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BIOMONITORING

Evaluation of human biomonitoring data in a health risk based context: An updated analysis of population level data from the Canadian Health Measures Survey [Review]

In order to characterize exposure of the Canadian population to environmental chemicals, a human biomonitoring component has been included in the Canadian Health Measures Survey (CHMS). This nationally-representative survey, launched in 2007 by the Government of Canada, has measured over 250 chemicals in approximately 30,000 Canadians during the last decade. The capacity to interpret these data at the population level in a health risk context is gradually improving with the development of biomonitoring screening values, such as biomonitoring equivalents (BE) and human biomonitoring (HBM) values. This study evaluates recent population level biomonitoring data from the CHMS in a health risk context using biomonitoring screening values. Nationally representative biomonitoring data for fluoride, selenium, molybdenum, arsenic, silver, thallium, cyfluthrin, 2,4-dichlorophenoxyacetic acid (2,4-D), 3-phenoxybenzoic acid (3-PBA), chlorpyrifos, deltamethrin, bisphenol A, triclosan, acrylamide, cadmium, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), bromoform, chloroform, benzene, toluene, xylene, ethylbenzene, styrene and tetrachloroethylene were screened as part as this study. For non-cancer endpoints, hazard quotients (HQs) were calculated as the ratio of population level concentrations of a specific chemical at the geometric mean and 95th percentile to the corresponding biomonitoring screening value. Cancer risks were calculated at the 5th, 25th, 50th, 75th and 95th percentiles of the population concentration using BEs based on a risk specific dose. Most of the chemicals analyzed had HQs below 1 suggesting that levels of exposure to these chemicals are not a concern at the population level. However, HQs exceeded 1 in smokers for cadmium, acrylamide and benzene, as well as in the general population for inorganic arsenic, PFOS and PFOA, 3-PBA and fluoride. Furthermore, cancer risks for inorganic arsenic, acrylamide, and benzene at most population percentiles of exposure were elevated (>10(-5)). Specifically, for inorganic arsenic in the general population, the HQ was 3.13at the 95th percentile concentration and the cancer risk was 3.4x10(-4) at the 50th percentile of population concentrations. These results suggest that the levels of exposure in the Canadian population to some of the environmental chemicals assessed might be of concern. The results of this screening exercise support the findings of previous risk assessments and ongoing efforts to reduce risks from exposure to chemicals evaluated as part of this study. Although paucity of biomonitoring screening values for several environmental contaminants may be a limitation to this approach, our assessment contributes to the prioritization of a number of chemicals measured as part of CHMS for follow-up activities such as more detailed characterization of exposure sources.

S. Faure, N. Noisel, K. Werry, S. Karthikeyan, L. L. Aylward, and A. St-Amand,Evaluation of human biomonitoring data in a health risk based context: An updated analysis of population level data from the Canadian Health Measures Survey, International journal of hygiene and environmental health, 2020, 223, 267-280.

MINING ANEMIA

Health Risk Assessment of Potentially Toxic Trace and Elements in Vegetables Grown Under the Impact of Kajaran Mining Complex

Mining industry is one of the priority sectors of Armenia's economy. However, mining complexes without treatment facilities, such as those in Armenia, have adverse environmental impact. Moreover, soil contamination can pose a potential risk to human health, particularly, through the consumption of food crops. In this study, 12 soil and 32 vegetable composite samples were collected from the city of Kajaran where Armenia's biggest copper and molybdenum mine is located. The concentrations of Cu, Mo, Cd, Hg, As, and Pb were analyzed using atomic absorption spectrophotometer. Diet study was conducted using food frequency questionnaire. Non-carcinogenic and carcinogenic risks to human health through vegetable consumption were assessed. The results indicated that different vegetables have different trace element uptakes. Also, the transfer factors (TFs) for each vegetable varied across elements. TFs were less than 1 for the majority of trace elements. Nevertheless, in some samples of studied vegetables, the concentrations of Hg, Cd, and Pb exceeded the maximum allowable levels. THQ of Mo exceeded 1 for all the studied vegetables, while THQ of Cu exceeded 1 for potato and bean, indicating a potential health risk posed by chronic exposure. Exceedingly high levels of Mo exposure can be related to high incidence of anemia among Armenians, since Mo interacts with Cu and is a potential cause of copper deficiency-induced anemia. With regard to cancer risk, none of the carcinogenic risk values exceeded the threshold level.

D. Pipoyan, S. Stepanyan, S. Stepanyan, M. Beglaryan, and N. Merendino,Health Risk Assessment of Potentially Toxic Trace and Elements in Vegetables Grown Under the Impact of Kajaran Mining Complex, Biol Trace Elem Res, 2019, 192,

               

 

 

INDUSTRIAL EXPOSURE

Urinary metal/metalloid levels in relation to hypertension among occupationally exposed workers

Occupational exposure to metals can have an adverse effect on the cardiovascular system. However, epidemiological studies of the associations of metals expose with hypertension among occupationally exposed workers were limited. The aim of this study was to investigate the potential association between urinary metal levels and the risk of hypertension among molybdenum miners and iron and steel foundry workers. The cross-sectional study had 395 participants. Urinary metal levels were determined by inductively coupled plasma mass spectrometry. Log-binomial regression model and two-piece-wise regression model were applied to assess the dose-response relationship between metal exposure and hypertension. We observed that increased prevalence ratios for hypertension among the quartile of urinary concentrations of molybdenum, arsenic and lead were positive (all P for trend <0.05). Compared with the lowest quartiles, participants in the highest quartiles of molybdenum, arsenic and lead had a 2.58-fold, 4.30-fold and 4.85-fold increased probability of having hypertension, respectively. In the threshold effect analyses, we found the relationship was nonlinear between urinary molybdenum, cobalt, cadmium, arsenic and lead concentrations and the prevalence of hypertension. In addition, Pb, Mo, As and Co may have joint effect, and a strong positive correlation with the prevalence of hypertension. Conversely, the association between the joint effect of Cd, Pb and Mo versus the prevalence of hypertension is not significant. We provide reference levels of molybdenum, cobalt, cadmium, arsenic and lead that can be used to assess the effects of occupational metal exposure on hypertension.

P. Shi, H. Jing, and S. Xi,Urinary metal/metalloid levels in relation to hypertension among occupationally exposed workers, Chemosphere, 2019, 234, 640-647.

               

               

HUMAN

Impact of Moybdenum Compounds as Anticancer Agents

The aim of this mini review was to report the moybdenum compound intervention to control cancer disease. The intervention explains its roles and progress from inorganic moybdenum compounds via organomoybdenum complexes to its nanoparticles to control oesophageal cancer and breast cancer as case studies. Main contributions of moybdenum compounds as anticancer agents could be observed in their nanofibrous support with suitable physicochemical properties, combination therapy, and biosensors (biomarkers). Recent areas in anticancer drug design, which entail the uses of selected targets, were also surveyed and proposed.

A. T. Odularu, P. A. Ajibade, and J. Z. Mbese,Impact of Moybdenum Compounds as Anticancer Agents, Bioinorganic Chemistry and Applications, 2019, 2019.

               

               

Urinary metal/metalloid levels in relation to hypertension among occupationally exposed workers

Occupational exposure to metals can have an adverse effect on the cardiovascular system. However, epidemiological studies of the associations of metals expose with hypertension among occupationally exposed workers were limited. The aim of this study was to investigate the potential association between urinary metal levels and the risk of hypertension among moybdenum miners and iron and steel foundry workers. The cross-sectional study had 395 participants. Urinary metal levels were determined by inductively coupled plasma mass spectrometry. Log-binomial regression model and two-piece-wise regression model were applied to assess the dose-response relationship between metal exposure and hypertension. We observed that increased prevalence ratios for hypertension among the quartile of urinary concentrations of moybdenum, arsenic and lead were positive (all P for trend <0.05). Compared with the lowest quartiles, participants in the highest quartiles of moybdenum, arsenic and lead had a 2.58-fold, 4.30-fold and 4.85-fold increased probability of having hypertension, respectively. In the threshold effect analyses, we found the relationship was nonlinear between urinary moybdenum, cobalt, cadmium, arsenic and lead concentrations and the prevalence of hypertension. In addition, Pb, Mo, As and Co may have joint effect, and a strong positive correlation with the prevalence of hypertension. Conversely, the association between the joint effect of Cd, Pb and Mo versus the prevalence of hypertension is not significant. We provide reference levels of moybdenum, cobalt, cadmium, arsenic and lead that can be used to assess the effects of occupational metal exposure on hypertension. (C) 2019 Elsevier Ltd. All rights reserved.

