Return To Main Page On Sucralose
Today, the Joint Subcommittee on
Toxicity and Food Additives under the Food Sanitation
Council has compiled a report on the result of
discussions conducted during the session held on December
18, 1998 on the adequacy of the designation of Sucralose
as an approved additive. The session was based on the
consultation made by the Minister of Health and Welfare
to the Food Sanitation Council on June 15, 1998. The Food
Chemistry Division hereby announces an outline of the
report and work schedule for the designation of
Sucralose.
1. Outline of the report
About the adequacy of the
designation of Sucralose
2. Schedule
(1) Presentation to the Conference
for Promotion of Food Import and Facilitation
(Presentation to embassies and EU representative in Tokyo)
(2) Notification given to WTO
(Notification given to the member countries, based on the Marrakech Agreement to Establish the World Trade Organization)
(3) A final report from the Food
Sanitation Council to the Minister of Health and Welfare
(4) Amendment of the Enforcement
Regulations under the Food Sanitation Law, and
announcement of the designation of Sucralose with newly
added regulations
* Translated by The San-Ei Gen
Foundation for Food Chemical Research. Please refer to
the Japanese version, if you find anything unclear on
this translation.
Food Sanitation Council Notice,
No.5
January 6, 1999
Mr. Masaaki Terada, Chairman
Food Sanitation Council
Today, the Joint Subcommittee on
Toxicity and Food Additives under the Food Sanitation
Council has compiled a report on the result of
discussions conducted during the session held on December
18, 1998 on the adequacy of the designation of Sucralose
as an approved additive. The session was based on the
consultation made by the Minister of Health and Welfare
with the Food Sanitation Council on June 15, 1998, under
Notice No. 109 issued by the Ministry of Health and
Welfare. We hereby jointly report the result to the
Chairperson of the Food Sanitation Council.
The Joint Subcommittee on
Toxicity and Food Additives
under the Food Sanitation
Council
1. The Joint Subcommittee on
Toxicity and Food Additives concerning the Designation of
Food Additives under the Food Sanitation Council
| 1) Date of session | December 18, 1998 |
| 2) Members' list | Omitted |
2. The Working Group on the
Designation of Food Additives
| 1) Dates of sessions | 1st August 6,
1998 2nd October 6, 1998 3rd November 13, 1998 |
| 2) Members' list | Omitted |
Designation of Sucralose
1. Name: sucralose
(Synonyms)
trichlorogalactosucrose
4,1',6'-trichlorogalactosucrose
2. Structural formula:
Chemical name : 1,6-dichloro-1,6-dideoxy-beta-D-fructofuranosyl-4-chloro-4-deoxy-alpha-D-garactopyranoside
Chemical formula: C12H19Cl3O8
Molecular weight: 397.64
CAS No.: 56038-13-2
INS No.: 955
3. Use:
Sweetening agent
Sucralose is used as a sweetening agent in more than 100 kinds of foods; e. g., drinks, desserts, and dressings.
4. Origin or details of development and use conditions
Sucralose is produced by
selectively replacing three hydroxy groups with
chlorine atoms.
Sucralose, which is 600 times
sweeter than sucrose, was discovered during
collaborative research between Queens Elizabeth College
in London and a private company, Tate & Lyle, after an
experiment involving chemical modification of sucrose
conducted by the same collage in the 1970's.
The Joint FAO/WHO Expert Committee
on Food Additives (JECFA) evaluated the safety of
sucralose. The JECFA allocated 0-3.5 mg/kg bw/day as a
temporay ADI for sucralose in 1988 and 0-15 mg/kg bw/day
as the ADI in 1990 at the 37th session.
5. Effectiveness
Sucralose will be able to be
used in various foods as a sweetener.
Sucralose has few of the drawbacks
in taste and stability exhibited by several of the
previously approved sweeteners. Sodium saccharine,
stevia extract, and licorice extract have
characteristic bitterness and stringency. Aspartame is
low in storage stability and heat stability in a
neutral or alkaline aqueous solution. Sucralose is well
examined in terms of these aspects. The attached
document mentions that this sweetener has similar
sweetness to sucrose and has no bitterness or metalic
and other unpleasant tastes. In addition, it mentions
the substance is superior in stability to other
sweeteners (Attachment 1). For example, 97.1% of
sucralose in a 1 % aqueous solution remains after a
336-day storage period under the condition of 30ｰC
and pH 3.0.
(Note: Approved sweeteners include
aspartame, xylitol, disodium glycyrrhizinate,
saccharin, sodium saccharin, and D-sorbitol, which
appear in Table 2 of the Enforcement Regulations under
the Food Sanitation Law, and N-acetyl glucosamine,
licorice extract, D-xylose, and stevia extract, which
appear in the List of Existing Food Additives (Ministry
of Health and Welfare Announcement No. 120).
6. Safety
(1) Acute Toxicity Studies - Rats and mice received a single oral dose of sucralose at 10.0g/kg and 16.0g/kg, respectively. The administration was by gavage. No deaths were observed during the 14-day observation period. The LD50 was estimated at more than 10.0g/kg for rats and more than 16.0g/kg for mice.
(2) Subacute Toxicity Studies -
No deaths were observed of rats fed sucralose in the
diet at levels of 10,000, 25,000 and 50,000 ppm for 4
weeks. Atrophy of lymph follicles in the spleen and
thymus was observed in the 50,000 ppm group. Rats
exposed to sucralose at dietary concentrations of 4 and
8% for 9 weeks exhibited a reduced growth rate and
increased cecal weights. For rats exposed to oral (gavage)
doses of 2,000, 3,000 and 4,000 mg/kg for 4, 9, and 13
weeks, increased cecal weights were observed in all
groups, but there was no apparent toxicological
significance. Increased cecal weights observed in these
studies were reported in animals exposed to
less-absorbable osmotically-active substances at high
dose levels and toxicological significance was
considered to be low. In addition, no remarkable
changes were noted in an oral 34-day toxicity study in
mice.
(3) Repeated Dose (Chronic)
Toxicology and Carcinogenicity Studies - In a 26-week
oral study, in which sucralose was fed to rats at doses
of 1 and 3 %, there were no toxicological effects,
except for reduction in body weight gain. In this
study, dietary restriction groups were also
investigated to elucidate the cause of the growth
retardation. It was concluded that the decreased body
weight gain in the 1% group was attributable to
decrease in food intake. It was also concluded that the
majority of the growth retardation in the 3% group
could be attributed to reduction in food consumption,
although some of the effect might be related to a
physiological response to the high concentration of
nondigestable sucralose in the diet. In a 12-month
repeated dose toxicity study in Beagle dogs, no
toxicological effect was observed at dietary levels of
0.3, 1 and 3%. In a combined chronic
toxicity/carcinogenicity study in mice exposed to
sucralose at dietary levels of 3,000, 10,000 and 30,000
ppm for 104 weeks, neither deaths nor any clinical
signs related to the treatment were observed. The
incidences of neoplastic lesions in treated and control
groups were similar. In both sexes of the 30,000 ppm
group, growth retardation, related to decreased food
intake, was observed, and females given sucralose at
dietary concentrations of 10,000 ppm or more showed
increased relative liver weights. A decreased red blood
cell count was noted for females of the 30,000ppm
group. These changes were not considered to be of
toxicological significance, since there were no
associated histopathologic lesions. No carcinogenicity
was observed in either sex of mice exposed to sucralose
at up to 30,000 ppm. In a combined chronic
toxicity/carcinogenicity study in rats, animals were
fed diets containing sucralose at concentrations of
3,000, 10,000 and 30,000 ppm for 104 weeks. Growth
retardation related to decreased food intake was
observed in all treated groups, but this was not
considered to be of toxicological significance. The
incidence of mild hyperplasia in the renal pelvis was
significantly increased in females of all treated
groups, accompanied by mineral deposition in 10,000 ppm
and 30,000 ppm females. This was considered to have a
causal relation, associated with a physiological
response of caecum enlargement induced by diet
containing high levels of poorly absorbable substances.
