Predicting the Accumulation of Ionizable Pharmaceuticals and Personal Care Products in Aquatic and Terrestrial Organisms

Abstract

The extent to which chemicals bioaccumulate in aquatic and terrestrial organisms represents a fundamental consideration for chemicals management efforts intended to protect public health and the environment from pollution and waste. Many chemicals, including most pharmaceuticals and personal care products (PPCPs), are ionizable across environmentally relevant pH gradients, which can affect their fate in aquatic and terrestrial systems. Existing mathematical models describe the accumulation of neutral organic chemicals and weak acids and bases in both fish and plants. Further model development is hampered, however, by a lack of mechanistic insights for PPCPs that are predominantly or permanently ionized. Targeted experiments across environmentally realistic conditions are needed to address the following questions: (1) What are the partitioning and sorption behaviors of strongly ionizing chemicals among species? (2) How does membrane permeability of ions influence bioaccumulation of PPCPs? (3) To what extent are salts and associated complexes with PPCPs influencing bioaccumulation? (4) How do biotransformation and other elimination processes vary within and among species? (5) Are bioaccumulation modeling efforts currently focused on chemicals and species with key data gaps and risk profiles? Answering these questions promises to address key sources of uncertainty for bioaccumulation modeling of ionizable PPCPs and related contaminants. Environ Toxicol Chem 2022;00:1–11. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Bioaccumulation Kinetics of Model Pharmaceuticals in the Freshwater Unionid Pondmussel, Sagittunio subrostratus

“…For example, we previously reported bioaccumulation of the ionizable base diphenhydramine in adult Pimephales promelas (fathead minnows) to be under predicted by log D ow (Nichols et al, 2015), an observation similar to the present study with sertraline. In the present study, the human pharmacokinetic proportionality factor, apparent volume of distribution (V D ; Table 1), appears particularly useful for advancing bioaccumulation modeling of ionizable contaminants because it describes internal distribution regardless of the basis for chemical behavior (Carter et al, 2023). For example, Zhang et al (2022) recently identified that V D was a better predictor of kinetic‐based BCF values for ionizable pharmaceuticals in zebrafish ( Danio rerio ) than log D ow or log D liposome‐water .…”

Generic Model for Plant Uptake of Ionizable Pharmaceuticals and Personal Care Products

“…It was recommended to standardize plant uptake test systems, and to record influential physiological and environmental parameters (Doucette et al, 2018), and it was found that plant-specific parameters can have as much influence on chemical uptake as physicochemical parameters (Trapp, 2015). Carter et al (2022) addressed current obstacles in the model development for the prediction of accumulation of PPCPs in aquatic and terrestrial organisms, and concluded that further progress is hampered by a lack of mechanistic insights, mainly for ions. The authors stimulated research into partitioning and sorption behavior, membrane permeabilities, salts and complexes, and on biotransformation and elimination processes of ions.…”

“…Among the most pressing research questions for PPCPs is “How can the uptake of ionizable PPCPs into aquatic and terrestrial organisms and through food chains be predicted?” (Boxall et al, 2012). It was concluded that “improved models should be developed for estimating uptake of ionizable PPCPs into organisms and through food chains,” and major obstacles and key research questions to derive such models were addressed in Carter et al (2022).…”

Laboratory‐Derived Bioaccumulation Kinetic Parameters for Four Per‐ and Polyfluoroalkyl Substances in Freshwater Mussels

“…Furthermore, PFAS have been found to bioaccumulate in tissues of aquatic organisms, wildlife, and birds, and this accumulation is dissimilar to legacy contaminants such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs; Giesy & Kannan, 2001) largely because PFAS have been found to bind to proteins and other biopolymers (Bischel et al, 2010; Liang et al, 2022; MacManus‐Spencer et al, 2009; Wen et al, 2019). Similar to other ionizable contaminants that fall outside the applicability domain of predictive bioaccumulation models for nonionizable organics (Carter et al, 2022; Nichols et al, 2015), kinetic information to model bioaccumulation of PFAS in freshwater ecosystems is needed (Bertin et al, 2016; Prosser et al, 2016). In addition, accumulation dynamics of PFAS by aquatic life may differ based on the organisms’ feeding and behavior (Lewis et al, 2022).…”