Registration Dossier

Administrative data

Description of key information

The substance N,N-dimethyl-p-toluidine is not a skin and eye irritant.

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)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Procured from GENTOX Bio services., Hyderabad, India
- Age at study initiation: 3 to 4 Months (Approximately)
- Weight at study initiation: Minimum: 1.796 kg and Maximum: 1.998 kg (Prior to Treatment)
- Housing: The animals were housed individually in stainless steel cages.
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rabbit diet (Nutrivet Life Sciences, Pune) ad libitum.
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum
- Acclimation period: 5 days (Animal No.-1) and 7 days (Animal No.-2 and 3)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 19.60 °C, Maximum: 22.30 °C
- Humidity (%): Minimum: 51.10 % , Maximum: 67.40 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: From: To:
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml


Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 female rabbits
Details on study design:
TEST SITE
- Area of exposure: Approximately 24 h prior to treatment, the fur coat of each rabbit was removed from dorsal lumbar region approximately 6 X 6 cm at contralateral sites on each rabbit using clipper, one as control and other site as treatment. Rabbits with healthy intact skin were selected for the study
- % coverage: 6 X 6 cm
- Type of wrap if used: porous gauze dressing and non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton soaked in distilled water
- Time after start of exposure: 4-hour exposure period


SCORING SYSTEM:
Gradation as per draize method
Irritation parameter:
erythema score
Basis:
animal: 1,2,3
Time point:
other: 24, 48 and 72 hours
Score:
0 - 1
Max. score:
3
Reversibility:
no data
Remarks on result:
other: Not irritating
Irritation parameter:
edema score
Basis:
animal: 1,2,3
Time point:
other: 24, 48 and 72 hours
Score:
0 - 0.33
Max. score:
3
Reversibility:
no data
Remarks on result:
other: Not irritating
Irritant / corrosive response data:
The following were observed in treated rabbits.
The patch was removed after 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours after patch removal, evaluated and graded as per draize method.
Animal No. 1, very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation. At 24 hour very slight erythema (barely perceptible) and no oedema was observed. At 48 and 72 hours observation no erythema and no oedema was observed in animal no 1.
Animal No. 2, revealed very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation post patch removal. At 24 hour well defined erythema and very slight oedema (barely perceptible) was observed. At 48 hour very slight erythema (barely perceptible) and no oedema was observed. At 72 hour no erythema and no oedema was observed. Animal No. 3, revealed very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation post patch removal. At 24 hour slight erythema (barely perceptible) and no oedema was observed. At 48 and 72 hour no erythema and no oedema was observed.
The individual mean score at 24, 48 and 72 hours for animal nos. 1, 2 and 3 were 0.33, 1.00, 0.33 and 0.00, 0.33, 0.00, for erythema and oedema formation, respectively
Other effects:
Clinical Observation
No systemic toxicity was observed at treated rabbits during the experimental period.

Mortality
No mortality was observed during the observation period.

Body Weights
Body weights were increased as compared to day 0 in all the three animals at terminal sacrifice

In Treated area Dose:0.5 ml of test item                                                              Sex:Female

 

Animal

No.

Test

Treated

 area*

Erythema score

Oedema score

1h

24h

48h

72h

1h

24h

48h

72h

1

Initial

Right

1

1

0

0

1

0

0

0

2

Confirmatory

Right

1

2

1

0

1

1

0

0

3

Right

1

1

0

0

1

0

0

0

In Control area  Dose:0.5 ml of distilled water                                               Sex:Female

 

Animal

No.

Test

Treated area*

Erythema score

Oedema score

1h

24h

48h

72h

1h

24h

48h

72h

1

Initial

Left

0

0

0

0

0

0

0

0

2

Confirmatory

Left

0

0

0

0

0

0

0

0

3

Left

0

0

0

0

0

0

0

0

Key:h = Hour.

 

Erythema                                                                               Oedema

0 =No erythema                                                                  0 =No oedema

1 = Very slight erythema (barely perceptible)                       1 = Very slight oedema(barely perceptible)

2 = Well defined erythema

Mean Individual Animal Score at 24, 48 and 72 hours

 

                     Animal Number                  

Observations                      

1

2

3

Erythema

0.33

1.00

0.33

Oedema

0.00

0.33

0.00

Individual Animal BodyWeight

Sex:Female

Animal

No.

Body Weight (kg)

Prior to Dosing

At termination

1

1.796

1.856

2

1.940

1.992

3

1.998

2.110

Key: kg = kilogram

Individual Animal Clinical Signs

Sex:Female

Animal

No.

