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IntroductionThe risk of asbestosis, malignant mesothelioma and lung cancer among motor vehicle mechanics is of concern because of potential exposure to chrysotile asbestos during brake, clutch and gasket repair and maintenance. Asbestos has also been used in insulation and exhaust systems.MethodsWe examined the long-term risk of incident mesothelioma, lung cancer, asbestosis and other lung diseases and mortality due to mesothelioma, lung cancer, asbestosis and other lung diseases in a nationwide cohort of all men registered as motor vehicle mechanics since 1970 in Denmark. This was compared with the corresponding risk in a cohort of male workers matched 10:1 by age and calendar year, with similar socioeconomic status (instrument makers, dairymen, upholsterers, glaziers, butchers, bakers, drivers, farmers and workers in the food industry, trade or public services).ResultsOur study included 138 559 motor vehicle mechanics (median age 24 years; median follow-up 20 years (maximum 45 years)) and 1 385 590 comparison workers (median age 25 years; median follow-up 19 years (maximum 45 years)). Compared with other workers, vehicle mechanics had a lower risk of morbidity due to mesothelioma/pleural cancer (n=47 cases) (age-adjusted and calendar-year-adjusted HR=0.74 (95% CI 0.55 to 0.99)), a slightly increased risk of lung cancer (HR=1.09 (95% CI 1.03 to 1.14)), increased risk of asbestosis (HR=1.50 (95% CI 1.10 to 2.03)) and a chronic obstructive pulmonary disease risk close to unity (HR=1.02 (95% CI 0.99 to 1.05)). Corresponding HRs for mortality were 0.86 (95% CI 0.64 to 1.15) for mesothelioma/pleural cancer, 1.06 (95% CI 1.01 to 1.12) for lung cancer, 1.79 (95% CI 1.10 to 2.92) for asbestosis, 1.06 (95% CI 0.86 to 1.30) for other lung diseases caused by external agents and 1.00 (95% CI 0.98 to 1.01) for death due to all causes.ConclusionsWe found that the risk of asbestosis was increased among vehicle mechanics. The risk of malignant mesothelioma/pleural cancers was not increased among vehicle mechanics.

Jennifer L Beebe-Dimmer,1,2 Jon P Fryzek,3 Cecilia L Yee,1,2 Tapashi B Dalvi,4 David H Garabrant,3 Ann G Schwartz,1,2 Shirish Gadgeel1,2 1Department of Oncology, Wayne State University School of Medicine, 2Barbara Ann Karmanos Cancer Institute, Detroit, 3EpidStat Institute, Ann Arbor, MI, 4AstraZeneca, Gaithersburg, MD, USA Introduction: Mesothelioma is a rare malignancy typically associated with exposure to asbestos and poor survival. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and overall survival (OS) utilizing the National Cancer Institute’s Surveillance, Epidemiology, and End Results–Medicare database. Materials and methods: Patients in this study were diagnosed with malignant mesothelioma of the pleura or peritoneum between January 1, 2005 and December 31, 2009 with follow-up for survival through December 31, 2010. We examined both patient and tumor characteristics at time of diagnosis and subsequent treatment patterns (surgery, radiation, and chemotherapy). Among patients treated with chemotherapy, we determined chemotherapy regimen and OS by line of therapy. Results: Of the 1,625 patients considered eligible for this investigation, the median age at diagnosis was 78 years. Nearly a third of patients (30%) had surgery as part of their treatment and 45% were given chemotherapy. The median OS was 8 months (range 1–69 months). Among chemotherapy patients, the most commonly (67%) prescribed regimen for first-line therapy was cisplatin or carboplatin (Ca/Ci) combined with pemetrexed (Pe). Among those prescribed Ca/Ci + Pe as first-line therapy, retreatment with Ca/Ci + Pe (28%) or treatment with gemcitabine (30%) were the most common second-line therapies. Median OS for those receiving first-line chemotherapy was 7 months, and among those receiving second-line therapy median OS was extended an additional 5 months. Conclusion: Irrespective of surgical resection, mesothelioma patients receiving some form of chemotherapy survived longer than patients who did not, with an additional survival benefit among those patients receiving multimodal treatment. Keywords: mesothelioma, chemotherapy, epidemiology, outcomes, mortality, morbidity, survival

The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non-Hodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans.

Workers engaged in the production of Portland cement may come into contact with potential occupational hazards, but existing epidemiological studies show wide variation in risk estimates for cancer incidence and mortality in relation to cement exposure. This report identified studies of cement workers and associations with cancer incidence and mortality in a systematic review and meta-analysis. A systematic review according to the PRISMA guidelines was conducted to identify studies of Portland cement workers and cancer outcomes. Meta-analyses were performed using random effects models for all cancers combined and for each cancer site with three or more reported measures of risk. A total of 26 studies were included in the review (14 occupational cohort studies and 12 case-control studies). Overall, the meta-relative risks did not provide convincing evidence for increased risks of any cancers in relation to cement exposure. Meta-SMR and 95% CIs were 0.94 (0.76 to 1.16) for six studies reporting all cancers combined, 0.93 (0.62 to 1.39) for seven studies reporting on lung cancer, 1.07 (0.72 to 1.59) for five studies reporting on stomach cancer, and 1.05 (0.79 to 1.40) for four studies reporting on colorectal cancer. Meta-relative risks for cancer incidence were similarly null for all sites with the exception of colorectal cancer which had a borderline statistically significant elevated risk (SIR=1.38, 95% CI 1.02 to 1.88). Overall, the meta-relative risks calculated across 26 published studies do not provide evidence of increased risks for cancer in relation to cement exposure.

Objective: Evaluate whether childhood cancer incidence is associated with counties with hydraulic fracturing (HF). Methods: We compared cancer incidence in children in Pennsylvania counties before and after HF drilling began, using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results: The total number of cancers observed was close to expected both before drilling began (SIR = 0.94; 95% CI, 0.90 to 0.99) and after drilling (SIR = 1.02; 95% CI, 0.98 to 1.07) for counties with oil and natural gas wells. Analyses for childhood leukemia were also unremarkable (SIR for leukemia before drilling = 0.97 [95% CI, 0.88 to 1.06]; SIR for leukemia after drilling = 1.01 [95% CI, 0.92 to 1.11]). A slightly elevated SIR was found for central nervous system tumors after drilling (SIR = 1.13; 95% CI, 1.02 to 1.25). This was because of a slight excess in those counties with the fewest number of wells. Conclusions: This study offers comfort concerning health effects of HF on childhood cancers.

