Sodium benzothiazol-2-yl sulphide

Carcinogenicity

Description of key information

There are no valid chronic toxicity studies or carcinogenicity studies available for SMBT. A read across approach (systemic effects) was conducted with study data from MBT (benzothiazole-2-thiol) (see discussion endpoint summary toxicokinetics). No carcinogenic activity was reported in the chronic carcinogenicity study in mice treated with MBT and no clear MBT related carcinogenic activity can be concluded from the chronic rat study. 

Justification for classification or non-classification

No classification is required according to the classification criteria 67/548/EWG and regulation no. 1272/2008 (GHS).

Additional information

There are no valid chronic toxicity studies or carcinogenicity studies available for SMBT.

A read across approach (systemic effects) was conducted with study data from MBT (benzothiazole-2-thiol) (see discussion endpoint summary toxicokinetics).

Read-across approach with MBT (systemic effects)

In a carcinogenicity study (NTP 1988) male and female Fischer 344 rats were administered with MBT for 103 weeks. Groups of 50 male rats were administered 0, 375, or 750 mg/kg 2-mercaptobenzothiazole in corn oil by gavage, 5 days per week for 103 weeks. Groups of 50 female rats were administered 0, 188, or 375 mg/kg 2-mercaptobenzothiazole in corn oil by gavage on the same schedule. For further details on material and methods and non-neoplastic outcome see chapter repeated dose toxicity.

The authors of the study reported evidence of increased incidences of monocular cell leukemia, pancreatic acinar cell adenomas, adrenal gland pheochromocytomas, and preputial gland adenomas or carcinomas (combined) in males and increased incidences of adrenal gland pheochromocytomas and piutiary gland adenomas in females.

However, the increase in mononuclear cell leukemia, pituitary gland adenomas and pancretic acinar cell adenomas in male rats were increased only in the low dose groups and thus not dose-dependent. The incidences of adrenal gland pheochromocytomas, and prepuitial gland adenomas or carcinomas (combined) were significant increased in low and high dose males. The increase noted was more pronounced in the low dose group than in the high dose group; thus no clear dose-effect relationship was revealed. In high dose females incidences of adenomas of the pituitary gland and adrenal gland pheochromocytomas were significant increased and occurred with significant positive trend. The observed incidences were within the bounds of historical control range. However, the relevance of adrenal gland pheochromocytomas in rats is questionable. Recent data analysis revealed that occurrence of pheochromocytomas in MBT treated rats, is associated with nephrotoxicity associated with endocrine disturbance (Greim 2009). The relevance of this finding for human is questionable. In addition it should be noted that the study is severely comprised by the poor survival rate in male rats, indicating that MTD (maximum tolerated dose) was presumable exceeded, and by the fact of the higher tumor rates in the low dose than in the high dose group in general (absence of a dose-response relationship). The observed differences in the tumor incidences of dosed animals compared to the concurrent controls do not appear to be significant when historical controls are taken into account. The overall rates of individual tumors in treated animals do not exceed the historical range. Overall, no clear carcinogenic activity can be concluded from this study.

In an additional NTP carcinogenicity study male and female B6C3F1 mice were administered with MBT for 103 weeks (NTP 1988). Groups of 50 male and 50 female mice were administered 0, 375, or 750 mg/kg 2-mercaptobenzothiazole in corn oil by gavage, 5 days per week for 103 weeks. For further details on material and methods and non-neoplastic outcome see chapter repeated dose toxicity. The Pathological and histopathological incidences of non-neoplastic lesions were in the range of the vehicle control. Neoplastic lesions noted were within the historical control data range.

Overall, no carcinogenic activity was reported in the chronic carcinogenicity study in mice and no clear MBT related carcinogenic activity can be concluded from the chronic rat study.