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Administrative data

Description of key information

The test item did not show any skin or eye irratation potential when tested according to OECD technical guideline in vivo skin and eye irritation tests.

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:
2003-09-03 - 2003-11-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 404) performed under GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted on 17th July 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
adopted on 31st July 1992
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Age at study initiation: 2 - 4 months old
- Body weight at study initiation: 2.9 ± 0.2 kg
- Housing: animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet: 110 pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 micron), ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Humidity: 30 - 70%
- Air changes: approximately 12 air changes/hour (filtered, non-recycled air)
- Photoperiod: 12 h / 12 h

IN-LIFE DATES: From: 2003-09-09 To: 2003-09-14
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: not applicable
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 500 mg, moistened with purified water (gauze pad)
Duration of treatment / exposure:
4 h;
In the first instance, the test item was applied for periods of 3 minutes and 4 hours to a single male rabbit
Since the test item was not severely irritant on this first animal, it was then applied for 4 h to two other animals.
Observation period:
72 hours after patch removal (assessment of skin reactions at 1, 24, 48 and 72 hour(s) after patch removal)
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: flank
- Type of wrap: adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage

REMOVAL OF TEST SUBSTANCE
- Washing: any residual test item was wiped off by means of a dry cotton pad
- Time after start of exposure: 4 hours

SCORING SYSTEM: Scoring system according to OECD guidelines
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(all animals)
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
(all animals)
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
After 3-minute exposure (one animal) slight erythema was observed on day 1 and 2. After 4-hour exposure (three animals) a slight erythema was observed in 1/3 animals 1 hour after the removal of the dressing, otherwise no cutaneous reactions were recorded during the study. Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for oedema.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
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:
2003-09-03 - 2003-12-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD TG 405) performed under GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted on 24th Feb 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
adopted on 31st July 1992
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Age at study initiation: 2 - 4 months old
- Body weight at study initiation: 3.2 ± 0.4 kg
- Housing: animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet: 110 pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 micron), ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Humidity: 30 - 70%
- Air changes: approximately 12 air changes/hour (filtered, non-recycled air)
- Photoperiod: 12 h / 12 h

IN-LIFE DATES: From: 2003-09-17 To: 2003-09-26
Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye, which remained untreated, served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg/rabbit
Duration of treatment / exposure:
Single treatment. The treated eyes were not rinsed after instillation.
Observation period (in vivo):
72 hours (assessment of eye reactions at 1, 24, 48 and 72 hour(s)).
The study was ended on day 4 in the absence of persistent ocular reactions.
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
TEST ITEM PREPARATION / TEST SITE
- 100 mg of the test item was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test item.

REMOVAL OF TEST SUBSTANCE
- Washing: The eyes were not rinsed after instillation.

SCORING SYSTEM: numerical scoring system according to the OECD guideline 405

TOOL USED TO ASSESS SCORE: UV lamp, fluorescein
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(all animals)
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
(all animals)
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

The potential of non-micronized ETH50 to induce skin irritation was evaluated in 3 New Zealand White rabbits (CIT 26396, 2003, OECD 404, GLP). A single dose of 500 mg of the test item in its original form was applied semi-occlusively to the closely-clipped skin of one flank. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing. After the 4-hour exposure, except for a very slight erythema noted in 1/3 animals one hour after the removal of the dressing, no cutaneous reactions were recorded during the study. Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for edema. Under the experimental conditions employed, the test item was non-irritant when applied topically to rabbits.

In a supporting study (Biotoxtech J06181, 2006), the non-micronized ETH50 (10, 20 or 40 % in PEG) was applied 14 times, application appr. 24 h apart, (uncovered) to the clipped skin of three New Zealand White rabbits. Observation of skin response was performed once daily at approximately 24 hours after last administration and the cumulative skin irritation was evaluated. No skin irritation an no cumulative skin irritation was observed at the application sites for all animals during the observation period. According to these results, it was concluded that the test item did not induce cumulative skin irritation under the conditions of this study.

Eye irritation:

The potential of non-micronized ETH50 to induce ocular irritation was evaluated in rabbits (CIT 26397, 2003, OECD 405, GLP). A single dose of 100 mg of the test item in its original form was introduced into the left conjunctival sac of the eye of three New Zealand White rabbits. The right eye was not treated and served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.3, 0.0 and 0.3 for chemosis, 1.0, 0.3 and 0.0 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity, respectively.

Under the experimental conditions employed ETH50 was non irritant when administered by ocular route to rabbits.

Justification for classification or non-classification

The present data on skin and eye irritation do not fulfill the criteria laid down in 67/548/EEC and regulation (EU) 1272/2008, and therefore, a non-classification is warranted.