Registration Dossier
Registration Dossier
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EC number: 943-730-3 | CAS number: -
Endpoint summary
Administrative data
Description of key information
Skin, rabbit (OECD 404): not irritating
Read-across from structural analogue source substances Dipentaerythritol hexaesters with fatty acids, C5 and C9iso (CAS No. 647028-25-9), Hexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl ester (CAS No. 7299-99-2), Fatty acids, C5-9 tetraesters with pentaerythritol (CAS No. 67762-53-2), and Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS No. 68424-31-7)
Eye, rabbit (OECD 405): not irritating
Read-across from structural analogue source substances Dipentaerythritol hexaesters with fatty acids, C5 and C9iso (CAS No. 647028-25-9), Hexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl ester (CAS No. 7299-99-2), Fatty acids, C5-9 tetraesters with pentaerythritol (CAS No. 67762-53-2), and Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS No. 68424-31-7)
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:
- weight of evidence
- Study period:
- 16 Dec - 23 Dec 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)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Qualifier:
- according to guideline
- Guideline:
- other: EPA OPPTS 879.2700 (draft)
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- The Department of Health of the Government of the United Kingdom, UK
- 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: 12-16 weeks
- Weight at study initiation: 2.71 - 2.85 kg
- Housing: individual in suspended metal cages.
- Diet: STANRAB SQC Rabbit Diet (Special Diets Services Ltd., Witham, Essex, UK), ad libitum
- Water: tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-20
- Humidity (%): 51-60
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- semiocclusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: untreated sites of the same animal served as control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 100% - Duration of treatment / exposure:
- 4 h
- Observation period:
- 14 days
Reading time points: 1, 24, 48 and 72 h and 7 days - Number of animals:
- 3
- Details on study design:
- TEST SITE
- Area of exposure: dorsal flank
- Type of wrap if used: The test material was introduced under a 6.25 cm² cotton gauze patch and held in position with a strip of surgical adhesive tape (BLENDERM: approximately size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP).
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
- Time after start of exposure: 4 h
SCORING SYSTEM: Draize scoring system - Irritation parameter:
- erythema score
- Basis:
- animal: #1 and #2
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritant / corrosive response data:
- Erythema: 2/3 animals showed slight erythema from 24 h up to 72 h being fully reversible after 7 days. In the remaining animal slight erythema was observed at the 24 and 48 h reading time point only.
Edema: No edema formation was apparent during the study period in any animal. - Other effects:
- No other local or systemic effects were reported.
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 02 Feb - 05 Feb 1999
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- adopted in 1992
- Deviations:
- yes
- Remarks:
- no analytical purity reported
- GLP compliance:
- no
- Species:
- rabbit
- Strain:
- other: Albino Rabbits; New Zealand White, HM: (NZW)fBR
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hare-Marland, Inc., Hewitt, NJ, USA
- Age at study initiation: at least 8 weeks old
- Weight at study initiation: 2.5 – 2.8 kg
- Housing: individually housed in suspended, stainless steel cages with wire mesh bottoms
- Diet: certified Lab Rabbit Diet, HF, No. 5325; PMI Feeds, Inc. St. Louis, MO (approx 125 g/day while on test)
- Water: automatic watering system, municipal water supply, ad libitum
- Acclimation period: 60 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 22
- Humidity (%): 30 – 70
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: untreated sites of the same animal served as control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL - Duration of treatment / exposure:
- 4 h
- Observation period:
- 3 days
reading time points: 24, 48, and 72 hours - Number of animals:
- 3 females
- Details on study design:
- TEST SITE
- Area of exposure: intact skin of the dorsal trunk surface
- Type of wrap if used: 6 cm² gauze square placed directly on the intact test site per animal and directly held in place with tape. Gauze was then wrapped around the animal and secured with tape to keep the test material in contact with the skin.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The site was wiped free of test material with 0.9% saline and gauze
- Time after start of exposure: At the end of the exposure period
SCORING SYSTEM: Draize scoring system - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritant / corrosive response data:
- All three animals showed a very slight or slight erythema 1 hour after the test item application. Within 48 hours after removal of the patches the dermal effect were completely reversible.
