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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
Skin irritation / corrosion
Administrative data
- Endpoint:
- skin 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 81-5 (Acute Dermal Irritation)
- Principles of method if other than guideline:
- To assess the irritancy potential of the test material to the skin 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, room temperature in the dark from 22 February, 1995
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Sex: Male and female
- Source: David Percival Ltd, Cheshire, U.K
- Age at study initiation: 12-20 weeks old
- Weight at study initiation: 2.23 -2.71 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): 17-21 deg C
- Humidity (%): 43-58%
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness
Test system
- Type of coverage:
- semiocclusive
- Preparation of test site:
- other: clipped intact skin
- Vehicle:
- water
- Controls:
- not specified
- Amount / concentration applied:
- 0.5 g of the test material moistened with 0.5 ml distilled water
- Duration of treatment / exposure:
- 4 hours
- Observation period:
- one hour following the removal of patches and 24, 48 and 72 hours after patch removal
- Number of animals:
- 6(3/sex)
- Details on study design:
- TEST SITE
- Area of exposure: dorsal/ flank area
- % coverage: 2.5 * 2.5 cm gauze patch
- Type of wrap if used: the patch was secured with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5*2.5 cm)
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: four hours after exposure, any residual material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated spirits
OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : one hour following the removal of patches and 24, 48 and 72 hours after patch removal
SCORING SYSTEM:
- Method of calculation: The test sites were scored and evaluated according to ECHA guidance on the application of CLP criteria v5.0 (July 2017)
Results and discussion
In vivo
Results
- Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- other: 24 and 72 hours
- Score:
- 2.8
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- probability of moderate irritation
- Irritant / corrosive response data:
- Very slight to well defined erythema was noted at the all test sites 24 and 28 hour observation period and at five treatment sites at 72 hour observation. Very slight to moderate edema was noted at the test sites. Desquamation was also noted at five treatment sites 7 days after treatment.This reaction was considered to be reversible.
- Other effects:
- No corrosive effects were observed
Any other information on results incl. tables
Table 1: Bitrex Acute dermal irritation test in the rabbit: Individual skin reactions
Skin reaction |
Observation time |
Individual scores: Rabbit number and sex (Bodyweight kg) |
||||||
177 Female (2.23) |
178 Male (2.63) |
188 Male (2.71) |
185 Male (2.68) |
192 Female (2.52) |
197 Female (2.44) |
Total |
||
Erythema/ Eschar formation |
1 hour |
1 |
0 |
1 |
1 |
1 |
1 |
(5) |
24 hours |
1 |
2 |
2 |
2 |
2 |
2 |
11 |
|
48 hours |
1 |
1 |
2 |
2 |
2 |
1 |
(9) |
|
72 hours |
0 |
1 |
2 |
2 |
2 |
1 |
8 |
|
7 days |
0 |
0D |
0D |
0D |
0D |
0D |
0 |
|
Edema formation |
1 hour |
1 |
0 |
2 |
2 |
1 |
0 |
(6) |
24 hours |
0 |
2 |
3 |
2 |
2 |
1 |
10 |
|
|
48 hours |
0 |
1 |
2 |
2 |
2 |
1 |
(8) |
72 hours |
0 |
0 |
1 |
2 |
1 |
1 |
5 |
|
7 days |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Sum of 24 and 72 hours readings [S] |
34 |
|||||||
Primary Irritation Index [S/12] |
34/12 = 2.8 |
|||||||
Classification |
Moderate irritant |
Where
() = values not required for calculation of Primary Irritation Index
D = desquamation
2.
