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EC number: 601-101-8 | CAS number: 111497-86-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
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:
- 01 December 1997 - 09 January 1998
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- not specified
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: Ace Animals, Boyertown, PA, USA- Weight at study initiation: 2.2 - 2.6 kg- Housing: Individually in suspended wire cages- Diet (e.g. ad libitum): Purina Rabbit Chow (Diet no. 5321)- Acclimation period: At least 5 daysENVIRONMENTAL CONDITIONS- Photoperiod (hrs dark / hrs light): 12/12
- Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 ml/rabbit
- Duration of treatment / exposure:
- 4 hours
- Observation period:
- 14 days
- Number of animals:
- 3
- Details on study design:
- TEST SITE- Area of exposure: 2.5 x 2.5 cm- Type of wrap if used: PlasticREMOVAL OF TEST SUBSTANCE- Washing (if done): Gentle washing with distilled water at the end of the exposure period, before scoring for dermal reactions- Time after start of exposure: 4 hoursSCORING SYSTEM: Numerical Draize technique
- Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 4
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2.33
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritant / corrosive response data:
- Erythema scores, very slight to well defined at 1 hour following patch removal, ranged from absent to severe through Day 1 and cleared by Day 14.One animal had poor hair regrowth on Day 7, which cleared by Day 14. Edema scores generally ranged from absent to slight through Day 7 and cleared by Day 14, with the exception of a score 3 (moderate) in one animal at 24 hours.
- Conclusions:
- Under the test conditions, the test substance was considered to be irritating but not corrosive to skin.
- Executive summary:
A study was performed to assess the skin irritation potential of the test substance to the skin of New Zealand White rabbits according to OECD Guideline 404.
0.5 mL of test substance was applied to the clipped skin area on the back of each animal under a 25 x 25 mm gauze pad. The pad was allowed to remain in contact with the skin for 4 h. Animals were scored for irritation reactions after 1, 24, 48 and 72 hours then 7 and 14 days.
The general health of the animals was monitored at each observation point (24, 48, 72 h, and 7 and 14 days). Bodyweights were recorded pre-test and at termination. Scoring was done according to the Draize methodology.
Erythema scores, very slight to well defined at 1 hour following patch removal, ranged from absent to severe through Day 1 and cleared by Day 14. One animal had poor hair regrowth on Day 7, which cleared by Day 14. Edema scores generally ranged from absent to slight through Day 7 and cleared by Day 14, with the exception of a score 3 (moderate) in one animal at 24 hours. The primary dermal skin irritation index was equivalent to 3.67.
Under the test conditions, the test substance was considered to be irritating but not corrosive to skin.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 06 April 1992 - 12 November 1992
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England- Age at study initiation: approximately 11 to 14 weeks of age- Weight at study initiation: range of 2.6 to 3.0 kg- Housing: individually- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: yesENVIRONMENTAL CONDITIONS- Temperature (°C): approximately 19°C- Humidity (%): at 30-70%- Air changes (per hr): approximately 19 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours of artificial light in each 24 hours period
- Type of coverage:
- semiocclusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not specified
- Amount / concentration applied:
- TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 ml
- Duration of treatment / exposure:
- 4 hours
- Observation period:
- 4 days
- Number of animals:
- 3 animals
- Details on study design:
- TEST SITE- Area of exposure: dorso-lumbar region, application under a 25 mm x 25 mm gauze pad- Type of wrap if used: covered with "Elastoplast" elastic adhesiveREMOVAL OF TEST SUBSTANCE- Washing (if done): Washing with warm water (30 - 40°C) (dried with absorbent paper)- Time after start of exposure: 4 hours post-exposure
- Irritation parameter:
- erythema score
- Basis:
- mean
- Score:
- 0
- Irritation parameter:
- edema score
- Basis:
- mean
- Score:
- 0
- Irritant / corrosive response data:
- No dermal response to the test substance was observed in any animal throughout the observation period.
- Other effects:
- There were no signs of toxicity or ill health in any rabbit during the observation period.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the test conditions, the test substance was considered non-irritating to skin.
- Executive summary:
A study was performed to assess the skin irritation potential of the test substance to the skin of New Zealand White rabbits according to EU Method B.4.
0.5 mL of test substance was applied to the shaved skin area on the back of each animal under a 25 mm x 25 mm gauze pad. The pad was applied and allowed to remain in contact with the skin for 4 h. Animals were scored for irritation reactions on day 1 (approximately 30 min after removal of the dressing), 2, 3 and 4 days.
A single 4 h semi-occluded application of the test substance to the intact skin of three male rabbits did not produced dermal response throughout the observation period.
