Risk assessments

Hazard assessment

At PARC we aim to overcome the major challenges in hazard assessment to protect human health and the environment. There are three main challenges currently facing hazard assessment of chemicals:

• Knowledge gaps and limited data for poorly characterised chemicals and new emerging hazards.
• Current testing methods accepted by regulators rely heavily on animal testing. For both ethical and economic reasons, in vivo tests are not suitable for assessing all sorts of chemicals and potential mixtures.
• Integrate scientific progress and innovative methodologies into hazard assessment practices that are both practical and feasible from a regulatory perspective.
   

Closing data gaps

The toxicity of many substances is poorly understood, particularly where existing regulatory procedures do not provide a means to require participants in the process to generate relevant data or where such participants are lacking. 

Following a prioritisation workshop and further consultation with partners involved in hazard and risk assessment in national and European agencies, two groups of substances have been selected for the first round of testing: 

1. natural toxins, in particular the mycotoxins enniatins (produced by fungi belonging to the Fusarium genus) and those derived from Alternaria, which is a genus of fungi commonly found in soil, plants, air, and water, and 
2. alternatives to bisphenol A (BPA). 

Unlike man-made chemicals, which are synthesized by manufacturers and subject to regulatory approval processes requiring data on their safety and toxicity, natural toxins do not have a designated manufacturer responsible for providing such data.

Nevertheless, they are present in food or consumer products and may pose risks to human health. For example, in humans, Alternaria species can be allergenic and are often implicated in respiratory allergies, especially in individuals with asthma or other respiratory conditions. Exposure to Alternaria spores, which are released into the air, can trigger allergic reactions such as sneezing, runny nose, itchy eyes, coughing, and wheezing. At PARC we conduct test to determine the toxicological properties of these toxins to ensure safety with the goal to establish health-based guidance values, which provide thresholds for safe exposure levels to natural toxins. For that, established toxicological tests are used in accordance with the Organisation for Economic Co-operation and Development ↗ (OECD) test guidelines, but also sensitive test methods are employed to ensure accurate assessment of natural toxins’ effect. The data generated is stored and made available to the scientific community in accordance with the FAIR criteria, which stands for Findable, Accessible, Interoperable, and Reusable.

The second group of substances selected are 7 alternatives to bisphenol A (BPA). Further information here.

Systems toxicology: Understanding the adverse effects of chemicals on biological systems as a whole 

Systems toxicology is about understanding how chemicals can harm the body by looking at their effects on biological systems as a whole. By closing data gaps and using innovative research methods, scientists can build better models to predict chemical hazards. These models are important for understanding risks and for regulatory decisions.

To make this data useful, it must be integrated into a well-recognised structure or framework. A useful tool to integrate mechanistic in vitro data with information on adversity from in vivo studies is provided by the so-called Adverse Outcome Pathways (AOPs). The AOPs link specific molecular changes caused by chemicals to the larger health effects they might trigger. The aim of PARC is to close data gaps in AOPs for prioritised endpoints (health impacts), developing new AOPs as needed with transparent and consistent methodologies in line with the FAIR data principles. In addition, to support the identification and biological characterisation of effect markers for monitoring purposes, priority chemicals are linked to events within AOPs using text mining and network analysis tools. 
 

Understanding how laboratory data relates to real-life effects

A big challenge is to figure out how well data from laboratory experiments (in vitro omics data), so studies done on cells or tissues, known as ‘in vitro’ studies match what happens in living organisms, the ‘in vivo’ situation. This is important because it helps us better estimate real-life risks from chemicals. At PARC, we are using advanced methods called New Approach Methodologies (NAMs) to gather data about how chemicals work in the body (mechanistic data). We analyse this data using computer-based methods (known as ‘in silico’ methods), and we also use data from human health studies available in public sources. The goal is to see how chemicals affect cells in the lab and compare this to real-life responses in humans. 
 

Predicting chemicals effects more accurately

To improve our predictions of chemicals harm, we combine different kinds of models that simulate how these chemicals move through and interact with the body.

First, we look at how the body processes the chemical, so we focus on understanding how it's absorbed, distributed, broken down (metabolised), and eliminated by the body, so-called ADME processes. We study these processes using laboratory tests (in vitro), computer models (in silico), and by comparing these to what actually happens in living organisms (in vivo).

Using this knowledge, we create models that mimic how the body deals with these chemicals, the so-called Physiologically Based Toxicokinetic or PBK models. These models estimate how much of a chemical is likely to end up inside the body over time. We then compare this estimated exposure to reference points from our laboratory tests to understand potential risks for specific chemicals and pathways.