Registration Dossier

Administrative data

Description of key information

Skin irritation:

The Evaluation The Acute Primary Cutaneous Irritation And Corrosivity of NECTARYL In The Rabbit was performed according the OECD Guideline No. 404 in 1989.

The substance is not irritant to the skin under those test conditions.

Eye irritation:

The Evaluation The Acute Ocular Irritation And reversibility of NECTARYL In The Rabbit was performed according the OECD Guideline No. 405 in 1989.

The test substance is considered to be irritating to eyes (Category 2) according to GHS criteria

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:
13 March 1989 to 25 September 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
Specific details on test material used for the study:
Substance name (as stated in the report): NECTARYL - LRG 1371
Identification for the study: 07683 D9 001
Description: colourless slightly viscous liquid
Batch: AS1241001
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
- Supplier: E.S.D. (Romans - 01400 Chatillon Sur Chalaronne - France)
- Age: adult
- Number and sex: 6 males
- Weight at the beginning of treatment 2.35 to 2.70 kg
- Cages: individually housed in polystyrene cages, with perforated flooring (interior dimensions 560 x 355 x 315 mm).
- Temperature: 17 to 21°C
- Humidity: 46 to 77 % R.H.
- Lighting: artificial, 12 hours out of 24 (photoperiod = 7h30 - 19h30)
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
test substance as supplied
Controls:
no
Amount / concentration applied:
- Dose level : 0.5 ml per animal of the test substance as supplied.

Duration of treatment / exposure:
- Frequency: the test substance was applied once only.
- Length of exposure: 4 hours during which the animals were immobilized in restraining boxes.
- The dressings were then removed and the rabbits were returned to their individual cages.
Observation period:
Cutaneous examinations were performed 1, 24, 48 and 72 hours after removal of the dressing.
Number of animals:
a single group of 6 male rabbits
Irritation parameter:
erythema score
Basis:
animal: 51422, 51440 and 51441
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal: 51433
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal: 51629
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal: 51631
Time point:
24/48/72 h
Score:
1.33
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal: 51422, 51433, 51440, 51441, 51629 and 51631
Time point:
24/48/72 h
Score:
0
Max. score:
0

As no excess of substance was observed to the application area after removal of the semi-occlusive patch, no wiping was carried out.

Interpretation of results:
GHS criteria not met
Conclusions:
After a 4-hour local cutaneous application, under a semi-occlusive patch, the test substance as supplied can be considered as NON-IRRITANT.
Executive summary:

The Evaluate The Acute Primary Cutaneous Irritation And Corrosivity of NECTARYL In The Rabbit was performed according the OECD Guideline No. 404.

The test substance was applied as supplied and at the dose level of 0.5 ml per animal, under a semi-occlusive patch for 4 hours, to the intact skin of 6 Zealand hybrid albino male rabbits.

The cutaneous examinations were performed , for erythema and oedema, according to the Draize scale, 1, 24, 48 and 72hours after removal of the patch.

Mean values were calculated from the evaluation of the cutaneous lesions performed in all the rabbits examined at 24, 48 and 72 hours.

From the results obtained under the experimental conditions employed, application of this test substance to the rabbit' skin can be designated as: NON-IRRITANT

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:
13 March 1989 to 25 September 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
Substance name (as stated in the report): NECTARYL - LRG 1371
Identification for the study: 07683 D9 001
Description: colourless slightly viscous liquid
Batch: AS1241001
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Species, strain: New-Zealand hybrid albino rabbit vaccinated against myxomatosis (Lyomyxovax N.D. - Rhone Merieux - 69223 Lyon - France).
- Supplier: E.S.D. (Romans - 01400 Chatillon Sur Chalaronne - France)
- Age: adult
- Number and sex: 6 males
- Weight at the beginning of treatment: 2.45 to 2.55 kg
- Cages: individually housed in polystyrene cages, with perforted flooring (interior dimensions 560 x 355 x 315 mm)
- Temperature : 17 - 21°C
- Humidity: 50 to 68 % R.H.
- Lighting artificial, 12 hours out of 24 (photoperiod = 7h30 - 19h30)
Vehicle:
unchanged (no vehicle)
Remarks:
test substance as supplied
Controls:
yes, concurrent negative control
Amount / concentration applied:
- Dose level : 0.1 ml per animal of the test substance as supplied (undiluted)
Duration of treatment / exposure:
- Frequency: the test substance was applied once only
- Duration: instillation
Observation period (in vivo):
Ocular examinations were performed in the order in which the animals were treated, 1 hour after administration of the test substance, then at 24, 48 and 72 hours
Number of animals or in vitro replicates:
- Group: a single treated group of 6 male rabbits.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48h
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72h
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 72h
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
not fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72h

The evaluation of ocular reversibility was not performed because no severe ocular lesion was observed 72 hours after administration of the test substance.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The test substance is considered to be irritating to eyes (Category 2) according to GHS criteria.
Executive summary:

The evaluation of acute ocular irritation and reversibility of NECTARYL in the rabbit was performed according the OECD Guideline No. 405.

