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EC number: 202-409-1 | CAS number: 95-31-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- TG compliant study undertaken to GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 981
- 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
- Principles of method if other than guideline:
- Santocure NS (N-tert-butylbenzothiazole-2-sulphenamide) was administered by dermal application to 3 groups of 10 male and 10 female rabbits, one-half with intact skin and one-half with abraded skin, five days per week for 3 consecutive weeks at dose levels of 125, 500 or 2000 mg/kg. An identical control group was treated with saline. Criteria evaluated for treatment effect included mortality, pharmacotoxic signs, body weights, dermal irritation, hematological and clinical biochemical determinations, organ weights and macroscopic and selected microscopic evaluation of tissue.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- 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-(1,3-benzothiazol-2-ylsulfanyl)-2-methylpropan-2-amine
- Details on test material:
- IUCLID4 Test substance: as prescribed by 1.1 - 1.4
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
Administration / exposure
- Type of coverage:
- semiocclusive
- Vehicle:
- physiological saline
- Details on exposure:
- The test article, Santocure NS (N-tert-butylbenzothiazole-2-sulphenamide), was ground with a mortar and pesle and then moinstened with saline and mixed into a spreadable paste. It was applied evenly over each test site with a glass stirring rod at dosage levels of 125, 500 or 2000 mg/kg bw.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 21 d
- Frequency of treatment:
- Five days per week for 3 consecutive weeks.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 125, 500, or 2000 mg/kg bw/d
Basis:
- No. of animals per sex per dose:
- Five 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
Examinations
- Observations and examinations performed and frequency:
- Dosing was repeated once daily, five days per week for three consecutive weeks. Individual doses were adjusted weekly based on the body weight obtained at the beginning of each study week.
General observations: rabbits were observed once daily for signs of dermal irritation, daily observations for pharmacotoxic signs and other findings, the rabbits were observed for mortality twice daily.
Body weight: recorded weekly.
Hematology: hemoglobin, hemocrit, erythrocyte count, total leucocyte count, platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), reticulocytes, differential leucocyte count.
Biochemistry: glucose, blood urea nitrogen, serum glutamic oxaloacetic transaminase (SGOT), alkaline phosphatase, albumin, serum glutamic pyruvic transaminase (SGPT), total protein, cacium, cholesterol, total bilirubin, creatinine, lactic dehydrogenase (LDH), sodium, potassium, chloride and globulin. - Sacrifice and pathology:
- Pathology: gross pathology.
Organ weights: liver, kidneys, heart, testes, ovaries, thyroid/parathyroid, adrenals and brain, pituitary.
Histopathology: treated and untreated skin, liver, kidneys and any gross lesions.
Recorded: erythema (score 0 to 3), edema (0 to3), atonia (0 to 3), coriaceousness (0 to 3), fissuring (0 to 3), eschar, exfoliation.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No effects with the exception of a few spontaneous observations noted in all groups.
- Dermal irritation:
- effects observed, treatment-related
- Description (incidence and severity):
- 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 were exhibited by a few rabbits. - Mortality:
- no mortality observed
- Description (incidence):
- No mortality were observed.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 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) - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 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 - Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- No statistically significant variations in the organ weights were noted in any of the test groups.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No treatment related effects on skin at the application site in any of the rabbits from the test groups.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 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 occurring in the control group. - Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- systemic
- Effect level:
- > 2 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No biologically relevant systemic effects
- Dose descriptor:
- NOAEL
- Remarks:
- local
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Acanthosis, hyperkeratosis, and dermal inflammatory cell infiltration in the treated skin of rabbits from the 2000 mg/kg
- Dose descriptor:
- LOAEL
- Remarks:
- local effects
- Effect level:
- 2 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Acanthosis, hyperkeratosis, and dermal inflammatory cell infiltration in the treated skin of rabbits from the 2000 mg/kg
Target system / organ toxicity
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 2 000 mg/kg bw/day
- System:
- other: skin
- Organ:
- skin
- Treatment related:
- yes
- Dose response relationship:
- yes
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 were exhibited 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 skin at 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.
Applicant's summary and conclusion
- Executive summary:
Study Design
Santocure NS (N-tert-butylbenzothiazole-2-sulphenamide) was administered by dermal application to 3 groups of 10 male and 10 female rabbits, one-half with intact skin and one-half with abraded skin, five days per week for 3 consecutive weeks at dose levels of 125, 500 or 2000 mg/kg. An identical control group was treated with saline. Criteria evaluated for treatment effect included mortality, pharmacotoxic signs, body weights, dermal irritation, hematological and clinical biochemical determinations, organ weights and macroscopic and selected microscopic evaluation of tissue.
Results
No mortality occurred in this study. The majority of rabbits in both the control and test groups appeared nomal with the exception of a few rabbits in all dose groups exhibiting occasional spontaneous pharmatoxic signs. No statistical significance was noted in body weights. No remarkable changes or differences in dermal irritation were observed between control and test groups. Statistically significant changes in hematological values occured in the 500 mg/kg males in lymphocytes and segmented neutrophils. A few statistically significant changes occurred in the biochemical values; 125 and 2000 mg/kg males showed a decrease in total bilirubin and 2000 mg/kg females showed a decrease in LDH.
No compound related macroscopic lesions or statistically significant organ weight variations were observed in this study.
Microscopically, compound related lesions consisting of acanthosis, hyperkeratosis, and dermal inflammatory cell infiltration were seen in the treated skin of rabbits from the 2000 mg/kg group. All other microscopic lesions observed were incidental in nature and not related to the application of the test substance.
Conclusion
Based on the results of the study, effects levels were determined as:
NOAEL for systemic effects: > 2000 mg/kg bw/day
NOAEL for local effects: 500 mg/kg bw/day
LOAEL for local effects: 2000 mg/kg bw/day, based on the recording of acanthosis, hyperkeratosis, and dermal inflammatory cell infiltration in the treated skin of rabbits at this dose level.
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