How NAMs in Fragrance Safety Assessment Support Predictive Approaches

Behind every scent lies a sophisticated risk assessment paradigm. Today, NAMs in fragrance safety assessment are accelerating a shift towards Next Generation Risk Assessment, or NGRA.

New Approach Methodologies are helping move fragrance safety away from traditional endpoint testing and towards a more mechanistic and exposure-driven understanding of safety. By combining in vitro, in silico and Read-Across approaches, NAMs can support hazard identification, quantitative risk assessment and predictive toxicology.

From Traditional Endpoint Testing to NGRA

Next Generation Risk Assessment represents a move from traditional endpoint testing towards approaches that consider mechanisms and exposure.

Within fragrance safety, this evolution supports a more detailed understanding of how effects are triggered and how different types of information can contribute to safety assessment.

Rather than relying on one approach in isolation, NGRA frameworks can integrate biological responses, computational predictions and information from analogue substances. This combination supports a more structured and predictive understanding of fragrance safety.

How NAMs in Fragrance Safety Assessment Contribute

Three complementary approaches are highlighted in the development of NAMs in fragrance safety assessment: in vitro methods, in silico methods and Read-Across.

In vitro approaches

In vitro NAMs include KE-based assays such as DPRA, KeratinoSens™ and h-CLAT, as well as advanced gene expression-based platforms such as GARD.

These approaches can:

• Capture biological responses across the sensitization pathway

• Provide mechanistic insight into how effects are triggered

In silico approaches

In silico NAMs include tools and approaches such as the OECD QSAR Toolbox, VEGA and PBK modeling.

They can:

• Predict reactivity, metabolism and systemic exposure

• Support hazard identification

• Contribute to quantitative risk assessment

Read-Across

Read-Across is based on structural similarity, metabolic pathways and mechanistic alerts.

This approach:

• Uses data from analogue substances

• Strengthens confidence through weight-of-evidence approaches

Together, these methods bring different types of information into fragrance safety assessment without relying on a single source of evidence.

What These Approaches Enable Together

The convergence of in vitro, in silico and Read-Across approaches can enable:

• AOP-informed hazard identification

• Quantitative potency estimation

• Integration into NGRA frameworks

• Reduced animal testing

• Increasing alignment with regulatory expectations and OECD frameworks

This includes frameworks such as TG 497 and the use of weight-of-evidence approaches.

Their combined use supports the evolution of fragrance safety towards methods that are more mechanistic, quantitative and predictive. It also contributes to safety assessment approaches with high human relevance.

Towards Quantitative and Predictive Fragrance Safety

Recent work cited in the original post, such as Natsch et al., 2026, illustrates how NAMs can go further by supporting the derivation of points of departure and NESIL-like values for fragrance ingredients.

This development brings fragrance assessment closer to fully NAM-based quantitative risk assessment.

As the fragrance industry continues to innovate, the convergence of in vitro, in silico and Read-Across approaches is also supporting the development of safe-by-design ingredients with high human relevance.

The Future of NAMs in Fragrance Safety Assessment

NAMs in fragrance safety assessment are contributing to a transition towards Next Generation Risk Assessment by combining mechanistic insight, exposure-driven science and quantitative approaches.

The future of fragrance safety is not only non-animal. It is also mechanistic, quantitative and predictive.

Learn more about Simply Predict’s expertise in NAMs, NGRA and predictive toxicology.