Case-control study of brain and other central nervous system cancer among workers at semiconductor and storage device manufacturing facilities.

OBJECTIVE: This study evaluated the relationship between brain and other central nervous system cancer ('CNS cancer') and exposures at two semiconductor and electronic module manufacturing facilities and at a storage device manufacturing facility. METHODS: The case-control study, nested in a cohort of 126 836 employees, compared 120 CNS cancer cases and 1028 matched controls with respect to employment in 10 process groups and estimated cumulative exposure to 31 known or possible carcinogens. RESULTS: CNS cancer was associated with module manufacturing operations at two facilities. Module manufacturing is a process that begins with production of ceramic substrates followed by attachment of completed semiconductor chips and metal-containing circuitry resulting in a high performing electronic device. Positive associations with the highest tertile of estimated cumulative exposure were found for several chemicals, including 2-butoxyethanol, cyclohexanone, ortho-dichlorobenzene, cadmium, molybdenum, trichloroethylene and vinyl chloride. CONCLUSIONS: Results suggested positive associations between CNS cancer and specific operations and chemicals experienced in the semiconductor and electronic module manufacturing industry. However, lack of external support for these findings precludes a causal interpretation, and the observed associations may have been due to chance.

Retrospective Exposure Assessment for Semiconductor and Storage Device Manufacturing Facilities.

OBJECTIVE: The aim of this study was to develop exposure estimates for a case-control study of central nervous system cancer in semiconductor and storage device manufacturing workers. METHODS: Over 700,000 records on sample measurements were obtained. Mean exposure intensity was estimated for 31 established/suspected carcinogens (agents of interest) in 10 primary exposure groups over three manufacturing eras. We assigned confidence ratings, based on number/type of measurements, to each estimate. RESULTS: Mean exposures decreased by an order of magnitude over the three manufacturing eras and were below applicable occupational exposure limits for 22 of 31 agents of interest. For 25 agents, at least 70% of the exposures were estimated with high confidence. CONCLUSION: This is the largest comprehensive study of exposures in the semiconductor/storage device industry and the first to include cumulative exposure estimates and measures of confidence in the exposure estimates.

A prospective cohort study of the association between drinking water arsenic exposure and self-reported maternal health symptoms during pregnancy in Bangladesh.

BACKGROUND: Arsenic, a common groundwater pollutant, is associated with adverse reproductive health but few studies have examined its effect on maternal health. METHODS: A prospective cohort was recruited in Bangladesh from 2008-2011 (N = 1,458). At enrollment (<16 weeks gestational age [WGA]), arsenic was measured in personal drinking water using inductively-coupled plasma mass spectrometry. Questionnaires collected health data at enrollment, at 28 WGA, and within one month of delivery. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CI) for self-reported health symptoms were estimated for each arsenic quartile using logistic regression. RESULTS: Overall, the mean concentration of arsenic was 38 µg/L (Standard deviation, 92.7 µg/L). A total of 795 women reported one or more of the following symptoms during pregnancy (cold/flu/infection, nausea/vomiting, abdominal cramping, headache, vaginal bleeding, or swollen ankles). Compared to participants exposed to the lowest quartile of arsenic (≤0.9 µg/L), the aOR for reporting any symptom during pregnancy was 0.62 (95% CI = 0.44-0.88) in the second quartile, 1.83 (95% CI = 1.25-2.69) in the third quartile, and 2.11 (95% CI = 1.42-3.13) in the fourth quartile where the mean arsenic concentration in each quartile was 1.5 µg/L, 12.0 µg/L and 144.7 µg/L, respectively. Upon examining individual symptoms, only nausea/vomiting and abdominal cramping showed consistent associations with arsenic exposure. The odds of self-reported nausea/vomiting was 0.98 (95% CI: 0.68, 1.41), 1.52 (95% CI: 1.05, 2.18), and 1.81 (95% CI: 1.26, 2.60) in the second, third and fourth quartile of arsenic relative to the lowest quartile after adjusting for age, body mass index, second-hand tobacco smoke exposure, educational status, parity, anemia, ferritin, medication usage, type of sanitation at home, and household income. A positive trend was also observed for abdominal cramping (P for trend <0.0001). A marginal negative association was observed between arsenic quartiles and odds of self-reported cold/flu/infection (P for trend = 0.08). No association was observed between arsenic and self-reported headache (P for trend = 0.19). CONCLUSION: Moderate exposure to arsenic contaminated drinking water early in pregnancy was associated with increased odds of experiencing nausea/vomiting and abdominal cramping. Preventing exposure to arsenic contaminated drinking water during pregnancy could improve maternal health.

