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Scientific Opinion on the re-evaluation of caramel colours (E 150 a,b,c,d) as food additives

EFSA Journal 2011;9(3):2004 [103 pp.]. doi:10.2903/j.efsa.2011.2004
  EFSA Panel on Food Additives and Nutrient Sources added to food (ANS) Panel Members F. Aguilar, B. Dusemund, P. Galtier, J. Gilbert, D.M. Gott, S. Grilli, R. Gürtler, J. König, C. Lambré, J-C. Larsen, J-C. Leblanc, A. Mortensen, D. Parent-Massin, I. Pratt, I.M.C.M. Rietjens, I. Stankovic, P. Tobback, T. Verguieva, R.A. Woutersen Acknowledgment The Panel wishes to thank the members of the Working Group A on Food Additives and Nutrient Sources: F. Aguilar, N. Bemrah, P. Galtier, J. Gilbert, S. Grilli, R. Gürtler, C. Lambré, J.C. Larsen, J-C. Leblanc, A. Mortensen, I. Pratt, Ch. Tlustos, I. Stankovic, and EFSA staff: A Rincon for the support provided to this scientific opinion. Contact ans@efsa.europa.eu
Type: Opinion of the Scientific Committee/Scientific Panel On request from: European Commission Question number: EFSA-Q-2008-237 , EFSA-Q-2008-238 , EFSA-Q-2008-239 , EFSA-Q-2008-240 Adopted: 03 February 2011 Published: 08 March 2011 Affiliation: European Food Safety Authority (EFSA), Parma, Italy
Abstract

The ANS Panel provides a scientific opinion re-evaluating the safety of the caramel colours (E150a (Class I), E150b (Class II), E150c (Class III), E150d (Class IV)) used as food additives. The caramel colours are a complex mixture of compounds produced by heating carbohydrates under controlled heat and chemical processing conditions; they are divided into four classes according to the manufacturing reactants used. The caramel colours were previously evaluated by the SCF and by JECFA, which concluded that a numerical ADI was not necessary for Class I, but established ADIs for the other classes of caramels, ranging from160-200 mg/kg bw/day. Given the consistency in the toxicological database, the Panel establishes a group ADI of 300 mg/kg bw/day for the caramel colours, by applying an uncertainty factor of 100 to a NOAEL of 30 g/kg bw/day (highest dose tested) identified in 13-week rat studies with Class IV and a similar NOAEL identified in a rat reproductive toxicity study, also with Class IV. Comparable NOAELS for Classes II, III and IV were reported in the SCF and JECFA evaluations. Within this group ADI, the Panel establishes an individual ADI of 100 mg/kg bw/day for Class III due to new information regarding the immunotoxicity of THI. The Panel concludes that the anticipated dietary exposure of child and adult populations may exceed the ADIs for Classes I, III and IV caramels, but exposure estimates to Class II were below the ADI. Exposure estimates for the caramel constituents THI, 4-MEI and SO2 are not of concern, but the Panel welcomes additional studies to clarify remaining uncertainties regarding effects of THI on the immune system. The Panel notes that other constituents of caramel colours including 5-HMF and furan may be present at levels that may be of concern, and considers that the specifications should include maximum levels for these constituents.

© European Food Safety Authority, 2011

Summary

Following a request from the European Commission, the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion re-evaluating the safety of caramel colours (E 150a,b,c,d) when used as food colouring substances.

Caramel colours are colouring substances authorised as food additives in the EU, and are classified according to the reactants used in their manufacture as follows: Class I Plain Caramel or Caustic Caramel (E 150a); Class II Caustic Sulphite Caramel (E 150b); Class III Ammonia Caramel (E 150c) and Class IV Sulphite Ammonia Caramel (E 150d).

