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Toxicological information

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 report

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 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Acute Dermal Irritation/corrosion Study of N, N-dimethyl-p-toluidine in Rabbits was performed as per OECD guideline No. 404.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material: N,N-dimethyl-p-toluidine
- Molecular formula: C9H13N
-- Molecular weight:135.165g/mol
- Substance type: Organic
- Batch number/ Lot no.: 18
- Storage conditions : Room temperature (20 - 30 °C)
- 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

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:

Test system

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

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: 1,2,3
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Not irritating
Irritation parameter:
edema score
Basis:
animal: 1,2,3
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible
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

Any other information on results incl. tables

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.

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, 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.
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. 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. At 48 and 72 hours observation no erythema and no oedema was observed in animal no 1.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 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 observation post patch removal. At 24 hour very slight erythema (barely perceptible) and no oedema was observed. At 48 and 72 hour no erythema and no oedema was observed. 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. 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.