Antimony (Sb) is a toxic metalloid and a global pollutant. Sb exposure is known to cause pulmonary, cardiovascular, liver and kidney damage, as well as cancer. In addition, data showing neurotoxic effects of Sb have been also obtained recently. Therefore, the objective of the present review was to discuss existing epidemiological findings linking Sb exposure to brain diseases and the underlying molecular mechanisms of Sb neurotoxicity. Laboratory findings revealed neurotoxic effects of high-dose Sb exposure. Specifically, in vitro and in vivo studies show that Sb induces neuronal apoptosis through induction of oxidative stress, altered Akt/mTOR and Wnt/β-catenin signaling, and potentially increased Ca2 + flux. Activation of ferroptosis due to reactive oxygen species (ROS) overproduction, autophagic GPX4 degradation, and NCOA4-mediated ferritinophagy also appear to mediate Sb neurotoxicity. Other mechanisms linked to adverse effects of Sb in brain include altered neurotransmitter metabolism, neuroinflammation, as well as impaired gut-brain axis and neurogenesis. Epidemiological findings show also that Sb exposure, both in single metal and multiple metal exposure models, is associated with increased risk of depression, sleep disorders, anxiety, cognitive dysfunction, and neurodevelopmental disorders like autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD), although controversial data exist. Evidence showing that maternal Sb exposure is also associated with adverse neurodevelopmental outcome in children also exists. While the precise role of Sb exposure in development of neurological diseases has yet to be established due to limited data, a complex of epidemiological and laboratory findings show that Sb should be considered a potential environmental neurotoxicant.

Since the 1950s, regulation of occupational carcinogen exposure has progressed from hazard identification to quantitative evaluation, driven by advances in cancer biology. This narrative review compares two approaches for setting Occupational Exposure Limits (OELs) for carcinogens, focusing on benzene. The first one applies a mode of action (MOA)-based approach to genotoxicity stratification, using linear extrapolation for direct genotoxicants and non-linear extrapolation for indirect genotoxicants. The second approach quantifies in vivo genotoxicity data, employing mathematical modeling to define the point of departure (POD) for non-linear extrapolation, regardless of the MOA. As benzene is an indirect genotoxicant, it is considered to have a threshold value. Applying the MOA-based approach to genotoxicity stratification, different European institutions and commissions have proposed OELs ranging from 0.05 to 0.25 ppm. The ACGIH has recommended a TLV-TWA of 0.02 ppm (skin notation). Based on a quantitative genotoxicity approach, the proposed OELs range from 0.021 to 0.07 ppm for benzene. Current evidence indicates that workplace benzene concentrations above 0.3 ppm do not adequately protect the health of exposed workers. Extending follow-up of existing cohorts and conducting robust quantitative genotoxicity assays in well-designed epidemiological and experimental studies are essential to reduce uncertainties and to confirm the most sensitive toxic effect, thereby supporting the establishment of a more realistic OEL for benzene and minimizing the likelihood of over- or underestimating the associated risks.

Environmental exposures to metals is a concern for public health, due to their association with various adverse health outcomes, especially in children. The aim of this study was to analyze 21 metals (V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Rb, Ag, Cd, Ba, Ti, Pb, U, Sn, Mo, Ce, La, and Th) in deciduous teeth of waste pickers' children from an open garbage dump region (Estrutural region- Group 1), and compare them with children living in two other regions in Brasilia (Ceilandia - Group 2, and Plano Piloto - Group 3). Three hundred and two children participated in the study, and a single deciduous whole tooth (dentine plus enamel) was analyzed from each child. Socio-demographic variables, breastfeeding time, visits to the dentist, drinking water consumption, among others, were obtained through a questionnaire provided to the parents or guardians of the children. Metal analyses were performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Significantly higher concentrations of V, Co, Cu, and As were found in children from G1, where most parents were waste pickers, compared to the other two regions (p < 0.01). Pb and Cd concentrations were significantly higher in children from G2 and G3 compared with G1 (p < 0.01). Significantly higher levels of Cr, Mn, Zn and Se were found in children from G2 (p < 0.01), where residents also have very low income, analogous to G1. We found a trend towards an increase in metal concentrations in incisor compared to canine and molar teeth of children in all three groups. This study provides novel data and reinforces the use of deciduous teeth as potential matrix for biomonitoring children's metal exposures.

