Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 616-436-5 | CAS number: 77098-07-8
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Tetrabromophthalic anhydride [CASRN 632-79-1] Review of the toxicological literature
- Author:
- Tice
- Year:
- 1 999
- Bibliographic source:
- http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/Tetrabromophthalic.pdf, pp. 1-15
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Tetrabromophthalic anhydride
- EC Number:
- 211-185-4
- EC Name:
- Tetrabromophthalic anhydride
- Cas Number:
- 632-79-1
- Molecular formula:
- C8Br4O3
- IUPAC Name:
- 4,5,6,7-tetrabromo-2-benzofuran-1,3-dione
- Details on test material:
- tetrabromophthalic anhydride
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River
- Age at study initiation: 12 weeks
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- see below
- Duration of treatment / exposure:
- days 6-15 of gestation
- Frequency of treatment:
- once/day
- Duration of test:
- just prior to parturition
Doses / concentrationsopen allclose all
- Dose / conc.:
- 30 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Dose / conc.:
- 3 000 mg/kg bw/day (nominal)
- Dose / conc.:
- 10 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5 f/dose
- Control animals:
- yes
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 15 - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- 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: - Fetal examinations:
- - External examinations: Yes:
- Soft tissue examinations: presumably Yes:
- Skeletal examinations: presumably Yes:
- Head examinations: presumably Yes: - Statistics:
- no data
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 10000 mg/kg bw: 4/5 animals died by gestation day 14. The deaths were linked to treatment. After 3rd day, staining of the anogenital area and red nasal and/or oral discharge were observed. The surviving rat also showed severely reduced body weight gains throughout the experiment
No effects observed at in the 30 to 3000 mg/kg bw dose groups. - Mortality:
- mortality observed, treatment-related
- Description (incidence):
- 10000 mg/kg bw: 4/5 animals died by gestation day 14. The deaths were linked to treatment.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 10000 mg/kg b dose group: The surviving rat also showed severely reduced body weight gains throughout the experiment
No effects on body weight and body weight gain in the other dose groups. - Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- no effects observed
- Details on results:
- 30-3000 mg/kg/day dose: No mortality occurred. No compound-related changes in appearance, behavior, and the number of viable or nonviable fetuses, resorptions, implantations, or corpora lutea observed
10,000 mg/kg/day dose: 4/5 animals died by gestation day 14. The deaths were linked to treatment. After 3rd day, staining of the anogenital area and red nasal and/or oral discharge were observed. The surviving rat also showed severely reduced body weight gains throughout the experiment.
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- 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 - Changes in number of pregnant:
- no effects observed
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- Only observed in the highest dose group that was obviously far above the MTD.
10,000 mg/kg/day dose: 4/5 animals died by gestation day 14. The deaths were linked to treatment. After 3rd day, staining of the anogenital area and red nasal and/or oral discharge were observed. The surviving rat also showed severely reduced body weight gains throughout the experiment.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Remarks:
- 3000 mg/kg
- Effect level:
- > 3 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - 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
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- >= 3 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: no effects observed even at maternally toxic dose levels
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Not a developmental toxicant.
- Executive summary:
When administered daily to pregnant rats on days 6-15 of gestation at dose levels ranging from 30 to 10,000 mg/kg (0.065-21.565 mmol/kg), no compound-related effects were seen in the number of viable or nonviable fetuses, resorptions, implantations, or corpora lutea at 3000 mg/kg or less. The deaths of 4 of 5 animals at the highest dose, however, were linked to treatment. The available international guidelines for conducting developmental toxicity studies recommend a limit dose of 1000 mg/kg.,The no-observed effect level of 3000 mg/kg in the developmental study supports that tetrabromophthalic anhydride is not a developmental toxicant.
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.
