In vivo and ex vivo percutaneous absorption of [14C]-bisphenol A in rats: a possible extrapolation to human absorption?

Abstract

Bisphenol A (BPA) is a monomer used mainly in the synthesis of polycarbonates and epoxy resins. Percutaneous absorption is the second source of exposure, after inhalation, in the work environment. However, studies on this route of absorption are lacking or incomplete. In this study, percutaneous BPA absorption was measured in vivo and ex vivo in the rat, and ex vivo in humans. An approximately 12-fold difference in permeability between rat skin and human skin was found, with permeability being higher in the rat. In addition, inter- and intra-individual variability of up to tenfold was observed in humans. No accumulation of BPA in the skin was found during exposure. The skin clearance rate following exposure was estimated at 0.4 μg/cm²/h. Ex vivo and in vivo percutaneous absorption fluxes of BPA in the rat were in the same range (about 2.0 μg/cm²/h), suggesting that extrapolation to the in vivo situation in humans may be possible. The European tolerable daily intake (TDI) of BPA is 50 μg/kg body weight. However, many research projects have highlighted the significant effects of BPA in rodents at doses lower than 10 μg/kg/day. A 1-h occupational exposure over 2,000 cm² (forearms and hands) may lead to a BPA absorption of 4 μg/kg/day. This is 8% of the European TDI and is very close to the value at which effects have been observed in animals. This absorption must therefore be taken into account when evaluating risks of BPA exposure, at least until more relevant results on the toxicity of BPA in humans are available.

Perinatal bisphenol A exposures increase production of pro-inflammatory mediators in bone marrow-derived mast cells of adult mice

“…BPA routinely leaches into the food and water supply from consumer products including food and liquid storage containers, baby bottles, and linings of aluminum cans. While the main route of human exposure to BPA is through indigestion of contaminated food and water, possible exposure through inhalation and dermal routes may exist due to the presence of BPA in dental sealants and thermal paper (Vandenberg et al, 2007; Marquet et al, 2011). Human exposure to BPA is widespread with National Health and Nutrition Examination Survey (NHANES) data revealing detectable amounts of BPA in the urine of 95% of study participants (Calafat et al, 2005; Vandenberg et al, 2012).…”

The safety of the use of bisphenol A in medical devices

“…Ex vivo and in vivo percutaneous absorption fluxes of BPA after 24 hour exposure in the rat were in the same range (1.48 and 2.2 μg/cm 2 /h) (Marquet et al, 2011). They found approximately 12-fold lower flux (0.12 ± 0.09 µg/cm 2 /h) in human skin samples treated in vitro in the same conditions ( 14 C-BPA in acetone: 4 mg BPA/mL; 50 and 200µl/cm 2 for human), however, inter-and intra-individual variability of up to tenfold was observed.…”

“…The half-life of BPA after dermal absorption was estimated to be 28 h (compared with the half-life of 10 h measured after i.v. administration in the same study) (Marquet et al, 2011). When dermal absorption was measured ex vivo in human and rat skin at the studied dose, BPA was not cytotoxic for the skin and did not affect the skin's integrity.…”

Bisphenol A exposure pathways in early childhood: Reviewing the need for improved risk assessment models

“…Studies of human skin explants to assess skin penetration of BPA have observed that~9.5-33% of the applied dose is transferred through the skin as free BPA within 24-48 h of topical application. [84][85][86] However, it is uncertain how these finding relate to living tissue, in particular in young children. The skin of human neonates is immature at birth and takes at least 3-5 months to attain similar barrier properties as those of adults.…”