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EC number: 203-757-7 | CAS number: 110-33-8
- 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: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Basic data given. No details on analytical purity and environmental conditions in the exposure chamber. The particle count median diameters were only estimated. Weekly food consumption was not determined and only a limited number of parameters was examined at haematology and clinical chemistry analysis. Not all organs and tissues were preserved and examined at histopathology.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 979
- Report date:
- 1979
- Reference Type:
- secondary source
- Title:
- ECB IUCLID set dihexyl adipate
- Author:
- ECB
- Year:
- 2 000
- Bibliographic source:
- EUROPEAN COMMISION – European Chemicals Bureau
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Deviations:
- yes
- Remarks:
- no analytical purity; particle count median diameters only estimated; food consumption not determined; not all parameters examined at blood analysis; not all organs and tissues preserved
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Dihexyl adipate
- EC Number:
- 203-757-7
- EC Name:
- Dihexyl adipate
- Cas Number:
- 110-33-8
- Molecular formula:
- C18H34O4
- IUPAC Name:
- 1,6-dihexyl hexanedioate
- Details on test material:
- - Name of test material (as cited in study report): Dihexyl Adipate
- Physical state: clear, colourless liquid
- Analytical purity: no data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, USA
- Age at study initiation: 6-7 weeks (males), 7 weeks (females)
- Weight at study initiation: 184-226 g (males), 137-180 g (females)
- Housing: Rats were housed individually in stainless steel wire mesh cages. During the inhalation study, rats were housed pairwise in the stainless steel and glass exposure chambers.
- Diet: Standard laboratory pellet diet (Purina Laboratory Chow®), ad libitum (out of chamber only)
- Water: ad libitum (out of chamber only)
- Acclimation period: approx. 3 weeks
IN-LIFE DATES: From: 13 Feb 1978 To: 10 Mar 1978
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Remarks on MMAD:
- MMAD / GSD: The particle count median diameters had to be estimated due to excessive coincidence counting in the lower diameter channels. This prevented the graphing of a complete particle size distribution. Estimates of the particle count median diameters (were possible) were:
15 mg/m³: ≤ 2.9 µm (Day 1), ≤ 2.5 µm (Day 2), ≤ 2.65 µm (Day 3)
130 mg/m³: could not be estimated on Day 1-3 due to measurement limit of the instrument
1430 mg/m³: ≤ 3.5 µm (Day 3, after reduction of the aerosol concentration by dilution with air) - Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel and glass exposure chamber
- System of generating particulates/aerosols: The aerosol was generated by spray atomising the material against the walls of a one-litre glass baffle chamber using a stainless steel Laskin nebuliser.
- Temperature, humidity, pressure in air chamber: no data
- Air flow rate: 130 L/min
- Air change rate: every 5.8 min
- Method of particle size determination: The optical particle size distribution was estimated for each exposure chamber during 3 days of exposure using the Royco Model 218 Portable Particle Monitor.
TEST ATMOSPHERE
- Brief description of analytical method used: mass reading using a GCA dust monitor
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Three air samples were drawn from each exposure chamber on each exposure day using the GCA dust monitor to determine the mass of test substance in the aerosol. The analytical concentrations of each air sample were determined by employing the equation 500 (mg)/(t-0.33), whereby “mg” was the mass read-out value of the instrument and “t” was the length of time of sampling. The equation provided correction for sampled time which was not reported by the instrument, as well as the conversion from units of mass to milligram per cubic meter. The analytical concentrations of the test atmosphere were 15, 130 and 1430 mg/m³. In addition, on each of 5 exposure days an air sample was drawn from each chamber using the GCA dust monitor in conjunction with a cyclone precollector to determine the level of respirable aerosol present in the exposure chamber. The percentage of respirable aerosol was determined to be 25%, 37% and 58% for concentrations of 15, 130 and 1430 mg/m³, respectively.
- Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- 6 h/day, 5 days/week
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
10, 100 amd 1000 mg/m³
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
0.01, 0.1 and 1 mg/mL
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
15, 130 and 1430 mg/m³
Basis:
analytical conc.
- Remarks:
- Doses / Concentrations:
0.015, 0.13 and 1.43 mg/L
Basis:
analytical conc.
- No. of animals per sex per dose:
- 20 (control), 10 (dose groups), 5 (pre-tesz)
- Control animals:
- yes
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Animals were observed daily for abnormal signs.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: A full, recorded, physical assessment was performed weekly.
BODY WEIGHT: Yes
- Time schedule for examinations: individual body weights were recorded weekly from 10 days prior to exposure through termination of the study (including the first day of exposure – Day 0).
