Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure.

OBJECTIVES: Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. METHODS: A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940-2002), a revised cadmium (Cd) exposure matrix and improved work history information. RESULTS: Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure-response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m(3) Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20-25 years. CONCLUSIONS: These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 µg/m(3) Cd.

Update of the NIOSH life table analysis system: a person-years analysis program for the windows computing environment.

BACKGROUND: Person-years analysis is a fundamental tool of occupational epidemiology. A life table analysis system (LTAS), previously developed by the National Institute for Occupational Safety and Health, was limited by its platform and analysis and reporting capabilities. We describe the updating of LTAS for the Windows operating system (LTAS.NET) with improved properties. SOFTWARE DEVELOPMENT PROCESS: A group of epidemiologists, programmers, and statisticians developed software, platform, and computing requirements. Statistical methods include the use of (indirectly) standardized mortality ratios, (directly) standardized rate ratios, confidence intervals, and P values based on the normal approximation and exact Poisson methods, and a trend estimator for linear exposure-response associations. SOFTWARE FEATURES: We show examples using LTAS.NET to stratify and analyze multiple fixed and time-dependent variables. Data import, stratification, and reporting options are highly flexible. Users may export stratified data for Poisson regression modeling. CONCLUSIONS: LTAS.NET incorporates improvements that will facilitate more complex person-years analysis of occupational cohort data.

Cohort mortality study of workers at seven beryllium processing plants: update and associations with cumulative and maximum exposure.

OBJECTIVES: To extend follow-up of cause-specific mortality in workers at seven beryllium processing plants and to estimate associations between mortality risk and beryllium exposure. METHODS: 9199 workers were followed for mortality from 1940 through 2005. Standardised mortality ratios (SMRs) were estimated based on US population comparisons for lung, nervous system and urinary tract cancers, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and categories containing chronic beryllium disease (CBD) and cor pulmonale. Associations with maximum and cumulative exposure were calculated for a subset of the workers. RESULTS: Overall mortality in the cohort compared with the US population was elevated for lung cancer (SMR 1.17; 95% CI 1.08 to 1.28), COPD (SMR 1.23; 95% CI 1.13 to 1.32), and the categories containing CBD (SMR 7.80; 95% CI 6.26 to 9.60) and cor pulmonale (SMR 1.17; 95% CI 1.08 to 1.26). Mortality rates for most diseases of interest increased with time-since-hire. For the category including CBD, rates were substantially elevated compared to the US population across all exposure groups. Workers whose maximum beryllium exposure was ≥ 10 µg/m(3) had higher rates of lung cancer, urinary tract cancer, COPD and the category containing cor pulmonale than workers with lower exposure. Significant positive trends with cumulative exposure were observed for nervous system cancers (p = 0.0006) and, when short-term workers were excluded, lung cancer (p = 0.01), urinary tract cancer (p = 0.003) and COPD (p < 0.0001). CONCLUSION: These findings reaffirm that lung cancer and CBD, and suggest that COPD and nervous system and urinary tract cancers, are related to beryllium exposure. Cigarette smoking and exposure to other lung carcinogens are unlikely to explain these elevations.

Risk of lung cancer associated with quantitative beryllium exposure metrics within an occupational cohort.

OBJECTIVES: Beryllium has been identified as a human carcinogen on the basis of animal and epidemiological studies. The authors recently reported updated associations between lung cancer and beryllium exposure in a large, pooled occupational cohort. The authors conducted the present study to evaluate the shape of exposure-response associations between different exposure metrics and lung cancer in this cohort, considering potential confounders (race, plant, professional and short-term work status, and exposure to other lung carcinogens). METHODS: The authors conducted Cox proportional hazards regression analyses of lung cancer risk with cumulative, mean and maximum 'daily weighted average' (DWA) exposure among 5436 workers, using age-based risk sets. Different exposure-response curves were fitted to the exposure metrics, including categorical, power, restricted cubic spline and piecewise log-linear fits. RESULTS: The authors found significant positive associations between lung cancer and mean (p < 0.0001) and maximum (p < 0.0001) exposure, adjusting for age, birth cohort and plant, and for cumulative (p = 0.0017) beryllium exposure, adjusting for these factors plus short-term work status and exposure to asbestos. The best-fitting models were generally categorical or piecewise log-linear, with the steepest increase in lung cancer risk between 0 and 10 µg/m(3) for both mean and maximum DWA exposure and between 0 and 200 µg/m(3)-days for cumulative DWA exposure. The estimated mean DWA beryllium exposure associated with 10(-3) excess lifetime risk based on the piecewise log-linear model is 0.033 µg/m(3). CONCLUSION: This study provides evidence that lung cancer risk is elevated at levels near the current US Occupational Safety and Health Administration beryllium exposure limit of 2.0 µg/m(3) DWA for workers.

Mortality and end-stage renal disease incidence among dry cleaning workers.

