Estimating impacts of reducing acrylonitrile exposure on lung cancer mortality in an occupational cohort with the parametric g-formula.

OBJECTIVES: To inform the potential human carcinogenicity of acrylonitrile, we estimate associations between acrylonitrile exposures and lung cancer mortality in US workers with the objectives of (1) assessing potential for healthy worker survivor bias and (2) adjusting for this bias while assessing the expected lung cancer mortality under different hypothetical occupational exposure limits on acrylonitrile exposure using the parametric g-formula. METHODS: We used data from a cohort of 25 460 workers at facilities making or using acrylonitrile in the USA. We estimated HRs to quantify associations between employment and lung cancer mortality, and exposure and leaving employment. Using the parametric g-formula, we estimated cumulative lung cancer mortality at hypothetical limits on acrylonitrile exposure. RESULTS: Recent and current employment was associated with lung cancer, and exposure was associated with leaving employment, indicating potential for healthy worker survivor bias. Relative to no intervention, reducing the historical exposure under limits of 2.0, 1.0 and 0.45 parts per million would have been expected to reduce lung cancer mortality by age 90 by 4.46 (95% CI 0.78 to 8.15), 5.03 (95% CI 0.96 to 9.11) and 6.45 (95% CI 2.35 to 10.58) deaths per 1000 workers, respectively. A larger lung cancer mortality reduction would be expected under elimination of exposure: 7.21 (95% CI 2.72 to 11.70) deaths per 1000 workers. CONCLUSIONS: Healthy worker survivor bias likely led to underestimation of excess risk. Our results corroborate previous study findings of an excess hazard of lung cancer among the highest exposed workers.

Critical reviews of exposure assessment in carcinogenic hazard identification: the IARC Monographs experience.

OBJECTIVES: To summarise the rationale, workflow and recommendations for the conduct of exposure assessment critiques in key human studies evaluated for International Agency for Research on Cancer (IARC) Monographs on the Identification of Carcinogenic Hazards. METHODS: Approaches to evaluating exposure assessment quality in human cancer and mechanistic studies were reviewed according to the precepts outlined in the IARC Monographs Preamble, using two agents as case studies. Exposure assessment 'domains', that is, salient aspects of exposure assessment for the agent under evaluation, were selected for review across the key human studies. RESULTS: The case studies of night shift work (volume 124) and 1,1,1-trichloroethane (volume 130) used a common approach, tailored to the agents' specific exposure scenarios, to evaluate exposure assessment quality. Based on the experiences of IARC Working Groups to date, the implementation of exposure assessment critique requires the need for agent-specific knowledge, consideration of the validity of time-varying exposure metrics related to duration and intensity, and transparent, concise reviews that prioritise the most important strengths and limitations of exposure assessment methods used in human studies. CONCLUSIONS: Exposure assessment has not historically been a fully appreciated component for evaluating the quality of epidemiological studies in cancer hazard identification. Exposure assessment critique in key human cancer and mechanistic studies is now an integral part of IARC Monographs evaluations and its conduct will continue to evolve as new agents are evaluated. The approaches identified here should be considered as a potential framework by others when evaluating the exposure assessment component of epidemiological studies for systematic reviews.

Fine particulate matter and incident coronary heart disease events up to 10 years of follow-up among Deepwater Horizon oil spill workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, in-situ burning and flaring were conducted to remove oil from the water. Workers near combustion sites were potentially exposed to burning-related fine particulate matter (PM2.5). Exposure to PM2.5 has been linked to increased risk of coronary heart disease (CHD), but no study has examined the relationship among oil spill workers. OBJECTIVES: To investigate the association between estimated PM2.5 from burning/flaring of oil/gas and CHD risk among the DWH oil spill workers. METHODS: We included workers who participated in response and cleanup activities on the water during the DWH disaster (N = 9091). PM2.5 exposures were estimated using a job-exposure matrix that linked modelled PM2.5 concentrations to detailed DWH spill work histories provided by participants. We ascertained CHD events as the first self-reported physician-diagnosed CHD or a fatal CHD event that occurred after each worker's last day of burning exposure. We estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for the associations between categories of average or cumulative daily maximum PM2.5 exposure (versus a referent category of water workers not near controlled burning) and subsequent CHD. We assessed exposure-response trends by examining continuous exposure parameters in models. RESULTS: We observed increased CHD hazard among workers with higher levels of average daily maximum exposure (low vs. referent: HR = 1.26, 95% CI: 0.93, 1.70; high vs. referent: HR = 2.11, 95% CI: 1.08, 4.12; per 10 µg/m3 increase: HR = 1.10, 95% CI: 1.02, 1.19). We also observed suggestively elevated HRs among workers with higher cumulative daily maximum exposure (low vs. referent: HR = 1.19, 95% CI: 0.68, 2.08; medium vs. referent: HR = 1.38, 95% CI: 0.88, 2.16; high vs. referent: HR = 1.44, 95% CI: 0.96, 2.14; per 100 µg/m3-d increase: HR = 1.03, 95% CI: 1.00, 1.05). CONCLUSIONS: Among oil spill workers, exposure to PM2.5 from flaring/burning of oil/gas was associated with increased risk of CHD.

