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Which molecular features affect the intrinsic hepatic clearance rate of ionizable organic chemicals in fish?
Citation:
Chen, Y., J. Hermens, M. Jonkers, J. Arnot, J. Armitage, T. Brown, J. Nichols, K. Fay, AND S. Droge. Which molecular features affect the intrinsic hepatic clearance rate of ionizable organic chemicals in fish? ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 50:12722-12730, (2016).
Impact/Purpose:
The bioaccumulation potential of ionizable organic chemicals (IOCs) in ecological receptors is of increasing interest to environmental chemists, toxicologists and risk assessors. However, modeling tools typically applied for predicting the bioaccumulation of neutral organic chemicals fail to consider the speciation of IOCs (i.e., the presence of a neutral and charged forms) and do not adequately represent sorption of charged species to blood and tissues. The objective of this paper was to review the state-of-the science regarding the bioaccumulation potential of IOCs, with a focus on the availability of empirical data for fish and development of predictive models. Based on this review, we identified data needs which must be addressed to reduce current uncertainty regarding the behavior of IOCs in fish. Recognizing the current need to perform bioaccumulation hazard assessments and ecological and exposure risk assessment for IOCs, we also provide a tiered strategy that progresses from conservative assumptions (models and associated data) to more sophisticated models requiring chemical-specific information. This paper provides critical guidance to risk assessors who deal with IOCs under several regulatory authorities (e.g., TSCA and FIFRA).
Description:
Greater knowledge of biotransformation rates for ionizable organic compounds (IOCs) in fish is required to properly assess the bioaccumulation potential of many environmentally relevant contaminants. In this study we measured in vitro hepatic clearance rates for 50 IOCs using a pooled batch of liver S9 fractions isolated from rainbow trout (Oncorhynchus mykiss). The IOCs included four types of strongly ionized acids (carboxylates, phenolates, sulfonates, and sulfates), three types of strongly ionized bases (primary, secondary, tertiary amines), and a pair of quaternary ammonium compounds (QACs). Included in this test set were several surfactants and a series of beta-blockers. For linear alkyl chain IOC analogues, biotransformation enzymes appeared to act directly on the charged terminal group, with the highest clearance rates for tertiary amines and sulfates, and no clearance of QACs. Clearance rates for C12-IOCs were higher than those for C8-IOC analogues. Several analogue series with multiple alkyl chains, branched alkyl chains, aromatic rings, and nonaromatic rings were evaluated. The likelihood of multiple reaction pathways made it difficult to relate all differences in clearance to specific molecular features the tested IOCs. Future analysis of primary metabolites in the S9 assay is recommended to further elucidate biotransformation pathways for IOCs in fish.
