Exposure‒response relationships for silicosis and its progression in industrial sand workers.

Objectives This study aimed to characterize the relationship between radiographic silicosis and exposure to respirable quartz and determine how exposure affects disease progression. Methods Surveillance chest radiographs from a cohort of 1902 workers were examined to identify 67 cases of radiographic silicosis and 167 matched controls. Exposures were estimated by linking work histories to a job exposure matrix (JEM) based on samples collected by the participating companies and historical estimates. Conditional logistic regression was used to examine exposure‒response relationships. Sequential radiographs from silicosis cases were used to assess associations between exposure and disease progression. Results Risk of silicosis increased with cumulative exposure [odds ratio (OR) 1.43 per 1 mg/m 3years, 95% confidence interval (CI) 1.23-1.66], average exposure concentration (OR 1.30 per 0.10 mg/m 3, 95% CI 1.11-1.51) and net exposure duration (OR 1.10 per year, 95% CI 1.05-1.16). Multivariate analyses indicated that the risk associated with cumulative exposure varied depending on exposure duration and concentration. Analysis of the time worked at differing exposure levels indicated that exposures ≤0.05 mg/m 3were not significantly associated with silicosis risk after adjustment for years worked at higher concentrations. Disease progression was related to subsequent exposure concentration, with a yearly increase in small opacity profusion of 0.052 subcategory per each 0.10 mg/m 3increase in concentration. Conclusions Workers with longer exposure at lower concentrations were at higher risk for silicosis than those with the same cumulative exposure who worked for a shorter time at higher concentrations. The rate of silicosis progression was related to subsequent exposure concentration.

Retrospective Assessment of Respirable Quartz Exposure for a Silicosis Study of the Industrial Sand Industry.

Background: In 2016, the OSHA PEL for crystalline silica was reduced, renewing interest in evaluating risk of silicosis from occupational exposures. The industrial sand industry, which deals with high-purity quartz sands, is the setting for a current epidemiologic investigation of silicosis risk and progression. In support of that investigation, respirable quartz (RQ) exposures were retrospectively estimated for 67 workers with silicosis and 167 matched control workers from 21 industrial sand plants, in which some started work as early as 1929. Methods: A job exposure matrix (JEM) was constructed by integrating a modern (post-1970) RQ exposure database containing more than 40000 measurements with archival particle count exposure data from a 1947 survey. A simulation algorithm was used to develop a conversion factor to convert the archival particle count data into modern measures of RQ by randomly generating 100000 virtual dust particles of varying diameters corresponding to the size distributions of 14 archival particle size distribution samples. The equivalent respirable mass and particle counts of the virtual particles were calculated, totalled, and ratioed to derive the conversion factor. The JEM was integrated with individual job histories to calculate average and cumulative exposure for each case and control. Multiple exposure estimates were derived for unprotected exposures as well as for exposures adjusted for estimated respiratory protective equipment use and efficiency. Results: The mean of the count to respirable mass conversion factors derived from 14 archival particle size samples was 157 µg m-3 per mppcf (SD: 42; range: 96-263) with no statistical difference across process areas (drying, screening, vibrating, binning, bulk loading, bagging), P = 0.29. The JEM demonstrated an industry-wide decrease in prevailing exposures to RQ of up to about 2 orders of magnitude from the distant (1929) to the recent (2012) past. Unadjusted cumulative exposures for cases and controls were statistically different (P < 0.001) with respective medians (range) of 3764 µg m-3 year (221-25121) and 1595 µg m-3 year (0-16446). Adjustment of exposure for use of respiratory protection showed modest reductions in estimated exposure: median adjusted cumulative exposures assuming a protection factor of 5 were 86% and 77% of the unadjusted values for cases and controls, respectively. Conclusions: The industrial sand industry offers a unique setting for examination of silicosis risk because of the high silica content of industrial sand and a long history of radiographic silicosis surveillance of industry workers. However, the great majority of silicosis cases in this industry are found among former workers and are associated with exposures occurring in the distant past, which necessitates extensive retrospective exposure assessment and increases the likelihood of exposure misclassification. Nonetheless, the estimated cumulative exposures for silicosis cases and controls in this work were significantly different, with the median cumulative exposure for cases being more than twice that of their matched controls.

Cigarette smoke represses the innate immune response to asbestos.

