLINE VESICLES - IMPLICATIONS FOR TOXICITY BY NARCOTIC CHEMICALS

In the membrane of an organism that dies due to exposure to narcotic c hemicals, the main phase transition temperature (T-tr) of the phosphol ipids is decreased and the fluidity is increased. The decrease in T-tr depends on the molar concentration of narcotics in the membrane (memb rane burden) and is irrespective of the physicochemical properties of the chemicals. If membrane-water partition coefficients, exposure conc entrations, and the amount of lipid in the system are known, membrane burdens of narcotic chemicals can be calculated and compared to membra ne burdens that yield toxicity. The partition coefficients of a series of chlorobenzenes between phospholipid vesicles and water (K-mw) were measured at different temperatures in a new experimental set-up. K-mw 's were higher in the liquid-crystalline phase than in the gel phase. Partitioning into the gel phase was entropy driven, partitioning into the liquid-crystalline phase was driven by entropy and enthalpy. The f luidity change in phospholipid vesicles, after accumulation of chlorob enzenes, was measured from the change in T-tr. The membrane burdens of various chlorobenzenes needed for a lowering of T-tr were comparable (e.g., 20-60 mmol/kg for a decrease of 1.0 degrees C). The membrane bu rden needed in vivo for lethality by narcotic chemicals such as chloro benzenes was calculated to be 40-160 mmol/kg membrane. By combining th e in vivo and in vitro data, it can be concluded that in organisms tha t die due to exposure to narcotic chemicals, the fluidity of the membr ane is increased.