A pathway-based analysis of urinary arsenic metabolites and skin lesions.

Inorganic arsenic is metabolized to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Limited evidence suggests that the ability to fully metabolize arsenic into DMA influences susceptibility to disease. To determine whether percentage of MMA was predictive of disease, the authors used data from a case-control study conducted in Bangladesh (2001-2003). Persons who were diagnosed with keratosis, melanosis, Bowen's disease, or squamous cell carcinoma were matched on age, sex, and village to persons without these conditions. This analysis was restricted to persons who had no missing data on covariates (859 cases, 868 controls). A path analysis was used to evaluate simultaneously the association between the percentage of all urinary arsenic metabolites and the odds of skin lesions using PROC CALIS in SAS, version 9.1 (SAS Institute, Inc., Cary, North Carolina) and Mplus, version 6.1 (Muthén & Muthén, Los Angeles, California). The odds of skin lesions were significantly associated with log(10) percentage of MMA (adjusted odds ratio (OR(adj)) = 1.56, 95% confidence interval (CI): 1.15, 2.12) but not log(10) percentage of inorganic arsenic (OR(adj) = 1.06, 95% CI: 0.75, 1.50) or log(10) percentage of DMA (OR(adj) = 1.07, 95% CI: 0.33, 3.46). This novel analysis confirmed that persons who excrete a higher proportion of MMA have a greater risk of skin lesions after data are adequately controlled for urinary arsenic metabolites, current arsenic exposure, and other risk factors.

Personal exposure, behavior, and work site conditions as determinants of blood lead among bridge painters.

Bridge painters are exposed to lead during several job tasks performed during the workday, such as sanding, scraping, and blasting. After the Occupational Safety and Health Administration standard was passed in 1993 to control lead exposures among construction workers including bridge painters, this study was conducted among 84 bridge painters in the New England area to determine the significant predictors of blood lead levels. Lead was measured in personal air and hand wipe samples that were collected during the 2-week study period and in blood samples that were collected at the beginning and at the end of the study period. The personal air and hand wipe data as well as personal behaviors (i.e., smoking, washing, wearing a respirator) and work site conditions were analyzed as potential determinants of blood lead levels using linear mixed effects models. Our results show that the mean air lead levels over the 2-week period were the most predictive exposure measure of blood lead levels. Other individual-level significant predictors of blood lead levels included months worked on bridge painting crews, education, and personal hygiene index. Of the site-level variables investigated, having a containment facility on site was a significant predictor of blood lead levels. Our results also indicate that hand wipe lead levels were significantly associated with higher blood lead levels at the end of the study period compared with the beginning of the study period. Similarly, smoking on site and respirator fit testing were significantly associated with higher blood lead levels at the end of the study period. This study shows that several individual-level and site-level factors are associated with blood lead levels among bridge painters, including lead exposure through inhalation and possible hand-to-mouth contact, personal behaviors such as smoking on site, respirator fit testing, and work site conditions such as the use of better containment facilities. Accordingly, reduction in blood lead levels among bridge painters can be achieved by improving these workplace practices.

Association between fine particulate matter and oxidative DNA damage may be modified in individuals with hypertension.