Under the test conditions, the application of the test substance to intact rabbit skin for 4 h elicited no dermal reactions.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 10 January 2006 - 01 February 2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK- Age at study initiation: 12-20 weeks- Weight at study initiation: 2.0-3.5 kg- Housing: Individually housed in suspended cages- Diet (e.g. ad libitum): Certified Rabbit Diet (Code 5322) supplied by BCM IPS Limited, London, UK; ad libitum- Water (e.g. ad libitum): Mains drinking water; ad libitum- Acclimation period: 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 17-23 °C- Humidity (%): 30-70 %- Air changes (per h): 15/h- Photoperiod (h dark / h light): 12 h dark / 12 h light
- Type of coverage:
- semiocclusive
- Preparation of test site:
- other: clipped
- 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:
- 3 min, 1 or 4 hours
- Observation period:
- 14 days
- Number of animals:
- Three
- Details on study design:
- TEST SITE- Area of exposure: 2.5 X 2.5 cm2- Type of wrap if used: Trunk of the rabbit was wrapped in an elasticated corset to prevent the animal interfering with the patches REMOVAL OF TEST SUBSTANCE- Washing (if done): Residual test material was removed by gentle swabbing with cotton wool soaked in distilled water- Time after start of exposure: 3 min, 1 or 4 hoursSCORING SYSTEM: Draize scoring system
- Irritation parameter:
- primary dermal irritation index (PDII)
- Basis:
- mean
- Time point:
- 24/48 h
- Score:
- 2
- Max. score:
- 8
- Reversibility:
- fully reversible within: 14 days
- Irritant / corrosive response data:
- Exposure period: 3 min- No evidence of skin irritationExposure period: 1 h- Very slight erythema was noted at the treated skin site at 24 and 48-h- Very slight oedema was noted at the treated skin site at 24-h- Treated skin site appeared normal at the 72-hExposure period: 4 h- Very slight to well-defined erythema was noted at all treated skin sites one hour after patch removal- Well-defined erythema was noted at all treated skin sites at the 24-h observation with very slight to well-defined erythema at the 48-h observation and very slight erythema at the 72-h observation- Very slight oedema was noted at all treated skin sites one hour after patch removal and at the 24 and 48-h observations- Slight desquamation was noted at one treated skin site with moderate desquamation at the remaining two treated skin sites at the 7-d observation- Two treated skin sites appeared normal at the 14-d observation
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the test conditions, the primary skin irritation score of the test substance was calculated to be 2.0.
- Executive summary:
A study was performed to assess the skin irritation potential of the test substance to the skin of New Zealand White rabbits according to GLP compliant OECD Guideline 404 and EU Method B.4. 0.5 mL of the test substance was applied to the clipped skin area on the back of each animal under a 2.5 cm X 2.5 cm cotton gauze patch. On one rabbit, patches were applied at three different sites and one patch was removed at each of the three time points: 3 min, 1 and 4 hours after application. On two additional rabbits, only one patch was applied and allowed to remain in contact with the skin for 4 hours. Animals were scored for irritation reactions at 1, 24, 48 and 72 h post-application and observed for reversibility on Days 7 and 14. A single 4 h, semi-occluded application of the test substance to the intact skin of three rabbits produced well-defined erythema and very slight oedema. Slight or moderate desquamation was also noted. Two treated skin sites appeared normal on day 14. 3 min and 1 h semi-occluded applications of the test substance to the intact skin of one rabbit produced no corrosive effects. All irritation reactions were observed to be completely reversible within 14 days. Under the test conditions, the primary skin irritation score of the test substance was calculated to be 2.0 (Sanders, 2006).
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 25 August 1999 - 25 February 2000
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2500 (Acute Dermal Irritation)
- Deviations:
- no
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- Himalayan
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: Boehringer Ingelheim Pharma KG- Age at study initiation: Young adult animals- Housing: single housing- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): tap water ad libitum- Acclimation period: acclimatization for at least 1 weekENVIRONMENTAL CONDITIONS- Temperature (°C): range of 20 - 24°C- Humidity (%): range of 30 - 70%- Photoperiod (hrs dark / hrs light): 12h/ 12h
- Type of coverage:
- semiocclusive
- Preparation of test site:
- other: intact untreated skin
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: untreated skin sites of the same animal
- Amount / concentration applied:
- 0.5 ml of unchanged liquid test substance
- Duration of treatment / exposure:
- 4 hours
- Observation period:
- 14 days (readings at 1 hour, 24 hours, 48 hours, 72 hours, 7 days and 14 days)
- Number of animals:
- 3 animals
- Details on study design:
- TEST SITE- Area of exposure: 2.5 cm x 2.5 cm- Type of wrap if used: The test substance was covered with a test patch (Idealbinde, Pfaelzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull (R) stretch (adhesive fleece), Beiersdorf AGREMOVAL OF TEST SUBSTANCE- Washing (if done): Removed at the end of the exposure period with Lutrol (R) and Lutrol (R)/water (1:1).Lutrol (R) E400 - Polyethyleneglycol DAB, BASF Aktiengesellschaft
- Irritation parameter:
- erythema score
- Basis:
- mean
- Score:
- 2
- Reversibility:
- not reversible
- Remarks:
- in all animals within 14 days
- Irritation parameter:
- edema score
- Basis:
- mean
- Score:
- 0.3
- Reversibility:
- fully reversible within: 24 h
- Irritant / corrosive response data:
- The average score (24 to 72 hours) for irritation was calculated to be 2.0 for erythema and 0.3 for edema.
- Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- Under the test conditions, the test substance was considered to be irritating to skin.
- Executive summary:
A study was conducted to evaluate the skin irritancy potential of the test substance using the in vivo acute dermal irritation/ corrosion assay in rabbits.
