US EPA

2215659 

Journal Article 

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

Sadakane, K; Ichinose, T; Takano, H; Yanagisawa, R; Koike, E 

2014 

Yes 

Immunopharmacology and Immunotoxicology
ISSN: 0892-3973
EISSN: 1532-2513 

INFORMA HEALTHCARE 

LONDON 

36 

1 

61-69 

English 

24328677 

10.3109/08923973.2013.866678 

WOS:000330711600008 

http://://CCC:000330711600008
Exit
 

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. 

Eosinophil; macrophage inflammatory protein-1α; mast cell; mite-allergen; no-observed-adverse-effect level