MULTIVARIATE MODE-OF-ACTION ANALYSIS OF ACUTE TOXICITY OF PHENOLS

Acute toxicity of eight phenols towards ten biological test systems is characterized with principal component analysis and partial least-squ ares regression in terms of underlying modes of action and associated compound properties. The test battery consists of nine different speci es: three fish, one waterflea, one ciliate, one marine bacterium in tw o different assays, two fish cell lines and one plant pollen. The comp ound set contains phenol, five chlorophenols and two nitrophenols, rep resenting polar narcotics and uncouplers of oxidative phosphorylation. Lipophilicity (log K-ow) and acidity (pK(a)) as well as respective bi linear decompositions in quantum chemical parameters are used as molec ular descriptors. The results reveal substantial differences in specif ic sensitivity of the test systems for uncoupling activity. Furthermor e, pentachlorophenol (as a classical uncoupler) exerts no significant excess toxicity over polar narcosis with any of the ten endpoints, and 4-nitrophenol apparently acts as uncoupler with most of the non-fish test species including procaryotic cells. The discussion includes alte rnative hypotheses about the underlying mechanism of uncoupling activi ty. (C) 1997 Elsevier Science B.V.