Registration Dossier

Administrative data

Description of key information

The test substance did not show skin and eye irritating potential under the test conditions chosen in two studies performed.

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:
1981-02-02 to 1981-02-09
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
(no data on test material purity, test site was covered by an occlusive dressing, exposure duration was 24 h)
Qualifier:
according to
Guideline:
other: Proposed Guidelines of the United States Environmental Agency (EPA) § 163.81-5 Vol. 43, No. 163, Auguust 22, 1978
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bred and raised on the premises
- Weight at study initiation: 2 - 3 kg
- Housing: Individually in metal cages
- Diet: Standard rabbit food - NAFAG, No. 814, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: For a minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 14/10
Type of coverage:
occlusive
Preparation of test site:
other: Shaved, one side intact, the other abraded
Vehicle:
other: polyethylene glycol (PAG 400) + saline (70 : 30 parts)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g
- Concentration: 50 % in vehicle
Duration of treatment / exposure:
24 h
Observation period:
7 days
Number of animals:
3 each sex
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape.

SCORING SYSTEM: According to Draize
Irritation parameter:
erythema score
Basis:
mean
Remarks:
over all 3 animals
Time point:
other: mean over 24, 48, and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Remarks:
over all 3 animals
Time point:
other: mean over 24, 48, and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: intact skin
Irritant / corrosive response data:
No signs of irritation during all time points.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance revealed no skin irritating potential.
Executive summary:

The acute skin irritation / corrosion property of the test substance was determined in a study similar to OECD guideline 404 after single dermal administration to rabbits. 0.5 g of the test substance was prepared as 50 % suspension in polyethylene glycol and saline (70 : 30 parts) on a gauze patch (2.5 x 2.5 cm) and applied occlusively to the intact and abraded skin of 3 New Zeeland White rabbits of each sex for 24 hours. The skin reaction was appraised upon removal and during an observation period of 7 days on the basis of the Draize scoring system. Mean 24 - 48 - 72 hour scores were 0 for erythema and edema for the intact skin. In conclusion, the test substance revealed no skin irritating potential, even under more stringent conditions as required in the guideline.

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:
1981-02-02 to 1981-02-09
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(no data on test material purity, eye irritation was not examined 1 hour after exposure, the solid test substance was removed from the rabbits' eye already after 30 seconds instead of 1 hour)
Qualifier:
according to
Guideline:
other: 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
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Bred and raised on the premises
- Weight at study initiation: 2 - 3 kg
- Housing: individually in metal cages
- Diet: Standard rabbit food, NAFAG, No. 814, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: For a minimum of 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 14/10

Only rabbits with normal ophtalmic findings were used for these tests.
Vehicle:
unchanged (no vehicle)
Controls:
other: The second eye served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 g
Duration of treatment / exposure:
Single application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: 10 ml of physiological saline (only 3 animals)
- Time after start of exposure: Approximately 30 seconds

SCORING SYSTEM: According to Draize

TOOL USED TO ASSESS SCORE: Slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over all 3 animals
Time point:
other: mean over 24, 48, and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: animals' eyes were rinsed after treatment
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over all 3 animals
Time point:
other: mean over 24, 48, and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: animals' eyes were not rinsed after treatment
Irritation parameter:
iris score
Basis:
mean
Remarks:
over all 3 animals
Time point:
other: mean over 24, 48, and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: animals' eyes were rinsed after treatment
Irritation parameter:
iris score
Basis:
mean
Remarks:
over all 3 animals
Time point:
other: mean over 24, 48, and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: animals' eyes were not rinsed after treatment
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
over all 3 animals
Time point:
other: mean over 24, 48, and 72 hours
Score:
0.4
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: animals' eyes were rinsed after treatment
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
over all 3 animals
Time point:
other: mean over 24, 48, and 72 hours
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: animals' eyes were not rinsed after treatment
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over all 3 animals
Time point:
other: mean over 24, 48, and 72 hours
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: animals' eyes were rinsed after treatment
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over all 3 animals
Time point:
other: mean over 24, 48, and 72 hours
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: animals' eyes were not rinsed after treatment
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance revealed no eye irritating properties under the test conditions.
Executive summary:

In an acute eye irritation study similar to OECD guideline 405, 0.1 g of the test substance was administered to 3 male and 3 female New Zeeland White rabbits. The test substance was placed into the conjunctival sac of the left eye of each animal; the right eye remained untreated and served as control. In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline. The eye irritation was evaluated according to Draize on day 1, 2, 3, 4, and 7. The cornea and iris scores were grade 0 in the mean over 24, 48 and 72 hours in all 6 animals (both with and without washing). The conjunctiva score was 0.4 for the animals whose eyes were washed and 0.3 for the animals whose eyes were not washed, respectively. The redness was reversible within 72 hours. The chemosis score was grade 0.1 in the mean over 24, 48 and 72 hours in all 6 animals (both with and without washing) and the eye irritating effect was fully reversible within 48 hours. Concluding, the test substance revealed no eye irritating properties under the test conditions.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

The acute skin irritation / corrosion property of the test substance was determined after a single dermal administration to rabbits. The study was conducted similar to the OECD-Guideline 404. 0.5 g of the test substance was prepared to a 50 % suspension in polyethylene glycol and saline (70 : 30 parts) on a gauze patch (2.5 x 2.5 cm), which was applied to the intact skin (back) of 3 New Zeeland White rabbits each sex for 24 hours. Hereby one flank of each animal was abraded. The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape. The skin reaction was appraised upon removal and during an observation period of 7 days on the basis of the Draize scoring system. Mean 24 - 48 - 72 hour scores were 0 for erythema and edema for the intact skin. Concluding, the test substance revealed no skin irritating potential, even under more stringent conditions as required in the guideline (occlusive dressing, 24 hours treatment) (Ciba-Geigy, 1981)

These results are supported by the findings of a second study conducted similar to the OECD guideline 404 after repeated dermal administration of the test substance to rabbits on 5 consecutive days (for 24 hours on day 1 to 4 and 8 hours on day 5). Gauze patches of 4 x 5 cm soaked with the test substance were applied to the intact skin of 3 New Zeeland White rabbits each sex. The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape. The skin reaction was recorded on each day of the test period and again on days 8, 9, and 10 (recovery period) on the basis of the Draize scoring system. Toxic symptoms were recorded daily. Mean 24 - 48 - 72 hour scores were 0.2 for erythema and the skin reactions were not fully reversible within 10 days (day 5 after the last treatment; one animals with an erythema score of 1, no effects in the other animals). In contrast, mean 24 - 48 - 72 hour scores were 0.1 for edema and the skin reactions were fully reversible within 3 days. The body weights were not decreased in the rabbits during the treatment period. No substance related gross organ changes were observed, which could be related to substance application. Concluding, the test substance revealed no skin irritating potential even after repetitive applications on 5 consecutive days (Ciba-Geigy, 1982).

 

Eye irritation

The acute eye irritation property of the test substance was determined after a single administration to 3 male and 3 female New Zeeland White rabbits. The study was conducted similar to the OECD-Guideline 405. 0.1 g of the test substance was placed into the conjunctival sac of the left eye of each animal; the right eye remained untreated and served as control. In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline. The eye irritation was evaluated according to Draize on day 1, 2, 3, 4, and 7. The cornea and iris scores were grade 0 in the mean over 24, 48 and 72 hours in all 6 animals (both with and without washing). The conjunctiva score was 0.4 for the animals whose eyes were washed and 0.3 for the animals whose eyes were not washed, respectively. The redness was reversible within 72 hours. The chemosis score was grade 0.1 in the mean over 24, 48 and 72 hours in all 6 animals (both with and without washing) and the eye irritating effect was fully reversible within 48 hours. Concluding, the test substance revealed no eye irritating properties under the test conditions (Ciba-Geigy, 1981).

These results are supported by the findings of a second study conducted similar to the OECD guideline 405 after repeated administration of the test substance to rabbits on 5 consecutive days. 0.1 ml of the test substance was placed into the conjunctival sac of the left eye of each animal; the right eye was treated with 0.1 ml of 0.9 % NaCl and served as control. The female animals’ eyes were rinsed after exposure. The eye irritation scores were assessed 24 hours after each instillation and on days 8, 9, and 10 according to Draize. The cornea and iris scores were grade 0 in the mean over 24, 48, and 72 hours in all 6 animals (both with and without washing). The conjunctiva score was 0.8 for the female animals whose eyes were washed and 0.3 for the male animals whose eyes were not washed, respectively. The redness was not fully reversible within 10 days (day 5 after the last treatment; one male and one female animal with a conjunctivae score of 1). In the mean over 24, 48, and 72 hours the chemosis score was grade 0.4 for the female animals whose eyes were washed and 0.3 for the male animals whose eyes were not washed,respectively.The effect was fully reversible within 10 days. Concluding, the test substance revealed no eye irritating potential even after repetitive applications on 5 consecutive days (Ciba-Geigy, 1982).

Justification for classification or non-classification

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

The available experimental test data is reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for skin and eye irritation / corrosion is not warranted.