Gap analysis of nickel bioaccessibility and bioavailability in different food matrices and its impact on the nickel exposure assessment.

The metal nickel is well known to cause nickel allergy in sensitive humans by prolonged dermal contact to materials releasing (high) amounts of nickel. Oral nickel exposure via water and food intake is of potential concern. Nickel is essential to plants and animals and can be naturally found in food products or contamination may occur across the agro-food chain. This gap analysis is an evaluation of nickel as a potential food safety hazard causing a risk for human health. In the first step, the available data regarding the occurrence of nickel and its contamination in food and drinks have been collected through literature review. Subsequently, a discussion is held on the potential risks associated with this contamination. Elevated nickel concentrations were mostly found in plant-based foods, e.g. legumes and nuts in which nickel of natural origin is expected. However, it was observed that dedicated and systematic screening of foodstuffs for the presence of nickel is currently still lacking. In a next step, published studies on exposure of humans to nickel via foods and drinks were critically evaluated. Not including bioaccessibility and/or bioavailability of the metal may lead to an overestimation of the exposure of the body to nickel via food and drinks. This overestimation may be problematic when the measured nickel level in foods is high and bioaccessibility and/or bioavailability of nickel in these products is low. Therefore, this paper analyzes the outcomes of the existing dietary intake and bioaccessibility/bioavailability studies conducted for nickel. Besides, the available gaps in nickel bioaccessibility and/or bioavailability studies have been clarified in this paper. The reported bioaccessibility and bioavailability percentages for different food and drinks were found to vary between

Plants as models for chromium and nickel risk assessment.

The adverse effects of Cr(III), Cr(VI), and Ni(II) expressed as root and shoot growth inhibition, metal accumulation and translocation throughout plants, and genotoxicity study were examined. To examine phytoxicity and metal accumulation, Vicia sativa, Raphanus sativus, Zea mays and Sinapis alba plants were used. Except for S. alba root growth inhibition, Ni had the strongest inhibitory effect on root and shoot growth. The inhibitory rank order based on IC50 values was Ni(II) > Cr(VI) > Cr(III). Z. mays was the least sensitive to all metals. While the accumulation of Cr was higher in the roots than the upper plant parts, Ni transport to shoots was at least two times higher than that of Cr. The highest accumulation of Cr was found in Z. mays and that of Ni in V. sativa and Z. mays roots. For all plants, the translocation factor was higher for Cr(VI) than for Cr(III). The translocation factor for Ni was several times higher than those of Cr. For mutagenicity assay, root tips of V. sativa, R. sativus and Z. mays were used. All metals exerted a significant increase of chromosomal aberrations and the rank order of aberrations was: Cr(VI) > Ni(II) > Cr(III). Genotoxic effects of metals were also determined by analysis of micronuclei frequency in the pollen tetrads of Tradescantia plants. None of metals significantly stimulated micronuclei frequency and the genotoxic effect decreased in the following order: Cr(VI) ≥ Ni(II) > Cr(III).

Oral bioaccessibility testing and read-across hazard assessment of nickel compounds.

In vitro metal ion bioaccessibility, as a measure of bioavailability, can be used to read-across toxicity information from data-rich, source substances to data-poor, target substances. To meet the data requirements for oral systemic toxicity endpoints under the REACH Regulation in Europe, 12 nickel substances underwent bioaccessibility testing in stomach and intestinal fluids. A read-across paradigm was developed based on the correlation between gastric bioaccessibility and in vivo acute oral toxicity. The oral LD50 values were well predicted by nickel release (R² = 0.91). Samples releasing <48% available nickel (mgNi released/mg available Ni × 100) are predicted to have an LD50 > 2000 mg/kg; while samples releasing > 76% available nickel are expected to have an LD50 between 300 and 2000 mg/kg. The hazard classifications (European Regulation on Classification, Labelling and Packaging of Chemical Substances and Mixtures) for all oral systemic endpoints were evaluated based on read-across from three source nickel compounds (sulfate, subsulfide, oxide). Samples releasing < 48% available nickel were read-across from nickel oxides and subsulfide. Samples releasing > 76% Ni were read-across from nickel sulfate. This assessment suggests that nickel chloride and dihydroxide should be less stringently classified and nickel sulfamate should receive a more stringent classification for oral systemic endpoints than currently assigned.

Assessment of nickel contamination in lakes using the phantom midge Chaoborus as a biomonitor.

Nickel (Ni) can be present in concentrations of concern in waters near mining and industrial sites. We tested species of the phantom midge Chaoborus as a biomonitor for this trace metal by collecting water and Chaoborus larvae from 15 lakes located along a Ni gradient mainly in the vicinity of smelters located in Sudbury, ON, Canada. We measured pH, trace metals, major ions, as well as inorganic and organic carbon concentrations in lakewater for use in calculating ambient metal speciation using the Windermere Humic Aqueous Model (WHAM). Nickel concentrations in Chaoborus species varied widely among our study lakes and could be related to concentrations of the free Ni2+ ion in lakewater if competitive interactions with hydrogen ions (H+) were taken into account We verified this inhibitory effect in the laboratory by exposing Chaoborus punctipennis to constantfree Ni2+ ion concentrations at various H+ ion concentrations. As expected, larvae exposed to high concentrations of H+ ions accumulated less Ni. Overall, our results suggest that Chaoborus larvae would be an excellent biomonitor for Ni in lakewater and as such would be a useful component of risk assessment strategies designed to evaluate Ni exposure to aquatic organisms in lakes.

Improving ecological risk assessment by including bioavailability into species sensitivity distributions: an example for plants exposed to nickel in soil.

The variability of species sensitivity distribution (SSD) due to contaminant bioavailability in soil was explored by using nickel as metal of concern. SSDs of toxicity test results of Avena sativa L. originating from different soils and expressed as total content and available (0.01 M CaCl2) extractable concentration were compared to SSDs for terrestrial plants derived from literature toxicity data. Also the 'free' nickel (Ni2+) concentration was calculated and compared. The results demonstrated that SSDs based on total nickel content highly depend on the experimental conditions set up for toxicity testing (i.e. selected soil and pH value) and thus on metal bioavailability in soil, resulting in an unacceptable uncertainty for ecological risk estimation. The use in SSDs of plant toxicity data expressed as 0.01 M CaCl2 extractable metal strongly reduced the uncertainty in the SSD curve and thus can improve the ERA procedure remarkably by taking bioavailability into account.

Transfer of chemicals from feed to animal products: The use of transfer factors in risk assessment.

The human risk assessment of feed contaminants has often been hampered by a lack of knowledge concerning their behaviour when consumed by livestock. To gain a better understanding of the transfer of contaminants from animal feed to animal products, a meta-analysis of public literature was made. Data concerning feed contaminant concentrations, feeding periods, residue levels in animal products, and other parameters were gathered and recorded. For each case a 'transfer factor', which was defined as the ratio of the concentration of a chemical in an animal product to the concentration of the chemical in animal feed, was calculated. Scientifically founded transfer factors were calculated and analysed for groups of chemicals based on their contaminant classes or physicochemical properties. These database-derived transfer factors enable a more accurate risk assessment in the case of a feed contamination, and enable rapid risk management decision-making and/or intervention.

Assessment of respiratory carcinogenicity associated with exposure to metallic nickel: a review.

Human studies prior to 1990 have shown an association between respiratory cancer and exposure to some nickel compounds, but not to metallic nickel. Numerous reviews have examined the nature of the association between nickel compounds and respiratory cancer, but little has been published on metallic nickel. This paper reviews the animal and human cancer-related data on metallic nickel to determine whether the conclusions regarding metallic nickel reached a decade ago still apply. Based upon past and current human studies, metallic nickel appears to show little evidence of carcinogenicity when present at the same or higher concentrations than those seen in current workplace environments. By comparison, animal studies currently available have shown mixed results. A number of studies have shown evidence of carcinogenicity in animals exposed to nickel powders via injection, but other studies have shown no or inconsistent results in animals exposed via inhalation or intratracheal instillation. Further studies in animals via inhalation and humans would be helpful in elucidating the respiratory carcinogenic potential of metallic nickel.