OBJECTIVE: To investigate the association between particulate matter (PM2.5) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in hypertensive and non-hypertensive individuals. METHODS: Twelve hypertensives and nine non-hypertensives were monitored during a 36-hour period using a repeated-measures panel study design. Personal exposure to PM2.5 was assessed using a real-time continuous monitor. Spot urine samples collected at 12-hour intervals were analyzed for 8-OHdG. RESULTS: Exposure to PM2.5 was associated with a decrease in 8-OHdG in hypertensives compared with an increase in non-hypertensives, after adjusting for age, gender, smoking status, and time of day. CONCLUSIONS: The results suggest modification of the association between PM2.5 exposure and urinary 8-OHdG by hypertension status. Antioxidant activity present in antihypertensive medications may play a role or PM2.5 exposure may reduce the capacity to repair DNA damage in hypertensives. These results should be confirmed with further investigation.

Beryllium sensitization and lung function among former workers at the Nevada Test Site.

BACKGROUND: Beryllium use at the Nevada Test Site (NTS) was not acknowledged until the late 1990's. Subsequently, the ongoing U.S. DOE funded medical screening program, which began in 1998, started testing former workers of the NTS for beryllium sensitization (BeS) in 2001 to identify individuals who may be at higher risk of developing chronic beryllium disease (CBD). METHODS: An observational study was conducted to identify work-related factors associated with the odds of having BeS. Work history questionnaires were administered and principal components analysis was used to identify categories of related tasks associated with BeS. RESULTS: Of the 1,786 former workers tested for BeS, 23 had a confirmed positive result. An increased risk of BeS was found among workers who performed cleanup (OR = 2.68, 95% CI: 1.10, 6.56) and those who worked in Building B where beryllium parts were machined (OR = 2.52, 95% CI: 1.02, 6.19), though no significant increased risk was found when categories of related tasks were used. Additionally, the number of years worked at the NTS was associated with increased risk of BeS. There was no difference in pulmonary function, chest X-ray abnormalities, or respiratory symptoms between those who were sensitized and normal. CONCLUSIONS: The prevalence of BeS among former workers of the NTS who participated in our screening program was 1.3%. Former workers who performed specific job tasks may be at greater risk of developing BeS.

A urinary metabolite of phenanthrene as a biomarker of polycyclic aromatic hydrocarbon metabolic activation in workers exposed to residual oil fly ash.

Residual oil fly ash is a chemically complex combustion product containing a significant component of potentially carcinogenic transition metals and polycyclic aromatic hydrocarbons (PAH). Various biomarkers of PAH exposure have been investigated previously, most notably 1-hydroxypyrene (1-OHP), in urine. In this study, we assessed the utility of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (trans, anti-PheT), a metabolite of phenanthrene, to detect occupational PAH exposure. Urine samples collected across the workweek were analyzed for 1-OHP and trans, anti-PheT in boilermakers (n = 20) exposed to residual oil fly ash. Median baseline urinary trans, anti-PheT concentrations were 0.50 microg/g creatinine in current tobacco smokers and 0.39 microg/g creatinine in nonsmokers. Median baseline urinary 1-OHP concentrations in smokers and nonsmokers were 0.31 and 0.13 microg/g creatinine, respectively. To study further the effect of smoking exposure on the urinary PAH markers, urinary cotinine was used. Although urinary trans, anti-PheT and 1-OHP concentrations were correlated (Spearman r = 0.63; P < 0.001) for all subjects, the regression coefficient between log-transformed trans, anti-PheT and log 1-OHP was statistically significant only for subjects with low levels of urinary cotinine or for nonsmokers. Each 1-unit increase in log 1-OHP was associated with a 0.77-unit increase (95% confidence interval, 0.45-1.09) in log trans, anti-PheT in subjects with low levels of urinary cotinine (P < 0.001). In these subjects, dichotomized occupational exposure status was a significant predictor of log trans, anti-PheT (P = 0.02) but not of log 1-OHP (P = 0.2). In conclusion, we found that urinary trans, anti-PheT was detected in levels comparable with 1-OHP in occupationally exposed workers, particularly nonsmokers. This study shows that urinary trans, anti-PheT may be an effective biomarker of uptake and metabolic activation of PAHs.