Validation of Vibrio fisheri acute toxicity data: mechanism of action-based QSARs for non-polar narcotics and polar narcotic phenols.
Quantitative structure-activity relationships (QSARs) have been utilized to validate toxicity data to Vibrio fisheri (the acute Microtox test) at each of the 5-, 15- and 30-min endpoints. Statistically robust QSARs were found for chemicals acting by a non-polar narcosis mechanism of action (MOA). The baseline, non-polar narcosis QSARs were similar to those found in other aquatic organisms, thus indicating that for this MOA, the acute V. fisheri assay makes a suitable surrogate for higher test species. For the toxicity of phenols, previously modeled in other species with parameters describing membrane transport (i.e. hydrophobicity) and soft electrophilicity or ionization, no significant relationships were obtained. The use of acute V. fisheri toxicity data is not recommended for extrapolation to higher species for these compounds. Despite this recommendation, it was noted, however, that a 'minimal' phenolic toxicity was apparent that was analogous to polar narcosis in other species. This confirmed that a polar narcosis MOA does operate in the acute V. fisheri system analogous to other species. For all the compounds considered, there were highly significant correlations between the toxicities at each endpoint, indicating that data from different time endpoints were effectively interchangeable.
Cronin
M T
MT
School of Pharmacy and Chemistry, Liverpool John Moores University, UK. m.t.cronin@livjm.ac.uk
Schultz
T W
TW
D009294:Narcotics / Q000633:toxicity*; D010636:Phenols / Q000633:toxicity*; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods*; D014733:Vibrio / Q000187:drug effects*
D009294:Narcotics; D010636:Phenols