Death Dilemma and Organism Recovery in Ecotoxicology

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.