title: Allometric scaling for predicting human clearance of bisphenol A.
abstract: The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady state volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man.
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UMR1331 (Unité Mixe de Recherche 1331), Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France; Université de Toulouse, INPT (Institut National Polytechnique de Toulouse), ENVT (Ecole Nationale Vétérinaire de Toulouse), EIP (Ecole d'Ingénieurs de Purpan), UPS (Université Paul Sabatier), F-31076 Toulouse, France. Electronic address: s.collet@envt.fr.
authors.forename: Séverine H
authors.initials: SH
authors.lastname: Collet
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UMR1331 (Unité Mixe de Recherche 1331), Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France; Université de Toulouse, INPT (Institut National Polytechnique de Toulouse), ENVT (Ecole Nationale Vétérinaire de Toulouse), EIP (Ecole d'Ingénieurs de Purpan), UPS (Université Paul Sabatier), F-31076 Toulouse, France. Electronic address: n.hagen-picard@envt.fr.
authors.forename: Nicole
authors.initials: N
authors.lastname: Picard-Hagen
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UMR1331 (Unité Mixe de Recherche 1331), Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France; Université de Toulouse, INPT (Institut National Polytechnique de Toulouse), ENVT (Ecole Nationale Vétérinaire de Toulouse), EIP (Ecole d'Ingénieurs de Purpan), UPS (Université Paul Sabatier), F-31076 Toulouse, France. Electronic address: m.lacroix@envt.fr.
authors.forename: Marlène Z
authors.initials: MZ
authors.lastname: Lacroix
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UMR1331 (Unité Mixe de Recherche 1331), Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France; Université de Toulouse, INPT (Institut National Polytechnique de Toulouse), ENVT (Ecole Nationale Vétérinaire de Toulouse), EIP (Ecole d'Ingénieurs de Purpan), UPS (Université Paul Sabatier), F-31076 Toulouse, France. Electronic address: s.puel@envt.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Puel
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UMR1331 (Unité Mixe de Recherche 1331), Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France; Université de Toulouse, INPT (Institut National Polytechnique de Toulouse), ENVT (Ecole Nationale Vétérinaire de Toulouse), EIP (Ecole d'Ingénieurs de Purpan), UPS (Université Paul Sabatier), F-31076 Toulouse, France. Electronic address: c.viguie@envt.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Viguié
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UMR1331 (Unité Mixe de Recherche 1331), Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France; Université de Toulouse, INPT (Institut National Polytechnique de Toulouse), ENVT (Ecole Nationale Vétérinaire de Toulouse), EIP (Ecole d'Ingénieurs de Purpan), UPS (Université Paul Sabatier), F-31076 Toulouse, France. Electronic address: a.bousquet-Melou@envt.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Bousquet-Melou
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UMR1331 (Unité Mixe de Recherche 1331), Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France; Université de Toulouse, INPT (Institut National Polytechnique de Toulouse), ENVT (Ecole Nationale Vétérinaire de Toulouse), EIP (Ecole d'Ingénieurs de Purpan), UPS (Université Paul Sabatier), F-31076 Toulouse, France. Electronic address: pltoutain@wanadoo.fr.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Toutain
authors.affiliation: INRA (Institut National de la Recherche Agronomique), UMR1331 (Unité Mixe de Recherche 1331), Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France; Université de Toulouse, INPT (Institut National Polytechnique de Toulouse), ENVT (Ecole Nationale Vétérinaire de Toulouse), EIP (Ecole d'Ingénieurs de Purpan), UPS (Université Paul Sabatier), F-31076 Toulouse, France. Electronic address: v.gayrard@envt.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Gayrard
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D049628:Body Size; D004285:Dogs; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D065669:Hepatobiliary Elimination; D006736:Horses; D006801:Humans; D008102:Liver Circulation; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008954:Models, Biological; D010636:Phenols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017208:Rats, Wistar; D034561:Sheep, Domestic; D013045:Species Specificity; D034421:Sus scrofa; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Allometric scaling; Bisphenol A; Pharmacokinetics; Species invariant time