title: Dermal absorption and hydrolysis of methylparaben in different vehicles through intact and damaged skin: using a pig-ear model in vitro.
abstract: Currently, there is a trend to reduce of parabens use due to concern about the safety of their unmetabolised forms. This paper focused on dermal absorption rate and effectiveness of first-pass biotransformation of methylparaben (MP) under in-use conditions of skincare products. 24-h exposure of previously frozen intact and tapestripped (20 strips) pig-ear skin to nine vehicles containing 0.1% MP (AD, applied dose of 10 μg/cm²), resulted in 2.0-5.8%AD and 2.9-7.6%AD of unmetabolised MP, and 37.0-73.0%AD and 56.0-95.0%AD of p-hydroxybenzoic acid, respectively, in the receptor fluid. The absorption rate of MP was higher from emulsions than from hydrogels, from enhancer-containing vehicles than from enhancer-free vehicles, and when skin was damaged. Experiments confirmed that the freezing of pig-ear skin slightly reduces hydrolysis of MP. After 4-h exposure of intact freshly excised and intact frozen stored skin, amount of <LOQ-2.3%AD and 2.3-3.3%AD unmetabolised MP, respectively, were found in the receptor fluid. Taking into account the number of useful properties of MP, but also the potential of systemic availability of unmetabolised MP, we consider that MP is more suitable for preserving rinse-off topical products than for leave-on products. Risk of systemic absorption of parabens should also be explored via the skin with damaged barrier.
authors.affiliation: Slovak University of Technology, Faculty of Chemical and Food Technology, Laboratories of Cosmetology, Bratislava, Slovak Republic.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pažoureková
authors.forename: Jarmila
authors.initials: J
authors.lastname: Hojerová
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Klimová
authors.forename: Marianna
authors.initials: M
authors.lastname: Lucová
mesh_terms: D000003:Abattoirs; D000279:Administration, Cutaneous; D000818:Animals; D001711:Biotransformation; D015925:Cryopreservation; D003879:Dermatologic Agents / Q000009:adverse effects / Q000032:analysis; D004423:Ear; D004655:Emulsions; D005260:Female; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008297:Male; D010226:Parabens / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*; D012867:Skin / Q000293:injuries* / Q000378:metabolism; D012869:Skin Absorption; D034421:Sus scrofa
chemical_list: D003879:Dermatologic Agents; D004655:Emulsions; D010226:Parabens; D014677:Pharmaceutical Vehicles; D011310:Preservatives, Pharmaceutical; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C015358:methylparaben; C038193:4-hydroxybenzoic acid
keywords: AD; ANOVA; BLOQ; BP; CIR; E; EP; EU Scientific Committee on Consumer Safety; FDA; FTS; Food and Drug Administration; Hydrolysis; In vitro dermal absorption; Intact and damaged pig-ear skin; J(ss); LOD; LOQ; MP; Metabolism; Metylparaben; OECD; Organization for Economic Co-operation and Development; P; PG; PHBA; PP; Permeation enhancer; RF; SC; SCCS; SD; SED; TC; TEC; Transcutol® CG; UR; US Cosmetic Ingredient Review; applied dose; below the limit of quantification; butylparaben; enhancer; ethylparaben; full-thickness skin membrane; limit of detection; limit of quantification; methylparaben; one-way analysis of variance; p-hydroxybenzoic acid; permeability coefficient; propylene glycol; propylparaben; receptor fluid; standard deviation; steady state flux; stratum corneum; systemic exposure dosage; transcutaneous electrical conductivity; unmMP; unmetabolised MP; urea