Registration Dossier
Registration Dossier
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EC number: 815-461-0 | CAS number: -
Endpoint summary
Administrative data
Description of key information
Acute skin irritation/corrosion: Not irritating (rabbits).
Acute eye irritation/corrosion: Not irritating (rabbits).
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:
- 08 to 18 July 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed inn accordance with OECD, EU & US EPA test guidelines in compliance with GLP.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2500 (Acute Dermal Irritation)
- Deviations:
- not specified
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- Species: Albino Rabbit, New Zealand White, (SPF-Quality) Recognised by international guidelines as the recommended test system (e.g. EC, OECD)
Source: Charles River Deutschland, Kisslegg, Germany
Number of animals: 3 Males.
Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification: Earmark.
ANIMAL HUSBANDRY
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 16.1-23.0°C), a relative humidity of 30-70% (actual range: 43 -79%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually in labelled cages with perforated floors (Scan bur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits,
Altromin, Lage, Germany) approx. 100 g per day. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.
Water: Free access to tap-water. - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- Each animal was treated by dermal application of 0.5 ml of the test substance.
- Duration of treatment / exposure:
- 4 hours.
- Observation period:
- 72 hours.
- Number of animals:
- 3 male rabbits
- Details on study design:
- TREATMENT
All available data relevant to the potential dermal irritation/corrosivity of the substance indicated that no severe effects were to be expected. An in-vitro skin irritation test was considered, but no validated test was found available. Therefore, this in-vivo skin irritation study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of skin irritation observed in the first animal.
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimetres (10x15 cm2). Whenever considered necessary the treated skin areas were re-clipped at least 3 hours before the observations, to facilitate scoring.
A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.
Each animal was treated by dermal application of 0.5 ml of the test substance. The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water.
OBSERVATIONS
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application) and at termination.
Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.
The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.
HISTOPATHOLOGY
No histopathology was performed. - Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 hours
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritant / corrosive response data:
- Irritation: Four hours exposure to 0.5 ml of HATCOL 3331 resulted in very slight erythema and/or very slight oedema in the treated skin-areas of the three rabbits. The skin Irritation had resolved within 24 hours in two animals and within 48 hours in the other animal.
Corrosion: There was no evidence of a corrosive effect on the skin. - Other effects:
- Colouration: No staining of the treated skin by the test substance was observed. Sticky remnants of the test substance were present on the edges of the treated skin area on day 1.
Toxicity / Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. - Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Not irritating.
- Executive summary:
Primary skin irritation/corrosion study with HATCOL 3331 in the rabbit (4-hour semi-occlusive application).
The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, B4, "Acute Toxicity - Skin irritation", OECD No 404, "Acute Dermal Irritation/Corrosion", US EPA, OPPTS 870.2500, Acute Dermal Irritation and JMAFF, JapaneseTest Guidelines.
Three rabbits were exposed to 0.5 ml of HATCOL 3331, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.
Exposure to HATCOL 3331 resulted in very slight erythema and/or very slight oedema in the treated skin-areas of the rabbits, which had resolved within 24 hours in two animals and within48 hours in the other animal.
Sticky remnants of the test substance were present on the edges of the treated skin area on day 1.
Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for skin irritation.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 08 to 18 July 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2500 (Acute Dermal Irritation)
- Deviations:
- not specified
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- Species: Albino Rabbit, New Zealand While, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD). Source: Charles River Deutschland, Kisslegg, Germany
Number of animals: 3 Males.
Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification: Earmark.
Conditions: Animals were housed in a controlled environment in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 16.1-23.0 °C), a relative humidity of 30-70% (actual range: 43-79%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures In the room might have caused the fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually In labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.
Water: Free access to tap-water. - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- The test substance was applied as delivered by the sponsor.
Each animal was treated by dermal application of 0.5ml of the test substance. - Duration of treatment / exposure:
- 4 hours
- Observation period:
- 72 hours
- Number of animals:
- 3 males
- Details on study design:
- TREATMENT
All available data relevant to the potential dermal irritation/corrosivity of the substance indicated that no severe effects were to be expected. An in-vitro skin irritation test was considered, but no validated test was found available. Therefore, this in-vivo skin irritation study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of skin irritation observed in the first animal.
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimetres (10x15 cm2). Whenever considered necessary the treated skin areas were re-lipped at least 3 hours before the observations, to facilitate scoring.
A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.
Each animal was treated by dermal application of 0.5ml of the test substance. The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water.
OBSERVATIONS
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application) and at termination.
Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.
The irritation scores and a description of all other (local) effect were recorded. Adjacent areas of the untreated skin of each animal served as controls.
The irritation was assessed according to a numerical scoring system. At each observation, the highest scores given were recorded. - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritant / corrosive response data:
- Irritation: Four hours exposure to 0.5 ml of HATCOL 3344 resulted in very slight erythema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 24 hours after exposure in all animals.
Corrosion: There was no evidence of a corrosive effect on the skin. - Other effects:
- Colouration: No staining of the treated skin by the test substance was observed. Fatty remnants of the test substance were present immediately after removal of the bandage.
Toxicity/Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. - Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3344 does not have to be classified and has no obligatory labelling requirement for skin irritation.
- Executive summary:
Primary skin irritation/corrosion study with HATCOL 334 in the rabbit (4-hour semi-occlusive application).
The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, B.4, "Acute Toxicity - Skin Irritation", OECD No404, "Acute Dermal Irritation/Corrosion", US EPA, OPPTS 870.2500, Acute Dermal Irritation and JMAFF. JapaneseTest Guidelines.
Three rabbits were exposed to 0.5 ml of HATCOL 3344, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.
Exposure to HATCOL 3344 resulted in very slight erythema In the treated skin-areas of the rabbits, which had resolved within 24 hours.
Fatty remnants of the test substance were present immediately after removal of the bandage.
Based on the results and according to the EC criteria for classification and labellingrequirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3344 does not have to be classified and has no obligatory labelling requirement for skin irritation.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 17 to 20 December 2002
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2500 (Acute Dermal Irritation)
- Deviations:
- not specified
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- Species: Albino Rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD). Source: Charles River Deutschland. Kisslegg, Germany
Number of animals: 3 Animals of one sex.
Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification: Earmark.
Conditions: A controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21±3°C, a relative humidity of 30-70% and 12 hours artificial fluorescent light and 12 hours dark per day.
Accommodation: Individually in labelled cages with perforated floors (Scan bur. Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits,
Allromin, Lage, Gennany) approx. 100 g. per day. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.
Water: Free access to tap-water. - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- The test substance was applied undiluted as delivered by the sponsor.
Each animal was treated by dermal application of 0.5 ml of the test substance. - Duration of treatment / exposure:
- Four hours
- Observation period:
- 72 hours
- Number of animals:
- 3 male rabbits treated with the test substance
- Details on study design:
- TREATMENT
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimetres (10x15 cm2). Whenever considered necessary the treated skin areas were re-lipped at least 3 hours before the observations, to facilitate scoring.
A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.
Each animal was treated by dermal application of 0.5 ml of the test substance. The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water.
OBSERVATIONS
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application) and at termination.
Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls. - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritant / corrosive response data:
- Irritation: Four hours exposure to 0.5 ml of HATCOL 5236 resulted in very slight erythema in the treated skin-areas of the three rabbits.
The skin irritation had resolved within 1 day after exposure in all animals.
Corrosion: There was no evidence of a corrosive effect on the skin. - Other effects:
- Colouration: Sticky and dry remnants of the test substance were present on the skin on days 1 and 2 in one animal and during the whole observation period in the other two animals.
Toxicity / Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. - Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- HATCOL 5236 does not have to be classified and has no obligatory labelling requirement for skin irritation.
- Executive summary:
Primary skin irritation/corrosion study with HATCOL 5236 in the rabbit (4-hour semi-occlusiveapplication).
The study was carried out based on the guidelines described in: EC Commission Directive
92/69/EEC, B.4 "Acute Toxicity - Skin irritation", OECD No.404, "Acute Dermal Irritation/Corrosion", US EPA, OPPTS 870.2500, Acute Dermal Irritation, EPA 712-C-98-196, August 1998 and JMAFF, Japanese Test Guidelines (draft), July 2000.
Three rabbits were exposed to 0.5 ml of HATCOL 5236, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.
Four hours exposure to 0.5 ml of HATCOL 5236 resulted in very slight erythema in the treated skin-areas of the three rabbits.
The skin irritation had resolved within 1 day after exposure in all animals.
Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 5236 does not have to be classified and has no obligatory labelling requirement for skin irritation.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with restrictions.Limited documentation but relevant data given.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- Adopted 24 April 2002
- Deviations:
- yes
- Remarks:
- limited documentation, limited information on test substance given, 2 h exposure only
- 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: mean: 3.7 kg
- Type of coverage:
- occlusive
- Preparation of test site:
- not specified
- Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL- Amount applied: 0.5 mL- Concentration: 100%
- Duration of treatment / exposure:
- 2 h
- Observation period:
- 72 hReading time points: 1, 24, 48 and 72 h
- Number of animals:
- 5 males
- Details on study design:
- TEST SITE- Area of exposure: 9 cm²- Type of wrap if used: the treated skin was covered with occlusive tape.REMOVAL OF TEST SUBSTANCE- Washing: Residual test material was removed with water- Time after start of exposure: 2 hSCORING SYSTEM: Draize scoring system
- Irritation parameter:
- erythema score
- Basis:
- mean
- Remarks:
- out of all 5 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0.24
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- out of all 5 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility not applicable
- Irritant / corrosive response data:
- At tape removal and after 1 h, no effects on the skin were observed. After 24 h, 3 animals showed erythema, which persisted in 1 animal for 48 h. 72 h after exposure, all animals were free of erythema.Edema were not observed at all.
