ABSTRACT
BACKGROUND: The delivery of safe drinking water has high public health relevance, as reflected in the Sustainable Development Goals (SDG6). Several precautionary actions have reduced the burden associated with infectious diseases in high-income countries; however, pollution in source waters, inadequate disinfection, and premise plumbing, along with an increased awareness that intrusion in the drinking water distribution system, represents risk factors for gastrointestinal illness linked to consume of drinking water. Sporadic cases of waterborne infections are expected to be underreported since a sick person is less likely to seek healthcare for a self-limiting gastrointestinal infection. Hence, knowledge on the true burden of waterborne diseases is scarce. The primary aim with the present study was to estimate the risk of gastrointestinal illness associated with drinking tap water in Norway. METHODS: We conducted a 12-month prospective cohort study where participants were recruited by telephone interview after invitation based on randomised selection. A start up e-survey were followed by 12 monthly SMS questionnaires to gather information on participants characteristics and drinking tap water (number of 0.2L glasses per day), incidence, duration and symptoms associated with gastrointestinal illness. Associations between the exposure of drinking tap water and the outcome of risk of acute gastrointestinal illness (AGI) were analysed with linear mixed effects models. Age, sex, education level and size of the drinking water supply were identified as potential confounders and included in the adjusted model. RESULTS: In total, 9,946 persons participated in this cohort study, accounting for 11.5% of all invited participants. According to the data per person and month (99,446 monthly submissions), AGI was reported for 5,508 person-months (5.5 per 100 person-months). Severe AGI was reported in 819 person-months (0.8 per 100 person-months). Our study estimates that 2-4% of AGI in Norway is attributable to drinking tap water. CONCLUSIONS: This is the largest cohort study in Norway estimating the burden of self-reported gastrointestinal infections linked to the amount of tap water drunk in Norway. The data indicate that waterborne AGI is not currently a burden in Norway, but the findings need to be used with caution. The importance of continued efforts and investments in the maintenance of drinking water supplies in Norway to address the low burden of sporadic waterborne cases and to prevent future outbreaks needs to be emphasised.
Subject(s)
Drinking Water , Gastrointestinal Diseases , Humans , Norway/epidemiology , Male , Female , Prospective Studies , Adult , Middle Aged , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Young Adult , Aged , Adolescent , Risk Assessment , Risk Factors , Waterborne Diseases/epidemiology , Surveys and Questionnaires , Water SupplyABSTRACT
2,5-Dimethylfuran (DMF) and furfuryl alcohol (FFA) are two substituted furans that are formed during the processing of foods and have also been used as food flavorings. DMF and FFA are proposed to be bioactivated by human sulfotransferases (SULTs) which are not expressed in conventional cell lines used for genotoxicity testing. Therefore, in addition to the standard V79 cell line, we used a transfected V79 derived cell line co-expressing human cytochrome P450 (CYP) 2E1 and human SULT1A1 to assess the genotoxicity of DMF and FFA. The alkaline single cell gel electrophoresis (SCGE) assay was used to detect DNA damage in the form of single strand breaks and alkali-labile sites after exposure to DMF (0.5h; 0.5, 1, 1.5 or 2mM) or FFA (3h; 1, 3, 6 or 15mM). DMF induced DNA damage in V79 cells in a concentration-dependent manner irrespective of the expression of human CYP2E1 and SULT1A1. Almost no increase in the level of DNA damage was detected after exposure to FFA, except for a weak effect at the highest concentration in the transfected cell line. The results suggest that DNA damage in V79 cells from exposure to DMF detected by the alkaline SCGE assay is independent of human CYP2E1 and SULT1A1, and the genotoxic effect of FFA, as assessed by SCGE, is minimal in V79 cells.
