Structure-toxicity relationships for three mechanisms of action of toxicity to Vibrio fischeri

Quantitative structure-activity relationships (QSAKs) have been developed with the logarithm of the inverse of 15-min toxicity (pT(15)) to Vibrio fischeri (the acute Microtox test), Statistically, robust QSARs were found for alkanones acting by the nonreactive, baseline narcosis mechanism of action [pT(15) = 0.99 (log K-ow)-2.08, n = 6, s = 0.24, r(2) = 0.988, F = 405]; aldehydes acting by the Schiff base-forming mechanism of electrophilicity [pT(15) = 0.55(log K-ow)-0.58, n = 6, s = 0.07, r(2) = 0.994, F = 782]; and alkenals acting by the Michael-type acceptor mechanism of electrophilicity [pT(15) = 0.52(logK(ow)) +0.35, n = 6, s = 0.19, r(2) = 0.914, F = 54.5]. Efforts to model toxicity across mechanism of action resulted in the development of a response surface [pT(15) = 0.79(logK(ow))-1.17 (E-LUMO)-0.41, n = 19, s = 0.46, r(2) = 0.892, F = 75.3]. In addition, an excellent correlation was found between Tetrahymena pyriformis [log(1/GC(50))] and V. fischeri. [log(1/IGC(50)) = 0.86(pT(15))0.25, n = 19, s = 0.25, r(2) = 0.957, F = 405] toxicity. (C) 1998 Academic Press.