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EC number: 242-604-9 | CAS number: 18824-74-3
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- the study does not need to be conducted because (i) the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), (ii) it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and (iii) there is no or no significant human exposure
- Justification for type of information:
- No effects were seen in a teratogenicity study
In 90 sub-chronic tests in mice and rats, extensive examiniations on sperm morphology and vaginal cytotoxicity were performed, together with full pathology examinations of the sexual organs. There were no adverse effects
Further animal testing is not considered to be justified.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 10 days dosing between gestation days 6 and 15
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data review as part of the US National Toxicity Program (NTP) and considered reliable.
Although testing performed on the acid form (the anhydride quickly hydrates to the acid on ingestion), the data is considered reliable with respect to simple salts such as potassium salt.
It is concluded that further animal testing cannot be justified - Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- Treatment during day 6 - 15 by oral gavage at doses from 30 - 10 000 mg/kg
- GLP compliance:
- not specified
- Remarks:
- Study performed 1978
- Limit test:
- no
- Specific details on test material used for the study:
- Although testing performed on the acid form (the anhydride quickly hydrates to the acid on ingestion), the data is considered reliable with respect to simple salts such as potassium salt.
- Species:
- rat
- Strain:
- CD-1
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Not described as study comenced on Day 6 of gestation
- Duration of treatment / exposure:
- From Day 6 - 15 (10 treatment days)
- Frequency of treatment:
- Daily
- Dose / conc.:
- 30 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 3 000 mg/kg bw/day
- Dose / conc.:
- 10 000 mg/kg bw/day
- No. of animals per sex per dose:
- Five females per treatment level
- Control animals:
- not specified
- Maternal examinations:
- Yes
- Ovaries and uterine content:
- Yes
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Death in four animals at 10000 mg/kg and greatly reduced bodyweight gain with anogenital staining
Parental NOAEL considered to be 3000 mg/kg/day - Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Death in four animals at 10000 mg/kg
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Reduced body weight in surviving animals at 10 000 mg/kg
- 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:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- Subdued
- 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:
- not specified
- 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:
- not specified
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Details on maternal toxic effects:
- NOEAL 3000 mg/kg/day
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 3 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- mortality
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Noting that maternal mortality was not taken into account
- Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- Noting that maternal mortality was not taken into account
- 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:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- No changes observed to the number of viable or non-viable foeti were observed. There were no compound related effects to resorptions, implantations or corpus lutea
- Dose descriptor:
- NOAEL
- Effect level:
- > 3 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Highest treatment level without significant maternal toxicity
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- In common with this class of substance, thre was no reported teratogenic effects up to the maximum tolerated maternal treatment level.
- Executive summary:
Although testing performed on the acid form (the anhydride quickly hydrates to the acid on ingestion), the data is considered reliable with respect to simple salts such as potassium salt.
It is noted that treatment levels were far in excess of those permitted in modern studies in Europe and that in view of the parental toxicity reported, these high treatment levels were inappropriate.
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 90 days
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Although testing was performed on the chloro derivative and not bromo, the use of this for read-across has been justified in other REACH dossiers on the basis that the chloro derivative will be more biologically active. The justification is driven by the need to avoid unecessary animal testing.
The anhydride will quickly hydrolyse to the acid form once ingested and will behave in the same way as salts that will dissociate under biological conditions.
The source data is from peer-reviewed US National Toxicity Program research. - Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Dosed for 5 days a week
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 94 mg/kg bw/day (nominal)
- Dose / conc.:
- 187 mg/kg bw/day (nominal)
- Dose / conc.:
- 375 mg/kg bw/day (nominal)
- Dose / conc.:
- 750 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 500 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10 males and 10 females
- Control animals:
- yes, concurrent vehicle
- Observations and examinations performed and frequency:
- Daily clinical observations
Weighed weekly - Sacrifice and pathology:
- Necropsies on all animals
- Other examinations:
- Clinical pathology performed in the 94, 375 and 1500 mg/kg groups on days 6, 20, and at the end of the study.
Hematology performed in all animals at end of study. - Clinical signs:
- no effects observed
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One female died, as a result of a dosing accident.
- Body weight and weight changes:
- no effects observed
- 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 examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- 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
- Description (incidence and severity):
- Sperm morphology evaluations were performed from the 0, 94, 375, and 750 mg/kg dose groups.
Vaginal cytology evaluations were performed from the 0, 94, 375, and 1500 mg/kg dose groups
For the 7 days prior to sacrifice, the vaginal vaults of the females of each species and dose group were lavaged, and the aspirated lavage fluid and cells were stained with Toluidine Blue. Relative numbers of leukocytes, nucleated epithelial cells, and large squamous epithelial cells were determined and were used to ascertain estrous cycle stage (i.e., diestrus, proestrus, estrus, or metestrus).
Sperm morphology was evaluated at necropsy in the following manner. The right epididymis was isolated and weighed. The tail of the epididymis (cauda epididymis) was then removed from the epididymal body (corpus epididymis) and weighed. Test yolk (rats) or Tyrode's buffer (mice) was applied to slides, and a small incision was made at the distal border of the epididymal tail. The sperm effluxing from the incision were dispersed in the buffer on the slides and the numbers of motile and nonmotile spermatozoa were counted for 5 fields per slide.
