Melanoma, thyroid cancer, and gynecologic cancers in a cohort of female flight attendants.

BACKGROUND: Flight attendants may have an increased risk of some cancers from occupational exposure to cosmic radiation and circadian disruption. METHODS: The incidence of thyroid, ovarian, and uterine cancer among ∼6000 female flight attendants compared to the US population was evaluated via life table analyses. Associations of these cancers, melanoma, and cervical cancer with cumulative cosmic radiation dose and metrics of circadian disruption were evaluated using Cox regression. RESULTS: Incidence of thyroid, ovarian, and uterine cancer was not elevated. No significant, positive exposure-response relations were observed. Weak, non-significant, positive relations were observed for thyroid cancer with cosmic radiation and time zones crossed and for melanoma with another metric of circadian disruption. CONCLUSIONS: We found little evidence of increased risk of these cancers from occupational cosmic radiation or circadian disruption in female flight attendants. Limitations include few observed cases of some cancers, limited data on risk factors, and misclassification of exposures.

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.

Cancer incidence among capacitor manufacturing workers exposed to polychlorinated biphenyls.

BACKGROUND: We evaluated cancer incidence in a cohort of polychlorinated biphenyl (PCB) exposed workers. METHODS: Incident cancers, identified using state registries, were compared to those in a national population using standardized incidence ratios. Trends in prostate cancer incidence with cumulative PCB exposure were evaluated using standardized rate ratios and Cox regression models. For selected sites, cumulative PCB exposure was compared between aggressive (fatal/distant stage) and localized/regional cancers. RESULTS: We identified 3,371 invasive first primary cancer diagnoses among 21,317 eligible workers through 2007. Overall relative incidence was reduced. Elevations were only observed for respiratory cancers and among women, urinary organ cancers. Among men, prostate cancer incidence was reduced and not associated with cumulative PCB exposure although median exposures were significantly higher for aggressive compared to localized/regional prostate cancers. CONCLUSION: Previously observed associations between cumulative PCB exposure and prostate cancer mortality were not confirmed in this analysis; prostate cancer stage at diagnosis may explain the discrepancy. Am. J. Ind. Med. 60:198-207, 2017. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

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.

Mortality from neurodegenerative diseases in a cohort of US flight attendants.

BACKGROUND: Concern exists about the potential chronic neurological effects among aircrew of exposure to chemical contaminants from engine oil in aircraft cabin air. We evaluated mortality from neurodegenerative diseases among 11,311 former US flight attendants. METHODS: Vital status was ascertained through 2007, and life table analyses were conducted to obtain standardized mortality ratios (SMRs). RESULTS: Amyotrophic lateral sclerosis (ALS) mortality was over twice as high in the cohort as in the US general population, based on nine observed ALS deaths. There was no clear pattern in risk when SMRs for ALS were stratified by exposure duration. Mortality from other neurodegenerative diseases was not elevated. CONCLUSIONS: Our findings are limited due to small numbers of observed deaths and reliance on mortality data, but suggest that flight attendants may have an increased risk of ALS. Additional research is needed. Am. J. Ind. Med. 59:532-537, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Mortality of lead smelter workers: A follow-up study with exposure assessment.

BACKGROUND: Lead exposure has been linked to impaired renal function and kidney failure. High lead exposures have been associated with increased mortality from certain cancers, hypertension, cardiovascular disease, and amyotrophic lateral sclerosis (ALS). METHODS: We extended vital status follow-up on a cohort of 1,990 lead smelter workers by 25 years and computed standardized mortality ratios and rate ratios (RR) stratified by cumulative lead exposure. RESULTS: The update added 13,823 person-years at risk and 721 deaths. Increased risk of mortality was observed for the a priori outcomes of lung cancer, cardiovascular disease (including cerebrovascular disease), chronic kidney disease, and ALS. However, of these outcomes, only cardiovascular, cerebrovascular, and chronic kidney diseases were associated with a positive exposure-response in RR analyses. CONCLUSIONS: This study reaffirms the association of lead exposure with cardiovascular and kidney diseases; however, increased mortality observed for certain cancers is not likely to be due to lead exposure. Am. J. Ind. Med. 59:979-986, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Miscarriage among flight attendants.