Animal No. |
OBSERAVTION TIME |
Average Score (ERY) |
Average Score (OED) |
|||||||||||
Erthyema (ERY) |
Oedema (OED) |
|||||||||||||
1hr |
24hr |
48hr |
72hr |
7days |
14days |
1hr |
24hr |
48hr |
72hr |
7days |
14days |
|||
177 |
1 |
1 |
1 |
0 |
0 |
NA |
1 |
0 |
0 |
0 |
0 |
NA |
0.66 |
0 |
178 |
0 |
2 |
1 |
1 |
OD* |
NA |
0 |
2 |
1 |
0 |
0 |
NA |
1.33 |
1 |
188 |
1 |
2 |
2 |
2 |
OD* |
NA |
2 |
3 |
2 |
1 |
0 |
NA |
2 |
2 |
185 |
1 |
2 |
2 |
2 |
OD* |
NA |
2 |
2 |
2 |
2 |
0 |
NA |
2 |
2 |
192 |
1 |
2 |
2 |
2 |
OD* |
NA |
1 |
2 |
2 |
1 |
0 |
NA |
2 |
1.66 |
197 |
1 |
2 |
1 |
1 |
OD* |
NA |
0 |
1 |
1 |
1 |
0 |
NA |
1.33 |
1 |
Evaluation is made based on the averge score per animal for 24/48/72 hours. |
0 |
0 |
||||||||||||
Table based on ECHA Guidence on the application of CLP criteria V5.0,July 2017. Examples 3 from section 3.2.5.1.3 on page 298 “test carried out”. |
0 |
0 |
||||||||||||
O.D.: Response of Desuamation judege to be reverbile. |
0 |
0 |
Applicant's summary and conclusion
- Interpretation of results:
- other: Not irritating
- Conclusions:
- A study was performed to assess the irritancy potential of Denatonium benzoate (BITREX) to the skin of New Zealand White rabbits according to EPA 81 -5 Guidelines.
Based on the observed scores in the study (the original 1995 Skin Irritation Toxicology Report), documented in table x, and when using the calculation method from ECHA Guidance on the application of the CLP criteria v 5.0 (July 2017), none of the average scores per animal (at 24, 48 and 72 hours), reached the cut off value of 2.3. So, no animals are positive for skin irritancy. Therefore, in conclusion Denatonium Benzoate (BITREX) is not classified as Skin Irritant under CLP. - Executive summary:
A study was performed to assess the irritancy potential of Denatonium benzoate (BITREX) to the skin 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 -5 Guidelines and 6 New Zealand White rabbits (3/sex) were used for the study.
One day before the test, the rabbits were clipped free of fur from the dorsal/flank area using veterinary clippers. On the day of the test, a suitable test site was selected on the back of each rabbits. 0.5 g of the test material moistened with 0.5 ml distilled water was applied under semi -occlusive conditions ( 2.5 * 2.5 cm gauze patch) on the shorn skin of rabbits. The patch was secured with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5*2.5 cm). To prevent the animals from interfering with the patches, the trunk of each rabbit was wrapped in elastic corset. and the rabbits were returned to their respective cages. After 4 hours of exposure, the patches and corset were removed. Also, any residual material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated spirits. The test sites were observed and scored according to Draize one hour following the removal of patches and 24, 48 and 72 hours after patch removal. The scores of erythema and edema at 24 and 72 hours readings were totaled for the six test animals(24 values) and divided by 12 to give the primary irritation index of the test material. The test material was classified according to the Draize classification criteria. Very slight to well defined erythema was noted at the all test sites 24 and 28 hour observation period and at five treatment sites at 72 hour observation. Very slight to moderate edema was noted at the test sites. Desquamation was also noted at five treatment sites 7 days after treatment. This reaction was considered to be reversible. No corrosive effects were observed.
Based on the observed scores in the study (the original 1995 Skin Irritation Toxicology Report), documented in table x, and when using the calculation method from ECHA Guidance on the application of the CLP criteria v 5.0 (July 2017), none of the average scores per animal (at 24, 48 and 72 hours), reached the cut off value of 2.3. So, no animals are positive for skin irritancy. Therefore, in conclusion Denatonium Benzoate (BITREX) is not classified as Skin Irritant under CLP.
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