Introducing TKPlate - food safety without animal testing?

Historically, safety assessments of chemicals in food and feed (as well as for medicines, consumer products, industrial and other chemicals) have relied on evidence from animal experiments. This core practice in evaluating risks from chemicals has, by and large, ensured the safety of our food since the 1950s.

However, society and scientists are increasingly questioning this practice, both for ethical and scientific reasons. We all want to reduce the suffering of the animals – improvements have been made in recent years thanks to promotion of the three Rs – to replace, reduce, and refine animal testing.

The use of alternative tools to generate more representative information about toxicokinetics The study of the processes by which potentially toxic substances are handled in the body. This involves an understanding of the absorption, distribution, metabolism and excretion of such substances. (TK) (how the body manages chemicals) and toxicity/ toxicodynamics The process of interaction of chemical substances with the body and the subsequent reactions leading to adverse effects. (TD) (what chemicals do to the body) is becoming a reality too.

Step forward, “TKPlate”!

Predicting toxicokinetics and toxicity with open-access software

Scientists at EFSA and several top European research organisations teamed up to create “TKPlate”. It is an online platform that offers a space and a suite of tools for scientists and regulators to model and predict TK and TD properties.

Two senior scientists at EFSA – toxicologist Jean-Lou Dorne, and statistician/modeller Jose Cortiñas Abrahantes – are leading this work.

Jean-Lou: “The idea for TKPlate started in 2014 with a scientific report on alternative methods to animal testing that could be used by EFSA’s experts. The report proposed the development of a series of TK and TD models. Toxicokinetics tells us how the body absorbs, distributes, metabolises and excretes the chemical. Toxicodynamics explores the toxic effects on molecules, cells, tissues, organs or a whole organism A living thing such as humans, animals, plants and microbes (e.g. bacteria, viruses).”

Jose: “Between 2015 and 2020, EFSA developed these TK models and produced many case studies for a range of species A subdivision of the genus, a species is a group of closely related and similar-looking organisms; for example, in the case of Homo sapiens (humans), the second part of the name (sapiens) represents the species. relevant to EFSA’s work: humans, test animals like rats and mice, farm animals and other species that have a role in the food and feed chain such as earth worms. We contracted out to academic partners and national agencies important parts of the work, which have resulted in several successful doctorates by young scientists.”

Unique in the food safety area – what can TKPlate do?

“As far as we are aware, this platform is unique in the food and feed safety area.” -Jean-Lou Dorne

Jean-Lou: “As far as we are aware, this platform is unique in the food and feed safety area.”

“It allows risk assessors and others involved in toxicology to model TK and TD processes in all the species included in the platform. Basically, you select the species, the chemical or group of chemicals, input parameters such as the type of exposure Concentration or amount of a particular substance that is taken in by an individual, population or ecosystem in a specific frequency over a certain amount of time., then you run the models with a click. 

“It calculates the concentrations of chemicals inside the body from the intakes (TK) and predicts the effects (TD) they can cause. These results can directly replace animal data, reducing the need for new experiments. It works in the opposite direction too; we can estimate exposure if there is data such as blood or urine concentrations. It has many more features including TK-TD modelling and a tool for assessing risks from chemical mixtures.

“You get an automated report at the end that provides details of all the inputs and outputs, data and graphs. This can go directly into the scientific assessment as part of the evidence base.”

Creating the platform – a mammoth effort

TKplate is more than just models, but they are an important part of what the platform offers.

Jose: “The types of models in TKPlate are complex to develop as they reflect a conceptual framework about how a substance interacts with an organism. Of course, all models are a simplification of reality, so the challenge lies in trying to capture the process as accurately as possible, reducing the complexity to achieve something generalisable.

“Trying to mimic the full process within the organism is not realistic, so the challenge is to consider which components to retain to make them as resilient as possible if our assumptions are inaccurate or faulty.

“Well-developed models like these take at least a year to develop.” -Jose Cortiñas Abrahantes

“Well-developed models like these, including testing and validation, take at least a year to develop, depending on the complexity of the organism and all components that you want to include. It’s a mammoth effort and the researchers who produced them deserve our thanks. As well as the models produced between 2015 and 2020, others are still being developed today.”

Reliability of TK models

With tools like TKPlate now becoming viable, the focus turns to their reliability as evidence sources.

Jean-Lou: “As with all scientific information, the predictions provided by these models have variability Natural variations observed between members of a population, or observed over time or in different geographical locations; for example, individual variations in susceptibility to a particular toxic chemical.  and uncertainty Scientific concept used in risk assessment to describe all types of limitations in available knowledge at the time an assessment is conducted, with the agreed resources, that affect the probability of possible outcomes to the assessment., depending on the data available for the species and the chemical you’re testing. These are reported transparently in a range of case studies using international standards to assess the reliability of each model.”

Jose: “All the modelling work we outsourced required extensive tuning, testing and validation, using not only existing experimental animal data but also additional lab data generated by the contractors. The case studies tested the model results in different contexts and for different species, producing results that are coherent with our expectations. As a result, we’re confident in the reliability and robustness of the models.”

Is TKPlate being used in risk assessments yet?

The integration of the TK models into a user-friendly interface – the platform launched today – is an important step to implement their use in chemical risk assessment  A specialised field of applied science that involves reviewing scientific data and studies in order to evaluate risks associated with certain hazards. It involves four steps: hazard identification, hazard characterisation, exposure assessment and risk characterisation. at EFSA and beyond.

Carlos Gonçalo das Neves is EFSA’s Chief Scientist and an avid promoter of “New Approach Methodologies” (NAMs) developments such as TKPlate.

Carlos: “The potential of TKPlate and other NAMs tools like it are astonishing. Some software-based NAMs are already in use at EFSA and playing a growing role in some of our risk assessments.

“TKPlate is not being used in EFSA’s assessments yet, but applications of its models are being explored to optimise the platform and to prioritise training for our staff and experts across Europe. This will support its use in risk assessment by EFSA’s scientific panels, hopefully in a near future. And of course we can and want to roll out this support to other EU agencies and national authorities.

“We are on the cusp of a new era in chemical risk assessment.” -Carlos Gonçalo das Neves

“We are on the cusp of a new era in chemical risk assessment, which will see not only a welcome reduction in the need for animal testing, much requested by our citizens, but also further improvements in the quality and relevance of the data used in our assessments. I really hope TKPlate will represent a big step forward in this direction.  

“Scientific advisory bodies like EFSA are lining up to deliver risk assessments with NAMs.  It’s important that regulators and society are reassured that all outputs for supporting decision-making are based on sound science. We are confident that that TKPlate will do its job.”

• Editorial – TKPlate 1.0: An Open-access platform for Toxicokinetic and Toxicodynamic modelling of chemicals in food and feed safety
• Technical report - User Guide for TKPlate 1.0: An open access platform for implementing new approach methodologies in chemical risk assessment through toxicokinetic and toxicodynamic modelling
• Technical report - Applications of TKPlate 1.0 for toxicokinetic and toxicodynamic modelling of chemicals: Case Studies
• External scientific report - Further development of a web-based open-source platform for Toxicokinetic and Toxicodynamic modelling: TKPlate 1.0