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EC number: 203-640-0 | CAS number: 109-02-4
- 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
Skin irritation: Mallory VT (1990) determined in a reliable K2 study, the skin irritation potential of the test substance in New Zealand White rabbits according to OECD Guideline 404. The test substance was observed to be corrosive to the skin. This study was selected as key study.
Eye irritation: BASF (1964) performed an eye irritation test in Angora rabbits according to a method equivalent to OECD Guideline 405. It is possible that the results in this eye irritation test were not as severe as expected as only 0.05 ml of the test substance instead of 0.1 ml as recommended in OECD guideline 405 was applied to the eye. On the basis of the findings of this study, the test substance would have to be classified as eye irritant Cat. 2B according to CLP. The test substance is however corrosive to the skin (Cat. 1B) and therefore is classified for eye damage category 1.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1990-08-22 - 1990-09-05
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Well documented GLP study performed according to a method similar to OECD Guideline 404 with the following deviations: an occlusive dressing was used (instead of semi-occlusive). Furthermore, next to application of the test substance on intact shaved skin, also abraded skin was tested.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- occlusive dressing used (instead of semi-occlusive); abraded skin was tested
- GLP compliance:
- yes
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 6398-24-20, Project #90-005
- Substance type: clear, colorless liquid
- Physical state: liquid
- Lot No.: 90-005
- Purity: responsibility of the sponsor
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration. - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hare-Marland, Hewitt, NJ, USA
- Age at study initiation: adult animals
- Weight at study initiation: males 2129-2507 g (mean 2351 g); females 2170-2633 g (mean 2468 g)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): not indicated
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- occlusive
- Preparation of test site:
- other: abraded and intact shaved skin
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/site - Duration of treatment / exposure:
- The test substance was kept in contact with the skin on the upper dorsal site (intact) for four hours and at the lower dorsal sites (intact and abraded) for twenty four hours.
- Observation period:
- Dermal irritation was scored at 30-60 minutes, 24, 48 and 72 hours and on Days 4 through 14 after patch removal. Dermal irritation of the lower dorsal sites (intact and abraded) were scored at 24, 48 and 72 hours and on Days 4 through 14 after application of the test material.
- Number of animals:
- 6 (3 males and 3 females)
- Details on study design:
- TEST SITE
- Area of exposure: one intact site on the upper dorsal trunk and at two sites, one intact and one abraded, on the lower dorsal trunk of the animal.
- Type of wrap if used: All application sites were clipped free of hair. The abraded site was prepared using a burred needle; the abrasion penetrated the stratum corneum but not the derma. Following the application of the test material, gauze patches were applied to each of the sites then wrapped with a rubber dam and an elastic bandage to retard evaporation.
REMOVAL OF TEST SUBSTANCE
At the end of each exposure period, the sites were wiped with water and gauze and observed for erythema and edema.
SCORING SYSTEM: Draize evaluation of dermal irritation - Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- edema score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- edema score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- edema score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- erythema score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- erythema score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritation parameter:
- erythema score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- not reversible
- Remarks on result:
- other: application on intact shaved skin (upper dorsal area)
- Irritant / corrosive response data:
- Moderate to severe erythema and edema were observed at the 30-60 minute observation period on the upper dorsal site. Severe erythema and edema were observed at the 24, 48 and 72 hours and on days 4 through 14 on the upper dorsal site. Severe erythema and edema were observed at the 24, 48 and 72 hours and on days 4 through 14 on the lower dorsal sites. Necrosis of the skin was observed at each application site at the 24, 48 and 72 hours and on days 4 through 14 observation periods at each application site. Sloughing of the skin at the application site was observed at the day 14 observation period on the upper dorsal site and at the day 13 and 14 observation periods at the lower dorsal sites. The study was terminated following the day 14 observation period.
