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EC number: 206-017-1 | CAS number: 288-13-1
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Acceptable, well documented publication/ study report which meets basic scientific principles.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 990
- Report date:
- 1990
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Pregnant female rats were exposed to the test substance on gestation days 6-15 to examine the maternal and developmental toxicity potential of the substance.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Pyrazole
- EC Number:
- 206-017-1
- EC Name:
- Pyrazole
- Cas Number:
- 288-13-1
- Molecular formula:
- C3H4N2
- IUPAC Name:
- 1H-pyrazole
- Details on test material:
- Purity 98.0%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Crl:CD®BR
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Portage, Michigan
- Weight at study initiation: mean of 225-278 g
- Fasting period before study: not reported
- Housing: Until pairing, all animals were individually housed in clean, wire-mesh cages suspended above cage-board. The animals were paired for mating in the home cage of the male. Following positive identification of mating, the females were returned to an individual suspended wire-mesh cage; nesting material was not required as the females were sacrificed prior to expected parturition
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 10 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 40+-66%
- Air changes (per hr): approximately 10-15
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:A sufficient amount of test material was weighed for all groups, transferred to a mortar and ground into a fine powder. The appropriate amount of the ground material was weighed for each group. The vehicle was added to the test material in small increments and ground with a pestle until a slurry was obtained. The mixture was transferred to a graduated cylinder via a series of vehicle rinses. A sufficient amount of vehicle was added to attain a volume of 200 mL. The cylinder was inverted several times to ensure adequate mixing and the contents were transferred to a labelled storage container. The cylinder was rinsed with an additional 60 mL of vehicle which was then added to the storage container. The solutions were visually inspected for homogeneity prior to dispensing on the first day of test material administration. Solutions for aldose groups were prepared once and were stored refrigerated. The solutions were stirred each day prior to dispensing and during the dosing procedures.
- Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:1
- Length of cohabitation: until mating occurred
- Proof of pregnancy: copulatory plug in the vagina or the presence of sperm in a vaginal smear - Duration of treatment / exposure:
- gestation days 6-15
- Frequency of treatment:
- daily
- Duration of test:
- 20 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 1 mg/kg bw/day
- Dose / conc.:
- 5 mg/kg bw/day
- Dose / conc.:
- 10 mg/kg bw/day
- Dose / conc.:
- 15 mg/kg bw/day
- Dose / conc.:
- 20 mg/kg bw/day
- No. of animals per sex per dose:
- 8
- Control animals:
- yes
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations checked: moribundity and mortality
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Days 0 through 20 of gestion (prior to dosing during the treatment period). In addition, animals were observed for signs of toxicity approximately 1 hour following dosing
BODY WEIGHT: Yes
- Time schedule for examinations: Individually on gestation days 0, 6, 9, 12, 16, 18, and 20. A group mean body weight was calculated. Mean body weight changes were calculated for each corresponding interval and also for days 6-16 and 0-20.
FOOD CONSUMPTION: No
WATER CONSUMPTION: No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: Liver, kidneys, spleen, and thyroid were excised, trimmed and weighed - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: Uteri with no macroscopic evidence of nidation were excised, opened and subsequently placed in 10% ammonium sulfide solution for detection of early implanation loss. - Fetal examinations:
- - External examinations: Yes: [all per litter]
- Soft tissue examinations: No
- Skeletal examinations: No
- Head examinations: No - Statistics:
- All analyse were conducted using two-tailed tests for a minimum significance level of 5% comparing each treated group to the control group. The numbers of early and late resorptions, dead foetuses and post implantation losses were compared by the Mann-Whitney U-test. The numbers of litters with malformations and variations were compared by Fisher’s Exact test. Mean numbers of corpora lutea, total implantations, viable foetuses, mean foetal and maternal body weights at each interval, maternal body weight gain and organ weights were analysed by a one-way analysis of variance and Dunnett’s test. The foetal sex ratios were compared by the Chi Square test with Yates correction factor.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- Occasional decreased defecation and/or urination was observed at 15 and 20 mg/kg. No other adverse clinical signs were observed. Hair loss occurred in all doses including controls.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean body weight was decreased at ≥15 mg/kg on gestation days 9, 12, 16, 18, and 20. The decreases were statistically significant only on days 12, 16, and 18 at 20 mg/kg. Body weights at 1, 5, and 10 mg/kg were comparable to control.
