Effects of oral administration of di-(2-ethylhexyl) and diisononyl phthalates on atopic dermatitis in NC/Nga mice.

Abstract

CONTEXT:

Subcutaneous injection of low dose of phthalates causes adjuvant effects on immunoglobulin production. Moreover, intraperitoneal injection of di-(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DINP) at doses lower than the no-observed-adverse-effect level (NOAEL) causes aggravation of atopic dermatitis-like skin lesions (ADSLs) in mouse models. However, the effects of oral exposure to these phthalates, including their effect on atopic dermatitis (AD) symptoms, remain unclear.

OBJECTIVE:

To investigate the effects of oral administration of DEHP and DINP at doses lower than the NOAEL on AD in an NC/Nga mouse model.

MATERIALS AND METHODS:

NC/Nga mice were subcutaneously injected with mite-allergen (Dermatophagoides pteronyssinus) to induce ADSLs and orally administered varying doses of DEHP (0, 8.3, 166.3 or 3325 µg/animal) or DINP (0, 6.6, 131.3 or 2625 µg/animal) once a week for four weeks. Skin disease symptomatology was subsequently evaluated and immunoglobulin production levels in serum and inflammatory cytokine levels in lesion sites were measured.

RESULTS:

Oral administration of low doses of both DEHP and DINP tended to increase infiltration of eosinophils; degranulation of mast cells and local expression of inflammatory cytokines, interleukin-13 and macrophage inflammatory protein-1 alpha in subcutaneous tissue, whereas DINP administration tended to aggravate allergen-induced ADSL production.

CONCLUSIONS:

Oral administration of both DEHP and DINP at doses lower than the NOAEL tends to increase the allergic response in animal AD models, but only DINP administration slightly aggravates allergen-induced ADSL production.

• Authors: Kaori Sadakane, Takamichi Ichinose, Hirohisa Takano, Rie Yanagisawa, Eiko Koike
• Journal: Immunopharmacology and immunotoxicology (Immunopharmacol Immunotoxicol) Vol. 36 Issue 1 Pg. 61-9 (Feb 2014) ISSN: 1532-2513 [Electronic] England
• PMID: 24328677 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Dermatophagoides
• Cytokines
• Phthalic Acids
• Plasticizers
• diisononyl phthalate
• Diethylhexyl Phthalate

Topics

• Administration, Oral
• Animals
• Antigens, Dermatophagoides (immunology, toxicity)
• Cytokines (immunology)
• Dermatitis, Atopic (chemically induced, drug therapy, immunology)
• Diethylhexyl Phthalate (pharmacology)
• Inflammation (chemically induced, drug therapy, immunology)
• Mice
• Phthalic Acids (pharmacology)
• Plasticizers (pharmacology)