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Formula

1. 1. — aspartyl — L — phenylalanjne methyl ester

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Aspartazias is a ~.tite, odourless crystalline powder, which is soluble in wwter(10.2 g/i at 25°C). The solubility is affected by pH, being about 18 g/l at p3~

3.7 and about 14 g/l at pH 5,7.

i~nufacture

2. There are two routes used for the manufacture of aspartame, both are &iven

below.

Route I

3. Phoegene (t) is reacted with benzyl ~lco1iol(fl) to produce carbobenzoxychloride (III); unreacted phosgene and hydrogen chloride are removed by the

passage of dry air through the reaction mixture. L—aspaflie acid (iv) is

dissolved in dilute sodium hydroxide, a strong solution of sodium hydroxido and

a solution of carbobenzoxy choride in 1 ,2—dichloroeth~,~e. are added dzt~’tzi.se

to the aapartic, acid solution. After the reaotion is complete water io Mded

to the r€action mixture, the aqueous layer is separated from the organic le.yex’

end acidified to produce N-carboben~~ragnanjc acid (v), N—earbobenzo:cyaspart;~~

acid is dissolved in I,2—dichloroethane and reacted with acetic acid to e.’ivo

N—carbobenzoxyaspartjc acid anhydride (vi). i~i~t~yi phcnylalanin~te (vu)

is dissolved in 1,2—dichioroethane and, reacted with the acid anhydride (VI) to

produce methyl—N—oarbobenzoxJe,spañyl_phe~lalwijnate (viii). The react ion

mixture is concentrated by evaporation to dryness, redissolved in methanol

and the residual. acetic acid is neutralised with sodin carbonate. The

solution is then hydrogenated using a palladised charcoal catalyst to

produce aepartame (u).

Route 2 -

4. Aspartic acid (i) ie reacted with phosphorous trichioride in acetic acidto produce aspartic acid anhydride hydrochloric acid salt (ii). The hydrochiori

acid salt is reacted with methyl phenylalaninate in I ,2—dichloroethane toproduce aspartame hydrochloric acid salt (III); treatment of the salt withsodium carbonate liberates asparta~ne.

A copy of the Food Q’~emicals Codex specification for aspartame is attached.

Current Status

5. Aspartame is not permitted, for iwo in Food in the UK.

The case of need for aspartaine was first considered by the WACO at its meeting c17 December 1975, The TSC also considered aspartaze and was of a mind, to

classify it in Group A but required clarificat ion of some of the toxicological

data. The WACO recons&dered the case on need at its October 1978 meeting and

agreed that a general case of need had. been established.

Stability

6. Mechanism: The transformation of aspartate in aqueous solution occurs

primarily by the hydrolysis of the methyl ester linkage to produce aspartylpheny

lalanine (reaction 1); higher pfls favour this reaction. Hydrolysis of the

snide linkages may occur (reaction 2) but this is much slower than hydrolysis of

the ester linkage and is favoured at lower pHa. Nethanol is formed regardless

of the hydrolysis mechanism. Aspartylphen,ylalanjne cyclises to form

diketopiperazjne (reaction 3) whiob can break down to give phenylalanine and

aspartic acid (reaction 4). The reactions are ~ho~m below.

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7. Stability in food: The following paragraphs sulmnarise information aboutthe stability of aspartame received in the submissions, The data fall into threc~

groups, the first is releva~yt to the stor~je of powdered aspartwno, the secondto the etorago of dry foods contaixilng aspaream~ and the, thiz~ to the stability

of aspartayn~ in linuid foods made up just prior to consumption [by adding a

powdered food containing aspartan,~ to a liquia.J

8. (a) Stability of aspartame powder. Storage trials mado with asnartame

powder contained in class bottles with plastic lids showed that after 52

weeks at 40°C the DIP level could rise to i.~% from an initial value ot

0.5% or less. The aspartyiphenylalanine level did not rise above ~

No free amino acids were detected in the samples, the limit of detection

was o.i%. Heating aspartame at 10500 gives 5% DIP after 70 hours, however

at 150°C and 12000 brecdcdown is much more rapid.

