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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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1995-01-10 to 1995-03-30
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
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:
- EPA OTS 798.4900 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Acetic acid, oxo-, sodium salt, reaction products with ethylenediamine and phenol, iron sodium salts
- EC Number:
- 283-044-5
- EC Name:
- Acetic acid, oxo-, sodium salt, reaction products with ethylenediamine and phenol, iron sodium salts
- Cas Number:
- 84539-55-9
- Molecular formula:
- non specified (UVCB substance)
- IUPAC Name:
- Acetic acid, oxo-, sodium salt, reaction products with ethylenediamine and phenol, iron sodium salts
- Test material form:
- other: microgranules
- Details on test material:
- - Test article: CGA65047 SG 100 (A-5787 A)
- Physical state: granules
- Storage condition of test material: room temperature
- Analytical purity: 100 % (UVCB)
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Sprague-Dawley derived; Tif:RAIf (SPF); hybrids of RII/1 x RII/2
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Animal Production, WST-455, CIBA-GEIGY Limited, 4332 Stein, Switzerland
- Age at mating: minimum 8 weeks
- Weight range on gestation day 0: 176.8 - 231.5 g (females)
- Diet: pelleted, certified standard diet (Nafag No. 890, tox; Nafag, Nähr- und Futtermittel AG, Gossau, Switzerland), provided ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 50 ± 20 %
- Air changes: about 16 air changes/hour
- Photoperiod: 12 hours dark / 12 hours light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5 % (w/w) aqueous solution
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS
Test substance-vehicle mixtures were prepared with a high speed homogeniser. Homogeneity of the mixtures during administration was maintained with a magnetic stirrer.
VEHICLE
A 0.5 % (w/w) aqueous solution of sodium carboxymethyl cellulose (CMC) was used
- Concentration in vehicle: 0, 0.5, 10.0 and 50.0 mg/mL mixture
- Amount of mixture: 10 mL/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples of test substance-vehicle mixtures were taken once before (samples taken from top, middle and bottom of the container) and once after dosing (sample taken from middle of the container) and analysed for content, homogeneity and stability of the test item in the vehicle.
- Details on mating procedure:
- - Impregnation procedure: cohoused
- M/F ratio per cage: 1/3
- Length of cohabitation: 3-6 hours
- The mating procedure was repeated for non-pregnant females
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- from day 6 to day 15 of gestation
- Frequency of treatment:
- 1x/day
- Duration of test:
- 21 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 5 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 24 rats
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
Dose levels were selected based on the results of a previous range finding study no. 941104 in pregnant rat:
"Virgin female albino rats, approximately two months old (Stock: Tif: RAI f (SPF), hybrids of RII/1 x RII/2) were used for this study. Four groups of eight mated females per group were treated by gavage with the test substance mixed in a 0.5% aqueous solution of sodium carboxymethylcellulose (CMC) in a volume of 10 mL/kg actual body weight, at daily doses of 0, 10, 500 and 1000 mg/kg body weight (groups 1, 2, 3, and 4, respectively), from day 6 through day 15 post coitum.
Maternal body-weight gain/weights and feed consumption were dose-dependent ly reduced in groups 3 and 4 during treatment (days 6 to 15 p.c). At cesarean section, one control animal (no. 8) and one mid dose group animal (no. 18) were not pregnant. All other dams had viable fetuses. Pre- and post-implantation losses, number of live fetuses per litter and fetal weights were not affected by treatment. There were no dead or aborted fetuses. Mean carcass weight and net body weight change from day 6 were dose dependently reduced in groups 3 and 4. At necropsy, kinked tail was observed in one control fetus.
In summary, in the present preliminary study, CGA 65047 F, A-5787 A was toxic to dams at 500 and 1000 mg/kg/day and was not toxic to embryos or fetuses at doses up to 1000 mg/kg/day. There was no indication of teratogenesis".
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS:
- Time schedule: daily (incl. mortality)
BODY WEIGHT:
- Time schedule for examinations: daily
FOOD CONSUMPTION
- Time schedule for examinations: days 6, 11, 16 and 21
POST-MORTEM EXAMINATIONS:
- Sacrifice on gestation day 21
- Organs examined: main organs of the thoracic and abdominal cavities, in particular the genitals - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination.
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: uterine content assessment (live and dead foetuses, early and late losses) - Fetal examinations:
- - External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [approximately half per litter]
- Skeletal examinations: Yes: [approximately half per litter]
- Head examinations: Yes: [all per litter] - Statistics:
- Statistical analysis of continuous data was performed using the Analysis of Variance Procedure (ANOVA) followed by Dunnett's t-test in case of a significant result in the ANOVA. Categorical data were analysed using Chi-Square test followed by Fisher's Exact test in case of a significant result in the Chi Square test. Non-parametric data were analysed during the Kruskal-Wallis non-parametric analysis of variance test followed by Mann-Whitney U-test.
- Indices:
- No indices were calculated
- Historical control data:
- Historical control data were included in the report.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related clinical signs in this study.
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- There were no treatment-related deaths in this study. One dam in the mid dose group was sacrificed moribund on day 11 p.c.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- There were no significant differences in mean maternal body weights between groups at any time during the study.