BACKGROUND: Cosmic radiation and circadian disruption are potential reproductive hazards for flight attendants. METHODS: Flight attendants from 3 US airlines in 3 cities were interviewed for pregnancy histories and lifestyle, medical, and occupational covariates. We assessed cosmic radiation and circadian disruption from company records of 2 million individual flights. Using Cox regression models, we compared respondents (1) by levels of flight exposures and (2) to teachers from the same cities, to evaluate whether these exposures were associated with miscarriage. RESULTS: Of 2654 women interviewed (2273 flight attendants and 381 teachers), 958 pregnancies among 764 women met study criteria. A hypothetical pregnant flight attendant with median first-trimester exposures flew 130 hours in 53 flight segments, crossed 34 time zones, and flew 15 hours during her home-base sleep hours (10 pm-8 am), incurring 0.13 mGy absorbed dose (0.36 mSv effective dose) of cosmic radiation. About 2% of flight attendant pregnancies were likely exposed to a solar particle event, but doses varied widely. Analyses suggested that cosmic radiation exposure of 0.1 mGy or more may be associated with increased risk of miscarriage in weeks 9-13 (odds ratio = 1.7 [95% confidence interval = 0.95-3.2]). Risk of a first-trimester miscarriage with 15 hours or more of flying during home-base sleep hours was increased (1.5 [1.1-2.2]), as was risk with high physical job demands (2.5 [1.5-4.2]). Miscarriage risk was not increased among flight attendants compared with teachers. CONCLUSIONS: Miscarriage was associated with flight attendant work during sleep hours and high physical job demands and may be associated with cosmic radiation exposure.

Breast cancer incidence in a cohort of U.S. flight attendants.

BACKGROUND: Flight attendants may have elevated breast cancer incidence (BCI). We evaluated BCI's association with cosmic radiation dose and circadian rhythm disruption among 6,093 female former U.S. flight attendants. METHODS: We collected questionnaire data on BCI and risk factors for breast cancer from 2002-2005. We conducted analyses to evaluate (i) BCI in the cohort compared to the U.S. population; and (ii) exposure-response relations. We applied an indirect adjustment to estimate whether parity and age at first birth (AFB) differences between the cohort and U.S. population could explain BCI that differed from expectation. RESULTS: BCI was elevated but may be explained by lower parity and older AFB in the cohort than among U.S. women. BCI was not associated with exposure metrics in the cohort overall. Significant positive associations with both were observed only among women with parity of three or more. CONCLUSIONS: Future cohort analyses may be informative on the role of these occupational exposures and non-occupational risk factors.

Bladder cancer incidence among workers exposed to o-toluidine, aniline and nitrobenzene at a rubber chemical manufacturing plant.

BACKGROUND: An earlier investigation found increased bladder cancer incidence among workers at a rubber chemical manufacturing plant that used o-toluidine, aniline and nitrobenzene. The cohort was expanded to include additional workers (n=1875) and updated through 2007 to assess bladder cancer with improved exposure characterisation. METHODS: Work histories were updated and exposure categories and ranks were developed for o-toluidine, aniline and nitrobenzene combined. Incident cancers were identified by linkage to six state cancer registries. Residency in time-dependent cancer registry catchment areas was determined. SIR and standardised rate ratios for bladder cancer were calculated by exposure category and cumulative rank quartiles for different lag periods. Cox regression was used to model bladder cancer incidence with estimated cumulative rank, adjusting for confounders. Indirect methods were used to control for smoking. RESULTS: Excess bladder cancer was observed compared to the New York State population (SIR=2.87, 95% CI 2.02 to 3.96), with higher elevations among workers definitely exposed (moderate/high) (SIR=3.90, 95% CI 2.57 to 5.68), and in the highest cumulative rank quartile (SIR=6.13, 95% CI 2.80 to 11.6, 10-year lag). Bladder cancer rates increased significantly with estimated cumulative rank (10-year lag). Smoking only accounted for an estimated 8% elevation in bladder cancer incidence. CONCLUSIONS: Bladder cancer incidence remains elevated in this cohort and significantly associated with estimated cumulative exposure. Results are consistent with earlier findings in this and other cohorts. Despite other concurrent chemical exposures, we consider o-toluidine most likely responsible for the bladder cancer incidence elevation and recommend a re-examination of occupational exposure limits.

Methods and feasibility of collecting occupational data for a large population-based cohort study in the United States: the reasons for geographic and racial differences in stroke study.