P. Shi, H. M. Jing, and S. H. Xi,Urinary metal/metalloid levels in relation to hypertension among occupationally exposed workers, Chemosphere, 2019, 234, 640-647.

 

A Prospective Study of Early Pregnancy Essential Metal(loid)s and Glucose Levels Late in the Second Trimester

Context: Studies suggest many essential trace metal(loid)s are involved in glucose metabolism, but the associations among pregnant women are unclear. Objective: To assess associations between early pregnancy plasma zinc, selenium, copper, and moybdenum levels and blood glucose levels later in the second trimester. Design: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort is a prospective cohort study conducted between July 2009 and January 2013. Setting: Twelve academic research hospitals in the United States. Patients: A total of 1857 multiracial, nonobese, healthy women. Main Outcome Measure: Blood glucose levels from 1-hour 50-g gestational load test (GLT) at 24 to 28 weeks of gestation. Results: Higher concentrations of first-trimester copper were associated with higher glucose levels from the GLT (i.e., every 50% increase in copper concentration was related to 4.9 mg/dL higher glucose level; 95% CI: 2.2, 7.5 mg/dL) adjusted for maternal sociodemographic characteristics and reproductive history. In contrast, every 50% increase in moybdenum concentration was associated with 1.2 mg/dL lower mean glucose level (95% CI: -2.3, -0.1 mg/dL). The magnitude of these associations was greater at the upper tails of glucose level distribution based on quantile regressions of the 10th, 50th, and 90th percentiles. Conclusions: Higher copper and lower moybdenum concentrations could increase the risk of glucose dysregulation during pregnancy, with women at higher risk of gestational diabetes mellitus potentially affected to a greater extent. Further work is needed to understand the mechanisms involved with early pregnancy essential metal(loid)s to inform clinical diagnosis and prevention of glucose intolerance during pregnancy.

Y. N. Zheng, C. L. Zhang, M. Weisskopf, P. L. Williams, P. J. Parsons, C. D. Palmer, G. M. B. Louis, and T. James-Todd,A Prospective Study of Early Pregnancy Essential Metal(loid)s and Glucose Levels Late in the Second Trimester, Journal of Clinical Endocrinology & Metabolism, 2019, 104, 4295-4303.

 

Differential Phagocytosis-Based Photothermal Ablation of Inflammatory Macrophages in Atherosclerotic Disease

Inflammatory macrophage (Mphi)-mediated atherosclerosis is a leading cause of mortality and morbidity worldwide. Photothermal therapy (PTT) has been demonstrated as an efficient strategy in killing target cells, and its application in the treatment of inflammation in atherosclerosis is developing. However, the choice of nanomaterials, mechanisms, and side effects are seldom considered. In this study, semiconductor nanomaterials, that is, MoO2 nanoclusters, were synthesized and used for the first time in PTT for inflammatory Mphi-mediated atherosclerosis. Based on cell differential phagocytosis, the optimum amount of MoO2 and treatment time were selected to exert the maximum ablation effect on Mphi and minimal damage on endothelial cells without requiring additional target or selective groups. Moreover, MoO2-based PTT shows an excellent therapeutic effect on atherosclerosis by eliminating Mphi in animal models, with no significant side effects observed. This study explores a new method of nanotechnology and pharmaceutical development by using and optimizing cost-effective metal oxide nanostructures in the treatment of atherosclerosis and motivates further research on minimizing the side effects of related materials.

X. Wang, X. Wu, J. Qin, K. Ye, F. Lai, B. Li, G. He, X. Lu, D. J. L. Brett, and I. P. Parkin,Differential Phagocytosis-Based Photothermal Ablation of Inflammatory Macrophages in Atherosclerotic Disease, ACS Appl Mater Interfaces, 2019.

               

Toxic Effects of Particulate Matter Derived from Dust Samples Near the Dzhidinski Ore Processing Mill, Eastern Siberia, Russia

Ambient particulate matter (PM) is associated with increased mortality and morbidity, an effect influenced by the metal components of the PM. We characterized five sediment samples obtained near a tungsten-moybdenum ore-processing complex in Zakamensk, Russia for elemental composition and PM toxicity with regard to pulmonary, vascular, and neurological outcomes. Elemental and trace metals analysis of complete sediment and PM10 (the respirable fraction, < 10 microm mass mean aerodynamic diameter) were performed using inductively coupled plasma optical emission spectrometry (ICP-OES) and mass spectrometry (ICP-MS). Sediment samples and PM10 consisted largely of silicon and iron and silicon and sodium, respectively. Trace metals including manganese and uranium in the complete sediment, as well as copper and lead in the PM10 were observed. Notably, metal concentrations were approximately 10 x higher in the PM10 than in the sediment. Exposure to 100 microg of PM10 via oropharyngeal aspiration in C56BL/6 mice resulted in pulmonary inflammation across all groups. In addition, mice exposed to three of the five PM10 samples exhibited impaired endothelial-dependent relaxation, and correlative analysis revealed associations between pulmonary inflammation and levels of lead and cadmium. A tendency for elevated cortical ccl2 and Tnf-alpha mRNA expression was induced by all samples and significant upregulation was noted following exposure to PM10 samples Z3 and Z4, respectively. Cortical Nqo1 mRNA levels were significantly upregulated in mice exposed to PM10 Z2. In conclusion, pulmonary exposure to PM samples from the Zakamensk region sediments induced varied pulmonary and systemic effects that may be influenced by elemental PM composition. Further investigation is needed to pinpoint putative drivers of neurological outcomes.

K. E. Zychowski, A. Wheeler, B. Sanchez, M. Harmon, C. R. Steadman Tyler, G. Herbert, S. N. Lucas, A. M. Ali, S. Avasarala, N. Kunda, P. Robinson, P. Muttil, J. M. Cerrato, B. Bleske, O. Smirnova, and M. J. Campen,Toxic Effects of Particulate Matter Derived from Dust Samples Near the Dzhidinski Ore Processing Mill, Eastern Siberia, Russia, Cardiovascular toxicology, 2019, 19, 401-411.

               

Fluorescence imaging of a potential diagnostic biomarker for breast cancer cells using a peptide-functionalized fluorogenic 2D material

Protein C receptor (PROCR) is a recently discovered transmembrane biomarker for several tissue stem cells and is highly expressed in triple-negative breast cancer (TNBC) patient-derived xenografts. Herein, to enrich the toolbox for the biochemical evaluation of PROCR, we have developed a peptide-functionalized fluorogenic 2D material based on the self-assembly between a fluorescent peptide probe and thin-layer moybdenum disulfide. The material developed was suitable for the sensitive detection of PROCR recombinant protein in buffer solution and the fluorescence imaging of TNBC cells that express high levels of PROCR.

W. T. Dou, L. F. Liu, J. Gao, Y. Zang, G. R. Chen, R. A. Field, T. D. James, J. Li, and X. P. He,Fluorescence imaging of a potential diagnostic biomarker for breast cancer cells using a peptide-functionalized fluorogenic 2D material, Chemical communications (Cambridge, England), 2019, 55, 13235-13238.

 

The first anticancer tris(pyrazolyl)borate molybdenum(IV) complexes: tested in vitro and in vivo - a comparison of O,O-, S,O-, and N,N-chelate effects

The synthesis, characterization and biological activity of molybdenum(IV) complexes containing Trofimenko's scorpionato ligand, hydrotris(3-isopropylpyrazolyl)borate (TpiPr), in addition to varying biologically active as well as other conventional ligands is described. Ligands employed include (O,O-) (S,O-) (N,N-) donors which have been successfully coordinated to the molybdenum center by means of oxygen-atom transfer (OAT) reactions from the known MoVI starting material, TpiPrMoO2Cl. The synthesized complexes were characterized by standard analytical methods, and where possible by X-ray diffraction analysis. The aqueous stability of the compounds was studied by means of UV/Vis spectroscopy and the impact of the attached ligand scaffolds on the oxidation potentials (MoIV to MoV) was studied by cyclic voltammetry. Utilizing polyvinylpyrrolidone (PVP) as a solubilizing agent, adequate aqueous solubility for biological tests was obtained. The anticancer activity and preliminary mode of action studies have been performed in vitro and in vivo.

