A benchmark concentration analysis for manganese in drinking water and IQ deficits in children

Kullar, Savroop S.; Shao, Kan; Surette, Céline; Foucher, Delphine; Mergler, Donna; Cormier, Pierre; Bellinger, David C.; Barbeau, Benoît; Sauvé, Sébastien; Bouchard, Maryse F.

doi:10.1016/j.envint.2019.05.083

Cited by 91 publications

(41 citation statements)

References 32 publications

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“…A cross-sectional study in Bangladesh also suggested infants exposed to drinking water manganese concentrations higher than 0.4 mg/L had increased mortality risk during the first year of life when compared with unexposed infants 34 . A recent study also showed a positive association between manganese concentrations in drinking water and reduced intellectual function of children ages 5.9-13.7 years in Canada 7 . As shown in Fig.…”

Section: Resultsmentioning

confidence: 89%

Human health risk assessment of elevated and variable iron and manganese intake with arsenic-safe groundwater in Jashore, Bangladesh

Ghosh¹,

Khan²,

Chakraborty³

et al. 2020

Sci Rep

126

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Groundwater through hand-operated tubewell (a type of water well) tapping is the main source of drinking water in Bangladesh. this study investigated iron and manganese concentration in groundwater across Jashore district-one of the worst arsenic contaminated area in Bangladesh. one working tubewell that had been tested previously for arsenic and marked safe (green) was selected from each unions of the district. Results revealed that approximately 73% and 87% of groundwater samples exceeded the limits for iron and manganese in Bangladesh drinking water, respectively. Additionally, spatial distribution of iron and manganese indicate that only 5% of the total surface area of groundwater is covered by safe level of iron and manganese. Human health risk due to ingestion of iron and manganese through drinking water was evaluated using hazard quotients (HQ) for adults and children. the result of the health risk assessment revealed that the non-carcinogenic health risks due to ingestion of iron (HQ up to 1.446 for adults and 0.590 for children) and manganese (HQ up to 2.459 for adults and 1.004 for children) contaminated groundwater are much higher among adults than children. on the basis of occurrences, spatial distribution and health risk assessment results, the area can be categorized as a high-risk zone for iron and manganese-related problems and needs special attention in order to protect public health of local residents. Groundwater is the main source of drinking water in Bangladesh and over 90% of the country's drinking water source is groundwater. Now, it is estimated that close to 98% of the population of Bangladesh have access to 'technologically improved water source' but this level is likely lower than 39% when considering Sustainable Development Goal water target (SDG goal 6.1) 1 of 'safely managed water' 2. Safely managed water services ensure access to a technologically improved water source which is available when needed, located on premises and free of fecal and priority chemical contamination. In Bangladesh, access to technologically improve water source came mainly due to installation of tubewells-a type of water well, a low-cost technology used to withdraw groundwater by hand powered. Since their large scale installation in the 1970s and 1980s for obtaining microbiologically safe water, tubewells have become popular in Bangladesh, with close to 95% of rural people and 70% of urban people using them today 3. Even though groundwater can be a safe and reliable source of drinking water, it can also be affected by geogenic contaminants, such as arsenic, iron and manganese. Therefore, increased consumption of groundwater in some area has led to long-term exposures to arsenic 4 , iron 5 and manganese 6,7 that are associated with adverse health effects. Iron and manganese are naturally occurring metals, and coexist in groundwater as they have many common chemical properties including similar valence charge in physiological conditions, ionic radius and absorptive mechanisms for individuals 8,9. Iron and manga...

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Section: Resultsmentioning

confidence: 89%

Human health risk assessment of elevated and variable iron and manganese intake with arsenic-safe groundwater in Jashore, Bangladesh

Ghosh¹,

Khan²,

Chakraborty³

et al. 2020

Sci Rep

126

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“…Both exposure to Mn in drinking water and high levels of Mn in biomarkers have been associated with a higher risk of adverse neurodevelopmental outcomes (Lucchini et al 2018). Evidence of sex differences in neurotoxic susceptibility to environmental Mn exposure has been reported in several studies (Broberg et al 2019;Kullar et al 2019;Lucchini et al 2018) and age-specific incidence rate patterns for ADHD differed between boys and girls in a comprehensive Danish study (Dalsgaard et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Exposure to Manganese in Drinking Water during Childhood and Association with Attention-Deficit Hyperactivity Disorder: A Nationwide Cohort Study