Enlargement of the caecum and mineral deposition in the
renal pelvis are reported to occur frequently in
response to feeding poorly-absorbable, osmotically-active
substances, such as xylitol, sorbitol or natural
sugars, to rats*1, 2), and it is considered that the
toxicological significance of this might be minimal.
The no-observed-adverse-effect level (NOAEL) in rats
was estimated to be 30,000 ppm (1,500 mg/kg bw/day). No
carcinogenicity was observed in either sex of rats.
* 1 Leegwater, D. C., DE
Groot, A. P. & VAN Kalmthout-Kuiper, M.
Fd. Cosmet. Toxicol.
(1974) The aetiology of caecal enlargement in the
rat. 12: 687-697
2 Lord, G. H. & Newberne, P. M.
Fd. Chem. Toxic
(1990) Renal mineralization - a ubiquitous lesion in
chronic rat studies (REVIEW). 28:449-455
(4) Reproduction Study -
Repeated oral administration of sucralose to male rats
at a dose level of 500 mg/kg/day for 28 days resulted
in no changes in 14CO2
production or ATP concentration of sperm. In a
two-generation reproduction study in rats, parents and
offspring rats given sucralose in the diet at dose
levels of 3,000, 10,000 and 30,000 ppm. No adverse
effects on parameters concerned with reproduction, such
as copulation rate, fertility rate, gestation rate,
birth rate and birth numbers, were observed in the
treated groups. Furthermore, in the derivation phase of
a two-year chronic toxicity/carcinogenicity study with
dietary levels of 3,000, 10,000 and 30,000 ppm,
sucralose had no adverse effects on any reproductive
parameter. Although slight extension of the pregnancy
period was observed, this was not considered as
biologically significant. In addition, no adverse
effects were found on their offspring.
(5) Teratogenicity Study -
Sucralose was administered by gavage to pregnant rats
(days 6 to 15 of gestation) at dose levels of 500,
1,000 and 2,000 mg/kg/day. In this study, no adverse
effects were observed on fetuses. No teratogenicity was
noted and therefore the NOAEL was estimated to be over
2,000 mg/kg. In another teratogenicity study in
rabbits, sucralose was administered to pregnant animals
(days 6 to 19 of gestation) at dose levels of 175, 350
and 700 mg/kg/day. At the highest level of 700 mg/kg,
the parent animals showed decreased body weights
accompanied with gastrointestinal disturbance
(diarrhea), and deaths and abortions were observed.
However, it was considered that this effect was related
to a high sensitivity of rabbits to poorly-absorbable,
osmotically-active substances. Sucralose at the dose
level of 700 mg/kg did not affect the growth and
development of fetuses. In this study, sucralose did
not exert any teratogenic effects, and the NOAEL was
estimated to be over 700 mg/kg.
(6) Antigenicity Study - In a
study using guinea pigs, animals were first
intradermally treated with Freunds Complete Adjuvant (FCA),
30% sucralose aqueous solution or 10% sucralose FCA
emulsion as the first sensitization treatment, and 7
days later 50% sucralose solution was applied topically
as the second sensitization treatment. No delayed
contact hypersensitivity was found.
(7)Mutagenicity Study - In a
reverse mutation test in
Salmonella typhimurium,
sucralose did not show any mutagenicity at levels of
16, 80, 400, 2,000 and 10.000
mg/plate.
In a DNA repair test with
Escherichia coli,
no genotoxic effects were observed at doses of 0.5, 1,
10, 100, 500, and 1000 mg/plate
under the test conditions. In a
in vitro
chromosome aberration test with human peripheral
lymphocytes, no significant effects were found at
levels of 8, 40 or 200 mg/ml.
On the other hand, in an
in vitro
mutagenesis assay using mouse lymphoma cells, with
sucralose at levels of 1,335, 1,780, 2,373, 3,164,
4,219, 5,625, 7,500 and 10,000
mg/ml,
weak mutagenicity was demonstrated at the two highest
doses. In a mouse bone marrow micronucleus assay, mice
were given a single oral dose of sucralose at 1,000 and
5,000 mg/kg. There was no evidence of induced
chromosomal damage leading to micronucleus formation.
In addition, in a rat bone marrow cytogenetic assay,
when rats were orally treated with sucralose at doses
of 500, 1,000 and 2,000 mg/kg for five days, no
chromosome aberrations were induced.
Thus, the positive result
from the in vitro
mutagenesis assay using mouse lymphoma cells was
judged to be of no toxicological significance, since
this adverse effect appeared only at very high
concentrations, and all other mutagenesis bioassays
gave negative results.
(8) General Pharmacological Studies - There were no adverse clinical signs or altered behavior exhibited by rats and mice in any of the relevant oral studies. Furthermore, no potential of sucralose to cause toxic effects to the central nervous system of mice, monkeys and humans was evident on neurological and/or histopathological examination. In addition, in clinical studies in human, sucralose did not affect the respiration rate, pulse, blood pressure, or electrocardiogram findings, and did not influence the respiratory or cardiovascular systems. In the gastrointestinal system, repeated administration of sucralose to rats caused increase in caecum weight. However, it was considered that the toxicological significance of this change was negligible, since no histopathological alterations were found. With regard to effects of sucralose on water and electrolyte metabolism, increase in water intake was noted, but no significant effects on electrolyte constituents or urine volume were observed.
(9) Other Toxicity Studies
The results from the studies,
listed in attachment 1, were submitted.
No major adverse effects and
signs were observed.
7. Absorption, Distribution, Metabolism and Elimination
(1) Absorption and Elimination
- When sucralose was orally administered to mice, rats,
dogs and humans, the results for absorption,
elimination and kinetics were similar between animal
species. Approximately 60 to 90% of the sucralose was
excreted in the feces, while the remaining 10 to 30%
was excreted in the urine. None was detected in the
expired air. Maximal plasma levels in these species
were observed 30 minutes to 3 hours after the
administration. For example, when sucralose was orally
administered to rats at a dose of 2,000 mg/kg, the
plasma concentration reached the highest level of 10 to
15 mg/ml
within an hour. The 'half-life' of sucralose in human
was determined to 2.5 to 23 hours.
(2) Distribution - In studies of
oral administration of radiolabeled sucralose to the
rat, maximal levels were observed in the liver, kidney,
and gastrointestinal tract, but those levels declined
to under the plasma level within 24 hours. There was no
indication of active transport across the blood brain
barrier, judging from levels in the brain.
(3) Metabolism - In rats, dogs and
humans, most of the excreted material in urine and
feces following oral administration was unchanged
sucralose, with a small amount of the glucuronic acid
conjugate identified in the urine of dogs and humans.
(4) Others - In a human study,
sucralose did not affect the absorption of sucrose, and
did not increase the secretion of insulin.
8. Determination of acceptable
daily intake(ADI)
Based on a accompanying
documents, we evaluated as follows.
No-observed-adverse-effect-level (NOAEL)
1,500mg/kg bw/day
Animal species rat
Dose levels 3%(30,000ppm) into the
diet
Duration of administration 104
weeks
Test species Combined toxicity /
carcinogenicity study
Safety factor 100
In the rabbit teratogenicity
study, some adverse effects were recognized in the
parent animals at a dose level of 700 mg/kg. Rabbits
are sensitive to substances with low absorbability and
positive osmotic pressure activity, and are subject to
diarrhea. Teratogenicity was not observed in fetal at a
dose level 700mg/kg. Therefore, though the NOAEL of
parent animal is estimated at 350mg/kg in this study,
it is inappropriate to use the NOAEL as a basis for
establishing the ADI of sucralose.
As mentioned above, as sucralose
ADI 15mg/kg bw/day
9. Estimation of daily intake
Sucralose is expected to be used in various foods as a sweetener. Based on food intakes according to food group obtained from the 1993 National Nutrition Survey, the daily intake of sweeteners is estimated at 35.0 g, converted into sucrose. Sucralose is 600 times sweeter than sucrose. Therefore, the estimated daily intake of sucralose is 58.3 g, when calculated by converting sucrose into sucralose. The estimated daily intake for the Japanese is 1.17 mg/kg, assuming that the Japanese average body weight is 50 kg.
10. Standards for use of
sucralose
|
Additives
|
Major use
|
Standards for use
|
||
|
Foods
|
Maximum Limit of use
|
Limitation of use
|
||
|
Sucralose
|
Sweetener
|
Confectionery | 1.8g/kg | The limits are not apply for foods approved for "special dietary use" labeling. |
| Chewing gum | 2.6g/kg | |||
| Jam | 1.0g/kg | |||
| Nonalcoholic
beverages "Sake"(rice wine) Wine Miscellaneous alcoholic beverages Milk drinks Lactic acid bacteria drinks |
0.40g/kg (This limitation is applied to a diluted product in case of a concentrated product.) |
|||
| Substitute for Sugar | 12g/kg | |||
| Other foods | 0.58g/kg | |||
11. Specifications
Specifications for components of sucralose should be established as given in Attachment 2. For information, Attachment 3 gives a table which compares the Japanese proposed specifications with those by JECFA and the Food Chemicals Codex (FCC).
The study results and other
information mentioned here were given in the accompanying
documents listed in Attachment 1.
Attachment 1
Contents of document
|
Contents
|
Reference
|
Document No
|
Vol.
|
| 1 Summary |
San-Ei Gen F.F.I., Inc.
|
1
|
1
|
2 Chronology on origin or
development and overseas use condition
| 2-1 Details of origin or development |
San-Ei Gen F.F.I., Inc.
|
2-1
|
2
|
| 2-2 Overseas use condition |
San-Ei Gen F.F.I., Inc.
|
2-2
|
2
|
3 Physicochemical characteristics
and specifications
| 3-1 Name |
San-Ei Gen F.F.I., Inc.
|
3-1
|
2
|
| 3-2 Structural formula or rational formula |
San-Ei Gen F.F.I., Inc.
|
3-2
|
2
|
| 3-3 Molecular formula and molecular weight |
San-Ei Gen F.F.I., Inc.
|
3-3
|
2
|
| 3-4 Assay |
San-Ei Gen F.F.I., Inc.
|
3-4
|
2
|
| 3-5 Methods of manufacturing |
San-Ei Gen F.F.I., Inc.
|
3-5
|
2
|
| 3-6 Description |
San-Ei Gen F.F.I., Inc.
|
3-6
|
2
|
| 3-7 Identification |
San-Ei Gen F.F.I., Inc.
|
3-7
|
2
|
| 3-8 Specific properties |
San-Ei Gen F.F.I., Inc.
|
3-8
|
2
|
| 3-9 Purity tests |
San-Ei Gen F.F.I., Inc.
|
3-9
|
2
|
| 3-10 Water |
San-Ei Gen F.F.I., Inc.
|
3-10
|
2
|
| 3-11 Residues on ignition |
San-Ei Gen F.F.I., Inc.
|
3-11
|
2
|
| 3-12 Method of assay |
San-Ei Gen F.F.I., Inc.
|
3-12
|
2
|
| 3-13 Stability |
Tate & Lyle Speciality
Sweeteners
|
3-13
|
2
|
| 3-14 Analytical method for the food additives in food |
Tate & Lyle Speciality
Sweeteners and
San-Ei Gen F.F.I., Inc. |
3-14
|
2
|
| 3-15 Specification |
San-Ei Gen F.F.I., Inc.
|
3-15
|
2
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| 3-16 Overall judgement table |
San-Ei Gen F.F.I., Inc.
|
3-16
|
2
|
4 Effectiveness
| 4-1 Effectiveness |
Tate & Lyle Speciality
Sweeteners
|
4-1
|
3
|
| 4-2 Comparison in the effects with other similar food additives |
Tate & Lyle Speciality
Sweeteners and
San-Ei Gen F.F.I., Inc. |
4-2
|
4
|
| 4-3 Stability in foods |
Tate & Lyle Speciality
Sweeteners and
San-Ei Gen F.F.I., Inc. |
4-3
|
4
|
5 Safety evaluation
(1) Toxicity studies
| 5-1 Investigation of report on the safety of sucralose |
San-Ei Gen F.F.I., Inc.
