Obesity and weight gain in relation to depression: findings from the Stirling County Study.

OBJECTIVE: This study concerns the question of whether obese subjects in a community sample experience depression in a different way from the nonobese, especially whether they overeat to the point of gaining weight during periods of depression. DESIGN: A representative sample of adults was interviewed regarding depression and obesity. SUBJECTS: The sample consisted of 1396 subjects whose interviews were studied regarding relationships between obesity and depression and among whom 114 had experienced a major depressive episode at some point in their lives and provided information about the symptoms experienced during the worst or only episode of major depression. MEASUREMENTS: The Diagnostic Interview Schedule (DIS) was used to identify major depressive episodes. Information was also derived from the section on Depression and Anxiety (DPAX) of the Stirling Study Schedule. Obesity was calculated as a body mass index >30. Logistic regressions were employed to assess relationships, controlling for age and gender, by means of odds ratios and 95% confidence intervals. RESULTS: In the sample as a whole, obesity was not related to depression although it was associated with the symptom of hopelessness. Among those who had ever experienced a major depressive episode, obese persons were 5 times more likely than the nonobese to overeat leading to weight gain during a period of depression (P<0.002). These obese subjects, compared to the nonobese, also experienced longer episodes of depression, a larger number of episodes, and were more preoccupied with death during such episodes. CONCLUSIONS: Depression among obese subjects in a community sample tends to be more severe than among the nonobese. Gaining weight while depressed is an important marker of that severity. Further research is needed to understand and possibly prevent the associations, sequences and outcomes among depression, obesity, weight gain and other adversities.

Anxiety and depression: a 40-year perspective on relationships regarding prevalence, distribution, and comorbidity.

OBJECTIVE: Building on a report about the prevalence of depression over time, this paper examines historical trends regarding anxiety in terms of its prevalence, its distribution by age and gender, and its comorbidity with depression. Methods for conducting such time trend analysis are reviewed. METHOD: Representative samples of adults were selected and interviewed in 1952, 1970, and 1992. Logistic regressions were used for statistical analysis. RESULTS: Although twice as common as depression, the prevalence of anxiety was equally stable. Anxiety was consistently and significantly more characteristic of women than men. A re-distribution of rates in 1992 indicated that depression but not anxiety had significantly increased among younger women (P = 0.03). Throughout the study, approximately half of the cases of anxiety also suffered depression. CONCLUSION: The relationships between anxiety and depression remained similar over time with the exception that depression came to resemble anxiety as a disorder to which women were significantly more vulnerable than men. Social and historical factors should be investigated to assess their relevance to this change.

Multiple informants: mortality associated with psychiatric disorders in the Stirling County Study.

This paper applies new statistical procedures for analyzing multiple-source information about the relation of psychiatric diagnoses to mortality. The data come from the Stirling County Study, a longitudinal community investigation of adults, that collected multiple-source reports (self-report and physician-report) about psychiatric disorders. These reports are used as predictors of mortality risk over a 16-year follow-up period (1952-1968). Despite extensive efforts, one or both of these reports were sometimes missing. Missingness of self-report was related to demographic characteristics as well as to physician-reports of psychiatric diagnosis. The statistical procedures used here draw together into a single frame of reference both informant reports for the initial Stirling survey and relate these to mortality risk using weighted generalized estimating equation regression models for time to event data. This unified method has two advantages over traditional approaches: 1) the relative predictiveness of each informant can be assessed and 2) all subjects contribute to the analysis. The methods are applicable to other areas of epidemiology where multiple informant reports are used. The results for self-reports and physician-reports of disorders were comparable: Psychiatric diagnosis was associated with higher mortality, particularly among younger subjects.

Exposure-response models based on extended follow-up of a cohort mortality study in the automobile industry.

OBJECTIVE: This report describes the extended follow-up of a cohort of 46 399 automobile manufacturing workers with potential exposure to metalworking fluids (MWF). The outcomes of interest were cancers of the esophagus, stomach, colon, rectum, liver, pancreas, larynx, skin, prostate, and brain, as well as leukemia. Additional follow-up increased the power to detect modest elevations in mortality rates in association with specific types of MWF, including synthetic fluids not in widespread use until the 1970s. METHODS: Standardized mortality ratios (SMR) were computed for the most recent 10 years of follow-up, as well as for the entire study period. Adjusted relative risks (RR) were estimated in Poisson regression models with categorical variables for cumulative exposure to each type of MWF and in proportional hazards models with continuous exposure variables. RESULTS: Associations were found between straight MWF and esophageal, laryngeal and rectal cancer; soluble MWF and cancer of the esophagus, larynx, skin, and brain; synthetic MWF and cancer of the esophagus, liver, and prostate. The elevated RR values were modest in magnitude (1.5 to 2.0). SMR values were increased for stomach, liver, and pancreatic cancer and also for leukemia in the last 10 years of follow-up. The SMR values were also elevated for stomach and liver cancer among the persons recently hired. CONCLUSIONS: The results provide further evidence that exposure to metalworking fluids causes cancer among workers in automobile manufacturing. Although airborne exposures declined over the study period, this study suggests that modest risk of several digestive cancers, as well as prostatic cancer and leukemia, may persist at current levels of exposure to water-based metalworking fluids.