Both cigarette smoke (CS) and asbestos cause lung inflammation and lung cancer, and at high asbestos exposure levels, populations exposed to both of these carcinogens display a synergistic increase in the development of lung cancer. The mechanisms through which these two toxic agents interact to promote lung tumorigenesis are poorly understood. Here, we begin to dissect the inflammatory signals induced by asbestos in combination with CS using a rodent inhalation model and in vitro cell culture. Wild-type C57BL/6 mice were exposed to room air as a control, CS, and/or asbestos (4 days per week to CS and 1 day per week to asbestos for 5 weeks). Bronchoalveolar lavage (BAL) fluid was collected following exposure and analyzed for inflammatory mediators. Asbestos-exposed mice displayed an increased innate immune response consistent with NLRP3 inflammasome activation. Compared to mice exposed only to asbestos, animals coexposed to CS + asbestos displayed attenuated levels of innate immune mediators and altered inflammatory cell recruitment. Histopathological changes in CS + asbestos-exposed mice correlated with attenuated fibroproliferative lesion development relative to their counterparts exposed only to asbestos. In vitro experiments using a human monocyte cell line (THP-1 cells) supported the in vivo results in that coexposure to cigarette smoke extract repressed NLRP3 inflammasome markers in cells treated with asbestos. These observations indicate that CS represses central components of the innate immune response to inhaled asbestos.

A comparison of two laboratories for the measurement of wood dust using button sampler and diffuse reflection infrared Fourier-transform spectroscopy (DRIFTS).

The current measurement method for occupational exposure to wood dust is by gravimetric analysis and is thus non-specific. In this work, diffuse reflection infrared Fourier transform spectroscopy (DRIFTS) for the analysis of only the wood component of dust was further evaluated by analysis of the same samples between two laboratories. Field samples were collected from six wood product factories using 25-mm glass fiber filters with the Button aerosol sampler. Gravimetric mass was determined in one laboratory by weighing the filters before and after aerosol collection. Diffuse reflection mid-infrared spectra were obtained from the wood dust on the filter which is placed on a motorized stage inside the spectrometer. The metric used for the DRIFTS analysis was the intensity of the carbonyl band in cellulose and hemicellulose at ~1735 cm(-1). Calibration curves were constructed separately in both laboratories using the same sets of prepared filters from the inhalable sampling fraction of red oak, southern yellow pine, and western red cedar in the range of 0.125-4 mg of wood dust. Using the same procedure in both laboratories to build the calibration curve and analyze the field samples, 62.3% of the samples measured within 25% of the average result with a mean difference between the laboratories of 18.5%. Some observations are included as to how the calibration and analysis can be improved. In particular, determining the wood type on each sample to allow matching to the most appropriate calibration increases the apparent proportion of wood dust in the sample and this likely provides more realistic DRIFTS results.

Exposures to thoracic particulate matter, endotoxin, and glucan during post-Hurricane Katrina restoration work, New Orleans 2005-2012.

In the aftermath of Hurricane Katrina, which devastated the city of New Orleans in August 2005, restoration workers were at risk for respiratory illness from exposure to airborne particles and microbial agents. In support of an epidemiologic investigation of this risk, an exposure assessment for restoration work activities (demolition, trash & debris management, landscape restoration, sewer/waterline repair, and mold remediation) was performed from 2005 to 2012. For 2005 and 2006, Occupational Safety and Health Administration (OSHA) data (n = 730) for personal and area monitoring of total and respirable dust exposures of restoration workers were accessed and analyzed. The most significant exposures were for demolition work, with average respirable dust exposures in 2005 above the action level of 2.5 mg/m(3) and 17.6% of exposures exceeding the permissible exposure limit (PEL) (5 mg/m(3)). Additional personal and area monitoring for thoracic particulate matter was performed from 2007 to 2012 (n = 774) and samples were assayed for endotoxin and (1→3, 1→6)-ß-D-glucan (n = 202). In order to integrate the OSHA data with the later monitoring data, three independent predictive models were developed to convert total and respirable dust measures into the equivalent thoracic dust. The three models were not statistically different and the modeling results were in good agreement with an overall coefficient of variation of 16% for the thoracic dust means across work activities estimated by each of the three models. Overall, thoracic dust exposure levels decreased by about an order of magnitude within the first year after Katrina and then more gradually declined and stabilized through 2012. Estimated average exposures to endotoxin and microbial glucan in 2005 were as high as 256 EU/m(3) and 118 µg/m(3), respectively, and likewise were seen to decrease dramatically and stabilize after 2005. The results of this exposure assessment support previously published reports of respiratory illness including sinusitis, toxic pneumonitis, and Katrina Cough among restoration workers in the years immediately after the hurricane.

