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EC number: 237-163-4 | CAS number: 13676-54-5
- 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
Endpoint summary
Administrative data
Description of key information
An in vitro skin irritation study is available according to OECD TG 439 and BMI was shown to be a non-irritant.
An in vitro eye study study (OECD TG 437) performed with BMI was inconclusive. Subsequently an in vivo eye irritation study was performed (OECD TG 405). Minimal irritation was observed and BMI was concluded not to be an eye-irritant.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 16 May to 18 June 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: Epidermal cells from adult donors
- Justification for test system used:
- 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
- Tissue batch number: 12-EKIN-024
- Surface: 0.38 cm^2
- Expiration date: 18 June 2012
CHECK FOR REDUCTION OF MTT BY TEST SUBSTANCE
- The MTT reducing capability of the test substance was investigated by mixing approximately 10 mg of the test substance with 2 mL of 0.3 mg/mL MTT solution in duplicate. A control of 10 μL of distilled water, mixed with 2 mL of 0.3 mg/mL MTT solution was also included in duplicate.
CHECK FOR COLOR INTERFERENCE OF MTT BY TEST SUBSTANCE
- The test substance was evaluated for its colour or ability to become coloured in contact with water (simulating a tissue humid environment). Evaluation was achieved by mixing 10.1 mg of the test substance with 91 μL of distilled water in a transparent container to give 10 mg/90 μL. 100 μL of distilled water was included as a control. The solution was mixed for 15 minutes on a shaker. At the end of the shaking period the colour of the solution was assessed by eye.
CHECK FOR PH
An estimate of the pH of the test substance as a 10% suspension in distilled water was determined using pH indicator paper and recorded.
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: at room temperature
- Temperature of post-treatment incubation (if applicable): 42 ± 1 hour at 37 ± 2°C in a humidified atmosphere of 5% CO2 in air + 3 hours ± 5 minutes with MTT .
REMOVAL OF TEST MATERIAL AND CONTROLS
- Volume and number of washing steps: each tissue was rinsed with 25 mL sterile Dulbeccos Phosphate Buffered Saline (DPBS) to remove residual test substance
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT :
- MTT concentration: 0.3 mg/mL
- Incubation time: 3 hours ± 5 minutes at 37 ± 2°C
- Wavelength of OD measurements: 540 nm
VIABILITY MEASUREMENTS PREPARATION
AFTER all the tissues had been punched, the tissues (epidermis and collagen matrix) were vortexed with 500 μL of acidic isopropanol (0.04 N HCl final concentration).
The tissues were extracted by storing at 2-8 ºC, protected from light, for 48 - 70 hours. After formazan extraction, duplicate 200 μL aliquots of the extractant from each micro tube were pipetted into the wells of flat-bottomed 96-well plates. The extractant was mixed by vortexing prior to taking the aliquots. The absorbance was read at 540 nm, with six wells containing acidified isopropanol (0.04 N HCl final concentration) as a blank.
NUMBER OF REPLICATE TISSUES: triplicate tissues with the test item, negative and positive control.
PREDICTION MODEL / DECISION CRITERIA
If the mean tissue viability was equal to or less than 50% of the negative control value, the sample was classed as Irritant R38 (EU classification) or Category 2 (GHS classification).
ACCEPTANCE CRITERIA:
The OD from the negative control tissue in the MTT assay is an indicator of tissue viability after the shipping and storage procedure and under the specific conditions of the assay. The mean absorbance of the triplicate negative control values should be ≥0.6 and ≤1.5. The Standard Deviation (SD) value of the % viability should be <18.
The OD of the positive control is an indicator of the sensitivity of the tissues. The mean viability should be ≤40% of the negative control and the SD <18. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount applied: 10 ± 2 mg (spread over the surface of the tissue using a curved spatula)
- The tissues were wetted with 5 μL of distilled water prior to application of the test material. - Duration of treatment / exposure:
- 15 ± 0.5 minutes
- Duration of post-treatment incubation (if applicable):
- 42 hour ± 1 hours ; + 3 hours ± 5 minutes with MTT
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- Mean of 3 experiments
- Value:
- 91.7
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Other effects / acceptance of results:
- Negative control
The mean absorbance of the triplicate negative control values was 0.917 which was between the minimum and maximum values of 0.6 and 1.5. The standard deviation (SD) of the % viability was 5.9 which was below the maximum value of 18.
Positive control
The percentage mean viability of the positive control was 10.9 ± 2.9 of the negative control. These were below the maximum acceptance values of 40% viability and SD of 18.
Results of individual reports are reported in "any other information" - Interpretation of results:
- GHS criteria not met
- Conclusions:
- In an in vitro skin irritation test, performed according to OECD guideline 439 and in accordance with GLP principles, BMI showed to be a non-irritant (tissue viability of 91.7± 5.3%). Therefore, the substance was predicted as non-irritant to the skin.
- Executive summary:
In an in vitro skin irritation test, performed according to OECD guideline 439 and in accordance with GLP principles. The influence of BMI on the viability of human skin was tested. Ca. 10 mg of test substance was applied directly on top of 0.38 cm2cultured skin. After 15 minutes, the substance was removed and cells were cultured for 42 hours. BMI showed to be a non-irritant (mean tissue viability of 91.7%). Therefore, the substance does not need to be classified according to regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
Reference
The results of the assay are summarised in the table below.