The average score (24 to 72 h) for irritation was calculated to be 2.0 for erythema and 0.3 for edema. The skin findings were not reversible in all animals within 14 days after removal of the patches. Symptoms observed and described in the respective observation table in detail together with the average score for irritation indicate an irritant property of the test substance to the skin.
Referenceopen allclose all
Table 1: Bodyweights (BW) | ||||
Rabbit N° | 1 | 2 | 3 | |
Pretest BW (kg) | 2.2 | 2.6 | 2.2 | |
Terminal BW | 2.5 | 2.5 | 2.6 |
Table 2: Erythema and eschar formation | ||||
Rabbit N° | 1 | 2 | 3 | Mean |
Time after patch removal | Score | |||
1 h | 1 | 1 | 2 | |
24 h | 1 | 2 | 4 | 2.33 |
48 h | 2 | 2 | 4 | |
72 h | 0 | 2 | 4 | 2.00 |
7 d | 0 | 2 | 4 | |
14 d | 0 | 0 | 0 | |
Table 3: Edema | ||||
Rabbit N° | 1 | 2 | 3 | Mean |
Time after patch removal | Score | |||
1 h | 0 | 0 | 2 | |
24 h | 0 | 3 | 2 | 1.67 |
48 h | 0 | 2 | 2 | |
72 h | 0 | 2 | 2 | 1.33 |
7 d | 0 | 1 | 2 | |
14 d | 0 | 0 | 0 | |
Sum of mean scores | 7.33 | |||
PDII | 3.67 | |||
Table 4: Systemic observations | ||||
Rabbit N° | 1 | 2 | 3 | |
Time after patch removal | ||||
1 h | A | A | A | |
24 h | A | A | A | |
48 h | A | A | A | |
72 h | A | A | A | |
7 d | A | A | A | |
14 d | A | D | A | |
A: normal; D: diarrhea |
Dermal reactions observed after application of UVECRYL P115:
(* Approximately 30 minutes after removal of the dressing)
Rabbit number & sex | E = Erythema O = Oedema |
Day | |||
1* | 2 | 3 | 4 | ||
288 - male | E / O | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
289 - male | E / O | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
290 - male | E / O | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Table 1: Individual skin reactions following 4 -h exposure
Skin reaction | Observation time | Individual Scores - Rabbit Number and Sex | Total | ||
Male 17 | Male 124 | Male 131 | |||
Erythema/Eschar formation | 1 h | 1 | 2 | 2 | 5 |
24 h | 2 | 2 | 2 | 6 | |
48 h | 1 | 1 | 2 | 4 | |
72 h | 1 | 1 | 1 | 3 | |
7 d | 0 D | 0 D* | 0 D* | 0 | |
14 d | - | 0 | 0 | 0 | |
Oedema formation | 1 h | 1 | 1 | 1 | 3 |
24 h | 1 | 1 | 1 | 3 | |
48 h | 1 | 1 | 1 | 3 | |
72 h | 0 | 0 | 0 | 0 | |
7 d | 0 | 0 | 0 | 0 | |
14 d | - | 0 | 0 | 0 | |
Sum of 24 and 72 h Readings (S) | 12 | ||||
Primary Irritation Index (S/6) | 2 |
D = Slight desquamation D* = Moderate desquamation
Table 2: Individual skin reactions following 1-hour and 3-minute exposures
Skin Reaction | Observation Time | Individual Scores -Rabbit Number and Sex | |
17 Male | |||
1-Hour Exposure | 3-Minute Exposure | ||
Erythema/Eschar Formation | 1 Hour | 0 | 0 |
24 Hours | 1 | 0 | |
48 Hours | 1 | 0 | |
72 Hours | 0 | 0 | |
7 Days | 0 | 0 | |
Oedema Formation | 1 Hour | 0 | 0 |
24 Hours | 1 | 0 | |
48 Hours | 0 | 0 | |
72 Hours | 0 | 0 | |
7 Days | 0 | 0 |
Tabulation of irritant response data for each individual animal at each observation time as well as calculation of the means.
Readings | Animal | Erythema | Edema | Symptoms (exposure period : 4 hours) |
1 hour | 01 | 2 | 2 | 24 |
02 | 2 | 0 | ||
03 | 2 | 0 | ||
24 hours | 01 | 2 | 2 | 15, 16, 24 |
02 | 2 | 1 | 15, 16 | |
03 | 2 | 0 | 15 | |
48 hours | 01 | 2 | 0 | 15, 24 |
02 | 2 | 0 | 15 | |
03 | 2 | 0 | 15 | |
72 hours | 01 | 2 | 0 | 15, 24 |
02 | 2 | 0 | ||
03 | 2 | 0 | ||
7 days | 01 | 2 | 0 | 15, 24 |
02 | 2 | 0 | S | |
03 | 2 | 0 | S | |
14 days | 01 | 2 | 0 | S, 15 |
02 | 2 | 0 | S | |
03 | 1 | 0 | S | |
Mean | 01 | 2.0 | 0.7 | |
02 | 2.0 | 0.3 | ||
03 | 2.0 | 0.0 | ||
Mean | 2.0 | 0.3 |
S: scaling
15: Erythema extending beyond the area of exposure
16: Edema extending beyond the area of exposure
24: Petechiae
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 28 November 1997 - 09 January 1998
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- not specified
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS- Source: Ace Animals, Boyertown, PA, USA- Weight at study initiation: 2.1 - 2.3 kg- Housing: Individually in suspended metal cages- Diet (e.g. ad libitum): Purina Rabbit Chow (Diet no. 5321)- Acclimation period: At least 5 daysENVIRONMENTAL CONDITIONS- Photoperiod (hrs dark / hrs light): 12/12
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: The contralateral eye remained untreated.
