Youcheng Liu

Skin Exposure to Isocyanates: Reasons for Concern

Objective Isocyanates (di- and poly-), important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not uncommonly in settings with minimal inhalation exposure but opportunity for skin exposure. In this review we evaluate the potential role of skin exposure in the development of isocyanate asthma. Data sources We reviewed the published animal and human literature on isocyanate skin-exposure methods, workplace skin exposure, skin absorption, and the role of skin exposure in isocyanate sensitization and asthma. Data extraction We selected relevant articles from computerized searches on Medline, U.S. Environmental Protection Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, and Google databases using the keywords “isocyanate,” “asthma,” “skin,” “sensitization,” and other synonymous terms, and our own extensive collection of isocyanate publications. Data synthesis Isocyanate production and use continues to increase as the polyurethane industry expands. There is substantial opportunity for isocyanate skin exposure in many work settings, but such exposure is challenging to quantify and continues to be underappreciated. Isocyanate skin exposure can occur at work, even with the use of personal protective equipment, and may also occur with consumer use of certain isocyanate products. In animals, isocyanate skin exposure is an efficient route to induce sensitization, with subsequent inhalation challenge resulting in asthma-like responses. Several lines of evidence support a similar role for human isocyanate skin exposure, namely, that such exposure occurs and can contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization. Conclusions Integrated animal and human research is needed to better understand the role of skin exposure in human isocyanate asthma and to improve diagnosis and prevention. In spite of substantial research needs, sufficient evidence already exists to justify greater emphasis on the potential risks of isocyanate skin exposure and the importance of preventing such exposures at work and during consumer use of certain isocyanate products.

Association of heart rate variability in taxi drivers with marked changes in particulate air pollution in Beijing in 2008.

Background Heart rate variability (HRV), a marker of cardiac autonomic function, has been associated with particulate matter (PM) air pollution, especially in older patients and those with cardiovascular diseases. However, the effect of PM exposure on cardiac autonomic function in young, healthy adults has received less attention. Objectives We evaluated the relationship between exposure to traffic-related PM with an aerodynamic diameter ≤ 2.5 μm (PM2.5) and HRV in a highly exposed panel of taxi drivers. Methods Continuous measurements of personal exposure to PM2.5 and ambulatory electrocardiogram monitoring were conducted on 11 young healthy taxi drivers for a 12-hr work shift during their work time (0900–2100 hr) before, during, and after the Beijing 2008 Olympic Games. Mixed-effects regression models were used to estimate associations between PM2.5 exposure and percent changes in 5-min HRV indices after combining data from the three time periods and controlling for potentially confounding variables. Results Personal exposures of taxi drivers to PM2.5 changed markedly across the three time periods. The standard deviation of normal-to-normal (SDNN) intervals decreased by 2.2% [95% confidence interval (CI), −3.8% to −0.6%] with an interquartile range (IQR; 69.5 μg/m3) increase in the 30-min PM2.5 moving average, whereas the low-frequency and high-frequency powers decreased by 4.2% (95% CI, −9.0% to 0.8%) and 6.2% (95% CI, −10.7% to −1.5%), respectively, in association with an IQR increase in the 2-hr PM2.5 moving average. Conclusions Marked changes in traffic-related PM2.5 exposure were associated with altered cardiac autonomic function in young healthy adults.

Isocyanate Exposures in Autobody Shop Work: The SPRAY Study

Isocyanates, known to cause respiratory sensitization and asthma, are widely used in automotive refinishing where exposures to aliphatic polyisocyanates occur by both inhalation and skin contact. The work reported here, the characterization of isocyanate exposure in the autobody industry, was part of an epidemiologic study of workers in 37 autobody shops in Connecticut. This article describes workplaces, tasks, and controls, and outlines the frequency, duration, and intensity of isocyanate exposures. Personal air samples taken outside of respirators had median concentrations of 66.5 μg NCO/m3 for primer, 134.4 μg (NCO)/m3 for sealer, and 358.5 μg NCO/m3 for clearcoat. Forty-eight percent of primer, 66% of sealer, and 92% of clearcoat samples exceeded the United Kingdom Health and Safety Executive guideline for isocyanate, though none exceeded the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit for monomer. Nonisocyanate-containing primers and sealers are used in more than half the shops, but nonisocyanate clearcoats are rare. Eighty-two percent of personal samples taken within a spray booth exceeded the U.K. guideline: 81% of those in downdraft spray booths, 74% in semidowndraft booths, and 92% in crossdraft booths. Only 8% of shops reported that spraying is done exclusively in spray booths. All painters wore some type of respirator. In 30% of shops, painters used supplied air respirators; the rest relied on half face organic vapor cartridge respirators with N95 overspray pads. All shops provided some type of gloves, usually latex, not recommended for isocyanate protection. Despite improvements in autobody shop materials, practices, and controls, there are still opportunities for substantial exposures to isocyanates.

