Registration Dossier

Administrative data

Description of key information

 The substance is not irritating to the skin in animals and humans. It is slightly irritating to the eye in animals, without classification being required. 
For skin and eye irritation the conclusion is “Not classified - based on specific, valid data on the substance”.
Considering these results in high-sensitivity assays, there is no reason to suspect any relevant respiratory irritation, especially as the granulometry of the substance (as the substance is in the form of pearls) leads to negligible exposure of terminal airways.
For this route, the conclusion is “Not classified - based on weight-of-evidence analysis”.
Value used for CSA:
Skin irritation/corrosion: not irritating
Eye irritation: not irritating

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:
2008/06/03-2008/06/13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: No deviation was registred during the study. The experimental protocol was established from the OECD guideline n°404 and was executed in compliance with the Good Laboratory Principles.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
2007/15/02
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Animals
- Rabbits: New Zealand male albino
- Supplier: elevage de Gérome (Quartier Labaste- F40260 Linxe)
- Acclimatisation period: 5 days
- Weight of animals: between 2.38 and 2.68kg (during the test)
- Age at the beginning of the test: 11 to 12 weeks old

Housing
Each animal was kept in an individual box installed in conventionnal air conditioned animal husbanding; the environmental conditions were:
- T°: between 19 and 23°C
- Relative humidity: between 39 and 52%
- Lighting time: 12 hours daily
- Rate of air exchange: at least ten changes per hour

Drinking water and foodstuff were supplied freely.
Microbiological and chemical analyses of the water were carried out once every six months by the Institut Européen de l'Environnement de Bordeaux.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: On the opposite flank, an untreated area was served as control.
Amount / concentration applied:
0.5g of the test item was applied on an undamaged skin area of one flank of one animal
Duration of treatment / exposure:
4 hours
Observation period:
If no reaction is observed 72 hours after the treatment, the study was terminated. In case of persistent reactions, additional observations can be carried out from D4 to D14 in order to determine the reversible character of the lesions observed.
Number of animals:
Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated during 4 hours.
Details on study design:
Approximatively 24 hours before the test, the rabbits' backs anf flancks were shorn using electric clippers equipped with a fine comb, so as to expose an area of skin about 6 cm².

0.5g of the test item was applied on an undamaged skin area of one flank of one animal. The patch was secured in position with a strip of surgical adhesive tape. After the removal of the patch, the treated area was rinsed with distilled water.
On the opposite flank, an untreated area was served as control.
Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated during 4 hours.

The skin reactions were appreciated 1 hour and then 24, 48 and 72 hours after removal of the patch.
This examination consists in assessing the irritant reactions in the treated zone, compared to a control area; the following scales are used:
Grading scales :
Erythema and Eschar formation Oedema
0...... No erythema 0 ......No oedema
1...... Very slight erythema (barely perceptible) 1 ......Very slight oedema (barely perceptible)
2......Well defined erythema 2 ...... Slight oedema (contour clearly defined)
3...... Moderate to severe erythema 3 ......Moderate oedema (raised approx. 1mm)
4...... Severe erythema (beef redness) with eschars formation 4 ...... Severe oedema (raised more than 1mm, preventing grading of erythema and extending beyond area of exposure)
Irritation parameter:
erythema score
Remarks:
mean value
Basis:
animal #1
Time point:
other: 24-72h
Score:
ca. 0.3
Reversibility:
fully reversible
Irritation parameter:
erythema score
Remarks:
mean value
Basis:
animal #2
Time point:
other: 24-72h
Score:
ca. 0
Irritation parameter:
erythema score
Remarks:
mean value
Basis:
animal #3
Time point:
other: 24-72h
Score:
ca. 0.3
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24-72h
Score:
ca. 0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24-72h
Score:
ca. 0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24-72h
Score:
ca. 0
Irritant / corrosive response data:
According to the calculated means, the item must not be classified in accordance with the European regulation 67/548/EEC.
Other effects:
It was noted, 1 hour after the test item application, on the treated area, a slight to well defined erythema in the three animals associated with a very slight oedema in one animal. The oedematous reaction was totally reversible at D1 and the erythematous reactions were totally reversible between D1 and D2.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The test item is non irritant to skin (Psi=0.3) according to the classification established in the journal officiel de la republique francaise dated February 21st, 1982.
The test item must not be classified, according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with EEC directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required.
In accordance with the globally harmonized system, the test item must not be classified in category 2 "irritant". No signal word and hazard statement are required.
Executive summary:

The test item lce 08083 was applied, as supplied, at the dose of 0.5 g, under semi occlusive dressing during 4 hours on an undamaged skin area of 3 rabbits. The experimental protocol was established from the OECD guideline n°404 dated April 24th, 2002 and the test method B.4 of the directive n°2004/73/EC

It was noted, 1 hour after the test item application, on the treated area, a slight to well defined erythema in the three animals associated with a very slight oedema in one animal. The oedematous reaction was totally reversible at D1 and the erythematous reactions were totally reversible between D1 and D2.