We conducted a systematic review of the epidemiologic literature for glyphosate focusing on non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM) – two cancers that were the focus of a recent review by an International Agency for Research on Cancer Working Group. Our approach was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. We evaluated each relevant study according to a priori criteria for study quality: adequacy of study size, likelihood of confounding, potential for other biases and adequacy of the statistical analyses. Our evaluation included seven unique studies for NHL and four for MM, all but one of which were case control studies for each cancer. For NHL, the case-control studies were all limited by the potential for recall bias and the lack of adequate multivariate adjustment for multiple pesticide and other farming exposures. Only the Agricultural Health (cohort) Study met our a priori quality standards and this study found no evidence of an association between glyphosate and NHL. For MM, the case control studies shared the same limitations as noted for the NHL case-control studies and, in aggregate, the data were too sparse to enable an informed causal judgment. Overall, our review did not find support in the epidemiologic literature for a causal association between glyphosate and NHL or MM.

Background: We published a meta-analysis of the association between work as a motor vehicle mechanic and mesothelioma in 2004. Since then, several relevant studies on this topic have been published. Thus, to update the state-of-the-science on this issue, we conducted a new systematic review and meta-analysis. Methods: A comprehensive PubMed literature search through May 2014 was conducted to identify studies that reported relative risk estimates for mesothelioma among motor vehicle mechanics (in general), and those who were engaged in brake repair (specifically). Studies were scored and classified based on study characteristics. Random-effects meta-analyses generated summary relative risk estimates (SRREs) and corresponding 95% confidence intervals (CI). Heterogeneity of results was examined by calculating Q-test P-values (P-H) and I 2 estimates. Sub-group and sensitivity analyses were conducted for relevant study characteristics and quality measures. Results: Ten case-control studies, one cohort study, and five proportionate mortality ratio (PMR)/standardized mortality odds ratio (SMOR) studies were identified and included in the quantitative assessment. Most meta-analysis models produced SRREs below 1.0, and no statistically significant increases in mesothelioma were observed. The SRRE for all studies was 0.80 (95% CI: 0.61-1.05) with significant heterogeneity (P-H

Context Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls that have toxic equivalency factors (TEFs) were measured in serum of 946 subjects in five Michigan counties. The study was motivated by concerns about human exposure to dioxin-contaminated sediments in the Tittabawassee River (TR). Most of the toxic equivalency in TR sediments is from two furan congeners, 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-pentaCDF). Case presentation The individual with the highest adjusted (for age, age squared, and body mass index) serum level of 2,3,4,7,8-pentaCDF in the study (42.5 ppt) reported a unique history of raising cattle and vegetables in the floodplain of the TR. Interviews and serum samples were obtained from the index case and 15 other people who ate beef and vegetables raised by the index case. 2,3,4,7,8-pentaCDF in beef lipid was estimated to have been more than three orders of magnitude greater than background (1,780 vs. 1.1 ppt). The mean, median, and 95th percentile for serum 2,3,4,7,8-pentaCDF in the study control population were 6.0, 5.4, and 13.0 ppt, respectively, and were 9.9, 8.4, and 20.5 ppt among beef and vegetable consumers, respectively. Back extrapolation for the index case suggests that his increase in serum concentration of 2,3,4,7,8-pentaCDF above background may have been as high as 146 ppt. Discussion Consumption of beef and/or vegetables raised on dioxin-contaminated soil may be an important completed pathway of exposure. Relevance to public health practice Animals and crops should not be raised for human consumption in areas contaminated with dioxins.

Background: Evidence indicates that vitamin E has anticarcinogenic properties for gastrointestinal cancers; however, few studies have examined this with respect to exocrine pancreatic cancer. Objective: The objective was to examine whether vitamin E intake and serum α-tocopherol concentrations were prospectively associated with exocrine pancreatic cancer. Design: We conducted a cohort analysis of prediagnostic vitamin E intake (4 tocopherols, 4 tocotrienols), serum α-tocopherol concentrations, and pancreatic cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male Finnish smokers aged 50–69 y at baseline. During follow-up from 1985 to 2004 (maximum: 19.4 y; median: 16 y), 318 incident cases were diagnosed among cohort participants with complete serum samples (n = 29,092); 306 cases had complete dietary data (n = 27,111). Cox proportional hazards models adjusted for age, smoking history, history of diabetes mellitus, and/or serum cholesterol were used to calculate hazard ratios (HRs) and 95% CIs. Results: Higher α-tocopherol concentrations were associated with lower pancreatic cancer risk (highest compared with lowest quintile, HR: 0.52; 95% CI: 0.34, 0.80; P for trend = 0.03; continuous HR: 0.91; 95% CI: 0.84, 0.99). Polyunsaturated fat, a putative prooxidant nutrient, modified the association such that the inverse α-tocopherol association was most pronounced in subjects with a high polyunsaturated fat intake (ie, >9.9 g/d; highest compared with lowest quintile, HR: 0.38; 95% CI: 0.20, 0.70; P for trend = 0.03; continuous HR: 0.86; 95% CI: 0.75, 0.97; P for interaction = 0.05 and 0.02, respectively). No associations were observed for dietary tocopherols and tocotrienols. Conclusion: Our results support the hypothesis that higher α-tocopherol concentrations may play a protective role in pancreatic carcinogenesis in male smokers.

Inherited predisposition to pancreas cancer accounts for approximately 10% of cases. Familial aggregation may be influenced by shared environmental factors and shared genes. We evaluate whether a family history of pancreas cancer is a risk factor for ten specified cancers in first-degree relatives: bladder, breast, colon, head and neck, lung, lymphoma, melanoma, ovary, pancreas, and prostate. Risk factor data and cancer family history were obtained for 1,816 first-degree relatives of pancreas cancer case probands (n = 247) and 3,157 first-degree relatives of control probands (n = 420). Unconditional logistic regression models using generalized estimating equations were used to estimate odds ratios (ORs), and 95% confidence intervals of having a first-degree relative a specified cancer. A family history of pancreas cancer was associated with a doubled risk of lymphoma (OR = 2.83, 95% CI = 1.02–7.86) and ovarian cancer (OR = 2.25, 95% CI = 0.77–6.60) among relatives after adjustment. Relatives with a family history of early-onset pancreas cancer in a proband had a sevenfold increased risk of lymphoma (OR = 7.31, 95% CI = 1.45 to 36.7). Relatives who ever smoked and had a family history of pancreas cancer had a fivefold increased risk of ovarian cancer (OR = 4.89, 95% CI = 1.16–20.6). Family history assessment of cancer risk should include all cancers. Assessment of other known and suspected risk factors in relatives will improve risk evaluation. As screening and surveillance methods are developed, identifying those at highest risk is crucial for a successful screening program.