Respiratory Protection from Isocyanate Exposure in the Autobody Repair and Refinishing Industry

This study, part of the Survey of Painters and Repairers of Auto bodies by Yale (SPRAY), evaluated the effectiveness of respiratory protection against exposure to aliphatic polyisocyanates. A total of 36 shops were assessed for respiratory protection program completeness; 142 workers were measured for respirator fit factor (FF) using PortaCount Plus respirator fit tester. Twenty-two painters from 21 shops were sampled using NIOSH method 5525 to determine the workplace protection factor (WPF) of negative pressure, air-purifying half-facepiece respirators equipped with organic vapor cartridges and paint prefilters during spray-painting and priming activities. Only 11 shops (30%) had written respiratory protection programs. Eighty percent of all fit tested workers passed the test on the first try with FF ≥ 100, and 92% passed the second test after respirator use training. Overall geometric mean (GM) FF was 1012 for all fit tested workers. Significant differences on pass rate (92% vs. 72%) and on FF (1990 vs. 736) were found between previously fit tested workers vs. nontested workers. Twenty-nine WPF samples were collected. The outside facepiece GM concentration of total isocyanate group (NCO) was 378.4 μ g NCO/m3 with 96% concentrations exceeding the U.K. short-term exposure limit, 70 μ g NCO/m3, but no in-facepiece concentrations exceeded the limit. The GM WPF of total NCO was 319 (GSD 4) and the 5th percentile was 54. WPF of total NCO was positively correlated with the duration of painting task. FF positively correlated with WPF when FF was ≤450 but negatively correlated with WPF when FF was >450. We conclude that negative pressure, air-purifying half-facepiece respirators equipped with organic vapor cartridges and paint prefilters provide effective protection against isocyanate exposure in spray and priming operations if workers are properly trained and fitted.

The relationship between traffic-related air pollutants and cardiac autonomic function in a panel of healthy adults: a further analysis with existing data.

Context: Epidemiological studies have linked particulate matter (PM) and carbon monoxide (CO) exposures with alterations in cardiac autonomic function as measured by heart rate variability (HRV) in populations. Recently, we reported association of several HRV indices with marked changes in particulate air pollution around the Beijing 2008 Olympic Games in a panel of healthy adults. Objective: We further investigated the cardiac effects of traffic-related air pollutants over wide exposure ranges with expanded data set in this panel of healthy adults. Methods: We obtained real-time data on nine taxi drivers’ in-car exposures to PM ≤2.5 µm in aerodynamic diameter (PM2.5) and CO and on multiple HRV indices during a separate daily work shift in four study periods with dramatically changing air pollution levels around the Beijing 2008 Olympic Games. Mixed effect models and a loess smoother method were used to investigate the associations of exposures with HRV indices. Results: Results showed overall negative associations of traffic-related air pollutants with HRV indices across periods, as well as differences in period-specific and individual associations. After stratifying the individuals into two different response groups (positive/negative), cardiac effects of air pollutants became stronger within each group. Exposure–response modeling identified changed curvilinear relationships between air pollution exposures and HRV indices with threshold effects. Discussion and conclusion: Our results support the association of exposure to traffic-related air pollution with altered cardiac autonomic function in young healthy adults free of cardiovascular compromises. These results suggest a complicated mechanism that traffic-related air pollutants influence the cardiovascular system of healthy adults.

