Registration Dossier

Administrative data

Description of key information

The substance was found not irritating to the skin or eye.

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:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
other: Proposed Guidelines of the United States Environmental Agency (EPA) § 163.81-5 "Primary dermal irritation study". Federal Register, Vol. 43, No. 163, August 22, 1978.
Principles of method if other than guideline:
Immediately before treatment the shaven skin on one side was slightly scarified. Gauze patches of 2.5 x 2.5 cm laden with 0.5 g of the test material were applied to the prepared abraded and intact skin for 24 hours under occlusive conditions.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy
- Weight at study initiation: 2-3 kg
- Housing: individual housing in metal cages
- Diet (ad libitum): rabbit food - NAFAG, No. 814, Gossau SG
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): 55+/-10
- Photoperiod (hrs dark / hrs light): 10 h light
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
other: propylene glycol + saline (70:30)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g

VEHICLE
- Concentration (if solution): 50%
Duration of treatment / exposure:
24 h
Observation period:
7 days
Number of animals:
3 males, 3 females
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm2
- Type of wrap if used: gauze patches, covered with an impermeable material and fastened to the body of the rabbit with adhesive tape.

REMOVAL OF TEST SUBSTANCE: after 24 h exposition

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
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Remarks on result:
other: The score was 0 for every animal at any time point on intact skin.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Remarks on result:
other: The score was 0 for every animal at any time point on intact skin.
Irritant / corrosive response data:
The test substance did not elicit any skin reactions when applied to intact skin. All scores in all animals at any time point were zero. Minimal dermal reactions were observed when applied to scarified skin, reversible within 7 days the latest (see table 1 "Any other information on results incl. tables").

Table 1: Individual erythema and edema score after 24, 48, 72 h, 4 d and 7 d at scarified skin:

Exposure time 24 h

Males

Females

 

Animal 1

Animal 2

Animal 3

Animal 4

Animal 5

Animal 6

 

24 h

 

 

 

 

 

erythema

1

1

1

1

0

0

edema

0

0

0

0

0

0

           

48 h

 

 

 

 

 

erythema

1

0

0

0

0

0

edema

0

0

0

0

0

0

 

72 h

 

 

 

 

 

erythema

1

0

0

0

0

0

edema

0

0

0

0

0

0

 

4 d

 

 

 

 

 

erythema

1

0

0

0

0

0

edema

0

0

0

0

0

0

 

7d

 

 

 

 

 

erythema

0

0

0

0

0

0

edema

0

0

0

0

0

0

 

 

 

 

 

 

 

 

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance has no potency as an irritant to skin, under the test conditions used.
Executive summary:

In a skin irritation study the test item in propylene glycol and saline (70:30) was applied by topical occlusive application to the back of three male and three female adult New Zealand White rabbits. One side of the shaven back was slightly scarified and Gauze patches of 2.5 x 2.5 cm laden with 0.5 g of the test material were applied to the prepared abraded and intact skin. The dressings were removed after a 24 hour application and the skin reaction was appraised at 24, 48, 72 h and after 4 and 7 days on the basis of the Draize soring scheme. To classify the irritating property of the test article, the mean values of erythema and edema formation were calculated for each individual, using the scores between 24 and 72 hours. All scores recorded for the intact skin were zero at any time point in all animals. Minimal dermal reactions were observed when applied to scarified skin, reversible within 7 days the latest. Thus, the test item did not induce significant irreversible damage to the skin and is therefore not regarded as a skin 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:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
other: EPA, §163.81-4"Primary eye irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
, number of animals used was 6 instead of 3.
GLP compliance:
no
Remarks:
Quality Assurance Unit statement was given.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy
- Weight at study initiation: 2-3 kg
- Housing: single housing in metal cages
- Diet: standard rabbit food - NAFAG, No. 814, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-10
- Photoperiod: 10 hrs light
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated right eye
Amount / concentration applied:
Test material: 0.1 g
Duration of treatment / exposure:
3 animals: single treatment, rinsing after 30 seconds
3 animals: single treatment, no rinsing
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 animals (with rinsing)
3 animals (no rinsing)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: with 10 ml lukewarm water (in 3/6 animals)
- Time after start of exposure: 30 seconds

Scoring system: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp

Study design
Amounts of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, they eyelids were heldopen for a few seconds. The right eye served as a control. The treated eyes of three rabbits were each rinsed with 10 ml lukewarm water about 30 seconds after treatment.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: without rinsing
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: without rinsing
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: without rinsing
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: without rinsing
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: without rinsing
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: without rinsing
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-72 h
Score:
0.1
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: without rinsing
Irritant / corrosive response data:
In the 3 animals where the test substance was rinsed after 30 seconds, no findings were observed within the whole observation period. Without rinsing 1/3 animals showed a conjunctivae score of 1 after 24 h, which was reversible within 48 h. No other effects were observed.

