Baseline toxicity and ion-trapping models to describe the pH-dependence of bacterial toxicity of pharmaceuticals

served for the validation of the suitability of the various tested models. We confirmed that most tested pharmaceuticals acted as baseline toxicants in this assay at all examined pH values, when toxicity was modeled with a mixture model of concentration addition between the neutral species and all charged species. An ion trapping model, that assumes that the membrane permeability of charged species is kinetically limited, improved model predictions for some pharmaceuticals and pH values. However, neither unhindered uptake nor no uptake of the charged species were ideal models; the reality lies presumably between the two limiting cases with a slower uptake of the charged species than the neutral species. For practical applications a previously developed QSAR model with the ionisation-corrected liposome-water distribution ratio as the sole physicochemical descriptor proved to be generally applicable for all ionisable organic chemicals including those with multiple charges and zwitterions.