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Exposure, Toxicity, and Health Impacts of Potentially Toxic Metals

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A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Toxicology and Public Health".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 16737

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Prof. Dr. José Antônio Menezes Filho

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Graduate Program in Food Science, Federal University of Bahia, Salvador 40170-115, BA, Brazil
Interests: environmental pollutants; food contaminants; human health; toxicological analyses of metals and organic metabolites in humans; risk assessment
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Dear Colleagues,

Toxic metals and microelements can pose a major threat to the health of the human population upon excessive exposure. Biological systems have learned to adapt to the presence of these elements through different mechanisms (immobilization or clearance processes), keeping their biological levels below safe threshold. However, anthropogenic activities have threatened this balance, and the most varied adverse effects have been imposed on populations, especially those in vulnerable situations. From subtle effects (intelligence impairment) caused by lead and manganese (Landrigan 1989; Menezes-Filho et al. 2011) to malformation and severe encephalopathy as those observed due to methylmercury exposure in Minamata (Japan), the establishment of causal association may take years, and measures to mitigate such exposure may never be implemented. This Special Issue of the International Journal of Environmental Research and Public Health (IJERPH) focuses on the current state of knowledge on the impacts of toxic metals and excessive exposure to micronutrients on human health, as well as risk assessment methods. Experimental studies with animal models and epidemiological studies focusing on general environmental, occupational, and diathetic exposure to those elements are welcome. New research papers, reviews, case reports, and conference papers are welcome to this issue. Papers dealing with new analytical approaches and quality assurance will also be considered.

Landrigan P.J. Toxicity of lead at low dose. Br. J. Ind. Med. 1989, 46, 593–596. https://doi.org/10.1136/oem.46.9.593.

Menezes-Filho, J.A.; Novaes, C.; Moreira, J.C.; Sarcinelli, P.N. and Mergler, D. Elevated manganese and cognitive performance in school-aged children and their mothers. Environ. Res. 2011, 111, 156–163. https://doi.org/10.1016/j.envres.2010.09.006.

Prof. Dr. José Antônio Menezes Filho
Guest Editor

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Keywords

toxic metals
micronutrient
health impacts
biomarkers
analytical methods
exposure evaluation
risk assessment
interlaboratory proficiency
certified reference material

Published Papers (8 papers)

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Research

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15 pages, 1395 KiB

Open AccessArticle

Maternal Exposure to Potentially Toxic Metals and Birth Weight: Preliminary Results from the DSAN-12M Birth Cohort in the Recôncavo Baiano, Brazil

by Homègnon A. Ferréol Bah, Nathália R. dos Santos, Erival A. Gomes Junior, Daisy O. Costa, Victor O. Martinez, Elis Macêdo Pires, João V. Araújo Santana, Filipe da Silva Cerqueira and José A. Menezes-Filho

Int. J. Environ. Res. Public Health 2023, 20(13), 6211; https://doi.org/10.3390/ijerph20136211 - 23 Jun 2023

Cited by 2 | Viewed by 1283

Abstract

Prenatal exposure to potentially toxic metals (PTM) may impair fetal growth (FG). We investigated the relationship between maternal exposure to lead (Pb), cadmium (Cd) and manganese (Mn) and birth weight (BW) of 74 newborns. Blood was collected during the second trimester of pregnancy to determine Pb (PbB) and Cd (CdB), while hair (MnH) and toenails (MnTn) were used for Mn. Samples were analyzed by graphite furnace atomic absorption spectrophotometry (GFAAS). Sociodemographic and BW data were collected from questionnaires and maternity records, respectively. The medians (P25th–P75th) of PbB, CdB, MnH, and MnTn were, respectively, 0.9 (0.5–1.8) µg/dL; 0.54 (0.1–0.8) µg/L; 0.18 (0.1–0.4) µg/g; and 0.65 (0.37–1.22) µg/g. The means (standard deviation) of birth weight according to sex were 3067 (426.3) and 3442 (431) grams, respectively, for girls and boys. MnTn presented an inverse correlation with the BW/gestational age ratio for girls (rho = −0.478; p = 0.018), suggesting the effect of sex modification. Although BW correlation with CdB was not statistically significant, hierarchical linear regression (beta = −2.08; 95% CI–4.58 to 0.41) suggested a fetotoxic effect. These results confirmed the threat PTMs may represent and the need for more extensive research to elucidate their role in inadequate FG in developing countries. Full article