Determination of airborne wood dust in Button samples by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS).

Emerging concerns regarding the toxicity of inhaled wood dust support the need for techniques to quantitate wood content of mixed industrial dusts. The diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) analysis technique was applied to the determination of wood content of 181 inhalable dust samples (geometric mean concentration: 0.895 mg/m(3); geometric standard deviation: 2.73) collected from six wood product industry factories using 25mm glass fibre filters with the Button aerosol sampler. Prior to direct DRIFTS analysis the filter samples were treated with ethyl acetate and re-deposited uniformly. Standards ranging from 125 µg to 4000 µg were prepared for red oak, southern yellow pine, and red cedar and used for quantitation of samples depending upon the wood materials present at a given factory. The oak standards spectra were quantitated by linear regression of response in Kubelka-Munk units at 1736 cm(-1), whereas the pine standards and the cedar standards spectra were quantitated by polynomial regression of response in log 1/R units at 1734 cm(-1), with the selected wavenumbers corresponding to stretching vibration of free C=O from cellulose and hemicelluloses. For one factory which used both soft- and hardwoods, a separate polynomial standard curve was created by proportionally combining the oak and pine standards polynomial regression equations based on response (log 1/R) at 1734 cm(-1). The analytical limits of detection were approximately 52 µg of oak, 20 µg of pine, 30 µg of cedar, and 16 µg of mixed oak and pine for the factory with mixed woods. Overall, the average of dry wood dust percentage of inhalable dust was approximately 56% and the average dry wood dust weight was 0.572mg for the Button samples. Across factories, there were statistically significant differences (p<0.001) for the percentage of dry wood dust in inhalable dust with factory averages ranging from 33.5 to 97.6%.

Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram.

Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228-270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery.

Respiratory health effects associated with restoration work in post-Hurricane Katrina New Orleans.

BACKGROUND: This study examines prevalence of respiratory conditions in New Orleans-area restoration workers after Hurricane Katrina. METHODS: Between 2007 and 2010, spirometry and respiratory health and occupational questionnaire were administered to 791 New Orleans-area adults who mostly worked in the building construction and maintenance trades or custodial services. The associations between restoration work hours and lung function and prevalence of respiratory symptoms were examined by multiple linear regression, χ², or multiple logistic regression. RESULTS: 74% of participants performed post-Katrina restoration work (median time: 620 hours). Symptoms reported include episodes of transient fever/cough (29%), sinus symptoms (48%), pneumonia (3.7%), and new onset asthma (4.5%). Prevalence rate ratios for post-Katrina sinus symptoms (PRR = 1.3; CI: 1.1, 1.7) and fever and cough (PRR = 1.7; CI: 1.3, 2.4) were significantly elevated overall for those who did restoration work and prevalence increased with restoration work hours. Prevalence rate ratios with restoration work were also elevated for new onset asthma (PRR = 2.2; CI: 0.8, 6.2) and pneumonia (PRR = 1.3; CI: 0.5, 3.2) but were not statistically significant. Overall, lung function was slightly depressed but was not significantly different between those with and without restoration work exposure. CONCLUSIONS: Post-Katrina restoration work is associated with moderate adverse effects on respiratory health, including sinusitis and toxic pneumonitis.

Wood dust sampling: field evaluation of personal samplers when large particles are present.