|
5-1
|
5
|
5-2 Safety evaluation for
sucralose
5-2-1 Acute toxicity study
| 5-2-1-1 Acute oral toxicity studies in the rat. |
Johnson & Johnson
Research Foundation (1980) |
5-2-1-1
(E002) |
6
|
| 5-2-1-2 Acute oral toxicity to mice. |
Life Science Research
(1977) |
5-2-1-2
(E001) |
6
|
5-2-2 Subacute toxicity study
| 5-2-2-1 8-week toxicity study in rat . |
Life Science Research
(1983) |
5-2-2-1
(E031) |
6
|
| 5-2-2-2 Dose range finding study in rat during lactation. |
Johnson & Johnson
Research Foundation (1984) |
5-2-2-2
(E060) |
6
|
| 5-2-2-3 9-weeks toxicity study in rat. |
Hazleton Lab. America
(1985) |
5-2-2-3
(E098) |
6
|
| 5-2-2-4 4, 9 and 13-week toxicity study in rat. |
Inveresk Res. International
(1988) |
5-2-2-4
(E151) |
6
|
| 5-2-2-5 Dose range finding study in mice (34 days). |
Johnson & Johnson
Research Foundation (1983) |
5-2-2-5
(E062) |
6
|
5-2-3 Chronic toxicity study
| 5-2-3-1 Dietary administration study in rat (1) |
Pharmaco-LSR
(1993) |
5-2-3-1
(E160) |
6
|
| 5-2-3-2 Dietary administration study in rat (2) |
Pharmaco-LSR
(1994) |
5-2-3-2
(E161) |
6
|
| 5-2-3-3 Oral toxicity study in dogs (12 months) |
Hazleton Lab. America
(1985) |
5-2-3-3
(E051) |
6
|
5-2-4 Reproduction study
| 5-2-4-1 Anti-fertility screen in male rats. |
Life Science Research
(1978) |
5-2-4-1
(E016) |
7
|
| 5-2-4-2 The effect of sucralose on the glycolytic ability of rat spermatozoa. |
University Whiteknights
(1987) |
5-2-4-2
(E107) |
7
|
| 5-2-4-3 Two generation reproductive study in rats. |
Life Science Research
(1986) |
5-2-4-3
(E056) |
7
|
| 5-2-4-4 104-Week combined toxicity and oncogenicity study in rats. ; Breeding phase. |
Life Science Research
(1987) |
5-2-4-4
(E057) |
7
|
5-2-5 Teratogenicity study
| 5-2-5-1 Effects of oral administration upon pregnancy in the rat. |
Life Science Research
(1983) |
5-2-5-1
(E030) |
7
|
| 5-2-5-2 Preliminary study in the pregnant rabbit. |
Life Science Research
(1987) |
5-2-5-2
(E115) |
7
|
| 5-2-5-3 Preliminary teratology study in the rabbit. |
Life Science Research
(1987) |
5-2-5-3
(E129) |
7
|
| 5-2-5-4 Teratology study in the rabbit. |
Life Science Research
(1987) |
5-2-5-4
(E134) |
7
|
5-2-6 Carcinogenicity study
| 5-2-6-1 104-Week oncogenicity study in mice. |
Life Science Research
(1987) |
5-2-6-1
(E055) |
8
|
5-2-7 Combined chronical
toxicity/carcinogenicity study
| 5-2-7-1 104-Week combined toxicity and oncogenicity study in rats. |
Life Science Research
(1986) |
5-2-7-1
(E057) |
9,10
|
5-2-8 Antigenicity study
| 5-2-8-1 Delayed contact hypersensitivity study in guinea-pigs. |
Life Science Research
(1986) |
5-2-8-1
(E113) |
11
|
5-2-9 Mutagenicity study
| 5-2-9-1 Reverse mutation test with Salmonella typhimurium. (1) |
Life Science Research
(1981) |
5-2-9-1
(E015) |
11
|
| 5-2-9-2 Reverse mutation test with Salmonella typhimurium. (2) |
Litton Bionetics Inc.
(1979) |
5-2-9-2
(E011) |
11
|
| 5-2-9-3 Gene mutation test in mouse lymphoma cells. |
E & G Mason
Research Institute (1981) |
5-2-9-3
(E014) |
11
|
| 5-2-9-4 Micronucleus test in mouse bone marrow erythrocytes. (1) |
Life Science Research
(1978) |
5-2-9-4
(E010) |
11
|
| 5-2-9-5 Micronucleus test in mouse bone marrow erythrocytes. (2) |
Life Science Research
(1986) |
5-2-9-5
(E114) |
11
|
| 5-2-9-6 Chromosome aberration test in the rat bone marrow. |
Litton Bionetics Inc.
(1981) |
5-2-9-6
(E013) |
11
|
| 5-2-9-7 Chromosome aberration test in cultured human peripheral lymphocytes. |
Life Science Research
(1981) |
5-2-9-7
(E012) |
11
|
| 5-2-9-8 DNA repair test in Escherichia coli. |
Litton Bionetics Inc.
(1979) |
5-2-9-8
(E011) |
11
|
5-2-10 General pharmacological
study
5-2-10-1 Effects on general
conditions
| 5-2-10-1-1 Acute oral toxicity studies in the rat. |
Johnson & Johnson
Research Foundation (1980) |
5-2-10-1-1
(E002) |
12
|
| 5-2-10-1-2 Acute oral toxicity to mice. |
Life Science Research
(1977) |
5-2-10-1-2
(E001) |
12
|
| 5-2-10-1-3 Neurotoxicity study in mice. |
Life Science Research
(1981) |
5-2-10-1-3
(E008) |
12
|
| 5-2-10-1-4 4, 9 and 13-week toxicity study in rat. |
Inveresk Res. International
(1988) |
5-2-10-1-4
(E151) |
12
|
| 5-2-10-1-5 Dietary administration study in rat (2) (26-week) |
Pharmaco-LSR
(1994) |
5-2-10-1-5
(E161) |
12
|
| 5-2-10-1-6 A study to observe the tolerance to orally administered single ascending doses of TGS followed by seven days administration in eight normal subjects. |
Medical Science Research
(1984) |
5-2-10-1-6
(E047) |
12
|
| 5-2-10-1-7 A tolerance study in normal subjects of varying doses of TGS administered continuously for a period of thirteen weeks. |
Medical Science Research
(1986) |
5-2-10-1-7
(E048) |
12
|
5-2-10-2 Effects on the central
nervous system
| 5-2-10-2-1 Neurotoxicity study in mice. |
Life Science Research
(1981) |
5-2-10-2-1
(E008) |
12
|
| 5-2-10-2-2 Neurotoxicity study in marmoset monkeys. |
Life Science Research
(1981) |
5-2-10-2-2
(E009) |
12
|
| 5-2-10-2-3 A study to observe the tolerance to orally administered single ascending doses of TGS followed by seven days administration in eight normal subjects. |
Medical Science Research
(1984) |
5-2-10-2-3
(E047) |
12
|
5-2-10-3 Effects on the respiratory
and cardiovascular systems
| 5-2-10-3-1 A study to observe the tolerance to orally administered single ascending doses of TGS followed by seven days administration in eight normal subjects. |
Medical Science Research
(1984) |
5-2-10-3-1
(E047) |
12
|
