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Optimizing and evaluating a simplified toxicokinetic toxicodynamic (TKTD) model for predicting effects of pulsed exposure to carbaryl on fathead minnow
Citation:
Kadlec-Groom, S., M. Etterson, K. Flynn, AND N. Pollesch. Optimizing and evaluating a simplified toxicokinetic toxicodynamic (TKTD) model for predicting effects of pulsed exposure to carbaryl on fathead minnow. SETAC North America, Sacramento, CA, November 04 - 08, 2018.
Impact/Purpose:
Currently, our understanding of the effects of environmental chemicals on fish populations relies mainly on simple or constant chemical laboratory exposures. However, in their native environments, fish are more likely to be exposed to fluctuating concentrations of chemicals. This work seeks to bridge that gap, by using fish early life stage toxicity test data and identifying how various model inputs can most accurately predict adverse outcomes following modeled real-world pesticide exposure scenarios, such as those that may be generated using EPA’s Pesticide in Water Calculator program. This information, along with a fish toxicity translator model we also have under development, will help to more accurately predict the risk from pesticides to fish populations.
Description:
The effects of pulsed and time-variable exposures to chemicals may be under- or over-estimated with environmental risk assessment approaches based on standard, constant-exposure toxicity tests. However, fully calibrating models to predict the effects of pulsed exposures requires experimental data that are resource-intensive to gather and are not routinely provided for the EPA’s pesticide registration process. Previous researchers have suggested that standard 96-h acute and 30-d early lifestage toxicity test data may be used to parameterize a simplified toxicokinetic, toxicodynamic (TKTD) model, resulting in predictive power equivalent to a full model. Our team is developing an efficient protocol using R to evaluate the characteristics of toxicological datasets that result in successful parameter estimation for this simplified model, and to select the toxicological data that results in models with optimal predictive power. We demonstrate our methods and results using the effects of carbaryl on fathead minnow survival as an example, with datasets derived from both standard and non-standard toxicity test endpoints, as well as literature-estimated parameters. We also discuss the possibility of accounting for size-dependent sensitivity and sublethal endpoints within these models, developing a generalized model for other species/chemical combinations, and using pulsed exposure effects model outputs to inform population models. This work is a part of the fish population model development at EPA-MED, presented elsewhere during this session.