Recent recommendations for wood dust sampling include sampling according to the inhalable convention of International Organization for Standardization (ISO) 7708 (1995) Air quality--particle size fraction definitions for health-related sampling. However, a specific sampling device is not mandated, and while several samplers have laboratory performance approaching theoretical for an 'inhalable' sampler, the best choice of sampler for wood dust is not clear. A side-by-side field study was considered the most practical test of samplers as laboratory performance tests consider overall performance based on a wider range of particle sizes than are commonly encountered in the wood products industry. Seven companies in the wood products industry of the Southeast USA (MS, KY, AL, and WV) participated in this study. The products included hardwood flooring, engineered hardwood flooring, door skins, shutter blinds, kitchen cabinets, plywood, and veneer. The samplers selected were 37-mm closed-face cassette with ACCU-CAP™, Button, CIP10-I, GSP, and Institute of Occupational Medicine. Approximately 30 of each possible pairwise combination of samplers were collected as personal sample sets. Paired samplers of the same type were used to calculate environmental variance that was then used to determine the number of pairs of samples necessary to detect any difference at a specified level of confidence. Total valid sample number was 888 (444 valid pairs). The mass concentration of wood dust ranged from 0.02 to 195 mg m(-3). Geometric mean (geometric standard deviation) and arithmetic mean (standard deviation) of wood dust were 0.98 mg m(-3) (3.06) and 2.12 mg m(-3) (7.74), respectively. One percent of the samples exceeded 15 mg m(-3), 6% exceeded 5 mg m(-3), and 48% exceeded 1 mg m(-3). The number of collected pairs is generally appropriate to detect a 35% difference when outliers (negative mass loadings) are removed. Statistical evaluation of the nonsimilar sampler pair results produced a finding of no significant difference between any pairing of sampler type. A practical consideration for sampling in the USA is that the ACCU-CAP™ is similar to the sampler currently used by the Occupational Safety and Health Administration for purposes of demonstrating compliance with its permissible exposure limit for wood dust, which is the same as for Particles Not Otherwise Regulated, also known as inert dust or nuisance dust (Method PV2121).

Deviations from Haber's Law for multiple measures of acute lung injury in chlorine-exposed mice.

Chlorine gas is considered a chemical threat agent that can cause acute lung injury. Studies in the early 20th century on war gases led Haber to postulate that the dose of an inhaled chemical expressed as the product of gas concentration and exposure time leads to a constant toxicological effect (Haber's Law). In the present work, mice were exposed to a constant dose of chlorine (100 ppm-h) delivered using different combinations of concentration and time (800 ppm/7.5 min, 400 ppm/15 min, 200 ppm/30 min, and 100 ppm/60 min). Significant effects of exposure protocol on survival evaluated 6 h after exposure were observed, ranging from 0% for the 7.5-min exposure to 100% for the 30- and 60-min exposures. Multiple parameters indicative of lung injury were examined to determine if any aspects of lung injury were differentially affected by the exposure protocols. Most parameters (pulmonary edema, neutrophil influx, and levels of protein, immunoglobulin M, and the chemokine KC [Cxcl1] in lavage fluid) indicated that lung injury was most pronounced for the 15-min exposure and least for the 60-min exposure. In contrast, changes in pulmonary function at baseline and in response to inhaled methacholine were similar following the three exposure regimens. The results indicate that the extent of lung injury following chlorine inhalation depends not only on total dose but also on the specifics of exposure concentration and time, and they suggest that evaluation of countermeasures against chlorine-induced lung injury should be performed using multiple types of exposure scenarios.

Exposing animals to oxidant gases: nose only vs. whole body.

Inhalation experiments using laboratory animals are performed under controlled conditions to assess the toxicity of and to investigate interventional strategies to ameliorate injury resulting from oxidant gas exposures. A variety of dynamic inhalation exposure systems that use whole-body or nose-only exposure chambers have been developed for rodents. In a whole-body exposure chamber, the animals are immersed in the test atmosphere, whereas in nose-only or head-only exposure systems, exposures are localized primarily to the head and/or nasal regions. There are advantages and disadvantages with both types of exposure approaches. Considerations such as animal number, exposure duration, end points of study, and availability of test material should influence the selection of a particular exposure system.

Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation.

Inflammation is associated with various pulmonary diseases and contributes to the pathogenesis of acute lung injury. We previously identified a proinflammatory signaling pathway triggered by G protein-coupled receptors (GPCRs) in which stimulation of G(q)-coupled GPCRs results in activation of the transcription factor NF-kappaB. Because damage to the lung causes the release of multiple mediators acting through G(q)-coupled GPCRs, this signaling pathway is likely to contribute to inflammatory processes in the injured lung. In an effort to identify novel inhibitors of lung inflammation, the National Institutes of Health Clinical Collection, a library of 446 compounds, was screened for inhibitory activity toward production of IL-8 induced by stimulation of the G(q)-coupled tachykinin 1 receptor with substance P in A549 cells. Twenty-eight compounds that significantly inhibited substance P-induced IL-8 production were identified. The most potent inhibitor was triptolide, a diterpenoid compound from Tripterygium wilfordii Hook F, a vine used in traditional Chinese medicine for the treatment of autoimmune diseases. Triptolide inhibited IL-8 production induced by substance P with an IC(50) of 2.3 x 10(-8) M and inhibited NF-kappaB activation in response to an agonist of the protease-activated receptor 2 with an IC(50) of 1.4 x 10(-8) M. Anti-inflammatory effects of triptolide were assessed in vivo using a chlorine gas lung injury model in mice. Triptolide inhibited neutrophilic inflammation and the production of KC (Cxcl1) in the lungs of chlorine-exposed mice. The results demonstrate that triptolide exhibits anti-inflammatory activity in cultured lung cells and in an in vivo model of acute lung injury.

