文摘
Baseline toxicity of a selection of industrial chemicalsand pharmaceuticals is determined experimentally with anew in vitro test system (Kinspec) using membranevesicles isolated from a photosynthetic bacterium,Rhodobacter sphaeroides. This test system is selectiveand more sensitive than other mechanistic test systems forbaseline toxicity. The only concomitantly determinedmechanism is uncoupling, which can be distinguishedfrom baseline toxicity by pH-dependent measurements.Because the tests system contains only the target site forbaseline toxicants, the biological membrane, effectivetarget site concentrations can be directly related to observedeffects by combining the in vitro test with membrane-water partition experiments. No differences were foundbetween the effective membrane concentrations of nonpolarand polar compounds, confirming the earlier hypothesisthat differences in lethal body burdens are primarily causedby unequal distribution of the compounds betweentarget and nontarget lipids and not by different mechanisms.A selection of pharmaceuticals with various specificmodes of toxic action exhibited the same constant effectivemembrane concentrations as found for pure baselinetoxicants. In mixtures of four to six components, thepharmaceuticals were concentration-additive with eachother and with the pure baseline toxicants. A potentialapplication of the proposed test system lies, therefore, inassessing the cumulative baseline toxicity in complexenvironmental mixtures.