Exposure to volatile hydrocarbons and neurologic function among oil spill workers up to 6 years after the Deepwater Horizon disaster.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, oil spill response and cleanup (OSRC) workers were exposed to toxic volatile components of crude oil. Few studies have examined exposure to individual volatile hydrocarbon chemicals below occupational exposure limits in relation to neurologic function among OSRC workers. OBJECTIVES: To investigate the association of several spill-related chemicals (benzene, toluene, ethylbenzene, xylene, n-hexane, i.e., BTEX-H) and total petroleum hydrocarbons (THC) with neurologic function among DWH spill workers enrolled in the Gulf Long-term Follow-up Study. METHODS: Cumulative exposure to THC and BTEX-H across the oil spill cleanup period were estimated using a job-exposure matrix that linked air measurement data to detailed self-reported DWH OSRC work histories. We ascertained quantitative neurologic function data via a comprehensive test battery at a clinical examination that occurred 4-6 years after the DWH disaster. We used multivariable linear regression and modified Poisson regression to evaluate relationships of exposures (quartiles (Q)) with 4 neurologic function measures. We examined modification of the associations by age at enrollment (<50 vs. ≥50 years). RESULTS: We did not find evidence of adverse neurologic effects from crude oil exposures among the overall study population. However, among workers ≥50 years of age, several individual chemical exposures were associated with poorer vibrotactile acuity of the great toe, with statistically significant effects observed in Q3 or Q4 of exposures (range of log mean difference in Q4 across exposures: 0.13-0.26 µm). We also observed suggestive adverse associations among those ≥ age 50 years for tests of postural stability and single-leg stance, although most effect estimates did not reach thresholds of statistical significance (p < 0.05). CONCLUSIONS: Higher exposures to volatile components of crude oil were associated with modest deficits in neurologic function among OSRC workers who were age 50 years or older at study enrollment.

Lung function in oil spill responders 4-6 years after the Deepwater Horizon disaster.

Oil spill response and clean-up (OSRC) workers were exposed to hazardous airborne chemicals following the 2010 Deepwater Horizon disaster. The aim of this study was to evaluate lung function in workers 4-6 years following the disaster using a prospective cohort. Participants who completed two spirometry test sessions 1-3 years, and 4-6 years after the spill (N = 1,838) were included and forced expiratory volume in 1 s (FEV1; ml), forced vital capacity (FVC; ml), and ratio (FEV1/FVC; %) determined. Linear mixed models were utilized to estimate relationships between OSRC exposures and lung function 4-6 years after the spill and changes since the prior measurement. Despite suggestive reduced lung function at 1-3 years, at the  4-6-year exam workers with total hydrocarbon (THC) exposure 1-2.99 ppm and ≥3 ppm compared to those with ≤0.29 ppm exhibited higher FEV1 (ß: 108 ml, 95% CI: 17, 198) and (ß: 118 ml, 95% CI: 5, 232), respectively. Compared with support workers, those in higher exposed jobs displayed greater improvement in FEV1 between visits: cleanup on water (ß: 143 ml, 95% CI: 35, 250), operations (ß: 132 ml, 95% CI: 30, 234) and response (ß: 149 ml, 95% CI: 43, 256). Greater FEV1 improvement was also associated with higher versus the lowest level THC exposure: 1-2.99 ppm (ß: 134 ml, 95% CI: 57, 210) and ≥3 ppm (ß: 205 ml, 95% CI: 109, 301). Lung function decrements seen shortly after the spill were no longer apparent 4-6 years later, with the greatest improvement among those with the highest exposures.

Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile.

We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.

Exposure to Total Hydrocarbons During Cleanup of the Deepwater Horizon Oil Spill and Risk of Heart Attack Across 5 Years of Follow-up.

Exposure to total hydrocarbons (THC) and volatile organic compounds from air pollution is associated with risk of coronary heart disease. THC exposure from oil spills might be similarly associated, but no research has examined this. We assessed the relationship between THC exposure during the response and cleanup of the Deepwater Horizon oil spill (Gulf of Mexico) and heart attack risk among 24,375 oil spill workers enrolled in the Gulf Long-Term Follow-up Study. There were 312 first heart attacks (self-reported physician-diagnosed myocardial infarction, or fatal coronary heart disease) ascertained during the study period (2010-2016). THC exposures were estimated using a job-exposure matrix incorporating self-reported activities and personal air measurements. We used Cox proportional hazards regression to estimate hazard ratios, with inverse-probability weights to account for confounding and censoring. Maximum THC levels of ≥0.30 parts per million (ppm) were associated with heart attack risk, with a 1.8-fold risk for exposure of ≥3.00 ppm versus <0.30 ppm (hazard ratio = 1.81, 95% confidence interval: 1.11, 2.95). The risk difference for highest versus lowest THC level was 10 excess cases per 1,000 workers. This is the first study of the persistent health impacts of THC exposure during oil spill work, and results support increased protection against oil exposure during cleanup of future spills.

Extended Mortality Follow-up of a Cohort of Dry Cleaners.

BACKGROUND: Dry cleaning workers are commonly exposed to tetrachloroethylene, a suspected bladder carcinogen, and other organic solvents. The health risks associated with solvent exposures in this industry are unclear. METHODS: We extended mortality follow-up of 5,369 dry cleaning union members in St. Louis to further investigate solvent-related risks. We added 22 years of follow-up, from 1993 through 2014, via linkage to the National Death Index. Using Cox proportional hazards modeling, we computed hazard ratios (HRs) and 95% confidence intervals (CIs) relating cause-specific mortality with levels of a solvent exposure index previously developed by an industrial hygienist based on workers' job titles from union records. The models were fit adjusting for age, sex, and decade of union enrollment, and assuming different exposure lags. RESULTS: In internal analyses of estimated solvent exposure with a 20-year lag, we observed exposure-response relationships for bladder cancer (HR medium exposure = 4.2; 95% CI = 0.7, 24.5 and HR high exposure = 9.2; 95% CI = 1.1, 76.7 vs. no exposure; Ptrend = 0.08) and kidney cancer (HR = 4.1; 95% CI = 0.7, 22.5 and 24.4; 2.9, 201.6; Ptrend = 0.004). High exposure was also associated with heart disease (HR = 1.6; 95% CI = 1.1, 2.2) and lymphatic/hematopoietic malignancies (HR = 4.3; 95% CI = 1.4, 13.6). CONCLUSIONS: These findings are, to the best of our knowledge, the first cohort evidence relating solvent exposure levels among dry cleaners to elevated risks of selected cancers and heart disease. Additional studies employing solvent-specific exposure assessment are needed to clarify cancer risks associated with tetrachloroethylene.

Diesel Exhaust, Respirable Dust, and Ischemic Heart Disease: An Application of the Parametric g-formula.

BACKGROUND: Although general population studies of air pollution suggest that particulate matter-diesel exhaust emissions in particular-is a potential risk factor for cardiovascular disease, direct evidence from occupational cohorts using quantitative metrics of exposure is limited. In this study, we assess counterfactual risk of ischemic heart disease (IHD) mortality under hypothetical scenarios limiting exposure levels of diesel exhaust and of respirable mine/ore dust in the Diesel Exhaust in Miners Study cohort. METHODS: We analyzed data on 10,779 male miners from 8 nonmetal, noncoal mines-hired after diesel equipment was introduced in the respective facilities-and followed from 1948 to 1997, with 297 observed IHD deaths in this sample. We applied the parametric g-formula to assess risk under hypothetical scenarios with various limits for respirable elemental carbon (a surrogate for diesel exhaust), and respirable dust, separately and jointly. RESULTS: The risk ratio comparing the observed risk to cumulative IHD mortality risk at age 80 under a hypothetical scenario where exposures to elemental carbon and respirable dust are eliminated was 0.79 (95% confidence interval [CI]: 0.64, 0.97). The corresponding risk difference was -3.0% (95% CI: -5.7, -0.3). CONCLUSION: Our findings, based on data from a cohort of nonmetal miners, are consistent with the hypothesis that interventions to eliminate exposures to diesel exhaust and respirable dust would reduce IHD mortality risk.

