Severity of parkinsonism associated with environmental manganese exposure.

BACKGROUND: Exposure to occupational manganese (Mn) is associated with neurotoxic brain injury, manifesting primarily as parkinsonism. The association between environmental Mn exposure and parkinsonism is unclear. To characterize the association between environmental Mn exposure and parkinsonism, we performed population-based sampling of residents older than 40 in Meyerton, South Africa (N = 621) in residential settlements adjacent to a large Mn smelter and in a comparable non-exposed settlement in Ethembalethu, South Africa (N = 95) in 2016-2020. METHODS: A movement disorders specialist examined all participants using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3). Participants also completed an accelerometry-based kinematic test and a grooved pegboard test. We compared performance on the UPDRS3, grooved pegboard, and the accelerometry-based kinematic test between the settlements using linear regression, adjusting for covariates. We also measured airborne PM2.5-Mn in the study settlements. RESULTS: Mean PM2.5-Mn concentration at a long-term fixed site in Meyerton was 203 ng/m3 in 2016-2017 - approximately double that measured at two other neighborhoods in Meyerton. The mean Mn concentration in Ethembalethu was ~ 20 times lower than that of the long-term Meyerton site. UPDRS3 scores were 6.6 (CI 5.2, 7.9) points higher in Meyerton than Ethembalethu residents. Mean angular velocity for finger-tapping on the accelerometry-based kinematic test was slower in Meyerton than Ethembalethu residents [dominant hand 74.9 (CI 48.7, 101.2) and non-dominant hand 82.6 (CI 55.2, 110.1) degrees/second slower]. Similarly, Meyerton residents took longer to complete the grooved pegboard, especially for the non-dominant hand (6.9, CI -2.6, 16.3 s longer). CONCLUSIONS: Environmental airborne Mn exposures at levels substantially lower than current occupational exposure thresholds in the United States may be associated with clinical parkinsonism.

Residential proximity to greenhouse crops and pesticide exposure (via acetylcholinesterase activity) assessed from childhood through adolescence.

BACKGROUND: Off-target drift of pesticides from farms increases the risk of pesticide exposure of people living nearby. Cholinesterase inhibitors (i.e. organophosphates and carbamates) are frequently used in agriculture and inhibit acetylcholinesterase (AChE) activity. Greenhouse agriculture is an important production method, but it is unknown how far pesticide drift from greenhouses can extend and expose people living nearby. METHODS: This study included 1156 observations from 3 exams (2008, Apr, 2016 and Jul-Oct 2016) of 623 children aged 4-to-17 years living in agricultural communities in Ecuador. AChE, a physiological marker of cholinesterase inhibitor exposure, was measured in blood. Geographic positioning of greenhouses and homes were obtained using GPS receivers and satellite imagery. Distances between homes and the nearest greenhouse edge, and areas of greenhouse crops within various buffer zones around homes were calculated. Repeated-measures regression adjusted for hemoglobin and other covariates estimated change in AChE relative to distance from greenhouses. RESULTS: The pooled mean (SD) of AChE activity was 3.58 U/mL (0.60). The median (25th-75th %tile) residential distance to crops was 334 m (123, 648) and crop area within 500 m of homes (non-zero values only) was 18,482 m2 (7115, 61,841). Residential proximity to greenhouse crops was associated with lower AChE activity among children living within 275 m of crops (AChE difference per 100 m of proximity [95% CI] = -0.10 U/mL [-0.20, -0.006]). Lower AChE activity was associated with greater crop area within 500 m of homes (AChE difference per 1000 m2 [95% CI] = -0.026 U/mL [-0.040, -0.012]) and especially within 150 m (-0.037 U/mL [-0.065, -0.007]). CONCLUSIONS: Residential proximity to floricultural greenhouses, especially within 275 m, was associated with lower AChE activity among children, reflecting greater cholinesterase inhibitor exposure from pesticide drift. Analyses of residential proximity and crop areas near homes yielded complementary findings. Mitigation of off-target drift of pesticides from crops onto nearby homes is recommended.

Herpesvirus Infections and Risk of Parkinson's Disease.

