Acute toxicity of substituted phenols to Rana japonica tadpoles and mechanism-based quantitative structure-activity relationship (QSAR) study.
Acute 12 h and 24 h lethal toxicity (12 h-LC50 and 24 h-LC50) of 31 substituted phenols to Rana japonica tadpoles was determined. Results indicate that toxicity of phenols to tadpoles varied only slightly with length of exposure and the 12-h test could serve as surrogate of the 24-h test. A mechanism-based quantitative structure-activity relationship (QSAR) method was employed and 1-octanol/water partition coefficient (log K(ow))-dependent models were developed to study different modes of toxic action. Most phenols elicited their response via a polar narcotic mechanism and an excellent logK(ow)-dependent model was obtained. Soft electrophilicity and pro-electrophilicity were observed for some phenols and a good log K(ow)-dependent model was also achieved. Additionally, the significant dissociation of carboxyl on benzoic acid derivatives sharply reduced their toxicity. A statistically robust QSAR model was developed for all studied compounds with the combined application of log K(ow), energy of lowest unoccupied orbital (E(lumo)), heat of formation (HOF) and the first-order path molecular connectivity dices (1chi(p)).
Wang
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Department of Environmental Science and Engineering, State Key Laboratory of Pollution Control and Resources Reuse, Nanjing University, People's Republic of China.
Dong
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Y
Wang
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L
Han
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D000818:Animals; D007814:Larva / Q000254:growth & development; D007928:Lethal Dose 50; D010636:Phenols / Q000633:toxicity*; D011898:Ranidae; D013329:Structure-Activity Relationship; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D010636:Phenols; D014874:Water Pollutants, Chemical