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Physiologically based pharmacokinetics of 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in rats and humans.
Toxicol Appl Pharmacol. 1994 Nov; 129(1):61-79.TA

Abstract

A physiologically based pharmacokinetic model was developed to describe the disposition of 2-butoxyethanol (CAS 111-76-2) and its major metabolite, 2-butoxyacetic acid, in rats and humans. A previous human inhalation model by Johanson (Toxicol. Lett. 34, 23 (1986)) was expanded to include additional routes of exposure, physiological descriptions for rats, competing pathways for metabolism of 2-butoxyethanol, and measured partition coefficients for 2-butoxyethanol and 2-butoxyacetic acid. Simulations were compared to data gathered from rats following either intravenous infusion or oral or inhalation exposure and from humans following either inhalation or dermal exposure to 2-butoxyethanol. It was necessary to add equations for both protein binding of 2-butoxyacetic acid in blood and saturable elimination of 2-butoxyacetic acid by the kidneys to consistently describe the data. While the model predicted that rats metabolize 2-butoxyethanol and eliminate the acid metabolite faster per kilogram body weight than humans, the balance of these two processes in addition to physiological differences between species resulted in higher predicted peak blood concentrations as well as total areas under the blood concentration time curves for 2-butoxyacetic acid for rats versus humans. These species differences in kinetics coupled with the fact that human blood is significantly less susceptible than rat blood to the hemolytic effects of 2-butoxyacetic acid indicate that there is considerably less risk for hemolysis in humans as a result of exposure to 2-butoxyethanol than would have been predicted solely from standard toxicity studies with rats.

Authors+Show Affiliations

Toxicology Research Laboratory, Dow Chemical Company, Midland, Michigan 48674.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

7974497

Citation

Corley, R A., et al. "Physiologically Based Pharmacokinetics of 2-butoxyethanol and Its Major Metabolite, 2-butoxyacetic Acid, in Rats and Humans." Toxicology and Applied Pharmacology, vol. 129, no. 1, 1994, pp. 61-79.
Corley RA, Bormett GA, Ghanayem BI. Physiologically based pharmacokinetics of 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in rats and humans. Toxicol Appl Pharmacol. 1994;129(1):61-79.
Corley, R. A., Bormett, G. A., & Ghanayem, B. I. (1994). Physiologically based pharmacokinetics of 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in rats and humans. Toxicology and Applied Pharmacology, 129(1), 61-79.
Corley RA, Bormett GA, Ghanayem BI. Physiologically Based Pharmacokinetics of 2-butoxyethanol and Its Major Metabolite, 2-butoxyacetic Acid, in Rats and Humans. Toxicol Appl Pharmacol. 1994;129(1):61-79. PubMed PMID: 7974497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physiologically based pharmacokinetics of 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in rats and humans. AU - Corley,R A, AU - Bormett,G A, AU - Ghanayem,B I, PY - 1994/11/1/pubmed PY - 1994/11/1/medline PY - 1994/11/1/entrez SP - 61 EP - 79 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 129 IS - 1 N2 - A physiologically based pharmacokinetic model was developed to describe the disposition of 2-butoxyethanol (CAS 111-76-2) and its major metabolite, 2-butoxyacetic acid, in rats and humans. A previous human inhalation model by Johanson (Toxicol. Lett. 34, 23 (1986)) was expanded to include additional routes of exposure, physiological descriptions for rats, competing pathways for metabolism of 2-butoxyethanol, and measured partition coefficients for 2-butoxyethanol and 2-butoxyacetic acid. Simulations were compared to data gathered from rats following either intravenous infusion or oral or inhalation exposure and from humans following either inhalation or dermal exposure to 2-butoxyethanol. It was necessary to add equations for both protein binding of 2-butoxyacetic acid in blood and saturable elimination of 2-butoxyacetic acid by the kidneys to consistently describe the data. While the model predicted that rats metabolize 2-butoxyethanol and eliminate the acid metabolite faster per kilogram body weight than humans, the balance of these two processes in addition to physiological differences between species resulted in higher predicted peak blood concentrations as well as total areas under the blood concentration time curves for 2-butoxyacetic acid for rats versus humans. These species differences in kinetics coupled with the fact that human blood is significantly less susceptible than rat blood to the hemolytic effects of 2-butoxyacetic acid indicate that there is considerably less risk for hemolysis in humans as a result of exposure to 2-butoxyethanol than would have been predicted solely from standard toxicity studies with rats. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/7974497/Physiologically_based_pharmacokinetics_of_2_butoxyethanol_and_its_major_metabolite_2_butoxyacetic_acid_in_rats_and_humans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(84)71229-4 DB - PRIME DP - Unbound Medicine ER -