Case-control investigation of occupational lead exposure and kidney cancer.

OBJECTIVES: Lead is a suspected carcinogen that has been inconsistently associated with kidney cancer. To clarify this relationship, we conducted an analysis of occupational lead exposure within a population-based study of kidney cancer using detailed exposure assessment methods. METHODS: Study participants (1217 cases and 1235 controls), enrolled between 2002 and 2007, provided information on their occupational histories and, for selected lead-related occupations, answered questions regarding workplace tasks, and use of protective equipment. Industrial hygienists used this information to develop several estimates of occupational lead exposure, including probability, duration and cumulative exposure. Unconditional logistic regression was used to compute ORs and 95% CIs for different exposure metrics, with unexposed subjects serving as the reference group. Analyses were also conducted stratifying on several factors, including for subjects of European ancestry only, single nucleotide polymorphisms in ALAD (rs1805313, rs1800435, rs8177796, rs2761016), a gene involved in lead toxicokinetics. RESULTS: In our study, cumulative occupational lead exposure was not associated with kidney cancer (OR 0.9, 95% CI 0.7 to 1.3 for highest quartile vs unexposed; ptrend=0.80). Other lead exposure metrics were similarly null. We observed no evidence of effect modification for the evaluated ALAD variants (subjects of European ancestry only, 662 cases and 561 controls) and most stratifying factors, although lead exposure was associated with increased risk among never smokers. CONCLUSIONS: The findings of this study do not offer clear support for an association between occupational lead exposure and kidney cancer.

Deepwater Horizon oil spill exposures and neurobehavioral function in GuLF study participants.

INTRODUCTION: The 2010 Deepwater Horizon (DWH) disaster exposed tens of thousands of oil spill response and cleanup (OSRC) workers to hydrocarbons and other hazardous chemicals. Some hydrocarbons, such as toluene and hexane, have been found to have acute adverse effects on the central nervous system in occupational settings. However, no studies have examined the association between oil spill exposures and neurobehavioral function. METHODS: We used data from the Gulf Long-term Follow-up Study, a cohort of adults who worked on the DWH response and cleanup. Total hydrocarbon (THC) exposure attributed to oil spill cleanup work was estimated from a job-exposure matrix linking air measurement data to detailed cleanup work histories. Participants were also categorized into 6 job categories, or OSRC classes, based on their activity with the highest exposure. Neurobehavioral performance was assessed at a clinical exam 4-6 years after the spill. We used multivariable linear regression to evaluate relationships of ordinal THC levels and OSRC classes with 16 neurobehavioral outcomes. RESULTS: We found limited evidence of associations between THC levels or OSRC classes and decreased neurobehavioral function, including attention, memory, and executive function. Workers exposed to ≥3 ppm THC scored significantly worse (difference1.0-2.9ppm = -0.39, 95% confidence interval (CI) = -0.74, -0.04) than workers exposed to <0.30 ppm THC for the digit span forward count test. There was also a possible threshold effect above 1 ppm THC for symbol digit test total errors (difference1.0-2.9ppm = -0.56 (95% CI = -1.13, -0.003), difference≥3.0ppm = -0.55 (95% CI = -1.20, 0.10)). Associations appeared to be stronger in men than in women. A summary latency measure suggested an association between more highly exposed jobs (especially support of operations workers) and decreased neurobehavioral function. CONCLUSION: OSRC-related exposures were associated with modest decreases in neurobehavioral function, especially attention, memory, and executive function.

Ischemic Heart Disease Mortality and Diesel Exhaust and Respirable Dust Exposure in the Diesel Exhaust in Miners Study.