An adverse effect on body weight gain appeared dose-related at dose of ≥5 mg/kg, primarily during the first 3 days of dosing. A statistically significant mean body weight loss was observed at 20 mg/kg during gestation days 6-9 and 9-12. Mean body weight gain remained inhibited in this group on gestation days 12-16 resulting in a statistically significant mean body weight loss on days 6-16 (treatment period). Similar body weight effects were observed in animals given 15 mg/kg. Statistically significant mean body weight loss was observed on gestation day 6-9, and gains remained slightly reduced on days 9-12 and 12-16 resulting in a statistically significant mean body weight loss on days 6-16 (treatment period). At both 15 and 20 mg/kg body weight gain was statistically increased on days 16-18, and was comparable to control on days 18-20. Slight, non-statistically significant body weight loss was observed at 5 and 10 mg/kg on gestation day 6-9, but mean body weight gains were comparable to control for the remainder of gestation. A slight decrease in mean body weight gain was observed for the days 6-16 (treatment period) at 10 mg/kg. No effects were observed at 1 mg/kg. - 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 examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- A non-statistically significant increase in mean thyroid weight (26% compared to control) was observed at 20 mg/kg.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One animal at 1 mg/kg had a pitted kidney and one animal had white precipitate in kidney, ureter, and bladder. Dilated renal pelvis was observed in one animal at 1 mg/kg and one animal at 10 mg/kg. Evidence of intubation trauma was observed as red fluid and gelatinous red material in the thoracic cavity in one animal at 1 mg/kg.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- effects observed, treatment-related
- Description (incidence and severity):
- A slight, non-statistically significant, increase in postimplantation loss was observed at 20 mg/kg.
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed - Changes in number of pregnant:
- no effects observed
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 mg/kg bw/day
- Basis for effect level:
- body weight and weight gain
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- A statistically significant decrease in foetal body weight was observed at ≥10 mg/kg.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- External malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- Cleft palate was observed in 6 foetus from 2 litters at 20 mg/kg.
- Skeletal malformations:
- not examined
- Visceral malformations:
- not examined
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 5 mg/kg bw/day
- Basis for effect level:
- other: Fetotoxicity: decrease in mean fetal weight at ≥10 mg/kg
- Dose descriptor:
- NOAEL
- Effect level:
- 15 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity: increased incidence of cleft palate at 20 mg/kg
Fetal abnormalities
- Abnormalities:
- effects observed, treatment-related
- Localisation:
- other: cleft palate at 20 mg/kg
Overall developmental toxicity
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 10 mg/kg bw/day
- Treatment related:
- yes
- Relation to maternal toxicity:
- developmental effects as a secondary non-specific consequence of maternal toxicity effects
Applicant's summary and conclusion
- Conclusions:
- NOAEL for developmental toxicity is 5 mg/kg bw/day. NOAEL for maternal toxicity was 1 mg/kg bw/day. There were no indications for developmental toxicity in doses below maternal toxic doses.
- Executive summary:
The ability of the test substance to cause maternal and developmental toxicity was evaluated. The test substance, suspended in corn oil, was administered to pregnant rats via gavage once daily on gestation days 6-15 at doses of 0, 1, 5, 10, 15, or 20 mg/kg. Throughout gestation the rats were observed for appearance and behaviour, and body weight were recorded. All animals were sacrificed on gestation day 20. The uteri and ovaries were examined and the number of foetuses, early and late resorptions, total implantations, and corpora lutea were recorded. The thyroid, kidneys, spleen, and liver of the females were weighed. Foetuses were weighed, sexed, and examined for external malformations or variations.
No mortality was observed. Maternal toxicity was observed at ≥5 mg/kg/day, expressed as a dose-related decrease in mean body weight gain. Developmental toxicity was observed at ≥10 mg/kg/day, expressed as a dose-related reduction in mean foetal body weight and the incidence of cleft palate in 6 foetuses at 20 mg/kg. The NOAELs are 1 mg/kg/day for maternal toxicity and 5 mg/kg/day for developmental toxicity.
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