What EFSA looks for in your toxicological data

The toxicology section is the longest in the average novel food opinion. What studies are required, when waivers apply, and where applicants most often fall short.

The toxicological data section is typically the most extensive part of a novel food dossier — and the most expensive to generate. In our analysis of published EFSA opinions, toxicological assessments averaged 9,600 characters per opinion, the longest of all ten sections. The studies required represent a significant investment, with industry estimates suggesting a standard toxicological package costs in the range of €80,000–€150,000.

Getting this section right matters. Toxicological deficiencies trigger additional data requests, and unlike some documentation gaps that can be resolved quickly, missing or inadequate studies can add six months or more to the timeline.

The standard package

EFSA's 2024 scientific guidance specifies a standard toxicological package for novel foods:

Genotoxicity battery. A set of in vitro tests to assess whether the novel food has the potential to damage DNA. The minimum battery includes a bacterial reverse mutation test (Ames test) and an in vitro mammalian cell micronucleus test. Depending on the results and the nature of the novel food, additional tests may be required — including, in some cases, an in vivo study.

90-day subchronic oral toxicity study. A repeat-dose study in rodents conducted according to OECD Test Guideline 408. This is the core study from which the NOAEL (No Observed Adverse Effect Level) or benchmark dose is derived. The study must use at least three dose levels plus a control group, with the highest dose selected to produce some toxicity without excessive suffering.

Additional studies when warranted. Depending on the novel food type, intended use, and preliminary findings, EFSA may require reproductive and developmental toxicity studies, chronic toxicity studies, or carcinogenicity studies. For novel foods intended for consumption by pregnant women or infants, reproductive toxicity data is more likely to be requested.

Common triggers for additional data requests

Test material mismatch. The most consequential and avoidable gap. The material tested in toxicological studies must be representative of the novel food as it will be placed on the market. If the production process changes between when the toxicological study was conducted and when the application is submitted, or if the test material was a different batch or specification, EFSA will flag the inconsistency. In some cases, the entire study must be repeated.

Incomplete genotoxicity battery. Submitting one genotoxicity test instead of the required battery. Each test addresses different endpoints — gene mutation, chromosomal damage — and they are not interchangeable.

NOAEL not clearly established. The highest dose in the study showing no adverse effects must be clearly identified, supported by statistical analysis, and distinguished from effects that are adaptive rather than adverse. Ambiguous NOAEL determinations lead to ADRs requesting clarification or additional dose groups.

Non-GLP studies. All toxicological studies must be conducted in compliance with Good Laboratory Practice principles. Studies conducted outside GLP-certified facilities, or without documented GLP compliance, will not be accepted by EFSA.

When waivers apply

Not every novel food requires the full toxicological package. EFSA's guidance allows for reduced requirements in specific circumstances:

If the novel food can demonstrate substantial equivalence to an existing food with established safety, the toxicological data requirements may be reduced. This requires detailed comparative analytical data — the equivalence claim must be substantiated, not assumed.

For novel foods that are simple, well-characterised substances with existing safety data in the literature (such as vitamins or minerals in new forms), a literature-based safety assessment may be sufficient, provided the data is comprehensive and directly applicable.

The decision to request reduced data must be justified in the application. Submitting without toxicological data and hoping EFSA will agree it was unnecessary is a poor strategy — it almost always results in an ADR.

The benchmark dose alternative

EFSA increasingly recommends the benchmark dose approach as an alternative to the traditional NOAEL for deriving the toxicological reference point. The BMD approach models the full dose-response relationship rather than relying on the specific dose levels tested, and provides a statistical confidence interval around the result.

Applicants can strengthen their toxicological assessment by providing a benchmark dose analysis alongside the traditional NOAEL determination. EFSA's BMD guidance and the PROAST software tool are publicly available.

Sources

- EFSA (2024). Scientific Guidance for the preparation of applications for authorisation of novel foods. *EFSA Journal*. - Own analysis of 152 published EFSA opinions (average section lengths). - Industry cost estimates for toxicological study packages (GreenQueen, 2025; CRO pricing data).