Registration Dossier

Administrative data

Description of key information

Skin irritation study, rabbit: non-irritant

Eye irritation study, rabbit: non-irritant

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:
Aug - Sep 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Before treatment the entire back and the flank of the rabbits were shaved with an electric clipper and immediately before treatment the shaven skin on one side was slightly scarified with the help of a "Schröpfschnäpper", Aesculap, Switzerland. Gauze patches of 2.5 x 2.5 cm with 0.5 g of the test material were applied to the prepared abraded and intact skin. The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape. The dressings were removed after a 24 hour application. The skin reaction was appraised upon removal and during an observation period of 7 days.
GLP compliance:
no
Remarks:
pre-GLP study
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited
- Weight at study initiation: 2 - 3 kg
- Housing: individually
- Diet: standard rabbit food (NAFAG, No. 814, Gossau SG); ad libitum
- Water: ad libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: polyethylene glycol (PEG 400) + saline (70:30 parts)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 50%

VEHICLE
- Concentration (if solution): polyethylene glycol (PEG 400) + saline (70:30 parts)

Duration of treatment / exposure:
24 h
Observation period:
7 days
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: gauze patches, covered with an impermeable material

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

OBSERVATION TIME POINTS
upon removal and during an observation period of 7 days

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 (beet redness) to slight eschar formation (injuries in depth)....................4
Total possible erythema score 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
Total possible edema score 4

Assessment of irritation:
0
0.1-1.0 = minimal
1.1-2.0 = slight
2.1-4.0 = moderate
4.1-6.0 = marked
6.1-8.0 = extreme
Irritation parameter:
overall irritation score
Remarks:
intact skin
Basis:
mean
Time point:
other: 24/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test substance was found to cause a minimal irritation when applied to abraded rabbit skin.
There were no irritating effects when the test substance was applied to intact skin.
Other effects:
No signs of systemic intoxication were observed throughout the whole test period.

Table 1: Calculation of the primary skin irritation index

 

MEAN REACTION SCORE

 

Time after exposure hours

eryth e ma

edema

 

 

 

 

intact skin

abraded skin

intact skin

abraded skin

24

0

0.3

0

0

72

0

0.2

0

0

 

 

 

 

 

total

0

+

0.5

+0

+

0

=

0.5

primary irritation index = 0.5 : 4 = 0.1

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present experiment the test substance was found to cause a minimal irritation when applied to abraded rabbit skin.
The calculated primary irritation index was 0.1.
There were no irritating effects when the test substance was applied to intact skin.
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:
Aug - Sep 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test material in an amount of 0.1 g was inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. In 3 of the 9 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline. The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7 and was scored for each individual rabbit.
GLP compliance:
no
Remarks:
pre-GLP study
Species:
rat
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited
- Weight at study initiation: 2 -3 kg
- Housing: individually
- Diet: standard rabbit food (NAFAG, No. 814, Gossau SG); ad libitum
- Water: ad libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 12 / 12


Only rabbits with normal ophthalmic findings were used for these tests.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:
- removal of test substance: approx. 30 sec
- no removal of test substance: until end of observation period
Observation period (in vivo):
until 7 days after application of the test substance
Number of animals or in vitro replicates:
3 males and 6 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: In 3 of the 9 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline.

SCORING SYSTEM:
CORNEA:
A Opacity and degree of density (most dense area scored)
No opacity - 0
Scattered or diffuse area, details of iris clearly visible - 1
Easily discernible translucent areas, details of iris slightly obscured - 2
Opalescent areas, no details of iris visible, size of pupil barely discernible - 3
Opaque, iris invisible - 4

B Area of cornea involved
One quarter (or less) but not zero - 1
Greater than one quarter, but less than half - 2
Greater than half, but less than three quarters - 3
Greater than three quarters, up to whole area - 4

A X B X 5 Maximum possible score = 80

IRIS:
A Values
Normal - 0
Folds above normal, congestion, swelling, circumcornea injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive) - 1
No reaction to light, hemorrhage, gross destruction (any or all of these) - 2

