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Skin irritation / corrosion

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Administrative data

Endpoint:
skin 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
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
The objective of the study was to assess the irritant and/or corrosive effects of N, N-dimethyl-p-toluidine (CAS No. – 99-97-8) after dermal application on the intact skin in rabbits.
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
N,N-dimethyl-p-toluidine
EC Number:
202-805-4
EC Name:
N,N-dimethyl-p-toluidine
Cas Number:
99-97-8
IUPAC Name:
N,N,4-trimethylaniline
Details on test material:
IUPAC name: N,N-dimethyl-p-toluidine
Molecular formula: C9H13N
Molecular weight: 135.209 g/mole
Smiles: c1(N(C)C)ccc(C)cc1
InChI: 1S/C9H13N/c1-8-4-6-9(7-5-8)10(2)3/h4-7H,1-3H3
Specific details on test material used for the study:
IUPAC name: N,N-dimethyl-p-toluidine
Molecular formula: C9H13N
Molecular weight: 135.209 g/mole
Smiles: c1(N(C)C)ccc(C)cc1
InChI: 1S/C9H13N/c1-8-4-6-9(7-5-8)10(2)3/h4-7H,1-3H3

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Sex: Female
- Source:Procured from RABBI ROOF, Hyderabad.
- Age at study initiation:4 to 5 Months (Approximately).
- Weight (Prior to Treatment):Minimum: 1.914 kg and Maximum: 2.358 kg
- Health Status :Healthy young adults and nulliparous and non-pregnant Rabbits were used for the study.
- Housing:The animals were housed individually in stainless steel cages.
- Room Sanitation:The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
- Cages and water bottle:All the cages and water bottles were changed minimum twice a week.
- 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:Rabbits were acclimatised to the test conditions for a period of 5 days (Animal No.-1) and 10 days (Animal No.-2 and 3) prior to the application of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 19.30 °C and Maximum: 22.50 °C
- Humidity (%):Minimum: 43.80 % and Maximum: 68.40 %
- Air changes (per hr):More than 12 changes per hour
- Photoperiod (hrs dark / hrs light):12:12

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 ml
- Concentration (if solution):N/A

VEHICLE
- Amount(s) applied (volume or weight with unit):N/A
- Concentration (if solution):N/A
- Lot/batch no. (if required):N/A
- Purity:N/A
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:The dorsal lumbar region at contralateral sites.
- % coverage:Approximately 6 X 6 cm.
- Type of wrap if used:A porous gauze dressing and non-irritating tape (Micropore 3”).

REMOVAL OF TEST SUBSTANCE
- Washing (if done):The residual test item was removed by using cotton soaked in distilled water.
- Time after start of exposure:4 hour

SCORING SYSTEM:Draize Method

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
no data
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
no data
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
no indication of irritation
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.


Any other information on results incl. tables

Table 1

Skin Reaction

 

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)

Table 1

Skin Reaction

 

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

                                                  Table 3 Individual AnimalClinicalSigns

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

 

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
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, it was concluded that “N, N-dimethyl-p-toluidine (CAS No. – 99-97-8)” was Non-Irritating to the skin of Female New Zealand White rabbits under the experimental conditions tested and Classified as “Category- Not Classified” as per CLP Regulation.
Executive summary:

Acute Dermal Irritation/corrosion Study of “N, N-dimethyl-p-toluidine (CAS No. – 99 -97 -8)”in Rabbits, was performed in a OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access). This study was performed as per OECD guideline No. 404.

 

Three healthy young adult female rabbits were used for conducting acute dermal irritation study. Body weights were re­corded on day 0 (prior to application) and at termination. 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) was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits. The other untreated side was kept as control area and 0.5 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. 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, there was 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.

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.

 

Hence, it was concluded that “N, N-dimethyl-p-toluidine (CAS No. – 99-97-8)” was Non-Irritating to the skin of Female New Zealand White rabbits under the experimental conditions tested and Classified as “Category- Not Classified” as per CLP Regulation.