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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 215-542-5 | CAS number: 1330-61-6
- 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:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 02 Apr 1985 - 19 July 1985
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- yes
- Remarks:
- see below
- Principles of method if other than guideline:
- The study was conducted according to OECD guideline 413 (1981). Compared to the actual version of the test guideline, validity is restricted in that food consumption was not recorded, lung tissues were not perfused, and laryngopharynx was not examined.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2-ethylhexyl acrylate
- EC Number:
- 203-080-7
- EC Name:
- 2-ethylhexyl acrylate
- Cas Number:
- 103-11-7
- Molecular formula:
- C11H20O2
- IUPAC Name:
- 2-ethylhexyl acrylate
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, D-7950 Biberach, Germany
- Age at study initiation: approximately 8-week old
- Weight at study initiation (mean): male rats: 223 g (213 - 234 g); female rats: 158 g (150 - 164 g)
- Housing: single
- Diet (ad libitum): Kliba Labordiaet Ratte/Maus A 343 10 mm Pellet, Klingentalmuehle AG, CH-4303 Kaiseraugst
- Water (ad libitum): tap water
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation chambers (glass/steel inhalation chambers) with a capacity of approx. 1.3 m3
- Method of holding animals in test chamber: animals in wire cages
- Temperature, humidity in air chamber: 22.8-23.6 °C, 36-41 %
TEST ATMOSPHERE
- Brief description of analytical method used: The test substance concentrations were checked intermittently (10 and 30 ppm) or continuously (100 ppm) by total hydrocarbons analyzers (THCA)/GC/FID.
- Samples taken from breathing zone: yes
EXPOSURE SYSTEM
The test and control animals were exposed to the test substance vapors and control air in a whole-body exposure system, respectively. All air streams, supply air and exhaust air of all test groups were adjusted by air flow meters (rotameters), measured continuously and recorded approximately every 2 hours. The air temperatures in the exposure systems were measured continuously with multipurpose thermometers (Diehl GmbH & Co) and recorded approximately every 2 hours. The pressures in the exposure systems were measured continuously (slanting tube pressure gage) and recorded once a day. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Measured test substance concentrations were within ± 5% of the nominal concentrations (see table below).
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- 6 h/day; 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
10; 30; 100 ppm (corresponding to approx. 0.075; 0.226; 0.753 mg/L)
Basis:
nominal conc.
- No. of animals per sex per dose:
- Groups of 10 male and 10 female rats per test concentration were exposed to test substance vapors in a whole-body exposure system on 6 hours per day, 5 days per week at 10, 30, and 100 ppm (corresponding to approximately 0.075 mg/L, 0.226 mg/L or 0.753 mg/L).
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale:
In order to obtain preliminary information about the profile of action of 2-EHA vapor, the maximum concentration during the 90-day study was to be within the saturation range of the test substance (estimated by extrapolation of the vapor-pressure curve: T = 20°C; p= 0.13 mbar = 130 ppm). For technical reasons (e.g. condensation phenomena and hence poor reproducibility with slight temperature fluctuations), the maximum concentration which could be reliably maintained under the study conditions was chosen to be 100 ppm. The minimum concentration of 10 ppm was based on the applicable MAC value for methyl acrylate (1984). The intermediate concentration was established between these two concentrations as 30 ppm in order to obtain any concentration-response relationships.
- Post-exposure period: none
- Control: An air control with 10 male and 10 female rats was run in parallel. - Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Mortality and clinical signs were checked each day.
BODY WEIGHT: Yes
- Time schedule for examinations: Body weight determinations were conducted once a week.
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: The eyes of the animals in the control group and the high dose group were checked with a focusable hand-held slit lamp for changes in the refracting media at the beginning of the pre-flow period (day -8) and at the end of the study (day 83).
- Dose groups that were examined: high-dose, control
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the exposure period
- Anaesthetic used for blood collection: No
- How many animals: 10
- Parameters were examined:
The following hematological examinations were carried out on 10 animals per test group and sex at the end of the exposure period: Hemoglobin, erythrocytes, hematocrit, mean hemoglobin content per erythrocyte, mean cell volume, mean corpuscular hemoglobin concentration, platelets, leukocytes.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of the exposure period
- How many animals:
- Parameters were examined:
The following clinicochemical examinations were carried out on 10 animals per test group and sex at the end of the exposure period: Total bilirubin, creatinine, urea, sodium, potassium, total protein, glucose, inorganic phosphate, calcium, chloride, triglycerides, cholesterol, albumine, globulins.