A X 5 Maximum possible score = 10

CONJUNCTIVAE:
A Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris)
Vessels normal - 0
Vessels definitely injected above normal - 1
More diffuse, deeper crimson red, individual vessels not easily discernible - 2
Diffuse beefy red - 3

B Chemosis
No swelling - 0
Any swelling above normal (includes nictitating membrane) - 1
Obvious swelling with partial eversion of lids - 2
Swelling with lids about half closed - 3
Swelling with lids about half closed to completely closed - 4

C Discharge
No discharge - 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) - 1
Discharge with moistening of the lids and hairs just adjacent to lids - 2
Discharge with moistening of the lids and hairs, and considerable area around the eye - 3

(A -K B + C) X 2 Maximum possible score = 20

Calculation of the primary eye irritation index:
The mean reaction scores for cornea, iris and conjunctiva observed after 1, 2, 3, 4 and 7 days were summed up and the sum divided by 5. This procedure was carried out separately for unrinsed (A) and rinsed (B) eyes respectively.

Index 0 = none
0.1 - 10.9 = minimal
11.0 - 25.9 = slight
26.0 - 55.9 = moderate
56.0 - 84.0 = marked
above 84.0 = extreme

TOOL USED TO ASSESS SCORE: slit lamp
Irritation parameter:
overall irritation score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
other: mean of 1/2/3/4 and 7 days after exposure
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Remarks:
rinsed eye
Basis:
mean
Time point:
other: mean of 1/2/3/4 and 7 days after exposure
Score:
0.1
Reversibility:
fully reversible within: 2 days after exposure
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
primary irritation index in unrinsed eyes = 0
primary irritation index in rinsed eyes = 0.1

No symptoms of intoxication were observed throughout the test period.

Table 1: Calculation of the primary irritation index

Time after exposure days

mean reaction score

 

 

unrinsed eyes (A)

rinsed eyes (B)

cornea

iris

conjunctiva

cornea

iris

conjunctiva

 

1

 

0

 

0

 

0

 

0

 

0

 

0.7

2

0

0

0

0

0

0

3

0

0

0

0

0

0

4

0

0

0

0

0

0

7

0

0

0

0

0

0

subtotal

0

0

0

0

0

0.7

total

 

0

0.7

Interpretation of results:
GHS criteria not met
Executive summary:

Under the conditions of this experiment the test material was found to cause no irritation when applied to the rabbit eye mucosa (primary irritation index: 0) and a minimal irritation when the application site was rinsed (primary irritation index: 0.1).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation study

In a pre-GLP skin irritation study the test substance was applied (as a 50% suspension in polyethylene glycol (PEG 400) + saline (70 : 30 parts)) once to intact and abraded skin of New Zealand White rabbits (3 males and 6 females).

Gauze patches of 2.5 x 2.5 cm with 0.5 g of the test material (50% suspension of the test substance in polyethylene glycol (PEG 400) + saline (70 : 30 parts)) were applied to the prepared abraded and intact skin. The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape. The dressings were removed after a 24 hour application. The skin reaction was appraised upon removal and 48 h, 72 h, 4 days and 7 days after application of the test substance.

Under the conditions of the present experiment the test substance was found to cause a minimal irritation when applied to abraded rabbit skin. There were no irritating effects when the test substance was applied to intact skin.

Eye irritation

In a pre-GLP eye irritation study in New Zealand White rabbits (3 males and 6 females) the test substance was applied once to the left eye of each animal. The right eye served as untreated control.

In 3 of the 9 rabbits approximately 30 seconds after treatment the treated eye was flushed. The eye irritation was appraised on day 1, 2, 3, 4 and 7 after application of the test substance.

The test substance was found to cause no irritation when applied to the rabbit eye mucosa. When the application site was rinsed, the irritation was found to be minimal and effects were reversible within 2 days after apllication.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008.