KWR at the International Conference on Toxicology (ICT2022)

Understanding potential risks of chemical pollution in the sources of our drinking water is essential to safeguard the production of safe drinking water. Toxicology is a critical research domain to help evaluate if measures should be taken when chemical pollution is detected. With many chemical compounds existing in the world, and many more unknown substances, a prioritization for focus can be made based on knowledge of  toxicity. At the International Congress of Toxicology (ICT2022) in Maastricht (19-21 September 2022), a joint conference by EUROTOX and the International Union of Toxicology (IUTOX) and the Dutch Society of Toxicology (NVT), many inspiring sessions and presentations brought the KWR delegates to the state of the art in toxicology. Some key findings and realizations are listed below.

The water sector may have use for the various innovative approaches presented at the ICT2022 to predict the toxicity and safety of compounds in the water. This is important as we are often confronted with chemicals for which toxicological information is scarce or lacking. Approaches come from different domains. Particularly in drug discovery, it is important to predict the toxicity of drug candidates early in the development process. For regulatory decision-making, it is crucial to assess the safety of industrial products. It was clear from the conference that, for predictions of chemical toxicity, read-across, Quantitative Structure-Activity Relationships (QSARs), machine learning or deep learning (‘artificial intelligence’, AI) are used. These are based on either chemical properties, or high-throughput measured biological properties such as in toxicogenomics approaches (expression of genes, proteins, metabolites), or cell structure changes.

A lively debate highlighted the possibilities as well as the pit-falls of using AI in toxicology. Efforts are currently directed mainly toward making machine and deep learning models self-implementing and more intuitive. This is a welcome development because, at the moment, the methods act as black boxes.

The concept of “Key Characteristics” was discussed in several presentations. This concerns a definite list of possible main characteristics (such as ‘is electrophilic’ or ‘modifies cellular differentiation’) of groups of chemicals that have a particular adverse effect (such as carcinogenicity, neurotoxicity, liver toxicity, etc.). With the help of the Key Characteristics, mechanistic evidence can be collected from scientific literature in order to link a chemical to  (potential) adverse effects by mechanism. This approach can be used complementary to the constituents in ‘adverse outcome pathways’ (AOP), which describe the events from molecular initiating events (by a chemical) to the adverse outcome. In the discussions, it was often made clear that mechanistic evidence is increasingly welcomed and required by regulatory authorities.

It was clear from several presentations that toxicity testing should not stop with the compound of interest but should always expand to possible metabolites. Textile dyes, for instance, are notorious for transforming or breaking into similarly toxic or even more toxic metabolites, especially in drinking water treatment. Defining a ‘metabolic space’ for compounds puts possible problematic metabolites forward. The necessity to assess the impact of metabolites through prediction was the object of various research, which pointed out the importance of comparing different methods to characterize the toxicological profile of “new” chemicals and their acute or chronic exposure to humans.

The Chemicals Strategy for Sustainability adopted by the EU in 2020 aims at a toxic-free environment by 2030. This goal requires a horizontal intervention in legislation, not only in the highly regulated pharmaceutical and industrial market, and the adoption of the precautionary principle at all levels. A transdisciplinary approach that uses different sources of information and various expert judgments is deemed necessary to assess the wide variety of chemicals found in the environment.

The KWR delegates contributed to the conference with talks on genotoxicity testing strategy in water for reuse in circular economies with different in vitro bioassays and on using in silico tools (read-across) to predict toxicity for water relevant compounds. In addition, there was a poster on the bioassay-track for evaluating chemical water quality as defined in the ‘knowledge impulse water quality’ research program, and a poster that illustrated an in silico approach for predicting and prioritizing the hazard assessment on the expected health-related impact of transformation products derived from pesticides during drinking water treatments. A poster was presented on required advanced risk assessment frameworks to address current challenges in risk assessment related to water quality, including less than lifetime exposures to chemicals via drinking water. Lastly, the expected impact of climate change as well as of climate solutions on water quality, how this could be addressed using risk-based monitoring approaches and an overview of EU climate impact projects was presented on a poster. This was an eye-opener to many toxicologists working in different sectors, which was the intended impact.

Very important was also the possibility of connecting with our peers and colleagues, and collaborative partners such as in PARC , MOMENTUM and VHP4Safety, discuss new project ideas and make new global connections.