Registration Dossier

Administrative data

Description of key information

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:
From Aug. 27, 1981 to Oct. 27, 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Method: Study performed according to method described in Federal Register, Volume 43, 37336, Part 163.81-5 and Federal
Register, Volume 44, 44054, Part 772.112-25 which is equilvalent or similar to OECD Guideline 404.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: MKS Research Inc., 428 Cedar Grove Lane, Somerset, New Jersey 08873
- Weight at study initiation: 2.9-3.8 kg
- Age at study initiation: Adult
- Housing: Individually housed in stainless steel cages with wire mesh walls and floors and automatic watering devices
- Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
- Water (e.g. ad libitum): Filtered tap water, ad libitum
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Air changes (per hr): 14/h
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light cycle
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration (if solution): Undiluted
Duration of treatment / exposure:
24 h
Observation period:
14 d
Number of animals:
Six male
Details on study design:
TEST SITE
- Area of exposure: 1 inch square
- Type of wrap if used: Patches were held in place with Blenderm tape and covered with an occlusive binder consisting of plastic wrap, gauze wrap, adhesive tape and masking tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were wiped (but not washed)
- Time after start of exposure: 24 h


SCORING SYSTEM: Draize scoring system
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 h
Score:
3.3
Max. score:
8
Reversibility:
not reversible
Irritation parameter:
erythema score
Remarks:
With intact skin
Basis:
mean
Remarks:
Mean of left and right side of 6 animals
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Remarks:
With abraded skin
Basis:
mean
Remarks:
Mean of left and right side of 6 animals
Time point:
24 h
Score:
2.17
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Remarks:
With intact skin
Basis:
mean
Remarks:
Mean of left and right side of 6 animals
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Remarks:
With abraded skin
Basis:
mean
Remarks:
Mean of left and right side of 6 animals
Time point:
24 h
Score:
1.42
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Remarks:
Mean of left and right side of 6 animals
Time point:
48 h
Remarks on result:
other: Data not available
Irritation parameter:
edema score
Basis:
mean
Remarks:
Mean of the left and right side of 6 animals
Time point:
48 h
Remarks on result:
other: Data not available
Irritation parameter:
erythema score
Remarks:
With intact skin
Basis:
mean
Remarks:
Mean of left and right side of 6 animals
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Remarks:
With abraded skin
Basis:
mean
Remarks:
Mean of left and right side of 6 animals
Time point:
72 h
Score:
2.25
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Remarks:
With intact skin
Basis:
mean
Remarks:
Mean of left and right side of 6 animals
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Remarks:
With abraded skin
Basis:
mean
Remarks:
Mean of left and right side of 6 animals
Time point:
72 h
Score:
1.42
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
Mean scores at 24 h:
- Erythema score at intact sites: 2.0
- Edema score at intact sites: 1.0
- Erythema score at abraded sites: 2.17
- Edema score at abraded sites: 1.42

Mean scores at 72 h:
- Erythema score at intact sites: 2.0
- Edema score at intact sites: 1.0
- Erythema score at abraded sites: 2.25
- Edema score at abraded sites: 1.42

- Scores for erythema ranged from very slight to severe for intact sites and from well-defined to severe for abraded sites
- Scores for edema ranged from none to slight for both intact and abraded sites
- All animals exhibited irritation at 72 hours
- By day 6, all sites showed eschar formation which persisted at all but 2 sites until termination at Day 13.
Interpretation of results:
Category 2 (irritant)
Conclusions:
Under the test conditions, the test material was considered to be moderately irritating to skin in rabbit.
Executive summary:

A study was conducted to evaluate the skin irritation of the test substance. The study was performed according to a method equivalent or similar to OECD Guideline 404, in compliance with GLP. The substance (0.5 mL) was applied to the intact and abraded skin of rabbits via a 24 h occlusive patch. Scoring was done at 24 and 72 h and continued until Day 13 post-dose. At the 24 and 72 h intervals, scores for erythema ranged from very slight to severe for intact sites and from well-defined to severe for abraded sites. Scores for edema ranged from none to slight for both intact and abraded sites. There were no important differences in skin irritation between intact and abraded sites. All animals exhibited irritation at 72 h. By Day 6, all sites showed eschar formation which persisted at all but 2 sites until termination. Under the test conditions, the primary irritation index was calculated to be 3.3 and therefore the test substance was considered to be moderately irritating to skin in rabbit (Knickerbocker, 1981).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2-3 kg
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2,000 mg/kg bw
- Concentration (if solution): Undiluted
Duration of treatment / exposure:
24 h
Observation period:
14 d
Number of animals:
Five/sex/group
Details on study design:
TEST SITE
- Type of wrap if used: Occlusive binder


