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EC number: 265-634-4 | CAS number: 65212-77-3
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2011
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- historical data are not given, food consumption data male animals third week are missing, missing details on mating procedure: how many attempts, replacement of male after unsuccesful mating and how females were caged after mating,
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Reference substance 002
- EC Number:
- 603-331-4
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: SPF breeding, VELAZ s.r.o., Kolec u Kladna, Czech Republic, RCH CZ 21760152
- Age at study initiation: 10 weeks
- Weight at study initiation: males 307.89 - 309.22g, females: 224.33 - 226.55g
- Housing: exept from mating period, two rats of the same sex per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: males from: 19.01.2011 To: 22.02.2011 females: 19.01.2011 - 13.03.2011
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- suspension
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): daily just before administration
- Storage temperature of food: test item was administered by gavage
VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw - Details on mating procedure:
- - M/F ratio per cage: 1 to 1
- Length of cohabitation: 7d
- Proof of pregnancy: sperm in vaginal smear, referred to as day 0 of pregnancy - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- According to the information from Sponsor the main component of the test substance is insoluble in the used vehicle (water for injection).
Mixture of sample and deionised water results in yellow non-transparent suspension but undissolved particles of the test substance were easily visible in the application form and homogeneity could be checked by eye. Stability of the test substance in the application form cannot be verified analytically. The application form was prepared just before the application and there was no indication that test substance would have been unstable in the suspension in deionised water for that short time period. - Duration of treatment / exposure:
- males and females - 2 weeks prior to the mating period and during the mating period,
pregnant females - during pregnancy and till the 3rd day oflactation,
males - after mating period - totally for 28 days,
nonpregnant females (mated females without parturition) - for 25 days after the confirmed mating - Frequency of treatment:
- daily, 7d/week
- Details on study schedule:
- Age at mating of the mated animals in the study: 12 weeks
Doses / concentrationsopen allclose all
- Dose / conc.:
- 160 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 400 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:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on data of 14d range finder
- Positive control:
- no
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
males - weekly
females - weekly in premating and mating period,
during pregnancy: day 0, 7th , 14th, 20th day, during lactation: 0. or 1st and 4th day;
pups (litters) - 0 or 1st and 4th day; - Sperm parameters (parental animals):
- Parameters examined in P male parental generations:
testis weight, epididymis weight, prostate gland weight, pituitary glands weight, sperm motility, sperm morphology - Litter observations:
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, presence of gross anomalies, physical or behavioural abnormalities
Dead pups were sexed and externally examined; the stomach was examined for the presence of milk. Pups killed on the 4th day of lactation were sexed and subjected to external examination of the cranium, and to macroscopic examination of the thoracic and abdominal tissues and organs.
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities- Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals, males were killed at the end of the administration period - after 28 days of administration
- Maternal animals: All surviving animals, parental females were killed on the 4th day of lactation. Mated females without delivery were killed 26th day after confirmed mating
GROSS NECROPSY
- macroscopically examined for any pathological changes with special attention to the organs of the reproductive systems
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated below were prepared for microscopic examination and weighed, respectively:
relevant gross lesions, pituitary gland, coagulation gland, prostate gland, seminal vesicles, epididymis and testes (fixed in Davidson's suspension), cervix of uterus, ovaries, uterus and vagina - Postmortem examinations (offspring):
- SACRIFICE
- sacrificed on day 4 of lactation
GROSS NECROPSY
- examination of thoracic and abdominal tissues and organs - Statistics:
- The ANOVA test - Analysis of Variance (QC.Expert 2.5) at significance level 0.05 was used for the statistical analysis. This statistical analysis was used for the results of body weight, biometry of organs and number of pups. Control group with vehicle was compared with three treated groups. The results statistically significant on probability level 0.05 are indicated by figures with asterisk in the summary tables.
- Reproductive indices:
- Post-implantation loss, Pre-implantation loss, Post-natal loss, Male mating index, Female mating index, Male fertility index, Female fertility index
- Offspring viability indices:
- Gestation index, Survival index
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- yellow stained feces at mid and high dose groups
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- atrophic changes in prostate gland of high dose males
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Details on results (P0)
- females: Dose dependent decreased relative weight of uterus was recorded in females at the dose level 1000 mg/kg/day (connection with oestrous cycle)
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 400 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- organ weights and organ / body weight ratios
- histopathology: non-neoplastic
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: no effects observed
- 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:
- reproductive performance
Target system / organ toxicity (P0)
- Critical effects observed:
- no
Results: P1 (second parental generation)
Effect levels (P1)
- Dose descriptor:
- other: not applicable
- Remarks on result:
- other: not applicable
Target system / organ toxicity (P1)
- Critical effects observed:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Overall reproductive toxicity
- Reproductive effects observed:
- no
Applicant's summary and conclusion
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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