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Environmental Health Perspectives (EHP) is a monthly journal of peer-reviewed research and news on the impact of the environment on human health. EHP is published by the National Institute of Environmental Health Sciences and its content is free online. Print issues are available by paid subscription.DISCLAIMER
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Environmental Health Perspectives Volume 114, Number 8, August 2006 Open Access
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Di-(2-ethylhexyl) Phthalate Enhances Atopic Dermatitis-Like Skin Lesions in Mice

Hirohisa Takano,1,2 Rie Yanagisawa,1 Ken-ichiro Inoue,1 Takamichi Ichinose,3 Kaori Sadakane,3 and Toshikazu Yoshikawa2

1Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Japan; 2Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, Japan

Abstract
Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in polyvinyl chloride products and has become ubiquitous in the developed countries. DEHP reportedly displays an adjuvant effect on immunoglobulin production. However, it has not been elucidated whether DEHP is associated with the aggravation of atopic dermatitis. We investigated the effects of DEHP on atopic dermatitis-like skin lesions induced by mite allergen in NC/Nga mice. NC/Nga male mice were injected intradermally with mite allergen on their right ears. In the presence of allergen, DEHP (0, 0.8, 4, 20, or 100 µg) was administered by intraperitoneal injection. We evaluated clinical scores, ear thickening, histologic findings, and the protein expression of chemokines. Exposure to DEHP at a dose of 0.8–20 µg caused deterioration of atopic dermatitis-like skin lesions related to mite allergen ; this was evident from macroscopic and microscopic examinations. Furthermore, these changes were consistent with the protein expression of proinflammatory molecules such as macrophage inflammatory protein-1alpha (MIP-1alpha) and eotaxin in the ear tissue in overall trend. In contrast, 100 µg DEHP did not show the enhancing effects. These results indicate that DEHP enhances atopic dermatitis-like skin lesions at hundred-fold lower levels than the no observed adverse effect level determined on histologic changes in the liver of rodents. DEHP could be at least partly responsible for the recent increase in atopic dermatitis. Key words: , , , , . Environ Health Perspect 114:1266–1269 (2006) . doi:10.1289/ehp.8985 available via http://dx.doi.org/ [Online 15 May 2006]


Address correspondence to H. Takano, Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, 305-8506, Japan. Telephone: 81-298-50-2336. Fax: 81-298-50-2334. E-mail: htakano@nies.go.jp

Supplemental Material is available online at http://www.ehponline.org/docs/2006/8985/suppl.pdf

We thank T. Sasakawa (Astellas Pharma Inc.) for his help in establishing the animal model and M. Sakurai and N. Ueki for their technical assistance.

The authors declare they have no competing financial interests.

Received 9 January 2006 ; accepted 15 May 2006.


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