(This article belongs to the Special Issue Exposure, Toxicity, and Health Impacts of Potentially Toxic Metals)

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14 pages, 934 KiB

Open AccessArticle

The Toxicological Risk Assessment of Dermal Exposure of Patients Exposed to Lead and Cadmium Due to Application of Ointments with Marjoram Herb Extract (Majoranae herbae extractum)

by Kamil Jurowski and Mirosław Krośniak

Int. J. Environ. Res. Public Health 2023, 20(3), 2701; https://doi.org/10.3390/ijerph20032701 - 2 Feb 2023

Cited by 1 | Viewed by 1571

Abstract

Potential heavy metal impurities (HMI) in pharmaceuticals/pharmaceutical products/drugs based on plant raw materials (e.g., herbs) are an important problem in the pharmaceutical industry; however, there is a lack of scientific articles on the comprehensive toxicological risk assessment of HMI in ointment applied dermally. To make the appropriate toxicological risk assessment, we consider: (1) the raw results of the levels of lead and cadmium in the ointments (metal per kg of mass), (2) one-time administration of the applied ointment, (3) daily exposure of Pb and Cd in the applied ointments according to the maximum daily dose of applied pharmaceuticals, including transcutaneous penetration, (4) human health risk assessment based on the USEPA model, and 5) the margin of exposure (MoE). The raw results indicated that lead (7.05–101.78 µg/kg) and cadmium (0.32–0.81 µg/kg) were present in all samples. The levels of analyzed HMI (independently of the producer and declared composition) were similar. Pb and Cd contamination associated with daily doses met the standards of the ICH Q3D (R2) guide on elemental impurities in pharmaceuticals, including the cutaneous route of administration. Taking into account the daily amount of lead and cadmium (ointment, ug/day) the results were satisfactory, confirming the safety of marjoram herb extract ointments available in Polish pharmacies according to the ICH guideline Q3D (R2) on elemental impurities. The HQ values obtained for Pb and Cd in all samples were less than 1; therefore, exposure to these HMI would not cause a health risk based on the USEPA model strategy. Furthermore, the obtained values of MoE for Pb and Cd in ointments were above 100, so exposure to these elements would not cause a health risk based on the MoE-based strategy. The original contribution of this work is that this is the first study on the triple approach strategy to evaluate the safety of heavy metal impurities in traditional herbal medicinal products applied dermally in solid form (ointments with marjoram herb extract). The research is novel and has not been previously published; The proposed procedure includes transcutaneous penetration of heavy metal (Pb and Cd) impurities described for the first time in the literature. Full article

(This article belongs to the Special Issue Exposure, Toxicity, and Health Impacts of Potentially Toxic Metals)

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16 pages, 3097 KiB

Open AccessArticle

The Control of Novel and Traditional Elemental Impurities: Ag, Au, Co, Cs, Li, Mo, Se, Sr, and V in Mint Tea Infusions (Peppermint, Mentha piperita L.) Available in Poland: A Health Risk Assessment

by Justyna Milan, Adrian Frydrych, Maciej Noga, Elżbieta Kondratowicz-Pietruszka, Mirosław Krośniak and Kamil Jurowski

Int. J. Environ. Res. Public Health 2022, 19(24), 16564; https://doi.org/10.3390/ijerph192416564 - 9 Dec 2022