OBJECTIVE: Perchloroethylene (PCE) is a known animal carcinogen and probable human carcinogen. Dry cleaning exposures, particularly PCE, are also associated with renal toxicity. The objective was to follow-up a cohort of dry cleaners to evaluate mortality and assess end-stage renal disease (ESRD) morbidity. METHODS: This study adds 8 years of mortality follow-up for 1704 dry cleaning workers in four cities. Employees eligible for inclusion worked for ≥1 year before 1960 in a shop using PCE as the primary solvent. Life table analyses for mortality and ESRD morbidity were conducted. Only employees alive on 1 January 1977 were included in ESRD analyses. RESULTS: Overall cancer deaths were in significant excess in this cohort (standardised mortality ratio (SMR) 1.22, 95% CI 1.09 to 1.36). Oesophageal, lung and tongue cancers had significant excesses of deaths. Oesophageal cancer risk was highest among those employed in a PCE-using shop for ≥5 years with ≥20 years' latency since first such employment. Deaths from non-malignant underlying diseases of the stomach and duodenum were in significant excess. Hypertensive ESRD morbidity was significantly elevated in the entire cohort (standardised incidence ratio (SIR) 1.98, 95% CI 1.11 to 3.27), and among workers employed only in PCE-using dry cleaning shops for ≥5 years. CONCLUSION: Employment in the dry cleaning industry and occupational exposure to PCE are associated with an increased risk for ESRD and for cancer at several sites. The employment duration findings for oesophageal cancer and hypertensive ESRD further support an association with PCE exposure instead of lifestyle or socioeconomic factors.

Mortality among members of a truck driver trade association.

Previous studies report that truck drivers are at increased risk for illness and on-the-job mortality. It is unknown whether owner-operator truck drivers face the same risks as employee drivers, yet few studies have targeted owner-operators as a study population. This study examined the overall and cause-specific mortality ratios for a cohort with owner-operator truck drivers constituting 69% of the study population. Of the 26 major disease classifications and 92 specific causes of death examined, only mortality due to transportation accidents was significantly elevated (standardized mortality ratio=1.52, 95% confidence interval=1.36-1.70). Leading causes of death were ischemic heart disease and lung cancer, although risk was below that of the general population. Transportation accidents pose a particular hazard for members of the trade association. The absence of excess disease mortality deserves careful interpretation, and may be due to both a strong healthy worker effect and a short monitoring period.

Bromide and N-acetyl-S-(n-propyl)-L-cysteine in urine from workers exposed to 1-bromopropane solvents from vapor degreasing or adhesive manufacturing.

OBJECTIVES: 1-Bromopropane (1-BP) is an alternative for ozone depleting and other solvents; it is used in aerosol products, adhesives, and cleaning solvents. There is concern that 1-BP may be a reproductive and neurological toxicant. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving debromination. The main objectives were to evaluate urinary bromide [Br(-)] and N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys) for assessing 1-BP exposure in workers with low exposure. METHODS: Workers' 1-BP exposures were measured in their breathing zones with gas chromatography-flame ionization detection via NIOSH 1025. Urine specimens were obtained over a 48-h period at five facilities using vapor degreasers and one adhesive manufacturer. All of the workers' urine was collected into composite samples and analyzed separately representing daily time intervals: at work, after work but before bedtime, and upon awakening. Urinary metabolites were analyzed using intra-coupled plasma-mass spectroscopy for Br(-), and high-performance liquid chromatography and electro-spray ionization mass spectroscopy for AcPrCys. RESULTS: Time-weighted average (TWA) geometric mean (GM) breathing zone concentrations of 1-BP at vapor degreasing facilities were 2.6 and 0.31 ppm, respectively, for workers near degreasers and those remote from degreasers. Urine metabolites showed the same trend as TWA exposures: higher levels were observed for workers near degreasers (48-h GM Br(-) = 8.9 vs. 3.7; 48-h GM AcPrCys = 1.3 vs. 0.12, respectively). Associations of Br(-) and AcPrCys concentrations with 1-BP TWA were statistically significant near degreasers (p < 0.01). CONCLUSIONS: This study shows that urinary Br(-) and AcPrCys are useful biomarkers of workers' 1-BP exposures using analyses sensitive enough to measure low exposure jobs.

High dietary antioxidant intakes are associated with decreased chromosome translocation frequency in airline pilots.

BACKGROUND: Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited. OBJECTIVE: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots. DESIGN: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders. RESULTS: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, beta-carotene, beta-cryptoxanthin, and lutein-zeaxanthin from food (P < 0.05). Translocation frequency was not associated with the intake of vitamin E, alpha-carotene, or lycopene from food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for > or =median compared with or =median compared with

N-acetyl-S-(n-propyl)-l-cysteine in urine from workers exposed to 1-bromopropane in foam cushion spray adhesives.