The test item is non irritant to skin (Psi=0.3) according to the classification established in the journal officiel de la republique francaise dated February 21st, 1982.

The test item must not be classified, according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with EEC directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required.

In accordance with the globally harmonized system, the test item must not be classified in category 2 "irritant". No signal word and hazard statement are required.

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:
2008/09/06 to 2008/09/06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: No deviation was registred during the study. The experimental protocol was established on the basis of the official method as defined in the OECD guideline n°405 and has been performed in compliance with the Good Laboratory Principles.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
2007
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animal:
- species: new zealand albino rabbits
- Origin: Elevage de Gérome (Quartier Labaste-F40260 Linxe)
- Acclimatation period: 5 days
- Weight: between 2.49 and 3.11 kg (during the test)
- Old: 12 to 13 weeks

Housing:
-T° between 19 and 23°C
- Relative humidity: between 38 and 50%
- Lighting time: 12 hours daily
- rate of air exchange: at least ten changes per hour

Food and drinking:
- Drinking water and foodstuff were supplied freely
- Microbiological and chemical analyses of the water were carried out once every six months by the Institut Européen de l'Environnement de Bordeaux
Vehicle:
unchanged (no vehicle)
Controls:
other: The other eye remained untreated serving as control.
Amount / concentration applied:
0.1g of the test item, reduced in fine powder were introduced into the conjunctival sac of the eye.
Observation period (in vivo):
if no reaction is observed 72 hours after instillation, the study is terminated. In case of persistent reactions, additional observations can be carried out from D4 to D21 in order to determine the reversible character of the lesions observed.
Number of animals or in vitro replicates:
Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal at D7, two additional animals were treated.
Details on study design:
Occular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment.
Irritation parameter:
iris score
Basis:
mean
Remarks:
the 3 animals
Time point:
other: 24-72h
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24-72h
Score:
ca. 2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24-72h
Score:
ca. 6
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24-72h
Score:
ca. 3
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24-72h
Score:
ca. 0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24-72h
Score:
ca. 2
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24-72h
Score:
ca. 0
Irritant / corrosive response data:
According to the calculated mean, the test item must not be classified, in accordance with the european regulation.
Other effects:
The occular reactions observed during the study have been slight to moderate, and totally reversible in the three animals:
- at the conjunctivae level: a slight redness, noted 1 hour after the test item instillation and totally reversible between D3 and D9, associated with a slight to moderate chemosis, noted 1 hour after the test item instillation and totally reversible between D1 and D3.
- at the corneal level: a moderate opacity, only rehistered 24 hours after the test item instillation in one animal.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item is
- slightly irritant for eye (I.O.=11.3) according to the classification established in the journal officiel de la république francaise dated July 10th, 1992.
- and must not be classified according to the criteria for classification, packaging and labelling of dangerous substances in compliance with EEC directive 67/548, 2001/59 and 99/45. No symbol and risk phrase are required.
In accordance with the GHS, the test item must not be classified category 2. No signal word and hazard statement are required.
Executive summary:

The test item LCE 08083 was instilled as supplied, at the dose of 0.1g into the eye of three New Zealand rabbits. The experimental protocol was established on the basis of the official method as defined in the OECD guideline n°405 dated April 24th, 2002 and the test method B.5 of the directive 2004/73/EC

The occular reactions observed during the study have been slight to moderate, and totally reversible in the three animals:

- at the conjunctivae level: a slight redness, noted 1 hour after the test item instillation and totally reversible between D3 and D9, associated with a slight to moderate chemosis, noted 1 hour after the test item instillation and totally reversible between D1 and D3.

- at the corneal level: a moderate opacity, only rehistered 24 hours after the test item instillation in one animal.

The test item must not be classified according to the criteria for classification, packaging and labelling of dangerous substances in compliance with EEC directive 67/548, 2001/59 and 99/45. No symbol and risk phrase are required.

In accordance with the GHS, the test item must not ba classified category 2. No signal word and hazard sttement are required.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification