In vitro skin absorption of butyl methoxydibenzoylmethane determined in human epidermis and in a reconstituted human epidermis model

Butyl methoxydibenzoylmethane (BM-DBM) is a UVA filter widely used in sun protection products, and listed in the EU Cosmetics Directive as safe if used up to 5%. In vivo studies on the phototoxic potential of BM-DBM in animals and humans showed absence of any phototoxic potential of BM-DBM. However, studies according to OECD TG 432 in the in vitro 3T3 NRU phototoxicity test revealed a phototoxic potential at low concentrations of 10 mg/mL. Additional in vitro phototoxicity studies performed with the reconstituted human epidermis model (EpiDerm, MatTek, Ashland, USA), confirmed absence of any phototoxicity at topical exposure. Because published data obtained in humans suggest negligible skin absorption of BM-DBM as possible reason for the absence of phototoxicity in vivo , our study aimed at a comparison of in vitro skin absorption of BM-DBM in human heat separated epidermis and in the epidermis model EpiDerm.Identical experimental designs were used for human epidermis and EpiDerm: finite dose, static Franz diffusion cell technique, and a sampling period of up to 30 hrs. To check validity of each experiment, concurrent parallel experiments were performed with caffeine, a reference standard recommended by OECD. With 3-4 replicate Franz cells, both, BM-DBM and caffeine were tested four times on samples from different human donors, or different batches of EpiDerm, and samples were analysed with high performance liquid chromatography.For BM-DBM, identical results were obtained with human epidermis and EpiDerm: BM-DBM was not detected in the acceptor medium up to 30 hrs, suggesting that skin absorption is indeed negligible also under in vitro conditions. In conclusion, the barrier of EpiDerm is sufficient to obtain a correct negative result in the in vitro EpiDerm phototoxicity test.