- Amount / concentration applied:
- A 0.1 ml amount of the test substance was placed into the conjunctival sac of the lower everted lid of one eye of each animal.
- Duration of treatment / exposure:
- The eyelids were then gently held together for one second before releasing.
- Observation period (in vivo):
- 7 days
- Number of animals or in vitro replicates:
- 3
- Details on study design:
- REMOVAL OF TEST SUBSTANCE- Washing (if done): NoneSCORING SYSTEM: Draize scaleTOOL USED TO ASSESS SCORE: hand-slit lamp
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 2
- Reversibility:
- fully reversible
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 2
- Reversibility:
- fully reversible
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 2
- Reversibility:
- fully reversible
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1.67
- Max. score:
- 3
- Reversibility:
- fully reversible
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 3
- Reversibility:
- fully reversible
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 3
- Reversibility:
- fully reversible
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2.33
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritant / corrosive response data:
- Corneal opacity and conjunctival irritation, noted in 3/3 eyes, cleared by Day 7. Iritis, noted in 3/3 eyes, cleared by Day 3.
- Other effects:
- One instance of diarrhea was the only abnormal physical sign noted during the observation period.
- Interpretation of results:
- Category 2 (irritating to eyes) based on GHS criteria
- Conclusions:
- Under the test conditions, the test substance was considered to be irritating but not corrosive to eyes.
- Executive summary:
A study was performed to assess the eye irritancy potential of the test substance in New Zealand White rabbits according to OECD Guideline 405.
A single ocular dose of 0.1 mL of test substance was applied into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. Examination of the eyes was made 1, 24, 48 and 72 hours post dose, then on Day 7. SCoring was conducted according to the method of Draize. The general health of the animals was monitored at each observation time. Bodyweights were recorded pretest.
Corneal opacity and conjunctival irritation, noted in 3/3 eyes, cleared by Day 7. Iritis, noted in 3/3 eyes, cleared by Day 3. One instance of diarrhea was the only abnormal physical sign noted during the observation period.
Under the test conditions, the test substance was considered to be irritating but not corrosive to eyes.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 13 December 1993 - 24 February 1998
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS- Source:Froxfield (U.K.) Ltd., Petersfield, Hampshire, England- Age at study initiation: approximately 13 to 15 weeks of age- Weight at study initiation: range of 2.9 to 3.5 kg- Housing: individually- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: yesENVIRONMENTAL CONDITIONS- Temperature (°C): approximately 19°C- Humidity (%): relative humidity at 30-70%- Air changes (per hr): approximately 19 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours of artificial light in each 24 hours period
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: The contralateral eye remained untreated.
- Amount / concentration applied:
- A 0.1 ml amount of the test substance was placed into the lower everted lid of one eye of each animal.
- Duration of treatment / exposure:
- The eyelids were then gently held together for one second before releasing.
- Observation period (in vivo):
- 14 days after instillation
- Number of animals or in vitro replicates:
- 3 animals
- Details on study design:
- TOOL USED TO ASSESS SCORE: handheld light
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 2
- Reversibility:
- fully reversible
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 2
- Reversibility:
- fully reversible
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- fully reversible
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 3
- Reversibility:
- fully reversible
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1.67
- Max. score:
- 3
- Reversibility:
- fully reversible
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1.67
- Max. score:
- 3
- Reversibility:
- fully reversible
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1.67
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1.33
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritant / corrosive response data:
- Corneal opacities developed in all three animals. Stripping of the corneal epithelial cells was seen in all three animals.Iridial inflammation was seen on one occasion only in two animals.A crimson colouration of the conjunctivae was seen in all three animals, accompanied by swelling with partial eversion of the eyelids.The eyes were normal 7 or 14 days after instillation.
- Other effects:
- There were no signs of toxicity or ill health in any rabbit during the observation period.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the test conditions, the test substance was considered to slightly irritating.
- Executive summary:
A study was performed to assess the eye irritancy potential of the test substance to the eye of New Zealand White rabbits according to EU Method B.5.
A single ocular dose of 0.1 mL of test substance was applied into the eye of the rabbit (into the lower everted lid of one eye of each animal). The eyelids were then gently held together for one second before releasing. Examination of the eyes was made 1 h and 1, 2, 3, 4, 7 and 14 days after instillation.
A single instillation of the test substance into the eye of the rabbits elicited corneal opacification, iridial inflammation and well-defined conjunctival irritation. All reactions had resolved 7 or 14 days after instillation.
