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 as a food additive in the European Union (EU) in accordance with Annex II and Annex III to Regulation (EC) No 1333/2008 on food additives.
In the EU, alginic acid and its salts (E 400–E 404) have been evaluated by the Scientific Committee for Food (SCF) in 1994 (SCF, 1994) who endorsed the evaluation of the Join FAO/WHO expert Committee on Food Additives (JECFA, 1993a): ‘Acceptable Daily Intake (ADI) not specified.’ In 1998, the SCF issued a report on certain additives for use in foods for infants and young children in good health and in foods for special medical purpose (FSMP) for infant and young children. The Committee concluded that ‘the use of sodium alginate is acceptable up to a level of 1 g/L in FSMP used from 4 months of age onwards’ (SCF, 1998a,b).
Alginic acid and its salts (E 400–E 404) were evaluated by JECFA in 1993 (JECFA, 1993a). Based on the available data on oral absorption, JECFA did not restrict the daily intake. The Committee therefore allocated a group ADI ‘not specified’ to alginic acid and derived salts; laxative effects that might occur at a high level of intake are assumed to be of minor toxicological relevance (JECFA, 1993a).
Alginic acid (E 400) is a linear glycuronoglycan polymer consisting mainly of β-(1→4)-linked d-mannuronic and α-(1→4)-linked l-guluronic acid units extracted from natural strains of various species of brown seaweeds (Phaeophyceae). Sodium (E 401), potassium (E 402), ammonium (E 403) and calcium alginates (E 404) are sodium, potassium, ammonium and calcium salts of alginic acid, respectively.
Specifications for these food additives have been defined in Commission Regulation (EU) 231/2012.
The Panel noted that, due to the possible hypersensitivity issues, limits for protein should be reduced as much as possible and included in the EC specifications.
The Panel noted that toxicological studies with an alginate–konjac–xanthan polysaccharide complex, called PGX, were available for its evaluation as novel food by the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) did not consider the results of these studies in its re-evaluation of the individual substance alginic acid and its salts (E 400–E 404). It is not possible to conclude to what extent are the reported effects attributable to one of the individual components of the complex. The physicochemical properties of the individual components might also have changed during the manufacturing process of PGX (see Section 1.2).
The in vitro degradation by microbiota from human colon and the in vivo metabolism of alginic acid and its salts in animals have been investigated. These studies demonstrated that the in vivo biological fate of alginic acid and its salts are similar. Alginic acid and its salts would not be absorbed intact regardless of the form administered; they would not be metabolised by enzymes present in the gastrointestinal tract. However, they would be partially fermented during their passage through the large intestine by the action of the intestinal microbiota. The rate of breakdown in the gastrointestinal tract in humans is unknown. However, it is expected that fermentation of alginic acid and its salts would lead to the production of products such as short-chain fatty acids, which were considered of no concern by the Panel.
No adverse effects were observed in short-term and subchronic toxicity studies in rats and in one subchronic study in dogs. In the rat studies, the caecal enlargement described by the authors was considered by the Panel as an adaptive process related to the high doses tested.
Alginic acid and sodium alginate were tested in several in vitro assays and in one in vivo assay that, despite some limitations, did not reveal any genotoxic effect for alginic acid and sodium alginate. No studies were available for calcium alginate, potassium alginate and ammonium alginate. However, the Panel considered that a read-across approach can be applied to calcium alginate, potassium alginate and ammonium alginate to exclude a potential genotoxicity also for these compounds. The Panel also noted that alginic acid would not be absorbed unchanged and would not be metabolised by enzymes present in the gastrointestinal tract but partially fermented during its passage through the large intestine by the action of the intestinal tract microflora leading to the production of its fermentation products such as short-chain fatty acids (SCFA) which do not raise concerns for genotoxicity (OECD Toolbox 4.0). On this basis, the Panel concluded that there is no concern with respect to the genotoxicity for alginic acid and its salts (E 400–E 404).
According to the results of long-term toxicity studies in mice and rats, the Panel considered that alginic acid and its salts were not of concern with respect to carcinogenicity.
The Panel noted that the data presented in a two-generation study in Sprague–Dawley rats fed diets containing 0% or 5% sodium alginate (equivalent to 0 and 2,500 mg/kg body weight (bw) per day) for a period of 2 years were insufficient for hazard characterisation. However, the Panel noted that in a 90-day study in rats (Documentation provided to EFSA n. 8), no effects were observed on testes and ovary weights and also no histopathological changes were observed in testes, ovaries and uteri. No prenatal developmental toxicity studies were available.
The Panel considered that there was no indication for immunotoxicity or for an allergenic potential of alginic acid and its salts used as food additives.
