Ni Exposure Research Articles

Tomato (Solanum lycopersicum L.) accumulation and allergenicity in response to nickel stress

Vegetables represent a major source of Ni exposure. Environmental contamination and cultural practices can increase Ni amount in tomato posing significant risk for human health. This work assesses the tomato (Solanum lycopersicum L.) response to Ni on the agronomic yield of fruits and the related production of allergens. Two cultivars were grown in pots amended with Ni 0, 30, 60, 120, and 300 mg kg−1, respectively. XRF and ICP-MS analyses highlighted the direct increase of fruit Ni content compared to soil Ni, maintaining a stable biomass. Leaf water content increased at Ni 300 mg kg−1. Total protein content and individual allergenic components were investigated using biochemical (RP-HPLC and N-terminal amino acid sequencing) and immunological (inhibition tests of IgE binding by SPHIAa assay on the FABER testing system) methodologies. Ni affected the fruit tissue concentration of pathogenesis-related proteins and relevant allergens (LTP, profilin, Bet v 1-like protein and TLP). This study elucidates for the first time that tomato reacts to exogenous Ni, uptaking the metal while changing its allergenic profiles, with potential double increasing of exposure risks for consumers. This evidence highlighted the importance of adequate choice of low-Ni tomato cultivars and practices to reduce Ni uptake by potentially contaminated matrices.

Geospatial modeling and ecological and human health risk assessments of heavy metals in contaminated mangrove soils

Heavy metal-contaminated wastes can threaten mangrove forests, one of the most biodiverse ecosystems in the world. The study evaluated the geospatial distribution of heavy metals concentrations in soils, the ecological and human health risks, and metal contents in soil fractions and mangrove organisms in the Botafogo estuary, Brazil, one of the most environmentally impacted estuaries in the country. The metal concentrations exceeded by up to 2.6-fold the geochemical background; 91%, 59%, 64%, 31%, and 82% of the soils were contaminated with Cr, Zn, Pb, Cu, and Ni, respectively. Adverse effects to the biota may occur due to Cr, Cu, Ni and Pb exposures. Contents of clay and organic matter were the main factors governing the distribution of metals in soil, contributing to up to 63% of the total variability. However, the geospatial modeling showed that the predictive ability of these variables varied spatially with the metal and location. The ecological and human health risks assessments indicated that the metal concentrations in soils are safe for the environment and human beings. There was a low transfer of metals from the soil to the biota, with values of sediment-biota accumulation factor (SBAF) and biological accumulation coefficients (BAC) lower than 1.0, except for Zn (SBAF = 13.1). The high Zn bioaccumulation by Crassostrea rhizophorae may be associated with the concentrations of Zn in the bioavailable fractions.

Nickel's Role in Pancreatic Ductal Adenocarcinoma: Potential Involvement of microRNAs.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types with a limited overall survival rate due to the asymptomatic progression of symptoms in metastatic stages of the malignancy and the lack of an early reliable diagnostic biomarker. MicroRNAs (miRs/miRNAs) are small (~18–24 nucleotides), endogenous, non-coding RNAs, which are closely linked to the development of numerous malignancies comprising PDAC. Recent studies have described the role of environmental pollutants such as nickel (Ni) in PDAC, but the mechanisms of Ni-mediated toxicity in cancer are still not completely understood. Specifically, Ni has been found to alter the expression and function of miRs in several malignancies, leading to changes in target gene expression. In this study, we found that levels of Ni were significantly higher in cancerous tissue, thus implicating Ni in pancreatic carcinogenesis. Hence, in vitro studies followed by using both normal and pancreatic tumor cell lines and increasing Ni concentration increased lethality. Comparing LC50 values, Ni-acetate groups demonstrated lower values needed than in NiCl2 groups, suggesting greater Ni-acetate. Panc-10.05 cell line appeared the most sensitive to Ni compounds. Exposure to Ni-acetate resulted in an increased phospho-AKT, and decreased FOXO1 expression in Panc-10.05 cells, while NiCl2 also increased PTEN expression in Panc-10.05 cells. Specifically, following NiCl2 exposure to PDAC cells, the expression levels of miR-221 and miR-155 were significantly upregulated, while the expression levels of miR-126 were significantly decreased. Hence, our study has suggested pilot insights to indicate that the environmental pollutant Ni plays an important role in the progression of PDAC by promoting an association between miRs and Ni exposure during PDAC pathogenesis.