- Interpretation of results:
- Category 1 (corrosive) based on GHS criteria
- Conclusions:
- Based on the test results and according to the criteria of the CLP Regulation, the substance is classified as category 1 corrosive.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1964
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Acceptable study comparable to guideline (non GLP; occlusive conditions; TS purity not specified, 1 min, 5 min, 15 min or 20 hours treatment duration; TS preparation: 50% in water, up to 8 days observation period)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- occlusive conditions; 1 min, 5 min, 15 min or 20 hours treatment duration; TS preparation: 50% in water, up to 8 days observation period
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 4-Methyl-morpholine
no further data. - Species:
- rabbit
- Strain:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 2.37 and 2.13 kg - Type of coverage:
- occlusive
- Preparation of test site:
- other: intact skin
- Vehicle:
- water
- Controls:
- not specified
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 50% - Duration of treatment / exposure:
- 1 min, 5 min, 15 min and 20 hours
- Observation period:
- up to 8 days
- Number of animals:
- 2 (all males)
- Details on study design:
- TEST SITE
- Area of exposure: 2.5x2.5 cm
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was washed with Lutrol (conc.) and Lutrol/water (1:1)
- Time after start of exposure: 1, 5 or 15 min / 1 hour
SCORING SYSTEM: comparable to the OECD scoring system - Irritation parameter:
- other: necrosis
- Time point:
- other: after 1 and 5 min exposure
- Reversibility:
- not specified
- Remarks on result:
- other: Exposure of rabbit skin to the test substance for 1 to 5 min under occlusive conditions did not lead to necrosis
- Irritation parameter:
- other: necrosis
- Time point:
- other: after 15 min and 1 hour exposure
- Reversibility:
- not fully reversible within: 8 days
- Remarks on result:
- other: Exposure of rabbit skin to the test substance for 15 min or 20 hours under occlusive conditions led to full thickness necrosis.
- Irritant / corrosive response data:
- Strong signs of irritation reactions were also seen, but are not reported here because corrosivity was the leading effect.
- Interpretation of results:
- Category 1B (corrosive) based on GHS criteria
- Conclusions:
- In this study, necrosis was observed after 15 min and 1 hour of exposure. Exposure of rabbit skin to the test substance for 15 min or 20 hours under occlusive conditions led to full thickness necrosis.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- No data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Non GLP study performed according to a method similar to OECD Guideline 404 with the following deviations: an occlusive dressing was used (instead of semi-occlusive), no irritation score readings at 48h and later than 72h, application to abraded skin sites (next to intact skin sites).
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- occlusive dressing used, abraded skin sites tested, no 48h score readings and no observations after 72h
- Qualifier:
- according to guideline
- Guideline:
- other: Hazardous Materials Regulations of the Department of Transportation (1976)
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Sample No. 4236-13-34, AUS-0099
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Pel-Freez, Inc. USDA No. 7I-B-16, Rogers, Arkansas 72756
- Age at study initiation: approximately 10-13 weeks of age
- Housing: The animals were housed in suspended, wire-bottomed steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days prior to experimental use - Type of coverage:
- occlusive
- Preparation of test site:
- other: one abraded and one intact shaved site
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/test site - Duration of treatment / exposure:
- 4 hours
- Observation period:
- One hour after removal of the test material, each abraded and intact test site was examined and scored separately for erythema and edema on a graded scale of 0 to 4. After 24 and 72 hours, the sites were again examined and scored.
- Number of animals:
- 6 animals
- Details on study design:
- TEST SITE
- Area of exposure: back and flank from each rabbit
- Two test sites located lateral to the midline of the back approximately 10 centimeters apart were selected. One of the test sites was abraded (with a slighly bent tip of a hypodermic needle) by making 4 epidermal abrasions, 2 perpendicular to the other 2, while the other test site remained intact. Each site was immediately occluded with a 2-inch square gauze patch which was secured with masking tape. The trunk of each animal was then wrapped with impervious plastic sheeting. The wrap held the patches in position but did not retard evaporation of the test material during the 4-hour exposure period.
REMOVAL OF TEST SUBSTANCE
At the end of the 4 hours, the plastic wrappings and patches were removed. In addition, all residual test material was removed by flooding the test sites with lukewarm tap water while gently rubbing the sites.
SCORING SYSTEM: In evaluating the average irritation present, the mean scores for erythema and edema of the intact test sites after 4, 24 and 72 hours were added. Similarly, the mean scores for erythema and edema of the abraded test sites after 4, 24 and 72 hours were added. These 2 values were totaled and divided by 6 to obtain the mean primary irritation score.
