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EC number: 203-187-9 | CAS number: 104-23-4
- 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:
- repeated dose toxicity: oral
- Remarks:
- combined repeated dose and carcinogenicity
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data is from secondary source
Data source
Reference
- Reference Type:
- secondary source
- Title:
- Repeated dose oral toxicity study of the test chemical
- Author:
- NCI
- Year:
- 1 977
- Bibliographic source:
- National Cancer Institute CARCINOGENESIS
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- A bioassay of the test chemical for possible combined repeated dose and carcinogenicity was conducted by administering the test material in feed to Fischer 344 rats and B6C3F1 mice.
- GLP compliance:
- no
Test material
- Reference substance name:
- Dapsone
- EC Number:
- 201-248-4
- EC Name:
- Dapsone
- Cas Number:
- 80-08-0
- Molecular formula:
- C12H12N2O2S
- IUPAC Name:
- 4,4'-Diaminodiphenyl Sulphone
- Details on test material:
- - Name of test material: Dapsone
- Molecular formula: C12H12N2O2S
- Molecular weight: 248.30 g/mol
- Substance type: Organic
- Physical state: Powder
- Impurities (identity and concentrations): > 99%
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Mixed shipments from A. R. Schmidt, Madison, Wisconsin, and from Charles River Laboratories
- Age at study initiation: Male animals were 34 days of age and females 38 days of age when placed on study
- Housing: Solid bottom stainless steel cages with clay bedding. Mice were housed seven per cage.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 4 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 40-60%
- Air changes (per hr): 15 times per hour
- Photoperiod (hrs dark / hrs light): In addition to natural light, illumination was provided by fluorescent light for 9 hours per day
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: Wayne Lab Blox
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): Test diets were formulated every 2 weeks using finely ground Wayne Lab Blox to which was added the required amount of the test chemical for each dietary concentration
- Mixing appropriate amounts with (Type of food): A given amount of the test chemical was first hand-mixed with a small amount of feed. This mixture was then added to a larger quantity of feed to give the desired concentration of the chemical, and mixed mechanically in a twin-shell blender for not less than 10 minutes to assure homogeneity of the mixture
- Storage temperature of food: Formulated diets were stored in plastic bags at room temperature until used - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 108 weeks
- Frequency of treatment:
- Animals were fed diets containing dapsone 5 days per week, and control diets 2 days per week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 500 or 1000 ppm (equivalent to 0, 71.42 or 142.85 mg/kg bw)
Basis:
nominal in diet
- No. of animals per sex per dose:
- Matched control: 14 males and 14 females
500 ppm: 35 males and 35 females
1000 ppm: 35 males and 35 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All animals were observed twice daily for signs of toxicity and palpated for masses at each weighing
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: yes
- Time schedule for examinations: Weighed individually each week for 8 weeks and every 2 weeks for the remainder of the study. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Gross examination of major tissues, major organs, and all gross lesions from killed animals and from animals found dead
HISTOPATHOLOGY: Yes
The following tissues were examined microscopically: skin, muscle, lungs and bronchi, trachea, bone and bone marrow, spleen, lymph nodes, thymus, heart, salivary gland, liver, gallbladder and bile duct (mice), pancreas, esophagus, stomach, small intestine, large intestine, kidney, urinary bladder, pituitary, adrenals thyroid, parathyroid, mammary gland, prostate or uterus, testis or ovary, brain and sensory organs. Peripheral blood smears were prepared from each animal. - Other examinations:
- No data
- Statistics:
- Probabilities of survival were estimated by the product-limit procedure of Kaplan and Meier.
Statistical analyses for a possible dose-related effect on survival used the method of Cox (1972) for testing two groups for equality and Tarone's (1975) extensions of Cox's methods for testing for a dose-related trend.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Description (incidence):
- The test chemical did not adversely affect the survival of mice. Several control males died early in the study, while survival of the other groups of mice was not affected until week 75.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Lower body weights in males
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- In the males, alveolar/bronchiolar adenoma was observed in 5/33 low-dose animals. Similar tumors were not observed in female mice.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not specified
- Details on results:
- Gross pathology: In the males, alveolar/bronchiolar adenoma was observed in 5/33 low-dose animals. Although significant when compared with pooled controls, the tumors cannot clearly be associated with treatment, because of the low incidence in the low-dose group, and because only one tumor was found in the high-dose group. Similar tumors were not observed in female mice
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 142.85 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The no observed adverse effect level (NOAEL) value of the test chemical is considered to be 1000 ppm (142.85 mg/Kg/day) for B6C3F1 mice, as no adverse effects were observed at this dose level.
- Executive summary:
The test chemical is the parent chemical of the sulfone drugs, and the major therapeutic agent in this group for the treatment of leprosy. This test chemical was selected for screening by the carcinogenesis program in an attempt to evaluate the carcinogenicity of certain drugs that are used extensively and for prolonged periods in humans. The test chemical was administered in diet to B6C3F1 mice at dose levels of 500 or 1000 ppm for 78 weeks and a further observation period of 28-30 weeks was provided. The test chemical did not adversely affect the survival of mice. Several control males died early in the study, while survival of the other groups of mice was not affected until week 75. In the males, alveolar/bronchiolar adenoma was observed in 5/33 low-dose animals. Although significant when compared with pooled controls, the tumors cannot clearly be associated with treatment, because of the low incidence in the low-dose group, and because only one tumor was found in the high-dose group. Similar tumors were not observed in female mice. Based on the observations made, the no observed adverse effect level (NOAEL) value of the test chemical is considered to be 1000 ppm (142.85 mg/Kg/day) for B6C3F1 mice, as no adverse effects were observed at this dose level.
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