WP1: Subchronic Toxicity Studies on Rodents
The development of subchronic toxicity studies (90-day feeding studies) using whole food or feed as test material is challenging. Present standardised 90-day toxicity studies (e.g. based on OECD Test guideline TG 408) are only available for chemicals as test material.
There is a big difference between whole food or feed and chemicals as test material for these kind of studies. Test animals can get chemicals at dose levels being much higher than the likely human exposure ones. Such a testing approach is not always possible with the bulky whole food or feed. Administering high dose levels of whole food or feed is likely to cause satiation or unbalanced diets. Therefore, an effective way to increase the chance of detecting any toxicologically-relevant effects should adapt design, conduct and analysis of the OECD TG 408 to specific whole food or feed testing.
The European Food Safety Authority (EFSA) has already developed draft guidance for carrying out 90-day feeding studies on whole food and feed in rodents based on OECD TG 408 (EFSA Scientific Committee, 2011), but this guidance does not provide prescriptive test protocols to carry out such experiments. Therefore, GRACE (WP1) will perform 90-day feeding trials with whole GM and non-GM plant material to validate and refine these suggested approaches.
90-day Animal Feeding Studies
As a starting point, the GRACE team surveyed the current evidence in literature on the performance of 90-day feeding trials and gathered viewpoints from relevant regulators, scientists and stakeholders throughout Europe. In this context GRACE also hosted a stakeholder/expert consultation on animal feeding studies in Vienna on 3 - 4 December 2012. This information and the consultation process formed a baseline for establishing a detailed experimental design appropriate to the test animals and a clear definition of the GM crops and components tested (see study plan A and B). Certified test laboratories conducted 90-day feeding studies on rodents with two different GM maize cultivars (MON810 maize) in 2013 and the GRACE team is currently evaluating the results.
The internal evaluation of all data will be followed by an evaluation by external experts/stakeholders to recommend future implementations for safety evaluations of GM food and feed in the EU. In this context GRACE will host the second stakeholder/expert consultation on animal feeding studies and in vitro studies taking place in Brussels, Belgium on May 19 and 20, 2014.
Longitudinal Metabolomics Study
An additional feeding study (based on the 90-day feeding study design) is scheduled to start in the beginning of 2014 to consider whether additional metabolic endpoints improve the evaluation of toxic effects through transgenic crops. Since the collection of samples of blood and urine throughout this longitudinal study means additional disturbance for the rats, a separate study is planned using the same plant material (Monsanto and Pioneer maize MON810) as for previous 90-day feeding studies. This study will also take into account OECD TG408 and the EFSA standard protocol on conducting repeated-dose 90-day oral toxicity study in rodents on whole food or feed. The related draft study plan has been subject of a written stakeholder consultation procedure (started on 6 Dec 2013, closed on 20 December 2014). The animal study will be conducted based on the revised plan. Once the results of these studies will be available, another stakeholder consultation will be organized in 2015 in order to discuss results and draft interpretations.
Based on the results, WP1 will draw conclusions and advise on
- the need for 90-day feeding trials for the assessment of GMO impacts on human health (by means of the ability of such animal feeding trials to detect changes in GM crops that may raise health concerns) and
- the appropriate design of such studies on the basis of whole GM food or feed.
All test results and recommended guidelines will be available on the GRACE project website and in the open-access database (WP6) and will be subject of upcoming stakeholder consultations.
Note: This webpage has been updated on March 2014 according to changes in the study plans. For reasons of transparency the former version can be viewed here.
GRACE involves stakeholders in research planning and drawing of conclusions. Read here for more information.
New Stakeholder Consultation Reports:
Consultation on Good Review Practice in GMO Impact Assessment
The database CADIMA (Central Access Database for Impact Assessment of Crop Genetic Improvement Technologies) contains quality assessed studies and conclusions on the health effects, socio-economic consequences and environmental impacts of GM plants as well as raw data of animal feeding studies and alternative in vitro approaches.