Registration Dossier

Administrative data

Description of key information

No irritant potential was detected in studies on rabbit skin and eyes in vivo

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Test performed before OECD and GLP guidelines. Important aspects (dosing, observation times, grading criteria) comparable with current OECD guidelines
Qualifier:
according to guideline
Guideline:
other: Regulation according to US Federal Hazardous Substance Labeling Act
Version / remarks:
17.09.1964
GLP compliance:
no
Remarks:
pre-guideline study
Species:
rabbit
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
other: shaved intact or shaved abraded with a scarifying instrument
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
24 h
Observation period:
examinations: 24 and 72 h after application, i.e. 0 and 48 h after the end of treatment/exposure
Number of animals:
3 males and 3 females
Details on study design:
0.5 g of the test substance is spread on a 25 cm2 gauze patch, which is applied on the abraded and intact skin of 6 rabbits, clipped free of hair under occlusive conditions. After 24 hours of exposure, the patches are removed. Reactions are recorded 0 and 48 h after the end of exposure.

Irritation parameter:
edema score
Basis:
animal: # 1-6 each
Time point:
other: mean of 0 and 48 h after the end of exposure
Score:
0
Max. score:
4
Reversibility:
other: no signs of irritation (edema) at any time
Remarks on result:
other: intact and abraded skin
Irritation parameter:
erythema score
Basis:
animal: # 1-6 each
Time point:
other: mean of 0 and 48 h after the end of exposure
Score:
0
Max. score:
4
Reversibility:
other: no signs of irritation (erythema) at any time
Remarks on result:
other: intact and abraded skin
Irritant / corrosive response data:
No skin reactions were observed in any animal at any time point.
At the first reading after end of exposure discolored skin, caused by the test item, was noted in all animals. This effect was no longer evident at the second reading 48 hours after end of exposure.
Other effects:
one female animal died (not test material related).
Interpretation of results:
GHS criteria not met
Remarks:
Regulation (EC) No 1272/2008
Conclusions:
According to the classification criteria of Regulation (EC) No 1272/2008 the test material is not irritating to skin under these test conditions.
Executive summary:

The test material was subject to an acute dermal irritation/corrosion test in 6 rabbits according to the regulation of the US Federal Hazardous Substance Labeling Act. Both intact and scarified skin sites of six rabbits were exposed to 500 mg test substance for 24 h under occlusive conditions and the skin responses were examined 0 and 48 h after the end of exposure. No signs of irritation were observed.

Therefore, the test item has not to be classified for skin irritation according to Regulation (EC) No 1272/2008.

 

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
according to OECD 405, GLP not specified
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Directive 79/831/EEC
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Remarks:
KFM
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, 4414 Fuellingsdorf, Switzerland
- Age at study initiation: 14 to 15 weeks
- Weight at study initiation: 2.5 to 2.7 kg
- Housing: iindividually in stainless steel cages equipped with an automatic cleaning and drinking system
- Diet (e.g. ad libitum): pelleted standard rabbit maintenance diet Kliba #341, batch 92/83 (Klingentalmuehle AG)
- Water (e.g. ad libitum): tap water
- Acclimation period: four days under test conditions, with a pre-treatment health examination by a veterinarian

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3, two females and one male
Details on study design:
a single dose of 0.1 g was administered to the left eye of each animal. The right eye remained untreated and was used as the reference control respectively. The eyes were not rinsed.


SCORING SYSTEM:
the eyes of each animal were examined 1, 24, 48 and 72 hours after administration. The irritation was assessed according to the OECD guideline 405. the corrosive properties of the test item and the color of the treated eyes were described and recorded.


TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
eye examinations were meda with a sllit-lamp 30 SL (C. Zeiss AG) and a Varta Cliotrix diagnostic lamp

Body weights were recorded at pre-test, day 1 and at termination of the study on a Mettler PK 4800 balance.
All animals were killed at the end of the observation period by an intraveneous injection of T61 (Hoechst) into the ear vein.


Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not relevant since no signs of irritation recorded at any observation time
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not relevant since no signs of irritation recorded at any observation time
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: 125 (M)
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal: 126 (F)
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal: 127 (F)
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks:
score 1 was still evident after 72 hours; but signs of irritation are regarded to reverse within a prolonged observation period of 21 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all animals
Time point:
24/48/72 h
Score:
0.89
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
Ocular Reactions

Blue coloured staining of the conjunctival membrane was noted in all animals at all observations.
No corneal or iridial effects were noted during the study.
Severe discharge was observed in all animals 1 hour after administration.
Moderate conjunctival irritation was noted in all treated eyes 1 hour after treatment with minimal conjunctival irritation noted at the 24 and 48 Hour observations.
2 treated eyes appeared normal at the 72-Hour observation, in one animal score 1 was still evident.

Table 1: individual results

rabbit no

evaluation interval

cornea opacity

Iris

conjunctivae

score

chemosis

score

discharge

staining

125 (M)

1 hour

0

0

1

2

x

x

126 (F)

 

0

0

1

2

x

x

127 (F)

 

0

0

1

2

x

x

125 (M)

24 hours

0

0

1

2

-

x

126 (F)

 

0

0

1

2

-

x

127 (F)

 

0

0

1

2

-

x

125 (M)

48 hours

0

0

1

0

-

x

126 (F)

 

0

0

1

1

-

x

127 (F)

 

0

0

1

1

-

x

125 (M)

72 hours

0

0

0

0

-

x

126 (F)

 

0

0

0

0

-

x

127 (F)

 

0

0

1

0

-

x

Interpretation of results:
GHS criteria not met
Conclusions:
The test item has not to be classified as eye irritant according to Regulation (EC) no 1272/2008.
Executive summary:

The primary eye irritation potential of the test item was investigated according to OECD test guideline No. 405 and Method B.5. The test item was applied by instillation of 0.1 g into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48, 72 hours after test item instillation. 

The mean score was calculated (separately) for each animal across three scoring times (24, 48 and 72 hours after instillation) for corneal opacity, iritis, redness and chemosis of the conjunctivae. No signs of irritation were recorded for corneal opacity and iritis in all animals. The mean score for chemosis was 0.89. The mean score for conjunctival reddening was 0.67 in two animals, for the remaining animal 1.0. 

The instillation of the test item into the eyes caused a severe discharge at the first examination after 1 hour. Blue coloured staining of the conjunctival membrane was noted in all animals at all observations.

With the exception of on female all signs of irritation were reversible and were no longer evident 72 hours days after treatment. Score 1.0 conjuctival reddening observed 72 hours after treatment in one animal is regarded to reverse within a prolonged observation period of 21 days.

No clinical signs of toxicity were observed.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

According to the findings in this study, the test item does not meet the criteria for classification according to Regulation (EC) no 1272/2008.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

no classification

No irritant potential was detected in studies on rabbit skin and eyes in vivo