Communities Actively Researching Exposure Study (CARES) CARES Research Findings

We studied the impact of joint exposure to manganese and lead on intelligence quotient (IQ) scores in school-aged children from East Liverpool, Ohio. The negative effect of blood lead on IQ was more pronounced at higher levels of hair and toenail manganese. Our findings suggest that joint exposure to manganese and lead may produce heightened neurocognitive impacts even at blood lead levels below the CDC reference concentration of 5 µg/dL.

Publication: Martin, K. V., Sucharew, H., Dietrich, K. N., Parsons, P. J., Palmer, C. D., Wright, R., Amarasiriwardena, C., Smith, D., Haynes, E. N. (2021). Co-exposure to manganese and lead and pediatric neurocognition in East Liverpool, Ohio. Environmental Research, 202, 111644. doi:https://doi.org/10.1016/j.envres.2021.111644

In this study, the US Environmental Protection Agency (EPA) air quality dispersion model (AERMOD) was used to estimate ambient air manganese levels near the refinery in Marietta, Ohio for the years 2008-2013. From 12,000-56,000 individuals, including over 2,000 children aged 0-14 years, were exposed to respirable annual average ambient air manganese levels exceeding 50 ng/m3 in five of the six years. The study shows that AERMOD modeling of ambient air Mn is a viable method for estimating exposure from refinery emissions and that the Marietta area population was at times exposed to Mn levels that exceeded US EPA guidelines.

Publication: Stolfi A, Fulk F, Reponen T, Hilbert TJ, Brown D, Haynes EN. AERMOD modeling of ambient manganese for residents living near a ferromanganese refinery in Marietta, OH, USA. Environ Monit Assess. 2021 Jun 13;193(7):419. doi: 10.1007/s10661-021-09206-8. PMID: 34120251.

A current review of the literature that resulted in the following conclusions: Manganese exposure is associated with cognitive and motor impairments in both occupational and community settings. Current studies utilize a variety of novel biomarkers to represent manganese exposure. Neuroimaging is an innovate tool to characterize manganese exposure within the brain and assess neurological outcomes. Elderly populations provide insight into the impacts of chronic manganese exposure and the role of manganese in the development and progression of neurodegenerative diseases.

Publication: Martin KV, Edmondson D, Cecil KM, Bezi C, Vance ML, McBride D, Haynes EN. Manganese Exposure and Neurologic Outcomes in Adult Populations. Neurol Clin. 2020 Nov;38(4):913-936. PubMed PMID: 33040869.

Children 7-9 years of age from East Liverpool and its surrounding communities were enrolled the CARES study between March 2013-June 2014. Blood and hair were analyzed for manganese and lead, and serum was analyzed for cotinine, a marker of environmental tobacco smoke exposure. Hair manganese was negatively associated with child IQ scores.

Publication: Haynes EN, Sucharew H, Hilbert TJ, Kuhnell P, Spencer A, Newman NC, Burns R, Wright R, Parsons PJ, Dietrich KN. Impact of air manganese on child neurodevelopment in East Liverpool, Ohio. Neurotoxicology. 2018 Jan;64:94-102. doi: 10.1016/j.neuro.2017.09.001. Epub 2017 Sep 6. PubMed PMID: 28888663; PubMed Central PMCID: PMC5809274.

A model evaluated routes of manganese ambient air exposure. Manganese found in household dust was a significant contributor to manganese found in children’s hair. Factors that contributed significantly to manganese in household dust were annual ambient manganese concentration, time the child spent outside, and manganese concentration in the soil.

Publication: Fulk F, Succop P, Hilbert TJ, Beidler C, Brown D, Reponen T, Haynes EN. Pathways of inhalation exposure to manganese in children living near a ferromanganese refinery: A structural equation modeling approach. Sci Total Environ. 2017 Feb 1;579:768-775.

This review of 27 publications regarding the relationship between Mn exposure and cognitive outcomes across the lifespan: early life, school-aged children, and adulthood. Included were 12 pediatric studies, 5 occupational studies and 10 adult environmental studies. The majority of these studies provided evidence of the negative effects of Mn exposure on cognition.

Publication: Vollet K, Haynes EN, Dietrich KN. Manganese Exposure and Cognition Across the Lifespan: Contemporary Review and Argument for Biphasic Dose-Response Health Effects. Curr Environ Health Rep. 2016 Dec;3(4):392-404.

The US Environmental Protection Agency's Air Dispersion Model AERMOD was used to develop ambient air manganese concentrations based on emissions from a ferromanganese factory. The modeled results were compared to measured stationary and personal air sampling and found to represent a suitable alternative.

Publication: Fulk F, Haynes EN, Hilbert TJ, Brown D, Petersen D, Reponen T. Comparison of stationary and personal air sampling with an air dispersion model for children's ambient exposure to manganese. J Expo Sci Environ Epidemiol. 2016 Sep;26(5):494-502.

An academic–community research partnership was formed in East Liverpool, Ohio to address community concern about manganese exposure, particularly among children. Children and their families were recruited to participate in a pilot study and community member assisted in the development of data disclosure strategies. The partnership proved valuable to researchers and community members.

