Article

Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds

University Computing Services, The University of Edinburgh, UK.
Occupational and environmental medicine (Impact Factor: 3.23). 05/2005; 62(4):243-50. DOI: 10.1136/oem.2004.016402
Source: PubMed

ABSTRACT To investigate quantitatively, relationships between chemical structure and reported occupational asthma hazard for low molecular weight (LMW) organic compounds; to develop and validate a model linking asthma hazard with chemical substructure; and to generate mechanistic hypotheses that might explain the relationships.
A learning dataset used 78 LMW chemical asthmagens reported in the literature before 1995, and 301 control compounds with recognised occupational exposures and hazards other than respiratory sensitisation. The chemical structures of the asthmagens and control compounds were characterised by the presence of chemical substructure fragments. Odds ratios were calculated for these fragments to determine which were associated with a likelihood of being reported as an occupational asthmagen. Logistic regression modelling was used to identify the independent contribution of these substructures. A post-1995 set of 21 asthmagens and 77 controls were selected to externally validate the model.
Nitrogen or oxygen containing functional groups such as isocyanate, amine, acid anhydride, and carbonyl were associated with an occupational asthma hazard, particularly when the functional group was present twice or more in the same molecule. A logistic regression model using only statistically significant independent variables for occupational asthma hazard correctly assigned 90% of the model development set. The external validation showed a sensitivity of 86% and specificity of 99%.
Although a wide variety of chemical structures are associated with occupational asthma, bifunctional reactivity is strongly associated with occupational asthma hazard across a range of chemical substructures. This suggests that chemical cross-linking is an important molecular mechanism leading to the development of occupational asthma. The logistic regression model is freely available on the internet and may offer a useful but inexpensive adjunct to the prediction of occupational asthma hazard.

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    • ") and other species which transform by decomposition, isomerization, or hydrolysis, leading to the formation of oxygenated compounds, such as alcohols, carbonyls , carboxylic acids, and hydroxycarbonyls (Atkinson and Arey, 2003; Finlayson-Pitts and Pitts, 2000; Forester et al., 2007; Kroll and Seinfeld, 2008; Orlando and Tyndall, 2012; Orlando et al., 2003; Wells, 2005). Oxygenated organics formed by O 3 or OH reactions can be acute or chronic irritants, and they can sorb to surfaces, oxidize further, contribute to aerosol formation, or be removed by air exchange (Aalto-Korte et al., 2005; Anderson et al., 2007, 2012; Bein and Leikauf, 2011; Jakubowski and Czerczak, 2010; Jarvis et al., 2005; Kroll and Seinfeld, 2008; Weschler, 2011). The quantification of OH indoors is challenging, but OH has been predicted or measured at ~10 À7 e10 À5 ppb (Carslaw, 2007; Sarwar et al., 2002; Weschler and Shields, 1996, 1997). "
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