Citation:

Mangold-Doring, A., C. Grimard, D. Green, S. Peterson, J. Nichols, N. Hogan, L. Weber, H. Hollert, M. Hecker, AND M. Brinkmann. A Novel Multispecies Toxicokinetic Modeling Approach in Support of Chemical Risk Assessment. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 55(13):9109-9118, (2021). https://doi.org/10.1021/acs.est.1c02055

Impact/Purpose:

Ecological risk assessments for chemicals are often supported by data for one or a small number of species tested under standardized conditions. It is of interest, therefore, to develop methods and models to relate this information to the full diversity of species requiring protection. Physiologically based toxicokinetic (PBTK) models for fish can be used to extrapolate chemical dosimetry information from one tested species to a second, untested species, but this requires detailed information for both and does not yield predictions for other, untested species. The goal of this effort was to employ a PBTK model to predict steady-state chemical bioconcentration factors for hypothetical fish species representing plausible combinations of model input parameter. To support this effort, a database of model inputs was developed by searching published literature for freshwater fishes of Canada. Additional model inputs were developed by direct observation. Eighty-two percent of predicted fish bioconcentration factors (BCFs) deviated by less than a factor of ten from measured data. These modeled predictions illustrate the plausible range of BCFs that can be expected to result from species differences in parameters that control chemical uptake and accumulation. As such, this new model enables more environmentally relevant predictions of chemical bioconcentration in fish without the need for additional animal experiments.

Description:

Standardized laboratory tests with a limited number of model species are a key component of chemical risk assessments. These surrogate species cannot represent the entire diversity of native species, but there are practical and ethical objections against testing chemicals in a large variety of species. In previous research, we have developed a multispecies toxicokinetic model to extrapolate chemical bioconcentration across species by combining single-species physiologically based toxicokinetic (PBTK) models. This “top-down” approach was limited, however, by the availability of fully parameterized single-species models. Here, we present a “bottom-up” multispecies PBTK model based on available data from 69 freshwater fishes found in Canada. Monte Carlo-like simulations were performed using statistical distributions of model parameters derived from these data to predict steady-state bioconcentration factors (BCFs) for a set of well-studied chemicals. The distributions of predicted BCFs for 1,4-dichlorobenzene and dichlorodiphenyltrichloroethane largely overlapped those of empirical data, although a tendency existed toward overestimation of measured values. When expressed as means, predicted BCFs for 26 of 34 chemicals (82%) deviated by less than 10-fold from measured data, indicating an accuracy similar to that of previously published single-species models. This new model potentially enables more environmentally relevant predictions of bioconcentration in support of chemical risk assessments.

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