The test material was classified corrosive if corrosion occurs when the material is tested on intact rabbit skin. Corrosion will be considered to have resulted if the substance in contact with the rabbit skin has caused destruction or irreversible alteration of the tissue after an exposure period of 4 hours or less. Tissue destruction is considered to have occurred if, at any of the readings, there is ulceration or necrosis. Tissue destruction does not include merely sloughing of the epidermis, or erythema, edema or fissuring. - Irritation parameter:
- erythema score
- Basis:
- mean
- Remarks:
- of 6 animals
- Time point:
- other: 24 and 72h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- no data
- Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- of 6 animals
- Time point:
- other: 24 and 72h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- no data
- Irritant / corrosive response data:
- Burns were severe and diffuse. Second degree chemical burns were observed after 4 hours (not resulting in fibrosis). Third degree chemical burns were observed after 24 and 72h (resulting in fibrosis).
Primary irritation score: 8 (max possible) - Interpretation of results:
- Category 1 (corrosive) based on GHS criteria
- Conclusions:
- A mean primary irritation score of 8.0 was observed after 4 hours application of the substance to New Zealand White rabbit skin. The substance shows chemical burns and is considered corrosive.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1979-01-05 - 1979-04-05
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Non GLP study performed according to a method similar to OECD Guideline 404 with the following deviations: an occlusive dressing was used (instead of semi-occlusive), abraded skin sites were tested, no scoring at 48h or later than 72h, 24h exposure (instead of 4h).
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- occlusive dressing used, abraded skin sites tested, no readings at 48h and later than 72h, 24h exposure time.
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): sample label 4236-24-30
- Substance type: clear liquid
- Physical state: liquid - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: at least 8 weeks old
- Housing: The animals were housed 2/cage in suspended wire mesh cages (30" x 18" x 18").
- Diet (e.g. ad libitum) and water (e.g. ad libitum): Fresh Purina rabbit chow and water were freely available.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21°C - Type of coverage:
- occlusive
- Preparation of test site:
- other: intact and abraded
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL - Duration of treatment / exposure:
- The test material was kept in contact with the skin for 24 hours.
- Observation period:
- Dermal reactions were scored at 24 and 72 hours
- Number of animals:
- 6 rabbits (2 males, 4 females)
- Details on study design:
- TEST SITE
The fur was clipped from the backs and sides of the animals. The back from the left of the spinal column of all animals was abraded. The abrasions, extending the length of the exposure site, scratched the stratum corneum but did not reach the derma or produce bleeding. The back to the right of the spinal cord column remained intact.
REMOVAL OF TEST SUBSTANCE
The test material was kept in contact with the skin for 24 hours, at which time the wrappings were removed.
SCORING SYSTEM: Draize scoring system - Irritation parameter:
- primary dermal irritation index (PDII)
- Basis:
- mean
- Time point:
- other: 24 and 72 hours
- Score:
- 2.29
- Max. score:
- 8
- Reversibility:
- no data
- Remarks:
- 72 hours
- Irritant / corrosive response data:
- Average erythema scores were very slight to well defined.
Average edema scores were very slight to slight. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The primary dermal index of the substance is determined to be 2.29 after 24 hours application to New Zealand White rabbit skin.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1978-08 - 1978-10
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- occlusive dressing used, abraded skin sites tested, no readings at 48h and later than 72h, 24h exposure time, limited data on test material, animals and environmental conditions.
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): RC-106 or RC-107
- Substance type: clear liquid
- Physical state: liquid
- Analytical purity: no data
- Lot/batch No.: no data
- Stability under test conditions: no data
- Storage condition of test material: no data - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Plummer Rabbitry
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data - Type of coverage:
- occlusive
- Preparation of test site:
- other: abraded and intact shaved skin
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml - Duration of treatment / exposure:
- 24h
- Observation period:
- 72h
- Number of animals:
- 6
- Irritation parameter:
- primary dermal irritation index (PDII)
- Basis:
- mean
- Remarks:
- of 6 animals, intact and abraded skin
- Time point:
- other: 24 and 72h
- Score:
- 6.25
- Max. score:
- 8
- Reversibility:
- no data
- Remarks on result:
- other: Test substance RC-106
- Irritation parameter:
- primary dermal irritation index (PDII)
- Basis:
- mean
- Remarks:
- of 6 animals, intact and abraded skin
- Time point:
- other: 24 and 72h
- Score:
- 6
- Max. score:
- 8
- Reversibility:
- no data
- Remarks on result:
- other: Test substance RC-107
- Irritant / corrosive response data:
- RC-106: necrosis, peripheral erythema and blanching of the skin was observed after 24h; coriaceous (entire site) and peripheral erythema was observed after 72h
RC-107: necrosis and blanching of the skin was observed after 24h; leathery and thickened texture (still flexible) was observed after 72h - Interpretation of results:
- study cannot be used for classification
- Conclusions:
- Corrosive effects were observed after application of the test substance to the rabbit skin during 24h.
