Registration Dossier

Administrative data

Description of key information

Skin irritation

The Primary Irritation Index (PII) of Everlan SL65 was 0 and Everlan SL65 was categorized as non-irritant (OECD TG404).

 

Eye irritation

Everlan SL65 did not cause positive irritating to the eye (OECD TG405).

 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Dec 28, 2015 - Nov 24, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
OECD 404:2015
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
- Source: WEI XIN HANG
- Weight at study initiation: 3.0608 to 3.6280 kg
- Housing: individually in a stainless steel wire mesh cage
- Water: ad libitum
- Acclimation period: 7 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 15%
- Photoperiod: 12hrs dark / 12hrs light
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
physiological saline
Controls:
yes, concurrent vehicle
Amount / concentration applied:
0.5 g test article was moistened with 0.5 mL normal saline
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 28 and 72 hours
Number of animals:
3 female
Details on study design:
- Area of exposure: upper left and lower right dorsal area
- Washing (if done): with distilled water
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation

Table 1. Body weight of the rabbits

Animal ID

Sex

Body weight (kg)

Day 1

Day 4

41

Female

3.6280

3.6626

42

Female

3.0608

3.1042

44

Female

3.3676

3.4082

Table 2. Individual skin reactions

Animal I.D.

Observation time (hours)

Grading (erythema / edema)

Test area

Control area

41

1

0/0

0/0

0/0

0/0

24± 1

0/0

0/0

0/0

0/0

48 ± 1

0/0

0/0

0/0

0/0

72 ± 1

0/0

0/0

0/0

0/0

42

1

0/0

0/0

0/0

0/0

24 ± 1

0/0

0/0

0/0

0/0

48 ± 1

0/0

0/0

0/0

0/0

72 ± 1

0/0

0/0

0/0

0/0

44

1

0/0

0/0

0/0

0/0

24 ± 1

0/0

0/0

0/0

0/0

48 ± 1

0/0

0/0

0/0

0/0

72 ± 1

0/0

0/0

0/0

0/0

Table 3. Individual animal primary irritation scores

Animal I.D.

Scoresa

Primary Irritation Scores (PIS)b

Test area

Control area

41

0

0

0

42

0

0

0

44

0

0

0

Primary Irritation Index (PII)c= 0

a Sum of scores at all time intervals on backside skin in each rabbit and divided the sum by the total number of observation.

b PIS = (scores of test area) – (scores of control area).

c PII = Sum of PIS÷number of animals.

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 404 test method and Evaluation table for single dermal irritation, the PII for Everlan SL65 was 0 and Everlan SL65 was categorized as non-irritant. Therefore, Everlan SL65 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the SuperLab Study Plan for M62-151100101001EN which is based on the SOP for the OECD 404 (SOPP-305) and OECD 404 (OECD, 2015).The sites were grades for erythema and edema at 1, 24, 48 and 72 hours after the patches removal. No clinical signs of toxicity were found. Body weight changes were within the normal range in all animals. All animals was no formation of erythema, eschar or edema on the test area within 72 hours after patch removal. The Primary Irritation Index for Everlan SL65 was calculated to be 0. On the basis of the test results given above and according to Evaluation table for single dermal irritation, the response of Everlan SL65 was categorized as non-irritant.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
[Specific explanation in addition to field 'Justification for data waiving']
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 11, 2016 - Dec 07, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
OECD 405:2012
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: WEI XIN HANG
- Weight at study initiation: 2.2684-2.3236 kg
- Housing: individually in a stainless steel wire mesh cage
- Water: ad libitum
- Acclimation period: 7 days
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 15%
- Photoperiod: 12-hrs dark / 12-hrs light
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
1, 24, 48, 72 hours
Number of animals or in vitro replicates:
three female rabbits
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 24hr
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 24hr
Remarks on result:
probability of weak irritation

Table 1. Body weight of the rabbits

Animal ID

Sex

Body weight (kg)

Day 1

Day 4

37

Female

2.2759

2.2789

38

Female

2.2684

2.2709

39

Female

2.3236

2.3259

Table 2. Individual response of the test rabbits

Animal I.D.

Timea

(hour)

 

Grades of the irritation reaction

Cornea

Conjunctivae

Iris

Opacity

Area

Redness

Chemosis

Discharge

37

1

Testb

0

0

0

4

2

0

Controlc

0

0

0

0

0

0

24 ± 1

Test

0

0

0

2

1

0

Control

0

0

0

0

0

0

48 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

72 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

38

1

Test

0

0

3

4

2

0

Control

0

0

0

0

0

0

24 ± 1

Test

0

0

1

2

0

0

Control

0

0

0

0

0

0

48 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

72 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

39

1

Test

0

0

1

3

2

0

Control

0

0

0

0

0

0

24 ± 1

Test

0

0

0

1

0

0

Control

0

0

0

0

0

0

48 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

72 ± 1

Test

0

0

0

0

0

0

Control

0

0

0

0

0

0

a Observation time was started after application of the test article

b Left eye of the test rabbits

c Right eye of the test rabbits

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 405 test method, Everlan SL65 did not show that positive irritant to the eye. Therefore, Everlan SL65 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the SuperLab Study Plan for M62-151100102001EN which is based on the SOP for the OECD 405 (SOPP-306) and OECD 405 (OECD, 2012). There were no test article effects on body weight. Everlan SL65 was given by a single ocular application at 0.1 g amount to NZW female rabbits and followed by ocular examination within 72 hours and a 4 days clinical observation period. Cornea and iris with score 0 during all study period. Irritant reaction that caused by test article was disappeared within 48 hours after dosing. On the basis of the test results given above, the response of the test article did not cause positive irritating to the eye.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
[Specific explanation in addition to field 'Justification for data waiving']
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The sites were grades for erythema and edema at 1, 24, 48 and 72 hours after the patches removal. No clinical signs of toxicity were found. Body weight changes were within the normal range in all animals. All animals were no formation of erythema, eschar or edema on the test area within 72 hours after patch removal. The Primary Irritation Index for Everlan SL65 was calculated to be 0. On the basis of the test results given above and according to Evaluation table for single dermal irritation, the response of Everlan SL65 was categorized as non-irritant.

 

Eye irritation

There were no test article effects on body weight. Everlan SL65 was given by a single ocular application at 0.1 g amount to NZW female rabbits and followed by ocular examination within 72 hours and a 4 days clinical observation period. Cornea and iris with score 0 during all study period. Irritant reaction that caused by test article was disappeared within 48 hours after dosing. On the basis of the test results given above, the response of the test article did not cause positive irritating to the eye.

Justification for classification or non-classification