Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.
Diss Factsheets
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: 239-784-6 | CAS number: 15687-27-1
- 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: oral
Administrative data
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- February 1980 to September 1981
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 982
- Report date:
- 1982
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 981
- Report date:
- 1981
Materials and methods
- Principles of method if other than guideline:
- The study was carried out according to HRC Standard Protocol (documentation of the protocol attached to the report).
In a repeated dose toxicity study, groups of male and female baboons (Papio hamadryas) were exposed to the test material in doses of 0, 16, 40 and 100 mg/kg bw for 1 year. The test substance was administered via capsules twice per day. The control group received a placebo. Cage side observations, detailed clinical observations, food and water consumption was monitored daily. Body weight was determined weekly. In addition, the following observations and examinations were evaluated: ophthalmoscopic examination, haematology, clinical chemistry, urinalysis, faecal blood loss and the serum blood levels of the test substance were determined. - GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Ibuprofen
- EC Number:
- 239-784-6
- EC Name:
- Ibuprofen
- Cas Number:
- 15687-27-1
- Molecular formula:
- C13H18O2
- IUPAC Name:
- 2-(4-isobutylphenyl)propanoic acid
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Ibuprofen B.P.
- Analytical purity: 99.8%, loss on drying: 0.05%
- Impurities (identity and concentrations): sulfated ash (0.02%), nickel (< 5 ppm), lead (< 5 ppm), heavy metals (< 10 ppm), TLC impurities (< 1%) GLC impurities (0.22%)
- Purity test date: 1981-03-12
- Lot/batch No.: CMG 103772
- Stability under test conditions: confirmed
- Storage condition of test material: at room temperature, protected from light
Test animals
- Species:
- monkey
- Strain:
- other: baboon (Papio hamadryas)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Shamrock farms Ltd., Henfield Sussex, UK (wild-caught animals)
- Age at study initiation: 2 - 3 years
- Weight at study initiation: 2.5 - 4.0 kg
- Fasting period before study: no
- Housing: individually
- Diet: Primate Mazuri (B.P. Nutrition, Witham, UK), 350 g/animal/day
- Water: ad libitum, except when specially withheld during urine collection
- Acclimation period: 8 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 22°C
- Humidity (%): ca. 50 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): no data, normal daylight was available to the animals and artificial lightning was used on workdays
IN-LIFE DATES: From: 1980-01-03 (delivery to testing facility), 1980-02-05 (start of dosing) continuing for 52 weeks To: not defined
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- The test substance was incorporated in gelatin capsules, size 0, obtained from Parke, Davis&Co. Limited, Hounslow, U.K.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- no details given
- Duration of treatment / exposure:
- 1 year
- Frequency of treatment:
- Twice a day (approximately 10:00 and 16:00 h each day).
Doses / concentrationsopen allclose all
- Dose / conc.:
- 16 mg/kg bw/day (actual dose received)
- Remarks:
- 8 mg/kg bw/application
- Dose / conc.:
- 40 mg/kg bw/day (actual dose received)
- Remarks:
- 20 mg/kg bw/application
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Remarks:
- 50 mg/kg bw/application
- No. of animals per sex per dose:
- 5 males and 5 females per group
- Control animals:
- yes
- Details on study design:
- - Post-exposure recovery period in satellite groups: none
- Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: on working days
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: on working days
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION: Yes, twice daily
WATER CONSUMPTION: Yes
- Time schedule for examinations: for 4 week during pretreatment, and again during weeks 1-4, 9-12, 22-25, 35-38 and 46-49 of the dosing period, measurement on weekdays only
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: prior to dosing period, after 6, 13, 26, 39 and 50 weeks of dosing
- Dose groups that were examined: all animals
LABORATORY INVESTIGATIONS
(1) HAEMATOLOGY: Yes
- Time schedule for collection of blood: on one occasion pre-dosing and again after 6, 13, 26, 39 and 50 weeks of dosing
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes, 16 h prior to collection of blood
- How many animals: all animals
- Parameters examined: erythrocyte sedimentation rate (ESR), packed cell volume (PCV), hemoglobin (Hb), red blood cell count (RBC), mean corpuscular cell volume (MCHC), mean cell volume (MCV), reticulocyte count, total white cell count (WBC), differential counts of neutrophils/lymphocytes/eosinophils/basophils/monocytes, platelet count, prothombin index (PTI) activated partial thromboplastin time (APTT), examination of blood film for morphology
(2) CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on one occasion pre-dosing and again after 6, 13, 26, 39 and 50 weeks of dosing
- Animals fasted: Yes, 16 h prior to collection of blood
- How many animals: all animals
- Parameters examined: serum urea, plasma glucose, total serum proteins, serum albumin, serum alkaline phosphates (SAP), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), serum leucine arylamidase (LAP), serum bilirubin, serum sodium (Na), serum potassium (K), serum inorganic phosphorus (P), serum chloride (Cl), serum calcium (Ca), serum creatinine, serum cholesterol
(3) URINALYSIS: Yes
- Time schedule for collection of urine: on one occasion pre-dosing and again after 6, 13, 26, 39 and 50 weeks of dosing; 16-hour collection period
- Metabolism cages used for collection of urine: No
- Animals fasted: Water was withheld from the housing cages 5 h before start of sampling
- Parameters examined: specific gravity, volume, pH, protein, reducing substances, glucose, ketones, bile pigments, urobilinogen, hemoglobin
microscopical examination for epithelial cells, polymorphonuclear and mononuclear leukocytes, erythrocytes, organisms, casts, abnormal constituents
(4) TEST ON OCCULT BLOOD
Faeces were collected and tested for the presence of occult blood on three consecutive days immediately prior to the commencement of dosing and again during week 1 and after 6, 13, 26, 39 and 50 weeks of dosing.
