Registration Dossier
Registration Dossier
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EC number: 221-882-5 | CAS number: 3268-49-3
- 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
Acute Toxicity: other routes
Administrative data
- Endpoint:
- acute toxicity: other routes
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Remarks:
- (limited documentation, purity of test material not indicated, no details on animals and environmental conditions)
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- adopted 09 Oct. 2017
- Deviations:
- yes
- Remarks:
- no experimental details given, no body weight and no clinical signs recorded, no scoring according to Draize criteria, no data on analytical purity, no details on animals and environmental conditions, occlusive dressing
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- other: OFA
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 250 g (males) and 200 g (females) - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Duration of exposure:
- 24 h
- Doses:
- 0.25, 0.5, 1, 2 mL/kg bw corresponding to 259, 518, 1036 and 2072 mg/kg bw
- No. of animals per sex per dose:
- 0.25, 0.5 and 1 mL/kg bw (corresponding to 259, 518, 1036 mg/kg bw): 5
2 mL/kg bw (corresponding to 2072 mg/kg bw): 10 - Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 673 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: corresponding to 0.65 mL/kg bw, dosel levels in mg/kg bw calculated with a density of 1036 mg/mL
- Mortality:
- 0.25 mL/kg bw corresponding to 259 mg/kg bw: 0/5 males and 1/5 females died within 24 h.
0.5 mL/kg bw corresponding to 518 mg/kg bw: 0/5 males and 4/5 females died within 24 h.
1 mL/kg bw corresponding to 1036 mg/kg bw: 4/5 males and 2/5 females died within 24 h.
2 mL/kg bw corresponding to 2072 mg/kg bw: 10/10 males and 10/10 females died within 2 h. - Clinical signs:
- Severe oedema was observed after 24 h. Scab formation was observed that detached from the skin between 4 to 15 days post application.
- Body weight:
- No information available
- Gross pathology:
- No significant macroscopic abnormalities were observed.
- Interpretation of results:
- Category 3 based on GHS criteria
- Conclusions:
- CLP: Acute Dermal 3, H311 according to Regulation (EC) No. 1272/2008
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Version / remarks:
- adopted 07 Sep 2009
- Deviations:
- yes
- Remarks:
- no experimental details, no information on analytical purity, no details on test animals, no information on frequency of observations, body weights not recorded, particle size distribution not determined, analytical concentrations not given for all doses
- GLP compliance:
- no
- Test type:
- traditional method
- Limit test:
- no
- Species:
- mouse
- Strain:
- other: Oncins France Strain 1 (OF1)
- Sex:
- not specified
- Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- 1.2, 6.0, 12 and 24 mL/m3, corresponding to 1.24, 6.22, 12.42 and 24.86 mg/L
- No. of animals per sex per dose:
- 8 / dose group (sex unspecified)
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes - Sex:
- not specified
- Dose descriptor:
- LC50
- Effect level:
- > 6.22 - < 12.43 mg/L air (nominal)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Remarks on result:
- other: corresponding to > 6 < 12 mL/mg3 air (nominal concentration), dose levels in mg/L air were calculated as follows: [dose level in ppm x molecular weight] / 24,200)
- Mortality:
- 1.2 mL/m3 air (corresponding to 1.24 mg/L air): no mortality occurred
6.0 mL/m3 air (corresponding to 6.22 mg/L air): 2/8 animals died (after 2 h of exposure and on Day 1)
12 mL/m3 air (corresponding to 12.43 mg/L air ): 8/8 animals died (within 3 h during exposure)
24 mL/m3 air (corresponding to 24.86 mg/L air): 8/8 animals died (within the first hour of exposure) - Clinical signs:
- other: Irritation of eyes and nasal mucosa was observed at the beginning of exposure.
- Body weight:
- No information on body weight available
- Gross pathology:
- There were no macroscopic lesions observed.