While previous studies have suggested associations between frequent red meat (RM) consumption with visible fat and cardiovascular disease, prospective evidence examining relationships with specific cardiometabolic risk factors remains limited. The objective of this population-based cohort study was to analyze the associations between RM consumption, including selecting lean cuts or removing visible fat, and changes in cardiometabolic risk factors in adults. The study included 1180 Brazilian adults 40 years of age and older, evaluated between 2011 and 2015. Linear regression models were adjusted by the main confounders to estimate the associations between daily RM and RM fat consumption with changes in body mass index, waist circumference (WC), blood pressure, and lipid profile. Of the initial participants, 884 (74.9%) were followed up, of whom 25.0% consumed RM daily and 36.5% regularly ate RM fat. Daily vs nondaily RM consumption showed no associations with changes in cardiometabolic risk factors. However, compared to participants who removed visible fat, those consuming RM fat showed significantly greater WC increases (β = 1.29 cm; 95% confidence interval: 0.34, 2.34) and high-density lipoprotein cholesterol decreases (β = -1.85 mg/dL; 95% confidence interval: -3.51, -0.19). Although the results were adjusted for baseline values, body mass index, sociodemographic and lifestyle factors, data on diet quality and energy intake were unavailable and could not be included. Daily RM consumption was not associated with adverse cardiometabolic changes. However, visible RM fat consumption was associated with modest but statistically significant increases in WC and decreases in high-density lipoprotein cholesterol in adults ≥40 years of age who consume RM regularly.

The objective of this state-of-the-art review is to summarize contemporary data on the potential toxic effects of aluminum nanoparticles (AlNPs) and discuss the underlying molecular mechanisms. In vivo studies using laboratory rodents demonstrate that lungs, liver, brain, and the immune system are the primary targets for AlNPs toxicity. Specifically, inhalation exposure to AlNPs induces lung damage by promoting inflammatory infiltration, airway remodeling, septal thickening, and bronchial hyperresponsiveness. AlNPs-induced liver damage is characterized by hepatocyte degeneration and necrosis, liver sinusoid congestion, inflammation, and fibrosis. AlNPs induces neurotoxicity resulting in neurodegeneration, neuroinflammation, altered neurotransmitter metabolism, and subsequent adverse neurobehavioral outcome. In turn, immunotoxicity of AlNPs is characterized by promotion of systemic inflammation along with impaired phagocytosis. In addition to the toxicity exerted by Al2O3NPs itself, the observed toxic effects of AlNPs may be attributed to Al3+ release from the particles with the subsequent induction of oxidative stress, inflammation, mitochondrial dysfunction, genotoxicity, cell cycle dysregulation, and cell death due to apoptosis, necrosis, and ferroptosis. It is also evident that both the size and the form of AlNPs significantly affect its cytotoxicity. However, further studies are required to explore the mechanisms of toxic effects of AlNPs, as well as its potential adverse effects on human health.

The objective of the present review is to discuss epidemiological evidence demonstrating the association between toxic metal (Cd, Pb, Hg, As, Sn, Ti, Tl) exposure and retinal pathology, along with the potential underlying molecular mechanisms. Epidemiological studies demonstrate that Cd, and to a lesser extent Pb exposure, are associated with age-related macular degeneration (AMD), while the existing evidence on the levels of these metals in patients with diabetic retinopathy is scarce. Epidemiological data on the association between other toxic metals and metalloids including mercury (Hg) and arsenic (As), are limited. Clinical reports and laboratory in vivo studies have shown structural alterations in different layers of retina following metal exposure. Examination of retina samples demonstrate that toxic metals can accumulate in the retina, and the rate of accumulation appears to increase with age. Experimental studies in vivo and in vitro studies in APRE-19 and D407 cells demonstrate that toxic metal exposure may cause retinal damage through oxidative stress, apoptosis, DNA damage, mitochondrial dysfunction, endoplasmic reticulum stress, impaired retinogenesis, and retinal inflammation. However, further epidemiological as well as laboratory studies are required for understanding the underlying molecular mechanisms and identifying of the potential therapeutic targets and estimation of the dose-response effects.

