Bioaccessibility of Metallic Nickel and Nickel Oxide Nanoparticles in Four Simulated Biological Fluids.

Bioaccessibility of metals from substances and alloys is increasingly used as part of the assessment to predict potential toxicity. However, data are sparse on the metal bioaccessibility from nanoparticle (NP) size metal substances. This study examines nickel ion release from metallic nickel and nickel oxide micron particles (MPs) and NPs in simulated biological fluids at various timepoints including those relevant for specific routes of exposure.

An Assessment of the Oral and Inhalation Acute Toxicity of Nickel Oxide Nanoparticles in Rats.

Nickel oxide nanoparticles (NiO NPs) have been the focus of many toxicity studies. However, acute toxicity studies that identify toxicological dose descriptors, such as an LC50 or LD50, are lacking. In this paper, the acute toxicity of NiO NPs was evaluated in albino-derived Sprague-Dawley rats through OECD guideline studies conducted by both the oral and inhalation routes of exposure.

Comparative pulmonary and genotoxic responses to inhaled nickel subsulfide and nickel sulfate in F344 rats.

Inhalation studies with nickel (Ni) subsulfide (Ni S ) and Ni sulfate hexahydrate (NiSO ·6H O) investigated differences in mode of action that could explain why the former induced lung tumors in rats and the latter did not. Male rats were exposed to ≤0.22 mg Ni/m NiSO ·6H O or 0.

A tiered approach to investigate the inhalation toxicity of cobalt substances. Tier 1: Bioaccessibility testing.

Bioelution tests measure in vitro the release of metal ion in surrogate physiological conditions (termed "bioaccessibility") and estimate the potential bioavailability relative to that of a known reference metal substance. Bioaccessibility of cobalt ion from twelve cobalt substances was tested in three artificial lung fluids (interstitial, alveolar and lysosomal) to gather information about the substances' fate and potential bioavailability in the respiratory tract after inhalation. The results can be used as one line of evidence to support grouping and read-across for substances lacking in vivo data, and where in vivo testing is not readily justifiable.

A T-dependent antibody response evaluation in CD-1 mice after an acute whole-body inhalation exposure to nickel (II) chloride hexahydrate.

Nickel (Ni) in ambient air may vary regionally with contributions from both natural processes and anthropogenic activities. Exposure to Ni compounds in ambient air above a certain level is associated with acute adverse effects, such as upper respiratory tract irritation, pneumonitis, and chronic adverse effects, such as respiratory cancer. Inhalation reference exposure standards are enacted in different jurisdictions to minimize exposures to ambient Ni above levels that can elicit adverse effects.

Copper alloys' metal migration and bioaccessibility in saliva and gastric fluid.

The oral bioaccessibility of copper alloys and pure metals was assessed using in vitro methods with synthetic saliva and gastric fluid. The metal-specific migration rates from polished alloy surfaces are higher in gastric (pH 1.5) than in saliva fluid (pH 7.

Gene (HPRT) and chromosomal (MN) mutations of nickel metal powder in V79 Chinese hamster cells.

Nickel metal is a naturally occurring element used in many industrial and consumer applications. Human epidemiological data and animal cancer bioassays indicate that nickel metal is not likely to be a human carcinogen. Yet, nickel metal is classified as a suspected human carcinogen (CLP) and possibly carcinogenic to humans (IARC).

Bioaccessibility of nickel and cobalt in synthetic gastric and lung fluids and its potential use in alloy classification.

This study investigated nickel and cobalt ion release from the metals and several alloys in synthetic gastric, as well as interstitial and lysosomal lung fluids. Results were used to calculate the relative bioaccessible concentrations (RBCs) of the metals. Nickel release from SS 316L powder in gastric fluid was >300-fold lower than from a simple mixture of powders of the same bulk composition.

Derivation of an oral toxicity reference value for nickel.

Nickel (Ni) is in the earth's crust and can be found in environmental compartments such as water, soil, and air, as well as food. This paper presents an assessment of the oral nickel toxicity data in support of non-cancer health-based oral exposure limits or toxicity reference values (TRVs). This paper derives TRVs for three populations of interest: adults, toddlers, and people who have been dermally sensitized to nickel.

Incorporation of dosimetry in the derivation of reference concentrations for ambient or workplace air: a conceptual approach.

Dosimetric models are essential tools to refine inhalation risk assessments based on local respiratory effects. Dosimetric adjustments to account for differences in aerosol particle size and respiratory tract deposition and/or clearance among rodents, workers, and the general public can be applied to experimentally- and epidemiologically-determined points of departure (PODs) to calculate size-selected (e.g.

Assessment of human exposure to environmental sources of nickel in Europe: Inhalation exposure.

The paper describes the inhalation nickel (Ni) exposure of humans via the environment for the regional scale in the EU, together with a tiered approach for assessing additional local exposure from industrial emissions. The approach was designed, in the context of REACH, for the purpose of assessing and controlling emissions and air quality in the neighbourhood of Ni producers and downstream users. Two Derived No Effect Level (DNEL) values for chronic inhalation exposure to total Ni in PM10 (20 and 60ngNi/m(3)) were considered.

