The same extraordinary properties that make nanomaterials so useful also demand a new science of safety.
Imagine a particle so tiny that it would take 800 of them, lined up end to end, to span the width of a single human hair. This is the invisible world of nanomaterials—materials with at least one dimension between 1 and 100 nanometers.
At this astonishing scale, ordinary substances reveal extraordinary new capabilities: copper becomes transparent, silver becomes antibacterial, and gold can melt at room temperature 4 .
These novel properties have propelled nanotechnology into nearly every sector of our lives, from medicine and electronics to cosmetics and clothing. Yet, the same unique characteristics that make nanomaterials so useful also raise important questions about how they interact with our bodies and the environment 1 . This has given rise to the crucial science of nanotoxicology—a discipline dedicated to understanding the potential risks of nanomaterials and ensuring their safe development 7 .
A human hair is approximately 800 times wider than a typical nanomaterial.
Nanotubes, spheres, and plates each interact differently with cells. Some shapes are more readily taken up by cells or clear more slowly from the body 5 .
A material's surface charge (positive or negative) and chemistry affect its stability and interaction with biological membranes 4 .
Note: These variables create a complex challenge for toxicologists. Two nanomaterials with identical chemical composition but different sizes or surface properties may have completely different biological effects 1 .
How do researchers determine whether a nanomaterial is safe? The process follows a structured framework similar to conventional chemical risk assessment but with nano-specific considerations 4 .
Scientists first investigate what, if any, harmful effects a nanomaterial might cause. This involves testing how materials interact with cells (in vitro) or laboratory animals (in vivo).
Modern approaches focus on understanding mechanisms of toxicity at the molecular level, often using "omics" technologies like transcriptomics to see how nanomaterials alter gene expression 1 2 .
A material's potential risk depends not just on its inherent toxicity but also on how likely we are to be exposed to it.
Researchers study how nanomaterials are released during manufacturing, use, and disposal, and how they might enter the body—through inhalation, ingestion, or skin contact 4 .
The final step combines toxicity and exposure information to characterize the actual risk.
If exposure levels are significantly lower than those causing observed effects, the risk may be acceptable. If not, additional safety measures or restrictions may be necessary 4 .
The field has increasingly moved toward alternative testing methods that reduce reliance on animal studies. These include advanced cell cultures that better mimic human organs and computational models that predict toxicity based on a nanomaterial's physical and chemical properties 2 3 .
An international team of scientists developed an innovative approach to classify nanomaterials based on their surface reactivity and oxidative potential—their ability to generate reactive oxygen species that can damage cells 8 .
Using methanol chemisorption and temperature-programmed surface reaction (TPSR), they identified and counted the number of reactive sites on various nanomaterial surfaces. Different surface sites produced distinct reaction products: acidic sites yielded dimethyl ether, while redox sites generated formaldehyde 8 .
They conducted a series of antioxidant consumption assays using biologically relevant molecules like glutathione (a natural antioxidant in cells) and reactive oxygen species (ROS) generation assays 8 .
The team calculated the Oxidative Turnover Frequency (OxTOF)—the rate of oxidative reactions per reactive site—creating a more accurate measure of intrinsic oxidative potential 8 .
The study analyzed fourteen common engineered nanomaterials and revealed striking differences in their surface reactivity and oxidative potential, which could be categorized into distinct groups 8 .
| Nanomaterial | Reactive Surface Sites (μmol/m²) | Oxidative Potential | Classification |
|---|---|---|---|
| ZnO NM-110 | 12.5 | High | Highly oxidant |
| CuO | 9.8 | High | Highly oxidant |
| Carbon Black | 6.3 | High | Highly oxidant |
| CeO₂ NM-211 | 4.1 | Medium | Redox-active |
| TiO₂ NM-101 | 2.2 | Low | Low oxidative potential |
| SiO₂ NM-200 | 0.5 | Very Low | Inert |
This work provided crucial insights for the Safe and Sustainable by Design (SSbD) framework, enabling manufacturers to select nanomaterials with lower intrinsic hazards early in product development 8 . By identifying surface reactivity as a key determinant of toxicity, the study also suggested a more predictive approach to risk assessment—one that could potentially reduce the need for extensive biological testing.
Nanotoxicology relies on specialized instruments and methods to characterize materials and assess their safety.
Quantifies and characterizes reactive surface sites
Measures depletion of glutathione, cysteine, or DTT
Detects formation of reactive oxygen species
Measures particle size distribution in liquids
Visualizes particle shape, size, and structure
Predicts tissue deposition and internal dose
These tools collectively enable scientists to build a comprehensive safety profile of nanomaterials, from their initial physical characterization to their biological effects .
"The ongoing work of nanotoxicologists ensures that as we continue to explore the incredible potential of the nanoscale world, we do so with our eyes wide open to both promise and potential pitfalls."
The journey to ensuring nanomaterial safety continues to evolve. Researchers are increasingly adopting Safe by Design principles, which incorporate safety considerations from the earliest stages of material development rather than as an afterthought 1 4 . This proactive approach recognizes that slight modifications to a nanomaterial's structure or coating can significantly reduce its hazard potential without compromising its functionality 8 .
Initiatives like the OECD's testing program and the NanoInformaTIX database are creating shared resources that accelerate our understanding of nanomaterial safety .
As we stand at the frontier of this invisible world, nanotoxicology represents both a cautionary tale and a testament to scientific responsibility. It reminds us that technological innovation must walk hand-in-hand with safety assessment, and that truly advanced materials are those that offer both remarkable functionality and assured safety.