Nitrotoluene

Endpoint summary

Description of key information

There is no skin or eye irritation study available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from 4-nitrotoluene (CAS 99-99-0):

Not irritating to the skin of rabbits;

Not irritating to the eyes of rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 18.03. 1986 To 21.03.1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): p-nitrotoluene
- Physical state: solid (yellow-green crystal)
- Analytical purity: 99%
- Product number/code: GGBE 155
- Storage condition of test material: in the dark at 22°C

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, Germany, conventional breeding
- Age at study initiation: 3-5 months
- Weight at study initiation: 2.2-2.9 kg
- Housing: in air conditioned room, in single cage
- Diet (e.g. ad libitum): Altromin 2123 rabbit breeding diet (Altromin GmbH, Lage/Lippe) as well as hay ad libitum
- Water (e.g. ad libitum): deionised, chlorinated water from automatic drinking trough ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 50 ± 20%
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: Polyethylenglycol 400

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg Test substance was moistened with 0.2 ml polyethylene glycol 400

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.2 mL Polyethylenglycol 400
- Lot/batch no. (if required): Ch-B 2322, Fa Riedel de Haen AG, Germany

Duration of treatment / exposure:

4 hour(s)

Observation period:

up to 72 hours

Number of animals:

3

Details on study design:

24 hours before start of the experiment rabbits were shaved at the dorsal region of the trunk (area 25 cm², intact skin). 500 mg test substance was moistened with 0.2 ml polyethylene glycol 400 and applied on a special tape with additional gauze (area: 2.5 cm²). This tape was fixed on the shaved area and covered by a semiocclusive dressing for 4 hours. After this time tape and test substance were carefully removed from the skin with lukewarm water. Reading were performed as follows: 30-60 min, 24, 48 and 72 hours after removing of the tape, according to DRAIZE score

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Readings	24 h (after removal of the tape)			48 h (after removal of the tape)			72h (after removal of the tape)			Average animal 1 (24 -72 h)	Averageanimal 2 (24 -72 h)	Averageanimal 3 (24 -72 h)	Totalaverage
Animals	1	2	3	1	2	3	1	2	3	1	2	3	-
Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0
Odema	0	0	0	0	0	0	0	0	0	0	0	0	0

 

Interpretation of results:

GHS criteria not met

Conclusions:

4-Nitrotoluene is not irritating to the skin of rabbits.

Executive summary:

4-Nitrotoluene, moistened with polyethylene glycol 400, was not irritating to the skin of rabbits, when applied under semi-occlusive condition for four hours according to OECD 404.

The mean Draize scores for edema and erythema were each "0".

4-Nitrotoluene is not irritating to the skin of rabbits.

 

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

There is no experimental test data available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from its components. Nitrotoluene (CAS 1321-12-6) is a mixture of mainly 4-nitrotoluene (CAS 99-99-0) and/or 2-nitrotoluene (CAS 88-72-2). In addition, the mixture is containing small amounts of 3-nitrotoluene (CAS 99-08-1). A wealth of data is existing for the hazard assessment of 2- and 4-nitrotoluene, which can be used for the classification of nitrotoluene (CAS 1321-12-6). Key data and classification are derived from the isomer with the most critical hazard identified for each specific end point. The available experimental test data are considered reliable and suitable for the classification of nitrotoluene (CAS 1321-12-6) under Regulation 1272/2008.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From: 18/03/1986 To: 21/03/1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): p-nitrotoluol
- Physical state: solid (yellow-green crystals)
- Analytical purity: 99%
- Storage condition of test material: in the dark at 22 °C

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, Germany. Conventional breeding
- Age at study initiation: 3-5 months
- Weight at study initiation: 2.7-3.7 kg
- Housing: the animals were housed in individual cages in air conditioned room
- Diet (e.g. ad libitum): Altromin 2123 Haltungsdiät-Kaninchen (Altromin GmbH, Lage/Lippe, Germany) and hay as well
- Water (e.g. ad libitum): deionised and chlorinated water from automatic drinking trough

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-3 °C
- Humidity (%):50+/-20 %
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 18/03/1986 To: 21/03/1986

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

Amount applied: 100 mg

Duration of treatment / exposure:

24 hour(s)

Observation period (in vivo):

24, 48, and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF THE TEST SUBSTANCE
Washing (if done): yes, with physiologic saline solution
- Time after start of exposure: at 24 hours after exposure, and at all the other time points. The washing was performed also when excretions were observed in the treate eyes and when the fluorescein test was performed on the cornea of the treated eyes.