The four classes of caramel colours have been previously evaluated by the EU Scientific Committee for Food (SCF), by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and by the Nordic Council of Ministers (TemaNord). Both JECFA and the SCF concluded that a numerical Acceptable Daily Intake (ADI) was not necessary for Class I Plain Caramel, considering that it contains no added ammonia or sulphite and that it is likely to be produced in normal cooking processes. For Class II Caustic Sulphite Caramel, JECFA established an ADI of 0-160 mg/kg bw/day, while the SCF included Class II Caustic Sulphite Caramel within the ADI of 200 mg/kg bw/day that it had already established for Class IV Sulphite Ammonia Caramel, based on information indicating that its chemical composition was similar to and intermediate between that of Class I Plain Caramel and Class IV Sulphite Ammonia Caramel. For Class III Ammonia Caramel, the SCF allocated an ADI of 200 mg/kg bw/day with the proviso that the content of the constituent 2-acetyl-4-tetrahydroxy-butylimidazole (THI) should not exceed 10 mg/kg colour on a colour intensity basis. JECFA has also allocated an ADI of 0-200 mg/kg bw/day to this colour, together with a specification for a maximum level for THI of 25 mg/kg caramel colour. For Class IV Sulphite Ammonia Caramel, both the SCF and JECFA have established an ADI of 200 mg/kg bw/day.

Specifications for the four classes of caramel colours have been defined in Commission Directive 2008/128/EC[1] and by JECFA (2006). The different classes of caramel colours are variously defined (in addition to their method of production) by the degree of binding to Diethylamino Ethyl (DEAE) cellulose and to phosphoryl cellulose (for Classes I Plain Caramel and Class III Ammonia Caramel), by the absorbance ratio (Classes II Caustic Sulphite Caramel and Class IV Sulphite Ammonia Caramel) and by their colour intensity. The solids content for the different classes range from 62-77% (Class I Plain Caramel), 65-72% (Class II Caustic Sulphite Caramel), 53-83% (Class III Ammonia Caramel) or 40-75% (Class IV Sulphite Ammonia Caramel). The maximum level of the constituent 4-methylimidazole (4-MEI), found in Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel only, is restricted to ≤ 250 mg/kg caramel on a colour intensity basis under Commission Directive 2008/128/EC, while the constituent THI, found in Class III Ammonia Caramel only, is restricted to ≤ 10 mg/kg caramel on a colour intensity basis.

The Panel noted that the caramel colours are poorly characterised, and it is not clear whether the controls on manufacturing processes are sufficient to minimise batch-to-batch variability, particularly with respect to levels of individual Low Molecular Weight (LMW) constituents. The wide range of starting materials and reactants that may be used for the production of caramel colours may result in a variety of end products, with different physical, chemical and toxicological properties. The Panel noted that concerns about e.g. chemical composition, purity and similarity of various caramel colours have also been raised in the past by the SCF. The Panel also noted that a number of the identified or theoretical LMW constituents of caramel colours are genotoxic under certain experimental conditions and in some cases have carcinogenic potential, e.g. furan and 5-hydroxymethyl-2-furfural (5-HMF), which may be relevant to the toxicological profile of the caramel colours. The Panel considered that the toxicological studies carried out on specific caramel colours would have involved exposure to these compounds, and therefore the anticipated toxicological effect should have been detected in these studies, as exemplified by the toxicological profiles of Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel due to the presence of the imidazoles THI and 4-MEI

According to information from industry, slight variation of manufacturing process parameters (starting material, temperature and time) allows the production of a large range of different qualities of product within each caramel category and also results in differences in chemical composition and physical properties. This is further evidenced by variation in THI and/or 4-MEI concentrations in Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel, respectively. The Panel noted that there was limited information about the relationship between processing parameters for the caramel colours and the formation and nature of heat-derived constituents of these colours.

