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Diss Factsheets

Administrative data

Description of key information

Test substance applied to the skin and eye of three New Zealand White rabbits produces in the 3 animals the outbreak of moderate to important erythema and oedema and very important irritation reaction at the level of the conjunctivae.

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:
23 October to 07 November, 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP study conducted in compliance with OECD Guideline 404 with deviations: age at study initiation, individual animal weights, environmental conditions, purity of test item not reported
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
age at study initiation, individual animal weights, environmental conditions, purity of test item not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL- Source and lot/batch No.of test material: Chimex / Batch M 303- Physical state: Yellowish limpid liquid- Date received: October 9, 1995- Purity test date: July 27, 1995STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: Stored at room temperature, away from the light and heat
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS- Source: elevage BERTHO, 22120 Yffiniac, France- Weight at study initiation: 2.3 kg (average weight)- Housing: Animals were housed individually on floor grids.- Diet: Complete pelleted rabbit maintenance diet Energie H326 (COFNA, 37000 - Tours, France), ad libitum- Acclimation period: 5 daysENVIRONMENTAL CONDITIONS: Environmental conditions and controls in accordance with the requirements of the 86/609/EEC guideline.IN-LIFE DATES: 23 October to 07 November, 1995
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL - Amount(s) applied (volume or weight with unit): 0.5 mL - Concentration (if solution): Undiluted
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48 and 72 h after patch removal and then on Days 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15.
Number of animals:
3 males
Details on study design:
PREPARATION OF TEST SITEApproximately 24 h before the test, fur was removed by clipping from the dorsal area of the trunk of the animals. Only animals with healthy intact skin were used.TEST SITE- Area of exposure: Dorsal area of the trunk- Type of wrap if used: Test material was applied to the clipped skin and covered with a gauze (2 x 2 cm) held in place by means of a 5 x 5 cm wide "Micropore" fastening tape. Then the animal's trunk was wrapped with a 10 cm wide stretch tape (varicose vein tape) fastened by adhesive tape of the same width and placed in such a way so as not to hinder respiratory movements. Then the rabbits were returned to their cages for 4 h at the end of which the dressing and the gauze patch were removed. REMOVAL OF TEST SUBSTANCE - Washing (if done): Residual test material was removed using absorbent paper moistened with water. - Time after start of exposure: 4 hOBSERVATION TIME POINTS- 1, 24, 48 and 72 h after patch removal and then on Days 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15. SCORING SYSTEM: - Draize scale, as described in OECD Guideline 404.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 11 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 11 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 15 days
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Test substance applied as such for 4 h to the skin of the rabbit produces in the 3 animals the outbreak of moderate to important erythema and oedema. These signs of irritation, while decreasing from Day 6, persist until Day 10 in one animal and at the end of the observation period (Day 15) in the two others. Scabs were noticed on Day 7 in two rabbits; they disappeared in about five days and gave way to cicatrices.
Other effects:
None

Table 7.3.1/1: Mean irritant/corrosive response data for each animal at each observation time up to removal of animals from the test

Score at time point

Erythema (Animal no 1 / 2 / 3)

Max. score 4

Oedema (Animal no 1 / 2 / 3)

Max. score 4

1 h

2 / 2 / 2

2 / 2 / 1

24 h

3 / 2 / 3

2 / 2 / 2

48 h

3 / 3 / 3

2 / 2 / 2

72 h

3 / 3 / 3

2 / 2 / 2

Day 5

3 / 3 / 3

2 / 2 / 2

Day 6

2 / 3 / 2

1 / 2/ 1

Day 7

2 / 2 / 2

1 / 2/ 1

Day 8

2 / 2 / 2

1 / 1 / 1

Day 9

2 / 2 / 2

1 / 1 / 1

Day 10

1 / 1 / 1

1 / 1 / 1

Day 11

1 / 0 / 1

1 / 0 / 1

Day 12

1 / - / 2

1 / - / 1

Day 13

1 / - / 2

1 / - / 1

Day 14

1 / - / 2

1 / - / 1

Day 15

1 / - / 2

0 / - / 1

Mean 24, 48 and 72 h

3.0 / 2.7 / 3.0

2.0 / 2.0 / 2.0

- : No reading

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
Under the test conditions, test substance is classified as "Category 1C: corrosive" to the skin according to Regulation (EC) No. 1272/2008 (CLP) and GHS.
Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of the test substance was applied on the clipped skin of three male New Zealand White rabbits. The test substance was held in contact with the skin by means of a semi-occlusive dressing for 4 h. Skin reactions were assessed and scored according to the Draize scale at 1, 24, 48 and 72 h after removal of the dressing and on Days 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15.

