New Guidance for Food Flavorings in Europe

The European Food Safety Authority (EFSA) clarifies regulations on flavorings

A little spice makes everything nice, but what about artificial flavoring? According to the European Food Safety Authority (EFSA), flavorings are “substances used to impart taste and/or smell to food.” In order for any flavoring to be sold in Europe, it has to pass safety testing for intake levels, absorption, metabolism, and toxicity. Typically, not much flavoring is needed in a product, meaning consumers’ exposure to the chemical is low. However, each substance must still pass every test to be included on the EFSA’s safe list.

Recently, the EFSA released a new guidance (adopted 9 November 2022, published 23 December 2022) on safety testing for food flavorings (under Regulation (EC) No 1331/2008). This guidance applies to applications for a new authorisation as well as for a modification of an existing authorisation of a food flavoring, submitted under Regulation (EC) No 1331/2008.

The new guidance defines scientific data requirements for characterization of food flavoring (identity, manufacturing process, composition, stability, and reaction and fate in foods), intended use, and use levels together with a dietary exposure assessment (for example, use in children under 16 weeks old).

Specific attention is paid in the guidance to small particles, read-across (use of relevant toxicological information from chemicals with a similar chemical structure), genotoxicity, and ADME (absorption, distribution, metabolism, and excretion).

 To learn more about this new guidance and what it could mean for researchers and manufacturers, we spoke with Sylvia Pelgrom, Charles River’s Section Head Regulatory Toxicology from Den Bosch, The Netherlands.

Eureka: Cutting through the jargon a bit, what exactly is being proposed that is different from current regulations?

Sylvia Pelgrom: The new guidance is specifically for food flavorings (smoke flavoring has its own guidance), proposing a tiered approach to considering information on (a) the characterization of the food flavoring, (b) its use and use levels and (c) safety data. Considering the safety data, the genotoxicity data are now the starting point, and needs to be considered (together with ADME) before performing any other toxicity study.’

For Tier I, genotoxicity studies begin with in vitro with in vivo follow up as needed, depending on the results of initial testing. ADME studies (OECD TG 417) are also required, and this data is considered crucial for read-across considerations.

For Tier II, if there is no genotoxicity concern and considering exposure information, they move on to read-across consideration. If there is negligible absorption, the EFSA will require repeated dose 90 day oral toxicity study (OECD TG 408). If absorption is not negligible, they will require reproductive toxicity studies EOGRTS (OECD TG443) for all cohorts.

Finally for Tier III, in case safety concerns are observed in the available toxicity information, EFSA can require specialized studies to investigate the relevance of effects observed in Tier II studies.

Eureka: Historically, what are some of the potential dangers of food flavorings that make it important to do these kinds of tests?

SP: Flavorings are not specifically dangerous, and since the intake of flavorings is limited, they were considered relatively harmless. Previously, the evaluation of food flavorings was based on application of the concept of thresholds of toxicological concern (TTC). In the new guidance, use levels and safety information are considered together.

Eureka: Will the new regulations make the approval process easier or harder?

SP: The new Scientific Guidance makes it clearer and considers also non-testing information (3R). EFSA uses a Tiered approach, so only the relevant information for the application needs to be given, and by providing the relevant data, the overall assessment can be made by EFSA. All relevant data needs to be considered (including information from the open literature and/or from comparable chemical compounds), and at CRL we have experience with both literature searches and read-across evaluation. This approach results in performing only the toxicity studies for which safety data is lacking. In addition, we have a good knowledge of in silico prediction (QSAR), which can also be helpful for read-across information and for the parameters to be included in the in vivo studies.

Eureka: Are there proposed changes underway for any similar regulations, like for example food coloring?

SP: Yes. The 3Rs will become more and more important, so for other EFSA regulations a tiered approach will become necessary (considering all available information and use of read-across information and in silico prediction). Using this tiered approach reduces the number of in vivo studies, helping support the EFSA’s commitment to the 3Rs.