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EC number: 201-557-4 | CAS number: 84-74-2
- 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
Specific investigations: other studies
Administrative data
- Endpoint:
- endocrine system modulation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: second stage of the validation of the OECD rodent uterotrophic assay (GLP, QAU)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: The aim of the study was to obtain initial data for the uterotrophic assay within the OECD validation project and based on the "Protocol for the Conduct of the OECD Rodent Uterotrophic Assay", Draft Protocol A of April 21, 2000
- GLP compliance:
- yes (incl. QA statement)
- Type of method:
- in vivo
Test material
- Reference substance name:
- Dibutyl phthalate
- EC Number:
- 201-557-4
- EC Name:
- Dibutyl phthalate
- Cas Number:
- 84-74-2
- Molecular formula:
- C16H22O4
- IUPAC Name:
- dibutyl phthalate
- Details on test material:
- - Name of test material (as cited in study report): dibutylphthalate
No additional details available
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: the dams and the pups (Wistar, CRL : WI (GLX/BRL/HAN) IGS BR) were supplied on July 25, 2000 (Supplier : Charles River Laboratories, Germany). The litters were standardized to 8(preferably female) pups/litter in order to have the same conditions for all animals. If there, were fewer than 8 female pups in one litter, male pups were supplemented to obtain the number of pups required. The pups had an age of 12 days (day of birth = day 0)
- Age at study initiation: at an age of 18 days the pups were weaned. Thereafter, the female pups were assigned to the different test groups using a randomization program, according to their weight one day before the beginning of the treatment period. The selected sexually immature females had an age of 19 days on study day 0 (first day of treatment)
- Weight at study initiation: body weight range, 31 .8 - 39.7 g; mean of means, 35.47 g; +/- 5%, 33.70 - 37.24 g; mean min., 35.27 g; mean max., 35.68 g
- Housing: the animals were housed in Makrolon cages (type M II, No. of animals per cage: 3)
- Diet (e.g. ad libitum): ground Kliba feed rat/mouse/hamster (supplied by Provimi Kliba SA, Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): tap water
- Acclimation period: the dams and the pups were allowed to acclimatize for at least 7 days prior to dosing. At an age of 18 days the pups were weaned
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Remarks:
- Olive oil EP/DAB
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): the preparations were carried out once in olive oil. For this purpose, the coded vials which had been weighed and coded by the sponsor were dissolved or dissolved partially in ethanol (about 99.8%), the amount of ethanol not to exceed 10 vol.% of the final volume. Subsequently, the preparations were topped up to their maximum volume (see table below) and stirred. The vessels were jacketed with aluminium foil to avoid the incidence of bright light.
- Storage temperature of food: the preparations were stored in a refrigerator. - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- No analyses of the test substance and the reference estrogen were carried out within the OECD validation project with the exception of the test substance characterization by the manufacturer.
- Duration of treatment / exposure:
- 3 consecutive days
- Frequency of treatment:
- once a day
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0 and 1000 mg/kg bw
Basis:
actual ingested
a dose volume of 5 ml/kg body weight/day was used
- No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - A dose volume of 5 ml/kg body weight/day was used. The calculation of the volume administered to each female was based on the individual body weight identified daily before the doses were administered.
- The carrier control group, consisting of 6 females, was dosed with the vehicle only (olive oil), in the same manner as the test substance treated animals.
Examinations
- Examinations:
- MORTALITY
Viability was checked twice daily.
BODY WEIGHT
Body weights of the animals were recorded daily before the daily intubations throughout the study period.
CLINICAL SIGNS
The state of health of the animals was checked each day.
NECROPSY AND UTERI WEIGHT
- The animals were anesthetized with CO2 and sacrificed by decapitation about 24 hours after the last substance administration on study day 3.
- The abdominal wall was opened in the region of the pubic symphysis. The uteri were detached from the abdominal wall together with the ovaries. Urinary bladder and ureters were removed ventrally and laterally from the uterus and vagina. Fibrous adhesions between the rectum and the vagina were detached until the junction of vaginal orifice and perineal skin was identified. The sectioning for removal was made caudal to the cervix.