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- limited documentation but relevant data given
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 5.0 - 5.2 g - Type of coverage:
- semiocclusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL - Duration of treatment / exposure:
- 4 h
- Observation period:
- 4 d
Reading time points: 30 - 60 min, 24, 48, 72 and 96 h - Number of animals:
- 3 (females)
- Details on study design:
- TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
REMOVAL OF TEST SUBSTANCE
- Washing (if done): cleansing with clean warm water
- Time after start of exposure: 4 h (upon removal of the dressing)
SCORING SYSTEM: Draize scoring system - Irritation parameter:
- erythema score
- Basis:
- animal: #1 and #3
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 4 days
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1.7
- Max. score:
- 4
- Reversibility:
- fully reversible within: 4 days
- Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Dec 1995
- 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:
- yes
- Remarks:
- scarified skin was also tested
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
- Deviations:
- yes
- Remarks:
- scarified skin was also tested
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: CARON-St GermainLaxis, 77950 Maincy, France
- Sex: male
- Weight at study initiation: about 2.5 - 3 kg
- Housing: in individual polysterene cages of standardized dimensions with perforated floor
- Diet: ALIMENT EXTRALABO C15 Ets Pietrement (77482 Provins), ad libitum
- Water: tap water provided in sterilized makrolon bottles equipped with stainless steel pipettes, ad libitum
- Acclimation period: 18 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 50 - 80
- Air changes (per hr): 3000 m³
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- semiocclusive
- Preparation of test site:
- other: shaved and abraded
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: not required, untreated sites of the same animal served as control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL - Duration of treatment / exposure:
- 4 h
- Observation period:
- 14 days
Reading time points: 4, 24, 48 and 72 h and 4 and 7 days - Number of animals:
- 3 males
- Details on study design:
- TEST SITE
- Area of exposure: left side (intact) and right side (scarified9) of the animal
- Site preparation: before the test, the skin sites were shaved with shears in order to cover a surface of about 14x14 cm. While the left side was intact, three parallel scarifications about 2.5 cm long were created on the right site.
- Type of wrap if used: sterile gauze patch (2.5x2.5 cm) held in place by adhesive strips (10 cm wide; Urgocrepe Fournier)
REMOVAL OF TEST SUBSTANCE
- Washing (if done): any trace of substance was eliminated with distilled water or, if necessary, with 5% SDS solution followed by careful rinsing
- Time after start of exposure: 4 h
SCORING SYSTEM:
Acc. to method outlined in the Official French Gazette of 21 Feb 1982, Draize scoring system - Irritation parameter:
- erythema score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Remarks on result:
- other: intact skin
- Irritation parameter:
- edema score
- Basis:
- animal: #1 and #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Remarks on result:
- other: intact skin
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Remarks on result:
- other: intact skin
- Irritant / corrosive response data:
- While one animal showed an slight edema reaction on the intact and scarified skin 4 hours after application, another animal had a slight edema reaction on the intact skin 24 h after application. From 48 h on, all animals showed no skin reactions.
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Referenceopen allclose all
Table 1. Results of skin irritation study.
