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Description of key information

Key study: Skin irritation. OECD guideline and EU method. GLP study.
Based on the available results, the test substance is not classified as skin irritating.
Key study: Eye irritation OECD guideline and EU method. GLP study.
Based on the available results, the test substance is not classified as eye 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:
From 06 December 2012 to 04 February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline and EU method. GLP 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)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Institute of Occupational Medicine, Łódź
- Age at study initiation: The experiment was conducted on one 5-month-old female and two females which were 5.5 months old.
- Weight at study initiation: 3.2-4.4 kg
- Housing: The animals were kept individually in metal cages with the following dimensions: 60 x 35 x 40 cm (length x width x height).
- Diet (e.g. ad libitum): LSK standard granulated laboratory fodder, ad libitum
- Water (e.g. ad libitum): drinking tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21°C
- Humidity (%): 35 – 68%
- Air changes (per hr): about 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light – 12 hours dark

IN-LIFE DATES: From: 7 December 2012 To: 15 December 2012
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: drenched with a few drops of water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after the end of the treatment.
Number of animals:
Three females
Details on study design:
TEST SITE
- Area of exposure: The area of skin treated with the test item was about 6 cm2.
- Type of wrap if used: The test item was applied to a multilayer gauze patch (2.5 x 2.5 cm) and drenched with a few drops of water. The gauze patch was laid on the prepared skin. The gauze patch was covered with PVC foil and protected using a non-irritating sticking plaster. The rabbit’s trunk was covered with lignin, and an elastic bandage was used to make a circular protecting band.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The band and the gauze patch were taken off and the residual test item was removed using water.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema and Eschar Formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beefy redness) to eschar formation preventing grading of erythema 4

Edema Formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond area of exposure) 4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
0
Irritant / corrosive response data:
During the reading which took place 1 hour after the end of the exposure, very slight erythema (barely perceptible) was stated on the skin in the site of the test item application in rabbit no. 1. During the readings which took place 24, 48 and 72 hours after the end of the exposure, no pathological changes were observed on the treated skin of the three rabbits.

 

 

Table 1: Dermal irritation scores

 

Erythema

Oedema

Animal No

1

2

3

1

2

3

after 24 h

0

0

0

0

0

0

after 48 h

0

0

0

0

0

0

after 72 h

0

0

0

0

0

0

Mean score 24 – 72 h

 

0

0

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the available results, the test substance is not classified as skin irritating.
Executive summary:

The acute skin irritation/corrosion study, according to the OECD Guideline No. 404 / EU Method B.4., was performed in order to obtain information on health hazards likely to arise from skin contact with the test item. The study commenced with a sighting study on one animal. The test item (grounded to a powder) in the amount of 0.5 g was applied only once to the shaved skin of one animal and covered with a protecting band. The exposure lasted 4 hours. After the evaluation of the treated skin, the test item was applied to the skin of the next two rabbits for 4 hours. General clinical observations of all animals for morbidity and mortality were performed daily during the entire experiment. Detailed clinical observations of the treated skin were performed 1, 24, 48 and 72 hours after the end of the exposure. The animals’ body weight was determined on the administration day (day 0) and on the last day of the experiment. During the reading which took place 1 hour after the end of the exposure, very slight erythema (barely perceptible) was stated on the skin in the site of the test item application in rabbit no. 1. During the readings which took place 24, 48 and 72 hours after the end of the exposure, no pathological changes were observed on the treated skin of the three rabbits.

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 06 December 2012 to 04 February 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline and EU method. GLP 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)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Institute of Occupational Medicine, Łódź
- Age at study initiation: The experiment was conducted on three females which were 5.5 months old.
- Weight at study initiation: 4.2-4.7 kg
- Housing: The animals were kept individually in metal cages with the following dimensions: 60 x 35 x 40 cm (length x width x height).
- Diet (e.g. ad libitum): LSK standard granulated laboratory fodder, ad libitum
- Water (e.g. ad libitum): drinking tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21°C
- Humidity (%): 30 – 65%
- Air changes (per hr): about 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light – 12 hours dark

