COMPARISON OF TOXICITIES AND MECHANISM OF ACTION OF N-ALKANOLS IN THESUBMITOCHONDRIAL PARTICLE AND THE VIBRIO-FISCHERI BIOLUMINESCENCE (MICROTOX(R)) BIOASSAY

Many studies on the toxicity of n-alkanols have been conducted and qua ntitative structure-activity relationships (QSARs) established compari ng bioassay toxicity data to carbon number. The results typically indi cate increasing toxicity with increasing n-alkanol chain length, but o ften higher homologues are not assessed, where toxicity no longer incr eases with carbon number-a phenomenon commonly called the cutoff effec t. The mode of toxic action of these compounds has been designated nar cosis I; however, the specific mechanism is unknown and widely debated . This study compares results for two commonly used bioassays, the sub mitochondrial particle (SMP) and the Microtox(R) bioassay, for the hom ologous series of n-alkanols ranging from methanol (C-1-OH) to stearyl alcohol (C-18-OH). Analysis of dose-response curve slopes indicates t hat the SMP assay exhibits a general mechanism of toxicity, whereas th e Microtox assay exhibits this general mechanism to short-chain alkano ls, but subsequently switches to specific interaction with the higher alkanols. This specific interaction is likely competitive inhibition o f the bacterial luciferase. Comparison of the toxicities in these assa ys with octanol/water partition coeffients (K-ow), the results of whol e-organism tests, and a bacterial luciferase assay further substantiat e this claim and indicate that the SMP is a better model of toxicity i n whole organisms.