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: EU
- Conclusions:
- CLP: not classifiedDSD: not classified
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 03 Nov - 06 Nov 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP-guideline study. For read-across, maximum reliability score is 2.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Version / remarks:
- September 1984
- Deviations:
- no
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: The Broekman Institute, Someren, The Netherlands- Age at study initiation: 20 - 21 weeks- Weight at study initiation: 3.1 kg ± 202.53 g- Housing: individually in plastic cages with perforated floors- Diet: 100 g / day, LK-01, Hope Farms, Woerden, The Netherlands- Water: tap-water, ad libitum- Acclimation period: at least 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 - 21- Humidity (%): 55 -65- Air changes: air conditioned room- Photoperiod (hrs dark / hrs light): 12 / 12
- Type of coverage:
- semiocclusive
- Preparation of test site:
- other: clipping
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: untreated site of the same animal served as control
- Amount / concentration applied:
- TEST MATERIAL- Amount applied: 0.5 mL- Concentration: 100 %
- Duration of treatment / exposure:
- 4 h
- Observation period:
- 72 hReading time points: 50 min, 24, 48, 72 h
- Number of animals:
- 3 females
- Details on study design:
- TEST SITE- Area of exposure: 6 cm²- Type of wrap: gauze patch attached with a drop of petrolatum to aluminium foil and mounted on permeable tape, held in place with flexible bandage.REMOVAL OF TEST SUBSTANCE- Washing: remaining test substance was removed, using a dry tissue and subsequently a tissue moistened with tap-water.- Time after start of exposure: 4 hSCORING SYSTEM: Draize scoring system
- Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0.66
- Max. score:
- 4
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritant / corrosive response data:
- Very slight erythema and edema were observed in all animals 24 h after treatment which were fully reversible latest within 72 h.
- Other effects:
- No signs of systemic toxicity were observed in any of the animals.
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: EU
- Conclusions:
- CLP: not classifiedDSD: not classified
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 13 Nov - 16 Nov 1990
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study. For read-across, maximum reliability score is 2.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- adopted in 1981
- Deviations:
- yes
- Remarks:
- Lack of details on test substance
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: Elevage Cunicole du Val de Selle, France- Weight at study initiation: 2.3 kg- Diet: ad libitum; Rabbit certified pellet diet (Rabbit sustenance ref. 112 C), ad libitum- Water: tap water, ad libitum- Acclimation period: 5 days-other: the animals received a preventive coccidiosis treatment during acclimation (Mucoxid, 137.5 mg/kg bw/day), via drinking waterENVIRONMENTAL CONDITIONS- Temperature (°C): 17-23- Humidity (%): 30-70- Photoperiod (hrs dark / hrs light): 12 / 12
- Type of coverage:
- semiocclusive
- Preparation of test site:
- other: clipped
- 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:
- 72 hReading time points: 1, 24, 48 and 72 h
- Number of animals:
- 3
- Details on study design:
- TEST SITE- Area of exposure: 6 cm², flanks were clipped a day before treatment- Type of wrap if used: adhesive hypoallergic aerated semi-occlusive dressing (Laboratoires de Pansements et d´Hygiène, France)REMOVAL OF TEST SUBSTANCE- Washing (if done): NoSCORING SYSTEM: According to Draize
- Irritation parameter:
- erythema score
- Basis:
- mean
- Remarks:
- of all three animals
- Time point:
- other: 24 h, 48 h and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Remarks on result:
- other: no cutaneous effects observed
- Irritation parameter:
- edema score
- Basis:
- mean
- Remarks:
- of all three animals
- Time point:
- other: 24 h, 48 h and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Remarks on result:
- other: no cutaneous effects observed
- Irritant / corrosive response data:
- No cutaneous reactions were observed in all the animals.
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: EU
- Conclusions:
- CLP: not classifiedDSD: not classified
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Remarks:
- in vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 03 April 2014 to 02 July 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed in accordance with OECD test guidelines in compliance with GLP.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
- Qualifier:
- according to guideline
- Guideline:
- other: EPA 40 CFR 158.340
- GLP compliance:
- yes
- Test system:
- human skin model
- Source species:
- other: EpiDerm™ tissues
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: Not specified
- Source strain:
- not specified
- Details on animal used as source of test system:
- EpiDerm™ tissues, Lot 19981 Kit D, were received from MatTek Corporation (Ashland, MA) on 08 Apr 2014 and refrigerated at approximately 4'C. Before use, tissues were incubated (37°C ± 1°C, 5% ± 1% CO2) with assay medium (MatTek) for a one-hour equilibration. Equilibration medium was replaced with fresh medium before dosing.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- Test Article Reduction of MTT: 100 µI of the test article were mixed with 1 ml of MTT solution (1 mg/ml Methyl thiazole tetrazolium diluted in Dulbecco's Modified Eagle's Medium (DMEM)). A Negative Control, 100 µI of tissue culture water, was tested concurrently. The solutions were incubated at room temperature in the dark for 60 minutes. After incubation, the solutions were visually inspected for purple coloration, which indicates that the test article reduced MTT. Since tissue Viability is based on MTT reduction, direct reduction by a test article can exaggerate viability, making a test article seem less irritating than it really is. The test article did not reduce MTT and the assay continued as per the protocol.Mesh Compatibility: Pre-cut nylon meshes supplied with the tissues were placed on a slide and 30 µI of the test article or tissue culture water were applied. After 60 minutes exposure, the mesh was checked microscopically. No interaction between the test article or tissue culture water and the mesh was observed so the test article was dosed using the mesh as a spreading aid.Dosing: 50 µI of the test article were applied to the top of each EpiDerm™ tissue. A nylon mesh was then placed on top to facilitate even distribution of the test article. The test article remained in contact with the EpiDerm™ tissue for 3 and 60 minutes. A Negative Control (TCH2O) and a Positive Control (KOH) were tested at 3 and 60 minutes. A nylon mesh was placed on top of each liquid control to facilitate even distribution of the material. Each treatment with test article or control was conducted in duplicate.All tissues were dosed at ambient temperature. Tissues treated with the test article and controls for 3 minutes were maintained at ambient temperature until analyzed for Tissue Viability (MTT Reduction). Tissues to be treated for 60 minutes were dosed and then returned to the Incubator (37°C ± 1°C, 5% ± 1% CO2) for the remainder of the 60-minute exposure periodTissue Viability (MTT Reduction): At the end of the exposure period, each EpiDerm™ tissue was rinsed with phosphate buffered saline (PBS) and transferred to a 24-well plate containing 300 µI of MTT solution (1 mg/ml MTT in DMEM). The tissues were then returned to the Incubator for a three-hour MTT incubation period. Following the MTT incubation period, each EpiDerm™ tissue was rinsed with PBS and then treated overnight with 2.0 ml of extractant solution (isopropanol) per well. The absorbency of an aliquot of the extracted MTT formazan was measured In triplicate at 540 nm using a microplate reader (µQuant Plate Reader, BioTek Instruments, Winooski, VT).Analysis of Data: The mean absorbance value for each time point was calculated from the optical density (OD) of the duplicate tissues and expressed as percent viability for each sample using the following formula:% viability = 100 X (OD sample/OD Negative Control)Quality Controls: The Negative Controls meets the acceptance criterion if the mean OD of the two tissues at each time point is greater than or equal to 0.8 and is less than or equal to 2.8 (0.8 ≤ OD ≤ 2.8).The Positive Control meets the acceptance criterion If the mean relative tissue viability at the 60 minute time point is less than 15% < 15%).Inter-tissue viability meets the acceptance criterion if the difference between two identically treated tissues is no greater than 30%. Re-testing of the chemical is recommended if the resulting viability is near to a classification cut-off. Note: If necessary, the percent difference will be calculated between the mean of the two tissues and one of the tissues. If this difference is greater than 15%, then rejection should be considered.Interpretation of Results: Skin Corrosion is defined as the production of irreversible tissue damage in skin following the application of test material. The percent viability calculated was used to determine corrosivity potential in the following manner:Mean Viability Mean Viability(3 min.) (60 min.) Predicted Corrosivity<50% Not Applicable Corrosive≥50% <15% Corrosive≥50% ≥15% Non-Corrosive
- Control samples:
- yes, concurrent no treatment
- Amount/concentration applied:
- 50 µI of the test article were applied to the top of each EpiDerm™ tissue.
- Duration of treatment / exposure:
- 3 and 60 minutes
- Duration of post-treatment incubation (if applicable):
- No observation period.
- Number of replicates:
- Tests were repeated in triplicate.
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 minutes exposure
- Value:
- 85.2
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 60 minutes exposure
- Value:
- 100
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Other effects / acceptance of results:
- No further information reported.
- Interpretation of results:
- other: non-corrosive
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- H2925 (CAS No. 68130-53-0), Lot# 2013090401 is predicted to be non-corrosive.
- Executive summary:
OBJECTIVE: To predict and classify the skin corrosivity potential of a chemical by using a three-dimensional human epidermis model. This study is designed based on MatTek protocol "In Vitro
EpiDerm™ Skin Corrosion Test" and follows the OECD Guideline for the Testing of Chemicals No. 431 In Vitro Skin Corrosion: Human Skin Model Test.
