Registration Dossier

Administrative data

Description of key information

Skin irritation: Slightly irritating
Eye irritation: Causes serious 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: FHSA
Principles of method if other than guideline:
24 hour exposure period on abraded and intact skin. Treated sites examined for reaction to treatment 24 and 72 hours following exposure.
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): TK 10 496
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: In-house breeding
- Age at study initiation: 12 - 15 weeks
- Weight at study initiation: 2.5 - 2.7 kg
- Housing: Individually caged
- Diet (e.g. ad libitum): Styles-Oxoid commercial rabbit diet, ad libitum
- Water (e.g. ad libitum): Sterile filtered water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21 deg C
- Humidity (%): 50 - 70%
- Photoperiod (hrs dark / hrs light): 10 hours light / 14 hours dark cycle
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: 50% (aq) polyethylene glycol
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.0 mL (500 mg test substance)
- Concentration (if solution): 10 g test substance mixed with 11 mL 50% (aq) polyethylene glycol
Duration of treatment / exposure:
24 hours
Observation period:
24 and 72 hours an 6 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Test sites: One abraded, one intact site / animal
- Type of wrap if used: Gauze pad covered with aluminium foil held in place by self adhesive bandage

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

SCORING SYSTEM: Draize scale
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test - observations at 24 and 72 hours only

Intact skin

Animal No.

Erythema

Oedema

24 hours

72 hours

24 hours

72 hours

11 M

0

0

1

0

13 M

0

0

0

0

15 M

0

0

1

0

12 F

0

0

2

0

14 F

0

0

0

0

16 F

0

0

0

0

Mean

0.0

0.33

 

Abraded skin

Animal No.

Erythema

Oedema

24 hours

72 hours

24 hours

72 hours

11 M

1

0

2

1

13 M

1

0

0

0

15 M

1

0

1

0

12 F

0

0

2

0

14 F

1

0

0

0

16 F

1

0

1

0

Mean

0.42

0.58

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
Primary skin irritation has been investigated according to FHSA test methods. The substance was slightly irritating to the skin of the albino rabbit.
Executive summary:

Primary skin irritation has been investigated according to FHSA test methods with 24 hours exposure to intact and abraded skin. The substance was slightly irritating to the skin of the albino rabbit.

Exposure was for a 24 hour period in contrast with 4 hours required by current OECD/EU test methods. However, the information obtained clearly demonstrate the substance to be only slightly irritating and classification as a skin irritant would not be required under the EU/GHS classification scheme.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: FHSA
Principles of method if other than guideline:
Test substance administered to the eye of 6 rabbits. Treated eyes of 3 rabbits washed after 30 seconds. Reaction assessed after 1, 24, 48 and 72 hours, 6, 10 and 14 days
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report):TK 10 946
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: In-house breeding
- Age at study initiation: 12 - 15 weeks
- Weight at study initiation: 2.5 - 2.7 kg
- Housing: Individually caged
- Diet (e.g. ad libitum): Styles-Oxoid commercial rabbit diet, ad libitum
- Water (e.g. ad libitum): Sterile filtered water, ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21 deg C
- Humidity (%): 50 - 70%
- Photoperiod (hrs dark / hrs light): 10 hours light / 14 hours dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
Single administration. The eyes of 3 animals washed 30 seconds after administration
Observation period (in vivo):
1, 24, 48 and 72 hours, 6, 10 and 14 days
Number of animals or in vitro replicates:
6, 3 unwashed and 3 washed
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, 3 rabbits, 200 mL warm water
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: fluorescein staining to aid visualisation of corneal lesions
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 6 days

 

 

Unwashed

 

 

Animal Number: 11

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

2

 

2

 

3

 

3

 

2

 

 

 

Conjunctivae:

Chemosis:

2

2

2

2

4

 

 

 

Redness:

2

3

3

3

2

 

 

 

Iris:

 

Inflammation:

 

0

 

1

 

1

 

1

 

1

 

 

 

 

 

Cornea:

 

Opacity:

 

2

 

1

 

1

 

1

 

2

 

 

 

 

Area:

4

4

4

4

4

 

 

 

 


 

 

Unwashed

 

 

Animal Number: 13

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

3

 

3

 

3

 

3

 

2

 

 

 

Conjunctivae:

Chemosis:

2

3

3

3

3

 

 

 

Redness:

2

3

3

3

3

 

 

 

Iris:

 

Inflammation:

 

0

 

1

 

1

 

1

 

1

 

 

 

 

 

Cornea:

 

Opacity:

 

2

 

1

 

1

 

1

 

2

 

 

 

 

Area:

4

4

4

4

3

 

 

 

 


 

 

Unwashed

 

 

Animal Number: 12

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

2

 

3

 

3

 

3

 

3

 

 

 

Conjunctivae:

Chemosis:

3

3

2

2

3

 

 

 

Redness:

2

3

3

3

3

 

 

 

Iris:

 

Inflammation:

 

0

 

1

 

1

 

1

 

1

 

 

 

 

 

Cornea:

 

Opacity:

 

2

 

1

 

1

 

2

 

2

 

 

 

 

Area:

4

4

4

3

3

 

 

 

 


 

 

Washed

 

 

Animal Number: 15

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

2

 

2

 

2

 

1

 

0

 

0

 

0

Conjunctivae:

Chemosis:

2

3

2

2

1

0

0

 

Redness:

2

3

3

3

3

3

1

 

Iris:

 

Inflammation:

 

1

 

1

 

1

 

0

 

0

 

0

 

0

 

 

Cornea:

 

Opacity:

 

1

 

1

 

1

 

1

 

1

 

1

 

1

 

Area:

4

4

4

4

4

2

1

 

 


 

 

Washed

 

 

Animal Number: 14

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

3

 

3

 

2

 

1

 

0

 

1

 

0

Conjunctivae:

Chemosis:

3

3

2

2

1

1

1

 

Redness:

2

3

3

3

3

3

3

 

Iris:

 

Inflammation:

 

0

 

0

 

0

 

0

 

0

 

0

 

0

 

Cornea:

 

Opacity:

 

1

 

1

 

1

 

1

 

1

 

1

 

1

 

Area:

4

4

4

3

3

1

1

 


 

 

Washed

 

 

Animal Number: 16

 

 

Ocular reaction

Region of eye

Parameter

Hours

Days

 

 

1

24

48

72

6

10

14

 

 

Discharge:

 

2

 

3

 

2

 

1

 

0

 

0

 

0

Conjunctivae:

Chemosis:

2

2

2

1

0

0

0

 

Redness:

2

3

3

3

3

3

3

 

Iris:

 

Inflammation:

 

0

 

0

 

0

 

0

 

0

 

0

 

0

 

Cornea:

 

Opacity:

 

1

 

1

 

1

 

1

 

1

 

1

 

1

 

Area:

3

4

2

2

2

1

1

 

 

Unwashed

 

 

Animal

Number

Conjunctival

Redness

 

 

Conjunctival

Chemosis

 

Iris

Inflammation

 

Corneal

Opacity

 

11

13

12

3.0

3.0

3.0

2.0

3.0

2.3

1.0

1.0

1.0

1.0

1.0

1.3

 

The mean score recorded for each animal is the average of the individual scores observed at the 24, 48 and 72 hour examinations.

 

 

 

Washed

 

 

Animal

Number

Conjunctival

Redness

 

 

Conjunctival

Chemosis

 

Iris

Inflammation

 

Corneal

Opacity

 

15

14

16

3.0

3.0

3.0

2.3

2.3

1.7

0.7

0.0

0.0

1.0

1.0

1.0

 

The mean score recorded for each animal is the average of the individual scores observed at the 24, 48 and 72 hour examinations.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Primary eye irritation has been investigated in the rabbit. Hexahydrophthalic anhydride causes serious eye damage.
Executive summary:

Acute eye irritation has been investigated in the rabbit following administration of a single dose and following FHSA test methods, which are similar to current OECD test methods. Hexahydrophthalic anhydride causes serious eye damage.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Primary skin irritation has been investigated according to FHSA test methods with 24 hours exposure to intact and abraded skin. The substance was slightly irritating to the skin of the albino rabbit. Exposure was for a 24 hour period in contrast with 4 hours required by current OECD/EU test methods. However, the information obtained clearly demonstrate the substance to be only slightly irritating and classification as a skin irritant would not be required under the EU/GHS classification scheme.

Acute eye irritation has been investigated in the rabbit following administration of a single dose and following FHSA test methods, which are similar to current OECD test methods. The substance was determined to be cause serious eye damage.


Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin and eye irritation, the test item is not classified as a skin irritant, but is to be classified as eye damaging cat. 1, H318 (causes serious eye damage) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.