REGULATION & COMPLIANCE
tools, followed— if needed— by in vitro methods or more in-depth studies. This structure aligns with the 3Rs( replacement, reduction, refinement) principles, promoted by Directive 2010 / 63 / EU on the protection of animals used for scientific purposes.
Practical applications & new challenges
In silico methods have numerous practical applications. They facilitate the selection of substances for pre-market screening and allow the environmental toxicity of new chemicals, such as pesticides, detergents and drugs, to be assessed. They support decisions on restrictions or authorisations under REACH and contribute to identifying persistent, bioaccumulative and toxic( PBT) and very persistent, very bioaccumulative( vPvB) substances.
ECHA has developed accessible tools, such as the QSAR Toolbox platform, to support the use of these approaches by businesses and competent authorities. These models are not only an ethical choice but also a modern scientific strategy to optimise time, costs and the quality of information.
However, the broad adoption of such tools faces some challenges. First, high-quality data availability is critical for building reliable models. Second, sector-specific training is necessary to ensure proper and informed use of in silico tools. Another crucial factor is international regulatory recognition, which is essential for harmonising methodological approaches and ensuring regulatory acceptance of results.
In addition to structural challenges, new emerging issues exist. Some substance classes, such as nanoparticles, have peculiar physicochemical properties that often fall outside the applicability domains of existing models. Likewise, pharmaceuticals— such as ibuprofen— show unique behaviours, such as high solubility and marked environmental mobility, making their assessment more complex.
Regulatory context
The adoption of in silico methods is encouraged by global initiatives aimed at chemical sustainability, such as the European Strategy for Sustainable Chemicals, a key part of the European Green Deal. In this scenario, the concept of New Approach Methodologies( NAMs) plays a key role.
Regulatory bodies like the European Food Safety Authority( EFSA), ECHA, the US EPA and the OECD are already integrating computational models into their regulatory processes. Notably, EFSA’ s guidance on the weight-ofevidence( WoE) approach defines a harmonised framework for integrating in silico methods into environmental risk assessment.
Complementary approaches
Another useful method is read-across, a technique that predicts the properties of an untested chemical using data from one or more structurally similar substances( analogues). It is a pragmatic and scientifically grounded approach to bridge gaps in experimental data, reducing the need for additional testing— especially animal testing.
This method is based on three key elements:
• The presence of common functional groups between the target substance and its analogues
• Similarity in chemical precursors or degradation products, suggesting comparable toxicokinetic behaviour
• Consistent patterns in physicochemical, biological or toxicological properties, justifying data inference
When multiple substances show these similarities, they can be grouped into a structural category, facilitating the systematic application of read-across. This approach is known as grouping and is a logical extension of read-across.
Despite their great potential, the widespread application of in silico methods requires overcoming several challenges, including model validation, access to quality data and regulatory acceptance. However, their growing integration into European policies, combined with ongoing research and training efforts, makes them an emerging cornerstone for environmental risk assessment under the REACH framework.
Conclusion
The integration of in silico methods into the regulatory system marks a fundamental shift in environmental risk assessment. QSAR models, alongside read-across and other computational tools, provide an effective response to the need to evaluate a growing number of chemical substances rapidly, ethically, and cost-effectively.
If properly developed, validated and applied, these methods can significantly contribute to protecting public health and the environment, in line with the foundational principles of European regulations and good scientific practices. Their integration into regulatory systems is now a concrete reality, supported by European legislation, international authorities and reliable software tools. ●
Paola Barone
REGULATORY AFFAIRS SPECIALIST, SDS & CLP
CHEMSAFE S. R. L. k + 39 0125 538888 J p. barone @ chemsafe-consulting. com j www. chemsafe-consulting. com
42 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981