Extending GUTS to account for oral exposure in bees: Preconditions, model options, and evaluation of published approaches

The General Unified Threshold model for Survival (GUTS) is the leading toxicokinetic–toxicodynamic (TKTD) framework for the endpoint mortality in aquatic ecotoxicology and risk assessment. Although GUTS is not specifically restricted to aquatic organisms, its use for terrestrial organisms requires a closer look at the toxicokinetic module, owing to the potentially different importance of various exposure routes. In recent years, there has been specific interest in applying GUTS to assess the risk of pesticides to adult (honey) bees. Standard tests expose the bees via spiked food, either for several hours (acute) or for 10 days (chronic). Three specific modifications of GUTS have been presented to deal with oral exposure: using standard GUTS with external concentration replaced by the daily dose rate from the toxicity test (European Food Safety Authority), calculating test-type-specific exposure patterns and feeding them into standard GUTS (BeeGUTS), and adding a generic buffer compartment to GUTS (BufferGUTS). These approaches do not delineate explicit models for the chemical kinetics in the gut, and are thus more descriptive than mechanistic. Therefore, it is good to take a step back and consider the preconditions for modelling oral uptake in the GUTS context. Two simple mechanistically-plausible model options are worked out in detail. Next, the three published approaches are evaluated, using the two mechanistic modules as a reference. A number of concerns are identified, making it clear that more research is needed before we can provide GUTS with a simple, mechanistic, gut module that can be relied upon for extrapolation. The work laid down in this study provides a basis for further model development.