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Dhimiter Bello,^1,2 Christina A. Herrick,³ Thomas J. Smith,¹ Susan R. Woskie,² Robert P. Streicher,⁴ Mark R. Cullen,⁵ Youcheng Liu,⁵ and Carrie A. Redlich⁵

¹Exposure, Epidemiology and Risk Program, Harvard School of Public Health, Boston, Massachusetts, USA; ²Department of Work Environment, University of Massachusetts Lowell, Lowell, Massachusetts, USA; ³Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA; ⁴Division of Applied Research and Technology, National Institute for Occupational Safety and Health, Cincinnati, Ohio, USA; ⁵Occupational and Environmental Medicine Program, Yale University School of Medicine, New Haven, Connecticut, USA

Abstract
Objective: Isocyanates (di- and poly-) , important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not uncommonly in settings with minimal inhalation exposure but opportunity for skin exposure. In this review we evaluate the potential role of skin exposure in the development of isocyanate asthma.

Data sources: We reviewed the published animal and human literature on isocyanate skin-exposure methods, workplace skin exposure, skin absorption, and the role of skin exposure in isocyanate sensitization and asthma.

Data extraction: We selected relevant articles from computerized searches on Medline, U.S. Environmental Protection Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, and Google databases using the keywords "isocyanate," "asthma," "skin," "sensitization," and other synonymous terms, and our own extensive collection of isocyanate publications.

Data synthesis: Isocyanate production and use continues to increase as the polyurethane industry expands. There is substantial opportunity for isocyanate skin exposure in many work settings, but such exposure is challenging to quantify and continues to be underappreciated. Isocyanate skin exposure can occur at work, even with the use of personal protective equipment, and may also occur with consumer use of certain isocyanate products. In animals, isocyanate skin exposure is an efficient route to induce sensitization, with subsequent inhalation challenge resulting in asthma-like responses. Several lines of evidence support a similar role for human isocyanate skin exposure, namely, that such exposure occurs and can contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization.

Conclusions: Integrated animal and human research is needed to better understand the role of skin exposure in human isocyanate asthma and to improve diagnosis and prevention. In spite of substantial research needs, sufficient evidence already exists to justify greater emphasis on the potential risks of isocyanate skin exposure and the importance of preventing such exposures at work and during consumer use of certain isocyanate products.

Key words: asthma, dermal exposure, isocyanates, sensitization, skin. Environ Health Perspect 115: 328–335 (2007) . doi:10.1289/ehp.9557 available via http://dx.doi.org/ [Online 28 November 2006]

Address correspondence to D. Bello, Department of Work Environment, KI 200, University of Massachusetts Lowell, One University Ave., Lowell, MA 01854 USA. Telephone: (978) 934-3343. Fax: (978) 452-5711. E-mail: dhimiter_bello@uml.edu

This study was supported by National Institute for Occupational Safety and Health (NIOSH) /Centers for Disease Control and Prevention (CDC) grants R01H3457 and 5 R01OH004246. D.B. was supported by National Research Service Award training grant T32 ES07069, and C.A.R. was supported by National Institutes of Health grant K24-ES00355.

Mention of company names and/or products does not constitute endorsement by the CDC. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of NIOSH.

Under contracts, the Yale Occupational and Environmental Medicine Program (YOEMP) , including M.R.C. and C.A.R, has provided consulting services related to occupational lung diseases, including isocyanate asthma. The resources from these contracts have gone to the YOEMP to support research, education, and patient care—all related to occupational diseases.The remaining authors declare they have no competing financial interests.

Received 27 July 2006 ; accepted 27 November 2006.