Increased body mass index has emerged as a potential risk factor for pancreatic cancer. The authors examined whether the association between body mass index and pancreatic cancer was modified by gender, smoking, and diabetes in residents of southeastern Michigan, 1996-1999. A total of 231 patients with newly diagnosed adenocarcinoma of the exocrine pancreas were compared with 388 general population controls. In-person interviews were conducted to ascertain information on demographic and lifestyle factors. Unconditional logistic regression models estimated the association between body mass index and pancreatic cancer. Males' risk for pancreatic cancer significantly increased with increasing body mass index (p(trend) = 0.048), while no relation was found for women (p(trend) = 0.37). Among nonsmokers, those in the highest category of body mass index were 3.3 times (95% confidence interval: 1.2, 9.2) more likely to have pancreatic cancer compared with those with low body mass index. In contrast, no relation was found for smokers (p(trend) = 0.94). While body mass index was not associated with pancreatic cancer risk among insulin users (p(trend) = 0.11), a significant increase in risk was seen in non-insulin users (p(trend) = 0.039). This well-designed, population-based study offered further evidence that increased body mass index is related to pancreatic cancer risk, especially for men and nonsmokers. In addition, body mass index may play a role in the etiology of pancreatic cancer even in the absence of diabetes.

Questions persist about adverse effects such as impaired cognition and attention, incoordination, spasticity, or parkinsonism from chronic, low-level exposures to organophosphate (OP) compounds. In a prospective cohort study, we evaluated chlorpyrifos-manufacturing workers and a referent group on 2 occasions, 1 year apart, to determine whether occupational exposure to chlorpyrifos produced clinically evident central nervous system (CNS) dysfunction. Chlorpyrifos subjects had significantly higher TCP excretion and lower average BuChE activity than referents in a range in which physiological effects on B-esterases exist. Few subjects had neurologic symptoms or signs, and there were no significant group differences in terms of signs at baseline or second examinations. Chronic chlorpyrifos exposure produced no clinical evidence of cortical, pyramidal tract, extrapyramidal, or other CNS dysfunction among chlorpyrifos subjects compared with referents, either at baseline or after 1 year of additional chlorpyrifos exposure.

Aims: To determine whether chronic occupational exposure to chlorpyrifos at levels associated with various aspects of manufacturing produced a clinically evident or subclinical peripheral neuropathy. Methods: Clinical and quantitative nerve conduction study (NCS) examinations were performed on two occasions on chlorpyrifos manufacturing workers who had measurable chlorpyrifos exposure and a referent group. Baseline evaluations were performed on 53 of 66 eligible chlorpyrifos subjects and on 60 of 74 eligible referent subjects; one-year evaluations were completed on 111 of the 113 subjects evaluated at baseline. Results: Chlorpyrifos and referent groups differed significantly in measures of 3,5,6 trichloro-2-pyridinol excretion and plasma butyrylcholinesterase (BuChE) activity, indicating substantially higher exposures among chlorpyrifos subjects. Few subjects had clinically important neurological symptoms or signs. NCS results were comparable to control values, and there were no significant group differences in NCS results at baseline, one year, or change over one year. No chlorpyrifos subject fulfilled conventional criteria for confirmed peripheral neuropathy at baseline or one-year examinations. The odds ratios for developing any diagnosable level of peripheral neuropathy among the chlorpyrifos subjects was not increased at baseline or at one year compared to referents at baseline. Mixed regression models used to evaluate subclinical group-by-time interactions showed numerous significant NCS differences attributable to near-nerve temperature differences among all subjects between the baseline and one-year examinations, but only a few disparate effects related to group. Conclusions: Chronic chlorpyrifos exposure during the manufacturing process sufficient to produce biological effects on BuChE activity was not associated with clinically evident or subclinical peripheral neuropathy at baseline or with measurable deterioration among chlorpyrifos subjects compared to referents after one year of additional exposure.

No abstract

Exposure to solvents has been reported to increase the risk of scleroderma. The authors investigated the relation between exposures to solvents in occupational and hobby settings and the development of scleroderma among women in a case-control study with population-based controls in Michigan (1980-1991) and Ohio (1980-1992). A total of 660 cases and 2,227 frequency-matched controls were interviewed by telephone. Diagnoses of scleroderma were verified by medical records review. Paint thinners and removers were significantly associated with scleroderma both by self-report (odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.4, 2.6) and after expert review (OR = 2.0, 95% CI: 1.5, 2.6). Other petroleum distillates (gasoline and mineral spirits) were not significantly associated with scleroderma after controlling for other correlated exposures in multivariable analyses. Trichloroethylene was associated with scleroderma both by self-report (OR = 2.0, 95% CI: 0.8, 4.8) and after expert review (OR = 1.9, 95% CI: 0.6, 6.6), but not significantly. Analyses by duration of exposure found that risk increased with the duration of use of any of the solvents (OR = 1.01/year of exposure, 95% CI: 1.01, 1.02), but there was no evidence of increasing risk with increasing duration of exposure for any specific solvent studied. In summary, exposures to paint thinners and removers were associated with scleroderma in women but showed no evidence of increasing risk with increasing duration. Exposures to other specific chlorinated and nonchlorinated hydrocarbon solvents were not clearly associated with scleroderma.

Although it is often claimed that health care workers are at increased risk of latex sensitization and type I allergies, there has been no systematic analysis of the epidemiologic studies that are relevant to this conclusion. A systematic analysis of the epidemiologic literature found that, in the past 14 years, there have been 48 epidemiologic studies of type I latex allergy among health care workers. Of these, 2 cohort studies estimated the incidence of latex sensitization by skin prick testing at between 1% and 2.5% per year. Neither compared the risk to that in the general population. The prevalence of sensitization in health care workers varied between 0% and 30%, yet this large variation was unexplained. Increased risk of sensitization was not clearly associated with the duration of work in health care, the time spent wearing latex gloves, the frequency of exposure, the specific job categories, the use of powdered versus nonpowdered latex gloves, the use of latex versus nonlatex gloves, or any measurements of ambient exposure to latex proteins. The epidemiologic studies do not support a conclusion that health care workers are at clearly increased risk of latex sensitization or type I allergies compared to other occupations in the United States. The role of latex gloves in causing latex sensitization and type I allergic symptoms remains poorly defined because of the inconsistent results across studies. Future epidemiologic studies are needed that include measured exposures to latex antigens, that compare health care workers to appropriate referent groups, and that address confounding by atopy, age, sex, and race.

We reviewed blink reflexes recorded from 51 railroad workers with long-term occupational exposure to solvents who were diagnosed by others with solvent-induced toxic encephalopathy. No worker fulfilled conventional clinical criteria for dementia or trigeminal mononeuropathy. All workers had normal R1 and R2 blink reflex latencies. Rl latencies correlated significantly with several nerve conduction measures, including F wave latencies, suggesting that some intersubject variability reflected intrinsic conduction properties, not isolated brain-stem function. Although normal, the workers' R1 latencies were significantly prolonged compared with historical control groups, including gender-matched control subjects of similar mean age (11.2 ms vs 9.9 ms; P < 0.0001). Stepwise multiple regression models demonstrated significant associations of R1 latency with age and use of CNS-active prescription medications (P = 0.003), but duration of occupational solvent exposure did not enter into the models. Paradoxically, workers using CNS-active medications had significantly shorter R1 latencies compared with workers not using such medications (10. 9 vs 11. 7 ms; P = 0.01). Job title, another potential surrogate measure of exposure, was not significantly related to reflex latencies. The geographical site of predominant solvent exposure did influence R1 latency, and workers from one site had longer exposure duration and longer R1 latencies than remaining workers. However, an interaction between age and exposure duration (r = 0.39; P = 0.003) confounded interpretation of this observation. Disability or work status, mental status findings, or classification of encephalopathy did not influence blink reflex latencies. The overall results do not support, but do not entirely exclude, a possible relationship between subclinical blink reflex abnormalities and occupational exposure to solvents. Nevertheless, it is clear from these results that the small group differences in R1 latency between exposed workers and control subjects are of no diagnostic importance and of uncertain physiologic importance, and they may reflect unrecognized confounders and technical factors.

