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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This opinion addresses the re‐evaluation of erythritol (E 968) as food additive and an application for its exemption from the laxative warning label requirement as established under Regulation (EU) No 1169/2011. Erythritol is a polyol obtained by fermentation with Moniliella pollinis BC or Moniliella megachiliensis KW3‐6, followed by purifications and drying. Erythritol is readily and dose‐dependently absorbed in humans and can be metabolised to erythronate to a small extent. Erythritol is then excreted unchanged in the urine. It does not raise concerns regarding genotoxicity. The dataset evaluated consisted of human interventional studies. The Panel considered that erythritol has the potential to cause diarrhoea in humans, which was considered adverse because its potential association with electrolyte and water imbalance. The lower bound of the range of no observed adverse effect levels (NOAELs) for diarrhoea of 0.5 g/kg body weight (bw) was identified as reference point. The Panel considered appropriate to set a numerical acceptable daily intake (ADI) at the level of the reference point. An ADI of 0.5 g/kg bw per day was considered by the Panel to be protective for the immediate laxative effect as well as potential chronic effects, secondary to diarrhoea. The highest mean and 95th percentile chronic exposure was in children (742 mg/kg bw per day) and adolescents (1532 mg/kg bw per day). Acute exposure was maximally 3531 mg/kg bw per meal for children at the 99th percentile. Overall, the Panel considered both dietary exposure assessments an overestimation. The Panel concluded that the exposure estimates for both acute and chronic dietary exposure to erythritol (E 968) were above the ADI, indicating that individuals with high intake may be at risk of experiencing adverse effects after single and repeated exposure. Concerning the new application, the Panel concluded that the available data do not support the proposal for exemption. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Xanthan gum (E 415) was re‐evaluated in 2017 by the former EFSA Panel on Food Additives and Nutrient sources added to Food. As a follow‐up to that assessment, the Panel on Food Additives and Flavourings (FAF) was requested to assess the safety of xanthan gum (E 415) for its uses as a food additive in food for infants below 16 weeks of age belonging to food category (FC) 13.1.5.1 (Dietary foods for infants for special medical purposes and special formulae for infants). In addition, the FAF Panel was requested to address the issues already identified during the re‐evaluation of the food additive when used in food for the general population. The process involved the publication of a call for data to allow the interested business operators to provide the requested information to complete the risk assessment. The Panel concluded that the technical data provided by the interested business operators support an amendment of the specifications for E 415 laid down in Commission Regulation (EU) No 231/2012. Due to the low validity of the available clinical studies, the Panel concluded that a reference point could not be derived from them but the results of the available studies on neonatal piglets could serve to derive a reference point. The Panel calculated the margin of exposure for infants below 16 weeks of age consuming food for special medical purposes (FC 13.1.5.1) for the highest xanthan gum exposure and concluded that there are no safety concerns for the use of xanthan gum (E 415) as a food additive in FC 13.1.5.1. [ABSTRACT FROM AUTHOR]

Sucrose esters of fatty acids (E 473) was re‐evaluated in 2004 by the former EFSA Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC Panel). In addition, the former EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS Panel) issued scientific opinions on the safety of sucrose esters of fatty acids (E 473) in 2010, 2012 and 2018. As a follow‐up to these assessments, the Panel on Food Additives and Flavourings (FAF) was requested to assess the safety of sucrose esters of fatty acids (E 473) for its uses as food additive in food for infants below 16 weeks of age. In addition, the FAF Panel was requested to address the issues already identified by the EFSA AFC and ANS Panels when used in food for the general population. The process involved the publication of calls for data to allow the interested business operators to provide the requested information to complete the risk assessment. The Panel concluded that the technical data provided by the interested business operators support an amendment of the specifications for sucrose esters of fatty acids (E 473) laid down in Commission Regulation (EU) No 231/2012. According to the available information, E 473 is not used in food categories (FCs) 13.1.1 and 13.1.5.1, including all types of food for infants below 16 weeks of age, and in FC 13.1.5.2. As a consequence, an assessment of the safety for the uses of E 473 as food additive in these FCs and age group was not performed. When the updated exposure estimates considering the provided use levels for some food categories are taken into account the estimates of exposure to sucrose esters of fatty acids (E 473) exceeded the group acceptable daily intake (ADI) of 40 mg/kg body weight (bw) per day for many population groups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The Panel on Food Additives and Flavourings (FAF) was requested to consider the JECFA evaluations of 28 flavouring substances in the Flavouring Group Evaluation 76 (FGE.76Rev2). Twenty‐one of these substances have been considered in FGE.76Rev1. Seven substances could not be evaluated, because of concerns with respect to genotoxicity. New genotoxicity data have been provided for 4‐methyl‐5‐vinylthiazole [FL‐no: 15.018] and 4,5‐dimethyl‐2‐isobutyl‐3‐thiazoline [FL‐no: 15.032], which are representative substances of [FL‐no: 15.005] and [FL‐no: 15.029, 15.030, 15.130 and 15.131], respectively. The Panel concluded that the concern for genotoxicity is ruled out for [FL‐no: 15.018 and 15.005]. The concerns for gene mutations and clastogenicity are ruled out for [FL‐no: 15.032, 15.029, 15.030, 15.130 and 15.131]. In vitro, [FL‐no: 15.032] induced micronuclei through an aneugenic mode of action. The available in vivo micronucleus study was not adequate to rule out the concern for potential aneugenicity in vivo. The Panel compared the lowest concentration resulting in aneugenicity in vitro with the use levels reported for [FL‐no: 15.032]. Based on this comparison, the Panel concluded that the use of [FL‐no: 15.032] at the maximum reported use levels does not raise a concern for aneugenicity. Based on structural similarity, for the remaining four substances [FL‐no: 15.029, 15.030, 15.130 and 15.131], an aneugenic potential may also be anticipated. Individual genotoxicity data are needed to establish whether they have aneugenic potential. The Panel agrees with JECFA conclusions for 24 flavouring substances 'No safety concern at estimated levels of intake as flavouring substances' when based on the MSDI approach. For six substances, more reliable information on uses and use levels are needed to refine the mTAMDI estimates. For 15 substances, use levels are needed to calculate the mTAMDIs. For [FL‐no: 15.109 and 15.113], information on the actual stereochemical composition is inadequate and the conclusion reached for the named substances cannot be applied to the materials of commerce. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.This publication is linked to the following EFSA Supporting Publications article: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2022.EN-7669/full [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We compared several families of algorithms for recursive integral time-extrapolation (RITE) algorithms for waves in isotropic and anisotropic media. These methods allow simulating accurate wave extrapolation with little numerical dispersion even when using larger time steps than are usually possible for conventional finite-difference methods. These various RITE algorithms all share the use of mixed space/wavenumber-domain operators derived from Fourier integral solutions of single-mode wave equations. We evaluated a taxonomy for RITE methods based on how they approximated the influence of medium heterogeneity. One family of methods uses mixed-domain series expansions to provide accurate approximations to heterogeneous extrapolators even for large time steps. We compared several methods for deriving coefficients for such series approximations. Another family of methods uses interpolation between different homogeneous extrapolations to approximate heterogeneous time extrapolation. Such methods can be based on interpolating either the extrapolators themselves or interpolating between reference wavefields extrapolated using different homogeneous parameters. Interpolation methods work well for smooth media, but can suffer from oscillatory artifacts at large velocity discontinuities unless the time step is small. We tested numerical examples of the various families of RITE algorithms to determine their relative strengths and limitations. [ABSTRACT FROM AUTHOR]