Comparative Morphology and Biochemical Analysis of Nickel Toxicity in Minor Fruit Species (Grewia asiatica L., Syzgium cumini (L.) Skeels and Tamarindus indica L.)

We evaluated the growth potential of three minor fruit species (Grewia asiatica L., Syzgium cummini and Tamarindus indica L.) after exposure to increasing Ni levels (0, 10, 20 and 40 µg kg−1 soil). The growth attributes, lipid peroxidation, photosynthetic machinery, macro nutrients and capacity of enzymatic antioxidants; Superoxide dismutase (SOD), Catalase (CAT) and Peroxidase (POD) in both leaves and roots were investigated under Ni exposure. A significant reduction in the biomass elongation of tissues (root and shoot) and enhanced oxidative damage via malondialdehyde (MDA) were noticed in all three species. Ni exposure triggered an induction of antioxidant enzyme response in a concurrent manner. Simultaneous increases in the antioxidant activities in the roots of G. asiatica and in the leaves of S. cumini suggest the existence of a sequence response against tissue damage. However, the activities of antioxidant enzymes in the tissues of T. indica were insufficient to counteract the elevated MDA levels. G. asiatica exhibited its resilience through the restricted transfer of Ni to aerial tissue, adequate uptake of nutrients, robust chloroplasts with lesser biodegradation of chlorophyll molecules and enhanced capacity of antioxidant enzyme biosynthesis. Thus, lesser modulations of morpho-biochemical expressions and the activity of antioxidants seem to contribute important defense mechanisms against Ni stress in the species.

Risk assessment of uptake of trace elements through consumption of cereals: a pilot study in Yerevan, Armenia.

The study aimed to assess the dietary exposure and related human health risks associated with trace elements through the intake of staple cereals, including buckwheat, rice, and emmer. The contents of Lead (Pb), Cadmium (Cd), Mercury (Hg), Nickel (Ni), Molybdenum (Mo), Iron (Fe), and Copper (Cu) were determined using Atomic Absorption Spectrometry. Cereal consumption data were obtained through a Semi-Quantitative Food Frequency Questionnaire amongst the Yerevan adult population. Concentrations of Pb, Cd, Hg, Ni, Mo, Fe and Cu were 0.75-5.56µg/kg, 1.21-6µg/kg, 6.7-6.99µg/kg, 50.6-111µg/kg, 20-429µg/kg, 2770-30500µg/kg and 601-1720µg/kg respectively. The estimated daily intakes (EDI) of all studied trace elements did not exceed the health-based guidance values. The margin of exposure (MOE) values of Pb, Cd, Hg, and Mo for all clusters were above the threshold (>10 for Pb, Cd, and >100 for Hg, Mo) and therefore did not indicate a health concern. Meanwhile, in the case of Ni exposure, the MOE values for the second and third clusters of buckwheat consumption and for the third cluster of emmer consumption were below the threshold (<10) indicating that a human health risk cannot be excluded. Future work is proposed.

Complementary square wave voltammetry and tandem mass spectrometry analysis to identify and detect compensatory genomic changes in nematodes due to nickel (II) exposure

