Toxicology of benzyl alcohols: a QSAR analysis

There is an evidence that benzyl alcohols may exhibit toxicity via a radica l mechanism. To test this possibility, we studied the toxicity of para subs tituted benzyl alcohols on rapidly dividing cancer cells (L1210 leukemia). This system has previously found utility in studying the apparent radical t oxicity of a variety of phenols. However, no evidence could be found for an electronic effect and the cellular toxicity was associated primarily with hydrophobicity. Comparison of this quantitative structure-activity relation ships (QSAR) with others for the reactions of benzyl alcohols in diverse sy stems provides insight into mechanisms of action. A QSAR for the interactio n of benzyl alcohols with protozoa yields an equation that is dependent on both hydrophobicity and acidity of the OH group versus a mixture of bacteri a and fungi, the critical dependence on hydrophobicity prevails with a smal l dependence on a resonance-stabilized, radical mediated electronic effect. The chloramphenicols provide an instructive example, where the radical med iated electronic effect overshadows the hydrophobic contribution to bacteri al toxicity. These various QSAR for benzyl alcohols indicate that mechanism s of growth inhibition in vitro vary depending on cell/organism type, the s trength of the bond and lability of the hydrogen, and the strength of the i nitiating radical reagent. (C) 2000 Elsevier Science Ltd. All rights reserv ed.