Subject(s)
Arylsulfotransferase/metabolism , Cytochrome P-450 CYP2E1/metabolism , DNA Damage , Furans/toxicity , Mutagens/toxicity , Animals , Arylsulfotransferase/genetics , Biotransformation , Cell Line , Comet Assay , Cricetulus , Cytochrome P-450 CYP2E1/genetics , DNA/drug effects , Furans/metabolism , Humans , Transfection , TransgenesABSTRACT
The EFSA Panel on Food Additives and Flavourings was requested to evaluate 14 flavouring substances assigned to the Flavouring Group Evaluation 80 (FGE.80), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Thirteen substances have already been considered in FGE.80 and its revision and in FGE.96 [FL-no: 10.005, 10.024, 10.025, 10.050, 10.061, 10.069, 10.070, 10.072, 10.169, 13.009, 13.012, 13.161 and 16.055]. The remaining flavouring substance 3a,4,5,7a-tetrahydro-3,6-dimethylbenzofuran-2(3H)-one [FL-no: 10.057] has been cleared with respect to genotoxicity in FGE.217Rev3 and it is considered in this revision 2 of FGE.80. The substance [FL-no: 10.057] was evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, threshold of toxicological concern (TTC) and available data on metabolism and toxicity. The Panel concluded that [FL-no: 10.057] does not give rise to safety concerns at its levels of dietary intake, when estimated on the basis of the 'Maximised Survey-derived Daily Intake' (MSDI) approach. Besides the safety assessment of the flavouring substance, the specifications for the material of commerce have also been considered and the information provided was complete for [FL-no: 10.057]. However, for the flavouring substance [FL-no: 10.057] in the present revision and for eight substances evaluated in previous revisions, the 'modified Theoretical Added Maximum Daily Intakes' (mTAMDIs) values are above the TTC for their structural class (III). For four substances previously evaluated in FGE.80Rev1 and in FGE.96, use levels are still needed to calculate the mTAMDI estimates. Therefore, in total for 13 flavouring substances, data on uses and use levels should be provided to finalise their safety evaluations. For [FL-no: 10.050, 10.069 and 13.161], information on the composition of stereoisomeric mixtures is needed.
ABSTRACT
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
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
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
This protocol describes the design and development of a tool for evaluation of the internal validity of in vitro studies, which is needed to include the data as evidence in systematic reviews and chemical risk assessments. The tool will be designed specifically to be applied to cell culture studies, including, but not restricted to, studies meeting the new approach methodology (NAM) definition. The tool is called INVITES-IN (IN VITro Experimental Studies INternal validity). In this protocol, three of the four studies that will be performed to create the release version of INVITES-IN are described. In the first study, evaluation of existing assessment tools will be combined with focus group discussions to identify how characteristics of the design or conduct of an in vitro study can affect its internal validity. Bias domains and items considered to be of relevance for in vitro studies will be identified. In the second study, group agreement on internal validity domains and items of importance for in vitro studies will be identified via a modified Delphi methodology. In the third study, the draft version of the tool will be created, based on the data on relevance and importance of bias domains and items collected in Studies 1 and 2. A separate protocol will be prepared for the fourth study, which includes the user testing and validation of the tool, and collection of users' experience.
ABSTRACT
Humans express sulfotransferases (SULTs) of the SULT1A subfamily in many tissues, whilst the single SULT1A gene present in rodents is mainly expressed in liver. The food processing contaminants, 5-hydroxymethylfurfural (HMF) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), are bioactivated by human SULT1A1 and SULT1A2. FVB multiple intestinal neoplasia (Min) mice, which spontaneously develop tumors and flat aberrant crypt foci (ACF) in intestine, were crossed with transgenic FVB mice expressing human SULT1A1 and 1A2 (hSULT) in several tissues, giving rise to wild-type and Min mice with and without hSULT. One-week-old Min mice with or without hSULT were given HMF (375 or 750 mg/kg bw) or saline by gavage three times a week for 11 wk. In another experiment, the F1 generation received subcutaneous injections of 50 mg/kg bw PhIP or saline 1 wk before birth, and 1, 2, and 3 wk after birth. HMF did not affect the formation of tumors, but may have induced some flat ACF (incidence 15-20%) in Min mice with and without hSULT. No control mouse developed any flat ACF. With the limitation that these putative effects were weak, they were unaffected by hSULT expression. The carcinogenic effect of PhIP increased in the presence of hSULT, with a significant increase in both incidence (31-80%) and number of colonic tumors (0.4-1.3 per animal). Thus, intestinal expression of human SULT1A1 and 1A2 might increase the susceptibility to compounds bioactivated via this pathway implying that humans might be more susceptible than conventional rodent models.
