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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 940-510-9 | CAS number: 103043-58-9
- 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:
- 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
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 (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- XPB 115
- IUPAC Name:
- XPB 115
- Reference substance name:
- 1,6-bis(2-propylheptyl) hexanedioate
- EC Number:
- 940-510-9
- Cas Number:
- 103043-58-9
- Molecular formula:
- C26 H50 O4
- IUPAC Name:
- 1,6-bis(2-propylheptyl) hexanedioate
- Test material form:
- other: liquid
- Details on test material:
- refer to confidential details on test material
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services GmbH, Sulzfeld, Germany
- Age at study initiation: 42 ± 1 days
- Weight at study initiation:
- Housing: 5 animals per cage, polysulfonate cages, floor area about 2065 cm2, Dust-free wooden bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 10 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light from 06.00-18.00 h, 12 hours dark from 18.00-06.00 h
IN-LIFE DATES: From: 31 Oct 2014 To: 03 Feb 2015
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food): ground Kliba maintenance diet mouse/rat “GLP”, meal, supplied by Provimi Kliba SA, Kaiseraugst, Switzerland
- Storage temperature of food: room temperature - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
1000 ppm
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
3000 ppm
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
12000 ppm (males); 15000 ppm (females)
Basis:
nominal in diet
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: 4 week dose finding study
- Rationale for animal assignment (if not random): random
- Section schedule rationale (if not random): random - Positive control:
- not required
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least once a day
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: prior to the start of the administration period and weekly thereafter
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
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: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations:Prior to the start of the administration period on day -1 and on study day 91
- Dose groups that were examined: all animals (day -1), control and high dose animals (day 91)
HAEMATOLOGY: Yes
- Time schedule for collection of blood: towards the end of the administration period
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: Yes
- How many animals: all
- Parameters checked in table [No.?] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: towards the end of the administration period
- Animals fasted: Yes
- How many animals: all
- Parameters checked in table [No.?] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: towards the end of the administration period
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [No.?] were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: at the end of the administration period
- Dose groups that were examined: all
- Battery of functions tested: sensory activity / grip strength / motor activity / Home cage observations / Open field observations - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table)
HISTOPATHOLOGY: Yes (see table)
Organ weights: The following weights were determined in all animals sacrificed on schedule:
1. Anesthetized animals
2. Adrenal glands
3. Brain
4. Epididymides
5. Heart
6. Kidneys
7. Liver
8. Ovaries
9. Spleen
10. Testes
11. Thymus
12. Thyroid glands
13. Uterus with cervix
Organ/tissue fixation: The following organs or tissues were fixed in 4% neutral-buffered formaldehyde solution or in modified Davidson’s solution:
1. All gross lesions
2. Adrenal glands
3. Aorta
4. Bone marrow (femur)
5. Brain
6. Cecum
7. Cervix
8. Coagulating glands
9. Colon
10. Duodenum
11. Epididymides (modified Davidson’s solution)
12. Esophagus
13. Extraorbital lacrimal glands
14. Eyes with optic nerve (modified Davidson’s solution)
15. Femur with knee joint
16. Harderian glands
17. Heart
18. Ileum
19. Jejunum (with Peyer’s patches)
20. Kidneys
21. Larynx
22. Liver
23. Lungs
24. Lymph nodes (mesenteric and axillary lymph nodes)
25. Mammary gland (male and female)
26. Nose (nasal cavity)
27. Ovaries
28. Oviducts
29. Pancreas
30. Parathyroid glands
31. Pharynx
32. Pituitary gland
33. Prostate
34. Rectum
35. Salivary glands (mandibular and sublingual glands)
36. Sciatic nerve
37. Seminal vesicles
38. Skeletal muscle
39. Skin
40. Spinal cord (cervical, thoracic and lumbar cord)
41. Spleen
42. Sternum with marrow
43. Stomach (forestomach and glandular stomach)
44. Testes (modified Davidson’s solution)
45. Thymus
46. Thyroid glands
47. Trachea
48. Urinary bladder
49. Uterus
50. Vagina
All gross lesions, liver and Thyroid glands were microscopically examined for all animals, all the other organs and tissues that have been fixed were examined for the control and the high dose group. - Statistics:
- Body weight, body weight change: A comparison of each group with the control group was performed using DUNNETT's test (two-sided) for the hypothesis of equal means
Feces, rearing, grip strength forelimbs, grip strength hindlimbs, foot-splay test, motor activity: Non-parametric one-way analysis using KRUSKAL-WALLIS test (two-sided). If the resulting p-value was equal or less than 0.05, a pairwise comparison of each dose group with the control group was performed using WILCOXON test (two-sided) for the equal medians
Blood parameters: For parameters with bidirectional changes: Non-parametric one-way analysis using KRUSKAL-WALLIS test. If the resulting p-value was equal or less than 0.05, a pairwise comparison of each dose group with the control group was performed using WILCOXON-test (two-sided) for the hypothesis of equal medians; For parameters with unidirectional changes: Pairwise comparison of each dose group with the control group using the WILCOXON-test (one-sided) with Bonferroni-Holm adjustment for the hypothesis of equal medians
Urinalysis parameters (apart from pH, urine volume, specific gravity, color and turbidity: Pairwise comparison of each dose group with the control group using the WILCOXON-test (one-sided) for the hypothesis of equal medians
Urine pH, volume, specific gravity, color and turbidity: Non-parametric one-way analysis using KRUSKAL-WALLIS test. If the resulting p-value was equal or less than 0.05, a pairwise comparison of each dose group with the control group was performed using WILCOXON-test (two-sided) for the hypothesis of equal medians. Urine color and turbidity are not evaluated statistically.
