Bio-monitoring Methylene Diphenyl Diisocyanate (MDI) exposure and body burden

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R42ES018021-02
Agency Tracking Number: R42ES018021
Amount: $1,356,039.00
Phase: Phase II
Program: STTR
Awards Year: 2011
Solicitation Year: 2011
Solicitation Topic Code: NIEHS
Solicitation Number: N/A
Small Business Information
BOX 8175, NEW HAVEN, CT, -
DUNS: 142406110
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 ADAM WISNEWSKI
 (203) 737-2544
 adam.wisnewski@yale.edu
Business Contact
 MARTIN MATTESSICH
Phone: (203) 393-9439
Email: mmattessich@L2dx.com
Research Institution
 YALE UNIVERSITY
 Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): Exposure to isocyanate, the essential cross-linker for making polyurethane, is a leading cause of occupational asthma world-wide. Three major types of isocyanate are used commercially, methylene-diphenyl diisocyanate (MDI) and toluene diisocyanate (TDI), or aliphatic, hexamethylene diisocyanate (HDI). Despite being the newest of the three, MDI has overtaken the isocyanate market in production and consumption, for many reasons, including its unique applications and properties. Importantly, at room temperature, MDI has a much lower vapor pressure than HDI or TDI, and exists as a solid, rather than a (volatile) liquid. Thus, MDI is presumed to be safer , because the potential for respiratory tract exposure is thought to be restricted to times when the chemical is heated or aerosolized (sprayed), i.e. during application. MDI is widely used in making flexible and rigid foams, coatings, elastomers and numerous other polyurethane-based products. Exposure to MDI is the best-recognized risk factor for the development of MDI asthma and exposure reduction is the primary strategy of disease prevention. Contemporary methods of monitoring MDI exposure are severely limited, and new approaches are needed to help protect millions of people exposed at work. In this new phase II application for the project Biomonitoring Methylene Diphenyl Diisocyanate (MDI) exposure and body burden , we aim to develop innovative biomonitoring approaches to exposure surveillance for MDI. The investigative team consists of scientists and physicians from Yale University School of Medicine and the small business, L2 Diagnostics, who are applying their expertise with immunoassays, to develop blood tests that measure (2) different MDI exposure biomarkers. One biomarker is MDI-specific antibodies (IgG), produced by the immune system in response to exposure. The second biomarker is the chemical (MDI) itself conjugated to albumin, the major protein adduct in vivo. To date, we have successfully completed the (4) Specific Aims of the projects 1st phase, and published supportive findings (Wisnewski et al Analytical Biochem 2010; PMID: 20123080), including the generation of key reagents, and their extensive characterization. Completion of these milestones demonstrates our readiness to embark on the specific aims of the project's 2nd phase (listed below), which should lead to new commercial assays for biomonitoring MDI exposure, which will help prevent ongoing exposures and new cases of MDI asthma. (Aim 1) Define the analytical performance characteristics of two new laboratory assays to measure (biomarkers of) MDI exposure. (Aim 2) Determine the clinical sensitivity of new MDI exposure (laboratory-based) assays, among MDI exposed workers and different populations of control unexposed individuals. (Aim 3) Using the new MDI exposure assays, establish the kinetics of MDI immune sensitization, and indications for use in evaluating exposed workers. PUBLIC HEALTH RELEVANCE: This application will develop two new immunoassays to bio-monitor MDI exposure in the workplace thus, ensuring adequate safety in polyurethane manufacture, and protecting the health of the US workforce.

* Information listed above is at the time of submission. *

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