Leon Brimer

Re‐evaluation of alginic acid and its sodium, potassium, ammonium and calcium salts (E 400–E 404) as food additives

Abstract The present opinion deals with the re‐evaluation of alginic acid and its sodium, potassium, ammonium and calcium salts (E 400–E 404) when used as food additives. Alginic acid and its salts (E 400–E 404) are authorised food additives in the EU in accordance with Annex II and Annex III to Regulation (EC) No 1333/2008. Following the conceptual framework for the risk assessment of certain food additives re‐evaluated under Commission Regulation (EU) No 257/2010, the Panel concluded that there was no need for a numerical Acceptable Daily Intake (ADI) for alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404), and that there was no safety concern at the level of the refined exposure assessment for the reported uses of alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) as food additives. The Panel further concluded that exposure of infants and young children to alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) by the use of these food additives should stay below therapeutic dosages for these population groups at which side‐effects could occur. Concerning the use of alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) in ‘dietary foods for special medical purposes and special formulae for infants’ (Food category 13.1.5.1) and ‘in dietary foods for babies and young children for special medical purposes as defined in Directive 1999/21/EC’ (Food category 13.1.5.2), the Panel further concluded that the available data did not allow an adequate assessment of the safety of alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) in infants and young children consuming the food belonging to the categories 13.1.5.1 and 13.1.5.2.

Re‐evaluation of guar gum (E 412) as a food additive

Abstract The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of guar gum (E 412) as a food additive. In the EU, guar gum was evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1970, 1974 and 1975, who allocated an acceptable daily intake (ADI) ‘not specified’. Guar gum has been also evaluated by the Scientific Committee for Food (SCF) in 1977 who endorsed the ADI ‘not specified’ allocated by JECFA. Following the conceptual framework for the risk assessment of certain food additives re‐evaluated under Commission Regulation (EU) No 257/2010, the Panel considered that adequate exposure and toxicity data were available. Guar gum is practically undigested, not absorbed intact, but significantly fermented by enteric bacteria in humans. No adverse effects were reported in subchronic and carcinogenicity studies at the highest dose tested; no concern with respect to the genotoxicity. Oral intake of guar gum was well tolerated in adults. The Panel concluded that there is no need for a numerical ADI for guar gum (E 412), and there is no safety concern for the general population at the refined exposure assessment of guar gum (E 412) as a food additive. The Panel considered that for uses of guar gum in foods intended for infants and young children the occurrence of abdominal discomfort should be monitored and if this effect is observed doses should be identified as a basis for further risk assessment. The Panel considered that no adequate specific studies addressing the safety of use of guar gum (E 412) in food categories 13.1.5.1 and 13.1.5.2 were available. Therefore, the Panel concluded that the available data do not allow an adequate assessment of the safety of guar gum (E 412) in infants and young children consuming these foods for special medical purposes.

Scientific Opinion of Flavouring Group Evaluation 410 (FGE.410): 4’,5,7‐trihydroxyflavanone from chemical group 25 (phenol derivatives containing ring‐alkyl, ring‐alkoxy, and side‐chains with an oxygenated functional group)

Abstract The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) of EFSA was requested to deliver a scientific opinion on the implications for human health of the flavouring substance 4′,5,7‐trihydroxyflavanone or naringenin [FL‐no: 16.132], in the Flavouring Group Evaluation 410 (FGE.410), according to Regulation (EC) No 1331/2008 of the European Parliament and of the Council. The substance occurs naturally in grapefruits, oranges and tomatoes. It is intended to be used as a flavouring substance with flavour‐modifying properties in specific categories of food. Information on specifications and manufacturing of [FL‐no: 16.132] were considered adequate; however, data on stability in food are incomplete. The Panel noted that the available genotoxicity studies have significant shortcomings and are insufficient to conclude on the genotoxic potential of naringenin. Therefore, [FL‐no: 16.132] cannot be evaluated through the Procedure. Additionally, the Panel noted that inhibition of CYP 450 by [FL‐no: 16.132] has been clearly demonstrated in animal species in vivo which implies that the substance may interact with the metabolism and elimination of medicines and no convincing information is available that this does not pose a risk to humans at the estimated levels of exposure. To continue with the safety assessment of [FL‐no: 16.132], a bacterial gene mutation assay and an in vitro micronucleus assay (according to OECD guidelines 471, 487 and GLP) are required. Even if these studies do not indicate a genotoxic potential, additional toxicological data are needed to finalise the evaluation.

Re-evaluation of tara gum (E 417) as a food additive

Abstract The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of tara gum (E 417) as a food additive. Tara gum (E 417) has been evaluated by the EU Scientific Committee for Food (SCF, 1992) and by the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 1987), who both allocated an acceptable daily intake (ADI) ‘not specified’ for this gum. Following the conceptual framework for the risk assessment of certain food additives, re‐evaluated under Commission Regulation (EU) No 257/2010, the Panel considered that adequate exposure and toxicity data were available for tara gum (E 417). Tara gum (E 417) is unlikely to be absorbed intact and is expected to be fermented by intestinal microbiota. No adverse effects were reported at the highest doses tested in subchronic, chronic and carcinogenicity studies and there is no concern with respect to the genotoxicity. The Panel concluded that there is no need for a numerical ADI for tara gum (E 417) and that there is no safety concern for the general population at the refined exposure assessment of tara gum (E 417) as a food additive at the reported uses and use levels.