Mortality after cerebral angiography with or without radioactive Thorotrast: an international cohort of 3,143 two-year survivors.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P < 0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with >20 ml Thorotrast and approached 50%.

Respiratory health of automobile workers and exposures to metal-working fluid aerosols: lung spirometry.

BACKGROUND: Despite substantial evidence that workers exposed to metal-working fluids (MWF) have increased respiratory morbidity, the few studies of chronic effects on lung function have not been conclusive. METHODS: Lung spirometry was measured and both current and past exposures to metal-working fluid (MWF) aerosols were estimated in this cross-sectional cohort of 1,811 male automobile workers. Satisfactory exposure data were available for 1,745 (96%): 239 assemblers (never-exposed to MWF), 487 assemblers (previously exposed), 352 machinists currently exposed to straight oils, 441 to soluble oils, and 226 to synthetic fluids. Operations were classified as either grinding or non-grinding machining. RESULTS: Current exposure was not found to be associated with either forced expiratory volume in 1 second (FEV(1)) or forced ventilatory capacity (FVC). Nor was past exposure to water-based fluids (soluble or synthetic MWF) related to pulmonary function. Past exposure to straight oils, however, was significantly associated with FVC. This association was more obvious among older workers and among workers who had never transferred from MWF exposed jobs to assembly. CONCLUSIONS: The magnitude of the association between FVC and lifetime exposure to straight MWF was slightly larger than the estimated cigarette effect, suggesting that the impact of an additional year of exposure to 1 mg/m(3) of mineral oil particulate in the thoracic particle size range, has the same impact on FVC as smoking one pack per day for one more year.

Arsenic in drinking water and skin cancers: cell-type specificity (Taiwan, ROC).

OBJECTIVE: The association between arsenic ingestion and cancer has been documented for more than a century. Previous studies showed that the carcinogenic effects of arsenic on the urinary system are cell-type specific. To evaluate whether this is also true for skin cancers, we conducted an ecological study in 243 townships in Taiwan. METHODS: The arsenic exposure was assessed on the basis of measurement reports from a previous survey, and cases of skin cancer were identified using the information gathered by the National Cancer Registry Program. We analyzed the data by regression models using multiple variables to describe the exposure status, and an urbanization index was also included in the models to adjust for the effects of urbanization. RESULTS: A total of 2369 patients with skin cancer, comprising 1415 men and 954 women, were registered between 1 January 1980 and 31 December 1989. Among the three major cell types of skin cancer, squamous cell carcinoma and basal cell carcinoma appear to be associated with ingestion of arsenic. Such an association was not observed for malignant melanoma. CONCLUSIONS: The results suggested that the carcinogenicity of arsenic on skin is cell-type specific, which is compatible with the findings in previous studies on urinary cancers.

Incidence of depression in the Stirling County Study: historical and comparative perspectives.

BACKGROUND: The Stirling County Study provides a 40-year perspective on the epidemiology of psychiatric disorders in an adult population in Atlantic Canada. Across samples selected in 1952, 1970 and 1992 current prevalence of depression was stable. This paper concerns time trends in annual incidence as assessed through cohorts selected from the first two samples. METHODS: Consistent interview data were analysed by a computerized diagnostic algorithm. The cohorts consisted of subjects at risk for a first depression: Cohort-1 (N = 575) was followed 1952-1970; Cohort-2 (N = 639) was followed 1970-1992. Life-table methods were used to calculate incidence rates and proportional hazards procedures were used for statistical assessment. RESULTS: Average annual incidence of depression was 4.5 per 1000 for Cohort-1 and 3.7 for Cohort-2. Differences by gender, age and time were not statistically significant. The stability of incidence and the similarity of distribution by gender and age in these two cohorts corresponds to findings about the two early samples. In contrast, current prevalence in the recent sample was distributed differently and showed an increase among women under 45 years. CONCLUSIONS: The stability of the incidence of depression emphasizes the distinctive characteristics of current prevalence in the recent sample and suggests that the dominance of women in rates of depression may have occurred among those born after the Second World War. The results offer partial support for the interpretation of an increase in depression based on retrospective data in other recent studies but they indicate that the increase is specific to women.