The test substance was applied as supplied in the amount of 0.1 ml per animal, into the inferior conjunctival sac of one eye of each of the 6 Zealand hybrid albino male rabbits.

The ocular examinations were performed 1 hour after after administration of the test substance, then at 24, 48 and 72 hours.

Mean values were calculated from the evaluation of the ocular lesions performed in all the rabbits examined at 24, 48 and 72 hours.

The test substance is considered to be irritating to eyes (Category 2) according to GHS criteria

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

A study was conducted to evaluate the acute primary cutaneous irritation and corrosivity of the test material in rabbits (OECD 404, GLP). The test material was applied as supplied and at a dose level of 0.5 ml per animal, under a semi-oclusive patch for 4 hours, to the intact skin of 6 New-Zealand hybrid albino male rabbits. The day before application of the test material, the back and flanks of the 6 rabbits were clipped free of hair exposing an area of skin approximately 14 cm x 14 cm. Animals were acclimated for at least 14 days before start of treatment. Animals weighed 2.35 to 2.70 kg at the beginning of treatment. Animals were housed individually in polystrene cages with perforated flooring. Animal room temperature was 17-21 C; relative humidity was 46-77%; artificial lighting was 12 hour light/dark. Animals received 150 g per animal of pelleted rabbit maintenance diet. Water (softened and filtered 15 um) mains drinking water was available ad libitum. 0.5 ml of test material per animal was applied directly to a surface of skin approximately 6 cm2. It was then covered with a square of 8 layer thick Codex hydrophillic gauze with an identical surface area. The test material and gauze square was held in contact with the skin by means of a semi-occlusive dressing: perforated adhesive tape (Peloplast) 10 cm wide applied onto a band of crepe gauze (Creplux) used to cover the entire clipped surface; this encircled the trunk of the animal. The test material was applied once and the dressing remained in place for 4 hours during which the animals were immobilised in restraining boxes. Dressings were then removed and the rabbits were returned to their individual cages. Skin reactions were evaluated for erythema and oedema according to the following Draize scale at 1, 24, 48 and 72 hours after removal of the patch: erythema and eschar formation - 0 = no erythema; 1 = very slight erythema (barely perceptible); 2 = well-defined erythema; 3 = moderate to severe erythema; 4 = severe erythema (beetroot red) to slight eschar formation (deep lesions). Oedema - 0 = no oedema; 1 = very slight oedema (barely perceptible); 2 = slight oedema (edges of area well defined by definite raising); 3 = moderate oedema (edges raised approximately 1 mm); 4 = severe oedema (raised more than 1 mmm extending beyond the area of exposure). Mean values were calculated from the evaluation of the cutaneous lesions performed in all rabbits examined at 24, 48 and 72 hours. Cutaneous corrosivity evaluation was not performed because no severe cutaneous lesion was observed 72 hours after application of the test material in at least one rabbit.

Under the conditions of the study, 0.5 ml test material was considered as non-irritant to rabbit skin.

Eye irritation:

An acute ocular irritation and reversibility study was conducted in the rabbit (OECD 405). The test material was administered as supplied, without rinsing and at the dose level of 0.1 ml per animal, into the inferior conjunctival sac of the right eye of 6 New-Zealand hybrid albino male rabbits. Animals weighed 2.45 to 2.55 kg at the beginning of treatment. Animals were acclimated for at least 21 days before the start of treatment. Animals were housed individually in polystyrene cages with perforated flooring. Animal room temperature was 17 to 21 C; relative humidity was 50 to 68%; artificial lighting was 12 hours light/dark. Animals received approximately 150 g per animal of complete pelleted rabbit maintenance diet. Water (softened and filtered (15 um) mains drinking water was provided ad libitum. Each animal was immobilised in a restraining box. 0.1 ml test material was instilled into the inferior conjuncitval sace of the right eye of each animal. The left eye served as the untreated control. The upper and lower eyelids were held together for a few seconds to avoid loss of the test material. The animals were kept in the restraining boxes for 1 hour. They were returned to their individual cages after the first observation. The test material was applied once. Exposure was 24 hours. After that time the eyes were rinsed with fluorescein which was eliminated with water. Ocular examinations were performed 1 hour after administration of the test material and then at 24, 48 and 72 hours. Examination of the cornea, iris and pupil was performed with the aid of a Hein ophthalmoscope. Mean values were calculated from the quantitative and qualitative evaluation of ocular lesions performed in all the rabbits examined at 24, 48 and 72 hours. Ocular reversibility was not performed because no severe ocular lesion was observed 72 hours after administration of the test material.

The test substance is considered to be irritating to eyes (Category 2) according to GHS criteria.

Justification for classification or non-classification

Based on the data available and key results described in this summary, the substance has shown no skin irritancy potential and should therefore not be classified according to the (EC) No 1272/2008 Regulation (CLP).

However, based on the results on eye irritation, the test substance is considered to be irritating to eyes (Category 2) according to GHS criteria.