Publication: Haynes EN, Elam S, Burns R, Spencer A, Yancey E, Kuhnell P, Alden J, Walton M, Reynolds V, Newman N, Wright RO, Parsons PJ, Praamsma ML, Palmer CD, Dietrich KN. Community Engagement and Data Disclosure in Environmental Health Research. Environ Health Perspect. 2016 Feb;124(2):A24-7.

Over 400 children ages 7-9 from Marietta and Cambridge, Ohio provided blood and hair samples and completed testing to measure their intellectual ability. Both high and low levels of manganese in blood and hair were associated with decreases in child IQ scores. Serum cotinine (an indicator that the child has been exposed to nicotine through second hand smoke) was also associated with declines in child mental function.

Publication: Haynes EN, Sucharew H, Kuhnell P, Alden J, Barnas M, Wright R, Parsons PJ, Aldous KM, Praamsma ML, Beidler, C, Dietrich KN. Manganese Exposure and Neurocognitive Outcomes in Rural School-Age Children: The Communities Actively Researching Exposure Study (Ohio, USA) Environmental Health Perspectives. 2015; 123(10):1066-71.

Over 400 children ages 7-9 from Marietta and Cambridge, Ohio completed testing regarding some of their physical abilities. Exposure to secondhand tobacco smoke was measured by levels of cotinine, an indicator that the child has been exposed to nicotine through second hand smoke. Higher levels of cotinine were associated with reduced abilities in children’s eye-hand coordination, control of small movements, balance, and strength.

Publication: Yeramaneni S, Dietrich KN, Yolton K, Parsons PJ, Aldous KM, Haynes EN. Secondhand Tobacco Smoke Exposure and Neuromotor Function in Rural Children. The Journal of Pediatrics. 2015; 167(2):253-9.e1.

A group of 55 children who were part of CARES from Marietta completed balance testing. Poorer balance was found with living closer to the ferromanganese refinery, having higher levels of manganese in hair or blood, and having elevated levels of lead in blood.

Publication: Rugless F, Bhattacharya A, Succop P, Dietrich KN, Alden J, Kuhnell P, Cox C, Wright R, Parsons PJ, Praamsma ML, Dalmer CD, Wittberg R, Haynes EN. Childhood exposure to manganese and postural instability in children living near a ferromanganese refinery in Southeastern Ohio. Neurotoxicology and Teratology. 2014;41:71-9.

A group of 38 children who participated in CARES from Marietta wore personal air monitors for two days. These children and their families recorded the child’s location during the two-day sampling period. Residential and school distance from the ferromanganese refinery (weighted by time spent at each) was associated with levels of manganese in children’s air.

Publication: Haynes EN, Ryan P, Chen A, Brown D, Roda S, Kuhnell P, Wittberg D, Terrell M, Reponen T. Assessment of personal exposure to manganese in children living near a ferromanganese refinery. The Science of the Total Environment. 2012; 427-428:19-25.

This publication documents the formation of an academic-community partnership based on community-based participatory research (CBPR) principles. Marietta, Ohio is an Appalachian-American community with a desire to understand the impact of manganese on the cognition and behavior of their children. We formed a community advisory board (CAB), jointly conducted pilot research studies, and used the results to develop a community-driven research agenda.

Publication: Haynes EN, Beidler C, Wittberg R, Meloncon L, Parin M, Kopras EJ, Succop P, Dietrich KN. Developing a bidirectional academic-community partnership with an Appalachian-American community for environmental health research and risk communication. Environ Health Perspect. 2011 Oct;119(10):1364-72.

This paper describes development of a lab-on-a-chip sensor for electrochemical detection of highly electronegative heavy metals such as manganese and zinc. The results were favorable and with further development, this sensor would provide reliable and sensitive detection of manganese in the blood for point-of-care monitoring.

Publication: Jothimuthu P, Wilson RA, Herren J, Haynes EN, Heineman WR, Papautsky I. Lab-on-a-chip sensor for detection of highly electronegative heavy metals by anodic stripping voltammetry. Biomed Microdevices. 2011 Aug;13(4):695-703.

A pilot study was conducted in Marietta, Ohio, home to one of the largest airborne manganese emission sources in the United States, a ferromanganese refinery, to assess residents’ exposure to manganese in the air and its relationship to manganese in hair and blood. 141 residents participated and the relationship between hair manganese and estimated ambient air manganese became significant when genes for iron metabolism were included in linear models

Publication: Haynes EN, Heckel P, Ryan P, Roda S, Leung YK, Sebastian K, Succop P. Environmental manganese exposure in residents living near a ferromanganese refinery in Southeast Ohio: a pilot study. Neurotoxicology. 2010 Sep;31(5):468-74.

A pilot study was conducted among Appalachian Ohio community members exposed chronically to elevated levels of manganese via a nearby ferromanganese refinery. 29 residents aged 19 to 68 provided blood and hair samples and were tested for postural balance. A significantly positive association was found between manganese levels in hair and postural balance (sway area and sway length).

Publication: Standridge JS, Bhattacharya A, Succop P, Cox C, Haynes E. Effect of chronic low level manganese exposure on postural balance: a pilot study of residents in southern Ohio. J Occup Environ Med. 2008 Dec;50(12):1421-9.