Sample |
Tissue viability as percentage of mean OD negative control |
Prediction MTT endpoint |
|||
Replicate Tissues |
Mean ± SD |
||||
a |
b |
c |
|||
Negative control |
99.2 |
106.3 |
94.6 |
100.0 ± 5.9 |
Not applicable |
Positive control |
12.9 |
12.3 |
7.6 |
10.9 ± 2.9 |
Irritant |
Test substance |
96.8 |
92.0 |
86.3 |
91.7 ± 5.3 |
Not-irritant |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14 August 2012 - 07 September 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- April 2002
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Version / remarks:
- May 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2400 (Acute Eye Irritation)
- Version / remarks:
- August 1998
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Eye Irritation (2-1-5), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 31 or 39 weeks
- Weight at study initiation: 3.69 to 4.46 kg
- Housing: Each animal was housed individually in a plastic cage with perforated floors
- Diet (e.g. ad libitum): standard laboratory rabbit diet per day
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 11 or 17 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16- 20
- Humidity (%): 40 to 70
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light - Vehicle:
- not specified
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL - Duration of treatment / exposure:
- After instillation of the test substance the eyelids of each animal were gently held together for one second before releasing
- Observation period (in vivo):
- 1, 24,48, 72 and 8 days after instillation
- Number of animals or in vitro replicates:
- 3
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): Eyes were flushed with saline for animal #1 24 hours after instillation, Eyes were flushed with saline for animal #2 24 hours and 48 hours after instillation. Eyes were not flushed for animal #3
SCORING SYSTEM: Kay and Calandra and EC (Regulation 1272/2008) and GHS classification - Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- Animal #1;#2;#3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: n/a
- Remarks on result:
- other: The scores are calculated at approximately 24, 48 and 72 hours after administration, separately for each animal
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- Animal #1;#2;#3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: n/a
- Remarks on result:
- other: The scores are calculated at approximately 24, 48 and 72 hours after administration, separately for each animal
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 8 days
- Remarks on result:
- other: The scores are calculated at approximately 24, 48 and 72 hours after administration, separately for each animal
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.7
- Max. score:
- 3
- Reversibility:
- fully reversible within: 72 hours
- Remarks on result:
- other: The scores are calculated at approximately 24, 48 and 72 hours after administration, separately for each animal
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 hours
- Remarks on result:
- other: The scores are calculated at approximately 24, 48 and 72 hours after administration, separately for each animal
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.7
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 hours
- Remarks on result:
- other: The scores are calculated at approximately 24, 48 and 72 hours after administration, separately for each animal
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 hours
- Remarks on result:
- other: The scores are calculated at approximately 24, 48 and 72 hours after administration, separately for each animal
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: n/a
- Remarks on result:
- other: The scores are calculated at approximately 24, 48 and 72 hours after administration, separately for each animal
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- An in vivo eye irritation test was performed in new zealand white rabbits. Based on the results, BMI does not have to be classified for eye irritation or serious eye damage according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
- Executive summary:
An in vivo eye irritation test was performed in new zealand white rabbits according to internationally accepted guidelines and in accordance with GLP principles. Following a instillation dose of 0.1 mL,
slight chemosis, slight to moderate discharge, and injection of the conjunctival blood vessels were noted in 1 or more animals, all clinical signs were reversed to normal within 8 days in all test animals.
Based on the results, BMI does not have to be classified for eye irritation or serious eye damage according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
SKIN IRRITATION
An in vitro skin irritation test, performed according to OECD TG 439 and in accordance with GLP principles. The influence of BMI on the viability of human skin was tested. Ca. 10 mg of test substance was applied directly on top of 0.38 cm2 cultured skin. After 15 minutes, the substance was removed and cells were cultured for 42 hours. BMI showed to be a non-irritant (mean tissue viability of 91.7%).
EYE IRRITATION
A Bovine Corneal Opacity and Permeability Assay (BCOP) (in vitro) was undertaken according to OECD TG 437 and in accordance with GLP principles. An In Vitro Irritancy Score (IVIS) was calculated using the following formula: In Vitro Irritancy Score = Corrected Opacity Value + (15 x Corrected OD490Value). The IVIS was calculated for each individual treatment and positive control cornea. The mean IVIS value for each treatment group was calculated from the IVIS of each individual cornea in the treatment group. For BMI, the IVIS score was 6.0± 0.8. Therefore BMI was predicted not to be a corrosive or severe eye irritant and additional testing should be performed for classification and labelling purposes. With the most recent update of OECD TG 437 (2017) the IVIS score of 6.0 would be interpreted as inconclusive.
An in vivo eye irritation test was performed in new zealand white rabbits according to internationally accepted guidelines (OECD TG 405) and in accordance with GLP principles. Following a instillation dose of 0.1 mL, slight chemosis, slight to moderate discharge, and injection of the conjunctival blood vessels were noted in 1 or more animals, all clinical signs were fully reversible within 8 days in all test animals. Based on the result BMI was concluded not to be an eye-irritant.
Justification for selection of skin irritation / corrosion endpoint:
The EPISKIN study (OECD TG 437) carried out by Huntingdon Life Sciences was carried out in accordance with GLP and to international guidelines and is thus reliable and is designated the key study.
Justification for selection of eye irritation endpoint:
The in vivo eye irritation study (OECD TG 405) carried out by Huntingdon Life Sciences was carried out in accordance with GLP and to international guidelines and is thus reliable and is designated the key study for this endpoint.
Justification for classification or non-classification
SKIN IRRITATION/CORROSION
Based on the results of the in vitro skin irritation test (OECD TG 439) BMI does not warrant classification for skin irritation according to regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
EYE IRRITATION
Based on the results of an in vivo eye irritation study (OECD TG 405) BMI does not warrant classification for eye irritation according to regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
RESPIRATORY IRRITATION
No information is available to enable classification as a respiratory irritant.
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