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EC number: 221-029-7 | CAS number: 2978-58-7
- 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
The test substance is determined to be corrosive to skin.
The test substance causes serious eye damage.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2017-01-17 to 2017-05-09
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
- Version / remarks:
- 2015-06-28
- Qualifier:
- according to guideline
- Guideline:
- other: New guidance document on an integrated approach on testing and assessment (IATA) for skin corrosion and irritation, Series on Testing and Assessment No. 203
- Version / remarks:
- 2014-07-11
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- - Name (as cited in the study): Golpanol MPA
- Purity: 99.2 area%
- Batch Nr.: 85603856PO
- Batch Nr.:
- Contet: w(C5H9N) = 89.2 g/100 g
- Homogeneity: the test substance was homogeneous by visual inspection
- pH value: ca. 6
- Physical state / color: liquid / colorless, clear
- Storage conditions: room temperature - Test system:
- artificial membrane barrier model
- Remarks:
- Corrositex assay
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- The Corrositex® assay was conducted according to the methods described in the Corrositex® Instruction Manual, InVitro International, Irvine CA, USA and Transia GmbH, 35510 Butzbach, Germany 10 April 2016.
- Test kit: Corrositex®, InVitro International, Irvine CA, USA, containing: reagents required for qualification and categorization screen,
biobarrier matrix powder and diluent, membrane discs and vials containing the Chemical Detection System.
- Fume hood: The assay was run in a fume hood - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- amount applied: single topical application of 500µL test substance
VEHICLE
- test substance was applied undiluted
NEGATIVE CONTROL
- amount apllied: 500 µL 10% citric acid
POSITIVE CONTROL
- amount applied: one pellet of sodium hydroxide - Duration of treatment / exposure:
- - min. 3 minutes, max. 60 minutes (negative control)
- Number of replicates:
- Four vials were used for the test substance and one vial for the positive control and negative control each.
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Duration of treatment / exposure:
- min. 3 minutes, max. 60 minutes (negative control)
- Details on study design:
- ACCEPTANCE CRITERIA
1. breakthrough time for the positive control substance was in the historic control range (mean ± 2-3x standard deviations)
2. negative control was not to induce membrance breakthrough within a 60-minute observation period. - Irritation / corrosion parameter:
- penetration time (in minutes)
- Value:
- 7.01
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Other effects / acceptance of results:
- ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Range of historical values if different from the ones specified in the test guideline: breakthrough time of NaOH (solid, historical data) was 12.10 minutes. - Interpretation of results:
- Category 1B (corrosive) based on GHS criteria
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2017-01-17 - 2017-05-09
- 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)
- Version / remarks:
- 2015-07-28
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Version / remarks:
- 2012-07-06
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- - Name (as cited in the study): Golpanol MPA
- Purity: 99.2 area%
- Batch Nr.: 85603856PO
- Contet: w(C5H9N) = 89.2 g/100 g
- Homogeneity: the test substance was homogeneous by visual inspection
- pH value: ca. 6
- Physical state / color: liquid / colorless, clear
- Storage conditions: room temperature - Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- TEST SYSTEM
- Test kit: EpiDerm™ 200, MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia, containing: 24 EPI-200 tissues (reconstructed epidermis); surface 0.6 cm² cultured in Millicells®, diameter 1 cm
- Tissue for MTT reduction control: EPI-200 tissue that is killed by freezing at –20°C
- Assay medium: EPI-100-ASY assay medium
- MTT diluent: Dulbecco's modified eagle's medium (DMEM) based medium used for diluting MTT (MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia / Sigma, Germany)
- Wash buffer: Dulbecco's phosphate buffered saline (PBS), w/o Ca2+, Mg2+ (MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia and
Biochrom, Germany)
- Detection agent: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) (MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia /
Sigma, Germany), 1.0 mg / mL MTT diluent
- Extracting agent: Isopropanol p.a.
