Report of the First ONTOX Stakeholder Network Meeting: Digging Under the Surface of ONTOX Together With the Stakeholders.

The first Stakeholder Network Meeting of the EU Horizon 2020-funded ONTOX project was held on 13-14 March 2023, in Brussels, Belgium. The discussion centred around identifying specific challenges, barriers and drivers in relation to the implementation of non-animal new approach methodologies (NAMs) and probabilistic risk assessment (PRA), in order to help address the issues and rank them according to their associated level of difficulty. ONTOX aims to advance the assessment of chemical risk to humans, without the use of animal testing, by developing non-animal NAMs and PRA in line with 21st century toxicity testing principles. Stakeholder groups (regulatory authorities, companies, academia, non-governmental organisations) were identified and invited to participate in a meeting and a survey, by which their current position in relation to the implementation of NAMs and PRA was ascertained, as well as specific challenges and drivers highlighted. The survey analysis revealed areas of agreement and disagreement among stakeholders on topics such as capacity building, sustainability, regulatory acceptance, validation of adverse outcome pathways, acceptance of artificial intelligence (AI) in risk assessment, and guaranteeing consumer safety. The stakeholder network meeting resulted in the identification of barriers, drivers and specific challenges that need to be addressed. Breakout groups discussed topics such as hazard versus risk assessment, future reliance on AI and machine learning, regulatory requirements for industry and sustainability of the ONTOX Hub platform. The outputs from these discussions provided insights for overcoming barriers and leveraging drivers for implementing NAMs and PRA. It was concluded that there is a continued need for stakeholder engagement, including the organisation of a 'hackathon' to tackle challenges, to ensure the successful implementation of NAMs and PRA in chemical risk assessment.

Prioritising veterinary medicines according to their potential indirect human exposure and toxicity profile.

Veterinary medicines are used widely in the United Kingdom (UK) to protect animal health, prevent economic loss, and to help ensure a safe food supply. Veterinary medicine active ingredients (AIs) have been detected in various environmental media, including surface and groundwater, suggesting the potential for indirect human exposure from such residues. To fully assess the potential level of such exposures and the resultant potential risks to humans from all veterinary medicine AIs would be resource intensive. This paper proposes a method for prioritising veterinary medicine AIs according to estimates of their potential for indirect human exposure via the environment and their toxicity profile, and demonstrates its feasibility using an initial set of 83 veterinary medicine AIs approved for use in the UK. Overall, 13 AIs were classified as 'High' priority for detailed risk assessment, 19 as 'Medium' priority, 5 as 'Low' priority, and 46 as 'Very low' priority. The veterinary medicine AIs classified as 'High' or 'Medium' priority for detailed risk assessment included 15 different chemical groups and 10 different therapeutic indications. Overall, the proposed prioritisation scheme was demonstrated to provide a scientifically robust and pragmatic means of assessing the relative priority of veterinary medicine AIs for further detailed risk assessment regarding human exposure. However, there remain a number of data gaps that, if filled, would improve the accuracy of the resultant prioritisation.