Diesel exhaust is a suggested risk factor for ischemic heart disease (IHD), but evidence from cohorts using quantitative exposure metrics is limited. We examined the impact of respirable elemental carbon (REC), a key surrogate for diesel exhaust, and respirable dust (RD) on IHD mortality, using data from the Diesel Exhaust in Miners Study in the United States. Using data from a cohort of male workers followed from 1948-1968 until 1997, we fitted Cox proportional hazards models to estimate hazard ratios for IHD mortality for cumulative and average intensity of exposure to REC and RD. Segmented linear regression models allowed for nonmonotonicity. Hazard ratios for cumulative and average REC exposure declined relative to the lowest exposure category before increasing to 0.79 and 1.25, respectively, in the highest category. Relative to the category containing the segmented regression change points, hazard ratios for the highest category were 1.69 and 1.54 for cumulative and average REC exposure, respectively. Hazard ratios for RD exposure increased across the full exposure range to 1.33 and 2.69 for cumulative and average RD exposure, respectively. Tests for trend were statistically significant for cumulative REC exposure (above the change point) and for average RD exposure. Our findings suggest excess risk of IHD mortality in relation to increased exposure to REC and RD.

Lung Function in Oil Spill Response Workers 1-3 Years After the Deepwater Horizon Disaster.

BACKGROUND: Little is known about the effects of inhalation exposures on lung function among workers involved in the mitigation of oil spills. Our objective was to determine the relationship between oil spill response work and lung function 1-3 years after the Deepwater Horizon (DWH) disaster. METHODS: We evaluated spirometry for 7,775 adults living in the Gulf states who either participated in DWH response efforts (workers) or received safety training but were not hired (nonworkers). At an enrollment interview, we collected detailed work histories including information on potential exposure to dispersants and burning oil/gas. We assessed forced expiratory volume in 1 second (FEV1; mL), forced vital capacity (FVC; mL), and the ratio (FEV1/FVC%) for differences by broad job classes and exposure to dispersants or burning oil/gas using multivariable linear and modified Poisson regression. RESULTS: We found no differences between workers and nonworkers. Among workers, we observed a small decrement in FEV1 (Beta, -71 mL; 95% confidence interval [CI], -127 to -14) in decontamination workers compared with support workers. Workers with high potential exposure to burning oil/gas had reduced lung function compared with unexposed workers: FEV1 (Beta, -183 mL; 95% CI, -316 to -49) and FEV1/FVC (Beta, -1.93%; 95% CI, -3.50 to -0.36), and an elevated risk of having a FEV1/FVC in the lowest tertile (prevalence ratio, 1.38; 95% CI, 0.99 to 1.92). CONCLUSIONS: While no differences in lung function were found between workers and nonworkers, lung function was reduced among decontamination workers and workers with high exposure to burning oil/gas compared with unexposed workers.

Case-control investigation of occupational exposure to chlorinated solvents and non-Hodgkin's lymphoma.

OBJECTIVES: Although many studies have investigated the association between trichloroethylene (TCE) exposure and non-Hodgkin's lymphoma (NHL), less is known about other chlorinated solvents. We extended our previous analysis of occupational TCE exposure in a multicentre population-based case-control study of NHL to investigate associations with five additional chlorinated solvents: 1,1,1,-trichloroethane, carbon tetrachloride, chloroform, methylene chloride and perchloroethylene. METHODS: Cases (n=1189) and controls (n=982) provided detailed information on their occupational histories and workplace exposure to chlorinated solvents for selected occupations using job-specific interview modules. An industrial hygienist used this information and a review of the literature to assess occupational exposure to chlorinated solvents. We computed ORs and 95% CIs for different exposure metrics, with the unexposed group as the referent. We also computed ORs by NHL subtype. RESULTS: High cumulative hours exposed to carbon tetrachloride was associated with NHL (>520 hours: OR 1.9; 95% CI 1.0 to 3.6; Ptrend=0.04). This association remained after restricting to jobs with high-intensity exposure (OR 2.0; 95% CI 1.1 to 3.8; P=0.03) and ≥90% exposure probability (OR 2.1; 95% CI 1.0 to 4.3; P=0.03), adjusting for TCE (OR 2.1; 95% CI 1.0- to 4.1; P=0.04) and incorporating a 15-year lag (OR 1.9; 95% CI 1.0 to 3.6; P=0.06). The other evaluated chlorinated solvents were not associated with NHL. CONCLUSIONS: This is the first study using high-quality quantitative exposure assessment methods to identify a statistically significant elevated association between occupational exposure to carbon tetrachloride and NHL. Our findings, although limited by a small number of exposed cases, offer evidence that carbon tetrachloride may be a lymphomagen.