Nickel is a toxic heavy metal that may cause negative health outcomes including cancer upon exposure [1]. Square wave voltammetry was used to assay DNA directly extracted from nickel-exposed nematodes that had originated from either high or low Ni-containing environments in order to assess the role of evolutionary genetics in the Ni toxicity process. Extracted DNA was immobilized on pyrolytic graphite (PG) electrodes following layer by layer (LbL) protocols and then electrochemically oxidized in the presence of Ru(bpy)3+ to generate electrocatalytic oxidative currents at ∼+1.05 V vs. SCE. Both C. elegans and P. pacificus nematodes were utilized, each with a volcanic or cosmopolitan soil source strain. DNA oxidative peak currents (Ip) increased for all nematode strains upon exposure to 50 μg/L Ni2+, but those originating from volcanic soils exhibited significantly (40–50%) lower Ip upon Ni2+ exposure compared to similarly exposed nematodes from cosmopolitan soils. Further SWV analysis was performed on DNA from a series of C. elegans N2xCB4856 recombinant inbred advanced intercross line populations (RIALs). A continuum of Ip magnitude was seen as a function of Ni2+ exposure among the RIAL strains indicating Ni-tolerance is complex and affected by multiple loci. The majority of the DNA from Ni-exposed individual RIAL strain cultures produced an increase in oxidative current in comparison to DNA from analogous Ni-unexposed cultures of the same RIAL strains. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis on acid hydrolyzed nematode DNA provided validation of the electrochemical findings. Guanine and oxidatively damaged guanine content were monitored via appropriate m/z mass transitions. Guanine content in all Ni-exposed RIAL DNA was lower, while oxidatively damaged guanine was elevated compared to unexposed nematodes in all but one analyzed RIAL. Combined, the complementary electrochemical and MS/MS data provide evidence that evolutionary genetics leads to genetic protection from environmental toxicants, suggesting a possibility that multiple genes are involved in the protection of the organism from Ni exposure.

Oxidative stress-mediated apoptosis and autophagy involved in Ni-induced nephrotoxicity in the mice

As an extensively environmental pollution, Nickel (Ni) represents a serious hazard to human health. The present study focused on exploring the mechanism of Ni-mediated nephrotoxicity, such as apoptosis, autophagy and oxidative stress. In the current work, NiCl2 treatment could induce kidney damage. Meanwhile, NiCl2 treatment elevated ROS production and MDA content and suppressed the antioxidant activity, which was characterized by reducing T-AOC, CAT, SOD activity and GSH content. For investigating the role of oxidative stress on NiCl2-mediated nephrotoxicity, N-acetyl cysteine (NAC, effective antioxidant and free radical scavenger) was co-treated with NiCl2. The results showed that NAC significantly suppressed the NiCl2-mediated oxidative stress and mitigated NiCl2-induced the kidney damage. Then, whether oxidative stress-induced autophagy and apoptosis were involved in NiCl2-induced nephrotoxicity was explored. The findings demonstrated that NAC relieved NiCl2-induced autophagy and reversed the activation of Akt/AMPK/mTOR pathway. Concurrently, the results indicated that NAC attenuated NiCl2-induced apoptosis, as evidenced by reduction of apoptotic cells and cleaved-caspase-3/− 8/− 9 together with cleaved-PARP protein levels. To sum up, our findings suggested that NiCl2-mediated renal injury was associated with oxidative stress-induced apoptosis and autophagy. This study provides new theoretical basis for excess Ni exposure nephrotoxic researches.

Epiphytic PGPB Bacillus megaterium AFI1 and Paenibacillus nicotianae AFI2 Improve Wheat Growth and Antioxidant Status under Ni Stress.

The present study demonstrates the Ni toxicity-ameliorating and growth-promoting abilities of two different bacterial isolates when applied to wheat (Triticum aestivum L.) as the host plant. Two bacterial strains tolerant to Ni stress were isolated from wheat seeds and selected based on their ability to improve the germination of wheat plants; they were identified as Bacillus megaterium AFI1 and Paenibacillus nicotianae AFI2. The protective effects of these epiphytic bacteria against Ni stress were studied in model experiments with two wheat cultivars: Ni stress-tolerant Leningradskaya 6 and susceptible Chinese spring. When these isolates were used as the inoculants applied to Ni-treated wheat plants, the growth parameters and the levels of photosynthetic pigments of the two wheat cultivars both under normal and Ni-stress conditions were increased, though B. megaterium AFI1 had a more pronounced ameliorative effect on the Ni contents in plant tissues due to its synthesis of siderophores. Over the 10 days of Ni exposure, the plant growth promotion bacteria (PGPB) significantly reduced the lipid peroxidation (LPO), ascorbate peroxidase (APX), superoxide dismutase (SOD) activities and proline content in the leaves of both wheat cultivars. The PGPB also increased peroxidase (POX) activity and the levels of chlorophyll a, chlorophyll b, and carotenoids in the wheat leaves. It was concluded that B. megaterium AFI1 is an ideal candidate for bioremediation and wheat growth promotion against Ni-induced oxidative stress, as it increases photosynthetic pigment contents, induces the antioxidant defense system, and lowers Ni metal uptake.