The Panel noted that data on the toxicokinetics of the caramel colours are very limited, but indicate little uptake of the high molecular weight fraction of the colours from the gastrointestinal tract, with the bulk of the material being excreted in the faeces. Specific data showed that the small fraction of Class IV Sulphite Ammonia Caramel that is absorbed has been shown to be distributed to lymphoreticular tissue, and eventually excreted in the urine. The Panel considered that individual constituents of the LMW fraction of caramel colours (e.g. MW less than 500 g/mol) are likely to be absorbed, although little information is available to confirm this assumption. The caramel colours are of low toxicity both in short-term tests and in chronic toxicity/carcinogenicity studies. The available short-term studies on Class I Plain Caramel, Class II Caustic Sulphite Caramel, Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel, employing generally high dose levels in drinking water, show some dose-related effects, including reduced body weight gain associated with reduced food and fluid consumption, pigmentation of mesenteric lymph nodes, enlargement of the caecum, reduced urinary output associated with increases in specific gravity of the urine, diarrhoea and increases in caecal and kidney weights, unaccompanied by any histopathological change. Additionally, animal studies on Class III Ammonia Caramel have shown evidence of lymphocyte depression and other evidence of immunotoxicity, which are considered to be due to the presence of THI, a potent immunosuppressant, in this caramel.

The Panel concluded that the effects on body-weight were in part due to the reduced water intake caused by poor palatability of the drinking water rather than toxic effects of the caramel colours per se, and that the other effects seen were secondary both to the reduced fluid intake and the intake of large quantities of osmotically-active caramel material. The Panel considered that these effects are not of toxicological significance in establishing the safety of the caramel colours.

Caramel colours have been extensively tested for genotoxic potential in a variety of assays in vitro and in vivo. The results in in vitro systems were generally negative, with a few marginally positive findings, and no positive findings have been reported in in vivo assays. Overall the Panel concluded that there were no concerns regarding the genotoxic potential of caramel colours.

The findings in the long-term toxicity studies carried out with Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel were similar to, and did not reveal any pattern of toxicity not already seen in, the 90-day oral toxicity studies carried out with these caramel colours. No evidence of carcinogenicity was seen in 2-year studies in rats on Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel. In a parallel study in mice, there was similarly no evidence for a carcinogenic potential of Class IV Sulphite Ammonia Caramel. The Panel noted that no long-term toxicity or carcinogenicity data were available for Class I Plain Caramel and Class II Caustic Sulphite Caramel. The Panel considered however that given the fact that Class I Plain Caramel is likely to be produced in normal cooking processes, also considering the long-term toxicity and carcinogenicity data available on Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel, and the rather similar toxicological profile of all the caramel colours, there are no concerns regarding the long-term toxicity or carcinogenicity of Class I Plain Caramel or Class II Caustic Sulphite Caramel, nor regarding the carcinogenicity of Class III Ammonia Caramel or Class IV Sulphite Ammonia Caramel.

In relation to the reproductive and developmental toxicity of the caramel colours, the Panel noted that no data were available for Class I Plain Caramel and Class II Caustic Sulphite Caramel. However given the data available on Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel and the toxicological similarities between all four classes of caramel colours, the Panel concluded that there are no concerns regarding reproductive and or developmental toxicity of Class I Plain Caramel or Class II Caustic Sulphite Caramel. There were no indications that either Class III Ammonia Caramel or Class IV Sulphite Ammonia Caramel can induce reproductive and or developmental toxicity in mice, rats, or rabbits following gavage administration at levels of up to 1600 mg/kg bw/day. In a reproductive toxicity study with Class IV Sulphite Ammonia Caramel in rats, at the top dose of 25% in the diet, equivalent to approximately 28 g/kg bw/day, pups showed a higher incidence of alopecia compared with pups in the control group and a generalized poor condition during the last 7 days of suckling. The number of implantation sites, litter size and of live pups at days 0, 4, and 21 of lactation in the 20%-dose group were significantly lower than control values, the Panel noted however that there was no dose-related trend, since in the 25% dose group these parameters were not statistically different from controls. The Panel considered that a No-Observed-Adverse-Effect-Level (NOAEL) of 25-30 g/kg bw/day for female rats could be identified in this study.

The Panel noted that no multigeneration study is available on any of the four classes of caramel colours.

Due to a lack of data, no definite conclusion can be drawn with respect to intolerance and allergenicity to the four classes of caramel colours under evaluation. The Panel noted, however that no cases of intolerance and allergenicity intolerance and allergenicity have been reported in published literature.

