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Administrative data

Description of key information

Skin irritation

Key, OECD 404, rabbit, semiocclusive, skin corrosive

Eye irritation
Key, OECD 405, rabbit, eye damage

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
Study period:
MAR - AUG 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
12 MAY 1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
19 SEP 1984
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK ltd.
- Weight at study initiation: 3 - 3.4 kg
- Housing: single caged (type III cage)
- Diet (e.g. ad libitum): ad libitum (ssniff K 4, Versuchstierdiäten GmbH, Soest/Westfalen)
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: 14 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (+/- 2)
- Humidity (%): 45 - 65
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg, moistened with water

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): moistened patch
Duration of treatment / exposure:
4 hour(s)
Observation period:
14 days
Number of animals:
6 (4 males + 2 females)
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: patch 'Hypoallergen' (Beiersdorf No. 2342), wrap 'Fixomull-Strech Klebevlies' (Beiersdorf No. 2039)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): exposed areas were washed with water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
24 h , 48 h, 72 h, 7 d, 14 d

SCORING SYSTEM:
- Method of calculation: Draize score
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.1
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.1
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
F85
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
F85
Time point:
24/48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
F85
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
G88
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
G88
Time point:
24/48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
G88
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
E91
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
E91
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
E91
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
E91
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
E91
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
E91
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
J3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
J3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
J4
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
J4
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
J4
Time point:
72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
J4
Time point:
24/48 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
J4
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
J5
Time point:
24/48 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
J5
Time point:
72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
J5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritant / corrosive response data:
In rabbit E91 the application site was necrotic from the 1st day of observation and in rabbits F85 and G88 from the 2nd day of observation. In rabbit J3 there was a necrotic application site at the 1 h assessment time point; in rabbits J4 and J5 the application site was hardened at the 1 h assessment time point. In rabbits F85, G88, E91, J3, J4 and J5, these skin changes persisted until the end of the observation period.
Based on these results the test item is assessed as 'skin corrossive'.
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
EU GHS
Conclusions:
Based on the results of this study the test item is assessed as 'skin corrossive'.
Executive summary:

The test item was tested ina study according to OECD TG 404. 500 mg of the test substance were applied for 4 h on the skin of six rabbits. The post observation time was 14 days. Erythrema and edema were observed in all animals. The findings were not reversible within 14 days. As a result, the test item was classified as corrosive.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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:
MAR - AUG 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
12 MAY 1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
19 SEP 1984
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK ltd.
- Weight at study initiation: 3.1 - 3.7 kg
- Housing: single caged (type III cage)
- Diet (e.g. ad libitum): ad libitum (ssniff K 4, Versuchstierdiäten GmbH, Soest/Westfalen)
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: 14 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (+/- 2)
- Humidity (%): 45 - 65
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
24 hour(s)
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with physiological NaCl solution
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein, UV light
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
F84
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
F84
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
F84
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 d
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
F84
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
D87
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
D87
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 21 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
D87
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 21 d
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
D87
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
D86
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 21 d
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
D86
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 21 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
D86
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 d
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
D86
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 21 d
Irritant / corrosive response data:
A positive fluorescein test was shown up to the 21st day of follow-up. Rabbits D87 and D86 showed a pannus effect from the 14th day of follow-up. In rabbit D86 there was swelling in the lower area of ​​the globe from the 14th day of observation.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
EU GHS
Conclusions:
Based on the results of this study the test item is assessed as 'irreversible effects on the eye', as the effects were irreversible in one out of three animals.
Executive summary:

The test item was tested for eye irritation in a study according to OECD TG 405. Three rabbits received a dose of 100 µL/animal in the conjunctival sac of the eye. After 24 h the eye was washed. The eyes were examined for a postexposure period of 21 days. As a result, the test item induced eye damage, as the effects were irreversible in one out of three animals.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

An in vivo study in rabbits according to OECD TG 404 was performed (Ruf 1986). The following results were obtained:

-mean value of edema score (24, 48, 72 h) = 2.1

-mean value of erythema (24, 48, 72 h) = 2.1

-The findings were not reversible within 14 days

-> As a result, thymol is corrosive to the skin.

Eye irritation

An in vivo study in rabbits according to OECD TG 405 was performed (Ruf 1986). The following results were obtained:

-mean value of conjunctiva score (24, 48, 72 h) = 2.3 (mean value animal 1 -3)

-mean value of the cornea score (24, 48, 72 h) = 2 (mean value animal 1 -3)

-mean value of the iris score (24, 48, 72 h) = 1 (mean value animal 1 -3)

-mean value of the chemosis score (24, 48, 72 h) = 2.1 (mean value animal 1 -3)

-The findings were not reversible within 21 days in one animal


-> As a result, thymol induces eye damage.

Justification for classification or non-classification

Based on the result of the skin irritation/corrosion study a classification as Skin Corr. 1B (H314) according to Regulation (EC) No 1272/2008 is justified. Classification as Eye Dam. 1 (H318) is also triggered by the classification as Skin Corr. 1B.

This outcome also correlates with the harmonised CLP classification of thymol for irritation/corrosion (H314).