Pregnancy complications effect on the nickel content in maternal blood, placenta blood and umbilical cord blood during pregnancy.

BACKGROUNDNickel (Ni) may accumulate in the human body and has biological toxicity and carcinogenicity. Ni has an extensive impact on the health of pregnant women and fetuses during gestation.AIMTo evaluate Ni exposure in pregnant women in Kunming, Yunnan Province, China; to describe the distribution of Ni in the maternal-fetal system and placental barrier function; and to investigate the effect of Ni exposure on fetal health in mothers with pregnancy complications.METHODSSeventy-two pregnant women were selected using a case-control design. The women were divided into two groups: The control group (no disease; n = 29) and the disease group [gestational diabetes (GDM), hypertensive disorder complicating pregnancy (HDCP), or both; n = 43]. The pregnant women in the disease group were further divided as follows: 14 cases with GDM (GDM group), 13 cases with HDCP (HDCP group) and 16 cases with both GDM and HDCP (disease combination group). Basic information on the pregnant women was collected by questionnaire survey. Maternal blood, placenta blood and cord blood were collected immediately after delivery. The Ni content in paired samples was determined using inductively coupled plasma mass spectrometry. RESULTSCompared to the control group, age was higher and body mass index was greater in pregnant women in the disease groups (28.14 ± 2.54 vs 28.42 ± 13.89, P < 0.05; 25.90 ± 3.86 vs 31.49 ± 5.30, P < 0.05). The birth weights of newborns in the HDCP group and the control group were significantly different (2.52 ± 0.74 vs 3.18 ± 0.41, P < 0.05). The content of Ni in umbilical cord blood in the entire disease group was higher than that in the control group (0.10 ± 0.16 vs 0.05 ± 0.07, P < 0.05).CONCLUSIONIn the maternal-fetal system of women with pregnancy complications, the barrier effect of the placenta against Ni is weakened, thus affecting healthy growth of the fetus in the uterus.

Health risk assessment of toxic metals and toxigenic fungi in commercial herbal tea samples from Belgrade, Serbia

This study aimed to: (i) determine the content of toxic metals and toxigenic fungi in 14 commercial herbal tea samples from the market of Belgrade, Serbia; and (ii) assess their risk to human health. After the microwave digestion (HNO3/H2O2, 7:1,v/v), toxic metal content was determined by graphite furnace atomic absorption spectroscopy (GF-AAS). The health risk as a result of Cd, Pb, As, Mn, Ni, and Cr exposure via herbal tea intake was assessed through estimated daily intake (EDI), target hazard quotient (THQ), and hazard index (HI). Fungi isolated from the tested herbal tea samples were identified on the basis of colony morphology and microscopic characteristics of reproductive structures. Toxic metals concentration in herbal tea samples for Cd, Pb, As, Mn, Ni and Cr ranged 0.04-0.93, 0.09-2.54, 0.03-0.77, 1.82-651.04, 0.97-9.01, 0.49-3.47 mg/kg of dried plant material, respectively. Values of THQ for investigated toxic metals and HI were below 1, indicating the absence of human health risk. All 14 samples of the tested herbal teas were contaminated with fungi, while total count of cultivable fungi in each sample did not exceed national standards (105 CFU/g). Presence of 23 morphologically different isolates suggested moderate fungal diversity of the samples, while the highest isolation frequency (IF) of 100% was documented for Penicillium spp. and Aspergillus spp. The obtained risk assessment results suggest that all the tested samples are safe for human health regarding the toxic metal and fungal content and provide an important basis for understanding the potential risks of toxic metals and toxigenic fungi intake via commercially available herbal teas.

