Plasma, liver, and kidney exposures in rats after oral doses of industrial chemicals predicted using physiologically based pharmacokinetic models: A case study of perï¬uorooctane sulfonic acid.
J Toxicol Sci
; 45(12): 763-767, 2020.
Article
in En
| MEDLINE
| ID: mdl-33268676
ABSTRACT
A simplified physiologically based pharmacokinetic (PBPK) model consisting of chemical receptor, metabolizing and/or excreting, and central compartments was recently proposed. In the current study, this type of PBPK model was set up for perï¬uorooctane sulfonate, an environmental toxicant with liver effects, as a model compound; the model was then used to estimate tissue concentrations. The pharmacokinetic parameter input values for the model were calculated to give the best fit to reported/measured blood substrate concentrations in rats. The maximum concentrations and areas under the concentration versus time curves in plasma, liver, and kidney extrapolated using PBPK models for perï¬uorobutane sulfonic acid, perï¬uorohexane sulfonic acid, and perï¬uorooctane sulfonic acid were consistent with the reported mean values in rats. Using the rat models and scaled-up human PBPK models, some accumulation of perï¬uorooctane sulfonic acid in plasma and liver was seen after repeated doses. The reported 50th and 95th percentile concentrations of perï¬uorooctane sulfonic acid in human blood (0.0048 and 0.0183 ng/mL, respectively) in the general population underwent reverse dosimetry analysis using our PBPK models. These human blood concentrations potentially imply exposures of 0.041 and 0.16 µg/kg/day, respectively, for 90 days, values that are roughly similar to the reference dose (0.02 µg/kg/day) with an uncertainty factor of 30. These results indicate the relatively good estimates for tissue and blood exposures of chemical substrates after oral doses generated using the latest PBPK models.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alkanesulfonic Acids
/
Fluorocarbons
/
Kidney
/
Liver
/
Models, Biological
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Toxicol Sci
Year:
2020
Document type:
Article