In relation to the potential haematotoxicity/immunotoxicity of caramel colours, effects have been identified in animal studies with Class III Ammonia Caramel, but not with the other classes of caramel colours. The Panel noted that lymphocytopenic and immunomodulatory effects have been seen in a number of studies with Class III Ammonia Caramel, and that the overall conclusion to be drawn from these studies is that THI, a constituent in Class III Ammonia Caramel, together with deficiency of pyridoxine (vitamin b6), as a dietary influence, was primarily responsible for these effects. The Panel also noted that these effects were (apparently) transient in nature, disappearing in the later stages of longer-term studies with Class III Ammonia Caramel. The Panel noted that in the pivotal 90-day study of MacKenzie et al. on Class III Ammonia Caramel, in which rats were dosed with up to 20 g/kg bw/day caramel colour, containing either 15 mg THI/kg caramel or 295 mg THI/kg caramel, on a solids basis, no dose-related lymphocytopenia occurred in the animals fed caramel containing approximately 15 mg THI/kg. The latter level is higher than the current maximum level for THI laid down in the specifications for Class III Ammonia Caramel. Class III Ammonia Caramel containing 295 mg THI/kg, at a dose level of 20 g/kg bw/day, induced a statistically significant decrease in lymphocyte counts in both sexes at 2 weeks and only in male rats at 6 weeks. All lymphocyte values in these groups were normal at the termination of the study. The Panel noted however that the results of a short-term oral study carried out by Thuvander and Oskarssen indicated that Class III Ammonia Caramel that meets the limit of less than 25 mg THI/kg established in the JECFA specifications may, nevertheless, interfere with the lymphoid system in mice with an adequate vitamin b6 status.

The 90-day oral toxicity study on Class III Ammonia Caramel in rats carried out by Mackenzie et al. included an evaluation of the toxicity of THI after a 4-week dosing period. In rats maintained on a normal, pyridoxine-replete diet, the short-term NOAEL of THI for the reduction of total lymphocytes was determined to be 120 µg/kg bw/day in female rats, and 380 µg/kg bw/day in male rats. Houben et al. reported intakes of THI alone or Class III Ammonia Caramel containing THI that, in combination with manipulation of dietary pyridoxine levels, resulted in lymphocytopenia and could therefore be regarded as Low-Observed-Adverse-Effect-Levels (LOAELs) for this effect. These ranged from 57.2 µg THI/kg bw/day (provided by a level of 0.4% Class III Ammonia Caramel in drinking water, in rats maintained on a low-pyridoxine diet, 2-3 mg/kg diet) to levels of 200 µg THI/kg bw/day or higher. Sinkeldam and co-workers reported decreases in lymphocyte counts in rats receiving 0.1% Caramel Colour (III) in drinking water, equivalent to 20 µg THI/ kg bw/day, for 1 week and maintained on a low-pyridoxine diet (2-3 mg/kg diet). The Panel considered that these findings in pyridoxine-deficient rats may be of limited relevance for human health risk assessment. Overall the Panel concluded from these results that a NOAEL for the lymphocytopenic effects of THI in pyridoxine-replete rats lies in the range of 120-400 µg/kg bw/day as indicated by the studies of MacKenzie et al, Sinkeldam et al and Houben et al.

The Panel noted that, in contrast to the findings in rats and mice, in the available short-term human studies consumption of Class III Ammonia Caramel had no effects on total or specified white blood cell counts at dose levels of up to 200 mg/kg bw/day (with THI levels almost 20 times above those permitted according to current specifications) albeit following short term exposure periods. The study of Houben et al. included subjects with (mild) pyridoxine deficiency, and the authors, in comparing the results obtained in this study with data in rats maintained on normal and pyridoxine-reduced diets, suggested that, with regard to oral intake of THI, humans are less sensitive to Class III Ammonia Caramel-induced lymphocytophenia than are rats. The Panel agreed with this interpretation, based on the available data.