METHOD SYNOPSIS: MatTek EpiDermTMtissues were treated in duplicate with the test article. Negative Control and Positive Control for 3 minutes and 60 minutes. Following treatment, the viability of thetissues was determined using Methyl thiazole tetrazolium (MTT) uptake and conversion, and theabsorbance of each tissue was measured at 540 nm. The mean viability was then expressed as apercent of control values. The percent viability was used to determine corrosivity potential.
SUMMARY/CONCLUSION:
Test and Control Article Identity
Mean Viability (3 min.)
Mean Viability (60 min.)
Predicted Corrosivity
H2925 (CAS No. 68130-53-0), Lot# 2013090401
85.2%
100.1%
Non-Corrosive
Tissue culture water (Negative Control)
100.0%
100.0%
Non-Corrosive
Potassium Hydroxide, 8.0 N (Positive Control)
31.7%
2.1%
Corrosive
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 03 April 2014 to 02 July 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed in accordance with OECD test guidelines in compliance with GLP.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Qualifier:
- according to guideline
- Guideline:
- other: EPA 40 CFR 158.340
- GLP compliance:
- yes
- Test system:
- human skin model
- Source species:
- other: EpiDerm™ tissues
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: Not specified
- Source strain:
- not specified
- Details on animal used as source of test system:
- EpiDerm™ tissues, Lot 19981 Kit D, were received from MatTek Corporation (Ashland, MA) on 08 Apr 2014 and refrigerated at approximately 4°C. Before use, tissues were incubated (37°C ± 1°C, 5% ± 1% CO2) with assay medium (MatTek) for a one-hour equilibration. Equilibration medium was replaced with fresh medium before dosing.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- Test Article Reduction of MIT: 100 µI of the test article were mixed with 1 ml of MTT solution (1 mg/ml Methyl thiazole tetrazolium diluted in Dulbecco's Modified Eagle's Medium (DMEM)), A Negative Control, 100 µI of tissue culture water (TCH2O), was tested concurrently, The solutions were incubated at room temperature in the dark for 60 minutes, After incubation, the solutions were visually inspected for purple coloration, which indicates that the test article reduced MTT Since tissue viability is based on MTT reduction, direct reduction by a test article can exaggerate viability, making a test article seem less irritating than it really is. The test article did not reduce MTT and the assay continued as per the protocol.Mesh Compatibility: Pre-cut nylon meshes supplied with the tissues were placed on a slide and 30 µI of the test article or TCH2O Negative Control were applied. After 60 minutes exposure, the mesh was checked microscopically, No interaction between the test article or TCH2O and the mesh was observed so the test article was dosed using the mesh as a spreading aid,Dosing:30 µI of the test article or control articles were applied to the EpiDerm ™ tissue. The nylon mesh was then placed on top to facilitate even distribution of the test material. A Negative Control (phosphate buffered saline (PBS)) and a Positive Control (5% sodium dodecyl sulfate (SDS) solution, MatTek) were tested concurrently, with a nylon mesh placed on top to facilitate even distribution of the material. Each treatment with test article or control was conducted in triplicate.The exposure period for the test article and controls was 60 minutes. The dosed tissues were placed in an incubator at 37° ± 1°C, 5% ± 1% CO2 for 35 ± 1 minutes, then returned to the sterile hood for the remainder of the 60-minute exposure period.After dosing and incubation, the tissues were rinsed with PBS, blotted to remove the test substance and dry the tissue, and transferred to fresh medium. The rinsed EpiDerm™ tissues were returned to the incubator for 24 ± 2 hours. Medium was changed at 24 ± 2 hours. Tissues were returned to the incubator for an additional 18 ± 2 hours.Tissue Viability (MTT Reduction): At the end of the incubation period, each EpiDerm™ tissue was rinsed with phosphate buffered saline (PBS) and transferred to a 24-well plate containing 300 µI of MTT solution (1 mg/ml MTT in DMEM). The tissues were then returned to the incubator for a three-hour MTT incubation period. Following the MTT incubation period, each EpiDerm TM tissue was rinsed with PBS and then treated with 2.0 ml of extractant solution (isopropanol) per well for at least two hours, with shaking, at room temperature. Two aliquots of the extracted MTT formazan were measured at 540 nm using a plate reader (µQuant Plate Reader, BioTek Instruments, Winooski, VT).Analysis of Data: The mean absorbance value for each time point was calculated from the optical density (OD) of the duplicate samples and expressed as percent viability for each sample using the following formula:% viability =100 X (OD sample/OD Negative Control)Quality Controls: The assay meets the acceptance criterion if the mean OD540 of the Negative Control tissues is ≥ 1.0 and ≤ 2.5, and the mean viability of Positive Control tissues, expressed as percentage of the Negative Control tissues, is ≤ 20%. In addition, the standard deviation (SD) calculated from individual percent tissue viabilities of the three identically-treated replicates is < 18%.
- Control samples:
- yes, concurrent no treatment
- Amount/concentration applied:
- 30 µI of the test article were applied to the top of each EpiDerm™ tissue.
- Duration of treatment / exposure:
- 60 minutes
- Duration of post-treatment incubation (if applicable):
- No observation period.
- Number of replicates:
- Tests were repeated in triplicate.
- Irritation / corrosion parameter:
- % tissue viability
- Value:
- 96.4
- Remarks on result:
- other:
- Remarks:
- Basis: mean. Time point: 60 minutes. Max. score: 100.0. Remarks: Viability score are reported as %. The lower the score the more harmful a substance is expected to be. . (migrated information)
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: EU
- Conclusions:
- H2925 (CAS No. 68130-53-0), Lot# 2013090401 is considered to be a non-irritant and therefore it is not classified in accordance with the CLP Regulation.
- Executive summary:
OBJECTIVE: To predict dermal irritation potential of test articles in the context of identification and classification of skin irritation hazard according to the European Union (EU) classification, United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) classification system (Category 2 and non-irritants), and OECD Guideline for the Testing of Chemicals No. 439 - In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method. This study is designed based on MatTek protocol in vitro EpiDerm™ Skin Irritation Test.
METHOD SYNOPSIS: MatTek EpiDerm™ tissue samples were treated in triplicate with the test article, Negative Control and Positive Control for 60 minutes. Following treatment and subsequent incubation time, the viability of the tissues was determined using Methylthiazole tetrazolium (MTT) uptake and reduction. The absorbance of each sample was measured at 540 nm. The viability was then expressed as a percent of control values. If the mean tissue viability was ≤ 50%, the test material was classified as an irritant; if the mean tissue Viability was >50%, the test material was classified as a non-irritant.
SUMMARY/CONCLUSION:
Test and Control Article Identity
Mean Tissue Viability
Irritancy Classification
H2925 (CAS No. 68130-53-0), Lot# 2013090401
96.4%
Non-Irritant
Phosphate Buffered Saline (Negative Control)
100.0%
Non-Irritant
5% Sodium Dodecyl Sulfate (Positive Control)
2.4%
Irritant
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Composition of test substance unclear.
- Principles of method if other than guideline:
- Application of 0.5 mL to an area of approx. 2.5 cm x 2.5 cm.
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- - Weight at study initiation: 3.3 - 4.0 kg
- 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
- Concentration (if solution): pure compound (containing up to 2% of an additive package which was not further specified by the sponsor) - Duration of treatment / exposure:
- 4 h
- Observation period:
- 12 d
Reading time points: 30 - 60 min, 24, 48, 72, 96 h, 7, 8 and 12 d - Number of animals:
- 3 males
- Details on study design:
- TEST SITE
- Area of exposure: 2.5 cm² on the shorn left flank (dorso-lumbar region)
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water upon the removal of the dressing
- Time after start of exposure: 4 h
SCORING SYSTEM: Draize scoring system - Irritation parameter:
- erythema score
- Basis:
- animal: #15
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 2.7
- Max. score:
- 4
- Reversibility:
- fully reversible within: 12 d
- Irritation parameter:
- erythema score
- Basis:
- animal: #16
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 8 d
- Irritation parameter:
- erythema score
- Basis:
- animal: #17
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 8 d
- Irritation parameter:
- edema score
- Basis:
- animal: #15
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 4 d
- Irritation parameter:
- edema score
- Basis:
- animal: #16
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 3.7
- Max. score:
- 4
- Reversibility:
- fully reversible within: 8 d
- Irritation parameter:
- edema score
- Basis:
- animal: #17
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 3.7
- Max. score:
- 4
- Reversibility:
- fully reversible within: 8 d
- Irritant / corrosive response data:
- Following the single 4-hour application, moderate to severe erythema and moderate to severe edema were observed for 2 or 3 days after application in all animals. This regressed and no signs of erythema or edema were evident 4 to 12 days after application. Thickening of the skin at the application site was seen on one animal between 4 and 7 days after application. No other signs of irritations were observed.
- Other effects:
- Yellow staining by the test sample was observed at the application site of one animal one day after application but this did not obscure the assessment of any erythema that was present.
