Registration Dossier

Administrative data

Description of key information

Skin irritation test (rabbit): not irritating

Eye irritation test (rabbit): 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst breed
- Weight at study initiation: 2.5 - 3.2 kg
- Housing: singly in cages
- Diet (e.g. ad libitum): ERKA 3800 (Futtermittelwerk Robert Koch oHG, Hamm/Westf.) ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not specified
Type of coverage:
occlusive
Preparation of test site:
clipped
Remarks:
50% of shorn area was aditionally scarified
Vehicle:
physiological saline
Remarks:
0.1 mL of 0.9% NaCl solution
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 0.9% NaCl solution
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 6 x 3 cm, half of the area was additionally scarified
- Type of wrap if used: test substance was applied to cellulose patches in Hansamed(R) surgical plaster measuring 2.5 x 2.5 cm. The plaster strips were secured in position and then covered with an indifferent, impervious PVC-foil (6-8 cm in width). Subsequently, the trunk of the animal was bandaged with an elastic polyurethane-wrap thrand-bandage (permanent dressing K, Lohmann).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified
- Time after start of exposure: 24 hours

OBSERVATION TIME POINTS
immediately after removal of the dressing and at 48 and 72 hours after treatment

SCORING SYSTEM:
- Method of calculation:
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Remarks:
scarified skin
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.6
Reversibility:
fully reversible within: 72h
Irritation parameter:
erythema score
Remarks:
scarified skin
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Reversibility:
fully reversible within: 48h
Irritation parameter:
erythema score
Remarks:
scarified skin
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Reversibility:
fully reversible within: 48h
Irritation parameter:
erythema score
Remarks:
scarified skin
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Remarks:
scarified skin
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.3
Reversibility:
fully reversible within: 48h
Irritation parameter:
erythema score
Remarks:
scarified skin
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Remarks:
intact / scarified skin
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Remarks:
no edema was observed in any animal
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:
Aug-Nov 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
yes
Remarks:
The relative humidity of the animal room (39-81%) exceeded the range specified in theprotocol (30-70%) during this study. This occurrence was considered to have had no impact on the outcome of the study.
Qualifier:
according to guideline
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
- Source: Myrtle's Rabbitry, Thompson Station, TN
- Females: nulliparous and non-pregnant
- Age at study initiation: not specified
- Weight at study initiation: not specified
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: min 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-72
- Humidity (%): 39-81
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.069 g
- Concentration (if solution): 100%

VEHICLE
- no vehicle used
Duration of treatment / exposure:
24 h
Observation period (in vivo):
1 h, 24 h, 48 h, 72 h, and up to 10 days
Number of animals or in vitro replicates:
4 males and 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: Follwing observations at 24 h

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.6
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Reversibility:
fully reversible within: 48h
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.6
Reversibility:
fully reversible within: 72h
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
Exposure to the test article produced iritis in 5/6 test eyes at the 1 hour scoring interval. The iridal irritation resolved completely in all animals at the 24 hour scoring interval. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1 hour scoring interval. The conjunctival irritation diminished during the remainder of the testperiod and resolved completely in all animals by study day 10. No corneal opacity, iritis or conjunctivitis was observed in the control eyes.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In a test conducted similar to OECD TG 404, single doses of 0.5 g test substance moistened with saline were applied to the clipped skin or New Zealand White rabbits. Additionally, 0.5 g of test substance was applied on one half of the shorn area where the epidermis had been scarified. The exposure time was 24 hrs. The resulting reactions were evaluated at 24, 48 and 72 hrs after application. The dermal irritation was scored and recorded according to the system of Draize.

Following application to the intact skin, only one animal exhibited erythema of intact skin 24 hrs after application, this reaction was resolved at the 48 hour time point. No edema was observed in any of the animals at 24, 48 or 72 hrs after application.

Following application to scarified skin, 4 of 6 animals exhibited erythema 24 hrs after application. Erythema was still observed 48 hrs after application in one of those animals. No oedema was observed in any of the animals at 24, 48 or 72 hrs after application.

Eye irritation:

Two studies are available regarding eye irritation.

A test for irritation of eyes was carried out by applying single doses each of 0.0690 g of test substance into the conjunctival sac of the right eye of 6 New Zealand White rabbits (4 males and 2 females). The eyes of the rabbits were rinsed using 0.9% physiological saline following macroscopic observations at the 24-h scoring interval. The resulting reactions were evaluated at 1, 24. 48 and 72 hrs after the treatment and at d 7 and 10 after application. The Draize scale was used to assess the degree of irritation.

Exposure to the test article produced iritis in 5 of 6 animals at the 1-h scoring interval. The irritation resolved completely in all animals at the 24 h scoring interval. Conjunctivitis (redness, swelling and discharge) was noted in 6 of 6 animals at the 1-h scoring interval. The conjunctival irritation diminished during the remainder of the test period and resolved completely in all animals by study d 10. The maximum conjunctiva score observed at 24/48/72 hrs was 1, the maximum chemosis score observed in this interval was 0.6.

A test for irritation of eyes was carried out by applying single doses each of 0.1 g test substance premixed with one drop of 0.9% NaCl-solution into the conjunctival sac of the left eye of 9 New Zealand rabbits. 1 min after the application of the test substance the eye of 3 animals was flushed with physiological sodium chloride solution. The eye of the remaining 6 animals was flushed after 24 hrs. The resulting reactions were evaluated at 1, 7, 24, 48 and 72 hrs after the treatment. A scale similar to the system of Draize was used to assess the degree of irritation.

In the rabbits whose eyes were rinsed 24 hrs after the application of the test substance following signs were observed: slight signs of irritation at iris (3/6 animals at 1 h scoring interval, no iritis was observed at 24/48/72h scoring interval), slight redness or redness of the conjunctivae (5/6 animals at 1 h scoring interval, 6/6 animals at 7 h scoring interval, 4/6 animals at 24 h scoring interval and 1/6 animals at 48 h scoring interval, maximum score in 24/48/72h interval was 0.6 in animal #5), swelling of lids and nictitating membranes (5/6 animals at 1 h scoring interval, 1/6 animals at 7 h scoring interval) and discharge with moistening of the lids (6/6 animals at 1 h scoring interval, 1/6 animals at 7 h scoring interval). Corneal opacity was not observed at any time point. All animals had recovered on d 3.

In the rabbits whose eyes were rinsed one minute after the application of the test substance the same signs of irritation at iris and conjunctivae were observed but fewer animals were involved. All those animals had recovered on d 2.

Justification for classification or non-classification

Based on the data available and according to Regulation (EC) 1272/2008 (CLP), no classification for skin and eye irritation is warranted.