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EC number: 211-185-4 | CAS number: 632-79-1
- 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

Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- sub-chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1975
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study is old, but well reported and included the majority of endpoints typical of a guideline study.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 975
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Repeated doses of test article applied to skin of rabbits for 28 days. Various parameters were monitored/measured throughout the study. Gross necropsy and histopathology performed at scheduled sacrifice. No guideline was available at the time of the study's conduct.
- GLP compliance:
- no
- Remarks:
- performed prior to GLPs
- 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:
- tetrabromo-1,3-dihydro-2-benzofuran-1,3-dione
- Details on test material:
- FM PHT4 (micronized) was used as test article.
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 12/12 M/F rabbits were used on the study. The rabbits were housed individually in metal metabolism cages and maintained in a temperature and humidity controlled room. Purina Rabbit Chow and water were available ad libitum.
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- other: saline
- Details on exposure:
- The test article was applied dermally at 0, 50, 500 or 5000 mg/kg/d, 5 days/week for 4 weeks. Three male and three female rabbits were used at each dose level. The control rabbits were treated with saline only at a volume of 12 ml on the same regimen as treated animals.
The dorsal skin of each rabbit was shaved with electric clippers as necessary during the study. The shin of one-half of the rabbits was abraded twice a week. The compound was mixed with a small amount (maximum of 12 ml) of saline to form a paste. The was spread over the skin with a glass rod. The rabbits were held in wooden stocks during the 6 hour test article administration period after which the backs were washed with tepid tap water and the rabbits were returned to their individual cages. Individual daily doses were based upont the body weights obtained weekly. - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 6 hrs/day
- Frequency of treatment:
- 5 days/week for 4 weeks
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 50, 500, 5000 mg/kg/d
Basis:
nominal per unit body weight
- No. of animals per sex per dose:
- 3M/3F per dose.
- Control animals:
- yes, concurrent vehicle
- Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- The rabbits were observed daily for changes in general behavior and apppearance. Observations for dermal irritation were done prior to and following the 6 hr test article administration period. Individual body weights were recorded weekly. Once in the control group and on study day 14 and 26, blood and urine samples were collected from all rabbits.
- Sacrifice and pathology:
- All rabbits were sacrificed following 28 d of treatment. Selected tissues (approximately 28) in the control and 500 mg/kg/d groups were examined by histopathology (paraffin embeddded, sectioned, stained with hematoxylin and eosin). Skin, liver, kidney and bone marrow from the 50 mg/kg/d group were also examined histologically.
- Other examinations:
- Hematology: hemoglobin, hematorcrit, total RBC, total and differential WBC. Serum chemistries: glucose, BUN, SGOT, SGPT, SAP. Urinalysis: volume, pH, specific gravity, color and appearance, qualatative tests for albumin, glucose, bilirubin and occult blood. Bromine analysis: in the 50 and 500 mg/kg/d groups liver, fat, kidney, skin and blood were analyzed by neutron activation analysis.
- Statistics:
- Statistics were run on bromide levels: one way ANOVA with Dunnet's post test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- 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
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- Very slight to slight and occasionally moderate erythema was noted in control rabbits and in rabbits at the 50 mg/kg/d dose. Very slight to moderate erythema was noted for rabbits at the 500 and 5000 mg/kg/d doses. Moderate desquamation was noted for 3 of the rabbits at the 5000 mg/kg/d dose. One rabbit at the 5000 mg/kg/d dose showed marked ataxia, unable to lift head or right itself and dyspnea and was sacrificed in extremis. All of the rabbits at the 5000 mg/kg/d dose died or were sacrificed in extremis between days 10 and 26 of the study.
Body weights were similar in control, 50 and 500 mg/kg/d groups. Rabbits at the 5000 mg/kg/d dose lost weight prior to death. Organ weights among groups appeared comparable.
At day 14, 1 rabbit in the high dose group had a moderate increase in BUN. At day 26, the hematology, serum chemistry and urinalysis results in the one surviving rabbit at the high dose were: neutrophilia with lymphopenia, nucleated erythrocytes, marked increase in glucose and BUN, and albumiand glucose in the urine.