Derivation of PM10 size-selected human equivalent concentrations of inhaled nickel based on cancer and non-cancer effects on the respiratory tract.

Abstract Nickel (Ni) in ambient air is predominantly present in the form of oxides and sulfates, with the distribution of Ni mass between the fine (particle aerodynamic diameter < 2.5 µm; PM2.5) and coarser (2.

Inter-laboratory validation of bioaccessibility testing for metals.

Bioelution assays are fast, simple alternatives to in vivo testing. In this study, the intra- and inter-laboratory variability in bioaccessibility data generated by bioelution tests were evaluated in synthetic fluids relevant to oral, inhalation, and dermal exposure. Using one defined protocol, five laboratories measured metal release from cobalt oxide, cobalt powder, copper concentrate, Inconel alloy, leaded brass alloy, and nickel sulfate hexahydrate.

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.

Acute oral toxicity of nickel compounds.

Acute oral toxicity studies were conducted on samples of nine unique nickel compounds and two complex materials to comply with the data and classification requirements of the new Registration, Evaluation, and Authorization of Chemicals Regulation (REACH) in Europe. The samples tested in this study confirmed the overall low oral toxicity of nickel substances and demonstrated a wide range of LD(50) values extending from 310 to >11,000 mg/kg. This variation highlights the differences in toxicological properties between various forms of nickel and underscores the importance of Ni(II) ion bioavailability in determining toxicity.

Assessment of indirect human exposure to environmental sources of nickel: oral exposure and risk characterization for systemic effects.

This paper describes the indirect human exposure to Ni via the oral route for the regional scale in the EU, together with a method to assess additional local exposure from industrial emissions. The approach fills a gap in the generic REACH guidance which is inadequate for assessing indirect environmental exposure of metals. Estimates of regional scale Ni dietary intake were derived from Ni dietary studies performed in the EU.

The nickel ion bioavailability model of the carcinogenic potential of nickel-containing substances in the lung.

The inhalation of nickel-containing dust has been associated with an increased risk of respiratory cancer in workplaces that process and refine sulfidic nickel mattes, where workers are exposed to mixtures of sulfidic, oxidic, water-soluble, and metallic forms of nickel. Because there is great complexity in the physical and chemical properties of nickel species, it is of interest which specific nickel forms are associated with carcinogenic risk. A bioavailability model for tumor induction by nickel has been proposed, based on the results of animal inhalation bioassays conducted on four nickel-containing substances.

Incorporation of particle size differences between animal studies and human workplace aerosols for deriving exposure limit values.

Inhalation animal studies usually employ homogeneous aerosols of small particle diameter. By contrast, workers are usually exposed to coarser and more heterogeneous aerosols. The particle size distribution of an aerosol will determine the deposited fraction of inhaled particles in the various regions of the respiratory tract in rodents and humans.

Temperature effect on nickel release in ammonium citrate.

Leaching in ammonium citrate has been extensively used to assess the fraction of water-soluble nickel compounds present in nickel producing and using workplace aerosols. Leaching in ammonium citrate according to the first step of the Zatka protocol was found to overestimate the water-soluble nickel fraction by more than ten-fold compared to synthetic lung fluid (37 degrees C), when nickel carbonate and subsulfide were present. These results suggest that exposure matrices based on this method should be reexamined.

Comparison of nickel release in solutions used for the identification of water-soluble nickel exposures and in synthetic lung fluids.

Chemical speciation of workplace nickel exposures is critical because nickel-containing substances often differ in toxicological properties. Exposure matrices based on leaching methods have been used to ascertain which chemical forms of nickel are primarily associated with adverse respiratory effects after inhalation. Misjudgments in the relative proportion of each of the main fractions of nickel in workplace exposures could translate into possible misattributions of risk to the various forms of nickel.

Inhalation carcinogenicity study with nickel metal powder in Wistar rats.

Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.

Oral carcinogenicity study with nickel sulfate hexahydrate in Fischer 344 rats.

Until now, existing data on the oral carcinogenicity of nickel substances have been inconclusive. Yet, the assessment of oral carcinogenicity of nickel has serious scientific and regulatory implications. In the present study, nickel sulfate hexahydrate was administered daily to Fischer 344 rats by oral gavage for 2 years (104 weeks) at exposure levels of 10, 30 and 50 mg NiSO(4).

Fluorescent tracking of nickel ions in human cultured cells.

The carcinogenic activity of various nickel (Ni) compounds is likely dependent upon their ability to enter cells and elevate intracellular levels of Ni ions. Water-insoluble Ni compounds such as NiS and Ni(3)S(2) were shown in vitro to enter cells by phagocytosis and potently induce tumors in experimental animals at the site of exposure. These water-insoluble nickel compounds are generally considered to be more potent carcinogens than the water-soluble forms.