ABSTRACT The aim of this cross-sectional study was to compare workplace conditions and metal exposures in 431 waste pickers who worked nearby at the Estrutural Dump in Brasilia utilizing hair (n = 310) and nail (n = 355) as matrices of exposure. Waste pickers were grouped according to their workplace (open waste dump: G1 and sorting plants: G2). Hair and nail samples were collected and analyzed using ICP-MS. The work duration in the facilities was significantly different between the groups with averages of 16.46 (8.48) yrs and 9.26 (6.28) yrs for hair donors in G1 and G2, and 15.92 (7.72) yrs and 8.55 (5.77) yrs for toenail donors in G1 and G2, respectively. The arithmetic means (μg/g) of cadmium, copper, lead, and manganese in hair were significantly higher in G2 (0.076 ± 0.133; 19.61 ± 18.16; 2.27 ± .56 and 3.87 ± 5.59, respectively) compared to G1 (0.069 ± 0.235; 15.72 ± 15.18; 1.72 ± 4.04 and 3.65 ± 5.5, respectively). Concentrations of arsenic, barium, cadmium, copper, cobalt, lead, manganese, and molybdenum in nail were significantly higher in G2 (0.57 ± 0.39; 22.74 ± 42.06; 0.1 ± 0.08; 22.7 ± 51.60; 0.48 ± 0.45; 4.69 ± 9.43; 19.07 ± 20.75; 1.80 ± 1.76, respectively) compared to G1 (0.40 ± 0.28; 15.32 ± 22.31; 0.08 ± 0.11; 11.91 ± 16.25; 0.37 ± 0.37; 3.94 ± 15.04; 13.01 ± 19.08; 1.16 ± 1.80, respective. Our findings suggest that the studied population was exposed to toxic metals and indicates the need for chemical exposure prevention policies to monitor chemical risk exposures in waste pickers.

The objective of the present study was to retrospectively evaluate hair mercury (Hg) content in reproductive-age women living in Central Russia (Moscow and Moscow region), and to calculate the potential costs of the potential Hg-induced IQ loss in a hypothetical national birth cohort. MATERIALS AND METHODS:A total of 36,263 occupationally non-exposed women aged between 20 and 40 years living in Moscow (n = 30,626) or Moscow region (n = 5637) in the period between 2005 and 2021 participated in this study. Hair Hg content was evaluated with inductively coupled plasma-mass spectrometry (ICP-MS). Hair Hg levels in reproductive-age women were used for assessment of the potential IQ loss and its costs. RESULTS:The results demonstrate that hair Hg content in the periods between 2010 and 2015, and 2016-2021 was significantly lower than that in 2005-2009 by 26 % and 51 %, respectively. The highest hair Hg level was observed in women in 2005 (0.855 µg/g), being more than 2.5-fold higher than the lowest value observed in 2020 (0.328 µg/g). Multiple regression analysis revealed a significant inverse association between the year of analysis and hair Hg content (β = -0.288; p < 0.001). The calculations demonstrate that in 2005 the costs of IQ loss in children exceeded 1.0 (1.6) billion USD, whereas in 2020 the costs of IQ loss accounted to approximately 0.15 (0.28) billion USD. CONCLUSION:Taken together, our data demonstrate that Hg accumulation in reproductive-age women reduced significantly in Russia from 2005 to 2021 resulting in predicted economic benefits by decreasing the costs of Hg-induced IQ loss.