Test substance applied as such for 4 h to the skin of the rabbit produces in the 3 animals the outbreak of moderate to important erythema and oedema. These signs of irritation, while decreasing from Day 6, persist until Day 10 in one animal and at the end of the observation period (Day 15) in the two others. Scabs were noticed on Day 7 in two rabbits; they disappeared in about five days and gave way to cicatrices.

 

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 3.0 / 2.7 / 3.0 for erythema and 2.0 / 2.0 / 2.0 for oedema.

Under the test conditions, test substance is classified as "Category 1C: corrosive" to the skin according to Regulation (EC) No. 1272/2008 (CLP) and GHS.

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:
23-26 October 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP study conducted in compliance with OECD Guideline 405 with deviations: age at study initiation, individual animal weights, environmental conditions not reported; non-ocular local and systemic adverse effects not followed
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
age at study initiation, individual animal weights, environmental conditions not reported; non-ocular local and systemic adverse effects not followed
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL- Source and lot/batch No.of test material: Chimex / Batch M 303- Physical state: Yellowish limpid liquid- Date received: October 9, 1995- Purity test date: July 27, 1995STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: Stored at room temperature, away from the light and heat
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: elevage ROUGIER (63370 - St Gervais, d'Auvergne.- Weight at study initiation: 2 kg (average weight)- Housing: Animals were housed individually on floor grids.- Diet: Complete pelleted rabbit maintenance diet Energie H326 (COFNA, 37000 - Tours, France), ad libitum- Acclimation period: 5 daysENVIRONMENTAL CONDITIONS: Environmental conditions and controls in accordance with the requirements of the 86/609/EEC guideline.IN-LIFE DATES: 23-26 October 1995
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
TEST MATERIAL - Amount(s) applied (volume or weight with unit): 0.1 mL/eye - Concentration (if solution): Undiluted
Duration of treatment / exposure:
No washing was done.
Observation period (in vivo):
1, 24, 48 and 72 h after instillation of the test substance. If lesions are too severe, to avoid unnecessary pain, animal is euthanatized.
Number of animals or in vitro replicates:
3 males
Details on study design:
TREATMENTTest substance was placed at a dose of 0.1 mL in the conjunctival sac of the right eye after gently pulling the lower lid away from the eyeball. The lids are then gently held together for about one second in order to prevent loss of the test substance. The other eye, which remains untreated, serves as a control. After a one hour period of contention, the animals were returned to its individual cage.REMOVAL OF TEST SUBSTANCE- Washing: NoSCORING SYSTEM: According to OECD Guideline 405TOOL USED TO ASSESS SCORE: - Ocular reactions were performed with a U. V. and white magnification light. After recording the observations at 24 h, the eyes of all rabbits were examined with the aid of fluorescein.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 h
Max. score:
4
Reversibility:
not reversible
Remarks:
impossible reading
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 h
Max. score:
2
Reversibility:
not reversible
Remarks:
impossible reading
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 h
Max. score:
4
Reversibility:
not reversible
Remarks:
impossible reading
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 h
Max. score:
2
Reversibility:
not reversible
Remarks:
impossible reading
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 h
Max. score:
4
Reversibility:
not reversible
Remarks:
impossible reading
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 h
Max. score:
2
Reversibility:
not reversible
Remarks:
impossible reading
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
One hour after instillation of the substance, very important irritation reactions were noticed at the level of the conjunctivae. The intensity of the conjunctival lesions made it not possible the evaluation of the iris and cornea reactions. A serious damage of iris and cornea was observed in one animal 24 hours after instillation. At the 72 hours reading conjunctival lesions remained unchanged, inflammatory phenomena increased. To avoid unnecessary pain, animals were sacrificed.
Other effects:
None

Table 7.3.2/1: Results of eye irritation

 

Animal no.

