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Pharmacokinetic profiles of perfluorobutane sulfonate and activation of hepatic genes in mice
Rumpler, J., K. Das, C. Wood, C. Lau, M. Strynar, AND J. Wambaugh. Pharmacokinetic profiles of perfluorobutane sulfonate and activation of hepatic genes in mice. Society of Toxicology Meeting, New Orleans, LA, March 13 - 17, 2016.
This abstract will be presented at the Society of Toxicology Meeting, March 13-17, 2016, New Orleans, LA
Polyfluoroalkyl substances (PFAS) are organic chemicals with wide industrial and consumer uses. They are found ubiquitously at low levels in the environment and detectable in humans and wildlife. Perfluorobutane Sulfonate (PFBS) is a short-chained PFAS used to replace perfluorooctane sulfonate in commerce. In general,the rate of clearance for the short-chained PFAS are faster than the long-chained congeners. This study evaluated the pharmacokinetic properties of PFBS and its hepatic transcriptional responses in CD-1 mice. Males and females were given PFBS by oral gavage at 30 or 300 mg/kg; controls received water vehicle. Trunk blood was collected at 0.5, 1,2, 4, 8,16,24 and 48 h and urine at 24 h; liver and kidney wereharvested at 24 h. Serum,urine and tissue concentrations of PFBS were determined by HPLC MS-MS. Expression of hepatic nuclear receptor target genes was determined by RT-PCR. Half-life of PFBS was estimated at 4.6 h in the males and 2.5 h in the females. Volume of distribution was similar between the two sexes (0.36-0.38 L/kg). Rate of PFBS clearance was linear with exposure doses. Within 24 h, >95% of serum PFBS was excreted into urine. PFBS was not accumulated in liver or kidney, as tissue levels of the chemical did not exceed those of serum. At 24 h after administration of 300 mg/kg dose, PFBS elevated expression of several hepatic genes targeted for PPARa and PPARy, but not for AhR or CAR, with responses more robust in males than females. Little to no transcriptional response was seen with the low dose. The short serum half lives of PFBS in the mouse were similar to those reported for the rat. Although PFBS did not accumulate appreciably in the liver, activation of hepatic nuclear receptors may represent one accumulate appreciably in the liver, activation of hepatic nuclear receptors may represent one of the acute responses to the chemical at a high dose. This abstract does not necessarily reflect U.S. EPA policy.