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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Review-like publication presenting studies on toxicokinetics as well as on acute toxicity, repeated dose toxicity, teratogenicity, and effects on endocrine organs in different species.
Data source
Reference
- Reference Type:
- publication
- Title:
- Absorption, Distribution and Toxicity of Ibuprofen.
- Author:
- Adams S.S., Bough R.G., Vliffe E.E., Lessel B., Mills R.F.N.
- Year:
- 1 969
- Bibliographic source:
- Toxicol Appl Pharmacol 15: 310-330.
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- To evaluate the potential developmental toxicity, Primiparous females and proven males were caged together, the presence of spermatozoa in the vaginal smear being taken as an indication of the first day of pregnancy. From this time, 180, 60,20, or 7.5 mg/kg/day of the test substance, was administered by oral intubation until day 20 of pregnancy. Control females received 10 mL/kg of water daily. The uterine contents were examined on day 21 of pregnancy, and the fetuses were examined for external, visceral, and skeletal abnormalities. Since the young of rats may show certain types of developmental abnormality at weaning which are not visible before birth, additional groups of rats were given 20 or 7.5 mg/kg/day of the test substance throughout pregnancy until parturition, and the young were examined 3 weeks after delivery. Litters were reduced to 9 at birth, and any underweight or neglected young were killed during the suckling period. All were examined in detail for gross abnormalities. From the litter records, the viability index at weaning was estimated.
- GLP compliance:
- no
- Remarks:
- pre-GLP study
- 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; i.e. 2-(4-isobutylphenyl)propionic acid)
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- male and female Boots Wistar rats (proven males and primiparous females); only females were treated.
- Source: Boots
- Diet: ad libitum
- Water: ad libitum
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test substance was administered as an aqueous solution of the sodium salt; ph of this solution was 8.
Control females received 10 mL/kg of water daily. - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: cohoused
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy - Duration of treatment / exposure:
- Experiment 1: days 1 through 20 of gestation (groups administered 7.5, 20, 60, 180 mg/kg bw/d)
Experiment 2: throughout gestation (two additional groups given 7.5 and 20 mg/kg bw) - Frequency of treatment:
- daily
- Duration of test:
- Experiment 1: until day 21 of gestation (groups administered 7.5, 20, 60, 180 m g/kg bw/d)
Experiment 2: until days 21 post partum (two additional groups given 7.5 and 20 mg/kg bw)
Doses / concentrationsopen allclose all
- Dose / conc.:
- 7.5 mg/kg bw/day (actual dose received)
- Remarks:
- Experiment 1
- Dose / conc.:
- 20 mg/kg bw/day (actual dose received)
- Remarks:
- Experiment 1
- Dose / conc.:
- 60 mg/kg bw/day (actual dose received)
- Remarks:
- Experiment 1
- Dose / conc.:
- 180 mg/kg bw/day (actual dose received)
- Remarks:
- Experiment 1
- Dose / conc.:
- 7.5 mg/kg bw/day (actual dose received)
- Remarks:
- Experiment 2
- Dose / conc.:
- 20 mg/kg bw/day (actual dose received)
- Remarks:
- Experiment 2
- No. of animals per sex per dose:
- no data
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
According to the authors, previous results by other investigators [Paget GE and Thorpe E (1964). A teratogenic effect of a sulphonamide in experimental animals. Brit J Pharmacol 23: 305-312.] had shown that the young of rats may show certain types of developmental abnormality at weaning which are not visible before birth. For this reason additional groups of rats were given 20 or 7.5 mg/kg bw/d of the test substance throughout pregnancy until parturition, and die young were examined 3 weeks after delivery (Experiment 2).
Examinations
- Maternal examinations:
- POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21 or on postnatal day # 21
- Organs examined: uterus and uterine contents, ovaries - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
The uterine contents were examined on day 21 of pregnancy. - Fetal examinations:
- - External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No data
In the additional groups given 7.5 or 20 or 7.5 mg/kg bw/d, the young were examined 3 weeks after delivery. Litters were reduced to 9 at birth (the normal practice in the investigator's breeding colony), and any underweight or neglected young were killed during the suckling period. All were examined in detail for gross abnormalities. From the litter records, the viability index at weaning was estimated. - Statistics:
- no data
- Indices:
- implantation index, viability index at weaning
- Historical control data:
- no data
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Only females on the highest dose had a diminished rate of growth. These animals had litters of normal size with fetuses of normal weight.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- In the first experiment females receiving 180, 60, or 20 mg/kg of test substance on days 1 to 20 of pregnancy were found to have gastrointestinal lesions graded in severity according to the dose; no lesions were observed in those an 7.5 mg/kg/day or in the controls.
Maternal developmental toxicity
- Other effects:
- no effects observed
- Description (incidence and severity):
- Animals form all groups had litters of normal size with fetuses of normal weight (experiment 1)
In the second experiment, in which dosing was continued throughout pregnancy until parturition, the animals had uneventful pregnancies and delivered their young without difficulty. A similar number of live young per litter was obtained from the test substance treated and control animals.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- General toxicity
- Effect level:
- 7.5 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- histopathology: non-neoplastic
Results (fetuses)
- Description (incidence and severity):
- Weaning weight was not significantly affected
- External malformations:
- no effects observed
- Description (incidence and severity):
- None of the fetuses obtained from animals given 180 mg/kg/day was malformed.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- Different types of skeletal abnormality were found, particularly in the young examined at weaning, but these generally fell within the accepted range of normal variation for the strain used in these investigations. One exception was a fetus with subcutaneous edema, wavy ribs and bilateral curvature of the radius and ulna, obtained from a female with a purulent exudate in the uterus.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- In both experiments various external and visceral malformations were observed; these were of low incidence and occurred in the treated and control groups
- Other effects:
- no effects observed
- Description (incidence and severity):
- Postnatal findings indicate that the viability index at weaning and weaning weight were not significantly affected. Microscopic examination of the organs revealed no histologic abnormalities.
- Details on embryotoxic / teratogenic effects:
- Postnatal findings indicate that the viability index at weaning and weaning weight were not significantly affected. In both experiments various external and visceral malformations were observed; these were of low incidence and occurred in the treated and control groups. None of the fetuses obtained from animals given 180 mg/kg/day was malformed, and microscopic examination of their organs revealed no histologic abnormalities.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 180 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental 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.