The existing data demonstrate that probiotic supplementation affords protective effects against neurotoxicity of exogenous (e.g., metals, ethanol, propionic acid, aflatoxin B1, organic pollutants) and endogenous (e.g., LPS, glucose, Aβ, phospho-tau, α-synuclein) agents. Although the protective mechanisms of probiotic treatments differ between various neurotoxic agents, several key mechanisms at both the intestinal and brain levels seem inherent to all of them. Specifically, probiotic-induced improvement in gut microbiota diversity and taxonomic characteristics results in modulation of gut-derived metabolite production with increased secretion of SFCA. Moreover, modulation of gut microbiota results in inhibition of intestinal absorption of neurotoxic agents and their deposition in brain. Probiotics also maintain gut wall integrity and inhibit intestinal inflammation, thus reducing systemic levels of LPS. Centrally, probiotics ameliorate neurotoxin-induced neuroinflammation by decreasing LPS-induced TLR4/MyD88/NF-κB signaling and prevention of microglia activation. Neuroprotective mechanisms of probiotics also include inhibition of apoptosis and oxidative stress, at least partially by up-regulation of SIRT1 signaling. Moreover, probiotics reduce inhibitory effect of neurotoxic agents on BDNF expression, on neurogenesis, and on synaptic function. They can also reverse altered neurotransmitter metabolism and exert an antiamyloidogenic effect. The latter may be due to up-regulation of ADAM10 activity and down-regulation of presenilin 1 expression. Therefore, in view of the multiple mechanisms invoked for the neuroprotective effect of probiotics, as well as their high tolerance and safety, the use of probiotics should be considered as a therapeutic strategy for ameliorating adverse brain effects of various endogenous and exogenous agents.

Vaccination campaigns played a crucial role in reducing the incidence of COVID-19. However, a scant number of studies evaluated the impact of vaccination on case fatality rates (CFRs), including in Brazil. Our study aimed to compare CFRs according to vaccination status among subjects living in Arapongas (Paraná State, Brazil), considering the age composition of the population. Several strategies adopted by the Arapongas City Hall to minimize the spread of the virus were also elaborated upon. We accessed the 2021 database of the Arapongas Municipal Health Department, in which a total of 16,437 confirmed cases and 425 deaths were reported. The CFR was calculated as the ratio between COVID-19 deaths and the number of confirmed cases. Differences in age composition between unvaccinated and fully vaccinated individuals were observed in our study. Considering that CFR is a crude indicator and is highly sensitive to the age composition of the population, we adopted the average age distribution of confirmed cases among the three vaccination statuses (unvaccinated, partially, and fully) as a standard age distribution. The age-standardized CFR for unvaccinated and fully vaccinated groups were 4.55% and 2.42%, respectively. Fully vaccinated individuals showed lower age-specific CFRs in all age groups above 60 years than unvaccinated populations. Our findings strengthen the role of vaccination as a critical measure for preventing deaths among infected people and is particularly important to the ongoing reassessment of public health interventions and policies.

The objective of the present study was to evaluate potential similar patterns and interactive effects of obesity and hypertension on hair essential trace element and mineral content in adult women. In this cross-sectional study, a total of 607 adult women divided into controls (n = 101), groups with obesity without hypertension (n = 199), hypertension without obesity (n = 143), and both obesity and hypertension (n = 164) were included in the study. Assessment of hair mineral and trace element levels was performed by inductively-coupled plasma mass-spectrometry. Hair Ca, Mg, Co, and Mn levels in women with obesity, hypertension, and both diseases were significantly lower, compared to controls. Hair Mg levels in women with obesity and hypertension were significantly lower, whereas hair Na and K were found to be higher when compared to other groups. Hair Fe and V content in obese patients was lower than in other groups. Obesity was associated with lower hair Cu levels, whereas patients with hypertension had higher hair Cu content. Hypertension was also associated with higher hair Cr and Se content irrespective of body weight. Hair Zn levels in obese women with and without hypertension were significantly lower than those in healthy controls and normal-weight women with hypertension. In multiple regression models hair Mg was considered as a significant negative predictor of both systolic and diastolic blood pressure values. The observed alterations in hair trace element and mineral content provide an additional link between obesity and hypertension, although further detailed studies are required.