- Interpretation of results:
- other: inconclusive
- Remarks:
- Criteria used for interpretation of results: EU
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Composition of test substance unclear.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- Lack of details in study documentation
- 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: 3.5 - 3.8 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:
- 12 d
Reading time points: 30 - 60 min, 24, 48, 72 h, 7, 11 and 12 d - Number of animals:
- 3 males
- Details on study design:
- TEST SITE
- Area of exposure: 2.5 cm² on the shorn left flank (dorso-lumbar region)
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water upon the removal of the dressing
- Time after start of exposure: 4 h
SCORING SYSTEM: Draize scoring system - Irritation parameter:
- erythema score
- Basis:
- animal: #15
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 12 d
- Irritation parameter:
- erythema score
- Basis:
- animal: #16
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 11 d
- Irritation parameter:
- erythema score
- Basis:
- animal: #17
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 d
- Irritation parameter:
- edema score
- Basis:
- animal: #15
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 d
- Irritation parameter:
- edema score
- Basis:
- animal: #16
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 1.7
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 d
- Irritation parameter:
- edema score
- Basis:
- animal: #17
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 1.7
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 d
- Irritant / corrosive response data:
- Following the single 4-hour application, very slight to well-defined erythema and very slight to slight oedema were observed in all animals. This regressed and no signs of erythema or oedema were evident 11 or 12 days after application. Slight desquamation at the application site of one animal was observed 7 days after application.
- Interpretation of results:
- other: inconclusive
- Remarks:
- Criteria used for interpretation of results: EU
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions. (Limited documentation but relevant data given)
- 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
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 4 d
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 1.7
- Max. score:
- 4
- Reversibility:
- fully reversible within: 4 d
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 1.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 4 d
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 0.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 0.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 0.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- CLP: not classified
DSD: not classified
Referenceopen allclose all
INDIVIDUAL SKIN IRRITATION SCORES
Following exposure, the treated skin-area remained fatty after removal of the test substance.
Animal# |
442 (sentinel) |
471 |
478 |
||||||
Time after exposure |
Erythema |
Oedema |
Comments |
Erythema |
Oedema |
Comments |
Erythema |
Oedema |
Comments |
1 hour |
1 |
0 |
R b |
1 |
0 |
R b |
1 |
0 |
R b |
24 hours |
0 |
0 |
- |
0 |
0 |
- |
0 |
1 |
- |
48 hours |
0 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
72 hours |
0 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
Comments: R. Erythema at the edges of the application-area; b. Sticky remnants of the test substance present at the edges of the application-area.
MEAN VALUE IRRITATION SCORES
Animal# |
Mean 24-72 hrs |
|
Erythema |
Oedema |
|
442 |
0.0 |
0.0 |
471 |
0.0 |
0.0 |
478 |
0.0 |
0.3 |
#Animal specification:
Animal no |
Sex |
Age at start (weeks) |
Bodyweights (grams) |
|
Prior to application |
At termination |
|||
442 |
Male |
8-10 |
1845 |
1976 |
471 |
Male |
7-9 |
1660 |
1805 |
478 |
Male |
7-9 |
1562 |
1705 |
INDIVIDUAL SKIN IRRITATION SCORES
Following exposure, fatty remnants of the test substance were present of the treated skin-areas.
Animal# |
439 (sentinel) |
468 |
470 |
||||||
Time after exposure |
Erythema |
Oedema |
Comments |
Erythema |
Oedema |
Comments |
Erythema |
Oedema |
Comments |
1 hour |
1 |
0 |
- |
1 |
0 |
- |
1 |
0 |
- |
24 hours |
0 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
48 hours |
0 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
72 hours |
0 |
0 |
- |
0 |
0 |
- |
0 |
0 |
- |
MEAN VALUE IRRITATION SCORES
Animal# |
Mean 24 – 72 hours |
|
Erythema |
Oedema |
|
439 |
0 |
0 |
468 |
0 |
0 |
470 |
0 |
0 |
#Animal specifications:
Animal no |
Sex |
Age at start (weeks) |
Body weights (grams) |
|
Prior to application |
At termination |
|||
439 |
Male |
8-10 |
1730 |
1829 |
468 |
Male |
7-9 |
1491 |
1566 |
470 |
Male |
7-9 |
1556 |
1710 |
INDIVIDUAL SKIN IRRITATION SCORES
Following exposure, sticky remnants of the test substances were found on the treated skin-area after removal of the test substance.
Animal# |
74 |
76 |
78 |
||||||
Time after exposure |
Erythema |
Oedema |
Comments |
Erythema |
Oedema |
Comments |
Erythema |
Oedema |
Comments |
1 hour |
1 |
0 |
b |
1 |
0 |
b |
1 |
0 |
b |
24 hours |
0 |
0 |
b1 |
0 |
0 |
b1 |
0 |
0 |
b1 |
48 hours |
0 |
0 |
b1 |
0 |
0 |
- |
0 |
0 |
b1 |
72 hours |
0 |
0 |
b1 |
0 |
0 |
- |
0 |
0 |
b1 |
Comments:
b. Sticky remnants of the test substance present.
b1. Dry remnants of the test substance present.
MEAN VALUE IRRITATION SCORES
Animal# |
Mean 24-72 hrs |
|
Erythema |
Oedema |
|
74 |
0 |
0 |
76 |
0 |
0 |
78 |
0 |
0 |
#Animal specifications:
Animal no |
Sex |
Age at start (weeks) |
Body weights (grams) |
|
Prior to application |
At termination |
|||
74 |
Male |
8-10 |
1678 |
1871 |
76 |
Male |
8-10 |
1803 |
1936 |
78 |
Male |
8-10 |
1742 |
1936 |
Erythema score
Animal Number |
1 h |
24 h |
48 h |
72 h |
1 |
0 |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
3 |
0 |
0 |
0 |
0 |
Edema Score
Animal Number |
1 h |
24 h |
48 h |
72 h |
1 |
0 |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
3 |
0 |
0 |
0 |
0 |
EXPERIMENTAL DATA
Test Article: |
H2925 (CAS No. 68130-53-0), Lot# 2013090401 |
||||||
Dose: |
50µl |
||||||
Conc: |
Neat |
||||||
TIME (min) |
OD 1 |
OD 2 |
OD 3 |
MEAN (OD) |
SD |
VIABILITY % |
ERROR % |
3.0 |
1.824 |
1.833 |
1.837 |
1.831 |
0.007 |
89.1 |
0.3 |
|
1.670 |
1.679 |
1.671 |
1.673 |
0.005 |
81.4 |
0.2 |
Neg control |
|
|
|
2.056 |
|
100.0 |
|
60.0 |
1.725 |
1.721 |
1.717 |
1.721 |
0.004 |
89.4 |
0.2 |
|
2.112 |
2.153 |
2.135 |
2.133 |
0.021 |
110.9 |
1.1 |
Neg control |
|
|
|
1.924 |
|
100.0 |
|
Mean % Viability at 3 min: |
85.2 |
|
|||||
Mean % Viability at 60 min: |
100.1 |
|
|||||
Predicted Corrosivity: |
Non-corrosive |
||||||
Negative Control: |
Tissue Culture Water |
||||||
Dose: |
50µl |
||||||
Conc: |
Neat |
||||||
TIME (min) |
OD 1 |
OD 2 |
OD 3 |
MEAN (OD) |
SD |
VIABILITY % |
ERROR % |
3.0 |
2.026 |
2.078 |
2.066 |
2.057 |
0.027 |
100.0 |
1.3 |
3.0 |
2.00 |
2.073 |
2.094 |
2.056 |
0.049 |
100.0 |
2.4 |
Mean |
|
|
2.056 |
|
100.0 |
|
|
60.0 |
1.959 |
1.936 |
1.961 |
1.952 |
0.014 |
101.4 |
0.7 |
60.0 |
1.859 |
1.932 |
1.899 |
1.897 |
0.037 |
98.6 |
1.9 |
Mean |
|
|
1.924 |
|
100.0 |
|
|
Predicted Corrosivity: |
Non-corrosive |
||||||
Positive Control: |
Potassium Hydroxide, 8.0 N |
||||||
Dose: |
50µl |
||||||
Conc: |
Neat |
||||||
TIME (min) |
OD 1 |
OD 2 |
OD 3 |
MEAN (OD) |
SD |
VIABILITY % |
ERROR % |
3.0 |
0.587 |
0.602 |
0.602 |
0.597 |
0.009 |
29.0 |
0.4 |
3.0 |
0.705 |
0.708 |
0.708 |
0.707 |
0.002 |
34.4 |
0.1 |
Neg control |
|
|
|
2.056 |
|
100.0 |
|
60.0 |
0.038 |
0.039 |
0.040 |
0.039 |
0.001 |
2.0 |
0.1 |
60.0 |
0.043 |
0.043 |
0.043 |
0.043 |
0.000 |
2.2 |
0.0 |
Neg control |
|
|
|
1.924 |
|
100.0 |
|
Mean % Viability at 3 min: |
31.7 |
|
|||||
Mean % Viability at 60 min: |
2.1 |
|
|||||
Predicted Corrosivity: |
Corrosive |
||||||
Table 1: Erythema score
Animal Number |
1 h |
24 h |
48 h |
72 h |
4 days |
7 days |
8 days |
12 days |
Mean Score (24 -72 h) |
15 |
4 |
3 |
3 |
2 |
2 |
1 |
0 |
1.0 | |
16 |
3 |
3 |
2 |
1 |
1 |
0 |
1.3 | ||
17 |
4 |
3 |
2 |
1 |
1 |
|
0 |
1.3 |
Table 2: Edema Score
Animal Number |
1 h |
24 h |
48 h |
72 h |
4 days |
7 days |
8 days |
12 days |
Mean Score (24 -72 h) |
15 |
4 |
3 |
4 |
2 |
0 |
0 |
- |
0 |
3.0 |
16 |
4 |
4 |
4 |
3 |
3 |
- |
0 |
- |
3.7 |
17 |
4 |
4 |
4 |
3 |
3 |
- |
0 |
- |
3.7 |
Table 1: Erythema score
Animal Number |
1 h |
24 h |
48 h |
72 h |
7 days |
11 days |
12 days |
Mean Score (24 -72 h) |
15 |
2 |
- |
1 |
1 |
1 |
- |
0 |
1.0 |
16 |
2 |
2 |
1 |
1 |
1 |
0 |
- |
1.3 |
17 |
1 |
2 |
1 |
1 |
0 |
- |
- |
1.3 |
Table 2:Edema Score
Animal Number |
1 h |
24 h |
48 h |
72 h |
7 days |
11 days |
12 days |
Mean Score (24 - 72 h) |
15 |
1 |
- |
1 |
1 |
0 |
- |
0 |
1.0 |
16 |
2 |
2 |
2 |
1 |
0 |
0 |
- |
1.7 |
17 |
1 |
2 |
2 |
1 |
0 |
- |
- |
1.7 |
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 |
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:
- key study
- Study period:
- 04 to 14 August 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2400 (Acute Eye Irritation)
- Deviations:
- not specified
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- Species: Albino Rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD) Source: Charles River Deutschland, Kisslegg, Germany
Number of animals: 3 Males.