Assessment of copper-nickel industry impact on a subarctic lake ecosystem.

The Kuetsjärvi lake ecosystem has been subject to intensive pollution generated by the Pechenganickel Company activities for more than 50 years. This article considers the effects of emissions from the copper-nickel smelter, that uses out-of-date technology, on a subarctic lake ecosystem. Six years of investigations revealed changes occurring at all ecosystem levels. It was found that the content of heavy metals (Cu, Ni, etc.) in lake sediments was dozens of times higher than the background values. Phyto- and zooplankton communities were in an unstable condition, while fish had pathologies of functionally important organs (gill, liver and kidney). The concentration of nickel in zoobenthos and fish was correlated its accumulation in sediments.

Porous titanium-nickel for intervertebral fusion in a sheep model: part 2. Surface analysis and nickel release assessment.

Porous titanium-nickel (PTN) devices represent an alternative to traditional cage implants. PTN materials possess an interconnecting network of pores with capillarity properties that may promote bone ingrowth, long-term fixation, and intervertebral fusion without the need for bone grafting. However, their considerable surface area and nickel content may elicit concerns over sensitization potential. Therefore, PTN surface corrosion and nickel release resistance must be carefully studied. To evaluate this possibility, a PTN interbody fusion device (IFD) was compared to a conventional nonporous cage made of TiAlV, a well-known biocompatible biomaterial, in a sheep model. PTN and TiAlV IFDs were inserted at two non-contiguous lumbar sites for 3, 6, and 12 months postsurgery. Their surface was then evaluated by scanning electron microscopy (SEM) combined with backscattered electron analysis (BSE). No evidence of surface corrosion was observed either pre- or postimplantation, regardless of device type. Dosage of nickel ions was also performed with the use of inductively coupled plasma-mass spectrometry (ICP-MS). Blood nickel levels were observed to be within acceptable levels at all postinstrumentation times. Nickel content in PTN-adjacent tissue, as well as in detoxification and remote organs, was equivalent both in PTN-treated and control sheep. Therefore, porous titanium-nickel demonstrated resistance to both in vivo surface corrosion and nickel ion release and compared very well with a conventional titanium implant in the course of a 12-month sheep study.

Respiratory carcinogenicity assessment of soluble nickel compounds.

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.

Assessment of plant uptake of radioactive nickel from soils.

As a result of isotopic dilution, the availability to plants of radioisotopes introduced into the soil solution should be directly related to the size of the isotopically exchangeable pool (E(t))-value). This work was undertaken to test this hypothesis for the radionuclide 63Ni. The demonstration was based on pot experiments conducted with seven soils representing a large range of Ni content (from 9.9 mg kg(-1) to 862.6 mg kg(-1)) which were mixed with a 63NiCl2 solution (100 kBq kg(-1)). Three plant species varying in Ni uptake, Triticum aestivum (wheat), Trifolium pratense (clover), and the Ni-hyperaccumulator Alyssum murale, were grown for 90 d, and their total Ni and 63Ni content determined at harvest. In parallel, the isotopically exchangeable kinetics method (IEK) was run on each soil sample to measure the E(t)-value. Results showed that plant uptake of radioactive nickel was negatively correlated with the E(t)-value with wheat and clover as a result of the dilution of 63Ni added in the isotopically exchangeable pool of soil Ni (alpha=5%); correlation was positive with the A. murale (alpha=10%). Hence, this provides a new approach for the assessment of soil-to-plant transfer of 63Ni at larger scale avoiding the carrying out of time consuming experiments.

Exposure assessment in the hard metal manufacturing industry with special regard to tungsten and its compounds.

