Metabolites of a tobacco-specific lung carcinogen in the urine of elementary school-aged children.

Limited data are available in the literature on carcinogen uptake by children exposed to environmental tobacco smoke (ETS). In this study, we quantified metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the urine of elementary school-aged children participating in the School Health Initiative: Environment, Learning, Disease study, a school-based investigation of the environmental health of children. The metabolites of NNK are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc). We also measured cotinine and its glucuronide (total cotinine). Urine samples were collected from 204 children. Seventy (34.3%) of these had total cotinine > or =5 ng/ml. NNAL or NNAL-Gluc was detected in 52 of 54 samples with total cotinine > or =5 ng/ml and in 10 of 20 samples with total cotinine < 5 ng/ml. Levels of NNAL plus NNAL-Gluc and total cotinine were significantly higher when exposure to ETS was reported than when no exposure was reported. However, even when no exposure to ETS was reported, levels of NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc were higher than in children with documented low exposure to ETS, as determined by cotinine levels < 5 ng/ml. Levels of NNAL, NNAL-Gluc, and cotinine were not significantly different in samples collected twice from the same children at 3-month intervals. Levels of NNAL plus NNAL-Gluc in this study were comparable with those observed in our previous field studies of adults exposed to ETS. There was a 93-fold range of NNAL plus NNAL-Gluc values in the exposed children. The results of this study demonstrate widespread and considerable uptake of the tobacco-specific lung carcinogen NNK in this group of elementary school-aged children, raising important questions about potential health risks. Our data indicate that objective biomarkers of carcinogen uptake are important in studies of childhood exposure to ETS and cancer later in life.

Abraham Lincoln's blue pills. Did our 16th president suffer from mercury poisoning?

It is well known that Abraham Lincoln took a medicine called "blue mass" or "blue pill," commonly prescribed in the 19th century. What is now hardly known is that the main ingredient of blue mass was finely dispersed elemental mercury. As his friends understood, mercury was often prescribed for melancholy or "hypochondriasis," a condition Lincoln famously endured. Mercury in the form of the blue pill is a potential neurotoxin, which we have demonstrated by recreating and testing the recipe. We present the testimony of many of Lincoln's contemporaries to suggest that Lincoln suffered the neurobehavioural consequences of mercury intoxication but, perhaps crucial to history, before the main years of his presidency; he was astute enough to recognize the effects and stop the medication soon after his inauguration.

A school-based strategy to assess children's environmental exposures and related health effects in economically disadvantaged urban neighborhoods.

The School Health Initiative: Environment, Learning, Disease (SHIELD) study is a novel school-based investigation of children's environmental health in economically disadvantaged urban neighborhoods of Minneapolis. This article describes the study design and summarizes lessons learned about recruiting and monitoring this historically understudied population. The SHIELD study focused on measuring children's exposures to multiple environmental stressors [volatile organic chemicals (VOCs), environmental tobacco smoke, allergens, bioaerosols, metals, pesticides, polychlorinated biphenyls (PCB), phthalates] and exploring related effects on respiratory health (e.g., lung function) and learning outcomes (e.g., standardized test scores, academic achievement). It involved intensive exposure monitoring, including environmental measurements inside and outside the children's schools and inside their homes, personal measurements with passive dosimeters worn by the children, and biological marker measurements in blood and urine. The SHIELD participants comprised a stratified random sample of 153 "index" children and 51 of their siblings enrolled in grades 2-5 at two adjacent elementary schools. The Minneapolis Public Schools (MPS) assisted with identifying, contacting, recruiting, and monitoring this population, which traditionally is difficult to study because families/children are highly mobile, speak a diversity of languages, frequently do not have a telephone, endure economic hardships, often do not trust researchers, and have a spectrum of unconventional lifestyles and living arrangements. Using a school-based approach, the overall SHIELD enrollment (response) rate was 56.7%, with a wide disparity between English-speaking (41.7%) and non-English-speaking (71.0%) families/children. Most children remained involved in the study through both monitoring sessions and exhibited an acceptable degree of compliance with study protocols, including providing blood and urine samples. Results indicate that it is both practical and affordable to conduct probability-based exposure studies in this population, but that it is also important to improve our understanding of factors (e.g., cultural, economic, psychological, social) affecting the willingness of families/children to participate in such studies, with special emphasis on developing cost-effective recruitment methods.

Respiratory health of automobile workers exposed to metal-working fluid aerosols: respiratory symptoms.

A total of 1,811 automobile workers at three General Motors facilities were evaluated by questionnaire for possible respiratory effects resulting from airborne exposures to metal-working fluids (MWF): 1,042 currently worked as machinists and were exposed to one of three types of MWF aerosols (straight mineral oils, soluble oil emulsions, or water-based synthetic fluids that contained no oils); 769 assembly workers, without direct exposure, served as an internal reference group (of these, 239 had never worked as machinists). Symptoms of usual cough, usual phlegm, wheezing, chest tightness, and breathlessness, as well as physician-diagnosed asthma, and chronic bronchitis were the primary outcomes examined. Machinists as a whole had higher prevalence of cough, phlegm, wheezing, and breathlessness than that of assembly workers. Adjusting for confounding, phlegm and wheeze were associated with increasing levels of current exposure to straight oils; cough, phlegm, wheeze, chest tightness, and chronic bronchitis were associated with increasing levels of current exposure to synthetics. In models that included both past and current exposure, only current exposures to straight and synthetic fluids were associated with current symptoms.

A strategy to reduce healthy worker effect in a cross-sectional study of asthma and metalworking fluids.

This report describes the reanalysis of a cross-sectional study of asthma in a large cohort of autoworkers with exposure to metalworking fluids (MWF). There is strong evidence from case reports, clinical studies, and medical surveillance data that exposure to MWF can cause asthma, yet no association was found in the original analysis. The central hypothesis of the reanalysis was that the absence of an association between asthma and MWF exposure was the result of bias caused by the self-selection of asthmatics out of exposed jobs. We addressed the potential job transfer bias by redefining exposure and disease status at the time of asthma onset, rather than at the time of the health survey. This permitted us to treat the cross-sectional study as if it were a historical cohort study, despite the fact that the population was a biased sample of the full cohort. This approach resulted in a significantly elevated incidence rate ratio of 3.2 (95% CI: 1.2-8.3) for synthetic MWF estimated in a Cox proportional hazards model. Although the cross-sectional design makes it impossible to document or control for differential selection out of the workforce, the approach described here provides a strategy for reducing the healthy-worker effect due to job transfer bias in cross-sectional studies.

Lessons learned and unsolved public health problems after large-scale disasters.

BACKGROUND: This paper examines the considerable medical and psychological problems that ensue after disasters in which massive populations are affected for extended and sometimes unknown time periods. The organization of disaster response teams after large-scale disasters is based on experiences as a medical specialist at Chernobyl immediately after this catastrophe. Optimal ways of dealing with the immediate medical and logistical demands as well as long-term public health problems are explored with a particular focus on radiation disasters. Other lessons learned from Chernobyl are explained. ISSUES: Current concerns involve the constant threat of a disaster posed by aging nuclear facilities and nuclear and chemical disarmament activities. The strategies that have been used by various groups in responding to a disaster and dealing with medical and psychological health effects at different disaster stages are evaluated. The emergence of specialized centers in the former Soviet Union to study long-term health effects after radiation accidents are described. Worldwide, there has been relatively little attention paid to mid- and long-term health effects, particularly the psychological stress effects. Problems in conducting longitudinal health research are explored. RECOMMENDATIONS: The use of a mobile diagnostic and continuously operating pre-hospital triage system for rapid health screening of large populations at different stages after a large-scale disaster is advisable. The functional systems of the body to be observed at different stages after a radiation disaster are specified. There is a particularly strong need for continued medical and psychosocial evaluation of radiation-exposed populations over an extended time and a need for international collaboration among investigators.