Pathology (Weight parameters): Non-parametric one-way analysis using KRUSKAL-WALLIS test (two-sided). If the resulting p-value was equal or less than 0.05, a pairwise comparison of each dose group with the control group was performed using WILCOXON-test (two-sided) for the equal medians
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- Test group 3: 12000 ppm in males and 15000 ppm in females
(875 mg/kg bw/d in males and 1361 mg/kg bw/d in females)
Clinical Examinations
• No treatment-related, adverse findings were observed.
Clinical Pathology
• Increased alkaline phosphatase (ALP) activities, urea and potassium levels were observed in male animals.
• Increased γ-glutamyltransferase (GGT) activities were observed in females.
• Decreased total protein and albumin levels were observed in females.
• Increased incidences of granulated and epithelial casts were observed in males.
Pathology
• Increased mean absolute and relative liver weights were observed in males and females (in combination with clinical pathology).
• Minimal diffuse hepatocellular hypertrophy was observed in 6 (out of 10) male and in 7 (out of 10) female animals (in combination with clinical pathology parameters).
Test group 2: 3000 ppm
(209 mg/kg bw/d in males and 244 mg/kg bw/d in females)
Clinical Examinations, Clinical Pathology and Pathology
• No treatment-related, adverse findings were observed.
Test group 1: 1000 ppm
(71 mg/kg bw/d in males and 85 mg/kg bw/d in females)
Clinical Examinations, Clinical Pathology and Pathology
• No treatment-related, adverse findings were observed.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 3 000 ppm
- Based on:
- other: test item in the diet
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Dose descriptor:
- NOAEL
- Effect level:
- 209 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Dose descriptor:
- NOAEL
- Effect level:
- 244 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Regarding clinical pathology, slightly increased alkaline phosphatase (ALP) activities in males of test group 3 (12000 ppm) and slightly increased γ-glutamyl transferase (GGT) activities in females of the same test group (15000 ppm) indicated a liver cell swelling because of liver enzyme induction. Higher urea levels in males of test group 3 (12000 ppm) and decreased total protein and albumin levels in females of the same test group (15000 ppm) were due to an increased protein metabolism in the liver.
Regarding pathology, target organs were the liver and the thyroid glands.
The absolute (♂ +16% / ♀ +26%) and relative (♂ +25% / ♀ +28%) liver weights were significantly increased in males and females of test group 3 (12000 [males] and 15000 [females] ppm).The increased liver weights correlated with a minimal diffuse hepatocellular hypertrophy that was observed in 6 (out of 10) male and in 7 (out of 10) female animals in this treatment group. These findings were considered to bea correlate for a microsomal enzyme induction in the liver. They were regarded to betreatment-related and adverse taking the changes in clinical pathology parameters into account.
The incidence of follicular hypertrophy/hyperplasia and of altered colloid in the thyroid glands was minimally increased in male animals of test group 3 (12000 ppm). These findings wereregarded to be secondary to an induced UDP-glucuronyl transferase activity in hepatocellular hypertrophy.The well-known phenomenon is characteristic for rodents (Curran et al., 1991) and leads to an accelerated degradation of T4 with a compensatory increase of TSH causing thyroid gland hypertrophy/hyperplasia of follicular cells. These findings were regarded to be treatment-related but not relevant for humans.
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.