Structure-activity relationships in PCBs: Use of principal components analysis to predict inducers of mixed-function oxidase activity

Of the 209 PCB congeners, over 50 are known or suspected inducers of mixed-function oxidase activities in mammalian liver. These include inducers of cytochromes P-448 (MC-type inducers), P-450 (PB-type inducers), both P-448 and P-450 (mixed-type inducers), and one “novel” inducer. To elucidate structure-activity relationships with respect to these inducers, a statistical approach was taken using principal components analysis. Ten principal components (PCs) were extracted from variables coded for the positions of chlorines on the biphenyl. Three of these PCs, including an “ ortho” component and a “ para” component, were used to graph a three-dimensional space in which patterns of inducers can be clearly recognized. These patterns include five groups of congeners dominated, respectively, by weak PB-type inducers, MC-type inducers, mixed-type inducers, PB-type inducers, and suspected PB-type inducers. The remaining spatial configuration is a large, heterogeneous group composed of inactive congeners and a few “outlier” PB-type inducers. Re-evaluation of these outliers may indicate that inducer activity is less than previously thought. Conversely, congeners not currently known to be inducers, but falling within the spatial boundaries of the five inducer groups, may also turn out to be inducers. The congeners of the suspected PB-type inducer group are predicted to be weak PB-type inducers, and certain congeners having PC configurations similar to the one novel inducer may possibly also be novel inducers.