Flavouring Group Evaluation 413 (FGE.413): Naringenin.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of naringenin [FL-no: 16.132] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. No other substances with sufficient structural similarity have been identified in existing FGEs that could be used to support a read-across approach. The information provided on the manufacturing process, the composition and the stability of [FL-no: 16.132] was considered sufficient. From studies carried out with naringenin, the Panel concluded that there is no concern with respect to genotoxicity. The use of naringenin as a flavouring substance at added portions exposure technique (APET) exposure levels is unlikely to pose a risk for drug interaction. For the toxicological evaluation of naringenin, the Panel requested an extended one-generation toxicity study on naringenin, in line with the requirements of the Procedure and to investigate the consequence of a possible endocrine-disrupting activity. The Panel considered that changes in thymus weight, litter size, post-implantation loss and a consistent reduced pup weight in the high-dose F2 generation could not be dismissed and selected therefore, the mid-dose of 1320 mg/kg body weight (bw) per day for the parental males as the no observed adverse effect level (NOAEL) of the study. The exposure estimates for [FL-no: 16.132] (31,500 and 50,000 µg/person per day for children and adults, respectively) were above the threshold of toxicological of concern (TTC) for its structural class (III). Using the NOAEL of 1320 mg/kg bw per day at step A4 of the procedure, margins of exposure (MoE) of 1590 and 630 could be calculated for adults and children, respectively. Based on the calculated MoEs, the Panel concluded that the use of naringenin as a flavouring substance does not raise a safety concern.

Flavouring group evaluation 419 (FGE.419): 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of 2-methyl-1-(2-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)butan-1-one [FL-no: 16.134] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. The substance has not been reported to occur naturally and is chemically synthesised. In food, it is intended to be used as a flavouring substance only in chewing gum. The chronic dietary exposure to [FL-no: 16.134] was estimated to be 45 µg/person per day for a 60-kg adult and 28.4 µg/person per day for a 15-kg 3-year-old child. [FL-no: 16.134] did not show genotoxicity in a bacterial reverse mutation test and an in vitro mammalian cell micronucleus assay. Based on the submitted toxicokinetic and metabolism data, it can be predicted that the flavouring substance is metabolised to innocuous products only. The Panel derived a lower confidence limit of the benchmark dose (BMDL) of 0.71 mg/kg bw per day for a 20% increase in the relative thyroid (including parathyroid) weight observed in a 90-day toxicity study in rats. Based on this BMDL, adequate margins of exposure of 887 and 374 could be calculated for adults and children, respectively. The Panel concluded that there is no safety concern for [FL-no: 16.134], when used as a flavouring substance at the estimated level of dietary exposure, based on the intended use and use levels as specified in Appendix B. The Panel further concluded that the combined exposure to [FL-no: 16.134] from its use as a food flavouring substance and from its presence in toothpaste and mouthwash is also not of safety concern.

Scientific opinion on the renewal of the authorisation of Smoke Concentrate 809045 (SF-003) as a smoke flavouring Primary Product.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Smoke Concentrate 809045 (SF-003), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Product Smoke Concentrate 809045 is obtained by pyrolysis of beech wood. The Panel concluded that the compositional data provided on the Primary Product are adequate. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.1 to 1.5 mg/kg body weight (bw) per day at the mean and from 0.2 to 5.2 mg/kg bw per day at the 95th percentile. The Panel concluded that eleven components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan-2(5H)-one and benzene-1,2-diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 µg/kg bw per day for DNA-reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Scientific opinion on the renewal of the authorisation of Zesti Smoke Code 10 (SF-002) as a smoke flavouring Primary Product.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Zesti Smoke Code 10 (SF-002), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Zesti Smoke Code 10 is obtained by pyrolysis of hickory and oak woods. Given the limitations of the quantification approach employed by the applicant, the Panel could not judge whether the applied methods meet the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.02 to 4.6 mg/kg body weight (bw) per day at the mean and from no dietary exposure to 13.0 mg/kg bw per day at the 95th percentile. The Panel concluded that four components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan-2(5H)-one and benzene-1,2-diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 µg/kg bw per day for DNA-reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Scientific opinion on the renewal of the authorisation of Scansmoke SEF7525 (SF-004) as a smoke flavouring Primary Product.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Scansmoke SEF7525 (SF-004), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Scansmoke SEF7525 is obtained from a tar produced from a mixture of red oak, white oak, maple, beech and hickory. Based on the compositional data, the Panel noted that the identified and quantified proportion of the solvent-free fraction amounts to 32.6 weight (wt)%, thus the applied method does not meet the legal quality criterion that at least 50% of the solvent-free fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with Food Additive Intake Model (FAIM) ranged from 0.6 to 3.8 mg/kg body weight (bw) per day at the mean and from 1.1 to 10.1 mg/kg bw per day at the 95th percentile. Based on the available information on genotoxicity on 44 identified components, the Panel concluded that two substances in the Primary Product, styrene and benzofuran, raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. Considering that the exposure estimates for styrene and benzofuran are above the threshold of toxicological concern (TTC) value of 0.0025 kg/kg bw per day for DNA-reactive mutagens and/or carcinogens and since further data are needed to clarify their potential genotoxicity, the Panel concluded that the potential safety concern for genotoxicity of the Primary Product cannot be ruled out.