The following enzyme activities were determined: - Glutamic-pyruvic transaminase - Alkaline phosphatase - Glutamic-oxalacetic transaminase. Clotting analyses were performed: Prothrombin timne (Hepato Quick's test).
URINALYSIS: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
The animals were sacrificed at the end of the 3-month inhalation period and each animal was completely necropsied. Histopathologic examination was carried out on 31 organs/tissues of high dose and control animals. The lungs, nasal cavity, thyroid and parathyroid glands, trachea and liver from all animals/all test groups were subjected to histopathology examination. - Statistics:
- T-test according to Williams.
WILLIAMS DA (1971 ). A test for differences between treatment means when several dose levels are compared with a zero dose control. Biometrics 27: 103 - 117
WILLIAMS DA (1972 ). The comparisdn of several dose levels with a zero dose control. Biometrics 28: 519 - 531
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- - 100 ppm (0.753 mg/L): Mild lethargy, eyelid closure during exposure.
- 30 ppm (0.226 mg/L): Mild lethargy and eyelid closure during exposure.
- 10 ppm (0.075 mg/L): As compared to control animals, no toxic effects which could be interpreted as being related to the test substance. - Mortality:
- no mortality observed
- Description (incidence):
- There were no deaths during the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- - 100 ppm (0.753 mg/L): Retarded body weight gain in both sexes on determination of the body weight change; retarded body weight gain in male animals only on determination of body weight.
- 30 ppm (0.226 mg/L): Slight retardation in body weight gain of the female animals.
- 10 ppm (0.075 mg/L): As compared to control animals, no toxic effects which could be interpreted as being related to the test substance. - 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:
- no effects observed
- Description (incidence and severity):
- No findings.
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No findings
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- - 100 ppm (0.753 mg/L): Increase in glutamic-pyruvic transaminase activity and alkaline phosphatase activity of female rats; reduction of total proteins in female animals and very slightly in male rats; slightly reduced albumin concentrations in both sexes (not statistically significant); reduction of glucose level in female animals.
- 30 ppm (0.226 mg/L): Reduced total protein and albumin levels in both sexes; only a tendency to a reduction in albumin levels in female animals.
- 10 ppm (0.075 mg/L): As compared to control animals, no toxic effects which could be interpreted as being related to the test substance.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- no findings
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- - 100 ppm (0.753 mg/L): Reduction in body weight resulted in darker coloration of liver parenchyma with indistinct lobular marking (decrease in liver lipids).
- 30 ppm (0.226 mg/L): No findings.
- 10 ppm (0.075 mg/L): No findings. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Nasal cavity:
Degeneration of olfactory mucosa was diagnosed. This degeneration was characterized by a reduction of cellular layers, reduction or loss of
apical cytoplasmic structures such as olfactory knobs and microvilli, and by necrosis. Identification of the remaining olfactory mucosa cells
was not possible. Occasional mitoses were present.
Level I: Degeneration of olfactory mucosa was diagnosed in all rats of 100 ppm group and in 4 males and 4 females each of 30 ppm group. In 100 ppm group, the degeneration affected the olfactory mucosa diffusely in the dorsal and dorsolateral area, and the severity was mainly moderate. In 30 ppm group, the degeneration affected only small areas of the dorsolateral olfactory mucosa and was minimal in severity.
LeveL II: Degeneration of olfactory mucosa was diagnosed in all rats of 100 ppm group, 1 male of group 2, 2 males and 1 femaLe of 10 ppm group 1, and 1 male of control group. In 100 ppm group, the degeneration was diffuse (dorsal, dorsolateral), whereas in the other groups, the degeneration was focal. The severity was minimal to marked in 100 ppm group, and mainly minimal in the other groups.
LeveL III: Degeneration of oLfactory mucosa was only diagnosed in one male and one female each of the 100 ppmgroup. The severity was slight.
Level IV: No degeneration of the olfactory mucosa was noted.
Liver
Fatty change, characterized by micro- to macrovesicular hepatocellular fat deposits was diagnosed in rats of all groups including controls.
The fatty change was mainly localized in zones 1 (periportal zone) and 2 (intermediate zone). In 5 males of 30 ppm group and in one male of 100 ppm group, fatty change was noted also in zone 3 (zone surrounding terminal hepatic venule). Generally, the severity of fatty change was higher in males than in females. In females, the severity of fatty change was similar in all groups. In males, the severity of fatty change was less in 100 ppmgroup when compared with the rats of the other groups.
