Skin Absorption of Bisphenol A and Its Alternatives in Thermal Paper

Objectives: Bisphenol A (BPA) is the most used colour developer in thermal paper for cashiers receipts, labels, and tickets. BPA can migrate onto the skin and be absorbed when handling these papers. BPA is a known endocrine disruptor and is therefore being replaced in thermal paper by some alternatives such as Bisphenol S (BPS), D-8, and Pergafast 201 (R) (PF201). To our knowledge, no studies have characterized skin permeation of these BPA alternatives. Methods: We measured/characterized skin absorption for BPA, BPS, D-8, and PF201 through ex vivo human skin using flow-through diffusion cells according to OECD guideline 428. Skin samples were 7-12 per test substance from three different skin donors. Skin metabolism was studied for BPA. Dermal absorption was expressed as the amount of the BPA alternatives in the receptor fluid over applied dose in percent (%). Results: The absorbed dose after 24 h of exposure was 25% for BPA, 17% for D-8, 0.4% for BPS, and <LLOQ for PF201. The amount of BPA-glucuronide in the receptor fluid after 24 h was under the limit of quantification (LLOQ = 0.2 mu g l(-1)). Despite the 10-fold lower concentration of the aq solution applied on the skin, D-8's permeation rate J(MAX) was 5-fold higher than the one for BPS (0.032 versus 0.006 mu g cm(-2) h(-1)). Neither D-8 nor BPS permeated readily through the skin (t(lag) = 3.9 h for D-8, 6.4 h for BPS). None of PF201's skin permeation kinetic parameters could be determined because this BPA analogue was not quantifiable in the receptor fluid in our test conditions. Conclusions: Skin absorption was in decreasing order: BPA > D-8 >> BPS > PF201. These results are in agreement with their log K-ow and molecular weights. We provided here the necessary data to estimate the extent of skin absorption of BPA analogues, which is a necessary step in risk assessment, and ultimately evaluate public health risks posed by D-8, BPS, and PF201.