Subject(s)
Carcinogens/toxicity , Food Handling , Furaldehyde/analogs & derivatives , Imidazoles/toxicity , Intestinal Neoplasms/chemically induced , Sulfotransferases/genetics , Animals , Furaldehyde/toxicity , Humans , Intestinal Neoplasms/enzymology , Mice , Mice, TransgenicABSTRACT
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
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.
ABSTRACT
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.
ABSTRACT
The EFSA Panel on Food Additives and Flavourings was requested to evaluate 55 flavouring substances assigned to the Flavouring Group Evaluation 07 (FGE.07), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Fifty-three substances have already been considered in FGE.07 and its revisions. This revision 6 includes two additional substances which have been cleared with respect to genotoxicity in FGE.201Rev2 (4-methyl-3-hepten-5-one [FL-no: 07.261]) and FGE.204Rev1 (non-2-en-4-one, [FL-no: 07.187]). The substances were evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, toxicological threshold of concern (TTC) and available data on metabolism and toxicity. The Panel concluded that none of the 55 substances gives rise to safety concerns at their levels of dietary intake, when estimated on the basis of the 'Maximised Survey-derived Daily Intake' (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate. Normal and maximum use levels were available for all flavouring substances. For 52 substances, including the newly included substances [FL-no: 07.187 and 07.261], their 'modified Theoretical Added Maximum Daily Intakes' (mTAMDIs) estimates were above the TTC for their structural classes (I and II). Therefore, for these 52 flavouring substances, more detailed data on uses and use levels should be provided to finalise their safety evaluations.
ABSTRACT
The EFSA Panel on Food Additives and Flavourings was requested to evaluate 43 flavouring substances assigned to the Flavouring Group Evaluation 63 (FGE.63), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Twenty-nine substances have already been considered in FGE.63 and its revisions ([FL-no: 02.023, 02.099, 02.104, 02.136, 02.155, 02.252, 07.015, 07.069, 07.081, 07.099, 07.100, 07.101, 07.102, 07.114, 07.123, 07.151, 07.190, 07.240, 07.247, 07.249, 07.256, 09.281, 09.282, 09.657, 09.658, 09.923, 09.924, 09.925 and 09.936]). The remaining 14 flavouring substances have been cleared with respect to genotoxicity in FGE.204Rev1 ([FL-no: 02.102, 02.193, 07.044, 07.048, 07.082, 07.104, 07.105, 07.106, 07.107, 07.121, 07.139, 07.177, 07.188 and 07.244]) and they are considered in this revision 4 of FGE.63. The substances were evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, toxicological threshold of concern (TTC) and available data on metabolism and toxicity. The Panel concluded that none of these 43 substances gives rise to safety concerns at their levels of dietary intake, when estimated on the basis of the 'Maximised Survey-derived Daily Intake' (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate for 43 flavouring substances. However, for 14 of these flavouring substances in the present revision and for 10 of the substances in the previous revision (FGE.63Rev3), the 'modified Theoretical Added Maximum Daily Intakes' (mTAMDIs) values are equal to or above the TTCs for their structural classes (I and II). For 15 substances previously evaluated in FGE.63Rev3, use levels are still needed to calculate the mTAMDI estimates. Therefore, in total for 39 flavouring substances, more data on uses and use levels should be provided to finalise their safety evaluations.