- Interpretation of results:
- study cannot be used for classification
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Version / remarks:
- adopted 07 Sep 2009
- Deviations:
- yes
- Remarks:
- no experimental details, no information on analytical purity, no details on test animals, no information on frequency of observations, body weights not recorded, particle size distribution not determined, analytical concentrations not given for all doses
- GLP compliance:
- no
- Test type:
- traditional method
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Oncins France Strain A (OFA)
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 200 - 300 g - Route of administration:
- inhalation: vapour
- Details on inhalation exposure:
- The rats were placed into a 500 L inhalation chamber . They were exposed to the test item as vapour in air at a flow rate of 1m3/h. A saturation of the atmosphere with the test item vapour was noticed at the highest concentrations tested (e.g. 12 and 24 mL/m3)
- Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- 1.2, 6.0, 12, 24 mL/m3, corresponding to 1.24, 6.22, 12.42 and 24.86 mg/L
- No. of animals per sex per dose:
- 1.2 and 6.0 mL/m3 (corresponding to 1.24 and 6.22 mg/L air): 10 / dose group (sex unspecified)
12 and 24 mL/m3 (corresponding to 12.43 and 24.86 mg/L air): 8 / dose group (sex unspecified) - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes - Sex:
- not specified
- Dose descriptor:
- LC50
- Effect level:
- > 1.24 - < 24.86 mg/L air (nominal)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Remarks on result:
- other: corresponding to > 12 < 24 mL/m3 air (nominal), dose levels in mg/L air were calculated as follows: [dose level in ppm x molecular weight] / 24,200)
- Mortality:
- 1.2 mL/m3 air: no mortality occurred
6.0 mL/m3 air: no mortality occurred
12 mL/m3 air: no mortality occurred
24 mL/m3 air: 8/8 animals died (6/8 died after 2-3 h of exposure, 2/8 died during post-exposure days 2 and 4) - Clinical signs:
- other: Irritation of eyes and nasal mucosa was observed at the beginning of exposure.
- Body weight:
- No information on body weight available.
- Gross pathology:
- There were no macroscopic lesions observed.
- Other findings:
- The test atmosphere was saturated with test item vapour at ≥ 12 mL/m3 air, corresponding to ≥ 12.43 mg/L air. Below the saturation limit (at 1.2 and 6 mL/mg air, corresponding to 1.24 and 6.22 mg/L air) no mortality was expected.
- Interpretation of results:
- study cannot be used for classification
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- adopted 09 Oct 2017
- Deviations:
- yes
- Remarks:
- no details on animals and environmental conditions, post observation period only 7 days, purity not indicated
- GLP compliance:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 2.5 kg
- Housing: Individually in cages measuring 600 x 540 x 315 cm
- Diet: granulated rabbit food (SANDERS), 200 g per rabbit per day
- Water: ad libitum - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 0.1 mL - Duration of treatment / exposure:
- 6 rabbits: single application of undiluted test item without washing
6 rabbits: single application of undiluted test item with rinsing after 30 seconds following test item instillation - Observation period (in vivo):
- 7 days
Reading time points: 1 h, 1, 2, 4 and 7 days - Number of animals or in vitro replicates:
- 12 (6 rabbits with eyes rinsed, 6 rabbits without eyes rinsed)
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing: with rinsing solution DACRYOSERUM (Laboratories CHIBRET, France) in 6/12 animals
- Time after start of exposure: 4 seconds after test item instillation
SCORING SYSTEM: Draize scoring system
TOOL USED TO ASSESS SCORE: ophthalmoscope - Irritation parameter:
- chemosis score
- Basis:
- animal: #1, #2, #3, #4 and #6
- Time point:
- 24/48/72 h
- Score:
- 3
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks:
- within 7 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- chemosis score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 3.67
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks:
- within 7 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- chemosis score
- Basis:
- animal: #7
- Time point:
- 24/48/72 h
- Score:
- 2.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- chemosis score
- Basis:
- animal: #8
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 3 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- chemosis score
- Basis:
- animal: #9
- Time point:
- 24/48/72 h
- Score:
- 2.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- chemosis score
- Basis:
- animal: #10
- Time point:
- 24/48/72 h
- Score:
- 2.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- chemosis score
- Basis:
- animal: #11
- Time point:
- 24/48/72 h
- Score:
- 3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- chemosis score
- Basis:
- animal: #12
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 3 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 3