Following completion of sperm motility estimates, each right cauda epididymis was placed in buffered 0.9% saline solution. Cauda were gently minced, and the tissue was incubated in the saline solution and then heat fixed at 65°C. Sperm density was then determined microscopically with the aid of a hemacytometer. - Dose descriptor:
- NOAEL
- Effect level:
- ca. 1 500 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 375 mg/kg bw/day (nominal)
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Conclusions:
- The toxicity to mice appears to be significantly lower than to the rat
Although the work was performed on the tetrachloro derivative instead of tetrabromo, the effects observed would not have been due to the presence of chlorine ions and can be attributed to the phthalic acid. The anhydride use in the test would quickly form as the acid on ingestion.
The substance is considered a valid read-across surrogate as the potassium salt will dissociate and behave in the same was as the acid form when exposed to biological media.
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 90 days
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Although testing was performed on the chloro derivative and not bromo, the use of this for read-across has been justified in other REACH dossiers on the basis that the chloro derivative will be more biologically active. The justification is driven by the need to avoid unecessary animal testing.
The anhydride will quickly hydrolyse to the acid form once ingested and will behave in the same way as salts that will dissociate under biological conditions.
The source data is from peer-reviewed US National Toxicity Program research. - Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344/DuCrj
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Six weeks old at start of study
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Dosed for 5 days a week
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 94 mg/kg bw/day (nominal)
- Dose / conc.:
- 187 mg/kg bw/day (nominal)
- Dose / conc.:
- 375 mg/kg bw/day (nominal)
- Dose / conc.:
- 750 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 500 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10 males and 10 females
- Control animals:
- yes, concurrent vehicle
- Observations and examinations performed and frequency:
- Daily clinical observations
Weighed weekly - Sacrifice and pathology:
- Necropsies on all animals
- Other examinations:
- Clinical pathology performed in rats in the 94, 375 and 1500 mg/kg groups on days 6, 20, and at the end of the study.
Hematology performed in all animals at end of study. - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- There were no compound-related clinical findings of toxicity in male rats, other than death.
Urine staining in most females in the 750 and 1500 mg/kg groups and diarrhea in all females in the 1500 mg/kg group were attributed to treatment - Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Five male rats dosed at 1500 mg/kg died during wks 5-8. A further two males died; one as a result of a dosing accident and one from unknown causes. These were not considerd treatment related
Two female rats died, one each dosed at 750 and 1500 mg/kg during wks 6 - 10 considered treatment related, One further female died as a result of a dosing accident. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean final body weights and weight gains of male rats in the 375, 750 and 1500 mg/kg groups and female rats in all dose groups were less than those of controls
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- All groups showed reduced food intake
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Absolute and relative kidney weights increase. Dose-dependent in female rats.
In males increased relative kidney weights from 187 mg/kg and above. - Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- In male rats, renal tubule degnerative changes at the higher dose levels and tubule dilation at lower dose levels. Necrosis of the tubule epithelium was seen in the nmajority of male and female rats in the 1500 mg/kg/day group
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- Sperm morphology evaluations were performed from the 0, 94, 375, and 750 mg/kg dose groups.
Vaginal cytology evaluations were performed from the 0, 94, 375, and 1500 mg/kg dose groups
For the 7 days prior to sacrifice, the vaginal vaults of the females of each species and dose group were lavaged, and the aspirated lavage fluid and cells were stained with Toluidine Blue. Relative numbers of leukocytes, nucleated epithelial cells, and large squamous epithelial cells were determined and were used to ascertain estrous cycle stage (i.e., diestrus, proestrus, estrus, or metestrus).
Sperm morphology was evaluated at necropsy in the following manner. The right epididymis was isolated and weighed. The tail of the epididymis (cauda epididymis) was then removed from the epididymal body (corpus epididymis) and weighed. Test yolk (rats) or Tyrode's buffer (mice) was applied to slides, and a small incision was made at the distal border of the epididymal tail. The sperm effluxing from the incision were dispersed in the buffer on the slides and the numbers of motile and nonmotile spermatozoa were counted for 5 fields per slide.
Following completion of sperm motility estimates, each right cauda epididymis was placed in buffered 0.9% saline solution. Cauda were gently minced, and the tissue was incubated in the saline solution and then heat fixed at 65°C. Sperm density was then determined microscopically with the aid of a hemacytometer. - Dose descriptor:
- LOAEL
- Effect level:
- ca. 187 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 375 mg/kg bw/day (nominal)
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Conclusions:
- Although the work was performed on the tetrachloro derivative instead of tetrabromo, the effects observed would not have been due to the presence of chlorine ions and can be attributed to the phthalic acid. The anhydride use in the test would quickly form as the acid on ingestion.
The substance is considered a valid read-across surrogate as the potassium salt will dissociate and behave in the same was as the acid form when exposed to biological media.
Data source
Materials and methods
Results and discussion
Applicant's summary and conclusion
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.