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Respiratory allergic and non-allergic sensitisation against low molecular weight organic compounds - Experimental models using organic acid anhydrides

Objective

Objectives:
To develop predictive experimental methods to assess risk of airways sensitization by chemicals, as well as a closer understanding of the pathomechanisms behind the organic acid anhydride (OAA) induced occupational disorders, including quantitative structure-activity relationships. The results will be compared with epidemiological studies of workers exposed to different OAAs.

Brief description:
Organic acid anhydrides have very good technical properties, and they thus have a wide and increasing use in industry, i.a., in epoxy and alkyd resin systems. They are volatile, and may be inhaled. About half of the exposed workers develop symptoms from the eyes and/or respiratory tract (including asthma), one third have specific IgE/and or IgG serum antibodies, even at extremely low exposures (a few pLg/m3). However, the OAAs also cause non-allergic sensitivity. Much is unknown on the mechanism(s) behind OAA-induced reactions. However, the OAAs have an interest, which reaches far beyond the occupational setting: Their high but varying sensitizing capacity, in combination with their simple chemical structure, make them a very interesting model for basic studies of sensitization. Further, there are currently available no validated methods for predictive, experimental identification and characterization of chemicals that are able to cause sensitization of the respiratory tract.
A network will be established by eight European research groups (one industry-associated), with complementary competencies in experimental sensitization an/or occupational airway disease caused by low-molecular weight chemicals. In a series of sub-projects, their methodological resources and/or access to unique populations of exposed workers will be combined.
The main part of the concerted action is experimental: Development of predictive experimental methods to assess risk of airway sensitization by chemicals, as well as a closer understanding of the pathomechanism behind the OAA-induced occupational disorders, including quantitative structure activity relationships (which is essentially unknown for any respiratory sensitizer). The results will be compared with epidemiological studies of workers exposed to different OAAs, including assessment of exposure intensity by levels in air and of biomarkers, as well of specific antibodies. Also, reactions on nasal challenge will be assessed, and, in addition, predisposing genetic traits.

Keywords:

Allergy, animal models, dose-effect relationship, low-molecular weight chemicals, occupational, organic acid anhydrides, predictive testing, structure-activity relationship, sensitization.

Funding Scheme

CON - Coordination of research actions

Coordinator

Lund University
Address

221 85 Lund
Sweden