Slow Curing of Aliphatic Polyisocyanate Paints in Automotive Refinishing: A Potential Source for Skin Exposure

Two-component, polyurethane paints containing aliphatic isocyanates are widely used in autobody spray painting. Such isocyanates can cause asthma, and skin exposure may be an important route of sensitization and may contribute to the development of isocyanate asthma. Autobody workers are frequently in contact with recently painted, dried auto parts. It is not known how fast the newly painted car surfaces are fully cured, that is, for how long unbound, isocyanate species remain on painted surfaces after initial drying. To address this question, scrap sections of auto bodies were painted and dried by autobody shop painters following regular practice. Routinely used paints were sprayed 23 different times on the parts. Drying was accomplished by baking the part in a paint spray booth by heating it with a heat lamp or air drying in the shop. The 23 sprayed surfaces were sampled at regular time intervals after drying to determine the presence of free NCO groups using the semiquantitative SWYPE technique. Quantitative isocyanate analysis was also performed on two sprayed parts using NIOSH method 5525. Geometric mean curing time of 23 painted surfaces was 56.4 hr (range: 0.8 hrs to 32 days). Unbound isocyanate species of similar composition to the original bulk material remained present on the majority of sampled painted surfaces for up to 120 hours for typical paint formulations and for 1 month for others. The actual curing of polyurethane paints in autobody refinishing can be a slow process. Unbound isocyanates may remain on the surface of painted car parts for prolonged periods (days to weeks) after dried. Such surfaces are an under-recognized potential source of skin exposure to autobody workers.

An FTIR investigation of isocyanate skin absorption using in vitro guinea pig skin

Isocyanates may cause contact dermatitis, sensitization and asthma. Dermal exposure to aliphatic and aromatic isocyanates can occur in various exposure settings. The fate of isocyanates on skin is an important unanswered question. Do they react and bind to the outer layer of skin or do they penetrate through the epidermis as unreacted compounds? Knowing the kinetics of these processes is important in developing dermal exposure sampling or decontamination strategies, as well as understanding potential health implications such exposure may have. In this paper the residence time of model isocyanates on hairless guinea pig skin was investigated in vitro using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrometry. Model isocyanates tested were octyl isocyanate, polymeric hexamethylene diisocyanate isocyanurate (pHDI), polymeric isophorone diisocyanate isocyanurate (pIPDI) and methylenediphenyl diisocyanate (MDI). Isocyanates in ethyl acetate (30 microL) were spiked directly on the skin to give 0.2-1.8 micromol NCO cm(-2) (NCO = -N=C=O), and absorbance of the isocyanate group and other chemical groups of the molecule were monitored over time. The ATR-FTIR findings showed that polymeric isocyanates pHDI and pIPDI may remain on the skin as unreacted species for many hours, with only 15-20% of the total isocyanate group disappearing in one hour, while smaller compounds octyl isocyanate and MDI rapidly disappear from the skin surface (80+% in 30 min). Isocyanates most likely leave the skin surface by diffusion predominantly, with minimal reaction with surface proteins. The significance of these findings and their implications for dermal exposure sampling and isocyanate skin decontamination are discussed.

Urinary Hexane Diamine to Assess Respiratory Exposure to Hexamethylene Diisocyanate Aerosol: A Human Inhalation Study

Abstract The use of urinary hexane diamine (HDA) as a biomarker to assess human respiratory exposure to hexamethylene diisocyanate (HDI) aerosol was evaluated. Twenty-three auto body shop workers were exposed to HDI biuret aerosol for two hours using a closed exposure apparatus. HDI exposures were quantified using both a direct-reading instrument and a treated-filter method. Urine samples collected at baseline, immediately post exposure, and every four to five hours for up to 20 hours were analyzed for HDA using gas chromatography and mass spectrometry. Mean urinary HDA (μg/ g creatinine) sharply increased from the baseline value of 0.7 to 18.1 immediately post exposure and decreased rapidly to 4.7, 1.9 and 1.1, respectively, at 4,9, and 18 hours post exposure. Considerable individual variability was found. Urinary HDA can assess acute respiratory exposure to HDI aerosol, but may have limited use as a biomarker of exposure in the workplace.

