Scientific Opinion on the re-evaluation of gold (E 175) as a food additive

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Article
Panel on Food Additives and Nutrient Sources Added to Food
EFSA Journal
EFSA Journal 2016;14(1):4362 [43 pp.].
doi
10.2903/j.efsa.2016.4362
Panel members at the time of adoption
Fernando Aguilar, Riccardo Crebelli, Alessandro Di Domenico, Birgit Dusemund, Maria Jose Frutos, Pierre Galtier, David Gott, Ursula Gundert-Remy, Claude Lambré, Jean-Charles Leblanc, Oliver Lindtner, Peter Moldeus, Alicja Mortensen, Pasquale Mosesso, Agneta Oskarsson, Dominique Parent-Massin, Ivan Stankovic, Ine Waalkens-Berendsen, Rudolf Antonius Woutersen, Matthew Wright and Maged Younes.
Acknowledgements

The Panel wishes to thank the members of the Standing Working Group on the re-evaluation of food colours: Fernando Aguilar, Riccardo Crebelli, Alessandro Di Domenico, Maria Jose Frutos, Pierre Galtier, David Gott, Claude Lambré, Jean-Charles Leblanc, Agneta Oskarsson, Jeanne Stadler, Paul Tobback, Ine Waalkens-Berendsen and Rudolf Antonius Woutersen, for the preparatory work on this scientific opinion and EFSA staff members: Alexandra Tard and Stavroula Tasiopoulou for the support provided to this scientific opinion. The ANS Panel wishes to acknowledge all European competent institutions and other organisations that provided data for this scientific output. 

Contact
Type
Opinion of the Scientific Committee/Scientific Panel
On request from
European Commission
Question Number
EFSA-Q-2011-00345
Adopted
9 December 2015
Approved
20 January 2016
Published
20 January 2016
Affiliation
European Food Safety Authority (EFSA), Parma, Italy
Note
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Abstract

The present opinion deals with the re-evaluation of the safety of gold (E 175) when used as a food additive. Gold (E 175) was previously evaluated by the Scientific Committee on Food (SCF) in 1975. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has not reviewed gold due to lack of data. None of the Committees established an acceptable daily intake (ADI). The Panel noted the limited data on absorption, distribution, metabolism and excretion (ADME) of elemental gold and the absence of toxicological data on gold used as a food additive (E 175) and considered the data to be too limited to perform a risk assessment for E 175. Elemental gold has a very low solubility and thus the systemic availability and effects are expected to be low. In contact with tissues ionic gold can be released from elemental gold and a high local concentration of gold can be reached at the site of contact. The Panel noted that no data on subchronic, chronic toxicity and genotoxicity of elemental gold were available. The Panel concluded that, despite the absence of toxicity data, but taking into account the low solubility of elemental gold, systemic availability and thus systemic effects of elemental gold would not be expected. The Panel recommended that the specifications for gold (E 175) should include the mean particle size and particle size distribution (± SD), as well as the percentage (in number) of particles in the nanoscale (with at least one dimension below 100 nm), present in the powder form of gold (E 175). The methodology applied should comply with the EFSA Guidance document. Exposure estimates of gold (E 175) reached up to 1.32 µg/kg body weight (bw)/day in the maximum level exposure assessment scenario and up to 0.33 µg/kg bw/day in the refined, non-brand-loyal, exposure scenario. 

Summary

Following a request from the European Commission (EC), the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion re-evaluating the safety of gold (E 175) when used as food colour.

The Panel was not provided with a newly submitted dossier and based its evaluation on previous evaluations and additional literature that has become available since then. No new toxicological or biological information was submitted to the Panel for the re-evaluation of gold (E 175) following European Food Safety Authority (EFSA) public calls for data. However, information on manufacturing processes was submitted.

To assist in identifying any emerging issue or any information relevant for the risk assessment, EFSA outsourced a contract to deliver an updated literature review on toxicological endpoints, dietary exposure and occurrence levels of gold (E 175), which covered the period up to the end of 2014. Further update has been performed by the Panel.

Gold (E 175) is authorised as a food additive in the European Union (EU) in accordance with Annex II to Regulation (EC) No 1333/2008, and specific purity criteria have been defined in Commission Regulation (EU) No 231/2012. The Scientific Committee on Food (SCF) has previously evaluated gold (E 175) and found the available data inadequate, but accepted the continued use of gold for external colouring and decoration of foods only (SCF, 1975). The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has not reviewed gold because of lack of data on toxicity, purity and of the exact nature of the gold used on or in foods (JECFA, 1978; 1984; 2001). None of the committees established an acceptable daily intake (ADI).

The common oxidation states of gold are +1 and +3, in addition to its metallic ground state (valence number 0), which is the chemical form of gold as a food additive (E 175). According to a manufacturer of gold as a food additive, the dimension of the gold powder used for the food additive is approximately 1 mm.