The Panel noted that another imidazole constituent of Class III Ammonia Caramel, 4-MEI, which is also found in Class IV Sulphite Ammonia Caramel, is considered to be responsible for the convulsions observed after administration of high doses of this caramel to a range of species. The Panel considered that the acute toxicity of 4-MEI is not of toxicological concern since the maximum level of 4-MEI is restricted to ≤ 250 mg/kg in these caramel colours under Commission Directive 2008/128/EC. The Panel noted that 4-MEI has been demonstrated to have a carcinogenic potential in mice in a recent National Toxicology Programme (NTP) study. The Panel considered, however, that the carcinogenic effect of 4-MEI seen in mice in this study was thresholded, based on the lack of genotoxicity of 4-MEI, also noting that alveolar/bronchiolar neoplasms occur spontaneously at high incidence in b6C3F1 mice. The Panel concluded therefore that the intermediate dose of 625 mg 4-MEI/kg diet, equivalent to 80 mg 4-MEI/kg bw/day could be considered to be a NOAEL in this study.

The Panel, in evaluating the overall toxicological database on the four classes of caramel colours, considered that while the potential constituents 4-MEI (present in Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel) and THI (found in Class III Ammonia Caramel only) must be taken into account in the safety evaluation of these caramel colours as food additives, as discussed above, all four caramel colours are otherwise similar in their toxicological effects. The Panel also noted that the effects produced by the caramel colours can be anticipated to be additive in nature.

The Panel considered that, in spite of the absence of full chemical characterisation of the four classes of caramel colours, given the consistency in the toxicological database, the caramel colours can be considered as a single group in terms of assessing their safety. The Panel considered therefore that a group ADI can be established for the caramel colours. Given, however, concerns regarding the immunotoxicity of THI, present in Class III Ammonia Caramel, the Panel decided to define an individual ADI for this caramel within the overall group ADI based on the currently available database. While the Panel noted the toxicological data gaps for caramel colours, including the generally sparse database on reproductive toxicity for caramel colours as a whole and the absence of long-term toxicity and carcinogenicity studies on Class I Plain Caramel and Class II Sulphite Caramel, the Panel considered that missing data for these classes of caramel colours can be accounted for by data from another class.

The Panel considered that several studies carried out in rats with the different caramel colours are relevant for establishment of a group ADI for the caramel colours. These include the three studies used previously by JECFA and SCF to define the respective ADIs for the individual Classes:

  • a 90-day study with Class II Caustic Sulphite Caramel, providing a NOAEL of 16 g/kg bw/day, the highest dose tested,
  • a 90-day study with Class III Ammonia Caramel, providing a NOAEL of 20 g/kg bw/day, the highest dose tested,
  • a 2-year oral toxicity study in rats with Class IV Sulphite Ammonia Caramel, providing a NOAEL of 10 g/kg bw/day, the highest dose tested.

The Panel considered that several additional toxicological studies should be taken into account when establishing the group ADI, and these include:

  • a 13-week toxicity study in rats with Class IV Sulphite Ammonia Caramel in drinking water , providing a NOAEL of 30 g/kg bw/day, the highest dose level tested,
  • another 13-week drinking water study in rats with Class IV Sulphite Ammonia Caramel providing a NOAEL of 30 g/kg bw/day, the highest dose level tested,
  • a 90-day study in Beagle dogs with Class IV Sulphite Ammonia Caramel providing a NOAEL of 6.25 g/kg bw/day, the highest dose tested,
  • a 96-week drinking water study in mice with Class III Ammonia Caramel, providing a NOAEL of 8.4 g/kg bw/day, the highest dose tested,
  • a 2-year dietary study in rats with Class III Ammonia Caramel providing a NOAEL of 3 g/kg bw/day, the highest dose tested,
  • a 104-week study in rats with Class III Ammonia Caramel, providing a NOAEL of 2 g/kg bw/day, the highest dose tested,
  • a reproductive toxicity study in rats with Class IV Sulphite Ammonia Caramel providing in the dams a NOAEL of 25-30 g/kg bw/day.