- Incubation conditions: 37°C ± 1°C, 5% ± 1%CO2, 90% ± 5% humidity
EQUIPMENT
- Laminar flow bench: HERAsafe KS 18 (Thermo ELECTRON CORPORATION)
- CO2 incubator: Heraeus BBD 6220
- Spectrophotometer: SunriseTM Absorbance Reader for the determination of the optical density of colored extracts (filter wavelength: 570 nm without reference filter)
CONTROLS
Negative control (NC): PBS, sterile
Positive control (PC): 5% (w/v) sodium dodecyl sulfate (SDS) in water
MTT reduction control: PBS, sterile or test substance (irritation test) - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- - 30 μL undiluted liquid test substance
- Control: 30 μL sterile PBS (negative control NC, NC KC) or with 30 μL 5% SDS (positive control PC) or test substance (killed control KC) - Duration of treatment / exposure:
- - 25 minutes at room temperature
- 35 minutes in the incubator - Duration of post-treatment incubation (if applicable):
- - First step: 24 +/- 2 hours
- Second step (after medium peplacement): 18 +/- 2 hours
- Step 3: 3 hours - Number of replicates:
- - Three tissues each for test substance, negative control, positive control and killed control
- Details on study design:
- ACCEPTANCE CRITERIA
1) Barrier function and Quality control (QC):
- lower acceptance limit: ET50 = 4.0 hours
- upper acceptance limit: ET50 = 8.7 hours
2) Negative control (NC):
- mean OD_570 of the NC is ≥ 0.8
- mean OD_570 of the NC should not exceed 2.8
3) Positive control (PC):
- viability of ≤ 20%
4) Inter-tissue variability (between all treatments):
- SD of % viability is ≤ 18%
5) Killed controls (KC):
- OD_570 for the KC of the NC should be ≤ 0.35
- OD_570 value for direct MTT reduction of a test substance should be ≤ 30% of the OD570 of the NC - Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- exposure period: 1 h
- Value:
- 2
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2017-01-17 to 2017-05-09
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- - Name (as cited in the study): Golpanol MPA
- Purity: 99.2 area%
- Batch Nr.: 85603856PO
- Contet: w(C5H9N) = 89.2 g/100 g
- Homogeneity: the test substance was homogeneous by visual inspection
- pH value: ca. 6
- Physical state / color: liquid / colorless, clear
- Storage conditions: room temperature - Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- TEST SYSTEM
- Test kit: EpiDerm™ 200, MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia, containing: 24 EPI-200 tissues (reconstructed epidermis): surface 0.6 cm² cultured in Millicells®, diameter 1 cm
- Tissue for MTT reduction control: EPI-200 tissue that is killed by freezing at –20°C
- Assay medium: EPI-100-ASY assay medium
- MTT diluent: Dulbecco's modified eagle's medium (DMEM) based medium used for diluting MTT (MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia / Sigma, Germany)
- Wash buffer: Dulbecco's phosphate buffered saline (PBS), w/o Ca2+, Mg2+ (MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia and
Biochrom, Germany)
- Detection agent: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) (MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia /
Sigma, Germany), 1.0 mg / mL MTT diluent
- Extracting agent: Isopropanol p.a.