INTRODUCTION: Herpesviruses might play a role in the pathogenesis of neurodegenerative disorders. We sought to examine a possible association between alpha herpesvirus infections and Parkinson's disease. METHODS: We conducted a population-based case-control study of incident Parkinson's disease in 2009 Medicare beneficiaries age 66-90 years (89,790 cases, 118,095 randomly selected comparable controls). We classified beneficiaries with any diagnosis code for "herpes simplex" and/or "herpes zoster" in the previous 5 years as having had the respective alpha herpesviruses. In beneficiaries with Part D prescription coverage, we also identified those prescribed anti-herpetic medications. We calculated odds ratios (OR) and 95% CI between alpha herpesvirus diagnosis/treatment and Parkinson's disease with logistic regression, with adjustment for age, sex, race/ethnicity, smoking, and use of medical care. RESULTS: Parkinson's disease risk was inversely associated with herpes simplex (OR 0.79, 95% CI 0.74-0.84), herpes zoster (OR 0.88, 95% CI 0.85-0.91), and anti-herpetic medications (OR 0.87, 95% CI 0.80-0.96). CONCLUSION: Herpesvirus infection or treatment might reduce risk of Parkinson's disease, but future studies will be required to explore whether this inverse association is causal.

Lifetime exposure to ultraviolet radiation and the risk of multiple sclerosis in the US radiologic technologists cohort study.

BACKGROUND: Low exposure to ultraviolet radiation (UVR) from sunlight may be a risk factor for developing multiple sclerosis (MS). Possible pathways may be related to effects on immune system function or vitamin D insufficiency, as UVR plays a role in the production of the active form of vitamin D in the body. OBJECTIVE: This study examined whether lower levels of residential UVR exposure from sunlight were associated with increased MS risk in a cohort of radiologic technologists. METHODS: Participants in the third and fourth surveys of the US Radiologic Technologists (USRT) Cohort Study eligible (N = 39,801) for analysis provided complete residential histories and reported MS diagnoses. MS-specialized neurologists conducted medical record reviews and confirmed 148 cases. Residential locations throughout life were matched to satellite data from NASA's Total Ozone Mapping Spectrometer (TOMS) project to estimate UVR dose. RESULTS: Findings indicate that MS risk increased as average lifetime levels of UVR exposures in winter decreased. The effects were consistent across age groups <40 years. There was little indication that low exposures during summer or at older ages were related to MS risk. CONCLUSION: Our findings are consistent with the hypothesis that UVR exposure reduces MS risk and may ultimately suggest prevention strategies.

Considerations for refining the risk assessment process for formaldehyde: Results from an interdisciplinary workshop.

Anticipating the need to evaluate and integrate scientific evidence to inform new risk assessments or to update existing risk assessments, the Formaldehyde Panel of the American Chemistry Council (ACC), in collaboration with the University of North Carolina, convened a workshop: "Understanding Potential Human Health Cancer Risk - From Data Integration to Risk Evaluation" in October 2017. Twenty-four (24) invited-experts participated with expertise in epidemiology, toxicology, science integration and risk evaluation. Including members of the organizing committee, there were 29 participants. The meeting included eleven presentations encompassing an introduction and three sessions: (1) "integrating the formaldehyde science on nasal/nasopharyngeal carcinogenicity and potential for causality"; (2) "integrating the formaldehyde science on lymphohematopoietic cancer and potential for causality; and, (3) "formaldehyde research-data suitable for risk assessment". Here we describe key points from the presentations on epidemiology, toxicology and mechanistic studies that should inform decisions about the potential carcinogenicity of formaldehyde in humans and the discussions about approaches for structuring an integrated, comprehensive risk assessment for formaldehyde. We also note challenges expected when attempting to reconcile divergent results observed from research conducted within and across different scientific disciplines - especially toxicology and epidemiology - and in integrating diverse, multi-disciplinary mechanistic evidence.

Occupation and Parkinson disease in the Women's Health Initiative Observational Study.