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: on Day 0 (pre-test animals) and at study termination after 4 weeks
- Anaesthetic used for blood collection: No
- Animals fasted: Yes, except for animals of the pre-test
- How many animals: 5/sex (pre-test animals); 10/sex from the control group and 5/sex from the treatment group at study termination
- Parameters examined: haemoglobin, haematocrit, erythrocyte count, clotting time and total and differential leukocytes
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on Day 0 (pre-test animals) and at study termination after 4 weeks
- Animals fasted: Yes, except for animals of the pre-test
- How many animals: 5/sex (pre-test animals); 10/sex from the control group and 5/sex from the treatment group at study termination
- Parameters examined: alanine aminotransferase, alkaline phosphatase, blood urea nitrogen and glucose
URINALYSIS: Yes
- Time schedule for collection of urine: 10/sex from the control group and 5/sex from the treatment group at study termination
- Parameters examined: appearance, specific gravity, pH, protein, bilirubin, ketones, glucose and occult blood - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (all animals of the pre-test and the main study), adrenals, bone marrow (sternal), brain, eye, gonad, heart (with coronary vessels), intestine, colon, duodenum, ileum, kidneys, liver, lung, lymph node (mesenteric), mammary gland, pancreas, pituitary, salivary gland, skeletal muscle, skin, spinal cord (cervical), spleen, stomach, thyroid, urinary bladder, uterus/prostate, gross lesions, tissue masses
HISTOPATHOLOGY: Yes (all animals of control and high dose group), adrenals, bone marrow (sternal), brain, eye, gonad, heart (with coronary vessels), intestine, colon, duodenum, ileum, kidneys, liver, lung, lymph node (mesenteric), mammary gland, pancreas, pituitary, salivary gland, skeletal muscle, skin, spinal cord (cervical), spleen, stomach, thyroid, urinary bladder, uterus/prostate
ORGAN WEIGHTS: Yes, adrenals, brain (sans pituitary), heart, kidneys, liver and lungs - Statistics:
- Mean values of haematology and clinical chemistry analysis from compound-treated groups were compared to control using the F-test and Student’s t-test. When variance differed significantly (F-test), Student’s t-test was appropriately modified using Cochran’s approximation (t’). The mean values of body weights from compound-treated groups were compared to controls using the Dunnett’s test. Furthermore, mean values of organ weights, organ/body weight ratios and organ/brain weight from treated and control groups were statistically evaluated.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Not treatment-related: all groups: dry rales, mucoid nasal discharge; 15 mg/m³: nasal discharge in 1 animal; 130 mg/m³: reduced activity and excessive lacrimation in 1 animal; 1430 mg/m³: red stain around the mouth in 1 animal
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Not treatment-related: all groups: dry rales, mucoid nasal discharge; 15 mg/m³: nasal discharge in 1 animal; 130 mg/m³: reduced activity and excessive lacrimation in 1 animal; 1430 mg/m³: red stain around the mouth in 1 animal
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Stat. significant, non-adverse: 15 mg/m³ (m): slightly elevated clotting time; 130 mg/m³ (m): slightly increased haemoglobin; 15 mg/m³ (f): reduced haemoglobin; 15 and 130 mg/m³ (f): slightly reduced haematocrit
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- control and treated groups: mild proteinuria (non-adverse)
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- non-adverse, males: 15 mg/m³: slight increase in abs. lung and rel. adrenal weight; 130 mg/m³: increase in abs. and rel. adrenal weight, slight increase in abs. lung weight; 1430 mg/m³: increase in abs. and rel. weight of lungs and adrenals
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No mortalities were observed up to the end of the study. During the study, several animals in all groups exhibited rales, but this was not considered unusual for this type of exposure. Some animals also showed nasal discharge, while 1 animal exposed to 15 mg/cm³ exhibited red nasal discharge. Reduced activity and excessive lacrimation were observed in 1 animal treated with 130 mg/m³ and a red stain around the mouth was observed in 1 animal exposed to 1430 mg/m³. However, none of these clinical signs were considered to be treatment-related.
BODY WEIGHT AND WEIGHT GAIN
Mean body weights and weight gains for all treated groups were similar compared to those of the control group.
HAEMATOLOGY
A slightly elevated clotting time was observed in males exposed to 15 mg/m³ and slightly increased haemoglobin value was observed in males treated with 130 mg/m³. In females, a slightly depressed haemoglobin value was observed at 15 mg/m³ as well as a reduction in haematocrit values at 15 and 130 mg/m³, respectively. Although these values were statistically significant (p ≤ 0.05) compared to controls, they were within the normal biological limits, and thus not considered to be treatment-related.
CLINICAL CHEMISTRY
All clinical chemistry parameters for treated and control groups were within the normal biological ranges and no statistically significant changes were observed.
URINALYSIS
Mild proteinuria was observed randomly throughout the control and treatment groups, and was thus not considered treatment-related. All other observations were considered normal or spontaneous, unremarkable and unrelated to treatment.
ORGAN WEIGHTS
Changes in organ weight were observed for adrenal and lungs of treated animals, while all other organ weights were considered to be within the normal biological ranges and not remarkably changed. Statistical analysis revealed a significant elevation (p ≤ 0.05) in mean absolute adrenal weights in males exposed to 130 mg/m³ when compared to controls. The adrenal/body weight ratio for this group was also elevated as did the adrenal weights and adrenal (body weight ratios for males exposed to 1430 mg/m³, but this change was not statistically significant compared to controls. The mean adrenal/brain weight ratios were also elevated in males of all dose groups, but statistically significant changes were only noted in males exposed to 130 mg/m³. Thus, a slight treatment-related response might be indicated, as these findings were similar to those observed for the mean adrenal weights and adrenal/body weight ratios. However, since no corresponding histopathological alterations were observed, changes in adrenal weights were considered to be non-adverse.
In animals of the high dose group (1430 mg/m³), a significant increase in mean lung/body weight ratio was observed compared to controls. Absolute lung weights of this group were also elevated, but did not reach statistical significance compared to controls. In the lower exposure groups (15 and 1430 mg/m³), slight increases in lung weight were also observed, but none being statistically significant. Since all values for lung weight were within normal biological limits, these findings were of doubtful toxicological significance.
GROSS PATHOLOGY
No gross pathology changes were observed in any of the treated animals that could be attributed to treatment with the test substance.
HISTOPATHOLOGY: NON-NEOPLASTIC
No histopathological changes were observed in any of the treated animals.
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- >= 1.43 other: mg/mL (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed upt ot the highest dose
- Dose descriptor:
- NOAEC
- Effect level:
- >= 1 430 mg/m³ air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed upt ot the highest dose
Target system / organ toxicity
- Critical effects observed:
- not specified
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.