| 5-2-10-3-2 A tolerance study in normal subjects of varying doses of TGS administered continuously for a period of thirteen weeks. |
Medical Science Research
(1986) |
5-2-10-3-2
(E048) |
12
|
5-2-10-4 Effects on the gastrointestinal system
| 5-2-10-4-1 9-week toxicity study in rat. |
Hazleton Lab. America
(1985) |
5-2-10-4-1
(E098) |
12
|
| 5-2-10-4-2 4, 9 and 13-week toxicity study in rat. |
Inveresk Res. International
(1988) |
5-2-10-4-2
(E151) |
12
|
| 5-2-10-4-3 Dietary administration study in rat (2) (26-week) |
Pharmaco-LSR
(1994) |
5-2-10-4-3
(E161) |
12
|
5-2-10-5 Effects on water and electrolyte metabolism
| 5-2-10-5-1 8-week toxicity study in rat. |
Life Science Research
(1983) |
5-2-10-5-1
(E031) |
13
|
| 5-2-10-5-2 9-week toxicity study in rat. |
Hazleton Lab. America
(1985) |
5-2-10-5-2
(E098) |
13
|
| 5-2-10-5-3 104-Week combined toxicity and oncogenicity study in rats. |
Life Science Research
(1986) |
5-2-10-5-3
(E057) |
13
|
5-2-11 Other toxicity study
| 5-2-11-1 Neurotoxicity study in mice. |
Life Science Research
(1981) |
5-2-11-1
(E008) |
14
|
| 5-2-11-2 Neurotoxicity study in marmoset monkeys. |
Life Science Research
(1981) |
5-2-11-2
(E009) |
14
|
| 5-2-11-3 Immunotoxicity study in rats. |
TNO Nutrition
and Food Research (1994) |
5-2-11-3
(E162) |
14
|
| 5-2-11-4 Eight-week palatability study in female rats. |
Life Science Research
(1985) |
5-2-11-4
(E058) |
14
|
| 5-2-11-5 14-week palatability study in rats. |
Life Science Research
(1988) |
5-2-11-5
(E143) |
14
|
| 5-2-11-6 An investigation of the acceptability of aqueous solutions of sucralose to rats. |
Life Science Research
(1987) |
5-2-11-6
(E130) |
14
|
| 5-2-11-7 An investigation of diet spillage among rats fed diet containing sucralose. |
Life Science Research
(1991) |
5-2-11-7
(E154) |
14
|
| 5-2-11-8 14-day palatability study in beagle dogs. |
Life Science Research
(1980) |
5-2-11-8
(E007) |
14
|
5-2-13 Clinical study
| 5-2-13-1 Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. |
Mezitis, N.M.E.
et al.
Diabetes Care, 19, 1004-1005, (1996) |
5-2-13-1
|
22
|
| 5-2-13-2 A six-month study of the effect of sucralose vs placebo on glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. |
Mount Sinai Hospital
(1997) |
5-2-13-2
(E157) |
22
|
| 5-2-13-3 An evaluation of specific clinical chemistry parameters and methods in Study E157 : A six-month study of the effect of sucralose vs placebo on glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. |
University of
Missouri-Columbia
(1996) |
5-2-13-3
(E168) |
22
|
| 5-2-13-4 A 12 week study of the effect of sucralose on glucose homeostasis and HbA1c in normal healthy volunteers. |
Leicester Clinical
Research Center Ltd. (1996) |
5-2-13-4
(E169) |
22
|
| 5-2-13-5 A three-month study of the effect of sucralose versus placebo on glucose homeostasis in subjects with non-insulin-dependent diabetes mellitus. |
University of California
San Diego, et al. (1997) |
5-2-13-5
(E171) |
22
|
5-3 Safety evaluation for the
hydrolysis products of sucralose and compounds related to
sucralose
5-3-1 Acute toxicity study
| 5-3-1-1 TGS-HP : Acute oral toxicity in the rat. (1) |
Life Science Research
(1982) |
5-3-1-1
(E028) |
18
|
| 5-3-1-2 TGS-HP : Acute oral toxicity in the rat. (2) |
Johnson & Johnson
Research Foundation (1980) |
5-3-1-2
(E002) |
18
|
| 5-3-1-3 TGS-HP : Acute oral toxicity in the mouse. |
Life Science Research
(1982) |
5-3-1-3
(E029) |
18
|
| 5-3-1-4 3/C334(6-CDG) : Acute oral toxicity in the rat. |
Life science Research
(1977) |
5-3-1-4
(E050) |
18
|
| 5-3-1-5 TCDS : Acute oral toxicity in the mouse. |
Life science Research
(1976) |
5-3-1-5
(E069) |
18
|
5-3-2 Subacute toxicity study
| 5-3-2-1 TGS-HP : 13-week toxicity study in rats. |
Life Science Research
(1986) |
5-3-2-1
(E054) |
18
|
| 5-3-2-2 TGS-HP : Dose range finding/toxicity study in the dog. |
Johnson & Johnson
Research Foundation (1984) |
5-3-2-2
(E061) |
18
|
5-3-3 Chronic toxicity study
| 5-3-3-1 TGS-HP : Twenty-six week oral toxicity study in dogs. |
Litton Bionetics Inc.
(1985) |
5-3-3-1
(E068) |
18
|
5-3-4 Reproduction study
| 5-3-4-1 TGS-HP : Two generation reproductive study in rats. |
Life Science Research
(1986) |
5-3-4-1
(E052) |
18
|
| 5-3-4-2 1,6-DCF : Effect on male fertility in the rat. |
Ortho Pharmaceutical Co.
(1982) |
5-3-4-2
(E090) |
18
|
| 5-3-4-3 3/C-339, 3/C-340 : Anti-fertility screen in male rats. |
Life science Research
(1978) |
5-3-4-3
(E016) |
18
|
| 5-3-4-4 3/C-343~346, 3/C-348 : Anti-fertility screen in male rats. |
Life science Research
(1978) |
5-3-4-4
(E038) |
18
|
| 5-3-4-5 6-CF : Anti-fertility evaluation in the male rat. |
Life science Research
(1984) |
5-3-4-5
(E037) |
18
|
| 5-3-4-6 4,6'-DGS : Anti-fertility evaluation in the male rat. |
Life science Research
(1986) |
5-3-4-6
(E100) |
18
|
| 5-3-4-7 TCDS : The effect on the glycolytic ability of rat spermatozoa. |
The University Whiteknights
(1987) |
5-3-4-7
(E107) |
18
|
| 5-3-4-8 6-CDG, 6-CDM : The effects on male fertility and motor function in several species. |
Ortho Pharmaceutical Co.
(1981) |
5-3-4-8
(E091) |
18
|
5-3-5 Teratogenicity study
| 5-3-5-1 TGS-HP : Effects of oral administration upon pregnancy in the rat. |
Life Science Research
(1983) |
5-3-5-1
(E032) |
18
|
5-3-6 Carcinogenicity study
| 5-3-6-1 TGS-HP : 104-week oncogenicity study in rats. |
Life Science Research
(1987) |
5-3-6-1
(E053) |
19
|
5-3-7 Antigenicity study
| 5-3-7-1 1,6-DCF : Primary skin irritation study. |
Toxicol Laboratories Ltd.
