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  • The pilosebaceous unit--a phthalate-induced pathway to skin sensitization.

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

Toxicology and applied pharmacology (2012-07-31)
Carl Simonsson, Anna-Lena Stenfeldt, Ann-Therese Karlberg, Marica B Ericson, Charlotte A M Jonsson
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Dibutyl phthalate, PESTANAL®, analytical standard
Supelco
Dibutyl phthalate, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Supelco
Di-n-butyl phthalate solution, certified reference material, 5000 μg/mL in methanol
Sigma-Aldrich
Dibutyl phthalate, 99%
Sigma-Aldrich
Dibutyl phthalate, SAJ special grade, ≥98.0%