I. Berasaluce, K. Cseh, A. Roller, M. Hejl, P. Heffeter, W. Berger, M. A. Jakupec, W. Kandioller, M. S. Malarek, and B. K. Keppler,The first anticancer tris(pyrazolyl)borate molybdenum(IV) complexes: tested in vitro and in vivo - a comparison of O,O-, S,O-, and N,N-chelate effects, Chemistry (Weinheim an der Bergstrasse, Germany), 2019.

               

In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among girls in Mexico City

There is increasing evidence that several metals are endocrine disrupting chemicals (EDCs). In utero development and adolescence are critical windows of susceptibility to EDC exposure. With the exception of a few heavy metals, few human studies have evaluated the impact of metal exposure on pubertal development. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among girls from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. We measured urinary concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), moybdenum (Mo), nickel (Ni), antimony (Sb), selenium (Se), and zinc (Zn) in samples collected from women during their third trimester of pregnancy and from their female children at 8-13 years (n=132). We measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG) at age 8-13, and assessed Tanner stages for sexual maturation (breast, pubic hair development, and menarche status), at two time points (8-13, 14-18 years). We used linear regression to independently examine in utero and peripubertal metal concentrations as predictors of peripubertal hormones. In a longitudinal analysis using generalized estimation equations, we evaluated Tanner stage and menarche progression in relation to individual in utero and peripubertal metal concentrations. We found that higher in utero Zn was associated with increased inhibin B. Several metals at 8-13 years were associated with higher DHEA-S and estradiol, while Ni was positively but Cu was negatively associated with testosterone. In utero Ni, Al, and Cd were associated with slower progression of breast development after adjustment for child age and BMI z-score. For example, an IQR increase in in utero Al exposure was associated with 0.82 times lower odds of progressing to a higher Tanner stage for breast development per year (95% CI: 0.68, 0.99). Peripubertal concentrations of Ba and Al were also associated with being at a higher pubic hair Tanner stage and menarche at 8-13, but lower odds of progressing to the next stage at 14-18 years. We used Bayesian kernel machine regression (BKMR) to model the joint effect of multiple metals while accounting for correlated exposures, as well as potential non-linear relationships between metals and outcomes of interest, which yielded results similar to individual analyses. These findings suggest that female reproductive development may be vulnerable to the effects of metal exposure, and using both Tanner stages and hormone levels may provide clues about underlying mechanisms in two sensitive periods of development.

P. Ashrap, B. N. Sanchez, M. M. Tellez-Rojo, N. Basu, M. Tamayo-Ortiz, K. E. Peterson, J. D. Meeker, and D. J. Watkins,In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among girls in Mexico City, Environmental research, 2019, 177, 108630.

               

Pluronic F127-functionalized moybdenum oxide nanosheets with pH-dependent degradability for chemo-photothermal cancer therapy

Traditional cancer therapies carry a risk of serious side effects and toxicity. Developing an alternative treatment modality that is highly effective, has low toxicity and is noninvasive is urgently required. Here, we exploited moybdenum oxide (MoOx) nanosheets as a drug carrier and degradable photothermal agent to provide a chemo-photothermal combination cancer therapy. The MoOx nanosheets were synthesized by a one-pot hydrothermal method and then modified with pluronic F127 to improve physiological stability and biocompatibility. The F127-modified nanosheets (MoOX@F127) showed ultrahigh drug loading efficiency (DLE) of doxorubicin (DOX) (DLE%; 65%, W(load DOX)/[W(load DOX)+WMoOx@F127]), strong near-infrared (NIR) absorption and desirable pH-dependent degradability. After intravenous injection, MoOx@F127 nanosheets were degraded at physiological pH and were rapidly excreted from normal organs, while they were effectively accumulated and retained long-term in the more acidic tumor tissue. This simultaneously ensured effective tumor ablation after NIR irradiation and avoided long-term retention and toxicity in vivo. Compared to chemotherapy or photothermal therapy alone, in vitro and in vivo tumor ablation studies have shown a notably improved synergistic effect of the combination therapy. Our study presents a multifunctional nanosystem with a desirable degradability for chemo-photothermal combination cancer therapy that has great potential in biomedical applications.

Y. Chen, A. R. Khan, D. Yu, Y. Zhai, J. Ji, Y. Shi, and G. Zhai,Pluronic F127-functionalized moybdenum oxide nanosheets with pH-dependent degradability for chemo-photothermal cancer therapy, J Colloid Interface Sci, 2019, 553, 567-580.

HUMAN HEALTH

Alloys biomedical

Biocompatibility of new low-cost (alpha plus beta)-type Ti-Mo-Fe alloys for long-term implantation

In this work, two new alpha + beta titanium alloys with low contents of ubiquitous and low-cost alloying elements (i.e., Mo and Fe) were designed on the basis of the electronic parameters and molybdenum equivalent approaches. The designed Ti - 2Mo - 0.5Fe at. % (TMF6) and Ti - 3Mo - 0.5Fe at. % (TMF8) alloys were produced using arc melting process for studying their mechanical, electrochemical and cytotoxicity compatibilities and comparing these compatibilities to those of Ti-6Al-4V ELI alloy. The cost of the used raw materials for producing the TMF6 and TMF8 alloys are almost 1/6 of those for producing the Ti-6Al-4V ELI alloy. The hardness of the two alloys are higher than that of the Ti-6Al-4V ELI alloy, while their Young's moduli (in the range of 85-82 GPa) are lower than that of the Ti-6Al-4V ELI alloy (110 GPa). Increasing the Mo equivalent from 6 (in TMF6 alloy) to 8 (in TMF8 alloy) led to an increase in the plastic strain percent from 4% to 17%, respectively, and a decrease in the ultimate tensile strength from 949 MPa to 800 MPa, respectively. The microstructure of TMF6 alloy consists of alpha'/alpha '' phases, while TMF8 alloy substantially consists of alpha '' phase. The corrosion current densities and the film resistances of the new alloys are in the range of 0.70-1.07 nA/cm(2) and on the order of 10(5) Omega.cm(2), respectively. These values are more compatible with biomedical applications than those measured for the Ti-6Al-4V ELI alloy. Furthermore, the cell viabilities of the TMF6 and TMF8 alloys indicate their improved compatibility compared to that of the Ti-6Al-4V ELI alloy. The CCK-8 (Cell Counting Kit-8) assay was conducted to investigate the cyto-toxicity, proliferation, and shape index of the cells of the candidate alloys. Overall, the measured compatibility of the new V-free low-cost alloys, particularly TMF8, makes them promising candidates for replacing the Ti-6Al-4V ELI alloy in biomedical applications.

Y. Abdelrhman, M. A. H. Gepreel, S. Kobayashi, S. Okano, and T. Okamoto,Biocompatibility of new low-cost (alpha plus beta)-type Ti-Mo-Fe alloys for long-term implantation, Materials Science & Engineering C-Materials for Biological Applications, 2019, 99, 552-562.

HUMAN

LUNG DISEASE

Assessment of 7 trace elements in serum of patients with nontuberculous mycobacterial lung disease

Nontuberculous mycobacterial (NTM) lung diseases are an emerging cause of pulmonary infection, becoming more common in the clinical setting as incidence of NTM lung diseases steadily increases worldwide. Trace elements are essential micronutrients and are known to play many important roles in infectious diseases. We investigated the concentrations of trace elements in patients with NTM lung disease and compared these values to patients with pulmonary tuberculosis and healthy controls. A case-control study was conducted to evaluate the serum trace element concentrations in 95 patients with NTM lung disease, 97 patients with pulmonary tuberculosis, and 99 healthy control subjects. The serum concentrations of 7 trace elements (cobalt, copper, chromium, manganese, molybdenum, selenium, and zinc) were measured using inductively coupled plasma-mass spectrometry. We also analyzed demographic data, clinical outcomes, and other biochemical parameters. The median serum concentrations of copper and molybdenum were higher in patients with NTM lung disease (109 vs. 91 mug/dL, p < 0.001 and 1.70 vs. 0.96 mug/L, p < 0.001). In contrast, the median serum concentrations of selenium and zinc were significantly lower in patients with NTM lung disease than in healthy controls (105 vs. 115 mug/L, p < 0.001 and 94 vs. 102 mug/dL, p < 0.001). Compared to patients with pulmonary tuberculosis, the serum concentrations of molybdenum and zinc were higher in patients with NTM lung disease, while cobalt and copper concentrations were lower (p < 0.001). Correlations among trace element concentrations were observed (copper and zinc, r = -0.367; cobalt and molybdenum, r = -0.360; selenium and zinc, r = 0.335; and manganese and zinc, r = 0.327, respectively). None of the 7 trace elements were associated with treatment outcomes. Patients with NTM lung disease showed different serum trace element concentrations. Our study indicates that altered trace element status is associated with mycobacterial disease. Further study investigating the clinical significance of individual trace elements and their association with nutritional status in patients with NTM lung disease would be required.

