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
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(2002)
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Crl:KBL(NZW)BR
- Sex: female
- Source: Charles River, 88353 Kißleg, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: 2.2-2.7 kg
- Housing: individually in cage units Metall/Noryl by EBECO
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 50 +/- 25 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: The surrounding untreated skin served as control
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
Due to animal welfare reasons only one animal was initially treated with three test patches. These were successively removed: after 3 minutes, after 1 hour and the third was allowed to remain 4 hours, in each case if no serious skin reactions were observed. Completion of the test was then carried out using 2 additional animals, exposed for 4 hours.

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
On the day before the test, the fur was shorn on the right and left side from the dorso-lateral area of the trunk of each of the rabbits. Care was taken to avoid abrading the skin. Only animals with healthy and intact skin were used. 0.5 mL of the pure liquid test substance was applied to the skin of the animal under a gauze patch. The treated skin area was approximately 2.5 cm by 2.5 cm in size. The patch was placed on the dorso-lateral areas of the trunk of each animal and was held in place with non-irritating tape for the duration of the exposure period. Thus, access by the animal to the patch and resultant ingestion of the test substance was prevented.

REMOVAL OF TEST SUBSTANCE
After the exposure period the dressing and patch were removed.
- Washing (if done): The exposed skin area was carefully washed with water.

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal: #1, #3
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24h, 48h, 72h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean score: 1
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
4
Other effects:
Animal 2, day 7 after patch removal: desquamation.
There were no relevant systemic intolerance reactions.
Conclusions:




Classification: not irritating
Executive summary:

An Acute Dermal Irritation/Corrosion test was conducted with the substance according to OECD TG 404. Under the conditions of the test the substance showed no up to very slight dermal irritation (Mean score of time points 24, 48, and 72 h: 0.3 for erythema, 0 for oedema). There were no relevant systemic intolerance reactions.

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
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(2002)
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: HsdIf:NZW
- Sex: female
- Source: Harlan France, 03800 Gannat, France
- Age at study initiation: young adult animals
- Weight at study initiation: 2.3-2.5 kg
- Housing: individually in cage units Metall/Noryl by EBECO
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 50 +/- 25 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: The other eye, which remained untreated, served as control.
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
The eye-lids were gently held together for about one second in order to prevent loss of the test compound. The eye was not rinsed for at least 24 hours following instillation.
Observation period (in vivo):
Examinations were terminated after 72 hours, since all changes had completely subsided then.
Number of animals or in vitro replicates:
3
Details on study design:
Due to animal welfare reasons only one animal was tested at first. If one hour after treatment a severe irritation was not observed, two further rabbits were treated.

PROCEDURE: On the day before the test, both eyes of each animal were examined including fluorescein examination. Only animals with healthy intact eyes were used.
0.1 mL of the pure liquid test substance was placed into the conjunctival sac of one eye ofthe first animal after having gently pulled the lower lid away from the
eyeball. The lids were gently held together for about one second in order to prevent loss of the test compound. The other eye, which remained untreated, served as control. The eye was not rinsed for at least 24 hours following instillation.

SCORING SYSTEM: Draize.
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48h, and 72h
Score:
0 - 1
Max. score:
3
Reversibility:
fully reversible within: 48h
Remarks on result:
other: mean score: 0.3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48, and 72h
Score:
0 - 2
Max. score:
3
Reversibility:
fully reversible within: 72h
Remarks on result:
other: mean score: 1.0
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
4
Other effects:
There were no systemic intolerance reactions.
Conclusions:



Classification: not irritating
Executive summary:

An Acute Eye Irritation/Corrosion test was conducted according to OECD 405. In this study no corneal damage, no iridial inflammation and no conjunctivae chemosis was observed (all scores zero). The substance elicited very slight conjunctival irritation (mean scores conjuncivae redness 0.43). There were no systemic intolerance reactions.

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 Skin or Eye Irritation/Corrosion according to OECD TG 404 or 405 revealed very slight skin and eye irritation properties.

The substance was proven to be respiratory irritating based on acute and repeated inhalation toxicity studies. In a pulmonary irritant potency study rats showed clinical signs of respiratory tract irritation after exposure to the aerosolised test substance at concentrations of 15.2 mg/m³ and above (cp. endpoint summary of chapter Acute Toxicity). Statistical analysis of bronchoalveolar lavage fluid (BALF) protein as most sensitive endpoint indicative for pulmonary irritation determined the NO(A)EL of 2.1 mg/m³. Furthermore, the aerosolized substance induced an increase in respiratory rate and characteristic changes in breathing patterns (apneic pause between expiration and inspiration) in a RD50-study (see chapter Acute toxicity: inhalation, report PH 28522, Bayer AG, 1999). This was seen as indicative for a lower tract pulmonary irritant. Due to this interfering mode of action (lower respiratory tract irritation), no reliable RD50 could be determined. The non-irritant threshold concentration in the RD50 -study was considered to be 3.9 mg/m³.


Justification for selection of skin irritation / corrosion endpoint:
Only one in vivo study available

Justification for selection of eye irritation endpoint:
Only one study available

Effects on respiratory irritation: irritating

Justification for classification or non-classification

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

According to Regulation (EC) No 1272/2008, Annex I, the substance has to be classified as STOT SE 3 (H335: May cause respiratory irritation).