title: 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.
authors.affiliation: †Department of Environmental Toxicology, Eawag - Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf, Switzerland.|‡Environment Department, University of York, Heslington, York YO10 5DD, United Kingdom.
authors.forename: Roman
authors.initials: R
authors.lastname: Ashauer
authors.affiliation: †Department of Environmental Toxicology, Eawag - Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf, Switzerland.
authors.forename: Isabel
authors.initials: I
authors.lastname: O'Connor
authors.affiliation: †Department of Environmental Toxicology, Eawag - Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Hintermeister
authors.affiliation: †Department of Environmental Toxicology, Eawag - Swiss Federal Institute of Aquatic Science and Technology, 8600 Dübendorf, Switzerland.|§Cell Toxicology, Helmholtz Centre for Environmental Research, UFZ, Leipzig 04318, Germany.|∥Environmental Toxicology, Center for Applied Geosciences, Eberhard Karls University, Tübingen 72074, Germany.
authors.forename: Beate I
authors.initials: BI
authors.lastname: Escher
mesh_terms: D031319:Aesculus / Q000187:drug effects; D033304:Amphipoda / Q000187:drug effects; D000818:Animals; D054750:Ecotoxicology; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity; D008962:Models, Theoretical; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D004785:Environmental Pollutants