Assessing reference levels of nickel and chromium in cord blood, maternal blood and placenta specimens from Ankara, Turkey

Objective:Placenta is a temporary organ that connects the developing fetus and the mother. However, it cannot protect the embryo against chromium (Cr) and nickel (Ni) exposure. Quantification of Cr and Ni in biological and ecological subjects is challenging. Thus, the first goal of this study was to provide a validated Graphite Furnace Atomic Absorption Spectrometry (GFAAS) method to determine Cr and Ni in mother-newborn specimens. The second goal was to assess the reference Ni and Cr contents in cord blood, maternal blood, and placenta samples in a population from Ankara.Material and Methods:Biological samples were collected from 100 healthy mother-newborn pairs. Metal levels were quantified by GFAAS. Method validation of this toxicological analysis was performed by the use of certified reference materials, and assessed through accuracy, precision, specificity, range, quantitation, and detection limits.Results:Mean Cr levels of maternal blood, placentas, and cord blood were 0.337±0.222 μg/L, 0.221±0.160 μg/kg, 0.121±0.096 μg/L, respectively while mean Ni concentrations were 0.128±0.093 μg/L, 0.124±0.067 μg/kg, 0.099±0.067 μg/L, respectively. The method showed linearity with excellent correlation coefficients (r2) for Cr (0.9994) and Ni (0.9999). Satisfactory recovery and coefficient of variation for Cr and Ni were 102.85% and 102.35%; 1.75% and 2.91%, respectively. Relative error did not exceed 3%, demonstrating the accuracy of the method. Control charts were drawn to assess inter-day stability. The predicted reference ranges for Cr and Ni concentrations in maternal blood, placenta and cord blood were: Cr 0.033-0.75 μg/L; 0.032-0.526 μg/kg; 0.031-0.309 μg/L and for Ni were 0.011-0.308 μg/L; 0.024-0.251 μg/kg; 0.066-0.209 μg/L, respectively.Conclusion:The reported reference values of biological specimens in this paper will provide complementary aid to health professionals in terms of assessment of environmental and occupational exposure.

The effect of marine dissolved organic carbon on nickel accumulation in early life-stages of the sea urchin, Strongylocentrotus purpuratus

Dissolved organic carbon (DOC) is known to ameliorate the toxicity of the trace metal nickel (Ni) to aquatic animals. In theory, this effect is mediated by the capacity of DOC to bind Ni, rendering it less bioavailable, with the resulting reduction in accumulation limiting toxicological effects. However, there is a lack of experimental data examining Ni accumulation in marine settings with natural sources of DOC. In the current study, radiolabelled Ni was used to examine the time- and concentration-dependence of Ni accumulation, using naturally sourced DOC, on developing larvae of the sea urchin Strongylocentrotus purpuratus. Contrary to prediction, the two tested natural DOC samples (collected from the eastern United States, DOC 2 (Seaview park, Rhode Island (SVP)) and DOC 7 (Aubudon Coastal Center, Connecticut)) which had previously been shown to protect against Ni toxicity, did not limit accumulation. The control (artificial seawater with no added DOC), and the DOC 2 sample could mostly be described as having saturable Ni uptake, whereas Ni uptake in the presence of DOC 7 was mostly linear. These data provide evidence that DOC modifies the bioavailability of Ni, through either indirect effects (e.g. membrane permeability) or by the absorption of DOC-Ni complexes. There was some evidence for regulation of Ni accumulation in later-stage embryos (96-h) where the bioconcentration factor for Ni declined with increasing Ni exposure concentration. These data have implications for predictive modelling approaches that rely on known relationships between Ni speciation, bioavailability and bioreactivity, by suggesting that these relationships may not hold for natural marine DOC samples in the developing sea urchin model system.

