The role of 14-day toxicology studies in feed additive safety evaluation

Why 14-Day Toxicology Studies Matter? 

The 14-day repeat-dose toxicity study is a cornerstone in ensuring the safety of feed additives. This early-stage study is essential for supporting dossier submissions, guiding dose selection and maintaining high standards of animal welfare.

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Purpose of the Study

Comprehensive toxicity data are necessary to confirm the safety of feed ingredients. The 14-day study is an early stage toxicology assessment designed to identify potential adverse effects of a test compound following short term repeated daily exposure. It provides foundational information on dose-response, indicates target organs, and helps determine whether repeated exposure could pose risks to animals or humans consuming animal-derived products.
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Dose Level Selection

Designing longer-term studies, such as 28-day or 90-day studies, requires evidence-based dose selection. Current guidance on dose level selection is largely based on advice within the Organisation for Economic Co-operation and Development (OECD) Test Guidelines (TG). Although the 14-day rat study is not OECD defined, the study aligns with key OECD frameworks of OECD TG 407 on Repeated Dose 28Day Oral Toxicity Study in Rodents and ICH guideline M3(R2). 

The 14-day study serves as a range-finding tool for further, longer term studies, ensuring that the doses chosen are appropriate, ethically justified, and scientifically sound for evaluation of the potential toxicity of the test compound.

In general, dose levels for repeated (long-term) exposure may be based on the results of repeated dose or range finding studies and should take into account any existing toxicological and toxicokinetic data available for the test compound. The highest dose level should be chosen with the aim of inducing toxic effects but not death or severe suffering, whereas the lowest dose shall be chosen with the aim as to produce no adverse signs.

Establishing NOAEL

 The 14-day study is a range-finding study that contributes to early safety evaluation of systemic toxicity, identifying the dose levels for further testing. 

The study can provide information on the major toxic effects, an estimate of a No Observed Adverse Effect Level (NOAEL) of exposure which can be used for establishing safety criteria for human exposure and in selecting dose levels for chronic studies. Dose selection nearly always involves a prediction of what might happen in a study of longer duration than available in the current data base (e.g., dose selection for a 28-day study and/or 90-day exposure period based on information from the 14-day study). 

Promoting Animal Welfare (3Rs Principles)

By refining high-dose levels and assessing compound tolerability early, the 14-day study reduces unnecessary animal exposure in long-term studies. 

This aligns with ethical commitments to Replacement, Reduction, and Refinement in animal research.

Do You Need Regulatory Support On Your Next Studies?

Experts in regulatory strategy and submissions

Did you know that for some feed additives there is no requirement for toxicological studies in the EU?

Argenta can support you navigate through complex regulatory requirements. Whether you are planning your next feed additive submission or refining study protocols and reports, we are here to help you move forward with confidence.

For further information or regulatory support, feel free to contact our regulatory affairs team.