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EC number: - | CAS number: -
- 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
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- polyethylene glycol
- Remarks:
- PEG 400 was dissolved in distilled water to be the ratio of 80% (v/v).
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples for homogeneity analysis were also analyzed for verification of dose level concentration. Results of dose formulation were 94.8, 91.1 and 104.5% at each dose levels of 25, 75 and 250 mg/mL. They were acceptable as the mean concentration was within ± 20% of the nominal concentration.
- Duration of treatment / exposure:
- Dosing of the males will begin 14 days prior to mating and continue through the day prior to sacrifice (at least 28 days). Dosing of the females will begin 14 days prior to mating and continue through lactation day (LD) 13. Animals in recovery group will not be mated and will be assigned to 2 weeks of recovery period after the completion of administration
- Frequency of treatment:
- once a day
- Dose / conc.:
- 0 mg/kg bw (total dose)
- Dose / conc.:
- 100 mg/kg bw (total dose)
- Dose / conc.:
- 300 mg/kg bw (total dose)
- Dose / conc.:
- 1 000 mg/kg bw (total dose)
- No. of animals per sex per dose:
- control: 18 animals
100, 300 mg/kg: 12 animals
1000 mg/kg: 18 animals - Control animals:
- yes
- Parental animals: Observations and examinations:
- One male to one female mating was used, and males and females were paired for 2 weeks. Animals of the recovery group were not mated.
Mating confirmation was checked every morning during the mating period. Mating was confirmed with vaginal plug(s) and/or sperm in the vaginal smear. Day 0 of pregnancy was defined as the day of mating confirmation. Pregnancy was confirmed by parturition or by implantation sites on the uterus at sacrifice.
Non-mated female was sacrificed after at least 24 days from final mating day as described in
Section 2.13.1, and dosing was continued until the day before of sacrifice. - Oestrous cyclicity (parental animals):
- A vaginal smear was taken daily for each female from the beginning of the 14 days prior to mating with continued monitoring into the mating period until there was evidence of mating.
Furthermore, regularity and length of the estrus cycle during the treatment period until mating was examined.
In addition, vaginal smear of sacrificed females were taken at termination to examine the stage of the estrus cycle and to allow a correlation with the histopathology of the female reproductive organs. - Postmortem examinations (offspring):
- External and visceral examinations were conducted in dead pups at parturition and in dead or moribund pups from birth to day 4 of lactation, if possible. After day 5 of lactation, dead pups were sacrificed by CO2 inhalation and necropsied with special attention to all vital organs.
- Reproductive indices:
- • Mating Index (%)
= (No. of males with evidence of mating/No. of males paired) × 100
= (No. of females with evidence of mating/No. of females paired) × 100
• Fertility Index (%)
= (No. of males impregnating a female/No. of males paired) × 100
= (No. of pregnant females/No. of females paired) × 100
• Fecundity Index and Pregnancy Index (%)
= (No. of males impregnating a female/No. of males with evidence of mating) × 100
= (No. of pregnant females/No. of females with evidence of mating) × 100
• Precoital Time: No. of days taken to mate - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- In males at 100, 300 and 1000 mg/kg, salivation was observed in 11, 12, and 18 animals, respectively. In females at 100, 300 and 1000 mg/kg, salivation was observed in 9, 11, and 18 animals, respectively. It was considered test item-related but not toxicologically statistically significant since it was considered to be attributed to the palatability of the test item.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- No test item-related deaths or moribund animals occurred in any group throughout the study.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in body weight and body weight gain were observed in both sexes during the study.
- Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in food consumption were observed in both sexes during the study.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Total red blood cell count (RBC) was significantly increased (1.07-fold over control, respectively) in males at 300 and 1000 mg/kg and mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were significantly increased (1.08 and 1.07-fold over control,
respectively) in females at 1000 mg/kg. These changes were fully recovered after recovery period and considered not to represent meaningful toxicity as there were no histopathological correlates. - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Inorganic phosphorus (IP) was significantly decreased (85% of control) in males at 1000 mg/kg. These changes were fully recovered after recovery period and considered not to represent meaningful toxicity as there were no histopathological correlates.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in functional behavior examination were observed in both sexes during the study.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Reproductive function: oestrous cycle:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in estrus cycle were observed during the study.
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in the reproductive and littering findings were observed during the study.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- <= 1 000 mg/kg bw (total dose)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive function (oestrous cycle)
- reproductive performance
- Key result
- Critical effects observed:
- no
- Lowest effective dose / conc.:
- 1 000 mg/kg bw (total dose)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- not examined
- 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:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- not examined
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in clinical signs were observed in both sexes of the F1 pups during the study.
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in the external examination were observed in both sexes of the F1 culled pups during the study.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in body weight were observed in both sexes of the F1 pups during the study.
- Food consumption and compound intake (if feeding study):
- not specified
- 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
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 1. F1 pups anogenital distance
No test item-related changes in anogenital distance (AGD) were observed in both sexes of F1 pups during the study.
Statistically significant changes in F1 male pups AGD was not considered test item-related since it was within the historical control data. [Normalized AGD (Min-Max, mm); Male: 2.0-2.2]
2. F1 male pups nipple retention
No test item-related changes in nipple retention of the F1 male pups were observed during the study. - Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Thyroid Hormone (T4) analysis:
No test item-related changes in the thyroid hormone (T4) were observed in the adult male animals, and in the male and female pups on PND 13. - Developmental immunotoxicity:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- <= 1 000 mg/kg bw (total dose)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- developmental neurotoxicity
- Key result
- Critical effects observed:
- no
- Lowest effective dose / conc.:
- 1 000 mg/kg bw (total dose)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- 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
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Key result
- Reproductive effects observed:
- no
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Additional information
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.