Re‐evaluation of acacia gum (E 414) as a food additive

Abstract The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of acacia gum (E 414) as a food additive. In the EU, acacia gum has not been formally evaluated by the Scientific Committee for Food (SCF), and therefore, no ADI has been allocated. However, it was accepted for use in weaning food (SCF, 1991). In 1999, the SCF considered ‘that the use of acacia gum/gum arabic in coatings for nutrient preparations containing trace elements is acceptable provided carry‐over levels in infant formulae, follow‐on formulae or FSMP do not exceed 10 mg/kg’. Acacia gum was evaluated by JECFA in 1982 and 1990 and the specifications were amended in 1998. Based on the lack of adverse effects in the available toxicity studies, an ADI ‘not specified’ was allocated. Following the conceptual framework for the risk assessment of certain food additives re‐evaluated under Commission Regulation (EU) No 257/2010, the Panel considered that adequate exposure and toxicity data were available. Acacia gum is unlikely to be absorbed intact and is slightly fermented by intestinal microbiota. No adverse effects were reported in subchronic and carcinogenicity studies at the highest dose tested and there is no concern with respect to the genotoxicity. Oral daily intake of a large amount of acacia gum up to 30,000 mg acacia gum/person per day (approximately equivalent 430 mg acacia gum/kg bw per day) for up to 18 days was well tolerated in adults but some individuals experienced flatulence which was considered by the Panel as undesirable but not adverse effect. The Panel concluded that there is no need for a numerical ADI for acacia gum (E 414), and there is no safety concern for the general population at the refined exposure assessment of acacia gum (E 414) as a food additive.

Re‐evaluation of propane‐1,2‐diol alginate (E 405) as a food additive

Abstract The present opinion deals with the re‐evaluation of propane‐1,2‐diol alginate (E 405) when used as a food additive. The Panel noted that absorption, distribution, metabolism and excretion (ADME) data on propane‐1,2‐diol alginate gave evidence for the hydrolysis of this additive into propane‐1,2‐diol and alginic acid. These two compounds have been recently re‐evaluated for their safety of use as food additives (EFSA ANS Panel, 2017, 2018). Consequently, the Panel considered in this opinion the major toxicokinetic and toxicological data of these two hydrolytic derivatives. No adverse effects were reported in subacute and subchronic dietary studies with propane‐1,2‐diol alginate. The available data did not indicate a genotoxic concern for propane‐1,2‐diol alginate (E 405) when used as a food additive. Propane‐1,2‐diol alginate, alginic acid and propane‐1,2‐diol were not of concern with respect to carcinogenicity. The Panel considered that any adverse effect of propane‐1,2‐diol alginate would be due to propane‐1,2‐diol. Therefore, the acceptable daily intake (ADI) of the food additive E 405 is determined by the amount of free propane‐1,2‐diol and the propane‐1,2‐diol released from the food additive after hydrolysis. According to the EU specification, the concentration of free and bound propane‐1,2‐diol amounts to a maximum of 45% on a weight basis. On the worst‐case assumption that 100% of propane‐1,2‐diol would be systemically available and considering the ADI for propane‐1,2‐diol of 25 mg/kg body weight (bw) per day, the Panel allocated an ADI of 55 mg/kg bw per day for propane‐1,2‐diol alginate. The Panel concluded that exposure estimates did not exceed the ADI in any of the population groups from the use of propane‐1,2‐diol alginate (E 405) as a food additive. Therefore, the Panel concluded that there is no safety concern at the authorised use levels.

Scientific opinion on flavouring group evaluation 77, revision 3 (FGE.77Rev3): consideration of pyridine, pyrrole and quinoline derivatives evaluated by JECFA (63rd meeting) structurally related to pyridine, pyrrole, indole and quinoline derivatives evaluated by EFSA in FGE.24Rev2

Abstract The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the EFSA was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of 22 pyridine, pyrrole and quinoline derivatives evaluated by JECFA (63rd meeting). The revision of this consideration is made since additional genotoxicity data have become available for 6‐methylquinoline [FL‐no: 14.042]. The genotoxicity data available rule out the concern with respect to genotoxicity and accordingly the substance is evaluated through the Procedure. For all 22 substances [FL‐no: 13.134, 14.001, 14.004, 14.007, 14.030, 14.038, 14.039, 14.041, 14.042, 14.045, 14.046, 14.047, 14.058, 14.059, 14.060, 14.061, 14.065, 14.066, 14.068, 14.071, 14.072 and 14.164] considered in this Flavouring Group Evaluation (FGE), the Panel agrees with the JECFA conclusion, ‘No safety concern at estimated levels of intake as flavouring substances’ based on the Maximised Survey‐derived Daily Intake (MSDI) approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been evaluated, and the information is considered adequate for all the substances. For the following substances [FL‐no: 13.134, 14.001, 14.030, 14.041, 14.042, 14.058, 14.072], the Industry has submitted use levels for normal and maximum use. For the remaining 15 substances, use levels are needed to calculate the modified Theoretical Added Maximum Daily Intakes (mTAMDIs) in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation.

