Death Dilemma and Organism Recovery in Ecotoxicology

Abstract

Why do some individuals survive after exposure to chemicals while others die? Either, the tolerance threshold is distributed among the individuals in a population, and its exceedance leads to certain death, or all individuals share the same threshold above which death occurs stochastically. The previously published General Unified Threshold model of Survival (GUTS) established a mathematical relationship between the two assumptions. According to this model stochastic death would result in systematically faster compensation and damage repair mechanisms than individual tolerance. Thus, we face a circular conclusion dilemma because inference about the death mechanism is inherently linked to the speed of damage recovery. We provide empirical evidence that the stochastic death model consistently infers much faster toxicodynamic recovery than the individual tolerance model. Survival data can be explained by either, slower damage recovery and a wider individual tolerance distribution, or faster damage recovery paired with a narrow tolerance distribution. The toxicodynamic model parameters exhibited meaningful patterns in chemical space, which is why we suggest toxicodynamic model parameters as novel phenotypic anchors for in vitro to in vivo toxicity extrapolation. GUTS appears to be a promising refinement of traditional survival curve analysis and dose response models.

Short‐term to long‐term extrapolation of lethal effects of an herbicide on the marine mysid shrimpAmericamysis Bahiaby use of the General Unified Threshold Model of Survival (GUTS)

“…The choice of the most appropriate dose metric depends on the available data and the hypotheses regarding the mechanism of action of the chemical. This choice will affect the interpretation of the toxicodynamic parameters and their dimensions (Jager et al ; Ashauer et al ). In the absence of body residue data, the use of the scaled internal concentration (SIC) as dose metric is recommended (Jager et al ).…”

“…In such a case, the reduced form of the GUTS model (GUTS‐RED) is employed (Jager and Ashauer, ). For further details on the models' equations and their derivation, see the studies by Jager et al (), Ashauer et al () and Jager and Ashauer ().…”

Physiological modes of action across species and toxicants: the key to predictive ecotoxicology

“…When analyzing toxicity data for a set of compounds or species, one can separate the information relating to toxicokinetics from that relating to toxicodynamics. 34 Accounting for variation in toxicity due to toxicokinetics is necessary if we want to learn about toxicodynamics. Accounting for toxicokinetics can be achieved by approximating the internal dose based on physicalchemical properties, by measuring body burdens or cell internal concentrations, or by using calibrated toxicokinetics models.…”

Toward refined environmental scenarios for ecological risk assessment of down-the-drain chemicals in freshwater environments

“…Using internal dose as a metric can begin to account for the species sensitivity differences caused by TK (Escher and Hermens ; Hendriks et al ; Nyman et al ). TK‐TD models can explicitly separate TK from TD processes (Ashauer et al ). Thus, it is possible to model the influence of physical‐chemical properties, some species traits (Buchwalter et al ; Rubach et al ; Poteat and Buchwalter ), and environmental factors (Ruotsalainen et al ) on TK, as well as the influence of toxicity pathways (Gunnarsson et al ; Lalone et al ), species traits (Rubach et al ), and environmental factors (Heugens et al ) on TD (Rubach et al ; Jager ; Ashauer et al ).…”

“…TK‐TD models can explicitly separate TK from TD processes (Ashauer et al ). Thus, it is possible to model the influence of physical‐chemical properties, some species traits (Buchwalter et al ; Rubach et al ; Poteat and Buchwalter ), and environmental factors (Ruotsalainen et al ) on TK, as well as the influence of toxicity pathways (Gunnarsson et al ; Lalone et al ), species traits (Rubach et al ), and environmental factors (Heugens et al ) on TD (Rubach et al ; Jager ; Ashauer et al ). A single parameter, such as temperature, can influence TK, by changing uptake, elimination, and biotransformation rates (Buchwalter et al ; Heugens et al ; Harwood et al ), as well as TD, by changing physiology and intrinsic sensitivity (Harwood et al ).…”