Observation time |
Rabbit number and body weight (kg) |
||||||
#77 (2.83) |
#79 (2.85) |
#80 (2.71) |
|||||
Erythema |
Edema |
Erythema |
Edema |
Erythema |
Edema |
||
1 h |
0 |
0 |
0 |
0 |
0 |
0 |
|
24 h |
1 |
0 |
1 |
0 |
1 |
0 |
|
48 h |
1 |
0 |
1 |
0 |
1 |
0 |
|
72 h |
1 |
0 |
1 |
0 |
0 |
0 |
|
7 days |
0 |
0 |
0 |
0 |
0 |
0 |
|
Mean value 24 + 48 + 72 h |
1.00 |
0.00 |
1.00 |
0.00 |
0.67 |
0.00 |
|
Table 1: Erythema scores
Animal Number |
24 hours |
48 hours |
72 hours |
96 hours |
Mean Score |
26 |
2 |
1 |
1 |
0 |
1.3 |
35 |
2 |
2 |
1 |
0 |
1.7 |
36 |
2 |
1 |
1 |
0 |
1.3 |
Table 2: Edema Score
Animal Number |
24 hours |
48 hours |
72 hours |
96 hours |
Mean Score |
26 |
1 |
0 |
0 |
0 |
0.3 |
35 |
1 |
0 |
0 |
0 |
0.3 |
36 |
1 |
0 |
0 |
0 |
0.3 |
Results:
| Time | Animal | Intact skin | ||||
| Erythema | Edema | Necrosis | Corrosion | Desquamation | ||
| 4 h | 1070 | 0 | 0 | 0 | 0 | 0 |
| 1071 | 0 | 0 | 0 | 0 | 0 | |
| 1072 | 0 | 1 | 0 | 0 | 0 | |
| 24 h | 1070 | 0 | 0 | 0 | 0 | 0 |
| 1071 | 0 | 1 | 0 | 0 | 0 | |
| 1072 | 0 | 0 | 0 | 0 | 0 | |
| 48 h | 1070 | 0 | 0 | 0 | 0 | 0 |
| 1071 | 0 | 0 | 0 | 0 | 0 | |
| 1072 | 0 | 0 | 0 | 0 | 0 | |
| 72 h | 1070 | 0 | 0 | 0 | 0 | 0 |
| 1071 | 0 | 0 | 0 | 0 | 0 | |
| 1072 | 0 | 0 | 0 | 0 | 0 | |
| 4 days | 1070 | 0 | 0 | 0 | 0 | 0 |
| 1071 | 0 | 0 | 0 | 0 | 0 | |
| 1072 | 0 | 0 | 0 | 0 | 0 | |
| 7 days | 1070 | 0 | 0 | 0 | 0 | 0 |
| 1071 | 0 | 0 | 0 | 0 | 0 | |
| 1072 | 0 | 0 | 0 | 0 | 0 | |
| mean 24 - 72 h | 1070 | 0 | 0 | 0 | 0 | 0 |
| 1071 | 0 | 0.3 | 0 | 0 | 0 | |
| 1072 | 0 | 0 | 0 | 0 | 0 | |
| mean | 0 | 0.1 | ||||
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 23 Dec 1998 - 1 Jan 1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- adopted in 1987
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2400 (Acute Eye Irritation)
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- The Department of Health of the Government of the United Kingdom, UK
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, United Kingdom
- Age at study initiation: 12 weeks
- Weight at study initiation: 2.93 - 3.13 kg
- Housing: individual in suspended metal cages
- Diet: STANRAB SQC Rabbit Diet (Special Diets Services Ltd, Witham, United Kingdom), ad libitum
- Water: mains, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-19
- Humidity (%): 43-64
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: not required, the untreated eye served as control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied: 0.1 mL - Duration of treatment / exposure:
- single application without washing
- Observation period (in vivo):
- 3 days
Reading time points: 1, 24, 48 and 72 h - Number of animals or in vitro replicates:
- 1 male and 2 females
- Details on study design:
- SCORING SYSTEM: Draize scoring system
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 3
- Reversibility:
- fully reversible within: 2 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 3
- Reversibility:
- fully reversible within: 2 days
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritant / corrosive response data:
- No effects on corneal opacity and iris were noted at any time point observed. Moderate conjuctival redness (score = 2) was noted in two treated animals at 1-hour observation. Minimal conjuctival redness (score = 1) was observed in one treated animal at 1-hour observation and persisted in two treated animals at 24-hour observation. Minimal chemosis (score = 1) was observed in all treated animals at 1-hour observation time. Treated eyes appeared normal 24 to 48 hours after treatment.