Exposures to inhalable and "total" oil mist aerosol by metal machining shop workers.

Several recent studies have compared worker personal aerosol exposures as measured by the current method with those obtained by a new approach based on collecting the inhalable fraction, intended to represent all the particles that are capable of entering through the nose and/or mouth during breathing. The present study investigated this relationship for a metal machining facility where aerosols were generated from severely refined, nonaqueous ("straight") cutting oils used during the lathe working of metal rod stock. Workers (n = 23) wore two personal aerosol samplers simulataneously, one of the 37-mm type (for "total" aerosol exposure, E37) and the other of the Institute of Occupational Medicine (IOM) type (for inhalable aerosol exposure, EIOM). The data were analyzed by weighted least squares linear regression to determine the coefficient S in the relation EIOM = S.E37. It was found that S = 2.96 +/- 0.60. This ratio-in which exposure to inhalable aerosol was greater than to "total" aerosol-is consistent with previous observations in other industries. The relative coarsenss of the oil mist aerosol, as estimated by cascade impactor measurements, probably explains the difference between the sampling methods. The collection of large "splash" droplets, may also contribute. Future occupational aerosol standards for metalworking fluids will be based on the new, health-related criteria, and exposures will be assessed on the basis of the inhalable fraction. Results of studies like that described here will enable assessment of the impact on future workplace aerosol exposure assessments of introducing new standards.

Size-selective pulmonary dose indices for metal-working fluid aerosols in machining and grinding operations in the automobile manufacturing industry.

The current metal-working fluid exposures at three locations that manufacture automotive parts were assessed in conjunction with epidemiological studies of the mortality and respiratory morbidity experiences of workers at these plants. A rationale is presented for selecting and characterizing epidemiologic exposure groups in this environment. More than 475 full-shift personal aerosol samples were taken using a two-stage personal cascade impactor with median size cut-offs of 9.8 microns and 3.5 microns, plus a backup filter. For a sample of 403 workers exposed to aerosols of machining or grinding fluids, the mean total exposure was 706 micrograms/m3 (standard error (SE) = 21 micrograms/m3). Among 72 assemblers unexposed to machining fluids, the mean total exposure was 187 +/- 10 (SE) micrograms/m3. An analysis of variance model identified factors significantly associated with exposure level and permitted estimates of exposure for workers in the unsampled machine type/metal-working fluid groups. Comparison of the results obtained from personal impactor samples with predictions from an aerosol-deposition model for the human respiratory tract showed high correlation. However, the amount collected on the impactor stage underestimates extrathoracic deposition and overestimates tracheobronchial and alveolar deposition, as calculated by the deposition model. When both the impactor concentration and the deposition-model concentration were used to estimate cumulative thoracic concentrations for the worklives of a subset of auto workers, there was no significant difference in the rank order of the subjects' cumulative concentration. However, the cumulative impactor concentration values were significantly higher than the cumulative deposition-model concentration values for the subjects.

Environmental endotoxin measurement: the Kinetic Limulus Assay with Resistant-parallel-line Estimation.