SCORING SYSTEM: Draize Method


TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritant / corrosive response data:

One hour post exposure all the animals presented a light and whit discharge. The conjunctiva was swollen in all the animals and showed a clear hyperaemia of the vasculature.
24 hours post exposure the animals showed still a clear hyperaemia of the vasculature up to carmine red coloration of the conjunctiva.
The effect described above were completely reversible within 48 hours.
One hour post exposure all the animals presented a light and whit discharge. The conjunctiva was swollen in all the animals and showed a clear hyperaemia of the vasculature.
24 hours post exposure the animals showed still a clear hyperaemia of the vasculature up to carmine red coloration of the conjunctiva.
The effects described above were completely reversible within 48 hours.

Time endpoint after application	24h			48h			72h			Average (24-72 h)animal 1	Average (24-72h) animal 2	Average(24-72 h)animal 3	Total average
Animal number	1	2	3	1	2	3	1	2	3	1	2	3	-
Conjuctiva: Chemosis	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjuctiva: redness	1	2	1	0	0	0	0	0	0	0.3	0.7	0.3	0.4
Iris	0	0	0	0	0	0	0	0	0	0	0	0	0
Corneal opacity	0	0	0	0	0	0	0	0	0	0	0	0	0
Fluoresceintest	0	0	0				0	0	0

 

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

4-Nitrotoluene is not irritating to the eyes of rabbits.

Executive summary:

In a test according to OECD TG 405, 100 mg of 4-nitrotoluene was applied into the conjunctival sac of the left eye of each of three rabbits. 24 hours later the eyes were rinsed. One hour post exposure all the animals presented a light and whit discharge. The conjunctiva was swollen in all the animals and showed a clear hyperaemia of the vasculature.

24 hours post exposure the animals showed still a clear hyperaemia of the vasculature up to carmine red coloration of the conjunctiva.

The effects described above were completely reversible within 48 hours.

4-Nitrotoluene is not irritating to the eyes of rabbits.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

There is no experimental test data available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from its components. Nitrotoluene (CAS 1321-12-6) is a mixture of mainly 4-nitrotoluene (CAS 99-99-0) and/or 2-nitrotoluene (CAS 88-72-2). In addition, the mixture is containing small amounts of 3-nitrotoluene (CAS 99-08-1). A wealth of data is existing for the hazard assessment of 2- and 4-nitrotoluene, which can be used for the classification of nitrotoluene (CAS 1321-12-6). Key data and classification are derived from the isomer with the most critical hazard identified for each specific end point. The available experimental test data are considered reliable and suitable for the classification of nitrotoluene (CAS 1321-12-6) under Regulation 1272/2008.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

chemosis score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

0.4

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal: 1-3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Mononitrotoluene is a mixture of mainly 4-nitrotoluene (CAS 99-99-0) and/or 2 -nitrotoluene (CAS 88-72-2). In addition the mixture is containing small amounts of 3-nitrotoluene (CAS 99-08-1). A wealth of data is existing for the hazard assessment of 2- and 4-nitrotoluene. Key data and classification is derived from the isomer with the most critical hazard identified for each specific end point. For completeness key data of the other isomer is added as supporting information.

Regarding irritation / corrosion classification is driven by 4-nitrotoluene.

Skin Irritation

4-Nitrotoluene, moistened with polyethylene glycol 400, was not irritating to the skin of rabbits when applied under semi-occlusive condition for four hours as described in OECD TG 404. The mean Draize scores for edema and erythema were each “0” (Hoechst, 1986a).

Eye Irritation

In a test according to OECD TG 405, 100 mg of neat 4-nitrotoluene was applied into the conjunctival sac of the left eye of each of three rabbits. 24 hours later the eyes were rinsed. There were no effects on cornea and iris, and only a slight redness (Draize scores between 1 and 2) was noted at 1 and 24 hours after instillation, which was completely reversible within 48 hours (Hoechst, 1986b).

Identical results were observed with 2-nitrotoluene on the skin and the eyes of rabbits (Hoechst, 1975).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. There is no skin or eye irritation study available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from 4-nitrotoluene (CAS 99-99-0). 4-nitrotoluene is not irritating to the skin and the eyes of rabbits.

Therefore, nitrotoluene (CAS 1321-12-6) is not considered to be classified for irritation under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.