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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 258-469-4 | CAS number: 53306-54-0
- 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:
- From 12 Sep 1994 To 21 Dec 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Bis(2-propylheptyl) phthalate
- EC Number:
- 258-469-4
- EC Name:
- Bis(2-propylheptyl) phthalate
- Cas Number:
- 53306-54-0
- Molecular formula:
- C28H46O4
- IUPAC Name:
- 1,2-bis(2-propylheptyl) benzene-1,2-dicarboxylate
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Identification: ear tattoo
- Age at study initiation: 38 days on arrival
- Weight at study initiation: mean 184 (176 - 194) g for the males, mean 149 (140 - 163) g for the females
- Fasting period before study: about 16 - 20 hours
- Housing: single, DK III stainless steel wire mesh cages (Becker, Castrop-Rauxel, Germany); floor area about 800 cm2
- Diet: commercial diet (ground Kliba laboratory diet rat/mouse/hamster 343 meal, Klingenthalmuehle AG, Kaiseraugst, Switzerland); ad libitum
- Water: drinking water ad libitum; ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test substance was weighed out and thoroughly mixed with a small amount of food in a beaker. Subsequently, a premix was prepared in a BOSCH household mixer by adding an appropriate amount of food and mixing for about 3 minutes. Then corresponding amounts of food, depending on the dose group, were added to this premix in order to obtain the desired concentrations, and mixing was carried out for about 10 minutes in a GEBR. LÖDIGE laboratory mixer.
DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): 343 meal, supplied by Klingentalmühle AG, Kaiseraugst, Switzerland.
- Storage temperature of food: room temperature - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The stability of the test substance in the diet at room temperature was proven for 4, 8 and 32 days. The homogeneous distribution of the test substance in the diet was checked in samples of the high and low concentration drawn at the beginning of the study. These analyses served also as concentration controls for low and high concentration. Further concentration control analyses were performed in samples drawn at the start of the administration period (mid concentration) and towards the end of the administration period (all concentrations).
- Duration of treatment / exposure:
- 3 months
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 500 ppm
- Remarks:
- Nominal in diet
- Dose / conc.:
- 2 500 ppm
- Remarks:
- Nominal in diet
- Dose / conc.:
- 15 000 ppm
- Remarks:
- Nominal in diet
- Dose / conc.:
- 39 mg/kg bw/day (actual dose received)
- Remarks:
- Mean actual dose received
- Dose / conc.:
- 196 mg/kg bw/day (actual dose received)
- Remarks:
- Mean actual dose received
- Dose / conc.:
- 1 266 mg/kg bw/day (actual dose received)
- Remarks:
- Mean actual dose received
- Dose / conc.:
- 36 mg/kg bw/day (actual dose received)
- Remarks:
- Actual dose received (males)
- Dose / conc.:
- 181 mg/kg bw/day (actual dose received)
- Remarks:
- Actual dose received (males)
- Dose / conc.:
- 1 187 mg/kg bw/day (actual dose received)
- Remarks:
- Actual dose received (males)
- Dose / conc.:
- 42 mg/kg bw/day (actual dose received)
- Remarks:
- Actual dose received (females)
- Dose / conc.:
- 211 mg/kg bw/day (actual dose received)
- Remarks:
- Actual dose received (females)
- Dose / conc.:
- 1 344 mg/kg bw/day (actual dose received)
- Remarks:
- Actual dose received (females)
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: The doses were chosen an the basis of a previous investigation with 5 animals/sex/group were dosed with concentrations of 0, 1000, 10000 and 20000 ppm (Administration in the diet for two weeks; BASF AG, Project No. 10C0110/94019)
- Positive control:
- not applicable
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: A check for overt clinical signs or mortality was made twice a day from Mondays to Fridays and once a day on Saturdays, Sundays and public holidays.