Days (Post dosing Observation)

0

1

2

3

1

1

1

1

1

2

1

1

1

1

3

1

1

1

1

Key: ./. = Not Applicable. 1 = Normal.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The individual mean score at 24, 48 and 72 hours for animal nos. 1, 2 and 3 were 0.33, 1.00, 0.33 and 0.00, 0.33, 0.00, for erythema and oedema formation, respectively. Hence, under the experimental conditions tested it is concluded that N, N-dimethyl-p-toluidine was Non-Irritating to the skin of female New Zealand White rabbits and Classified as “Category- Not Classified as Skin Irritant" as pre CLP criteria
Executive summary:

Acute Dermal Irritation/corrosion Study of N, N-dimethyl-p-toluidine in Rabbits was performed as per OECD guideline No. 404. Three healthy young adult female rabbits were used. Rabbits with good intact skin were selected for the study. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment.A dose of0.5 ml of test item (as such) wasappliedto the skin,over an area of approximately 6 x 6 cm clippedof haironone side of rabbits.The other untreated side was kept as control area and0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water without altering the integrity of the epidermis. Animal No. 2, revealed very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observationpost patch removal. At 24 hour well defined erythema andvery slight oedema (barely perceptible) was observed. At 48 hour very slight erythema (barely perceptible) and no oedema was observed. At 72 hour no erythema and no oedema was observed. Animal No. 3, revealed very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observationpost patch removal. At 24 hourvery slight erythema (barely perceptible)andno oedema was observed. At 48 and 72 hour no erythema and no oedema was observed.The patch was removed after 4 hours and rabbits wereobservedfor erythema and oedemaat 1, 24, 48 and 72 hours after patch removal, evaluatedand graded as per draize method.

The individual mean score at 24, 48 and 72 hoursfor animal nos. 1, 2 and 3 were 0.33, 1.00, 0.33 and 0.00, 0.33, 0.00, for erythema and oedema formation, respectively

Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch.After 4 hours of exposure in animal no. 1, very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation. At 24 hour very slight erythema (barely perceptible) and no oedema was observed.Hence the confirmatory test was conducted after 24 hours on additional two rabbits (No. 2 and 3)to confirm the non irritant nature of the test item. At 48 and 72 hours observation no erythema and no oedema was observed in animal no 1. Hence, under the experimental conditions tested it is concluded that N, N-dimethyl-p-toluidine was Non-Irritating to the skin of female New Zealand White rabbits and Classified as “Category- Not Classified as Skin Irritant" as pre CLP criteria

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)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Procured from LIVEON BOLABS PVT. LTD,
- Age at study initiation: 2.0 to 3.5 Months (Approximately)
- Weight at study initiation: Minimum: 1.644 kg and Maximum: 1.674 kg (Prior to Treatment)
- Housing: The animals were housed individually in stainless steel cages
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rabbit diet (Nutrivet Life Sciences, Pune) ad libitum
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum
- Acclimation period: 6 days (Animal No.-1) and 9 days (Animal No. 2 and 3)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 19.50 °C and Maximum: 21.30 °C
- Humidity (%): Minimum: 47.90 % and Maximum: 59.70 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: From: To:
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution):N/A

Duration of treatment / exposure:
1 hrs
Observation period (in vivo):
All the three treated animals were observed at 1, 24, 48 and 72 hours after instillation of test item
Number of animals or in vitro replicates:
3 female rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing was done with normal saline
- Time after start of exposure:N/A

SCORING SYSTEM:
Grading of irritation lesions was carried out as per draize method

TOOL USED TO ASSESS SCORE: ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
animal: 1,2,3
Time point:
other: 24,48,72 hrs
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks:
within 72 hrs
Remarks on result:
other: not irritating
Irritation parameter:
iris score
Basis:
animal: 1,2,3
Time point:
other: 24,48,72 hrs
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks:
within 72 hrs
Remarks on result:
other: Not itrritating
Irritation parameter:
conjunctivae score
Basis:
animal: 1,2,3
Time point:
other: 24,48,72 hrs
Score:
0.67
Max. score:
3
Reversibility:
fully reversible
Remarks:
within 72 hrs
Remarks on result:
other: Not irritating
Irritation parameter:
chemosis score
Basis:
animal: 1,2,3
Time point:
other: 24,48,72 hrs
Score:
0 - 0.33
Max. score:
3
Reversibility:
fully reversible
Remarks:
within 72 hrs
Remarks on result:
other: Not irritating
Irritant / corrosive response data:
The following were observed in treated rabbits.
Observation at 1 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all the animals.

Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris:Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in animal no. 2 whereas no swelling (normal) in animal no. 1 and 3.
At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0% damage in all the animals.

Observation at 48 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris:Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: No swelling (normal)was observed in all the animals.

