Influence of experimental parameters on in vitro human skin permeation of Bisphenol A. (June 2021)

• Record Type: Journal Article
• Authors: Reale, E.; Berthet, A.; Wild, P.; Vernez, D.; Hopf, N.B.
• Is Part Of: Toxicology in vitro. Volume 73(2021)
• Publication Date: 2021-06
• Subjects: BPA -- Percutaneous absorption -- Human skin -- Skin thickness -- Vehicle volume -- Permeation constant; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2021.105129
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Bisphenol A (BPA) in vitro skin permeation studies have shown inconsistent results, which could be due to experimental conditions. We studied the impact of in vitro parameters on BPA skin permeation using flow-through diffusion cells with ex-vivo human skin (12 donors, 3–12 replicates). We varied skin status (viable or frozen skin) and thickness (200, 400, 800 μm), BPA concentrations (18, 250 mg/l) and vehicle volumes (10, 100 and 1000 μl/cm 2 ). These conditions led to a wide range of BPA absorption (2%–24% after 24 h exposure), peak permeation rates (J = 0.02–1.31 μg/cm 2 /h), and permeability coefficients (Kp = 1.6–5.2 × 10 −3 cm/h). This is the first time steady state conditions were reached for BPA aqueous solutions in vitro (1000 μl/cm 2 applied at concentration 250 mg/l). A reduction of the skin thickness from 800 and 400 μm to 200 μm led to a 3-fold increase of J ( P < 0.05). A reduction of the vehicle volume from 1000 to 100 led to a 2-fold decrease in J ( P > 0.05). Previously frozen skin led to a 3-fold increase in J compared to viable skin ( P < 0.001). We found that results from published studies were consistent when adjusting J according to experimental parameters. We propose appropriate J values for different exposure scenarios to calculate BPA internal exposures for use in risk assessment. Highlights: Steady-state conditions were reached with a saturated BPA solution at 1 ml/cm 2 . BPA Kp increased from 1.6 to 5.2 × 10 −3 cm/h with decreasing skin thickness. Worst-case scenario: J = 1.3 μg/cm 2 /h and Kp = 5.2 × 10 −3 cm/h for 200 μm thick skin. Different experimental conditions explain inconsistencies in published BPA results.