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

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)

Deviations:

yes

Remarks:

(animals tested: one-half with intact skin, one-half with abraded skin)

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

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on exposure:

Route of administration: dermal

Duration of treatment / exposure:

21d

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 125, 500, 2000 mg/kg bw
Basis:
nominal per unit body weight

No. of animals per sex per dose:

5 per sex and dose with intact skin, 5 per sex and dose with abraded skin

Control animals:

yes

Details on study design:

Post-exposure period: no

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Remarks:

systemic effects

Effect level:

> 2 000 mg/kg bw/day

Based on:

not specified

Sex:

male/female

Basis for effect level:

other: No biological relevant systemic effects

2

Dose descriptor:

NOAEL

Remarks:

local effects

Effect level:

ca. 500 mg/kg bw/day (nominal)

Based on:

not specified

Sex:

male/female

Basis for effect level:

other: not specified

3

Dose descriptor:

LOAEL

Remarks:

local effects

Effect level:

ca. 2 000 mg/kg bw/day (nominal)

Based on:

not specified

Sex:

male/female

Basis for effect level:

other: Acanthosis, hyerkeratosis, and dermal inflammatory cell infiltration in the treated skin of rabbits from the 2000 mg/kg

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

General observations: no effects with the exception of a few spontaneous observations noted in all groups (control group: a few rabbits exhibited hair loss around neck in area of collar, right eye: red, swollen and clear discharge, possible anorexia, mucoid diarrhea and brown stain around anogenital region; treated animals:signs of mucoid stool, brown stain around the anogenital region, hair loss on neck in area of collar and soft stool were observed for all of the dosage levels; possible nasal congestion, diarrhea, mucoid diarrhea, soft stool, clear ocular discharge, possible anorexia and a spontaneous injury to back (impaired use hind leg) were also exhibited in the test groups.

Mortality:No mortality were observed Dermal irritation: the majority of rabbits in both the control and test groups exhibited no dermal irritation except for the following observations: control group:a few rabbits exhibited very slight erythema, atonia and desquamation, and red raised areas and dry chappped areas on the shaved backs 125 mg/kg bw/d:a few rabbits exhibited very slight to slight erythema, very slight desquamation and dry chapped areas on the shaven backs 500 mg/kg bw/d:a few rabbits exhibited very slight erythema, very slight to slight desquamation and red and chapped areas on the shaven backs 2000 mg/kg bw/d: very slight to slight erythema and desquamation and very slight edema wereexhibited by a few rabbits

Body weights: no effects

Hematology: 500 mg/kg bw/d (males): lymphocytes increased, neutrophiles, segmented decreased no other differences were noted in any of the treated animals compared to control (one male at 125/mg/kg bw/d and one male at 500 mg/kg bw/d had signs of aregenerative anemia)

Biochemistry: Statistically significant differences compared to control were noted in: 125 mg/kg bw/d (males): total bilirubin decreased 2000 mg/kg bw/d (males): total bilirubin decreased 2000 mg/kg bw/d (females): LDH decreased no other differences were noted in any treatment group when compared to control Macroscopic pathology: No treatment related effects on skinat the application site in any of the rabbits from the test groups Organ weights: no statistically significant variations in the organ weights were noted in any of the test groups

Histopathology: 2000 mg/kg bw/d: slight to moderate acanthosis and hyperkeratosis 125, 500 mg/kg bw/d: the intensity of the acanthosis and hyperkeratosis was much less as in the highest dose group or almost similar to that observed in the control group control group and treated animals: dermal inflammatory cell infiltration in all animals control and treated animals; however severity of this lesion was judged to be slightly greater in the 2000 mg/kg bw/d group compared to control. In the other two lower dosage groups, the intensity of this lesion was almost simular to that in the control group

Authors concluded: compound related effects consisting of acanthosis, hyperkeratosis and dermal inflammatory cell infiltrate were seen in the treated skin of rabbits from the 2000 mg/kg bw/d group but not in the two lower dosage groups in which these lesions were judged to be almost similar to those occuring in the control group.