Overview

This project is focusing its research on developing New Approach Methodologies (NAMs ↗) to assess how chemicals effect the immune system. This addresses three key areas: organ-specific immune effects, particularly in the respiratory system and related allergic reactions; immune system suppression, measured through its response to vaccination; and improved models for studying how chemicals impact immune cells by identifying key biological processes involved.

The goal is to create innovative testing methods for these aspects of immune system effects.

To achieve this, well-understood reference chemicals will be used to develop and refine the methods. Once established, these methods will be tested on substances prioritised by the Partnership for the Assessment of Risks from Chemicals (PARC), where relevant. They will also contribute to the development of Adverse Outcome Pathways ↗, which link chemical exposure to harmful health effects, and integrated strategies for assessing chemical risk.

The results of this project will be relevant to improving chemical safety regulations across Europe.

Policy relevance

• REACH ↗: several immune related outcomes are relevant for REACH such as skin sensitisation, respiratory sensitisation, immunosuppression. Currently under REACH, the immunotoxicity investigations are triggered based on repeated dose toxicity studies (28- or 90-day) in case there are some indications of immunotoxicity. If indications of immunosuppression are seen, one can include e.g. Cohort 3 into the study design of EOGRTS (developmental immunotoxicity) or request to have an immunotoxicity investigation included in a standard repeated dose toxicity study (adult immunotoxicity).
• CLP (Reg EC 1272/2008): While respiratory sensitisation is mentioned as a hazard in the CLP regulation, it is acknowledged that there is no respective method to detect respiratory sensitisers. Hence, a need to develop methods to detect respiratory sensitisers is recognized. On top of that, the CLP regulation foresees that non-animal testing is conducted wherever possible, implying support for the development of NAMs.
• Plant protection products (Reg EC 1107/2009) and biocides (Reg EC 528/2012): Sensitisation is analysed as part of the data requirements for plant protection products and biocides. The need to develop methods for respiratory sensitisation as well as alternative testing strategies is recognized.
• Cosmetic products: skin sensitisation.
• Food contact materials (Regulation (EC) No 1935/2004): allergenicity.
• Food contaminants (Regulation (EC) No 1881/2006) and enzymes (Regulation (EC) No 1332/2008): allergenicity.
• ECHA's KARC document ↗ (2023) stated the need for developmental immunotoxicity (DIT). NAMs developed and/or models characterized in this project could also feed the DIT needs.