Temporal trend of the dietary exposure to metals/metalloids: A case study in Tarragona County, Spain

In 2018, samples of various food groups were randomly purchased in different establishments of Tarragona County (Catalonia, Spain). The levels of As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sn, Tl and V were determined in the analyzed foodstuffs and their dietary intakes were estimated. Manganese was the element showing the highest concentration, while Be, Cr and Tl were not detected in any of the samples. Fish and shellfish was the only food group with detectable traces of all the remaining elements. The current levels were compared with the results of two previous surveys conducted in 1998 and 2013 in the same area. Although the levels of the analyzed elements in foodstuffs increased during the period 2013–2018, their intakes decreased by an average of 60%, due to consumption patterns changes by the population. Children and adolescents exceeded the maximum recommended intake of Ni set by the EFSA, while the dietary exposure to Pb for children was also above safety values. Compared with the concentrations found in 2013, Ni was the only element showing an increase, as well as an increase of human dietary intake. Meat, vegetables and milk were identified as the main contributors to Ni exposure. This trend was also correlated with changes in the biological burden of the same elements previously reported for the population of the area, for whom an increase of Ni in lungs was reported. Based on these results, Ni should be included as a target metal by food safety authorities, being suggested its inclusion in future Total Diet Studies.

Developmental toxicity in marine medaka (Oryzias melastigma) embryos and larvae exposed to nickel

As an important trace metal, nickel (Ni) has been reported extensively in the studies on freshwater animals. However, the toxic effects of Ni on marine organisms are not clearly understood. Therefore, in order to investigate the toxic effects of Ni on the early development of marine fish, the marine medaka (Oryzias melastigma) embryos and larvae were immersed in 0.13–65.80 mg/L Ni solution. The results showed that Ni exposure changed the egg size and heart rate of the embryos, lowered the hatchability, increased the deformity rate, and shortened the total body length of newly hatched larvae. Besides, it was found that before organogenesis and post-hatching periods were the sensitive periods of embryos to Ni. The 25 d LC50 value of embryos was 49.28 mg/L, and the 5 d LC50 of larvae was 55.92 mg/L, indicating that the embryos were more sensitive to Ni than the larvae. Furthermore, the expressions of the metallothionein (MT) gene, the skeletal development-related gene (Cyp26b1) and the cardiac development-related genes (ATPase, smyd1, cox2 and bmp4) were determined, and the results showed that the expressions of ATPase and smyd1 were up-regulated, while MT, Cyp26b1 and cox2 were significantly down-regulated at 9 days post-fertilization (dpf). Overall, Ni exposure caused a significant toxic effect on the early development of the O. melastigma embryos and larvae. Our findings could provide an important supplement to the toxicity data of tropical Ni and provide a reference for the exploration of the molecular mechanisms of Ni toxicity.

Intraspecific Variation in Nickel Tolerance and Hyperaccumulation among Serpentine and Limestone Populations of Odontarrhena serpyllifolia (Brassicaceae: Alysseae) from the Iberian Peninsula

Odontarrhena serpyllifolia (Desf.) Jord. & Fourr. (=Alyssum serpyllifolium Desf.) occurs in the Iberian Peninsula and adjacent areas on a variety of soils including both limestone and serpentine (ultramafic) substrates. Populations endemic to serpentine are known to hyperaccumulate nickel, and on account of this remarkable phenotype have, at times, been proposed for recognition as taxonomically distinct subspecies or even species. It remains unclear, however, to what extent variation in nickel hyperaccumulation within this taxon merely reflects differences in the substrate, or whether the different populations show local adaptation to their particular habitats. To help clarify the physiological basis of variation in nickel hyperaccumulation among these populations, 3 serpentine accessions and 3 limestone accessions were cultivated hydroponically under common-garden conditions incorporating a range of Ni concentrations, along with 2 closely related non-accumulator species, Clypeola jonthlaspi L. and Alyssum montanum L. As a group, serpentine accessions of O. serpyllifolia were able to tolerate Ni concentrations approximately 10-fold higher than limestone accessions, but a continuous spectrum of Ni tolerance was observed among populations, with the least tolerant serpentine accession not being significantly different from the most tolerant limestone accession. Serpentine accessions maintained relatively constant tissue concentrations of Ca, Mg, K, and Fe across the whole range of Ni exposures, whereas in the limestone accessions, these elements fluctuated widely in response to Ni toxicity. Hyperaccumulation of Ni, defined here as foliar Ni concentrations exceeding 1g kg−1 of dry biomass in plants not showing significant growth reduction, occurred in all accessions of O. serpyllifolia, but the higher Ni tolerance of serpentine accessions allowed them to hyperaccumulate more strongly. Of the reference species, C. jonthlaspi responded similarly to the limestone accessions of O. serpyllifolia, whereas A. montanum displayed by far the lowest degree of Ni tolerance and exhibited low foliar Ni concentrations, which only exceeded 1 g kg−1 in plants showing severe Ni toxicity. The continuous spectrum of physiological responses among these accessions does not lend support to segregation of the serpentine populations of O. serpyllifolia as distinct species. However, the pronounced differences in degrees of Ni tolerance, hyperaccumulation, and elemental homeostasis observed among these accessions under common-garden conditions argues for the existence of population-level adaptation to their local substrates.

