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

Decisions 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 ( LC 50 ). Regulatory documents recommend concentration-response (or concentration-effect) model fitting on standard toxicity test data to get LC 50 values. 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, LC 50 values can be obtained from the reduced General Unified Threshold model of Survival (GUTS-RED) with both variants, Stochastic Death and Individual Tolerance, that include parameter h b , the background mortality. Estimating h b during the fitting process or not depends on studies and fitting habits, while it may strongly influence the other GUTS-RED parameters, and consequently the LC 50 estimate. We hypothesized that estimating h b from all data in all replicates over time should provide more precise LC 50 estimates. We then explored how estimating h b impacted: (i) GUTS-RED model parameters; (ii) goodness-of-fit criteria (fitting plot, posterior predictive check, parameter correlation); (iii) LC 50 accuracy and precision. We finally show that estimating h b does not impact the LC 50 precision while providing more accurate and precise GUTS parameter estimates. Hence, estimating h b would lead to a more protective ERA. Graphical abstract Specifications table