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Measurement of the penetration of 56 cosmetic relevant chemicals into and through human skin using a standardized protocol.

ABSTRACT: OECD test guideline 428 compliant protocol using human skin was used to test the penetration of 56 cosmetic-relevant chemicals. The penetration of finite doses (10 ?L/cm2 ) of chemicals was measured over 24 hours. The dermal delivery (DD) (amount in the epidermis, dermis and receptor fluid [RF]) ranged between 0.03 ± 0.02 and 72.61 ± 8.89 ?g/cm2 . The DD of seven chemicals was comparable with in vivo values. The DD was mainly accounted for by the amount in the RF, although there were some exceptions, particularly of low DD chemicals. While there was some variability due to cell outliers and donor variation, the overall reproducibility was very good. As six chemicals had to be applied in 100% ethanol due to low aqueous solubility, we compared the penetration of four chemicals with similar physicochemical properties applied in ethanol and phosphate-buffered saline. Of these, the DD of hydrocortisone was the same in both solvents, while the DD of propylparaben, geraniol and benzophenone was lower in ethanol. Some chemicals displayed an infinite dose kinetic profile; whereas, the cumulative absorption of others into the RF reflected the finite dosing profile, possibly due to chemical volatility, total absorption, chemical precipitation through vehicle evaporation or protein binding (or a combination of these). These investigations provide a substantial and consistent set of skin penetration data that can help improve the understanding of skin penetration, as well as improve the prediction capacity of in silico skin penetration models.

SUBMITTER: Hewitt NJ

PROVIDER: S-EPMC7027575 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Measurement of the penetration of 56 cosmetic relevant chemicals into and through human skin using a standardized protocol.

Hewitt Nicola J NJ Grégoire Sébastien S Cubberley Richard R Duplan Hélène H Eilstein Joan J Ellison Corie C Lester Cathy C Fabian Eric E Fernandez Julien J Géniès Camille C Jacques-Jamin Carine C Klaric Martina M Rothe Helga H Sorrell Ian I Lange Daniela D Schepky Andreas A

Journal of applied toxicology : JAT 20191222 3

OECD test guideline 428 compliant protocol using human skin was used to test the penetration of 56 cosmetic-relevant chemicals. The penetration of finite doses (10 μL/cm<sup>2</sup> ) of chemicals was measured over 24 hours. The dermal delivery (DD) (amount in the epidermis, dermis and receptor fluid [RF]) ranged between 0.03 ± 0.02 and 72.61 ± 8.89 μg/cm<sup>2</sup> . The DD of seven chemicals was comparable with in vivo values. The DD was mainly accounted for by the amount in the RF, although ...[more]

PMID: 31867769

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Project description:BackgroundThe filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene FLG may increase dermal absorption of chemicals.ObjectiveThe objective of the study was to clarify if dermal absorption of chemicals differs depending on FLG genotype.MethodWe performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations (FLG null) in 432 volunteers from the general population in southern Sweden and identified 28 FLG null carriers. In a dermal exposure experiment, we exposed 23 FLG null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects' urine over 48 h following exposure. Furthermore, we used long-range PCR to measure FLG repeat copy number variants (CNV), and we performed population toxicokinetic analysis.ResultsLag times for the uptake and dermal absorption rate of the chemicals differed significantly between FLG null and wt carriers with low (20-22 repeats) and high FLG CNV (23-24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve (AUC(0-40h)) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUC(0-40h)) for pyrimethanil than wt carriers with low and high CNV, respectively.ConclusionWe conclude that FLG genotype influences the dermal absorption of some common chemicals. Overall, FLG null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low FLG CNV resulted in increased dermal absorption of chemicals. https://doi.org/10.1289/EHP7310.

Dataset Information

Measurement of the penetration of 56 cosmetic relevant chemicals into and through human skin using a standardized protocol.

Publications

Measurement of the penetration of 56 cosmetic relevant chemicals into and through human skin using a standardized protocol.

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