INCUBATION CONDITIONS
- 37°C ± 1°C, 5% ± 1%CO2, 90% ± 5% humidity
EQUIPMENT
- Laminar flow bench: HERAsafe KS 18 (Thermo ELECTRON CORPORATION)
- CO2 incubator: Heraeus BBD 6220
- Spectrophotometer: SunriseTM Absorbance Reader for the determination of the optical density of colored extracts (filter wavelength: 570 nm without reference filter)
CONTROLS
- Negative control (NC): Deionized water
- Positive control (PC): 8-N potassium hydroxide solution
- MTT reduction control: Deionized water or test substance - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- yes, concurrent MTT non-specific colour control
- Amount/concentration applied:
- - 50 μL undiluted liquid test substance
- Control: 50 μL deionized water (negative control NC, NC KC) or with 50 μL 8 N potassium hydroxide (positive control PC) or test substance (KC) - Duration of treatment / exposure:
- 3 min, 1 h
- Number of replicates:
- - 2 tissues per exposure time (3 minutes at room temperature or 1 hour in the incubator) and test group (test material, negative control and positive control; 12 tissues per test)
- 2 killed control tissues per exposure time were treated with the test substance and the NC, respectively, to detect direct MTT reduction - Details on study design:
- ACCEPTANCE CRITERIA
1) Barrier function and Quality control (QC):
- Lower acceptance limit: ET50 = 4.0 hours
- Upper acceptance limit: ET50 = 8.7 hours
2) Negative control NC:
- mean OD_570 of the NC is ≥ 0.8
- mean OD_570 of the NC should not exceed 2.8
3) Positive control PC:
- tissue viability of ≤ 30% is acceptable for the 3-minute exposure
- mean viability of the tissues exposed for 1 hour should be <15%
4) Variability of the tissues:
- coefficient of variation (CV) of % viability is ≤ 30% (in the range of 20% and 100% viability)
5) Killed controls KC:
- OD_570 for the KC of the NC should be ≤ 0.35
- OD_570 value for direct MTT reduction of a test substance should be ≤ 30% of the OD570 of the NC - Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- Exposure period: 3 min
- Run / experiment:
- 1
- Value:
- 78.2
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- Exposure period: 1 h
- Run / experiment:
- 2
- Value:
- 5.2
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- In the first run, the results of the KC indicated an increased MTT reduction (mean viability 0.5 % of NC). Thus, for the test substance the final mean viability is given after KC correction.
- Interpretation of results:
- Category 1B (corrosive) based on GHS criteria
- Remarks:
- According to OECD TG 431 a combination of optional Sub-categories 1B-and-1 C
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1979-10-06
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Qualifier:
- no guideline followed
- Qualifier:
- according to guideline
- Guideline:
- other: internal method comparabel to OECD TG 404
- Principles of method if other than guideline:
- Documentation insufficient.
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Concentration: 8% and 16% aqueous solution
- Physical state: liquid - Species:
- rabbit
- Strain:
- not specified
- Type of coverage:
- not specified
- Preparation of test site:
- not specified
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- not specified
- Duration of treatment / exposure:
- 1, 5, 15 minutes; 20 hours
- Observation period:
- 24 hours
- Number of animals:
- 2
- Details on study design:
- no details available
- Irritation parameter:
- other:
- Remarks:
- See any other information on results including table
- Basis:
- other:
- Remarks:
- See any other information on results including table
- Time point:
- other: See any other information on results including table
- Score:
- ca.
- Reversibility:
- other:
- Remarks:
- See any other information on results including table
- Remarks on result:
- probability of severe irritation
- Remarks:
- See any other information on results including table
- Interpretation of results:
- study cannot be used for classification
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- internal test method, grading and scoring according to Draize (1959)
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Purity: assumed to contain 100% active ingredient
- Appearance: clear, colorless liquid, pungent odor
- Date received:1969-03-25 - Species:
- rabbit
- Strain:
- other: White New Zealand
- Details on test animals or test system and environmental conditions:
- - test animals were immobilized in a multiple animal restrainer during exposure
- feed (Purina Rabbit Chow and water) was available ad libitum after exposure - Type of coverage:
- occlusive
- Preparation of test site:
- other: clipped, abraded, intact
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- not specified
- Amount / concentration applied:
- 0.5 mL
- Duration of treatment / exposure:
- 24 hours
- Observation period:
- 24, 48, and 72 hours after application
- Number of animals:
- 6
- Details on study design:
- - 24-hour patch test comparable to OECD Guideline 404
- single application of 0.5 mL undiluted test substance on intact (three animals) and abraded skin (three animals)
- trunks of the test animals were wrapped with a rubber dam after application
- test animals were immobilized in a multiple animal restrainer during exposure period
- patches removed after exposure period
- evaluated for gross signs of primary irritation at 24, 48, and 72 hours after application.
- posttreatment: feed (Purina Rabbit Chow and water) was available ad libitum.