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 0.075 mg/L air (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Local effects: degeneration of the olfactory epithelial layer in the cranial part of the nasal cavity
- Dose descriptor:
- LOAEC
- Effect level:
- 0.226 mg/L air (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Local effects: degeneration of the olfactory epithelial layer in the cranial part of the nasal cavity
- Dose descriptor:
- NOAEC
- Effect level:
- 0.226 mg/L air (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Systemic effects: Clinical chemistry: elevated activities of transaminase and alkaline phosphatase
- Dose descriptor:
- LOAEC
- Effect level:
- 0.753 mg/L air (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Systemic effects: Clinical chemistry: elevated activities of transaminase and alkaline phosphatase
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Concentrations in the inhalation chambers:
A study mean with standard deviation was calculated from the daily means of the individual chamber concentrations of the test groups:
Concentration
Nominal Measured
[ppm] [mg/L] [ppm] [mg/L]
----------------------------------------------
10 0.075 9.9 ± 0.47 0.0745
30 0.226 30 ± 1.7 0.226
100 0.753 100 ± 4.6 0.753 ----------------------------------------------
Applicant's summary and conclusion
- Conclusions:
- In this subchronic repeated dose study by the inhalation route a NOAEC of 0.075 mg/l (10 ppm) was determined in rats for local effects (degeneration of the olfactory epithelial layer in the cranial part of the nasal cavity). The respective NOAEC for systemic effects was 0.226 mg/l (30 ppm) based on clinical chemistry (elevated activities of transaminase and alkaline phosphatase).
- Executive summary:
In a valid 90-day inhalation study, Wistar rats were administered in a whole-body exposition on 6 hours per day, 5 days per week, to 2-EHA vapour at concentrations of 0 ppm, 10 ppm, 30 ppm or 100 ppm (approximately 0.075 mg/l, 0.226 mg/l or 0.753 mg/l for the treatment groups) (2-EHA purity 99.7 %). The study design was conducted according to OECD 413 (1981).
Clinical observations:
There were no treatment-related premature deaths. Repeated exposure to 10 ppm was tolerated without signs by male and female Wistar rats. At 30 ppm and 100 ppm the clinical signs (eyelid closure, lethargy) were not very pronounced and possibly point to the irritant effect of the 2-EHA vapors.. Body weight gain was lower in both sexes of the high dose during and at the end of the study. A transiently reduced body weight gain was observed in mid dose females. From day 21 onwards mean body weight (absolute) was lower in high dose males compared to the control group. This parameter was not significantly altered in any other group at any time point during the study.
Clinical-chemical changes:
In the 100 ppm dose group an increase in the glutamic-pyruvic transaminase and alkaline phosphatase activities of the female rats as well as in some cases a reduction of total protein values and albumin concentrations were described. These effects were considered to be the only systemic ones of toxicological significance.
Gross Pathology:
The only effect of the test substance found on gross pathological assessment of the male animals in the 100 ppm group was a dark coloration of the liver parenchyma associated with indistinct lobular marking This finding is attributable to the decrease in the liver lipid content and is a consequence of the reduction in body weight.
Histopathology:
The inhalation of 2-EHA in rats was associated with degeneration of the olfactory mucosa in the dorsal and dorsolateral areas of the anterior parts of the nasal cavity. In 100 ppm group, the degenenation is considered to be treatment-related. In 30 ppm group , the degeneration was mainly minimal and similar to the histopathologic changes diagnosed in affected rats of the 10 ppm group and 0 ppm group (control). However, the incidence of degeneration was higher in mid group.
Slight to moderate hepatic fatty change in males and minimal to slight hepatic fatty change in females was a common finding in rats of all dose groups. In the males of 100 ppm group, the severity of the fatty change was less than in the rats of the other dose groups. This finding was compatible with the macroscopic findings in the liver of the rats of 100 ppm group (darker than normal, less distinct lobular pattern). This effect in the males of 100 ppm group is also considered to be related to the inhalation of the test article. However, this effect is presumed not to be a direct toxic effect of the test article, but rather reflect the poor body condition of the rats. A specific target organ could not be identified, electron microscopical examinations revealed no indication for peroxisome proliferation.
The other lesions noted in this study are not considered to be related to treatment.
NOAEC local effects: 0.075 mg/l (10 ppm)
NOAEC systemic 0.226 mg/l (30 ppm)
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.