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Diss Factsheets
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EC number: 500-109-8 | CAS number: 43011-20-7
- 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: oral
Administrative data
- Endpoint:
- chronic toxicity: oral
- Remarks:
- combined repeated dose and carcinogenicity
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study but predates OECD guidelines and GLP
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 979
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- Deviations:
- yes
- Remarks:
- precedes establishment of guideline
- GLP compliance:
- no
- Remarks:
- precedes establishment of GLP
Test material
- Reference substance name:
- Phthalic anhydride
- EC Number:
- 201-607-5
- EC Name:
- Phthalic anhydride
- Cas Number:
- 85-44-9
- IUPAC Name:
- 2-benzofuran-1,3-dione
- Test material form:
- other: granular solid
- Details on test material:
- White granular solid, obtained from Koppers Co. Purity 98.8% with one impurity, via HPLC. Melting point = 131 degrees C.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: NCI Frederick Cancer Research Center farm, Frederick, MD.
- Age at study initiation: 6 weeks
- Weight at study initiation:
- Fasting period before study: no
- Housing: Housed 4/cage in polycarbonate cages, suspended from aluminum racks and covered by nonwoven polyester0fiber 12 mm thick filter paper (Hoeltge, Inc., Cincinnati, OH). The bedding was Absorb-dri (R) hardwood chips (Northeastern Products, Inc, Warrensburg, NY). Cages were sanited twice weekly in a tunnel-type cagewasher using detergents Clout (R), Pharmacal Research Laboratories, Greenwich, CT or Oxford d'Chlor (Oxford Chemicals, Atlanta, GA).
- Diet (e.g. ad libitum): presterilized Wayne Sterilizable Lab meal, ad libitum. Suspended in steel hoppers and replendished three times weekly. Hoppers and sippers were sanitized twice monthlyusing Calgen Commercial Division detergen (St. Louis, MO)
- Water (e.g. ad libitum): acidified to pH 2.5, ad libitum from glass bottles, via sipper tubes through the tops of the cages.
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24
- Humidity (%): 45-55
- Air changes (per hr): 15. Fresh air was filtered prior to delivery and not recirculated. Air pressure was maintained negative to a clean hallway and positive to a return hallway.
- Photoperiod (hrs dark / hrs light): 12/12, Fluorescent light.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis by the Frederick Cancer Research Center indicated that when phthalic anhydride was mixed with Lab Meal at a concentration of 15,000 ppm and stored at room temperature for 2 weeks, the loss was 2.59% (372 ppm) per day.
- Duration of treatment / exposure:
- 8 weeks (7 weeks of adminstration of test chemical and 1 week of further observation)
- Frequency of treatment:
- daily in feed
Doses / concentrations
- Remarks:
- Doses / Concentrations:
6200, 12500, 25000 and 50000 ppm
Basis:
nominal in diet
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, plain diet
- Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: no data
BODY WEIGHT: Yes
- Time schedule for examinations: twice weekly
- Sacrifice and pathology:
- Animals were euthanized using CO2.
- Other examinations:
- Pathology evaluation consisted of gross and microscopic examination of major tissues, major organs and all gross lesions.
- Statistics:
- The maximally tolerated dose was determined by least squares regressions of mean body weights vs days on study (49). Probits of the percent weights at day 49 relative to weights in corresponding controls were plotted against the log of the doses, and least squares regressions were fitted to the data. The dose associated with a 10% depression in body weight was identified.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The MTD was set at 15000 ppm, based on a 10% weight depression at higher doses.
- 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:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- Hepatic centrilobular cytoplasmic vacuolation in male rats
- Details on results:
- Mean body weights of males were lower than those of controls from weeks 1-8 at 25000 ppm and higher. There were no effects of phthalic anhydride on the survival of rats for 8 weeks. In males at 25000 ppm, there were trace amounts of hepatic centrilobular cytoplasmic vacuolation; however, this was not seen in animals dosed at 50000 ppm. No other adverse effects were noted. The MTD was less than 25000 ppm. The doses for the chronic bioassay were set at 7500 ppm and 15000 ppm.
Effect levels
- Dose descriptor:
- LOAEL
- Effect level:
- 25 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: The lowest dose at which histopathologic findings were observed in male/females at 25000 ppm.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- An 8 week repeated dose toxicity assay was undertaken in F344 rats with phthalic anhydride in the feed, at doses of 6200, 12500, 25000 and 50000 ppm. The test material was administered for 7 weeks with a 1 week recovery period. The MTD was less than 25000 ppm. In males at 25000 ppm, hepatic centrilobular cytoplasmic vacuolation was observed, but this was not dose related. The doses for the chronic bioassay were set at 7500 ppm and 15000 ppm. This study is informative for evaluation of the toxicity of members of the selected cyclic acid anhydride category.
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