Observation at 72 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Blood vessels normal in all the animals; Chemosis: No swelling (normal) was observed in all the animals.
The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.67, 0.00; 0.00, 0.00, 0.67, 0.33 and 0.00, 0.00, 0.67, 0.00 respectively.
Other effects:
Clinical Observation
No systemic toxicity was observed in treated rabbits during the experimental period.

Mortality
No mortality was observed during the observation period.

Body weight
All rabbits were increased in body weight at termination when compared to day 0.

Individual Animal Eye Irritation Scores

 

In Treated area Dose:0.1 ml of test item (as such, undiluted)                             Sex:Female

Animal Numbers

1

2

3

Application Side

Right

Right

Right

Eye Reactions

At hour

At hour

At hour

*

1

24

48

72

*

1

 24

48

72

*

1

24

48

72

Corneal Opacity

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Area of Opacity

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Iris

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Conjunctiva

0

1

1

1

0

0

1

1

1

0

0

1

1

1

0

Chemosis

0

1

0

0

0

0

1

1

0

0

0

1

0

0

0

Corneal Damage%

0

0

0

 

Dose:Untreated (Control Eye)                                                                             Sex:Female

Animal Numbers

1

2

3

Application Side

Left

Left

Left

Eye Reactions

At hour

At hour

At hour

*

1

24

48

72

*

1

 24

48

72

*

1

24

48

72

Corneal Opacity

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Area of Opacity

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Iris

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Conjunctiva

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Chemosis

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Corneal Damage%

0

0

0

Key:*= Pre-exposure eye examination.

Eye Irritation Scores - Mean Values after 24, 48, 72 Hours (Treated eye)

            Animal No.

 Eye Reaction

1

2

3

Corneal Opacity

0.00

0.00

0.00

Iris

0.00

0.00

0.00

Conjunctiva

0.67

0.67

0.67

Chemosis

0.00

0.33

0.00

Formula :

Mean Eye Irritation Score =

                          

Sum of the Individual Animal Score for eye reactionat24, 48 and 72 hours

Number of the Observations (3)

Individual AnimalClinicalSigns

 

Sex:Female

Animal No.

Days (Post application observation)

0

1

2

3

1

1

1

1

1

2

1

1

1

1

3

1

1

1

1

Key:1 = Normal

Individual Animal Body Weight

Sex :Female

Animal No.

Animal Body Weight (kg)

Prior to application

At termination

1

1.674

1.750

2

1.644

1.690

3

1.658

1.706

Key:kg = Kilogram

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.67, 0.00; 0.00, 0.00, 0.67, 0.33 and 0.00, 0.00, 0.67, 0.00 respectively and reversibility of effects on eyes of rabbits was observed within 72 hours.. Hence, under the experimental conditions this it is concluded that N, N-dimethyl-p-toluidine is “Non Irritant” to New Zealand White female rabbit eyes and is being classified as Category “Not Classified as an Eye Irritant” as per CLP criteria.
Executive summary:

Acute Eye Irritation/Corrosion Study of “N, N-dimethyl-p-toluidine in Rabbits was performed as per OECD guideline no. 405. Rabbitsfree from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas; 0.1 ml (as such, undiluted)of test itemwas instilled in the other (treated) eye of each rabbit. The eye was observed at 1, 24, 48 and 72 hour after test item instillation.Ophthalmoscope was used for scoring of eye lesions. In the initial test,0.1 ml of test itemwas applied into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 0.1 mlof test itemwas instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control.

Untreated eye of all the three rabbits was normal throughout the experimental period of 72 hours.

Observation at 1 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all the animals.

Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris: Normal in all the animals. Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis:Some swelling above normal (includes nictitating membranes) was observed inanimal no. 2 whereas no swelling (normal) in animal no. 1 and 3.

At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0% damage in all the animals.

Observation at 48 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris: Normal in all the animals. Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observedin all the animals; Chemosis: No swelling (normal) was observed in all the animals.

Observation at 72 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris: Normal in all the animals. Conjunctivae - Blood vessels normal in all the animals; Chemosis:No swelling (normal) was observed in all the animals.