Under the test conditions, the application of the test substance into the eye of the rabbit elicited slight irritation.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 06 February 2006 - 14 March 2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK- Age at study initiation: 12-20 weeks- Weight at study initiation: 2.0-3.5 kg- Housing: Individually housed in suspended cages- Diet (e.g. ad libitum): Certified Rabbit Diet (Code 5322) supplied by BCM IPS Limited, London, UK; ad libitum- Water (e.g. ad libitum): Mains drinking water; ad libitum- Acclimation period: 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 17-23 °C- Humidity (%): 30-70 %- Air changes (per h): 15/h- Photoperiod (h dark / h light): 12 h dark / 12 h light
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- TEST MATERIAL- Amount(s) applied (volume with unit): 0.1 mL
- Duration of treatment / exposure:
- Single exposure
- Observation period (in vivo):
- 21 days
- Number of animals or in vitro replicates:
- Three
- Details on study design:
- SCORING SYSTEM: Draize Scoring SystemTOOL USED TO ASSESS SCORE: Standard ophthalmoscope
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Time point:
- other: 24, 48 and 72 hours
- Score:
- ca. 0.47
- Max. score:
- 4
- Reversibility:
- fully reversible within: 21 days
- Irritation parameter:
- iris score
- Basis:
- mean
- Time point:
- other: 24, 48 and 72 hours
- Score:
- ca. 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Time point:
- other: 24, 48 and 72 hours
- Score:
- ca. 1.23
- Max. score:
- 4
- Reversibility:
- fully reversible within: 14 days
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Time point:
- other: 24, 48 and 72 hours
- Score:
- ca. 1.1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- maximum mean total score (MMTS)
- Basis:
- mean
- Time point:
- other: 48 hours
- Score:
- 19
- Max. score:
- 110
- Irritant / corrosive response data:
- - Average cornea opacity, iritis, conjunctival redness and conjuctival chemosis at 24, 48 and 72 hours for the three animals was observed to be 0.7/1.0+/1.7/1.3; 0.0/0.7/1.0/1.0 and 0.7/0.3/1.0/1.0, respectively- Maximum group mean score of the test material was calculated to be 19.0/110
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the test conditions, the maximum mean eye irritation score of the test substance was calculated to be 19.0/110.
- Executive summary:
A study was performed to assess the eye irritation potential of the test substance to the eyes of the New Zealand White rabbits according to GLP compliant OECD Guideline 405 and EU Method B.5.
0.1 mL of the test substance was instilled into the conjuctival sac of the right eye of each rabbit. The left eye of each animal served as a control. Without washing, eyes were scored (Draize scoring system) for irritation reactions at 1, 24, 48, 72 h and 7, 14 and 21days post-instillation.
A single application of the test substance to the non-irritated eye of three rabbits produced scattered or diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation. Petechial haemorrhage of the nictitating membrane was also noted. Two treated eyes appeared normal at the 7 days observation and the remaining treated eye appeared normal at the 21 days observation. Average cornea opacity, iritis, conjunctival redness and conjuctival chemosis at 24, 48 and 72 h for the three animals was observed to be 0.7/1.0+/1.7/1.3; 0.0/0.7/1.0/1.0 and 0.7/0.3/1.0/1.0 respectively.
Under the test conditions, the maximum group mean eye irritation score of the test substance was calculated to be 19.0/110.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 23 September 1999 - 25 February 2000
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2400 (Acute Eye Irritation)
- Deviations:
- no
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- Himalayan
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS- Source: Boehringer Ingelheim Pharma KG- Age at study initiation: Young adult animals- Housing: single housing- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): tap water ad libitum- Acclimation period: acclimatization for at least 1 weekENVIRONMENTAL CONDITIONS- Temperature (°C): range of 20 - 24°C- Humidity (%): range of 30 - 70%- Photoperiod (hrs dark / hrs light): 12h/ 12h
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: untreated eye
- Amount / concentration applied:
- 0.1 ml (the test substance was applied in a single dose to the conjunctival sac of the right eyelid)
- Duration of treatment / exposure:
- 24 hours
- Observation period (in vivo):
- up to 14 days (1 hour, 24 hours, 48 hours, 72 hours, 7 days and 14 days)
- Number of animals or in vitro replicates:
- 3 animals(As the irritant potential of the test substance was unknown 1 animal was tested in a first step. As no severe findings were noted in the animal, another 2 animals were tested. The results of the 3 animals were pooled for evaluation.)
- Details on study design:
- Both eyes of the animal(s) were examined before application of the test material for signs of pre-existing irritation, reaction or abnormality which would prevent it from being used in the study.REMOVAL OF TEST SUBSTANCE- Washing (if done): washed out with tap water - Time after start of exposure: about 24 hours after application
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Score:
- 0.8
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- mean
- Score:
- 0.4
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Score:
- 1.7
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Score:
- 0.6
- Max. score:
- 4
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the test conditions, the test substance was considered to be slightly irritating to the eye.
- Executive summary:
A study was conducted to evaluate the eye irritancy potential of the test substance using in vivo acute eye irritation assay in rabbits.
