Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 225-625-8 | CAS number: 4979-32-2
- 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:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- TG study undertaken to GLP.
- Justification for type of information:
- Read across: repeated dose toxicity: dermal
There were no dermal repeated dose data and valid human skin sensitizing data available for the sulfonamide DCBS. To overcome this uncertainty a read across approach were conducted with the structure analogs sulfenamides CBS, TBBS and MBS.
Physicochemical parameter and toxicological parameters of these compounds were compared with each other to reveal a substantial toxicological profile of DCBS.
The substances CBS, DCBS, TBBS and MBS have a solid physical state and a powder-like appearance. The vapor pressure of the substances is very low; therefore inhalation exposure to the vapor might be negligible (see dossier: CBS, DCBS, TBBS and MBS).
The water solubility differs substantially, reflecting the different functional groups which are linked to the basic structure, the MBT. DCBS is practically insoluble in water (1.9 µg/l at 25°C), CBS (0.32 mg/l, Monsanto Co. 1980) and TBBS (0.3 mg/l, Monsanto Co. 1978) are also poorly soluble in water; whereas MBS (54.6 mg/l at RT, Monsanto Co. 1978) is soluble in water.
The molecular mass of the five substances range from 238.39 g/mol to 346.59 g/mol and the n-octanol/water coefficient (log Pow) is between 3.9 to ca. 4.93, thus suggest intestinal absorption subsequent to oral ingestion.
This assumption is confirmed by data from acute oral toxicity studies and repeated dose toxicity studies, which revealed systemic availability after oral application.
In acute oral toxicity studies with rats, clinical signs like reduced appetite and activity were seen in survivors; whereas increasing weakness, collapse and death were noted in decedents (CBS Monsanto Co. 1973, DCBS Monsanto 1985, TBBS Monsanto Co. 1973, MBS Monsanto Co. 1973). Systemic availability of the test substances were also noted in several repeated dose toxicity studies.
The acute oral toxicity of all five substances is low, indicated by oral LD50 values above 5000 mg/kg bw for the sulfenamides (CBS, DCBS, TBBS and MBS).
The sulfenamides (CBS, DCBS, TBBS, and MBS) were evaluated in several oral repeated dose toxicity studies.
The test substance CBS was evaluated in a 28-day gavage study with Crj: CD rats (MHWJ 1997). The NOAEL was suggested to be 80 mg/kg bw and day. CBS-related effects were present in males and female rats = 250 mg/kg bw and day (LOAEL). Suppression of food consumption and body weight gain were noted in treated rats. There were also signs of coagulopathy of the blood in both sexes and effects in the kidney of male rats.
Several repeated dose toxicity studies were performed to evaluate the toxicity of DCBS. The consistent finding made in all studies is a reduction of body weight, body weight gain and/or food consumption in treated animals. The NOAEL from the key study (TG 408) was suggested to be 36.9 mg/kg bw and day. DCBS-related effects were present in males and female rats = 176.7 mg/kg bw and day; indicated by a decrease in body weight gain (Monsanto Co. 1989).
Several repeated dose gavage studies were conducted to evaluate the toxicity of TBBS. Temporary salivation after test substance administration, a reduction of food consumption and body weight gain were noted in the highest dose groups evaluated. Moreover, an increase in absolute and/or relative kidney weights were noted in treated animals. The subchronic gavage study (Monsanto Co 1985) was used as key study. The NOAEL was suggested to be 100 mg/kg bw and day. A LOAEL of 300 mg/kg bw and day was suggested, which based on a decreased body weight gain and urine specific gravity in treated animals.
The repeated dose toxicity of MBS was evaluated in a chronic feeding study with Sprague-Dawley rats (Monsanto Co. 1982). The NOAEL was indicated at 50 mg/kg bw and day. A LOAEL of 400 mg/kg bw and day was suggested, which based on a reduction of body weight gain and increase in absolute and/or relative liver and kidney weights.
In summary, several oral repeated dose studies were conducted to evaluate the toxicity of the sulfenamides CBS, DCBS, TBBS and MBS. Mainly effects on body weight gain and effects on kidney and liver were noted in treated animals. The NOAEL values ranged from 37 mg/kg bw and day (DCBS Monsanto 1989) to 100 mg/kg bw and day (TBBS, Monsanto 1985) and thus are within the same dose range.
The acute dermal toxicity of the sulfenamides CBS, DCBS, TBBS and MBS is very low, indicated by dermal LD50 values in the rabbit above 5000 mg/kg bw. The effects noted after dermal application are slight and transient like reduced appetite and activity (CBS, MBS, Monsanto 1973) or nasal discharge and few occurrences of ocular irritation (DCBS, Monsanto 1985). Neither mortality nor gross pathological lesions were observed in any of the substances evaluated.
Dermal repeated dose studies were conducted with CBS (Monsanto 1981), TBBS (Monsanto 1981) and MBS (Monsanto 1981). In general, no local or systemic effects were noted in CBS and MBS treated animals up to 2000 mg/kg bw and day (Monsanto 1981). For the TBBS no biological relevant systemic effects were noted up to 2000 mg/kg bw and day; whereas slight local effects were noted in treated animals of the highest dose group (LOAEL 2000 mg/kg bw and day, Monsanto 1981).
Table: read-across: see IUCLID chapter 7.5.3
Data source
Materials and methods
Test material
- Reference substance name:
- N,N-dicyclohexylbenzothiazole-2-sulphenamide
- EC Number:
- 225-625-8
- EC Name:
- N,N-dicyclohexylbenzothiazole-2-sulphenamide
- Cas Number:
- 4979-32-2
- Molecular formula:
- C19H26N2S2
- IUPAC Name:
- N-(1,3-benzothiazol-2-ylsulfanyl)-N-cyclohexylcyclohexanamine
- Details on test material:
- no data
Constituent 1
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
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- 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:
- no effects observed
- 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
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 biological 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:
- 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 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 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.
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.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.