1,2-benzisothiazol-3(2H)-one 1,1-dioxide

Carcinogenicity

Description of key information

NOAEL and non-carcinogenic effect level was considered to be 1000 mg/kg/day when Nctr:SI I(SD)BR Sprague-Dawley female rats treated with Sodium saccharin.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is of K2 level from peer reviewed publication

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

On the basis of available data, the substance is not classified as a carcinogen.

Additional information

In a repeated dose and carcinogenicity study by West et Al (1994), Nctr:SI I(SD)BR Sprague-Dawleyfemale rats treated with Sodium saccharinin the concentration of 0, 1000, 2500 and 5000 mg/kg/day orally in diet. No effect was observed on survival of treated female rats as compared to control. Increase in body weight gain and slightly decreasing food consumption per kg body weight was observed in treated rats as compared to control. In addition, at 4 to 8 weeks, similar incidence of tumours was observed as in control. As the dosing period varied from 4 to 8, through 6 to 10, to 8 to 12 week, showed higher tumour incidences for 1% saccharin at 6-10 week (40.0%), and for 2.5% saccharin at 6-10 week (38.9%) and 8-12 week (47.6%). None of these differences was statistically significant at the 95% confidence level. Therefore, NOAEL and non-carcinogenic effect level was considered to be 1000 mg/kg/day when Nctr:SI I(SD)BR Sprague-Dawley female rats treated with Sodium saccharin orally for 12 weeks.

Also from the other repeated dose and carcinogenicity study by Uwagawa et al (1994), NCI-Black-Reiter (NBR) male rats treated with Sodium Saccharin in the concentration of 0 and 5000 mg/kg/day orally in feed. No effect was observed on survival of treated rats as compared to control. Soft feces and decrease body weight were observed in treated male rats. Similarly, moderate decreased in food consumption, Slight increase in water consumption and significantly increased urinary pH and Na ion concentrations were observed in treated rats as compared to control. In addition, No effect was observed on BrdU labeling indices and No calculus formation, hyperplasia, papillomatosis and diffuses epithelial hyperplasia of the bladder epithelium and no cells having ropy or leafy microridges and pleomorphic microvilli and necrotic epithelial cells with silicate crystals were observed in treated rats as compared to control. Therefore, LOAEL and non-carcinogenic effect level was considered to be 5000 mg/kg/day (5%) when NCI-Black-Reiter (NBR) male rats were treated with Sodium Saccharin orally in diet for 8 weeks.

In a study by Clay et al (1989), BALB/cStCrlfC3H/Nctr female mice treated with Sodium saccharin in the concentration of 0, 143, 714, 1428.5 and 7143 mg/kg/day orally in diet initiated with dose of 200 ppm

2-Acetylaminofluorene (2-AAF) for 13 weeks, followed by 2 weeks of control diet. No effect was observed on survival and food consumption of treated mice as compared to control and 2-AAF pre-treated dose groups. Slight decrease in body weight was observed in 7143 mg/kg/day treated mice as compared to control and 2-AAF pretreated dose groups. In addition, Harderian neoplasm was observed in 7143 mg/kg/day dose group as compared to control and 2-AAF pretreated dose groups. Therefore, NOAEL and non-carcinogenic effect level was considered to be 1428.5 mg/kg/day (1%) when BALB / cStCrlfC3H / Nctr female mice were treated with Sodium saccharin orally for 116 weeks.

Thus based on the above studies it can be concluded that sodium saccharin is not considered to be carcinogenic which is further adapted by USEPA in their report confirm sodium saccharin as non-carcinogenic substance.

The EPA has officially removed saccharin and its salts from their list of hazardous constituents and commercial chemical products. In a December 14, 2010 release, the EPA stated that saccharin is no longer considered a potential hazard to human health.

Justification for selection of carcinogenicity via oral route endpoint:
NOAEL and non-carcinogenic effect level was considered to be 1000 mg/kg/day when Nctr:SI I(SD)BR Sprague-Dawley female rats treated with Sodium saccharin.