ABSTRACT
The Panel on Food Additives and Flavourings (FAF) was requested to consider the JECFA evaluations of 25 flavouring substances assigned to the Flavouring Group Evaluation 67 (FGE.67Rev3), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Eleven substances have already been considered in FGE.67 and its revisions (FGE.67Rev1 and FGE.67Rev2). During the current assessment, two substances were no longer supported by industry, therefore 12 candidate substances are evaluated in FGE.67Rev3. New genotoxicity and toxicity data are available for 2-pentylfuran [FL-no: 13.059] and 2-acetylfuran [FL-no: 13.054], which are representative substances of subgroup IV [FL-no: 13.069, 13.106, 13.148] and VI-B [FL-no: 13.045, 13.070, 13.083, 13.101, 13.105, 13.138, 13.163], respectively. Based on these data, the Panel concluded that the concern for genotoxicity is ruled out for both [FL-no: 13.054] and [FL-no: 13.059] and consequently for the substances that they represent. Since the candidate substances cannot be anticipated to be metabolised to innocuous products only, they were evaluated along the B-side of the Procedure. The Panel derived a NOAEL of 22.6 mg/kg bw per day and a BMDL of 8.51 mg/kg bw per day, for 2-acetylfuran and 2-pentylfuran, respectively. For all 12 substances sufficient margins of safety were calculated when based on the MSDI approach. Adequate specifications for the materials of commerce are available for all 23 flavouring substances. The Panel agrees with JECFA conclusions, for all 23 substances, 'No safety concern at estimated levels of intake as flavouring substances' based on the MSDI approach. For 18 substances [FL-no: 13.021, 13.022, 13.023, 13.024, 13.031, 13.045, 13.047, 13.054, 13.059, 13.074, 13.083, 13.101, 13.105, 13.106, 13.138, 13.148, 13.163 and 13.190], the mTAMDI intake estimates are above the threshold of toxicological concern (TTC) for their structural classes and more reliable data on uses and use levels are required to finalise their evaluation.
ABSTRACT
The Panel on Food additives and Flavourings of the EFSA was requested to update Flavouring Group Evaluation 13 using the Procedure as outlined in Commission Regulation (EC) No 1565/2000, to include an evaluation of the flavouring substances 2-ethyl-5-methylfuran [FL-no: 13.125] and 2-octylfuran [FL-no: 13.162]. FGE.13 revision 3 (FGE.13Rev3) deals with 26 flavourings substances of which 24 have been already evaluated to be of no safety concern. For [FL-no: 13.125] and [FL-no: 13.162], a concern for genotoxicity was raised in FGE.13Rev1. This concern could be ruled out based on new genotoxicity data on supporting substances in FGE.67Rev3. Subsequently, [FL-no: 13.125 and 13.162] were evaluated, through a stepwise approach that integrates intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity, along the B-side of the Procedure, making use of a BMDL of 8.51 mg/kg body weight (bw) per day. The Panel derived this BMDL from an oral subchronic toxicity study with the supporting substance 2-pentylfuran [FL-no: 13.059]. Using this BMDL, for [FL-no: 13.125 and 13.162], adequate margins of safety were calculated based on the MSDI approach. The Panel concluded that the 26 candidate substances in FGE.13Rev3 do not give rise to safety concerns at their levels of dietary intake, when estimated on the basis of the MSDI approach. Adequate specifications for the materials of commerce have been provided for all 26 substances. Data on uses and use levels are needed for [FL-no: 13.130]. For 21 flavouring substances [FL-no: 13.011, 13.102, 13.108, 13.113, 13.114, 13.122, 13.125, 13.127, 13.129, 13.132, 13.133, 13.135, 13.136, 13.139, 13.141, 13.143, 13.146, 13.149, 13.162, 13.178 and 13.185], the mTAMDI intake estimates are above the TTC for their structural class and more reliable data on uses and use levels are required to finalise their evaluation.
