NBS monograph

From Introduction Purpose and Scope of Report: "This report is one of a series prepared for the Research Information Center and Advisory Service on Information Processing (RICASIP), and intended as a contribution to improved cooperation in the fields of information selection systems development, information retrieval research and mechanized translation.

Occupational allergy to low molecular weight organic chemicals: the role of structure in determining chemical hazard

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 approximately 75 respiratory sensitisers were identified by critical appraisal of published case literature. The respiratory sensitisers (asthmagens) were systematically compared in turn with suitable control chemicals and the skin sensitisers using a case-control methodology. The control chemicals were selected from known hazardous LMW organic chemicals for which no reports of respiratory sensitisation could be found.Several potential methods of differentiating 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 the 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. Furthermore, certain sub-structural fragments such as chlorine atoms appeared to provide a protective effect from OA hazard. For differentiating between skin sensitisers 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 greater than 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