J. Oh, S. H. Shin, R. Choi, S. Kim, H. D. Park, S. Y. Kim, S. A. Han, W. J. Koh, and S. Y. Lee,Assessment of 7 trace elements in serum of patients with nontuberculous mycobacterial lung disease, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2019, 53, 84-90.

 

Lung cancer        

Circulating essential metals and lung cancer: Risk assessment and potential molecular effects

OBJECTIVE: Essential metals play important roles in the carcinogenic process. However, seldom longitudinal investigations have evaluated their roles in lung cancer development. We aimed to investigate the associations between multiple essential metals and lung cancer incidence and to explore the potential mechanisms. METHODS: A nested case-control study of 440 incident lung cancer cases and 1:3 frequency matched 1320 healthy controls from the Dongfeng-Tongji Cohort was conducted. The baseline plasma concentrations of 11 essential metals (cobalt, copper, iron, manganese, molybdenum, rubidium, selenium, strontium, stannum, vanadium, and zinc) were measured, and their associations with lung cancer incidence were estimated. Effect of positive metal (zinc) on 4-year telomere attrition was then evaluated among an occupational cohort of 724 workers. We also assessed the transcriptional regulation effects of plasma zinc on mRNA expression profiles, and the expressions of zinc-related genes were further compared in pair-wised lung tumor and normal tissues. RESULTS: Elevated plasma level of zinc was associated with lower incident risk of lung cancer [OR (95% CI)=0.89 (0.79, 0.99)] and decreased 4-year telomere attrition [beta (95% CI)=-0.73 (-1.27, -0.19)]. These effects were pronounced among males. In particularly, zinc could regulate the expressions of 8 cancer-related genes, including SOD1, APE, TP53BP1, WDR33, LAPTM4B, TRIT1, HUWE1, and ZNF813, which were over-expressed in lung tumor tissues. CONCLUSIONS: We propose that high plasma zinc could prevent incident lung cancer, probably by slowing down telomere attrition and regulating the expressions of cancer-related genes. These results provided a new insight into lung cancer prevention.

Y. Bai, G. Wang, W. Fu, Y. Lu, W. Wei, W. Chen, X. Wu, H. Meng, Y. Feng, Y. Liu, G. Li, S. Wang, K. Wang, J. Dai, H. Li, M. Li, J. Huang, Y. Li, S. Wei, J. Yuan, P. Yao, X. Miao, M. He, X. Zhang, H. Yang, T. Wu, and H. Guo,Circulating essential metals and lung cancer: Risk assessment and potential molecular effects, Environment international, 2019, 127, 685-693.

 

HUMAN

Mo URINE

Association of plasma and urine metals levels with kidney function: A population-based cross-sectional study in China

OBJECTIVES: Although environmental exposure to multiple metals is common, epidemiological studies on the associations of exposure to 23 metals with kidney function have not been analyzed. We aimed to investigate the associations of 23 metals levels with renal function. METHODS: We conducted a cross-sectional study in four rural regions of Hunan province. Plasma and urine metals levels were determined by inductively coupled plasma mass spectrometer (ICP-MS). Two-level logistic regression was used to investigate the associations of metals levels with estimated glomerular filtration rate (eGFR) with adjustment for confounding factors. We conducted a sensitivity analysis of the results using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS: A total of 3553 participants completed the investigation. Five metals (plasma arsenic and molybdenum; urine copper, rubidium, and strontium) were identified to be significantly associated with renal function. Participants in the highest quartile of plasma arsenic and molybdenum were at 17.95 (95% CI: 6.35-50.76) and 24.23 (95% CI: 7.42-79.19) fold risk of abnormal eGFR, respectively, compared with the lowest quartile. The highest quartiles of urine copper, rubidium, and strontium were associated with 3.70 (95% CI:1.92-7.14), 0.16 (95% CI:0.07-0.37) and 0.08 (95% CI: 0.03-0.21) fold risk of abnormal eGFR. The sensitivity analysis revealed that plasma arsenic, molybdenum and urine copper, rubidium and strontium levels retained similar associations with abnormal eGFR. CONCLUSION: Plasma arsenic and molybdenum, and urine copper are risk factors for abnormal renal function, while urine rubidium and strontium are protective factors for renal function.

F. Yang, X. Yi, J. Guo, S. Xu, Y. Xiao, X. Huang, Y. Duan, D. Luo, S. Xiao, Z. Huang, H. Yuan, M. He, M. Shen, and X. Chen,Association of plasma and urine metals levels with kidney function: A population-based cross-sectional study in China, Chemosphere, 2019, 226, 321-328.

 

MoS2 tumour markers

Molybdenum disulfide-integrated photonic barcodes for tumor markers screening

As a new class of two-dimensional (2D) materials, molybdenum disulfide (MoS2) has huge potential in biomedical area; while its applications in multiplex bioassays are still a challenge. Here, we present novel MoS2-integrated silica colloidal crystal barcode (SCCB) for multiplex microRNA (miRNA) screening. MoS2 was adsorbed on SCCBs by electrostatic interaction, and quantum dots (QDs) decorated hairpin probes were coupled on MoS2 by covalent linkage. As the MoS2 could quench the QDs of the hairpin probes, they together formed a molecular beacon (MB) structure before the detection. When used in assays, target miRNA could form a double strand with the probe and made QDs keep away from MoS2 sheets to recovery their fluorescence. Because the released QDs were positively correlated with the concentration of the hybridized nucleic acid, the target miRNAs could be quantified by measuring the fluorescence signal of the QDs on the SCCBs. In addition, by utilizing different MoS2-integrated structural color encoded SCCBs, multiplexed miRNA quantification could also be realized. Based on this strategy, we have demonstrated that several pancreatic cancer-related miRNAs could be selectivity and sensitivity detected with a detection limit of 4.2+/-0.3nM. These features make the MoS2-integrated SCCB ideal for many potential applications.

F. Bian, L. Sun, L. Cai, Y. Wang, Y. Zhao, S. Wang, and M. Zhou,Molybdenum disulfide-integrated photonic barcodes for tumor markers screening, Biosens Bioelectron, 2019, 133, 199-204.

Molybdenum disulfide nano tumour chemo-photothermal therapy

Molybdenum disulfide-based hyaluronic acid-guided multifunctional theranostic nanoplatform for magnetic resonance imaging and synergetic chemo-photothermal therapy

The construction of multifunctional theranostic nanoplatforms to integrate accurate imaging and enhanced therapy to treat tumors is highly attractive but remains a challenge. Here, we developed a molybdenum disulfide (MoS2)-based hyaluronic acid (HA)-functionalized nanoplatform capable of achieving the targeted co-delivery of the gadolinium (Gd)-based contrast agents (CAs) and the anticancer drug gefitinib (Gef) for magnetic resonance imaging (MRI) and synergetic chemo-photothermal therapy of tumors. Gd(3+) ions were coupled to HA-grafted MoS2 nanosheets with diethylenetriaminepentaacetic acid (DTPA) as a linker, followed by the incorporation of Gef. The resulting MoS2-HA-DTPA-Gd/Gef exhibited enhanced relaxivity, 3.3 times greater than that of the commercial CA DTPA-Gd, which facilitated the MRI in vivo. Moreover, the nanoplatform effectively converted the absorbed near-infrared (NIR) light into heat, which not only induced the photothermal ablation of cancer cells but also triggered the release of Gef from MoS2-HA-DTPA-Gd/Gef, enabling the synergetic chemo-photothermal therapy. The results of in vitro and in vivo experiments revealed that MoS2-HA-DTPA-Gd/Gef upon NIR irradiation effectively blocked the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway and activated apoptosis-related proteins to induce cell apoptosis and suppress cell proliferation, thus inhibiting the tumor growth in lung cancer cell-bearing mice. Taken together, this multifunctional theranostic nanoplatform has significant promise for the diagnosis and treatment of cancer.