A Limulus assay method was specifically designed for environmental endotoxin aerosols. Application of new statistical and sample preparation methods strengthened the validity and precision of the Limulus test. Statistically, the Kinetic Limulus Assay with Resistant-parallel-line Estimation (KLARE) differed from conventional analytic methods (as used in chromogenic assays and other kinetic methods) by routinely using a dilution series of the unknown sample as well as the standard to compute potency and an estimate of variance for each sample. Analysis of dose-response slopes for the standard and unknowns detected inhibition and enhancement effects--without multiple assay. Concentration-dependent interference and a more complex, concentration-independent interference with the Limulus assay were detected. Resistant regression and a standardized data analysis corrected for concentration-dependent interference. Sample preparation in a buffer eliminated concentration-independent interference and, thus, improved both the validity and the precision of potency measurements. The utility of a sample buffer and of parallel-line analysis, with both turbidimetric and chromogenic lysates, was demonstrated by assay of three control standard LPS and reference LPS (EC5). The limit of detection for endotoxin was less than 1 pg/ml in buffer. Samples containing greater than or equal to 10 pg/ml were measured with a coefficient of variation of approximately 6% in a single assay. Reproducibility of potency estimates for four samples over 3 days was compared on the basis of standard errors of the mean. The conventional method gave on average a CV of 65% while the resistant-parallel-line method gave, on average, a CV of 6%. Also, the conventional method failed to detect interference and, thus, included data from invalid assays. Conventional analysis of environmental aerosol samples was highly sensitive to the choice of dilution factor causing as much as 1000% variation in the result. By contrast, KLARE results changed by at most 30% with similar changes in initial dilution because KLARE was able to detect, and correct for, the influence of interferant compounds.

Toxicity of intratracheally instilled cotton dust, cellulose, and endotoxin.

Cotton dust includes respirable particles containing endotoxin and elastase, agents associated with emphysema. To examine whether a respirable fraction of cotton dust could produce emphysema in an animal model, we intratracheally instilled hamsters with respirable cotton dust particles (0.75 mg/100-g animal), mass median aerodynamic diameter less than or equal to 4.8 microns, twice weekly for 6 wk. We also examined whether instilled endotoxin (255 micrograms/100-g animal) could produce emphysema in hamsters and whether cellulose (0.75 mg/100-g animal) is an appropriate inert comparison dust. A saline-instilled group was the control. Hamsters were killed 8 wk after the last instillation. Static pressure-volume deflation curves of air-filled excised lungs were analyzed to measure lung distensibility. Lungs were fixed in inflation using glutaraldehyde and were examined morphometrically to obtain surface area and numbers of granulomata. Endotoxin-treated animals had increased distensibility, reduced surface-to-volume (S/V) ratio, and morphologically apparent mild centrilobular emphysema. Cellulose-treated animals had decreased distensibility, normal S/V ratio, and significant numbers of granulomata with patchy areas of thickened interalveolar septa. Cotton-dust-instilled animals had normal distensibility, reduced S/V ratio, significant numbers of granulomata, and mild centrilobular emphysema. These data suggest that cotton dust produces a significant parenchymal lesion with elements similar to both the emphysematous response to endotoxin and the fibrotic nodular response to cellulose.

Endotoxin measurement: aerosol sampling and application of a new Limulus method.

A new Limulus test was designed specifically for measuring endotoxin in environmental aerosols. The new Limulus method has a detection limit for airborne endotoxin of 2.2 pg (NP-1 activity)/m3 and can precisely quantitate aerosols containing 14 or more pg/m3 from samples representing 6.5 m3 of air. Aerosols in the range 100 to 500 pg/m3 were measured with 95% confidence of +/- 32% and an aerosol of 10 pg/m3 with 95% confidence of +/- 50%. Qualitative information about airborne endotoxin was also obtained from the assay. A wide variety of filter media were found to inactivate lipopolysaccharide in solution. This implies that airborne endotoxin can be measured only relative to the conditions of a particular study and that comparison of endotoxin aerosol measurements made under different circumstances are invalid. The research and policy implications of this observation are discussed. The need for improved collection and extraction methods notwithstanding, it was proposed that a buffered, parallel-line Limulus assay method be adopted as the standard method for measuring environmental endotoxin. The kinetic-turbidimetric Limulus assay with resistant-parallel-line estimates (KLARE), rate response method, should be considered a prime candidate for the standard method because of its precision, sensitivity, resistance to interference by pH, internal validation of estimates, and ability to provide qualitative as well as quantitative information about airborne endotoxin.

Investigation of reports of sexual dysfunction among male chemical workers manufacturing stilbene derivatives.

