Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
CAS No.: 078567-28-9; Batch No.: WDJ 1853 D-3; Purity: 100 %; Appearance: yellowish liquid
Species:
rabbit
Strain:
Himalayan
Details on test animals and environmental conditions:
Species / strain / stock / breeder: rabbit / Himalayan / LPT Laboratory of Pharmacology and Toxicology KG branch Lohndorf, D-24601 Lohndorf/Post Wankendorf,
Number of animals examined: 3 male rabbits,
Initial age: approx. 5 - 5.5 months,
Body weight at start of study: 2.4 - 2.6 kg,
Identification: by tattooed number assigned by the Lohndorf breeding station and continuous number 1 - 3,
Duration of study: at least 20 adaptation days,
Administration route: 0.5 ml/patch and animal, once epicutaneous.

Diet: ssniff K-H (ssniff Spezialdiaten GmbH, D-59494 Soest: Composition of the diet) served as food. The food was available ad libitum before and after the exposure period. At regular intervals (at least twice a year) the food is analysed for contaminants by AUA.

Drinking water: Tap water was offered ad libitum before and after the exposure period.
Samples of the drinking water are taken twice a year by the Wasserbeschaffungsverband Harburg, and are analysed according to the Deutsche Trinkwasserverordnung, Bundesgesetzblatt, 1990. In addition, drinking water samples taken at LPT are analysed by LUFA-ITL.

Housing: For 8 hours following test substance application, the animals were kept singly in special restrainers which allowed free movement of the head but prevented a complete body turn and wiping of the eyes.
During the acclimatisation period and after the 8-hour period in restrainers, the rabbits were kept separately in cages with dimensions of 425 mm x 600 mm x 380 mm at a room temperature of 20 °C ± 3 °C (maximum range). Relative humidity was 55 % ± 15 % (maximum range).
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 ml of the test substance was applied to the test site (area: approx. 6 cm2).
Duration of treatment / exposure:
4 hours
Observation period:
Based on most recent guidelines the skin reactions are monitored until the changes observed have completely subsided, however for not more than 14 days after application. Animals that do not reveal any lesions anymore for 24 hours following the first 72 hours of observation are sacrificed.
Number of animals:
3
Details on study design:
Approximately 24 hours before the test, the fur was removed by shaving from the dorsal area of the trunk of the animals. Care was taken to avoid abrading the skin. Only animals with healthy intact skin were used. A dose of 0.5 ml was applied to the test site (area: approx. 6 cm2).
The test substance was applied to the test site and then covered with a gauze patch, which was held in place with non-irritating tape for the duration of the exposure period. The surrounding untreated skin served as a control. Exposure time was four hours. During the exposure the animals were kept in comfortable restrainers.
Examination of the skin: the skin sites were evaluated immediately before the application of the test substance. After the 4 hour exposure period the patch was removed and the skin sites were evaluated. Scores were taken 60 minutes, 24, 48, 72 hours and 4 days after patch removal.
General criteria: body weight of all animals was measured at the beginning of the study.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 4 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 4 d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
animal #1
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:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the test substance was not considered to be irritating to rabbit skin
Executive summary:

A study was conducted to determine a skin irritation potential of the test substance in male Himalayan rabbits according to OECD Guideline 404 and EU Method B.4. 0.5 mL of the test substance was applied to the shaved rabbit skin and then covered with a gauze patch, which was held in place with non-irritating tape for a duration of 4 h. The surrounding untreated skin served as a control. The skin sites were evaluated immediately before the application of the test substance. After the 4 h exposure period the patch was removed and the skin sites were evaluated 60 min, 24, 48, 72 h and 4 d after patch removal. Rabbit number 3 showed an erythema of grade 1 at 48 h after patch removal and animal no. 1 and 2 until 72 h after patch removal. Under the study conditions, the the substance was not considered to be irritating to rabbit skin (Leuschner, 2002).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From July 24, 2002 to July 24, 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
CAS No.: 078567-28-9; Batch No.: WDJ 1853 D-3; Purity: 100 %; Appearance: yellowish liquid
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
Species / strain / stock / breeder: rabbit / Himalayan / LPT Laboratory of Pharmacology and Toxicology KG branch Lohndorf, D-24601 Lohndorf/Post Wankendorf,
Number of animals examined: 3 male rabbits,
Initial age: approx. 4 - 5.5 months,
Body weight at start of study: 2.2 - 2.3 kg,
Identification: by tattooed number assigned by the Lohndorf breeding station and continuous number 1 - 3,
Duration of study: at least 20 adaptation days, 1 test day and a follow-up period of 72 hours,
Administration route: single instillation into the conjunctival sac.

Diet: ssniff K-H (ssniff Spezialdiaten GmbH, D-59494 Soest: Composition of the diet) served as food. The food was available ad libitum before and after the exposure period. At regular intervals (at least twice a year) the food is analysed for contaminants by AUA.

