Bisphenol A: An endocrine disruptor present in sales receipts

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Bisphenol A: An endocrine disruptor present in sales receipts ISSA/INRS International Symposium Paris, 2 nd June 2016

Bisphenol A exposure Plastic polycarbonate Epoxy resin Thermal paper 2

Thermal paper Dye Color developer Thermal reactive layer Pre-coat Sensitizer Base paper 3

How much BPA is absorbed by the skin? Analysis performed according to OECD TG428 (in vitro) with frozen skin (200 µm thickness) Cumulative amount of BPA recovered in the receptor fluid [µg/cm2) ± SD 0,25 0,20 0,15 0,10 0,05 0,00 Absorption kinetics Dose applied: 1.82 µg/cm 2 0 5 10 15 20 25 Time (h) Permeation rate (1-4h) (J) 0.022 (± 0.011) µg/cm 2 /h Permeation constant (K p ) 1.14 (± 0.57) x 10-4 cm/h Lag time (T lag ) 1h Demierre et al (2012) Toxicol Letters 4

BPA absorption into viable skin (Preliminary results) Similar analysis performed with viable skin (800 µm thickness) from plastic surgery Absorption kinetics Mean cumulative amount of BPA recovered in the receptor fluid [µg/cm2) ± SD 5 4 3 2 1 0 Dose applied: 25 µg/cm 2 0 5 10 15 20 25 Time (h) Permeation rate (J) 0.23 (±0.12) µg/cm 2 /h Permeation constant (K p ) 9.2 (± 4.95) x 10-4 cm/h Lag time (T lag ) 8.5 (± 0.2) h Results in similar range Variation due to different skin (frozen vs viable), skin thickness, dose and volume applied 5

First conclusions Thermal papers are a BPA source of exposure Sales workers are particularly exposed Dermal absorption rate is around 10% Ban on BPA in thermal paper in Japan (2001), Taiwan (2011), Connecticut USA (2015) Process currently ongoing in EU Another color developer is still needed 6

Market analysis in Switzerland Analysis of 124 thermal papers (cashier receipts, ATM receipts, parking tickets, bus tickets ) between Sep 2013 and Jan 2014 11 Bisphenol S 4 9 Bisphenol A D-8 100 Pergafast 201 Goldinger et al (2015) Regul Toxicol Pharmacol 7

What are these alternatives? Bisphenol S Endocrine disruptor (weak estrogenic) More persistent than BPA in the environment D-8 (also known as Wincon-8 or BPSIP) Few data available Limited information on endocrine disruption Highly toxic for the environment Pergafast 201 Few data available Limited information on endocrine disruption Very persistent and highly toxic for the environment US EPA DfE Report: Bisphenol A alternatives in thermal paper (2014) 8

ED activity of BPA and its alternatives Steroidogenesis Assay (OECD TG456): In vitro evaluation of impact on production of estradiol (female hormone) and testosterone (male hormone) Goldinger et al (2015) Regul Toxicol Pharmacol 9

ED activity of BPA and its alternatives Estradiol Testosterone Bisphenol A Inducer of estradiol production Inhibitor of testosterone production Bisphenol S No effect on estradiol production Inhibitor of testosterone production Goldinger et al (2015) Regul Toxicol Pharmacol 10

ED activity of BPA and its alternatives Estradiol Testosterone D-8 (WinCon-8) Pergafast 201 No effect on estradiol nor testosterone production Goldinger et al (2015) Regul Toxicol Pharmacol 11

Conclusions Replacement of BPA already ongoing Confirmation of endocrine activity of BPA and BPS No significant effect on estradiol or testosterone production has been shown for Pergafast 201 and D-8 Non-Bisphenol alternatives look safer than BPA But further studies required to affirm that they are really safe 12

Blick, 24.9.2013 Finally! Soon will be all receipts nontoxic Blick, 24.9.2013 13

Thanks to Institut universitaire romand de Santé au Travail Elena Reale Aurélie Berthet Nancy Hopf Federal Food Safety and Veterinary Office Otmar Zoller Hans Reinhard Heinz Rupp Roxane Magnin Federal Office of Public Health Daniela Goldinger Martine Bourqui-Pittet 14