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The prediction and confirmation of potential respiratory sensitizers generated from indoor air samples.

Anderson-S; Wells-R; Fedorowicz-A; Meade-BJ; Butterworth-LF; Munson-AE
Toxicologist 2007 Mar; 96(1):238
Of the 89 million people in the US working in indoor office environments, between 35 and 60 million experience symptoms such as eye, nose and throat irritation, headache, and fatigue. Several investigations into these complaints have ascribed the effects to volatile organic compounds (VOC) emitted from building materials, cleaning formulations or other consumer products. Additional compounds can result from these VOC's, being transformed by hydroxyl or nitrate radicals and ozone, present in indoor environments. Several dicarbonyls, such as glyoxal (GX), methylglyoxal (MG), glycolaldehyde (GA) and diacetyl (DA) have been identified as VOC reaction products of indoor environment chemistry. The sensitization potential of these compounds was assessed using three quantitative structure-activity relationship (QSAR) programs. DEREK for Windows and Logistic Regression predicted all compounds as sensitizers, while TOPKAT 6.1 predicted all compounds except for MG. Next the compounds were tested in a combined irritancy and local lymph node assay (LLNA). Mice were exposed dermally to GX (0.35-1.5%) MG (0.05-1%), GA (0.8-3.2%) or DA (1.25-12%). All compounds except for GX were found to be irritants. All compounds were found to be sensitizers resulting in EC3 values of 0.74, 0.18, 1.8, and 1.9%, respectively. No changes in organ, body weight, or serum IgE levels were observed following exposure to the compounds. MG, GX, and GA did not significantly increase IgE+B220+ cell populations in the draining lymph nodes, but 5% DA resulted in significant increases in both B220+ and IgE+B220+ cells. The four compounds generated by indoor air chemistry were predicted by QSAR analysis to be sensitizers and confirmed using an animal model. The identification of these compounds as sensitizers may help to explain some of the health effects associated with indoor air complaints.
Organic-chemicals; Organic-compounds; Physical-reactions; Environmental-health; Environmental-exposure; Chemical-analysis; Chemical-hypersensitivity; Chemical-reactions; Mathematical-models; Statistical-analysis; Animal-studies; Cellular-reactions; Chemical-indicators
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The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina