Development and validation of a quantitative structure–activity relationship for chronic narcosis to fish

Development and validation of a quantitative structure–activity relationship for chronic narcosis to fish

etcQuantitative structure–activity relationship models (QSAR models) typically relate a set of predictor variables to the response variable. These models are useful tools in predictive ecotoxicology as the can be used to predict the (adverse) biological activity of a chemical (the response variable) based on the physico-chemical properties of the chemical (the predictor variables). As animal testing, and especially vertebrate testing, are generally strongly discouraged, the use of QSAR models offers an alternative. However, in ecotoxicology, QSAR models that describe the relationship between the physico-chemical properties of chemicals and their chronic toxicity to vertebrates are scarce. This lagoon in our knowledge is filled by the research described in our latest paper.

 

Scientific abstract

Vertebrate testing under the European Union's regulation on Registration, Evaluation, Authorisation and Restriction of Chemical substances (REACH) is discouraged, and the use of alternative nontesting approaches such as quantitative structure–activity relationships (QSARs) is encouraged. However, robust QSARs predicting chronic ecotoxicity of organic compounds to fish are not available. The Ecological Structure Activity Relationships (ECOSAR) Class Program is a computerized predictive system that estimates the acute and chronic toxicity of organic compounds for several chemical classes based on their log octanol–water partition coefficient (KOW). For those chemical classes for which chronic training data sets are lacking, acute to chronic ratios are used to predict chronic toxicity to aquatic organisms. Although ECOSAR reaches a high score against the Organisation for Economic Co-operation and Development (OECD) principles for QSAR validation, the chronic QSARs in ECOSAR are not fully compliant with OECD criteria in the framework of REACH or CLP (classification, labeling, and packaging) regulation. The objective of the present study was to develop a chronic ecotoxicity QSAR for fish for compounds acting via nonpolar and polar narcosis. These QSARs were built using a database of quality screened toxicity values, considering only chronic exposure durations and relevant end points. After statistical multivariate diagnostic analysis, literature-based, mechanistically relevant descriptors were selected to develop a multivariate regression model. Finally, these QSARs were tested for their acceptance for regulatory purposes and were found to be compliant with the OECD principles for the validation of a QSAR.

 

Full reference

Claeys L, Iaccino F, Janssen CR, Van Sprang P, Verdonck F. 2013. Development and validation of a quantitative structure–activity relationship for chronic narcosis to fish. Environmental Toxicology and Chemistry, 32: 2217–2225. doi:10.1002/etc.2301

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