Probabilistic survival methods have been used in health research to analyze risk factors and adverse health outcomes associated with COVID-19. The aim of this study was to employ a probabilistic model selected among three distributions (exponential, Weibull, and lognormal) to investigate the time from hospitalization to death and determine the mortality risks among hospitalized patients with COVID-19. A retrospective cohort study was conducted for patients hospitalized due to COVID-19 within 30 days in Londrina, Brazil, between January 2021 and February 2022, registered in the database for severe acute respiratory infections (SIVEP-Gripe). Graphical and Akaike Information Criterion (AIC) methods were used to compare the efficiency of the three probabilistic models. The results from the final model were presented as hazard and event time ratios. Our study comprised of 7,684 individuals, with an overall case fatality rate of 32.78%. Data suggested that older age, male sex, severe comorbidity score, intensive care unit admission, and invasive ventilation significantly increased risks for in-hospital mortality. Our study highlights the conditions that confer higher risks for adverse clinical outcomes attributed to COVID-19. The step-by-step process for selecting appropriate probabilistic models may be extended to other investigations in health research to provide more reliable evidence on this topic.

The objective of the present study was to evaluate serum and hair trace element and mineral levels in women with osteoporosis, as well as to estimate the impact of menopausal status on the profile of trace element and mineral status in women with osteoporosis. 207 women with diagnosed osteoporosis 22–85 years-of-age, and 197 healthy women of the respective age participated in the present study. Analysis of the levels of mineral and trace element in hair and serum samples was performed by inductively-coupled plasma mass-spectrometry (ICP-MS). Women with osteoporosis were characterized by significantly lower hair Ca, Mg, Co, I, Li, and Mn levels, as well as serum Ca, Mg, Co, Fe, V, and Zn concentrations compared to women in the control group. After additional grouping according to menopausal status, the lowest hair Ca and Mg content was observed in postmenopausal osteoporotic women, whereas serum Ca and Mg concentrations were the lowest in premenopausal osteoporotic women. Hair Co, Mn, and Zn levels in postmenopausal osteoporotic women were lower than in healthy postmenopausal women. The lowest circulating Zn levels were observed in osteoporotic postmenopausal women. Taken together, decreased hair and serum levels in osteoporotic women are indicative of increased risk of Ca, Mg, Co, and Zn deficiency in women with osteoporosis. In turn, alterations in hair trace element and mineral levels in osteoporosis are more profound in postmenopausal women. Hypothetically, improvement in trace element and mineral metabolism especially in postmenopausal women may be considered as a potential strategy for mitigating osteoporosis.

[This retracts the article DOI: 10.1016/j.toxrep.2021.03.003.].

The present study aims to review epidemiological and experimental toxicology studies published over the last two decades linking mercury (Hg) exposure and carcinogenesis, with a special emphasis on the potential underlying mechanisms. While some epidemiological studies have observed a strong association between environmental/occupational Hg exposure levels, measured in blood, toenail, and hair, and cancer risk and mortality, others failed to reveal any association. In experimental models, high-dose Hg exposure has been linked with cytotoxicity, whereas low-dose exposure was posited to induce proliferative responses in both normal and cancerous cells by interference with estrogen receptor, ERK1/2, JNK, NADPH-oxidase and, potentially, Nrf2 signaling. Combined with reduced apoptosis and pro-survival signaling upon low-dose Hg exposure, accumulation of DNA lesions in cells may predispose to an increased risk of malignant transformation. In addition, the pro-oxidant activity of Hg species may induce oxidative DNA modifications and inhibits DNA repair mechanisms. Furthermore, epigenetic effects of Hg exposure seem to contribute to the carcinogenic activity, although the particular mechanisms have yet to be characterized. Therefore, even after 20 years of research, one cannot consider Hg as a non-carcinogenic agent, whereas specific mechanisms of Hg-induced toxicity may promote carcinogenic risk.

