Manufactured Nanomaterials: Small Substances, Big Regulatory Challenges

09 Jun 2026

Nanomaterials are an expanding class of substances used across industries ranging from medicine and construction to personal care and agriculture. Their small size gives them unique chemical, physical, environmental, toxicological, and biological properties compared with their macro counterparts.

However, these distinctive properties also make it challenging to characterize them and fully understand how they interact with biotic and abiotic environments. This creates difficulties for regulators, who must assess risk management needs differently than they would for conventional chemicals.

Are there internationally accredited test guidelines that regulatory authorities will accept for nanomaterial registrations? What work is underway to address the characterization challenges for nanomaterials? How can available data be leveraged to support registration or notification of a nanomaterial in a regulatorily defensible way?

These questions reflect a broader regulatory challenge: nanomaterials do not fit neatly within conventional chemical risk assessment frameworks.

What do Regulators Consider a “Nanomaterial”?

Regulatory authorities in Canada, the United States, and the European Union generally consider a substance to be a nanomaterial if it has at least one external dimension between 1 to 100 nm. In addition to size, regulators may consider other physical characteristics such as surface-active functional groups, particle morphology, and the degree of aggregation or agglomeration.

Once a substance is identified as a nanomaterial, the central challenge becomes determining how its properties should be tested in a way that is both scientifically appropriate and acceptable to regulatory authorities.

How Are Nanomaterials Tested Today?

The Organisation for Economic Co-operation and Development (OECD) is actively reviewing the applicability of existing standardized testing guidelines to nanomaterials, while also developing new guidelines and guidance documents specifically to address gaps in existing protocols. The European Union Observatory for Nanomaterials (EUON) monitors these developments and provides updates on both established and emerging approaches relevant to nanomaterial safety assessment.

In 2022, the OECD published a status report outlining ongoing efforts to adapt or develop OECD Test Guidelines (TGs) and Guidance Documents (GDs) for nanomaterials. These efforts span physical-chemical characterization, aquatic toxicity, environmental fate and behavior, and mammalian toxicity.

Physical‑Chemical Characterization

Regulators currently rely on a limited set of OECD TGs for nanomaterial characterization, including:

• OECD TG 124 –‍ Determination of Volume Specific Surface Area
• OECD TG 125 –‍ Particle Size and Size Distribution
• OECD TG 318 –‍ Dispersion Stability

While these guidelines provide a foundation, they often do not fully capture the complexity of nanomaterial behavior. Additional characterization and scientific justification are frequently needed to demonstrate the relevance and reliability of the generated data.

Mammalian Toxicity

For mammalian toxicity assessment, regulators rely on:

• OECD TG 412 – Sub-Acute Inhalation Toxicity: 28-Day Study
• OECD TG 413 – Sub-Acute Inhalation Toxicity: 90-Day Study

Although oral exposure is typically the preferred route for chemical toxicity testing, nanomaterials often have higher fractions of inhalable or respirable particles due to their small size distributions. Consequently, inhalation exposure is usually a more relevant route for assessing the potential for toxicity. OECD TGs 412 and 413, along with OECD GD 39, have therefore been updated to accommodate nanomaterial testing.

Genetic Toxicity

Currently accepted in vitro genetic toxicity assays for nanomaterials include:

• OECD TG 473 – In Vitro Mammalian Cell Chromosomal Aberration Test
• OECD TG 487 – In Vitro Mammalian Cell Micronucleus Test
• OECD TG 476 – In Vitro Mammalian Cell Gene Mutation Test Using the HPRT and XPRT Genes
• OECD TG 490 – In Vitro Mammalian Cell Gene Mutation Test Using Thymidine Kinase

The bacterial reverse mutation assay (OECD TG 471, the Ames test), commonly used as an initial screen for conventional chemicals, is generally not suitable for nanomaterials. Bacteria lack the cellular uptake mechanisms required to internalize nanoparticles, making mammalian cell–‍based assays the preferred approach.

In vivo genotoxicity testing may also be limited if a nanomaterial does not reach the target organ. In the absence of toxicokinetic data demonstrating systemic availability, assessment of genotoxic potential is typically focused on site-of-contact tissues.

Environmental Toxicity

For environmental hazard assessment, the following OECD methods are widely accepted:

• OECD TG 211: Fish, Early-Life Stage Toxicity Test
• OECD TG 202: Daphnia Acute Immobilisation Test
• OECD TG 201: Freshwater Alga and Cyanobacteria, Growth Inhibition Test

These guidelines are generally considered applicable to nanomaterials. However, because nanomaterials may behave differently from their macro-scale counterparts in environmental media, consultation with OECD GD 319 is essential to ensure appropriate test design, exposure characterization, and data interpretation.

Implications for Nanomaterial Registrations

While many OECD TGs have been reviewed or adapted for nanomaterials, uncertainties remain around the selection of appropriate, cost-effective testing strategies. The uncertainty lies not in the absence of testing methods, but in determining which established approaches remain scientifically sound and regulatorily defensible at the nanoscale.

As a result, companies are often required to make strategic decisions in the absence of fully harmonized regulatory guidance, balancing scientific relevance, regulatory acceptability, timelines, and cost. Early testing choices can have significant downstream implications if regulators later determine that data are insufficient or inadequately justified for the nanoscale.

Navigating an Evolving Regulatory Landscape

For organizations seeking to register or notify nanomaterial products, this changing landscape can make it challenging to determine what information is required and how best to generate it. Support is often needed to interpret jurisdiction‑specific expectations, develop a coherent global registration strategy, and identify the best testing approaches.

Are you looking to register a nanomaterial product but uncertain how to characterize it for regulatory authorities?

Do you need support in developing a global registration strategy or in identifying and commissioning the appropriate testing for a nanomaterial?

Contact our experts at Intertek—‍we’re here to help.

References

https://www.canada.ca/en/health-canada/services/chemical-substances/nanomaterials.html

https://echa.europa.eu/regulations/nanomaterials

https://www.epa.gov/chemical-research/research-nanomaterials

https://www.oecd.org/en/topics/sub-issues/testing-of-chemicals/nanomet.html

https://euon.echa.europa.eu/reach-test-methods-for-nanomaterials