Age and body weight: Animals used within the study were at least 6 weeks old and bodyweights were at least 1.0 kg.
Identification: Earmark.
ANIMAL HUSBANDRY
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0:! 3.0°C (actual range: 18.1 - 23.9°C), a relative humidity of 30-70% (actual range: 44 - 81%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromln, Lage, Germany) approx. 100 g per day.
Water: Free access to tap-water. - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- Each animal was treated by instilation of 0.1 ml of the test substance in the conjunctival sac of one of the eyes after gently pullng the lower lid away from the eyeball.
- Duration of treatment / exposure:
- 24 hours
- Observation period (in vivo):
- 72 hours
- Number of animals or in vitro replicates:
- 3
- Details on study design:
- This eye irritation study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of eye irritation observed in the first animal.
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.
Each animal was treated by instillation of 0.1 ml of the test substance in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.
OBSERVATIONS
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to instillation) and at termination.
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.
The irritation was assessed according to the following numerical scoring system. - Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritant / corrosive response data:
- Irritation: Instillation of 0.1 ml of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae, which was seen as redness and chemosis. The irritation had completely resolved within 24 hours in all animals.
No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.
Corrosion: There was no evidence of ocular corrosion. - Other effects:
- Colouration/Remnants: No staining was observed and no remnants of the test substance were seen on (peri) ocular tissues.
Toxicity/Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. - Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Not irritating
- Executive summary:
Acute eye irritation/corrosion study with HATCOL 3331 in the rabbit.
The study was carried out based on the guidelines described in: EC Commission Directive92169/EEC, B.5, "Acute Toxicity - Eye irritation", OECD No.405, "Acute Eye Irritation/Corrosion"and US EPA, OPPTS 870.2400, Acute Eye Irritation, EPA 712-C-98-195, August 1998.
Single samples of 0.1 ml of HATCOL 3331 were instilled into one eye of each of three rabbits.
Observations were made 1, 24, 48 and 72 hours after instillation.
Instillation of the test substance resulted in irritation of the conjunctivae, which was seen as redness and chemosis. The irritation had completely resolved within 24 hours in all animals.
Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for eye irritation.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 04 to 14 August 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2400 (Acute Eye Irritation)
- Deviations:
- not specified
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- Species: Albino Rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD)
Source: Charles River Deutschland, Kisslegg, Germany
Number of animals: 3 Males.
Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification: Earmark.
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour. a temperature of 21.0 ± 3.0 °C (actual range: 18.1- 23.9°C), a relative humidity of 30-70% (actual range: 44 - 81%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.
Water: Free access to tap-water. - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- The test substance was instilled as delivered by the sponsor.
Each animal was treated by instillation of 0.1 ml of the test substance. - Duration of treatment / exposure:
- 24 hours
- Observation period (in vivo):
- 72 hours
- Number of animals or in vitro replicates:
- 3 males
- Details on study design:
- This eye irritation study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of eye irritation observed in the first animal.
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.
Each animal was treated by instillation of 0.1 ml of the test substance in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to instillation) and at termination.
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The Irritation scores and a description of all other (local) effects were recorded.
The irritation was assessed according to a numerical scoring system. At each observation, the highest scores given were recorded.
INTERPRETATION
The results were evaluated according to the EC criteria for classification and labelling of dangerous substances and preparations (Council Directive 67/548/EEC and all adaptations to technical progress and amendments of this Directive published in the Official Journal of the European Communities). - Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritant / corrosive response data:
- Irritation: Instillation of 0.1 ml of the test substance Into one eye of each of three rabbits resulted in irritation of the conjunctivae, which was seen as redness and chemosis. The Irritation had completely resolved within 24 hours In all animals.
No iridial irritation or corneal opacity was observed and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.
Corrosion: There was no evidence of ocular corrosion. - Other effects:
- Colouration/Remnants: No staining was observed and no remnants of the test substance were seen on (peri) ocular tissues.
Toxicity/Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. - Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- HATCOl 3344 does not have to be classifed and has no obligatory labellng requirement for eye Irritation.
- Executive summary:
Acute eye Irritation/corrosion study with HATCOL 3344 in the rabbit.
The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, B.5, "Acute Toxicity - Eye irritation", OECD No 405, "Acute Eye Irritation/Corrosion"and US EPA, OPPTS 870.2400, Acute Eye Irritation, EPA 712-C-98-195, August 1998.
Single samples of 0.1 ml of HATCOL 334 were instilled into one eye of each of three rabbits.
Observations were made 1, 24, 48 and 72 hours after instillation.
Instillation of the test substance resulted in Irritation of the conjunctivae, which was seen as redness and chemosis. The irritation had completely resolved within 24 hours in all animals.
Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 334 does not have to be classified and has no obligatory labelling requirement for eye irritation.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 17 to 20 December 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed in accordance with OECD, EU & US EPA test guidelines in compliance with GLP.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2400 (Acute Eye Irritation)
- Deviations:
- not specified
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- Species: Albino Rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD). Source: Charles River Deutschland, Kisslegg, Germany
Number of animals: 3 Animals of one sex.
Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification: Earmark
Conditions: A controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21 ± 3°C, a relative humidity of 30-70% and 12 hours artificial fluorescent light and 12 hours dark per day.
Accommodation: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits,
A1tromin, Lage, Germany) approx. 100 g. per day. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.
Water: Free access to tap-water. - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent no treatment
- Amount / concentration applied:
- Each animal was treated by instillation of 0.1 ml of the test substance
- Duration of treatment / exposure:
- 24 hours
- Observation period (in vivo):
- 72 hours
- Number of animals or in vitro replicates:
- 3 male rabbits
- Details on study design:
- TREATMENT
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.
Each animal was treated by instillation of 0.1 ml of the test substance in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to instillation) and at termination.
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded. - Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritant / corrosive response data:
- Irritation: Instillation of 0.1 ml of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae, which was seen as redness on day 1.
No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.
Corrosion: There was no evidence of ocular corrosion. - Other effects:
- Colouration / Remnants: No staining of (peri) ocular tissues by the test substance was observed.
Toxicity / Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. - Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- HATCOL 5236 does not have to be classified and has no obligatory labelling requirement for eye irritation.
- Executive summary:
Acute eye irritation/corrosion study with HATCOL 5236 in the rabbit.
The study was carried out based on the guidelines described in: EC Commission Directive92/69/EEC, B.5, "Acute Toxicity - Eye irritation", OECD No 405, "Acute Eye Irritation/Corrosion"and US EPA, OPPTS 870.2400, Acute Eye Irritation, EPA 712-C-98-195, August 1998.
Single samples of 0.1 ml of HATCOL 5236 were instilled into one eye of each of three rabbits.
Observations were made 1, 24, 48 and 72 hours after instillation.
Instillation of 0.1 ml of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae, which was seen as redness on day 1.
Based on these results and according to the EC criteria for classffcation and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 5236 does not have to be classified and has no obligatory labelling requirement for eye irritation.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions.Limited documentation but relevant data given.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- Adopted 24 April 2002
- Deviations:
- yes
- Remarks:
- limited documentation, limited information on test substance given
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: the untreated eye served as control
- Amount / concentration applied:
- TEST MATERIAL- Amount applied: 0.1 mL- Concentration: 100 %
- Duration of treatment / exposure:
- Group 1: 10 sGroup 2: 72 h (continuous treatment)
- Observation period (in vivo):
- 72 hReading time points: 1, 24, 48 and 72 h
- Number of animals or in vitro replicates:
- Group 1: 4 malesGroup 2: 4 males
- Details on study design:
- REMOVAL OF TEST SUBSTANCEGroup 1- Washing: yes- Time after start of exposure: 10 sGroup 2- Washing: noSCORING SYSTEM: Draize scoring systemTOOL USED TO ASSESS SCORE: fluorescein
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- out of all 4 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- out of all 4 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Remarks:
- out of all 4 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- out of all 4 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility not applicable
- Irritant / corrosive response data:
- No effects on cornea and iris were observed. Slight redness of the conjunctivae was observed both, after 10 s and after continuous treatment. The effects were obvious after 1 and 6 h. After 10 s treatment, the effects were reversible within 48 h. After continuous treatment, redness reversed within 24 h. In addition, exsudation was observed in both treatment groups, being reversible within 24 h (continuous treatment) and 48 h (10 s treatment), respectively. Chemosis was not observed.