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- conjunctivae score
- Basis:
- animal: #4, #5 and #6
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- conjunctivae score
- Basis:
- animal: #7
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- other: reversibility not applicable
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal: #8 and #9
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 3
- Reversibility:
- fully reversible within: 3 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal: #10
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 3 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal: #11
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal: #12
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- iris score
- Basis:
- animal: #1 and #5
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 2
- Reversibility:
- not fully reversible within: 7 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- iris score
- Basis:
- animal: #2, #3, #4 and #6
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 2
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- iris score
- Basis:
- animal: #7
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 2
- Reversibility:
- fully reversible within: 3 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- iris score
- Basis:
- animal: #8
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- fully reversible within: 24 hours
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- iris score
- Basis:
- animal: #9 and #12
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 2
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- iris score
- Basis:
- animal: #10
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 2
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- iris score
- Basis:
- animal: #11
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 2
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- cornea opacity score
- Basis:
- animal: #1, #2 and #3
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks:
- within 7 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- cornea opacity score
- Basis:
- animal: #4 and #6
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks:
- within 7 days
- Remarks on result:
- other: single application without washout
- Irritation parameter:
- cornea opacity score
- Basis:
- animal: #7, #10 and #12
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 4 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- cornea opacity score
- Basis:
- animal: #8
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 2 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- cornea opacity score
- Basis:
- animal: #9
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritation parameter:
- cornea opacity score
- Basis:
- animal: #11
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 3 days
- Remarks on result:
- other: eye rinsed 4 sec after instillation
- Irritant / corrosive response data:
- In rinsed eyes, erythema (conjunctivae redness) was observed in all animals, which fully reversed at the end of the 7 days observation period. In addition, moderate edema (chemosis was observed at the beginning of the observation period, which fully reversed by Day 7. Slight iris lesions and corneal opacity were observed most animals, but the adverse effects were fully reversible in all animals latest by study Day 7.
In non-rinsed eyes, moderate erythema and well defined edema were observed in all animals throughout the whole study period. The adverse effects persistent in all animals until study termination. In addition, slight iris lesions and corneal opacity were observed. Adverse effects on the iris was fully reversible in 4/6 rabbits, but persisted in 2/6 rabbits by study Day 7. Similarly, opacity was reversible in 2/6 rabbits but remained in 4/6 rabbits until study termination. - Interpretation of results:
- Category 1 (irreversible effects on the eye) based on GHS criteria
- Conclusions:
- CLP: Eye Dam. 1 H318 according to Regulation (EC) No. 1272/2008.
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- The study was not performed according to modern standards. The dose levels were to high and caused severe local effects. Furthermore the skin was abraded in half of the animals. Purity not stated, too few animals, no statistical evaluation, no details on experimental procedure, type of coverage or frequency of observations, half of the animals were treated at abraded skin, body weight and food consumption were not recorded, few parameters in haematology, clinical chemistry and urinalysis investigated, time of death for individual animals unclear
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test:
Repeated dose dermal toxicity
- Short description of test conditions: Male and female rabbits (6/sex/group) were dermally treated at 0.2, 0.4, 0.8 and 1.6 mL/kg bw/day for 3 consecutive weeks. The animals were exposed 5 days/week, 6 h exposure per day.
- Parameters analysed / observed: clinical signs, mortality, dermal reactions, gross pathology and histopathology.
