QSTR Studies Regarding the ECOSAR Toxicity of Benzene-Carboxylic Acid' Esters to Fathead Minnow Fish (Pimephales promelas)
Laszlo Tarko, Mihai V. Putz, Cosmin Ionascu and Ana-Maria Putz
Affiliation: (Laszlo Tarko) Center of Organic Chemistry “C.D. Nenitzescu” of Romanian Academy, 202B Spl. Independentei, PO Box 35-108, RO-060023, Bucharest - 6th Sector, Romania.
Keywords: Benzene-carboxylic acid esters, ECOSAR toxicity, fathead minnow, QSTR, PRECLAV.
The present work employs 152 benzene-carboxylic acid' esters having computed the toxicity within the range
[2.251, 10.222] for fathead minnow fish (Pimephales promelas). Calibration set includes many pairs having very similar
chemical structure, size, shape and hydrophilicity, but very different value of ECOSAR toxicity or vice versa. The QSTR
study, which uses all esters as calibration set, emphasized a large percent (16.2%) of outliers. In this QSTR study most of
the estimated values of toxicity for outliers are much lower than ECOSAR toxicity. The LogP and some aromaticity
descriptors are predictors. The best QSTR for esters having low value (< 5.5) of ECOSAR toxicity and the best QSTR for
esters having high value (> 5.5) of ECOSAR toxicity are obtained when the number of outliers is very small. These
QSTRs are different enough and highlight opposite influences of certain descriptors on toxicity. The results emphasize
two possibilities: (a) the esters having low value of ECOSAR toxicity and the esters having high value of ECOSAR
toxicity are included in two different classes from the point of view of structure-toxicity relationship and/or (b) many high
values of ECOSAR toxicity are wrong. By comparison, a QSTR using experimental values of toxicity against rats for 37
benzene-carboxylic esters included in the same database gives good correlation experimental/computed values of toxicity,
the number of outliers is null and the result of validation test is good.
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