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EC number: 602-997-3 | CAS number: 124495-18-7
- 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:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 83-3 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: 87/302/EEC Part B, Methods for the determination of toxicity, teratogenicity test - rodent and non-rodent.
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: JMAFF Notice 59, NohSan N4200
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- Reference substance 001
- Cas Number:
- 124495-18-7
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- Substance ID: TSN 100097
Name of substance: XDE-795 (Technical grade)
Purity: 97.4%
Test animals
- Species:
- rat
- Strain:
- other: Crl: CD(SD) BR VAF/Plus
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, UK Limited, Manston Road, Margate, Kent, England.
- Age at study initiation: 8-10 weeks old
- Housing: The animals were housed individually in suspended stainless-steel cages equipped with solid sides and wire grid front, back, floor and top. The cages constituting each treatment group were dispersed within the batteries so that possible environmental influences arising from their spatial distribution were equilibrated as far as possible for all treatments.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Not specified
ENVIRONMENTAL CONDITIONS
- Temperature: 18-23°C
- Humidity: 45-60%
- Photoperiod: 12 hrs dark /12 hrs light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 1% methylcellulose
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Dose suspensions were prepared daily and used within 4 hours of preparation. The test substance was ground in a mortar with a small amount of the vehicle, 1% methylcellulose, until a smooth paste was formed. The formulation was then gradually made up to volume and mixed using a high shear homogeniser. A series of suspensions was made by serial dilution to achieve the required concentrations. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The achieved concentration of prepared formulations was assessed on the first day of treatment and results for all groups were within the range -1% to +5% of nominal.
- Details on mating procedure:
- - Impregnation procedure: Purchased timed pregnant
- Verification of same strain and source of both sexes: Yes
- Proof of pregnancy: Vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy
- Any other deviations from standard protocol: None - Duration of treatment / exposure:
- GD6 to GD15
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day
- Dose / conc.:
- 300 mg/kg bw/day
- Dose / conc.:
- 1 000 mg/kg bw/day
- No. of animals per sex per dose:
- 30 time mated females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dosages of 0, 100, 300 and 1000 mg/kg/day were selected on the basis of a preliminary study where no conclusive toxicity was apparent at dosages up to 750 mg/kg/day.
Examinations
- Maternal examinations:
- CLINICAL OBSERVATIONS
- Time schedule: All animals were regularly handled and observed daily for obvious changes or signs of reaction to treatment.
BODY WEIGHT
- Time schedule for examinations: All animals were weighed by the supplier on the day of mating (Day 0 of pregnancy), on receipt at test facility (Day 1, batch A or Day 2, batch B of pregnancy) and on Days 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20.
FOOD CONSUMPTION
- Food consumption for each animal determined and mean daily diet consumption calculated as g/rat/day
POST-MORTEM EXAMINATIONS
- Sacrifice on gestation day # 20
- Organs examined: Liver, ovaries, uteri - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination include:
- 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: number and distribution of live young, individual foetal weight (from which the litter weight was calculated) and foetal abnormalities - Fetal examinations:
- - External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [half per litter]
- Skeletal examinations: Yes: [half per litter] - Statistics:
- Significance tests, employing analysis of variance or covariance followed by an intergroup comparison with the control, were performed on the following parameters and results are presented in relevant tables of this report:
bodyweight change, food consumption, liver weight, litter data, sex ratios, foetal anomalies and variants.
For maternal parameters the tests employed were dependent on the heterogeneity of variance between treatment groups. Parametric tests (analysis of variance or covariance (Snedecor and Cochran, 1967) followed by Williams' test (Williams, 1971/2) or non-parametric tests (Kruskal-Wallis (Hollander and Wolfe, 1971) followed by Shirley's test (Shirley, 1977) were used to analyse these data, as appropriate. For litter data and foetal changes, the basic sample unit was the litter and, due to the preponderance of non-normal distributions the above mentioned non-parametric analyses were used. Analysis of malformations and anomalies was performed using a trend test on the number of litters affected followed by a 2 sample permutation test (Edgington, 1980; Franck, 1986).
All significant (i.e., P ≤0.05) intergroup differences from the control were reported and are supported by a significant analysis of variance (p ≤0.05.
Where a non-parametric test was usually employed but 75% or more of the values for a given variable were the same (i.e., late embryonic deaths), a Fisher's exact test (Fisher, 1950) was used.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, non-treatment-related
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- There was a single mortality at 1000 mg/kg/day, one female died prior to dosing on Day 12 post coitum during weighing. Clinical findings noted immediately prior to death were pallor, lethargy and respiratory distress. Post mortem examination indicated this death was due to an intubation error, probably on Day 11 post coitum and not, therefore, related to treatment.
- 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:
- no effects observed
- Description (incidence and severity):
- Liver weight, as assessed at Day 20 of pregnancy (5 days after the end of the dosing period), showed no notable or significant (P>0.05) intergroup differences.
- Gross pathological findings:
- no effects observed
Maternal developmental toxicity
- Pre- and post-implantation loss:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There was one notable litter with a single viable implantation. Preimplantation loss, which is considered to occur prior to the start of treatment, was very high for this litter and influenced other values, especially size and weight of the litter.
- Total litter losses by resorption:
- no effects observed
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Remarks on result:
- other: Highest dose tested
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At 100 mg/kg/day (the low dosage), the 6 malformed foetuses came from one litter. Findings in these foetuses included translucent or mottled white appearance to skin, brachygnathia, cleft palate, mal rotated hindlimbs, apparent ring of constriction around lower thorax and symphalangy, oligodactyly or syndactyly. Microscopic examination of abdominal skin from one of these foetuses with mottled appearance, revealed marked dermal oedema with absent hair follicles/adnexa. In view of the absence of similar effects at this or higher dosages and considering this event as an isolated cluster of foetuses in a single litter showing the same syndrome of defects, no association with treatment was indicated.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At 1000 mg/kg/day, there was a slightly higher number of foetuses with extra (14) ribs but differences did not attain statistical significance, were well inside the historical control range and were considered not to be treatment-related.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: Highest dose tested
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- NOEL (Rat, maternal and developmental toxicity): 1000 mg/kg/day (highest dose tested)
- Executive summary:
This study was conducted to assess the effect of the test substance on pregnancy of the rat according to the guidelines OECD 414 and EPA OPP 83-3. Dosages of 0 (Control), 100, 300 or 1000 mg/kg/day were administered by gavage to groups of 30 time-mated CD rats from Day 6 to 15 of pregnancy, inclusive. The animals were killed on Day 20 of pregnancy and in utero development was assessed by determination of litter values and subsequent examination of foetuses for visceral or skeletal abnormalities.
No effects of treatment on maternal clinical signs, bodyweight gain, food intake, liver weight or macroscopic abnormalities at autopsy were observed.
No effects of treatment on in utero development were observed. Litter size, pre- and post-implantation losses, litter and mean foetal weight, sex ratio and the distribution of foetuses with abnormalities were considered unaffected by treatment.
Treatment of parent females with the test substance at dosages up to 1000 mg/kg/day was determined as being without adverse effect on the mother or developing conceptus in this study.
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