Background/Objective: Whether environmental exposure to Manganese (Mn) in adults is associated with poorer results in cognitive and motor function is unclear. We aimed to determine these associations through a meta-analysis of published studies. Methods: A systematic review was conducted to identify epidemiological studies on a population ≥18 years old exposed to environmental airborne Mn, and in which results on specific tests to evaluate cognitive or motor functions were reported. We consulted Medline through PubMed, Web of Science and SCOPUS databases. We also performed a manual search within the list of bibliographic references of the retrieved studies and systematic reviews. To weight Mn effects, a random effects versus fixed effect model was chosen after studying the heterogeneity of each outcome. Results. Eighteen studies met the inclusion criteria. Among them, eleven studies reported data susceptible for meta-analysis through a pooled correlation or a standardized means difference (SMD) approach between exposed and non-exposed groups. Regarding cognitive function, the results of the studies showed heterogeneity among them (I² = 76.49%, p < 0.001). The overall effect was a statistically significant negative correlation in the random effects model (pooled r = −0.165; 95%CI: −0.214 to −0.116; p < 0.001). For SMD, the results showed a lower heterogeneity with a negative SMD that did not reach statistical significance under the fixed effects model (SMD = −0.052; 95%CI −0.108 to 0.004; p = 0.068). Regarding motor function, heterogeneity (I² = 75%) was also observed in the correlation approach with a pooled r (random effect model) = −0.150; 95%CI: −0.219 to −0.079; p < 0.001. Moderate heterogeneity was observed according to the SMD approach (I² = 52.28%), with a pooled SMD = −0.136; 95%CI: −0.188 to−0.084; p < 0.001, indicating worse motor function in those exposed. Conclusions: Correlation approach results support a negative effect on cognitive and motor functions (the higher the Mn levels, the poorer the scores). Regarding the SMD approach, results also support a worse cognitive and motor functions in those exposed, although only for motor function statistical significance was obtained.

The environmental exposure to trace metal(loid)s (As, Cd, Cu, Fe, Mn, Pb, and Zn) was assessed near a ferromanganese alloy plant using filters from personal particulate matter (PM) samplers (bioaccessible and non-bioaccessible fine and coarse fractions) and whole blood as short-term exposure markers, and scalp hair and fingernails as long-term biomarkers, collected from volunteers (n = 130) living in Santander Bay (northern Spain). Bioaccessible and non-bioaccessible metal(loid) concentrations in coarse and fine PM from personal samplers were determined by ICP-MS after extraction/digestion. Metal(loid) concentration in biomarkers was measured after alkaline dilution (whole blood) and acid digestion (fingernails and scalp hair) by ICP-MS as well. Results were discussed in terms of exposure, considering the distance to the main Mn source, and sex. In terms of exposure, significant differences were found for Mn in all the studied fractions of PM, As in whole blood, Mn and Cu in scalp hair and Mn and Pb in fingernails, with all concentrations being higher for those living closer to the Mn source, with the exception of Cu in scalp hair. Furthermore, the analysis of the correlation between Mn levels in the studied biomarkers and the wind-weighted distance to the main source of Mn allows us to conclude that scalp hair and mainly fingernails are appropriate biomarkers of long-term airborne Mn exposure. This was also confirmed by the significant positive correlations between scalp hair Mn and bioaccessible Mn in coarse and fine fractions, and between fingernails Mn and all PM fractions. This implies that people living closer to a ferromanganese alloy plant are exposed to higher levels of airborne metal(loid)s, mainly Mn, leading to higher levels of this metal in scalp hair and fingernails, which according to the literature, might affect some neurological outcomes. According to sex, significant differences were observed for Fe, Cu and Pb in whole blood, with higher concentrations of Fe and Pb in males, and higher levels of Cu in females; and for Mn, Cu, Zn, Cd and Pb in scalp hair, with higher concentrations in males for all metal(loid)s except Cu.

An alternative metric to account for particulate matter (PM) composition-based toxicity is the ability of PM-species to generate reactive oxygen species (ROS) and deplete antioxidants, the so-called oxidative potential (OP). Acellular OP assays are the most used worldwide, mainly those based on ascorbic acid (AA) and dithiothreitol (DTT) depletion; OP values are calculated from AA/DTT concentration over time kinetic curves. Since a great variability in OP-DTT and OP-AA values can be found in the literature, the understanding of those factors affecting the kinetic rate of AA and DTT oxidation in the presence of PM-bound species will improve the interpretation of OP values. In this work, a kinetic study of the oxidation rate of AA and DTT driven by species usually found in PM (transition metals and naphthoquinone (NQ)) was carried out. In particular, the influence of the concentration of Cu(II), Fe(II), Fe(III), Mn(II), Mn(III), and 1,4-NQ, and the type of fluid used in the assay (phosphate buffer (PB), phosphate buffer saline (PBS) and artificial lysosomal fluid (ALF)) is analysed and discussed. The reaction orders with respect to the AA/DTT and the active compound, and the kinetic rate constants were also determined. The results show great variability in OP values among the studied species depending on the fluid used; the OP values were mostly higher in PB0.05 M, followed by PBS1x and ALF. Moreover, different species concentration-responses for OP-DTT/OP-AA were obtained. These differences were explained by the different reaction orders and kinetic rate constants obtained for each active compound in each fluid.

