Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
data is from experimental reports

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Acute Eye Irritation/Corrosion Study of “N, N-dimethyl-p-toluidine (CAS No. – 99-97-8)” was conducted in New Zealand White Rabbits as per OECD guideline no. 405 (Acute Eye Irritation / Corrosion).
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material: N,N-dimethyl-p-toluidine
- Molecular formula: C9H13N
Molecular weight : 135 g/mol
Substance type: Organic
- Physical state: Liquid
Specific details on test material used for the study:
- Name of test material: N,N-dimethyl-p-toluidine
- Molecular formula: C9H13N
-- Molecular weight:135.165g/mol
- Substance type: Organic
- Physical state: Liquid

Test animals / tissue source

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:

Test system

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):100%

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

Results and discussion

In vivo

Resultsopen allclose all
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:
0.33
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.

Any other information on results incl. tables

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

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

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

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
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.
Executive summary:

Acute Eye Irritation/Corrosion Study of “N, N-dimethyl-p-toluidine (CAS No. – 99-97-8)” in Rabbits, sponsored by Sustainability Support Services (Europe) ABwas conducted at sa-FORD (Sanctuary for Research and Development), Maharashtra, India. This study was 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 item was 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.