Schullehner

Thygesen

Kristiansen

et al. 2020

Environ Health Perspect

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Background: Manganese (Mn) in drinking water may increase the risk of several neurodevelopmental outcomes, including attention-deficit hyperactivity disorder (ADHD). Earlier epidemiological studies on associations between Mn exposure and ADHD-related outcomes had small sample sizes, lacked spatiotemporal exposure assessment, and relied on questionnaire data (not diagnoses)—shortcomings that we address here. Objective: Our objective was to assess the association between exposure to Mn in drinking water during childhood and later development of ADHD. Methods: In a nationwide population-based registry study in Denmark, we followed a cohort of 643,401 children born 1992–2007 for clinical diagnoses of ADHD. In subanalyses, we classified cases into ADHD-Inattentive and ADHD-Combined subtypes based on hierarchical categorization of International Classification of Diseases (ICD)-10 codes. We obtained Mn measurements from 82,574 drinking water samples to estimate longitudinal exposure during the first 5 y of life with high spatiotemporal resolution. We modeled exposure as both peak concentration and time-weighted average. We estimated sex-specific hazard ratios (HRs) in Cox proportional hazards models adjusted for age, birth year, socioeconomic status (SES), and urbanicity. Results: We found that exposure to increasing levels of Mn in drinking water was associated with an increased risk of ADHD-Inattentive subtype, but not ADHD-Combined subtype. After adjusting for age, birth year, and SES, females exposed to high levels of Mn (i.e., ) at least once during their first 5 y of life had an HR for ADHD-Inattentive subtype of 1.51 [95% confidence interval (CI): 1.18, 1.93] and males of 1.20 (95% CI: 1.01, 1.42) when compared with same-sex individuals exposed to . When modeling exposure as a time-weighted average, sex differences were no longer present. Discussion: Mn in drinking water was associated with ADHD, specifically the ADHD-Inattentive subtype. Our results support earlier studies suggesting a need for a formal health-based drinking water guideline value for Mn. Future Mn-studies should examine ADHD subtype-specific associations and utilize direct subtype measurements rather than relying on ICD-10 codes alone. https://doi.org/10.1289/EHP6391

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“…Manganism is characterized by rigidity, bradykinesia, emotional instability, and intellectual and memory impairment at an early stage. Environmental and occupational Mn exposure occurs mainly by welding, mining, smelters, lacquers, dry cell batteries, and Mn-rich agrochemicals 2 . Bailey 3 reported that Mn overexposure during development produces long-term cognitive deficits and reduces brain-derived neurotrophic factor (BDNF) in the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

Alpha-synuclein is involved in manganese-induced spatial memory and synaptic plasticity impairments via TrkB/Akt/Fyn-mediated phosphorylation of NMDA receptors

Liu

et al. 2020

Cell Death Dis

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Manganese (Mn) overexposure produces long-term cognitive deficits and reduces brain-derived neurotrophic factor (BDNF) in the hippocampus. However, it remains elusive whether Mn-dependent enhanced alpha-synuclein (α-Syn) expression, suggesting a multifaceted mode of neuronal toxicities, accounts for interference with BDNF/TrkB signaling. In this study, we used C57BL/6J WT and α-Syn knockout (KO) mice to establish a model of manganism and found that Mn-induced impairments in spatial memory and synaptic plasticity were related to the α-Syn protein. In addition, consistent with the long-term potentiation (LTP) impairments that were observed, α-Syn KO relieved Mn-induced degradation of PSD95, phosphorylated CaMKIIα, and downregulated SynGAP protein levels. We transfected HT22 cells with lentivirus (LV)-α-Syn shRNA, followed by BDNF and Mn stimulation. In vitro experiments indicated that α-Syn selectively interacted with TrkB receptors and inhibited BDNF/TrkB signaling, leading to phosphorylation and downregulation of GluN2B. The binding of α-Syn to TrkB and Fyn-mediated phosphorylation of GluN2B were negatively regulated by BDNF. Together, these findings indicate that Mn-dependent enhanced α-Syn expression contributes to further exacerbate BDNF protein-level reduction and to inhibit TrkB/Akt/Fyn signaling, thereby disturbing Fyn-mediated phosphorylation of the NMDA receptor GluN2B subunit at tyrosine. In KO α-Syn mice treated with Mn, spatial memory and LTP impairments were less pronounced than in WT mice. However, the same robust neuronal death was observed as a result of Mn-induced neurotoxicity.

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A benchmark concentration analysis for manganese in drinking water and IQ deficits in children

Cited by 91 publications

References 32 publications

Human health risk assessment of elevated and variable iron and manganese intake with arsenic-safe groundwater in Jashore, Bangladesh

Human health risk assessment of elevated and variable iron and manganese intake with arsenic-safe groundwater in Jashore, Bangladesh

Exposure to Manganese in Drinking Water during Childhood and Association with Attention-Deficit Hyperactivity Disorder: A Nationwide Cohort Study

Alpha-synuclein is involved in manganese-induced spatial memory and synaptic plasticity impairments via TrkB/Akt/Fyn-mediated phosphorylation of NMDA receptors

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