Background: Pancreatic cancer is the fifth leading cause of cancer-related mortality in the United States. Although smoking and age are known risk factors for pancreatic cancer, several case reports and case-control studies have suggested that there is also a familial risk. We evaluated whether a family history of pancreatic cancer increases the risk of pancreatic cancer in first-degree relatives and whether smoking and younger age at cancer diagnosis further increase this risk. Methods: We conducted in-person interviews with 247 patients (case probands) with pancreatic cancer and 420 population-based control probands to collect risk factor data and pancreatic cancer family history for 1816 first-degree relatives of the case probands and 3157 first-degree relatives of the control probands. We analyzed the data by unconditional logistic regression models, with adjustment for correlated data by use of generalized estimating equations. All statistical tests were two-sided. Results: A positive family history of pancreatic cancer (i.e., being related to a case proband) or ever-smoking cigarettes approximately doubled the risk of pancreatic cancer (relative risk [RR] = 2.49; 95% confidence interval [CI] = 1.32 to 4.69; RR = 2.04; 95% CI = 1.09 to 3.83, respectively). The RR increased to 8.23 (95% CI = 2.18 to 31.07) for relatives who ever smoked and were related to a case proband who was diagnosed before age 60 years. Conclusion: Routine questioning of patients about a family history of pancreatic cancer, the age of onset of this cancer in their relatives, and the patient's smoking status may identify individuals at high risk of pancreatic cancer. Future research exploring the genetic and environmental interactions associated with the risk of pancreatic cancer is critically important.

Aim: To use biological monitoring data to evaluate the soundness of job based exposure classifications. Methods: The authors studied 52 chlorpyrifos manufacturing workers and 60 referent workers to compare chlorpyrifos exposure estimations from job titles and work areas to urinary excretion of 3,5,6 trichloro-2-pyridinol (TCP), a metabolite of chlorpyrifos. Work history records and industrial hygiene monitoring data were used to establish cumulative interim exposure. Chlorpyrifos exposure during the study year was assessed biologically by urinary excretion of TCP. Results: Exposure as measured by three urinary TCP samples was significantly higher among the chlorpyrifos workers (188 μg/l) than it was for the referent subjects (7 μg/l). Urinary TCP also correlated well with specific exposure categories of negligible (0.73–1.98 mg/m 3 days), low (1.99–4.91 mg/m 3 days), and moderate (4.92–15.36 mg/m 3 days). The weighted Kappa coefficient was 0.80 (95% CI 0.72 to 0.87) for the mean TCP over the study period. Conclusions: The estimates of chlorpyrifos exposure based on job classifications and industrial hygiene measurements were significantly related to urinary TCP excretion, indicating that the ambient estimates are useful for providing exposure estimates among chlorpyrifos manufacturing workers.

A case-control study of pancreas cancer in residents, aged 30-79 years, of 18 counties in southeastern Michigan was conducted to investigate the risks of exposure to DDT and related materials in the general population. Sixty-six people with cytologically diagnosed pancreas cancer were identified using 7 participating hospitals in metropolitan Detroit and Ann Arbor. One hundred and thirty-one controls were frequency-matched to the cases on age, sex, ethicity and county of residence by random-digit dialing. All study participants were administered a questionnaire to assess life-time exposure to pesticides from both environmental and occupational sources, family history of cancer, past medical history, smoking history and demographic information. A statistically significant increased risk was found for self-reported exposure to ethylan (1,1-dichloro-2,2-bis(4-methoxyphenyl) ethane). Increased odds ratios were observed for self-reported exposures to chloropropylate and DDT, as well as for the summary group of organochlorine pesticides which included all of these materials, though these associations were not significant.

Twenty-three of 34 workers who had worked in the injection molding operation making polyurethane foam parts at an automobile parts manufacturing plant developed respiratory symptoms and/or systemic symptoms over a 2-month period following the full production use of a new diisocyanate paint that contained 1,3-bis(isocyanatomethyl)cyclohexane pre-polymer (BIC) (CAS #75138-76-0, 38661-72-2). At 3 months, all subjects underwent an interview, physical examination, pre- and post-shift pulmonary function tests, and either methacholine challenge test or bronchodilator challenge at an occupational health clinic. The most frequently cited symptoms were dyspnea (65%), cough (61%), chest tightness (57%), chills (57%), wheezing (30%), and myalgias, arthralgias, and nausea (26%). Thirteen subjects had either a positive methacholine challenge test or a positive response to bronchodilator challenge, making the overall prevalence of airway hyperresponsiveness 38%. The overall prevalence of hypersensitivity pneumonitis-like reactions among line operators in the injection molding process was 27%. This disease outbreak suggests that 1,3-bis(isocyanatomethyl)cyclohexane pre-polymer may cause asthma and hypersensitivity pneumonitis-like reactions. The use of BIC was discontinued 6 months after the first workers developed symptoms. © 1996 Wiley-Liss, Inc.

This study examined work-related chronic abnormality in pulmonary function and work-related acute irritant symptoms associated with exposure to borate dust in mining and processing operations. Chronic effects were examined by pulmonary function at the beginning and end of a 7-year interval. Time-specific estimates of sodium borate particulate exposures were used to estimate cumulative exposure during the study interval. Change in pulmonary function over the 7 years was found unrelated to the estimate of cumulative exposure during that interval. Exposure-response associations also were examined with respect to short-term peak exposures and incidence of five symptoms of acute respiratory irritation. Hourly measures of health outcome and continuous measures of particulate exposure were made on each subject throughout the day. Whenever a subject reported one of the irritant symptoms, a symptom intensity score was also recorded along with the approximate time of onset. The findings indicated that exposure-response relationships were present for each of the specific symptoms at several symptom intensity levels. The associations were present when exposure was estimated by both day-long and short-term (15-min) time-weighted average exposures. Associations persisted after taking account of smoking, age, and the presence of a common cold. No significant difference in response rate was found between workers exposed to different types of sodium borate dusts.