- grading and scoring according to index scheme of Draize (1959) - Irritation parameter:
- primary dermal irritation index (PDII)
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 2.67
- Reversibility:
- not specified
- Remarks on result:
- positive indication of irritation
- Remarks:
- Index arbitrary because of blanching effect on abraded sites
- Irritant / corrosive response data:
- Very slight (one intact site only) to severe erythema noted on abraded and intact sites from 24 hours through 72 hours and slight edema at 24 hours on one intactsite only. Blanching was noted on the abraded sites from 24 hours through 72 hours and dark brown areas observed on exposed sites of two abraded and one intact animal.
- Interpretation of results:
- Category 2 (irritant) based on GHS criteria
Referenceopen allclose all
Breakthrough times of the test substance, the negative control (NC) and positive control (PC). NB = no breakthrough within maximum observation period (60 minutes).
Test Substance |
Break Through Time [min:s] |
||||
Vial 1 |
Vial 2 |
Vial 3 |
Vial 4 |
Mean |
|
8:48 |
6:49 |
7:01 |
5:26 |
7:01 |
|
Controls: |
|||||
PC: sodium hydroxide, solid |
13:27 |
- |
- |
- |
- |
NC: 10% citric acid |
NB |
- |
- |
- |
- |
Individual and mean OD570 values, individual and mean viability values and standard deviations (SD).
Exposure period: 1 h |
|||||||
Test substance identification |
|
|
tissue 1 |
tissue 2 |
tissue 3 |
mean |
SD |
Negative control |
viable tissues |
mean OD570 |
1.900 |
1.797 |
1.810 |
1.836 |
|
viability [% of NC] |
103.5 |
97.9 |
98.6 |
100.0 |
3.1 |
||
KC tissues |
mean OD570 |
0.055 |
0.065 |
0.052 |
0.057 |
|
|
viability [% of NC] |
3.0 |
3.5 |
2.8 |
3.1 |
0.4 |
||
Test substance |
viable tissues |
mean OD570 |
0.037 |
0.036 |
0.036 |
0.036 |
|
viability [% of NC] |
2.0 |
2.0 |
2.0 |
2.0 |
0.0 |
||
KC tissues |
mean OD570 KC NC corrected |
0.000 |
0.000 |
0.000 |
0.000 |
|
|
viability [% of NC] |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
||
Final mean viability of tissues after KC correction [% of NC] |
5.2 |
2.0 |
|
||||
Positive control |
viable tissues |
mean OD570 |
0.036 |
0.041 |
0.036 |
0.037 |
|
viability [% of NC] |
1.9 |
2.2 |
1.9 |
2.0 |
0.2 |
Exposure period 3 min: Individual and mean OD570 values, individual and mean viability values, standard deviations (SD) and coefficient variation (CV).
Exposure period: 3 min |
|||||||
Test substance identification |
|
|
tissue 1 |
tissue 2 |
mean |
SD |
CV [%] |
Negative control |
viable tissues |
mean OD570 |
1.527 |
1.721 |
1.624 |
|
|
viability [% of NC] |
94.0 |
106.0 |
100.0 |
8.5 |
8.5 |
||
KC tissues |
mean OD570 |
0.085 |
0.091 |
0.088 |
|
|
|
viability [% of NC] |
5.2 |
5.6 |
5.4 |
0.2 |
|
||
Test substance |
viable tissues |
mean OD570 |
1.195 |
1.364 |
1.279 |
|
|
viability [% of NC] |
73.6 |
84.0 |
78.8 |
7.4 |
9.3 |
||
KC tissues |
mean OD570 KC NC corrected |
0.005 |
0.012 |
0.009 |
|
|
|
viability [% of NC] |
0.3 |
0.8 |
0.5 |
0.3 |
|
||
Final mean viability of tissues after KC correction [% of NC] |
78.2 |
|
|
||||
Positive control |
viable tissues |
mean OD570 |
0.159 |
0.244 |
0.202 |
|
|
viability [% of NC] |
9.8 |
15.0 |
12.4 |
3.7 |
29.8 |
Exposure period 1 hour: Individual and mean OD570 values, individual and mean viability values, standard deviations (SD) and coefficient variation (CV).
