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EC number: 223-095-2 | CAS number: 3734-33-6
- 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
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Justification for type of information:
- data is from experimental reports following standard procedures
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 81-4 (Acute Eye Irritation)
- Principles of method if other than guideline:
- To assess the irritancy potential of the test material to the eyes of New Zealand White rabbits
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Denatonium benzoate
- EC Number:
- 223-095-2
- EC Name:
- Denatonium benzoate
- Cas Number:
- 3734-33-6
- Molecular formula:
- C21H29N2O.C7H5O2
- IUPAC Name:
- N-benzyl-2-[(2,6-dimethylphenyl)amino]-N,N-diethyl-2-oxoethanaminium benzoate hydrate
- Test material form:
- solid
- Details on test material:
- - Name of test material (as cited in study report): N-benzyl-2-[(2,6-dimethylphenyl)amino]-N,N-diethyl-2-oxoethanaminium benzoate hydrate
-Common name: Denatonium benzoate
- Molecular formula: C21H29N2O.C7H5O2
- Molecular weight: 446.58 g/mol
- Substance type: organic
- Physical state: Solid
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): N-benzyl-2-[(2,6-dimethylphenyl)amino]-N,N-diethyl-2-oxoethanaminium benzoate hydrate
-Common name: Denatonium benzoate
- Molecular formula: C21H29N2O.C7H5O2
- Molecular weight: 446.58 g/mol
- Substance type: organic
- Physical state: Solid
- Form: white granules
- Batch Number: 22362
- Storage conditions: room temperature in the dark
Test animals / tissue source
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Sex: male
- Source: David Percival Ltd, Cheshire, U.K
- Age at study initiation: 12-20 weeks old
- Weight at study initiation: 2.84 kg
- Housing: individually housed in separate suspended metal cages
- Diet (e.g. ad libitum): STANRAB SQC Rabbit diet, ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: minimum acclimatisation period of 5 days to each animal
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-22 deg C
- Humidity (%): 48-66%
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- 0.1 ml volume (approximately 40 mg)
- Duration of treatment / exposure:
- 1 second
- Observation period (in vivo):
- approximately 1, 24,48 and 72 hours following treatment. Additional observations were made on day 7,14 and 21 to check the reversibility of effects.
- Duration of post- treatment incubation (in vitro):
- no data available
- Number of animals or in vitro replicates:
- 1 male rabbit
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): not washed
- Time after start of exposure: no data available
SCORING SYSTEM: Draize method
TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: One day prior to the test, both the eyes of the test rabbit were examined under ultra-violet light, after treatment with Sodium Fluorescien BP. The cornea, iris and conjunctivae were examined for lesions. Immediately before treatment, the rabbit eyes were again examined with the aid of a light source from a standard ophthalmoscope. For scoring of ocular lesions, the examination of the eye was facilitated by the use of a standard ophthalmoscope.
Results and discussion
In vivo
Results
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- 7 d
- Score:
- 18
- Max. score:
- 110
- Reversibility:
- not fully reversible within: 21 days
- Remarks on result:
- positive indication of irritation
- Irritant / corrosive response data:
- Single application of test material produced areas of translucent opacity, iridial inflammation and moderate conjuncitval irritation. Vascularisation of the cornea was present on day 7 and was still apparent on day 21. The ocular reactions were therefore considered to be irreversible.
Any other information on results incl. tables
Table 1:Bitrex Acute eye irritation test in the rabbit: Individual reactions
Rabbit number and sex (bodyweight kg) |
IPR =3 |
||||||
27 Male (2.84) |
|||||||
1 hours |
24 hours |
48 hours |
72 hours |
7 days |
14 days |
21 days |
|
Cornea |
|
|
|
|
|
|
|
E –degree of opacity |
2SI |
2SI |
1 |
2 |
1V |
0V |
0V |
F –Area of opacity |
4 |
4 |
4 |
2 |
2 |
0 |
0 |
Score – E*F*5 |
40 |
40 |
20 |
20 |
10 |
0 |
0 |
Iris |
|
|
|
|
|
|
|
D |
1 |
1 |
1 |
1 |
0 |
0 |
0 |
Score –D*5 |
5 |
5 |
5 |
5 |
0 |
0 |
0 |
Conjunctivae |
|
|
|
|
|
|
|
A -redness |
2 |
2 |
2W |
2W |
1W |
0 |
0 |
B – chemosis |
2 |
2 |
2 |
2 |
1 |
0 |
0
|
C –discharge |
3 |
3 |
3 |
3 |
2 |
0 |
0 |
Score (A+B+C)*2 |
14 |
14 |
14 |
14 |
8 |
0 |
0 |
Total score |
59 |
59 |
39 |
39 |
18 |
0 |
0 |
IPR – initial pain reaction, W- white area over the nictitating membrane, approximate size 3 mm-*3mm, V – Vascularistion along the bottom edge of the cornea, approximately 4mm in length and invading up to 2mm onto the cornea, Sl –Sloughing of the cornea
Applicant's summary and conclusion
- Interpretation of results:
- Category 1 (irreversible effects on the eye) based on GHS criteria
- Conclusions:
- Single application of test material produced areas of translucent opacity, iridial inflammation and moderate conjuncitval irritation. Vascularisation of the cornea was present on day 7 and was still apparent on day 21. The ocular reactions were therefore considered to be irreversible.
Hence, Denatonium benzoate (BITREX) was considered to be corrosive to rabbit eyes. - Executive summary:
A study was performed to assess the irritancy potential of Denatonium benzoate (BITREX) to the eyes of New Zealand White rabbits. The study was conducted in a GLP certified laboratory (Sustainability Support Services (Europe) AB has letter of access) according to EPA 81 -4 Guidelines.
Initially one male New Zealand white rabbit was used for the study. After consideration of ocular responses in the first rabbit, no additional rabbits were treated.
For the purpose of this study, the test material was ground to a fine powder. One day prior to the test, both the eyes of the test rabbit were examined under ultra-violet light, after treatment with Sodium Fluorescien BP. The cornea, iris and conjunctivae were examined for lesions. Immediately before treatment, the rabbit eyes were again examined with the aid of a light source from a standard ophthalmoscope. 0.1 ml volume (approximately 40 mg) of the finely ground powder was instilled in to the right conjunctival sac of the rabbit. The upper and lower eyelids were held together for about one second immediately after application to prevent loss of the test material and then released. The left eye remained untreated and served as control. The assessment and scoring of ocular reactions was done approximately 1, 24, 48 and 72 hours following treatment. Additional observations were made on day 7,14 and 21 to check the reversibility of effects. For scoring of ocular lesions, the examination of the eye was facilitated by the use of a standard ophthalmoscope. The ocular reactions were scored according to the Draize method. Single application of test material produced areas of translucent opacity, iridial inflammation and moderate conjunctival irritation. Vascularisation of the cornea was present on day 7 and was still apparent on day 21. The ocular reactions were therefore considered to be irreversible. Hence, Denatonium benzoate (BITREX) was considered to be corrosive to rabbit eyes.
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