BACKGROUND: Coronary heart disease and stroke are major contributors to preventable mortality. Evidence links work conditions to these diseases; however, occupational data are perceived to be difficult to collect for large population-based cohorts. We report methodological details and the feasibility of conducting an occupational ancillary study for a large U.S. prospective cohort being followed longitudinally for cardiovascular disease and stroke. METHODS: Current and historical occupational information were collected from active participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. A survey was designed to gather quality occupational data among this national cohort of black and white men and women aged 45 years and older (enrolled 2003-2007). Trained staff conducted Computer-Assisted Telephone Interviews (CATI). After a brief pilot period, interviewers received additional training in the collection of narrative industry and occupation data before administering the survey to remaining cohort members. Trained coders used a computer-assisted coding system to assign U.S. Census codes for industry and occupation. All data were double coded; discrepant codes were independently resolved. RESULTS: Over a 2-year period, 17,648 participants provided consent and completed the occupational survey (87% response rate). A total of 20,427 jobs were assigned Census codes. Inter-rater reliability was 80% for industry and 74% for occupation. Less than 0.5% of the industry and occupation data were uncodable, compared with 12% during the pilot period. Concordance between the current and longest-held jobs was moderately high. The median time to collect employment status plus narrative and descriptive job information by CATI was 1.6 to 2.3 minutes per job. Median time to assign Census codes was 1.3 minutes per rater. CONCLUSIONS: The feasibility of conducting high-quality occupational data collection and coding for a large heterogeneous population-based sample was demonstrated. We found that training for interview staff was important in ensuring that narrative responses for industry and occupation were adequately specified for coding. Estimates of survey administration time and coding from digital records provide an objective basis for planning future studies. The social and environmental conditions of work are important understudied risk factors that can be feasibly integrated into large population-based health studies.

Coronary artery disease and cancer mortality in a cohort of workers exposed to vinyl chloride, carbon disulfide, rotating shift work, and o-toluidine at a chemical manufacturing plant.

BACKGROUND: We updated through 2007 the mortality experience of 1,874 workers employed at a New York State chemical manufacturing plant between 1946 and 2006. METHODS: Reassessed exposures to vinyl chloride, carbon disulfide, and shift work and categories of o-toluidine exposure were based on year, department and job title. Standardized mortality ratios (SMR) compared mortality to that of the US population. Internal comparisons used directly standardized rate ratios. RESULTS: Hepatobiliary cancer mortality was elevated among workers ever exposed to vinyl chloride (SMR = 3.80, 95% confidence interval 1.89-6.80); directly standardized rates increased with increasing vinyl chloride exposure duration. No increase in non-Hodgkin lymphoma mortality was observed with vinyl chloride and shift work exposures. Internal comparisons showed increased coronary artery disease mortality among long-term workers exposed to carbon disulfide and shift work for 4 years or more. CONCLUSIONS: Excess coronary artery disease mortality confirms earlier results; further investigation is needed to understand risk factors.

The Upper Midwest Health Study: gliomas and occupational exposure to chlorinated solvents.

OBJECTIVES: Occupational exposure to chlorinated aliphatic solvents has been associated with an increased cancer risk, including brain cancer. However, many of these solvents remain in active, large-volume use. We evaluated glioma risk from non-farm occupational exposure (ever/never and estimated cumulative exposure) to any of the six chlorinated solvents--carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, tetrachloroethylene or 1,1,1--trichloroethane-among 798 cases and 1175 population-based controls, aged 18-80 years and non-metropolitan residents of Iowa, Michigan, Minnesota and Wisconsin. Methods Solvent use was estimated based on occupation, industry and era, using a bibliographic database of published exposure levels and exposure determinants. Unconditional logistic regression was used to calculate ORs adjusted for frequency matching variables age group and sex, and age and education. Additional analyses were limited to 904 participants who donated blood specimens (excluding controls reporting a previous diagnosis of cancer) genotyped for glutathione-S-transferases GSTP1, GSTM3 and GSTT1. Individuals with functional GST genes might convert chlorinated solvents crossing the blood-brain barrier into cytotoxic metabolites. RESULTS: Both estimated cumulative exposure (ppm-years) and ever exposure to chlorinated solvents were associated with decreased glioma risk and were statistically significant overall and for women. In analyses comparing participants with a high probability of exposure with the unexposed, no associations were statistically significant. Solvent-exposed participants with functional GST genes were not at increased risk of glioma. CONCLUSIONS: We observed no associations of glioma risk and chlorinated solvent exposure. Large pooled studies are needed to explore the interaction of genetic pathways and environmental and occupational exposures in glioma aetiology.

