N-cyclohexylbenzothiazole-2-sulfenamide

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Remarks:

subacute oral toxicity study

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: subacute oral toxicity study (weight of sex organs, and histological examination of the testis documented)

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1997

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Guidelines for 28-day repeated dose toxicity testing of chemicals (Japan)

Principles of method if other than guideline:

N-cyclohexyl-2-benzothiazolesulfenamide was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 25, 80, 250 or 800 mg/kg/day. At termination of the study weight of organs ovaries, testis, epididymis were determined, and a and histological examination of the testis and epidididymis conducted.

GLP compliance:

yes

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

N-cyclohexylbenzothiazole-2-sulfenamide

EC Number:

202-411-2

EC Name:

N-cyclohexylbenzothiazole-2-sulfenamide

Cas Number:

95-33-0

Molecular formula:

C13H16N2S2

IUPAC Name:

N-(1,3-benzothiazol-2-ylsulfanyl)cyclohexanamine

Test material form:

solid: granular

Remarks:

greyish white

Details on test material:

Purity: 98.8 %

Specific details on test material used for the study:

Purity: 98.8 %

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on exposure:

Exposure period: 28 days

Duration of treatment / exposure:

Exposure period: 28 days.

Frequency of treatment:

Daily.

Duration of test:

28 days with a recovery period of 14 days.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Remarks:

Control

Doses / concentrations 2

Dose / conc.:

25 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

80 mg/kg bw/day

Doses / concentrations 4

Dose / conc.:

250 mg/kg bw/day

Doses / concentrations 5

Dose / conc.:

800 mg/kg bw/day

No. of animals per sex per dose:

6 per dose and sex

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No effects on testis, but dose range with systemic adverse effects (signs of a coagulopathy, adverse effects in the kidney

2

Dose descriptor:

LOAEL

Effect level:

800 mg/kg bw/day

Based on:

test mat.

Sex:

male

Basis for effect level:

other: increase of the relative testis weights, 1/6 moderate diffuse atrophy of the seminiferous tubule, a slight diffusse interstitial cell hyperplasia and a market decreased sperm content on the epididymis

3

Dose descriptor:

NOAEL

Effect level:

800 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

other: see 'Remarks'

Remarks on result:

other:

Remarks:

No substance-related effects on absolute and relative ovary weights, no abnormalities were detected in ovary from animals of 800 mg/kg groups, but dose range with systemic adverse effects (e.g. signs of a coagulopathy, reduced body weight gain, reduced food consumption)

Any other information on results incl. tables

All animals survived until the end of the study. Body weight gain and food consumption were reduced in females of the 250  and 800 mg/kg-groups and in males of the 800 mg/kg-group Clinical signs: Deterioration of general condition (piloerection, soiled fur) in females  of the 800 mg/kg-group (for more details see chapter repeated dose toxicity: oral  Relative organ weights of ovary and epididymis were comparable to the control; the testis weight was increased in males of the 800 mg/kg-group (P < 0.01). In one male of the 800 mg/kg/recovery group each there was  observed a moderate diffuse atrophy of the seminiferous tubule, a slight diffuse interstitial cell hyperplasia and a marked decreased sperm content in the epididymis. In the ovary there were no substance-related effects seen.

Histopathological findings in male rats

Organ	Findings	Grade	Dose (mg/kg bw and day)
			after administration period		after recovery period
Testis			0	800	0	800
	Atrophy, seminiferous tubule, diffuse	++	0/6	0/6	0/6	1/6
	Hyperplasia, interstitial cell, diffuse	+	0/6	0/6	0/6	1/6
	Epididymis: decreased sperm	+++	0/6	0/6	0/6	1/6

+: slight, ++: moderate, +++: market  

The NOAEL for males concerning adverse effects on the reproductive organs   was 250 mg/kg bw/day; the NOAEL for females concerning adverse effects on the reproductive organs was 800 mg/kg bw/day (highest dose tested).

Applicant's summary and conclusion

Executive summary:

In a subacute gavage study groups of Crj:CD (SD) rats were treated with 0, 25, 80, 250 and 800 mg/kg bw and day CBS (MHWJ 1997). No treatment related changes in absolute and relative weights of ovaries and absolute weights of testis were observed. Relative weights of testis were significant higher in animals treated with 800 mg/kg bw and day than in control animals concomitant to decrease body weights. In the recovery group in one out of 6 rats histopathological changes were seen after a 14 day recovery period at 800 mg/kg bw and day (moderate diffuse atrophy of seminiferous tubuli, slight diffuse interstitial cell hyperplasia and market decreased sperm content on the epididymis). No such effects were observed in male terminated immediately after the administration period. No histopathological abnormalities were detected in ovary from females of 800 mg/kg groups.