To address the hypotheses that electrical workers are exposed to higher magnetic fields and are at higher risk of leukemia than nonelectrical workers, we performed a registry-based case-control study among men aged 20-64 years with known occupation who were diagnosed with cancer in Los Angeles County between 1972 and 1990. Controls were men with cancers other than those of the central nervous system or leukemia. Magnetic field measurements on workers in each electrical occupation and in a random sample of occupations presumed to be nonelectrical were used to estimate magnetic field exposures for each occupation. Among men in electrical occupations, 121 leukemias were diagnosed. With the exception of electrical engineers, magnetic field exposures were higher among workers in electrical occupations than in nonelectrical occupations. A weakly positive trend in leukemia risk across average occupational magnetic field exposure was observed (odds ratio [OR] per 10 milligauss increase in average magnetic field = 1.2, 95% confidence interval [CI] 1.0-1.5). A slightly stronger association was observed for chronic myloid leukemia, although only 28 cases occurred among electrical workers (OR 10 milligauss increase = 1.6, 95% CI = 1.2-2.0). The results were not materially altered by adjustment for exposure to several agents known or suspected to cause leukemia. Although not conclusive, these results are consistent with findings from studies based on job title alone that electrical workers may be at slightly increased risk of leukemia.

A meta-analysis of the relation between asbestos exposure and colorectal cancer mortality was conducted, using published reports of 20 asbestos-exposed cohorts. Summary standardized mortality ratios (SMRs) for colorectal cancer were examined in relation to asbestos type and estimates of dust exposure (as direct estimators of asbestos exposure) and in relation to lung cancer SMR and the proportion of all deaths due to mesothelioma (as proxy estimators of asbestos exposure). An elevated summary SMR was observed in cohorts exposed to amphibole asbestos (summary SMR = 1.47; 95% confidence interval (CI) 1.09-2.00), but not in cohorts exposed to serpentine asbestos (summary SMR = 1.04; 95% CI 0.81-1.33) or in cohorts exposed to both serpentine and amphibole asbestos (summary SMR = 1.03; 95% CI 0.74-1.42). Cohorts having a lung cancer SMR greater than 2.00 had a summary SMR of 1.51 (95% CI 1.29-1.76), and cohorts in which more than 1% of all deaths were attributed to mesothelioma had a summary SMR of 1.24 (95% CI 0.94-1.64). After stratifying the cohorts based on mortality due to all cancers excluding those known or suspected to be associated with asbestos exposure, lung cancer mortality was not clearly associated with colorectal cancer mortality, suggesting that the crude association between these factors may be due to misdiagnosis of lung cancer as other types of cancer in the reported causes of death. These results suggest that exposure to amphibole asbestos may be associated with colorectal cancer, but these findings may reflect an artifact of miscertification of cause of death. The results also suggest that serpentine asbestos is not associated with colorectal cancer.

Dioxins are a family of chemical compounds that has received considerable attention, both historically and currently. This article reviews scientific field studies that examine the relationship between living on soil contaminated with dioxins and the level of dioxins in people's serum, with an emphasis on the University of Michigan Dioxin Exposure Study (UMDES), the largest and most comprehensive study of its kind. These studies conclude that the levels of dioxins in serum are most strongly correlated with age, gender, body mass index, weight loss, breast feeding, and smoking. Levels of dioxins in soil are not significant predictors for dioxin concentrations in serum. The increase in serum dioxin levels that is seen with age results from historic exposure and does not represent ongoing exposure. Based on the scientific field studies conducted to date, it appears that, in the absence of the consumption of contaminated animal products, there is little evidence of ongoing exposure from contaminated soil.

The goal of the present study was to quantify the population-based background serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by using data from the reference population of the 2005 University of Michigan Dioxin Exposure Study (UMDES) and the 2003-2004 National Health and Nutrition Examination Survey (NHANES).Multiple imputation was used to impute the serum TCDD concentrations below the limit of detection by combining the 2 data sources. The background mean, quartiles, and 95th percentile serum TCDD concentrations were estimated by age and sex by using linear and quantile regressions for complex survey data.Any age- and sex-specific mean, quartiles, and 95th percentiles of background serum TCDD concentrations of study participants between ages 18 and 85 years can be estimated from the regressions for the UMDES reference population and the NHANES non-Hispanic white population. For example, for a 50-year-old man in the reference population of UMDES, the mean, quartiles, and 95th percentile serum TCDD concentrations are estimated to be 1.1, 0.6, 1.1, 1.8, and 3.3 parts per trillion, respectively. The study also shows that the UMDES reference population is a valid reference population for serum TCDD concentrations for other predominantly white populations in Michigan.The serum TCDD concentrations increased with age and increased more over age in women than in men, and hence estimation of background concentrations must be adjusted for age and sex. The methods and results discussed in this article have wide application in studies of the concentrations of chemicals in human serum and in environmental samples.

The diets of 746 colon cancer cases in Los Angeles County, California (USA) were compared with those of 746 controls matched on age, sex, race, and neighborhood. In both genders, total energy intake was associated with significantly increased risk, and calcium intake was associated with significantly decreased risk. These effects were reduced only slightly after adjustment for the nondietary risk factors (weight, physical activity, family history, and, if female, pregnancy history). In men, total fat and alcohol intakes were responsible for the calorie effect; in women, no individual source of calories was associated independently with risk. Neither saturated fat nor fat from animal sources was responsible for the fat effect. There were no additional independent significant effects for sucrose, fiber, cruciferous vegetables, beta-carotene, other vitamins, or any other nutrient or micronutrient. In univariate analyses, meats, poultry, breads, and sweets were associated with excess risk, and yogurt was protective. After adjustment for sources of calories, no individual food was associated with excess risk, but yogurt remained significantly protective. Total calories were associated with excess risk throughout the colon while the effects of calcium, fat, and alcohol appeared somewhat stronger in the distal colon. After adjustment, crude fiber was significantly protective in the ascending colon but not even weakly protective in the distal colon.

Background A cohort mortality study among 5886 chemical manufacturing workers was completed in 1987 and showed increased mortality due to pancreatic cancer. Purpose We conducted a nested case-control study of pancreatic cancer among these chemical manufacturing workers to identify risk factors for this disease. Methods Twenty-eight verified cases of pancreatic cancer and 112 matched controls were studied. Next of kin of each subject were interviewed to determine lifestyle factors, including tobacco, alcohol, and coffee consumption. Written work records and interviews with co-workers were used to determine chemical exposures at the plant under study. Results DDT was associated with pancreatic cancer (risk ratio [RR] for ever exposed compared with never exposed = 4.8; 95% confidence interval = 1.3-17.6). Among subjects who had a mean exposure to DDT of 47 months, the risk was 7.4 times that among subjects with no exposure. Two DDT derivatives, Ethylan and DDD, were additionally associated with pancreatic cancer (RR = 5.0 and 4.3, respectively); exposures to these two chemicals were correlated, and it was not possible to determine whether each acted independently of the other. Smoking was identified as an independent risk factor, but controlling for smoking (and other potential confounders) in the analyses did not appreciably alter the risks seen for DDT, DDD, or Ethylan. Conclusions Exposure to DDT was associated with pancreatic cancer. The association was not explained by exposure to lifestyle factors or other chemicals, and risk increased with both duration of exposure and latency since first exposure. Implications These results may indicate that DDT can cause pancreatic cancer in humans under circumstances of heavy and prolonged exposure.