Cited by 5 | Viewed by 1857

Abstract

The purpose of our studies is the evaluation of the health risks of the novel elemental impurities (Ag, Au, Co, Cs, Li, Mo, Se, Sr, and V) in mint tea infusions (Mentha piperita L.) available in Poland. For this purpose, we applied ICP-MS-based methodology for content analysis (elemental profile and µg/L of the infusion) and also the specific health risk assessment for a comprehensive assessment. Our strategy was based on weekly intake (µg/L of infusion/week) considering weekly tea consumption. Then, based on the weekly consumption of tea per adult, individuals were compared to the Temporary Tolerated Weekly Intake (PTWI) designated by the Joint FAO Expert Committee on Food Additives (JECFA), and the weekly consumption per body weight (µg/L of infusion/week/bw) was estimated. Daily exposure to Co in the tested products is in a range of 0.093–0.238 µg/day. In comparison, the established PDE (oral exposure) for Co by the ICH guideline (the ICH guideline Q3D (R1), 2019) is 50 µg/day. For lithium, PDE is approximately 560 µg/day and, in our study, the estimated daily exposure for Li in investigated products is in a range of 0.226–2.41 µg/day. Our studies found also low levels of Cs (in a range of 0.0598–0.195 µg/L), Mo (in a range of 0.663–3.261 µg/L), and Sr (0.223–65.842 µg/L) in infusions. For Molybdenum, the established PDE is approximately 3400 µg/day. There are no documents about Sr and Co in the Joint FAO/WHO Expert Committee on Food Additives (JECFA) database and the ICH guideline Q3D (R1). In the case of V, the established PDE is 120 µg/day, and the level of V in analyzed infusions is in a range of 0.284–0.702 µg/L. Silver and gold were present only in a few samples, and the estimated daily exposure for Ag is approximately 0.04575 µg/day for product A and approximately 0.1885 µg/day for product O, except for Au, which is in a range of 0.000356–0.114 µg/L. The estimated daily exposure for Ag is 167 µg/day and, for Au, it is in a range of 8.9 × 10⁵–0.0285 µg/day. It can be concluded that levels of all investigated elements (novel and also traditional elemental impurities) in the daily dose should not threaten the consumer’s health after consuming mint tea infusions. Full article

(This article belongs to the Special Issue Exposure, Toxicity, and Health Impacts of Potentially Toxic Metals)

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11 pages, 675 KiB

Open AccessArticle

Chronic Cadmium Exposure and Genetic Polymorphisms of MMP-2 and MMP-9 in a Population Exposed to Steel Slag in the State of Rio de Janeiro, Brazil: A Cross-Sectional Study

by Jamila A. Perini, Mayara C. da Silva, Lorena V. Correa, Yasmin M. Silva, Renato M. Borges and Maria de Fátima R. Moreira

Int. J. Environ. Res. Public Health 2022, 19(22), 15304; https://doi.org/10.3390/ijerph192215304 - 19 Nov 2022

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Abstract

Genetic polymorphisms in the matrix metalloproteinases (MMPs) family genes may be associated with cadmium (Cd) levels and its adverse effects. This study investigated the impact of MMP-2 and MMP-9 polymorphisms on Cd levels in 238 residents of a condominium in Rio de Janeiro, Brazil, built over an industrial steel slag waste. Polymorphisms were genotyped using TaqMan validated assays, and the Cd levels were measured in blood (BCd) and urine (UCd) samples by atomic absorption spectrometry. Associations were evaluated by linear correlation coefficients and multiple logistic regression, using odds ratios (OR) and 95% confidence intervals (CI). Mean age was 50 ± 15 years; 58% were female, 69% non-smokers. Mean concentrations for BCd and UCd were 0.70 ± 0.2 μg L⁻¹ and 0.56 ± 0.55 μg L⁻¹, respectively. Smoking status was associated with BCd ≥ 0.70 μg L⁻¹ (OR = 2.9; 95% CI = 1.6–5.9). MMP-9 rs17576 A > G was associated with BCd ≥ 0.70 μg L⁻¹ (OR = 2.11; 95% CI = 1.10–4.05) and UCd ≥ 0.56 μg L⁻¹ (OR = 3.38; 95% CI = 1.82–7.65). Knowing possible individual predisposing factors is essential to understand Cd toxicity, and to improve the monitoring of high-risk populations. Full article

(This article belongs to the Special Issue Exposure, Toxicity, and Health Impacts of Potentially Toxic Metals)