Harvard report on cancer prevention volume 4: Harvard Cancer Risk Index. Risk Index Working Group, Harvard Center for Cancer Prevention.

OBJECTIVE: Prediction of cancer risk is a minor component of current health risk appraisals. Perception of individual cancer risk is poor. A Cancer Risk Index was developed to predict individual cancer risk for cancers accounting for 80% of the cancer burden in the United States. METHODS: We used group consensus among researchers at the Harvard Medical School and Harvard School of Public Health to identify risk factors as definite, probable and possible causes of cancer. Risk points were allocated according to the strength of the causal association and summed. Population average risk of cancer and cumulative 10-year risk was obtained from SEER data. Individual ranking relative to the population average was determined. The risk index was evaluated for validity using colon cancer incidence in prospective cohort data. RESULTS: The Harvard Cancer Risk Index provides a broad classification of cancer risk. Validation against cohort data shows good agreement for colon cancer. CONCLUSION: The Harvard Cancer Risk Index offers a simple estimation of personal risk of cancer. It may help inform users of the major risk factors for cancer and identify changes in lifestyle that will reduce their risk. It offers the potential for tailored health-promotion messages.

A 40-year perspective on the prevalence of depression: the Stirling County Study.

BACKGROUND: According to epidemiologic studies that use recall of lifetime episodes, the prevalence of depression is increasing. This report from the Stirling County Study compares rates of current depression among representative samples of adults from a population in Atlantic Canada. METHODS: Sample sizes were 1003, 1201, and 1396 in 1952, 1970, and 1992, respectively. The depression component of the study's method, the DPAX (DP for depression and AX for anxiety), was employed. The original procedure (DPAX-1) was applied in all years. A revision (DPAX-2) was used in 1970 and 1992. The Diagnostic Interview Schedule (DIS) was also used in 1992. RESULTS: With the DPAX-1, the overall prevalence of current depression was steady at 5% over the 2 early samples but declined in 1992 because of vernacular changes referring to dysphoria. The DPAX-2 gave a stable overall prevalence of 5% in the 2 recent samples, but indicated that women and younger people were at greater risk in 1992 than in 1970. The DIS, like the DPAX-2, found a current 1992 rate of 5% for major depressive episodes combined with dysthymia. Recalled lifetime rates using the DIS showed the same profile interpreted in other studies as suggesting an increase in depression over time. CONCLUSIONS: Three samples over a 40-year period showed a stable current prevalence of depression using the DPAX methods that was comparable in 1992 with the current rates using the DIS. This casts doubt on the interpretation that depression is generally increasing. Within the overall steady rate observed in this study, historical change was a matter of redistribution by sex and age, with a higher rate among younger women being of recent origin.

A comparison of diagnostic interviews for depression in the Stirling County study: challenges for psychiatric epidemiology.

BACKGROUND: High prevalence rates in psychiatric epidemiologic studies raise questions about whether data-gathering procedures identify transient responses rather than clinical disorders. This issue is explored relevant to depression using data from the Stirling County Study. METHODS: The study's customary method, the DPAX (DP for depression and AX for anxiety) was compared with the Diagnostic Interview Schedule (DIS), both of which were administered to a sample of 1396 subjects selected in 1992. Reasons for discordance were analyzed, and demographic correlates of responses to questions about dysphoria were examined. These lay-administered interviews were then compared with clinician-administered interviews that used the Structured Clinical Interview for DSM-III-R (SCID) with 139 subjects. The kappa statistic and logistic regression were used for statistical assessment. RESULTS: For the level of agreement between the DPAX and the DIS for current and lifetime depression, kappa = 0.40 and kappa = 0.33, respectively. Subjects diagnosed only by the DPAX tended to have less education than those diagnosed only by the DIS. Some idioms for dysphoria seemed to work better than others. Using SCID interviews as a clinical standard, the DPAX had 15% sensitivity and 96% specificity and the DIS had 25% sensitivity and 98% specificity. CONCLUSIONS: Comprehension of an interview can be improved by using multiple questions for dysphoria and a simpler mode of inquiry. Clinician-administered interviews tend to corroborate disorders identified in lay-administered interviews but suggest that survey methods underestimate prevalence. Further research is needed to evaluate the validity of both types of interviews, but evidence from a 16-year follow-up evaluation indicates that depression diagnosed by the DPAX is a serious disorder in terms of morbidity and mortality.

