Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Undiluted o-toluidine was applied to the intact and to the scarified skin of the flank of rabbits under occlusive conditions (according to Fed. Reg, 38, No, 187, §1500.41, p. 27029). Overall, o-toluidine was evaluated as skin irritating.
An eye irritation study was conducted on 6 rabbits, according to Fed. Reg. 38 No 187,1500.42, 1973. o-toluidine was judged to be highly irritating and not all effects were fully reversible during the observation time of 8 days..

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:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given
Qualifier:
according to guideline
Guideline:
other: Draize Test according Fed. Reg, 38, No,187, §1500.41, p. 27029 (1973/sept./ 27)
Principles of method if other than guideline:
Draize Test according Fed. Reg, 38, No,187, §1500.41, p. 27029 (1973/sept./ 27)
GLP compliance:
no
Remarks:
GLP was not mandatory at the time of the study
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Germany
- Age at study initiation: male: 3.1kg, 2.88kg, 2.71kg; female: 2.94 kg, 2.79kg, 3.17kg



Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Undiluted o-Toluidine was applied on a cotton pad (2.5cmx2.5cm) for application on the skin
Duration of treatment / exposure:
24 hour(s)
Observation period:
After application of patch: 24h, 48h, 72h and 7 days and 8 days
Number of animals:
6
Details on study design:
Each animal received two applications of the test material. One on the intact skin of the right flank and the other one on the scarified skin of the left flank. 24h, post application, the skin of the animals were washed with water. The assessment of the dermal changes was based on the OECD Draize scoring method. Moreover, the animals were observed for mortality and clinical signs of toxicity
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24h, 48h, 72h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24h, 48h, 72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24h, 48h, 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
with 8 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 24h, 48h, 72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 24h, 48h, 72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 24h, 48h, 72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24h, 48h, 72h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24h, 48h, 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24h, 48h, 72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
within 8 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: 24h, 48h, 72h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 24h, 48h, 72h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 8 days
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 24h, 48h, 72h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritant / corrosive response data:
The treatment led to slight or moderate erythema and moderate edema in 5/6 animals up to 72h and 24h after start of the application, respectively. At 72 h after application, the same five animals exhibited scaling, which persisted till day 8 of the study. Necrosis (soft, parchment like or leathery) was observed in one animal till the termination of the study. The clinical finding of the necrosis was confirmed by macroscopic pathology.

Other effects:
Systematic Toxicity: No mortality occurred. There were no clinical signs of systemic toxicity from the dermal exposure

Scoring Method used: OECD Draize scores

Time (hrs)

Individual scoring

Animal 1

Animal 2

Animal 3

Animal 4

Animal 5

Animal 6

Erythema

24 h

2

2

4

2

2

2

48 h

2

2

4

2

2

2

72 h

2

1

4

1

1

1

mean

2

1.66

4

1.66

1.66

1.66

Edema

24 h

2

2

2

2

2

2

48 h

2

2

2

2

2

2

72 h

0

0

2*

0

0

0

mean

1.33

1.33

2

1.33

1.33

1.33

Time (hrs)

Individual scoring

Animal 1

Animal 2

Animal 3

Animal 4

Animal 5

Animal 6

Erythema

 

8 days

0

0

4

0

0

0

 

Edema

 

8 days

0

0

2*

0

0

0

 

*= signs extends beyond the area of exposure

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS-CLP
Executive summary:

BASF (1979)

Undiluted o-toluidine was applied to the intact and to the scarified skin of the flank of rabbits under occlusive conditions (according to Fed. Reg, 38, No, 187, §1500.41, p. 27029). Following the 24-hour treatment time the treated area was washed with water. Slight to moderate erythema and moderate edema of the intact skin were observed for 72 hours. At 72 hours these animals exhibited scaling, which was still observed on day 8. Necrosis was observed in 1/6 animals (intact skin).

Overall, o-toluidine was evaluated as skin irritating.