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15 pages, 2192 KiB

Open AccessArticle

Use of Generalized Weighted Quantile Sum Regressions of Tumor Necrosis Factor Alpha and Kidney Function to Explore Joint Effects of Multiple Metals in Blood

by Kuei-Hau Luo, Hung-Pin Tu, Cheng-Hong Yang, Chen-Cheng Yang, Tzu-Hua Chen and Hung-Yi Chuang

Int. J. Environ. Res. Public Health 2022, 19(12), 7399; https://doi.org/10.3390/ijerph19127399 - 16 Jun 2022

Cited by 5 | Viewed by 2625

Abstract

Exposure to heavy metals could lead to adverse health effects by oxidative reactions or inflammation. Some essential elements are known as reactors of anti-inflammatory enzymes or coenzymes. The relationship between tumor necrosis factor alpha (TNF-α) and heavy metal exposures was reported. However, the interaction between toxic metals and essential elements in the inflammatory response remains unclear. This study aimed to explore the association between arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn) in blood and TNF-α as well as kidney function. We enrolled 421 workers and measured the levels of these seven metals/metalloids and TNF-α in blood; kidney function was calculated by CKD-EPI equation. We applied weighted quantile sum (WQS) regression and group WQS regression to assess the effects of metal/metalloid mixtures to TNF-α and kidney function. We also approached the relationship between metals/metalloids and TNF-α by generalized additive models (GAM). The relationship of the exposure–response curve between Pb level and TNF-α in serum was found significantly non-linear after adjusting covariates (p < 0.001). Within the multiple-metal model, Pb, As, and Zn were associated with increased TNF-α levels with effects dedicated to the mixture of 50%, 31%, and 15%, respectively. Grouped WQS revealed that the essential metal group showed a significantly negative association with TNF-α and kidney function. The toxic metal group found significantly positive associations with TNF-α, serum creatinine, and WBC but not for eGFR. These results suggested Pb, As, Zn, Se, and mixtures may act on TNF-α even through interactive mechanisms. Our findings offer insights into what primary components of metal mixtures affect inflammation and kidney function during co-exposure to metals; however, the mechanisms still need further research. Full article

(This article belongs to the Special Issue Exposure, Toxicity, and Health Impacts of Potentially Toxic Metals)

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17 pages, 670 KiB

Open AccessArticle

Manganese and Lead Exposure and Early Puberty Onset in Children Living near a Ferromanganese Alloy Plant

by Nathália Ribeiro dos Santos, Juliana Lima Gomes Rodrigues, Matheus de Jesus Bandeira, Ana Laura dos Santos Anjos, Cecília Freitas da Silva Araújo, Luis Fernando Fernandes Adan and José Antonio Menezes-Filho

Int. J. Environ. Res. Public Health 2022, 19(12), 7158; https://doi.org/10.3390/ijerph19127158 - 10 Jun 2022

Cited by 2 | Viewed by 1727

Abstract

Manganese (Mn) and lead (Pb) have been associated with the deregulation of the neuroendocrine system, which could potentially favor the appearance of precocious puberty (PP) in environmentally exposed children. This study aims to evaluate the exposure to Mn and Pb and their potential effects in anticipating puberty in school-aged children living near a ferromanganese alloy plant in Bahia, Brazil. Toenail, occipital hair and blood samples were collected from 225 school-aged children. Tanner’s scale was used for pubertal staging. Mn in blood (MnB), toenail (MnTn) and hair (MnH) and blood lead (PbB) levels were measured by graphite furnace atomic absorption spectrometry. Puberty-related hormone concentrations were determined by chemiluminescence. The age at which girls’ breasts began to develop was inversely correlated with weight-for-age, height-for-age and BMI-for-age Z-scores (p < 0.05); pubarche also had similar results. Mn biomarker levels did not present differences among pubertal classification nor among children with potential PP or not. Furthermore, Mn exposure was not associated with the age of onset of sexual characteristics for either girls or boys. However, PbB levels were positively correlated with boys’ pubic hair stages (rho = 0.258; p = 0.009) and associated with the age of onset of girls’ pubarche (β = 0.299, 95%CI = 0.055–0.542; p = 0.017). Testosterone and LH concentrations were statistically higher in boys with an increased PbB (p = 0.09 and p = 0.02, respectively). Prospective studies are needed to better assess the association between exposure to Mn and Pb and the early onset of puberty. Full article

