The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO 2 nanoparticles ( NP s) and data from an extended one‐generation reproductive toxicity ( EOGRT ) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension < 100 nm. In addition, the Panel noted that constituent particles < 30 nm amounted to less than 1% of particles by number. The Panel therefore considered that studies with TiO 2 NP s < 30 nm were of limited relevance to the safety assessment of E 171. The Panel concluded that although gastrointestinal absorption of TiO 2 particles is low, they may accumulate in the body. Studies on general and organ toxicity did not indicate adverse effects with either E 171 up to a dose of 1,000 mg/kg body weight (bw) per day or with TiO 2 NP s (> 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E 171 and potential neurotoxicity with TiO 2 NP s, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO 2 particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico‐chemical properties of TiO 2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO 2 particles that may be present in E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO 2 particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut‐off value for TiO 2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO 2 NP s. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E 171 can no longer be considered as safe when used as a food additive.

The EFSA Scientific Committee was asked to provide guidance on the most appropriate in vivo tests to follow up on positive in vitro results for aneugenicity, and on the approach to risk assessment for substances that are aneugenic but not clastogenic nor causing gene mutations. The Scientific Committee confirmed that the preferred approach is to perform an in vivo mammalian erythrocyte micronucleus test with a relevant route of administration. If this is positive, it demonstrates that the substance is aneugenic in vivo . A negative result with evidence that the bone marrow is exposed to the test substance supports a conclusion that aneugenic activity is not expressed in vivo . If there is no evidence of exposure to the bone marrow, a negative result is viewed as inconclusive and further studies are required. The liver micronucleus assay, even though not yet fully validated, can provide supporting information for substances that are aneugenic following metabolic activation. The gastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenic potential at the initial site of contact for substances that are aneugenic in vitro without metabolic activation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committee concluded that, in principle, health‐based guidance values can be established for substances that are aneugenic but not clastogenic nor causing gene mutations, provided that a comprehensive toxicological database is available. For situations in which the toxicological database is not sufficient to establish health‐based guidance values, some approaches to risk assessment are proposed. The Scientific Committee recommends further development of the gastrointestinal micronucleus test, and research to improve the understanding of aneugenicity to support risk assessment.

Following a request from the European Commission, EFSA developed updated scientific guidance to assist applicants in the preparation of applications on smoke flavouring primary products. This guidance describes the scientific data to be included in the applications for the authorisation of new smoke flavouring primary products, as well as for the renewal or for the modification of existing authorisations, submitted respectively under Articles 7, 12 and 11 of Regulation (EC) No 2065/2003. Information to be provided in all applications relates to: the characterisation of the primary product, including the description of the source materials, manufacturing process, chemical composition, specifications and stability; the proposed uses and use levels and the assessment of the dietary exposure; the safety data, including information on the genotoxic potential of the identified components and of the unidentified fraction of the primary product, toxicological data other than genotoxicity and information on the safety for the environment. For the toxicological studies a tiered approach is applied, for which the testing requirements, key issues and triggers are described. A description of the standard uncertainties relevant for the evaluation of primary products and how these are considered in the standardised risk assessment procedure is also included. The applicant should generate the data requested in each section to support the safety assessment of the smoke flavouring primary product. On the basis of the submitted data, EFSA will assess the safety of the primary product and conclude whether or not it presents risks to human health and to the environment under the proposed conditions of use.

The additive is a preparation of 3-phytase which is produced by a genetically modified strain of Komagataella pastoris. The production strain and its recombinant DNA were not detected in the final product. Therefore, the additive does not give rise to safety concerns with regard to the genetic modification of the production strain. Based on the results of the tolerance studies provided, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive is safe for chickens for fattening and laying hens at the dose of 1,000 FTU/kg feed. However, a margin of safety could not be established for laying hens. The production strain belongs to a species considered to qualify for the qualified presumption of safety (QPS) approach to safety assessment when used for enzyme production. Since the identity of the strain was unambiguously established and the genetic modification raised no concerns, the FEEDAP Panel concludes that the use of the additive as a feed additive is of no concerns for consumers. The additive is not an irritant to eyes and skin, and it is not a dermal sensitiser. Owing to the proteinaceous nature of the active substance, the additive is a potential respiratory sensitiser, however, exposure may be limited. The use of the product as a feed additive does not pose risks to the environment. The Panel concluded that the additive has a potential to increase the availability of phytate phosphorus in chickens for fattening at 500 FTU/kg and in laying hens at 1,000 FTU/kg feed. This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made.The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. SummaryFollowing a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of 3-phytase FLF1000 (3-phytase) as a feed additive for chickens for fattening and laying hens.The additive contains a 3-phytase (EC 3.1.3.8.) which is produced by a genetically modified strain of Komagataella pastoris. The identity of the strain was confirmed as K. pastoris. The viable production strain and its recombinant DNA were not detected in the final product. The additive does not give rise to safety concerns with regard to the genetic modification of the production strain.Based on the results of the two studies provided, the FEEDAP Panel concluded that the additive is safe for chickens for fattening and laying hens at the dose of 1,000 FTU/kg feed. However, in the tolerance study in laying hens, the 10-fold dose group showed a tendency to have a lower body weight at the end of the study and had a significantly higher concentration of alkaline phosphatase in blood compared to the hens fed the negative control diet. Consequently, a mar...

No abstract