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Dermal penetration and metabolism of p-aminophenol and p-phenylenediamine: application of the EpiDerm human reconstructed epidermis model.
- Source :
-
Toxicology letters [Toxicol Lett] 2009 Jul 24; Vol. 188 (2), pp. 119-29. Date of Electronic Publication: 2009 Mar 31. - Publication Year :
- 2009
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Abstract
- To address the provision of the 7th Amendment to the EU Cosmetics Directive banning the use of in vivo genotoxicity assays for testing cosmetic ingredients in 2009, the 3D EpiDerm reconstructed human skin micronucleus assay has been developed. To further characterise the EpiDerm tissue for potential use in genotoxicity testing, we have evaluated the dermal penetration and metabolism of two hair dye ingredients, p-aminophenol (PAP) and p-phenylenediamine (PPD) in this reconstructed epidermis model. When EpiDerm tissue was topically exposed to PAP or PPD for 30 min (typical for a hair dye exposure), the majority (80->90%) of PAP or PPD was excluded from skin tissue and removed by rinsing. After a 23.5h recovery period, the PAP fraction that did penetrate was completely N-acetylated to acetaminophen (APAP). Similarly, 30 min topical application of PPD resulted in the formation of the N-mono- and N,N'-diacetylated metabolites of PPD. These results are consistent with published data on the dermal metabolism of these compounds from other in vitro systems as well as from in vivo studies. When tissue was exposed topically (PAP) or via the culture media (PPD) for 24h, there was good batch-to-batch and donor-to-donor reproducibility in the penetration and metabolism of PAP and PPD. Overall, the results demonstrate that these two aromatic amines are biotransformed in 3D EpiDerm tissue via N-acetylation. Characterising the metabolic capability of EpiDerm tissue is important for the evaluation of this model for use in genotoxicity testing.
- Subjects :
- Aminophenols pharmacokinetics
Biotransformation
Calibration
Chromatography, High Pressure Liquid
Consumer Product Safety
Hair Dyes chemistry
Hair Dyes pharmacokinetics
Hair Dyes toxicity
Humans
Mass Spectrometry
Organ Culture Techniques
Phenylenediamines pharmacokinetics
Solutions
Aminophenols metabolism
Epidermis metabolism
Models, Biological
Phenylenediamines metabolism
Skin Absorption
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 188
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 19446244
- Full Text :
- https://doi.org/10.1016/j.toxlet.2009.03.019