N-(1,1-dimethylethyl)bis(2-benzothiazolesulfen)amide

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study, basic data given (abstract and tables)

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-tert-butylbenzothiazole-2-sulphenamide

EC Number:

202-409-1

EC Name:

N-tert-butylbenzothiazole-2-sulphenamide

Cas Number:

95-31-8

Molecular formula:

C11H14N2S2

IUPAC Name:

N-tert-butylbenzothiazole-2-sulphenamide

Details on test material:

purity 96.4%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 5% gum arabic

Details on mating procedure:

No data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Males 42 days, females 38 days (from 14 days prior to mating to day 3 of lactation)

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 40, 200, 1000 mg/kg bw and day
Basis:

No. of animals per sex per dose:

13 per dose and sex

Control animals:

yes

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

ca. 40 mg/kg bw/day

Sex:

female

Basis for effect level:

other: no effects

2

Dose descriptor:

LOAEL

Effect level:

ca. 200 mg/kg bw/day

Sex:

female

Basis for effect level:

other: slight histopathological changes in kidney and in the liver

3

Dose descriptor:

NOAEL

Effect level:

ca. 1 000 mg/kg bw/day

Sex:

female

Basis for effect level:

other: no biologically relevant effects

Remarks on result:

other: Generation: fertility

Results: F1 generation

Effect levels (F1)

Remarks on result:

other: no further infomation available

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Maternal toxicity:

40 mg/kg bw and day

no effects

200 mg/kg bw and day

temporary salivation after each administration at autopsy on postpartum day 4, slight vacuolar degeneration in the proximal tubules of kidney was observed slight increase in the relative kidney weights slight hypertrophy of hepatocytes in the central zone

1000 mg/kg bw and day

temporary salivation after each administration food consumption was decreased prior mating and along with slight suppressiomn of body weight gain during pregnancy at autopsy on postpartum day 4, slight vacuolar degeneration in the proximal tubules of kidney was observed slight increase in the relative kidney weights slight hypertrophy of hepatocytes in the central zone increase in relative liver weights deposition of brown pigment in the spleen (tended to increase but in many cases comparable to control group)

Fertility:

40 mg/kg bw/d:

No effects on copulation and ovulation, no dose-related abnormalities with regard to parturition and lactation Fertility index was lower than control level; however the low index observed seemed to be an accidental finding because all females in the

200 mg/kg bw/d group were found to be fertile, thus the authors concluded that this decreased is not biologically relevant

200 mg/kg bw/d:

No effects on copulation and ovulation, no dose-related abnormalities with regard to parturition and lactation no effects on fertility index

1000 mg/kg bw/d: No effects on copulation and ovulation, no dose-related abnormalities with regard to parturition and lactation Fertility indice was lower than control level, however, the relvance of this finding is questionable. This decrease was not reflected by other fertility parameter like the number of corpora lutea, number of implantation sites and implantation index (see table). The values noted at 1000 mg/kg bw and day were all within the variation range of the current negative control and were not statistically significant. Moreover, the decrease of the fertility index noted was not dose-dependent. No test substance-related adverse effects on the reproductive organs were indicated in the 90 day toxicity study (Monsanto Co 1985). Fetal: No adverse effects on viability, the sex ratio and body weights of pups in any of the treated animals. TBBS at the dose levels applied did not demonstrate teratogenicity

Summary of reproductive performance in parental rats