1 The median fatal concentrations (EC50) of various types of drugs are shown to be determined solely by their aqueous solubilities (S). Among the test substances, EC50 values show a range of 2000-fold, whereas the ratio EC 50/S is essentially constant. This behaviour is typical of 'Ferguson substances', and enables the fatal toxicity of other (depressant) drugs and related compounds to be calculated.
2 The mean relative saturation (EC50/S) is 0.006, a value which shows that humans are more sensitive to narcotic agents than are the lower animals.
3 The Ferguson principle provides a broad framework for quantitative structure-activity relations in fatal drug toxicity. The empirical Hansch equation can be derived from the same thermodynamic concept of free energy which underlies the Ferguson principle.
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