Use of a Simple in vitro Test to Assess Loss of Chemical due to Volatility during an in vitro Human Skin Absorption Study.
Absorption
Human skin
In vitro test
Mass balance
Vapour pressure
Volatility
Journal
Skin pharmacology and physiology
ISSN: 1660-5535
Titre abrégé: Skin Pharmacol Physiol
Pays: Switzerland
ID NLM: 101188418
Informations de publication
Date de publication:
2019
2019
Historique:
received:
30
10
2018
accepted:
18
01
2019
pubmed:
20
3
2019
medline:
21
11
2019
entrez:
20
3
2019
Statut:
ppublish
Résumé
We tested the cutaneous distribution of 50 chemicals in frozen human skin. The mass balance (MB) values for 48% of the chemicals were < 90%, possibly due to evaporation. We confirmed the reduction in MB was due to evaporation for two chemicals tested in skin penetration experiments using a carbon filter above the skin to trap airborne chemical. An in vitro assay was used to predict the reduction in MB due to evaporation by comparing the recovery of chemicals after 4 h of incubation at room temperature in open and closed vials. Evaporative losses in vitro correlated well with measured MBs (i.e., < 90%) in skin penetration experiments (R2 = 0.81). There was a correlation of the MB with the vapour pressure (VP) which could be used to group chemicals according to their likelihood to evaporate during the course of a skin penetration study. There was also a correlation of MB with Henry's law constants, melting and boiling points. Our data support the use of a quick and simple test for volatility to account for the loss of MB in skin penetration experiment due to volatility. The best parameter to indicate the potential of a chemical to evaporate is the VP.
Sections du résumé
BACKGROUND
BACKGROUND
We tested the cutaneous distribution of 50 chemicals in frozen human skin. The mass balance (MB) values for 48% of the chemicals were < 90%, possibly due to evaporation.
METHODS
METHODS
We confirmed the reduction in MB was due to evaporation for two chemicals tested in skin penetration experiments using a carbon filter above the skin to trap airborne chemical. An in vitro assay was used to predict the reduction in MB due to evaporation by comparing the recovery of chemicals after 4 h of incubation at room temperature in open and closed vials.
RESULTS
RESULTS
Evaporative losses in vitro correlated well with measured MBs (i.e., < 90%) in skin penetration experiments (R2 = 0.81). There was a correlation of the MB with the vapour pressure (VP) which could be used to group chemicals according to their likelihood to evaporate during the course of a skin penetration study. There was also a correlation of MB with Henry's law constants, melting and boiling points.
CONCLUSION
CONCLUSIONS
Our data support the use of a quick and simple test for volatility to account for the loss of MB in skin penetration experiment due to volatility. The best parameter to indicate the potential of a chemical to evaporate is the VP.
Identifiants
pubmed: 30889606
pii: 000497105
doi: 10.1159/000497105
doi:
Substances chimiques
Pharmaceutical Preparations
0
Carbon
7440-44-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
117-124Informations de copyright
© 2019 S. Karger AG, Basel.