Graphene Oxide Side Effects in Humans: What We Know So Far

Graphene oxide (GO) is a nanomaterial with promising applications in medicine, electronics, and environmental science. However, concerns have emerged about its potential health effects, particularly regarding unintended exposure through inhalation, ingestion, or skin contact. While research on GO toxicity is still developing, early studies suggest it may cause biological responses depending on dose, exposure route, and individual susceptibility.

Understanding these possible side effects is crucial for assessing risks associated with graphene-based technologies. This article explores the known impacts of graphene oxide on human health based on current scientific findings.

General Mechanisms of Tissue Irritation

Graphene oxide (GO) interacts with biological tissues in ways that can lead to irritation due to its physicochemical properties. Its sharp edges, high surface area, and oxidative potential contribute to mechanical and chemical disturbances at the cellular level. GO can disrupt cellular membranes, leading to structural damage and increased permeability. This triggers localized stress responses, including the release of inflammatory mediators. Studies indicate that smaller GO sheets penetrate cells more easily, while larger ones accumulate on surfaces, causing prolonged irritation.

GO’s oxidative nature further amplifies tissue irritation by generating reactive oxygen species (ROS), which can damage lipids, proteins, and DNA. Research in Nature Nanotechnology has shown that GO exposure leads to lipid peroxidation, compromising membrane integrity and disrupting cellular function. This oxidative damage is particularly concerning in tissues with high metabolic activity, where an imbalance in ROS levels can interfere with essential physiological processes.

GO also adsorbs biomolecules, including proteins and enzymes, altering their structure and function. A study in ACS Nano found that GO exposure affected key structural proteins, impairing biological activity. Such disruptions interfere with normal tissue homeostasis, leading to irritation and, in some cases, prolonged dysfunction. The severity of these effects depends on concentration, exposure duration, and tissue type.

Respiratory Effects from Inhalation

Inhalation of graphene oxide (GO) raises concerns due to its potential impact on lung function. Airborne GO nanoparticles can be inhaled into the respiratory tract, where their size, shape, and surface charge influence their interaction with lung tissues. Smaller particles, typically below 100 nm, reach deep into the alveoli, while larger ones accumulate in the upper airways. Once deposited, GO can disrupt epithelial cells lining the respiratory tract.

Research in Particle and Fibre Toxicology has shown that GO exposure compromises the pulmonary epithelial barrier. In vitro studies using human bronchial epithelial cells indicate that GO sheets adhere to cell surfaces, altering tight junction proteins and increasing permeability. Animal studies support these findings; inhalation experiments in rodents have shown epithelial thickening and mucus hypersecretion, which can impair normal respiratory function.

GO’s high surface area and oxidative potential contribute to oxidative stress in lung tissues. A study in Toxicology Letters reported that rats exposed to GO aerosols exhibited elevated malondialdehyde (MDA) levels, indicating oxidative damage. This stress can lead to mitochondrial dysfunction, impairing energy production and promoting apoptosis. The severity of these effects appears dose-dependent, with prolonged or high-dose exposure exacerbating lung injury.

GO inhalation also triggers inflammation in the respiratory system. Research in Environmental Science & Technology found that mice exposed to GO aerosols had increased levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). This inflammation was associated with alveolar immune cell infiltration, which can contribute to lung tissue remodeling and fibrosis over time. Histopathological examinations of exposed lung tissues have revealed fibrotic lesions, suggesting chronic exposure may lead to long-term pulmonary complications.

Gastrointestinal Effects from Ingestion

When graphene oxide (GO) enters the digestive system, its interaction with the gastrointestinal (GI) tract depends on particle size, surface charge, and aggregation behavior. In the stomach, GO can adsorb gastric mucins, altering the protective mucus barrier. This disruption increases susceptibility to irritation, particularly in individuals with pre-existing conditions such as gastritis or peptic ulcers.

As GO moves into the intestines, it interacts with the epithelial lining. Research in Small has shown that GO adheres to microvilli, potentially interfering with nutrient absorption. In vitro studies using human intestinal cells indicate that GO exposure alters the expression of tight junction proteins, which regulate intestinal permeability. A decrease in these proteins can compromise barrier integrity, allowing unwanted substances to enter systemic circulation. This phenomenon, known as “leaky gut,” has been linked to inflammatory disorders.