INTRODUCTION: There is a lack of consistent study findings on associations between workplace exposures and the risk of Parkinson disease (PD) and a paucity of such data on women. We assessed PD risk among occupational groups to derive insights about potential occupation-specific exposures in a large cohort of women. METHODS: The Women's Health Initiative Observational Study (WHI-OS) is a prospective cohort that enrolled 91 627 postmenopausal women, 50 to 79 years of age, from 01 October 1993 through 31 December 1998, at 40 clinical centers across the United States, with average follow-up interval of 11 years. These women reported up to three paid jobs, held the longest since age 18; these jobs were coded and duration of employment calculated. We defined a case by self-report of doctor-diagnosed PD (at baseline or follow-up), death attributed to PD, or taking medication consistent with PD. RESULTS: Among 2590 PD cases, we found evidence of excess risk among "counselors, social workers, and other community and social service specialists," and there was a suggestion of increased in risk among postsecondary teachers, and "building and grounds cleaning and maintenance" workers. There was also evidence of a deficit in risk among women who worked in sales. Results according to ever-employed and job duration were similar, except for evidence of excess risk among "health technologists and technicians" with more than 20 years of employment. Longer duration of life on a farm was associated with higher risk. CONCLUSION: Our findings paint a largely reassuring picture of occupational risks for PD among US women.

Peak Exposures in Epidemiologic Studies and Cancer Risks: Considerations for Regulatory Risk Assessment.

We review approaches for characterizing "peak" exposures in epidemiologic studies and methods for incorporating peak exposure metrics in dose-response assessments that contribute to risk assessment. The focus was on potential etiologic relations between environmental chemical exposures and cancer risks. We searched the epidemiologic literature on environmental chemicals classified as carcinogens in which cancer risks were described in relation to "peak" exposures. These articles were evaluated to identify some of the challenges associated with defining and describing cancer risks in relation to peak exposures. We found that definitions of peak exposure varied considerably across studies. Of nine chemical agents included in our review of peak exposure, six had epidemiologic data used by the U.S. Environmental Protection Agency (US EPA) in dose-response assessments to derive inhalation unit risk values. These were benzene, formaldehyde, styrene, trichloroethylene, acrylonitrile, and ethylene oxide. All derived unit risks relied on cumulative exposure for dose-response estimation and none, to our knowledge, considered peak exposure metrics. This is not surprising, given the historical linear no-threshold default model (generally based on cumulative exposure) used in regulatory risk assessments. With newly proposed US EPA rule language, fuller consideration of alternative exposure and dose-response metrics will be supported. "Peak" exposure has not been consistently defined and rarely has been evaluated in epidemiologic studies of cancer risks. We recommend developing uniform definitions of "peak" exposure to facilitate fuller evaluation of dose response for environmental chemicals and cancer risks, especially where mechanistic understanding indicates that the dose response is unlikely linear and that short-term high-intensity exposures increase risk.

Occupational health risks and intervention strategies for US taxi drivers.

Research has shown that taxi drivers are at risk for numerous health concerns, such as low back and leg pain, linked to their highly sedentary occupation, long work hours and stressors related to the job (e.g. low income, safety threats). The goal of this study was to explore occupational health risks and opportunities for health interventions with taxi drivers using community-based participatory research (CBPR) methods. A mixed methods approach included first a convenience sample of 19 East African taxi drivers participating in focus group discussions. Second, a convenience sample of 75 current taxi drivers (M age = 45.7 years) and 25 non-driver comparison participants (M age = 40.3 years) were recruited to complete a structured self-reported questionnaire and objective measures of health. Health education was provided alongside the research to address common health concerns and to ensure mutual benefit and an action orientation. The focus groups described numerous health concerns that drivers attributed to their occupation, including chronic pain, sleep deprivation, cardiovascular disease, diabetes, kidney disease and eye problems, as the most common. Participants offered ideas for health interventions that include workplace reform and driver education. Quantitative data indicate that 44% of drivers reported their health as 'fair' or 'poor'. Drivers were more likely to report musculoskeletal pain, less sleep, more fatigue and less physical activity as compared to non-drivers. The majority of drivers reported financial and job dissatisfaction. The research provides data to inform targeted health interventions that support the health and safety of taxi drivers.

Exposure-Lag-Response in Longitudinal Studies: Application of Distributed-Lag Nonlinear Models in an Occupational Cohort.

