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A comparison of physiologically based pharmacokinetic model predictions and experimental data for inhaled ethanol in male and female B6C3F1 mice, F344 rats, and humans.
Toxicol Appl Pharmacol. 1997 Jul; 145(1):147-57.TA

Abstract

Ethanol is added to unleaded gasoline as an oxygenate to decrease carbon monoxide automobile emissions. This introduces inhalation as a new possible route of environmental exposure to humans. Knowledge of the pharmacokinetics of inhaled ethanol is critical for adequately assessing the dosimetry of this chemical in humans. The purpose of this study was to characterize the pharmacokinetics of inhaled ethanol in male and female B6C3F1 mice and F344 rats and to develop a physiologically based pharmacokinetic (PBPK) model for inhaled ethanol in mice, rats, and humans. During exposure to 600 ppm for 6 hr, steady-state blood ethanol concentrations (BEC) were reached within 30 min in rats and within 5 min in mice. Maximum BEC ranged from 71 microM in rats to 105 microM in mice. Exposure to 200 ppm ethanol for 30 min resulted in peak BEC of approximately 25 microM in mice and approximately 15 microM in rats. Peak BEC of about 10 microM were measured following exposure to 50 ppm in female rats and male and female mice, while blood ethanol was undetectable in male rats. No sex-dependent differences in peak BEC at any exposure level were observed. Species-dependent differences were found following exposure to 200 and 600 ppm. A blood flow limited PBPK model for ethanol inhalation was developed in mice, rats, and humans which accounted for a fractional absorption of ethanol. Compartments for the model included the pulmonary blood and air, brain, liver, fat, and rapidly perfused and slowly perfused tissues. The PBPK model accurately simulated BEC in rats and mice at all exposure levels, as well as BEC reported in human males in previously published studies. Simulated peak BEC in human males following exposure to 50 and 600 ppm ranged from 7 to 23 microM and 86 and 293 microM, respectively. These results illustrate that inhalation of ethanol at or above the concentrations expected to occur upon refueling results in minimal BEC and are unlikely to result in toxicity.

Authors+Show Affiliations

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

9221833

Citation

Pastino, G M., et al. "A Comparison of Physiologically Based Pharmacokinetic Model Predictions and Experimental Data for Inhaled Ethanol in Male and Female B6C3F1 Mice, F344 Rats, and Humans." Toxicology and Applied Pharmacology, vol. 145, no. 1, 1997, pp. 147-57.
Pastino GM, Asgharian B, Roberts K, et al. A comparison of physiologically based pharmacokinetic model predictions and experimental data for inhaled ethanol in male and female B6C3F1 mice, F344 rats, and humans. Toxicol Appl Pharmacol. 1997;145(1):147-57.
Pastino, G. M., Asgharian, B., Roberts, K., Medinsky, M. A., & Bond, J. A. (1997). A comparison of physiologically based pharmacokinetic model predictions and experimental data for inhaled ethanol in male and female B6C3F1 mice, F344 rats, and humans. Toxicology and Applied Pharmacology, 145(1), 147-57.
Pastino GM, et al. A Comparison of Physiologically Based Pharmacokinetic Model Predictions and Experimental Data for Inhaled Ethanol in Male and Female B6C3F1 Mice, F344 Rats, and Humans. Toxicol Appl Pharmacol. 1997;145(1):147-57. PubMed PMID: 9221833.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A comparison of physiologically based pharmacokinetic model predictions and experimental data for inhaled ethanol in male and female B6C3F1 mice, F344 rats, and humans. AU - Pastino,G M, AU - Asgharian,B, AU - Roberts,K, AU - Medinsky,M A, AU - Bond,J A, PY - 1997/7/1/pubmed PY - 1997/7/1/medline PY - 1997/7/1/entrez SP - 147 EP - 57 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 145 IS - 1 N2 - Ethanol is added to unleaded gasoline as an oxygenate to decrease carbon monoxide automobile emissions. This introduces inhalation as a new possible route of environmental exposure to humans. Knowledge of the pharmacokinetics of inhaled ethanol is critical for adequately assessing the dosimetry of this chemical in humans. The purpose of this study was to characterize the pharmacokinetics of inhaled ethanol in male and female B6C3F1 mice and F344 rats and to develop a physiologically based pharmacokinetic (PBPK) model for inhaled ethanol in mice, rats, and humans. During exposure to 600 ppm for 6 hr, steady-state blood ethanol concentrations (BEC) were reached within 30 min in rats and within 5 min in mice. Maximum BEC ranged from 71 microM in rats to 105 microM in mice. Exposure to 200 ppm ethanol for 30 min resulted in peak BEC of approximately 25 microM in mice and approximately 15 microM in rats. Peak BEC of about 10 microM were measured following exposure to 50 ppm in female rats and male and female mice, while blood ethanol was undetectable in male rats. No sex-dependent differences in peak BEC at any exposure level were observed. Species-dependent differences were found following exposure to 200 and 600 ppm. A blood flow limited PBPK model for ethanol inhalation was developed in mice, rats, and humans which accounted for a fractional absorption of ethanol. Compartments for the model included the pulmonary blood and air, brain, liver, fat, and rapidly perfused and slowly perfused tissues. The PBPK model accurately simulated BEC in rats and mice at all exposure levels, as well as BEC reported in human males in previously published studies. Simulated peak BEC in human males following exposure to 50 and 600 ppm ranged from 7 to 23 microM and 86 and 293 microM, respectively. These results illustrate that inhalation of ethanol at or above the concentrations expected to occur upon refueling results in minimal BEC and are unlikely to result in toxicity. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/9221833/A_comparison_of_physiologically_based_pharmacokinetic_model_predictions_and_experimental_data_for_inhaled_ethanol_in_male_and_female_B6C3F1_mice_F344_rats_and_humans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(97)98161-8 DB - PRIME DP - Unbound Medicine ER -