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

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

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: see 'Remark'

Remarks:

Accpetable documented study report with restriction (test substance purity not indicated; the study is limited concerning the recommended particle-size distribution given in current guidelines and thus an exposure of all relevant regions of the respiratory tract was presumably not given. The biologically relevance of findings from this study, especially systemic effects are questionable, whereas local effects noted in the inhalation study could be used for supporting purpose.

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 412 (Subacute Inhalation Toxicity: 28-Day Study)

GLP compliance:

no

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, lot no. MIC 270582

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: aerodynamic mass medium diameter: 8.4 micrometer with a geometric standard deviation of 4.31

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

6 hours/day, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0.0, 0.0024, 0.029, 0.084 mg/L
Basis:

No. of animals per sex per dose:

10 animals per dose and sex

Control animals:

yes

Details on study design:

Post-exposure period: no

Results and discussion

Effect levels

Dose descriptor:

other:

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Remarks on result:

not measured/tested

Remarks:

Effect level not specified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Nominal concentrations: 0.058, 0.17 and 0.52 mg/l Analytical concentrations: mean analytical concentrations: 0.0024, 0.029 and 0.084 mg/l

Gravimetric concentrations: mean gravimetric concentrations: 0.0024, 0.028, 0.088 mg/l

Dust particle size distribution analyses: the equivalent aerodynamic mass medium diameter: 8.4 μm , geometric standard deviation of 4.31

Clinical studies Appearance and general behavior: Nasal irritation was observed in the rats and ranged in severity from slight to market. The symptom was usually present after exposure and had generally disappeared by the following morning. The severity of nasal irritation appeared to be concentration dependent during the first half of the study, several rats in the highest dose group exhibited an urogenital discharge. This symptom was observed after exposure and was still apparent the following morning. Alopecia was observed in two rats of the highest dose group.

Body weights: no effects

Food consumption: no time or test material related differences were observed

Hematology:no effects

Blood chemistry: at 0.029 and 0.084 mg/l: SGOT values for males and females were significant elevated compared to control (II) at 0.0024 mg/l: SGOT values were comparable to control all other parameters appeared comparable to one or both control groups

Urinalysis: no effects

Gross pathology: No gross lesions interpreted as compound induced observed in any animal at necropsy

Organ weights:

Some variations in absolite and rel. weights, but the variations did not appear to be dose dependent and there were no compound related microscopic alterations associated with the involved tissue, therefore the biological signifcance of the variations could not be determined

Histopathology: 0.084 mg/l: brown pigments within sinusoidal macrophages in lymph nodes (6/20)was slightly increased when compared to controls (2 control I, 1 control II)concurrent erythrophagocytosis in the lymph nodes was also slightly increased in the Santocure NS treated group (4/20) as compared to controls (0 control T, 1 control II) Very slight to moderate focal to multifocal hepatocellular necrosis was observed in 3/20 animals; an associated acute inflammatory infiltrate was present in 2 of the 3 affected animals. This lesions was not present in controls While the previously described lesions may represent a compound effect, they have been observed in control rats at the facility and therefore the possibility that they are spontaneous in origin cannot be excluded. The ocurence and incidence of all other microscopic lesions were similar to that observed in controls. Histological examinations of treated animals (highest dose group) of the nasal turbinate area, trachea, lung and olfactory bulb revealed no biologically relevant differences compared to the controls.