6-methyl-1,2,3-oxathiazin-4(3H)-one 2,2-dioxide, potassium salt

Carcinogenicity

Description of key information

Acesulfame potassium did not show any tumorigenic activity in male and female rats, which had been exposed in utero and then continuously throughout the major part of their life-time or in mice fed the compound for 80 weeks at dietary levels up to 3% (30000 ppm, corresponding to about 1500 mg/kg bw in rats and 5000 mg/kg bw/day in mice), clearly exceeding the current limit dose of 1000 mg/kg bw/day. 
This conclusion is in line with the assessment of the Joint FAO/WHO Expert Committee on Food Additives (1990) and re-evaluation of the European Scientific Committee on Food (SCF, 2000). 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

Study duration:

chronic

Species:

rat

Quality of whole database:

The quality of the whole data base is considered to be sufficient and not critical.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Acesulfame potassium did not show a carcinogenic potential in rats and mice after repeated oral administration up to the highest dose levels tested.

The study results triggers the following classification/labelling:

EU Directive 1999/45/EC (as amended):        none

Regulation (EC) No 1272/2008 (CLP):           none

GHS (rev. 4) 2011:                                      unclassified

Additional information

A combined chronic toxicity and carcinogenicity study with Acesulfame potassium was carried out by feeding the substance to groups of 60 male and 60 female rats at levels of 0 (control), 0.3, 1.0 or 3.0% in the diet for more than two years. The rats were descendants from parents which had been kept on the same diets since weaning age. Observations were made of general appearance, behaviour and mortality, growth, food and water intake, haematological factors and clinical constituents in blood and urine. At weeks 120-123 all surviving rats were killed by decapitation and examined grossly. Eight different organs were weighed. Tissue samples of a wide variety of organs and of all abnormal tissues were collected for histological examination.

 

There were no differences in mortality rate amongst the various groups attributable to the feeding of Acesulfame potassium. Decreased body weights, not associated with decreased food intake, occurred in the high dose group in both sexes. Food efficiency, calculated over the period of rapid growth, was decreased in the high dose group in both sexes and in the mid dose group in males only. An increased water intake was noticed in the high dose group. A slight decrease in haemoglobin content, haematocrit value and red blood cell count was observed in females fed 3.0% Acesulfame potassium, only at weeks 102 and 119 of the study. Enzyme activities or levels of glucose, urea nitrogen and protein of the blood did not show any treatment-related effects. No indication of kidney damage was noticed in the volume, specific gravity, glutamic-oxalacetic transaminase activity or osmolarity of the urine. Urine composition was essentially normal. Relative organ weights did not show any treatment-related differences amongst the groups. Gross and microscopic examination did not reveal pathological changes which could be ascribed to the ingestion of the test substance.

 

Thus, it was concluded that the feeding of Acesulfame potassium at dietary levels up to 3% to male and female rats, which had been exposed in utero and then continuously throughout the major part of their life-time failed to show carcinogenic properties or other effects of obvious toxicological significance.

 

 

The carcinogenic potential of Acesulfame potassium was investigated by feeding the material to groups of 100 male and 100 female mice at dietary levels of 0, 0.3, 1 and 3% (0, 3000, 10000, 30000 ppm) for 80 weeks. After 80 weeks all surviving mice were autopsied, examined grossly and, together with the mice that died during the experimental period, subjected to a microscopic search for tumours.

The feeding did not cause adverse effects on general appearance, behaviour or survival at any of the dietary levels. Body weights were slightly decreased at the 3% level in both sexes. The relative, weights of the livers were decreased at all dietary levels in males only, but there was no evidence of a dose-related response and therefore, this observation is considered as incidential. Gross and microscopic examination revealed a variety of tumours in both, test animals and controls. The evaluation of the data on type, location, and incidence of the various tumours in test- and control groups did reveal evidence of the test compound possessing carcinogenic activity.

 

Finally, it was demonstrated that Acesulfame potassium did not show any tumorigenic activity in mice fed the compound for 80 weeks at dietary levels up to 3% (30000 ppm, corresponding to about 5000 mg/kg bw/day), clearly exceeding the current limit dose of 1000 mg/kg bw/day.

 

The conclusions with regards to the combined carcinogenicity and chronic toxicity in rats and the carcinogenicity study in mice is in line with the assessment of theJoint FAO/WHO Expert Committee on Food Additives (1990) and re-evaluation of the European Scientific Committee on Food (SCF, 2000). The SCF concluded in addition that “although the carcinogenicity studies are old they could still be used in the safety evaluation of Acesulfame potassium. […]. Thus there is no reason to require any additional studies of chronic toxicity/ carcinogenicity or mutagenicity”.

Justification for selection of carcinogenicity via oral route endpoint:
The carcinogenic potential of Acesulfame potassium was investigated in rats, which had been exposed in utero and then continuously throughout the major part of their life-time. The respective study is assessed as appropriate and valid since they were performed comparable to internationally accepted testing guideline with only minor deviations. Reporting, assessment and data presentation in the study report was considered as appropriate.