title: Effects of oral administration of di-(2-ethylhexyl) and diisononyl phthalates on atopic dermatitis in NC/Nga mice.
abstract: BACKGROUND
  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.
  
  
  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: Department of Health Sciences, Oita University of Nursing and Health Sciences , Oita , Japan .
authors: Kaori
authors: K
authors: Sadakane
authors: Takamichi
authors: T
authors: Ichinose
authors: Hirohisa
authors: H
authors: Takano
authors: Rie
authors: R
authors: Yanagisawa
authors: Eiko
authors: E
authors: Koike
mesh_terms: D000284:Administration, Oral; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000633:toxicity; D016207:Cytokines / Q000276:immunology; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D010795:Phthalic Acids / Q000494:pharmacology*; D010968:Plasticizers / Q000494:pharmacology*
chemical_list: D039741:Antigens, Dermatophagoides; D016207:Cytokines; D010795:Phthalic Acids; D010968:Plasticizers; C012125:diisononyl phthalate; D004051:Diethylhexyl Phthalate