(This article belongs to the Special Issue Exposure, Toxicity, and Health Impacts of Potentially Toxic Metals)

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12 pages, 364 KiB

Open AccessArticle

Higher Lead and Lower Calcium Levels Are Associated with Increased Risk of Mortality in Malaysian Older Population: Findings from the LRGS-TUA Longitudinal Study

by Theng Choon Ooi, Devinder Kaur Ajit Singh, Suzana Shahar, Razinah Sharif, Nurul Fatin Malek Rivan, Asheila Meramat and Nor Fadilah Rajab

Int. J. Environ. Res. Public Health 2022, 19(12), 6955; https://doi.org/10.3390/ijerph19126955 - 7 Jun 2022

Cited by 3 | Viewed by 1472

Abstract

The main objective of this study is to determine the association of various trace elements’ status with the 5-year mortality rate among community-dwelling older adults in Malaysia. This study was part of the Long-term Research Grant Scheme—Towards Useful Ageing (LRGS-TUA). The participants were followed up for five years, and their mortality status was identified through the Mortality Data Matching Service provided by the National Registration Department, Malaysia. Of the 303 participants included in this study, 34 (11.2%) participants had died within five years after baseline data collection. As compared to the survivors, participants who died earlier were more likely (p < 0.05) to be men, smokers, have a lower intake of total dietary fiber and molybdenum, higher intake of manganese, lower zinc levels in toenail samples, lower calcium and higher lead levels in hair samples during baseline. Following the multivariate Cox proportional hazard analysis, lower total dietary fiber intake (HR: 0.681; 0.532–0.871), lower calcium (HR: 0.999; 95% CI: 0.999–1.000) and higher lead (HR: 1.309; 95% CI: 1.061–1.616) levels in hair samples appeared as the predictors of mortality. In conclusion, higher lead and lower calcium levels are associated with higher risk of mortality among community-dwelling older adults in Malaysia. Our current findings provide a better understanding of how the trace elements’ status may affect older populations’ well-being and mortality rate. Full article

(This article belongs to the Special Issue Exposure, Toxicity, and Health Impacts of Potentially Toxic Metals)

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29 pages, 628 KiB

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Availability, Toxicology and Medical Significance of Antimony

by Argyrios Periferakis, Ana Caruntu, Aristodemos-Theodoros Periferakis, Andreea-Elena Scheau, Ioana Anca Badarau, Constantin Caruntu and Cristian Scheau

Int. J. Environ. Res. Public Health 2022, 19(8), 4669; https://doi.org/10.3390/ijerph19084669 - 12 Apr 2022

Cited by 21 | Viewed by 4035

Abstract

Antimony has been known and used since ancient times, but its applications have increased significantly during the last two centuries. Aside from its few medical applications, it also has industrial applications, acting as a flame retardant and a catalyst. Geologically, native antimony is rare, and it is mostly found in sulfide ores. The main ore minerals of antimony are antimonite and jamesonite. The extensive mining and use of antimony have led to its introduction into the biosphere, where it can be hazardous, depending on its bioavailability and absorption. Detailed studies exist both from active and abandoned mining sites, and from urban settings, which document the environmental impact of antimony pollution and its impact on human physiology. Despite its evident and pronounced toxicity, it has also been used in some drugs, initially tartar emetics and subsequently antimonials. The latter are used to treat tropical diseases and their therapeutic potential for leishmaniasis means that they will not be soon phased out, despite the fact the antimonial resistance is beginning to be documented. The mechanisms by which antimony is introduced into human cells and subsequently excreted are still the subject of research; their elucidation will enable us to better understand antimony toxicity and, hopefully, to improve the nature and delivery method of antimonial drugs. Full article

(This article belongs to the Special Issue Exposure, Toxicity, and Health Impacts of Potentially Toxic Metals)

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