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EC number: 201-004-7 | CAS number: 77-09-8
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 28 April 1987 - 29 July 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 996
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Remarks:
- Food and Drug Administration Good Laboratory Practice Regulations (21 CFR, Part 58)
- Limit test:
- no
Test material
- Reference substance name:
- Phenolphthalein
- EC Number:
- 201-004-7
- EC Name:
- Phenolphthalein
- Cas Number:
- 77-09-8
- Molecular formula:
- C20H14O4
- IUPAC Name:
- 3,3-bis(4-hydroxyphenyl)-1,3-dihydro-2-benzofuran-1-one
- Test material form:
- solid
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: Taconic Farms (Germantown, NY)
- Age at study initiation: 6 weeks
- Weight at study initiation: 132 g (males) and 109 g (females)
- Housing: Polycarbonate suspended cages (Lab Products, Inc., Rochelle Park, NJ), changed twice per week
- Diet: NIH-07 open formula meal diet (Zeigler Brothers, Inc., Gardners, PA), available ad libitum, changed weekly
- Water: Tap water (Bethesda municipal supply) via automatic watering system (Edstrom Industries, Inc., Waterford, WI), available ad libitum, changed every 2 weeks
- Acclimation period: 12 to 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 50-67
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet: The dose formulations for all studies were prepared weekly by mixing test item with feed
- Mixing appropriate amounts with feed: A test item premix was prepared by hand and was then blended with feed in a Patterson-Kelly twin-shell blender for 15 minutes using an intensifier bar for the initial 5 minutes.
- Storage temperature of food: Formulations were stored in double plastic bags at temperatures at or below -20° C for up to 3 weeks. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Stability was monitored during the 13-week using high-performance liquid chromatography. No degradation of the bulk chemical was detected. Homogeneity was confirmed and the stability of the dose formulation was confirmed for at least 3 weeks when stored protected from light at room temperature. All of the dose formulations analyzed during the were within 10% of the target concentrations.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- continuously via feed
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 ppm
- Dose / conc.:
- 3 000 ppm
- Remarks:
- equivalent to average daily doses of approximately 200 mg/kg bw/day
- Dose / conc.:
- 6 000 ppm
- Remarks:
- equivalent to average daily doses of approximately 400 mg/kg bw/day
- Dose / conc.:
- 12 000 ppm
- Remarks:
- equivalent to average daily doses of approximately 800 mg/kg bw/day
- Dose / conc.:
- 25 000 ppm
- Remarks:
- males: equivalent to average daily doses of approximately 1600 mg/kg bw/day
females: equivalent to average daily doses of approximately 1700 mg/kg bw/day
- Dose / conc.:
- 50 000 ppm
- Remarks:
- males: equivalent to average daily doses of approximately 3500 mg/kg bw/day
females: equivalent to average daily doses of approximately 3600 mg/kg bw/day
- No. of animals per sex per dose:
- 10 males and 9 or 10 females
- Control animals:
- yes, plain diet
- Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: animals were weighed initially, weekly, and at the end of the studies
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
Feed consumption was recorded weekly by cage.
WATER CONSUMPTION AND COMPOUND INTAKE: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Blood was collected from the retroorbital sinus of rats in the clinical pathology groups on days 5 and 21 and of core study rats at the end of the study for hematology and clinical chemistry.
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: all
- Parameters checked: hematocrit, hemoglobin, erythrocyte and reticulocyte counts, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, platelet count, and total leukocyte counts and differentials. Clinical chemistry: urea nitrogen, creatinine, total protein, albumin, alanine aminotransferase, alkaline phosphatase, creatine kinase, sorbitol dehydrogenase, and bile acids.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood was collected from the retroorbital sinus of rats in the clinical pathology groups on days 5 and 21 and of core study rats at the end of the study for hematology and clinical chemistry.
- Animals fasted: Not specified
- How many animals: all
- Parameters checked: urea nitrogen, creatinine, total protein, albumin, alanine aminotransferase, alkaline phosphatase, creatine kinase, sorbitol dehydrogenase, and bile acids.
URINALYSIS: Yes
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Necropsy was performed on all core study rats . Organs weighed were brain, heart, right kidney, liver, lung, right testis, and thymus.
