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Administrative data

Description of key information

Skin irritation: OECD 404, rabbit (2016): not irritating

Eye irritation: OECD 405, rabbit (2016): not irritating

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:
08 Mar - 24 Mar 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:
Current version adopted in 2015
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Guideline in place during study conduct: adopted in 2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
National Good Laboratory Practice (GLP) Compliance Monitoring Authority (NGCMA), Department of Science and Technology, Government of India
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sri Raghavendra Enterprises, Bangalore, India
- Age at study initiation: 8 months
- Body weight at study initiation: 2.41 - 2.74 kg (females)
- Housing: individually, in stainless steel cages (sized: 60 cm (L) x 45 cm (W) x 45 cm (H)) provided with stainless steel mesh bottom
- Diet: extruded pelleted rabbit feed 'Amrut' (Pranav Agro Industries Ltd., Sangli, India), ad libitum
- Water: filtered and UV irradiated water in drinking water quality, ad libitum
- Acclimation period: 7 - 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22
- Humidity (%): 48 - 64
- Air changes (per hr): 12.36
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 Mar 2016 To: 24 Mar 2016
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
The test substance was moistened with water.
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g, moistened with water at the time of application
Duration of treatment / exposure:
Initial test: 3 min, 1 h and 4 h
Confirmatory test: 4 h
Observation period:
Initial test: 3 days; reading time points: immediately after the patch was removed after 3 min, 1 and 4 h exposure and 1, 24, 48 and 72 h post exposure (after removing the patches)
Confirmatory test: 3 days; reading time points: 1, 24, 48, and 72 h post 4-h exposure (after removing the patches)
Number of animals:
3 animals in total (initial test: 1 animal, confirmatory test: 2 animals)
Details on study design:
TEST SITE
- Area of exposure: 6 cm² on the dorsal skin of the animal
- Type of wrap: The applied test substance was covered with a gauze patch, the latter being fixed with a gauze bandage wrapped around the animal and secured with tape.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test substance was wiped off and the treatment area was gently washed with analytical grade water.
- Time after start of exposure: 4 h

SCORING SYSTEM:
Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema 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:
The test substance did not cause any skin reaction in the form of erythema or oedema in neither of the animals tested.
Other effects:
No clinical signs of systemic toxicity were observed. Body weights were not affected during the study period.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
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:
18 Mar - 29 Mar 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:
Current version adopted in 2020
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Guideline in place during study conduct: adopted in 2012
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
National Good Laboratory Practice (GLP) Compliance Monitoring Authority (NGCMA), Department of Science and Technology, Government of India
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Sri Raghavendra Enterprises, Bangalore, India
- Age at study initiation: 8 months
- Body weight at study initiation: 2.43 - 2.55 kg (male)
- Housing: individually, in stainless steel cages (sized: 60 cm (L) x 45 cm (W) x 45 cm (H)) provided with stainless steel mesh bottom
- Diet: pelleted rabbit feed 'Amrut' (Pranav Agro Industries Ltd., Sangli, India), ad libitum
- Water: filtered and UV irradiated water in drinking water quality, ad libitum
- Acclimation period: 5 - 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- Humidity (%): 48 - 66
- Air changes (per hr): 12.36 - 13.25
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 Mar 2016 To: 29 Mar 2016
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL, equating to 83 mg
Duration of treatment / exposure:
single application
Observation period (in vivo):
3 days
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
3 males in total (initial test: 1 animal, confirmatory test: 2 animals)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: eyes were rinsed with analytical grade water
- Time after start of exposure: 1 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: Fluorescein
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:
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:
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:
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:
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:
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:
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:
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:
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 #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 #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 #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Test substance instillation into the rabbit eye induced no iridial, corneal and conjunctival changes.
Other effects:
There were no mortalities during the study. No signs of systemic toxicity were observed during the study period. All animals gained weight during the observation period. No local effects were noted.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

The skin irritating potential of the test substance was investigated in rabbits following OECD TG 404 and in compliance with GLP (M-580701-01-1, 2016). The unchanged test substance (0.5 g) was moistened with water and applied to the clipped, dorsal skin of female rabbits under semiocclusive conditions. An adjacent area of untreated skin served as control for each animal separately. Initially, 3 test patches were applied sequentially to one animal tested in an initial test. The first patch was removed after 3 min. Since no skin reaction was observed a second patch was applied at a different site and removed after 1 h. As the observations at this stage indicated that exposure could be extended to 4 h, a third patch was applied and removed after 4 h. All dermal responses were graded. The observations of the initial test were confirmed using 2 additional animals, each with one patch, for an exposure period of 4 h (confirmatory test). At the end of each designated exposure period, the patches were removed and skin reaction was evaluated immediately (initial test) and after 1, 24, 48 and 72 h after removal of the patches (initial and confirmatory test). Animals were observed for clinical signs of toxicity throughout the study period. Body weights were recorded on the day of treatment and at study termination.Single application of the test substance elicited no irritation to the rabbit skin. No signs of local or systemic toxicity were seen. The mean erythema and oedema scores over 24, 48 and 72 h were 0 for all 3 animals. Based on the results of this study, the test substance did not exhibit skin irritation properties.

These findings are further supported by the results of a previously performed study in which the skin irritating potential of the test substance was investigated following OECD test guideline (TG) 404 and in compliance with GLP (M-192394-01-1, 1997a). The unchanged test substance (0.5 g) was prepared on a moistened patch and applied to the clipped skin of the right flank of 6 female rabbits for 4 h under semiocclusive conditions. The skin of the left flank remained untreated and served as control site. Skin reactions at the treated sites were evaluated 1, 24, 48 and 72 h after removal of the patches (and washing off residual test substance). Single application of the test substance elicited no irritation or any dermal reactions to the rabbit skin. No signs of local or systemic toxicity were observed. The mean erythema and oedema scores over 24, 48 and 72 h were 0 for all 6 animals.

 

 

 

Eye irritation:

An eye irritation study was conducted with the test substance according to OECD TG 405 and under GLP conditions (M-580704-01-1, 2016). Initially, the test was performed using one male animal (initial test). As the observations did not suggest the test substance being irritating or corrosive to the rabbit eye, the study was continued to conduct a confirmatory test involving two additional male animals. The unchanged test substance (100 µL, 83 mg) was placed into the lower conjunctival sac of the left eye of the animals. Eyes were rinsed with analytical grade water 1h post exposure. The right eye remained untreated and served as control. The animals received local and systemic analgesics pre- and/or post treatment, according to guideline. The eyes were examined and scored 1, 24, 48 and 72 h after test substance application. Body weights were recorded on the day of treatment and at study termination. Test substance application into the rabbit eye induced no iridial, corneal or conjunctival effects. No local or systemic toxic effects were observed. The mean cornea, iris, conjunctivae and chemosis scores over 24, 48, and 72 h were 0 for all 3 animals. Based on the results of the conducted study, the test substance did not possess irritation potential towards the eyes.

 

A previously conducted eye irritation study supported those findings, which was conducted according to OECD TG 405 and under GLP conditions (M-192396-01-1, 1997b). The unchanged test substance (100 mg) was placed into the lower conjunctival sac of the left eye of 6 female rabbits. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. Test substance instillation into the rabbit eye induced no iridial, corneal or conjunctival effects. No local or systemic toxic effects were observed. The mean cornea, iris, conjunctivae and chemosis scores over 24, 48, and 72 h were 0 for all 6 animals.

 

Overall, the test substance did not exhibit irritating properties towards the skin and eyes in the conducted studies.

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.