Registration Dossier
Registration Dossier
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EC number: - | CAS number: -
Endpoint summary
Administrative data
Description of key information
Skin irritation: irritating (OECD 404, GLP, Rel.1, K)
Eye irritation: irritating (OECD 405, GLP, Rel.1, K)
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:
- 02/08/1991-28/11/1991
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- According to the OECD Guideline and in compliance with GLP
- 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: Broekman Institute, Someren, The Netherlands
- Age at study initiation: 17 weeks
- Weight at study initiation: 2856-2986 g
- Housing: Individually in labelled cages, with perforated floors and equipped with an automatic drinking system.
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands), approx.100 gram per day.
- Water (e.g. ad libitum): free access to tap water diluted with decalcified water.
- Acclimation period: five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- semiocclusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL - Duration of treatment / exposure:
- 4 hours
- Observation period:
- Body weight: Day 1 of test (application day)
Irritation: Days 1, 2, 3, 4, 8, 15 and 22 - Number of animals:
- 3 females
- Details on study design:
- TEST SITE
- Area of exposure: dorsal/flank area
- Type of wrap if used: test substance was applied to the intact skin using a surgical gauze patch 2 x 3 cm mounted on Micropore tape. The dressing was wrapped around the abdomen and secured with an elastic bandage.
REMOVAL OF TEST SUBSTANCE
- Washing: the remaining test substance was removed using a tissue moistened with tap water and subsequently a dry tissue.
- Time after start of exposure: 4h
OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : approx 1, 24, 48, 72 hours and 7, 14 and 21 days after the removal of the dressings and test substance
SCORING SYSTEM:
Erythema and eschar formation
No erythema: 0
Very slight erythem: 1
Well-defined erythema:2
Moderate to severe erythema: 3
Severe erythema to slight eschar formation: 4
Oedema formation
No oedema:0
Very slight oedema: 1
Slight oedema:2
Moderate oedema:3
Severe oedema:4 - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24 h
- Score:
- 2
- Reversibility:
- not reversible
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24 h
- Score:
- 3
- Reversibility:
- not reversible
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24 h
- Score:
- 1
- Reversibility:
- not reversible
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24 h
- Score:
- 3
- Reversibility:
- not reversible
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24 h
- Score:
- 2
- Reversibility:
- not reversible
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24 h
- Score:
- 3
- Reversibility:
- not reversible
- Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 48 h
- Score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 48 h
- Score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 48 h
- Score:
- 3
- Reversibility:
- not reversible
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 48 h
- Score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 48 h
- Score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 72 h
- Score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 72 h
- Score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 72 h
- Score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 72 h
- Score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 72 h
- Score:
- 4
- Reversibility:
- not reversible
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 72 h
- Score:
- 4
- Reversibility:
- not reversible
- Irritant / corrosive response data:
- The observed skin irritation consisted of slight eschar formation, fissuring of the skin and severe oedema in all three animals. The skin irritation had not resolved completely within the study period (22 days) in all three animals.
Very slight erythema and very slight oedema were observed in animals No. 689 and 711 and very slight erythema only was observed in animal No. 710 on day 22.
There was no evidence of a corrosive effect on the skin. - Other effects:
- No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occured.
- Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- Under the test conditions, test material is classified as H315 "Causes Skin Irritation" Category 2 according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
- Executive summary:
In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of test material was applied on the clipped skin of the dorsal flank area of 3 female New Zealand rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours, followed by seven observations at approximately 1, 24, 48 and 72 hours and 7, 14 and 21 days after removal of dressings and remaining test substance.
The observed skin irritation consisted of slight eschar formation, fissuring of the skin and severe oedema in all three animals. The skin irritation had not resolved completely within the study period (22 days) in all three animals.
Very slight erythema and very slight oedema were observed in animals No. 689 and 711 and very slight erythema only was observed in animal No. 710 on day 22.
There was no evidence of a corrosive effect on the skin.
The individual mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 3.3 / 2.7 / 3.3 for erythema and 3.7 / 3.7 / 3.7 for oedema.
Under the test conditions, test material is classified as H315 "Causes Skin Irritation" Category 2 according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.
