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Title: The pilosebaceous unit—a phthalate-induced pathway to skin sensitization

Abstract

Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we have explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. -- Highlights: ► Vehicle effectsmore » on sensitization potency were investigated in the LLNA. ► In vivo cutaneous absorption of contact sensitizers was visualized using TPM. ► Sensitizing potency of isothiocyanates depends on the presence of a phthalate. ► Phthalate induced cutaneous absorption via the pilosebaceous units. ► Vehicle-dependent reactivity regulates sensitization potency.« less

Authors:
 [1]; ;  [1];  [1]
  1. Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96, Gothenburg (Sweden)
Publication Date:
OSTI Identifier:
22215930
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 264; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETONE; BIOLOGICAL AVAILABILITY; CONSUMER PRODUCTS; DBP; DERMATITIS; DMSO; FLUORESCEIN; FLUORESCENCE; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; IN VIVO; ISOTHIOCYANATES; LYMPH NODES; MASS SPECTROSCOPY; MICROSCOPY; MOLECULAR WEIGHT; NEOPRENE; PHOSPHATES; PHOTONS; PHTHALATES; RECEPTORS; RISK ASSESSMENT; SENSITIZERS; SKIN

Citation Formats

Simonsson, Carl, Stenfeldt, Anna-Lena, Karlberg, Ann-Therese, Ericson, Marica B., E-mail: marica.ericson@physics.gu.se, and Jonsson, Charlotte A.M. The pilosebaceous unit—a phthalate-induced pathway to skin sensitization. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.07.023.
Simonsson, Carl, Stenfeldt, Anna-Lena, Karlberg, Ann-Therese, Ericson, Marica B., E-mail: marica.ericson@physics.gu.se, & Jonsson, Charlotte A.M. The pilosebaceous unit—a phthalate-induced pathway to skin sensitization. United States. https://doi.org/10.1016/J.TAAP.2012.07.023
Simonsson, Carl, Stenfeldt, Anna-Lena, Karlberg, Ann-Therese, Ericson, Marica B., E-mail: marica.ericson@physics.gu.se, and Jonsson, Charlotte A.M. 2012. "The pilosebaceous unit—a phthalate-induced pathway to skin sensitization". United States. https://doi.org/10.1016/J.TAAP.2012.07.023.
@article{osti_22215930,
title = {The pilosebaceous unit—a phthalate-induced pathway to skin sensitization},
author = {Simonsson, Carl and Stenfeldt, Anna-Lena and Karlberg, Ann-Therese and Ericson, Marica B., E-mail: marica.ericson@physics.gu.se and Jonsson, Charlotte A.M.},
abstractNote = {Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we have explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. -- Highlights: ► Vehicle effects on sensitization potency were investigated in the LLNA. ► In vivo cutaneous absorption of contact sensitizers was visualized using TPM. ► Sensitizing potency of isothiocyanates depends on the presence of a phthalate. ► Phthalate induced cutaneous absorption via the pilosebaceous units. ► Vehicle-dependent reactivity regulates sensitization potency.},
doi = {10.1016/J.TAAP.2012.07.023},
url = {https://www.osti.gov/biblio/22215930}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 264,
place = {United States},
year = {Mon Oct 01 00:00:00 EDT 2012},
month = {Mon Oct 01 00:00:00 EDT 2012}
}