Decision rule approach applied to estimate occupational lead exposure in a case-control study of kidney cancer.

BACKGROUND: We developed a systematic, data-driven approach to estimate metrics of occupational exposure to lead to aid in epidemiologic analyses in a case-control study of kidney cancer. METHODS: Probability of exposure to ten lead sources was assigned using decision rules developed from an extensive literature review and expert judgement. For jobs with >50% probability of exposure, we assigned source-specific frequency based on subjects' self-reported task frequencies or means of subjects' job-groups and source-specific intensity estimates of blood lead (µg/dL). RESULTS: In our study, 18.7% of employed person-years were associated with high (≥80%) probability of exposure to any lead source. The most common medium (>50%) or high probability source of lead exposure was leaded gasoline (2.5% and 11.5% of employed person-years, respectively). The median blood lead attributed to occupational exposure was 3.1 µg/dL. CONCLUSIONS: These rules can aid in future studies after population-specific adaption for geographic differences and different exposure scenarios.

Multivariate left-censored Bayesian model for predicting exposure using multiple chemical predictors.

Environmental health exposures to airborne chemicals often originate from chemical mixtures. Environmental health professionals may be interested in assessing exposure to one or more of the chemicals in these mixtures, but often exposure measurement data are not available, either because measurements were not collected/assessed for all exposure scenarios of interest or because some of the measurements were below the analytical methods' limits of detection (i.e. censored). In some cases, based on chemical laws, two or more components may have linear relationships with one another, whether in a single or in multiple mixtures. Although bivariate analyses can be used if the correlation is high, often correlations are low. To serve this need, this paper develops a multivariate framework for assessing exposure using relationships of the chemicals present in these mixtures. This framework accounts for censored measurements in all chemicals, allowing us to develop unbiased exposure estimates. We assessed our model's performance against simpler models at a variety of censoring levels and assessed our model's 95% coverage. We applied our model to assess vapor exposure from measurements of three chemicals in crude oil taken on the Ocean Intervention III during the Deepwater Horizon oil spill response and clean-up.

Occupational exposure to chlorinated solvents and kidney cancer: a case-control study.

OBJECTIVES: Trichloroethylene, a chlorinated solvent widely used for metal degreasing, is classified by the International Agency for Research on Cancer as a kidney carcinogen. Other chlorinated solvents are suspected carcinogens, most notably the cleaning solvent perchloroethylene, although it is unclear whether they are associated with kidney cancer. We investigated kidney cancer associations with occupational exposure to 6 chlorinated solvents (trichloroethylene, perchloroethylene, 1,1,1-trichloroethane, carbon tetrachloride, chloroform, and methylene chloride) within a case-control study using detailed exposure assessment methods. METHODS: Cases (n=1217) and controls (n=1235) provided information on their occupational histories and, for selected occupations, on tasks involving potential exposure to chlorinated solvents through job-specific interview modules. Using this information, an industrial hygienist assessed potential exposure to each solvent. We computed ORs and 95% CIs for different exposure metrics, with unexposed participants as the referent group. RESULTS: 1,1,1-trichloroethane, carbon tetrachloride, chloroform, and methylene chloride were not associated with kidney cancer. Among jobs with high exposure intensity, high cumulative hours exposed to perchloroethylene was associated with increased risk, both overall (third tertile vs unexposed: OR 3.1, 95% CI 1.3 to 7.4) and after excluding participants with ≥50% exposure probability for trichloroethylene (OR 3.0, 95% CI 0.99 to 9.0). A non-significant association with high cumulative hours exposed to trichloroethylene was observed (OR 1.7, 95% CI 0.8 to 3.8). CONCLUSIONS: In this study, high exposure to perchloroethylene was associated with kidney cancer, independent of trichloroethylene. Additional studies are needed to further investigate this finding.

Agreement between two methods for retrospective assessment of occupational exposure intensity to six chlorinated solvents: Data from The National Birth Defects Prevention Study.

