Toxicokinetic-Toxicodynamic Modeling of the Effects of Pesticides on Growth of

Ecological risk assessment is carried out for chemicals such as pesticides before they are released into the environment. Such risk assessment currently relies on summary statistics gathered in standardized laboratory studies. However, these statistics extract only limited information and depend on duration of exposure. Their extrapolation to realistic ecological scenarios is inherently limited. Mechanistic effect models simulate the processes underlying toxicity and so have the potential to overcome these issues. Toxicokinetic-toxicodynamic (TK-TD) models operate at the individual level, predicting the internal concentration of a chemical over time and the stress it places on an organism. TK-TD models are particularly suited to addressing the difference in exposure patterns between laboratory (constant) and field (variable) scenarios. So far, few studies have sought to predict sublethal effects of pesticide exposure to wild mammals in the field, even though such effects are of particular interest with respect to longer term exposure. We developed a TK-TD model based on the dynamic energy budget (DEB) theory, which can be parametrized and tested solely using standard regulatory studies. We demonstrate that this approach can be used effectively to predict toxic effects on the body weight of rats over time. Model predictions separate the impacts of feeding avoidance and toxic action, highlighting which was the primary driver of effects on growth. Such information is relevant to the ecological risk posed by a compound because in the environment alternative food sources may or may not be available to focal species. While this study focused on a single end point, growth, this approach could be expanded to include reproductive output. The framework developed is simple to use and could be of great utility for ecological and toxicological research as well as to risk assessors in industry and regulatory agencies.