Evaluation of semi-generic PBTK modeling for emergency risk assessment after acute inhalation exposure to volatile hazardous chemicals

Olie, J.D.N.; Bessems, Jos; Clewell, Harvey J.; Meulenbelt, Jan; Hunault, Claudine C.

doi:10.1016/j.chemosphere.2015.02.048

Cited by 3 publications

(2 citation statements)

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“…Firstly, the literature was searched for prior instances of generic PBTK models examining VOCs, which would have aggregated toxicokinetic information available for those compounds. A number of modeling papers were identified ( 20 – 26 ) and available information was recorded. The second strategy involved a text mining search of abstracts to identify papers that included inhalation concentration vs. time data used to describe the disposition of VOCs in their analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Other generalized PBTK models have been described previously, though these models are often described as “semi-generic” and utilize empiric fitting of data and chemical-specific parameters to derive certain constants and multiplicative factors. ( 20 – 26 ) While these models represent an important step towards the goal of a model that can be prospectively applied to new chemicals in a high-throughput manner, the process of fitting to any data may inhibit the overall generalizability of the model. As such, the aim of this investigation was to develop a reasonable inhalation model, useful for prospective and/or high-throughput investigations of volatile chemicals, for implementation in the httk package.…”

Section: Introductionmentioning

confidence: 99%

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Development and evaluation of a high throughput inhalation model for organic chemicals

Linakis

Sayre

Pearce

et al. 2020

J Expo Sci Environ Epidemiol

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Currently it is difficult to prospectively estimate human toxicokinetics (particularly for novel chemicals) in a high-throughput manner. The R software package httk has been developed, in part, to address this deficiency, and the aim of this investigation was to develop a generalized inhalation model for httk . The structure of the inhalation model was developed from two previously published physiologically-based models from Jongeneelen et al. (2011) and Clewell et al. (2001) while calculated physicochemical data was obtained from EPA’s CompTox Chemicals Dashboard. In total, 142 exposure scenarios across 41 volatile organic chemicals were modeled and compared to published data. The slope of the regression line of best fit between log-transformed simulated and observed combined measured plasma and blood concentrations was 0.46 with an r 2 = 0.45 and a Root Mean Square Error (RMSE) of direct comparison between the log-transformed simulated and observed values of 1.11.. Approximately 5.1% (n = 108) of the data points analyzed were > 2 orders of magnitude different than expected. The volatile organic chemicals examined in this investigation represent small, generally lipophilic molecules. Ultimately this paper details a generalized inhalation component that integrates with the httk physiologically-based toxicokinetic model to provide high-throughput estimates of inhalation chemical exposures.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%