ABSTRACT
The EFSA Panel on Food Additives and Flavourings was requested to evaluate 35 flavouring substances attributed to the Flavouring Group Evaluation 69 (FGE.69), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Thirty-two substances have already been considered in FGE.69 [FL-no: 02.033, 02.034, 02.036, 02.064, 02.065, 02.080, 07.004, 07.013, 07.022, 07.023, 07.025, 07.026, 07.028, 07.029, 07.032, 07.038, 07.040, 07.042, 07.070, 07.079, 07.086, 07.087, 09.144, 09.178, 09.179, 09.189, 09.200, 09.231, 09.249, 09.476, 09.486 and 09.501]. The remaining three substances [FL-no: 02.066, 07.024 and 07.027] have been cleared with respect to genotoxicity in FGE.215Rev1 and are considered in this revision FGE.69Rev1. The substances were evaluated through a stepwise approach, namely the Procedure, that integrates information on the structure-activity relationships, intake from current uses, Threshold of Toxicological Concern (TTC) and available data on metabolism and toxicity. The Panel considered that for 33 flavouring substances evaluated through the Procedure the specifications are adequate and the Panel agrees with JECFA conclusions 'No safety concern at estimated levels of intake as flavouring substances' when based on the MSDI approach. For two flavouring substances [FL-no: 07.038 and 07.042], there is insufficient information on their chemical identity to reach a final conclusion. For six substances [FL-no: 02.066, 07.013, 07.024, 07.028, 07.032 and 07.086], there is no concern when the exposure was estimated based on the 'modified Theoretical Added Maximum Daily Intake' (mTAMDI) approach. For 28 substances, use levels are needed to calculate the mTAMDI estimates in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation accordingly. For one substance [FL-no: 07.027], more reliable data on uses and use levels are required in order to finalise the safety evaluation.
ABSTRACT
The EFSA Panel on Food Additives and Flavourings was requested to evaluate 12 flavouring substances attributed to the Flavouring Group Evaluation 61 (FGE.61), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Nine substances have already been considered in FGE.61 and FGE.61Rev1 [FL-no: 06.001, 06.004, 06.005, 06.008, 06.009, 06.015, 06.028, 06.037, 06.081]. The remaining three substances [FL-no: 06.025, 06.031 and 06.072] have been cleared with respect to genotoxicity in FGE.200Rev1 and are considered in this revision 2 of FGE.61. The substances were evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity. The Panel concluded that none of the 12 substances gives rise to safety concerns at their levels of dietary intake, estimated on the basis of the 'Maximised Survey-derived Daily Intake' (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate. For nine flavouring substances [FL-no: 06.001, 06.004, 06.005, 06.008, 06.009, 06.015, 06.028, 06.037 and 06.081], use levels are still needed to calculate the modified Theoretical Added Maximum Daily Intake (mTAMDI) values in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation accordingly.
ABSTRACT
The EFSA Panel on Food Additives and Flavourings was requested to evaluate 39 flavouring substances assigned to the Flavouring Group Evaluation 71 (FGE.71), using the Procedure in Commission Regulation (EC) No 1565/2000. Nine substances have already been considered in FGE.71 [FL-no: 08.054, 08.073, 08.123, 09.037, 09.156, 09.157, 05.158, 09.235, 09.239]. The remaining 30 substances [FL-no: 02.020, 02.050, 02.090, 02.112, 02.137, 02.156, 02.210, 05.037, 05.060, 05.070, 05.073, 05.076, 05.078, 05.102, 05.109, 05.150, 05.171, 05.179, 09.276, 09.277, 09.303, 09.385, 09.394, 09.395, 09.396, 09.397, 09.398, 09.399, 09.678 and 09.841] have been cleared with respect to genotoxicity in FGE.200Rev1 and they are considered in this revision. The substances were evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, toxicological threshold of concern (TTC), and available data on metabolism and toxicity. The Panel concluded that none of the 39 substances gives rise to safety concerns at their levels of dietary intake, estimated on the basis of the 'Maximised Survey-derived Daily Intake' (MSDI) approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered and found adequate, except for [FL-no: 08.073 and 09.235]. For these two substances, data on the composition of the stereoisomeric mixture should be requested. Normal and maximum use levels should be provided for nine flavouring substances [FL-no: 08.054, 08.073, 08.123, 09.037, 09.156, 09.157, 05.158, 09.235, 09.239]. For two flavouring substances [FL-no: 02.020 and 05.076], the 'modified Theoretical Added Maximum Daily Intake' (mTAMDI) estimates are above the TTC for their structural class I. Therefore, additional information on uses and use levels should be provided for these eleven substances in order to finalise their evaluation.