Scientific opinion on the renewal of the authorisation of Fumokomp (SF-009) as a smoke flavouring Primary Product.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product Fumokomp (SF-009), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003 (in the renewal application the Primary Product is reported as 'Fumokomp Conc.'). This opinion refers to an assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. Fumokomp Conc. is produced by pyrolysis of beech and hornbeam woods. Gas chromatography-mass spectrometry (GC-MS) was applied for both identification and quantification of the volatile constituents of the Primary Product. Given the limitations of the method, the Panel cannot judge with confidence whether the applied method meets the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. Moreover, the Panel concluded that the absence of furan-2(5H)-one from the Primary Product was not convincingly demonstrated. At the maximum proposed use levels, dietary exposure estimates calculated with FAIM ranged from 0.04 to 0.9 mg/kg body weight (bw) per day at the mean and from 0.1 to 1.5 mg/kg bw per day at the 95th percentile. The information available on the 32 identified components of the Primary Product, although limited, did not indicate a concern for genotoxicity for any of these substances. However, whole mixture testing in an in vitro mouse lymphoma assay gave positive results which would require an adequate in vivo follow-up study. In addition, the potential for aneugenicity of the Primary Product has not been adequately investigated. Accordingly, the potential safety concern for genotoxicity of the Primary Product cannot be ruled out.

Scientific opinion on the renewal of the authorisation of SmokEz C-10 (SF-005) as a smoke flavouring Primary Product.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product SmoKEz C-10 (SF-005), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. SmoKEz C-10 is obtained by pyrolysis of maple, oak, hickory, ash, birch, beech and cherry woods. Given the limitations of the quantification approach employed by the applicant, the Panel could not judge whether the applied methods meet the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.01 to 5.1 mg/kg body weight (bw) per day at the mean and from no dietary exposure to 18.1 mg/kg bw per day at the 95th percentile. The Panel concluded that five components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan-2(5H)-one and benzene-1,2-diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 µg/kg bw per day for DNA-reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Scientific opinion on the renewal of the authorisation of proFagus Smoke R714 (SF-001) as a smoke flavouring Primary Product.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product proFagus Smoke R714 (SF-001), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. ProFagus Smoke R714 is obtained by pyrolysis of beech and oak woods as main source materials. Based on the compositional data, the Panel noted that the identified and quantified proportion of the solvent-free fraction amounts to 39 weight (wt)%, thus the applied method does not meet the legal quality criterion that at least 50% of the solvent-free fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.7 to 10.9 mg/kg body weight (bw) per day at the mean and from 2.2 to 42.5 mg/kg bw per day at the 95th percentile. The Panel concluded that three components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan-2(5H)-one, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for this component are above the threshold of toxicological concern (TTC) of 0.0025 µg/kg bw per day for DNA-reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Scientific opinion on the renewal of the authorisation of SmokEz Enviro-23 (SF-006) as a smoke flavouring Primary Product.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product SmokEz Enviro-23 (SF-006), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. SmokEz Enviro-23 is obtained by pyrolysis of oak, maple, hickory, ash, birch, beech and cherry woods. Given the limitations of the quantification approach employed by the applicant, the Panel could not judge whether the applied methods meet the legal quality criterion that at least 80% of the volatile fraction shall be identified and quantified. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.01 to 3.2 mg/kg body weight (bw) per day at the mean and from no dietary exposure to 9.5 mg/kg bw per day at the 95th percentile. The Panel concluded that four components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan-2(5H)-one and benzene-1,2-diol, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for these two components are above the threshold of toxicological concern (TTC) of 0.0025 µg/kg bw per day for DNA-reactive mutagens and/or carcinogens, the Panel concluded that the Primary Product raises concern with respect to genotoxicity.

