Make use of New Approach Methodologies in regulatory chemical risk assessment

Animal studies are subject to many ethical considerations, and at the same time they are very expensive, and time-consuming and subject to ethical considerations. Traditionally, animal tests have been a cornerstone of chemical safety evaluation. However, modern toxicology is currently shifting towards a system using primarily in vitro and in chemico assays in combination with computational (in silico) methods and information on (estimated) exposure. The terms New Approach Methodologies (NAMs), and Integrated Assessment to Testing Approaches (IATA) have emerged to describe the new ways of chemical safety evaluation. NAMs represent any methodology, technology, or approach, which can be used in combination for the prediction of chemical hazard and risk assessment in the place of animal studies. NAMs may include in chemico, in vitro, and in silico tools. The term IATA encompasses the overall vision of integrating all type of information from multiple methodologies into chemical safety decision-making towards an animal-free testing paradigm.

In the field of pharmaceuticals, cosmetics and food ingredients NAMs and IATA already are the basis for safety and hazard assessment. The road was paved by the EU setting a worldwide example back in 2013, on how NAMs can replace animal testing, by adopting the ban on animal testing for Cosmetics. However, implementation of NAMs in risk assessment of other chemicals for regulatory purposes is still slow. On one hand, EU regulatory bodies, promote alternatives to animal testing by promoting the use of NAMs for regulatory purposes. For example, according to Article 25 of the REACH Regulation testing on vertebrates shall be performed only as a last resort to meet the legislation’s information requirements. On the other hand, at the moment NAMs are not seen as part of the standard information requirements under REACH, neither under the Biocidal Product Regulation (BPR) and Plant Protection Product Regulation (PPPR). As such, this limited regulatory acceptance discourages the use of NAMs by the chemical industry and risk assessors.

Nevertheless, societal pressure worldwide on pursuing the reduction or even elimination of animal testing will eventually result in change. In fact, NAMs are currently an important element in the agenda of several EU regulatory bodies, and agencies like ECHA and EFSA are involved in many ongoing projects, intending to translate NAMs for regulatory frameworks. This was clearly seen in the recent ONE “Health, Environment & Society” Conference 2022 (About | ONE Conference 2022 (one2022.eu)), where opportunities for the application of NAMs at the current regulatory scenery were discussed. In addition, in line with the EU Chemicals Strategy for Sustainability (link here) the Commission is intending to shift further away from animal testing via possible changes in chemical regulations, such as REACH and CLP. EFSA has recently also published its roadmap for action on NAMs in chemical risk assessment (EFSA Roadmap May 2022).

The forthcoming changes will give opportunities for industry to prevent the need for animal testing. And although NAMs are currently not a part of standard dossier information requirements they can still be used for several purposes:

1. Strengthen your read-across approach by combining data from QSARs (in silico computational toxicology), chemical categories, grouping and physiologically based pharmacokinetic (PBPK) modelling.
2. Support your read-across documents by application of PBPK modelling for quantitative in vitro to in vivo extrapolations (QIVIVE).
3. Evaluate the ADME process and complete your toxicokinetic assessments with the application of PBPK modelling in combination with in vitro kinetic data.
4. Define substance-specific assessment factors for the route-to-route extrapolations during DNEL derivation in accordance with the REACH Guidance.
5. Assist you in screening and prioritizing your chemicals to be taken for further assessments within regulatory contexts.

Are you interested in exploring how to assess the safety of your chemicals with the application of NAMs and IATA? Are you looking for alternative approaches to animal testing for certain endpoints? TRISKELION’s regulatory professionals are ready to assist you to take advantage of the new methodologies and in designing innovative testing strategies based on assessments performed without the use of animals.