The Panel noted that data on elemental gold are inadequate for risk assessment. Data on toxicity of gold nanoparticles and gold(I) complexes have been published. Considering the possibility of the presence of minute amounts of gold nanoparticles in the food additive as a consequence of the manufacturing process of gold powder, the Panel found it relevant to consider the data on toxicity of nanoparticles of gold as supportive evidence. Although data on nanoparticulate gold or gold(I) complexes were not of direct relevance for the risk assessment of elemental gold as a food additive, these data were reviewed by the Panel as indicative of potential health hazard.

In vivo data on kinetics of metallic gold are very limited, but systemic absorption of gold is presumed to be very low due to the low solubility of elemental gold. However, ionic gold released from metallic gold in contact with tissues and cells, and a local high concentration of gold can be reached at the site of contact. A low uptake and a high retention of gold nanoparticles have been demonstrated in experimental animals. In vitro data and results from experimental animals demonstrate that cellular internalisation and gastrointestinal uptake of gold nanoparticles depends on particle size and physico-chemical characteristics of the particles.

The Panel noted that no data on subchronic, chronic toxicity or genotoxicity of elemental gold are available.

Gold nanoparticles of different size and shape have been tested in several in vitro genotoxicity assays, and to a more limited extent also in vivo. In vitro, gold nanoparticles were positive in studies performed in mammalian cells, where induction of DNA strand breaks, micronuclei, chromosomal aberrations and aneuploidy was observed, together with the expression of markers of oxidative stress. Less conclusive results were obtained in mammals in vivo: positive in two studies using the intraperitoneal route of administration, which however is considered not relevant for oral risk assessment, and negative in an oral study in rats, in which however no evidence of exposure of the target tissue was provided. Overall, the Panel concluded that the available data do not allow evaluation of the genotoxic hazard associated to the use of gold as a food additive.

No studies on reproductive or developmental toxicity of elemental gold were available.

It has been reported that gold, used in medicines or dentistry, could elicit hypersensitivity reactions and effects such as lichen planus and skin eruption. However, the Panel noted that this exposure was not representative of the oral intake of gold used as a food additive, and therefore were not relevant to the risk assessment of E 175. There are a few case reports on induction of a lichen planus skin eruption following ingestion in the form of a gold-containing liqueur.

Monovalent gold complexes have been used extensively in the treatment of rheumatoid arthritis. One of the medical drugs, auranofin (1-thio-β-d-glucopyranosatotriethyl phosphine gold-2,3,4,6-tetraacetate), is administered perorally. The Panel noted that the toxicokinetics of auranofin is not clarified, but there are findings indicating that orally administered auranofin is rapidly degraded in the gastrointestinal tract before absorption, and gold is released. The main target organs for toxicity of auranofin were the gastrointestinal tract, skin and kidney. Auranofin caused fetal abdominal anomalies in rabbits, but not in rats. The Panel considered that the studies with auranofin provided supplemental information about hazards due to exposure to gold but considered that these results were not directly applicable to the risk assessment of gold as a food additive.

For the maximum level exposure assessment, mean estimates ranged from <0.01 to 0.33 µg/kg body weight (bw)/day across all population groups. Estimates based on the high percentile (95th percentile) ranged from 0 to 1.32 µg/kg bw/day across all population groups.

For the refined estimated exposure scenario, in the brand-loyal scenario, mean exposure to gold (E 175) from its use as a food additive ranged from < 0.01 µg/kg bw/day for infants and the elderly to 0.31 µg/kg bw/day in children. The high exposure to gold (E 175) ranged from 0 µg/kg bw/day for infants to 1.3 µg/kg bw/day in children. In the non-brand-loyal scenario, mean exposure to gold (E 175) ranged from < 0.01 µg/kg bw/day for infants, adults and the elderly to 0.08 µg/kg bw/day in children. The high exposure ranged from 0 µg/kg bw/day for infants to 0.33 µg/kg bw/day in children.

The Panel concluded that, despite the absence of toxicity data, but taking into account the low solubility of elemental gold, systemic availability and thus systemic effects of elemental gold would not be expected.

The Panel recommended that the specifications for gold (E 175) should include the mean particle size and particle size distribution (± SD), as well as the percentage (in number) of particles in the nanoscale (with at least one dimension between 0 and 100 nm), present in the powder form of gold (E 175) used as a food additive. The methodology applied should comply with the EFSA Guidance document (EFSA Scientific Committee, 2011), e.g. scanning electron microscopy (SEM) or transmission electron microscopy (TEM).

Keywords
gold, E 175, food additive, CAS No 7440-57-5, CI 77480
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Number of Pages
43