Measurement of PCBs, DDE, and hexachlorobenzene in cord blood from infants born in towns adjacent to a PCB-contaminated waste site.

There are limited data on the concentrations of common contaminants--polychlorinated biphenyls (PCBs), dichlorodiphenyl dichloroethene (pp'-DDE) and hexachlorobenzene (HCB)--in umbilical cord blood. Cord blood provides the primary direct measure of prenatal exposure to these contaminants, the key determinant of PCBs' neurodevelopmental toxicities. The objective of this study was to characterize cord blood levels of PCBs, pp'-DDE, and HCB among 751 infants who were born between 1993 and 1998 to mothers residing adjacent to a PCB-contaminated harbor in New Bedford, Massachusetts, and for whom the neurodevelopmental toxicities of these compounds are being studied. We refined standard analytic methods to optimize the sensitivity and precision of trace-level PCB, p,p'-DDE, and HCB measurements in blood. Using these methods, we measured the concentrations of 51 individual PCBs, their sum (sum(PCB)), p,p'-DDE, and HCB in cord serum. With correction for background contamination, the respective mean+/-SD cord serum concentrations of sum(PCB), p,p'-DDE, and HCB were 0.54+/-0.83, 0.48+/-0.94, and 0.03+/-0.04 ng/g serum. These concentrations were generally lower than those in most of the few published studies with congener-specific measures of PCBs in cord blood. However, for less-chlorinated PCB congeners (e.g., congeners 99 and 118), study samples had concentrations comparable to those in other populations, including groups at risk for high dietary PCB exposure. Of note, the contaminated harbor sediment has a relatively high proportion of less-chlorinated PCB congeners. Thus, although the sum(PCB) in study infants was not higher than concentrations in infants studied elsewhere, the relative predominance of less-chlorinated congeners was generally consistent with the characteristics of the contaminated site.

Analysis of chlorpyrifos exposure and human health: expert panel report.

This report summarizes the deliberations of an eight-member panel of scientists convened by Dow AgroSciences in cooperation with the U.S. Environmental Protection Agency (EPA). The panel was charged with evaluating the scientific literature on the health effects potentially associated with exposure to the insecticide chlorpyrifos. Specifically, the panel was asked to (1) evaluate human experience data available and address the adequacy of the available current literature; (2) develop a list of recommendations for epidemiology studies, including appropriate endpoints and study populations, and strengths and weaknesses of each approach; and (3) draft a report to summarize its recommendations. The panel assessed the quality of the existing epidemiologic literature on chlorpyrifos and specific outcomes such as neuropathy (including organophosphate induced delayed neurotoxicity), behavior (cognition and affect), immunologic, and multiple complaints (also referred to as multiple chemical sensitivities). The majority of panel members (five members) agreed that the literature reviewed provided little or no scientific evidence that chlorpyrifos exposure causes harm to human health other than its known cholinergic effects associated with acute poisoning. Those panel members voting in the minority (three members) agreed that the studies reviewed provided inadequate evidence to preclude the possibility of adverse effects to human health from chlorpyrifos exposure at levels associated with its manufacture or professional application. Those voting in the minority suggested further investigation of cohort(s) of workers engaged in either the manufacture or the professional application of chlorpyrifos, or both. Compared to the general population, these groups have relatively high levels of exposure to chlorpyrifos. The primary health outcomes recommended for study were cognitive and affective disorders, with consideration of the assessment of peripheral neuropathy also suggested for at least a subset of the cohort.

Using ecological data to estimate a regression model for individual data: the association between arsenic in drinking water and incidence of skin cancer.

In ecologic studies, participants are studied by groups, and the exposure status of each group is usually represented by a single indicator, mostly the mean exposure. In this paper, we propose using multiple variables derived from dummy variables at the individual level to describe the exposure. An analysis of the association between arsenic in drinking water and skin cancer was used as an example. Well water arsenic levels and skin cancer incidence from 1980 to 1987 were assessed for 243 townships in Taiwan. We first analyzed the data using the mean arsenic concentration in each township as the only exposure variable. The second analysis used multiple variables to describe arsenic exposure; each variable denoted the percentage of wells with arsenic levels within a specific range in each township. Although the first approach did not identify associations between arsenic levels and skin cancer, the multiple-variable approach identifies a positive association at the highest arsenic exposure category (>0.64 mg/L) in both men and women. Therefore, using multiple variables to describe an exposure in ecologic studies may facilitate a better description of the exposure status and thereby lead to more accurate risk assessment, especially when the dose-response relationship is not linear.

