First draft prepared by

Dr Peter J. Abbott
Food Standards Australia New Zealand, Canberra, Australia

Professor R. Walker
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, England

and Dr C. Leclercq
National Institute for Food and Nutrition Research, Rome, Italy

Alitame is an intense sweetener, with a sweetness potency 2000 times greater than that of sucrose. It is a dipeptide of L-aspartic acid and D-alanine, with a terminal N-substituted tetramethylthietanyl-amine moiety. Alitame is prepared by a multistep synthesis involving the reaction between two intermediates, (S)-[2,5-dioxo-(4-thiazolidine)] acetic acid and (R)-2-amino-N-(2,2,4,4-tetramethyl-3-thietanyl) propanamide. The final product is isolated and purified by crystallization of an alitame-4-methylbenzenesulfonic acid adduct, followed by additional purification steps, and finally recrystallization from water.

Alitame was considered by the Committee at its forty-fourth and forty-sixth meetings (Annex 1, references 116 and 122). Most of the toxicological studies were examined at the forty-fourth meeting, and specifications and a toxicological monograph were prepared; however, an ADI could not be allocated because of concern about deficiencies in the studies of carcinogenicity. At its forty-sixth meeting, the Committee reconsidered this issue in the light of a general discussion of the survival rates of animals in contemporary long-term studies and a further statistical analysis of the data from the two available studies. At that meeting, the Committee concluded that there was no evidence that alitame is carcinogenic. An ADI of 0–1 mg/kg bw was allocated on the basis of the NOEL of 100 mg/kg bw per day in an 18-month study in dogs. The Committee noted that, although not specifically requested, a further study of tolerance to repeated doses of alitame in persons with diabetes was under way and that, as is customary, the results should be forwarded to the Committee when available.

While consideration of the 90-day study of tolerance in diabetic subjects was on the agenda of the present meeting, it was postponed pending receipt of the final report.

According to the Codex draft General Standard for Food Additives (GSFA), alitame is permitted for use at a maximum level of 40–300 mg/kg in a wide range of foods and beverages, including bakery wares, water-based flavoured drinks, dairy-based drinks, dairy-based desserts, cream, edible ices, jams, confectionery and some dietetic foods. It is permitted for use within good manufacturing practice in table-top sweeteners and in some sugars (brown) and syrups (maple). The permitted uses in the Joint Food Standards Code of Australia and New Zealand, which was provided to the Committee, largely overlap with those in the Codex draft GSFA but also include use in flour products (including noodles and pasta), some processed fruit and vegetables, custard, jelly, sauces and toppings. In contrast, the Joint Food Standards Code allows its use only in specific bakery wares, not including bread (Australia New Zealand Food Authority, 2002).

The budget method was used to estimate the theoretical maximum level of use as a food additive in the proportion of food and beverages likely to contain alitame that would not result in exceedance of the ADI by the population (Table 1). The proportion of solid food and beverages that might contain alitame was set at 50%, since, according to the GSFA, it is allowed for use in food categories 7.0 (bakery wares which include a staple food, bread) and 14.1.4 (all carbonated and non-carbonated drinks.

Table 1. Theoretical maximum level of alitame estimated by the budget method

The theoretical maximum level of use of alitame is less than the maximum level permitted in solid foods and beverages by both the GSFA and the Australia New Zealand Food Authority. A detailed assessment of use of alitame in both solid and liquid foods was therefore required.

National assessments of intake based on a dietary survey at the individual level were provided by Australia and New Zealand (Hambridge, 2002a,b). National projections of intake of alitame in the USA, prepared for the Food and Drug Administration in 1986 (MRCA Information Services, 1986), were also available. The main results of these assessments are presented in Table 2.

