2-nitrotoluene

Endpoint summary

Description of key information

Skin irritation: not a skin irritant (eq. OECD TG 404, pre-GLP, Key, rel.2).

Eye irritation: not an eye irritant (eq. OECD TG 405, pre-GLP, Key, rel.2).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye 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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no GLP conform. No analytical purity reported

Qualifier:

according to guideline

Guideline:

other: Federal Register, Vol 38, No. 187, 1973

GLP compliance:

no

Remarks:

GLP was not mandatory at the time of the study

Species:

rabbit

Strain:

other: Himalayan (SPF-Albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: the animals were housed individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

Amount applied
TEST MATERIAL
- Amount(s) applied: 0.1 ml instilled in to the conjunctival sac of the eye
- Concentration: undiluted test substance

REMOVAL OF TEST SUBSTANCE
- Washing: Yes
- Time schedule for washing: Eyes were washed with physiological saline solution after the 24h reading

SCORING SYSTEM
- according Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp or magnifying glass and fluorescein (1:10,000)
-Time schedule for scoring: 1, 7, 24, 48, 72h after application

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

until 72 hours

Number of animals or in vitro replicates:

6

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritant / corrosive response data:

The results were the following:
- Cornea Opacity: 0/6 animals throughout observation period
- Redness: slight erythema (after 24h), initially seen in 6 and 5 animals (after 1 and 7h, respectively). Erythema was totally reversed in all but 1 animal whose eye still manifested slight erythema. No erythema in any animal at 48 and 72h post instillation of the eye.
- Iris: 0/6 animals throughout observation period
- Swelling: 1/6 after 7h. Reversible after 24 h. No swelling observed

	Animal	Cornea Opacity	Iris	Conjunctiva Redness	Swelling
Readings
24h	26	0	0	0	0
	27	0	0	0	0
	28	0	0	0	0
	29	0	0	1	0
	30	0	0	0	0
	31	0	0	0	0
48h	26	0	0	0	0
	27	0	0	0	0
	28	0	0	0	0
	29	0	0	0	0
	30	0	0	0	0
	31	0	0	0	0
72d	26	0	0	0	0
	27	0	0	0	0
	28	0	0	0	0
	29	0	0	0	0
	30	0	0	0	0
	31	0	0	0	0
Mean (24h-72h)	26	0.0	0.0	0.0	0.0
	27	0.0	0.0	0.0	0.0
	28	0.0	0.0	0.0	0.0
	29	0.0	0.0	0.3	0.0
	30	0.0	0.0	0.0	0.0
	31	0.0	0.0	0.0	0.0
Mean (24h-72h)	allanimals	0.0	0.0	0.1	0.0

 

Executive summary:

Hollander and Weigand (1975):

The skin irritation of 2-nitrotoluene has been investigated in a study similar to OECD guideline 405 with deviations (no details on substance purity, prior to GLP).

The test substance (purity not given) was applied undiluted (0.1 ml/rabbit) in the conjunctival sac of 6 rabbits. The exposure lasted 24 h exposure, and observations were conducted at 1, 7, 24, 48 and 72 h. The irritation evaluation was made by means the Draize score method.

The results were the following:

-         Cornea score: 0

-         Conjunctiva score: 0.1 (fully reversible)

-         Iris score: 0

-         Chemosis score: 0

 

In accordance with the criteria laid down by the EU and GHS for the evaluation of eye irritation, 2 -nitrotoluene does not need to be classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

A key study is available. 2-nitrotoluene was applied undiluted 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).

 

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 individual erythema scores (24/48/72 h): 0.0 / 0.0 / 0.0 / 0.33 / 0.33 / 0.0 (fully reversible within 48 h);

Mean individual edema scores (24/48/72 h): 0.0 / 0.33 / 0.0 / 0.0 0.0 / 0.0.

 

Eye irritation:

A key study is identified. The skin irritation of 2-nitrotoluene has been investigated in a study similar to OECD guideline 405 with deviations (no details on substance purity, prior to GLP).

The individual scores (24/48/72 h) were the following:

-         Cornea score: 0.0 / 0.0 / 0.0 / 0.0 / 0.0 / 0.0;

-         Conjunctiva score: 0.0 / 0.0 / 0.0 / 0.33 / 0.0 / 0.0 (fully reversible within 48 h);

-         Iris score: 0.0 / 0.0 / 0.0 / 0.0 / 0.0 / 0.0;

-         Chemosis score: 0.0 / 0.0 / 0.0 / 0.0 / 0.0 / 0.0.

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonised classification for irritation / corrosion according to the Regulation (EC) No. 1272/2008 (CLP). 

 

Self classification:

Based on the available information no additional self-classification is proposed regarding both skin and eye irritation according to the CLP and to the GHS. 

No data was available regarding respiratory irritation, however the substance not being classified for skin and eye irritation, no classification is expected for respiratory irritation.