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 5 Feb 1999 - 12 Feb 1999
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- no data on test substance purity given
- GLP compliance:
- no
- Species:
- rabbit
- Strain:
- other: albino rabbits; New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Hare-Marland, Inc., Hewitt, NJ, USA
- Age at study initiation: at least 8 weeks
- Weight at study initiation: 2.8 – 2.9 kg
- Housing: individually housed in suspended, stainless steel cages with wire mesh bottoms
- Diet: certified Lab Rabbit Diet HF, No. 5325; PMI Feeds, Inc. St. Louis, MO (approximately 125 g/day while on test)
- Water: automatic watering system (municipal water supply), ad libitum
- Acclimation period: 53 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 34-54
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: the untreated eye served as control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL - Duration of treatment / exposure:
- 24 h, single application without washing
- Observation period (in vivo):
- 3 days
reading time points: 24, 48, and 72 h - Number of animals or in vitro replicates:
- 3 (1 male and 2 females)
- Details on study design:
- SCORING SYSTEM: Draize scoring system
TOOL USED TO ASSESS SCORE: fluorescein - Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0.67
- Max. score:
- 3
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility not applicable
- Irritant / corrosive response data:
- One animal exhibited moderate conjunctival redness whereas the other 2 animals showed mild conjuctival redness; all three animals exhibited severe discharge. No iridial or corneal changes were evident throughout the study. At 24 h post-treatment, one animal was free of conjuctival redness. All 3 animals were free of ocular irritation within 72 h after treatment.
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- (lack of details on test substance and animal husbandry)
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 3.6 - 4.6 kg
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL - Duration of treatment / exposure:
- single application without washing
- Observation period (in vivo):
- 3 d
- Number of animals or in vitro replicates:
- 3 females
- Details on study design:
- SCORING SYSTEM: Draize scoring system
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritant / corrosive response data:
- No corneal or iridial effects were observed. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approx. 1 h after dosing.
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Dec 1995
- 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: CARON-St Germain-Laxis, 77950 Maincy, France
- Sex: male
- Weight at study initiation: about 2.5 - 3 kg
- Housing: in individual polysterene cages of standardized dimensions with perforated floor
- Diet: Pietrement C15, ad libitum
- Water: tap water provided in sterilized makrolon bottles equipped with stainless steel pipettes, ad libitum
- Acclimation period: 19 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 50 - 80
- Air changes (per hr): 3000 m³
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: the untreated eye served as control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL - Duration of treatment / exposure:
- single application without washing
- Observation period (in vivo):
- 7 days
Reading time points: 4, 24, 48, 72 h and 7 days - Number of animals or in vitro replicates:
- 3 males
- Details on study design:
- SCORING SYSTEM:
Draize scoring system according to EEC guideline 67/548
TOOL USED TO ASSESS SCORE: 2% aequous solution of sodium fluorescein - Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- over all 3 animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritant / corrosive response data:
- The observed lesions in all 3 animals were benign, exclusively conjunctival and of low intensity. They are fully reversible by day 2.
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Referenceopen allclose all
Table 1: Individual scores of the animals.
Reading time point |
Animal No. |
Cornea |
Iris |
Conjunctiva |
|||
Area of opacity |
Opacity |
Redness |
Chemosis |
Lacrimation |
|||
4 h |
1100 |
0 |
0 |
0 |
2 |
0 |
0 |
1101 |
0 |
0 |
0 |
2 |
0 |
0 |
|
1102 |
0 |
0 |
0 |
2 |
0 |
0 |
|
24 h |
1100 |
0 |
0 |
0 |
1 |
0 |
0 |
1101 |
0 |
0 |
0 |
1 |
0 |
0 |
|
1102 |
0 |
0 |
0 |
1 |
0 |
0 |
|
48 h |
1100 |
0 |
0 |
0 |
0 |
0 |
0 |
1101 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1102 |
0 |
0 |
0 |
0 |
0 |
0 |
|
72 h |
1100 |
0 |
0 |
0 |
0 |
0 |
0 |
1101 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1102 |
0 |
0 |
0 |
0 |
0 |
0 |
|
7 days |
1100 |
0 |
0 |
0 |
0 |
0 |
0 |
1101 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1102 |
0 |
0 |
0 |
0 |
0 |
0 |
|
mean 24-48-72 h |
1100 |
0.0 |
0.0 |
0.0 |
0.3 |
0 |
0.0 |
1101 |
0.0 |
0.0 |
0.0 |
0.3 |
0 |
0.0 |
|
1102 |
0.0 |
0.0 |
0.0 |
0.3 |
0 |
0.0 |
|
mean |
0.0 |
0.0 |
0.0 |
0.3 |
0 |
0.0 |
|
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for grouping of substances and read-across
The read-across from analogue source substances approach comprises aliphatic esters of poly-functional alcohols containing two to six reactive hydroxyl groups and one to six fatty acid chains. The analogue approach contains mono constituent, multi-constituent and UVCB substances with fatty acid carbon chain lengths ranging from C5 - C28, which are mainly saturated but also mono unsaturated C16 and C18, polyunsaturated C18, branched C5 and C9, branched C14 - C22 building mono-, di-, tri-, and tetra esters with an alcohol (i.e. the polyol).
