Systemic exposure to parabens: Pharmacokinetics, tissue distribution, excretion balance and plasma metabolites of [14C]-methyl-, propyl- and butylparaben in rats after oral, topical or subcutaneous administration

Parabens (PB) are preservatives used in food, drugs and personal care products preventing microbial and fungal contamination. We investigated ADME profiles of [C-14]-methyl-, propyl- or butylparaben (MP, PP, BP) following single oral, dermal or subcutaneous (BP) doses at 100 mg/kg to Sprague-Dawley rats. Plasma C-max and AUC values after oral or subcutaneous doses were 4- to 10-fold higher relative to respective values after dermal administration. t(max) ranged from 0.5, 2 or 8 h after oral, subcutaneous or dermal administration, respectively. MP produced higher blood C-max and AUC levels relative to those after PP or BP. Following oral or subcutaneous administration, urinary excretion was predominant (>70%, mainly during the first 24 h), less than 4% were eliminated in the feces, 2% were retained in the tissues and carcasses. Following dermal application, >50% of the dose was unabsorbed, 14-27% or <2% were respectively excreted in the urine or feces, respectively. Overall, parabens were well absorbed after oral and subcutaneous, and partially absorbed after dermal administration. All administration routes produced a single peak in the plasma, corresponding to that of para-hydroxybenzoic acid (PHBA) suggesting that PB produce no significant systemic exposure of mammalian organisms after oral, topical or subcutaneous administration. (C) 2012 Elsevier Ltd. All rights reserved.