Reported evidence regarding relationships between polychlorinated biphenlys (PCBs) and thyroid homeostasis in adults has been considered contradictory. The objective of this systematic review is to determine a possible association between PCB exposure and the circulating thyroid hormones and thyrotropin (TSH) levels in adults, by analyzing the quality of published studies. A systematic review of epidemiological papers was conducted using PubMed. An evaluation of the quality of 22 studies was performed, and the papers were classified into two tiers: Tier I for studies with higher quality scores (eight) and Tier II for studies with lower quality scores (14). It appears that PCBs can interfere with thyroid hormone homeostasis; however epidemiological evidence is not entirely clear. For triiodothyronine (T3) and thyroxine (T4), Tier I studies showed either an inverse (four cases for T3; five cases for T4) or no significant association (two cases for T3; five cases for T4) with PCBs. In the case of free thyroxine and TSH, the Tier I papers observed no clear association with PCB levels. Rigorous study design, assessment of potential confounding factors, and fuller reporting of methods and results in future studies will facilitate understanding of whether PCB exposure is associated with changes in thyroid function.

We conducted interviews on 306 histologically confirmed incident cases of nasopharyngeal carcinoma (NPC) occurring in residents of Guangzhou City, China, who were under the age of 50, and an equal number of age-, sex-, and neighborhood-matched controls. We also interviewed 110 mothers of patients under 45 and 139 mothers of controls who were matched to patients under age 45, to obtain information on childhood exposures of study subjects. Occupational exposure to products of combustion (RR = 2.4, p = 0.001) and cotton dust (RR = 0.3, P = 0.01) was independently related to risk of NPC. Use of tobacco products showed a moderate association with NPC; a lifetime exposure of 30+ pack-year equivalents conferred a 2-fold increased risk. A history of chronic ear or nose condition (rhinitis, sinusitis, nasal polyp, otitis media) was another risk factor for NPC (RR = 2.2, p less than 0.0005), and 18 cases compared to 3 controls had a first-degree relative with NPC (RR = 6.0, p = 0.001).

Pancreatic cancer is a major contributor to cancer mortality. Studies suggest that a few risk factors, including cigarette smoking, body mass index, having a relative with pancreatic cancer, and diabetes may be related to pancreatic cancer risk. We conducted a case–control study in southeastern Michigan to examine the relation between the abovementioned risk factors and mutations of the K-ras oncogene and p53 tumor suppressor gene. Two hundred forty-five patients with newly diagnosed pancreatic cancer and 420 general population controls were enrolled in the study. For this analysis, all case subjects were restricted to the pancreatic cancer patients that had tissue blocks available for study (n = 51). In-person interviews were conducted to ascertain information on demographic and lifestyle factors. Adjusted logistic regression analyses were conducted to compare various subject characteristics of pancreatic cancer patients with K-ras and p53 mutations and their subtypes to the characteristics of the general population controls. Smoking (adjusted odds ratio [aOR] = 2.0; 95% confidence interval [95%CI] = 0.9–4.3) and diabetes diagnosed 5 or more years before interview (aOR = 3.4; 95%CI = 1.3–8.8) were associated with pancreatic cancer patients positive for K-ras codon 12 mutations, but not with pancreatic cancer patients negative for K-ras codon 12 mutations. On the other hand, none of the examined risk factors were meaningfully related to patients with p53 mutations. This study suggests that some recognized risk factors for pancreatic cancer may also be associated with K-ras codon 12 mutations. However, further large-scale studies are warranted.

e18544 Background: Mesothelioma is a rare malignancy typically associated with exposure to asbestos and poor survival. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns and survival, both overall and according to treatment course utilizing the National Cancer Institute’s SEER-Medicare database. Methods: Patients in this study were diagnosed with malignant mesothelioma of the pleura, peritoneum or other site between 01/01/2005 and 12/31/2009 with follow-up for survival through 12/31/2010. We determined the distribution of patient and tumor characteristics at time of diagnosis, and subsequent treatment patterns (surgery, radiation and chemotherapy). Among patients treated with chemotherapy, we determined chemotherapy regimen and estimated survival by line of therapy. Results: Of the 1,625 patients considered eligible for this investigation, the median age at time of diagnosis was 78 years (age range; 66 to 103 years) and 78% were male. 30% of these pa...

Concerns regarding the safety of silver–mercury amalgam fillings continue to be raised in the absence of any direct evidence of harm. The widespread population exposure to amalgam mandated that a thorough investigation be conducted of its potential effects on the nervous system. The National Institute of Dental and Craniofacial Research and U.S. Air Force investigators collaborated in the ongoing Air Force Health Study (AFHS) of Vietnam era veterans. The primary study question involved adverse health effects associated with exposure to herbicides or dioxin. An assessment of exposure to dental amalgam fillings was added to the 1997–1998 health examination to investigate possible associations between amalgam exposure and neurological abnormalities. Our study population consisted of 1663 dentate AFHS participants, comprised of 986 AFHS controls and 677 Ranch Hand veterans who were exposed to dioxin in Vietnam. Two hundred and fifty-two of the participants had confirmed diabetes mellitus. Study outcomes included clinical neurological signs, vibrotactile thresholds, and summary variables for different levels of peripheral neuropathy. A limitation of our study is that our database did not include more sensitive continuous measures such as nerve conduction studies. No significant associations were found between amalgam exposure and clinical neurological signs of abnormal tremor, coordination, station or gait, strength, sensation, or muscle stretch reflexes or for any level of peripheral neuropathy among our study participants. A statistically significant association was detected between amalgam exposure and the continuous vibrotactile sensation response for the combined non-diabetic participants and separately for non-diabetic AFHS controls. No significant association in this measure was detectable for non-diabetic Ranch Hand veterans or among the combined diabetic participants. The association is a sub-clinical finding that was not associated with symptoms, clinically evident signs of neuropathy, or any functional impairment. Overall, we found no association between amalgam exposure and neurological signs or clinically evident peripheral neuropathy. Our findings do not support the hypothesis that exposure to amalgam produces adverse, clinically evident neurological effects.