Table 2. Intake of alitame estimated from individual surveys

Estimates based on individual consumption and levels of use in the GSFA and the Joint Food Standards Code showed that the ADI is slightly exceeded by consumers at high percentiles in both Australia and New Zealand. It should be noted, however, that high levels of consumption measured in short surveys, such as 24-h recall, overestimate long-term intake. Intake of alitame from ‘other sugars and syrups’ (category 11.2) was not assessed, as there was no maximum permitted level of use in this food category and no data were available on the levels of use in industry. Nevertheless, this food category is unlikely to contribute much to overall intake, in view of the low percentages of consumers (6% and 8%) and their low level of intake (9 g/day and 7 g/day) observed in the surveys in Australia and New Zealand, respectively. On the basis of permitted levels in Australia and New Zealand, the main contributors to the mean estimated intake of alitame were biscuits, cakes and pastries, flour products and water-based flavoured drinks in Australia and biscuits, cakes and pastries, sauces, toppings, mayonnaises and salad dressings and flour products including noodles and pasta in New Zealand. The estimated intake of alitame from the categories biscuits, cakes and pastries and flour products were widely overestimated in both countries, as alitame was assumed to be present in all items (no data were available on the presence of artificial sweeteners). The same was true for sauces and toppings in New Zealand.

Assuming Codex draft GSFA permissions, the category breads and bakery products accounted for 89% of the overall intake of alitame from all food categories in Australia and 88% in New Zealand.

The projections of intake in the USA were based on frequency of intake over 14 days, giving a better indication of long-term intake and thus a smaller overestimate of high intake. Nevertheless, the projected use levels in 1986 may not be reliable for adequately assessing current intake. The sponsors did not provide current manufacturers’ levels of use in the USA to the Committee.

While consideration of the 90-day study of tolerance in diabetic subjects was on the agenda of the present meeting, it was postponed pending receipt of a final report.

No data on the dietary intake of alitame were available at the previous meetings of the Committee. At its present meeting, the Committee compared the maximum levels of alitame listed in the Codex draft General Standard on Food Additives (GSFA) with the theoretical maximum level calculated by the budget method (see Annex 1, reference 137). On the assumption that alitame is used in all foods, the theoretical maximum level of alitame, based on the current ADI, was calculated to be 40 mg/kg. The maximum levels in the GSFA are up to 300 mg/kg in a wide range of foods and beverages, with no limit in ‘other sugars and syrups’ or in table-top sweeteners. Detailed assessments of the intake of alitame when used in foods were therefore required.

National assessments of intake based on recent individual dietary records and GSFA maximum levels were provided by Australia and by New Zealand. These data showed that the ADI might be exceeded by some consumers, at levels representing 140% of the ADI in Australia and 140% of the ADI in New Zealand for consumption at the 95th percentile. These are likely to be overestimates, as the surveys were of short duration (24 h) and because it was assumed that alitame was systematically present in some major food categories. The intake of alitame from ‘other sugars and syrups’ was not assessed since no manufacturer’s use levels were available. In both Australia and New Zealand, the main contributor to the mean estimated intake was sweet bakery wares, which was responsible for 89% of the overall estimated intake from all food categories in Australia and 88% in New Zealand. These estimates are based on data from only two countries, and further work is required to refine the intake estimates with recent data from other countries.

The estimates of intake were based on data from only three countries, and they should be further refined with intake estimates from other countries. The levels of use of alitame in ‘other sugars and syrups’ should be provided.

The Committee identified GSFA category 7 (bakery wares, including bread) as a food group that might contribute to a high intake of alitame, since this group includes foods that are staples in many countries. It therefore suggested that the Codex Committee on Food Additives and Contaminants consider reviewing standards for use of alitame.

The ADI of 0–1 mg/kg bw allocated by the Committee at its forty-sixth meeting was retained.

Australia New Zealand Food Authority (2002) Australia New Zealand Food Standards Code, Standard 1.3.1 Food Additives, Canberra (available at http://www.anzfa.gov.au)

Hambridge, T. (2002a) Information sheet for Australia on alitame. Canberra, Australia New Zealand Food Authority. Submitted to WHO by the Australia New Zealand Food Authority.

Hambridge, T. (2002b) Information sheet for New Zealand on alitame. Canberra, Australia New Zealand Food Authority. Submitted to WHO by the Australia New Zealand Food Authority.

MRCA Information Services (1986) Frequency distributions of the 14-day average daily intake and the sources of mean intake, of CP-54,802 in milligrams per kilogram of body weight for grand total and by 10 food subgroups for the period from July 1984 through June 1985. (Confidential) report to Pfizer, Inc. Submitted to WHO by Danisco USA, Inc., Ardsley, New York.

    See Also:
       Toxicological Abbreviations
       Alitame (WHO Food Additives Series 35)
       Alitame (WHO Food Additives Series 37)
       ALITAME (JECFA Evaluation)