After the uteri had been thoroughly dissected free from the surrounding adipose tissue, the ovaries were detached. At necropsy, care was taken that any existing fluid in the uterus was not getting lost before weighing. After the ovaries had been removed, the uteri were transferred into petri dishes. Subsequently, each uterus was weighed with luminal fluid (wet weight) and without luminal fluid (blotted weight). For blotting, both uterus horns were pierced with the tip of a scalpel, topped with a dry filter paper (Schleicher & Schüll) and gently pressed to absorb the luminal fluid with a covered bale of cellulose. Thereafter, the uteri were fixed in 4% formaldehyde solution to be available for possible histopathological examination in the future. - Positive control:
- The test substance was tested together with 17-Ethinyl estradiol (CAS 57-63-6; 0.001 and 0.003 mg/kg per day); methoxychlor (CAS 72-43-5; 300 mg/kg per day); genistein (CAS 446-72-0; 300 mg/kg per day); 2,4'-DDT (CAS 789-02-6; 300 mg/kg per day); bisphenol A (CAS 80-05-7; 600 mg/kg per day); and nonylphenol (CAS 104-40-5; 250 mg/kg per day)
Results and discussion
- Details on results:
- CLINICAL OBSERVATIONS AND MORTALITY
None of the female rats, which received the test substance orally at 1000 mg/kg body weight/day showed abnormal clinical signs or any disturbances of the general behavior during the administration period. Moreover, there were no unscheduled mortalities.
BODY WEIGHT (See Table 1)
Mean body weights and mean body weight gains were not influenced by the oral administration of 1000 mg test substance/kg body weight/day. All differences between the test substance - treated rats and the vehicle control group concerning mean body weight data are without any biological relevance. They did not attain statistical significance.
UTERUS WEIGHT (See Table 1)
Mean absolute and relative uterus weights (wet and blotted) of the animals receiving 1000 mg test substance/kg body weight/day were not influenced by the oral administration and were similar to the concurrent control values.
Any other information on results incl. tables
Table 1: Mean body and uterine weights
Parameter |
Test group (dose in mg/kg per fay) |
Olive oil |
17-Ethinyl estradiol (0.001) |
17-Ethinyl estradiol (0.003) |
Dibutylphthalate (1000) |
Methoxychlor (300) |
Genistein (300) |
2,4’-DDT (300) |
Bisphenol A (600) |
Nonyphenol (250) |
Body weight (g) |
Day 0 |
34.2±2.36 |
33.1±3.04 |
33.3±3.16 |
34.8±2.51 |
34.5±2.94 |
34.4±2.56 |
36.3±2.43 |
34.3±2.81 |
34.6±2.88 |
Day 1 |
36.7±2.52 |
36.5±3.81 |
35.2±2.79 |
36.3±3.18 |
36.0±3.47 |
36.4±3.21 |
36.2±2.28 |
36.4±2.81 |
31.8±3.68* |
|
Day 2 |
39.3±3.13 |
39.6±3.65 |
39.6±2.34 |
39.8±2.76 |
37.7±4.28 |
38.8±5.26 |
36.1±3.85 |
39.3±3.04 |
29.4±1.25* |
|
Day 3 |
40.8±4.67 |
42.3±4.22 |
41.7±2.10 |
42.5±2.94 |
39.7±4.81 |
41.0±6.62 |
37.1±5.61 |
42.9±3.14 |
26.0±1.27* |
|
Uterine weight (g or %) |
Absolute wet |
0.031±0.006 |
0.103±0.0273* |
0.159±0.0745* |
0.032±0.007 |
0.094±0.0187* |
0.080±0.0065* |
0.184±0.0687* |
0.043±0.0044* |
0.061±0.0071 |
Relative wet |
0.077±0.011 |
0.248±0.0867* |
0.379±0.1639* |
0.076±0.171 |
0.239±0.0493* |
0.200±0.0424* |
0.512±0.2144* |
0.099±0.0066* |
0.234±0.0157 |
|
Absolute blotted |
0.030±0.006 |
0.084±0.0123* |
0.111±0.0206* |
0.030±0.006 |
0.089±0.0157* |
0.076±0.0061* |
0.108±0.0123* |
0.041±0.0044* |
0.049±0.0007 |
|
Relative blotted |
0.073±0.01 |
0.202±0.045* |
0.266±0.0456* |
0.071±0.0155 |
0.255±0.0418* |
0.191±0.0416* |
0.296±0.0494* |
0.095±0.0062* |
0.191±0.0121 |
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.
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