We conducted a systematic review and analysis of the epidemiological literature that examines the risk of lung cancer and mesothelioma among motor vehicle mechanics who may have been engaged in brake repair and, thus, were potentially exposed to asbestos. All relevant studies were classified into three tiers according to their quality. Tier III (lowest quality) studies were cited for completeness, but were not included in the meta-analysis. Meta relative risks (meta-RRs) were calculated for mesothelioma and lung cancer using both fixed and random effects models for Tiers I and II, separately, followed by stratified analyses based on study design or exposure characterization (garage workers versus brake workers) and, for lung cancer studies, based on adequate adjustment for smoking. The meta-analysis for Tier I (higher quality) and Tier II (lower quality) studies of mesothelioma yielded RR estimates of 0.92 (95% CI 0.55-1.56) and 0.81 (95% CI 0.52-1.28), respectively. Further stratification according to exposure characterization did not affect the results. The meta-analysis for lung cancer produced RR estimates of 1.07 (95% CI 0.88-1.31) for Tier I and 1.17 (95% CI 1.01-1.36) for Tier II. When the lung cancer analysis was limited to studies that used adequate control for smoking, the resulting RR estimate was 1.09 (95% CI 0.92-1.28). Based on these findings, we conclude that employment as a motor vehicle mechanic does not increase the risk of developing mesothelioma. Although some studies showed a small increase in risk of lung cancer among motor vehicle mechanics, the data on balance do not support a conclusion that lung cancer risk in this occupational group is related to asbestos exposure.

Several studies have reported the occurrence of sensory neuropathy with exposure to chlorpyrifos and other organophosphorus insecticides, at levels not associated with overt toxicity. We evaluated 113 chemical workers, including 53 of 66 (80%) eligible chlorpyrifos workers and 60 of 74 (81%) randomly selected referent workers, to identify evidence of sensory neuropathy or subclinical neuropathy. Compared to referents, chlorpyrifos subjects had significantly longer duration of work in chlorpyrifos-exposed areas (9.72 vs. 0.01 years; P < 0.0001), greater cumulative chlorpyrifos exposure (64.16 vs. 0.69 mg/m3 · day; P < 0.0001), higher urine 3,5,6-trichloro-2-pyridinol (TCP) excretion (108.6 vs. 4.3 μg/g creatinine; P < 0.0001), and lower plasma butyrylcholinesterase (BuChE) activity (7281 vs. 8176 mU/ml; P = 0.003). Despite exposures among chlorpyrifos subjects to levels at which well-described physiological effects on B-esterases exist, the frequency of symptoms or signs of neuropathy did not differ significantly between groups, and the only 2 subjects fulfilling criteria for confirmed neuropathy were both in the referent group. Mean nerve conduction study results were comparable to established control values and did not differ significantly between groups. We found no evidence of sensory neuropathy or isolated peripheral abnormalities among subjects with long-term chlorpyrifos exposure at levels known to be associated with the manufacturing process. Muscle Nerve 29: 677–686, 2004

Cancer incidence and mortality were summarized in Air Force veterans of the Vietnam War. The index subjects were Operation Ranch Hand veterans who sprayed 2,3,7,8 tetrachlorodibenzo-p-dioxin (dioxin)-contaminated herbicides in Vietnam. Comparisons served in Southeast Asia during the same period but did not spray herbicides. We assessed cancer incidence and mortality using national rates and contrasted cancer risk in each of three Ranch Hand dioxin exposure categories relative to comparisons. The incidence of melanoma and prostate cancer was increased among white Ranch Hand veterans relative to national rates. Among veterans who spent at most 2 years in Southeast Asia, the risk of cancer at any site, of prostate cancer and of melanoma was increased in the highest dioxin exposure category. These results appear consistent with an association between cancer and dioxin exposure.

Objectives Concern has been raised that the occurrence of cancer may be increased in neighbourhoods around a former manufactured gas plant in Champaign, Illinois, USA. Thus, we compared historical rates of cancer in this area to comparison communities as well as with nationally standardised rates. Design Retrospective population-based community cancer assessment during 1990–2010. Setting Champaign County, Illinois, USA, and zip codes encompassing the location of the former manufactured gas plant to counties that were similar demographically. Participants Residents of the counties and zip codes studied between 1990 and 2010. Main outcome measures The relative risk (RR) and 95% CI were used to compare cancer incidence and mortality in the areas near the gas compression site to the comparison counties. Standardised incidence ratios (SIRs) were calculated to compare rates in the areas near the gas compression site to expected rates based on overall US cancer rates. Results Total cancer mortality (RR=0.91, 95% CI 0.88 to 0.94) and incidence (RR=0.95, 95% CI 0.94 to 0.97) were reduced significantly in Champaign County versus the comparison counties. Similarly, a reduced rate of total cancer was observed in analyses by zip code (proximal to the former gas plant) when compared with either similar counties (RR=0.89, 95% CI 0.86 to 0.93) or national standardised rates of cancer (SIR=0.88, 95% CI 0.85 to 0.91). Conclusions This historical cancer assessment did not find an increased risk of total cancer or specific cancer types in communities near a former manufactured gas plant site.

A case-control study was conducted among 205 women in Michigan and Ohio who were diagnosed with undifferentiated connective tissue disease (UCTD) to investigate the significance of self-reported past exposures to implanted silicone-containing or non-silicone-containing medical devices. The 205 UCTD cases were compared with 2,095 controls who were sampled by random digit dialing. When silicone-containing devices, including shunts and catheters, were analyzed collectively, a significant association was observed (odds ratio (OR) = 2.81, 95% confidence interval (CI): 1.34, 5.89). The odds ratio for exposure to breast implants was increased, but not significantly (OR = 2.22, 95% CI: 0.65, 7.57). Among the non-silicone-containing devices, artificial joints (OR = 5.01, 95% CI: 1.60, 15.71) and orthopedic metallic fixation devices (OR = 1.95, 95% CI: 1.05, 3.60) were associated with UCTD. The estimations of risk associated with implanted medical devices in UCTD cases were explored in a comparison with 660 scleroderma patients who were ascertained concurrently in Michigan and Ohio. In general, the associations that were observed with non-silicone-containing devices, and more specifically with the fixation devices, persisted in the comparison of UCTD cases with scleroderma patients. The studies conducted among populations in Michigan and Ohio are intended to stimulate new hypotheses, innovative approaches, and the fostering of understanding of the environmental determinants of autoimmune disease.

Epidemiology is the study of the patterns of disease and patterns of exposures in human populations. The main goals of epidemiology are to determine whether specific population groups have an increased risk of developing particular diseases and to determine what factors may be associated with increased risks of disease. In this article, the author focuses on epidemiologic studies of potential neurotoxic exposures, reviewing the basic principles involved and the special challenges associated with providing evidence of causal relationships between exposure and adverse health conditions.

Accurate assessment of occupational history is critical in case-control studies of disease risk associated with employment. However, in some studies of rapidly fatal diseases, a surrogate or next of kin is interviewed rather than the study subject. In a unique re-interview study of subjects from a community-based case-control study originally interviewed 5 years earlier, we evaluated the level of agreement between (1) subjects and their surrogates on re-interview among those who had died since the first interview, and (2) subjects themselves and their responses at re-interview among those still living (to use as a comparison) regarding work history and specific occupational exposures. For employment start and stop dates, number of years worked, and number of jobs reported in the 1980 interview, exact agreement was poor for surrogate respondents and for self-respondents in the re-interview, with percentages ranging from 4% to 40%. Agreement was similar for surrogates and self-respondents for job and industry worked the longest, but percent of agreement among surrogates was significantly lower than among the self-respondents for job and industry worked last. Five (28%) of the kappa values for the industry in which the subject worked had high agreement (kappa > 0.75) for self-respondents and surrogates. None of the kappa statistics for materials handled by subjects in their jobs had high agreement, and 57% of the kappa statistics had poor agreement (kappa 0.0 to 0.39). This study suggests that occupational histories obtained by interview are poorly reproduced, and existing methods may need improvement to collect reliable occupational data. Further, the findings indicate that caution should be exercised when creating a job-exposure matrix based on such data.