Human biokinetic model for soluble nickel addressing inter-individual variation

Worker-specific Biological Exposure Action Levels (BEALs) for nickel (Ni) exposure are a urinary Ni concentration that reflects a dose that can be experienced on a daily basis without adverse systemic health effects. Several health-based reference values for systemic exposure to Ni have been derived as oral daily Ni dosing levels (e.g., 2007 WHO tolerable daily intake for Ni). To support evaluation of urinary nickel biomonitoring data in workers based on such health-based criteria, new human biokinetic models for nickel (Ni) were fit jointly to data obtained for 18 adult volunteers from four newly reported human studies and to data from two previously reported studies involving a total of 14 adult volunteers. This model and associated statistical analyses characterize and predict human Ni biokinetics after ingestion of Ni doses ≤ 20 µg/kg bw and associated inter-individual variation in urinary Ni excretion. Using this approach, we illustrate how available health-based reference values for daily Ni exposure by the oral route developed to protect against adverse health effects can be applied to derive urinary nickel BEALs for nickel workers based on their individual characteristics (e.g., shift pattern, body weight). Such worker-specific BEALs can provide health-based reference values to evaluate measures obtained through urinary Ni biomonitoring programs to complement existing industrial hygiene air monitoring programs.

Histone hypoacetylation contributes to neurotoxicity induced by chronic nickel exposure in vivo and in vitro

Nickel (Ni) is a heavy metal that is both an environmental pollutant and a threat to human health. However, the effects of Ni on the central nervous system in susceptible populations have not been well established. In the present study, the neurotoxicity of Ni and its underlying mechanism were investigated in vivo and in vitro. Ni exposure through drinking water (10 mg Ni/L, 12 weeks) caused learning and memory impairment in mice. Reduced dendrite complexity was observed in both Ni-exposed mouse hippocampi and Ni-treated (200 μM, 72 h) primary cultured hippocampal neurons. The levels of histone acetylation, especially at histone H3 lysine 9 (H3K9ac), were reduced in Ni-exposed mouse hippocampi and cultured neurons. RNA sequencing and chromatin immunoprecipitation (ChIP) sequencing analyses revealed that H3K9ac-modulated gene expression were downregulated. Treatment with sodium butyrate, a histone deacetylase inhibitor, attenuated Ni-induced H3K9 hypoacetylation, neural gene downregulation and dendrite complexity reduction in cultured neurons. Sodium butyrate also restored Ni-induced memory impairment in mice. These results indicate that Ni-induced H3K9 hypoacetylation may be a contributor to the neurotoxicity of Ni. The finding that Ni disturbs histone acetylation in the nervous system may provide new insight into the health risk of chronic Ni exposure.

Occupational exposure to potentially toxic elements in the foundry industry: an integrated environmental and biological monitoring

Industrial foundry processes release metal dust and fumes into the environment. Our study evaluated the exposure to potentially toxic elements in foundry workers. The assessed samples consisted of air particulate matter (n = 42), urine (n = 194), and blood (n = 167). Six workers had high concentrations of arsenic (As) in urine and one of them had a high cadmium (Cd) content in blood, according to Biological Exposure Index from the American Conference of Governmental Industrial Hygienists. The work task significantly influenced the concentrations of cobalt (Co), copper (Cu), iron (Fe), and manganese (Mn) in air, barium (Ba) in urine, and lead (Pb) and cesium (Cs) in blood, while the employment years affected concentrations of Mn, tin (Sn), and uranium (U) in urine and iodine (I) in blood. Arsenic, Pb, Co, and Cd in particulate matter and biological matrices presented significant covariation by working activity, supporting the occupational exposure. In this study, subjects were occupationally exposed to multiple potentially toxic elements. Carcinogenic and noncarcinogenic risks were associated with As, Co, Ni, and Mn exposure.

