title: Absorption, distribution, metabolism, excretion, and kinetics of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid ammonium salt following a single dose in rat, mouse, and cynomolgus monkey.
abstract: Ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate has been developed as a processing aid used in the manufacture of fluoropolymers. The absorption, distribution, elimination, and distribution (ADME) and kinetic behavior of this substance has been evaluated in rats, mice, and cynomolgus monkeys by oral and intravenous routes of exposure and studied in both plasma and urine. The test substance is rapidly and completely absorbed in both rats and mice and both in vivo and in vitro experiments indicate that it is not metabolized. The test substance is rapidly eliminated exclusively in the urine in both rats and mice, with rats eliminating it more quickly than mice (approximately 5h elimination half-life in rats, 20 h half-life in mice). Pharmacokinetic analysis in monkeys, rats, and mice indicate rapid, biphasic elimination characterized by a very fast alpha phase and a slower beta phase. The beta phase does not contribute to potential accumulation after multiple dosing in rats or monkeys. Comparative pharmacokinetics in rats, mice, and monkeys indicates that the rat is more similar to the monkey and is therefore a more appropriate rodent model for pharmacokinetics in primates.
authors.affiliation: The Chemours Company, Wilmington, DE, USA. Electronic address: shawn.a.gannon@chemours.com.
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Gannon
authors.affiliation: E I. duPont de Nemours and Company, Haskell Global Centers for Health & Environmental Sciences, Newark, DE 19714, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Fasano
authors.affiliation: E I. DuPont de Nemours and Company, Wilmington, DE, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mawn
authors.affiliation: E I. duPont de Nemours and Company, Haskell Global Centers for Health & Environmental Sciences, Newark, DE 19714, USA.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Nabb
authors.affiliation: The Chemours Company, Wilmington, DE, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Buck
authors.affiliation: The Chemours Company, Wilmington, DE, USA.
authors.forename: L William
authors.initials: LW
authors.lastname: Buxton
authors.affiliation: The Chemours Company, Wilmington, DE, USA.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jepson
authors.affiliation: E I. duPont de Nemours and Company, Haskell Global Centers for Health & Environmental Sciences, Newark, DE 19714, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Frame
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D065569:Gastrointestinal Absorption; D006207:Half-Life; D022781:Hepatocytes / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D008657:Metabolic Clearance Rate; D008813:Mice, Inbred ICR; D008954:Models, Biological; D011422:Propionates / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D005466:Fluorocarbons; D011422:Propionates; C000611729:ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate
keywords: ADME; Fluoropolymer; Monkey; Pharmacokinetics; Rodent; Toxicokinetics