We examined 52 railroad workers with long-term occupational solvent exposures (average 22 years duration) who had been previously diagnosed by others as having solvent-induced toxic encephalopathy. All described episodes of transient intoxication associated with occupational solvent exposure. Persistent symptoms developed, an average, 16 years after exposure onset and included impaired memory (38), altered mood (21), imbalance (18), and headache (17). Thirteen workers had mild mental status abnormalities, but none fulfilled conventional clinical criteria for encephalopathy or dementia. None had abnormal blink reflex (51) or abnormal electroencephalographic (39) studies. Eight of 47 magnetic resonance imaging studies showed evidence of scattered ischemic lesions among workers with known diabetes mellitus (2), elevated blood pressure (4), or peripheral vascular disease (2). One magnetic resonance imaging scan showed mild cortical atrophy. In stepwise multiple linear and logistic regression models, no statistically significant (P < 0.05) dose-response relationships were found between exposure duration and symptoms or signs that were suggestive of encephalopathy. However, the number of symptoms (P < 0.001) and the number of signs (P = 0.05) were associated with current use of central nervous system-active medications. Further, lower Mini-Mental Status Examination scores were associated with a history of alcohol abuse (P = 0.01) and lower educational level (P = 0.03). The number of chief symptoms involving memory, mood, balance, or headache differed significantly among workers in different geographic sites (F(3.48) = 2.94, P = 0.04), a finding that was not explained by job title or exposure duration. There also was a significant (P = 0.0001) inverse relationship between initial exposure year (r2 = 0.60) or total years of exposure through 1987 (r2 = 0.56) and interval to major neurologic symptom onset, suggesting that factors other than solvent exposure account in part for worker complaints. We found no objective neurologic evidence supportive of toxic encephalopathy or any other uniform syndrome among these individuals, and most complaints were explained by neuropsychological factors or conditions unrelated to occupational solvent exposure.

Occupational solvent exposure may increase the risk of connective tissue disease (CTD). The objective of this case-control study was to investigate the relation between undifferentiated connective tissue disease (UCTD) and solvent exposure in Michigan and Ohio. Women were considered to have UCTD if they did not meet the American College of Rheumatology classification criteria for any CTD but had at least two documented signs, symptoms, or laboratory abnormalities suggestive of a CTD. Detailed information on solvent exposure was ascertained from 205 cases, diagnosed between 1980 and 1992, and 2,095 population-based controls. Age-adjusted odds ratios (OR) and 95 percent confidence intervals (CI) were calculated for all exposures. Among 16 self-reported occupational activities with potential solvent exposure, furniture refinishing (OR = 9.73, 95 percent CI 1.48-63.90), perfume, cosmetic, or drug manufacturing (OR = 7.71, 95 percent CI 2.24-26.56), rubber product manufacturing (OR = 4.70, 95 percent CI 1.75-12.61), work in a medical diagnostic or pathology laboratory (OR = 4.52, 95 percent CI 2.27-8.97), and painting or paint manufacturing (OR = 2.87, 95 percent CI 1.06-7.76) were significantly associated with UCTD. After expert review of self-reported exposure to ten specific solvents, paint thinners or removers (OR = 2.73, 95 percent CI 1.80-4.16) and mineral spirits (OR = 1.81, 95 percent CI 1.09-3.02) were associated with UCTD. These results suggest that exposure to petroleum distillates increases the risk of developing UCTD.

Previous studies of workers exposed to wood dusts have shown a decreased risk of cancer of the colon in these workers. However, none of these studies adequately controlled for potential confounders, such as physical activity, diet, and family history of colorectal cancer. The purpose of this case-control study was to evaluate the association between exposure to wood dust and risk for colon cancer after adjusting for potential confounders. Four hundred nineteen male cases of adenocarcinoma of the colon, identified from the Los Angeles County Cancer Surveillance Program, were individually matched to neighborhood controls based on gender and date of birth. Exposure to wood dust was associated with reduced risk of colon cancer that was partially masked before adjustment for confounders, and was limited to workers with frequent exposures that had begun at least 30 years before diagnosis [unadjusted and adjusted ORs, respectively, to exposures 5+ times a week beginning 30+ years before diagnosis = 0.63 (95% CI 0.36-1.13) and 0.39 (95% CI 0.20-0.77)]. This study provides additional evidence that heavy exposure to wood dusts may be associated with reduced risk of colon cancer in males after adjustment for other known causes of colon cancer.

In Indonesia, prior studies to identify risk factors for hepatitis A have not provided prevalence estimates in the general population. This study was conducted to measure the prevalence of antibody to hepatis A virus (anti-HAV), and to identify high risk populations and risk factors in preparation for an immunization program. Using randomly selected households in Jakarta, 987 adults and adolescents aged 15 and older were interviewed in 1994 to ascertain demographic information, socioeconomic status and risk factors for anti-HAV. Blood samples were taken for anti-HAV, SGOT and SGPT. Eighty seven percent of the participants were positive for anti-HAV. Risk increased with age, reaching an 18.8-fold risk (95 percent CI 8.0-44.2) among those aged 51 years and over, compared to the reference group aged 15-20 years. Anti-HAV was strongly associated with low socioeconomic status (odds ratio 4.9, 95 percent CI 2.5-9.4). Immunization against hepatitis B was associated with reduced risk of anti-HAV, and a history of foundice increased the risk of anti-HAV. Immunization against HAV should be targeted to adolescents and young adults, particularly those in higher socioeconomic groups, who are least likely to have natural immunity and who are most susceptible to HAV infection in adulthood.

Transdermal nicotine patches are widely prescribed as part of smoking cessation programs, but their efficacy beyond 6 months is not well established. We evaluated the efficacy of a 70-day treatment regimen among 75 subjects in an industrial setting where follow-up was conducted for 11 months. The median time free of cigarettes was 73 days, and the overall smoking abstinence rate was 9% after 11 months of follow-up. Smoking abstinence was significantly higher among those subjects who completed the full course of treatment than among those who did not (25 vs 6%, respectively). Smoking abstinence was also higher among subjects who started smoking after age 17 than among those who started at younger ages and was higher among male than female subjects. We conclude that transdermal nicotine patches are of limited efficacy in achieving long-term smoking cessation and that the relative costs and benefits of this treatment are not adequately specified.