Toxicokinetics and bioavailability of sulfolane, a ground water contaminant, following oral and intravenous administration in rodents
A dose, species, and sex comparison
Waidyanatha, S., Black, S. R., Fennell, T. R., Watson, S. L., Patel, P. R., Cooper, S. D., Blake, J., Robinson, V. G., Fernando, R. A., & Blystone, C. R. (2019). Toxicokinetics and bioavailability of sulfolane, a ground water contaminant, following oral and intravenous administration in rodents: A dose, species, and sex comparison. Toxicology and Applied Pharmacology, 379, Article 114690. Advance online publication. https://doi.org/10.1016/j.taap.2019.114690
Sulfolane is a ground water contaminant near refinery sites. The objective of this work was to investigate the toxicokinetics and bioavailability of sulfolane in male and female Harlan Hsd:Sprague Dawley® SD® rats and B6C3F1/N mice following a single oral administration of 10, 30, or 100 mg/kg. Sulfolane was rapidly absorbed in rats with the maximum plasma concentration, Cmax, reached at ≤1.47 h. Although Cmax increased proportionally to the dose, the half-life of elimination increased with the dose and the area under the concentration versus time curve (AUC) increased more than proportionally to the dose. In male and female rats, plasma elimination half-life increased with the dose from 1.97 to 6.33 h. Absorption of sulfolane in mice following oral administration was more rapid than in rats with Cmax reached at ≤0.55 h. In addition, mice had a shorter half-life (≤ 1.25 h) and a lower AUC than rats. In male and female mice, both Cmax and AUC increased more than proportionally to the dose. Bioavailability of sulfolane was higher in rats (81-83%) than mice (59-63%) at 10 mg/kg; at 30 and 100 mg/kg, bioavailability >100% in both species and sexes suggesting that the saturation of metabolism and clearance processes of sulfolane may begin at a single oral dose of ~30 mg/kg. There was no apparent sex difference in toxicokinetic parameters of sulfolane in rats and mice. These data demonstrate that sulfolane was well-absorbed following oral administration with high bioavailability in rats and mice with some species differences, but no sex difference.