Exposure period: 1 h |
|||||||
Test substance identification |
|
|
tissue 1 |
tissue 2 |
mean |
SD |
CV [%] |
Negatvie control |
viable tissues |
mean OD570 |
1.659 |
1.564 |
1.612 |
|
|
viability [% of NC] |
102.9 |
97.1 |
100.0 |
4.1 |
4.1 |
||
KC tissues |
mean OD570 |
0.101 |
0.123 |
0.112 |
|
|
|
viability [% of NC] |
6.3 |
7.6 |
7.0 |
1.0 |
|
||
Test substance |
viable tissues |
mean OD570 |
0.086 |
0.083 |
0.084 |
|
|
viability [% of NC] |
5.3 |
5.1 |
5.2 |
0.1 |
2.5 |
||
KC tissues |
mean OD570 KC NC corrected |
0.000 |
0.000 |
0.000 |
|
|
|
viability [% of NC] |
0.0 |
0.0 |
0.0 |
0.3 |
|
||
Final mean viability of tissues after KC correction [% of NC] |
5.2 |
|
|
||||
Positive control |
viable tissues |
mean OD570 |
0.097 |
0.085 |
0.091 |
|
|
viability [% of NC] |
6.0 |
5.3 |
5.6 |
0.5 |
9.7 |
Table 1: Reported test results.
Body site | Duration of exposure |
Findings after 24 hours |
Findings after 6 days |
back |
1 minute |
no effects |
no effects |
back |
5 minutes |
erythema (doubtful) |
|
back |
15 minutes |
intense erythema |
|
back |
20 hours |
slight necrosis / surrounded by an erythematous border |
massive necrosis |
ear |
20 hours |
intense redness / blisters / anemic |
Table 2: Data reported transferred into the OECD TG 404 scoring system according to GAMER & ROSSBACHER (2002).
Exposure duration |
Observation period |
|
24 hours after exposure |
8 days after exposure |
|
1 min. |
0 |
0 |
5 min. |
0-1 |
0 |
15 min. |
1-2 |
0 |
20 hours |
2 (necrosis) |
2 (necrosis) |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (corrosive)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2017-01-05 to 2017-04-28
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- 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)
- Qualifier:
- according to guideline
- Guideline:
- EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
- Version / remarks:
- 2010-12-08
- Qualifier:
- according to guideline
- Guideline:
- other: see remarks
- Version / remarks:
- Schrage A, Kolle SN, Rey Moreno MC, Norman K, Raabe H, Curren R, van Ravenzwaay B, and Landsiedel R (2011). The Bovine Corneal Opacity and Permeability Test in Routine Ocular Irritation Testing and its Improvement within the Limits of OECD Test Guideline 437. ATLA 39: 37–53.
- Qualifier:
- according to guideline
- Guideline:
- other: see remarks
- Version / remarks:
- Kolle SN, Rey Moreno MC, Mayer W, van Cott A, van Ravenzwaay B, Landsiedel R. (2015). The EpiOcular™ Eye Irritation Test is the Method of Choice for the In Vitro Eye Irritation Testing of Agrochemical Formulations: Correlation Analysis of EpiOcular Eye Irritation Test and BCOP Test Data According to the UN GHS, US EPA and Brazil ANVISA Classification Schemes. ATLA 43: 181-198.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)
- Version / remarks:
- Test was waived.
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- - Name (as cited in the study): Golpanol MPA
- Purity: 99.2 area%
- Content: w(C5H9N) = 89.2 g/100 g
- pH value: ca. 6 (undiluted test substance, determined in the lab prior to start of the GLP study)
- Physical state / color: liquid / colorless, clear
- Storage conditions: room temperature - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- - Test substance: 750 μL (single topical application of undiluted test substance to the epithelial surface of isolated bovine corneas)
- Negative control (NC): 750 μL of deionized water
- Positive controls (PC 1 /PC 2): 750 μL 100% ethanol / 100% dimethylformamide - Duration of treatment / exposure:
- - 10 minutes
- Duration of post- treatment incubation (in vitro):
- - 2 hours
- Number of animals or in vitro replicates:
- The test substance, a negative control (NC; deionized water) and positive controls (PC1 / PC2; 100% ethanol / 100% dimethylformamide) were applied to three corneas each.
