Assessment of Pergafast 201 absorption and metabolism in viable human skin: A comparative study with bisphenol A and bisphenol S

• Absorption of PF201 by viable human skin is significantly lower compared to BPA. • PF201 persists in human skin 24 h after exposure, almost entirely as parent compound. • Most PF201, regardless of the dose, is located in the deepest stratum corneum layers. • PF201 absorbed dose and dermal delivery are constant over a large range of doses. • Kinetic studies lead to classify PF201 as a “very slow” skin penetrant. For 50 years, bisphenol A (BPA) has been extensively used as a colour developer in thermal printing papers. The European Union and several other countries have drastically restricted BPA’s use in thermal paper, due to its endocrine-disrupting properties. Consequently, bisphenol S (BPS) and Pergafast 201 (PF201) are increasingly used as substitutes, despite their percutaneous absorption remains poorly documented. We conducted an ex vivo study to achieve a comparative assessment of the skin absorption and metabolism of BPA, BPS and PF201. Tritium-labelled compounds were topically applied to viable human skin explants mounted on static Franz diffusion cells, providing complete mass-balance data compliant with OECD recommendations (n° 428, 28, 156). Absorbed doses were 5.1 ± 2.4 % for BPA, and below 1 % for BPS and PF201 (BPA > BPS ∼ PF201). Dermal delivery reached 16.1 ± 3.5 % for BPA, 8.7 ± 4.2 % for BPS and 3.5 ± 1.3 % for PF201 (BPA > BPS > PF201). Additional experiments were conducted for PF201 at five different doses (7.8–638.5 ng/cm 2 ) to determine skin permeation parameters. PF201′s absorbed dose and dermal delivery remained constant, its permeability coefficient was found to range between 0.63 and 2.0·10⁻⁶ cm/h, and its flux between 0.75 and 84.0 ng/cm 2 /h. No PF201 metabolism or degradation were observed in skin explants. Our results demonstrate that despite limited absorption, PF201 remains in the skin after 24 h, suggesting prolonged bioavailability. This study closes major knowledge gaps related to the absorption and metabolism of PF201 through viable human skin and provides useful data for improved risk assessment.