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Description of key information

Y-15099 was found to be neither irritating to human or rabbit skin nor to the rabbit eye. 

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
Study period:
22 May - 30 Jul 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
certified by the Federal Office of Public Health, 2000
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 10 - 11 weeks
- Weight at study initiation: 2.2 - 2.6 kg
- Housing: Individually in stainless steel cages
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 90/01) provided by Provimi Klima AG, CH-4303 Kaiseraugst
- Water: Community tap water from Füllinsdorf, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15 air changes / hour
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark, music was played during the light period

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: left flank
- Type of wrap if used: surgical gauze pad (ca. 2.5 cm x 2.5 cm)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize system
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean value of readings at
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean value of readings at
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean value of readings at
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
mean
Remarks:
3/3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No classification is warranted according to DSD (67/548/EEC) and CLP (1272/2008/EC), respectively.
Executive summary:

The primary skin irritation potential of Y-15099 was investigated in a GLP study according to OECD 404. The shaved left flank of three young adult New Zealand White rabbits was exposed to 0.5 mL undiluted test material for 4 hours under semi-occlusive conditions. The scoring of skin reactions was performed 1, 24, 48 and 72 hours, as well as 7 days after removal of the dressing.

Well-defined erythema was observed in all animals 1 hour after treatment. Slight to well-defined erythema persisted in one animal up to the 24-hour reading and in the two other animals up to the 72-hour reading. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval. No abnormal findings were observed at the test site of any animal on test day 7.

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:
26 Jun - 30 Jul 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
certified by Federal Office of Public Health, 2000
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: males: 10 - 11 weeks; females: 11 - 12 weeks
- Weight at study initiation: no data
- Housing: individually in stainless steel cages
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 90/01) provided by Provimi Kliba AG, CH-4303 Kaiseraugst
- Water: Community tap water from Füllinsdorf, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark, music was played during the light period

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL per animal
Duration of treatment / exposure:
single eye instillation
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): eyes were not rinsed after instillation

SCORING SYSTEM: Draize system
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean of readings at
Time point:
24/48/72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean value of readings at
Time point:
24/48/72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
mean value of readings at
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3/3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3/3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
3/3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No classification is warranted according to DSD (67/548/EEC) and CLP (1272/2008/EC), respectively.
Executive summary:

The primary eye irritation potential of Y-15099 was investigated in a GLP study according to OECD 405. Three young adult New Zealand White rabbits were exposed to the undiluted test item by instillation 0.1 mL into one eye. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item application.

The instillation of the test item into the eye resulted in mild, early onset and transient ocular changes in all animals (observation time 1 hour after application). Observations included slight reddening and swelling of the conjunctivae and reddening of the sclera. These effects were reversible and were no longer evident 72 hours after treatment at termination. No abnormal findings were observed in the cornea or iris of any animal at any reading. No staining of the treated eyes by the test item was observed and no evidence of corrosion was evident at any of the measuring intervals. No classification is warranted according to DSD (67/548/EEC) and CLP (1272/2008/EC) classification criteria for eye irritation.

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

Additional information

The primary skin irritation potential of Y-15099 was investigated in a GLP study according to OECD 404 (Arcelin, 2001). The shaved left flank of three young adult New Zealand White rabbits was exposed to 0.5 mL undiluted liquid test material for 4 hours under semi-occlusive conditions. The scoring of skin reactions was performed 1, 24, 48 and 72 hours, as well as 7 days after removal of the dressing.

Well-defined erythema was observed in all animals 1 hour after treatment. Slight to well-defined erythema persisted in one animal up to the 24-hour reading and in the two other animals up to the 72-hour reading. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval. No abnormal findings were observed at the test site of any animal on test day 7.

 

In a human volunteer study, the test substance, Y-15099, was evaluated as solution in dried peanut oil and undiluted to determine the highest concentration causing the least irritation to the skin in an 8-day range finding patch study (Dosik, 2002). Twenty subjects were exposed on days 1, 3 and 5 to test substance concentrations of 10, 50 and 100% for 24 hours under semi-occlusive conditions. Treated skin sites were evaluated after each exposure.

The irritation scores for all concentrations were 0.0 in all subjects. There was no difference in irritation potential between the 3 concentrations of the test substance. Based on the results of this study, undiluted Y-15099 did not show irritating potential to human skin. 

 

The primary eye irritation potential of Y-15099 was investigated in a GLP study according to OECD 405 (Arcelin, 2001). Three young adult New Zealand White rabbits were exposed to the undiluted test item by instillation 0.1 mL into one eye. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item application.

The instillation of the test item into the eye resulted in mild, early onset and transient ocular changes in all animals (observation time 1 hour after application). Observations included slight reddening and swelling of the conjunctivae and reddening of the sclera. These effects were reversible and were no longer evident 72 hours after treatment at termination. No abnormal findings were observed in the cornea or iris of any animal at any reading. No staining of the treated eyes by the test item was observed and no evidence of corrosion was evident at any of the measuring intervals.

 

Justification for classification or non-classification

No classification is warranted according to DSD (67/548/EEC) and CLP (1272/2008/EC) classification criteria for irritation/corrosion.