Nanoceria exposure, uptake, disposition, persistence, and resultant adverse effects

What is it about?

This critical review focuses on the most relevant routes of human nanoceria exposure, uptake, disposition, persistence, and resultant adverse effects of nanoceria. The pulmonary, oral, dermal, and topical ocular exposure routes are addressed as well as the intravenous route that provides a reference for the pharmacokinetic fate of nanoceria once introduced into blood. From blood nanoceria is primarily distributed to the liver, spleen, and bone marrow. Nanoceria's distribution is not greatly affected by dose, shape, or dosing schedule. Significant attention has been paid to the inhalation exposure route. Nanoceria distribution from the lung to the rest of the body is less than 1% of the deposited dose, and from the gastrointestinal tract even less. Intracellular nanoceria and organ burdens persist for at least months, suggesting very slow clearance. The acute toxicity of nanoceria is very low. However, large/accumulated doses produce inflammation in the lung and liver, and fibrosis in the lung. Toxicity, including genotoxicity, increases with exposure time; the effects disappear slowly, possibly due to nanoceria's biopersistence. Nanoceria may exert toxicity through oxidative stress. Adverse effects seen at sites distant to exposure may be due to nanoceria translocation or released molecules. An example is elevated oxidative stress indicators in the brain, in the absence of appreciable brain nanoceria. Nanoceria may change its nature in biological environments and cause changes in biological molecules. Increased toxicity has been related to greater surface Ce3+ (at the expense of Ce4+) which increases as particle size decreases and the ratio of surface area to volume increases. Given its biopersistence and resulting increased toxicity with time, there is a risk that long-term exposure to low nanoceria levels may eventually lead to adverse health effects. This critical review provides recommendations for research to resolve some of the many unknowns of nanoceria's fate and adverse effects.

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