Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.652967
Title: Occupational allergy to low molecular weight organic chemicals : the role of chemical structure in determining sensitisation hazard
Author: Jarvis, J. E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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Abstract:
A number of low molecular weight (LMW) organic chemicals are known to cause occupational respiratory or skin sensitisation. A set of 200 LMW organic skin and 75 respiratory sensitisers was identified by systematic search and critical appraisal of published cases and epidemiologic literature. In addition a set of 302 control chemicals was selected from known hazardous LMW organic chemicals for which no reports of respiratory sensitisation could be found. Several approaches based on chemical structure and using a case-control methodology were investigated to differentiate between asthmagens and controls, or asthmagens and skin sensitisers (by chemical structure alone) were investigated. These comprised hazardous fragment identification by calculating odds ratios for hazard (HOR's), cluster analysis and logistic regression analysis. Of these methods the most effective approach was the logistic regression analysis. Using these methods several known or suspected hazardous substructures were confirmed to present statistically significant occupational asthma (OA) hazard. These included isocyanates, acid anhydrides, acrylates and (oligo)-amines. Many hazardous compounds contained pairs of hazardous substructures. Furthermore, certain sub-structural fragments such as chlorine atoms appeared to provide a protective effect from OA hazard. For differentiating between skin sensitizers and asthmagens it was noted that fragments with carbon double bonded to nitrogen or oxygen atoms were significantly more prevalent in the respiratory sensitisers set. A predictive model of chemical asthma hazard was created using logistic regression and the model tested on a validation set of chemicals yielded a predictive kappa value of 0.7. This model is available for predictive testing of compounds for asthma hazard via the World Wide Web. This work demonstrates that simple structural information may, in conjunction with a well designed methodology, be used to identify occupational sensitisers with reasonable reliability.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.652967  DOI: Not available
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