Print Email Facebook Twitter Repeated topical treatment, in contrast to single oral doses, with Vitamin A-containing preparations does not affect plasma concentrations of retinol, retinyl esters or retinoic acids in female subjects of child-bearing age Title Repeated topical treatment, in contrast to single oral doses, with Vitamin A-containing preparations does not affect plasma concentrations of retinol, retinyl esters or retinoic acids in female subjects of child-bearing age Author Nohynek, G.J. Meuling, W.J.A. Vaes, W.H.J. Lawrence, R.S. Shapiro, S. Schulte, S. Steiling, W. Bausch, J. Gerber, E. Sasa, H. Nau, H. TNO Kwaliteit van Leven Publication year 2006 Abstract Background: Vitamin A is widely used in cosmetic preparations. Given that oral Vitamin A and its metabolites present a potential reproductive risk, the present study investigated the effect of topical Vitamin A on human endogenous plasma levels of Vitamin A and its metabolites. Methods: Two groups of 14 female volunteers of child-bearing age were kept on a Vitamin A-poor diet and treated topically for 21 days with creams containing 0.30% retinol or 0.55% retinyl palmitate on approximately 3000 cm2 of their body surface area, amounting to a total of approximately 30,000 IU Vitamin A/subject/day. After a 12-day wash-out period, the study groups received single oral doses of 10,000 IU or 30,000 IU retinyl palmitate (RP), corresponding to the maximal EU allowance during pregnancy or three-times higher, respectively. Blood samples were collected over 24 h on study days -3 (pre-study), 1, 21 (first and last days of topical treatment) and 34 (oral administration) at 0, 1, 2, 4, 6, 8, 12, 14-16 h and 24 h after treatment for determination of plasma concentrations of retinol (REL), retinyl palmitate (RP), oleate (RO) and stearate (RS), 9-cis-, 13-cis-, all-trans- (AT), 13-cis-4-oxo- or AT-4-oxo-retinoic acids (RAs). Results: With the exception of transient mild (RP-group) to moderate (REL-group) local irritation on the treatment sites, no adverse local or systemic effects were noted. On days 1 or 21 of topical treatment, no changes were measured in individual or group mean plasma Cmax, AUC0-24 h or other pharmacokinetic parameters of REL, retinyl esters or RAs relative to pre-study data. In contrast, single oral doses of RP at 10,000 IU or 30,000 IU produced dose-related and sustained increases in Cmax and AUC0-24 h values of plasma RP, RO, RS, 13-cis- and 13-cis-4-oxo-RAs, as well as a transient increase in AT-RA. In conclusion, our results provide evidence that human topical exposure to retinol- or retinyl ester-containing cosmetic creams at 30,000 IU/day and maximal use concentrations do not affect plasma levels of retinol, retinyl esters or RAs, whereas single oral doses at 10,000 IU or 30,000 IU produce significant increases in plasma retinyl esters and RAs. © 2005 Elsevier Ireland Ltd. All rights reserved. Subject NutritionAnalytical researchBiomonitoringCAS 68-26-8CAS 79-81-2Human subjectsPlasma concentrationsRetinoic acidsRetinolRetinyl palmitateTeratogenicityTopical and oral administration4 oxoretinoic acidoleic acidretinoic acidretinolretinol esterretinol palmitatestearic acidabsence of side effectsadultarea under the curvearticleblood samplingbody surfaceclinical articlecontrolled studydose responsefemalehumanpregnancypriority journalretinol deficiencyskin irritationstatistical analysisvitamin blood levelAdministration, OralAdministration, TopicalAdultCosmeticsFemaleHumansRisk AssessmentVitamin A To reference this document use: http://resolver.tudelft.nl/uuid:72e2220f-81c7-42bf-ba8a-0ec9322afcf2 DOI https://doi.org/10.1016/j.toxlet.2005.09.029 TNO identifier 239268 ISSN 0378-4274 Source Toxicology Letters, 163 (1), 65-76 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.