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: EU
- Conclusions:
- CLP: not classified
DSD: not classified - Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with acceptable restrictions.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- Adopted: 24 April 2002
- Deviations:
- yes
- Remarks:
- limited information on test substance
- 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: 3408 - 3935 g
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: the untreated eye served as control
- Amount / concentration applied:
- TEST MATERIAL- Amount applied: 0.1 mL- Concentration: 100 %
- Duration of treatment / exposure:
- 5 days (single application without washing)
- Observation period (in vivo):
- 5 daysReading time points: 2, 24, 48 and 72 h
- Number of animals or in vitro replicates:
- 3 males
- Details on study design:
- REMOVAL OF TEST SUBSTANCE: noSCORING SYSTEM: Draize scoring system
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- out of all 3 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- out of all 3 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Remarks:
- out of all 3 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0.3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- out of all 3 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible within: reversibility not applicable
- Irritant / corrosive response data:
- No effects on the cornea and the iris were observed. Conjunctival effects included slight to moderate redness and slight to severe discharge. No chemosis was seen. Additional signs of irritation included erythema and dried secretion on the upper and lower eyelids and convoluted eyelids. All effects were completely reversible within 48 h after application.
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: EU
- Conclusions:
- CLP: not classified
DSD: not classified - Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with acceptable restrictions.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: 16 CFR 1500.42
- Deviations:
- yes
- Remarks:
- limited documentation
- GLP compliance:
- no
- Species:
- rabbit
- Strain:
- other: albino rabbit, not further specified
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS- Acclimation period was carried out, not further specified.
- 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):
- 72 hReading time points: 24, 48 and 72 h
- Number of animals or in vitro replicates:
- 6
- Details on study design:
- REMOVAL OF TEST SUBSTANCE- Washing: no washing was doneSCORING SYSTEM: Draize scoring system
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- out of all 6 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- out of all 6 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility: not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Remarks:
- out of all 6 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0.4
- Max. score:
- 3
- Reversibility:
- fully reversible within: 72 h
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- out of all 6 animals
- Time point:
- other: mean over 24, 48 and 72 h
- Score:
- 0.1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 h
- Irritant / corrosive response data:
- No effects on the cornea or iris were observed in test animals. Slight redness of the conjunctivae was observed after 24 h in 3 animals and after 48 h in 4 animals which were fully reversible in all animals within 72 h.Slight chemosis of the conjunctiva was detected in 1 animal after 24 h which was fully reversible within 48 h.
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: EU
- Conclusions:
- CLP: not classified
DSD: not classified - Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 03 April 2014 to 02 July 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed in accordance with OECD test guidelines in compliance with GLP.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- GLP compliance:
- yes
- Species:
- other: bovine eyes
- Strain:
- other: not applicable
- Details on test animals or tissues and environmental conditions:
- The bovine eyes were received from Spear Products on 10 Apr 2014 and transported to MB Research in Hank's Balanced Salt Solution with Penstrep in a refrigerated container.
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes
- Amount / concentration applied:
- Using the closed chamber method, a volume of 0.75 ml of the ethanol, MEM or liquid test article was applied to the epithelium of each of the three positive controls, three negative controls, or three test article-treated corneas in a manner, which ensured the entire cornea was covered.
- Duration of treatment / exposure:
- 10 minutes
- Observation period (in vivo):
- 2 hours
- Number of animals or in vitro replicates:
- 9 cornea's used in total (3 positive control, 3 negative controls and 3 test article treated)
- Details on study design:
- Pretest ProceduresFresh assay solutions were prepared prior to use. MEM solution was prepared by stirring together one jar of MEM powder (sufficient to make one liter of solution), 2.2 g Sodium Bicarbonate, 0.292 g L-Glutamine, 10 ml of Fetal Bovine Serum (FBS) and brought to a final volume of 1000 ml with distilled water. The MEM solution was kept in a 32°C (± 1°C) incubator for the duration of testing. Hanks Balanced Salt Solution (HBSS) was prepared by stirring together one jar of HBSS powder (sufficient to make one liter), 0.35 g Sodium Bicarbonate and brought to a final volume of 1000 ml with distilled water. HBSS was maintained at room temperature.In addition, MEM solution with Phenol Red was prepared by stirring together 9.3 g MEM with Phenol Red (sufficient to make one liter), 2.2 g Sodium Bicarbonate, 0.292 g L-Glutamine, 10 mL Fetal bovine Serum and brought to a final volume of 1000 mL with distilled water. The MEM solution with Phenol Red was kept in a 32°C (± 1°C) incubator for the duration of testing.The eyes were examined prior to use on the day of dosing. Any eye with a cornea exhibiting evidence of vascularization, pigmentation, opacity or scratches was discarded.Corneas from eyes that were free of defects were dissected from the surrounding tissues. A 2-3 mm rim of sclera was left attached to each cornea. The Corneas were then placed in a container of fresh HBSS.The dissected Corneas were mounted in specially designed holders that were separated into anterior and posterior chambers and filled separately. Each Cornea was mounted allowing the epithelium of the Cornea to project into the anterior chamber. The posterior chamber was filled with MEM solution ensuring contact with the endothelium. The anterior chamber was filled with MEM solution, ensuring contact with the epithelium. Each Cornea was visually inspected again to ensure there were no defects.The entire holder was incubated at 32°C (± 1°C) and allowed to equilibrate for at least one hour but not longer than two hours.Following the equilibration period, a pre-exposure (baseline) determination of opacity was made for each cornea by measuring each against the blank supplied with the opacitometer. Any cornea with a value greater than 7 opacity units was discarded.Study ProcedureFollowing the pretest observations, the MEM solution was removed from the anterior chamber. Using the closed chamber method, a volume of 0.75 ml of the ethanol, MEM or liquid test article was applied to the epithelium of each of the three positive controls, three negative controls, or three test article-treated corneas in a manner, which ensured the entire cornea was covered.All holders and corneas were placed in a horizontal position (anterior side up) in the 32°C (± 1°C) incubator. After 10 (± 1) minutes, the test article, ethanol or MEM solution in the controls were removed from the epithelium of the cornea and anterior chamber of the holder by washing with MEM solution containing phenol red. Following the 1O-minute (±1 minute) exposure, the corneal epithelium was thoroughly rinsed with MEM solution containing phenol red until the test article, ethanol, or MEM solution (in the negative controls) were washed off. A final rinse was made with MEM without phenol red. The anterior and posterior chambers of the holders were refilled with fresh MEM solution. Opacity measurements were made following the 10-minute exposure and MEM solution refill.All corneas were incubated at 32°C (± 1°G) for an additional two hours at which time the MEM solution in the anterior and posterior chambers was removed and the holders refilled with fresh MEM solution. A measurement of opacity was taken with each treated cornea compared to the blank supplied with the OPKIT. This reading was used in the final IVIS calculations.The corneas were visually inspected for abnormalities immediately following the 10-minute exposure period, and again at 2 hours post-exposure. There were no abnormalities noted.Immediately following the two-hour opacity measurement, the MEM solution was removed from the anterior chamber and replaced with 1.0 ml of 0.4% sodium fluorescein solution in Dulbecco's Phosphate Buffered Saline (PBS). Each holder was returned to the 32°C (±1°C) incubator in a horizontal position (anterior side up) ensuring contact of the fluorescein with the cornea.After 90 (± 5) minutes, the fluid from the posterior chamber was removed and the amount of dye, which passed through the cornea (permeability), was measured as the optical density at 490 nm by a spectrophotometer. A 1: 1000 dilution of the fluorescein was prepared and measured in the spectrophotometer as a measure of consistency.Analysis of DataIndividual corrected opacity scores were calculated by subtracting the pretest score from the ten minute and two-hour scores. Corrected mean opacity scores were calculated by averaging the individual two-hour corrected opacity scores for a given dose group and subtracting the mean opacity score for the negative control group. A corrected mean opacity score was not calculated for the negative control rather only the mean of the individual two-hour corrected opacity scores were calculated (with no subtraction of mean opacity score for negative control).Individual corrected optical densities were calculated by subtracting the mean optical density for the negative control group from the individual optical density values. Individual corrected optical densities were not calculated for the negative control group. Corrected mean optical densities were calculated by averaging the individual corrected optical density values for a given dose group. A corrected mean optical density was not calculated for the negative control, rather only the mean of the individual optical densities.The In Vitro Irritancy Score (IVIS) for the test article and positive control were calculated by adding the corrected mean opacity score to fifteen times the corrected mean optical density as shown by the equation below. The calculations to obtain an IVIS for the positive control was performed in the same manner as the test article.In Vitro Irritancy Score = Corrected Mean+15 (Corrected Mean Optical Density Score) (IVIS) Opacity ScoreOECD Guideline #437 defies a substance, which produces an IVIS of >55.1 as Category 1, a substance that causes “Serious eye damage”.IVISUN GHS≤ 3No Category>3; ≤55No prediction can be made>55Category 1
- Irritation parameter:
- in vitro irritation score
- Run / experiment:
- Mean
- Value:
- -2.42
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Other effects / acceptance of results:
- Test Article: The corrected mean opacity score was -2.33. The corrected mean optical density (permeability) score was -0.006. The in vitro irritancy score (IVIS) was calculated as -2.42.Negative Control: The corrected mean opacity score was 2.33. The mean optical density (permeability) score was 0.024. The IVIS was calculated as 2.69.Positive Control: The corrected mean opacity score was 17.67. The corrected mean optical density (permeability) score was 0.187. The IVIS was calculated as 20.48.All controls were within normal limits.