(5) BONE MARROW EXAMINATION
Samples of bone marrow were obtained by aspiration from the sternum immediately prior to death.
(6) SERUM LEVELS OF IBUPROFEN
Blood samples were collected from 2 males and 2 females from each dose group immediately before the 2nd daily dose on day 1, and on one day during weeks 4, 16, and 32 and terminally.
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- On completion of 52 weeks' dosing all animals were killed. Each animal was immobilised with phencyclidinehydrochloride given by the intramuscular route, and then received an intravenous injection of pentobarbitone sodium. When deeply unconscious the animal was rapidly exsanguinated by incision of the carotid blood vessels.
GROSS PATHOLOGY: Yes
- full macroscopic examination of tissues
- determination of organ weights for brain, pituitary, thyroids, spleen, heart, liver, kidneys, lungs, adrenals, ovaries, testes including epididymis, thymus, pancreas, prostate including seminal vesicles
HISTOPATHOLOGY: Yes
Aorta (arch and abdominal), trachea, heart (auricle and ventricle) lungs, thymus, lymph nodes (cervical and mesenteric), liver, gall bladder, spleen, pancreas, kidneys, urinary bladder, uterus, ovaries, testes and epididymis, prostate and seminal vesicles, thyroids, adrenals, sub-mandibular salivary gland, esophagus, stomach (body and antrum), duodenum, jejunum, ileum, cecum, colon, skin, skeletal muscle (biceps femoris), mammary gland, tongue, eyes and optic nerves, brain (cerebral cortex, thalamic nuclei, mid-brain, medulla, cerebellum), pituitary, sciatic nerve, femoral bone sternum - Other examinations:
- An interim examination (no sacrifices) was conducted after six months of treatment.
- Statistics:
- Whenever it was necessary to determine whether significant differences existed between mean values relating to test and control animals, analysis of variance was carried out. If heterogeneity of variance was present at the 1% level of significance, the data were transformed using logarithmic or other transformation in order to stabilise the variance. If transformation of the data was not successful in stabilising the variance, non-parametric methods based on Kruskal-Wallis mean ranks were used. The group mean values were compared using the method of least significant differences (LSD) in conjunction with Williams' test for contrasting increase in dosage levels of treatment groups with control. Significance testing was carried out at the 5% and 1% levels only. The Kruskal-Wallis mean ranks were compared using a non-parametric version of this test.
The organ weights were compared using analysis of covariance and adjusted for final body weight where there was a relationship between organ weights and body weight. Where there was no relationship, analysis of variance was carried out on the unadjusted values. The group mean values (adjusted or unadjusted) were compared using the method of LSD in conjunction with Williams' test.
The results obtained from the laboratory investigations during the pre-dosing period were described by the grand mean, the standard deviation and the full range.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- The only adverse sign that could be related to the test substance was subdued behaviour in a single high dose male during study week 17. A few incidental observations (vomiting, loose feces, sore areas [self-inflicted by biting]) were considered not unusual for laboratory animals.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Apart from small losses in weight during the first week for some of the high dose animals, administration of the test substance had no effect on body weight gain.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Administration of the test substance at levels up to 100 mg/kg/day had no adverse effect on food consumption.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- Administration of the test substance at levels up to 100 mg/kg/day had no adverse effect on water consumption.
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- No abnormalities were detected during any of the examinations that could be related to administration of the test substance.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Isolated abnormal values were noted for animals receiving ibuprofen and the controls. Statistical analysis of laboratory investigation results revealed a reduction in the values for activated partial thromboplastin time (APTT) after 6 weeks for the high dose group and a reduction in the urine specific gravity after 6, 39 and 50 weeks, also for the high dose group. However, for both these parameters, the majority of individual values were within the normal ranges.
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistical analysis of laboratory investigation results revealed a reduction in the urine specific gravity after 6, 39 and 50 weeks, for the high dose group.
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Apart from the kidney weights of one animal receiving 100 mg/kg/day all individual organ weights were considered to be within normal limits. Statistical analysis revealed higher kidney weights for the animals receiving 100 mg/kg/day, which was considered to be related to dosing with the test substance.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Examination of the kidneys revealed areas of cortical pitting in 2/10 animals receiving 40 mg/kg/day and 9/10 receiving 100 mg/kg/day. There were no other macroscopic abnormalities that could be related to dosing with the test substance.
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- There was an increased incidence of renal cortical scarring in animals receiving 100 mg/kg/day compared with other groups receiving the test substance and the control group. In addition, three animals at 100 mg/kg/day showed minor focal papillary changes, characterised by focal hyalinised connective tissue with irregular folding of the papillary epithelium. These changes were considered possibly related to administration of the test substance at 100 mg/kg/day.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- no effects observed
- Description (incidence and severity):
- DETERMINAL OF OCCULT BLOOD
There was no evidence of persistent gastro-intestinal bleeding.
BONE MARROW EXAMINATION:
There were no abnormalities observed that could be related to dosing.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 40 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
- histopathology: non-neoplastic
Target system / organ toxicity
- Critical effects observed:
- no
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.