Registration Dossier

Administrative data

Description of key information

Skin irritation

The Primary Irritation Index (PII) of Evercion SR61 was 0 and Evercion SR61 was categorized as non-irritant (OECD TG404).

 

Eye irritation

Evercion SR61 was categorized as mildly irritating to eyes (OECD TG405). Based on the testing results, the test substance is not classified under CLP regulation.

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:
From February 16, 2016 to November 08, 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)
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: 2.6952 to 3.0700 kg
- Housing: individually in a stainless steel 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:
- Amount(s) applied (volume or weight with unit): 0.5 g test article was moistened with 0.5 mL normal saline
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours
Number of animals:
three
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)
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

16

Female

3.0700

3.1088

17

Female

2.6952

2.7374

23

Female

2.9372

2.9776

Table 2. Individual skin reactions

Animal I.D.

Observation time (hours)

Grading (erythema / edema)

Test area

Control area

16

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

17

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

23

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

16

0

0

0

17

0

0

0

23

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 Evercion SR61 was 0 and Evercion SR61 was categorized as non-irritant. Therefore, Evercion SR61 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the SuperLab Study Plan for M62-151100093001EN 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 Evercion SR61 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 Evercion SR61 was categorized as non-irritant.

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 February 16, 2016 to November 08, 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)
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: 2.6412-3.4180 kg
- Housing: individually in a stainless steel 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 and 72 hours
Number of animals or in vitro replicates:
Three
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:
0.3
Max. score:
1
Reversibility:
fully reversible within: 1 day
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 1 day
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
probability of weak irritation

Table 1. Body weight of the rabbits

Animal ID

Sex

Body weight (kg)

Day 1

Day 4

21

Female

3.4180

3.4394

22

Female

2.8186

2.8698

24

Female

2.6412

2.6926

Table 2. Individual response of the test rabbits

Animal I.D.

Timea (hour)

Observation site

Grades of the irritation reaction

Cornea

Conjunctivae

Iris

Opacity

Area

Redness

Chemosis

Discharge

21

1

Testb

0

0

1

2

0

1

Controlc

0

0

0

0

0

0

24 ± 1

Test

0

0

1

0

0

1

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

22

1

Test

0

0

1

1

0

1

Control

0

0

0

0

0

0

24 ± 1

Test

0

0

1

0

0

1

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

24

1

Test

0

0

1

2

0

1

Control

0

0

0

0

0

0

24 ± 1

Test

0

0

1

0

0

1

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, Evercion SR61 cause mildly irritating to the eye. Based on the testing results, Evercion SR61 is not classified under the CLP criteria.
Executive summary:

This test using the procedures outlined in the SuperLab Study Plan for M62-151100094001EN which is based on the SOP for the OECD 405 (SOPP-306) and OECD 405 (OECD, 2012). Evercion SR61 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. There were no test article effects on body weight. Redness and chemosis of conjunctivae and iris with score of 1 -2 were observed within 24 hours after test article application and fully recovered within 48 hours. On the basis of the test results given above, the response of the test articlecause mildly irritating to the eye. Based on the testing results, Evercion SR61 is not classified under the CLP criteria.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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 was no formation of erythema, eschar or edema on the test area within 72 hours after patch removal. The Primary Irritation Index for Evercion SR61 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 Evercion SR61 was categorized as non-irritant.

 

Eye irritation

Evercion SR61 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. There were no test article effects on body weight. Redness and chemosis of conjunctivae and iris with score of 1-2 were observed within 24 hours after test article application and fully recovered within 48 hours. On the basis of the test results given above, the response of the test article cause mildly irritating to the eye.

Based on the testing results, the test substance is not classified under CLP regulation.

Justification for classification or non-classification