Isocyanate exposure and respiratory health effects in the spray painting industry

Abstract

In this thesis exposure-response relationships between isocyanate exposure and respiratory health end-points and specific sensitization in spray painters were investigated. Isocyanates, a group of compounds characterized by reactive N=C=O groups, are among the most frequently identified causes of occupational asthma in industrialized countries. Isocyanates are used as polymerizing agents in polyurethane products, such as kits, glues, lacquers and insulation materials. Spray painters comprise a large population at risk with potentially high isocyanate exposure. Large scale (n=566) personal task based inhalation sampling showed that hexamethylene diisocyanate (HDI) oligomers were dominant in frequency of occurrence and had the highest exposure levels. Exposure was highest during spray painting. Exposure to monomeric HDI was far below current occupational exposure levels. An ad hoc method was developed for dermal exposure sampling (n=95) and showed that dermal exposure occurred during tasks that involve direct handling of paint. Personal inhalation exposure was estimated by combining results from task-based personal inhalation exposure assessment and task activity information. Association between exposure and respiratory symptoms were studied in 581 workers. Log-linear exposure-response associations were found for asthma-like symptoms (wheezing or chest tightness), COPD-like symptoms (chronic cough or phlegm or shortness of breath) and work-related chest tightness (prevalence ratios (PRs) for an interquartile range (IQR) increase in exposure of 1.2, 1.3 and 2.0 respectively, p?0.05). Bronchial hyperresponsiveness (BHR), assessed by methacholine challenge (n=229), was more prevalent among exposed workers than office workers and a positive association was found with exposure (PR (95 % CI) IQR: 1.8 (1.1-3.0)). Exposure related obstructive effects on lung function, independent of BHR, were also found (FEV1, FEV1/FVC and flow parameters associated with exposure, p<0.05). Specific IgE and IgG were assessed by various immunoassays based on HDI-HSA conjugates prepared with HDI in the liquid (HDIL) or vapor phase (HDIv), or with HDI-oligomers (N100, N3300) and the commercial ImmunoCAP assay (n=581). The prevalence of specific IgE sensitization was low (up to 4.2 % in spray painters) suggesting that at most, specific IgE plays a role in a minority of individuals with symptoms. The prevalence of specific IgG was higher (2-50 %) and strongly associated with exposure. When comparing the immunoassays, EIAs with HSA-conjugated HDI oligomers seemed to provide the best combination of sensitivity and specificity in this industry. This suggests that exposure to specific isocyanates should be taken into account when assessing isocyanate specific sensitization. In a subset of the population (n=101) the use of a new cellular diagnostic test based on the production of the cytokine monocyte chemotactic protein-1 (MCP-1) by peripheral blood mononuclear cells stimulated with isocyanate conjugates was explored. Crude data did not suggest that HDI-induced MCP-1 release differed between exposure categories or between individuals with and without asthma-like symptoms, BHR or specific IgE or IgG antibodies. Taken together, the associations found in this study indicate that isocyanate oligomers can induce respiratory health effects at levels commonly found in this industry. No indications for a role of specific sensitization (IgE or IgG) were found. The results stress the importance of regulation and control of isocyanate oligomer exposure.