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EC number: 246-771-9 | CAS number: 25265-77-4
- 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
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol
- EC Number:
- 246-771-9
- EC Name:
- Isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol
- Cas Number:
- 25265-77-4
- Molecular formula:
- C12H24O3
- IUPAC Name:
- 3-hydroxy-2,2,4-trimethylpentyl 2-methylpropanoate
- Details on test material:
- The test substance, identified as 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, Lot #: E175/1053, was received on September 6, 2011 and was further identified with EPSL Reference Number 110906-1D. The test substance was stored at room temperature in a dry area protected from direct sunlight. The sample was instilled as received. Documentation of the methods of synthesis, fabrication, or derivation of the test substance is retained by Perstop Oxo Belgium AB, Durmakker 33, B-9940 Evergem, Belgium.
The following information related to the characterization of the test substance was provided by the Sponsor:
Composition: 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate- 99%
Physical description: Colorless liquid
pH: 2.54 at 20°C
Solubility: Water solubility: 1.5 giL at 20°C (OECD 105)
Stability: Test substance was expected to be stable for the duration of testing.
Expiration Date: August 31, 2012
Constituent 1
Test animals / tissue source
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- Husbandry
Housing:
The animals were singly housed in suspended stainless steel caging with mesh floors which confonn to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Litter paper was placed beneath the cage and was changed at least three times per week.
Animal Room Temperature and Relative Humidity Ranges:
19-23°C and 53-84%, respectively. Humidity was above the targeted upper limit for 3 days during the study. A portable dehumidifier was used to lower the humidity levels during this time.
Animal Room Air Changes/Hour:
Airflow measurements are evaluated regularly and the records are kept on file at Product Safety Labs.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 26 days
Food:
Harlan Teklad Global High Fiber Rabbit Diet® #2031. A designated amount of the diet was available to each rabbit (approximately 150 grams/day).
Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system.
Contaminants:
There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Product Safety Labs.
Identification
Cage: Each cage was identified with a cage card indicating at least the study number and identification and sex of the animal.
Animal: A number was allocated to each rabbit on receipt and a stainless steel ear tag bearing this number was attached to the animal. This number, together with a sequential animal number assigned to study 33026, constituted unique identification.
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- Prior to instillation, 2-3 drops of ocular anesthetic (Tetracaine Hydrochloride Ophthalmic Solution, 0.5%) were placed into both the treated and control eye of each animal. One-tenth of a milliliter of the test substance was then instilled into the conjunctival sac of the right eye of each rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The other eye of each rabbit remained untreated with the test substance and served as a control. The rabbits were then returned to their designated cages.
- Duration of treatment / exposure:
- Test substance was applied once and allowed to remain in the treated eye for the duration of the study.
- Observation period (in vivo):
- Ocular irritation was evaluated at 1, 24, 48, and 72 hours and at 4 days post-instillation.
- Number of animals or in vitro replicates:
- 3
- Details on study design:
- Preparation and Selection of Animals
Prior to test initiation, both eyes of a group of animals were examined using a white light source and a fluorescein dye procedure. One drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit. The eyes were rinsed with physiological saline (0.9% NaCl) approximately 30 seconds after instillation of the fluorescein and then evaluated for corneal damage using an ultraviolet light source. Prior to instillation, the eyes were re-examined and scored for abnormalities according to the "Scale for Scoring Ocular Lesions". Three healthy animals without pre-existing ocular irritation were selected for test.
Ocular Scoring
Ocular irritation was evaluated using a high-intensity white light (Mag Lite) at 1, 24, 48, and 72 hours and at 4 days post-instillation. The fluorescein dye evaluation procedure described in Section 5.A. was used in the treated eye at 24 hours and as needed at subsequent scoring intervals to evaluate the extent of corneal damage or to verify reversal of effects. Individual scores were recorded for each animal. In addition to observations of the cornea, iris and conjunctivae, any other observed lesions were noted. The average score for all rabbits at each scoring period was calculated to aid in data interpretation .
Classification of Eye Scores
The time interval with the highest mean score (Maximum Mean Total Score - MMTS) for all rabbits was used to classify the test substance by the system of Kay and Calandra. The average individually-determined irritation scores for cornea, iris and conjunctiva (redness and chemosis)
across 24, 48 and 72 hours were calculated for EC3 classification.
Cage-Side Observations
The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 10
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: See table for scores at individual time points
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: See table for scores at individual time points
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 2
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: See table for scores at individual time points
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- other: 1 hour, and 1,2,3,4 days after instillation.
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: See table for scores at individual time points
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- other: 1 hour, and 1,2,3,4 days after instillation.
- Score:
- 0
- Max. score:
- 1
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: See table for scores at individual time points
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- other: 1 hour, and 1,2,3,4 days after instillation.
- Score:
- 1
- Max. score:
- 1
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: See table for scores at individual time points
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- other: 1 hour, and 1,2,3,4 days after instillation.
- Score:
- 2
- Max. score:
- 0
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: See table for scores at individual time points
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- other: 1 hour, and 1,2,3,4 days after instillation.