A sample of 0.1 mL was instilled into the conjuctival sac of the right eye of each rabbit. Effects were scored according to the Draize methodology after 1, 24, 48 and 72 hours, then 7 and 14 days. Calculation of the mean according to 93/21/EEC criteria of April 27th, 1993 (for calculation of the means of cornea opacity, redness and swelling of the conjunctiva only the readings of 24, 48 and 72 h were used).
The mean in vivo irritation score (24 to 71 h) for the test substance was calculated to be 0.8 for cornea opacity, 0.4 for iris, 1.7 for conjunctiva redness and 0.6 for chemosis. The findings were reversible in all animals within 7days (animal 1) or within 14 days (animals 2 and 3) after application, thus this study was terminated after 7 or 14 days. Symptom observed and described in the respective observation table in detail together with the average score for irritation indicate a slight irritant property of the test substance to the eye.
Under the test conditions, the test substance was considered to be slightly irritant to the eye.
Referenceopen allclose all
Table 1: Ocular findings and systemic observations | ||||||||
Animal no. | Item | Tissue | Reading | 1 h | 24 h | 48 h | 72 h | 7 d |
1 | A | Cornea | Opacity | 2 | 2 | 2 | 2 | 0 |
B | Area | 2 | 2 | 2 | 1 | 0 | ||
1. Total = (AxB)x5 | 20 | 20 | 20 | 10 | 0 | |||
C | Iris | 0 | 1 | 1 | 0 | 0 | ||
2. Total = Cx5 | 0 | 5 | 5 | 0 | 0 | |||
D | Conjunctiva | Redness | 2 | 2 | 2 | 1 | 0 | |
E | Chemosis | 3 | 3 | 2 | 2 | 0 | ||
F | Discharge | 2 | 2 | 2 | 2 | 0 | ||
3. Total = (D+E+F)x2 | 14 | 14 | 12 | 10 | 0 | |||
Total = 1+2+3 | 34 | 39 | 37 | 20 | 0 | |||
Systemic observations | A | A | A | A | A | |||
Pretest bodyweight | 2.2 kg | |||||||
Animal no. | Item | Tissue | Reading | 1 h | 24 h | 48 h | 72 h | 7 d |
2 | A | Cornea | Opacity | 2 | 2 | 2 | 2 | 0 |
B | Area | 2 | 2 | 2 | 1 | 0 | ||
1. Total = (AxB)x5 | 20 | 20 | 20 | 10 | 0 | |||
C | Iris | 1 | 1 | 0 | 0 | 0 | ||
2. Total = Cx5 | 5 | 5 | 0 | 0 | 0 | |||
D | Conjunctiva | Redness | 2 | 2 | 1 | 1 | 0 | |
E | Chemosis | 2 | 2 | 2 | 2 | 0 | ||
F | Discharge | 2 | 2 | 2 | 0 | 0 | ||
3. Total = (D+E+F)x2 | 12 | 12 | 10 | 6 | 0 | |||
Total = 1+2+3 | 37 | 37 | 30 | 16 | 0 | |||
Systemic observations | A | A | A | D | A | |||
Pretest bodyweight | 2.3 kg | |||||||
Animal no. | Item | Tissue | Reading | 1 h | 24 h | 48 h | 72 h | 7 d |
3 | A | Cornea | Opacity | 2 | 2 | 2 | 2 | 0 |
B | Area | 2 | 3 | 3 | 2 | 0 | ||
1. Total = (AxB)x5 | 20 | 30 | 30 | 20 | 0 | |||
C | Iris | 1 | 1 | 0 | 0 | 0 | ||
2. Total = Cx5 | 5 | 5 | 0 | 0 | 0 | |||
D | Conjunctiva | Redness | 2 | 2 | 1 | 1 | 0 | |
E | Chemosis | 2 | 2 | 2 | 2 | 0 | ||
F | Discharge | 2 | 2 | 2 | 2 | 0 | ||
3. Total = (D+E+F)x2 | 12 | 12 | 10 | 10 | 0 | |||
Total = 1+2+3 | 37 | 47 | 40 | 30 | 0 | |||
Systemic observations | A | A | A | A | A | |||
Pretest bodyweight | 2.1 kg | |||||||
Mean scores | 36 | 41 | 36 | 22 | 0 | |||
A: normal; D: diarrhea |
Ocular reactions observed after instillation of P115:
(* - pilot animal; a - stripping of corneal epithelial cells; D - Dulling)
Rabbit number and sex | Region of eye | One hour | Day after instillation | ||||||
1 | 2 | 3 | 4 | 7 | 14 | ||||
2765 female * | Cornea | aD | a1 | 1 | 1 | 2 | 1 | 0 | |
Iris | 0 | 0 | 1 | 0 | 0 | 0 | 0 | ||
Conjunctiva | Redness | 2 | 2 | 2 | 2 | 2 | 0 | 0 | |
Chemosis | 2 | 2 | 2 | 2 | 2 | 0 | 0 | ||
2773 female | Cornea | aD | 1 | 2 | 1 | 1 | 0 | ||
Iris | 0 | 1 | 0 | 0 | 0 | 0 | |||
Conjunctiva | Redness | 2 | 2 | 2 | 1 | 1 | 0 | ||
Chemosis | 2 | 2 | 2 | 1 | 0 | 0 | |||
2775 female | Cornea | aD | 1 | 1 | 1 | 1 | 0 | ||
