Critical body residues linked to octanol-water partitioning, organism composition, and LC50 QSARs:: Meta-analysis and model

To protect thousands of species from thousands of chemicals released in the environment, various risk assessment tools have been developed. Here, we link quantitative structure-activity relationships (QSARs) for response concentrations in water (LC50) to critical concentrations in organisms (C-50) by a model for accumulation in lipid or non-lipid phases versus water K-pw. The model indicates that affinity for neutral body components such as storage fat yields steep K-pw-K-ow relationships, whereas slopes for accumulation in polar phases such as proteins are gentle. This pattern is confirmed by LC50 QSARs for different modes of action, such as neutral versus polar narcotics and organochlorine versus organophosphor insecticides. LC50 GSARs were all between 0.00002 and 0.2K(ow)(-1). After calibrating the model with the intercepts and, for the first time also, with the slopes of the LC50 GSARs, critical concentrations in organisms C-50 are calculated and compared to an independent validation data set. About 60% of the variability in lethal body burdens C-50 is explained by the model. Explanations for differences between estimated and measured levels for 11 modes of action are discussed. In particular, relationships between the critical concentrations in organisms C-50 and chemical (K-ow) or species (lipid content) characteristics are specified and tested. The analysis combines different models proposed before and provides a substantial extension of the data set in comparison to previous work. Moreover, the concept is applied to species (e.g., plants, lean animals) and substances (e.g., specific modes of action) that were scarcely studied quantitatively so far.