(1984) |
5-3-7-1
(E080) |
19
|
5-3-8 Mutagenicity study
| 5-3-8-1 TGS-HP : Reverse mutation test with Salmonella typhimurium. |
Life Science Research
(1981) |
5-3-8-1
(E015) |
20
|
| 5-3-8-2 TGS-HP : Dominant lethal test in mice. |
Life Science Research
(1983) |
5-3-8-2
(E034) |
20
|
| 5-3-8-3 1,6-DCF : Reverse mutation test with Salmonella typhimurium. (1) |
Life Science Research
(1980) |
5-3-8-3
(E020) |
20
|
| 5-3-8-4 1,6-DCF : Reverse mutation test with Salmonella typhimurium. (2) |
EG & G Mason
Research Institute (1981) |
5-3-8-4
(E023) |
20
|
| 5-3-8-5 1,6-DCF : Gene mutation test in mouse lymphoma cells. (1) |
EG & G Mason
Research Institute (1981) |
5-3-8-5
(E022) |
20
|
| 5-3-8-6 : Gene mutation test in mouse lymphoma cells. (2) |
EG & G Mason
Research Institute (1981) |
5-3-8-6
(E024) |
20
|
| 5-3-8-7 1,6-DCF : Assessment of its mutagenic potential in Drosophila melanogaster, using the sex-linked recessive lethal test. |
Life Science Research
(1981) |
5-3-8-7
(E021) |
20
|
| 5-3-8-8 1,6-DCF : Single exposure dose selection study for in vivo micronucleus assay in the mouse. |
Hazleton Lab. America
(1988) |
5-3-8-8
(E152) |
20
|
| 5-3-8-9 1,6-DCF : In vivo micronucleus assay in the mouse. |
Hazleton Lab. America
(1988) |
5-3-8-9
(E149) |
20
|
| 5-3-8-10 1,6-DCF : Investigation of effects on bone marrow chromosomes of the rat after acute and subacute oral administration. |
Life Science Research
(1981) |
5-3-8-10
(E019) |
20
|
| 5-3-8-11 1,6-DCF : In vitro assessment of the clastogenic action on mouse bone marrow erythrocytes in the micronucleus test. |
Life Science Research
(1981) |
5-3-8-11
(E012) |
20
|
| 5-3-8-12 1,6-DCF : In vivo sister chromatid exchange assay in the mouse. |
Hazleton Lab. America
(1988) |
5-3-8-12
(E150) |
20
|
| 5-3-8-13 1,6-DCF : Study to evaluate the potential of 1,6-dichlorofructose to induce unscheduled DNA synthesis (UDS) in isolated rat hepatocytes in vitro. |
Hazleton Europe
(1994) |
5-3-8-13
(E165) |
20
|
| 5-3-8-14 4-CG : Reverse mutation test with Salmonella typhimurium. |
Life Science Research
(1980) |
5-3-8-14
(E025) |
20
|
| 5-3-8-15 4-CG : Gene mutation test in mouse lymphoma cells. |
EG & G Mason
Research Institute (1981) |
5-3-8-15
(E026) |
20
|
| 5-3-8-16 4-CG : Mutagenicity evaluation in the rat bone marrow cytogenetic assay. |
Litton Bionetics, Inc.
(1981) |
5-3-8-16
(E027) |
20
|
| 5-3-8-17 4-CG : In vitro assessment of the clastogenic action on mouse bone marrow erythrocytes in the micronucleus test. |
Life Science Research
(1981) |
5-3-8-17
(E012) |
20
|
| 5-3-8-18 C/334(6-CDG) : The micronucleus test in mouse bone marrow erythrocytes.. |
Life Science Research
(1978) |
5-3-8-18
(E010) |
20
|
| 5-3-8-19 C/337 : The micronucleus test in mouse bone marrow erythrocytes.. |
Life Science Research
(1978) |
5-3-8-19
(E010) |
20
|
| 5-3-8-20 3/C340(1-CF) : Reverse mutation test with Salmonella typhimurium. |
Life Science Research
(1981) |
5-3-8-20
(E074) |
20
|
| 5-3-8-21 C/339 : The micronucleus test in mouse bone marrow erythrocytes. |
Life Science Research
(1978) |
5-3-8-21
(E072) |
20
|
| 5-3-8-22 C/338 : The micronucleus test in mouse bone marrow erythrocytes. |
Life Science Research
(1978) |
5-3-8-22
(E072) |
20
|
5-3-9 Other toxicity study
| 5-3-9-1 TGS-HP : Neurotoxicity study in mice. |
Life Science Research
(1981) |
5-3-9-1
(E008) |
20
|
| 5-3-9-2 TGS-HP : Neurotoxicity study in marmoset monkeys. |
Life Science Research
(1981) |
5-3-9-2
(E009) |
20
|
| 5-3-9-3 TGS-HP : Palatability study in dogs. |
Litton Bionetics Inc.
(1984) |
5-3-9-3
(E065) |
20
|
(2) Metabolism and pharmacokinetic
studies
5-2-12 Metabolism and
pharmacokinetic studies (Sucralose)
| 5-2-12-1 Absorption, tissue distribution and excretion in the rat. |
Life Science Research
(1981) |
5-2-12-1
(E004) |
15
|
| 5-2-12-2 Dietary toxicity study in rat (8 weeks).-A study on the metabolism |
Life Science Research
(1981) |
5-2-12-2
(E031) |
15
|
| 5-2-12-3 104-Week combined toxicity and oncogenicity study in rats. -Mesurement of metabolic adaptation. |
Life Science Research
(1981) |
5-2-12-3
(E057) |
15
|
| 5-2-12-4 A study on the metabolism of sucralose after oral and intravenous administration to the rat. |
University of Southampton
(1987) |
5-2-12-4
(E137) |
15
|
| 5-2-12-5 Comparative pharmacokinetics after dietary and oral gavage administration to rats. |
Huntingdon Research
Centre Ltd. (1994) |
5-2-12-5
(E163) |
15
|
| 5-2-12-6 Pharmacokinetic studies after oral administration to pregnant rabbits and rats. |
Huntingdon Research
Centre Ltd. (1994) |
5-2-12-6
(E164) |
15
|
| 5-2-12-7 Studies of the absorption, excretion and metabolism in the mouse. |
Huntingdon Research
Centre Ltd. (1987) |
5-2-12-7
(E146) |
15
|
| 5-2-12-8 Pharmacokinetics in dogs following intravenous administration. |
Life Science Research
(1984) |
5-2-12-8
(E049) |
15
|
| 5-2-12-9 Intravenous-oral cross over dog metabolism study. |
Huntingdon Research
Centre Ltd. (1986) |
5-2-12-9
(E123) |
16
|
| 5-2-12-10 Isolation and identification of an unknown radioactive component present in urine after intravenous administration of sucralose. |
Huntingdon Research
Centre Ltd. (1987) |
5-2-12-10
(E133) |
16
|
| 5-2-12-11 Studies of the metabolism in the rabbit. |
Huntingdon Research
Centre Ltd. (1987) |
5-2-12-11
(E124) |
16
|
| 5-2-12-12 Preliminary teratology study in the rabbit. |
Life Science Research
(1987) |
5-2-12-12
(E129) |
16
|
| 5-2-12-13 Urinary excretion in human after a single oral dose. |
Tate & Lyle
(1981) |
5-2-12-13
(E003) |
16
|
| 5-2-12-14 Absorption and excretion in human. |
Life Science Research
(1983) |
5-2-12-14
(E033) |
16
|
| 5-2-12-15 The examination of the radioactive material in the stored urine taken from three human volunteers given an oral dose of [14C]TGS. |
Tate & Lyle
(1986) |
5-2-12-15
(E033a) |
17
|
| 5-2-12-16 A randomized double-blind study in normal subjects to investigate the influence of TGS on the absorption of sucrose and the secretion of insulin. |
Medical Science
Research UK (1984) |
5-2-12-16
(E046) |
17
|