Iris | 0 | 0 | 0 | 0 | 0 | 0 | |||
Conjunctiva | Redness | 2 | 2 | 2 | 1 | 1 | 0 | ||
Chemosis | 2 | 2 | 1 | 1 | 0 | 0 |
Table 1: Individual and Mean Scores for Cornea, Iris and Conjunctivae for EU Labelling Regulations
Rabbit Number and Sex | Time After Treatment | Corneal Opacity | Iridial Inflammation | Conjunctival Redness | Conjunctival Chemosis |
20 Male | 24 h | 0 | 1 | 2 | 2 |
48 h | 1 | 1 | 2 | 1 | |
72 h | 1 | 1 | 1 | 1 | |
Total | 2 | 3 | 5 | 4 | |
Mean | 0.7 | 1.0+ | 1.7 | 1.3 | |
159 Male | 24 h | 0 | 1 | 1 | 1 |
48 h | 0 | 1 | 1 | 1 | |
72 h | 0 | 0 | 1 | 1 | |
Total | 0 | 2 | 3 | 3 | |
Mean | 0 | 0.7 | 1 | 1 | |
161 Male | 24 h | 1 | 1 | 1 | 1 |
48 h | 1 | 0 | 1 | 1 | |
72 h | 0 | 0 | 1 | 1 | |
Total | 2 | 1 | 3 | 3 | |
Mean | 0.7 | 0.3 | 1 | 1 |
+ = Positive criteria
Tabulation of irritant response data for each individual animal at each observation time as well as calculation of the means.
Readings | Animal | Cornea op | Cornea ar | Iris | Conjunctiva red | Conjunctiva sw | Conjuntiva di | Symptoms |
1 h | 01 | 0 | 0 | 0 | 2 | 2 | 2 | |
02 | 0 | 0 | 0 | 2 | 1 | 1 | ||
03 | 0 | 0 | 0 | 2 | 1 | 2 | Suppuration | |
24 h | 01 | 1 | 2 | 0 | 2 | 1 | 0 | |
02 | 1 | 3 | 1 | 2 | 0 | 0 | ||
03 | 1 | 2 | 1 | 2 | 1 | 3 | Suppuration | |
48 h | 01 | 0 | 0 | 0 | 1 | 1 | 0 | |
02 | 1 | 4 | 0 | 2 | 0 | 0 | ||
03 | 1 | 4 | 1 | 2 | 1 | 2 | Suppuration | |
72 h | 01 | 0 | 0 | 0 | 1 | 0 | 0 | |
02 | 1 | 4 | 0 | 1 | 0 | 0 | ||
03 | 1 | 4 | 1 | 2 | 1 | 2 | Suppuration | |
7 d | 01 | 0 | 0 | 0 | 0 | 0 | 0 | Study discontinued because the animal was free of symptoms |
02 | 0 | 0 | 0 | 1 | 0 | 0 | ||
03 | 0 | 0 | 0 | 1 | 0 | 0 | ||
14 d | 02 | 0 | 0 | 0 | 0 | 0 | 0 | Study discontinued because the animal was free of symptoms |
03 | 0 | 0 | 0 | 0 | 0 | 0 | Study discontinued because the animal was free of symptoms | |
Mean | 01 | 0.3 | 0.0 | 1.3 | 0.7 | |||
02 | 1.0 | 0.3 | 1.7 | 0.0 | ||||
03 | 1.0 | 1.0 | 2.0 | 1.0 | ||||
Mean | 0.8 | 0.4 | 1.7 | 0.6 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation
A study was performed to assess the skin irritation potential of amine synergist in New Zealand White rabbits according to OECD Guideline 404 and EU Method B.4. A sample of 0.5 mL was applied to the clipped skin on the back of each animal under a 2.5 x 2.5 cm cotton gauze patch. Animals were scored for irritation reactions at 1, 24, 48 and 72 h post-application and observed for reversibility on Days 7 and 14. Well-defined erythema and very slight oedema occurred. Slight or moderate desquamation was also noted. Two treated skin sites appeared normal on Day 14. Three minutes and 1 h semi-occluded applications of the test substance to the intact skin of one rabbit produced no corrosive effects. All irritation reactions were observed to be completely reversible within 14 days. The primary skin irritation score was calculated to be 2.0. The substance thereby qualifies as mildly irritating (Sanders, 2006).
A study was conducted in Himalayan rabbits to evaluate the skin irritation potential of the substance using thein vivoacute dermal irritation/ corrosion assay in rabbits (OECD Guideline 404 and EU Method B.4). The average score (24 to 72 h) for irritation was calculated to be 2.0 for erythema and 0.3 for edema. On Day 14 after removal of the patches, scaling was seen in 3 animals and erythema extending beyond the area of exposure in one. Edema was resolved within 24 h. The authors conclude that the substance gives indications of irritant properties since some effects persisted until end of the 14 day observation period (Wiemann and Hellwig, 2000).
