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

Journal Article · Mon Oct 01 00:00:00 EDT 2012 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2012.07.023· OSTI ID:22215930

Simonsson, Carl ^[1]; Stenfeldt, Anna-Lena; Karlberg, Ann-Therese ^[1]; Jonsson, Charlotte A.M. ^[1]

---

1. Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96, Gothenburg (Sweden)

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.

• OSTI ID: 22215930
• Journal Information: Toxicology and Applied Pharmacology, Vol. 264, 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); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

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