hb or not hb - when and why accounting for background mortality in toxicological survival models matters?

Abstract

AbstractDecisions in Environmental Risk Assessment (ERA) about impacts of chemical compounds on different species are based on critical effect indicators such as the 50% lethal concentration (LC50). Regulatory documents recommend concentration-response (or concentration-effect) model fitting on standard toxicity test data to getLC50values. However, toxicokinetic-toxicodynamic (TKTD) models proved their efficiency to better exploit toxicity test data, at Tier-2 but also at Tier-1, delivering time-independent indicators. In particular,LC50values can be obtained from the reduced General Unified Threshold model of Survival (GUTS-RED) with both variants, Stochastic Death and Individual Tolerance, that include parameterhb, the background mortality. Estimatinghbduring the fitting process or not depends on studies and fitting habits, while it may strongly influence the other GUTS-RED parameters, and consequently theLC50estimate. We hypothesized that estimatinghbfrom all data in all replicates over time should provide more preciseLC50estimates. We then explored how estimatinghbimpacted: (i) GUTS-RED model parameters; (ii) goodness-of-fit criteria (fitting plot, posterior predictive check, parameter correlation); (iii)LC50accuracy and precision. We finally show that estimatinghbdoes not impact theLC50precision while providing more accurate and precise GUTS parameter estimates. Hence, estimatinghbwould lead to a more protective ERA.Graphical abstractSpecifications table