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Description of key information

The test substance was found to be not irritating or corrosive to the skin. An evaluation of all available data on eye irritation including an OECD 405 eye irritation study, an OECD 406 guinea pig maximilisation test and an OECD 410 28-day repeated dose dermal toxicity study indicated that the substance is capable of discolouring the eye. As reversibility of such discolouration was not investigated in any of these in vivo studies, a conservative approach has been apllied by classifying the substance as irritating to the 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414, Fuellinsdorf, Switzerland
- Age at study initiation: 15-16 weeks
- Weight at study initiation: 2.0-2.6 kg
- Housing: Individually in stainless steel cages equipped with an automatic cleaning and drinking system (Dipl. Ing. W. Ehret GmbH, Versuchstiertechnik, D-7830 Emmendingen / FRG)
- Diet (e.g. ad libitum): Pelleted standard Kliba 341, batch 8/85 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, Switzerland) ad libitum
- Water (e.g. ad libitum): Community tap water from Itingen ad libitum
- Acclimation period: Four days under test conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
The test article was applied moistened with tap water.
Controls:
no
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
up to 72 hours
Number of animals:
3; 1 male and 2 females
Details on study design:
Approximately 24 hours before treatment, the dorsal fur was shaved with an electric clipper, exposing an area of approximately 100 square centimeters (10 cm x 10 cm). On test day 1, 0.5 g of the test article was applied to the intact skin of the shaved area. It was covered with a 3.0 cm x 3.0 cm patch of surgical gauze. The gauze was covered with aluminium foil and then covered with an occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. Four hours after the application, the dressing was removed and the skin was flushed with lukewarm tap water. The skin reaction was assessed at 1, 24, 48 and 72 hours intervals after the removal of the dressing, gauze patch and test article.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 hour
Score:
1
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: average 24, 48, 72 hours
Score:
0
Max. score:
8
Irritant / corrosive response data:
Irritation: FAT 40181/B showed a primary irritation score of 0.0 when applied to intact rabbit skin.
Corrosion: No destructions or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin.
Other effects:
Coloration: In the area of application in all animals a black, clear visible discoloration of the treated skin was observed, which could be related to effects of the test article.
Body weights: The body weight gain of all rabbits was similar.
Toxic symptoms/mortality: No acute toxic symptoms were observed in the animals during the test period, and no mortality occurred.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.
Executive summary:

In a GLP compliant skin irritation study, performed according to OECD guideline 404, the test substance (moistened, 0.5 g) was applied occlusive, to the skin of three New Zealand White rabbits for 4 hours. After 4 hours, the treated skin was flushed with water and observation were made for an additional 72 hours. A primary irritation score of 0.00 was observed. An edema score of 1 after 1 hour was observed, but erythema and edema scores for the other time points were 0.00. No corrosive effect was evident on the skin. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.

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

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In a GLP compliant skin irritation study, performed according to OECD guideline 404, the test substance (moistened, 0.5 g) was applied occlusive to the skin of three New Zealand White rabbits for 4 hours (RCC 1985). After 4 hours, the treated skin was flushed with water and observation were made for an additional 72 hours. A primary irritation score of 0.00 was observed. An edema score of 1 after 1 hour was observed, but erythema and edema scores for the other time points were 0.00. No corrosive effect was evident on the skin. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.

Eye irritation:

In a GLP compliant eye irritation study, performed according to OECD guideline 405, the test substance (0.1 g) was placed in the conjunctival sac of the left eye of three New Zealand White rabbits. The eyes were examined for 72 hours. The test substance showed a mean conjunctivae score of 0.33 at 24 hours and a chemosis score of 1 after 1 hour. At the other time points, the conjunctivae and chemosis scores were 0.00. Cornea and iris scores were 0.00 during the whole observation period. The primary irritation score was 0.3. No corrosion of the cornea was observed at any of the measuring intervals. Under the conditions of this experiment, the test substance was found to be not irritating or corrosive.

In this eye irritation study, blue discoloration of the cornea and conjunctivae was reported referring to the area of application without specifying to what extent the cornea was affected. Corneal opacity was not evident. In the 28-day repeated dose dermal toxicity study in the rat (OECD 410), one incidence of a high dose female rat with an opalescent and slightly bluish discoloured cornea at termination of treatment was reported. In the skin sensitisation study (Magnusson Kligman Maximisation test, OECD 406), bluish discoloration of the eyes and extremities of all test animals was reported. Reversibility of such discolouration was not checked in any of these in vivo studies, but as the test substance is highly water soluble (water solubility 246 g/L), reversibility of any such finding in the human eye is highly likely (fostered by natural lachrymation. The latter is considered to be higher in the human eye than in the rabbit).


Justification for selection of skin irritation / corrosion endpoint:
Only study available

Justification for selection of eye irritation endpoint:
An evaluation of all available data on eye irritation including an OECD 405 eye irritation study, an OECD 406 guinea pig maximilisation test and an OECD 410 28-day repeated dose dermal toxicity study.

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the findings in the skin and eye irritation studies the test substance does not need to be classified according to the CLP (Reg. EC 1272/2008) or DSD (Dir. 67/548/EEC) regulations. However, to conservatively rule out the highly unlikely possibility of an eye hazard resulting from discolouration, the test material is classified as “Serious eye damage/eye irritation, Category 2, H319: Causes serious eye irritation” according to Reg. (EC) 1272/2008 and as “Eye irritation Xi; R36 irritating to eyes” according to Dir. 67/548/EEC.

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