Scientific opinion on the renewal of the authorisation of proFagus Smoke R709 (SF-008) as a smoke flavouring Primary Product.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the smoke flavouring Primary Product proFagus Smoke R709 (SF-008), for which a renewal application was submitted in accordance with Article 12(1) of Regulation (EC) No 2065/2003. This opinion refers to the assessment of data submitted on chemical characterisation, dietary exposure and genotoxicity of the Primary Product. ProFagus Smoke R709 is obtained by pyrolysis of beech and oak wood as main source materials. The panel concluded that the compositional data provided on the Primary Product are adequate. At the maximum proposed use levels, dietary exposure estimates calculated with DietEx ranged from 0.8 to 12.2 mg/kg body weight (bw) per day at the mean and from 2.3 to 51.4 mg/kg bw per day at the 95th percentile. The Panel concluded that three components in the Primary Product raise a potential concern for genotoxicity. In addition, a potential concern for genotoxicity was identified for the unidentified part of the mixture. The Primary Product contains furan-2(5H)-one, for which a concern for genotoxicity was identified in vivo upon oral administration. Considering that the exposure estimates for this component are above the TTC of 0.0025 µg/kg bw per day for DNA-reactive mutagens and/or carcinogens, the panel concluded that the Primary Product raises concern with respect to genotoxicity.

Flavouring Group Evaluation 217 Revision 3 (FGE.217Rev3): consideration of genotoxic potential for α,ß-unsaturated ketones and precursors from chemical subgroup 4.1 of FGE.19: lactones.

The Panel on Food Additives and Flavourings of the European Food Safety Authority was requested to evaluate the genotoxic potential of four flavouring substances [FL-no: 10.023, 10.030, 10.057 and 13.012] from subgroup 4.1 of FGE.19. For three of these substances [FL-no: 10.023, 10.030 and 13.012], the concern for genotoxicity has been ruled out in previous revisions of Flavouring Group Evaluation 217 (FGE.217). However, in FGE.217Rev2, a concern for genotoxicity could not be ruled out for 3a,4,5,7a-tetrahydro-3,6-dimethylbenzofuran-2(3H)-one [FL-no: 10.057]. After publication of FGE.217Rev2, industry provided additional genotoxicity studies for [FL-no: 10.057], which are evaluated in the present opinion FGE.217Rev3. The flavouring substance [FL-no: 10.057] did not induce gene mutations or numerical or structural chromosomal aberrations in vitro. Based on these data, the Panel concluded that the concern for genotoxicity is ruled out for [FL-no: 10.057]. Consequently, it can be evaluated through the Procedure.

Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs.

In 2015, EFSA established a temporary tolerable daily intake (t-TDI) for BPA of 4 µg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re-evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re-evaluation, a pre-established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2 ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57-73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2 ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure.

Flavouring Group Evaluation 21 Revision 6 (FGE.21Rev6): thiazoles, thiophenes, thiazoline and thienyl derivatives from chemical groups 29 and 30.

The Panel on Food additives and Flavourings (FAF) was requested to evaluate the flavouring substances 2,4-dimethyl-3-thiazoline [FL-no: 15.060] and 2-isobutyl-3-thiazoline [FL-no: 15.119] in Flavouring Group Evaluation 21 revision 6 (FGE.21Rev6). FGE.21Rev6 deals with 41 flavouring substances of which 39 have been already evaluated to be of no safety concern when based on the MSDI approach. For [FL-no: 15.060 and 15.119], a concern for genotoxicity was raised in FGE.21. Genotoxicity data have been submitted for the supporting substance 4,5-dimethyl-2-isobutyl-3-thiazoline [FL-no: 15.032] evaluated in FGE.76Rev2. The concerns for gene mutations and clastogenicity are ruled out for [FL-no: 15.032] and for the structurally related substances [FL-no: 15.060 and 15.119], but not for aneugenicity. Therefore, the aneugenic potential of [FL-no: 15.060 and 15.119] should be investigated in studies with the individual substances. For [FL-no: 15.054, 15.055, 15.057, 15.079 and 15.135], (more reliable) information on uses and use levels is needed to (re)calculate the mTAMDIs in order to finalise their evaluation. Provided that information is submitted for [FL-no: 15.060 and 15.119] with respect to potential aneugenicity, that would allow evaluation of these substances through the Procedure, also for these two substances, more reliable data on uses and use levels would be required. Upon submission of such data, additional data on toxicity may become necessary for all seven substances. For [FL-no: 15.054, 15.057, 15.079 and 15.135], information on the actual percentages of stereoisomers in the material of commerce based on analytical data should be provided.