Induction of NUPR1 and AP‑1 contributes to the carcinogenic potential of nickel.

Nickel (Ni) is carcinogenic to humans, and causes cancers of the lung, nasal cavity, and paranasal sinuses. The primary mechanisms of Ni‑mediated carcinogenesis involve the epigenetic reprogramming of cells and the ability for Ni to mimic hypoxia. However, the exact mechanisms of carcinogenesis related to Ni are obscure. Nuclear protein 1 (NUPR1) is a stress‑response gene overexpressed in cancers, and is capable of conferring chemotherapeutic resistance. Likewise, activator protein 1 (AP‑1) is highly responsive to environmental signals, and has been associated with cancer development. In this study, NUPR1 was found to be rapidly and highly induced in human bronchial epithelial (BEAS‑2B) cells exposed to Ni, and was overexpressed in Ni‑transformed BEAS‑2B cells. Similarly, AP‑1 subunits, JUN and FOS, were induced in BEAS‑2B cells following Ni exposure. Knockdown of JUN or FOS was found to significantly suppress NUPR1 induction following Ni exposure, demonstrating their importance in NUPR1 transactivation. Reactive oxygen species (ROS) are known to induce AP‑1, and Ni has been shown to produce ROS. Treatment of BEAS‑2B cells with antioxidants was unable to prevent NUPR1 induction by Ni, suggesting that NUPR1 induction by Ni relies on mechanisms other than oxidative stress. To determine how NUPR1 is transcriptionally regulated following Ni exposure, the NUPR1 promoter was cloned and inserted into a luciferase gene reporter vector. Multiple JUN binding sites reside within the NUPR1 promoter, and upon deleting a JUN binding site in the upstream most region within the NUPR1 promoter using site‑directed mutagenesis, NUPR1 promoter activity was significantly reduced. This suggests that AP‑1 transcriptionally regulates NUPR1. Moreover, knockdown of NUPR1 significantly reduced colony formation and anchorage‑independent growth in Ni‑transformed BEAS‑2B cells. Therefore, these results collectively demonstrate a novel mechanism of NUPR1 induction following Ni exposure, and provide a molecular basis by which NUPR1 may contribute to lung carcinogenesis.

An ICP-MS Study for Quantitation of Nickel and Other Inorganic Elements in Urine Samples: Correlation of Patch Test Results with Lifestyle Habits.

Nickel (Ni) is a frequently used metal in the production of many products, and Ni exposure occurs in humans through food, inhalation, and skin. Studies reported Ni as the most common allergen diagnosed in the serial patch test. The main purpose of our study was to determine the concentration of Ni and other elements in the urine samples of individuals with Ni-sensitivity and to determine the effect of lifestyle habits on these variables. This study was conducted with 388 participants; additionally, both Ni patch test and inorganic analysis (for 24 elements)method in urine with inductively coupled plasma-mass spectrometry (ICP-MS)were applied to all participants. Ninety-two (23.7%) of the participants were found to have nickel sensitivity with a mean urine concentration of 4.475 μg/g creatinine (median=4.260; SD=2.527). The urine nickel concentration was significantly different between female and male participants (p =0.001). We found a significant correlation between Ni and other metals alongside various element pairs. The mean urine Ni concentration of the individuals with a positive Ni sensitivity test result was not different from that of the participants without Ni sensitivity (4.475 vs 4.256 μg/g creatinine, respectively; p = 0.068). The high accuracy, recovery, and repeatability data obtained from the analyses indicate that this study is efficient and appropriate for the quantitative determination of nickel and other elements in urine samples. Ni-containing objects and Ni-rich foods should be of concern for individuals with hypersensitivity reactions to the element.