Maternal body weight gain was statistically significantly reduced in the 500 mg/kg group during the second half of the dosing period (days 11 to 16 p.c.). Body weight gain was unaffected by treatment in the 5 and 100 mg/kg groups. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- At 500 mg/kg, there was a statistically significant reduction in food consumption during the second half of the dosing period (days 11 to 16 p.c.). At 5 and 100 mg/kg, values for food consumption were similar to those of the control group throughout the study.
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- Mean carcass weight and gravid uterus weights were not affected by treatment. Net body weight gain was significantly reduced in the 500 mg/kg group.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No macroscopic findings were noted at necropsy of the dams on day 21 p.c.
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- There were no dead or aborted fetuses. The number of live fetuses per litter and fetal weights were not affected by treatment.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- Preimplantation losses and early and late postimplantation losses were comparable between groups.
- Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- Preimplantation losses were comparable between groups.
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- Preimplantation losses were comparable between groups.
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- There were no dead or aborted fetuses. The number of live fetuses per litter and fetal weights were not affected by treatment.
- Changes in number of pregnant:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Of the 24 mated animals per group, three, one and three were not pregant in the low, mid and high dose groups, respectively. Thus the number of pregnant animals per group was 24, 21, 23 and 21, respectively. One dam in the mid dose group was sacrificed moribund on day 11 p.c. At necropsy, the number of dams per group with viable fetuses was therefore 24, 21, 22, and 21, respectively.
- Details on maternal toxic effects:
- There was a reduction in mean food consumption and body weight gain during the second half of the dosing period at 500 mg/kg bw/day.
Effect levels (maternal animals)
- Dose descriptor:
- NOEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
Maternal abnormalities
- Abnormalities:
- not specified
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Mean fetal body weights were not affected by treatment.
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- Fetal sex ratios were not affected by treatment.
- External malformations:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related external fetal abnormalities.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no treatment-related skeletal malformations. Incidental malformations were seen in two control fetuses (no. 13/3: runt, and no. 5/1: umbilical hernia) and one low dose group fetus (no. 33/3: generalized edema, cleft lower jaw and cleft palate). The overall incidence of external, visceral and skeletal anomalies and variations were not affected by treatment.
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment-related findings were observed. Incidental malformations were seen in two control fetuses (no. 13/3: runt, and no. 5/1: umbilical hernia) and one low dose group fetus (no. 33/3: generalized edema, cleft lower jaw and cleft palate). The overall incidence of external, visceral and skeletal anomalies and variations were not affected by treatment.
- Details on embryotoxic / teratogenic effects:
- There was no indication for test item related embryotoxicity or teratogenic effects under the conditions of this study.
Effect levels (fetuses)
- Dose descriptor:
- NOEL
- Effect level:
- 500 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Chemical Analysis
Administration / Treatment 1:
The mean concentrations of the test item in the vehicle were 88.1 % (0.5 mg/mL) , 94.0 % (10 mg/mL) and 93.3 % (50 mg/mL) of the nominal concentrations for the low mid and high dose groups, respectively. The homogeneity varied in the range from -2 % to 4 % of the mean concentration. The test item was stable in the vehicle.
Administration / Treatment 2:
The mean concentrations of the test item in the vehicle were 94.9 % (0.5 mg/mL) , 93.9 % (10 mg/mL) and 94.1 % (50 mg/mL) of the nominal concentrations for the low mid and high dose groups, respectively. The homogeneity varied in the range from -1 % to 1 % of the mean concentration. The test item was stable in the vehicle.
Applicant's summary and conclusion
- Conclusions:
- Evidence of maternal toxicity, in terms of reduced body weight gain and reduced food consumption, was observed in the high dose group (500 mg/kg). No adverse effects on pregnancy or fetal parameters were observed. On the basis of the results obtained in this study, the no observed effect level (NOEL) was 100 mg/kg body weight/day for the dams and 500 mg/kg body weight/day for the progeny. There was no indication of teratogenic potential.
- Executive summary:
In a developmental toxicity study FeNaEDDHA was administered once daily to groups of 24 mated female Sprague-Dawley derived rats by oral gavage at dose levels of 5, 100 or 500 mg/kg bw/day (10 mL/kg bw) from day 6 through day 15 of gestation. Control group females received the vehicle, 0.5 % (w/w) CMC in distilled water, only. The nominal concentrations, homogeneity and stability of the test item in the vehicle were confirmed by chemical analysis of dose formulations. All dams were sacrificed on day 21 of the gestation period and foetuses removed for examination. In dams, there were no treatment-related clinical signs or incidences of mortality. The body weight gain was reduced at 500 mg/kg bw/day for the period of day 6 -16 of gestation, and reduced food consumption was also noted at this dose level. No adverse effects on pregnancy and no embryo-/foetotoxic effects were observed. There was no indication of teratogenic potential. On the basis of these results, the NOEL was 100 mg/kg bw/day for maternal toxicity and 500 mg/kg bw/day for developmental toxicity and teratogenicity.
The developmental toxicity study in the rat is classified as acceptabel and satisfies the requirements of test guideline OECD 414.
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