Fig. 1. Blood exposure to graphene oxide may cause anaphylactic death in non-human primates.
Fig. 1. Blood exposure to graphene oxide may cause anaphylactic death in non-human primates.

Carbon nanomaterials have emerged as promising new materials and are beginning to be used in applications. Graphene oxide (GO), one of the newest, is finding favor for industrial applications such as optical/electronic circuitry, energy generation and storage because of its ultrahigh surface area. But questions over the in vivo safety of GO remain. These concerns will not be allayed by a recent study reporting anaphylactic shock in a small number of non-human primates exposed to apparently safe levels of GO [Yin et al., Nano Today (2020),].

“Toxicological evaluation of GO has been actively pursued under the context of large-scale industrial production and the potential for clinical translation,” point out Ying Zhu of Shanghai Advanced Research Institute and Chunhai Fan of Shanghai Jiao Tong University, who led the work. “The safety of GO remains largely debated, especially due to the lack of toxicological profile in higher mammals.”

Together with coworkers at Sichuan University, Zhu and Fan investigated the impact of blood exposure to GO on mice and macaques at the maximum safe dose. The effects of two-dimensional GO were compared in similar tests to one-dimensional single-walled carbon nanotubes (SWCNTs) and zero-dimensional nanodiamonds. To their surprise, one out of the five macaques and seven out of 121 mice tested experienced a fatal reaction to GO, which the researchers believe was induced by acute anaphylactic shock (Fig. 1). Exposure to SWCNTs or nanodiamonds did not produce a similar reaction in any of the animals.

The researchers found elevated levels of antibodies and severe lung damage in the affected animals. Other biological indicators suggest that exposure to GO caused acute liver and heart damage as well. Having found evidence of GO deposits in the lungs, the researchers compared the circulation times of the different carbon materials. While SWCNTs are largely cleared from the bloodstream of mice and monkeys in 6–12 h and nanodiamonds in 1–8 h, GO continues to circulate for up to 72 h. The researchers believe that the relative longevity of GO in the blood compared with SWCNTs and nanodiamonds could offer an explanation.

“[We believe] that long-circulation [times] and distal lung deposition contribute to the anaphylactic reaction,” say Zhu and Fan. “This study highlights the urgent need to evaluate the hypersensitivity risks of graphene,” they add.

Although exposure to GO did not result in acute or long-term adverse effects in most of the mice or macaques tested, anaphylactic reactions in some animals raise serious safety concerns.

“This suggests that case-by-case allergy tests are indispensable prior to the biomedical use of nanomaterials,” point out Zhu and Fan.

This article originally appeared in Nano Today 36 (2021) 101050.