QSAR FOR ACUTE TOXICITY OF SATURATED AND UNSATURATED HALOGENATED ALIPHATIC-COMPOUNDS

Training-set of 19 compounds - 11 haloalkanes and 8 haloalkenes - was selected from a group of 58 halogenated aliphatic hydrocarbons using s tatistical experimental design. Strictly defined method was used for p reparation of water solutions and toxicity measurements of volatile an d poorly water-soluble halogenated aliphatic substances. The acute tox icity expressed as the effective concentrations (EC50) was determined for the compounds in the training set using the Microtox test. The qua ntitative structure-activity relationships (QSAR) models for haloaliph atic compounds were constructed using the Projection ot latent structu res method. Size of the molecules was the most important parameter for toxicity of saturated haloaliphatic compounds. This characteristics c an be related to accumulation of the haloalkanes in biological membran es or binding to biomacromolecules. Toxicity of 2-chlorobutane was sig nificantly higher than expected from its size. This compound, as the o nly representative of beta-substituted chloroderivatives in the data s et, has probably different mode of action than terminally substituted compounds. Three unsaturated compounds - cis-1,2-dichloroethylene, tra ns-1,4-dichlorobutene, and cis-1,4-dichlorobutene - displayed similar mode of action to that observed for haloalkanes, while another two hal oalkenes 3-chloropropylene, and 2,3-dibromopropylene displayed differe nt - reactive - type of toxicity. The steric parameters had to be comp lemented by four electronic descriptors for explanation of their high toxicity. (C) 1998 Elsevier Science Ltd.