Scientific Guidance on the data required for the risk assessment of flavourings to be used in or on foods.

Following a request from the European Commission, EFSA developed a new scientific guidance to assist applicants in the preparation of applications for the authorisation of flavourings to be used in or on foods. This guidance applies to applications for a new authorisation as well as for a modification of an existing authorisation of a food flavouring, submitted under Regulation (EC) No 1331/2008. It defines the scientific data required for the evaluation of those food flavourings for which an evaluation and approval is required according to Article 9 of Regulation (EC) No 1334/2008. This applies to flavouring substances, flavouring preparations, thermal process flavourings, flavour precursors, other flavourings and source materials, as defined in Article 3 of Regulation (EC) No 1334/2008. Information to be provided in all applications relates to: (a) the characterisation of the food flavouring, including the description of its identity, manufacturing process, chemical composition, specifications, stability and reaction and fate in foods; (b) the proposed uses and use levels and the assessment of the dietary exposure and (c) the safety data, including information on the genotoxic potential of the food flavouring, 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. Applicants should generate the data requested in each section to support the safety assessment of the food flavouring. Based on the submitted data, EFSA will assess the safety of the food flavouring and conclude whether or not it presents risks to human health and to the environment, if applicable, under the proposed conditions of use.

Scientific opinion on Flavouring group evaluation 216 revision 2 (FGE.216Rev2): consideration of the genotoxicity potential of α,ß-unsaturated 2-phenyl-2-alkenals from subgroup 3.3 of FGE.19.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the genotoxic potential of five flavouring substances from subgroup 3.3 of FGE.19, in the Flavouring Group Evaluation 216 (FGE.216). In FGE.216 and in FGE.216Rev1, the CEF Panel requested additional genotoxicity data on 2-phenylcrotonaldehyde [FL-no: 05.062], the representative for these five substances. New experimental data on [FL-no: 05.062] were provided and are evaluated in the present revision of FGE.216 (FGE.216Rev2). Based on the new data, the Panel concluded that, for all the five substances, the concerns for gene mutations and clastogenicity are ruled out by the negative results observed in an in vivo gene mutation assay and in an in vivo comet assay, respectively. In vitro, [FL-no: 05.062] induced micronuclei through an aneugenic mode of action. The available in vivo micronucleus studies were inconclusive and cannot be used to rule out potential aneugenicity of [FL-no: 05.062] in vivo. Therefore, the Panel compared the lowest concentration resulting in aneugenicity in vitro with the use levels reported for this substance. Based on this comparison, the Panel concluded that the use of the flavouring substance [FL-no: 05.062] at the reported use levels in several food categories would raise a concern for aneugenicity. Based on structural similarity, for the remaining four substances in this FGE [FL-no: 05.099, 05.100, 05.175 and 05.222], an aneugenic potential may also be anticipated. For these four substances, individual data are needed to establish whether they have aneugenic potential. Accordingly, it is currently not appropriate to assess any of these five substances through the Procedure for the evaluation of flavouring substances.

Scientific opinion on flavouring group evaluation 415 (FGE.415): (E)-3-benzo[1,3]dioxol-5-yl-N,N-diphenyl-2-propenamide.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the substance (E)-3-benzo[1,3]dioxol-5-yl-N,N-diphenyl-2-propenamide [FL-no: 16.135] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. The substance has not been reported to occur naturally and it is chemically synthesised. It is intended to be used as a flavouring substance in specific categories of food, but not intended to be used in beverages. The chronic dietary exposure to [FL-no: 16.135] estimated using the added portions exposure technique (APET), is calculated to be 780 µg/person per day for a 60-kg adult and 480 µg/person per day for a 15-kg 3-year-old child. [FL-no: 16.135] did not show genotoxic effects in bacterial mutagenicity and mammalian cell micronucleus assays in vitro. Developmental toxicity was not observed in a study in rats at the dose levels up to 1,000 mg/kg body weight (bw) per day. The Panel derived a BMDL of 101 mg/kg bw per day from a 90-day toxicity study. Based on this BMDL, adequate margins of exposure of 7,800 and 3,200 could be calculated for adults and children, respectively. The Panel concluded that there is no safety concern for [FL-no: 16.135], when used as a flavouring substance at the estimated level of dietary exposure calculated using the APET approach, based on the intended uses and use levels as specified in Appendix B. The Panel further concluded that the combined exposure to [FL-no: 16.135] from its use as a food flavouring substance and from its presence in toothpaste is also not of safety concern.

