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Description of key information

The test item was tested negative for acute dermal irritating properties according to OECD 404. The substance caused severly eye irritating effects in an acute eye irritation/corrosion study in rabbits according to OECD 405.

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:
1989-09-12 to 1989-10-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Age at study initiation: adult rabbits were used
- Weight at study initiation: 2.8 to 3.3 kg
- Housing: individually in stainless steel cages
- Diet: "Ssniff K 4" (Ssniff Spezialdiäten GmbH, Soest), approx 100-120 g per animal and day feeding once per day in the morning
- Water: tap water was available for ad libitum consultion (between 7 and 19 hrs from automatic watering apparatus)
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): ca. 50
- Air changes (per hr): ca 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1989-09-12 to 1989-09-19
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g moistened with water

Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: hypoallergenic Hansamed® - patch (Beiersdorf no. 2342 PV3) covered with semiocclusive dressing (Fixomull® - Stretch Klebevlies, Beiersdorf no. 2293)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to Draize

Irritation parameter:
erythema score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritant / corrosive response data:
no irritating effects

Table 2: Results of the test for irritant effects on the skin (exposure 4 hours)
aninmal number body weight Draize grade after
1h 24h 48h 72h 7d
e o e o e o e o e o
 
K35 3.3 kg 0 0 0 0 0 0 0 0 0 0
K6 3.3 kg 0 0 0 0 0 0 0 0 0 0
K9 2.8 kg 0 0 0 0 0 0 0 0 0 0

e: erythema and eschar formation

o: oedema formation

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal irritation/corrosion study according to OECD 404 the test substance was found to be non-irritating to the skin.
Executive summary:

In a primary dermal irritation study (OECD guideline 404), three female New Zealand white rabbits were dermally exposed to 0.5 g of the test item for 4 hours to a body surface area of 6 cm² under semi-occlusive conditions. Animals then were observed for 1, 24, 48, 72 hours and 7 days and irritation was scored by the method of Draize. The test substance did not cause any skin effects and is considered under the conditions of this study as not irritating to the 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:
1989-09-12 to 1989-10-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Age at study initiation: adult rabbits were used
- Weight at study initiation: 2.8 to 3.3 kg
- Housing: individually in stainless steel cages
- Diet: "Ssniff K 4" (Ssniff Spezialdiäten GmbH, Soest), approx 100-120 g per animal and day feeding once per day in the morning
- Water: tap water was available for ad libitum consultion (between 7 and 19 hrs from automatic watering apparatus)
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): ca. 50
- Air changes (per hr): ca 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1989-09-12 to 1989-09-19
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 µL pulverized test substance = ca. 60 mg
Duration of treatment / exposure:
24 h
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): physiological saline
- Time after start of exposure: 24 hours

SCORING SYSTEM: according to Draize and McDonals and Shadduck

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hours
Score:
3.33
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: two animals showed a mean score of 4.0 and one animal showed a mean score of 2.0
Irritation parameter:
iris score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hours
Score:
1.2
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: two animals showed an mean score of 1.3 and one animal showed an mean score of 1.0
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hours
Score:
2.43
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: two animals showed a mean score of 2.3 and one animal of 2.7
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of three animals
Time point:
other: 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: all animals showed a mean chemosis score of 4
Irritant / corrosive response data:
The mucous membranes became whitishly discolored after 24 hours in two animals. One day thereafter all rabbits showed this discoloration. 72 hours following exposure necrosis of the conjunctivae was observed in all animals. In one rabbit the nictitating membrane was blood-covered. Discharge became white-yellowishly discolored in two animals.
Since these findings had to be considered as irreversible animals were sacrificed after 72 hours.
Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute eye irritation/corrosion study according to OECD 405, the test substance causes severe eye-irritating effects.
Executive summary:

In a primary eye irritation study, 0.1 mL of the test item was instilled into the conjunctival sac of one eye of each of three female New Zealand White rabbits for 24 hours, and subsequently washed out with physiological saline. The animals were observed for a period of 72 hours. Irritation was scored by the method by Draize. In this study, the test item is corrosive to the eye based on necrosis of the conjunctivae and severe effects on the corneal opacity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The test item was tested negative for acute dermal irritating properties according to OECD 404. After a dermal exposure period of 4 hours no skin effects were observed in rabbits within an observation period of 7 days. In contrast, the test item was severely irritating to the eyes of rabbits in acute eye irritation studies (OECD 405). Based on these results, the test substance is considered to be not irritating to skin, but severely irritating/corrosive to the eye.


Justification for selection of skin irritation / corrosion endpoint:
GLP guideline study according to OECD 404

Justification for selection of eye irritation endpoint:
GLP guideline study according to OECD 405

Effects on eye irritation: corrosive

Justification for classification or non-classification

The test item did not cause any skin effects in acute dermal irritating studies according to OECD test guideline 404. Therefore, the target substance does not warrant classification for skin irritation.

In contrast, the test item was severely irritating to the eyes of rabbits in an OECD 405 study. The application of the substance to the eye of rabbits produces in two animals a positive response of corneal opacity of >3 as calculated as the mean score following grading at 24, 48, 72 hours after instillation. Therefore, the test item meets the classification criteria according to the CLP regulation. The substance is classified for irreversible effects on the eye (Category 1).

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