Registration Dossier

Administrative data

Description of key information

Diisopropanol-p-toluidin was not irritating on the rabbit skin, but showed eye irritating properties.

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:
other: non GLP OECD guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 1981
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hacking & Churchill Ltd., Huntingdon, UK
- Diet : ad libitum
- Water : ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 40-60 %

- Photoperiod (hrs dark / hrs light):12 hours light/12 hours dark

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 g of the test material
Duration of treatment / exposure:
4 hours
Observation period:
1 hour after application
24 hours after application
48 hours after application
72 hours after application
7 days after application
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 25 mm x 25 mm patch
- Type of wrap if used: elastic, adhesive dressing pervious to air

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Draize Evaluation of dermal irritation (according to OECD guideline 404)
Irritation parameter:
erythema score
Basis:
animal: 1-3
Time point:
other: 1 h, 24 h, 48 h, 72 h, 7 days
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: 1-3
Time point:
other: 1 h, 24 h, 48 h, 72 h, 7 days
Score:
0
Max. score:
4
Conclusions:
After application of the test substance to the skin of rabbits no irritating effects were observed.
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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented scientifically fully acceptable, non-GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 1981
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hacking & Churchill Ltd., Huntingdon, UK
- Diet : ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 40-60 %
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 µL






Duration of treatment / exposure:
24h
Observation period (in vivo):
1h, 24h, 48h, 72 h, 7 days
Number of animals or in vitro replicates:
3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): NaCl solution
- Time after start of exposure: 24 h
- Procedure:Test material was placed in the conjunctival sac of one eye each animal. The lids are then gently held together for about one second in order to prevent loss of the material.

SCORING SYSTEM: Draize Evaluation for eye irritation (according to OECD guideline 405)

TOOL USED TO ASSESS SCORE: optical device, eyes were further examined with the aid of fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 72h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible
Remarks:
within 72h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 h, 48 h, 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible
Remarks:
within 72h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 72h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible
Remarks:
within 72h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean: 24 h, 48 h, 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 72h
Other effects:
Lacrimation was observed in all animals at the 1h reading and in 2/3 animals at the 24h reading.
Conclusions:
The test substance caused eye irritation after application into conjunctival sac of the rabbit eye.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

In a key skin irritation study (Bayer AG, 1984), according to OECD guideline 404, three female rabbits were exposed with 0.5 g dipropoxy-p-toluidin by semiocclusive dressing for 4 hours. Thereafter the dressing was removed and the treated skin area was washed with water. Skin reactions were scored using the grading system according to OECD guideline 404 1h, 24h, 72h and7 days after patch removal. No skin irritating effects could be observed at any of the scoring time points.

In a second dermal irritation study (BASF AG, 1978), performed according to an BASF-internal standard method, two rabbits were dermally exposed to diisopropanol-p-toluidin (dissolved in 50 % water). The test site (intact skin) was covered with an occlusive dressing for 1min, 5 min, 15 min and 20 hours. Furthermore, rabbit ear was exposed to the test substance for 20 hours. Rabbits then were observed for 8 days. Erythema grade 1 observed in one animal at the 24 h reading was the only sign at skin. Diisopropanol-p-toluidin exhibited to be not irritating.

Eye

A first eye irritation study (Bayer AG, 1984) was performed according to OECD guideline 405 and classified as key study. At this 100 µL dipropoxy-p-toluidin was applied to the conjunctival sac of one eye of three rabbits (female). According to the Draize evaluation for eye irritation the effects to the conjunctivae, iris, chemosis, cornea and the lacrimation were scored. The treated eyes were washed 24h after instillation. Diisopropanol-p-toluidin caused slight signs of irritation (corneal opacity, conjunctional redness and chemosis of maximum grade 1 up to 72h after installation and lacrimation up to 24h after installation) only with relevance for C&L according to GHS.

In a second eye irritation study (BASF AG, 1978), performed according to an BASF-internal standard method,

50 mg of diisopropanol-p-toluidin was placed in the conjunctival sac of one eye of two Vienna White rabbits. The eyes were not rinsed. Eye reaction was examined at 1 h, 24 h and 8 days after treatment. The test substance revealed minimal eye irritating effects (conjunctivae score 1, cornea score 1, chemosis score 1) which had not fully revised at the end of the 8 days observation period. This result is not relevant for C&L, as the treated eyes were not rinsed and the effects might have been caused by mechanical irritation due to reminants of the solid test item. Furthermore, the observation period was only 8 days instead of 14 days and the key study, in compliance with OECD 405, did not show any irritating effects relevant for C&L.

Justification for classification or non-classification

Based on the available data dipropoxy-p-toluidin is subject for C&L regarding eye irritation according to Regulation 1272/2008/EC: Cat. 2, H319 "causes serious eye irritation".