Deficiencies when compared to OECD guideline 410:
The study was not performed according to modern standards. The dose levels were too high and caused severe local effects. Furthermore the skin was abraded in half of the animals. The analytical purity of the test material was not stated, too few animals, no statistical evaluation, no details on experimental procedure, type of coverage or frequency of observations, body weight and food consumption were not recorded, few parameters in haematology, clinical chemistry and urinalysis investigated and time of death for individual animals unclear. - GLP compliance:
- no
- Limit test:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- TEST SITE
- Area of exposure: Animals were treated in the dorsal region 24 h after preparation (shaving and scarification).
- Time intervals for shavings or clipplings: The animals were shaved and then closely shaved again. After 24 h, 12 superficial scarifications (3 cm length and spaced 2 cm apart) were made in half of the animals.
REMOVAL OF TEST SUBSTANCE
- Washing: The treated zones were washed with lukewarm water.
- Time after start of exposure: 6 h
TEST MATERIAL
- Amount(s) applied: 0.2, 0.4, 0.8 and 1.6 mL - Duration of treatment / exposure:
- 21 days
- Frequency of treatment:
- daily, 5 days/week
- Dose / conc.:
- 0.2 other: mL/kg bw/day
- Remarks:
- corresponding to 207 mg/kg bw/day
- Dose / conc.:
- 0.4 other: mL/kg bw/day
- Remarks:
- corresponding to 414 mg/kg bw/day
- Dose / conc.:
- 0.8 other: mL/kg bw/day
- Remarks:
- corresponding to 829 mg/kg bw/day
- Dose / conc.:
- 1.6 other: mL/kg bw/day
- Remarks:
- corresponding to 1658 mg/kg bw/day
- No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale:
Doses were selected based on the results of a preliminary 4-days range-finding study in which skin reactions were assessed for doses in the range of 1 and 2 mL/kg bw/day.
- No post-exposure recovery group included. - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
DERMAL IRRITATION (if dermal study): Yes
BODY WEIGHT: No data
FOOD CONSUMPTION: No
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: before and at the end of treatment
- Parameters examined: leukocyte count
- How many animals: all surviving animals
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: before and at the end of treatment
- Parameters examined: glucose, urea, bilirubin, alkaline phosphatase, serum glutamate pyruvic transferase, serum glutamate oxaloacetic transaminase
- How many animals: all surviving animals
URINALYSIS: Yes
- Time schedule for collection of urine: before and at the end of treatment
- Parameters examined: pH, protein, glucose, ketone bodies, occult blood
- How many animals: all surviving animals
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 1.6 mL/kg bw/day: Paraplegia and loss of movement coordination were observed and considered as neurotoxic effects. The animals died within 48 h. The effects were considered adverse and related to treatment.
- Dermal irritation:
- effects observed, treatment-related
- Description (incidence and severity):
- A dose-related increase in the intensity of edema was observed. There was no perceptible difference between scarified and non-scarified animals. At 1.6 mL/kg bw/day 6/12 animals showed slight erythema. the observations were considered treatment-related and of toxicological relevance. Despite daily washings the cutaneous alteration induced a formation of a thick crust, cracked and dry, which persisted until study termination.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Mortality occured from the second day of dosing in all test item treated groups:
0.2 mL/kg bw/day: 2/12 animals died
0.4 mL/kg bw/day: 3/11 animals died
0.8 mL/kg bw/day: 10/12 animals died
1.6 mL/kg bw/day: 12/12 animals died - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weight development was disturbed in the animals which died or had to be sacrificed.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- Haematology of surviving animals (0.2 and 0.4 mL/kg bw/day) was not affected by treatment.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There was a slight, statistically not significant increase of uremia in the non-sacrificed treated animals. The effect was not considered treatment-related.
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 1.6 mL/kg bw/day: Paraplegia and loss of movement coordination were observed and considered as neurotoxic effects. The animals died within 48 h. The effects were considered adverse and related to treatment.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The thickness of the skin (described as oedema) increased immediately after exposure in all animals; it was proportional to the applied dose. At high doses slight erythema was observed as well. Acanthosis, hyperkeratosis and dryness was observed up to the end of the treatment.
