Assessing the bioaccumulation potential of ionizable organic compounds: Current knowledge and research priorities

Abstract

Abstract:The objective of the present study was to review the current knowledge regarding the bioaccumulation potential of ionizable organic compounds (IOCs), with a focus on the availability of empirical data for fish. Aspects of the bioaccumulation potential of IOCs in fish that can be characterized relatively well include the pH dependence of gill uptake and elimination, uptake in the gut, and sorption to phospholipids (membrane-water partitioning). Key challenges include the lack of empirical data for biotransformation and binding in plasma. Fish possess a diverse array of proteins that may transport IOCs across cell membranes. Except in a few cases, however, the significance of this transport for uptake and accumulation of environmental contaminants is unknown. Two case studies are presented. The first describes modeled effects of pH and biotransformation on the bioconcentration of organic acids and bases, while the second employs an updated model to investigate factors responsible for accumulation of perfluorinated alkyl acids. The perfluorinated alkyl acid case study is notable insofar as it illustrates the likely importance of membrane transporters in the kidney and highlights the potential value of read-across approaches. Recognizing the current need to perform bioaccumulation hazard assessments and ecological and exposure risk assessment for IOCs, the authors provide a tiered strategy that progresses (as needed) from conservative assumptions (models and associated data) to more sophisticated models requiring chemical-specific information. Environ Toxicol Chem 2017;36:882-897. # 2016 SETAC

Uptake and Effects of the Beta‐Adrenergic Agonist Salbutamol in Fish: Supporting Evidence for the Fish Plasma Model

“…Log K OW as a descriptor of lipophilicity has therefore frequently been replaced in Fitzsimmons' equation with the log D OW at the relevant pH. Although this pragmatic approach has been criticized (Armitage et al 2017), it produced remarkably good agreements between predicted and measured fish plasma concentrations of weak bases dominantly present as cations at ambient pH, namely, atenolol with a log D OW (pH 7.4) of -1.61 (Winter et al 2008), sertraline with a log D OW (pH 8.5) of 3.77 (Valenti et al 2012), propranolol with a log D OW (pH 7.4) of 1.12 (Giltrow et al 2009;Owen et al 2009), and fluoxetine with a log wileyonlinelibrary.com/ETC © 2019 SETAC D OW (pH 7.4) of 1.99 (Margiotta-Casaluci et al 2014). Uptake of the weak base diphenhydramine into fathead minnow (measured in whole-body content as well as blood plasma) was found to increase with increasing pH (Nichols et al 2015).…”

Recommendations for Improving Methods and Models for Aquatic Hazard Assessment of Ionizable Organic Chemicals

“…Experimental bioaccumulation of IOCs and associated prediction models have been recently reviewed (Armitage et al ). Models range from simple equilibrium partitioning models to time‐resolved toxicokinetic models.…”

Towards Sustainable Environmental Quality: Priority Research Questions for the Australasian Region of Oceania

“…Many of the algorithms used in risk assessments were developed for hydrophobic organic compounds under temperate conditions. Similarly, K ow -based approaches have limitations for ionizable chemicals such as pharmaceuticals and per-and polyfluoralkyl substances (PFAS), which partition by nonhydrophobic mechanisms (e.g., ion exchange, protein binding; Armitage et al 2017). For example, the octanol-water partition coefficient log K ow is used as an indicator of enhanced accumulation, with molecules that have log K ow values greater than 3 predicted to accumulate.…”

“…However, some uncharged molecules with low log K ow values have also been shown to accumulate in organisms (e.g., Emnet et al 2015). Similarly, K ow -based approaches have limitations for ionizable chemicals such as pharmaceuticals and per-and polyfluoralkyl substances (PFAS), which partition by nonhydrophobic mechanisms (e.g., ion exchange, protein binding; Armitage et al 2017). There is a need to undertake a metaanalysis of the available data on the linkages between the structural and physicochemical properties of substances and their environmental fate and bioavailability.…”