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EC number: 222-437-8 | CAS number: 3470-98-2
- 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
- Study period:
- 2014-02-10 to 2014-03-10
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2400 (Acute Eye Irritation)
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- 1-butylpyrrolidin-2-one
- EC Number:
- 222-437-8
- EC Name:
- 1-butylpyrrolidin-2-one
- Cas Number:
- 3470-98-2
- Molecular formula:
- C8H15NO
- IUPAC Name:
- 1-butylpyrrolidin-2-one
- Test material form:
- other: liquid
- Details on test material:
- - Substance type: organic
- Physical state: clear colourless liquid
- Composition of test material, percentage of components: 0.18 % (water) by coulometry
- Purity test date: 2013-11-07
- Expiration date of the lot/batch: 31 December, 2016
- Stability under test conditions: responsibility of the sponsor
- Storage condition of test material: Kept in a controlled room temperature area
Constituent 1
Test animals / tissue source
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Covance, Denver, PA.
- Age at study initiation: 29 weeks
- Weight at study initiation: between 2.9 kg to 3.2 kg at initiation of dosing
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): ad libitum (PMI Nutrition International Certified Rabbit Chow No. 5322)
- Water (e.g. ad libitum): ad libitum (Municipal tap water following treatment by reverse osmosis and ultraviolet irradiation)
- Acclimation period: at least 12 days before the first day of dosing
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 69°F to 72°F (21°C to 22°C)
- Humidity (%): 37 - 43
- Air changes (per hr): Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.
- Photoperiod (hrs dark / hrs light): 12 /12
IN-LIFE DATES: From: 2013-02-11 To: 2013-03-10
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL - Duration of treatment / exposure:
- single exposure
- Observation period (in vivo):
- 1, 24, 48, and 72 hours and up to 10 days after dosing
- Number of animals or in vitro replicates:
- 3
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
SCORING SYSTEM: according to the Ocular Grading System (based on Draize) (see attached pdf)
TOOL USED TO ASSESS SCORE: fluorescein
The eyes were macroscopically examined with the aid of an auxiliary light source for signs of irritation at 1, 24, 48, and 72 hours and up to 10 days after dosing according to the Ocular Grading System presented above which is based on Draize. Following macroscopic observations at the 24-hour scoring interval, the fluorescein examination procedure was repeated on all test and control eyes and any residual test substance was gently rinsed from the eye at that time using physiological saline. If fluorescein findings were noted at 24 hours, a fluorescein exam was conducted on the affected eyes at each subsequent interval until a negative response was obtained and/or until all corneal opacity had cleared.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 1
- Reversibility:
- fully reversible within: 10 days
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 1
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 1
- Reversibility:
- fully reversible within: 10 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 10 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2.67
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 2
- Reversibility:
- fully reversible within: 10 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 2
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 2
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 1
- Reversibility:
- fully reversible within: 48 hours
- Irritant / corrosive response data:
- Exposure to the test article produced corneal opacity in 1/3 test eyes by the 24-hour scoring interval and complete resolution occurred by the Day 7 scoring interval. Iritis was observed in 1/3 test eyes by the 1-hour scoring interval and in 2/3 test eyes by the 24-hour scoring interval. Complete resolution of the iritis occurred in 1/3 test eyes by the Day 7 scoring interval and in 2/3 test eyes by the Day 10 scoring interval. Conjunctivitis (redness, swelling, and/or discharge) occurred in 3/3 test eyes by the 1-hour scoring interval and complete resolution occurred in 1/3 test eyes by the Day 7 scoring interval and in 2/3 test eyes by the Day 10 scoring interval. An additional ocular finding of neovascularization (2/3 test eyes) was noted during the study.
- Other effects:
- Decreased faecal output, including reduced faecal size and absence of faeces, was observed in all animals on at least 1 day during the study. Animals were treated with buprenorphine, an opioid, from Days 1 through 5, and opioids are known to cause decreased faecal output. Therefore, the decreased faecal output is likely an effect of the buprenorphine treatment.