- Cage side observations checked in table were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: before the start of the administration period in order to randomize the animals. During the conduct of the study, the body weight was determined on day 0 (start of administration period) and thereafter at weekly intervals.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Three days prior to the start of the administration period and 91 days after start of the administration period
- Dose groups that were examined: the animals in the highest dose group and in the control group
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 3 days prior and at the end of administration period; in the morning
- Anaesthetic used for blood collection: No
- Animals fasted: No
- How many animals: 10
- Parameters examined: leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, differential blood count, prothrombin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 3 days prior and at the end of administration period; in the morning
- Animals fasted: No
- How many animals: 10/sex/group
- Parameters examined: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum-y-glutamyltransferase, cyanide-insensitive palmitoyl-CoA-oxidation, sodium, potassium, chloride, inorganic phosphate, calcium, urea, creatinine, glucose, total bilirubin, total protein, albumin, globulins, triglycerides, cholesterol, magnesium
URINALYSIS: Yes
- Time schedule for collection of urine: overnight
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No
- Parameters examined: volume, color, turbidity, nitrite, pH, protein, glucose, ketones, urobilinogen, bilirubin, blood, specific gravity, sediment
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- The statistical evaluation and calculation of the data were carried out on the computer systems of the Department of Toxicology of BASF AG:
For the parameters body weight and body weight change a parametric one-way analysis of variance was done via the F-test (ANOVA). If the resulting p-values were equal or less than 0.05, a comparison of each dose group with the control group was carried out. These comparisons were performed simultaneously via DUNNETT's test for the hypothesis of equal means. If the results of this test were significant, labels (* for p < 0.05, ** for p < 0.01) were printed together with the group means in the tables. Both tests were performed two-sided.
For all clinical chemistry and hematology parameters, excepting the differential blood count, a parametric one-way analysis of variance was done via the F-test (ANOVA). If the resulting p-value was equal or less than 0.05, a comparison of each dose group with the control group was carried out. These comparisons were performed simultaneously via DUNNETT's test for the hypothesis of equal means. If the results of this test were significant, labels (* for p < 0.05, ** for p < 0.01) were printed together with the group means in the tables. Both tests were performed two-sided.
With the exception of volume, color, turbidity, pH and specific gravity the scale for the urine parameters is divided into 4 sections (0, 1, 2, 3). For the parameter "Nitrite" only a division in two sections (0, 1) is made. The parameters were sorted into 2 classes. This was done for the statistical analysis. A pairwise comparison of each dose group with the control was carried out using FISHER's exact test for the hypothesis of equal proportions. If the results of this test are significant, labels (* for p < 0.05, ** for p < 0.01) were printed in the tables.
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):
- - 15000 ppm: the body weight values of the high dose group were slightly decreased in comparison to the control values. At the end of the administration period values of body weight were 6% below controls in males and 8% below controls in females. Although statistically significant only in females on days 63 to 91, the effects in both sexes were assessed as being substance-related. Corresponding body weight change values at the end of the administration period were 11% below controls in males and 17% below controls in females. Statistical significance was obtained for males on day 7 and for females on several days from day 42 onwards. This was assessed as being substance-related.
- 2500 ppm: no statistically or biologically relevant changes
- 500 ppm: no statistically or biologically relevant changes - Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- - 15000 ppm: at the end of the administration period statistically significantly decreased hemoglobin concentrations were found in the peripheral blood of the high dose animals of either sex. Furthermore, in the high dose males statistically significantly decreased hematocrit values (-5.1%) and increased platelet counts were observed (+20%). In the high dose females mean corpuscular hemoglobin (MCH) was statistically significantly decreased (-5.2%); in the males only a trend towards reduced mean corpuscular hemoglobin was seen.