IN-LIFE DATES: From: 12 December 2012 To: 24 December 2012
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test item (grounded to a powder) in a volume of 0.1 mL (0.049 g) was administered to the conjunctival sac of one eye of the animal by gently pulling the lower eyelid away from the eyeball.
Observation period (in vivo):
1, 24, 48 and 72 hours as well as 7 days after the administration of the test item.
Number of animals or in vitro replicates:
Three females
Details on study design:
SCORING SYSTEM:

Cornea
Opacity: degree of density (readings should be taken from most dense area) *
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4
Maximum possible: 4 * The area of corneal opacity should be noted

Iris
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, iris reactive to light (a sluggish reaction is considered to be an effect 1
Hemorrhage, gross destruction, or no reaction to light 2
Maximum possible: 2

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae, excluding cornea and iris)
Normal 0
Some blood vessels hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3
Maximum possible: 3

Chemosis
Swelling (refers to lids and/or nictitating membranes)
Normal 0
Some swelling above normal 1
Obvious swelling, with partial eversion of lids 2
Swelling, with lids about half closed 3
Swelling, with lids more than half closed 4
Maximum possible: 4
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
0
Irritant / corrosive response data:
After the administration of the test item, some pathological changes were observed in the conjunctivas of the animals’ eyes. No pathological changes were stated in the cornea and iris.

During the reading which took place 1 hour after the administration of the test item, congestion of the nictitating membrane was observed in three animals. Moreover, erythema in the form of congestion (injection) of some blood vessels and circumcorneal injection were stated in animals no. 2 and 3. Swelling of the nictitating membrane was observed in animal no. 2.

During the reading which took place 24 hours after the administration of the test item, congestion of the nictitating membrane was observed in animals no. 2 and 3. Moreover, circumcorneal injection was stated in animal no. 2. No conjunctival edema was observed.

During the reading which took place 48 hours after the administration of the test item, congestion of the nictitating membrane was observed in animals no. 2 and 3.

During the reading which took place 72 hours after the administration of the test item, congestion of the nictitating membrane was observed in animal no. 2.

During the reading which took place 7 days after the administration of the test item, no pathological changes were observed in rabbit no. 2.

Table 1: Eye irritation scores

Animal

Region of eye

24 h

48 h

72 h

7 d

1

Cornea

 

0

0

0

-

Iris

 

0

0

0

-

Conjunctivae

erythema

0

0

0

-

Conjunctivae

swelling

0

0

0

-

2

Cornea

 

0

0

0

0

Iris

 

0

0

0

0

Conjunctivae

erythema

1

1

1

0

Conjunctivae

swelling

0

0

0

0

3

Cornea

 

0

0

0

-

Iris

 

0

0

0

-

Conjunctivae

erythema

1

1

0

-

Conjunctivae

swelling

0

0

0

-

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the available results, the test substance is not classified as eye irritating.
Executive summary:

The acute eye irritation/corrosion study, according to the OECD Guideline No. 405 / EU Method B.5., was performed in order to obtain information on health hazards likely to arise from possible contact of the test item. The study started with a preliminary study on one animal. The test item was grounded to a powder and administered to the conjunctival sac of one eye of the animal (rabbit no. 1). Its volume was 0.1 mL. The second eye served as a control. After the evaluation of the treated eye, the test item was applied to the eyes of the next two animals (rabbit no. 2 and 3). General clinical observations of the animals for morbidity and mortality were performed daily during the entire experiment. Detailed clinical observations for changes in the cornea, iris and conjunctiva were performed 1, 24, 48 and 72 hours (all animals) as well as 7 days (rabbit no. 2) after the administration of the test item. The animals’ body weight was determined on the administration day (day 0) and on the last day of the experiment. After the administration of the test item, some pathological changes were observed in the conjunctivas of the animals’ eyes. No pathological changes were stated in the cornea and iris. Based on the available results, the test substance is not classified as eye irritating.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Key study: Skin irritation. OECD guideline and EU method. GLP study.

Based on the available results, the test substance is not classified as skin irritating.

Key study: Eye irritation OECD guideline and EU method. GLP study.

Based on the available results, the test substance is not classified as eye irritating.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available. Klimisch 1 and the study was carried out in accordance with internationally valid GLP principles.

Justification for selection of eye irritation endpoint:
Only one study available. Klimisch 1 and the study was carried out in accordance with internationally valid GLP principles.

Justification for classification or non-classification

Based on the available data, the substance is not classified as skin or eye irritating.