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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: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study, comparable to guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 985
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- Twenty male and twenty female Sprague-Dawley rates received 0, 100, 300 or 1000 mg N-tert-butylbenzothiazole-2-sulphenamide/kg bw by gavage. The animals were examined for mortality, overt signs of toxicity, body weight and food consumption. Clinical chemistry, haematological and urinalysis determinations were performed. At sacrifice animals were subjected to a complete gross necropsy and a microscopic examination for the control and high dose group performed.
- 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:
- Santocure NS, purity (end of the study): 96.44 %
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- The animals were ca. six week of age and weighed 175-213 g for males and 130-159 g for females at the start.
Administration / exposure
- Route of administration:
- oral: gavage
- Details on route of administration:
- Oral gavage is a commonly applied route of administration for studies of this type.
- Vehicle:
- corn oil
- Details on oral exposure:
- Dosing suspensions were prepared weekly. All animals were administered a constant volume of suspensions (0.5 ml of suspension per 100 g of body weight).
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples were analysed weekly using a liquid chromatographic procedure. Analytical results demonstrated that the test material was stable and appropriate dose suspensions had been prepared.
- Duration of treatment / exposure:
- 90 d
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Vehicle control
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- Low
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Remarks:
- Mid
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- High
- No. of animals per sex per dose:
- 20 per dose and sex
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: no
- Positive control:
- No.
Examinations
- Observations and examinations performed and frequency:
- Examinations:
Mortality: twice daily observations
Body weight gain and food consumption: determination weekly
Clinical appearance: checked daily
Hematology (total erythrocyte count (RBC), total leukocyte count (WBC), platelets count (Plt), hematocrit (Hct), level of hemoglobin, red blod cell indices (MCV, MCH, MCHC), determination of the leukocyte differential, reticulocyte count
Clinical Chem.: albumin, total protein, blood urea nitrogen (BUN), total bilirubin, direct bilirubin, glucose, glutamic pyruvic transaminase (D-GPT/ALT), alkaline phosphatase, glutamic oxaloacetate transaminase (D-GOT/AST), gamma glutamyl transpeptidase (Gamma-GT, phosphorous, creatine, cholesterol (Chol), calcium, chloride, sodium, potassium and globulin
Urine analysis: pH, urine protein, blood, glucose, ketone, bilirubin, urobilinogen, urine specific gravity - Sacrifice and pathology:
- Organ weights:brain, kidney, liver, testes
Organs prepared: aorta, adrenal glands, bone and bone marrow, brain, epididymis, esophagus, eyes, heart, pancreas, prostate gland, pituitary gland, salivary gland, skin, small intestine, kidneys, colon, lesions, liver, lung, lymph node, mammary gland, muscle, nerve, spinal cord, spleen, stomach, testes, ovaries, thymus, thyroid, parathyroid, trachea, uterus, urinary bladder - Statistics:
- Quantitative data were analyzed by Dunnett's t-test to determine significant differences in treatment values versus control at the 95% confidence level. Organ weight/terminal body weights were analyzed by the Mann-Whitney U test and incidence of microscopic abnormalities with the Fischer exact test, both utilizing the Bonferri Inequality procedure.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Animals in all treatment groups salivated after dosing and mid and high dose animals salivated prior to dosing or sometimes resisted dosing. High dose females exhibited urine stained abdomens. Other than the above, no clinical signs or abnormal behavior related to treatment were observed. Due to the lack of gross or microscopic findings of gastrointestinal effects, the behavioral reactions were considered to be related to poor palatability of the test material rather than a toxic response.
- Mortality:
- no mortality observed
- Description (incidence):
- All animals survived three months of exposure to the test substance.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced body weights were noted for males at the middle and highest dose groups (300 and 1000 mg/kg bw/day, respectively). Most affected were the high dose group males with 13 weeks reduction at 99% statistical confidence. Middle group males were affected the final 11 out of 13 weeks, primarily at 95% statistical confidence. Body weights were unaffected for the low dose males (100 mg/kg bw/day) and all three female treatment groups as compared to controls.