Scientific Opinion of Flavouring Group Evaluation 406 (FGE.406): (S)‐1‐(3‐(((4‐amino‐2,2‐dioxido‐1H‐benzo[c][1,2,6]thiadiazin‐5‐yl)oxy)methyl)piperidin‐1‐yl)‐3‐methylbutan‐1‐one

Abstract The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) of EFSA was requested to deliver a scientific opinion on the safety of the use of the substance (S)‐1‐(3‐(((4‐amino‐2,2‐dioxido‐1H‐benzo[c][1,2,6]thiadiazin‐5‐yl)oxy)methyl)piperidin‐1‐yl)‐3‐methylbutan‐1‐one [FL‐no: 16.129], as a flavouring substance. The substance is intended to be used in the form of its sodium salt as a flavour modifier in beverages. The Panel concluded that [FL‐no: 16.129] would not raise a concern with respect to genotoxicity under conditions where it remains stable and does not undergo photodegradation. However, the data provided do not rule out genotoxicity for the degradation products. A 90‐day toxicity study with [FL‐no: 16.129] in rats showed no adverse effects at exposure up to 100 mg/kg body weight (bw) per day. No developmental toxicity was observed in rats at dose levels up to 1,000 mg/kg bw per day. An adequate margin of safety was calculated for [FL‐no: 16.129]. The Panel concluded that [FL‐no: 16.129] and its sodium salt are not expected to be of safety concern at the estimated levels of intake. This conclusion applies only to the use of the substance as a flavour modifier at levels up to those specified in beverages, but not to the degradation products that may be formed upon exposure to ultraviolet‐A (UV‐A) light. The conditions protecting [FL‐no: 16.129] from photodegradation have not been adequately investigated. It is also unclear if degradation occurs in the absence of UV light. Based on the data provided, the Panel cannot conclude on the safety of [FL‐no: 16.129] when used as a flavour modifier.

Re‐evaluation of gellan gum (E 418) as food additive

Abstract The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of gellan gum (E 418) as a food additive. Following the conceptual framework for the risk assessment of certain food additives re‐evaluated under Commission Regulation (EU) No 257/2010, the Panel considered that adequate exposure and toxicity data were available. Based on the reported use levels, a refined exposure of up to 72.4 mg/kg body weight (bw) per day in toddlers at the 95th percentile was estimated. Gellan gum is unlikely to be absorbed intact and would not be fermented by human intestinal microbiota. There is no concern with respect to carcinogenicity and genotoxicity. No adverse effects were reported in chronic studies at the highest doses tested in mice and rats (3,627 and 1,460 mg gellan gum/kg bw per day, respectively). Repeated oral intake up to 200 mg/kg bw per day for 3 weeks had no adverse effects in humans. The Panel concluded that there is no need for a numerical acceptable daily intake (ADI) for gellan gum (E 418), and that there is no safety concern at the refined exposure assessment for the reported uses and use levels of gellan gum (E 418) as a food additive. The Panel recommended to better define the specifications of gellan gum including the absence of viable cells of the microbial source and the presence of polyhydroxybutyrate (PHB), protein and residual bacterial enzymatic activities.

Scientific Opinion of Flavouring Group Evaluation 411 (FGE.411): 2‐(4‐methylphenoxy)‐N‐(1H‐pyrazol‐3‐yl)‐N‐(thiophen‐2‐ylmethyl)acetamide from chemical group 30 (miscellaneous substances)

Abstract EFSA was requested to deliver a scientific opinion on the implications for human health of the flavouring substance 2‐(4‐methylphenoxy)‐N‐(1H‐pyrazol‐3‐yl)‐N‐(thiophen‐2‐ylmethyl)acetamide [FL‐no: 16.133], in the Flavouring Group Evaluation 411 (FGE.411), according to Regulation (EC) No 1331/2008 of the European Parliament and of the Council. The substance has not been reported to occur in natural source materials of botanical or animal origin. It is intended to be used as a flavouring substance in specific categories of food but not intended to be used in beverages, except for milk and dairy based beverages that are opaque. The chronic dietary exposure to the substance estimated using the added portions exposure technique (APET), is calculated to be 225 μg/person per day for a 60‐kg adult and 142 μg/person per day for a 15‐kg 3‐year‐old child. A 90‐day oral gavage study in rats showed no adverse effects at doses up to 100 mg/kg body weight (bw) per day, providing an adequate margin of safety. Developmental toxicity was not observed in a study with rats at the dose levels up to 1,000 mg/kg bw per day. The Panel concluded that there is no safety concern for [FL‐no: 16.133], when used as a flavouring substance at the estimated level of dietary exposure calculated using the APET approach and based on the recommended uses and use levels as specified in Appendix B. This conclusion does not apply for use in beverages where the substance can be subject to phototransformation.