Acute lung injury induced by chlorine inhalation in C57BL/6 and FVB/N mice.

Humans may be exposed to chlorine gas via accidental or intentional release, and effective countermeasures for the resulting lung injury are lacking. To develop a model in which therapeutic measures could be evaluated, lung injury induced by chlorine inhalation in two inbred mouse strains was examined. C57BL/6 and FVB/N mice were exposed for 1.1 h to varying doses of chlorine (197-289 ppm-h) and were evaluated for indices of lung injury at different times after exposure (6-48 h). Chlorine induced increases in lung weight that were more evident in FVB/N mice than in C57BL/6 mice. Both strains exhibited sloughing of airway epithelium observed within 6 h after exposure. As judged by Ly-6G immunostaining, chlorine exposure caused widespread neutrophil influx into the lung parenchyma at 6 h followed by a clustering of neutrophils around damaged airways by 24 h. High levels of cellular proliferation revealed by Ki-67 staining were observed in airway epithelium 48 h after exposure. Lavage fluid parameters showed consistent trends in both strains. Lavage fluid protein content was elevated throughout the times examined. Lavage fluid neutrophils were significantly increased beginning 12 h after exposure and were highest at 48 h. The concentration of the neutrophil chemoattractant KC peaked 6 h after exposure and was near baseline by 48 h. In summary, chlorine inhalation resulted in lung injury characterized by edema, epithelial cell death, and neutrophilic inflammation in C57BL/6 and FVB/N mice. Characterization of such responses in these mice will allow testing of therapeutic agents to treat chlorine-induced lung injury.

Longitudinal respiratory health study of the wood processing industry.

BACKGROUND: A 5-year longitudinal study examined nonmalignant respiratory effects of wood processing dust exposure. METHODS: Ten study plants, investigator selected from 447 candidate plants, included 1 sawmill-planing-plywood, 1 plywood, 1 milling, 3 cabinet and 4 furniture facilities. Personal dust samples (2363) were divided into three size fractions (extrathoracic, tracheobronchial, and respirable) which were apportioned into wood solids (WS) and residual particulate matter (RPM), and used to compute each individuals TWA exposure for the 6 exposure types. Serial spirometric tests and medical, smoking and occupational questionnaires were collected with 1,164 subjects having adequate follow-up (minimum 3 datapoints over at least 2.5 years) for analyses. Forward selection regression was used to evaluate the effect of exposure on annual change in FEV(1), FVC, FEF(25-75), and FEV(1)/FVC. RESULTS: There were no significant adverse effects of WS exposures (overall means were 0.66, 0.32, and 0.05 mg/m(3), for extrathoracic, tracheobronchial, and respirable fractions, respectively). Statistically significant effects were only to respirable RPM in the milling facility (mean exposures of 0.147 mg/m(3) associated with changes in FEV(1) = -32 ml/year, FEV(1)/FVC = -0.48%/year, and FEF(25-75) = -0.11 l/s/year) and in the sawmill-planing-plywood facility (mean exposures of 0.255 mg/m(3) associated with changes in FEV(1) = -59 ml/year and FVC = -103 ml/year). CONCLUSION: Exposure to WS was not associated with significant adverse effects. Respirable RPM was associated with an obstructive effect in the milling facility, and respirable RPM was also associated with a restrictive effect in the sawmill-planing plywood facility. Finally, this study does not exclude the possibility that other exposures common to this industry can cause respiratory effects, only that none were noted in this population for wood solids for the exposure levels and durations studied.

Neuronal modulation of lung injury induced by polymeric hexamethylene diisocyanate in mice.