Any other information on results incl. tables
Table 1. Individual ocular irritation scores
Animal No. /sex/ body weight (kg) |
|
Cornea |
Iris |
Conjunctivae |
Total |
Test Eye |
Control Eye |
||||||||
Interval |
O |
A |
OxAx5 |
I |
Ix5 |
R |
S |
D |
(R+S+D) x 2 |
|
Fluorescein examination |
Secondary ocular findings |
Fluorescein examination |
Secondary ocular findings |
|
5981/M/ 3.241 |
1 hour |
0 |
0 |
0 |
0 |
0 |
2 |
3 |
2 |
14 |
14 |
|
|
|
|
24 hours |
2 |
1 |
10 |
1 |
5 |
3 |
2 |
2 |
14 |
29 |
FAO |
|
NFE |
|
|
48 hours |
3 |
1 |
15 |
1 |
5 |
3 |
2 |
2 |
14 |
34 |
FAO |
|
|
|
|
72 hours |
1 |
1 |
5 |
1 |
5 |
3 |
2 |
2 |
14 |
24 |
FAO |
|
|
|
|
day 7 |
0 |
0 |
0 |
1 |
5 |
2 |
0 |
0 |
4 |
9 |
|
|
|
|
|
day 10 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
|
|
5984/M/ 2.861 |
1 hour |
0 |
0 |
0 |
0 |
0 |
2 |
3 |
2 |
14 |
14 |
|
|
|
|
24 hours |
0 |
0 |
0 |
1 |
5 |
2 |
2 |
1 |
10 |
15 |
NFE |
|
NFE |
|
|
48 hours |
0 |
0 |
0 |
1 |
5 |
3 |
2 |
1 |
12 |
17 |
|
VAS-1 |
|
|
|
72 hours |
0 |
0 |
0 |
1 |
5 |
3 |
2 |
1 |
12 |
17 |
|
VAS-3 |
|
|
|
day 7 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
VAS-1 |
|
|
|
5985/M/ 3.057 |
1 hour |
0 |
0 |
0 |
1 |
5 |
2 |
3 |
2 |
14 |
19 |
|
|
|
|
24 hours |
0 |
0 |
0 |
1 |
5 |
2 |
1 |
1 |
8 |
13 |
NFE |
|
NFE |
|
|
48 hours |
0 |
0 |
0 |
1 |
5 |
2 |
0 |
1 |
6 |
11 |
|
|
|
|
|
72 hours |
0 |
0 |
0 |
1 |
5 |
2 |
0 |
1 |
6 |
11 |
|
VAS-1 |
|
|
|
day 7 |
0 |
0 |
0 |
1 |
5 |
1 |
0 |
0 |
2 |
7 |
|
VAS-4 |
|
|
|
day 10 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
VAS-1 |
|
|
O - opacity; A - Area of cornea involved; I - Iritis; R - redness; S - swelling; D - discharge;
FAO - Fluorescein dye retention associated with the area of corneal opacity;
NFE - No fluorescein retention was observed;
VAS - 1: Total area of vascularized corneal tissue was < 10 % of corneal surface (neovascularization - very slight);
VAS - 2: Total area of vascularized corneal tissue was > 10 % but < 25 % of corneal surface (neovascularization - mild);
VAS - 3: Total area of vascularized corneal tissue was > 25 % but < 50 % of corneal surface (neovascularization - moderate);
VAS - 4: Total area of vascularized corneal tissue was > 50 % of corneal surface (neovascularization - severe).
Table 2. Mean ocular score
1 hour |
15.67 |
24 hours |
19.00 |
48 hours |
20.67 |
72 hours |
17.33 |
day 7 |
5.33 |
day 10 |
0.00 |
Applicant's summary and conclusion
- Interpretation of results:
- Category 2 (irritating to eyes) based on GHS criteria
- Conclusions:
- According to the Kay and Calandra Evaluation Criteria, the test item is considered to be a moderate irritant to the ocular tissue of the rabbit.
The total ocular irritation score for the 24-, 48-, and 72-hour intervals was individually added for corneal opacity, iris lesion, conjunctival redness, and conjunctival oedema. According to the EEC Ocular Evaluation Criteria, the test substance is classified as non-irritant for corneal opacity, irritant for iris lesions, conjunctival redness and oedema. According to the CLP criteria, the test item is classified as a Category 2 irritant to the eye (potential to induce reversible eye irritation). - Executive summary:
The objective of this study was to assess the irritant and/or corrosive effects of the test substance when given as a single ocular administration to rabbits. Each of 3 rabbits received a 0.1 mL dose of the test substance in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 10 days following dosing.
Exposure to the test article produced corneal opacity in 1/3 test eyes by the 24-hour scoring interval and complete resolution occurred by the Day 7 scoring interval. Iritis was observed in 1/3 test eyes by the 1-hour scoring interval and in 2/3 test eyes by the 24-hour scoring interval. Complete resolution of the iritis occurred in 1/3 test eyes by the Day 7 scoring interval and in 2/3 test eyes by the Day 10 scoring interval. Conjunctivitis (redness, swelling, and/or discharge) occurred in 3/3 test eyes by the 1-hour scoring interval and complete resolution occurred in 1/3 test eyes by the Day 7 scoring interval and in 2/3 test eyes by the Day 10 scoring interval. An additional ocular finding of neovascularization (2/3 test eyes) was noted during the study. Decreased faecal output was observed in all animals. This observation, which is a known pharmacological effect of opioids, was likely due to the buprenorphine treatment that the animals received from Days 0 to 5. According to the Kay and Calandra Evaluation Criteria, the test substance is considered to be a moderate irritant to the ocular tissue of the rabbit. The total ocular irritation score for the 24-, 48-, and 72-hour intervals was individually added for corneal opacity, iris lesion, conjunctival redness, and conjunctival oedema. According to the EEC Ocular Evaluation Criteria, the test substance is classified as indicated below:
Animal No./Sex
Corneal Opacity
Iris Lesion
Conjunctival Redness
Conjunctival Edema
5981/M
2.00
1.00
3.00
2.00
5984/M
0.00
1.00
2.67
2.00
5985/M
0.00
1.00
2.00
0.33
Irritation Rating
Nonirritant
Irritant
Irritant
Irritant
According to the CLP criteria, the test substance is classified as a Category 2 irritant to the eye (potential to induce reversible eye irritation).
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.
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