A study was performed to assess the skin irritation potential of the test substance to the skin of New Zealand White rabbits according to OECD Guideline 404. 0.5 mL of test substance was applied to the clipped skin area on the back of each animal under a 25 x 25 mm gauze pad. The pad was allowed to remain in contact with the skin for 4 h. Animals were scored for irritation reactions after 1, 24, 48 and 72 hours then 7 and 14 days. Erythema scores, very slight to well defined at 1 hour following patch removal, ranged from absent to severe through Day 1 and cleared by Day 14. One animal had poor hair regrowth on Day 7, which cleared by Day 14. Edema scores generally ranged from absent to slight through Day 7 and cleared by Day 14, with the exception of a score 3 (moderate) in one animal at 24 hours. The primary dermal skin irritation index was equivalent to 3.67. Under the test conditions, the test substance was considered to be irritating but not corrosive to skin (Kieffer, 1998).
A study was performed to assess the skin irritation potential of the substance in New Zealand White rabbits according to EU Method B.4. 0.5 mL were applied to the shaved skin area on the back of each animal under a 25 x 25 mm gauze pad. The pad was allowed to remain in contact with the skin for 4 h. Animals were scored for irritation reactions on Days 1 (approximately 30 minutes after removal of the dressing), 2, 3 and 4. No dermal reactions were observed (Liggett, 1992).
The skin irritation potential of the substance was determined using anin vivomethod, as described in the Code of Federal Regulations, Title16, Section 1500.41. Six New Zealand White rabbits were administered a dermal dose of 0.5 ml to one intact and one abraded skin site under occlusive conditions for 24 hours and observed for three days. Well-defined moderate to severe dermal irritation was noted. The Primary Irritation Index (PII) was calculated to be 4.1 (Parcell, 1998). This study was disregarded because the protocol is not in line with classification and labelling requirements: exposure was 24 h rather than 4 h and abraded skin was also evaluated.
Eye irritation
A study was performed to assess the eye irritation potential of amine synergist in New Zealand White rabbits according to OECD Guideline 405 and EU Method B.5. The left eye served as a control. Without washing, eyes were scored (Draize scoring system) for irritation reactions at 1, 24, 48, 72 h and 7, 14 and 21days post-instillation. Scattered or diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation were seen. Petechial haemorrhage of the nictitating membrane was also noted. Two treated eyes appeared normal at Day 7 and the remaining treated eye appeared normal at Day 21. The maximum group mean eye irritation score was calculated to be 19.0/110 (Sanders, 2006).
A further study was performed to assess the eye irritation potential of the substance in Himalayan rabbits according to OECD Guideline 405 and EU Method B.5. A sample of 0.1 mL was instilled into the conjuctival sac of the right eye of each rabbit. Effects were scored according to the Draize methodology after 1, 24, 48 and 72 hours, then 7 and 14 days. Calculation of the mean according to 93/21/EEC criteria of April 27th, 1993 (for calculation of the means of cornea opacity, redness and swelling of the conjunctiva only the readings of 24, 48 and 72 h were used). The meanin vivoirritation score (24 to 72 h) was calculated to be 0.8 for cornea opacity, 0.4 for iris, 1.7 for conjunctiva redness and 0.6 for chemosis. The findings were reversible in all animals within 7 or 14 days. Under the test conditions, the test substance was considered to be slightly irritating to the eye (Wiemann, 2000).
A study was performed to assess the eye irritation potential of the substance in New Zealand White rabbits according to EU Method B.5. A single ocular dose of 0.1 mL was applied into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. Examination was made after 1 h and 1, 2, 3, 4, 7 and 14 days. Corneal opacification, iridial inflammation and well-defined conjunctival irritation were seen. All reactions had resolved within 7 or 14 days (Parcell, 1998).
A study was performed to assess the eye irritancy potential of the test substance in New Zealand White rabbits according to OECD Guideline 405. A single ocular dose of 0.1 mL of test substance was applied into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. Examination of the eyes was made 1, 24, 48 and 72 hours post dose, then on Day 7. Scoring was conducted according to the method of Draize. The general health of the animals was monitored at each observation time. Bodyweights were recorded pretest. Corneal opacity and conjunctival irritation, noted in 3/3 eyes, cleared by Day 7. Iritis, noted in 3/3 eyes, cleared by Day 3. One instance of diarrhoea was the only abnormal physical sign noted during the observation period. Under the test conditions, the test substance was considered to be irritating but not corrosive to eyes (Cerven, 1998).
Justification for classification or non-classification
Amine synergist was only mildly or not irritating to skin in two of four reliable studies. In a third study, certain effects (scaling in three animals, erythema extending beyond the area of exposure in one animal) were still seen at the end of the 14 day observation period, so that the authors concluded that the substance gave indications of irritant properties. In the fourth test, the substance was clearly irritating, with symptoms resolving by end of the 14 day observation period. Individual animal scores from the two last studies suggest that classification as Skin Irrit. 2 – H315 (Causes skin irritation) is required according to CLP (EC 1271/2008) criteria.
The substance was not irritating in one study and slightly irritating in two studies. In a last study, individual irritation scores suggest classification under CLP (EC 1271/2008) criteria. Classification of the substance as Eye Irrit. 2 - H319 (Causes serious eye irritation) according to CLP (EC 1271/2008) criteria is proposed.
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