Prolonged exposures can have complex relationships with health outcomes, as timing, duration, and intensity of exposure are all potentially relevant. Summary measures such as cumulative exposure or average intensity of exposure may not fully capture these relationships. We applied penalized and unpenalized distributed-lag nonlinear models (DLNMs) with flexible exposure-response and lag-response functions in order to examine the association between crystalline silica exposure and mortality from lung cancer and nonmalignant respiratory disease in a cohort study of 2,342 California diatomaceous earth workers followed during 1942-2011. We also assessed associations using simple measures of cumulative exposure assuming linear exposure-response and constant lag-response. Measures of association from DLNMs were generally higher than those from simpler models. Rate ratios from penalized DLNMs corresponding to average daily exposures of 0.4 mg/m3 during lag years 31-50 prior to the age of observed cases were 1.47 (95% confidence interval (CI): 0.92, 2.35) for lung cancer mortality and 1.80 (95% CI: 1.14, 2.85) for nonmalignant respiratory disease mortality. Rate ratios from the simpler models for the same exposure scenario were 1.15 (95% CI: 0.89, 1.48) and 1.23 (95% CI: 1.03, 1.46), respectively. Longitudinal cohort studies of prolonged exposures and chronic health outcomes should explore methods allowing for flexibility and nonlinearities in the exposure-lag-response.

Estimating Counterfactual Risk Under Hypothetical Interventions in the Presence of Competing Events: Crystalline Silica Exposure and Mortality From 2 Causes of Death.

Exposure to silica has been linked to excess risk of lung cancer and nonmalignant respiratory disease mortality. In this study we estimated risk for both these outcomes in relation to occupational silica exposure as well as the reduction in risk that would result from hypothetical interventions on exposure in a cohort of exposed workers. Analyses were carried out using data from an all-male study population consisting of 2,342 California diatomaceous earth workers regularly exposed to crystalline silica and followed between 1942 and 2011. We estimated subdistribution risk for each event under the natural course and interventions of interest using the parametric g-formula to adjust for healthy-worker survivor bias. The risk ratio for lung cancer mortality, comparing an intervention in which a theoretical maximum exposure limit was set at 0.05 mg/m3 (the current US regulatory limit) with the observed exposure concentrations, was 0.86 (95% confidence interval: 0.63, 1.22). The corresponding risk ratio for nonmalignant respiratory disease mortality was 0.69 (95% confidence interval: 0.52, 0.93). Our findings suggest that risks from both outcomes would have been considerably lower if historical silica exposures in this cohort had not exceeded current regulatory limits.

Lifetime exposure to estrogen and progressive supranuclear palsy: Environmental and Genetic PSP study.

BACKGROUND: Studies suggesting a protective effect of estrogen in neurodegenerative diseases prompted us to investigate this relationship in progressive supranuclear palsy (PSP). METHODS: This case-control study evaluated the self-reported reproductive characteristics and estrogen of 150 women with PSP and 150 age-matched female controls who participated in the Environmental Genetic-PSP study. Conditional logistic regression models were generated to examine associations of PSP with estrogen. RESULTS: There was no association between years of estrogen exposure duration and PSP. There was a suggestion of an inverse association between composite estrogen score and PSP that did not reach statistical significance (P = .06). Any exposure to estrogen replacement therapy halved the risk of PSP (odds ratio = 0.52; 95% confidence interval = 0.30-0.92; P = .03). Among PSP cases, earlier age at menarche was associated with better performance on Hoehn and Yahr stage (ß = -0.60; SE = 0.26; P = .02) and Unified Parkinson's Disease Rating Scale II score (ß = -5.19; SE = 2.48; P = .04) at clinical examination. CONCLUSIONS: This case-control study suggests a protective role of lifetime estrogen exposure in PSP. Future studies will be needed to confirm this association. © 2018 International Parkinson and Movement Disorder Society.

Acetylcholinesterase activity and time after a peak pesticide-use period among Ecuadorian children.

