Quantitative structure-activity relationships of comparative toxicity to aquatic organisms.
Quantitative Strcuture-Activity relationship (QSAR) attempt statistically to
relate the physico-chemical properties of a molecule to its biological activity.
A QSAR analysis was perforned on the toxicities of upto 75 organic chemicals to
two aquatic species, Photobacterium phospherum (known as the Microtox test), and
the fathead minnow. To model the toxicities 49 physico-chemical and structural
paraneters were produced including measures of hydrophobicity, molecular size and
electronic effects from techniques such as computational chemistry and the use of
molecular oonnectivity indices. These were reduced to a statistically more
manageable number by cluster analysis, principal component analysis, factor
analysis, and canonical correlation analysis. The de-correlated data were then
used to form relationships with the toxicities. All the techniques were validated
using a testing set. Some good predictions of toxicity came from regression
analysis of the original de-correlated variables. Although successful in
sinplifying the complex data matrix, principal component analysis, factor
analysis, and canonical content analysis were disappointing as predictors of
toxicity. The performance of each of the statistical techniques is discussed.
The inter-species relationships of toxicity between four Commonly utilised
aquatic endpoints, fathead minnow 96 hour IC50, Microtox 5 minute EC50, Daphnia magna 48 hour IC50, and Tetrahymena pyriformis 60 hour IG50, were investigated.
Good relationships was found between the fathead minnow and both T. pyriformis and D. magna toxicities indicating that these species oould be used to model fish
toxicity. The outliers from individual relationships were assessed in order to
elucidate if any molecular features may be causing greater relative toxicity in
one species as compared to another. It is concluded that in addition to the
intrinsic differences between species, the greater length of the test time for
any species may result in increases bioaccumulation, metabolisn, and
detoxification of certain chemical classes. The relationships involving fish
toxicity were moderately improved by the addition of a hydrophobic parameter.