Drinking water: Tap water was offered ad libitum before and after the exposure period.
Samples of the drinking water are taken twice a year by the Wasserbeschaffungsverband Harburg, and are analysed according to the Deutsche Trinkwasserverordnung, Bundesgesetzblatt, 1990. In addition, drinking water samples taken at LPT are analysed by LUFA-ITL.

Housing: For 8 hours following test substance application, the animals were kept singly in special restrainers which allowed free movement of the head but prevented a complete body turn and wiping of the eyes.
During the acclimatisation period and after the 8-hour period in restrainers, the rabbits were kept separately in cages with dimensions of 425 mm x 600 mm x 380 mm at a room temperature of 20 °C ± 3 °C (maximum range). Relative humidity was 55 % ± 15 % (maximum range).

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Dose level: 0.1 mL/animal
Duration of treatment / exposure:
Based on most recent guidelines, the eye reactions are monitored until the changes observed have completely subsided, however not for more than 21 days after application.
Observation period (in vivo):
Animals that do not reveal any lesions anymore for 24 hours following the first 72 hours of observation are sacrificed.
Number of animals or in vitro replicates:
3
Details on study design:
A dose of 0.1 ml of the test substance was administered into the conjunctival sac of the right eye of rabbits after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about one second in order to prevent loss of test material. The left eye, which remained untreated, served as a control.
After the administration, the animals were kept separately in special restrainers which allowed free movement of the head but prevented a complete body turn, wiping of the eyes by the paws and excluded irritation of the eyes by excrements and urine.
Examination of the eyes: the eyes were examined ophthalmoscopically with a slit lamp prior to the administration and also 1, 24, 48 and 72 hours after the administration. The eye reactions were observed and registered.
Twenty-four (24) hours after administration, the eyes were treated additionally with fluorescein and examined. The effects observed were graded.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 1 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Corneal opacity (grade 1) was observed in animal no. one 1 hour after instillation. The fluorescein test performed 24 hours after instillation did not reveal any pathological findings. The iris and conjunctivae were not affected by instillation of the test compound. There were no systemic intolerance reactions.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the test substance was not considered to be irritating to rabbit eye.
Executive summary:

A study was conducted to determine the eye irritation potential of the test substance in male Himalayan rabbits according to OECD Guideline 405 and EU Method B.5. A dose of 0.1 mL of the test substance was administered into conjunctival sac of the right eye of the rabbits. The eyelid was then gently held together for about one second in order to prevent loss of test substance. The left eye, which remained untreated, served as a control. The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and at 1, 24, 48 and 72 h after the administration. 24 h after administration, the eyes were treated additionally with fluorescein and examined. The effects observed were graded. Under the study conditions, exposure to the test substance revealed the following effect only: Corneal opacity (grade 1) was observed in animal no. 1 at 1 h after instillation. The fluorescein test performed 24 h after instillation did not reveal any pathological findings. The iris and conjunctivae were not affected. There were no systemic intolerance reactions. Under the study conditions, the test substance was not considered to be irritating to rabbit eye (Leuschner, 2017).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

A study was conducted to determine a skin irritation potential of the test substance in male Himalayan rabbits according to OECD Guideline 404 and EU Method B.4. 0.5 mL of the test substance was applied to the shaved rabbit skin and then covered with a gauze patch, which was held in place with non-irritating tape for a duration of 4 h. The surrounding untreated skin served as a control. The skin sites were evaluated immediately before the application of the test substance. After the 4 h exposure period the patch was removed and the skin sites were evaluated 60 min, 24, 48, 72 h and 4 d after patch removal. Rabbit number 3 showed an erythema of grade 1 at 48 h after patch removal and animal no. 1 and 2 until 72 h after patch removal. Under the study conditions, the substance was not considered to be irritating to rabbit skin (Leuschner, 2002).

Eye irritation:

A study was conducted to determine the eye irritation potential of the test substance in male Himalayan rabbits according to OECD Guideline 405 and EU Method B.5. A dose of 0.1 mL of the test substance was administered into conjunctival sac of the right eye of the rabbits. The eyelid was then gently held together for about one second in order to prevent loss of test substance. The left eye, which remained untreated, served as a control. The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and at 1, 24, 48 and 72 h after the administration. 24 h after administration, the eyes were treated additionally with fluorescein and examined. The effects observed were graded. Under the study conditions, exposure to the test substance revealed the following effect only: Corneal opacity (grade 1) was observed in animal no. 1 at 1 h after instillation. The fluorescein test performed 24 h after instillation did not reveal any pathological findings. The iris and conjunctivae were not affected. There were no systemic intolerance reactions. Under the study conditions, the test substance was not considered to be irritating to rabbit eye (Leuschner, 2017).

Justification for classification or non-classification

The available in vivo studies on the test substance indicate that the substance is not a skin or eye irritant and hence, does not warrant classification according to EU CLP (EC 1272/2008) criteria.