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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 700-831-5 | CAS number: -
- 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
Endpoint summary
Administrative data
Description of key information
A 90-day repeated dose toxicity study (oral) on the rat, using 2-ethylhexanoic acid as the test item is presented for the purposes of HCAT hazard assessment. The study is considered equivalent to EPA OTS 795.2600 (Subchronic Oral Toxicity Test). The NOAEL for dermal exposure and the NOAEC for inhalation exposure were derived using route-to-route extrapolation.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- This study was conducted according to GLP, but individual data are not presented in the paper. The study is essentially in accordance with OECD Guideline 408, except that only 5 animals per sex group were assessed for haemotology and clinical chemistry, and no neurotixicology assessment was conducted (this was in line with the guideline at the time of the study being conducted).
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OTS 795.2600 (Subchronic Oral Toxicity Test)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Wilmington, MA
- Age at study initiation: 6 weeks
- Diet (e.g. ad libitum): Agway Prolab Animal Diet (RMH 3200), certified ground chow; ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- The test substance was mixed with ground certified chow using a Hobart cafeteria-type food mixer (Model M-802) to yield target concentrations of 0.0, 0.1, 0.5 and 1.5 % (w/w) of the test item. Diets were prepared monthly and the concentrations of test diets were verified analytically.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- No details available.
- Duration of treatment / exposure:
- 91-93 days
- Frequency of treatment:
- 7 days per week
- Remarks:
- Doses / Concentrations:
0, 0.1, 0.5 and 1.5 %
Basis:
nominal in diet - Remarks:
- Doses / Concentrations:
0, 61, 303 and 917 mg/kg/day for male rats; 0, 71, 360 and 1068 mg/kg/day for females
Basis:
other: actual dose - No. of animals per sex per dose:
- 10
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: based on a 14-day feeding study in rats
- Post-exposure recovery period in satellite groups: 28-29 days - Positive control:
- Not incluced
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS: Yes
- Detailed observations: on the mornings of body weight measurement.
- Cage side observations: every workday afternoon and on mornings on which body weights were not collected. Animals were checked for mortality on weekends.
BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 4, 7, and at least once weekly thereafter.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Feed weights (g) were collected on days 4, 7, and at least once weekly thereafter.
OPHTHALMOSCOPIC EXAMINATION: Yes, using an indirect ophthalmoscope after dilation of the pupils with 1% Mydriacyl.
All rats were examinde prior to the start of the study. During the last week of exposure, five male and five female non-recovery animals from each dose level were examined.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at necropsy
- Anaesthetic used for blood collection: Yes (CO2 anaesthesia)
- Animals fasted: overnight
- How many animals: five animals per sex, per dose.
- Parameters: Non-recovery groups: hemoglobin concentration, hematocrit, red blood cell count, white blood cell count, differential white blood cell count, platelet count, red blood cell indices, prothrombin time, and examination of the blood smears for cellular morphology. Recovery groups: hemoglobin concentration, hematocrit, red blood cell count, white blood cell count, platelet count, red blood cell indices.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at necropsy
- Animals fasted: overnight
- How many animals: five animals per sex per dose
- Parameters: Non-recovery groups: aspartate aminotransferase, alanine aminotransferase, total bilirubin, total protein, albumin, creatinine, urea nitrogen, glucose, gamma glutamyl transpeptidase, triglycerides, cholesterol, sodium, potassium, chloride, calcium and phosphorus. Recovery groups: albumin, urea nitrogen, triglycerides, cholesterol.
URINALYSIS: Yes
In the week prior to termination of exposure, five males and five females from each dose group were place in metabolism cages for 24-hour urine collections. Parameters: Non recovery-groups: specific gravity, osmolality, volume, glucose, bilirubin, ketones, blood, protein, urobilinogen, nitrite, leukocytes and pH. Recovery-groups: specific gravity, osmolality and volume. - Sacrifice and pathology:
- Organ weights: liver, kidneys, adrenal glands, testes, ovaries, brain.
Histopathology: all non-recovery high-dose and control animals: trachea, lungs, heart, aorta, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, rectum, pancreas, liver, salivary glands, kidneys, urinary bladder, pituitary gland, adrenal glands, thyroid glands, parathyroid glands, thymus, spleen, mesenteric lymph nodes, bone marrow (femoral), brain (including sections of medulla/pons, cerebellar cortex, and cerebral cortex), sciatic nerve, quadriceps femoris, testes, ovaries, vagina, uterus, fallopian tubes, sternum with bone marrow, and gross lesions.
The liver, kidneys, lungs, target organs, and gross lesions for animals from all dose levels were examined.
Because no signs of toxicity or target organ involvement was observed, no histopathology was performed on cervical/mid-thoracic/lumbar spinal cord, epididymides, male accessory sex glands, male mammary gland, female mammary gland, femur (including articular surface), skin, and exorbital lachrymal glands.