| 5-2-12-17 A study to observe the tolerance to orally administered single ascending doses of TGS followed by seven days administration in eight normal subjects. |
Medical Science
Research UK (1984) |
5-2-12-17
(E047) |
17
|
| 5-2-12-18 A tolerance study in normal subjects of varying doses of TGS administered continuously for a period of thirteen weeks. |
Medical Science
Research UK (1986) |
5-2-12-18
(E048) |
17
|
| 5-2-12-19 A study of the metabolism and pharmacokinetics following oral administration to healthy human volunteers. |
Univ. Southampton
(1986) |
5-2-12-19
(E128) |
17
|
| 5-2-12-20 A study of the metabolism of 14C-TGS following oral administration to healthy human volunteers. |
Univ. Southampton
(1988) |
5-2-12-20
(E145) |
17
|
| 5-2-12-21 Stability of chlorinated disaccharides to hydrolysis by microbial, plant and mammalian glycosidases. |
Tate & Lyle Group
Research & Development (1986) |
5-2-12-21
(E104) |
17
|
| 5-2-12-22 The effect of oral administration on some aspects of the metabolism of D-glucose by tissues of the rat. |
University of Reading
(1978) |
5-2-12-22
(E005) |
17
|
| 5-2-12-23 The influence of sucralose on carbohydrate metabolism in the rat. |
Med. Sch. St. George's
Hospital, London |
5-2-12-23
(E064) |
17
|
| 5-2-12-24 Enzyme induction studies of TGS in the rat. |
Huntingdon Research
Centre Ltd. (1988) |
5-2-12-24
(E144) |
17
|
5-3-10 Metabolism and pharmacokinetic studies (the hydrolysis products of sucralose and compounds related to sucralose)
| 5-3-10-1 Enzyme induction studies of TGS-HP in the rat. |
Huntingdon Research
Centre Ltd. (1988) |
5-3-10-1
(E144) |
21
|
| 5-3-10-2 1,6-DCF : Distribution in blood, brain, testes and urine at intervals after oral dosing of male rats. |
Life Science Research
(1981) |
5-3-10-2
(E017) |
21
|
| 5-3-10-3 1,6-DCF : Metabolism and dechlorination in the rat. |
University College, UK
(1987) |
5-3-10-3
(E116) |
21
|
| 5-3-10-4 4-CG and 1,6-DCF : Metabolic disposition in the rat. |
Life Science Research
(1980) |
5-3-10-4
(E018) |
21
|
| 5-3-10-5 1,6-DCF : Metabolism in the rat. |
University College, UK
(1988) |
5-3-10-5
(E147) |
21
|
| 5-3-10-6 The cellular effects of 1,6-DCF : Preliminary studies. |
Univ. Med. And Rent.
New Jersey (1985) |
5-3-10-6
(E085) |
21
|
| 5-3-10-7 4-CG : Metabolism in the rat. |
University College, UK
(1987) |
5-3-10-7
(E139) |
21
|
| 5-3-10-8 In vitro studies on the hepatic metabolism of some chlorodeoxysugars. |
University of Surrey
(1980) |
5-3-10-8
(E136) |
21
|
(3) The daily intake of the food
additive
| 5-4 The daily intake of sucralose. |
San-Ei Gen F.F.I., Inc.
|
5-4
|
21
|
6 Standards for use
| 6-1 Documentation on the target foods and use. |
San-Ei Gen F.F.I., Inc.
|
6-1
|
21
|
| 6-2 Documentation on the amount of use. |
San-Ei Gen F.F.I., Inc.
|
6-2
|
21
|
Attachment 2
|
Specification
|
|
| Name | Sucralose |
| Chemical name |
Trichlorogalactosucrose (4,1',6'-trichlorogalactosucrose) |
| Chemical structure |
|
| Chemical formula | C12H19Cl3O8 |
| Molecular weight | 397.64 |
| CAS No. | 56038-13-2 |
| Contents | Sucralose, when dried, contains 98.0-102.0% of sucralose (C12H19Cl3O8) |
| Description |
Sucralose occurs as a white to grayish-white crystalline powder. It is odorless*, has a strong sweet taste and is freely soluble in water, methanol and ethanol, and is slightly soluble in ethyl acetate. |
| Identification | (1) The infrared
absorption spectrum of a potassium bromide dispersion
sample has a similar absorption bands to the standard
spectrum of sucralose with a similar intensity at
similar wavelength. (2) Dissolve 1.0g of sucralose in 10ml of methanol, apply 5l of this solution for thin-layer chromatography to the bottom of the chromatographic plate. Place the plate in mobile phase which contains mixture of sodium chloride (dissolve 1g in a solvesnt to make 20m) and acetonitrile (7:3), and allow the solvent front to ascend approximately 15cm. Remove the plate, allow it to dry, and spray it with the solution which contains 15%(v/v) sulfuric acid in methanol. Heat the plate in an oven at 125ｰC for 10 min. Chromatographic plate coated with octadesyl silyl silica gel can be used in this methods. The Rf value as a spot of sucralose is 0.4-0.6 under the conditions described above. |
| Purity (1) Clarity and color of solution |
Clear (1.0g, in 10ml water) |
| (2) Specific rotation |
|
| (3) pH | pH= 3.0~6.0 (2.0g, in 20 ml water) |
| (4) Heavy metals | Not more than 10 mg/g (1.0g, method 2, 1.0ml lead standard solution as control solution) |
| (5) Arsenic | Not more than 4.0 mg/g as As2O3. (0.50g, method 2, apparatus B) |
| (6) Other
chlorinated disaccharide |
Not more than
0.5% Dissolve 1.0 g of sucralose in 10 ml of methanol (sample solution). Take 0.5ml of this sample solution and add methanol to make 100ml (standard solution). Apply 5l of sample or control solution to the bottom of the chromatographic plate for thin-layer chromatography as described on Identification(2). The spot of sample solution is only detected on same position to that of standard solution. If other spot in sample solution is detected, the detected spot in sample solution is not more intense in color than that in standard solution. |
| (7) Chlorinated monosaccharide |
Not more than
0.16% as calculated on fructose. Dissolve 2.5 g of sucralose and add methanol to make 10ml exactly (sample solution). Take exactly 10.0g of D-mannitol and add water to make 100ml, exactly (standard [A] solution). Take exactly both 10.0g of D-mannitol and 40mg of fructose and add water to make 100ml, exactly (standard [B] solution). Apply 1l of sample, standard [A] or [B] solution to silicagel thin-layer plate of 0.25mm in thickness for thin-layer chromatography and dry. Repeat another 4 times this process. Spray the plate with the solution which contains p-anisidine phtalate. Heat the plate in an over at 98-102ｰC for 10min. The spot in sample solution is not more intense in color than that in standard [B] solution. The spot in standard [A] solution results from a overheating of the plate, and the test should be repeated again in use of another plate. |