9. (i’) Stability in powdered foods. A considerable volume of data has beensubmitted on the stability during storage of flavoured gelatin dessertmixes and powdered soft drink mixes sweetened with aspartarne. Storage

trials were made with the powdered mixes in etwidaM packaging for 24 weeks

under accelerated storage conditions including temperatures of up to 3800

and relative humidities of up to 85%. At no tine did the DIP level erceed2% of the aspartarne level in the product. The meximum level of aspartarnewas in a grape beverage mix and was 15.8%. If the DIP level rose to 2%

of the a.spartwne concentz~ation, it would be 3160 nc/kg in the product essoil; the Secretariat calculate that this would correspond to DIP levelof 130 mg/i in the grape beverage as consumed. In general DIP was presentin the powdered mixes at between 1—1.8% of the aspartame level.

10. (c) Stability in liquid foods. A powdered soft drink was dissolved in

cold, water and to this was added 6oo mg/i of aspartane, the pH of the drinkwas 2.5. The initial level of diketopiperazine ;•ss 9.6 mg/i and after 7

days at about 1000 this had risen to 15.5 mg/I. The Secratariat estimatefrom the data in the submission that, had the drink been stored at 20°C for

7 days, the DIG’ concentration would have been approximately 25 mg/i.Measurements of the aspartame concentration in drinks made from powderedmixes sweetened with aspartame show that there was no significant decrease

in the aspartwne concentration of the drink after 5 days storage at room

temperature or at 70Q in the case of a grape drink, but with a lemonade

drink up to 3.1% of the aopartamb was hyth’olysed. There are considerable

variations in the results because of uncertainties arising from the methodof analysis for aspartame.

11. The foregoing information is summarised below:

(a) Aspartame powder breaks down during storage to yield I;)’?, however

after storage for 1 year at 4o Th the level of DIG’ is unlikely to exceed

1.5;~. The breeicdo~,n is more rapid at elevated temperatures.

(b) The level of D!G’ in powkred products containing aspartame and Stored

at up to 3~ C in unlikely to exceed 2% of the aspartwne level. I~ the

extreme this would correspond to about 130 mg/kg (o.i$) DKP in the food

as consumed.

(a) The level of DIG’ in liquid foo.jo intended to be made up just prior to

Consumption ~ncreaseL3 if the Prepared food is stored. The rate of break

down of aspafl~e to give DI~ is both pH and temperature dependant. In

extreme conditions the level of DIG’ may increase by a factor of about 3.

PROPOSED USES AND LEVELS OF USE

level of use g/kg or

g/i.Food

Food as sold Food as consumed

Confectionery up to 20 up to 20

Soft drink — up to 1

po~’dored beverages 85.9 0.66*

18.3 0.75*

diet dessert m~zces

gelatin dessert 79.3 2.24*

pudding/filling/topping mixes 9.8 0.65*

whipped topping 4.2 0.98*

presweetened cenals 3.3 depends upon added

milkchewing gum 6.5 6.5

wator ices, mou~rsc and saucec — —

—

* Calculated by the Secretariat from the date. in the submissions.

12. The Committee win wink to note that a 115 p~Sent has been granted for

the use of DIG’ ii3 food at levels from 10 to 200 rag/ha. The DIP enhances

or imprnves the gustative effect of cheese flcwourc.

13. Potential Intake: 11 all the saccharin consumed in the UK Nto replaced ~.y

aspartame, then assuming that:

1. the relative sweetness of i~aocharin is 300;

2. t~ relative sweetness of aspartame is 200; and

3. the average daily intake of saccharin is 33.6 rag/person.

then the average daily intake of aspartame iqou]4 be 50.4 mg/person. however‘the main use of saccharin in food is with liquid soft drink aM aupartw,1e isnot suitable for use in such food because of ite susceptibility to

hydrolysis. If aepartame replaced all uses of saccharin in food includingIts use as a table—top sweetener but excluding its use in liq~dd Boft drink1

then the daily intake of aspartaxae would be 25.7 mg/person.

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