Critical Body Residues Linked to Octanol−Water Partitioning, Organism Composition, and LC₅₀QSARs:  Meta-analysis and Model

Abstract

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 (C50) by a model for accumulation in lipid or non-lipid phases versus water Kpw. The model indicates that affinity for neutral body components such as storage fat yields steep Kpw-Kow 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 QSARs were all between 0.00002 and 0.2Kow(-1). After calibrating the model with the intercepts and, for the first time also, with the slopes of the LC50 QSARs, critical concentrations in organisms C50 are calculated and compared to an independent validation data set. About 60% of the variability in lethal body burdens C50 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 C50 and chemical (Kow) 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.

Development and evaluation of a mechanistic bioconcentration model for ionogenic organic chemicals in fish

“…Following Hendriks et al [52], phospholipids were assumed to account for 1% of the organism on a whole-body basis whereas neutral lipids account for 4%, NLOM for 15%, and the remainder is water [16]. The octanol-water distribution ratio (D OW ) and membrane-water distribution ratio (D MW ) are estimated as a weighted average of the respective partition coefficients for the neutral and charged form, that is,…”

Testing the coherence between occupational exposure limits for inhalation and their biological limit values with a generalized PBPK-model: The case of 2-propanol and acetone

“…The lungs are subdivided into bronchioles, mucosa, and alveolae to model the washin-washout effect of solvent vapors in the respiratory tract, following Mork et al (2009) and Mork and Johanson (2006). Partitioning between different compartments is based on a QSAR for tissue:water partitioning, originally developed by Hendriks et al (2005). Metabolism (Michaelis-Menten kinetics) is based on the metabolic parameters V max (maximum velocity of metabolism) and K m (Michaelis-Menten constant).…”

Bioaccumulation potential of air contaminants: Combining biological allometry, chemical equilibrium and mass-balances to predict accumulation of air pollutants in various mammals

“…The chemical affinity for both neutral lipids and polar lipids is approximately linearly related to the affinity for octanol (Hendriks et al 2005). Substance affinity for proteins can also be related to the octanolwater partition coefficient, but the relationship is less than linear due to the polar nature of proteins (Hendriks et al 2005).…”

“…Recently, Hendriks et al (2005) developed a general description for chemical equilibrium partitioning in various tissues, distinguishing between neutral lipids and polar lipids and including non-lipid fractions such as proteins. It is important to investigate whether this generic approach can be used to accurately predict blood-air partition coefficients for various mammals and a range of chemicals.…”