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

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study, comparable to guideline study with acceptable restrictions (purity of test substance not indicated)

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1981

Reference 2

Reference Type:

publication

Title:

Teratology studies on benzothiazolesulfenamides

Author:

Stevens M., W.

Year:

1982

Bibliographic source:

Toxicologist, 2, 73

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

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:

Santocure NS

Test animals

Species:

rat

Strain:

Sprague-Dawley

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

M/F ratio per cage: 1:1

Duration of treatment / exposure:

days 6-15 of gestation

Frequency of treatment:

daily

Duration of test:

days 6 tot 20 of gestation

No. of animals per sex per dose:

25 animals per dose

Control animals:

yes

Details on study design:

Sex: female

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

ca. 500 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

ca. 500 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Clinical signs and mortality: No mortality occured in any of the treated animals 50 and 150 mg/kg bw/d: no biologically meaningfuldifferences in appearance or behavior in rats when compared to the control group Matting of the ventral or anogenital haircoat was noted in all four dosage groups with the greatest incidence occuring in rats in the 500 mg/kg bw/d dose group (4, 1, 2 and 10 respectively).A post-dose response of reduced activity was noted in two of these 10 rats of the highest dose group on gestation day 6 and 7. Incidentalfindings of hair loss and/or red matter on the nasal region were noted on several rats in the treated groups as well as the control group at various times during gestation

Necropsy observations at Cesarean section

control: 1/25 hydrometra

150 mg/kg bw/d: 1/25 ovarian cyst

500 mg/kg bw/d: 1/25 fibrinous pleuritis and congested lungs, 1/25 hydrometra, 1/25 ovarian cyst

Body weights

50 and 150 mg/kg bw/d: no biologically relevant differences compared to control 500 mg/kg bw/d: very slight decrease in mean maternal body weight gain (ca. 1 -2 %) during the treatment period. however, no differences were noted in comparing the corrected gestation day 20 body weights (gestation day 20 body weight minus uterus weight) of the treated groups to the control group

Cesarean section observations

50, 150, 500 mg/kg bw/d:no biologically meaningful or statistically significant differences in the mean numbers of postimplantation loss, early resorptions, mean fetal body weight or fetal sex distribution compared to control Slight decrease were noted in the mean numbers of corpora lutea (4 %, 1%, 4 % at 50, 150 and 500 mg/kg bw/d, respectively)and total implantations in all three treatment groups (7 %, 6% amd 8 % at 50, 150 and 500 mg/kg bw/d). These decreases were attributed to random occurence as ovulation and implantation occur prior to treatment. A corresponding decrease in the mean numbers of viable fetuses in these groups was not considered biologically meaningful as the values were comparable to the historical control value.

Fetal morphological observations: 50, 150 and 500 mg/kg bw/d: no biologically meaningful differences in the total numbers of fetuses or litters with malformations compared to control A slight increase in the number of litters and fetuses with undeveloped renal papillae and/or distended ureters was noted in the three treated groups but was not considered biologically meaninful since this increase was within the range estabished in the historical control data. Renal papillae not developed and/or distended ureters:

control: fetuses: 3(1.7%), litters: 2( 8.3 %)

50 mg/kg bw/d:fetuses: 7(4.6 %), litters: 5( 22.7 %)

150 mg/kg bw/d:fetuses: 8(5.1 %), litters: 5( 21.7 %)

500 mg/kg bw/d:fetuses: 7(4.8 %), litters: 6( 27.3 %)