Cohort mortality study of garment industry workers exposed to formaldehyde: update and internal comparisons.

BACKGROUND: To further evaluate the association between formaldehyde and leukemia, we extended follow-up through 2008 for a cohort mortality study of 11,043 US formaldehyde-exposed garment workers. METHODS: We computed standardized mortality ratios and standardized rate ratios stratified by year of first exposure, exposure duration, and time since first exposure. Associations between exposure duration and rates of leukemia and myeloid leukemia were further examined using Poisson regression models. RESULTS: Compared to the US population, myeloid leukemia mortality was elevated but overall leukemia mortality was not. In internal analyses, overall leukemia mortality increased with increasing exposure duration and this trend was statistically significant. CONCLUSIONS: We continue to see limited evidence of an association between formaldehyde and leukemia. However, the extended follow-up did not strengthen previously observed associations. In addition to continued epidemiologic research, we recommend further research to evaluate the biological plausibility of a causal relation between formaldehyde and leukemia.

Lung cancer mortality in North Carolina and South Carolina chrysotile asbestos textile workers.

OBJECTIVES: Studies of workers in two US cohorts of asbestos textile workers exposed to chrysotile (North Carolina (NC) and South Carolina (SC)) found increasing risk of lung cancer mortality with cumulative fibre exposure. However, the risk appeared to increase more steeply in SC, possibly due to differences in study methods. The authors conducted pooled analyses of the cohorts and investigated the exposure-disease relationship using uniform cohort inclusion criteria and statistical methods. METHODS: Workers were included after 30 days of employment in a production job during qualifying years, and vital status ascertained through 2003 (2001 for SC). Poisson regression was used to estimate the exposure-response relationship between asbestos and lung cancer, using both exponential and linear relative rate models adjusted for age, sex, race, birth cohort and decade of follow-up. RESULTS: The cohort included 6136 workers, contributing 218,631 person-years of observation and 3356 deaths. Cumulative exposures at the four study facilities varied considerably. The pooled relative rate for lung cancer, comparing 100 f-yr/ml to 0 f-yr/ml, was 1.11 (95% CI 1.06 to 1.16) for the combined cohort, with different effects in the NC cohort (RR=1.10, 95% CI 1.03 to 1.16) and the SC cohort (RR = 1.67, 95% CI 1.44 to 1.93). CONCLUSIONS: Increased rates of lung cancer were significantly associated with cumulative fibre exposure overall and in both the Carolina asbestos-textile cohorts. Previously reported differences in exposure-response between the cohorts do not appear to be related to inclusion criteria or analytical methods.

Occupational exposure to chlorinated solvents and risks of glioma and meningioma in adults.

OBJECTIVES: Chlorinated solvents are classified as probable or possible carcinogens. It is unknown whether exposure to these agents increases the risk of malignant or benign brain tumours. Our objective was to evaluate associations of brain tumour risk with occupational exposure to six chlorinated solvents (i.e., dichloromethane, chloroform, carbon tetrachloride, 1,1,1-trichloroethane, trichloroethylene and perchloroethylene). METHODS: 489 glioma cases, 197 meningioma cases and 799 controls were enrolled in a hospital-based case-control study conducted at three U.S.A. hospitals in Arizona, Massachusetts and Pennsylvania. Information about occupational history was obtained through a detailed inperson interview that included job-specific modules of questions such that the interview was tailored to each individual's particular work history. An industrial hygienist assessed potential solvent exposure based on this information and an exhaustive review of the relevant industrial hygiene literature. Unconditional logistic regression models were used to calculate OR and 95% CI for each solvent for ever/never, duration, cumulative, average weekly and highest exposure. RESULTS: Overall, we found no consistent evidence of an increased risk of glioma or meningioma related to occupational exposure to the six chlorinated solvents evaluated. There was some suggestion of an association between carbon tetrachloride and glioma in analyses restricted to exposed subjects, with average weekly exposure above the median associated with increased risk compared with below the median exposure (OR = 7.1, 95% CI 1.1 to 45.2). CONCLUSIONS: We found no consistent evidence for increased brain tumour risk related to chlorinated solvents.

Cause-specific mortality among a cohort of U.S. flight attendants.