J. Liu, J. Zheng, H. Nie, D. Zhang, D. Cao, Z. Xing, B. Li, and L. Jia,Molybdenum disulfide-based hyaluronic acid-guided multifunctional theranostic nanoplatform for magnetic resonance imaging and synergetic chemo-photothermal therapy, Journal of colloid and interface science, 2019, 548, 131-144.

 

HUMAN HEALTH

Urban and rural area differences in the interaction between oxidative process elements in human femoral bone

Elements in the human body come from contaminated food, water, and air from the living area. Bones are a marker of long-term exposure to elements and show a relationship between them. The aim of the study was to analyze the correlation between the contents of Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femoral head (cancellous bone) and femoral neck (cortical bone) in rural and urban populations. The study included 96 patients who were operated on for total hip replacement (THR), acquired in a surgical procedure with atomic absorption spectrometry, and the content of Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb was evaluated. In rural areas, significant negative correlations were observed for Mo/Cr, Mo/Cu, and Ni/Fe, and positive correlations were observed for Fe/Zn and Pb/Zn. In urban areas, a negative correlation was found for Pb/Mo. Pb and Ni increased with age only in villagers, and Zn and Sr decreased with age in urban citizens. Ba decreased with age in people from rural areas. The correlation showed variances mainly in molybdenum, nickel, and oxidative elements between rural and urban populations.

M. Dabrowski, A. Ziola-Frankowska, L. Kubaszewski, P. Rogala, and M. Frankowski, Urban and rural area differences in the interaction between oxidative process elements in human femoral bone, Environ Sci Pollut Res Int, 2018.

 

Urine

Urinary metal concentrations among mothers and children in a Mexico City birth cohort study

Personal care product use is a potential source of metals exposure among children, but studies have been limited. We measured urinary concentrations of 10 metals (aluminum, arsenic [As], barium [Ba], cadmium, cobalt [Co], lead [Pb], manganese [Mn], molybdenum [Mo], nickel, and zinc [Zn]) in third trimester pregnant women (n = 212) and their children at 8-14 years of age (n = 250). Demographic factors (child sex, age, socioeconomic status, and maternal education), body mass index (BMI) z-score, and child personal care product use in the 24 h prior to urine collection were examined as predictors of urinary metal concentrations. Metals were detected in 80-100% of urine samples, with significant differences in maternal versus childhood levels. However, metal concentrations were not strongly correlated within or between time points. In linear regression models including all demographic characteristics, BMI z-score, and specific gravity, age was associated with higher Co (6% [95% CI: 2, 10]), while BMI z -score was associated with lower Mo (-6% [95% CI: -11, -1). In addition, significantly higher metal concentrations were observed among users of colored cosmetics (Mo: 42% [95% CI: 1, 99]), deodorant (Ba: 28% [3, 58]), hair spray/hair gel (Mn: 22% [3, 45]), and other toiletries (As: 50% [9, 108]), as well as with an increasing number of personal care products used (As: 7% [3, 11]) after adjustment for child sex, age, total number of products used, and specific gravity. However, significantly lower metal concentrations were noted for users of hair cream (As and Zn: -20% [-36, -2] and -21% [-35, -2], respectively), shampoo (Pb: -40% [-62, -7]), and other hair products (Pb: -44% [-65, -9]). We found that personal care product use may be a predictor of exposure to multiple metals among children. Further research is recommended to inform product specific exposure source identification and related child health risk assessment efforts.

R. C. Lewis, J. D. Meeker, N. Basu, A. M. Gauthier, A. Cantoral, A. Mercado-Garcia, K. E. Peterson, M. M. Tellez-Rojo, and D. J. Watkins, Urinary metal concentrations among mothers and children in a mexico city birth cohort study, International Journal of Hygiene and Environmental Health, 2018, 221, 609-615.

 

Xanthinuria

Thiopurine-induced toxicity is associated with dysfunction variant of the human molybdenum cofactor sulfurase gene (xanthinuria type ii)

Background The aim of our study was to identify the genetic background of thiopurine-induced toxicity in a patient with a wild-type thiopurine methyltransferase genotype and activity. A 38-year-old Caucasian woman presented with cutaneous necrotizing vasculitis pancytopenia one month after starting azathioprine therapy. Methods: During a routine biochemical follow-up of the patient, undetectable serum uric acid (< 10 mu l) was observed. A high performance liquid chromatography analysis of urinary purines revealed increased levels of xanthine (137 mmol/mol creatinine). The suspected diagnosis of hereditary xanthinuria, a rare autosomal recessive disorder of the last two steps of purine metabolism, was confirmed by sequence analysis. Results: An analysis of XDH/XO and AOX1 revealed common polymorphisms, while analysis of the MOCOS gene identified a rare homozygous variant c.362C > T. Dysfunction of this variant was confirmed by significantly decreased xanthine dehydrogenase/oxidase activity in the patient's plasma (< 2% of control mean activity). Conclusions: We present a biochemical, enzymatic, and molecular genetic case study suggesting an important association between a hitherto undescribed dysfunction variant in the MOCOS gene and thiopurine-induced toxicity. The identified variant c.362C > T results in slower thiopurine metabolism caused by inhibition of 6-mercaptopurine oxidation (catabolism) to 6-thioxanthine and 6-thiouric acid, which increases the formation of the nucleotide 6-thioguanine, which is toxic. This is the first clinical case to identify the crucial role of the MOCOS gene in thiopurine intolerance and confirm the impact of genetic variability of purine enzymes on different therapeutic outcomes in patients undergoing thiopurine treatment.

B. Stiburkova, K. Pavelcova, L. Petru, and J. Krijt, Thiopurine-induced toxicity is associated with dysfunction variant of the human molybdenum cofactor sulfurase gene (xanthinuria type ii), Toxicology and Applied Pharmacology, 2018, 353, 102-108.

 

Systemic sclerosis

Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls

Objective: This case control study assessed: 1) the relationship of systemic sclerosis (SSc) related to exposure to heavy metals; and 2) the risk of SSc related to occupational exposure in male and female patients.

Methods: From 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habit matched controls were selected for each patient. All SSc patients and controls underwent detection and quantification of heavy metal traces in hair samples, using multi-element inductively coupled plasma mass spectrometry (ICP-MS).

Results: SSc patients exhibited higher median levels of the following metals: antimony (p = 0.001), cadmium (p = 0.0003), lead (p = 0.02), mercury (p = 0.02), molybdenum (p = 0.04), palladium (p < 0.0001) and zinc (p = 0.0003). A marked association between SSc and occupational exposure was further found for: 1) antimony (p = 0.008) and platinum (p = 0:04) in male patients; and 2) antimony (p = 0.02), cadmium (p = 0.001), lead (p = 0.03), mercury (p = 0.03), palladium (p = 0.0003) and zinc (p = 0.0001) in female patients

Conclusion: The results show the impact of occupational risk factors in the development of SSc for: antimony, cadmium, lead, mercury, molybdenum, palladium and zinc. Thus, occupational exposure should be systematically checked in all SSc patients at diagnosis. Finally, the association between SSc and occupational exposure may be variable according to patients' gender. (C) 2017 Elsevier B.V. All rights reserved.

I. Marie, J. F. Gehanno, M. Bubenheim, A. B. Duval-Modeste, P. Joly, S. Dominique, P. Bravard, D. Noel, A. F. Cailleux, J. Benichou, H. Levesque, and J. P. Goulle,Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls, Autoimmunity Reviews, 2017, 16, 223-230.

[Systemic scleroderma, also called diffusescleroderma or systemic sclerosis, is an autoimmune disease of the connective tissue. It is characterized by thickening of the skin caused by accumulation of collagen, and by injuries to small arteries. https://en.wikipedia.org/wiki/Systemic_scleroderma.

Scleroderma is caused by the immune system attacking the connective tissue under the skin and around internal organs and blood vessels. This causes scarring and thickening of the tissue in these areas.

There are two main types of scleroderma: localised scleroderma – just affects the skin systemic sclerosis – may affect blood circulation and internal organs as well as the skin.

https://www.nhs.uk/conditions/scleroderma/]

 

Industrial and Environmental Exposure of Humans

Humans are exposed to molybdenum compounds in industrial operations and in the environment. As with other elements maximum exposure limits for molybdenum are laid down in government legislation and regulatory controls. The limits may vary from country to country and are not always consistent. The basis for the limits is not always clear. Here we list the regulatory limits, the natural levels of molybdenum and the levels derived from industrial activity including mining.

