Work-Related Asthma.

OBJECTIVE: Summarize developed evidence-based diagnostic and treatment guidelines for work-related asthma (WRA). METHODS: Comprehensive literature reviews conducted with article critiquing and grading. Guidelines developed by a multidisciplinary expert panel and peer-reviewed. RESULTS: Evidence supports spirometric testing as an essential early test. Serial peak expiratory flow rates measurement is moderately recommended for employees diagnosed with asthma to establish work-relatedness. Bronchial provocation testing is moderately recommended. IgE and skin prick testing for specific high-molecular weight (HMW) antigens are highly recommended. IgG testing for HMW antigens, IgE testing for low-molecular weight antigens, and nitric oxide testing for diagnosis are not recommended. Removal from exposure is associated with the highest probability of improvement, but may not lead to complete recovery. CONCLUSION: Quality evidence supports these clinical practice recommendations. The guidelines may be useful to providers who diagnose and/or treat WRA.

Risk assessment for consumer exposure to toluene diisocyanate (TDI) derived from polyurethane flexible foam.

Polyurethanes (PU) are polymers made from diisocyanates and polyols for a variety of consumer products. It has been suggested that PU foam may contain trace amounts of residual toluene diisocyanate (TDI) monomers and present a health risk. To address this concern, the exposure scenario and health risks posed by sleeping on a PU foam mattress were evaluated. Toxicity benchmarks for key non-cancer endpoints (i.e., irritation, sensitization, respiratory tract effects) were determined by dividing points of departure by uncertainty factors. The cancer benchmark was derived using the USEPA Benchmark Dose Software. Results of previous migration and emission data of TDI from PU foam were combined with conservative exposure factors to calculate upper-bound dermal and inhalation exposures to TDI as well as a lifetime average daily dose to TDI from dermal exposure. For each non-cancer endpoint, the toxicity benchmark was divided by the calculated exposure to determine the margin of safety (MOS), which ranged from 200 (respiratory tract) to 3×10(6) (irritation). Although available data indicate TDI is not carcinogenic, a theoretical excess cancer risk (1×10(-7)) was calculated. We conclude from this assessment that sleeping on a PU foam mattress does not pose TDI-related health risks to consumers.

Issues in diisocyanate antibody testing.

Diisocyanates are used to produce a wide variety of polyurethane products; they are also recognized as an important cause of occupational asthma. Their chemical reactivity presents challenges to toxicologists and clinicians alike seeking to understand the mechanisms underlying diisocyanate asthma. In this article, we review the literature on immunoassay detection of IgE and IgG binding to diisocyanate-protein conjugates and assess the utility of such testing as a diagnostic tool and exposure indicator. Data from 29 studies of occupational exposure to diisocyanates revealed considerable variability in assay methodology and heterogeneity in the prevalence of positive antibody responses across laboratories. In studies that included both confirmed diisocyanate asthma subjects and exposed nonasthmatics, positive IgE responses identified cases with low sensitivity (18-27%), but high specificity (96-98%). Detection of IgG binding to diisocyanate conjugates is an indirect, qualitative indicator of disease status and past diisocyanate exposure. The utility of these assays is limited, however, due to a lack of (1) method standardization, (2) population norms to guide interpretation of results, and (3) demonstration that the assays improve either on disease prediction or on exposure confirmation beyond that of other indicators. Sources of assay heterogeneity are discussed and suggestions are offered for improving test performance and interpretability.

Respiratory effects of toluene diisocyanate in the workplace: a discussion of exposure-response relationships.

Toluene diisocyanate (TDI) is an important industrial intermediate used in manufacturing flexible polyurethane (PUR) foams, surface coatings, cast elastomers, sealants, and adhesives. In this review long-term trends in workplace exposures to TDI are assessed in both the producing and using industries, and respiratory health effects of TDI are evaluated in relation to workplace TDI concentrations. The key respiratory health effects associated with repeated or long-term TDI exposure are bronchial asthma and an accelerated rate of decline in lung function. In the early years of the industry, annual incidence rates of occupational asthma (OA) due to TDI ranged from 1% to as high as 5 to 6%, depending on the extent of engineering and work practice controls in the various workplaces. Since the mid-1970s, annual OA incidence rates have been <1%, where 8 h TDI concentrations have been maintained below 5 ppb as determined by personal monitoring, even where short-termTDI concentrations above 20 ppb and less frequently above 40 ppb were routinely detected. In these latter settings, there is evidence that the majority of OA cases may be attributable to TDI concentrations well above 20 ppb associated with overexposure incidents. Further study is needed regarding the role of such incidents in inducing respiratory sensitization. Cross-sectional and longitudinal studies of lung function have indicated that continued exposure after development of work-related respiratory symptoms can lead to transient or accelerated fixed declines in forced expiratory volume in 1 sec (FEV1). These findings are congruent with the FEV1 declines demonstrated in general population studies of persons with persistent bronchial hyperresponsiveness or nonoccupational asthma. More recent longitudinal studies in settings with ongoing medical surveillance have provided no consistent evidence of accelerated FEV1 loss among employees exposed up to 5 ppb TDI on an 8 h time-weighted average basis.