PURPOSE: Mother's Day (May) is a holiday with substantial demand for flowers, associated with heightened flower production and escalated pesticide use. The effect of spray seasons on pesticide exposures of children living in agricultural communities but who do not work in agriculture is poorly understood. In this study, we estimated the association of time after Mother's Day harvest with children's acetylcholinesterase (AChE) activity. AChE is a physiological marker of organophosphate/carbamate pesticide exposures that may take up to 3 months to normalize after its inhibition. METHODS: We examined 308 children, aged 4-9 years, in Ecuadorian agricultural communities during a low flower-production season but within 63-100 days (mean: 81.5 days, SD: 10.9) after Mother's Day harvest. We quantified AChE activity (mean: 3.14 U/mL, SD: 0.49) from a single finger-stick sample. RESULTS: We observed positive linear associations between time after the harvest and AChE among participants living near plantations. The associations were strongest among participants living within 233 m [(0.15 U/mL (95% CI 0.02, 0.28)], slightly weaker among participants living within 234-532 m [0.11 U/mL (0.00, 0.23)], and not associated among participants at greater distances. Similar findings were observed across categories of areas of flower plantations within 500 m of homes. CONCLUSIONS: These cross-sectional findings suggest that a peak pesticide-use period can decrease AChE activity of children living near plantations. These seasonal pesticide exposures could induce short- and long-term developmental alterations in children. Studies assessing exposures at multiple times in relation to pesticide spray seasons among children who do not work in agriculture are needed.

Occupational exposures and parkinsonism among Shanghai women textile workers.

BACKGROUND: Endotoxin, a contaminant of cotton dust, is an experimental model for parkinsonism (PS). METHODS: We investigated associations between exposures to endotoxin, solvents, magnetic fields, and night shift work, and neurologist-determined PS among Shanghai women textile workers, including 537 retired cotton factory workers ages ≥50 years and an age-matched reference group of 286 retired textile workers not exposed to cotton dust. Repeat exams were conducted 2.5 years after enrollment among 467 cotton workers and 229 reference workers. RESULTS: We identified 39 prevalent PS cases and 784 non-cases. No consistent or statistically significant associations were observed for endotoxin, solvents, magnetic fields, or shift work with PS risk, severity, or progression. CONCLUSIONS: Despite the null findings, additional studies of endotoxin exposure and risk of PS in other well-characterized occupational cohorts are warranted in view of toxicological evidence that endotoxin is a pathogenic agent and its widespread occurrence in multiple industries worldwide.

Anticoagulant Use in High Stroke-Risk Patients With Nonvalvular Atrial Fibrillation.

Background Oral anticoagulants (OACs) are recommended for nonvalvular atrial fibrillation (NVAF) patients with moderate-to high-stroke risk. Objective To examine nationally reflective OAC usage in incident NVAF patients longitudinally. Design Three-year retrospective cohort analysis. Setting Medicare Part D recipients in the contiguous United States. PARTICIPANTS: 52,465 Medicare beneficiaries with incident NVAF in 2010 with two or more atrial fibrillation diagnoses seven or more days apart. Main outcome measure Stroke risk via congestive heart failure, hypertension, age greater than or equal to 75, diabetes, stroke, vascular disease, age 65-74, sex category (CHA2DS2-VASc) score. Primary outcome was proportion of patients receiving one or more OACs post-NVAF diagnoses. Results Of 48,980 high-risk patients, 32.7% received one or more OAC within 60 days of diagnosis. By close of 2011, 48% had one or more OAC. OAC use increased to 52.9% by close of 2012. Conclusions Fewer than 33% of high-risk NVAF patients received OACs within 60 days of diagnosis in 2010. Despite increased use over time, oral anticoagulation was below 53% at study end. Use of OACs declined with CHA2DS2-VASc greater than 6. Expanded efforts are warranted to augment OAC use in high stroke-risk patients.

Cognitive control dysfunction in workers exposed to manganese-containing welding fume.

BACKGROUND: Chronic exposure to manganese (Mn) is a health concern in occupations such as welding because of well-established motor effects due to basal ganglia dysfunction. We hypothesized that cognitive control (the ability to monitor, manipulate, and regulate ongoing cognitive demands) would also be affected by chronic Mn exposure. METHODS: We examined the relationship between Mn exposure and cognitive control performance in 95 workers with varying intensity and duration (median 15.5 years) of exposure to welding fume. We performed linear regression to assess the association between exposure to Mn-containing welding fume and cognitive control tasks. RESULTS: Overall performance was inversely related to intensity of welding exposure (P = 0.009) and was driven by the Two-Back and Letter Number Sequencing tests that assess working memory (both P = 0.02). CONCLUSIONS: Occupational exposure to Mn-containing welding fume may be associated with poorer working memory performance, and workers may benefit from practices that reduce exposure intensity. Am. J. Ind. Med. 60:181-188, 2017. © 2016 Wiley Periodicals, Inc.