- Details on study design:
- TEST SYSTEM
- Test system: isolated bovine cornea
- Source: obtained as a by-product of freshly slaughtered cattle (age of the animals: minimum 12 months, maximum 60 months)
- Supplier: Schlachthof Mannheim, Schlachthofstr. 21, 68165 Mannheim, Germany
DATA EVALUATION
- In Vitro Irritancy Score (IVIS)
- Permeability Score
- In Vitro Irritancy score (IVIS)
- Histopathological findings
TREATMENT GROUPS
- Test substance
- Negative control (NC): Deionized water
- Positive control (PC): 100% ethanol (PC1) / 100% dimethylformamide (PC2) for liquid test substances and surfactants
- 100% dimethylformamide was additionally used to increase the historic database of the PC.
ACCEPTANCE CRITERIA
1) PC gives an IVIS that falls within two standard deviations of the current historic mean
2) NC responses should result in opacity and permeability values that are not higher than the established upper limits
3) variability between the corneas treated per test substance should be acceptably low
MATERIALS
- Corneal holder: Supplier: BASF SE, Germany
- Incubator: Temperature 32 ± 1°C
- Opacitometer: Kit BASF-OP3.0, BASF SE, Germany
- Spectrophotometer: SunriseTM Absorbance Reader
- Measurement using wavelength of 490 nm
REAGENTS
- Hanks' Balanced Salt Solution with Ca2+ and Mg2+ (HBSS) (Biochrom, Germany) containing Fetal Bovine Serum (FBS) and/or Penicillin/Streptomycin (P/S)
- Eagle’s MEM without phenol red (Biochrom, Germany) containing FBS and P/S
- Eagle´s MEM with phenol red (Biochrom, Germany)
- Sodium fluorescein diluted in DPBS
ANALYSIS
- No analysis of test substance preparation was performed because the test substance was applied undiluted
POST-EXPOSURE TREATMENT
- washed at least 3 times with Eagle’s MEM (containing phenol red) and once with Eagle’s MEM (without phenol red)
- incubation (2 hours)
INCUBATION CONDITIONS
- Temperature: 32°C
MEASUREMENT OF FINAL CORNEAL OPACITY
- visual observations
- opacitometer
REMARKS
Two in vitro assays were part of this in vitro eye irritation test strategy: The Bovine Corneal Opacity and Permeability Test (BCOP Test) and EpiOcular Eye Irritation Test. However, in case of Golpanol MPA, the results derived with BCOP alone were sufficient for a final assessment. Therefore, further testing in EpiOcular was waived. - Irritation parameter:
- cornea opacity score
- Value:
- 38.4
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- in vitro irritation score
- Value:
- 73.6
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- fluorescein leakage
- Value:
- 2.352
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: mean corrected OD490 value
- Irritation parameter:
- other: histopathological score of irritation (HSI)
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Remarks:
- severe findings
- Interpretation of results:
- Category 1 (irreversible effects on the eye) based on GHS criteria
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1969-05-06
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- internal method
- Principles of method if other than guideline:
- The potential of acute eye irritation was assessed by a single instillation of 0.1 mL test substance into the conjunctival sac of the left eye of nine rabbits. Three eyes were irrigated with tap water two seconds after application, three after four seconds and three eyes were not irrigated, but held closed for one second. During the test, untreated right eyes served as controls. Body weights were recorded both initially and terminally. Corneal demage was proven on day 7, 10 or 14 with 2.0% sodium fluorescein stain. Observations on gross pathology and systematic toxicology were made 24, 48, and 72 hours and 4, 7, 10, and 14 days following application. The acute eye irritation was graded according to Draize, J. H., from the Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics, Assn. of Food and Drug Offcials of the U. S., Austin, Texas, 1959.
