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EC number: 860-695-9 | CAS number: 88247-41-0
- 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 vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 29 Mar 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
- Version / remarks:
- adopted in 2020
- Deviations:
- yes
- Remarks:
- demonstration of technical proficiency of the testing facility was not included in the study report but provided separately
- GLP compliance:
- yes
Test material
- Reference substance name:
- N,N-bis(2-ethylhexyl)formamide
- EC Number:
- 860-695-9
- Cas Number:
- 88247-41-0
- Molecular formula:
- C17H35NO
- IUPAC Name:
- N,N-bis(2-ethylhexyl)formamide
- Test material form:
- liquid
Constituent 1
Test animals / tissue source
- Species:
- cattle
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: Hokkaido Livestock Corporation, Douo Plant, Hayakita Factory
- Characteristics of donor animals: The eyeballs of healthy cattle aged from 12 months to less than 60 months were used.
- Storage, temperature and transport conditions of ocular tissue: The eyeballs collected were immersed in HBSS (Hank’s Buffered Salt Solution) and transported at less than 20 °C until use in test operation. During storage and transportation, the temperature ranged from 10 – 13 °C.
- Time interval prior to initiating testing: The corneas were isolated on the same day after delivery of the eyes and directly used in the BCOP test on the same day.
- Indication of any existing defects or lesions in ocular tissue samples: The eyeballs were macroscopically observed and examined for defects including corneal opacity, scratches and neovascularisation.
- Preparation of corneas: The corneas were dissected with a 2 – 3 mm rim of the sclera remaining and were immersed in HBSS. A specifically designed corneal holder was used to mount each cornea.
- Quality check of the isolated corneas: Following equilibration, the opacity value of each cornea was measured using the opacitometer (BASF-OP3.0).
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL (also negative and positive controls)
- Amount applied: 750 µL
- Duration of treatment / exposure:
- 10 min at 32 ± 1 °C
- Duration of post- treatment incubation (in vitro):
- 2 h at 32 ± 1 °C
- Number of animals or in vitro replicates:
- Three corneas were used for each treatment group.
- Details on study design:
- TREATMENT METHOD: Open chamber method
Each isolated cornea was mounted in a specially designed cornea holder, which consists of anterior and posterior compartments, which interfaced with the epithelial and the endothelial sides of the cornea, respectively. Both compartments of the holder were filled with phenol red-free minimum essential medium. Thereafter, the corneas were immersed in the medium and equilibrated for 1 h 7 min at 32 ± 1 °C (actual temperature: 32.0 – 32.2 °C). Following the equilibration, the medium of both chambers was exchanged and the basal opacity was determined. The cornea was then macroscopically observed again for defects including opacity, scratches and neovascularisation. In the measurement and observation, no abnormalities were observed in any cornea. For treatment, the medium in the anterior chamber of the corneal holder was removed and 750 µL of the test item, negative or positive control were added on the surface of the cornea. The cornea holder was kept in a horizontal position and incubated at 32 ± 1 °C for 10 min (actual temperature: 32.1 – 32.2 °C).
REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: After exposure, the test item or the control items were removed from the anterior chamber of the corneal holder and the epithelial layer was washed with phenol red-containing minimum essential medium at least 3 times until no visual evidence of the test article was observed. At the end of washing with phenol red-containing medium, the epithelial layer was finally washed with phenol red-free medium.
- POST-EXPOSURE INCUBATION: 2 h at 32 ± 1 °C in phenol red-free medium (actual temperature: 31.9 – 32.2 °C).
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: Following the 2 h post-incubation after exposure, each cornea was macroscopically observed for tissue peeling, residual test article and non-uniform opacity patterns. No abnormalities were noted in each group. Thereafter, the anterior and posterior chambers were refilled with fresh phenol red-free medium and the opacity value of each cornea was measured using the opacitometer (BASF-OP3.0).
- Corneal permeability: After measurement of the corneal opacity, the medium was removed from the anterior chamber of the cornea holder and 1 mL of sodium fluorescein was injected into the anterior chamber. In a horizontal position, the cornea holder was incubated for 90 min at 32.0 - 32.1 °C. The passage of sodium fluorescein dye was measured at 490 nm and recorded as optical density (OD490) with an ultraviolet visible spectrophotometer (UV-2600, Shimadzu Corporation).
SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
DECISION CRITERIA:
Test substance with an IVIS > 55 was regarded as Category 1.
Test substance with an IVIS ≤ 3 was regarded as No Category.
Test substance with an IVIS > 3 ≤ 55: no stand-alone prediction can be made.
Results and discussion
In vitro
Results
- Irritation parameter:
- in vitro irritation score
- Remarks:
- mean value of 3 corneas
- Run / experiment:
- 10 min exposure
- Value:
- 5.6
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- DEMONSTRATION OF TECHNICAL PROFICIENCY:
Demonstration of technical proficiency of the testing laboratory was not included in the study report but provided as a separate document. 8 of the 13 proficiency chemicals indicated by the OECD guideline 437 were tested in the BCOP test. All proficiency chemicals were correctly categorised.
ACCEPTANCE OF RESULTS: (refer to Table 1 under "Any other information on results incl. tables")
- Acceptance criteria met for negative control: yes, the opacity and permeability values of the negative control were less than the upper limit of the historical control range of opacity and permeability values.
- Acceptance criteria met for positive control: yes, the IVIS of the positive control was within 2 standard deviations of the latest historical control mean of the IVIS of the testing facility.
Any other information on results incl. tables
Table 1: Summary of results
Test group | Number of corneas | Opacity | Permability | IVIS |
Mean corrected final opacity# | Mean corrected OD490 change## | |||
Negative control (distilled water) |
3 | 1.0x | 0.000xx | 1.0 |
Test item | 3 | 5.0 | 0.043 | 5.6 |
Positive control (Dimethylformamide) |
3 | 109.3 | 1.221 | 127.6 |
x mean final opacity; xx: mean OD490 change #: (Mean final opacity) - (Mean final opacity of negative control) ##: (OD490 change) - (Mean OD490 change of negative control) |
Table 2: Historical control data generated in the testing facility from Jul 2012 - Feb 2021
Control | No. of data | IVIS | Permeability | Opacity | |||||||
Mean ± SD | Range | Mean ± 2 SD | Mean ± SD | Range | Mean ± 2 SD | Mean ± SD | Range | Mean ± 2 SD | |||
Negative | Distilled water | 176 | 0.4 ± 0.8 | -2.0 - 2.4 | -1.2 - 2.0 | 0.005 ± 0.005 | -0.003 - 0.030 | -0.005 - 0.015 | 0.4 ± 0.8 | -2.0 - 3.0 | -1.2 - 2.0 |
Positive | Dimethylformamide | 115 | 101.3 ± 15.1 | 42.3 - 143.4 | 71.1 - 131.5 | 0.953 ± 0.346 | 0.171 - 1.966 | 0.261 - 1.645 | 87.0 ± 11.6 | 38.0 - 120.0 | 63.8 - 110.2 |
Applicant's summary and conclusion
- Interpretation of results:
- other: not corrosive
- Conclusions:
- Based on the experimental results, the test item produced an IVIS score of 5.6, which is classified in "no stand-alone prediction is possible" based on GHS criteria.
There is regulatory acceptance in the EU that a substance can be considered corrosive (Eye Corrosive Cat. 1) based on a positive result in the Bovine corneal opacity and permeability test method. A result for which no prediction can be made is not conclusive with respect to non-classification or classification as an eye irritant and therefore requires further evaluation and/or data generation.
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