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Description of key information

For skin and eye irritation valid in-vivo studies in rabbits according to OECD TG 404 and OECD TG 405 are available.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
other: New Zealand
Type of coverage:
other: patch 2.5*2.5 cm pulp
Preparation of test site:
abraded
Vehicle:
other: polyethylene glycol
Controls:
not specified
Duration of treatment / exposure:
4 hours
Observation period:
The animals were observed after 30 minutes, 60 minutes, 24, 48 and 72 hours after patch removal. Due to the fact that after 72 hours still findings in the skin could be observed, additional observations after 7, 14, and 22 days were performed.
Number of animals:
3
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.1
Max. score:
4
Reversibility:
fully reversible within: 14 days
 Time after patch removal        30 -60 min        24 hours        48 hours        72 hours         7 days    14 days         22 days   
 Animal No.  1  2  3  1  2  3  1  2  3  1  2  3  1  2  3  1  3 1  2
 Formation of erythema and eschar  2  2  1  2  1  2  2  2  2  2  3  2  1*  2  1*  0  0  0  0  0  0
 Formation of edema  2  2  1  1  0  2  1  2  1  1  1  1  0  1  0  0  0  0  0  0  0
 Surface of skin                                          
 -dry, rough                    x  x  x  x  x  x    x        
 - fine-flaked                            x      x        
 -coarse-flaked                          x    x  x    x      
 - hardened                              x            
 - parchmenty                                        
 Skin discolouration                                          
 -small surface: light brown          x      x    x  x  x                  
 -large surface: light brown        x      x            x    x            

*- thickened, reddish-bluish, circular location (diameter 1 -1.5 cm).

Interpretation of results:
GHS criteria not met
Executive summary:

In a skin irritation study according to OECD TG 404, 3 hours before starting the experiment, 3 rabbits were depilated in the dorsal area of the torso. Only animals having an intakt skin were used. The test substance (made into a paste with polyethylene glycol) was applied to the skin using a patch. The patch was removed after 4 hours and the skin was washed with lukewarm water.

30 to 60 minutes up to 7 days after patch removal the treated skin of the animals showed marginal observable up to moderate erythema and marginal observable up to slight edema. Swelling was observed and the skin was colored on a small up to large surface, dry, rough, sclerotic and parchmenty. 14 days p.a. no erythema or edema were observed anymore. The skin surface was dry-rough. in 2 rabbits a swelling of skin with and a reddish- bluish colour was abserved. After 22 days all signs were reversible.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: One eye of each rabbit served as control
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48, 72 hours, 7 days after application of test substance the eyes were examined
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
reddening of conjunctiva
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2.4
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Remarks:
swelling of conjunctivae
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Other effects:
One hour after application of test substance clearly defined swelling of the conjunctiva was observed. Some bloodvessels showed a defined hyperemia. The iris was reddened in two animals. On the cornea diffuse opacity regions were seen. These findings came along with white-brownish defluxion.
24 up to 72 Hours after application of test substance slight to clear swelling of conjunctiva was observed. The conjunctiva showed a considerable hyperemia up to diffuse strong reddening. The iris of all animals was reddened. On the cornea diffuse opacoty regions were seen. In two animals bleeding in the conjunctiva were observed. These findings came along with a white defluxion.
7 days after application of the test substance the appearance of irritation was reversible.

Results:

 Time post application        1 hour        24 hours        48 hours       72 hours         7 days
 Animal Number  1  2  3  1  2  3  1  2  3  1  2  3  1  2  3
 Swelling of conjunctiva  2  2  2  2  2  1  1  1  1  1  1  1  0  0  0
 Reddening of conjunctiva  1  1  1  2  1  2  3  3  3  3  2  3  0  0  0
 Iris  0  1  1  1  1  1  1  1  1  1  1  1  0  0  0
 Corneal turbidity  1  1  1  1  1  1  1  1  1  1  1  1  0  0  0
 Fluorescein-Test        2  3  2        1  4  0  0 0
 Eye defluxion                              
 -white-brownish  x  x  x                        
 -white        x  x  x  x    x  x    x      
Bloody Conjunctiva    x  x  x  x  x  x  x  x  x  x  x      
 Reddened Iris    x  x  x  x  x  x  x  x  x  x  x      
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Executive summary:

In an eye irritation study according to OECD TG 405 the test substance was tested in the eyes of 3 New Zealand White rabbits.

24 hours before application of test substance, the eyes of the test rabbits were examined to detect posible damages on the cornea. Only animals showing no findings were used. 100 mg test substance was applied in a single dose into the conjunctival sac of the left eye of the test animals, the other eye served as control. 1, 24, 48, 72 hours and 7 days after application of test substance the eyes were examined.

One hour after application of test substance clearly defined swelling of the conjunctiva was observed. Some bloodvessels showed a defined hyperemia. The iris was reddened in two animals. On the cornea diffuse opacity regions were seen. These findings came along with white-brownish defluxion.

24 up to 72 Hours after application of test substance slight to clear swelling of conjunctiva was observed. The conjunctiva showed a considerable hyperemia up to diffuse strong reddening. The iris of all animals was reddened. On the cornea diffuse opacoty regions were seen. In two animals bleeding in the conjunctiva were observed. These findings came along with a white defluxion.

7 days after application of the test substance the appearance of irritation was reversible.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Eye Irrit. 2 ( H319: Causes serious eye irritation.) is justified.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

According to Directive 67/548 EWG 3-chloro-p-toluidine was classified as R38 (irritating to skin). According to CLP a classification for skin irritation is not required.

Justification for classification or non-classification

In a OECD Guideline study (404) with rabbits, the dermal application of 0.5 g of the test substance to three animals for 4 hours, a mean erythema score of 2 and an edema score of 1.1 was found.

The findings were reversible within 14 days. According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

In an eye irritation study according to OECD TG 405 the test substance was tested in the eyes of 3 New Zealand White rabbits.100 mg test substance was applied in a single dose into the conjunctival sac of the left eye of the test animals, the other eye served as control. 1, 24, 48, 72 hours and 7 days after application of test substance the eyes were examined.

A mean cornea opacity score of 1, a mean conjunctiva score of ca. 2.4, a mean iris score of ca.1 and a mean chemosis score of ca. 1.2 were found. The findings were reversible within 7 days.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Eye Irrit. 2 ( H319: Causes serious eye irritation) is justified.

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