In human studies, the oral intake of sodium alginate was well tolerated. The Panel also noted that for the medicinal use of a combination of sodium alginate and magnesium alginate in infants and young children with a maximum daily dosage ranging from 417 to 834 mg/kg bw calculated as sodium alginate, constipation, diarrhoea, intestinal obstruction, flatulence, abdominal distension and bezoar are indicated as adverse effects. However, in a multicentre study in infants, no significant differences in the incidences of gastrointestinal adverse events between the groups treated with the combination of sodium alginate and magnesium alginate or with placebo were observed.
Alginic acid and its salts (E 400–E 404) are authorised in a wide range of foods. The Panel did not identify brand loyalty to a specific food category, and therefore, the Panel considered that the non-brand-loyal scenario covering the general population was the more appropriate and realistic scenario for risk characterisation because it is assumed that the population would probably be exposed over the long term to the food additive present at the mean reported use in processed food.
A specific estimated exposure assessment scenario taking into account the food for special medical purpose for infants and young children (Food Category (FC) 126.96.36.199 and FC 188.8.131.52) was also performed to estimate exposure for infants and toddlers and children who may be on a specific diet. Considering that this diet is required due to specific needs, it is assumed that consumers are loyal to the food brand; therefore, the refined brand-loyal estimated exposure scenario was performed using the maximum permitted level for the FSMPs. The Panel noted that no data on use levels were submitted by industry for the food categories 184.108.40.206 and 220.127.116.11, which is in agreement with the absence of data in the Mintel database.
The refined estimates are based on 23 out of 75 food categories in which alginic acid and its salts (E 400–E 404) are authorised. The Panel considered that the uncertainties identified would, in general, result in an overestimation of the exposure to alginic acid and its salts (E 400–E 404) as a food additive in European countries for the refined scenario if it is considered that the food additive may not be used in food categories for which no usage data have been provided.
The Panel also noted that the refined exposure estimates are based on information provided on the reported level of use of alginates (E 400–E 404). If actual practice changes, this refined estimates may no longer be representative and should be updated.
Following the conceptual framework for the risk assessment of certain food additives re-evaluated under Commission Regulation (EU) No 257/2010 (EFSA ANS Panel, 2014), and given that:
- from all the data received, data were adequate for a refined exposure assessment for 23 out of 75 food categories;
- based on the reported use levels, a refined exposure (non-brand-loyal scenario) of up to 208 mg/kg bw per day in infants (from 12 weeks up to and including 11 months of age) was estimated;
- alginic acid and its salts were practically undigested, not absorbed intact, but partially fermented by intestinal microbiota in humans;
- adequate toxicity data were available;
- no adverse effects were reported in subchronic studies in rodents at the highest dose tested, of 13,500 mg sodium alginate/kg bw per day in rats;
- there was no concern with respect to the genotoxicity of alginic acid and its salts;
- no carcinogenic effects were reported at the highest dose tested of 37,500 mg sodium alginate/kg bw per day in mice;
- oral intake of 175 mg sodium alginate/kg bw per day for 7 days, followed by 200 mg/kg bw per day for further 16 days was well tolerated in healthy human adults;
- oral treatment of 14 patients on dialysis with approximately 120 mg calcium alginate/kg bw per day over a period of 1 year was well tolerated without side-effects;
- for higher therapeutic daily doses corresponding to 417–834 mg sodium alginate/kg bw in the treatment of infants and young children for gastric reflux, reported side-effects were gastrointestinal disorders including rare formation of intragastric ‘mass’;
- available data support read-across in safety parameters among alginic acid and its salts (E 400–E 404);
the Panel concluded that there was no need for a numerical 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.
Infants and young children consuming foods for special medical purposes and special formulae
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 18.104.22.168) and ‘in dietary foods for babies and young children for special medical purposes as defined in Directive 1999/21/EC’ (Food category 22.214.171.124), and given that:
- for populations consuming dietary foods for special medical purposes and special formulae, the highest refined exposure estimate (p95) calculated based on MPL were for toddlers (12–35 months) up to 290.4 mg/kg bw per day (brand-loyal scenario);
- infants and young children consuming foods belonging to these food categories may show a higher susceptibility to the gastrointestinal effects of alginic acid and its salts than their healthy counterparts due to their underlying medical condition;
- no adequate specific studies addressing the safety of use of alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) in this population under certain medical conditions were available;
- no data on use levels were submitted by industry for the food categories 126.96.36.199 and 188.8.131.52, which is in agreement with the absence of data in the Mintel database;
the Panel 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 184.108.40.206 and 220.127.116.11.
The Panel recommended that the European Commission considers:
- revising the current limits for toxic elements (arsenic, cadmium, lead and mercury) in the EU specifications for alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) in order to ensure that alginic acid and its salts (E 400, E 401, E 402, E 403 and E 404) as food additives will not be a significant source of exposure to those toxic elements in food, in particular for infants and children;
- defining a suitable validated analytical method of appropriate accuracy for the determination of formaldehyde in the specifications for alginic acid and its salts (E 400–E 404).
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