There was a linear decrease in terminal body weights of males from Groups 1, 2 and 3. There were, however, essentially no changes in weights of females from treated groups as compared to controls. - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Similar amounts of food were consumed by both sexes from all three treatment groups when compared to their control groups. Two exceptions were mid dose group males (300 mg/kg/day) at week 9 and high dose males (1,000 mg/kg/day) at week 1, however, these exceptions appear random and are probably not related to exposure with the test item.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were several statistically significant changes in mean values for hematologic or serum chemistry parameters. Statistically significant increases in reticulocyte counts occurred in Group 2 males (300 mg/kg bw/d) and Group 3 (1000 mg/kg bw/d) females. These values remained well within normal limits and were of no toxicological significance.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- There were several statistically significant changes in mean values for hematologic or serum chemistry parameters. Depressions of SGOT and SGPT at 100 and 1000 mg/kg bw in females were probably artifactual due to high group mean values for these enzymes in control females. When clearly abnormal values for NFOO4 and NFO15 are deleted, a minimal (p 0.05) depression was found affecting only Group 1 females (100 mg/kg bw/d). These changes were not considered to be relevant. Minimal depressions in sodium affected all dose level of females and Group 2 (300 mg/kg bw/d) males. These were within normal range and were not considered to be toxicologically relevant. The only change which may have been biologically relevant was a mild increase in the mean cholesterol value for females from Group 3 (1000 mg/kg bw /d).
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Urine specific gravity was increased in males from Group 3 (1000 mg/kg bw) and females from Groups 2 and 3 (300 and 1000 mg/kg bw/d). The increased values for males and females from Group 3 were statistically significant. There were increases in the occurrence of mild ketonuria in male Groups 1, 2 and 3.
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- The only significant changes in absolute organ weights were decreased mean brain weight in females from Group 3 (1000 mg/kg bw/d) and increased mean hepatic weight in females from Group 3 (1000 mg/kg bw/d). Organ to body weight ratios were increased in a dose related manner for all male organs for which weights were obtained (statistically significant in most instances) for Groups 2 and 3. Kidneys to body weight ratios were increased in females from Group 3 (statistically significant) as were liver to body weight ratios in females from Groups 2 and 3 (300 and 1000 mg/kg bw/d).
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no gross lesions associated with chemical administration.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- There were no microscopic lesions with an apparent association with chemical administration.
- Histopathological findings: neoplastic:
- not specified
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects
- Dose descriptor:
- LOAEL
- Effect level:
- 300 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: decreased body weight in males, increase in urine specific gravity in females
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- 100 mg/kg bw/day produced no toxicologically significant changes and is therefore set as NOAEL.
The LOAEL is set at 300 mg/kg bw/day, based on decreased body weight in males, an increase in urine specific gravity in females and increase in relative liver and kidney organ weights.
NB. Some parameters (neurobehavioral examinations, endocrine parameters) are not present in the current study when compared to the modern OECD 408 test guideline. A testing proposal is in place for an OECD 443 EOGRTS, which will provide fully up to date data on not only reproduction endpoints but also endocrine and systemic toxicity. - Executive summary:
Study design
The test substance was administered orally by gavage to four groups of 20 male and 20 female Sprague-Dawley rats at doses of 0, 100, 300 or 1000 mg/kg/day for 3 months.
Results
All animals survived the treatment period. changes appearently associated with the test substance exposure at 1000 mg/kg7day included increased urine specific gravity and decreased body weights among males. Females at this dose level had stained abdomens, increased urine specific gravity, elevated cholesterol values, and increased liver weights. Middle dose level (300 mg/kg/day) males had decreased body weight and females had increased urine specific gravity.
Conclusion
100 mg/kg bw/day produced no toxicologically significant changes and is therefore set as NOAEL.
The LOAEL is set at 300 mg/kg bw/day, based on decreased body weight in males, an increase in urine specific gravity in females and increase in relative liver and kidney organ weights.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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