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EC number: 224-580-1 | CAS number: 4418-26-2
- 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:
- Circa 1980
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Reference
- Reference Type:
- publication
- Title:
- The effect of oral administrations of sodium dehydroacetate (DHA-NA) on pregnant mice and their fetuses
- Author:
- Shiobara S
- Year:
- 1 980
- Bibliographic source:
- Japanese Journal of Public Health Vol 27, No. 2
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- Similar to Japanese MHW Teratogenicity Study
- Deviations:
- not specified
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Sodium 1-(3,4-dihydro-6-methyl-2,4-dioxo-2H-pyran-3-ylidene)ethanolate
- EC Number:
- 224-580-1
- EC Name:
- Sodium 1-(3,4-dihydro-6-methyl-2,4-dioxo-2H-pyran-3-ylidene)ethanolate
- Cas Number:
- 4418-26-2
- Molecular formula:
- C8H7O4.Na
- IUPAC Name:
- sodium 1-(6-methyl-2,4-dioxo-2H-pyran-3(4H)-ylidene)ethanolate
Constituent 1
- Specific details on test material used for the study:
- Supplier: Taisho Technos Co. Ltd.
Test animals
- Species:
- mouse
- Strain:
- other: ICL-ICR Stated as JCL-ICR in publication mouse
- Details on test animals or test system and environmental conditions:
- The animals were reared in an animal laboratory under the following conditions: five to ten dams were housed in a single plastic cage and allowed free access to solid feed (CE-2, manufactured by CLEA Japan, Inc.) and drinking water, at a room temperature of 20 ± 1°C, and a humidity of 55 ± 5%. Animals were 8 weeks old and acclimatised for 1 to weeks before pairing.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Two females to one male, overnight mating confirmed by copulation plug.
- Duration of treatment / exposure:
- Day 6 to 15 of presumed gestation.
- Frequency of treatment:
- Daily during treatment period.
- Duration of test:
- From day 0 to day 17 of gestation.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- The experimental animals used were 8-week-old, nulliparous male and female JCL-ICR mice . After 1 to 2 weeks of preliminary rearing, two female and one male mice were cohabitated one night for the purpose of mating. If a copulatory plug was confirmed on the following morning, this was designated as gestational day (GD) 0.
Examinations
- Maternal examinations:
- Body weight of the pregnant mice recorded every day for 17 days, from GD 0 until the end of the experiment in order to examine the effects on the dams, and the clinical course of pregnancy monitored daily.
- Ovaries and uterine content:
- Autopsies carried out on the pregnant mice in the control group and DHA-Na administration groups on GD 17. During the autopsies, blood tests for maternal hemoglobin (Hb) and hematocrit (Ht), performed macroscopic examination were undertaken and organ weight measurements for several internal organs, including the liver, kidneys and spleen. Histology specimens were prepared a histopathological examination undertaken. The same examinations were undertaken on non-pregnant mice in whom the presence of a copulatory plug was not observed after mating.
- Fetal examinations:
- Uterine weight measured, intrauterine fetuses assessed as were: the number of implantations sites, the number of live fetuses, body weight of the live fetuses, the number of dead fetuses (classified the dead fetuses into early and late deaths). Systematic macroscopic examination of the live fetuses from the cephalic to caudal regions, examination of congenital malformations, focusing on exencephaly, cleft palate, failed sternebral fusion, brachyury and knotty tails. Stained skeletal specimens were examined using the Dawson method and examined to determine the state of ossification of the skeletal system, as well as the presence of anomalies or malformations, using the calvarium, vertebrae, sternebrae, and ribs.
- Statistics:
- Yes, but methods not specified. Significance at the 5% level used for data.
- Indices:
- Not calculated but data clearly presented to illustrate the in utero findings.
- Historical control data:
- None specified.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- At 200 mg/kg bw/day effects on maternal hemoglobin (Hb) and hematocrit (Ht), but no dose response relationship evident. See data table below.
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- See data table below.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- See data table below.
- Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- See data table below.
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- See data table below.
- Dead fetuses:
- effects observed, treatment-related
- Description (incidence and severity):
- See data table below.
At 200 mg/kg bw/day only. However this group had a significanlty higher number of live fetuses and implantations and therefore greater stress on the mother. The biological significance of the fetal deaths may therefore be questionable. See data table below. - Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.DescriptionIncidenceAndSeverityEffectsOnPregnancyDuration): See data table below. - Changes in number of pregnant:
- no effects observed
- Other effects:
- no effects observed
Effect levels (maternal animals)
open allclose all
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- >= 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- haematology
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: No adverse maternal or ebmryo-fetal toxicity at 100 mg/kg bw/day.