Given that:

-  the NOAELs in all these studies were the highest dose levels tested,

-  the effects of the caramel colours in 90-day studies were generally similar to those reported in the long-term studies,

-  available reproduction and developmental toxicity studies, although limited, do not reveal any effects of concern,

-  the studies reveal no effects on the reproductive organs,

-  the effect of most concern, i.e. lymphocytopenia, can, as also stated by JECFA, best be evaluated from short-term studies, and

-  the long-term studies support the conclusion that the caramel colours are not carcinogenic,

the Panel decided to use the highest NOAEL of 30 g/kg bw/day reported in several of these studies, still the highest dose level tested, as the basis to derive a group ADI for the caramel colours. The Panel noted that whilst there were arguments for increasing the default uncertainty factor of 100, to compensate for limitations in the toxicological databases on reproductive toxicity, equally compelling arguments could be advanced for deriving a chemical-specific adjustment factor below the default uncertainty factor. The Panel therefore applied an uncertainty factor of 100 to the NOAEL of 30 g/kg bw/day to derive a group ADI of 300 mg/kg bw/day. Overall, based on the available database, the Panel considered that this would provide a sufficient margin of safety.

In relation to Class III Ammonia Caramel, the Panel considered the available data on the immunotoxicity of THI, a constituent of this caramel class only. The Panel noted that no dose-related effects on haematological parameters were reported in the 90-day study of MacKenzie, using a Class III Ammonia Caramel containing a THI level of 15 mg/kg, while with a Class III Ammonia Caramel containing a much higher level of THI of 295 mg/kg, only transient effects on lymphocytes were seen. The study of MacKenzie provided a NOAEL of 20 g/kg bw/day for Class III Ammonia Caramel, the highest dose tested. The Panel also noted, however, the results of the study of Thuvander and Oskarssen, indicating that Class III Ammonia Caramel that meets the limit of less than 25 mg THI/kg established in the JECFA specifications may, nevertheless, interfere with the lymphoid system in mice with an adequate vitamin b6 status. While the Panel considered that this study should not be used as a pivotal study for the purposes of risk assessment without further substantiation, given a number of studies in rats showing no effect on haematological parameters over longer periods and at higher dose levels than those used in the study of Thuvander and Oskarssen, the Panel considered that it should be taken into account in establishing an ADI for Class III Ammonia Caramel. The Panel applied an additional uncertainty factor of 2 together with the default uncertainty factor of 100 to the NOAEL of 20 g/kg bw/day identified from the MacKenzie study. The Panel therefore establishes, within the group ADI for all caramel colours and based on the currently available database, an ADI of 100 mg/kg bw/day for Class III Ammonia Caramel.

The Panel noted that this means that within the group ADI of 300 mg/kg bw/day established for the four caramel colours, only 100 mg/kg bw/day of this 300 mg/kg bw/day can be made up by Class III Ammonia Caramel.

The exposure assessment approach goes from the conservative estimates that form the First Tier of screening, to progressively more realistic estimates that form the Second and Third Tiers. As caramel colours Class I, II, III and IV are authorised quantum satis in almost all categories, the refined exposure estimates have been performed only for Tier 3 using the maximum reported use levels or when no usages were reported to EFSA, values defined by decision rules for quantum satis usages were used.

Exposure estimates for children (1-14 years old) have been done by the Panel for 11 European countries (Belgium, France, the Netherlands, Spain, Czech Republic, Italy, Finland, Germany, Denmark, Cyprus, Greece) based on detailed individual food consumption data provided by the EXPOCHI consortium. As the UK is not part of the EXPOCHI consortium, estimates for UK children (aged 1.5- 4.5 years) were made by the Panel with the use of detailed individual food consumption data available from the Union of European Beverage Associations (UNESDA) report. For the adult population, the Panel has selected the UK population as representative of the EU consumers for estimates of exposure.