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: EU
- Conclusions:
- Based on the In Vitro Irritation Score, H2925 (CAS No. 68130-53-0), Lot# 2013090401, is not classfied as an eye irritant in accordance with the CLP Regulation.
- Executive summary:
Objective: To determine the potential for ocular irritation using an alternative to the Draize methodology.
This protocol is based on the methodology described in the current OECD Guideline for the Testing of Chemicals #437.
Method Synopsis: Three bovine corneas per group were dosed with 0.75 ml of H2925 (CAS No. 6813053-0), Lot# 2013090401, Minimal Essential Media (MEM) (negative control), or 100% Ethanol (positive control). Following a ten-minute exposure for each group of dosed corneas, opacity measurements and sodium fluorescein permeability were determined.
Summary/Conclusion:
Test Article: The corrected mean opacity score was -2.33. The corrected mean optical density (permeability) score was -0.006. The in vitro irritancy score (IVIS) was calculated as -2.42.
Negative Control: The corrected mean opacity score was 2.33. The mean optical density (permeability) score was 0.024. The IVIS was calculated as 2.69.
Positive Control: The corrected mean opacity score was 17.67. The corrected mean optical density (permeability) score was 0.187. The IVIS was calculated as 20.48.
All controls were within normal limits.
Based on the In Vitro Irritation Score, H2925 (CAS No. 68130-53-0), Lot# 2013090401, is not classfied as an eye irritant in accordance with the CLP Regulation.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 20 Nov - 23 Nov 1990
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study; only few details on study substance). For read-across, maximum reliability score is 2.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- adopted in 1987
- Deviations:
- yes
- Remarks:
- lack of details on test substance
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS- Source: Elevage Cunicole du Val de Selle, France- Weight at study initiation: 2.6 kg- Housing: individually- Diet: Certified pellet (Rabbits sustenance ref. 112 C; ad libitum- Water: tap water, ad libitum- Acclimation period: 5 days-other: the animals received a preventive coccidiosis treatment during acclimation (Mucoxid, 137.5 mg/kg bw/day, via drinking water)ENVIRONMENTAL CONDITIONS- Temperature (°C): 17-23- Humidity (%): 30-70- 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 dose, no rinsing
- Observation period (in vivo):
- 72 hReading time points: 1, 24, 48 and 72 h
- Number of animals or in vitro replicates:
- 3 males
- Details on study design:
- REMOVAL OF TEST SUBSTANCE- Washing (if done): NoSCORING SYSTEM: according to 84/499/EEC appendix V B5, i.e., according to the Draize scoring systemTOOL USED TO ASSESS SCORE: fluorescein
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritant / corrosive response data:
- In 2 animals slight exsudation (grade 1) was obsevered at 1 h. At 24 h slight exsudation (grade 1) was observed in 1 animals. These effects were completely reversible at 48 h.
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: EU
- Conclusions:
- CLP: not classified
DSD: not classified - Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study with acceptable restrictions (lack of data on test substance and animal husbandry).
- 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:
- out of all three animals
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- out of all three animals
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Remarks:
- out of all three animals
- Time point:
- other: mean over 24 h, 48 h and 72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- other: reversibility not applicable
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Remarks:
- out of all three animals
- Time point:
- other: mean over 24 h, 48 h and 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:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- CLP: not classified
DSD: not classified
Referenceopen allclose all
INDIVIDUAL EYE IRRITATION SCORES
Time after dosing |
Cornea |
Iris |
Conjunctivae |
Comments |
||||
Opacity |
Area |
Flour area (%) |
Redness |
Chemosis |
Discharge |
|||
No 518# (Sentinel) |
||||||||
1 hour |
0 |
0 |
|
0 |
1 |
1 |
0 |
|
24 hours |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
48 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
72 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
No 528# |
||||||||
1 hour |
0 |
0 |
|
0 |
1 |
0 |
0 |
|
24 hours |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
48 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
72 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
No 529# |
||||||||
1 hour |
0 |
0 |
|
0 |
1 |
0 |
0 |
|
24 hours |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
48 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
72 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
Flour area (%): green staining (percentage of total cornea area) after fluorescein treatment
MEAN VALUE EYE IRRITATION SCORES
Animal# |
Mean 24 – 72 hours |
|||
|
Corneal opacity |
Iris |
Conjunctivae |
|
Redness |
Chemosis |
|||
518 |
0 |
0 |
0 |
0 |
528 |
0 |
0 |
0 |
0 |
529 |
0 |
0 |
0 |
0 |
#Animal specifications:
Animal no |
Sex |
Age at start (weeks) |
Bodyweights (grams) |
|
Prior to application |
At termination |
|||
518 |
Male |
7-9 |
1492 |
1705 |
528 |
Male |
8-10 |
1807 |
1905 |
529 |
Male |
8-10 |
1691 |
1768 |
INIDVIDUAL EYE IRRITATION SCORES
Time after dosing |
Cornea |
Iris |
Conjunctivae |
Comments |
||||
Opacity |
Area |
Fluor area (%) |
Redness |
Chemosis |
Discharge |
|||
Male No 517# (sentinel) |
||||||||
1 hour |
0 |
0 |
|
0 |
1 |
1 |
0 |
|
24 hours |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
48 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
72 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
Male No 530# |
||||||||
1 hour |
0 |
0 |
|
0 |
1 |
0 |
0 |
|
24 hours |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
48 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
72 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
Male No 513# |
||||||||
1 hour |
0 |
0 |
|
0 |
1 |
0 |
0 |
|
24 hours |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
48 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
72 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
|
Fluor area (%): green staining (percentage of total cornea area) after fluorescein treatment
MEAN VALUE EYE IRRITATION SCORES
Animal# |
Mean 24 – 72 hours |
|||
Corneal opacity |
Iris |
Conjunctivae |
||
Redness |
Chemosis |
|||
517 |
0 |
0 |
0 |
0 |
530 |
0 |
0 |
0 |
0 |
531 |
0 |
0 |
0 |
0 |
#Animal specification:
Animal no |
Sex |
Age at start (weeks) |
Body weights (grams) |
|
Prior to application |
At termination |
|||
517 |
Male |
7-9 |
1539 |
1675 |
530 |
Male |
8-10 |
2002 |
2140 |
531 |
Male |
8-10 |
1912 |
2002 |
INDIVIDUAL EYE IRRITATION SCORES
Time after dosing |
Cornea |
Iris |
Conjunctivae |
Comments |
||||
Opacity |
Area |
Fluor area (%) |
|
Redness |
Chemosis |
Discharge |
||
M No 61# |
||||||||
1 hour |
0 |
0 |
|
0 |
1 |
0 |
0 |
- |
24 hours |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
- |
48 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
- |
72 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
- |
M No 66# |
||||||||
1 hour |
0 |
0 |
|
0 |
1 |
0 |
0 |
- |
24 hours |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
- |
48 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
- |
72 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
- |
M No 85# |
||||||||
1 hour |
0 |
0 |
|
0 |
1 |
0 |
0 |
- |
24 hours |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
- |
48 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
- |
72 hours |
0 |
0 |
|
0 |
0 |
0 |
0 |
- |
Fluor area (%): green staining (percentage of total corneal area) after fluorescein treatment
MEAN VALUE EYE IRRITATION SCORES
Animal# |
Mean 24-72 hours |
|||
Corneal opacity |
Iris |
Conjunctivae |
||
Redness |
Chemosis |
|||
61 |
0 |
0 |
0 |
0 |
66 |
0 |
0 |
0 |
0 |
85 |
0 |
0 |
0 |
0 |
#Animal specifications:
Animal no |
Sex |
Age at start (weeks) |
Bodyweights (grams) |
|
Prior to application |
At termination |
|||
61 |
Male |
12-14 |
2950 |
2953 |
66 |
Male |
12-14 |
2535 |
2622 |
85 |
Male |
9-11 |
2260 |
2361 |
RESULTS
TEST ARTICLE – H2925 (CAS No. 68130-53-0), Lot# 2013090401
INDIVIDUAL TEST VALUES
CORNEA# |
Pretest Opacity Scores |
10-Minute Scores |
2-Hour Scores |
O.D. ay 490 nm (Permeability) |
7 |
2 |
2 |
2 |
0.028 |
8 |
2 |
2 |
3 |
0.020 |
9 |
1 |
1 |
0 |
0.007 |
INDIVIDUAL AND MEAN CALCULATED VALUES
CORNEA# |
Corrected Opacity Scores |
Individual Corrected O.D.2 |
|
Individual 10-Minute Corrected Opacity Score1 |
Individual 2-Hour Corrected Opacity Score1 |
||
7 |
0 |
0 |
0.004 |
8 |
0 |
1 |
-0.004 |
9 |
0 |
-1 |
-0.017 |
Corrected Mean Opacity Density3= |
-0.006 |
||
2-Hour Corrected Mean Opacity Score4= |
-2.33 |
||
1Individual Corrected Opacity Score = 10-minute or 2-hour opacity score minus the pretest opacity score
2Individual Corrected Opacity Density = Individual test article OD minus the mean OD for negative control group. No correction was made for the negative control group.
3Corrected Mean Optical Density = Mean of the individual corrected optical density values for a given dose group.
42-Hour Corrected Mean Opacity Score = Mean of the individual 2-hour corrected opacity scores for a given dose group minus the mean opacity score for the negative control group.