Reference
Individual findings:
| time after exposure | Rabbit No. | Erythema | Oedema | Comments |
| 45 min | 689 | 2 | 2 | - |
| 710 | 2 | 1 | - | |
| 711 | 2 | 2 | - | |
| 24h | 689 | 2 | 3 | - |
| 710 | 1 | 3 | - | |
| 711 | 2 | 3 | - | |
| 48h | 689 | 4 | 4 | The treated skin showed less elasticity. |
| 710 | 3 | 4 | - | |
| 711 | 4 | 4 | - | |
| 72h | 689 | 4 | 4 | Treated area showed fissuring of the skin and slight eschar formation. |
| 710 | 4 | 4 | Treated area showed fissuring of the skin and slight eschar formation. | |
| 711 | 4 | 4 | The treated skin showed less elasticity. | |
| 7 days | 689 | 1 | 1 | The treated area showed new skin formation and was covered with scales. |
| 710 | 4 | 3 | Treated area showed fissuring of the skin and slight eschar formation. The treated skin also showed less elasticity. | |
| 711 | 4 | 3 | Treated area showed fissuring of the skin and slight eschar formation. | |
| 14 days | 689 | 1 | 1 | The treated area showed new skin formation and was covered with scales. |
| 710 | 1 | 1 | Approx. 75% of the treated area showed new skin formation and approx. 25% showed scaliness. | |
| 711 | 1 | 1 | Approx. 75% of the treated area showed new skin formation and approx. 25% showed scaliness. | |
| 21 days | 689 | 1 | 1 | - |
| 710 | 1 | 0 | - | |
| 711 | 1 | 1 | - |
Note: The observed skin irritation was noted on a skin area covering approximately 6 x 4 cm, due to spreading of the test substace during exposure.
Calculations for EEC Classification:
| Rabbit No. 689 | Rabbit No. 710 | Rabbit No. 711 | ||||
| observation time | Erythema | Oedema | Erythema | Oedema | Erythema | Oedema |
| 24 h | 2 | 3 | 1 | 3 | 2 | 3 |
| 48 h | 4 | 4 | 3 | 4 | 4 | 4 |
| 72 h | 4 | 4 | 4 | 4 | 4 | 4 |
| mean value | 3.3 | 3.7 | 2.7 | 3.7 | 3.3 | 3.7 |
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:
- 02/08/1991-28/11/1991
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- According to the OECD Guideline and in compliance with GLP
- 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: Broekman Institute, Someren, The Netherlands
- Age at study initiation: 73 weeks
- Weight at study initiation: 2214-2789 g
- Housing: Individually in labelled cages, with perforated floors and equipped with an automatic drinking system.
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands), approx.100 gram per day.
- Water (e.g. ad libitum): free access to tap water diluted with decalcified water.
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL - Duration of treatment / exposure:
- 7 days
- Observation period (in vivo):
- 1, 24, 48 and 72 hours and 7 days after instillation of test material
- Number of animals or in vitro replicates:
- 3 females
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing: not reported
SCORING SYSTEM: Draize scoring system
TOOL USED TO ASSESS SCORE: fluorescein - Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- other: not applicable
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- fully reversible within: 24 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1.7
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.7
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- other: not applicable
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- fully reversible within: 24 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 2
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.7
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- other: not applicable
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- fully reversible within: 24 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 2
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1
- Reversibility:
- fully reversible within: 7 days
- Irritant / corrosive response data:
- Instillation of the test substance into one eye of each of three female albino rabbits affected the iris and conjunctivae of all three animals. The injection of the iris had resolved within 24 hours and the irritation of the conjunctivae had resolved within 7 days in all three animals.
Treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.
There was no evidence of ocular corrosion. - Other effects:
- No toxic symptoms were observed in the animals during the test period and no mortality occured.
- Interpretation of results:
- Category 2B (mildly irritating to eyes) based on GHS criteria
- Conclusions:
- Under the test conditions, the test material is classified as H319 "Causes serious eye irritation" Category 2 according to the Regulation (EC) No. 1272/2008 (CLP) and Category 2B according to the GHS.
- Executive summary:
In an eye irritation study performed according to the OECD Guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted test material was instilled into one eye of 3 female New Zealand White rabbits following a sequential testing strategy. The other eye remained untreated and served as control. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test material, and then released. The eyes were examined and the changes were observed at 1, 24, 48, 72 h and 7 days after treatment and graded according to the Draize method.
Instillation of the test substance into one eye of each of three female albino rabbits affected the iris and conjunctivae of all three animals. The injection of the iris had resolved within 24 hours and the irritation of the conjunctivae had resolved within 7 days in all three animals.
Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0 / 0 / 0 for cornea score; 0 / 0 / 0 for iris score; 1.7 / 2.0 / 2.0 for conjunctivae score and 0.7 / 0.7 / 1.0 for chemosis score.
Under the test conditions, the test material is classified as H319 "Causes serious eye irritation" Category 2 according to the Regulation (EC) No. 1272/2008 (CLP) and Category 2B according to the GHS.
This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.