The mean dietary exposure of European children including UK pre-school children ranged from 76.9 to 427.2 mg/kg bw/day for Class I Plain Caramel, from 8.7 to 34.6 mg/kg bw/day for Class II Caustic Sulphite Caramel, from 21.7 to 302.4 mg/kg bw/day for Class III Ammonia Caramel, and from 23.2 to 506.2 mg/kg bw/day for Class IV Sulphite Ammonia Caramel. At the 95th or 97.5th percentile, estimates ranged from 179.6 to 882.2 mg/kg bw/day for Class I Plain Caramel, from 18.5 to 117.3 mg/kg bw/day for Class II Caustic Sulphite Caramel, from 107.9 to 757.3 mg/kg bw/day for Class III Ammonia Caramel, and from 129.7 to 1480.2 mg/kg bw/day for Class IV Sulphite Ammonia Caramel.

The main contributors (>10% in all or several countries) to the total anticipated exposure of children were for Class I Plain Caramel: non alcoholic flavoured drinks (12% to 55%), fine bakery wares (15% to 32%), desserts including flavoured milk products (11% to 48%), sauces, seasonings (e.g. curry powder, tandoori) and pickles (12% to 56%), soups (11% to 32%) and malt bread (16% to 49%). For Class II Caustic Sulphite Caramel the main contributors were fine bakery wares (12% to 53%), desserts including flavoured milk products (11% to 41%), edibles ices (11% to 22%), sauces, seasonings (e.g. curry powder, tandoori) and pickles (12% to 45%), soups (18% to 54%) and malt bread (19% to 55%). For Class III Ammonia Caramel the main contributors were fine bakery wares (13% to 45%), desserts including flavoured milk products (12% to 44%), sauces, seasonings (e.g. curry powder, tandoori) and pickles (12% to 79%), and vinegar (12% to 45%), while in one country non alcoholic flavoured drink, malt bread confectionery, and sausages, pates and terrines contributed 29%, 15%, 13% and 10%, respectively. For Class IV Sulphite Ammonia Caramel the main contributors were non alcoholic flavoured drinks (13% to 51%), confectionery (20% to 81%), fine bakery wares (10% to 29%), sauces, seasonings (e.g. curry powder, tandoori) and pickles (10% to 24%), and malt bread (10% to 34%).
The anticipated dietary exposure reported for the UK adult population gives a mean of 136.6 mg/kg bw/day and a 97.5th percentile of 429.3 mg/kg bw/day for Class I Plain Caramel; a mean of 21.7 mg/kg bw/day and a 97.5th percentile of 109.5 mg/kg bw/day for Class II Caustic Sulphite Caramel; a mean of 60.8 mg/kg bw/day and a 97.5th percentile of 295.0 mg/kg bw/day for Class III Ammonia Caramel; and a mean of 89.4 mg/kg bw/day and 97.5th percentile of 368.9 mg/kg bw/day for Class IV Sulphite Ammonia Caramel. The main contributors to the total anticipated exposure of adults were for Class I Plain Caramel non alcoholic flavoured drinks (30%), beer and cidre bouché (27%), soups (16%), and sauces, seasonings (e.g. curry powder, tandoori) and pickles (10%). For Class II Caustic Sulphite Caramel the main contributors were beer and cidre bouché (50%) and soups (20%). For Class III Ammonia Caramel the main contributors were beer and cidre bouché (48%) and sauces, seasonings (e.g. curry powder, tandoori) and pickles (22%). For Class IV Sulphite Ammonia Caramel the main contributors were confectionery (65%) and non alcoholic flavoured drinks (23%).

The Panel also evaluated combined anticipated dietary exposure to all four classes of caramel colours, taking into account the highest maximum reported level for all caramel classes, described in Table 8, from each food category. When considering this scenario, as presented in Table 10, anticipated mean combined dietary exposure reported for European children, including UK pre-school children, ranged from 83.5 to 698.3 mg/kg bw/day. At the 95th/97.5th percentile, estimates ranged from 224.8 to 1672.3 mg/kg bw/day. For the UK adult population this scenario gave a range of exposures of 194.8 and 474.3 mg/kg bw/day for the mean and the 97.5th percentile, respectively.

