Registration Dossier

Administrative data

Description of key information

The substance is not significantly 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 (only 0.7% of particles are smaller than 1 mm as the substance is in the form of pellets or flakes) leads to negligible exposure of terminal airways. For this route, the conclusion is “Not classified - based on weight-of-evidence analysis”.

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:
2007-11-21 to 2008-03-03
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Male albino New Zealand rabbits were supplied by the Elevage de Gérome (Quartier Labaste –F40260 Linxe). They were kept during a minimal 5-day acclimatisation period. During the test, the animals weighed between 2.36 kg and 3.56 kg. At the beginning of the test, the animals were 11 and
14-week old.
Each animal was kept in an individual box installed in conventional air conditioned animal husbanding; the environmental conditions were:
- temperature : between 19°C and 21°C
- relative humidity : between 40% and 55%
- lighting time: 12 hours daily
Drinking water (tap-water from public distribution system) 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 (I.E.E.B.).
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
The test item was applied, after being reduced in fine powder, at a dose of 0.5 g in an area of about 6 cm2.
Duration of treatment / exposure:
4 hours
Observation period:
until 72 hours after removal of the patch
Number of animals:
3 rabbits
Details on study design:
Approximately 24 hours before the test, the rabbits’ backs and flanks were shorn using electric clippers equipped with a fine comb, so as to expose an area of skin about 6 cm2.
The test item was applied, after being reduced in fine powder, at a dose of 0.5 g, on an undamaged skin area of one flank of each animal, during 4 hours. 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 the control.
Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.
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:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Score:
ca. 0
Max. score:
0
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 hours
Score:
ca. 0
Max. score:
0
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hours
Score:
ca. 0
Max. score:
0
Irritant / corrosive response data:
No cutaneous reactions (erythema and oedema) were observed whatever the examination time (1, 24,
48 and 72 hours).
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The results obtained, under these experimental conditions, enable to conclude that the test substance, according to the scales of interpretation retained:
- is non irritant to skin (PSi = 0) according to the classification established in the Journal Officiel de la République Française dated February 21st, 1982,
- and, must not be classified, according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with the E.E.C. Directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required.
In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must not be classified in category 2 “irritant”. No signal word and hazard statement are required.
Executive summary:

The test substance was applied, after being reduced in fine powder, at the dose of 0.5 g, under semi-occlusive dressing during 4 hours on an undamaged skin area of three rabbits. The experimental protocol was established from the O.E.C.D. guideline n° 404 dated April 24th, 2002 and the test method B.4 of the directive n° 2004/73/EC. No cutaneous reactions (erythema and oedema) were observed whatever the examination time (1, 24, 48 and 72 hours). The results obtained, under these experimental conditions, enable to conclude that the test substance must not be classified, according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with the E.E.C. Directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required. In accordance with the Globally Harmonized System (COM(2007)355 final), the test substance 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:
2007-12-11 to 2008-03-03
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Male albino New Zealand rabbits were supplied by the Elevage de Gérome (Quartier Labaste –F40260 Linxe). They were kept during a minimal 5-day acclimatisation period. During the test, the animals weighed between 2.91 kg and 3.33 kg. At the beginning of the test, the animals were 13 to 14-
week old.
Each animal was kept in an individual box installed in conventional air conditioned animal husbanding; the environmental conditions were:
- temperature : between 19°C and 21°C
- relative humidity : between 41% and 67%
- lighting time: 12 hours daily
Drinking water (tap-water from public distribution system) 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 (I.E.E.B.).
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 g of the test item was instilled, after being reduced in fine powder, into the conjunctival sac of one eye.
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
0.1 g of the test item was instilled, after being reduced in fine powder, into the conjunctival sac of one eye. The other eye remained untreated serving as control.
Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal at D3, two additional animals were treated.
Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72h
Score:
ca. 0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
ca. 0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
ca. 0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 hours
Score:
ca. 1
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
- 1 hour after instillation: total score = 22, average irritation index = 7.3
- 24 hours after instillation: total score = 2, average irritation index = 0.7
- 48 hours after instillation: total score = 0, average irritation index = 0
- 72 hours after instillation: total score = 0, average irritation index = 0

Maximal ocular irritation index (MAX OI) = 7.3
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The results obtained, under these experimental conditions, enable to conclude that the test substance:
- is slightly irritant for the eye (Max. O.I = 7.3) according to the classification established in the Journal Officiel de la République Française dated July 10th, 1992.
- and, must not be classified according to the criteria for the classification, packaging and labelling of dangerous substances in compliance with the E.E.C. Directive n° 67/548, 2001/59 and 99/45. No symbol and risk phrase are required.
In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must not be classified in category 2 “irritating to eyes”. No signal word and hazard statement are required.
Executive summary:

The test substance was instilled after being reduced in fine powder, at the dose of 0.1 g into the eye of three New Zealand rabbits. The experimental protocol was established on the basis of the official method as defined in the O.E.C.D. guideline n° 405 dated April 24th, 2002 and the test method B.5 of the directive 2004/73/EC. The ocular conjunctivae reactions observed during the study have been slight and totally reversible in the three animals: a slight redness, noted 1 hour after the test item instillation and totally reversible between D1 and D2, associated with a slight chemosis only noted 1 hour after the test item instillation. In conclusion, the results obtained, under these experimental conditions, enable to conclude that the test substance must not be classified according to the criteria for the classification, packaging and labelling of dangerous substances in compliance with the E.E.C. Directive n° 67/548,2001/59 and 99/45. No symbol and risk phrase are required. In accordance with the Globally Harmonized System (COM(2007)355 final), the test substance must not be classified in category 2 “irritating to eyes”. No signal word and hazard statement are required.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

The substance is not classified irritating to eyes or skin according to GHS criteria.