BACKGROUND: We evaluated mortality among 11,311 former U.S. flight attendants. The primary a priori outcomes of interest were breast cancer and melanoma. METHODS: Vital status was ascertained through 2007, and life table analyses was conducted. Cumulative exposure to cosmic radiation and circadian rhythm disruption were estimated from work history data and historical published flight schedules. RESULTS: All-cause mortality was less than expected among women but was elevated among men, primarily due to elevated HIV-related disease mortality. Mortality from breast cancer among women and melanoma was neither significantly elevated nor related to metrics of exposure. Mortality was elevated for non-Hodgkin's lymphoma among men; for alcoholism, drowning, and intentional self-harm among women; and for railway, water, and air transportation accidents. CONCLUSIONS: We found no evidence of increased breast cancer or melanoma mortality. Limitations include reliance on mortality data and limited power resulting from few melanoma deaths and relatively short employment durations.

Exposure to o-toluidine, aniline, and nitrobenzene in a rubber chemical manufacturing plant: a retrospective exposure assessment update.

The National Institute for Occupational Safety and Health previously conducted a retrospective cancer incidence and mortality study of workers employed at a rubber chemical manufacturing plant. Compared with New York State incidence, the bladder cancer risk was 6.5 times higher for workers considered to have definite exposure to ortho-toluidine and aniline, and 4 times higher for workers with possible exposure. Exposure characterization in the original study utilized a surrogate measure based only on departments in which each worker was ever employed. As part of an update of that study, some departments in the three original exposure groups were reclassified based on a follow-up site visit; interviews with employees, management, and union representatives; and review of records including exposure data. An additional evaluation of department-job combinations, rather than only departments, was used to stratify exposure into four categories. An approximate rank of "relative" exposure level for each department-job-year combination was also assigned using a ranking scale of 0 to 10. The ranks were supported by quantitative exposure levels and by professional judgment. The numerical ranking scale was applied to each worker by multiplying the exposure rank by duration for each job held based on comprehensive individual work histories. The cumulative rank scores for this cohort ranged from 0 to 300 unit-years. The medians of the cumulative rank scores for the exposure categories showed very good agreement with increasing exposure classifications (e.g., 0.72, 4.6, 11, 14 unit-years for the four exposure categories). Workers' breathing zone air sampling data collected at this plant from 1976-2004 were well below published occupational exposure limits for these chemicals, but additional cases of bladder cancer have been reported. The exposure assessment revisions and rank estimates will be used to analyze the updated bladder cancer incidence data.

Evaluating bias from birth-cohort effects in the age-based cox proportional hazards model.

The nested case-control design is frequently used to evaluate exposures and health outcomes within the confines of a cohort study. When incidence-density sampling is used to identify controls, the resulting data can be analyzed using conditional logistic regression (equivalent to stratified Cox proportional hazards regression). In these studies, exposure lagging is often used to account for disease latency. In light of recent criticism of incidence-density sampling, we used simulated occupational cohorts to evaluate age-based incidence-density sampling for lagged exposures in the presence of birth-cohort effects and associations among time-related variables. Effect estimates were unbiased when adjusted for birth cohort; however, unadjusted effect estimates were biased, particularly when age at hire and year of hire were correlated. When the analysis included an adjustment for birth cohort, the inclusion of lagged-out cases and controls (assigned a lagged exposure of zero) did not introduce bias.

Analysis of lognormally distributed exposure data with repeated measures and values below the limit of detection using SAS.

Studies of determinants of occupational exposure frequently involve left-censored lognormally distributed data, often with repeated measures. Left censoring occurs when observations are below the analytical limit of detection (LOD); repeated measures data results from taking multiple measurements on the same worker. A common method of dealing with this type of data has been to substitute a value (such as LOD/2) for the censored data followed by statistical analysis using the 'usual' methods. Recently, maximum likelihood estimation (MLE) methods have been employed to reduce bias associated with the substitution method. We compared substitution and MLE methods using simulated lognormally distributed exposure data subjected to varying amounts of censoring using two procedures available in SAS: LIFEREG and NLMIXED. In these simulations, the MLE method resulted in less bias and performed well even for censoring up to 80%, whereas the substitution method resulted in considerable bias. We illustrate the NLMIXED procedure using a dataset of chlorpyrifos air measurements collected from termiticide applicators on consecutive days over a 5-day workweek. We provide sample SAS code for several situations including one and two groups, with and without repeated measures, random slopes, and nested random effects.

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.