Smoking and haptoglobin phenotype modulate serum ferritin and haptoglobin levels in Parkinson disease.

The phenotype Hp 2-1 of haptoglobin has been previously associated with increased risk of Parkinson disease (PD) and with serum iron abnormalities in PD patients. Tobacco smoking has been consistently observed in epidemiology studies to be inversely related to PD risk, with mechanisms that remain uncertain. We recently observed that the protective effect of smoking on PD risk is stronger among subjects of haptoglobin Hp 2-2 and Hp 1-1 phenotypes, and weaker among subjects of haptoglobin Hp 2-1 phenotype. In this PD case-control study, we investigated whether tobacco smoking was associated with changes in serum haptoglobin and ferritin concentration that depended on haptoglobin phenotype among 106 PD patients and 238 controls without PD or other neurodegenerative disorders. Serum ferritin concentration, serum haptoglobin concentration, haptoglobin phenotype, and smoking data information of cases and controls were obtained. Differences in haptoglobin and ferritin concentration by smoking status and pack-years of smoking were calculated as well as regression between pack-years and haptoglobin and ferritin concentration, and the effect of haptoglobin phenotype on these parameters. Tobacco smoking was associated with an elevation in serum haptoglobin concentration, especially among healthy controls of haptoglobin Hp 2-2 phenotype, and with an elevation in ferritin concentration especially among PD patients of haptoglobin Hp 2-1 phenotype. These findings suggest that an elevation in haptoglobin concentration, preferentially among subjects of haptoglobin Hp 2-2 phenotype, could be a contributing factor to the protective effect of smoking on PD risk.

Maternal body burden of cadmium and offspring size at birth.

Increasing evidence suggests an inverse association between cadmium (Cd) and size at birth, potentially greatest among female neonates. We evaluated whether greater maternal body burden of Cd is associated with reduced neonatal anthropometry (birthweight, birth length, head circumference, and ponderal index) and assessed whether these associations differ by infant sex. The analytic sample for the present study (n=396) was derived from a subcohort of 750 women randomly drawn from among all participants (N=4344) in the Omega Study, a prospective pregnancy cohort. Creatinine-corrected Cd in maternal clean-catch spot urine samples (U-Cd) was quantified by inductively coupled plasma mass spectrometry. Continuous log2-transformed Cd (log2-Cd) and U-Cd tertiles (low<0.29µg/g creatinine, middle 0.29-0.42µg/g creatinine, high≥0.43µg/g creatinine) were used in multivariable linear regression models. Females had reduced birth length with greater U-Cd tertile, whereas males birth length marginally increased [ß(95% CI) females: low=reference, middle=-0.59cm (-1.37, 0.19), high=-0.83cm (-1.69, 0.02), p-trend=0.08; males: low=reference, middle=0.18cm (-0.59, 0.95), high=0.78cm (-0.04, 1.60), p-trend=0.07; p for interaction=0.03]. The log2-Cd by infant sex interaction was statistically significant for ponderal index [p=0.003; ß(95% CI): female=0.25kg/m(3) (-0.20, 0.70); male=-0.63kg/m(3) (-1.01, -0.24)] and birth length [p<0.001; ß(95% CI): female=-0.47cm (-0.74, -0.20), male=0.32cm (0.00, 0.65)]. Our findings suggest potential sex-specific reversal of Cd's associations on birth length and contribute to the evidence suggesting Cd impairs fetal growth.

Shift work and breast cancer among women textile workers in Shanghai, China.

