Can We Keep Our Food and Water Safe? Unraveling Chemical Hazards Through Alternative Approaches and Computational Models to Guarantee Non-Toxic Exposure Levels

Humans and the environment are constantly exposed to thousands of synthetic and naturally occurring chemicals, some of which can be hazardous. The goal of chemical risk assessment is to regulate the level of exposure in the environment, food and drinking water to guarantee safety for human and animal health. This is a challenging task due to an increasing number of chemicals and their limitless combinations, often lacking information about their hazard. In addition, the health consequences from low real-life exposure concentrations associated with molecular perturbations are poorly understood.

Therefore, there is a pressing societal need for the development of New Alternative Approaches such as the use of the zebrafish embryo model for risk assessment as an alternative to animal testing, advanced technologies to investigate early molecular perturbations, and computational models. These approaches seek to enhance our understanding of toxicity mechanisms across a wide range of exposure levels, enabling high-throughput toxicity tests of many chemicals and thus aim to replace, reduce, and refine animal testing.

My research focuses on translating experimentally observed effects using New Alternative Approaches to real exposure scenarios for human and animals. To this end, predictive toxicokinetic models, which describe how chemicals are absorbed, distributed, metabolized, and eliminated in the body, are developed and applied. These computational models are instrumental in extrapolating toxicity data between species, exposure concentrations, and effect biomarkers, and thus enable the integration of New Alternative Approaches in risk assessment. I generally followed three main objectives to accomplish my research aim:

1. Real-life exposures: Analyzing biomonitoring data to estimate real exposure scenarios from the environment, food and drinking water.
2. Hazard characterization: Studying effects at molecular and phenotypical levels in zebrafish embryo exposed to low (environmentally relevant exposure) and high (health effect relevant) exposure levels.
3. In vitro to in vivo extrapolation: Translating critical effects measured with New Alternative Methods to real-life exposure concentrations using toxicokinetic modelling.

Much of my research has focused on addressing the PFAS (per- and polyfluorinated alkyl substances) issue as a proof-of-concept. PFAS have emerged as a significant chemical threat to drinking water security worldwide and with levels in food that are currently too high from a health perspective in many countries, including Sweden. Together with various collaborators, we have so far (i) associated PFAS in food and drinking water with serum concentrations measured in adults and adolescences, (ii) established hazard data at molecular and phenotypical effect level in zebrafish embryo, and (iii) developed toxicokinetic models for PFAS in zebrafish embryo and pregnant women.

This research is at the pivotal point to translate critical neurotoxic effects measured in zebrafish embryo to PFAS concentrations in food and drinking water. The integrated results will support risk assessment and management by providing estimations of safe exposure levels in food and drinking water to protect humans and animals from potential harmful PFAS exposures.