QUANTITATIVE STRUCTURE-TOXICITY RELATIONSHIPS FOR 80 CHLORINATED COMPOUNDS USING QUANTUM-CHEMICAL DESCRIPTORS

The acute toxicity to Photobacterium phosphoreum (Microtox(TM) test) o f a set of 80 chlorinated compounds, containing aliphatics, benzenes, toluenes, phenols and anilines, was investigated using 'Theoretical Li near Solvation Energy Relationship' (TLSER) parameters. Quantitative S tructure-Activity Relationships (QSARs) were developed for chemical an d toxicological subsets. Molecular volume (V-mc) revealed to be the mo st important TLSER descriptor. For the complete data set and for the p henols the TLSER descriptors are superior to log P alone. In the case of the phenols this is related to electronic information being inheren t in the electrostatic parameter q(-) which is correlated to the pK(a) of the compounds. For the benzenes a quadratic term in V-mc was very useful for the description of the toxicity. Many of the chlorinated al iphatics do not fit the narcosis I QSAR. Enhanced chemical reactivity due to the chlorine substitution may lead to activation or biodegradat ion of these compounds. The attempt to establish narcosis II QSARs for the polar narcotic chloroanilines and -phenols was unsuccessful. It s eems that some chloroanilines interact directly with the bioluminescen ce system of P. phosphoreum. The authors emphasize that the concept of baseline narcosis implies that the 'pure' narcosis II mechanism decre ases with increasing log P. The site of toxic action for narcosis II i s therefore thought to be hydrophilic. Uncoupling of oxidative phospho rylation seems to play a minor role in the photobacterium than it does in fish. Reasons for this may be the ability of bacteria to crack and detoxify aromatic rings or the relative robustness of oxidative phosp horylation in bacteria.