PURPOSE: Although night-shift work has been associated with elevated risk of breast cancer in numerous epidemiologic studies, evidence is not consistent. We conducted a nested case-cohort study to investigate a possible association between shift work including a night shift and risk of breast cancer within a large cohort of women textile workers in Shanghai, China. METHODS: The study included 1,709 incident breast cancer cases and 4,780 non-cases. Data on historical shift work schedules were collected by categorized jobs from the factories, where the study subjects had worked, and then were linked to the complete work histories of each subject. No jobs in the factories involved exclusively night-shift work. Therefore, night shift was evaluated as part of a rotating shift work pattern. Hazard ratios and 95 % confidence intervals were calculated using Cox proportional hazards modeling adapted for the case-cohort design for years of night-shift work and the total number of nights worked. Additionally, analyses were repeated with exposures lagged by 10 and 20 years. RESULTS: We observed no associations with either years of night-shift work or number of nights worked during the entire employment period, irrespective of lag intervals. Findings from the age-stratified analyses were very similar to those observed for the entire study population. CONCLUSIONS: The findings from this study provide no evidence to support the hypothesis that shift work increases breast cancer risk. The positive association between shift work and breast cancer observed in Western populations, but not observed in this and other studies of the Chinese population, suggests that the effect of shift work on breast cancer risk may be different in Asian and Caucasian women.

Extended follow-up of lung cancer and non-malignant respiratory disease mortality among California diatomaceous earth workers.

OBJECTIVES: Millions of workers worldwide are employed in occupations involving potentiality hazardous exposure to crystalline silica. The diatomaceous earth industry can have particularly high exposures, but there is a lower likelihood of simultaneously occurring confounding exposures. We extended follow-up for diatomaceous earth industry workers previously studied for mortality. METHODS: The cohort included 2342 white men who were employed for at least 1 year at a diatomaceous earth plant in Lompoc, California beginning in 1942. Workers' vital status was updated using the National Death Index through 2011, an extension of 19 years from earlier studies. Detailed work history and quantitative air monitoring measurements estimated exposure intensity. Cox proportional hazards modelling estimated HRs and 95% CIs. SMRs were calculated. RESULTS: Elevated mortality was observed by quartile of cumulative crystalline silica exposure for lung cancer (HR=2.03, 95% CI 1.07 to 3.85, highest quartile, unlagged) and non-malignant respiratory disease (NMRD) (HR=3.59, 95% CI 1.94 to 6.67, highest quartile, unlagged), although trends were not statistically significant. Associations were attenuated when adjusted for smoking and asbestos exposure. Mortality from NMRD was significantly increased over the entire follow-up compared to the general population (SMR=1.37, 95% CI 1.17 to 1.60). An increase for lung cancer was confined to the earlier follow-up (SMR=1.29, 95% CI 1.01 to 1.61). CONCLUSIONS: The risk of lung cancer and NMRD mortality remained elevated, although generally non-significant, and exposure-response trends with cumulative crystalline silica persisted on extended follow-up of this cohort. The findings support a generally consistently observed aetiological relation between crystalline silica and lung cancer.

Blood α-synuclein in agricultural pesticide handlers in central Washington State.

Epidemiologic studies suggest that occupational exposure to pesticides might increase Parkinson disease risk. Some pesticides, such as the organophosphorus insecticide chlorpyrifos, appear to increase the expression of α-synuclein, a protein critically involved in Parkinson disease. Therefore, we assessed total blood cell α-synuclein in 90 specimens from 63 agricultural pesticide handlers, mainly Hispanic men from central Washington State, who participated in the state's cholinesterase monitoring program in 2007-2010. Additionally, in age-adjusted linear regression models for repeated measures, we assessed whether α-synuclein levels were associated with butyrylcholinesterase-chlorpyrifos adducts or cholinesterase inhibition measured in peripheral blood, or with self-reported pesticide exposure or paraoxonase (PON1) genotype. There was no evidence by any of those indicators that exposure to chlorpyrifos was associated with greater blood α-synuclein. We observed somewhat greater α-synuclein with the PON1-108T (lower paraoxonase enzyme) allele, and with ≥ 10 h of exposure to cholinesterase inhibiting insecticides in the preceding 30 days, but neither of these associations followed a clear dose-response pattern. These results suggest that selected genetic and environmental factors may affect α-synuclein blood levels. However, longitudinal studies with larger numbers of pesticide handlers will be required to confirm and elucidate the possible associations observed in this exploratory cross-sectional study.