SCORING SYSTEM: Draize scoring system
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: Day 14
Score:
ca. 3.9
Max. score:
8
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Day 14
Score:
ca. 3.9
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Day 14
Score:
0
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Remarks:
5 male and 5 female animals
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Remarks:
5 male and 5 female animals
Time point:
48 h
Score:
0.4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Remarks:
5 male and 5 female animals
Time point:
72 h
Score:
0.2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Remarks:
5 male and 5 female animals
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
mean
Remarks:
5 male and 5 female animals
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
mean
Remarks:
5 male and 5 female animals
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Irritant / corrosive response data:
- Mean score at Day 1, 2, 3, 4, 7 and 14 was 1.0, 0.4, 0.2, 2.8, 3.6 and 3.9 respectively
- Maximum erythema score (mean) at Day 1, 2, 3, 4, 7 and 14 was 1.0, 0.4, 0.2, 2.8, 3.6 and 3.9 respectively
- Mean edema score at Day 1, 2, 3, 4, 7 and 14 was 0
Other effects:
- Mortality: 1/10 animals died on Day 4
- Body weight: Reduced body weight gain in 1/10 animals
Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: other: EU CLP
Conclusions:
Under the test conditions, the test material was considered to be moderately irritating to skin in rabbit.
Executive summary:

A study was conducted to evaluate the acute dermal toxicity and skin irritation of the test substance according to a method equivalent or similar to the OECD Guideline 404, in compliance with GLP. The substance was applied at a dose of 2000 mg/kg bw topically to the abraded skin of 5 rabbits/sex via 24 h occlusive patches. All animals were observed twice daily throughout the study and sacrificed on Day 15. A gross post-mortem examination was performed and samples of the treated skin were retained. One death occurred on Day 4 but no specific signs of systemic toxicity were observed. The degree of dermal irritation was scored with the Draize technique on Days 1, 2, 3, 4, 7 and 14. Mean irritation score, maximum erythema score and edema score was 3.9/8, 3.9/4 and 0/4, respectively. Gross post-mortem examination revealed no treatment-related significant effects. Under the test conditions, the test substance was considered to be moderately irritating to skin in rabbit (Koschier, 1981).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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
Study period:
1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: New Zealand White, H.A.R.E. Rabbits For Research, Hewitt, N.J.
- Housing: Individually in wire mesh suspension cages
- Diet (e.g. ad libitum): Certified Rabbit Chow 5322, Ralston Purina Co., ad libitum
- Water (e.g. ad libitum): Potable water, ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 h dark/ 12 h fluorescent light

Vehicle:
unchanged (no vehicle)
Controls:
other: Left eye served as untreated control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Single treatment
Observation period (in vivo):
14 d; eye irritation scored on Days 1, 2, 3, 4, 7, 10 and 13
Number of animals or in vitro replicates:
Nine
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Eyes in three rabbits rinsed with sterile water for 60 sec
- Time after start of exposure: 30 sec


SCORING SYSTEM: Draize method
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
15.1
Max. score:
110
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other: with washout
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
13.6
Max. score:
110
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other: without washout
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Mean of 6 animals
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
iris score
Basis:
mean
Remarks:
mean of 6 animals
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
mean of 6 animals
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
other:
Remarks:
With washout
Irritation parameter:
iris score
Basis:
mean
Remarks:
Mean of 6 animals
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
other:
Remarks:
With washout
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.6
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.67
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.6
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.67
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
conjunctivae score
Basis:
animal: 7
Time point:
24/48/72 h
Score:
1.67
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
With washout
Irritation parameter:
conjunctivae score
Basis:
animal: 8
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
With washout
Irritation parameter:
conjunctivae score
Basis:
animal: 9
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
With washout
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.3
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.3
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3.67
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
Without washout
Irritation parameter:
chemosis score
Basis:
animal: 7
Time point:
24/48/72 h
Score:
2.67
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
With washout
Irritation parameter:
chemosis score
Basis:
animal: 8
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
With washout
Irritation parameter:
chemosis score
Basis:
animal: 9
Time point:
24/48/72 h
Score:
3.67
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other:
Remarks:
With washout
Irritant / corrosive response data:
Irritation to the conjunctivae appeared to dissipate but still persisted at the termination of the study.
For details, see 'table 1' and 'table 2'
Other effects:
- No corneal damage at any time
- All treated eyes responded to light and no iridal score was observed in any rabbit
- Discharge, chemosis and redness of the conjunctivae were observed in all animals
- Rinsing appeared to lessen the irritation

Table 1. Ocular irritation (Draize) scores (mean)