1,6-Hexamethylene diisocyanate biuret trimer (HDI-BT) is a nonvolatile isocyanate that is a component of polyurethane spray paints. HDI-BT is a potent irritant that when inhaled stimulates sensory nerves of the respiratory tract. The role of sensory nerves in modulating lung injury following inhalation of HDI-BT was assessed in genetically manipulated mice with altered innervation of the lung. Knockout mice with a mutation in the low-affinity nerve growth factor receptor (NGFR), which have decreased innervation by nociceptive nerve fibers, and transgenic mice expressing nerve growth factor (NGF) from the lung-specific Clara cell secretory protein (CCSP) promoter, which have increased innervation of the airways, were exposed to HDI-BT aerosol and evaluated at various times after exposure. NGFR knockout mice exhibited significantly more, and CCSP-NGF transgenic mice exhibited significantly less injury and inflammation compared with wild-type mice, indicative of a protective effect of nociceptive nerves on the lung following HDI-BT inhalation. Transgenic mice overexpressing the tachykinin 1 receptor (Tacr1) in lung epithelial cells also showed less severe injury and inflammation compared with wild-type mice after HDI-BT exposure, establishing a role for released tachykinins acting through Tacr1 in mediating at least part of the protective effect. Treatment of lung fragments from Tacr1 transgenic mice with the Tacr1 ligand substance P resulted in increased cAMP accumulation, suggesting this compound as a possible signaling mediator of protective effects on the lung following nociceptive nerve stimulation. The results indicate that sensory nerves acting through Tacr1 can exert protective or anti-inflammatory effects in the lung following isocyanate exposure.

On-filter determination of collected wood dust by diffuse reflectance infrared Fourier-transform spectroscopy (DRIFTS).

A new analytical technique based on DRIFTS spectroscopy has been developed for the specific and sensitive determination of size-fractionated wood dust from 37 mm glass fiber filter samples collected with the Respicon sampler. A translational diffuse reflectance apparatus was modified to accept filter samples by incorporating a special filter holder in the sample stage and a clockwork motor to drive the translational stage during infrared scanning, thus providing an average analysis across the filter face. Filter samples were pre-treated with ethyl acetate to uniformly redeposit dust onto the filter and extract potential chemical interferences. Two absorbance maxima (1251 and 1291 cm(-1)), corresponding to the cellulose content of the wood, were suitable for quantitation of wood dust. Analysis of seven species of wood at 1291 cm(-1) showed an equivalent quantitative response for all species except maple. The response at 1251 cm(-1) was more variable across species but more sensitive for the softwoods. There was a statistically significant effect of particle size on the analytical response, so that analytical standards should be matched to the samples in terms of particle size distribution. Analytical limit of detection was approximately 0.08 mg of wood dust per sample with overall precision of about 6%. Comparison of DRIFTS and gravimetric analyses of 51 pure wood dust samples ranging from about 0.2 to 2 mg yielded a slope of 1.08 and r2 equal to 0.9. Other particulate contaminants common in the industrial wood processing industry showed little or no interference with the determination of wood dust by this method.

Mortality from lung and kidney disease in a cohort of North American industrial sand workers: an update.

BACKGROUND: A previously published cohort study of some 2670 employees of the North American sand industry, followed through 1994, provided strong evidence of a causal relationship between quartz exposure and death from both silicosis and lung cancer, after allowance for cigarette smoking and in the absence of known occupational carcinogens. Unexpectedly, a significant excess mortality from chronic non-malignant renal disease [observed 16; expected 7.6; standardized mortality ratio (SMR) 212] was also found, whereas deaths from renal cancer at this stage were close to expectation (observed 6; expected 5.2). OBJECTIVES: Our primary aim was to discover whether death from chronic renal disease was related to the estimated intensity of crystalline silica exposure. A further aim was to determine whether or not our previous estimates of lung cancer and silicosis risk were confirmed by mortality in the cohort 6 years later. METHODS: With help from the US National Death Index, surviving members of the cohort, with the exception of employees of a small plant in Canada, were traced through 2000. The cause of death was determined for all who had died, for comparison against National and State mortality rates. Nested case-referent analyses were then undertaken, as previously, of deaths from lung cancer and silicosis, plus end-stage renal disease and kidney cancer, in relation to quantitative re-estimates of quartz exposure. RESULTS: The total number of deaths through 1994 was 990; there were 231 additional deaths during the period 1995-2000. The SMRs were significantly higher in the later than the earlier period, mainly due to a relative increase in heart disease and external causes. The updated odds ratios for lung cancer and silicosis were almost identical to those published previously, with lung cancer risk again related to average silica concentration and cumulative exposure, but not to length of employment. In contrast, risks of neither end-stage renal disease nor renal cancer were related to cumulative exposure, although now based on 19 cases (SMR 239), and 10 cases (SMR 202), respectively, in fact, opposite trends were apparent for both diseases. However, because of the small numbers there was only limited power to assess the statistical significance of these trends or of any separate relationship with the duration or intensity of exposure. CONCLUSIONS: Our findings support a causal relationship between lung cancer and quartz exposure after allowance for cigarette smoking, in the absence of other known carcinogens, but failed to find similar evidence to explain the excess mortality from either chronic renal disease or kidney cancer.