- Endpoint:
- skin irritation: in vitro / ex vivo
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Referenceopen allclose all
Exposure of rabbit skin to the test substance for 15 min or 20 hours under occlusive conditions led to full thickness necrosis of the skin. No full thickness necrosis was observed, when the test substance was applied for 1 or 5 minutes.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (corrosive)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1964
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Acceptable study comparable to guideline (no GLP, TS purity not specified, 50 µl TS, 8-day observation period).
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- 50 µl TS, 8-day observation period
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): 4-Methylmorpholin
- Species:
- rabbit
- Strain:
- Angora
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 2.54 and 2.61 kg
ENVIRONMENTAL CONDITIONS
no data - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: left eye of the same rabbits treated with NaCl (0.9%)
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 0.05 ml - Duration of treatment / exposure:
- single application
- Observation period (in vivo):
- 8 days
- Number of animals or in vitro replicates:
- 2 (all females)
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
SCORING SYSTEM: comparable to the OECD scoring system
TOOL USED TO ASSESS SCORE: hand-slit lamp - Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 8 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 8 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible within: 24 hours
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible within: 24 hours
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 2
- Reversibility:
- fully reversible within: 8 days
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 2
- Reversibility:
- fully reversible within: 8 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 8 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 8 days
- Irritant / corrosive response data:
- The mean scores (24/48/72 hours) of the individual animals were:
- cornea score: 1 in 2/2 animals
- iris score: 1 in 2/2 animals
- conjunctivae score: 1 in 2/2 animals
- chemosis score: 0 in 2/2 animals - Other effects:
- Mucous bleeding, pupil retraction, ciliary injection and misty opacity were generally present, but also reversible within 5-8 days.
- Interpretation of results:
- Category 2B (mildly irritating to eyes) based on GHS criteria
- Conclusions:
- In a skin irritation test, the test substance was corrosive.
It might be possible that the results in this eye irritation test were not as severe as expected as only 0.05 ml of the test substance instead of 0.1 ml as recommended in OECD 405 were applied to the eye. Due to the findings of this study, the test substance would have to be classified as eye irritant Cat. 2B according to CLP criteria, although the test substance is corrosive to the skin (Cat. 1B). - Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1978-08 - 1978-10
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- limited data on test material, animals and environmental conditions, no 21 day observation period
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): RC-106 or RC-107
- Substance type: clear liquid
- Physical state: liquid
- Analytical purity: no data
- Lot/batch No.: no data
- Stability under test conditions: no data
- Storage condition of test material: no data - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Plummer Rabbitry or Sweetwater Farm, Inc.