Scientific opinion on Prosmoke BW 01.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of Prosmoke BW 01 as a new smoke flavouring primary product, in accordance with Regulation (EC) No 2065/2003. Prosmoke BW01 is produced by pyrolysis of beechwood (Fagus sylvatica L.) sawdust. Its water content is estimated at 56 wt%, the total identified volatile fraction accounts for 28 wt% of the primary product, corresponding to 64% of the solvent-free mass, while the unidentified fraction amounts to 16 wt% of the primary product. Analytical data provided for three batches demonstrated that their batch-to-batch-variability was sufficiently low. However, for the batch used for the toxicological studies, there were substantial deviations in the concentration of nearly all the constituents compared to the other three batches. The dietary exposure of Prosmoke BW 01 was estimated to be between 6.2 and 9.2 mg/kg body weight (bw) per day, respectively, using SMK-EPIC and SMK-TAMDI. Using the FAIM tool, the 95th percentile exposure estimates ranged from 3.2 mg/kg bw per day for the elderly to 17.9 mg/kg bw per day for children. The Panel noted that furan-2(5H)-one is present in all batches of the primary product at an average concentration of 0.88 wt%. This substance was evaluated by the FAF Panel as genotoxic in vivo after oral exposure. The Panel considered that the (geno)toxicity studies available on the whole mixture were not adequate to support the safety assessment, due to limitations in these studies and because they were performed with a batch which may not be representative for the material of commerce. Considering that the exposure estimates for furan-2(5H)-one are above the TTC value of 0.0025 µg/kg bw per day (or 0.15 µg/person per day) for DNA-reactive mutagens and/or carcinogens, the Panel concluded that Prosmoke BW 01 raises a concern with respect to genotoxicity.

Scientific opinion on flavouring group evaluation 414 (FGE.414): 2-hydroxy-4-methoxybenzaldehyde.

The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of the substance 2-hydroxy-4-methoxybenzaldehyde [FL-no: 05.229] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. 2-Hydroxy-4-methoxybenzaldehyde belongs to chemical group 23 (Commission Regulation (EC) No 1565/2000) and is structurally related to the hydroxy- and alkoxy-ring substituted benzyl derivatives evaluated in FGE.52 and in FGE.20Rev4. The Panel considered the structural/metabolic similarity sufficient to evaluate the candidate substance following a group-based approach according to the EFSA Guidance on the data required for the risk assessment of flavourings to be used in or on foods. The information provided on the manufacturing process, the composition and the stability of [FL-no: 05.229] was considered sufficient. From studies carried out with this substance, the Panel concluded that there is no concern with respect to genotoxicity. Based on QSAR evaluation of possible metabolism, and based on information from structurally related substances, various metabolic routes can be anticipated, which only result in the formation of innocuous metabolites. The exposure estimates for [FL-no: 05.229] (24 and 60 µg/person per day for children and adults, respectively) were below the Threshold of Toxicological Concern (TTC) for its structural class (I). Accordingly, toxicity studies are not required and the Panel concluded at step A3 of the Procedure that 2-hydroxy-4-methoxybenzaldehyde is not of safety concern when used as a flavouring substance at the intended uses and use levels. Cumulative exposure estimates for 2-hydroxy-4-methoxybenzaldehyde and three structurally related substances (2.4 and 6.2 mg/kg body weight (bw) per day for adults and children, respectively) are above the TTC for structural class I, but below the ADI (acceptable daily intake) of 0-10 mg/kg bw per day for vanillin, which is one of these structurally related substances. Therefore, the cumulative exposure to these four substances [FL-no: 05.015, 05.018, 05.229 and 09.749] also does not raise a safety concern.

Guidance on aneugenicity assessment.

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.

Safety assessment of titanium dioxide (E171) as a food additive.

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 TiO2 nanoparticles (NPs) 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 TiO2 NPs < 30 nm were of limited relevance to the safety assessment of E 171. The Panel concluded that although gastrointestinal absorption of TiO2 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 TiO2 NPs (> 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 TiO2 NPs, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO2 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 TiO2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO2 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 TiO2 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 TiO2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO2 NPs. 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.