Field Comparison of Impingers and Treated Filters for Sampling of Total Aliphatic Isocyanates with the MAP Reagent

Results of a comparative field study on the performance of 25-mm inhalable samplers (Institute of Occupational Medicine [IOM]) and midget impingers for the collection of total isocyanates in air using the 1-(9-anthracenylmethyl)piperazine (MAP) reagent are presented. Air sampling and analysis was performed according to the National Institute for Occupational Safety and Health MAP draft method 5525. Midget impingers filled with 15 mL of 1 x 10(-4) M MAP in butyl benzoate were operated at 1 L/min. IOM cassettes loaded with 25-mm quartz fiber filters impregnated with 500 microg MAP, were operated at 2 L/min. Filters were field extracted with 10 mL of 1 x 10(-4) M MAP in acetonitrile. Thirty-four impinger-IOM pairs were collected in three autobody shops during spray painting tasks. Regression analysis [Ln (IOM) = 1.0 Ln (impinger), R2 = 0.98] and a paired t-test (Pr > 0.9) demonstrated that impingers and IOMs perform equally in their collection efficiency for the monomer and total oligomeric hexamethylene diisocyanate (HDI). IOM performance did not deteriorate at longer sampling times compared with the impinger performance. Within-sampler variability was calculated from the individual coefficients of variation (CV) of the 17 pairs of like samplers. The mean of CVs (SD)% for the monomer and total oligomeric HDI was approximately 12 (12)% and 15 (13)% for the IOM and the impinger sampler, respectively. Poor correlation (Pearson correlation coefficient < 0.3) and statistically nonsignificant differences (P > 0.74 two-sided) were found for the between-sampler CVs. Factors that might have influenced the observed sampler agreement are also discussed. It is concluded that MAP impregnated filters can be successfully used for sampling of slow curing total aliphatic isocyanates in air.

Skin Exposure to Aliphatic Polyisocyanates in the Auto Body Repair and Refinishing Industry: III. A Personal Exposure Algorithm

OBJECTIVES Isocyanate skin exposure may play an important role in sensitization and the development of isocyanate asthma, but such exposures are frequently intermittent and difficult to assess. Exposure metrics are needed to better estimate isocyanate skin exposures. The goal of this study was to develop a semiquantitative algorithm to estimate personal skin exposures in auto body shop workers using task-based skin exposure data and daily work diaries. The relationship between skin and respiratory exposure metrics was also evaluated. METHODS The development and results of respiratory exposure metrics were previously reported. Using the task-based data obtained with a colorimetric skin exposure indicator and a daily work diary, we developed a skin exposure algorithm to estimate a skin exposure index (SEI) for each worker. This algorithm considered the type of personal protective equipment (PPE) used, the percentage of skin area covered by PPE and skin exposures without and underneath the PPE. The SEI was summed across the day (daily SEI) and survey week (weekly average SEI) for each worker, compared among the job title categories and also compared with the respiratory exposure metrics. RESULTS A total of 893 person-days was calculated for 232 workers (49 painters, 118 technicians and 65 office workers) from 33 auto body shops. The median (10th-90th percentile, maximum) daily SEI was 0 (0-0, 1.0), 0 (0-1.9, 4.8) and 1.6 (0-3.5, 6.1) and weekly average SEI was 0 (0-0.0, 0.7), 0.3 (0-1.6, 4.2) and 1.9 (0.4-3.0, 3.6) for office workers, technicians and painters, respectively, which were significantly different (P < 0.0001). The median (10th-90th percentile, maximum) daily SEI was 0 (0-2.4, 6.1) and weekly average SEI was 0.2 (0-2.3, 4.2) for all workers. A relatively weak positive Spearman correlation was found between daily SEI and time-weighted average (TWA) respiratory exposure metrics (microg NCO m(-3)) (r = 0.380, n = 893, P < 0.0001) and between weekly SEI and TWA respiratory exposure metrics (r = 0.482, n = 232, P < 0.0001). CONCLUSIONS The skin exposure algorithm developed in this study provides task-based personal daily and weekly average skin exposure indices that are adjusted for the use of PPE. These skin exposure indices can be used to assess isocyanate exposure-response relationships.