The oxidative potential (OP) is defined as the ability of inhaled PM components to catalytically/non-catalytically generate reactive oxygen species (ROS) and deplete lung antioxidants. Although several studies have measured the OP of particulate matter (PM OP) soluble components using different antioxidants under neutral pH conditions, few studies have measured PM OP with acidic lung fluids. This study provides new insights into the use of acidic rather than neutral fluids in OP assays. Thus, the first aim of this study was to clarify the effect of using an acidic lung fluid on ascorbic acid (AA) depletion. This was achieved by measuring the oxidative potential (OP-AA) of individual compounds known to catalyze the AA oxidation (CuSO₄, CuCl₂, and 1,4-NQ) in artificial lysosomal fluid (ALF, pH 4.5), a commonly used acidic simulated lung fluid, and in a neutral fluid (phosphate-buffered saline (PBS1x), pH 7.4). Our results from these individual compounds showed a significant decrease of OP-AA in the acidic fluid (ALF) with respect to the neutral fluid (PBS). Then, the second aim of this work was to investigate whether the OP-AA assay could be applied to PM_2.5 samples extracted in acidic conditions. For this purpose, OP-AA and bioaccessible concentrations of metal(loid)s (V, Mn, Fe, Ni, Cu, Zn, As, Mo, Cd, Sb, and Pb) of PM_2.5 samples collected in an urban-industrial area that were extracted in ALF were analyzed. The mean volume-normalized OP (OP-AAv) value was 0.10 ± 0.07 nmol min⁻¹ m⁻³, clearly lower than the values found in the literature at neutral pH. OP-AAv values were highly correlated with the ALF-bioaccessible concentration of most of the studied metal(loid)s, mainly with Cu and Fe.

Santander, the capital of Cantabria, Spain (172,000 inhabitants) is 7 km from an industrial emission source (IES) of Mn located in a 10,000 inhabitants town (Maliaño) (annual air Mn arithmetic mean = 231.8 ng/m³; reference WHO guideline = 150 ng/m³). Our objective was to compare the motor function of adult healthy volunteers living in both places. Cross-sectional study analyzing 130 consecutive participants. Exposure to Mn was assessed in terms of source distance from the IES, by Personal Environmental Monitors (PEMs) carried for 24 h by participants consisting of a portable impactor connected to a personal pump, and by biomarkers (blood, hair and fingernails). The impactor allowed the separation of fine (PM2.5) and coarse (PM10-2.5) particles and for each particle size in-vitro bioaccessibility tests with biologically active fluids were performed to separate the soluble (bioaccessible) from the insoluble (non-bioaccessible) fraction. Mean Differences (MDs) adjusted for age, sex, and study level, were obtained for motor function tests results. Regarding Grooved Pegboard, overall mean time to complete the test was 59.31 and 65.27 seconds (Standard Deviation = 10.11 and 11.69) for dominant and nondominant hands respectively. Statistically significant higher times (indicating worse function) were observed when living near the IES in both hands but MDs of only 1.22 and 2.05 seconds were obtained after adjusting for the predefined confounders (p = 0.373 and 0.221 respectively). Regarding Mn levels in their PEMs (in both bioaccessible and non-bioaccessible coarse&fine fractions) higher times were computed in participants with higher levels for the bioaccessible-fine fraction, with a MD that diminished but still yielded statistical significance after controlling for confounding: adjusted MD = 3.01 more seconds; 95%CI (0.44-5.38), p = 0.022. Poorer results were also observed for fingernails levels. Regarding Finger Tapping Test, no statistically significant differences were found with the exception of Mn fingernails levels. Our results suggest poorer motor function as assessed by Grooved Pegboard test in relation to "proximity to IES", "bioaccessible-fine fraction as determined by PEMs and "Mn fingernails levels". However, our findings were affected by confounding, and only the adjusted MD for the Mn bioaccessible-fine fraction remained of sufficient magnitude to maintain statistical significance.