Dermal absorption, skin retention and urinary elimination of bisphenol S in rats: in vitro, in vivo and intravenous comparative analysis

Bisphenol S (BPS) is widely used as a substitute for bisphenol A (BPA) in industrial applications, raising concerns about its dermal absorption and potential systemic toxicity. This study investigated the toxicokinetics of BPS following dermal and intravenous (IV) exposure in rats, with complementary in vitro dermal absorption studies. A single dose of 20 g/cm (50 L/cm ) of [ C]-BPS was applied in vitro and in vivo on rat skin, while IV administration was conducted at 0.05, 0.5, or 5 mg/kg.<br/>
In vitro percutaneous absorption varied by solvent, with the highest uptake in artificial sebum (~5,000 ng/cm over 40 h). Most absorbed BPS remained unmetabolized (78 85%), with a significant skin reservoir (25 60% of the applied dose). In vivo dermal exposure resulted in low systemic absorption (~10%), with BPS persisting in the skin beyond 72 h. Urinary elimination was the primary excretion route (60 70%), mainly as BPS-glucuronide. IV administration confirmed rapid metabolism, with BPS-G dominating plasma and urinary profiles.<br/>
Using the Triple-Pack approach, human in vivo dermal absorption was estimated at 1.4% of the applied dose, integrating in vitro and in vivo rat data with prior human in vitro findings. These results highlight prolonged skin retention and limited systemic absorption of BPS, raising concerns about chronic low-level exposure via dermal contact. Further studies are needed to refine risk assessments, particularly to enhance toxicokinetic modeling and forward dosimetry for improved exposure prediction and regulatory decision-making.