4621

4622

4623

Observation points

 

Conjunctiva

Iris

Cornea

Conjunctiva

Iris

Cornea

Conjunctiva

Iris

Cornea

A

B

C

D

E

F

A

B

C

D

E

F

A

B

C

D

E

F

D1 (1 h)

4

3

3

*

*

*

4

3

3

*

*

*

4

3

3

*

*

*

24 h

4

2

3

*

*

*

4

3

3

*

*

*

4

3

3

2

4

*

48 h

4

3

3

*

*

*

4

3

3

*

*

*

4

3

3

*

*

*

72 h

4

3

3

*

*

*

4

3

3

*

*

*

4

3

3

*

*

*

M

4

2.7

3

-

-

-

4

3

3

-

-

-

4

3

3

-

-

-

 

* impossible reading; A: Chemosis; B: Discharge; C: Redness; D: Iris lesion; E: Opacity; F: Opacity area; M: Mean

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the test conditions, test substance is classified as "Irreversible effects on the eye (Category 1)" according to the Regulation (EC) N° 1272-2008 (CLP) and GHS.
Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy male rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted test substance in their right eye while the left eye remained untreated and served as control. The eyelids were then gently held together for about one second to avoid any loss of test substance. At 24 h after treatment, fluorescein solution was instilled into the eyes and they were examined under UV-lamp to detect possible corneal damage. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the method of OECD Guideline 405.

One hour after instillation of the substance, very important irritation reactions were noticed at the level of the conjunctivae. Severity of conjunctival reactions (Chemosis with lids more than half closed) made it not possible the evaluation of cornea and iris lesions. 24 h later, serious lesions of iris and cornea were observed in one rabbit. At the 72 h reading conjunctival lesions remained unchanged, inflammatory phenomena increased. To avoid unnecessary pain, animals were sacrificed.  

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 3.0, 3.0, 3.0 for conjunctivae score and 4.0, 4.0, 4.0 for chemosis score; no impossible reading for cornea and iris.

 

Under the test conditions, test substance is classified as "Irreversible effects on the eye (Category 1)" according to the Regulation (EC) N° 1272-2008 (CLP) and GHS.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of the test substance was applied on the clipped skin of three male New Zealand White rabbits. Test substance applied as such for 4 h to the skin of the rabbit produces in the 3 animals the outbreak of moderate to important erythema and oedema. These signs of irritation, while decreasing from Day 6, persist until Day 10 in one animal and at the end of the observation period (Day 15) in the two others. Scabs were noticed on Day 7 in two rabbits; they disappeared in about five days and gave way to cicatrices.

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy male rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted test substance in their right eye while the left eye remained untreated and served as control. One hour after instillation of the substance, very important irritation reactions were noticed at the level of the conjunctivae. Severity of conjunctival reactions (Chemosis with lids more than half closed) made it not possible the evaluation of cornea and iris lesions. 24 h later, serious lesions of iris and cornea were observed in one rabbit. At the 72 h reading conjunctival lesions remained unchanged, inflammatory phenomena increased. To avoid unnecessary pain, animals were sacrificed.

Justification for selection of skin irritation/corrosion endpoint:

only one study assessing the irritant potential of the substance.

Justification for selection of eye irritation endpoint:

only one study assessing the irritant potential of the substance.

Justification for classification or non-classification

As corrosive effects were observed on the skin of a New-Zealand white rabbits exposed by dermal route to Chimexane CL for 4 h, Chimexane CL is classified as corrosive category 1C according to CLP Regulation (EC) N° (1272-2008).

As very important irritation reaction were observed on the eye of a New-Zealand white rabbits exposed to Chimexane CL, Chimexane CL is classified as "irriversible effects on the eye" category 1 according to CLP Regulation (EC) N° (1272-2008).