Allometric scaling for predicting human clearance of bisphenol A

Toxicol Appl Pharmacol. 2015 May 1;284(3):323-9. doi: 10.1016/j.taap.2015.02.024. Epub 2015 Mar 7.

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.

Keywords: Allometric scaling; Bisphenol A; Pharmacokinetics; Species invariant time.

MeSH terms

  • Administration, Intravenous
  • Animals
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / blood
  • Benzhydryl Compounds / pharmacokinetics*
  • Body Size*
  • Dogs
  • Environmental Pollutants / administration & dosage
  • Environmental Pollutants / blood
  • Environmental Pollutants / pharmacokinetics*
  • Female
  • Half-Life
  • Hepatobiliary Elimination
  • Horses
  • Humans
  • Liver Circulation
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Models, Biological*
  • Phenols / administration & dosage
  • Phenols / blood
  • Phenols / pharmacokinetics*
  • Rats, Wistar
  • Sheep, Domestic
  • Species Specificity
  • Sus scrofa

Substances

  • Benzhydryl Compounds
  • Environmental Pollutants
  • Phenols
  • bisphenol A