N-cyclohexylbenzothiazole-2-sulfenamide

Carcinogenicity

Description of key information

- In vivo carcinogenicity study in the mouse: not carcinogenic B6C3F1 strains and the B6AK1 strains of mouse at dose level corresponding to a time weight average dose of 95.3 mg/kg bw and day.(NCI 1968, Key/Sup, Rel.2).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

acceptable well-documented publication, which meets basic scientific principles (This long-term carcinogenicity study is not in accordance with current testing procedures as proposed by guidelines on carcinogenicity and/or combined chronic toxicity carcinogenicity. However, this study is performed in accordance with generally accepted scientific standards.)

Principles of method if other than guideline:

In a carcinogenicity study in B6C3F1 and B6AKF1 mice (each 18 males and 18 females) received a continuous daily oral application by stomach tube from 7th day of age until the mice were at weanling age (28 days) following which the compound was mixed with the ground feed for 18 month in total.

GLP compliance:

no

Species:

mouse

Strain:

other: B6C3F1 and B6AKF1

Sex:

male/female

Route of administration:

oral: unspecified

Vehicle:

other: 0.5% gelatin

Duration of treatment / exposure:

18 months

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
7th to 28th day of age: 215 mg/kg bw/d by stomach tube, thereafter administration of 692 mg/kg diet (appr. 95.3 mg/kg bw/d according to EU risk assessment 2007).

No. of animals per sex per dose:

18 per dose and sex

Control animals:

yes

Details on study design:

Post-exposure period: no

Key result

Dose descriptor:

dose level: Surviving and tumors

Effect level:

ca. 95.3 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: No statistically significant differences between CBS-treated and control mice in the incidence of the individual types of tumors

Key result

Critical effects observed:

no

Mice surviving 18 months:

Gelatin Control: B6C3F1 mice:(m:16/18, f: 16/18), B6AKF1 mice: (m:18/18, f: 15/18).

Treatment group:B6C3F1 mice: (m: 16/18; f: 15/18), B6AKF1 mice: (m:18/18, f: 17/18).

 

No adverse effects reported.

 

Tumors were found in all groups but there were no statistically significant differences between CBS-treated mice and controls.The total number of tumors were not statistically significant different from CBS-treated and control mice.

 

Total number of tumors:

Gelalatin control:B6C3F1 mice: (m:3; f: 4), B6AKF1 mice: (m: 3, f:3).

Treatment group:B6C3F1 mice: (m: 8, f: 6), B6AKF1 mice: (m:3/3).

 

No increased tumor incidence.

Conclusions:

No adverse effects reported.

Executive summary:

Groups of 18 mice per sex of the B6C3F1 strains and the B6AK1 strains, were given 215 mg/kg bw and day CBS by repeated oral gavage for 21 days followed by exposure for nearly 17 months to diet containing CBS at a concentration equivalent to ca. 90 mg/kg bw/d (corresponding to a time weight average dose of 95.3 mg/kg bw and day. An equal number of mice served as vehicle control. Survival of the CBS-treated mice of both strains was comparable to the control group (vehicle control B6C3F1: male 16/18, females 16/18; B6AKF1 male: 18/18, female: 15/18; CBS treated B6C3F1 mice: male 16/18, females: 15/18; B6AKF1 male: 18/18, female: 17/18. No adverse effects were reported. Tumours were found in all groups but there were no statistically significant differences between CBS-treated and control mice in the incidence of the individual types of tumour. The total number of tumours was not statistically significant different in CBS-treated and control mice (vehicle control B6C3F1 mice male/female: 3/4, B6AKF1 mice male/female: 3/3; CBS treated B6C3F1 mice male/female: 8/6, CBS treated B6AKF1 mice male/female: 3/3). In summary there was no evidence of a carcinogenic effect in both strains of mice (NCI 1968).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

95.3 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

Study was performed in accordance with generally accepted scientific standard.

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

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Additional information

Carcinogenicity: oral

Groups of 18 mice per sex of the B6C3F1 strains and the B6AK1 strains, were given 215 mg/kg bw and day CBS by repeated oral gavage for 21 days followed by exposure for nearly 17 months to diet containing CBS at a concentration equivalent to ca. 90 mg/kg bw/d (corresponding to a time weight average dose of 95.3 mg/kg bw and day. An equal number of mice served as vehicle control. Survival of the CBS-treated mice of both strains was comparable to the control group (vehicle control B6C3F1: male 16/18, females 16/18; B6AKF1 male: 18/18, female: 15/18; CBS treated B6C3F1 mice: male 16/18, females: 15/18; B6AKF1 male: 18/18, female: 17/18. No adverse effects were reported. Tumors were found in all groups but there were no statistically significant differences between CBS-treated and control mice in the incidence of the individual types of tumor. The total number of tumors was not statistically significant different in CBS-treated and control mice (vehicle control B6C3F1 mice male/female: 3/4, B6AKF1 mice male/female: 3/3; CBS treated B6C3F1 mice male/female: 8/6, CBS treated B6AKF1 mice male/female: 3/3). In summary there was no evidence of a carcinogenic effect in both strains of mice (NCI 1968).

 

Carcinogenicity: other route (dermal)

Groups of 18 B6C3F1 and 18 B6AKF1 mice of each sex received a single subcutaneous injection in 0.05 ml suspension (1000 mg/kg) CBS in the nape of the neck with sacrifice at ca. 17 months after injection (no more data available). An equal number of mice of each strain served as vehicle control. Survival of the CBS-treated mice was comparable to the control group in both strains. No adverse effects were reported and no statistically increase in tumor incidences were observed in mice of both strains. The total number was similar in treated and control mice (vehicle control B6C3F1 male/female mice: 4/0, B6AKF1mice male/female: 1/1; CBS treated B6C3F1 mice male/female: 3/1, CBS B6AKF1 mice male and female 0/2). In summary there was no evidence of a carcinogenic effect of CBS in both strains of mice (NCI 1968).

 

The metabolite 2-Mercaptobenzothiazole (MBT) is the relevant and common metabolite for all category members (CBS, TBBS, MDS and DCBS), data on 2-Mercaptobenzothiazole (MBT) CAS No. 149-30-4, EC no. 205-736-8 are also relevant for consideration of the carcinogenic potential of the category of substances. Refer to section 13.2 for the statement of carcinogenic potential of 2-Mercaptobenzothiazole (MBT) for more information.