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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 911-926-8 | 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
Skin irritation / corrosion
Administrative data
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 27.06.2018-01.10.2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- GLP compliance:
- yes
Test material
- Reference substance name:
- 3-benzoyloxy-2,2,4-trimethylpentyl isobutyrate
- EC Number:
- 245-054-8
- EC Name:
- 3-benzoyloxy-2,2,4-trimethylpentyl isobutyrate
- Cas Number:
- 22527-63-5
- Molecular formula:
- C19H28O4
- IUPAC Name:
- [2,2,4-trimethyl-1-(2-methylpropanoyloxy)pentan-3-yl] benzoate
- Reference substance name:
- 2,2,4-trimethylpentane-1,3-diyl dibenzoate
- EC Number:
- 268-316-3
- EC Name:
- 2,2,4-trimethylpentane-1,3-diyl dibenzoate
- Cas Number:
- 68052-23-3
- Molecular formula:
- C22H26O4
- IUPAC Name:
- (3-benzoyloxy-2,2,4-trimethylpentyl) benzoate
- Reference substance name:
- 1-isopropyl-2,2-dimethyltrimethylene diisobutyrate
- EC Number:
- 229-934-9
- EC Name:
- 1-isopropyl-2,2-dimethyltrimethylene diisobutyrate
- Cas Number:
- 6846-50-0
- Molecular formula:
- C16H30O4
- IUPAC Name:
- [2,2,4-trimethyl-3-(2-methylpropanoyloxy)pentyl] 2-methylpropanoate
- Test material form:
- liquid
- Details on test material:
- Density: 1.027
- Moisture content: 0.02%
Constituent 1
Constituent 2
Constituent 3
- Specific details on test material used for the study:
Batch (Lot) Number: V046812101
Expiry date: Clear colourless liquid
Storage Conditions: At room temperature
Test Facility test item number: 209637/A
Test item handling: No specific handling conditions required
In vitro test system
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Justification for test system used:
- In the interest of sound science and animal welfare, a sequential testing strategy is recommended to minimize the need of in vivo testing. One of the validated in vitro skin irritation tests is the EPISKIN test, which is recommended in international guidelines (e.g. OECD and EC).
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN Small Model TM (SkinEthic Laboratories, Lyon, France).
- Tissue batch number(s): EPISKIN-SMTM, 0.38 cm2, Batch no.: 18 EKIN 035
- Production date: August 28, 2018
- Date of initiation of testing: August 28, 2018
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature
- Temperature of post-treatment incubation (if applicable): 37°C
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: the tissues were washed with phosphate buffered saline
- Observable damage in the tissue due to washing: No
- Modifications to validated SOP: No
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 2 ml MTT solution (0.3 mg/ml in PBS)
- Incubation time: 3h
- Spectrophotometer: TECAN Infinite® M200 Pro Plate Reader
- Wavelength: 570 nm
NUMBER OF REPLICATE TISSUES: 2 - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 μl
- Concentration (if solution): undiluted
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 25 μl
- Concentration (if solution): PBS
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 25 μl
- Concentration (if solution): 5% SDS in PBS - Duration of treatment / exposure:
- 15 ± 0.5 minutes
- Duration of post-treatment incubation (if applicable):
- 42 hours
- Number of replicates:
- 3
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 μl
- Concentration (if solution): 100% (undiluted)
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 25 μl
- Concentration (if solution): PBS
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 25 μl
- Concentration (if solution): 5% SDS in PBS - Duration of treatment / exposure:
- 15 ± 0.5 minutes
- Observation period:
- 42 hours
- Number of animals:
- not used, in vitro study
- Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the tissues were washed with phosphate buffered saline to remove residual test item
- Time after start of exposure: 15 ± 0.5 minutes
OBSERVATION TIME POINTS
The skin tissues were incubated for 42 hours at 37°C. After incubation, cell culture inserts were dried carefully to remove excess medium and were transferred into a 12-wells plate prefilled with 2 mL MTT-solution (0.3 mg/mL in PBS). The tissues were incubated for 3 h at 37°C. After incubation the tissues were placed on blotting paper to dry the tissues. Total biopsy was made by using a biopsy punch. Epidermis was separated from the collagen matrix and both parts were placed in pre-labeled microtubes and extracted with 500 µL isopropanol (Merck, Darmstadt, Germany). Tubes were stored refrigerated and protected from light for 69 hours.
SCORING SYSTEM:
A test item is considered irritant in the skin irritation test if:
The relative mean tissue viability of three individual tissues after 15 minutes of exposure to the test item and 42 hours of post incubation is ≤ 50% of the mean viability of the negative controls.
A test item is considered non-irritant in the in vitro skin irritation test if:
The relative mean tissue viability of three individual tissues after 15 minutes of exposure to the test item and 42 hours of post incubation is > 50% of the mean viability of the negative controls.
