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EC number: 639-263-7 | CAS number: 200575-15-1
- 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
Endpoint summary
Administrative data
Description of key information
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 07 October 1998 to 13 November 1998
- Reliability:
- 1 (reliable without restriction)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- Revised 1995 version
- GLP compliance:
- yes
- Limit test:
- no
- Specific details on test material used for the study:
- 4- [2-Ethoxy-5-(4 methyl-l-piperazinylsulphonyl) benzam ido]-1-methy1-3-propy1-1H-pyrazole-5- carboxamide, white crystalline powder, 95% purity
- Species:
- rat
- Strain:
- other: Crl: CD BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- The rats were 27 ± 2 days old, in a weight range of 79 - 88 g for males and 68 - 80 g for females on arrival.
A 12 day acclimatisation period was allowed between delivery of the animals and start of treatment. During this period a review of animal health was undertaken by a Veterinary officer. All rats were caged, as far as possible, in groups of five according to sex in metal cages with wire mesh
floors. Each cage measured 35.8 cm wide, 53 cm deep and 25.7 cm high.
A standard pelleted laboratory rodent diet (Special Diets Services Rat and Mouse Maintenance Diet No. 1) and drinking water were provided ad libitum. The batches of diet used for the study were analysed for nutrients, possible contaminants and microorganisms.
Animal room temperature was set in the range 19 to 23°C and relative humidity was set in the range 40 to 70%.
Air exchange was maintained at approximately 19 air changes per hour and lighting was controlled to provide 12 hours artificial light (0700 - 1900 hours) in each 24-hour period.
The health status of all animals was monitored, by daily observation throughout the acclimatisation period, to ensure that the rats selected for final assignment to the study were satisfactory.
Seven days prior to the start of treatment each animal was weighed and 40 rats were randomly allocated to four groups, each consisting of five males and five females. Each rat was identified within each cage by earmark and foot mark (tattoo). - Route of administration:
- oral: gavage
- Vehicle:
- methylcellulose
- Remarks:
- 1%
- Details on oral exposure:
- The test substance was administered by oral gavage to rats of Groups 2 to 4 inclusive at a dose volume of 10 ml/kg/day.
Control animals received the vehicle (1% w/v methylcellulose) alone at the same dose volume (10 ml/kg/day) and in the same manner as for treated animals. - Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- 7 days
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 150 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 5 Male/5 Female
- Control animals:
- yes, concurrent no treatment
- Observations and examinations performed and frequency:
- Clinical Sign: During treatment period prior to dosing and at regular intervals following dosing daily. All animals checked daily (early and late afternoon)
Bodyweight: Animals weighed prior to treatment (day 7), prior to doing on Day 1, weekly intervals from day 1 to day 22 and on day 28.
Food Consumption: individual rat food consumption recorded weekly
Behaviour: full functional observational battery and motor activity assessment were performed on all animals during the predose period and in Week 4
Clinical Pathology: Prior to termination - Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- All males and females receiving 1000 mg,/kg/day showed salivation after dosing, from Day 18 of treatment. Usually, this was onset within minutes of dosing, but not evident more than 1 hour post dose.
This sign is not considered to be of treatment related - Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- During the first week of treatment (Days 1 to 8), all treated female groups showed slightly lower bodyweight gains compared with controls, though not dose-related in degree and not attaining statistical significance. Overall (Days 1 - 28), bodyweight gain for all treated female groups was comparable with controls, though remained slightly lower for those receiving 50 mg/kg/day. These findings are not considered to be treatment-related.
All treated male groups showed group mean bodyweight gains that were comparable with controls over the treatment period - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Slightly lower food consumption in all females during week 1, not dose related as overall fodd consumption in females (day 1-28) was considered comparable to controls. No effects seen in males
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- All treated groups showed marginally higher group mean Prothrombin Time (PT) values compared with controls, with statistical significance being attained for both sexes receiving 1000 mg/kg/day and males receiving 150 mg/kg/day. The magnitude of these differences is so small that they are considered to be coincidental.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Both sexes receiving 150 or 1000 mg/kg/day showed lower group mean triglyceride values compared with controls, with statistical significance being attained for females at these dosages though in the absence of strict dosage-relationship. In females, the statistical significance was probably due to a single high control value. Males receiving 1000 mg/kg/day also showed statistically significantly lower group mean cholesterol and calcium values compared with controls. These minor differences were considered to be of no toxicological importance, which is supported by the lack of corroborative microscopic findings
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Description (incidence and severity):
- Slightly higher group mean bodyweight adjusted and relative liver weights were seen in both sexes receiving 1000 mg/kg/day, statistically significant for females. All treated female groups showed statistically significantly higher group mean bodyweight adjusted and relative kidney weights compared with controls, dose-related in degree. Females receiving 1000 mg/kg/day showed marginally, but statistically significantly higher mean spleen weight compared with controls. The liver, kidneys and
spleen differences were marginal and in the absence of corroborative histopathology findings were considered to have been coincidental and of no toxicological relevance. Treated female groups also showed higher bodyweight adjusted and relative group mean ovary weights compared with controls, dose-related in degree and statistically significant at 1000 mg/kg/day and for the relative value at 150 mg/kg/day only. At 1000 mg,/kg/day these findings in the ovaries, correlate with histopathological results of slightly increased mean numbers of corpora lutea compared with concurrent controls.
All other differences are considered to be due to natural variation and not an effect of treatment. - Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Increased number of corpea lutea were present in the ovaries of rats recieving 1000mg/kg/day when conpared to the control group. In view of the small number of rats per group, and the absence of other changes in the reproductive tract,
the significance of this finding is uncertain, although this change may explain the increased ovary weights seen in rats receiving 1000 mg/kg/day when compared with control.
No other findings were detected to explain the increased liver weights seen in both sexes receiving 1000 mg/kg/day, nor the increased spleen and kidney weights seen in treated females. - Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: The only finding in this study that was considered attributable to treatment was the post dose salivation at the highest dose of 1000 mg/kg/day.
- Key result
- Critical effects observed:
- no
- Conclusions:
- Not classified; NOAEL of 1000mg/kg/day was determined
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
Additional information
Justification for classification or non-classification
NOAEL of 1000mg/kg/day was derivied therefore no classification is needed
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