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Considerations on the applicability of OECD TG 453 to whole food/feed testing

EFSA Journal 2013;11(7):3347 [18 pp.]. doi:10.2903/j.efsa.2013.3347
European Food Safety Authority Acknowledgment EFSA wishes to thank: the EFSA staff Saghir Bashir, José Cortiñas Abrahantes, Daniele Court Marques, Wolfgang Gelbmann, Andrea Germini, Yi Liu, Claudia Paoletti and Didier Verloo for the preparatory work on this scientific output, and the external reviewers Alicja Mortensen, Hanspeter Naegeli, Joe Perry and Josef Schlatter and the Member State representatives of the EFSA GMO Network for the comments provided to this scientific output. Contact scientific.committee@efsa.europa.eu
Type: Scientific Report of EFSA On request from: European Commission Question number: EFSA-Q-2013-00316 Approved: 26 July 2013 Published: 31 July 2013 Affiliation: European Food Safety Authority (EFSA) Parma Italy
Abstract

Upon request from the European Commission, the European Food Safety Authority prepared a scientific report that would aid the future establishment of protocols for chronic toxicity and/or carcinogenicity studies in rodents with whole food/feed. This scientific report provides a commentary on OECD TG 453 with considerations on its applicability to support the safety assessment of long term consumption of a given food with respect to its chronic toxicity or carcinogenicity potential. The decision to conduct chronic toxicity and/or carcinogenicity studies with whole food/feed should be taken on a case-by case basis. It should be based on the evaluation of all the available information on the whole food/feed resulting from compositional analyses and any other available nutritional and toxicological studies. The conduct of the study and its reporting should be in line with good laboratory practice standards. Preparation of appropriate test diets is a key element of the experiment with respect to characterisation of the starting material and of the diet, level of inclusion of whole food/feed, nutritional balance, processing and storage. Statistical considerations are discussed to assist in estimating the number of animals necessary to obtain a suitable sample size capable of detecting biologically relevant effects with a pre-specified power and significance level. A comprehensive set of endpoints as set out in the OECD TG 453 should be measured during and at the end of the study, as appropriate. The collection of data and reporting should ensure a thorough biological and statistical evaluation. Recommendations on the relevant issues to be considered when designing chronic toxicity and/or carcinogenicity studies in rodents with whole food/feed are provided throughout the report and summarised in the conclusions.

© European Food Safety Authority, 2013

Summary

Upon request from the European Commission, the European Food Safety Authority (EFSA) was asked to develop guiding principles that would aid the future establishment of protocols for chronic toxicity and/or carcinogenicity studies in rodents with whole food/feed. It was agreed that this EFSA scientific report would be a commentary on OECD TG 453, with specific considerations related to whole food/feed. The mandate was assigned to an internal EFSA task force composed of staff members with different key scientific expertise and was endorsed by the EFSA Scientific Committee. Experts in the role of external reviewers and Member State representatives of the EFSA GMO Network provided valuable comments during the development of the document.

This scientific report comments on the applicability of OECD Test Guideline 453 for the carcinogenicity and chronic toxicity testing of chemicals (OECD, 2009a) for the purpose of testing whole food/feed. The report includes specific recommendations for performing and reporting experiments carried out with whole food/feed. These recommendations are in line with the guiding principles previously developed in the EFSA scientific opinion on conducting repeated-dose 90-day oral toxicity studies in rodents with whole food/feed (EFSA Scientific Committee, 2011a).

OECD Test Guideline 453 was established for the chronic toxicity and carcinogenicity testing of chemicals including the provision of dose-response data on chemicals. Its adaptation to whole food/feed presents limitations that should be considered when developing the test protocol such as: limitations in the maximum whole food/feed dose that can be incorporated into the experimental diet; the fact that toxic effects can be detected only if these are present at levels compatible with a balanced diet formulation; and the availability of proper historical control data.

The evaluation of potential hazards identified by compositional analyses and any other available nutritional and toxicological studies on the whole food/feed would provide indications on the decision to conduct chronic toxicity and/or carcinogenicity testing of a whole food/feed. The study should be carried out according to Good Laboratory Practice (GLP) standards and should take into account animal welfare issues.

Rodents are the preferred test animals and should be housed in cages in pairs of the same sex throughout the duration of the study. The starting material and the diet should be thoroughly characterised and the storage conditions and stability of the feeds should be documented over the course of the whole test.

The decision on the most appropriate study design should be made on a case-by-case basis according to the objectives of the study and the particular hypotheses to be tested. The number of animals per group depends upon the specific objectives of the study and should be adequate to conduct a thorough biological and statistical evaluation. Statistical considerations are discussed that aid the derivation of appropriate sample sizes for continuous and categorical variables.

The parameters to be considered for both the chronic toxicity phase and the carcinogenicity phase should be in line with those detailed in OECD TG 453. Additional markers of potentially adverse nutritional and/or metabolic effects should be considered on a case-by-case basis, according to the available body of evidence and the type of whole food/feed under investigation.

All details of the design, the conduct and the analysis should be clearly justified, documented and reported. A specific chapter on assumptions and uncertainty analysis should be included in the study report.

Keywords

2-year feeding study, whole food/feed, carcinogenicity, chronic toxicity, experimental design, statistical analysis