Reference
Individual findings:
| Animal No. 736 | ||||
| Time after instillation | Tissue | Score | Fluor. Area % | Comments |
| 1 hour | Corneal opacity | 0 | Redness grade 2 for scleral conjunctivae. Chemosis grade 2 for nictating membrane. Lacrimation was observed. |
|
| area | 0 | |||
| Iris | 1 | |||
| Conj. Redness | 2 | |||
| chemosis | 2 | |||
| Discharge | 1 | |||
| 24 hours | Corneal opacity | 0 | 0 | |
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 2 | |||
| chemosis | 1 | |||
| Discharge | 1 | |||
| 48 hours | Corneal opacity | 0 | Chemosis grade 1 for nictating membrane. | |
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 2 | |||
| chemosis | 1 | |||
| Discharge | 1 | |||
| 72 hours | Corneal opacity | 0 | ||
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 1 | |||
| chemosis | 0 | |||
| Discharge | 0 | |||
| 7 days | Corneal opacity | 0 | ||
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 0 | |||
| chemosis | 0 | |||
| Discharge | 0 | |||
| Animal No. 737 | ||||
| Time after instillation | Tissue | Score | Fluor. Area % | Comments |
| 1 hour | Corneal opacity | 0 | Lacrimation was observed. | |
| area | 0 | |||
| Iris | 1 | |||
| Conj. Redness | 1 | |||
| chemosis | 2 | |||
| Discharge | 1 | |||
| 24 hours | Corneal opacity | 0 | 0 | Lacrimation was observed. |
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 2 | |||
| chemosis | 1 | |||
| Discharge | 1 | |||
| 48 hours | Corneal opacity | 0 | Chemosis grade 1 for nictating membrane. | |
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 2 | |||
| chemosis | 1 | |||
| Discharge | 1 | |||
| 72 hours | Corneal opacity | 0 | Redness grade 2 for scleral conjunctivae. | |
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 2 | |||
| chemosis | 0 | |||
| Discharge | 0 | |||
| 7 days | Corneal opacity | 0 | ||
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 0 | |||
| chemosis | 0 | |||
| Discharge | 0 | |||
| Animal No. 738 | ||||
| Time after instillation | Tissue | Score | Fluor. Area % | Comments |
| 1 hour | Corneal opacity | 0 | Redness grade 2 for scleral conjunctivae. Lacrimation was observed. |
|
| area | 0 | |||
| Iris | 1 | |||
| Conj. Redness | 2 | |||
| chemosis | 2 | |||
| Discharge | 1 | |||
| 24 hours | Corneal opacity | 0 | 0 | Lacrimation was observed. |
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 2 | |||
| chemosis | 1 | |||
| Discharge | 1 | |||
| 48 hours | Corneal opacity | 0 | Lacrimation was observed. | |
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 2 | |||
| chemosis | 1 | |||
| Discharge | 2 | |||
| 72 hours | Corneal opacity | 0 | Redness grade 2 for scleral conjunctivae. | |
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 2 | |||
| chemosis | 1 | |||
| Discharge | 1 | |||
| 7 days | Corneal opacity | 0 | ||
| area | 0 | |||
| Iris | 0 | |||
| Conj. Redness | 0 | |||
| chemosis | 0 | |||
| Discharge | 0 | |||
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation/corrosion:
A key study was identified (NOTOX 1991, rel. 1). This dermal irritation study was performed according to the OECD Guideline No. 404, and in compliance with GLP.
The observed skin irritation consisted of slight eschar formation, fissuring of the skin and severe oedema in all three animals. The skin irritation had not resolved completely within the study period (22 days) in all three animals.
Very slight erythema and very slight oedema were observed in two animals and very slight erythema only was observed the remaining animal on day 22.
There was no evidence of a corrosive effect on the skin.
The individual mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 3.3 / 2.7 / 3.3 for erythema and 3.7 / 3.7 / 3.7 for oedema.
Eye irritation:
A key study was identified (NOTOX 1991, rel. 1). This eye irritation study was performed according to the OECD Guideline No. 405, and in compliance with GLP.
Instillation of the test substance into one eye of each of three female albino rabbits affected the iris and conjunctivae of all three animals. The injection of the iris had resolved within 24 hours and the irritation of the conjunctivae had resolved within 7 days in all three animals.
Individual mean scores at 24, 48 and 72 h after exposure for the 3 animals were 0 / 0 / 0 for cornea score; 0 / 0 / 0 for iris score; 1.7 / 2.0 / 2.0 for conjunctivae score and 0.7 / 0.7 / 1.0 for chemosis score.
Justification for classification or non-classification
Harmonized classification:
The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.
Self classification:
Skin irritation:
Based on the available information, the substance should be classified as Skin irr. Category 2 (H315: Causes skin irritation) according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and according to the GHS.
Eye irritation:
Based on the available information, the substance should be classified as Eye irr. Category 2 (H319: Causes serious eye irritation) according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and Category 2B according to the GHS.
Respiratory irritation:
No data was available.
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