| (8) Triphenylphosphine oxide | Not more than
150mg/g Dissoluve 100 mg of sucralose or triphenylphosphine oxide in mixture of acetonitrile and water (67:33) and make exact 10 ml solution, separately. Take exactly 1ml of triphenylphosphine oxide solution and add mixture of acetonitrile and water (67:33) to make 100 ml solution, exactly (standard solution). Take 25ml of sample solution or standard solution for liquid chromatography under the condition described below. System Detector : UV-detector ( 220 nm) Column packing material : 5 mm octadecyl silyl silica gel Column : A stainless steel tube of 4.6 mm (internal diameter) ｴ15 cm (length) Column temperature : 40ｰC Mobile phase : a mixture of acetonitrile and water (67 : 33) Flow rate : 1.5 ml/min. Record the mean peak areas for the standard and test solution as As and At, respectively. Calculate the concentration of triphenylphosphine oxide in the sample from the following formula. |
| (9) Methanol | Not more than
0.1% Dissolve exactly 2.0 g of sucralose, add water to make 10 ml exactly and mix (sample solution). Take exactly 2 ml of methanol, add water to make 100 ml exactly and mix. Take exactly 1ml of this solution, add water to make 100 ml exactly and mix (standard solution). Take 1ml of sample solution or standard solution for liquid chromatography under the condition described below. System Detector : Hydrogen frame ionization detector Column packing material : 150~180 mm of porous polymer beads for gas chromatography Column : glass column of 2~4 mm (internal diameter) ｴ about 2 m (length) Column temperature : constant temperature at about 150ｰC Inlet temperature : 200ｰC Detector temperature : 250ｰC Carrier gas and flow rate : Use nitrogen or helium. Adjust flow rate or temperature to detect a peak of methanol in about 4 min. Record the mean peak areas for the standard and test solution as SA and AS, respectively. Calculate the concentration of methanol in the sample from the following formula. where CS is the concentration of methanol in the standard in percent. |
| Residue in Ignition | Not more than 0.7%. |
| Water | Not more than 2.0% (1g, Direct titration) |
| Method of assay | Dissolve 1g of
sucralose add water to make 100ml, exactly. Take
exactly 10ml of this solution, add 10ml of sodium
hydroxide (dissolve 1g in a solvesnt to make 10ml),
equip with a reflux condenser, boil gently for 30min,
cool and neutralize it by diluted-nitric acid.
Titrate with 0.1 mol/l of silver as electric
indicator and silver-silver chloride as reference
electrode. Perform a blank test in the same manner,
make any necessary correction, and calculate on the
dried basis. 0.1mol/l Silver nitrate 1ml = 13.255mg C12H19Cl3O8 |
*The term "odorless" means
odorless or practically odorless on the Japanese
Standards for Food Additives.
Attachment 3
|
Definition
|
Specification (draft)
|
JECFA
|
FCC
|
|
|
Description |
Description
|
White to grayish-white, crystalline powder. | White to off-white, crystalline powder. | White to off-white, crystalline powder. |
|
Odorless
|
Odorless*
|
Practically odorless
|
Practically odorless
|
|
|
Sweet taste
|
Sweet taste
|
Sweet taste
|
Sweet taste
|
|
|
Solubility
|
It is freely soluble in water, in methanol and ethanol and is slightly soluble in ethyl acetate. | It is freely soluble in water, in methanol and in alcohol and slightly soluble in ethyl acetate. | It is freely soluble in water, in methanol and in alcohol and slightly soluble in ethyl acetate. | |
|
Identification
|
Infrared absorption
|
The infrared absorption spectrum of a potassium bromide dispersion sample has a similar absorption bands to the standard spectrum with a similar intensity at similar wavelength. | The infrared absorption spectrum of a potassium bromide dispersion of the sample exhibits relative maxima at similar wavenumbers as those shown in the reference spectrum. | The infrared absorption spectrum of a potassium bromide dispersion of the sample exhibits relative maxima at similar wavelengths as those shown in Sucralose Standard for analytical use. |
|
Thin-layer chromatography
|
The Rf value is from 0.4 to 0.6. | The main spot has the same Rf value as that of the main spot of Standard Solution A. | The main spot has the same Rf value as that of the main spot of Standard Solution A. | |
|
Purity |
Clarity
|
Clear
(1.0g,in 10ml water) |
-
|
-
|
|
Specific rotation
|
+84.0~+87.5ｰ
(1.0g, in 10ml water, calculated on the anhydrous basis) |
+84.0~+87.5ｰ
(10%w/v,calculated on the anhydrous basis.) |
+84.0~+87.5ｰ
(1g,water,100ml,calculated on the anhydrous basis.) |
|
|
pH
|
3.0~6.0
(2.0g, in 20ml water) |
-
|
-
|
|
|
Heavy metals
|
Not more than 10mg/g
(1.0g,Method 2, 1.0ml lead standard solution as control solution) |
Not more than 10mg/kg as Pb.
|
Not more than 10mg/kg as Pb.
|
|
|
Arsenic
|
Not more than 4.0g/g as As2O3.
(0.50g,method 2,apparatus B) |
Not more than 3mg/kg as As.
|
Not more than 3mg/kg as As.
|
|
|
Other chlorinated
disaccharides
|
Not more than 0.5%
|
The main spot has the same Rf
value as the main spot in Solution A. No other spot
is more intense than the spot in Solution B.
|
The main spot has the same Rf
value as the main spot in Solution A. No other spot
is more intense than the spot in Solution B.
|
|
|
Chlorinated monosaccharide
|
Not more than 0.16% as
calculated on fructose
|
Not more colored than the spot
from Reference solution B.
|
Not more colored than the spot
from Reference solution B.
|
|
|
Triphenylphosphine oxide
|
Not more than 150
mg/g
|
Not more than 150mg/kg
|
-
|
|
|
Methanol
|
Not more than 0.1%
|
Not more than 0.1%
|
Not more than 0.1%.
|
|
|
Residue in Ignition
|
Not more than 0.7%.
|
Not more than 0.7%.
|
Not more than 0.7%.
|
|
|
Water
|
Not more than 2.0%.
|
Not more than 2.0%.
|
Not more than 2.0%.
|
|
|
Content
|
98~102.0%
|
98~102%
|
98.0~102.0%
|
|
*The term "odorless" means odorless or practically odorless on the Japanese Standards for Food Additives.
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