PARENT SESSION

1F - QSAR
Poster Hall
8:30 AM - Tuesday, 29 April 2003
Chair: Schüürmann, G.¹, ¹
Co-chair: Verhaar, H.J.M.², Cronin, M.³, ^{2 3}

(TUP/39) Comparative QSAR for Bacterial Toxicity.

Lessigiarska, Iglika¹, Dearden, John², Netzeva, Tatiana², Worth, Andrew¹, Cronin, Mark², ¹ European Chemicals Bureau, Ispra, VA, Italy² Liverpool John Moores University, Liverpool, Merseyside, England

ABSTRACT- There is an increasing need for high quality quantitative structure-activity relationships (QSARs) to assist in the prediction of toxicity. High quality QSARs are defined as being those meeting a number of criteria, namely the utilisation of reliable toxicity and physico-chemical data, transparent modelling methods, a strong mechanistic basis, and appropriate validation. It is acknowledged that there is a paucity of toxicity data for the development of high quality QSARs. However, a novel source of toxicity data has recently become available (Botsford J.L., ATLA, 30, 539, 2002) describing the toxicity of over 250 miscellaneous compounds to the bacterium Sinorhizobium meliloti (in terms of the conversion of MTT dye), all data having been measured in the same laboratory. The data set is highly heterogeneous in terms of both chemistry and mechanisms of toxic action. A definite baseline effect is demonstrated by compounds known to act by narcotic mechanisms of action i.e. a strong relationship is observed with the logarithm of the octanol-water partition coefficient (log K_ow). Prediction of the toxicity of more reactive compounds (i.e. those electrophilic in nature, or acting by specific mechanisms) requires the use of further descriptors. The diversity of the data base allows for the comparison of QSAR techniques and predictive strategies. Further, development of QSARs for the database illustrates some of the problems and issues associated with modelling a database containing information on a diverse series of compounds, namely assignment of chemicals to an appropriate mechanism of action, missing data (i.e. those reported to be non-toxic), problems with modelling mixtures and inorganics, and practical considerations regarding validation.

Key words: bacterial toxicity, aquatic systems, QSAR, mechanism of action