A Health Hazard Evaluation was conducted by the National Institute for Occupational Safety and Health in an area of a large chemical plant that manufactured the stilbene derivative 4,4'-diaminostilbene-2,2'-disulfonic acid, an intermediate used for the production of optical brightening agents. Men employed in the area reported problems with impotence. The study population consisted of 44 men aged 20-57 years (mean age 37) employed in the area at the time of the evaluation. An industrial hygiene investigation, health and work history questionnaire survey, physical examinations, and blood chemistry and serum hormone evaluation were conducted. Fourteen percent of the men reported symptoms of impotence over the preceding 6 or more months, 7% had potency problems of shorter duration, and 7% were not currently impotent but had experienced impotence for 6 or more months in the past; 36% experienced decreased libido, all since beginning work in the production area. Low levels of serum testosterone (less than 350 ng/dl) were observed in 37% of the men. The low serum testosterone concentrations were not accounted for fully by diurnal variation or an effect of rotating shift work. It is suggested that exposures to chemicals possessing estrogenic activity may be related to the observed health effects in these workers.

Evaluation of the ATS respiratory diseases questionnaire among French-speaking silicon carbide workers.

The American Thoracic Society (ATS) respiratory disease questionnaire for adults was translated by two fluently bilingual Quebec health professionals into simple, everyday French easily understood by an adult population of varying age and educational background. After independent assessment by professional translators, it was field-tested on 165 silicon carbide production workers. Responses to the ATS cough questions were significantly related to those obtained by a semiquantitative estimate of cough frequency. ATS questions on cough and phlegm were significantly associated with the physical sign of productive cough on request. A significant association was found between answers to questions on mild or moderate breathlessness and self-evaluation of breathing on a linear scale. Workers with cough, wheeze, or breathlessness had significantly lower percent-predicted FEV1, and FEV1 decreased as the severity of breathlessness increased. Highly significant, dose-dependent associations with current cigarette smoking habit were found for cough, phlegm and wheeze. Significant, dose-dependent associations with phlegm, wheeze and mild breathlessness also occurred with exposure to sulfur dioxide. All of these relationships are similar to findings from studies of English-speaking populations. Minor problems with the original English ATS questionnaire were discovered on translation, and suggestions for improvements were made. Preliminary experience with this French translation suggests that it is a useful, comparable version of the English ATS questionnaire.

Work related decrement in pulmonary function in silicon carbide production workers.

The relation between pulmonary function, cigarette smoking, and exposure to mixed respirable dust containing silicon carbide (SiC), hydrocarbons, and small quantities of quartz, cristobalite, and graphite was evaluated in 156SiC production workers using linear regression models on the difference between measured and predicted FEV1 and FVC. Workers had an average of 16 (range 2-41) years of employment and 9.5 (range 0.6-39.7) mg-year/m3 cumulative respirable dust exposure; average dust exposure while employed was 0.63 (range 0.18-1.42) mg/m3. Occasional, low level (less than or equal to 1.5 ppm) sulphur dioxide (SO2) exposure also occurred. Significant decrements in FEV1 (8.2 ml; p less than 0.03) and FVC (9.4 ml; p less than 0.01) were related to each year of employment for the entire group. Never smokers lost 17.8 ml (p less than 0.02) of FEV1 and 17.0 (p less than 0.05) of FVC a year, whereas corresponding decrements of 9.1 ml (p = 0.12) in FEV1 and 14.4 ml (p less than 0.02) in FVC were found in current smokers. Similar losses in FEV1 and FVC were related to each mg-year/m3 of cumulative dust exposure for 138 workers with complete exposure information; these findings, however, were generally not significant owing to the smaller cohort and greater variability in this exposure measure. Never smokers had large decrements in FEV1 (40.7 ml; p less than 0.02) and FVC (32.9 ml; p = 0.08) per mg-year/m3 of cumulative dust exposure and non-significant decrements were found in current smokers (FEV1: -7.1 ml; FVC: -11.7 ml). A non-significant decrement in lung function was also related to average dust exposure while employed. No changes were associated with SO(2) exposure or and SO(2) dust interaction. These findings suggest that employment in SiC production is associated with an excessive decrement in pulmonary function and that current permissible exposure limits for dusts occurring in this industry may not adequately protect workers from developing chronic pulmonary disease.

