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Testing in Vitro Bioavailability of Nickel in Metal Nanoparticles

Understanding the potential health effects of exposure to nickel nanoparticles


To understand the behavior of nickel micro- and nanoparticles in the body after exposure to nickel.


We tested and measured nickel ion released in simulated body fluids through vitro testing for the Nickel Producers Environmental Research Association (NiPERA).


Our work provides important information on potential risks from occupational exposures to nickel nanoparticles.

Nickel and nickel-containing alloys have a wide range of uses, including jewelry, medical implants, stainless steel, and machinery. Nickel compounds are used in surface treatments, batteries, catalysts, and pigments. However, the use of these compounds does not come without consequences.

Is exposure to nickel dangerous?

Since the 1990s, researchers have known about potentially serious health hazards from inhalation and contact with some nickel-containing substances. Exposure in sufficient amounts is associated with several health effects, including skin allergies, lung fibrosis, and lung and nasal cancers. These illnesses depend on the specific nickel substance and the amount of its exposure to humans.

Nickel nanoparticles’ unique composition and potential health effects of exposure to nickel

Recently, nickel nanoparticles have attracted interest because of their unique physical and chemical properties.

What is a nanoparticle?

A nanoparticle is an ultra-fine particle measured in nanometers. Their properties have resulted in additional industrial applications for nickel substances.

How are nickel nanoparticles used?

Nickel nanoparticles are used for automotive parts like fuel cells and catalytic converters and to make coatings, magnetic fluids, and catalysts.

Why are nickel nanoparticles more dangerous than larger particles?

Nickel-containing nanoparticles might be more toxic than larger-sized particles because they have a higher surface area, which could release more nickel ions. Physiochemical properties of the nanoparticles, including particle size, shape, and surface changes, are the most important factors affecting nanoparticle-cell interactions and the nanoparticle internalization into cells. Because people working in the production, processing, or disposal of nickel nanoparticles can potentially be exposed on the job, it is important to understand the biochemistry of different sizes and shape of nanoparticles and chemical compositions as indicators of toxicity.

What is bioavailability and bioaccessibility in relation to toxins?

For metal-containing substances, the dissolution of metal ions in the body is related to the substance’s toxicity. This is because of a phenomenon known as bioavailability, or the amount of the substance that the body can take up into the blood that can have toxic effects. For nickel-containing nanoparticles, it is crucial to understand the bioavailability of nickel ion from different types of particles and in different routes of exposure to better understand their health effects. Bioavailability can be estimated by measuring bioaccessibility.

What is bioaccessibility?

In this case, bioaccessibility is the measure of nickel released from a nickel substance in synthetic body fluids (as surrogate physiological conditions) that is potentially available for absorption into systemic circulation such as blood circulation.

RTI studying bioaccessibility of nickel ions from different exposure routes

RTI’s Analytical Science Division worked with Nickel Producers Environmental Research Association (NiPERA) to understand the nickel bioaccessibility of various nanoparticles as an indication of their potential toxicity through different exposure pathways. To obtain this understanding, we used simulated biological fluids (gastric fluid, sweat, and lung fluid) to monitor the breakdown of nickel containing compounds, including different particle sizes and shapes. These studies helped us understand the potential fate of the nickel substance after human exposure. The results provided important information, allowing our collaborators to know the effect of the particle size and type on the nickel releases and to better understand the results of in vivo toxicity studies.

Overall, our studies showed that nickel nanoparticles did not release more nickel ions than the microparticles, proving that nanoparticles are not more hazardous than nickel microparticles of the same substance. 

Our findings provide important information on the potential for nanoparticle toxicity through different exposure pathways. We used in vitro testing methodology, part of our evidence approach, to evaluate hazard. This methodology minimizes cost and removes the need to perform in vivo testing while providing bioavailability data to estimate the relative toxicity of nickel substances. Ultimately, these results will benefit workers by informing the safety practices for handling and use of nickel nanoparticles in the workplace and prevent negative health effects associated with nickel substances.