Table 1: Eye irritation scores of treated animals without rinsing at 24 h, 48 h, and 72 h.

 

 

24 h

48 h

72 h

 

 

Rabbit No.

111

112

113

111

112

113

111

112

113

 

Cornea

Opacity

0

0

0

0

0

0

0

0

0

 

 

Area

0

0

0

0

0

0

0

0

0

 

 

 

 

 

 

 

 

 

 

 

 

 

Iris

Iris

0

0

0

0

0

0

0

0

0

 

 

 

 

 

 

 

 

 

 

 

 

 

Conjunctivae

Redness

0

0

1

0

0

0

0

0

0

 

 

Chemosis

0

0

0

0

0

0

0

0

0

 

 

Discharge

0

0

2

0

0

1

0

0

0

 

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this experiment the test material was found to to be not irritating to the rabbit eye mucosa.
Executive summary:

The substance was tested on 6 New Zealand White rabbits (3 males/3 females) according to the Proposed Guidelines of the United States Environmental Protection Agency (EPA) §163.81-4 "Primary eye irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978. Amounts of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, they eyelids were held open for a few seconds. The right eye served as a control. The treated eyes of three rabbits were each rinsed with 10 ml lukewarm water about 30 seconds after treatment. The reactions were appraised with a slit-lamp after 24 hours and after 2, 3, 4 and 7 days. The eyes were scored daily from 24 h until day 4 and again at 7 d after begin of treatment. No findings regarding cornea, iris or chemosis were observed within the whole study period in animals without rinsing of test substance. Slight redness was observed in 1/3 animals (score: 0.3; 24 -72 h), which was fully reversible within 48 h. Thus, the test substance has no potential as an eye irritant.

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

Additional information

Skin Irritation

In a skin irritation study the test item in propylene glycol and saline (70:30) was applied by topical occlusive application to the back of three male and three female adult New Zealand White rabbits. One side of the shaven back was slightly scarified and Gauze patches of 2.5 x 2.5 cm laden with 0.5 g of the test material were applied for an exposure period of 24 hours. Following removal of the dressing the skin reactions were appraised at 24, 48 and 72 h and after 4 and 7 days according to the Draize scoring scheme. All scores recorded for the intact skin were zero at any time point in all animals. Minimal dermal reactions were observed when applied to scarified skin, reversible within 7 days the latest. Thus, the test item did not induce signs of irritation when applied to the intact skin and is therefore not regarded as a skin irritant. A second study for investigation skin irritation potential is available, however this study was conducted by a contract research institute that was discredited for manipulating data and falsifying study reports (IBT, 1971). Therefore, the reliability of the available study is questionable. However, the data presented in this report is in line with the reliable report and provides additional support of the above finding.

Eye irritation

Two studies are available investigating the irritation potential of the test item. In the key study the test substance was tested according to a guideline from the Environmental Protection Agency from 1978 and a statement from the Quality Assurance Unit was available. No findings regarding cornea, iris or chemosis were observed within the whole study period in animals with rinsing of test substance. Slight redness was observed in 1/3 animals without rinsing (score: 0.3; 24 -72 h), which was fully reversible within 48 h. Thus, the test substance has no potential as an eye irritant.

In a supporting study the test substance was tested in the same way as in the key study. No findings regarding cornea, iris, conjunctivae, or chemosis were observed within the whole study period in animals with or without rinsing of the test substance. Thus, the test substance is considered as not irritating to the rabbit eye.

In a third study performed by a contract research institute that was discredited for manipulating data and falsifying study reports (IBT, 1974), Iris and conjunctivae showed ocular reactions upon treatment, reversible within 72 hours. No effects were observed for cornea.

Respiratory irritation

No standard test method for the assessment of respiratory irritation exists. However, there is no evidence that the test substance possesses a potential for respiratory irritation based on the negative findings in skin/eye irritation and sensitization studies performed.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, the test substance is not classified as skin or eye irritant.