In view of the significant role of H2S in brain functioning, it is proposed that H2S may also possess protective effects against adverse effects of neurotoxicants. Therefore, the objective of the present review is to discuss the neuroprotective effects of H2S against toxicity of a wide spectrum of endogenous and exogenous agents involved in the pathogenesis of neurological diseases as etiological factors or key players in disease pathogenesis. Generally, the existing data demonstrate that H2S possesses neuroprotective effects upon exposure to endogenous (amyloid β, glucose, and advanced-glycation end-products, homocysteine, lipopolysaccharide, and ammonia) and exogenous (alcohol, formaldehyde, acrylonitrile, metals, 6-hydroxydopamine, as well as 1-methyl-4-phenyl- 1,2,3,6- tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenyl pyridine ion (MPP)) neurotoxicants. On the one hand, neuroprotective effects are mediated by S-sulfhydration of key regulators of antioxidant (Sirt1, Nrf2) and inflammatory response (NF-κB), resulting in the modulation of the downstream signaling, such as SIRT1/TORC1/CREB/BDNF-TrkB, Nrf2/ARE/HO-1, or other pathways. On the other hand, H2S appears to possess a direct detoxicative effect by binding endogenous (ROS, AGEs, Aβ) and exogenous (MeHg) neurotoxicants, thus reducing their toxicity. Moreover, the alteration of H2S metabolism through the inhibition of H2S-synthetizing enzymes in the brain (CBS, 3-MST) may be considered a significant mechanism of neurotoxicity. Taken together, the existing data indicate that the modulation of cerebral H2S metabolism may be used as a neuroprotective strategy to counteract neurotoxicity of a wide spectrum of endogenous and exogenous neurotoxicants associated with neurodegeneration (Alzheimer's and Parkinson's disease), fetal alcohol syndrome, hepatic encephalopathy, environmental neurotoxicant exposure, etc. In this particular case, modulation of H2S-synthetizing enzymes or the use of H2S-releasing drugs should be considered as the potential tools, although the particular efficiency and safety of such interventions are to be addressed in further studies.

Background: Recent studies have established that vaccination plays a significant role in reducing COVID-19related deaths. Here, we investigated differences in COVID-19 case fatality rates (CFRs) among vaccinated and unvaccinated populations, and analyzed whether the age composition of confirmed cases has a significant effect on the variations in the observed CFRs across these groups. Methods: The study considered 59,853 confirmed cases and 1,687 deaths from COVID-19, reported between January 1 to October 20, 2021, by the Health Department of Londrina, a city in Southern Brazil. We used Negative Binomial regression models to estimate CFRs according to vaccination status and age range. Results: There are significant differences between the CFR for fully vaccinated and unvaccinated populations (IRR = 0.596, 95% CI [0.460 - 0.772], P < .001). Vaccinated populations experience fatality rates 40.4% lower than non-vaccinated. In addition, the age composition of confirmed cases explains more than two-thirds of the variation in the CFR between these 2 groups. Conclusions: Our novel findings reinforce the importance of vaccination as an essential public health measure for reducing COVID-19 fatality rates in all age groups. The results also provide means for accurately assessing differences in CFRs across vaccinated and unvaccinated populations. Such assessment is essential to inform and determine appropriate containment and mitigation interventions in Brazil and elsewhere. 0 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Neurotoxicology is a specialty that aims to understand and explain the impact of chemicals, xenobiotics and physical conditions on nervous system function throughout the life span. Herein, we point to the need for integration of novel translational bioinformatics and chemo-informatics approaches, such as machine learning (ML) and artificial intelligence (AI) to the discipline. Specifically, we advance the notion that AI and ML will be helpful in identifying neurotoxic signatures, provide reliable data in predicting neurotoxicity in the context of genetic variability, and improve the understanding of neurotoxic outcomes associated with exposures to mixtures, to name a few.

The objective of the study was to evaluate the association between smoking and essential metal (Co, Cr, Cu, Fe, Mn, V, Zn) and metalloid (Se) levels in hair and serum of adult women using inductively coupled plasma-mass spectrometry (ICP-MS). In this cross-sectional study, a total of 344 women 20-70 years old including 199 smokers and 145 non-smoking women were enrolled. Serum Cu, Fe, and Zn levels in smoking women were found to be 6%, 8%, and 3% lower of levels in non-smokers, respectively. In contrast, circulating Mn, V, and especially Cr concentrations in smoking women exceeded the respective values in non-smoking women by 5%, 14%, and 54%. Hair Fe and Se levels in smoking women were 17% and 23% lower as compared to non-smoking controls, respectively. In multiple regression models, smoking severity was inversely associated with serum and hair Se concentrations, whereas the relationship to serum and hair Cr was positive. In addition, serum Zn and hair Fe levels were found to be inversely associated with the number of cigarettes per day. These findings hypothesize that health hazards of smoking may be at least in part be mediated by alteration in essential metal and metalloid metabolism.