N,N-dimethyl-p-toluidine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

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 the test chemical after dermal application on the intact skin in rabbits.

GLP compliance:

yes

Test material

Test material information

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

Molecular formula:

C9H13N

IUPAC Name:

N,N,4-trimethylaniline

Test material form:

liquid

Details on test material:

- Name of test material: Benzenamine, N,N,N-trimethyl-
- Common Name: N,N-Dimethyl-p-toluidine
- Molecular formula: C9H13N
- Molecular weight: 135.209 g/mol
- Smiles notation: c1(N(C)C)ccc(C)cc1
- InChl: 1S/C9H13N/c1-8-4-6-9(7-5-8)10(2)3/h4-7H,1-3H3
- Substance type: Organic
- Physical state: liquid
- Purity: Greater than 99%.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

> 0 - <= 1

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

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.

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 was concluded that the test chemical was Non-Irritating to the skin of female New Zealand White rabbits and Classified as “Category- Not Classified as Skin Irritant" as per CLP criteria

Executive summary:

Acute Dermal Irritation/corrosion Study of the test chemical was performed as per OECD guideline No. 404. Three healthy young adult female New Zealand White 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 chemical (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 chemical application site was wiped with water without altering the integrity of the epidermis.  Initially, the test chemical was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. At 1 hour of observation, very slight erythema (barely perceptible) and very slight oedema (barely perceptible) was observed in animal no. 1. 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 chemical. At 48 and72 hours observation no erythema and no oedema was observed in animal no 1.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.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 observationpost 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 very slight erythema (barely perceptible)andno 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, under the experimental conditions tested it was concluded that the test chemical was Non-Irritating to the skin of female New Zealand White rabbits and Classified as “Category- Not Classified as Skin Irritant" as per CLP criteria.