HISTOPATHOLOGY: Yes
Complete histopathology was performed on 0 and 50,000 ppm rats . In addition to gross lesions and tissue masses, the tissues examined included: adrenal gland, brain, clitoral gland (rats), esophagus, femur (including marrow), heart, gallbladder (mice), large intestine (cecum, colon, and rectum), small intestine (duodenum, jejunum, and ileum), kidney, liver, lungs (and mainstem bronchi), lymph nodes (mandibular and mesenteric), mammary gland, nose, ovaries, pancreas, parathyroid gland, pituitary gland, preputial gland (rats), prostate gland, salivary gland, skin, spleen, stomach (including forestomach and glandular stomach), testes (with epididymis and seminal vesicle), thymus, thyroid gland, trachea, urinary bladder, and uterus. In rats, the liver (females), lung (males), and ovaries were examined to a no effect level. In mice, the bone marrow and spleen (males) were examined to a no effect level. - Other examinations:
- At the end of the study, sperm samples were collected from male rats (core study) in the 0, 12,000, 25,000, and 50,000 ppm groups for sperm morphology evaluations. The parameters evaluated included sperm density, morphology, and motility. The right cauda, right epididymis, and right testis were weighed. Vaginal fluid samples were collected for up to 7 consecutive days prior to the end of the studies from female rats (core study) in the 0, 12,000, 25,000, and 50,000 ppm groups. The parameters evaluated were relative frequency of estrous stages and estrous cycle length.
- Statistics:
- Williams' or Dunnett's test
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Description (incidence):
- All rats survived to the end of the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The final mean body weight of the 50,000 ppm females and the body weight gains of the 25,000 and 50,000 ppm females were significantly lower than those of the controls. The final mean body weights and body weight gains of all other exposed groups were similar to those of the controls.
- Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Feed consumption by exposed groups was similar to that by the controls. Dietary levels of 3,000, 6,000, 12,000, 25,000, or 50,000 ppm test item resulted in average daily doses of approximately 200, 400, 800, 1,600, or 3,500 mg test item/kg body weight to males and 200, 400, 800, 1,700, or 3,600 mg/kg to females.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The few differences in the hematology parameters were sporadic and were not considered to be chemical related.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The few differences in the clinical chemistry parameters were sporadic and were not considered to be chemical related.
- Urinalysis findings:
- no effects observed
- 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):
- The absolute and relative liver weights of 25,000 and 50,000 ppm males and the relative liver weights of 12,000 ppm males and of 25,000 and 50,000 ppm females were significantly greater than those of the controls.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No chemical-related gross lesions were observed.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No chemical-related microscopic lesions were observed.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The percentage of motile sperm in the 12,000 ppm males was significantly greater than that in the controls, but no other significant differences in sperm morphology or vaginal cytology were observed between exposed and control groups.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 6 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- organ weights and organ / body weight ratios
- Remarks on result:
- other: Corresponding to 400 mg/kg bw/d.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 12 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- organ weights and organ / body weight ratios
- Remarks on result:
- other: Corresponding to 800 mg/kg bw/d.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Based on the results of this study, the NOAEL was 12000 ppm (800 mg/kg bw/day) for males and females.
- Executive summary:
A study similar to OECD TG 408 was performed to assess the cumulative toxicity of the test item when administered daily to rats in feed for a period of 13 weeks.
Groups of 10 male and 9 or 10 female F344/N rats were given 0, 3000, 6000, 12000, 25000, or 50000 ppm test item (equivalent to average daily doses of approximately 200, 400, 800, 1600, or 3500 mg test item/kg body weight to males and 200, 400, 800, 1700, or 3600 mg/kg to females) in feed for 13 weeks. Additional groups of 10 male and 10 female rats designated for clinical pathology evaluations were also given 0, 3000, 6000, 12000, 25000, or 50000 ppm test item in feed until day 21.
All core study rats survived to the end of the study. The final mean body weight of the 50000 ppm females and the mean body weight gains of the 25000 and 50000 ppm females were significantly lower than those of the controls. The final mean body weights and mean body weight gains of all other exposed groups were similar to those of the controls. There was no cathartic action or any other clinical finding attributed to exposure to the test item. The few differences in the haematology and clinical chemistry parameters were sporadic and were not considered being chemical related. The percentage of motile sperm in the 12000 ppm males was significantly greater than that in the controls, but no other significant differences in sperm morphology or vaginal cytology between exposed and control groups were observed. Absolute and relative liver weights of 25000 and 50000 ppm males were significantly greater than those of the controls. No chemical-related gross or microscopic lesions were observed.
Based on the results of this study, the NOAEL was 12000 ppm (800 mg/kg bw/day) for males and females.
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