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- At 200 mg/kg bw/day only. However this group had a significanlty higher number of fetuses which may have affected this parameter, the biological significance may therefore be questionable. No clear dose response relationship was evident. See data table below.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): effects observed, treatment-related
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): At 200 mg/kg bw/day only. However this group had a significanlty higher number of fetuses which may have affected this parameter, the biological significance may therefore be questionable. No clear dose response relationship was evident. See data table below. - Reduction in number of live offspring:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The number of live fetuses at 200 mg/kg bw/day was increased as was the number of dead fetuses. This apparent ambiguity may have been as a result of the greater number of implantations, thus the greater in utero burden to the mothers may have affected in utero development in this strain of mouse. See data table below.
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- The number of fetuses with 14 ribs was higher in the treated groups, however this may be related to the number of dams with 14 ribs that were similarly higher in these groups compare to the control. Such skeletal finding may be regarded as a minor skeletal anomaly and thus a relationship to treament was cinsidered unlikely. See data table below. Compared to the control group, there was significantly delayed sternebral ossification observed in the DHA-Na administration groups. Based on the examination of metacarpal, metatarsal and coccygeal vertebral staining, overall, delayed ossification was observed in the DHA-Na 100 mg and 200 mg administration groups. Skeletal anomalies observed in the 50 mg and 100 mg groups included a number of cases with bifurcated and fused cervical vertebrae and ribs, although no significant difference was observed in comparison to the control group.
- Visceral malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- A single case with cleft palate in the 100 mg/kg bw/day administration group during the examination for congenital malformations, no anomalies were seen in the control group or any other administration groups. A relationship to treatment is considered unlikely. The authors state that cleft palate is a spontaneous malformation in this strain of mouse. See data table below.
- Other effects:
- no effects observed
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Skeletal variants: number of metacarpals
Fetal abnormalities
- Abnormalities:
- effects observed, non-treatment-related
- Localisation:
- other: skeletal variants
- Description (incidence and severity):
- see tabulated data
Overall developmental toxicity
- Developmental effects observed:
- yes
- Lowest effective dose / conc.:
- 200 mg/kg bw/day (nominal)
- Treatment related:
- yes
- Relation to maternal toxicity:
- developmental effects as a secondary non-specific consequence of maternal toxicity effects
- Dose response relationship:
- no
- Relevant for humans:
- not specified
Any other information on results incl. tables
Effect of DHA-Na on pregnant mice |
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Dose (mg/kg)
|
0 |
50 |
100 |
200 |
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Mated
|
25 |
25 |
25 |
25 |
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Pregnant (%)a
|
20 (80.0) |
18(72.0) |
21(84.0) |
20(80.0) |
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Premature delivery
|
0 |
0 |
0 |
0 |
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Maternal death
|
0 |
0 |
0 |
0 |
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Total litter loss
|
0 |
0 |
0 |
0 |
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Dams with alive fetuses (%)b |
20(100.0) |
18(100.0) |
21(100.0) |
20(100.0) |
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Numerals in parentheses indicate |
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a: percentages to the number of mated dams. |
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b: percentages to the number of pregnant dams Effect of DHA-Na on pregnant mice (continued)
(m); mean (σ); S.D.
* Significant at 5%
level in comparison with the control group
|
Applicant's summary and conclusion
- Conclusions:
- Maternal toxicity was evident at 200 mg/kg bw/day as changes in haematological parameters with increases in haemoglobin and haematocrit. Some fetal effects were noted as an increase in fetal mortality and body weight at 200 mg/kg bw/day. Increased incidences of fetal 14th (a common anomaly in this mouse strain) were closely associated with the same rib count in the dams. Some delayed sternebral ossification was observed in all the DHA-Na administration groups. Skeletal an
omalies observed in the 50 or 100 mg/kg bw/day but there was no significant difference observed in comparison to the control group. - Executive summary:
In this developmental toxicity study DHA-Na was administered daily by oral gavage to pregnant JCLICR mice from GD 6 to GD 15 at concentrations of 0, 50, 100 or 200 mg/kg bw/day. Maternal toxicity was evident at 200 mg/kg bw/day as changes in haematological parameters with increases in haemoglobin and haematocrit. Some fetal effects were noted as an increase in fetal mortality and body weight at 200 mg/kg bw/day. This may have reflected the increased number of implantations and live foetuses in this group. Increased incidences of fetal 14thwere closely associated with the same rib count in the dams. Some delayed sternebral ossification was observed in all the DHA-Na administration groups. Skeletal anomalies observed in the 50 or 100 mg/kg bw/day groups included a few cases of bifurcated and fused cervical vertebrae and ribs, however there was no significant difference observed in comparison to the control group.
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