- GLP compliance:
- no
- Specific details on test material used for the study:
- - clear, colorless liquid with a pungent odor
- material assumed to contain 100% active ingredient - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- - Body weight range at initiation: 2.0 to 3.1 kg.
- Diet: Purina Rabbit Chow and water available ad libitum
- eyes judged free of irritation and corneal damage (confirmed by sodium fluorescein examination) prior to initiation of study - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes
- other: untreated right eyes served as controls.
- Amount / concentration applied:
- - 0.1 mL
- Duration of treatment / exposure:
- - two and four seconds
- Observation period (in vivo):
- 14 days
- Number of animals or in vitro replicates:
- 9 individuals
- Details on study design:
- - Application of test substance: single application into the conjunctival sac of the left eye
- Posttreatment: 3 eyes irrigated with 20 mL tap water two seconds after application; 3 eyes not irrigated but held closed for 2 seconds - Irritation parameter:
- other: histopathological observations
- Remarks on result:
- other: See "Any other information on results incl. tables"
- Interpretation of results:
- study cannot be used for classification
Referenceopen allclose all
Test substance identification |
Mean Opacity Value |
Mean Permeability Value |
Mean In Vitro Irritancy Score |
Test Substance |
38.4 |
2.352 |
73.6 |
Negative Control |
2.4 |
0.000 |
2.4 |
Positive Control 1 (Ethanol) |
24.1 |
0.931 |
38.0 |
Positive Control 2 (DMF) |
99.6 |
0.517 |
107.4 |
1. Principal Toxic Effects
On day 4, one animal with the eye irrigated after two seconds died. Several animals blinked and preened themselves immediately after application of the test item. Four animals showed moderate weight loss.
2. Gross Pathology
The following gross signs were observed: Blanched conjunctivae, marked conjunctival erythema in one irrigated eye, slight to marked chemosis and discharge, slight to moderate iritis, and slight to marked corneal opacity was noted from day through day 14. On Day 7, Day 10, and Day 14 corneal vascularization was noted in two eyes irrigated after two seconds. Due to extreme irritation and destruction of the eye, four irrigated eyes and the three nonirrigated eyes could not be completely graded by Day 10 or Day 14.
3. Terminal Fluorescein Examination
Corneal damage was shown on day 14 in two eyes irrigated after two seconds, in two eyes irrigated after four seconds and in the three nonirrigated eyes. Staining was not possible in the remaining two irrigated eyes because the animal died or the eye was destructed completely.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irreversible damage)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin:
In vitro
An in vitro irritation test (BASF SE, 70V0058/16A191, 2017) was conducted under GLP conditions according to OECD TG 439 and EU Method B 46 by a single topical application of 30 μL undiluted test substance to a reconstructed three-dimensional human epidermis model (EpiDerm™). The test was performed with three EpiDerm™ tissues which were incubated with the test substance for 1 hour followed by a 42-hour post-incubation period. The mean viability of the tissues treated with the test substance was 2.0%. All validity criteria were fulfilled. According to the decision criteria in OECD TG 439, the test substance is to be regarded as irritant.
The potential of the test item to cause dermal corrosion was investigated under GLP conditions according to OECD TG 435 (BASF SE, 70V0058/16A191, 2017) in the in vitro membrane barrier test (CorrostexTM). 500 µL of the undiluted test substance were given to the Corrositex® Biobarrier Membrane by a single topical application. Simultaneously, a positive control (sodium hydroxide, solid) and a negative control (10% citric acid, 500µL) were investigated. Four vials were used for the test substance and one vial for the positive control and negative control each. The exposure duration was between min. 3 minutes and max. 60 minutes (negative control). In result, the mean breakthrough time of the test substance was 7 minutes and 1 second. Therefore, the test substance has to be regarded as corrosive.
