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)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: HC:NZW
- Source: Interfauna UK Ltd.
- Age at study initiation: adult animals
- Weight at study initiation: 2.8, 3.1, and 3.5 kg
- Housing: singly in wire mesh cages (Typ III) on low dust wood granulate bedding
- Diet and water: ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 45-65
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: yes, the skin areas of the contralateral flank (treated with moistened plaster) served as control
Amount / concentration applied:
500 µL
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
One day prior to test substance administration the contralateral skin areas of the flanks of 3 rabbits were shorn (approx. 6x6 cm).
On the day of administration 500 µL of the test item was given on a hypoallergenic plaster (Beiersdorf No. 2342) and applied onto the skin. For negative control a further plaster was moistened with water and applied to the skin of the opposite flank. Each treatment site was then covered with elastic dressings (Fixomull-Strech Klebevlies, Beiersdorf No 2039) under semiocclusive conditions. After the 4-hours exposure period dressings and plaster were removed and the treated skin areas washed with water.
Readings were after 1, 24, 48, and 72 hours and after 7 and 14 days.

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean score: 1.3
Irritation parameter:
erythema score
Basis:
animal: #2, #3
Time point:
other: 24, 48, 72 hours
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: at least 14 days
Remarks on result:
other: mean score: 1.7
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Executive summary:

Dermal irritation/corrosion of the substance was tested according to OECD TG 404 on three rabbits. In this study 500 µL of the test item was applied semiocclusively on the previously shorn skin of the flanks. The opposite areas of the skin were used for negative control (plaster moistened with water, semiocclusive dressings). Readings were after a 4 hour-exposure period according to Draize at time points 1, 24, 48, and 72 hours and after 7 and 14 days.

The substance led to slight irritant effects after 24, 48, and 72 hours (mean score erythema 1.3, 1.7, 1.7; mean score edema 0, 0, 0). Complete reversibility was shown after 14 days at the latest.

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)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: HC:NZW
- Source: Interfauna UK Ltd.
- Age at study initiation: adult animals
- Weight at study initiation: 2.9, 3.1, and 3.1 kg
- Housing: singly in wire mesh cages (Typ III) on low dust wood granulate bedding
- Diet and water: ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 45-65
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral untreated eye was used as negative control
Amount / concentration applied:
100 µL
Duration of treatment / exposure:
The eyelids were gently held together for approx. 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
Details on study design:
100 µL of the test substance were instilled into the conjunctival sac of the eye and the lids were gently held together for approx. one second before releasing. 24 hours after the treatment the eye was rinsed with saline solution.
Readings were after 1, 24, 48, and 72 hours and after 7, 14, and 21 days.

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein and UV-light
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
>= 0 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: mean score: 0.7
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
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
Executive summary:

The potential of damage to the eye was investigated according to OECD TG 405 in three rabbits. In this study 100 µL of the test substance was instilled into the conjunctival sac of one eye, and the eye-lid was gently held together for approx. one second before releasing. The contralateral untreated eye of the animal served as negative control. Readings were according to Draize after 1, 24, 48, and 72 hours and after 7 days. Since all changes were subsided by then, the study was terminated.

The substance led to no findings for iris, cornea, chemosis and to a slight effect after 24 hours solely in one rabbit (mean score iris, cornea, chemosis 0; mean score conjunctiva redness 0.2). Complete reversibility was shown after 48 hours.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

For an assessment of skin irritation/corrosion two in vivo studies are available for the substance. Both studies were conducted according to OECD TG 404, but the reporting was more detailed in one study. In this study 500 µL of the test item was applied semiocclusively on the previously shorn skin of the flanks of three rabbits. The opposite areas of the skin were used for negative control (plaster moistened with water, semiocclusive dressings). Readings were after a 4 hour-exposure period according to Draize at time points 1, 24, 48, and 72 hours and after 7 and 14 days.

The substance led to slight irritant effects after 24, 48, and 72 hours (mean score erythema 1.3, 1.7, 1.7; mean score edema 0, 0, 0). Complete reversibility was shown after 14 days at the latest.

The second study confirmed the slight irritant property of the test substance.

Also two studies are available for the assessment on the potential of damage to the eye. Both studies were conducted according to OECD TG 405, but the reporting was more detailed in one study. In this study 100 µL of the test substance was instilled into the conjunctival sac of one eye of in total three rabbits, and the eye-lids were gently held together for approx. one second before releasing. The contralateral untreated eyes of the animals served as negative control. Readings were according to Draize after 1, 24, 48, and 72 hours and after 7 days. Since all changes were subsided by then, the study was terminated.

The substance led to no findings for iris, cornea, chemosis and to a slight effect after 24 hours solely in one rabbit (mean score iris, cornea, chemosis 0; mean score conjunctiva redness 0.2). Complete reversibility was shown after 48 hours.

The second study confirmed the slight eye irritancy of the test substance.

Indications for respiratory irritation were revealed from the acute inhalation study. In this study (cp. chapter Acute Toxicity) clinical signs like irregular breathing, nose and nostrils with red encrustrations, serous nasal discharge and mortality pattern typical of an irritation-related acute lung edema were reported. Moreover, the database with acute and repeated studies for substances with similar compositions (HDI homopolymers, CAS No. 28182 -81 -2, including HDI oligomers, isocyanurate, iminooxadiazindione, biuret, uretdione and allophanate type) consistently demonstrates respiratory irritant potential.


Justification for selection of skin irritation / corrosion endpoint:
Most reliable study available

Justification for selection of eye irritation endpoint:
Most reliable study available

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/or eye irritation/corrosion.

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