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 chemicals, the main phase transition temperature (T(tr)) of the phospholipids is decreased and the fluidity is increased. The decrease in T(tr) depends on the molar concentration of narcotics in the membrane (membrane burden) and is irrespective of the physicochemical properties of the chemicals. If membrane- water partition coefficients, exposure concentrations, and the amount of lipid in the system are known, membrane burdens of narcotic chemicals can be calculated and compared to membrane 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 fluidity change in phospholipid vesicles, after accumulation of chlorobenzenes, 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°C). The membrane burden needed in vivo for lethality by narcotic chemicals such as chlorobenzenes was calculated to be 40-160 mmol/kg membrane. By combining the in vivo and in vitro data, it can fie concluded that in organisms that die due to exposure to narcotic chemicals, the fluidity of the membrane is increased.