- 2500 ppm: no statistically or biologically relevant changes
- 500 ppm: no statistically or biologically relevant changes - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- - 1500 ppm: the blood chemistry examinations revealed statistically significantly decreased chloride concentrations (-2.5% and -3%) and increased albumin levels in the high dose males and females, respectively. However, in the females of the highest dose group only a trend towards increased albumin concentrations was seen. Furthermore, a statistically significant decrease in triglycerides was found in the high dose males (-43%); in the sera of the females statistically significantly increased creatinine concentrations (+9%) and decreased glucose levels (-12.5%) were detected. After 3 month, alkaline phosphatase activities were statistically significantly increased in the sera of the high dose males and females. Moreover, a marked increase in cyanide-insensitive palmitoyl-CoA-oxidation was detected in the liver of the high dose animals of either sex (+824% in male, +680% in females). No other statistically or biologically relevant changes were noted.
- 2500 ppm: statistically significant increases in magnesium (9%) and liver cyanide-insensitive palmitoyl-Coenzyme A-oxidation (47%) in females and a statistically significant increase in albumin (6%) in males. No other statistically or biologically relevant changes were noted.
- 500 ppm: no statistically or biologically relevant changes - Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- - 15000 ppm: Males and females of the highest dose group produced slightly greater volumes of urine than the corresponding controls. No other treatment-related changes were seen in the urinalytical parameters examined.
- 2500 ppm: no statistically or biologically relevant changes
- 500 ppm: no statistically or biologically relevant changes - 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):
- - 15000 ppm: statistically significant increases in absolute (51.1% M, 59.4% F) and relative (64.2% M, 73.6% F) liver weights; a statistically significant decrease in absolute adrenal weight (15.5%) was observed in males, along with increases in relative kidney (14% M, 10% F) and relative brain (10% M, 8% F) weights
- 2500 ppm: increase in absolute liver weight in females and relative liver weight in males
- 500 ppm: no treatment-related weight changes - Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- - 15000 ppm: liver cell hypertrophy due to peroxisome proliferation in both sexes, increase of basophilic (thyreotrophic cells in the anterior part of the pituitary gland in male rats (8/10), hypertrophy of the follicular epithelium of the thyroid glands in both sexes
- 2500 ppm: liver cell hypertrophy in one male, increase of basophilic (thyreotrophic cells in the anterior part of the pituitary gland in male rats
(3/10), hypertrophy of the follicular epithelium of the thyroid glands in 8 males and 4 females
- 500 ppm: no treatment-related changes - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were some additional statistically significant inter-group differences in the results of clinical pathology testing. These deviations are marginal, incidental or inconsistent, when compared with the other sex, or lack dose-response relationship. Accordingly, these findings are considered to be of no toxicological significance.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- other: NOAEL disregarding peroxisomal proliferation
- Effect level:
- 2 500 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- haematology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- Key result
- Dose descriptor:
- other: NOAEL disregarding peroxisomal proliferation
- Effect level:
- 196 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- haematology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 500 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: liver weight (peroxisomal proliferation)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 39 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: liver weight (peroxisomal proliferation)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Mean body weight (g):
Day | 0 ppm | 500 ppm | 2500 ppm | 15000 ppm | |
Males | 7 | 183.5 | 185.2 | 183.2 | 185.6 |
28 | 336.6 | 337 | 338.7 | 327.2 | |
56 | 412.5 | 413.7 | 410.4 | 388.8 | |
91 | 447 | 458.3 | 449.7 | 420.7 | |
Females | 0 | 148.7 | 149.9 | 151.9 | 147.3 |
28 | 212.4 | 218.6 | 222.5 | 209 | |
56 | 249.6 | 254.2 | 258.2 | 236.9 | |
91 | 269.5 | 273.5 | 283.8 | 248.0* |
*p<0.05 (Dunnett's tests and ANOVA)
Mean food consumption (g):
Day | 0 ppm | 500 ppm | 2500 pppm | 15000 ppm | |
Males | 7 | 26.4 | 25.7 | 25.9 | 21.6 |
28 | 27.4 | 27.5 | 27.1 | 29.2 | |
56 | 26.6 | 26.8 | 26.1 | 28 | |
91 | 23 | 23.3 | 22.5 | 24.1 | |
Females | 0 | 19.6 | 19.6 | 20.5 | 17.6 |
28 | 19.3 | 19.9 | 20.4 | 20.7 | |
56 | 19.6 | 19.5 | 19.6 | 19.9 | |
91 | 23 | 23.3 | 22.5 | 24.1 |
Clinical chemistry, hematology and urinalysis:
0 ppm | 500 ppm | 2500 pppm | 15000 ppm | |||
Males | HGB | (mM/L) | 9.6 | 9.6 | 9.8 | 9.1** |
HCT | (L/L) | 0.451 | 0.452 | 0.464 | 0.428* | |
MCH | (FM) | 1.11 | 1.09 | 1.09 | 1.08 | |
PLT | (Giga/l) | 728 | 763 | 770 | 877** | |
ALP | (Mykat/L) | 5.42 | 5.47 | 5.52 | 10.28** | |
Pal CoA | (Mu/mg P) | 6.03 | 6 | 9.07 | 55.75** | |
Cl | (mM/L) | 104.7 | 103.9 | 103.4 | 102.0* | |
Crea | (MyM/L) | 55 | 53.2 | 55.9 | 54.5 | |
Gluc | (mM/L) | 7.48 | 7.79 | 7.91 | 7.78 | |
Alb | (G/L) | 33.4 | 33.38 | 35.41* | 37.52** | |
Trig | (G/L) | 2.75 | 3.19 | 2.25 | 1.56** | |
Urine | ml | 4.7 | 5 | 4.2 | 7.2 | |
Females | HGB | (mM/L) | 9.6 | 9.7 | 9.5 | 9.1** |
HCT | (L/L) | 0.436 | 0.44 | 0.439 | 0.424 | |
MCH | (FM) | 1.13 | 1.15 | 1.14 | 1.10* | |
PLT | (Giga/l) | 794 | 759 | 692 | 805 | |
ALP | (Mykat/L) | 4.04 | 4.32 | 4.87 | 5.10* | |
Pal CoA | (Mu/mg P) | 5.07 | 5.8 | 7.46* | 39.71** | |
Cl | (mM/L) | 106.3 | 106 | 104.9 | 102.8** | |
Crea | (MyM/L) | 54.2 | 56.2 | 57.9 | 59.1* | |
Gluc | (mM/L) | 8.38 | 7.92 | 8.29 | 7.33* | |
Alb | (G/L) | 36.07 | 37.28 | 37.2 | 38.93 | |
Trig | (G/L) | 1.58 | 1.9 | 2.71 | 1.23 | |
Urine | ml | 3.4 | 2.6 | 3.6 | 4.8 |
*p<0.05; **p<0.01 (Dunnett's test and ANOVA)
Liver weight:
0 ppm | 500 ppm | 2500 pppm | 15000 ppm | |||
Males | Absolute | (g) | 13.01 | 14.29 | 14.76 | 19.66** |
Relative | (%) | 3.08 | 3.29 | 3.47 | 5.05 | |
Females | Absolute | (g) | 7.76 | 7.97 | 9.28* | 12.38** |
Relative | (%) | 3.1 | 3.16 | 3.47 | 5.39** |
*p<0.05; **p<0.01 (Dunnett's test and ANOVA)
Histopathological incidences:
0 ppm | 500 ppm | 2500 pppm | 15000 ppm | |||
Males | Liver: | diffuse hypertrophy | 0/10 | 0/10 | 1/10 | 10/10 |
Pituitary: | increased basophilic cells | 0/10 | 0/10 | 3/10 | 8/10 | |
Thyroid: | hypertrophy | 1/10 | 2/10 | 8/10 | 10/10 | |
Females | Liver | diffuse hypertrophy | 0/10 | 0/10 | 0/10 | 10/10 |
Pituitary: | increased basophilic cells | 0/10 | 0/10 | 0/10 | 0/10 | |
Thyroid: | hypertrophy | 0/10 | 0/10 | 4/10 | 10/10 |
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.