Registration Dossier

Administrative data

Description of key information

Skin irritation

Everzol SR98 was non-irritant to skin (OECD TG404).

                          

Eye irritation

Everzol SR98was non-irritant to eye(OECD TG405).

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 December 08, 2017 to August 24, 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Source: Granja RG (Suzano/SP-Brazil)
- Age at study initiation: 10 weeks old
- Weight at study initiation: 2443.8-3006.7 g
- Housing: individually in stainless steel cages
- Water: ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 22.8-23.0 °C
- Humidity (%): 50-64 %
- Photoperiod: 12hrs dark / 12hrs light
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.5 g test substance was moistened with 0.5 mL water
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after removing the bandage.
Number of animals:
Three
Details on study design:
- Area of exposure: the skin of back
Irritation parameter:
erythema score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation

Table 1. Results of Dermal Irritation in the Periods of Evaluation.

Animal’s data

Reactions evaluation after application

Reactions evaluation after removal of the patch

3 min

1 h

4 h

1 h

24 h

48 h

72 h

Animal#

Initial Weight

(g)

Final Weight

(g)

Sex

O

E

O

E

O

E

O

E

O

E

O

E

O

E

1

2443.8

2924.4

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

3006.7

3274.4

-

-

-

-

-

-

0

0

0

0

0

0

0

0

3

2852.5

2885.3

-

-

-

-

-

-

0

0

0

0

0

0

0

0

O: Oedema; E: Erythema

 

Table 2. Clinical Signs.

Animal#

Clinical Signa

After application

After removal of the patch

3 min

1 hour

4 hours

1 hour

24 hours

48 hours

72 hours

1

0

0

0

0

0

0

0

2

-

-

-

0

0

0

0

3

-

-

-

0

0

0

0

0: None visual alterations observed.

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 404 test method test method, Everzol SR98 was non-irritant to skin. Therefore, Everzol SR98 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the BIOAGRI Study Plan for 16264.466.088.17. 0.5 g of Everzol SR98 moistened in 0.5 mL of purified water was applied to the skin of three New Zealand White rabbits and then covered with a gauze patch. After the 4 hours exposure period, the patches were removed, any residual test item removed using purified water and the animal #1 was evaluated after the application in the period of 3 minutes, 1 and 4 hours. After removing the bandage semiocclusive, three animals were examined skin reactions, behavioral and clinical alterations in approximately 1, 24, 48 and 72 hours. Adjacent untreated shaved areas of the skin were used as a negative control. Under test conditions, three rabbits do not showed any skin reactions and no treatment-related behavioral or clinical changes were observed during the observation period. On the basis of the test results given above, the response of Everzol SR98 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 December 08, 2017 to March 19, 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
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: Granja RG Suzano/SP, Brasil
- Age at study initiation: 10 weeks old
- Weight at study initiation: 2413.6 to 2616.7 g
- Housing: individually in stainless steel cages
- Water: ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 22.8 to 23.0 °C
- Humidity (%): 50 to 64 %
- 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 Hours
Observation period (in vivo):
Approximately 1, 24, 48, 72 hours after the application of test substance.
Number of animals or in vitro replicates:
Three
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2 and #3
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and #2
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Irritation parameter:
chemosis score
Basis:
animal: #1, #2 and #2
Time point:
24/48/72 h
Score:
0.33

Table 1. Initial and Final Weights of the Animals and Grading of Ocular Reactions Observed during the Test.

Animal #

01

02

03

Weight (g)

Initial

2413.6

2413.8

2616.7

Final

2775.6

2473.3

2751.7

Sex

Observation period

Hours

Hours

Hours

1

24

48

72

1

24

48

72

1

24

48

72

Cornea

Opacity

0

0

0

0

0

0

0

0

0

0

0

0

Area

0

0

0

0

0

0

0

0

0

0

0

0

Iris

Irite

0

0

0

0

0

0

0

0

0

0

0

0

Conjunctivae

Hyperemia

1

0

0

0

1

0

0

0

1

1

0

0

Chemosis

2

1

0

0

2

1

0

0

2

1

0

0

Secretion

-

-

-

-

-

-

-

-

-

-

-

-

Lesion

Fluorescein retention

NR

-

-

-

NR

-

-

-

NR

-

-

-

+: Presence; -: Ausence; NR: Not realized

Table 2. Clinical Signs

Animal #

Clinical Signs / Period of Evaluation

01 hour

24 hours

48 hours

72 hours

1

0

0

0

0

2

0

0

0

0

3

0

0

0

0

0: None visual alterations observed.

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 405 test method, Everzol SR98 showed that non-irritant to the eye. Therefore, Everzol SR98 was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the BIOAGRI Study Plan for 16264.465.102.17. All the animals presented body weight gain during the observation period. The test was initially conducted using one New Zealand White rabbit. Because no severe ocular reaction was observed in the initial test, two additional New Zealand White rabbits were tested to confirm the response. Each animal received a 0.1 g dose of pure test item in the conjunctival sac of the right eye. After application the animals were examined the ocular reaction, behavioral and clinical alterations at approximately 1, 24, 48 and 72 hours. The untreated left eye was used as a negative control. The Everzol SR98 applied in tested eye of all rabbits caused hyperemia and chemosis and do not have retention of fluorescein sodium dye on the surface of the cornea. After the evaluation of 48 hours, there was regression of eyes reactions in tested eyes of all rabbits. After the evaluation of 72 hours, finalizing the study and all rabbits do not note any behavioral or clinical change related to treatment during the observation period.

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

Additional information

Skin irritation

0.5 g of Everzol SR98 moistened in 0.5 mL of purified water was applied to the skin of three New Zealand White rabbits and then covered with a gauze patch. After the 4 hours exposure period, the patches were removed, any residual test item removed using purified water and the animal #1 was evaluated after the application in the period of 3 minutes, 1 and 4 hours. After removing the bandage semiocclusive, three animals were examined skin reactions, behavioral and clinical alterations in approximately 1, 24, 48 and 72 hours. Adjacent untreated shaved areas of the skin were used as a negative control. Under test conditions, three rabbits do not showed any skin reactions and no treatment-related behavioral or clinical changes were observed during the observation period. On the basis of the test results given above, the response of Everzol SR98 was categorized as non-irritant.

 

Eye irritation

Everzol SR98 was given by a single ocular application at 0.1 g amount to NZW rabbits and followed by ocular examination within 72 hours. Three rabbits resulted in irritation of the conjunctivae, which consisted ofhyperemia and chemosis. The observed irritation had completely resolved within 48 hours in all animal. No iridial irritation or corneal opacity was observed. On the basis of the test results given above, the response of the test article was not any irritant to the eye.

Justification for classification or non-classification