The wide variety of jobs encountered in population-based studies makes retrospective exposure assessment challenging in occupational epidemiology. In this analysis, two methods for estimating exposure intensity to chlorinated solvents are compared: rated (assigned by an expert rater) and modeled (assigned using statistical models). Estimates of rated and modeled intensities were compared for jobs held by mothers participating in the National Birth Defects Prevention Study with possible exposure to six chlorinated solvents: carbon tetrachloride, chloroform, methylene chloride, perchloroethylene, 1,1,1-trichloroethane, and trichloroethylene. For each possibly exposed job, an industrial hygienist assigned (1) an exposure intensity (rated intensity) and (2) determinants of exposure to be used in a statistical model of exposure intensity (modeled intensity). Of 12,326 reported jobs, between 31 (0.3%) and 746 (6%) jobs were rated as possibly exposed to each of the six solvents. Agreement between rated and modeled intensities was low overall (Spearman correlation coefficient range: -0.09 to 0.28; kappa range: -0.23 to 0.43). Although no air measurements were available to determine if rated or modeled estimates were more accurate, review of participants' job titles showed that modeled estimates were often unexpectedly high given the low-exposure tasks found in these jobs. Differences between the high-exposure jobs used to create the statistical models (obtained from air measurements in the published literature) and the low-exposure jobs in the actual study population is a potential explanation for the disagreement between the two methods. Investigators should be aware that statistical models estimating exposure intensity using existing data from one type of worker population might not be generalizable to all populations of workers.

A case-control study of occupational sunlight exposure and renal cancer risk.

Epidemiological evidence of a relationship between vitamin D and kidney cancer risk has been inconsistent despite experimental data indicating that vitamin D and its metabolites may inhibit carcinogenesis. Previously we reported an inverse association between renal cell carcinoma (RCC) risk and occupational ultraviolet (UV) exposure among European men. In this study, we examined the association between occupational UV exposure and RCC risk among US residents and investigated whether this association varied by race and sex. Lifetime occupational data for 1,217 RCC cases and 1,235 controls in a population-based case-control study, conducted from 2002 to 2007, were assessed for occupational UV exposure. We evaluated exposure metrics in quartiles based on control exposure levels and calculated associations between RCC risk and occupational UV exposure using unconditional logistic regression adjusted for sex, race, body mass index, smoking, hypertension, center, education, family history of cancer and dietary vitamin D intake. A general pattern of decreasing RCC risk with increasing UV exposure was observed. Cases had significantly lower cumulative occupational UV exposure than controls (fourth quartile vs. first: odds ratio = 0.74 [95% confidence interval = 0.56-0.99], p-trend = 0.03). Similar results were observed for other UV exposure metrics. The association with occupational UV exposure was stronger for women than for men, but did not differ by race. Our findings suggest an inverse association between occupational UV exposure and RCC, particularly among women. Given the sex finding discrepancies in this study versus our previous study, additional research is need to clarify whether the protective effects of occupational UV exposure and RCC risk are real.

A Comparison of the ß-Substitution Method and a Bayesian Method for Analyzing Left-Censored Data.

Classical statistical methods for analyzing exposure data with values below the detection limits are well described in the occupational hygiene literature, but an evaluation of a Bayesian approach for handling such data is currently lacking. Here, we first describe a Bayesian framework for analyzing censored data. We then present the results of a simulation study conducted to compare the ß-substitution method with a Bayesian method for exposure datasets drawn from lognormal distributions and mixed lognormal distributions with varying sample sizes, geometric standard deviations (GSDs), and censoring for single and multiple limits of detection. For each set of factors, estimates for the arithmetic mean (AM), geometric mean, GSD, and the 95th percentile (X0.95) of the exposure distribution were obtained. We evaluated the performance of each method using relative bias, the root mean squared error (rMSE), and coverage (the proportion of the computed 95% uncertainty intervals containing the true value). The Bayesian method using non-informative priors and the ß-substitution method were generally comparable in bias and rMSE when estimating the AM and GM. For the GSD and the 95th percentile, the Bayesian method with non-informative priors was more biased and had a higher rMSE than the ß-substitution method, but use of more informative priors generally improved the Bayesian method's performance, making both the bias and the rMSE more comparable to the ß-substitution method. An advantage of the Bayesian method is that it provided estimates of uncertainty for these parameters of interest and good coverage, whereas the ß-substitution method only provided estimates of uncertainty for the AM, and coverage was not as consistent. Selection of one or the other method depends on the needs of the practitioner, the availability of prior information, and the distribution characteristics of the measurement data. We suggest the use of Bayesian methods if the practitioner has the computational resources and prior information, as the method would generally provide accurate estimates and also provides the distributions of all of the parameters, which could be useful for making decisions in some applications.