NEGATIVE CONTROL – MEM
INDIVIDUAL AND MEAN CALCULATED VALUES
Cornea# |
Pretest Opacity Score |
10-Minute Scores |
10-Minute Corrected Opacity Score1 |
2-Hour Scores |
2-Hour Corrected Opacity Score1 |
O.D. at 490 nm (Permeability) |
C1 (neg) |
2 |
3 |
1 |
4 |
2 |
0.027 |
C2 (neg) |
2 |
3 |
1 |
3 |
1 |
0.027 |
C3 (neg) |
5 |
5 |
0 |
9 |
4 |
0.018 |
Mean of Individual Optical Density = |
0.024 |
|||||
2-Hour Corrected Mean Opacity Score = |
2.33 |
|||||
POSITIVE CONTROL – ETHANOL
INDIVIDUAL AND MEAN CALCULATED VALUES
Cornea# |
Individual Pretest Opacity Score |
Individual 10-Minute Scores |
Individual 10-Minute Corrected Opacity Score1 |
Individual 2-Hour Scores |
Individual 2-Hour Corrected Opacity Score1 |
O.D. at 490 nm (Permeability) |
Individual Corrected O.D.2 |
C4 (pos) |
3 |
9 |
6 |
3 |
0 |
0.192 |
0.168 |
C5 (pos) |
3 |
34 |
31 |
34 |
31 |
0.266 |
0.242 |
C6 (pos) |
1 |
32 |
31 |
30 |
29 |
0.175 |
0.151 |
Corrected Mean Optical Density3= |
0.187 |
||||||
2-Hour Corrected Mean Opacity Score4= |
17.67 |
||||||
1Individual Corrected Opacity Score = 10-Minute or 2-Hour opacity score minus pretest opacity score.
2Individual Corrected Optical Density = Individual positive control OD minus the mean OD for negative control group.
3Corrected Mean Optical Density = Mean of the individual corrected optical density values for a given dose group.
42-Hour Corrected Mean Opacity Score = Mean of the individual 2-hour corrected opacity scores for a given dose group minus the mean opacity score for the negative control group.
CALCULATED IN VITRO IRRITATION SCORES
Test Article (H2925 (CAS No. 68130-53-0), Lot# 2013090401) -2.33 + 15 (-0.006) -2.33 + (-0.09) IVIS: -2.42 |
Negative Control (MEM) 2.33 + 15 (0.024) 2.33 + 0.36 IVIS: 2.69 |
Positive Control (Ethanol) 17.67 + 15 (0.187) 17.67 + 2.805 IVIS: 20.48 |
Animal |
Hours after application |
|||||||||||||||||||
1 |
24 |
48 |
72 |
|||||||||||||||||
A |
B |
C |
D |
E |
A |
B |
C |
D |
E |
A |
B |
C |
D |
E |
A |
B |
C |
D |
E |
|
1 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
A = Cornea Score
B = Iris Score
C = Erythema Score
D = Chemosis Score
E = Exsudation Score
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
HATCOL 3331
Primary skin irritation/corrosion study with HATCOL 3331 in the rabbit (4-hour semi-occlusive application).
Three rabbits were exposed to 0.5 ml of HATCOL 3331, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.
Exposure to HATCOL 3331 resulted in very slight erythema and/or very slight oedema in the treated skin-areas of the rabbits, which had resolved within 24 hours in two animals and within48 hours in the other animal.
Sticky remnants of the test substance were present on the edges of the treated skin area on day 1.
Based on the results HATCOL 3331 does not have to be classified for skin irritation.
Acute eye irritation/corrosion study with HATCOL 3331 in the rabbit.
Single samples of 0.1 ml of HATCOL 3331 were instilled into one eye of each of three rabbits.
Observations were made 1, 24, 48 and 72 hours after instillation.
Instillation of the test substance resulted in irritation of the conjunctivae, which was seen as redness and chemosis. The irritation had completely resolved within 24 hours in all animals.
Based on these results HATCOL 3331 does not have to be classified for eye irritation.
HATCOL 3344
Primary skin irritation/corrosion study with HATCOL 3344 in the rabbit (4-hour semi-occlusive application).
Three rabbits were exposed to 0.5 ml of HATCOL 3344, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.
Exposure to HATCOL 3344 resulted in very slight erythema in the treated skin-areas of the rabbits, which had resolved within 24 hours.
Fatty remnants of the test substance were present immediately after removal of the bandage.
Based on the results HATCOL 3344 does not have to be classified for skin irritation.
Acute eye Irritation/corrosion study with HATCOL 3344 in the rabbit.
Single samples of 0.1 ml of HATCOL 334 were instilled into one eye of each of three rabbits.
Observations were made 1, 24, 48 and 72 hours after instillation.
Instillation of the test substance resulted in Irritation of the conjunctivae, which was seen as redness and chemosis. The irritation had completely resolved within 24 hours in all animals.
Based on these results HATCOL 3344 does not have to be classified for eye irritation.
HATCOL 5236
Primary skin irritation/corrosion study with HATCOL 5236 in the rabbit (4-hour semi-occlusive application).
Three rabbits were exposed to 0.5 ml of HATCOL 5236, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure.
Four hours exposure to 0.5 ml of HATCOL 5236 resulted in very slight erythema in the treated skin-areas of the three rabbits.
The skin irritation had resolved within 1 day after exposure in all animals.
Based on the results HATCOL 5236 does not have to be classified for skin irritation.
Acute eye irritation/corrosion study with HATCOL 5236 in the rabbit.
Single samples of 0.1 ml of HATCOL 5236 were instilled into one eye of each of three rabbits.
Observations were made 1, 24, 48 and 72 hours after instillation.
Instillation of 0.1 ml of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae, which was seen as redness on day 1.
Based on these results HATCOL 5236 does not have to be classified for eye irritation.
HATCOL 1510
A GLP study was conducted in accordance with OECD Guideline 431; based on the results of this study, H2925 (CAS No. 68130-53-0), Lot# 2013090401 is considered to be non-corrosive.
A GLP study H2925 was conducted in accordance with OECD Guideline 439; based on the results of this study, H2925 (CAS No. 68130-53-0), Lot# 2013090401 is considered to be a non-irritant and therefore it is not classified in accordance with the CLP Regulation.
Three in vivo skin irritation studies are also available for read-across substances:
The first study was conducted with CAS 11138-60-6 in accordance with OECD Guideline 404. No cutaneous reactions occurred in the 3 New Zealand White rabbits tested. Therefore, it was concluded that the test substance is not irritating to the skin.
The second study was conducted with CAS 91050-89-4 in accordance with OECD Guideline 404. After 24 h, 3 animals (New Zealand White rabbits) showed erythema, which persisted in 1 animal for 48 h. 72 h after exposure, all animals were free of erythema. Therefore, it was concluded that the test substance is not irritating to the skin.
The third study was conducted with CAS 78-16-0 in accordance with EU Method B.4. Very slight erythema and edema were observed in all animals (3 New Zealand White rabbits) 24 h after treatment which were fully reversible latest within 72 h. Therefore, it was concluded that the test substance is not irritating to the skin.
A GLP study was conducted in accordance with OECD Guideline 437; based on the results of this study, H2925 (CAS No. 68130-53-0), Lot# 2013090401, is not classfied as an eye irritant in accordance with the CLP Regulation.
Four in vivo eye irritation studies are available for read-across substances:
The first study was conducted with CAS 11138-60-6 in accordance with OECD Guideline 405. In 2 animals (New Zealand White rabbits) slight exudation (grade 1) was observed at 1 h. At 24 h slight exudation (grade 1) was observed in 1 animals. These effects were completely reversible at 48 h. Therefore, it was concluded that the test substance is not irritating to the eyes.
The second study was conducted with CAS 78-16-0 in accordance with guideline 16 CFR 1500.42. No effects on the cornea or iris were observed in test animals. Slight redness of the conjunctivae was observed after 24 h in 3 animals (albino rabbits) and after 48 h in 4 animals which were fully reversible in all animals within 72 h. Slight chemosis of the conjunctiva was detected in 1 animal after 24 h which was fully reversible within 48 h.Therefore, it was concluded that the test substance is not irritating to the eyes.
The third study was conducted with CAS 91050-89-4 in accordance with OECD Guideline 405. No effects on cornea and iris were observed. Slight redness of the conjunctivae was observed both, after 10 s and after continuous treatment. The effects were obvious after 1 and 6 h. After 10 s treatment, the effects were reversible within 48 h. After continuous treatment, redness reversed within 24 h. In addition, exudation was observed in both treatment groups, being reversible within 24 h (continuous treatment) and 48 h (10 s treatment), respectively. Chemosis was not observed. Therefore, it was concluded that the test substance is not irritating to the eyes.
The fourth study was conducted with CAS 78-16-0 in accordance with OECD Guideline 405 in New Zealand White rabbits. No effects on the cornea and the iris were observed. Conjunctival effects included slight to moderate redness and slight to severe discharge. No chemosis was seen. Additional signs of irritation included erythema and dried secretion on the upper and lower eyelids and convoluted eyelids. All effects were completely reversible within 48 h after application. Therefore, it was concluded that the test substance is not irritating to the eyes.
In conclusion, the substance is not considered to be irritating to either the skin or the eyes.
Justification for selection of skin irritation / corrosion endpoint:
Endpoint conclusion derived in experimental conditions in accordance with OECD guideline 404, EU test standard B4 and US EPA guidance 870.2500
Justification for selection of eye irritation endpoint:
Endpoint conclusion derived in experimental conditions in accordance with OECD guideline 405, EU test standard B5 and US EPA guidance 870.2400
Justification for classification or non-classification
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