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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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- 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:
- read across substance
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:
- other: OECD 421 screening
- 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
- 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 - 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. - Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1 to 1
- Length of cohabitation: one week
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy - 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
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
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly in premating and mating period,
during pregnancy: day 0, 7th , 14th, 20th day, during lactation: 0. or 1st and 4th day; - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- weight of ovaries and pituitary gland - Fetal examinations:
- - External examinations: Yes
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: No
- Head examinations: No data
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 - 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.
- Indices:
- Male mating index
number of males with confirmed mating x 100 / number ofmales cohabited
Female mating index
number of sperm-positive females x l00 / number of females cohabited
Male fertility index
number of males impregnating a females x 100 / number ofmales cohabited
Female fertility index
number ofpregnant females x 100 / number of sperm-positive females
Gestation index
number of females with live born pups x l00 / number of pregnant females
Survival index
number of live pups on day 4 post partum* x l00 / number of pups born alive+
Note: * WIthout shll born pups (dead pups WIth anaenallungs)
+ with dead pups with aerial lungs
Pre-implantation loss: Number of corpora lutea - number of implantations
Post-implantation loss: Number of implantations - number of live births
Post-natal loss: Number of live births - number of alive at postuatal day 4 - Historical control data:
- yes, 13 control groups from Reproduction / Developmental Toxicity Screening tests
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- yellow discolored feces at 400 and 1000 mg/kg bw/day dose levels.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Statistically significant differences were not detected.
- Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Pregnant animals: The mean food consumption was slightly decreased at all dose levels for the whole time of pregnancy.
Lactating animals: Mean food consumption of treated females was slightly lower than in control females. - 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:
- no effects observed
- Description (incidence and severity):
- Relative and absolute weights of ovaries, uterus and pituitary gland were similar in the control females and females of the dose levels 160 and 400 mg/kglday.
In females of the dose level 1000 mg/kglday absolute weights of evaluated organs were slightly lower whilst relative weights of ovaries and pituitary gland were quite balanced. In uterus of females at the dose level 1000 mg/kglday relative weight was decreased against the control.
No statistically significant differences were detected. - Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Macroscopic changes of genital organs were recorded in both control and treated females:
dilatation of uterine horns in 3-1-0-4 females, atrophy of one uterine horn and absence of one oviduct in 0-0-0-1 female.
In all females of the middle and the highest dose level and one female of the lowest dose level the content of intestine and stomach was test substance-colored. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Microscopic changes were found in uterus and vagina, however, in treated animals as well as in control animals. Other microscopical changes were recorded only sporadically.
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One female in the control and lowest dose group each and two females in the 400 and 1000 mg/kg bw/day group each had an abortion.
- Pre- and post-implantation loss:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Pre-implantation losses were slightly increased at 1000 mg/kg bw/day. Slightly increased post-implantation losse at 160 mg/kg bw/day. No significant differences were detected in post-natal losses
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The number of corpora lutea and implantations was insignificantly decreased at the dose level 1000 mg/kg/day compared to control.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: no effects observed
- Remarks on result:
- other: no effects observed
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- Balanced weights of the litters except for the mean weight of litter at the lowest dose level on the 4th day of lactation.
- Changes in postnatal survival:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One male pup died during lactation period (400 mg/kg bw/day)
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- One stillborn pup at the highest dose level. No pathological findings.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental 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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