 Carcinogenicity of welding, molybdenum trioxide, and indium tin oxide


Guha, N., Loomis, D., Guyton, K. Z., Grosse, Y., El Ghissassi, F., Bouvard, V., Benbrahim-Tallaa, L., Vilahur, N., Muller, K., Straif, K., and Int Agcy Res Canc Monograph, W.,Carcinogenicity of welding, molybdenum trioxide, and indium tin oxide, Lancet Oncology, 2017, 18, 581-582.

Atmospheric exposure - welders

Biological monitoring of welders' exposure to chromium, molybdenum, tungsten and vanadium

BACKGROUND: Welders are exposed to a number of metallic elements during work. Bioaccessibility, that is important for element uptake, has been little studied. This study addresses Bioaccessibility and uptake of chromium (Cr), molybdenum (Mo), tungsten (W) and vanadium (V) among welders.

METHODS: Bioaccessibility of Cr, Mo, V and W was studied in airborne particulate matter collected by personal sampling of the workroom air among shipyard welders by using the lung lining fluid simulant Hatch solution. Associations between concentrations of Hatch soluble and non-soluble elements (Hatchsol and Hatchnon-sol) and concentrations of the four elements in whole blood, serum, blood cells and urine were studied.

RESULTS: Air concentrations of the four elements were low. Only a small fraction of Cr, V and W was Hatchsol, while similar amounts of Mo were Hatchsol and Hatchnon-sol. Welders (N=70) had statistically significantly higher concentrations of all four elements in urine and serum when compared to referents (N=74). Highly statistically significant associations were observed between urinary W and Hatchsol W (p<0.001) and serum V and Hatchsol V (p<0.001), in particular when air samples collected the day before collection of biological samples were considered.

CONCLUSIONS: Associations between Hatchsol elements in air and their biological concentrations were higher than when Hatchnon-sol concentrations were considered. Associations were generally higher when air samples collected the day before biological sampling were considered as compared to air samples collected two days before.

Ellingsen, D. G., Chashchin, M., Berlinger, B., Fedorov, V., Chashchin, V., and Thomassen, Y.,Biological monitoring of welders' exposure to chromium, molybdenum, tungsten and vanadium, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2017, 41, 99-106.

 

Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls

OBJECTIVE: This case control study assessed: 1) the relationship of systemic sclerosis (SSc) related to exposure to heavy metals; and 2) the risk of SSc related to occupational exposure in male and female patients.

METHODS: From 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habit matched controls were selected for each patient. All SSc patients and controls underwent detection and quantification of heavy metal traces in hair samples, using multi-element inductively coupled plasma mass spectrometry (ICP-MS).

RESULTS: SSc patients exhibited higher median levels of the following metals: antimony (p=0.001), cadmium (p=0.0003), lead (p=0.02), mercury (p=0.02), molybdenum (p=0.04), palladium (p<0.0001) and zinc (p=0.0003). A marked association between SSc and occupational exposure was further found for: 1) antimony (p=0.008) and platinum (p=0.04) in male patients; and 2) antimony (p=0.02), cadmium (p=0.001), lead (p=0.03), mercury (p=0.03), palladium (p=0.0003) and zinc (p=0.0001) in female patients

CONCLUSION: The results show the impact of occupational risk factors in the development of SSc for: antimony, cadmium, lead, mercury, molybdenum, palladium and zinc. Thus, occupational exposure should be systematically checked in all SSc patients at diagnosis. Finally, the association between SSc and occupational exposure may be variable according to patients' gender.

Marie, I., Gehanno, J. F., Bubenheim, M., Duval-Modeste, A. B., Joly, P., Dominique, S., Bravard, P., Noel, D., Cailleux, A. F., Benichou, J., Levesque, H., and Goulle, J. P.,Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls, Autoimmunity reviews, 2017, 16, 223-230.

[Systemic Sclerosis (Scleroderma): multisystem autoimmune disease à increased fibroblast activity à abnormal growth of connective tissue. Vascular manifestations include secondary Raynaud's phenomenon, ischaemia of extremities, pulmonary arterial hypertension .

https://patient.info/doctor/systemic-sclerosis-scleroderma_green.]

COAL MINING

Appalachian Mountaintop Mining Particulate Matter Induces Neoplastic Transformation of Human Bronchial Epithelial Cells and Promotes Tumor Formation .

Epidemiological studies suggest that living near mountaintop coal mining (MTM) activities is one of the contributing factors for high lung cancer incidence. The purpose of this study was to investigate the long-term carcinogenic potential of MTM particulate matter (PMMTM) exposure on human bronchial epithelial cells. Our results show that chronic exposure (3 months) to noncytotoxic, physiological relevant concentration (1 μg/mL) of PMMTM, but not control particle PMCON, induced neoplastic transformation, accelerated cell proliferation, and enhanced cell migration of the exposed lung cells. Xenograft transplantation of the PMMTMexposed cells in mice caused no apparent tumor formation, but promoted tumor growth of human lung carcinoma H460 cells, suggesting the tumor-promoting effect of PMMTM. Chronic exposure to the main inorganic chemical constituent of PMMTM, molybdenum but not silica, similarly induced cell transformation and tumor promotion, suggesting the contribution of molybdenum, at least in part, in the PMMTM effects. These results provide new evidence for the carcinogenic potential of PMMTM and support further risk assessment and implementation of exposure control for PMMTM.

Luanpitpong,S., Michael Chen, Travis Knuckles, Sijin Wen, Juhua Luo, Emily Ellis, Michael Hendryx, and Yon Rojanasakul, Appalachian Mountaintop Mining Particulate Matter Induces Neoplastic Transformation of Human Bronchial Epithelial Cells and Promotes Tumor Formation Sudjit Environ. Sci. Technol. 2014, 48, 12912−12919.

SEE ALSO COMMENT ON THIS PAPER:

Richard A. Winschel 
Environ. Sci. Technol. 2015, 49, 9384−9384 DOI: 10.1021/acs.est.5b01781
"... there is a giant disconnect between the high percentage-point concentrations of PM Mo originally reported by Luanpitong for the PMMTM sample and the low mg/kg concentrations we find in coals."

The low molybdenum (trioxide) concentration calls into question the Luanpitpong suggestion that the cancer incidence is due to molybdenum.

 

Workplace exposure to molybdenum and molybdenum compounds and regulatory limits

Regulatory limits are listed in a number of publications. Useful summaries are at

http://www.3rd1000.com/elements/Molybdenum.htm#RegulatoryHealth
http://nj.gov/health/eoh/rtkweb/documents/fs/0105.pdf

We take as an example regulatory data from the United States. Other data are listed later in this section.

Note that the values are listed on the basis of the molybdenum content of a substance.

In the United States the National Institute for Occupational Safety and Health (NIOSH) conducts studies of workplace hazards and proposes standards to the Federal Occupational Safety and Health Administration (OSHA), which adopts and enforces health and safety standards.

The OSHA legal airborne Permissible Exposure Limit (PEL) for insoluble molybdenum compounds, expressed as the eight-hour Time Weighted Averages (TWA,average value of exposure over the course of an 8 hour work shift), is15 mg Mo/m3 (date last revised 09/06/2012) (http://www.osha.gov/dts/chemicalsampling/data/CH_255100.html and for soluble compounds is 5 mg/m3 (revision date:01/15/1993) (http://www.osha.gov/dts/chemicalsampling/data/CH_255100.html).

The American Conference of Governmental Industrial Hygienists (ACGIH) publishes guidelines called threshold limit values (TVLs) for exposure to workplace chemicals, the respirable fraction averaged over an eight hour work shift. The TLV for molybdenum compounds is 0.5 mg (Mo)/m3.

The National Institute for Occupational Safety and Health (NIOSH) publishes Documentation for Immediately Dangerous To Life or Health Concentrations (IDLHs). For soluble molybdenum compounds a revised IDLHis 1,000 mg Mo/m3 (May 1994).

