EFSA issues guiding principles for two-year whole food studies

EFSA has set out guiding principles that will help scientists carry out two-year whole food feeding studies to assess the risk of cancer and/or toxicity from the long-term consumption of such foods by humans. The report gives advice on how to design and conduct long term whole food feeding trials on rodents in line with internationally-recognised standards and identifies the limitations of these types of studies. In addition, the Authority highlights that a decision on whether these studies are needed should be taken on a case-by-case basis and only after all existing toxicological, nutritional and compositional data have been evaluated. Setting clear and specific objectives prior to launching a study is also crucial. EFSA said its guiding principles would contribute to the future establishment of protocols for two-year carcinogenicity and chronic toxicity feeding studies for both whole food and whole feed.

The European Commission asked EFSA to develop these guiding principles after noting that no guidance existed on conducting two-year feeding studies to assess the safety of whole food. It was agreed that the Authority would assess the extent to which established guidance currently used to evaluate the safety of individual chemical substances could be applied to whole food testing. EFSA identified testing guidelines (TG) 453 from the Organisation for Economic Co-operation and Development (OECD) as the best framework document for this purpose. In its scientific report, the Authority evaluates the suitability of this internationally-agreed test method to provide information on potential toxic or carcinogenic effects linked to the long-term consumption of an individual whole food. When formulating its guiding principles EFSA also considered the views of experts from EU Member States, who were consulted through the Scientific Network for the Risk Assessment of GMOs,

In delivering its assessment, EFSA said it is essential that scientists implementing its guiding principles should define clear and specific objectives before starting a two-year feeding study for whole food. Identifying the exact nature of the risk that the study seeks to assess is key to this process if potential hazards have previously been identified which warrant further investigation. The decision on the need for a two-year study should be based on an evaluation of all available information, such as results from previous analyses of the food’s composition and findings from earlier nutritional and toxicological studies. As the design of the study is dependent on the specific questions to be answered by the feeding trial, EFSA recommends a case-by-case approach to this process.

Based on OECD (TG) 453, EFSA comments on the applicability of core parameters such as methodology, procedure and observations, as well as data and reporting. The Authority concludes that the general principles laid down in OECD (TG) 453 can be applied to two-year toxicity and carcinogenicity studies.

However, EFSA recognises that there are a number of limitations that need to be taken into account in using OECD (TG) 453 for this purpose due to fundamental differences between testing individual chemicals and testing whole food. The main difference is that chemicals can be given to animals at much higher doses than likely human exposure levels, making it easier to detect any adverse effects. This testing approach is often not possible with whole food due to its bulk and the relatively low concentration of individual chemicals in food. Administering higher doses of foods to test animals therefore, may result in adverse effects caused by dietary imbalance rather than any potential toxicity of the whole food itself. A key recommendation made in the report is that test diets must be carefully designed to avoid dietary imbalance.

There is a limit to the amount of food it is possible for a test animal to eat, which leads to these studies being less sensitive in detecting possible toxicological effects than studies on individual chemicals. As a consequence, scientists conducting whole food studies need to use a larger number of animals in order to reliably confirm low levels of toxicity. A further limitation is that potential effects from whole food can only be detected in an animal feeding study at levels that occur as part of a balanced test diet. Adverse effects that would appear at doses above these levels will not be detected by the study.

EFSA’s report recommends a number of principles that should be taken into account when planning a two-year animal study with whole food. The Authority highlights that the decision on whether to conduct such a study should be taken on a case-by-case basis and be based on an evaluation of all available information on the whole food.  These recommendations are in line with guidance previously developed in the Authority’s scientific opinion on conducting a 90-day oral toxicity study in rodents with whole food/feed[1].

Notes to editors

Whole food or feed refers to a product to be consumed in its entirety by humans or by animals, and not specifically to unrefined or unprocessed foods such as whole grain cereals. It ranges from plant-based products, such as maize or potatoes, to more refined products such as fruit juices or flour. It also includes food and feed consisting of microorganisms, as well as animal-derived food products such as meat and milk.

The OECD is an international body that aims to promote policies to improve the economic and social well-being of people around the world. OECD Test Guidelines are a collection of the most relevant internationally-agreed test methods used by government, industry and independent laboratories to determine the safety of a range of substances such as genetically modified organisms (GMOs) as well as chemicals and chemical preparations, including pesticides.

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