Deaths or declining condition necessitating early sacrifice of all rabbits at the high dose were considered compound-related. At necropsy, several rabbits in the high dose group had pale livers, accentuated liver lobulation and gastric irritation. These effects observed at necropsy may have been compound-related. No gross lesions were observed in the low and mid-dose groups. Microscopically, the only lesion seen in animals in the low and mid-dose groups considered compound related was a very slight hyperkeratosis of the application site in one rabbit in the mid-dose group.
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Remarks:
- mortality
- Effect level:
- 500 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Mortality in the 5000 mg/kg/d group.
- Dose descriptor:
- NOAEL
- Remarks:
- systemic toxicity
- Effect level:
- 500 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Lack of effect on body weights, organ weights, hematology, urinalysis, serum chemistries. Slight effects on skin at site of application of test article.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
After treatment for 28 days, bromine levels measured in skin (50, 500 mg/kg/d) and blood (500 mg/kg/d) were statististically significantly higher when compared to the control group. In skin, mean measured bromine levels in the control, 50 and 500 mg/kg/d groups were 39.6, 712.0 and 726.5 ppm, respectively. Similarly, mean measured bromine levels in blood were 8.7, 10.0 and 13.3 ppm. No statistical differences were observed between the control and 50 or 500 mg/kg/d groups in bromine levels measured in the liver, fat or kidney. For the purposes of statistical comparison, meausrements from male and female rabbits in each dose group were combined (n=6/group).
Applicant's summary and conclusion
- Conclusions:
- The NOEL for mortality was 500 mg/kg/d. The NOAEL for systemic toxicity was 500 mg/kg/d.
- Executive summary:
The test article was applied dermally at 0, 50, 500 or 5000 mg/kg/d, 5 days/week for 4 weeks. Three male and three female rabbits were used at each dose level. The control rabbits were treated with saline only at a volume of 12 ml on the same regimen as treated animals. The rabbits were observed daily for changes in general behavior and apppearance. Observations for dermal irritation were done prior to and following the 6 hr test article administration period. Individual body weights were recorded weekly. Once in the control group and on study day 14 and 26, blood and urine samples were collected from all rabbits. All rabbits were sacrificed following 28 d of treatment. Selected tissues (approximately 28) in the control and 500 mg/kg/d groups were examined by histopathology (paraffin embeddded, sectioned, stained with hematoxylin and eosin). Skin, liver, kidney and bone marrow from the 50 mg/kg/d group were also examined histologically. All rabbits were sacrificed following 28 d of treatment. Selected tissues (approximately 28) in the control and 500 mg/kg/d groups were examined by histopathology (paraffin embeddded, sectioned, stained with hematoxylin and eosin). Skin, liver, kidney and bone marrow from the 50 mg/kg/d group were also examined histologically.
Very slight to slight and occasionally moderate erythema was noted in control rabbits and in rabbits at the 50 mg/kg/d dose. Very slight to moderate erythema was noted for rabbits at the 500 and 5000 mg/kg/d doses. Moderate desquamation was noted for 3 of the rabbits at the 5000 mg/kg/d dose.
One rabbit at the 5000 mg/kg/d dose showed marked ataxia, unable to lift head or right itself and dyspnea and was sacrificed in extremis. All of the rabbits at the 5000 mg/kg/d dose died or were sacrificed in extremis between days 10 and 26 of the study. Body weights were similar in control, 50 and 500 mg/kg/d groups. Rabbits at the 5000 mg/kg/d dose lost weight prior to death. Organ weights among groups appeared comparable. At day 14, 1 rabbit in the high dose group had a moderate increase in BUN. At day 26, the hematology, serum chemistry and urinalysis results in the one surviving rabbit at the high dose were: neutrophilia with lymphopenia, nucleated erythrocytes, marked increase in glucose and BUN, and albumin in the urine.
Deaths or declining condition necessitating early sacrifice of all rabbits at the high dose were considered compound-related. At necropsy, several rabbits in the high dose group had pale livers, accentuated liver lobulation and gastric irritation. These effects observed at necropsy may have been compound-related. No gross lesions were observed in the low and mid-dose groups. Microscopically, the only lesion seen in animals in the low and mid-dose groups considered compound related was a very slight hyperkeratosis of the application site in one rabbit in the mid-dose group.
The NOEL for mortality was 500 mg/kg/d. The NOAEL for systemic toxicity was 500 mg/kg/d.
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