A background account of molybdenum PELs and TLVs is in Hamilton and Hardy’s Industrial Toxicology 2015 p. 170. Quote:

‘The permissible exposure limit (PEL) values are established by the Occupational Safety and Health Administration (OSHA) and the threshold limit values (TLV) are set by the ACGIH. The PEL for insoluble molybdenum compounds (e.g. molybdenum disulphide), molybdenum dioxide and metallic molybdenum) is 15 mg/m3 total dust and 5 mg/m3 for respirable dust (OSHA 2008). These values were promulgated in 1971 as part of the original establishment of the OSHA, and have not changed (Federal Register, 1971). The ACGIH TLV for insoluble molybdenum is 10 mg/m3 total dust and 3 mg/m3 respirable dust. The TLV for insoluble molybdenum compounds is based on ACGIH’s intent to bring TLV values for low toxicity, poorly absorbed materials into agreement with each other. The TLV for soluble molybdenum compounds of 0.5 mg/m3 (respirable fraction) is based on the NTP (1979) inhalation study of molybdenum trioxide wherein the observed no effect level was 10 mg/m3 (ACGIH, 2008). Several safety factors were then incorporated for the development of this criterion.’

Workplace Exposure TLV-TWA USA

Workplace Exposure TLV USA
MaterialTLV-TWA /mg m-3
Soluble Mo
respirable particulate

0.5
Insoluble Mo
inhalable particulate
respirable particulate

10
3

Threshold Limit Values and Biological Exposure Indices for 2001: American Conference of Governmental Industrial Hygienists (ACGIH), Cincinatti, Ohio, 2001.

Notes

The number of workers in the United States potentially exposed to molybdenum trioxide during the years 1981 to 1983 was approximately 17,072

National Occupational Exposure Survey (NOES): National Institute for Occupational Safety and Health (NIOSH), 1995.

Occupational standards of exposure established by the Occupational Safety and Health Administration (OSHA) are 5 mg/m3 for soluble molybdenum compounds and 15 mg/m3 for insoluble molybdenum compounds

Hammond, P.B. and Beliles, R.P. Metals. In Casarett and Doull's Toxicology:The Basic Science of Poisons ,ed. Doull, J., Klaasen C. D. and Amdur, M. O., Macmillan, New York, 2nd Ed. 1980, 409.

The American Conference of Governmental Industrial Hygienists [ACGIH, 1995, 2001] recommends a threshold limit value-time-weighted average of  0.5 mg/m3 for soluble molybdenum compounds and 10 mg/m3 for insoluble molybdenum.

Maximum Allowable Concentration (MAC) Limits for Insoluble and Soluble Molybdenum Compounds

Maximum Allowable Concentration (MAC) Limits for Insoluble and Soluble Molybdenum Compounds
CountryMAC Limit (mg/m3) 
Insoluble molybdenum compounds
Holland 10 (mean)  
Romania 5 (mean)  
Germany 15 (mean)  
Russia (USSR), Hungary, Bulgaria 6 (peak)  
USA 20 (peak) 10 as TWA
Soluble molybdenum compounds
Holland 5 (mean)  
Romania 2 (mean)  
Germany, USA, Austria, Belgium, Italy 5 (mean)  
Russia (USSR), Bulgaria, Poland 4 (peak)  
Romania, USA 10 (peak) 5 as TWA

ILO, Occupational Exposure Limits, 2nd (revised) Ed., Occupational Safety and Health Series, 1980, 37, ILO Geneva.

Molybdenum Regulatory Limits International

Molybdenum Regulatory Limits
Process or materialLimitUnitsAveraging periodSource of limit
Air emission
Dust collectors 15 mg Mo dust/m3   Holland-permit
Calciner dust collector 0.126 kg Mo oxide/h   Holland-permit
Dryer dust collector 0.024 kg ADM/h   Holland-permit
As dust 10 mg/m3   NER (Dutch emission guidelines)
Soluble compounds 5 mg Mo/m3   UK Health and Safety Executive
Insoluble compounds 10 mg Mo/m3   UK Health and Safety Executive
Exhaust air from production plants 5 mg Mo/m3 0.5 - 3 h total Austria
For non-ferrous metals after filter stations 0.2 mg Mo/m3 0.5 - 3 h Austria-regional authority
Soluble Mo TLV 5 mg Mo/m3 0.5 - 3 h Austria
Insoluble Mo TLV 15 mg Mo/m3 0.5 - 3 h Austria
Water quality
Drinking 0.07 mg/l   Austria-WHO guideline
  0.01 mg/l   Chile-N Ch 1333 - 1978
Industrial 1 - 2 kg/day   Holland-permit
  5 mg/l   Austria-country
  5 mg/l 2 h average Germany-municipal authorities
Ground 300 mg/l   Holland-intervention values
  5 ppm   Holland-authorisation
  none     Belgium-80/68/EEC
  0.1 mg/l   US EPA
  0.07 mg/l   Japan
target limit 5 mg/l   Belgium-MILBOWA (DBO 07494013)
intervention limit 300 mg/l   Belgium-MILBOWA (DBO 07494013)
Soil
soil sanitation 200 mg/kg   Holland-intervention values
arableland pastures 10 mg/kg dry   Austria-TLV
  30 kg/ha   Austria-TLV
  3 g/m2   Austria-TLV
target limit 10 mg/kg dry   Belgium-MILBOWA (DBO 0749013)
intervention limit 200 mg/kg dry   Belgium-MILBOWA (DBO 0749013)
emission limit 150 mg/kg dry   Belgium-MILBOWA (DBO 0749013)
Solid waste
waste 5000 mg/kg   Holland-(BAGA)
to landfill 50 mg/l   Germany-approval DIN 38414
landfill leachate limit 125 mg/kg dry   OVAM proposals to Belgium Government
leachate limit 35 mg/m2   OVAM proposals to Belgium Government
  150 mg/m3/100y   Belgium-NEM 7340 Decision 23/11/95
sludge from dredging 10 mg/kg dry   Belgium-Decision 25/11/93
fly ash leachate limit 3 mg/kg   Belgium- NEM 7343 Decision 20/1/93
Sewage sludge
agricultural disposal 20 mg/kg dry   Austria
  0.5 mg/l   Chile
land application ceiling concentration 75 mg/kg   US EPA
Milk
  0.2 mg/kg   Austria

Data assembled by IMOA Health and Safety Committee, 1999.

Health surveillance study of workers who manufacture multi-walled carbon nanotubes

While many in vivo and in vitro toxicology studies of multi-walled carbon nanotubes (MWCNTs) have already indicated that exposure to MWCNTs can potentially induce health effects in humans, the actual health effects of MWCNTs among exposed workers are not yet known. Moreover, the levels of exposure and internal doses of MWCNTs are becoming more and more important for estimating the health effects resulting from exposure to MWCNTs. However, information on biomonitoring and exposure to MWCNTs remains limited. Therefore, the authors conducted a health surveillance study in a workplace that manufactures MWCNTs, including assessment of the personal and area exposure levels to MWCNTs, a walk-through evaluation of the manufacturing process, and collection of blood and exhaled breath condensates (EBCs) from the MWCNT manufacturing and office workers. In addition, a pulmonary function test was also conducted on the MWCNT manufacturing workers (9) and office workers (4). The worker exposure to elemental carbon was found to be 6.2-9.3 mug/m3 in the personal samplings and 5.5-7.3 mug/m3 in the area samplings. Notwithstanding, the workers exhibited a normal range of hematology and blood biochemistry values and normal lung function parameters. When analyzing the EBCs, the malondialdehyde (MDA), 4-hydroxy-2-hexenal (4-HHE) and n-hexanal levels in the MWCNT manufacturing workers were significantly higher than those in the office workers. The MDA and n-hexanal levels were also significantly correlated with the blood molybdenum concentration, suggesting MDA, n-hexanal and molybdenum as useful biomarkers of MWCNT exposure.

Lee, J. S., Choi, Y. C., Shin, J. H., Lee, J. H., Lee, Y., Park, S. Y., Baek, J. E., Park, J. D., Ahn, K., and Yu, I. J.,Health surveillance study of workers who manufacture multi-walled carbon nanotubes, Nanotoxicology, 2015, 9, 802-11.

Molybdenum trioxide (?) welding fumes

Studies in the field of environmental epidemiology indicate that for the adverse effect of inhaled particles not only particle mass is crucial but also particle size is. Ultrafine particles with diameters below 100 nm are of special interest since these particles have high surface area to mass ratio and have properties which differ from those of larger particles. In this paper, particle size distributions of various welding and joining techniques were measured close to the welding process using a fast mobility particle sizer (FMPS). It turned out that welding processes with high mass emission rates (manual metal arc welding, metal active gas welding, metal inert gas welding, metal inert gas soldering, and laser welding) show mainly agglomerated particles with diameters above 100 nm and only few particles in the size range below 50 nm (10 to 15%). Welding processes with low mass emission rates (tungsten inert gas welding and resistance spot welding) emit predominantly ultrafine particles with diameters well below 100 nm. This finding can be explained by considerably faster agglomeration processes in welding processes with high mass emission rates. Although mass emission is low for tungsten inert gas welding and resistance spot welding, due to the low particle size of the fume, these processes cannot be labeled as toxicologically irrelevant and should be further investigated.

