A fugacity-based toxicokinetic model for narcotic organic chemicals in fish

Abstract

A novel dynamic fugacity-based model is described, developed, and tested that simulates the uptake of narcotic organic chemicals in fish from water as occurs in aquatic bioconcentration and toxicity tests. The physiologically based toxicokinetic model treats the time course of chemical distribution in 4 compartments (tissue groups) in the fish, including the liver, in which biotransformation may occur. In addition to calculating bioconcentration and toxicokinetics, 5 possible toxic endpoints are defined corresponding to chemical concentration, fugacity, or activity reaching a critical value that causes 50% mortality. The mathematical description of multicompartment uptake is simplified by expressing the equations in the fugacity format. The model is parameterized and tested against reported empirical data for the bioconcentration of pentachloroethane in rainbow trout and for uptake and mortality from aquatic exposures to naphthalene and 1,2,4-trichlorobenzene in fathead minnows. Model performance is evaluated, and it is concluded that with suitable parameterization it has potential for application for assessment of both bioconcentration and toxicity expressed as median lethal concentrations, critical body residues, and chemical activity as a function of time to death.

In Memoriam: Don Mackay

“…Don and colleagues generated, collected, curated, and published databases of physical–chemical properties (Mackay et al, 2006); demonstrated relationships between solubilities and partition ratios; and developed methods for addressing the uncertainty inherent in measured and predicted chemical properties (Beyer et al, 2002; Cole & Mackay, 2000; Mackay, Bobra, et al, 1980; Shiu et al, 1988). Don repeatedly showed the principal relationships between partitioning properties and chemical activity with baseline toxicity (“narcosis”) in algae, invertebrates, fish, and mammals (Abernethy et al, 1986, 1988; Bobra et al, 1983, 1985; Celsie et al, 2016; Mackay et al, 2009, 2014; McCarty et al, 1992; Schmidt et al, 2018). He wrote and edited texts and numerous articles seeking to transfer this foundational knowledge to the research and regulatory communities (see Boethling & Mackay, 2000; Mackay, 1991; Thibodeaux & Mackay, 2010).…”

Bioconcentration, bioaccumulation, biomagnification and trophic magnification: a modelling perspective

“…For toxicokinetic and toxicodynamic or PBPK models in which uptake or effects in a target organ are evaluated it is essential to include that compartment explicitly. 17,27 An extreme example is the recent model by Larisch et al 28 that treats 10 internal organs and 3 external organs.…”

Screening of pesticide distributions in foods of animal origin: a matrix-based approach for biotransfer factor modeling of grazing mammals

“…26,27 Additionally, simplied partitioning rules can predict general pesticide distribution trends in mammal bodies; however, certain processes, such as metabolic rates in the liver, are oen omitted as part of conservative assumptions. 28 These modeling approaches, in addition to other bioaccumulation and PBK models, [29][30][31][32][33][34][35][36][37][38] have generally advanced our understanding of the fate of pesticides in animal bodies.…”