A Reconstructed Human Epidermis (RHE) Test under GLP conditions according to OECD TG 431 (BASF SE, 70V0058/16A191, 2017) was performed. Endpoint chosen was the reduction of mitochondrial dehydrogenase activity measured by reduced formazan production after incubation with a tetrazolium salt (MTT). Two EpiDerm™ tissues per exposure time and test group were treated by a single topical application with 50 µL undiluted test substance (test item and freeze-killed control), with 50 µL deionized water (negative control, freeze-killed control) or with 50 µL 8 N potassium hydroxide (positive control). The mean viability of the tissues treated with the test substance determined after an exposure period of 3 minutes was 78.2%, and it was 5.2% after an exposure period of 1 hour. All validity criteria were fulfilled. Based on these results, the test item is considered to be corrosive according to OECD TG 431.
In vivo
In an in vivo study (Dow AgroSciences, DR-0385-4500-099, 1969), the primary skin irritation was assessed by a 24-hour patch test comparable to OECD Guideline 404. Three adult albino rabbits of the New Zealand strain were dermally exposed (intact sites) to 0.5 mL undiluted test substance for 72 hours under occlusive conditions (patches were removed after 24 hours of exposure). Grading and scoring of skin irritation was performed following the index scheme of Draize (1959). Several clinical and gross pathological signs were observed. After 24 hours slight edema and from 24 hours through 72 hours severe erythema were noted. In result, the mean Primary Irritation Index for intact sites was 2.25. Under the conditions of the present experiment the test substance was found to be irritant and corrosive when applied to the rabbit skin.
In an additional study with low reliability due to methodological, reporting and assessment deficiencies, the skin irritation potential (BASF, XXI-245, 1972) was investigated according to an internal method. The report describes findings after 24 hours and 8 days. The obtained results indicated a strong irritation potential.
Eye:
In vitro
To assess the eye irritating effect of the test substance, a Bovine Corneal Opacity and Permeability Test (BCOP Test) according to OECD TG 437, EU method B.47 and the methods described in Schrage et al. (2011) and Kolle et al. (2015) was conducted. The epithelial surface of three isolated bovine corneas was exposed to a single topical application of 750 μL undiluted test substance for the duration of 10 minutes at 32 °C. Simultaneously, a negative control (750 μL deionized water) and positive controls (750μL 100% ethanol and 100% dimethylformamide respectively) were investigated with three replicates each. In result, a mean In Vitro Irritancy Score (IVIS) of 73.6 was derived, based on a mean Opacity Score of 38.4. The mean Permeability Value was 2.352. Furthermore, severe histopathological damages occured. All validity criteria were fulfilled. Based on the decision criteria cited in OECD TG 437, the test substance has to be classified as GHS Category 1.
In vivo
In an in vivo study (Dow AgroSciences, DR-0385-4500-099, 1969), the potential of acute eye irritation was assessed by a single instillation of 0.1 mL test substance into the conjunctival sac of the left eye of nine rabbits. Three eyes were irrigated with tap water two seconds after application, three after four seconds and three eyes were not irrigated, but held closed for one second. During the test, untreated right eyes served as controls. The acute eye irritation was graded according to Draize (1959). Several clinical signs were noted during the study period. By staining with fluorescein, corneal damage was shown on day 14 in two eyes irrigated after two seconds, in two eyes irrigated after four seconds as well as in the three non-irrigated eyes. Staining was not possible in the remaining two irrigated eyes because either the animal died or the eye was destructed completely. According to GHS criteria, the test substance has to be regarded as irritating to the eyes (GHS Category 1).
In an additional study with low reliability due to methodological, reporting and assessment deficiencies, the e
ye irritation potential was investigated according to an internal test method (BASF SE.XXI245, 1972). Reported test results indicated a severe eye irritation potential.
Justification for classification or non-classification
Classification, Labelling, and
Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for
classification purposes. Based on available data on skin
irritation/corrosion and eye irritation, the test item is classified
for skin corrosion GHS Category 1B (H 314: Causes severe skin
burns and eye damage) and for eye irritation Category 1 ( H318:
Causes serious eye damage) according to Regulation (EC)
No 1272/2008 (CLP) as amended for the tenth time in Regulation (EU) No
2017/776.
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