- Histopathological findings: neoplastic:
- not examined
- Dose descriptor:
- LOAEL
- Effect level:
- ca. 0.2 other: mL/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- dermal irritation
- mortality
- Remarks on result:
- other: corresponding to 207 mg/kg bw/day
- Critical effects observed:
- not specified
- Conclusions:
- The test item repeatedly applied by cutaneous administration induced skin necrosis at all tested dose levels. At the highest dose (1.6 mL/kg bw/day) death occurred between study Day 2-4. Clinical signs at this dose level included paralysis and motion disorders. No clinical signs were seen at the lower dose levels. A death occurred also in the lowest dose group, a NOAEL could not be determined.
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- 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
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: Draize test
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- adopted 28 Jul 2015
- Deviations:
- yes
- Remarks:
- 24 h instead of 4 h application, occlusive instead of semi-occlusive application, no details on animals and environmental conditions, reading time points 24 and 72 h only, test item administration application onto abraded and to intact skin area
- GLP compliance:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 2.5 - 3.5 kg
- Housing: Individually in cages measuring 600 x 540 x 315 cm
- Diet: granulated rabbit food (SANDERS), 200 g per rabbit per day
- Water: ad libitum - Type of coverage:
- occlusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 0.5 g - Duration of treatment / exposure:
- 24 h
- Observation period:
- 3 days
Reading time points: 24 and 72 h - Number of animals:
- 6
- Irritation parameter:
- erythema score
- Basis:
- animal: #1, #3, #4, #5 and #6
- Time point:
- other: 24/72 h
- Score:
- 0.5
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- other: 24/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- edema score
- Basis:
- animal: #1 and #3
- Time point:
- other: 24/72 h
- Score:
- 1.5
- Max. score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- edema score
- Basis:
- animal: #2, #5 and #6
- Time point:
- other: 24/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- edema score
- Basis:
- animal: #4
- Time point:
- other: 24/72 h
- Score:
- 0.5
- Max. score:
- 4
- Reversibility:
- not reversible
- Irritant / corrosive response data:
- Barely perceptible erythema (score 0.5) was observed in 5/6 rabbits, which was fully reversible in all animals within 72 hours after test item instillation. Barely perceptible edema (score 0.5) was observed in 1/6 rabbits, slight edema (score 1) in 3/6 rabbits and slight to well defined edema (score 1.5) was observed in 2/6 rabbits and remained unreversible until study termination 72 hours after test item instillation.
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- The test conditions (24 h exposure under occlusive conditions) may have led to more detrimental skin reactions than those specified in current guidelines. In the 3-days observation period the reversibility of the local skin reactions could not fully be assessed.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 975
- Report date:
- 1973
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test:
Acute toxicity after intraperitoneal injection in rats
- Short description of test conditions: 5 rats/sex received a single intraperitoneal injection
- Parameters analysed / observed: Mortality, clinical signs, gross necropsy - GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- 3-(methylthio)propionaldehyde
- EC Number:
- 221-882-5
- EC Name:
- 3-(methylthio)propionaldehyde
- Cas Number:
- 3268-49-3
- Molecular formula:
- C4H8OS
- IUPAC Name:
- 3-(methylthio)propionaldehyde
Constituent 1
Test animals
- Species:
- rat
- Sex:
- male/female
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- water
- Doses:
- 420, 210, 105 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
Results and discussion
Effect levels
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- ca. 300 mg/kg bw
- Based on:
- test mat.
- Mortality:
- 105 mg/kg bw: no mortality occurred.
210 mg/kg bw: no mortality occurred.
420 mg/kg bw: 4/5 males and 5/5 females died within 1 hour post injection. - Clinical signs:
- The only clinical symptom that was reported consisted of a pronounced prostration.
- Gross pathology:
- Gross necropsy revealed no macroscopic findings.
Applicant's summary and conclusion
- Conclusions:
- The acute lethal dose after intraperitoneal injection in rats was 300 mg/kg bw.
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