Data interpretation of test items
Relative mean viability of 3 individual tissues after 15 minutes of exposure and 42 hours of post incubation Prediction to be considered
≤ 50% of the mean viability of the negative controls Category 1 or Category 2
(additional information on corrosion needed)
> 50% of the mean viability of the negative controls No category
Optical Density readings were transferred into Microsoft Excel to allow further calculations to be performed.
The corrected OD (ODc) for each sample or control was calculated by subtracting the value of the blank mean (ODbl) from each reading (ODraw).
ODc = ODraw – ODbl
The OD value representing 100% cell viability is the average OD of the negative controls (ODlt_u+MTT).
The %Viability for each sample and positive control is calculated as follows:
%Viability = (ODc/mean ODlt_u+MTT) * 100
Results and discussion
In vitro
Results
- Irritation / corrosion parameter:
- % tissue viability
- Value:
- 105
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- - OTHER EFFECTS:
- Visible damage on test system: no
- Direct-MTT reduction: The test item was checked for possible direct MTT reduction before the study was started. To assess the ability of the test item to reduce MTT, at least 25 μl of the test item was added to 2 ml MTT solution (0.3 mg/ml in PBS). The mixture was incubated for 3 hours at 37°C. A negative control, sterile Milli-Q water was tested concurrently. At the end of the incubation period a color check was performed. No color change were observed.
- Colour interference with MTT: The test item was checked for possible color interference before the study was started. Some non-colored test items may change into colored items in aqueous conditions and thus stain the skin tissues during the exposure. To assess the color interference, 10 μl of the test item was added to 90 μl Milli-Q water. The mixture was mixed for approximately 15 minutes. A negative control, 10 μl Milli-Q water was tested concurrently. At the end of the shaking period a color check was performed. No color changes were observed.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with the test item compared to the negative control tissues was 105%. The absolute mean OD570(optical density at 570 nm) of the three tissues of the negative control should reasonably be within the laboratory historical control data range.
- Acceptance criteria met for positive control: the positive control had a mean cell viability of 26% after 15 ± 0.5 minutes exposure. The mean relative tissue viability of the positive control should be <=40% relative to the negative control.
- Acceptance criteria met for variability between replicate measurements: The standard deviation value of the percentage viability of three tissues treated identically was less than 8%. The SD calculated from individual % tissue viabilities of the three identically treated replicates should be <=18.
Any other information on results incl. tables
Mean Absorption in the In Vitro Skin Irritation Test
|
A (OD570) |
B (OD570) |
C (OD570) |
Mean (OD570) |
|
SD |
Negative control |
1.012 |
1.109 |
1.170 |
1.097 |
± |
0.079 |
Test substance |
1.218 |
1.168 |
1.082 |
1.156 |
± |
0.069 |
Positive control |
0.288 |
0.327 |
0.253 |
0.290 |
± |
0.037 |
OD = optical density
SD = Standard deviation
Triplicate exposures are indicated by A, B and C.
In this table the values are corrected for background absorption (0.0422). Isopropanol was used to measure the background absorption.
Mean Tissue Viability in the In VitroSkin Irritation Test
|
Mean tissue viability (percentage of control) |
Standard deviation (percentage) |
Negative control |
100 |
7.2 |
Test substance |
105 |
6.3 |
Positive control |
26 |
3.4 |
|
Negative control (absorption; OD570) |
Positive control (absorption; OD570) |
Range |
0.422 – 1.547 |
0.023 – 0.437 |
Mean |
0.98 |
0.13 |
SD |
0.18 |
0.08 |
n |
174 |
173 |
SD = Standard deviation
n = Number of observations
The above mentioned historical control data range of the controls were obtained by collecting all data over the period of November 2014 to November 2017.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- In conclusion, Reaction Mass of 1-isopropyl-2,2 dimethyltrimethylene diisobutyrate and 3-benzoyloxy-2,2,4-trimethyl pentyl isobutyrate and 2,2,4-trimethylpentane-1,3-diyl dibenzoate is non-irritant in the in vitro skin irritation test under the experimental conditions described and should not be classified according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations.
- Executive summary:
The objective of this study was to evaluate the test substance for its ability to induce skin irritation on a human three dimensional epidermal model (EPISKIN Small model (EPISKIN-SMTM)). The possible skin irritation potential of the test item was tested through topical application for 15 minutes. The study procedures described in this report were based on the most recent OECD and EC guidelines. The test item was applied undiluted (25 µl), directly on top of the skin tissue for 15 ± 0.5 minutes. After a 42 hour post-incubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.
The positive control had a mean cell viability of 26% after 15 ± 0.5 minutes exposure. The absolute mean OD570(optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was less than 8%, indicating that the test system functioned properly.
Skin irritation is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with the test item compared to the negative control tissues was 105%. Since the individual values were above 50% test item is considered to be non-irritant.
In conclusion, the test substance is non-irritant in the in vitro skin irritation test under the experimental conditions described in this report andshould not be classified.
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.