1-Bromopropane (1-BP) has been marketed as an alternative for ozone depleting and other solvents; it is used in aerosol products, adhesives, metal, precision, and electronics cleaning solvents. Mechanisms of toxicity of 1-BP are not fully understood, but it may be a neurological and reproductive toxicant. Sparse exposure information prompted this study using 1-BP air sampling and urinary metabolites. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving debromination. Research objectives were to evaluate the utility of urinary N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys) for assessing exposure to 1-BP and compare it to urinary bromide [Br((-))] previously reported for these workers. Forty-eight-hour urine specimens were obtained from 30 workers at two factories where 1-BP spray adhesives were used to construct polyurethane foam seat cushions. Urine specimens were also obtained from 21 unexposed control subjects. All the workers' urine was collected into composite samples representing three time intervals: at work, after work but before bedtime, and upon awakening. Time-weighted average (TWA) geometric mean breathing zone concentrations were 92.4 and 10.5 p.p.m. for spraying and non-spraying jobs, respectively. Urinary AcPrCys showed the same trend as TWA exposures to 1-BP: higher levels were observed for sprayers. Associations of AcPrCys concentrations, adjusted for creatinine, with 1-BP TWA exposure were statistically significant for both sprayers (P < 0.05) and non-sprayers (P < 0.01). Spearman correlation coefficients for AcPrCys and Br((-)) analyses determined from the same urine specimens were highly correlated (P < 0.0001). This study confirms that urinary AcPrCys is an important 1-BP metabolite and an effective biomarker for highly exposed foam cushion workers.

Ethnic, racial, and gender variations in health among farm operators in the United States.

PURPOSE: The purpose of this study was to collect baseline prevalence data on the health problems faced by minority, white, and female farm operators. METHODS: An occupational health survey of farm operators was conducted by the U.S. Department of Agriculture, National Agricultural Statistics Service between February and August 2000. A stratified random sample of farm operators from 50 U.S. states based on the 1997 Census of Agriculture was selected for telephone interview. Interviews were primarily conducted using a computer assisted telephone instrument system. RESULTS: Population prevalences were calculated for 7137 farm operators. Prevalences were greatest for musculoskeletal discomfort, followed by respiratory problems, hearing loss, and hypertension. Generally, Latino and Asian American operators had lower prevalences for health problems than white non-Latino and white operators, respectively. African-American operators had greater prevalences for hypertension, and osteoarthritis, but lower prevalences for hearing loss, skin problems, heart problems, and cancer than white operators. American Indian or Alaska Native operators had higher prevalences for musculoskeletal problems, skin problems, and hypertension. CONCLUSIONS: Prevalences for the different ethnicity and race groups are not the same. Studies that combine racial and ethnic groups, or study only white and non-Latino farm operators may overestimate or underestimate the prevalence of health conditions in the entire farm operator population.

Race, occupation, and lung cancer: detecting disparities with death certificate data.

OBJECTIVES: To determine whether the analysis of death certificate data would reveal the same relationship among race, occupational exposure, and lung cancer mortality observed by a large cohort study. METHODS: An occupation-specific mortality odds ratio (MOR) for lung cancer (ICD-162) versus all other causes was calculated for 218,341 black men and white men who had been employed in the metal industries. RESULTS: Black men were at increased risk for lung cancer mortality when compared with white men among the 4668 oven workers (MOR = 1.38, 95% CI = 1.10 to 1.73), but not among the 33,605 white-collar workers (MOR = 0.95, 95% CI = 0.74 to 1.23). CONCLUSIONS: Our findings corroborate a previously demonstrated association among exposure to carcinogenic coke oven emissions, race, and lung cancer mortality, and support the use of death certificate data to help identify occupations with racial disparities in lung cancer mortality.

DNA adducts in granulocytes of hospital workers exposed to ethylene oxide.

BACKGROUND: Ethylene oxide (EtO), an important industrial chemical intermediate and sterilant, is classified as a human carcinogen. Occupational EtO exposure in many countries is regulated at 1 ppm (8-hr TWA), but levels of EtO-DNA adducts in humans with low occupational EtO exposures have not been reported. METHODS: We examined the formation of N7-(2'-hydroxyethyl)guanine (N7-HEG), a major DNA adduct of EtO, in 58 EtO-exposed sterilizer operators and six nonexposed workers from ten hospitals. N7-HEG was quantified in granulocyte DNA (0.1-11.5 microg) by a highly sensitive and specific gas chromatography-electron capture-mass spectrometry method. Cumulative exposure to EtO (ppm-hour) was estimated during the 4-month period before the collection of blood samples. RESULTS: There was considerable inter-individual variability in the levels of N7-HEG with a range of 1.6-241.3 adducts/10(7) nucleotides. The mean levels in the nonexposed, low (< or =32 ppm-hour), and high (>32 ppm-hour) EtO-exposure groups were 3.8, 16.3, and 20.3 adducts/10(7) nucleotides, respectively, after the adjustment for cigarette smoking and other potential confounders, but the differences were not statistically significant. CONCLUSIONS: This study has demonstrated for the first time, detectable levels of N7-HEG adducts in granulocytes of hospital workers with EtO exposures at levels less than the current U.S. standard of 1 ppm (8-hr TWA). A nonsignificant increase in adduct levels with increasing EtO exposure indicates that further studies of EtO-exposed workers are needed to clarify the relationship between EtO exposure and N7-HEG adduct formation.