Polar narcosis: Designing a suitable training set
- Utrecht Univ. (Netherlands). Research Inst. of Toxicology
Substituted phenols, anilines, pyridines and nitrobenzenes can be classified as polar narcotics. These chemicals differ from non-polar narcotic compounds not only in that they exhibit a 5 to 10 times higher toxicity, but also in their Fish Acute Toxic Syndromes, together suggesting a different mode of action. For 97 polar narcotics, which are not ionized under physiological conditions, 11 physico-chemical and quantum-chemical descriptors were calculated. Using Principal Components Analysis 91% of the total variance could be explained by three Principal Components, which were subsequently used as factors in a Statistical Design. Eleven compounds were selected based on a two-level full factorial design, including three compounds near the center (2{sup 3} + 3). QSARs were developed for both, the design set and a set of 63 polar narcotics for which guppy and/or fathead minnow data were available in the literature. Both QSAR, based on PLS, resulted in good models (R{sup 2} = 0.96 and Q{sup 2} = 0.8{sup 2}; R{sup 2}= 0.86 and Q{sup 2} = 0.83 respectively) and gave similar Pseudo Regression Coefficients. In addition the model based on the designed chemicals was able to predict the toxicity of the 63 compounds (R{sup 2} = 0.85). These results show that these 11 chemicals are a well-balanced set for further studies of polar narcosis.
- OSTI ID:
- 382734
- Report Number(s):
- CONF-9511137--; ISBN 1-880611-03-1
- Country of Publication:
- United States
- Language:
- English
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