The main contributors to the total combined anticipated exposure to caramel colours for children were non alcoholic flavoured drinks (11% to 28%), confectionery (19% to 58%), fine bakery wares (15% to 29%), desserts including flavoured milk products (10% to 31%), sauces, seasonings (e.g. curry powder, tandoori) and pickles (14% to 44%), and malt bread (16% to 46%). Soups were estimated to contribute from 25% to 28% in two countries and vinegar was estimated to contribute 20% in one country. For the adult population the main contributors (>10%) were confectionery (30%), non alcoholic flavoured drinks (21%), beer, cidre bouché (19%) and soups (11%).

The Panel noted that the anticipated dietary exposure of the adult population at the 97.5th percentile to Class I Plain Caramel exceeds the group ADI of 300 mg/kg bw/day proposed for the caramel colours. Similarly, the anticipated dietary exposure of the adult population at the 97.5th percentile to Class IV Ammonia Caramel exceeds this group ADI. For children, the upper end of both the mean intake ranges and also the 95th/97.5th percentile intakes for Class I Plain Caramel exceed the group ADI of 300 mg/kg bw/day. Similarly, for children, the upper end of both the mean intake ranges and also the 95th/97.5th percentile intakes for IV Sulphite Ammonia Caramel exceed the group ADI of 300 mg/kg bw/day.

The anticipated dietary exposure to Class II Sulphite Caramel for both adults and children was below the group ADI of 300 mg/kg bw/day.

For Class III Ammonia Caramel the upper end of the mean intake range for children exceeds the individual ADI of 100 mg/kg bw/day established for this colour within the group ADI, while the 97.5th percentile anticipated dietary exposures of both the child and adult populations are above this ADI of 100 mg/kg bw/day.

The Panel noted that anticipated combined dietary exposures of both adults and children to all caramel colours exceed the group ADI of 300 mg/kg bw/day at the 95th/97.5th percentile, while the ADI is also exceeded by the combined mean intake for children. In the case of children, this exceedance applies to the upper end of the exposure range only.

Reflecting the concerns regarding the immunotoxicity seen in a number of studies with either Class III Ammonia Caramel or with THI alone, found as a constituent in Class III Ammonia Caramel, and the carcinogenicity of 4-MEI, found as a constituent in Class III Ammonia Caramel and Class IV Sulphite Ammonia Caramel, the Panel has estimated exposure to THI and 4-MEI as a result of consumption of these caramel colours in the diet. Additionally the Panel has also estimated exposure to sulphur dioxide, present in Class II and Class IV caramel colours as a result of the production method. The Panel concludes overall that the exposure estimates for THI, 4-MEI or sulphur dioxide are not of concern, but notes remaining uncertainties regarding the effects of THI on the immune system. The Panel would welcome additional studies to clarify these effects.

The Panel notes that variations in the manufacturing processes of the caramel colours may result in a wide variability in the nature and levels of the various constituents, including constituents of toxicological concern such as 5-HMF and furan. Given this likely variability, the Panel considers that in order to further guarantee the safety of caramel colours with respect to their minor constituents, such as THI, 4-MEI, 5-HMF and furan, it would be prudent to reduce their levels as much as technologically feasible. The Panel considers therefore that the specifications for the caramel colours should be updated and extended to also include maximum levels for constituents of possible concern not yet included in the specifications, such as for example 5-HMF and furan.

The Panel additionally concludes that there is limited information about the relationship between processing parameters for the caramel colours and the formation and nature of heat-derived constituents, which is also relevant for the control of manufacturing processes. Future research work is recommended in this respect.

Keywords

Plain Caramel, Caustic Caramel, caramel colour I, E 150a, Caustic Sulphite Caramel, caramel colour II, E 150b, Ammonia Caramel, caramel colour III, E 150c, Sulphite Ammonia Caramel, caramel colour IV, E 150d, CAS Registry Number 8028-89-5, food colouring