Brand, P., Lenz, K., Reisgen, U., and Kraus, T.,Number size distribution of fine and ultrafine fume particles from various welding processes, Ann Occup Hyg, 2013, 57, 305.

Reported daily molybdenum intakes from industrial sources

Molybdenum dusts and fumes, as can be generated by mining or metalworking, are not toxic. There are no long-term effects associated with exposure to molybdenum; however, prolonged exposure (to high levels) can cause irritation to the eyes and skin. The direct inhalation or ingestion of molybdenum should be avoided.

Inhaling molybdenum dust can irritate the nose and throat and may cause coughing and wheezing. Mining and metallurgy workers chronically exposed to 60 to 600 mg Mo/m3 reported an increased incidence of nonspecific symptoms that included weakness, fatigue, headache, anorexia, and joint and muscle pain.

Lener J. and Bibr B., J Hyg Epidemiol Microbiol Immunol, 1984, 29:405-419. Effects of molybdenum on the organism: a review.

Routes of Exposure areinhalation; ingestion; skin and eye contact.

Target Organs areeyes, respiratory system, liver, kidneys.

Levels In Humans: naturally occurring levels of molybdenum in the typical human (NOT recommended daily allowances) are reported 

·Blood/mg dm-3: 0.001

·Bone/p.p.m: <0.7

·Liver/p.p.m: 1.3-5.8

·Muscle/p.p.m: 0.018

·Daily Dietary Intake: 0.05-0.35 mg

-Total Mass In Avg. 70kg human: 5 mg

http://www.3rd1000.com/elements/Molybdenum.htm#Regulatory%20/%20Health

Reported daily molybdenum intakes from industrial sources

Average daily intakes of Mo 0.1 – 0.5 mg Mo increasing to 1 mg if contamination from industrial sources

Friberg, L., Lener, J., Molybdenum, in Handbook on the Toxicology of Metals Vol II, Friberg, L., Nordberg, G.F., and Vouk, V.B., eds., Elsevier, 1986, 446 – 461.

56 adults in Germany 47 – 89 microg

Anke, M., Groppel, B., Krause, U., Arnhold, W., Langer, M., Trace element intake of humans , J. Trace Elemen. Electrolytes Health Dis., 1991, 5, 69 – 74.

Adults in Denver 120 – 240 microg Mo/d av 180

Tsongas, T.A., Meglen, R.R., Walravens, P.A., Chappell W.R., Molybdenum in the diet, Am. J. Clin. Nutr., 1980, 33, 1103 –1107.

NE US 74 – 126 microg Mo/d

Pennington, J.A.T., Young, B.E., Wilson, D., Nutritional elements in US diets, J. Am. Diet. Assoc., 1989, 89, 659 – 664.

Average daily intakes of Mo 0.1 – 0.5 mg Mo increasing to 1 mg if contamination from industrial sources

Friberg, L., Lener, J., Molybdenum, in Handbook on the Toxicology of Metals Vol II, Friberg, L., Nordberg, G.F., and Vouk, V.B., eds., Elsevier, 1986, 446 – 461.

56 adults in Germany 47 – 89 microg

Anke, M., Groppel, B., Krause, U., Arnhold, W., Langer, M., Trace element intake of humans , J. Trace Elemen. Electrolytes Health Dis., 1991, 5, 69 – 74.

Adults in Denver 120 – 240 microg Mo/d av 180

Tsongas, T.A., Meglen, R.R., Walravens, P.A., Chappell W.R., Molybdenum in the diet, Am. J. Clin. Nutr., 1980, 33, 1103 –1107.

NE US 74 – 126 microg Mo/d

Pennington, J.A.T., Young, B.E., Wilson, D., Nutritional elements in US diets, J. Am. Diet. Assoc., 1989, 89, 659 – 664.

Mo uptake from industrial sources: Impact of Dust Filter Installation in Ironworks and Construction on Brownfield Area on the Toxic Metal Concentration in Street and House Dust (Celje, Slovenia)

This article presents the impact of the ecological investment in ironworks (dust filter installation) and construction works at a highly contaminated brownfield site on the chemical composition of household dust (HD) and street sediment (SS) in Celje, Slovenia.

The evaluation is based on two sampling campaigns: the first was undertaken 1 month before the ecological investment became operational and the second 3 years later.

The results show that dust filter installations reduced the content of Co, Cr, Fe, Mn, Mo, W and Zn on average by 58% in HD and by 51% in SS. No reduction was observed at sampling points in the upwind direction from the ironworks.

By contrast, the impact of the construction works on the highly contaminated brownfield site was detected by a significant increase (on average by 37%) of elements connected to the brownfield contamination in SS. Such increase was not detected in HD

Zibret, Gorazd, Impact of Dust Filter Installation in Ironworks and Construction on Brownfield Area on the Toxic Metal Concentration in Street and House Dust (Celje, Slovenia), Ambio, 2012, 41, 292-301.

Ergonomic study of an operator's work of a molybdenum plant

This study was part of an ergonomic program which is being carried out through an agreement between the University of Concepcion and a Chilean private mining company. The purpose of this case study was to identify working conditions in which the physical and mental workload could be over the capabilities of the operator. He was responsible for loading trucks with sacks of molybdenum and for downloading reagents and handles them. The methods employed in this study included electronic records, interviews, surveys, review of the company standards, a time study and physical and mental workload analysis. Results showed that 84% of the time the operator was carrying out principal and secondary activities and no break periods were detected. It was found that the pace of work and the shift system generated unfavorable conditions by imbalance in the workload on the different days of the week. In the light of the results recommendations were made for a number of ergonomic changes. Most of them were accepted by the company. The most important achievement was a change in the shift system. The overload of the operator was due to the fact that he was in a shift working 5 days and resting on weekends. The imbalance was mainly because the work of the week end was accumulated for Monday. As a result of the study, the company contracted a second worker for this job and adopted a 7x7 shift system, meaning that they work seven days and rest seven days. An evaluation carried out two month after adopting the new shift revealed that changes were well accepted by the worker

Onate,E. and Meyer, F., Ergonomic study of an operator's work of a molybdenum plant, Work-A Journal of Prevention Assessment & Rehabilitation, 2012, 41, 5950-5955.

Guinea pigs exposed to the dust or fumes of molybdenum trioxide

For guinea pigs exposed to the dust or fumes of molybdenum trioxide (150-300 mg/m3) for 1 h per day, 5 times per week, for 5 weeks [Fairhall et al., 1945]. Low concentrations of molybdenum (20-270 microg/10g fresh tissue) were found in the lungs, liver, kidneys, spleen and bone. The molybdenum concentrations in these tissues decreased after exposure was stopped to 20% of the original level after 2 weeks. After an oral gavage dose of 50 mg molybdenum trioxide was administered to guinea pigs, molybdenum was distributed to the kidneys, spleen, blood, bile, liver, and lungs within 4 h. The concentrations of molybdenum in the organs decreased, whereas in the blood and bile molybdenum titres were higher at 48 h. Bone retained molybdenum longer than any other tissues [Fairhall et al., 1945]. Based on the amount recovered in faeces for up to 48 h, Fairhall et al. (1945) calculated that 85 % of the oral dose was absorbed. Excess hexavalent forms of molybdenum are excreted rapidly through the kidneys and the bile. Twice as much molybdenum is eliminated in urine as in the faeces. The urinary and faecal concentrations of molybdenum returned to normal after an oral dose of molybdenum trioxide was administered to guinea pigs [Fairhall et al., 1945]. The predominant urinary metabolite of molybdenum was in the form of molybdate complexes [Venugopal and Luckey, 1978].

Fairhall, L. T., Dunn, R. C., Sharpless, N. E. and Pritchard, E. A., U. S. Public Health Bull., 1945, 293, 1.
Venugopal, B. and Luckey, T. D., Metal Toxicity in Mammals, 1978, Vol. 2, Chemical Toxicity of Metals and Metalloids, Plenum Press, New York.

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