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
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given (comparable to guidelines/standards)
Qualifier:
according to guideline
Guideline:
other: Fed. Reg. 38, No. 187, §1500.42, p. 27019
Principles of method if other than guideline:
Draize test
GLP compliance:
no
Remarks:
GLP was not mandatory at the time of the study
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
-Source: Gaukler; Germany
-Sex: male and female
-Age at test initiation: no data
-Weight at test initiation: male: 3.12kg, 2.91kg, 2.76kg, 2.99kg; female: 2.50kg, 2.61kg
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
100 µl of the test substance were applied into the conjunctival sac of one eye of each of 6 White Vienna rabbits
Duration of treatment / exposure:
single eye instillation, the lids are then gently held together for one second and the animal is released
Observation period (in vivo):
The animals were observed once on the treatment day and 24, 48, 72 hours as well as 8 days after application
Number of animals or in vitro replicates:
6
Details on study design:
100 µl of the test substance were applied into the conjunctival sac of one eye of each of 6 White Vienna rabbits; the lids are then gently held together for one second and the animal is released.The animals were observed once on the treatment day and 24, 48, 72 hours as well as 8 days after application : SCORING SYSTEM: according to Draize Score


Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48, and 72 hours
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48, and 72 hours
Score:
0.6
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48, and 72 hours
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24, 48, and 72 hours
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritant / corrosive response data:
Treatment led to slight corneal opacity, slight to moderate conjunctival edema and redness. All findings were not fully reversible within the 8 days observation period. The control eyes, which were not treated did not show any reaction except for one animal, which showed slight conjunctival redness after 48h.

Time (hrs)

Individual scoring

Animal 1

Animal 2

Animal 3

Animal 4

Animal 5

Animal 6

Corneal opacity

24 h

1

1

1

1

1

1

48 h

1

1

1

*

1

1

72 h

1

1

1

1

1

1

Mean

1

1

1

1

1

1

Iris

24 h

0

0

0

0

1

0

48 h

0

0

1

*

1

1

72 h

1

1

1

1

1

1

Mean

0.33

0.33

0.66

0.5

1

0.66

Redness

24 h

2

2

2

2

2

2

48 h

2

2

2

*

2

2

72 h

2

2

2

2

2

2

Mean

2

2

2

2

2

2

Chemosis

24 h

2

2

2

2

2

2

48 h

1

2

2

2

2

2

72 h

1

2

1

2

1

1

Mean

1.33

2

1.66

2

1.66

1.66

*= evaluation not possible, because eyelids sticked together

Time (hrs)

Individual scoring

Animal 1

Animal 2

Animal 3

Animal 4

Animal 5

Animal 6

Corneal opacity

8 days

1

1

1

1

1

1

Iritis

8 days

1

1

1

1

1

1

Redness

8 days

1

1

1

1

1

1

Chemosis

8 days

1

1

0

1

1

0
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Executive summary:

BASF, 1979:

An eye irritation study was conducted on 6 rabbits, according to Fed. Reg. 38 No 187,1500.42, 1973. o-toluidine was judged to be irritating due to slight corneal opacity of the total corneal area, slight to moderate conjunctival edema and redness. The effects were not fully reversible within the short observation time of 8 days instead of 21 days as usual nowadays.

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

Additional information

Skin irritation test

Undiluted o-toluidine was applied to the intact and to the scarified skin of the flank of rabbits under occlusive conditions (according to Fed. Reg, 38, No, 187, §1500.41, p. 27029). Following the 24-hour treatment time the treated area was washed with water. Slight to moderate erythema and moderate edema of the intact skin were observed for 72 hours. At 72 hours these animals exhibited scaling, which was still observed on day 8. Necrosis was observed in 1/6 animals (intact skin). Overall, o-toluidine was evaluated as skin irritating.

Eye irritation test

An eye irritation study was conducted on 6 rabbits, according to Fed. Reg. 38 No 187,1500.42, 1973. o-toluidine was cautiously judged to be irreversible eye damaging due to slight corneal opacity of the total corneal area, slight to moderate conjunctival edema and redness as incomplete reversibility was observed up to the termination of the study on day 8.


Justification for selection of skin irritation / corrosion endpoint:
This is a reliable study which complies with the requirements of today and is therefore evaluated with Klimisch Score 2

Justification for selection of eye irritation endpoint:
This is a reliable study which complies with the requirements of today and is therefore evaluated with Klimisch Score 2

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irreversible damage

Justification for classification or non-classification

Based on the data used for evaluation a classification as irreversible eye damaging is proposed; based on the data used for evaluation skin iritation property additional classification as skin irritant is required. Thus, according to Regulation (EC) No 1272/2008 o-toluidine should be allocated to category 2 of skin irritant and category 1 irreversible eye damaging substances (H315, H318).