- Score:
- 1
- Max. score:
- 2
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: See table for scores at individual time points
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 10
- Reversibility:
- fully reversible
- Remarks on result:
- not determinable
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 10
- Reversibility:
- fully reversible
- Remarks on result:
- not determinable
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 10
- Reversibility:
- fully reversible
- Remarks on result:
- not determinable
- Irritant / corrosive response data:
- The incidence of positive effects is presented in Table 1. All animals appeared active and healthy during the study. Apart from the eye irritation noted below, there were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior. There was no iritis observed in any treated eye during this study. One hour after test substance instillation, all three treated eyes exhibited 'positive' conjunctivitis. By 24 hours, corneal opacity also developed in two animals. The overall incidence and severity of irritation decreased thereafter. All animals were free of ocular irritation by Day 4 (study termination). The Maximum Mean Total Score of2,2,4-trimethyl-1,3-pentanediol monoisobutyrate is 16.0. The individually determined mean irritation (EC Mean Score) scores for each animal for corneal opacity, iris lesion and conjunctival (redness and chemosis) for the 24, 48 and 72-hour intervals are presented in Table 2. The mean scores for severity are presented in table 3.
Any other information on results incl. tables
Cornea
Opacity-degree of density (area most dense taken for reading)
No Opacity ........................................................................................................................................................................ 0
Scattered or diffuse area, details of iris clearly visible ........................................................................................................... 1
Easily discernible translucent areas, details of iris slightly obscured ....................................................................................... 2 Opalescent areas, no details of iris visible, size of pupil barely discernible ............................................................................. 3 Opaque, iris invisible .......................................................................................................................................................... 4
Area of cornea involved
One quarter (or less) but not zero ........................................................................................................................................ 1 Greater than one quarter, but less than half ........................................................................................................................... 2 Greater than half, but less than three quarters ........................................................................................................................ 3 Greater than three quarters, up to whole area ....................................................................................................................... 4
A X B X 5 Total Maximum = 80
Iris
Values
Normal ............................................................................................................................................................................... O Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof)
iris still reacting to light (sluggish reaction is positive) .............................................................................................................. 1
No reaction to light, hemorrhage, gross destruction (any or all ofthese) .................................................................................. 2
A X 5 Total Maximum= 10
Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal ..................................................................................................................................................................... 0 Vessels definitely injected above normal ................................................................................................................................ 1 More diffuse, deeper crimson red, individual vessels not easily discernible .............................................................................. 2
Diffuse beefy red .................................................................................................................................................................. 3
Chemosis
No swelling ......................................................................................................................................................................... 0
Any swelling above normal (includes nictitating membrane) ................................................................................................... 1
Obvious swelling with partial eversion of lids ........................................................................................................................ 2 Swelling with lids about half-closed ...................................................................................................................................... 3 Swelling with lids about half-closed to completely closed ...................................................................................................... 4
Discharge
No discharge ....................................................................................................................................................................... 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) .................... 1
Discharge with moistening of the lids and hairs just adjacent to lids ........................................................................................ 2 Discharge with moistening of the lids and hairs, and considerable area around the eye ............................................................ 3
Score (A+ B + C) X 2
Total Maximum= 20 Total Maximum Score: 110 represents the sum of all scores obtained for the cornea, iris and conjunctivae.
Classification of eye irritation scores
MMTS | Irritation classification | Requirement for Maintenance of Classification |
0.0 - 0.5 | non | Up to 0.5 at 1 hour with zeros at 24 hours; otherwise, increase one level |
0.6-2.5 | practically non | with zeros at 24 hours; otherwise, increase one level |
2.6- 15.0 | minimally | with zeros at 48 hours; otherwise, increase one level |
15.1-25.0 | mildly | with zeros at 96 hours; otherwise, increase one level |
25.1- 50.0 | moderately | with 7 day mean ~20 and individual total scores ~1 0 in at least 60% of the rabbits with no total score >30; otherwise, increase one level |
50.1 - 80.0 | severely | with 7 day mean ~ 40 and individual total scores ~3 0 in at least 60% of the rabbits with no total score> 60; otherwise, increase one level |
80.1 - 100.0 | extremely | with 7 day mean ~80 and individual total scores ~60 in at least 60% of the rabbits with no total score > 1 00; otherwise, increase one level |
100.1- 110 | maximally | with 7 day mean > 80 and individual total scores > 60 in at least 60% of the rabbits; otherwise, decrease one level |
Applicant's summary and conclusion
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: OECD GHS
- Conclusions:
- Under the conditions of this study, 2,2,4-trimethyl-1 ,3-pentanediol monoisobutyrate was considered to be mildly irritating to the eye. Based on the results of this study, 2.2.4-trimethyl-1 ,3-pentanediol monoisobutyrate does not meet the criteria for GHS Toxicity and EC classification, and therefore, no risk phrase for ocular irritation is required .
- Executive summary:
A primary eye irritation test was conducted with rabbits to determine the potential for 2,2,4- trimethyl-1,3-pentanediol monoisobutyrate to produce irritation from a single instillation via the ocular route. One-tenth of a milliliter of the test substance was instilled into the right eye of three healthy rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize et al.. There was no iritis observed in any treated eye during this study. One hour after test substance instillation, all three treated eyes exhibited 'positive' conjunctivitis. By 24 hours, corneal opacity also developed in two animals. The overall incidence and severity of irritation decreased thereafter. All animals were free of ocular irritation by Day 4 (study termination). Under the conditions of this study, 2,2,4-trimethyl-1 ,3-pentanediol monoisobutyrate was considered to be mildly irritating to the eye. Based on the results of this study, 2.2.4-trimethyl-1 ,3-pentanediol monoisobutyrate does not meet the criteria for GHS Toxicity and EC classification, and therefore, no risk phrase for ocular irritation is required .
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