Linking existing in vitro dermal absorption data to physicochemical properties: Contribution to the design of a weight-of-evidence approach for the safety evaluation of cosmetic ingredients with low dermal bioavailability.

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Ates, G ; Steinmetz, FP ; Doktorova, TY ; Madden, JC ; Rogiers, V

To characterize the risk of cosmetic ingredients when threshold toxicity is assumed, often the "margin of safety" (MoS) is calculated. This uncertainty factor is based on the systemic no observable (adverse) effect level (NO(A)EL) which can be derived from in vivo repeated dose toxicity studies. As in vivo studies for the purpose of the cosmetic legislation are no longer allowed in Europe and a validated in vitro alternative is not yet available, it is no longer possible to derive a NO(A)EL value for a new cosmetic ingredient. Alternatively, cosmetic ingredients with a low dermal bioavailability might not need repeated dose data, as internal exposure will be minimal and systemic toxicity might not be an issue. This study shows the possibility of identifying compounds suspected to have a low dermal bioavailability based on their physicochemical properties (molecular weight, melting point, topological polar surface area and log P) and their in vitro dermal absorption data. Although performed on a limited number of compounds, the study suggests a strategic opportunity to support the safety assessor's reasoning to omit a MoS calculation and to focus more on local toxicity and mutagenicity/genotoxicity for ingredients for which limited systemic exposure is to be expected.
  • References (2)

    45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 Magnusson BM, Anissimov YG, Cross SE, Roberts MS. Molecular size as the main determinant of solute maximum flux across the skin. Journal of Investigative Dermatology 2004; 122(4):993-9. DOI: 10.1111/j.0022-202X.2004.22413.x Moda TL, Montanari CA, Andricopulo AD. Hologram QSAR model for the prediction of human oral bioavailability. Bioorganic and Medicinal Chemistry 2007; 15(24): 7738-45. DOI: 10.1016/j.bmc.2007.08.060 Newby D, Freitas AA, Ghafourian T. Decision trees to characterise the roles of permeability and solubility on the prediction of oral absorption. European Journal of Medicinal Chemistry 2015; 90:751-65. DOI: 10.1016/j.ejmech.2014.12.006 Partosch F, Mielke H, Stahlmann R, Kleuser B, Barlow S, Gundert-Remy U. Internal threshold of toxicological concern values: enabling route-to-route extrapolation. Archives of Toxicology 2015; 89:941-48. DOI: 10.1007/s00204-014-1287-6 Potts RO, Guy RH. Predicting skin permeability. Pharmaceutical Research 1992; 9:663-9.

    Pugh WJ, Degim IT, Hadgraft J. Epidermal permeability-penetrant structure relationships: 4, QSAR of permeant diffusion across human stratum corneum in terms of molecular weight, H-bonding and electronic charge. International Journal of Pharmaceutics 2000; 197(1-2):203-11.

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