GO exposure also affects gut microbiota. A study in Environmental Science: Nano found that GO altered bacterial populations in mice, reducing beneficial species such as Lactobacillus and Bifidobacterium. These changes can impact digestion, immune function, and even mood regulation. The extent of microbiota disruption appears dose-dependent, with higher concentrations causing more pronounced shifts in bacterial diversity. While long-term effects remain under investigation, early findings suggest repeated ingestion of GO could have broader implications for gut health.

Dermal and Ocular Reactions

Graphene oxide (GO) interacts with the skin and eyes, raising concerns about irritation. Due to its sharp edges and high surface reactivity, GO can disrupt the skin’s outer protective layers. Studies using reconstructed human epidermis models have shown that GO exposure alters skin barrier function, increasing transepidermal water loss and affecting lipid organization. These disruptions may lead to dryness, redness, or mild inflammation, particularly in individuals with pre-existing skin conditions.

The severity of dermal irritation varies based on GO concentration and exposure duration. Experiments with human keratinocyte cultures have shown that prolonged exposure to high concentrations results in cytoskeletal disruptions and oxidative stress. While lower doses may not cause immediate damage, repeated contact could lead to cumulative effects, increasing skin sensitivity over time. GO’s ability to adsorb biomolecules raises additional concerns about its interaction with skincare products, as it may alter the efficacy of topical medications and cosmetics.

In the ocular environment, GO’s impact is linked to its ability to disrupt the tear film and corneal epithelium. Studies using rabbit corneal models have demonstrated that GO particles can adhere to the ocular surface, causing transient discomfort, foreign body sensation, or increased tear production. Mechanical interactions between GO and corneal epithelial cells have been observed to cause minor microabrasions, potentially increasing the risk of irritation or secondary infections. Individuals handling GO in laboratory or industrial settings are advised to use protective eyewear to minimize exposure.

Cellular and Immune Responses

Graphene oxide (GO) interacts with cells in ways that can affect viability and function. Its ability to penetrate cell membranes varies based on particle size, surface charge, and aggregation state. Studies using human fibroblasts and endothelial cells indicate that smaller GO sheets enter cells via endocytosis, leading to intracellular accumulation. This internalization can interfere with mitochondrial activity and protein synthesis. Research in Biomaterials Science has reported that GO exposure results in mitochondrial depolarization, reducing ATP production and triggering apoptosis. These disruptions are particularly relevant in tissues with high cellular turnover, where impaired energy metabolism affects regeneration and repair.

GO also influences immune function. Macrophages, responsible for detecting foreign materials, exhibit altered behavior when exposed to GO. A study in Nature Communications found that GO exposure increased phagocytosis and altered cytokine secretion. Elevated levels of inflammatory mediators such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α) indicate an activated immune response. While acute inflammation is a protective mechanism, prolonged immune activation can contribute to tissue damage and chronic inflammatory conditions. Additionally, GO has been observed to modulate adaptive immunity by affecting T-cell proliferation and differentiation, which may have implications for long-term immune regulation.

Potential Neurological Implications

Research on graphene oxide’s (GO) neurological effects is still emerging. Given its nanoscale properties, GO can cross physiological barriers like the blood-brain barrier (BBB). Studies using in vitro BBB models indicate that GO alters endothelial tight junction integrity, increasing permeability. A study in Advanced Healthcare Materials found that GO exposure reduced expression of key tight junction proteins, raising concerns about potential accumulation in brain tissues.

Once inside the brain, GO’s ability to generate reactive oxygen species (ROS) could contribute to oxidative stress, a factor implicated in neurodegenerative diseases. Research in Nanotoxicology has shown that neuronal cultures exposed to GO exhibited increased oxidative damage markers, including lipid peroxidation and DNA fragmentation. These effects were accompanied by disruptions in calcium homeostasis, which plays a critical role in synaptic transmission. Animal studies suggest GO exposure may also influence neuroinflammatory pathways, with increased microglial activation observed in rodent models. Since neuroinflammation is associated with conditions such as Parkinson’s and Alzheimer’s disease, these findings highlight the need for further investigation into potential long-term neurological risks.