For recovery animals, histopathology was performed on the liver, kidneys, lungs, and gross lesions. - Other examinations:
- Sections of the liver were prepared for electron microscopy and stored for possible future examination.
- Statistics:
- Means were calculated for body weight, feed consumption, and organ weights. Numerical data were evaluated using Bartlett's test, one-way ANOVA, and Duncan's multiple range test. Feed consumption was not analyzed statistically because animals were group housed.
- Details on results:
- CLINICAL SIGNS AND MORTALITY
- Urine-soaked inguinal, abdonimal, scrotal, and/or thigh haircoats, discolored yellow, and/or unkempt: observed periodically during treatment in males and frequently in females, at all dose levels.
No mortality occured during the study.
BODY WEIGHT AND WEIGHT GAIN
A reduced mean body weight was observed in males and females of the high-dose group (8% and 10% below control weights at necropsy, respectively). Because of a caging problem, decreased body weights were observed in the mid-dose females on day 21. No effects on body weights were observed in the other groups.
During the recovery phase, the rate of body weight gain for the high-dose animals increased, but was still slightly below control level at study termination.
FOOD CONSUMPTION
During the first few days of the study, average feed consumption was moderately reduced in the high-dose group. Average consumption from day 4 to the end of the treatment period for the 1.5% males and females was 3.5 and 8.5% (non-recovery) and 4.7 and 9.5% (recovery) lower than controls, respectively. During the recovery period, average food intake was 3.7% and 0.8% higher than controles for the males and females of the exposed groups, respectively. Feed consumption was comparable to control levels in the low- and mid-dose groups.
HAEMATOLOGY
Mean corpuscular hemoglobin (MCH) was very slightly decreased in males of the mid- and high-dose groups. Females of the high-dose group had lower values for MCH and mean corpuscular volume (MCV) and the mid-dose females had a decreased mean hemoglobin concentration. Slight poikilocytosis was observed at all dose levels for males and at the mid- and high-dose for the females. Additional erythrocyt changes consisted of spherocytosis (two high-dose males), microcytosis (one high-dose female) and decreased polychromasia (in high-dose males and control, low- and high-dose females).
In the high-dose recovery group, males showed a lower MCH and females a decreased MCV, relative to controls.
CLINICAL CHEMISTRY
Cholesterol levels were increased in a dose-dependent manner for the males and the high-dose males showed elevated levels of urea, nitrogen and albumin. All anomalies returned to control level after the recovery period.
URINALYSIS
Urine volumes were decreased at all treatment levels in females and specific gravity levels were slightly increased in the high-dose females. These effects are probably due to chance or are related to decreased fee inatke in the high-dose group. No abnormalities were observed at the end of the recovery period.
ORGAN WEIGHTS
- Absolute liver weight and relative liver/body and liver/brain weights were increased for the mid- and high-dose animals in a dose-dependent manner. For the high-dose males, the relative liver/body remained elevated after the recovery period.
- Relative kidney/body weights were slightly increased for the high-dose males and females and for the mid-dose females. Relative kidney/brain weights were slightly increased for the mid- and high-dose females. Absolute kidney weights were slightly decreased in the high-dose recovery animals. The observed kidney effects are most likely a reflection of the decreased body weights.
- The differences in brain weights (viz. decreased absolute and increased relative weights at the high dose) are those expected because of differences in body weight and indicate sparing of the brain during growth inhibition.
- Relative testes weights were increased for the mid- and high-dose males (also in the recovery group) and reflect slightly decreased body weights, rather than target organs effects.
HISTOPATHOLOGY: NON-NEOPLASTIC
Hepatocyte hypertrophy with dose-dependent severity, primarily located in the portal area, was observed in all animals of the high-dose group and in males of the mid-dose group. The hypertrophy was characterized by an increase in the cell size with compression of the adjoining sinusoidal spaces. Furthermore, a decreased incidence of small cytoplasmic vacuoles was observed in a dose-dependent manner. No treatment-related effects were observed in the recovery group.
The minimal hyperplasia of bile ducts, observed in the control and high-dose recovery group, was considered not to be biologically significant. - Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: Reduced feed consumption and decreased rate of body weight gain
- Critical effects observed:
- not specified
- Conclusions:
- The study determined the NOAEL of 2-ethylhexanoic acid to rats to be 300 mg/kg bw/day.
Reference
The liver enlargement was considered to be primarily an adaptive change rather than a toxic effect.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 300 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Supporting study of adequate quality for use in hazards assessment and risk characterisation for the purpose of supporting qualitative risk management with quantitative assessments to ensure adequate protection against the other significant health effects.
Justification for classification or non-classification
A NOAEL of 300 mg/kg bw/d in the rat, indicate that there is no impact of 2-ethylhexanoic acid subchronic toxicity studies on HCAT Classification.
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.