The individual mean score for animal nos. 1, 2 and 3at 24, 48, 72 hoursfor corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.67, 0.00; 0.00, 0.00, 0.67, 0.33 and 0.00, 0.00, 0.67, 0.00 respectively and reversibility of effects on eyes of rabbits was observed within 72 hours.. Hence, under the experimental conditions this it is concluded that N, N-dimethyl-p-toluidine is “Non Irritant” to New Zealand White female rabbit eyes and is being classified as Category “Not Classified as an Eye Irritant” as per CLP criteria.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation/Corrosion:

Acute Dermal Irritation/corrosion Study of N, N-dimethyl-p-toluidinein Rabbitswas performed as per OECD guideline No. 404. Three healthy young adult female rabbits were used.Rabbits with good intact skin were selected for the study. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment.A dose of0.5 ml of test item (as such) wasappliedto the skin,over an area of approximately 6 x 6 cm clippedof haironone side of rabbits.The other untreated side was kept as control area and0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water without altering the integrity of the epidermis. Animal No. 2, revealed very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observationpost patch removal. At 24 hour well defined erythema andvery slight oedema (barely perceptible) was observed. At 48 hour very slight erythema (barely perceptible) and no oedema was observed. At 72 hour no erythema and no oedema was observed. Animal No. 3, revealed very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observationpost patch removal. At 24 hourvery slight erythema (barely perceptible)andno oedema was observed. At 48 and 72 hour no erythema and no oedema was observed.The patch was removed after 4 hours and rabbits wereobservedfor erythema and oedemaat 1, 24, 48 and 72 hours after patch removal, evaluatedand graded as per draize method.

The individual mean score at24, 48 and 72 hoursfor animal nos. 1, 2 and 3 were 0.33, 1.00, 0.33 and 0.00, 0.33, 0.00, for erythema and oedema formation, respectively

Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch.After 4 hours of exposure in animal no. 1, very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation. At 24 hour very slight erythema (barely perceptible) and no oedema was observed.Hence the confirmatory test was conducted after 24 hours on additional two rabbits (No. 2 and 3)to confirm the non irritant nature of the test item. At 48 and 72 hours observation no erythema and no oedema was observed in animal no 1. Hence, under the experimental conditions tested it is concluded that N, N-dimethyl-p-toluidine was Non-Irritating to the skin of female New Zealand White rabbits and Classified as “Category- Not Classified as Skin Irritant" as pre CLP criteria.

Eye Irritation:

Acute Eye Irritation/Corrosion Study of “N, N-dimethyl-p-toluidinein Rabbitswas performed as per OECD guideline no. 405. Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas; 0.1 ml (as such, undiluted)of test itemwas instilled in the other (treated) eye of each rabbit. The eye was observed at 1, 24, 48 and 72 hour after test item instillation.Ophthalmoscope was used for scoring of eye lesions.In the initial test,0.1 ml of test itemwas applied into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 0.1 mlof test itemwas instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control.

Untreated eye of all the three rabbits was normal throughout the experimental period of 72 hours.

Observation at 1 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all the animals.

Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris: Normal in all the animals. Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis:Some swelling above normal (includes nictitating membranes) was observed inanimal no. 2 whereas no swelling (normal) in animal no. 1 and 3.

At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0% damage in all the animals.

Observation at 48 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris: Normal in all the animals. Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observedin all the animals; Chemosis: No swelling (normal) was observed in all the animals.

Observation at 72 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris: Normal in all the animals. Conjunctivae - Blood vessels normal in all the animals; Chemosis:No swelling (normal) was observed in all the animals.

The individual mean score for animal nos. 1, 2 and 3at 24, 48, 72 hoursfor corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.67, 0.00; 0.00, 0.00, 0.67, 0.33 and 0.00, 0.00, 0.67, 0.00 respectively and reversibility of effects on eyes of rabbits was observed within 72 hours.. Hence, under the experimental conditions this it is concluded that N, N-dimethyl-p-toluidine is “Non Irritant” to New Zealand White female rabbit eyes and is being classified as Category “Not Classified as an Eye Irritant” as per CLP criteria.


Justification for selection of skin irritation / corrosion endpoint:
The individual mean score at 24, 48 and 72 hours for animal nos. 1, 2 and 3 were 0.33, 1.00, 0.33 and 0.00, 0.33, 0.00, for erythema and oedema formation, respectively. Hence, under the experimental conditions tested it is concluded that N, N-dimethyl-p-toluidine was Non-Irritating to the skin of female New Zealand White rabbits and Classified as “Category- Not Classified as Skin Irritant" as pre CLP criteria.

Justification for selection of eye irritation endpoint:
The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.67, 0.00; 0.00, 0.00, 0.67, 0.33 and 0.00, 0.00, 0.67, 0.00 respectively and reversibility of effects on eyes of rabbits was observed within 72 hours.. Hence, under the experimental conditions this it is concluded that N, N-dimethyl-p-toluidine is “Non Irritant” to New Zealand White female rabbit eyes and is being classified as Category “Not Classified as an Eye Irritant” as per CLP criteria.

Justification for classification or non-classification

The substance N,N-dimethyl-p-toluidine is not irritating to skin and eye of rabbit and hence not classified as skin and eye irritant as per CLP criteria