Spray-painting and chronic airways obstruction.

BACKGROUND: The aim was to investigate the respiratory response of HDI-based paint aerosol within the context of the protection afforded by current exposure guidelines. METHODS: A cross-sectional study of 240 painters spraying polyurethane enamels was undertaken at four aircraft maintenance plants. Questionnaire and spirometric data were related to gravimetric measures of cumulative total and respirable paint aerosol (TPA and RPA) and estimated isocyanate in total and respirable aerosols (TIA and RIA). RESULTS: Average cumulative exposures in mg/m(3)-years +/- SD were 159.0 +/- 115.2 TPA, 19.1 +/- 13.8 RPA, 15.8 +/- 11.5 TIA, and 1.9 +/- 1.4 RIA. After adjusting for smoking and asthma symptoms, higher exposures were associated with statistically significant reduction in expiratory flowrates. Significant smoking-related reductions were also observed, without exposure interactions. CONCLUSIONS: These results suggest important respiratory effects from exposures to spray paint aerosols at levels generally in compliance with existing standards for otherwise unregulated particulates and for the isocyanate component of the paint.

An HDI polyisocyanate aerosol exposure system for large-scale animal experiments.

An exposure system that allows large-scale exposure of animals to 1,6-hexamethylene diisocyanate (HDI)-based polyisocyanates at a stable concentration and aerosol size distribution was developed. The HDI polyisocyanate aerosol is generated by nebulizing a solution of a commercial polyisocyanate product dissolved in acetone. The aerosol is delivered with a constant airflow into a horizontal flow chamber. Complete mixing of aerosol in the chamber is ensured by a circulating fan. This method has been used to generate atmospheres containing HDI polyisocyanates at a concentration of 10.46+/-0.23 mg/m(3) over a 5-hour period. The overall mass median aerodynamic equivalent diameter was found to be 1.42 microm with a geometric standard deviation of 1.26. The HDI monomer concentration was 0.15+/-0.04 mg/m(3). The average chamber acetone concentration was determined to be 2481+/-222 ppm (mean+/-standard deviation). Different HDI polyisocyanate concentrations in the chamber can be achieved by altering the concentration of the commercial polyisocyanate product in acetone and the chamber flow rate. The described exposure system will be useful for performing toxicological studies involving HDI polyisocyanates.

Pulmonary toxicity of polymeric hexamethylene diisocyanate aerosols in mice.

The acute pulmonary response of male C57BL/6 mice exposed to respirable polymeric hexamethylene diisocyanate biuret trimer aerosol (HDI-BT), a component of polyurethane spray paints, was examined. Mice were exposed to concentrations of 1 and 10 mg/m(3) HDI-BT for 5 h and were evaluated 6, 18, 42, 90, 186, and 378 h after the end of exposure. Mice exposed to 1 or 10 mg/m(3) HDI-BT exhibited dose-dependent lung function impairment, edema, neutrophilic inflammation, cellular proliferation, and histologic lesions in terminal bronchioles and alveolar ducts. Impairment of pulmonary function, indicated by decreased frequency and increased enhanced pause (Penh), was maximal immediately after exposure and progressively recovered at later time points. Lung weight and lavage fluid protein content peaked at 6 and 18 h after exposure, respectively. Total cells and macrophages recovered in lavage fluid peaked 90 h after exposure. Neutrophils recovered in lavage fluid peaked between 18 and 42 h after exposure. Proliferative lesions, as identified histologically and by bromodeoxyuridine incorporation, were maximal 90 h after exposure. In contrast, no inflammatory cell influx, protein leakage, or lung pathology were observed in mice exposed to 360 ppb HDI monomer vapor. This model will be useful for investigating molecular mechanisms by which HDI-BT causes lung injury, which is known to occur in humans exposed occupationally to this pulmonary toxicant.