The available data allows for an accurate hazard and risk assessment of the target substance and the read-across concept is applied for the assessment of environmental fate and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substances within the group by interpolation to the target substance applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.
A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 7.1 and 13).
Skin irritation / corrosion
Several studies assessing the skin irritation potential of structural analogue source substances are available which are considered in a Weight-of-Evidence approach.
The skin irritation / corrosion potential of Dipentaerythritol hexaesters with fatty acids, C5 and C9iso (CAS No. 647028-25-9) was investigated in a study following OECD Guideline 404 and according to GLP provisions (WoE, RA-A, 647028-25-9, 1999c). The unchanged test item was applied for 4 h to the shaved dorsal flanks of 3 New Zealand White rabbits under semiocclusive conditions. Residual test material was removed by gentle swabbing with cotton wool. Evaluation of the treated sites was done according to the Draize scoring system 1, 24, 48 and 72 h and 7 days after treatment. Formation of slight erythema (score 1) was observed in 2/3 from 24 h up to 72 h being fully reversible after 7 days. In the remaining animal slight erythema (score 1) was observed at the 24 h and 48 h reading time point only. No edema formation was apparent during the study period in any animal at any time point (score 0). The test substance was therefore considered to be not irritating to skin.
A skin irritation study according to OECD Guideline 404 and in compliance with GLP is available for the structural analogue Hexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl ester (CAS No. 7299-99-2) (Stearinerie, 1998a). Three male New Zealand White rabbits received a topical application of 0.5 mL of the test substance on previously shaved and abraded skin sites under semi-occlusive conditions. The treated sites were washed 4 h after application and were evaluated 4, 24, 48 and 72 h and 4 and 7 days later. No erythema was noted in any of the animals at any reading time points resulting in the mean score of 0 for all animals. Only slight edema was visible in one animal, but this effect was fully reversible within 48 h. Consequently the mean score for edema was 0.1 in this animal, while the score for the other two animals were 0. Based on the study results, the test substance was considered to be not skin irritating.
A primary dermal irritation study was performed comparable to OECD Guideline 404 with Fatty acids, C5-9 tetraesters with pentaerythritol (CAS No. 67762-53-2) (Exxon, 1999c). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 h under semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 h after removal of the test substance. All three animals showed a very slight or slight erythema 1 hour after the test item application. Within 48 h after removal of the patches the dermal effect was completely reversible. All treated skin sites appeared normal at the 72 h observation. The mean erythema scores over 24, 48 and 72 h were 0 for animal #1 and #2 and 0.33 for animal #3. No edema occurred in any of the tested animals at any reading time point. The test material is not considered irritating to the skin in this study.
In a primary skin irritation study with Fatty acids, C5-10, esters with pentaerythritol (CAS No. 68424-31-7), which was performed according to OECD Guideline 404 (WoE, RA-A, 68424-31-7, 1991b), the shaved skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test substance for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48, 72 and 96 h after removal of the test substance. The exposure period of 4 h caused slight edema (grade 1) in all animals 24 h after removal of the test substance. The effect fully reversed within 48 h. Erythema was seen at the test site of one animal (grade 2) and slightly at the test site of the other two animals (grade 1). Erythema reactions were completely reversed within 96 h after removal of the test substance in all three animals. The mean erythema score over 24, 48 and 72 h was 1.3 for animal #1 and #3 and 1.7 for animal #2. The mean edema score over 24, 48 and 72 h was 0.3 for all three animals. All treated skin sites appeared normal at the 96 h observation.
Eye irritation
Again, several adequate and reliable studies investigating the eye irritation potential using structural analogue source substances are available.
