The European Food Safety Authority (EFSA) has introduced new guidance for evaluating nanoparticles in food that may dissolve in lipids before consumption. By using the 1-octanol-water partition coefficient (K_OW) method nanospecific considerations for safety assessments may potentially be waived. However, EFSA also outlines scenarios where the K_OW method is not applicable, such as materials with coatings, surface modifications, or heterogeneous mixtures.

EFSA published new Annex to guidance for assessing nanoparticles in food

In July 2024, the European Food Safety Authority (EFSA) published an Annex to its 2021“Guidance on technical requirements for regulated food and feed product applications to establish the presence of small particles including nanoparticles”. This Annex B explains that the 1-octanol-water partition coefficient (K_OW) can be used to waive nanospecific considerations for particles that dissolve in lipids before consumption, similar to the waiver for substances that dissolve in aqueous media.

The use of K_OW to determine nanoparticle solubility in fat

K_OW is a ratio that describes how a substance distributes between two immiscible solvents: octanol (organic) and water (aqueous). For nanoparticles, however, the K_OW method is not suitable, in contrast with its common use in chemical risk assessment. For organic nanoparticles, EFSA states that an estimated or measured K_OW value for the organic core can also provide a good indication of how well that nanoparticle dissolves in fatty media. If the log K_OW value is above 3, solubility in fats is very likely.

Limitations of the K_OW method

EFSA also outlines several scenarios where the use of K_OW is not applicable. These include materials with coatings, surface modifications, or encapsulation, as well as materials with surface active or amphiphilic properties. Additionally, the K_OW method is not suitable for chemically heterogeneous mixtures of organic substances, or for mixtures of organic and/or inorganic substances.

Reflections by RIVM

For organic powders consisting of small particles, risk assessors must decide whether nanospecific considerations should be included in the safety evaluation. If hydrophobic organic substances dissolve in fatty or hydrophobic matrices before consumption, particles will no longer be present and nanospecific considerations will not be relevant.

The new Annex helps to avoid unnecessary work for industry and regulators, as the K_OW can be easily estimated by mathematical models. It offers a method to identify situations where nanospecific considerations are not needed for the safety assessment of food and feed related applications. It is important to note that EFSA has identified several cases where using K_OW is inappropriate.

Typically, the dissolution of substances can be affected by coatings and surface modifications, meaning that the dissolution may not depend solely on the chemical composition of the particle core. The phrase “before consumption” further constrains the use of K_OW. These limitations make it difficult to apply this method to risk assessments of nanoparticles used in applications other than food and feed. Nonetheless, this approach could help identify situations where read-across to non-nanoforms is possible and when nanospecific considerations may not be needed.

Reed the Dutch summary: Nieuw EFSA-richtsnoer voor nanomaterialen die oplossen in vet