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Structure—activity relationship studies on the toxicity of benzene derivatives: III. Predictions and extension to new substituents
Author(s) -
Hall Lowell H.,
Maynard Ellen L.,
Kier Lemont B.
Publication year - 1989
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.5620080509
Subject(s) - toxicity , chemistry , quantitative structure–activity relationship , partition coefficient , benzene derivatives , additive function , benzene , stereochemistry , medicinal chemistry , toxicology , computational chemistry , organic chemistry , mathematics , biology , biochemistry , in vitro , chemical synthesis , mathematical analysis
The additivity model developed earlier for 65 substituted benzenes has been extended to 105 compounds for the fathead minnow system. Toxicity is predicted for 10 compounds not included in the original data set. Four new substituents have been evaluated and their toxicity contributions have been determined by regression analysis. For the whole data set, the following statistics were obtained for the 12—variable model: r =0.921, s =0.31, F =43. The order of toxicity contributions for all substituents now investigated is as follows: —NO 2 ≈ —Cl > —Br > —CHO > —CH 3 ≈ —F > —NH 2 ≈ —CN > —OH ≈ —OCH 3 > —COCH3. Also identified in these analyses is the additional toxicity conferred by the ortho —hydroxybenzaldehyde combination. Such a structural arrangement increases toxicity by 1.45 units over both the meta and para arrangements. For the 11 substituents, relationships have been sought between the toxicity contribution and physicochemical parameters, including partition coefficient (π) and electronic parameters, but no significant relation has been found. Also evaluated were five additional substituents for which there are few data. Approximate toxicity contributions are reported for these substituents.