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Administrative data

Description of key information

A valid skin irritation/corrosion study according OECD 404 and a valid eye irritation study according OECD 405 are available. Additional 2 guideline studies for skin irritation/corrosion and eye irritation without information on GLP were conducted.

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:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
Himalayan
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6 month
- Weight at study initiation: ca 3 kg
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: at least 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: moistened with water
Controls:
other: the oposite flank served as control
Amount / concentration applied:
500 mg pulverised substance
Duration of treatment / exposure:
4 h
Observation period:
Up to 72 hours because no effects were observed up to then.
Number of animals:
3 females
Details on study design:
Approximately 24 hours before the test, the fur was removed by shaving from the dorsal area of the trunk of the animal . Only animals with health intact skin were used. A dose of 500 mg was applied to the test site and were moistened sufficiently with water to ensure good contact with the skin. The test site was then covered with a gauze patch. The patch was held in contact with the skin by means of semi-occlusive dressing for the duration of the exposure period. The surrounding untreated skin served as a control. exposure time was 4 hours. After termination the exposure period the coverage was removed and . the skin sites were evaluated for erythema and edema. scores according to Draize were taken 60 min., 24. 48, and 72 hours after patch removal .
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 60 min, 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: no erythema was observed
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 60 min, 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: no edema was observed
Irritant / corrosive response data:
No effects were observed
Interpretation of results:
GHS criteria not met
Conclusions:
No erythema (E) and no oedema (Oe) was observed after 60 min., 24 h, 48 h and 72 h.
Executive summary:

According to OECD TG 404 and GLP 3 female Himalayan rabbits received dermal application on the shaved back for 4 hours held in place by semi-occlusive dressing, 60 min, 24, 28, and 72 hours after removal of the dressing the treated area was examined and the effects scored according to Draize. None of the animals showed erythema or edema. Therefore the compound was evaluated to be non-irritating to the skin of rabbits.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 5 months
- Weight at study initiation: 2.8-3 kg
- Housing: singly
- Diet ad libitum
- Water ad libitum
- Acclimation period: at leats 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 50
- Photoperiod (hrs dark / hrs 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye served as control
Amount / concentration applied:
100 mg/animal
Duration of treatment / exposure:
once
Observation period (in vivo):
Up to 72 hours
Number of animals or in vitro replicates:
3 males
Details on study design:
A dose of 100 mg Macrolex Rot E2G was administered into th conjunctival sac of the right eye of each of 3 male rabbits after gently pulling the lower lid away fron the eyeball. The lid was thengently held together for about one second in order to prevent losss of test material.The left eye which remains untreated seved as a control.. the eyes were examined phthalmoscopically with a slit lamp prior to the administration and also 1,24, 48 and 72 hours after administration. Eyes were evaluated for cornea opacity, iris and conjunctival changes Scoring was done according to Draize.
24 hours after administration the eyes were treated additionally with fluorescein and examined
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: before dosing, and 1, 24, 48 and 72 hours afterwards
Score:
0
Max. score:
4
Remarks on result:
other: no effects were observed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: before and 1, 24, 48, 72 hours post application
Score:
0
Max. score:
2
Remarks on result:
other: no effects were observed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: before and 1, 24, 48, 72 hours post application
Score:
0
Max. score:
3
Remarks on result:
other: no effects were observed
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: before and 1, 24, 48, 72 hours post application
Score:
0
Max. score:
4
Remarks on result:
other: no effects were observed
Irritant / corrosive response data:
No irritational effects were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
Cornea, iris, conjunctiva and chemosis score = 0 at any time point (before dosing, and 1, 24, 48 and 72 hours afterwards).
Executive summary:

According to OECD 405 and GLP each of 3 male rabbits received instillations of 100 mg test substance into the conjunctival sac of the right eye; the respective left eye remained untreated and seved as control. The eyes of the animals were observed 1, 24, 48 and 72 hours post application. Additionally, 24 hours post application the eyes were treated with fluorescein and examined. The scoring was done according to Draize. In none of the animals the eyes were affected by treatment. Therefore the test substance was evaluated to be non-irritating to the eyes of rabbits.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key study for skin irritation/corrosion 3 female Himalayan rabbits received dermal application on the shaved back for 4 hours held in place by semi-occlusive dressing, 60 min, 24, 28, and 72 hours after removal of the dressing the treated area was examined and the effects scored according to Draize. None of the animals showed erythema or edema. No erythema and no edema were found in the additional study conducted by Suberg (1984).

In the key study for eye irritation 3 male rabbits received instillations of 100 mg test substance into the conjunctival sac of the right eye; the respective left eye remained untreated and served as control. The eyes of the animals were observed 1, 24, 48 and 72 hours post application. Additionally, 24 hours post application the eyes were treated with fluorescein and examined. The scoring was done according to Draize. In none of the animals the eyes were affected by treatment. Therefore the test substance was evaluated to be non-irritating to the eyes of rabbits.

In the additional eye irritation study by Suberg (1984) the cornea, iris, conjunctivae and chemosis score according Draize was 0 after 24, 48 and 72 hours.

Justification for classification or non-classification

In the available study Macrolex E2G was not skin - or eye irritating. According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.