Pharmacokinetic scaling of bisphenol A by species-invariant time methods.

1. The study was performed to predict the pharmacokinetic disposition of bisphenol A in humans using simple allometry and several species-invariant time methods based on animal data. Bisphenol A was injected intravenously to mouse, rat, rabbit and dog (1-2 mg kg(-1) doses). 2. The obtained serum concentration-time profiles were best described by bi-exponential equations in all these animal species, with the mean Cl, V(ss) and t(1/2) of 0.3 l h(-1), 0.1 litres and 39.9 min in mouse, 1.9 l h(-1), 1.3 litres and 37.6 min in rat, 12.6 l h(-1), 7.1 litres and 40.8 min in rabbit, and 27.1 l h(-1), 20.0 litres and 43.7 min in dog, respectively. 3. The human pharmacokinetic parameters of Cl, V(ss) and t(1/2) were predicted by simple allometry as well as by normalization according to species-invariant times of kallynochrons, apolysichrons and dienetichrons. 4. The simple allometric scaling and different time transformation methods predicted the human Cl, V(ss) and t(1/2) ranging from 46.0 to 127.1 l h(-1), 125.3 to 229.7 litres and 43.6 to 196.2 min, respectively. Species-invariant time transformations showed that all animal data from the four species were superimposable. These preliminary parameter values may be useful in interpreting toxicity data in humans on environmental exposure to bisphenol A.