On February 9, 2021, news provider Chemical Watch reported on a study led by Sylvain Bart from the University of York published in the journal Environmental Science Technology that adapted the General Unified Threshold model for Survival (GUTS) for the environmental risk assessment of chemical mixtures.
Classical mixture effect models often exclude time-dependent effects e.g., mixtures that vary in concentration over time or when chemicals are applied sequentially. However, this may result in very different assessment outcomes and prevent meaningful prediction for environmental risk assessments (ERAs). In 2018, the European Food Safety Authority (EFSA) recognized the GUTS framework as a tool to predict survival rates in the environment without prior testing, integrating toxicokinetic–toxicodynamic (TKTD) models. So far, the method has not been applied for the assessment of mixtures and was the aim of the presented study. According to the authors, the described adapted GUTS-RED model for mixtures can provide a “[..] process-based simulation that is more mechanistically based and more widely applicable than conventional dose-response approaches.”
In their study, the researchers focused on binary mixtures but conclude that “the approach can be, in theory, extended to multiple compounds.” In addition, the adapted model is described as also potentially being a suitable tool to find interactions in mixtures and to evaluate whether chemicals act together additively or synergistically.
The authors concluded: “Once calibrated, a GUTS model with a few parameters can be applied on real, time-variable mixture exposure scenarios without the need for additional experimental work.”
Emma Davies (February 9, 2021). “UK researchers model mixture toxicity over time.” Chemical Watch
Bart et al (January 18, 2021). “Predicting Mixture Effects over Time with Toxicokinetic− Toxicodynamic Models (GUTS): Assumptions, Experimental Testing, and Predictive Power.” Environmental Science & Technology
Jager et al (March 02, 2011). “General Unified Threshold Model of Survival – a Toxicokinetic, Toxicodynamic Framework for Ecotoxicology.“ Environmental Science & Technology