Mortality studies of metalworking fluid exposure in the automobile industry: VI. A case-control study of esophageal cancer.

BACKGROUND: Results are reported from a nested case-control study of 60 esophageal cancer deaths among 46,384 automobile manufacturing workers potentially exposed to metalworking fluids (MWF) in machining and grinding operations. METHODS: By using incidence-density sampling, controls were selected with a sampling ratio of 20:1 from among co-workers who remained at risk by the age of death of the case, matched on race, gender, plant, and year of birth. Conditional logistic regression was used to evaluate the risk associated with cumulative exposure (mg/m3-years) to each of three types of metalworking fluid (straight, soluble, and synthetic MWF), as well as with years of exposure to selected components of MWF, including nitrosamines, sulfur, biocides, and several metals. RESULTS: Esophageal cancer was found to be significantly associated with exposure to both soluble and synthetic MWF in grinding operations. The odds ratios (ORs) for grinding with soluble MWF were elevated at 2.5 or greater in all categories of cumulative exposure, although the exposure-response trend was statistically significant only when exposure was measured as duration. Those with 12 or more years exposure to soluble MWF in grinding operations experienced a 9.3-fold relative risk of esophageal cancer mortality (95% CI = 2.1-42.1). The OR for ever grinding with synthetic MWF was 4.1 (95% CI = 1.1-15.0). Elevated risk was also associated with two agents found in both synthetic and soluble fluids, nitrosamines, and biocides. For exposure to nitrosamines, the OR was 5.4 (95% CI = 1.5-19.9); for biocides the OR was 3.8 (95% CI = 0.8-18.9). However, because the same workers were exposed to grinding with synthetics, nitrosamines and biocides, it was not possible to separate the specific risks associated with these components.

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

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

Mortality studies of machining fluid exposure in the automobile industry. V: A case-control study of pancreatic cancer.

Results are presented from a case-control study of 97 cases of pancreatic cancer nested in a cohort of workers from three automobile manufacturing plants. Risk was examined for lifetime exposure to straight, soluble, and synthetic metalworking fluids, as used in specific machining or grinding operations, as well as for constituents of the fluids. Pancreatic cancer was associated with exposure to synthetic fluids in grinding operations, with an odds ratio of 3.0 (95% CI: 1.2-7.5) among those with more than 1.4 mg/m3-years of exposure. We were unable to examine synthetic exposure in the absence of grinding because there was virtually no exposure to synthetics in machining operations in this study population. Although a disproportionately high percent of the cases were black, no black workers had any exposure to synthetic fluids, and no other measured exposure was found to be related to risk. Thus, the previously documented excess risk of pancreatic cancer among blacks in this cohort remains unexplained.

Arsenic in drinking water and incidence of urinary cancers.

The associations between arsenic ingestion and cancers of the bladder and kidney have been documented in Taiwan. To evaluate further such associations for urinary cancers of various cell types, we conducted an ecologic study encompassing 243 townships using cancer registry data of patients diagnosed between 1980 and 1987. We used the proportions of wells with various specified arsenic levels in each township as indicators of exposure and evaluated the effects of urbanization and smoking by an urbanization index and the number of cigarettes sold per capita. In both genders, we observed associations of high arsenic levels in drinking water with transitional cell carcinomas of the bladder, kidney, and ureter and all urethral cancers combined. We also observed such associations in adenocarcinomas of the bladder in males, but not in squamous cell carcinomas of the bladder or renal cell carcinomas or nephroblastomas of the kidney. There was also a positive association between the urbanization index and transitional cell carcinomas of the ureter in males. The number of cigarettes sold per capita was not a good predictor for urinary cancers. The results indicate that the carcinogenicity of arsenic may be cell type specific.

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

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

Mortality studies of machining fluid exposure in the automobile industry. IV: A case-control study of lung cancer.

Machining fluids are diverse products that contain numerous additives and contaminants, including polycyclic aromatic hydrocarbons. Studies treating machining fluids as an aggregate exposure have found both positive and negative associations with lung cancer. In this nested case-control study of automotive workers (667 cases and 3,041 matched controls), individual estimates of exposure quantity and duration for specific classes of machining fluids were derived. An inverse dose-response relationship was found between synthetic machining fluids and lung cancer mortality, with an odds ratio of 0.6 (95% CI = 0.4, 0.8) for the highest level of lifetime exposure. The relationship was strongest for recent exposures. There was little evidence of an association with soluble or straight oil machining fluids. Risks were inconsistently elevated in workers exposed to aluminum. Results from this study provide strong evidence that exposure to machining fluids is not associated with an increased risk of lung cancer mortality in automotive workers.