Group

No

Washed

1

2

3

4

7

10

13

1

6

No

18.0

15.3

12.0

13.0

13.3

13.0

11.7

2

3

Yes

15.3

13.3

12.0

13.3

12.7

12.0

10.7

Table 2: Mean ocular irritation scores observed at 24, 48 and 72 h

Animal No. Corneal opacity Iritis Conjunctivae Chemosis
1 0 0 2.6 3.3
2 0 0 2.3 3.3
3 0 0 1.67 3.3
4 0 0 2.6 3
5 0 0 2 3
6 0 0 2.67 3.67
7* 0 0 1.67 2.67
8* 0 0 2 2
9* 0 0 2 3.67

* Eyes in three rabbits rinsed with sterile water for 60 sec

Interpretation of results:
Category 2A (irritating to eyes)
Conclusions:
Under the test conditions, the test material was considered to be irritating to eyes in rabbit.
Executive summary:

A study was conducted to evaluate the ocular toxicity of the test substance in rabbits. The study was performed similar to the OECD Guideline 405. 0.1 mL of the test substance was instilled into the right eye of nine rabbits; the left eye served as an untreated control. One group of six rabbits received no further treatment. In the second group of three rabbits, eyes were rinsed 30 sec post-instillation for 60 sec. Irritation was scored by Draize scoring system at 1, 2, 3, 4, 7, 10 and 13 d post-instillation. Mean irritation scores at 24, 48 and 72 h for animals in group 1 (eyes without washing) were 0/0/2.6/3.3; 0/0/2.3/3.3; 0/0/1.67/3.3; 0/0/2.6/3.0; 0/0/2/3.0 and 0/0/2.67/3.67. Mean irritation scores at 24, 48 and 72 h for animals in group 2 (eyes with washing) were 0/0/1.67/2.67; 0/0/2/2 and 0/0/2/3.67. Irritation to the conjunctivae appeared to dissipate but still persisted at the termination of the study. Mean overall irritation score for 24, 48 and 72 h was 15.1/110 and 13.6/110 in the washed and unwashed eyes, respectively (Chow, 1981).

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Remarks:
on individual irritation score
GLP compliance:
yes
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
other: Left eye served as untreated control
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.1 mL (undiluted)

Duration of treatment / exposure:
Single treatment
Observation period (in vivo):
14 d
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washing done in three animals
- Time after start of exposure: 30 sec


SCORING SYSTEM: Draize system
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: Days 2, 3, 4, 5, 8, 11 and 14
Score:
ca. 18
Max. score:
110
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other: without washout
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: Days 2, 3, 4, 5, 8, 11 and 14
Score:
ca. 15
Max. score:
110
Reversibility:
not fully reversible within: 13 d
Remarks on result:
other: with washout
Irritation parameter:
overall irritation score
Remarks:
Without washout
Basis:
mean
Remarks:
Mean of 6 animals
Time point:
24 h
Score:
18
Max. score:
110
Reversibility:
not fully reversible within: 13 d
Irritation parameter:
overall irritation score
Remarks:
With washout
Basis:
mean
Remarks:
Mean of 6 animals
Time point:
24 h
Score:
15.3
Max. score:
110
Reversibility:
not fully reversible within: 13 d
Irritation parameter:
overall irritation score
Remarks:
Without washout
Basis:
mean
Time point:
48 h
Score:
15.3
Max. score:
110
Reversibility:
not fully reversible within: 13 d
Irritation parameter:
overall irritation score
Remarks:
With washout
Basis:
mean
Remarks:
Mean of 6 animals
Time point:
48 h
Score:
13.3
Max. score:
110
Reversibility:
not fully reversible within: 13 d
Irritation parameter:
overall irritation score
Remarks:
Without washout
Basis:
mean
Remarks:
Mean of 6 animals
Time point:
72 h
Score:
12
Max. score:
110
Reversibility:
not fully reversible within: 13 d
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Score:
12
Max. score:
110
Reversibility:
not fully reversible within: 13 d
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
other:
Remarks:
no effects observed
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
other:
Remarks:
no effects observed
Irritant / corrosive response data:
- Irritation score at Day 2, 3, 4, 5, 8, 11 and 14 in unrinsed group was 18.0, 15.3, 12.0, 13.0, 13.3, 13.0 and 11.7, respectively
- Irritation score at Day 2, 3, 4, 5, 8, 11 and 14 in rinsed group was 15.3, 13.3, 12.0, 13.3, 12.7, 12.0 and 10.7, respectively
Other effects:
- None of the animals had alterations of the cornea or iris
- All rabbits had moderate to severe conjunctival effects
Conclusions:
Under the test conditions, the test material was considered to be mildly irritating to eyes in rabbit.
Executive summary:

A study was conducted to evaluate the ocular toxicity of test substance in rabbits. The study was performed equivalent or similar to OECD Guideline 405, in compliance with GLP. 0.1 mL of the test substance was instilled into the right eye of each rabbit; the left eye served as an untreated control. Eyes were rinsed 30 sec post-instillation and irritation was scored by the Draize system at 1, 2, 3, 4, 7, 10 and 13 days post-instillation. The overall irritation score was 18/110 and 15/110 in the unrinsed and rinsed groups, respectively. Under the test conditions, the test substance was considered to be mildly irritating to eyes in rabbit (Koschier, 1981).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin

A study was conducted to evaluate the skin irritation of the test substance. The study was performed according to a method equivalent or similar to OECD Guideline 404, in compliance with GLP. The substance (0.5 mL) was applied to the intact and abraded skin of rabbits via a 24 h occlusive patch. Scoring was done at 24 and 72 h and continued until Day 13 post-dose. At the 24 and 72 h intervals, scores for erythema ranged from very slight to severe for intact sites and from well-defined to severe for abraded sites. Scores for edema ranged from none to slight for both intact and abraded sites. There were no important differences in skin irritation between intact and abraded sites. All animals exhibited irritation at 72 h. By Day 6, all sites showed eschar formation which persisted at all but 2 sites until termination. Under the test conditions, the primary irritation index was calculated to be 3.3 and therefore the test substance was considered to be moderately irritating to skin in rabbit (Knickerbocker, 1981).

A study was conducted to evaluate the acute dermal toxicity and skin irritation of the test substance according to a method equivalent or similar to the OECD Guideline 404, in compliance with GLP. The substance was applied at a dose of 2000 mg/kg bw topically to the abraded skin of 5 rabbits/sex via 24 h occlusive patches. All animals were observed twice daily throughout the study and sacrificed on Day 15. A gross post-mortem examination was performed and samples of the treated skin were retained. One death occurred on Day 4 but no specific signs of systemic toxicity were observed. The degree of dermal irritation was scored with the Draize technique on Days 1, 2, 3, 4, 7 and 14. Mean irritation score, maximum erythema score and edema score was 3.9/8, 3.9/4 and 0/4, respectively. Gross post-mortem examination revealed no treatment-related significant effects. Under the test conditions, the test substance was considered to be moderately irritating to skin in rabbit (Koschier, 1981).

Eyes

A study was conducted to evaluate the ocular toxicity of the test substance in rabbits. The study was performed similar to the OECD Guideline 405. 0.1 mL of the test substance was instilled into the right eye of nine rabbits; the left eye served as an untreated control. One group of six rabbits received no further treatment. In the second group of three rabbits, eyes were rinsed 30 sec post-instillation for 60 sec. Irritation was scored by Draize scoring system at 1, 2, 3, 4, 7, 10 and 13 d post-instillation. Mean irritation scores at 24, 48 and 72 h for animals in group 1 (eyes without washing) were 0/0/2.6/3.3; 0/0/2.3/3.3; 0/0/1.67/3.3; 0/0/2.6/3.0; 0/0/2/3.0 and 0/0/2.67/3.67. Mean irritation scores at 24, 48 and 72 h for animals in group 2 (eyes with washing) were 0/0/1.67/2.67; 0/0/2/2 and 0/0/2/3.67. Irritation to the conjunctivae appeared to dissipate but still persisted at the termination of the study. Mean overall irritation score for 24, 48 and 72 h was 15.1/110 and 13.6/110 in the washed and unwashed eyes, respectively (Chow, 1981).

A study was conducted to evaluate the ocular toxicity of test substance in rabbits. The study was performed equivalent or similar to OECD Guideline 405, in compliance with GLP. 0.1 mL of the test substance was instilled into the right eye of each rabbit; the left eye served as an untreated control. Eyes were rinsed 30 sec post-instillation and irritation was scored by the Draize system at 1, 2, 3, 4, 7, 10 and 13 days post-instillation. The overall irritation score was 18/110 and 15/110 in the unrinsed and rinsed groups, respectively. Under the test conditions, the test substance was considered to be mildly irritating to eyes in rabbit (Koschier, 1981).

Justification for classification or non-classification

In studies conducted with rabbits, m-TMXDI was irritating to skin, with irreversible erythema and oedema observed in the test animals, as well as to eyes. Hence, it qualifies for classification as Skin Irrit. 2 - H315 (causes skin irritation) and Eye Irrit. 2 - H319 (causes serious eye irritation) according to CLP (EC 1272/2008) criteria.

Respiratory irritation was seen in rat and mouse studies, therefore appropriate risk management measures and the use of personal protection equipment are recommended to reduce exposure at the workplace.