In a study according to OECD Guideline 405 and compliant to GLP provisions, the eye irritation potential of Dipentaerythritol hexaesters with fatty acids, C5 and C9iso (CAS No. 647028-25-9) was assessed (WoE, RA-A, 647028-25-9, 1999d). 0.1 mL of the unchanged test substance was instilled into the conjunctival sack of 1 male and 2 female New Zealand White rabbits in a single application without washing. Effects were recorded 1, 24, 48 and 72 h after treatment and evaluated following the Draize scoring system. No effects on corneal opacity and iris were noted at any time point in any animal, resulting in 24/48/72 h mean scores of 0. Moderate conjuctival redness (score 2) was noted in 2/3 treated animals at the 1 h observation. Minimal conjuctival redness (score 1) was observed in 1/3 treated animal 1 h after application and persisted in 2/3 animals at the 24 h reading. All treated eyes appeared normal 24 h to 48 hours after treatment. The 24/48/72 h mean value regarding conjunctival redness was therefore 0 in 1/3 and 0.33 in 2/3 animals. Minimal chemosis (score 1) was observed in all treated animals at the 1 h reading but was fully reversed in all animals 24 h after application. Thus the 24/48/72 h mean score was 0 for all animals. In conclusion, the test substance is not considered to be irritating to eyes.
The eye irritation potential of the structural analogue Hexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl ester (CAS No. 7299-99-2) was evaluated in a study with three New Zealand White rabbits in accordance with OECD guideline 405 and under GLP conditions (Stearinerie, 1998b). The readings of the treated eyes 4, 24, 48 and 72 h and 7 days post-instillation revealed slight conjunctival effects in all 3 animals (score 2 at 4 h; score 1 at 24 h), which were fully reversible within 48 h. As a consequence, the mean scores over 24, 48, and 72 h and over all 3 animals for redness were 0.3. The mean scores for cornea and iris were 0 in all animals. Based on the study results, the test substance was considered to be not eye irritating.
Fatty acids, C5-9, tetraesters with pentaerythritol (CAS No. 67762-53-2) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 (Exxon, 1999d). The undiluted test material (0.1 mL) was applied into the conjunctival sac of 3 (1 male, 2 female) New Zealand White rabbits each. The animals were observed for 3 days and reactions were assessed 1, 24, 48 and 72 h after instillation according to the Draize scoring system. One animal exhibited moderate conjunctival redness and two animals showed mild conjuctival redness. All three animals exhibited severe discharge. No iridial or corneal changes were evident throughout the study. At 24 h post treatment, one animal was free of conjuctival redness. All three animals were free of ocular irritation within 72 h of treatment. The mean conjunctivae score out of all three animals over 24, 48 and 72 h was 0.67. Thus, the test material is not considered irritating to the eyes in this study.
Fatty acids, C5-10, esters with pentaerythritol (CAS No. 68424-31-7) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 (WoE, RA-A, 68424-31-7, 1991c). The undiluted test material (0.1 mL) was applied into the conjunctival sac of three female New Zealand White rabbits each. The animals were observed for three days and reactions were assessed 1, 24, 48 and 72 h after instillation according to the Draize scoring system. No corneal or iridial effects were observed. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approximately 1 h after dosing. Thus, the test material is not considered irritating to the eyes in this study.
Conclusion on skin and eye irritation
Based on the results of the available studies, none of the structural analogue source substances is considered either skin or eye irritating. Therefore, on the basis of these findings, no skin and eye irritation potential for the target substance Monopentaerythritol tetraesters and dipentaerythritol hexaesters of 2-ethylhexanoic and n-valeric acids is identified as well.
Justification for classification or non-classification
According to Article 13 of Regulation (EC) No. 1907/2006 information on intrinsic properties of substances may be generated by means other than tests, e.g. using information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the read-across concept is applied to the target substance Monopentaerythritol tetraesters and dipentaerythritol hexaesters of 2-ethylhexanoic and n-valeric acids, data gaps can be filled by interpolation from representative structural analogue source substances to avoid unnecessary animal testing.
The read-across concept is also used to derive the classification of the target substance taking the properties of the source substances into account. Based on the read-across concept, all available data on skin and eye irritation / corrosion do not meet the classification criteria according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.
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