Registration Dossier

Administrative data

Description of key information

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:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(1992)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Regal Group UK, Great Bookham, Surrey, UK.
- Age at study initiation: approx. 13 to 14 weeks
- Weight at study initiation: weight range of 3.0 - 3.4 kg
- Housing: individually in metal cages with perforated floors
- Diet and water: ad libitum
- Acclimation period: All rabbits were acclimatised to the experimental environment. No information concerning period of time.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 19
- Humidity (%): 30-70
- Air changes (per hr): approx. 19
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin areas of the test animal served as control
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
Examinations were terminated after 6 days, since all changes had completely subsided then.
Number of animals:
3 (two males, one female)
Details on study design:
TEST SITE: Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 100 mm x 100 mm. Approximately 0.5 mL of the test substance was applied under a 25 mm x 25 mm gauze pad to one intact site on each animal. Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours.

REMOVAL OF TEST SUBSTANCE: At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with warm water (30-40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.

SCORING SYSTEM:
Erythema and eschar formation: No erythema 0; very slight erythema (barely perceptible) 1; well-defined erythema 2; moderate to severe erythema 3; severe erythema (beef redness) to slight eschar formation (injuries in depth) preventing erythema reading 4.
Oedema formation: No oedema - 0; very slight oedema (barely perceptible) 1; slight oedema (edges of area well-defined by definite raising) 2; moderate oedema (raised approximately 1 millimetre) 3; severe erythema (raised more than 1 millimetre and extending beyond the area of exposure) 4.
Irritation parameter:
erythema score
Basis:
animal: #1, #3
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: mean score: 0.66
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: mean score: 1.7
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
Very slight erythema with or without very slight to slight oedema was seen in all animals. These reactions gradually ameliorated and had resolved in all instances by Day 5 or Day 6.
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period.
Executive summary:

An Acute Dermal Irritation/Corrosion test was conducted according to OECD TG 404. In this study very slight erythema with or without very slight to slight oedema was seen in all animals (Mean scores of time points 24, 48, and 72 h: 1 for erythema, 0.8 for oedema). These reactions gradually ameliorated and had resolved in all instances by Day 5 or Day 6. No signs of toxicity or ill health were observed.

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:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1987)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Regal Group UK, Great Bookham, Surrey, UK.
- Age at study initiation: approx. 14 to 17 weeks
- Weight at study initiation: weight range of 3.4 - 3.8 kg
- Housing: individually in metal cages with perforated floors
- Diet and water: ad libitum
- Acclimation period: All rabbits were acclimatised to the experimental environment. No information concerning period of time.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-19.5
- Humidity (%): 44-76
- Air changes (per hr): approx. 19
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the contralateral eye remained untreated and served as control
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
The eyelids were gently held together for one second before releasing.
Observation period (in vivo):
Examinations were terminated after 7 days, since all changes had completely subsided then.
Number of animals or in vitro replicates:
3 (two males, one female)
Details on study design:
PROCEDURE: The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial or conjunctival inflammation.
One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed. Approximately 0.1 mL of the test substance was placed into the lower everted lid of one eye of each animal. The eyelids were gently held together for one second before releasing.

SCORING SYSTEM:
Cornea opacity - degree of density: No ulceration or opacity 0; Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible 1; Easily discernible translucent areas, details of iris slightly obscured 2; Nacreous areas, no details of iris visible, size of pupil barely discernible 3; Opaque cornea, iris not discernible through the opacity 4
Iris: Normal 0; Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) 1; No reaction to light, haemorrhage, gross destruction (any or all of these) 2
Conjunctivae redness: Blood vessels normal 0; Some blood vessels definitely hyperaemic (injected) 1; Diffuse, crimson colour, individual vessels not easily discernible 2; Diffuse beefy red 3
Chemosis: No swelling 0; Any swelling above normal (includes nictating membranes) 1; Obvious swelling with partial eversion of lids 2; Swelling with lids about half-closed 3; Swelling with lids more than half-closed 4

TOOL USED TO ASSESS SCORE: Observation of the eyes was aided by the use of a handheld light.
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: #2, #3
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
animal: #1, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: mean score: 0.7
Irritant / corrosive response data:
No corneal damage or iridial inflammation was observed. Hyperaemia of blood vessels with slight swelling was seen in all animals. These reactions had resolved in all instances by four or seven days after instillation.
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period.
Executive summary:

An Acute Eye Irritation/Corrosion test was conducted according to OECD TG 405. In this study no corneal damage or iridial inflammation was observed (all scores zero). Hyperaemia of blood vessels with slight swelling was seen in all animals (Mean scores for time points 24, 48, and 72 h: 1 for conjuntiva/redness, 0.2 for chemosis). These reactions had resolved in all instances by four or seven days after instillation. No signs of toxicity or ill health were observed.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

In vivo studies on acute dermal or eye irritation/corrosion according to OECD TG 404 or 405 revealed slight skin irritation and very slight eye irritation properties, respectively.

The substance was proven to be respiratory irritating based on acute and repeated inhalation toxicity studies. In the key pulmonary irritant potency study rats showed clinical signs of respiratory tract irritation after exposure to the aerosolised test substance at concentrations of 60 mg/m³ and above (cp. Endpoint Summary of chapter Acute Toxicity). Statistical analysis of bronchoalveolar lavage fluid (BALF) endpoints, as the most sensitive endpoints indicative for pulmonary irritation, determined a NO(A)EL of 3 mg/m³. Furthermore, in a mice study on the acute respiratory tract sensory irritation potency the aerosolized substance induced an increase in respiratory rate with a decrease in tidal volume (RD50-study, according to ASTM E981 -84; see chapter Acute toxicity: inhalation, report no. 18851, Bayer AG, 1990). This was seen as a characteristic indication for a pulmonary irritant. Derivation of a RD50-value was not regarded as adequate in this study, because the changes in respiratory rate induced by pulmonary irritation interfered with that of sensory irritation, and therefore the delineation of a reliable RD50-value was not possible.


Justification for selection of skin irritation / corrosion endpoint:
One representative study of the fully reliable studies selected. In any case no classification for skin irritation/corrosion is warranted according to Regulation (EC) No 1272/2008, Annex I, based on the available studies.

Justification for selection of eye irritation endpoint:
One representative study of the fully reliable studies selected. In any case no classification for eye irritation/corrosion is warranted according to Regulation (EC) No 1272/2008, Annex I, based on the available studies.

Effects on respiratory irritation: irritating

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008, Annex I, no classification is warranted for skin and eye irritation/corrosion.

According to Regulation (EC) No 1272/2008, Annex I, classification as STOT SE 3 (H335: May cause respiratory irritation) is warranted.