EPIDEMIOLOGICAL AND PATHOGENETIC ASPECTS OF NICKEL POISONING

Nickel is widely distributed in the environment. High consumption of nickel containing products inevitably leads to environmental pollution by nickel and its derivatives at all stages of production, utilization, and disposal.Human exposure to nickel occurs primarily via inhalation and ingestion and is particularly high among nickel metallurgy workers. In addition, implantation of nickel-containing endoprostheses and iatrogenic administration of nickel-contaminated medica-tions leads to significant parenteral exposures. Exposure to nickel compounds can produce a variety of adverse effects on human health. Nickel allergy in the form of contact dermatitis is the most common reaction.A frontal headache, vertigo, nausea, vomiting, insomnia, and irritability are the most common signs of acute poisoning with nickel compounds. The respiratory tract, kidneys and liver suffer the most significant changes like nickel pneumoconiosis, chronic rhinitis and sinonasal tumors and transitory nephropathy. Although the accumulation of nickel in the body through chronic exposure can lead to lung fibrosis, cardiovascular and kidney diseases, the most serious concerns relate to nickel’s carcinogenic activity. Nickel compounds are carcinogenic to humans and metallic nickel is possibly carcinogenic to humans

Special Occupational Hazard Review and Control Recommendations for Nickel Carbonyl

The known hazards of nickel carbonyl are reviewed and recommendations are made for control measures in occupational environments. Human effects resulting from accidental exposure to nickel carbonyl include pulmonary edema, interstitial pneumonitis, reduced lung capacity, heart disorders, liver enlargement, and in severe exposure cases, death. In animal carcinogenicity studies, rats developed lung tumors from both long term and acute exposure to nickel carbonyl vapor. Human epidemiologic data are insufficient to either confirm or deny a causal relationship between the increased incidence of lung and nasal cancers and nickel carbonyl exposure in nickel refinery workers. The 1 part per billion nickel carbonyl standard should protect workers from any carcinogenic and other adverse health effects associated with nickel carbonyl exposure. Methods for detecting nickel carbonyl in the air are described.CurrentPrevention and ControlEnvironmental Healt

Physiologically-based pharmacokinetic and toxicokinetic models for estimating human exposure to five toxic elements through oral ingestion

Biological monitoring and physiologically-based pharmacokinetic (PBPK) modelling are useful complementary tools in quantifying human exposure to elements in the environment. In this work, we used PBPK models to determine the optimal time for collecting biological samples in a longitudinal study to determine if participants who consumed allotment produce had been exposed to arsenic, cadmium, chromium, nickel or lead. There are a number of PBPK models for these elements published in the literature, which vary in size, complexity and application, given the differences in physiochemical properties of the elements, organs involved in metabolism and exposure pathways affected. We selected PBPK models from the literature to simulate the oral ingestion pathway from consumption of allotment produce. Some models required modification by reducing or removing selected compartments whilst still maintaining their original predictability. The performance of the modified models was evaluated by comparing the predicted urinary and blood elemental levels with experimental data and other model simulations published in the literature. Overall, the model predictions were consistent with literature data (r > 0.7, p < 0.05), and were influential in predicting when samples should be collected. Our results demonstrate the use of mathematical modelling in informing and optimising the design of longitudinal studies

Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats

Continuing concern regarding the potential health and environmental effects of depleted uranium and lead has resulted in many countries adding tungsten alloy (WA)-based munitions to their battlefield arsenals as replacements for these metals. Because the alloys used in many munitions are relatively recent additions to the list of militarily relevant metals, very little is known about the health effects of these metals after internalization as embedded shrapnel. Previous work in this laboratory developed a rodent model system that mimicked shrapnel loads seen in wounded personnel from the 1991 Persian Gulf War. In the present study, we used that system and male F344 rats, implanted intramuscularly with pellets (1 mm × 2 mm cylinders) of weapons-grade WA, to simulate shrapnel wounds. Rats were implanted with 4 (low dose) or 20 pellets (high dose) of WA. Tantalum (20 pellets) and nickel (20 pellets) served as negative and positive controls, respectively. The high-dose WA-implanted rats (n = 46) developed extremely aggressive tumors surrounding the pellets within 4–5 months after implantation. The low-dose WA-implanted rats (n = 46) and nickel-implanted rats (n = 36) also developed tumors surrounding the pellets but at a slower rate. Rats implanted with tantalum (n = 46), an inert control metal, did not develop tumors. Tumor yield was 100% in both the low- and high-dose WA groups. The tumors, characterized as high-grade pleomorphic rhabdomyosarcomas by histopathology and immunohistochemical examination, rapidly metastasized to the lung and necessitated euthanasia of the animal. Significant hematologic changes, indicative of polycythemia, were also observed in the high-dose WA-implanted rats. These changes were apparent as early as 1 month postimplantation in the high-dose WA rats, well before any overt signs of tumor development. These results point out the need for further studies investigating the health effects of tungsten and tungsten-based alloys

Preventive effect of zinc on nickel-induced oxidative liver injury in rats

This study pertains to the potential ability of zinc, used as nutritional supplements, to alternate oxidative stress induced by nickel. Male rats were randomly divided into four groups of eight each. Group I served as the controls; group II received in their drinking water ZnSO4 (227 mg/l); group III received NiSO4 (2 mg/100b.w/day intraperitoneally); group IV was treated with ZnSO4 and NiSO4. The exposure of rats to nickel sulfate for 21 days resulted in a significant decrease in body weight gain and absolute liver weight, relative liver weight. Nickel treatment also produced oxidative liver injury characterized by increasing serum glucose concentration, glutamate-pyruvate transaminase (GPT), alanine aminotransferase (GOT) and alkaline phosphatase (ALP) activities. Meanwhile nickel supplementation decreased serum total protein and albumin in animals. In addition, liver glutathione level, catalase and glutathione peroxidase (GSH-Px) activities were diminished. The administration of zinc with nickel (Ni + Zn) corrective effects on Ni-induced oxidative stress in liver was observed. In conclusion, this study demonstrates that intraperitoneally injection with Ni caused reduction in enzymes activities in rat’s liver and treatment with zinc offers a relative protection against nickel induced oxidative liver injury and lipid peroxidation probably due to its antioxidant proprieties.Key words: Nickel, zinc, rats, oxidative stress, liver

Prethodna terapija vitaminom C štiti od niklom izazvane nefrotoksičnosti u miševa

Nickel is an abundant carcinogenic and nephrotoxic metal whose activity leads to renal impairment. Previous studies have shown a protective effect of simultaneous vitamin C administration on acute and chronic nickel toxicity. However, very little research relating to the effect of vitamin C pretreatment in preventing nickel-induced acute nephrotoxicity is available. Therefore, the present study aimed to determine the efficiency of vitamin C (VC) pretreatment in preventing acute renal toxicity of nickel. Mice were pretreated orally with vitamin C (16.6 mg kg-1 body weight, b.w.) for seven consecutive days, prior to intraperitoneal (i.p.) administration of nickel chloride at different doses (3, 5, and 10 mg Ni kg-1 b.w.) for an exposure period of 24 hours. Thereafter, animals were killed and kidney tissue and blood samples were taken for histological examination and biochemical marker analyses. Vitamin C pretreatment alone did not alter the levels of serum kidney markers (creatinine, urea, and uric acid). However, treatment with Ni alone showed a significant increase in the levels of serum creatinine, urea, and uric acid with marked necrotic epithelial cells and infiltration by inflammatory cells in kidney sections as compared to the control group. Pretreatment with vitamin C and treatment with Ni at all doses tested for 24 hours showed a significant decrease in the levels of serum creatinine, urea, and uric acid, as well as an improvement in histological changes compared to those previously seen in the group treated with Ni alone. It is concluded that vitamin C pretreatment effectively improved renal function and tissue damage caused by nickel.Nikal je sveprisutan kancerogeni i nefrotoksični metal čije djelovanje dovodi do oštećenja bubrežne funkcije. Rezultati prethodnih istraživanja dokazali su zaštitni učinak istodobne terapije vitaminom C na akutnu i kroničnu toksičnost izazvanu niklom. Međutim, vrlo je malo istraživanja o učinku prethodne terapije vitaminom C radi sprječavanja niklom izazvane akutne nefrotoksičnosti. Stoga se ovim ispitivanjem nastojala utvrditi učinkovitost prethodne terapije vitaminom C (VC) u sprječavanju akutne bubrežne toksičnosti izazvane niklom. Prije intraperitonealnog (IP) ubrizgavanja različitih doza (3, 5 i 10 mg Ni kg-1 tjelesne težine) nikal klorida u razdoblju izlaganja od 24 sata, miševi su sedam dana uzastopce dobivali oralnu terapiju vitaminom C (16,6 mg kg-1 tjelesne težine). Nakon toga životinje su usmrćene, a bubrežno tkivo i uzorci krvi uzeti su radi histološke obrade i analize biokemijskih markera. U miševa koji su dobivali samo terapiju vitaminom C, serumske razine bubrežnih markera (kreatinin, urea i mokraćna kiselina) nisu bile promijenjene. Međutim, tretiranje samo niklom dovelo je do značajnog povećanja razina kreatinina, ureje i mokraćne kiseline te do značajnog broja nekrotičnih epitelnih stanica i infiltracije upalnih stanica u presjecima bubrega u usporedbi s kontrolnom skupinom. Prethodna terapija vitaminom C i tretiranje niklom u svim navedenim dozama tijekom 24 sata doveli su do značajnog smanjenja razina kreatinina, ureje i mokraćne kiseline u serumu te do poboljšanja histoloških promjena u usporedbi sa skupinom koja je tretirana samo niklom. Zaključuje se da prethodna terapija vitaminom C učinkovito poboljšava bubrežnu funkciju i oštećenje tkiva uzrokovano niklom