OBJECTIVES: To assess the exposure to tungsten, cobalt, and nickel in a plant producing hard metals. The main components of hard metals are tungsten carbide and cobalt metal. According to recent studies, these two components may be responsible for both fibrogenic and carcinogenic effects. METHODS: 87 workers were investigated (86 male, one female) with a median age of 42 (range 22-58) and a mean duration of exposure of 13 years (range 1-27 years). Stationary and personal air sampling, and biological monitoring were carried out. RESULTS: Ambient monitoring yielded maximum tungsten concentrations of 417 microg/m3 in the production of heavy alloys. A maximum cobalt concentration of 343 microg/m3 and a maximum nickel concentration of 30 microg/m3 were found at the sintering workshop. The highest urinary cobalt concentrations were found in the powder processing department. The mean concentration was 28.5 microg/g creatinine and the maximum value was 228 microg/g creatinine. The maximum nickel concentration in urine of 6.3 microg/g creatinine was detected in the department producing heavy alloys. The highest tungsten concentrations excreted in urine were found in grinders and had a mean value of 94.4 microg/g creatinine and a maximum of 169 microg/g creatinine. Due to the different solubility and bioavailability of the substance, there was no correlation between the tungsten concentrations in air and urine on a group basis. CONCLUSIONS: Despite its low solubility, tungsten carbide is bioavailable. The different bioavailability of tungsten metal and tungsten compounds has to be considered in the interpretation of ambient and biological monitoring data in the hard metal producing industry. The bioavailability increases in the order: tungsten metal, tungsten carbide, tungstenate. Only if both monitoring strategies are considered in combination can a valid and effective definition of high risk groups be derived.

Carcinogenicity assessment of selected nickel compounds.

The early epidemiological data indicated different carcinogenic risks from inhalation of different nickel compounds, but it was not clear what characteristics governed the intrinsic carcinogenic hazard of the various nickel compounds. Based on the earlier results, all soluble and insoluble nickel compounds were assumed to have the same carcinogenic mechanism albeit different potencies. Recent in vivo and in vitro studies challenged this assumption. In this paper an attempt is made to integrate the most relevant human, animal, and in vitro data into a general model that can help understand the different carcinogenic potentials of the various nickel compounds. In this perspective, it is recognized that there are two main components that could contribute to the development of lung cancer via exposure to certain nickel compounds. The first component corresponds to the heritable changes (genetic or epigenetic) derived from the direct or indirect actions of nickel compounds. The second component may be the promotion of cell proliferation elicited by certain nickel compounds. The different contributions of three nickel compounds to these two components are presented. This paper emphasizes the importance of recognizing the individuality of the different nickel species in reaching regulatory decisions and the fact that different risk assessment considerations may apply for compounds that appear to produce immortality and cancer by genetic/epigenetic mechanisms (like nickel subsulfide), compounds that may present a threshold for the induction of tumors in rats (like high-temperature nickel oxide), or compounds that may only have an enhancing effect on carcinogenicity (like nickel sulfate).

Risk assessment of nickel carcinogenicity and occupational lung cancer.

Recent progress in risk assessment of nickel carcinogenicity and its correlation with occupational lung cancer in nickel-exposed workers is reviewed. Epidemiological investigations provide reliable data indicating the close relation between nickel exposure and high lung cancer risk, especially in nickel refineries. The nickel species-specific effects and the dose-response relationship between nickel exposure and lung cancer are among the main questions that are explored extensively. It is also suggested that some confounding factors such as cigarette smoking cannot be neglected. The determination of nickel concentration in lung tissue may be conducive to estimating the nickel exposure level, but it is uncertain whether the high nickel content in lung tissue indicates high lung cancer risk in nickel-exposed workers. Immunologic studies suggest that the suppressive effect of nickel on NK cell activity and interferon production may also be involved in the mechanisms of nickel carcinogenesis. As a potential mutagen, nickel can cause chromosome damage both in vitro and in vivo; and on a molecular basis, nickel is found to induce DNA damage (DNA strandbreaks and crosslinks, infidelity of DNA replication, inhibition of DNA repair, and the helical transition of B-DNA to Z-DNA) by binding of nickel ions to DNA and nuclear proteins. The discovery of oncogene promises both a challenge and an opportunity for nickel carcinogenesis research. It can be predicted that, with the rapid development of molecular biology and oncology, new approaches will be established for both understanding and controlling nickel-induced occupational lung cancer.