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: left eye were untreated and served as controls
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml - Duration of treatment / exposure:
- 6 animals: no rinsing
3 animals: rinsed after 30 sec - Observation period (in vivo):
- 7 days
- Number of animals or in vitro replicates:
- 9
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- of 6 animals (unrinsed)
- Time point:
- 24/48/72 h
- Score:
- 1.78
- Max. score:
- 4
- Reversibility:
- other: not reversible within 7 days
- Remarks on result:
- other: Test substance RC-106
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- of 6 animals (unrinsed)
- Time point:
- 24/48/72 h
- Score:
- 0.5
- Max. score:
- 2
- Reversibility:
- other: not reversible within 7 days
- Remarks on result:
- other: test substance RC-106
- Irritation parameter:
- conjunctivae score
- Remarks:
- erythema
- Basis:
- mean
- Remarks:
- of 6 animals (unrinsed)
- Time point:
- 24/48/72 h
- Score:
- 2.44
- Max. score:
- 3
- Reversibility:
- other: not reversible within 7 days
- Remarks on result:
- other: test substance RC-106
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- of 6 animals (unrinsed)
- Time point:
- 24/48/72 h
- Score:
- 2.22
- Max. score:
- 4
- Reversibility:
- other: not reversible within 7 days
- Remarks on result:
- other: test substance RC-106
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- of 6 animals (unrinsed)
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- other: not reversible within 7 days
- Remarks on result:
- other: test substance RC-107
- Irritation parameter:
- conjunctivae score
- Remarks:
- erythema
- Basis:
- mean
- Remarks:
- of 6 animals (unrinsed)
- Time point:
- 24/48/72 h
- Score:
- 3
- Max. score:
- 3
- Reversibility:
- other: not reversible within 7 days
- Remarks on result:
- other: test substance RC-107
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- of 6 animals (unrinsed)
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- other: not reversible within 7 days
- Remarks on result:
- other: test substance RC-107
- Irritant / corrosive response data:
- Corneal opacity in eyes of RC-107 treated animals prevented scoring of iris.
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- According to the criteria of CLP, RC-106 would be classified as irritating to eyes, and RC-107 would be classified as causing serious damage to eyes. However, the study is considered not reliable as the documentation was not sufficient.
- Endpoint:
- eye irritation: in vitro / ex vivo
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Referenceopen allclose all
In a skin irritation test, the test substance was corrosive. It might be possible that the results in this eye irritation test were not as severe as expected as only 0.05 ml of the test substance instead of 0.1 ml as recommended in OECD guideline 405 were applied to the eye. Due to the findings of this study, the test substance would have to be classified as eye irritant Cat. 2B according to GHS-criteria. The test substance is however corrosive to the skin (Cat. 1B).
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation / corrosion:
Mallory VT (1990c) studied skin irritation/corrosion by applying the test substance on one intact site on the upper dorsal trunk and at two sites, one intact and one abraded, on the lower dorsal trunk of the animal. At the end of each exposure period, the sites were wiped with water and gauze and observed for erythema and edema. Moderate to severe erythema and edema were observed at the 30-60 minute observation period on the upper dorsal site. Severe erythema and edema were observed at the 24, 48 and 72 hours and on days 4 through 14 on the upper dorsal site. Severe erythema and edema were observed at the 24, 48 and 72 hours and on days 4 through 14 on the lower dorsal sites. Necrosis of the skin was observed at each application site at the 24, 48 and 72 hours and on days 4 through 14 observation periods at each application site. Sloughing of the skin at the application site was observed at the day 14 observation period on the upper dorsal site and at the day 13 and 14 observation periods at the lower dorsal sites. The study was terminated following the day 14 observation period.
In addition, the test substance was observed to be corrosive in a non GLP primary skin irritation test (Scibon G, 1977) after 4 hours application of the substance to New Zealand White rabbit skin. Also, BASF (1964) observed necrosis in rabbits after 15 min and 1 hour of exposure, but not after 1 or 5 min of exposure. Exposure of rabbit skin to the test substance for 15 min or 20 hours under occlusive conditions led to full thickness necrosis.These studies were used as supporting evidence.
Based on the test results and according to the criteria of the CLP Regulation, the substance is classified as category 1B corrosive.
Eye irritation:
BASF (1964) performed an eye irritation test in Angora rabbits according to a method equivalent to OECD Guideline 405 (single application in 2 female rabbits). The left eye of the same rabbits treated with NaCl (0.9%) served as control. In a skin irritation test, the test substance was corrosive. It is possible that the results in this eye irritation test were not as severe as expected as only 0.05 ml of the test substance instead of 0.1 ml as recommended in OECD guideline 405 was applied to the eye. Due to the findings of this study, the test substance would have to be classified as eye irritant Cat. 2B according to CLP. The test substance is however corrosive to the skin (Cat. 1B) and therefore is classified for eye damage category 1.
Justification for classification or non-classification
Based on all available data and according to the criteria of the CLP Regulation and as burns were excessive at 24 hours onward the substance is classified as corrosive category 1B (H314, causes severe skin burns and eye damage). In addition, the substance is classified for eye damage category 1 (H318).
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