Harvey Checkoway

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 PM_2.5-Mn in the study settlements. Results: Mean PM_2.5-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.

Environmental Health Perspectives is an Open Access journal published by the National Institute of Environmental Health Sciences. Environmental Health Perspectives is an Open Access journal published by the National Institute of Environmental Health Sciences.

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.

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.

Introduction: There is a lack of consistency in associations between workplace factors and risk of Parkinson disease (PD), and paucity of such data on women. We took a classic occupational epidemiology approach that assesses associations with occupational groups in order to derive insights about potential occupation-specific exposures that may be causal. Methods: The Women’s Health Initiative (WHI-OS) is a prospective cohort that enrolled 91,627 postmenopausal women, 50 to 79 years of age from 10/01/93 to 12/31/98, at 40 clinical centers across the US with average follow-up of 11 years, who reported up to three paid jobs held the longest since age 18; these jobs were coded and duration of employment calculated. We defined the case by self-report of doctor-diagnosed PD (at baseline or follow-up), death attributed to PD, or medication consistent with PD. Results: Among 2,590 cases, we report evidence of excess risk among “counselors, social workers, and other community and social service specialists”. There was a suggestion of increase in risk among post-secondary teachers, and “building and grounds cleaning and maintenance”. There was also evidence of deficit in risk among women who worked in sales. Results with ever-employed and duration were similar, except for evidence of excess of 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, especially for trades largely unaffected by recent technological advances.

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.

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.