2-nitrotoluene

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Reference 2

Reference Type:

secondary source

Title:

European Union Risk Assessment Report - 2-Nitrotoluene

Author:

European Commission - European Chemicals Bureau

Year:

2008

Bibliographic source:

Office for Official Publications of the European Communities

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(occlusive coverage, 24h exposure duration, no details on substance purity; prior to GLP)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Fed. Reg. 38, No. 187, p. 27019, 1973

GLP compliance:

no

Remarks:

GLP was not mandatory at the time of the study

Test material

Test material information

Constituent 1

Reference substance name:

2-nitrotoluene

EC Number:

201-853-3

EC Name:

2-nitrotoluene

Cas Number:

88-72-2

Molecular formula:

C7H7NO2

IUPAC Name:

1-methyl-2-nitrobenzene

Details on test material:

- Name of test material (as cited in study report): o-nitrotoluene
- Physical state: yellow liquid
- Analytical purity: no data

Test animals

Species:

rabbit

Strain:

other: Himalayan (SPF-Albino)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.5 - 2.0 kg
- Housing: animals were housed individually
- Diet: ad libitum, ERKA 8300 (Robert Koch oHG/Hamm, Germany)
- Water: ad libitum, tap water

Test system

Type of coverage:

occlusive

Preparation of test site:

other: one flank shaved and the other abraded

Vehicle:

other: sesame oil

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 ml
- Concentration: 10% (left flank) and undiluted (right flank)

Duration of treatment / exposure:

24 hour(s)

Observation period:

72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 3 cm2 on the flanks
- Type of wrap if used: 2.5 cm² surgical gauze soaked in test substance was covered with 6-8 cm wide PVC foil

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM:
- According: Draize scoring system
- Time schedule for scoring: 24, 48, 72 hours after application

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hrs

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Any other information on results incl. tables

Table 1.Summary of results of skin irritation in rabbits after 24 h occlusive exposure of intact rabbit skin to the undiluted test substance

Readings	Animal	Erythema	Edema
24h	26	0	0
	27	1	1
	28	1	0
	29	1	0
	30	1	0
	31	0	0
48h	26	0	0
	27	0	0
	28	0	0
	29	0	0
	30	0	0
	31	0	0
72h	26	0	0
	27	0	0
	28	0	0
	29	0	0
	30	0	0
	31	0	0
Mean(24h-72h)	26	0.0	0.0
	27	0.3	0.3
	28	0.3	0.0
	29	0.3	0.0
	30	0.3	0.0
	31	0.0	0.0
Mean(24h-72h)	allanimals	0.2	0.1

Table 2. Summary of results of skin irritation in rabbits after 24 h occlusive exposure of abraded rabbit skin to the undiluted test substance

Readings	Animal	Erythema	Edema
24h	26	0	1
	27	1	1
	28	1	0
	29	1	1
	30	1	0
	31	0	0
48h	26	0	0
	27	1	1
	28	0	0
	29	1	0
	30	0	0
	31	0	0
72h	26	0	0
	27	0	0
	28	0	0
	29	0	0
	30	0	0
	31	0	0
Mean(24h-72h)	26	0.0	0.3
	27	0.7	0.7
	28	0.3	0.0
	29	0.7	0.3
	30	0.3	0.0
	31	0.0	0.0
Mean(24h-72h)	allanimals	0.3	0.2

Table 3: Summary of results of skin irritation in rabbits after 24 h occlusive exposure of intact rabbit skin to 10% of the 2-nitrotoluene in sesame oil.

Readings	Animal	Erythema	Edema
24h	26	0	0
	27	0	0
	28	0	0
	29	1	1
	30	0	0
	31	0	0
48h	26	0	0
	27	0	0
	28	0	0
	29	0	0
	30	0	0
	31	0	0
72h	26	0	0
	27	0	0
	28	0	0
	29	0	0
	30	0	0
	31	0	0
Mean(24h-72h)	26	0.0	0.0
	27	0.0	0.0
	28	0.0	0.0
	29	0.3	0.3
	30	0.0	0.0
	31	0.0	0.0
Mean(24h-72h)	allanimals	0.1	0.1

Table 4: Summary of results of skin irritation in rabbits after 24 h occlusive exposure of abraded rabbit skin to 10% of the of 2 nitro toluene in sesame oil.

Readings	Animal	Erythema	Edema
24h	26	0	0
	27	0	1
	28	0	0
	29	1	0
	30	1	0
	31	0	0
48h	26	0	0
	27	0	0
	28	0	0
	29	0	0
	30	0	0
	31	0	0
72h	26	0	0
	27	0	0
	28	0	0
	29	0	0
	30	0	0
	31	0	0
Mean (24h-72h)	26	0.0	0.0
	27	0.0	0.3
	28	0.0	0.0
	29	0.3	0.0
	30	0.3	0.0
	31	0.0	0.0
Mean(24h-72h)	allanimals	0.1	0.1

 

Applicant's summary and conclusion

Executive summary:

Hollander and Weigand (1975):

 

2-nitrotoluene was applied undiluted (0.5 mL/rabbit) and diluted in sesame oil (0.5 mL 10% dilution/rabbit) to clipped intact and scarified areas of the skin, with a method similar to OECD guideline 404 (occlusive coverage, 24h exposure duration, no details on substance purity; prior to GLP) and according to the FDA Register 38 No. 187 (1973-09-27) and

The exposure lasted 24 hours and the observations were conducted at 24, 48 and 72 h according to the Draize score method.

 

Treatment with undiluted 2-nitrotoluene: 24 hours after exposure (no washing) the test substance produced very slight erythema (4/6 animals) and very slight edema (1/6 animals) After 48h, all signs of skin irritation were reversed. Mean erythema and edema scores (after 24, 48, 72h) are 0.2 and 0.1, respectively.

With respect to abraded skin treatment with undiluted 2-nitrotoluene: 24 hours after exposure 2-nitrotoluene produced very slight erythema (4/6 animals) and very slight edema (3/6 animals). 48 hours after exposure 2/6 animals produced very slight erythema and 1/6 very slight edema. After 72 hours all signs of skin irritation were reversed. Mean erythema and edema scores (after 24, 48, 72h) are 0.3 and 0.2.

Treatment with 10% 2 -nitrotoluene in sesame oil: 24hours after exposure (no washing) very slight erythema (1/6 animals) and very slight edema (1/6 animals) seen after of 2 -nitrotoluene to rabbit skin. After 48h, all signs of skin irritation were reversed. Mean erythema and edema scores (after 24, 48, 72h) are 0.1 and 0.1, respectively.

Treatment with 10% 2 -nitrotoluene in sesame oil on abraded skin: 24hours after exposure (no washing) very slight erythema (2/6 animals) and very slight edema (1/6 animals) seen after of 2 -nitrotoluene to rabbit skin. After 48h, all signs of skin irritation were reversed. Mean erythema and edema scores (after 24, 48, 72h) are 0.1 and 0.1, respectively.

2 -Nitrotoluene did not provoke skin irritation, hence it does not need to be classified according to the criteria laid down by the EU and GHS for the evaluation of skin irritation.