Respiratory symptoms associated with low level sulphur dioxide exposure in silicon carbide production workers.

Relations between pulmonary symptoms and exposure to respirable dust and sulphur dioxide (SO2) were evaluated for 145 silicon carbide (SiC) production workers with an average of 13.9 (range 3-41) years of experience in this industry. Eight hour time weighted average exposures to SO2 were 1.5 ppm or less with momentary peaks up to 4 ppm. Cumulative SO2 exposure averaged 1.94 (range 0.02-19.5) ppm-years. Low level respirable dust exposures also occurred (0.63 +/- 0.26 mg/m3). After adjusting for age and current smoking status in multiple logistic regression models, highly significant, positive, dose dependent relations were found between cumulative and average exposure to SO2, and symptoms of usual and chronic phlegm, usual and chronic wheeze, and mild exertional dyspnoea. Mild and moderate dyspnoea were also associated with most recent exposure to SO2. Cough was not associated with SO2. No pulmonary symptoms were associated with exposure to respirable dust nor were any symptoms attributable to an interaction between dust and SO2. Cigarette smoking was strongly associated with cough, phlegm, and wheezing, but not dyspnoea. A greater than additive (synergistic) effect between smoking and exposure to SO2 was present for most symptoms. These findings suggest that long term, variable exposure to SO2 at 1.5 ppm or less was associated with significantly raised rates of phlegm, wheezing, and mild dyspnoea in SiC production workers, and that current threshold limits for SO2 may not adequately protect workers in this industry.

Acute pulmonary responses among automobile workers exposed to aerosols of machining fluids.

Previous investigations of workers exposed to machining fluids have shown increased rates of cough and phlegm and have shown that these exposures may cause occupational asthma. To examine acute responses to these agents, cross-shift lung function changes related to machining fluid aerosols among 89 machine operators at two factories producing automobile parts were measured and compared with the findings for 42 unexposed assembly workers studied similarly at the same factories. Workers wore a personal air-sampling device on a Monday and Friday of a working week, and spirometry was performed before and after the work shifts on both days. On Mondays, a 5% or greater decrease in the forced expiratory volume in 1-second (FEV1), regarded as an "FEV1-response," occurred in 23.6% of the machinists and in only 9.5% of the assembly workers (relative risk = 2.5, p less than .05). After adjusting statistically for a history of childhood asthma, for smoking prior to lung function testing, and for race, odds ratios for an FEV1-response of 4.4 among workers exposed to aerosols of straight mineral oils, 5.8 for oil emulsions, and 6.9 for synthetic fluids were found. The FEV1-responses on Fridays were similar to those on Mondays. There was no progressive decline in FEV1 over the work week. Personal air samples, collected with a two-stage impactor, allowed aerosol masses to be measured in three size fractions: less than 3.5 microns, 3.5-9.8 microns, and greater than 9.8 microns aerodynamic diameter. Exposure levels to each type of machining fluid were remarkably similar within each size fraction and for total aerosol levels. Total aerosol concentrations for assembly workers ranged from 0.07 to 0.44 mg/M3, and for machinists from 0.16 to 2.03 mg/m3. Inhalable particle (less than or equal to 9.8 microns) levels were derived from the sum of the air concentrations in the two smallest-size fractions, and significant cross-shift decrements in FEV1 on Mondays and Fridays were associated with inhalable aerosol levels greater than 0.20 mg/m3. These findings show that acute airflow obstruction is associated with exposures to aerosols of various machining fluids and that airway responses occur well below current recommended exposure limits.