4-nitrotoluene

Endpoint summary

Description of key information

Skin irritation: not a skin irritant (eq. OECD TG 404, GLP, Key, rel.1).

Eye irritation: not an eye irritant (eq. OECD TG 405, GLP, Key, rel.1).

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:

From 18.03. 1986 To 21.03.1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

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: Polyethylene glycol 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:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

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)	Average animal 2 (24 -72 h)	Average animal 3 (24 -72 h)	Total average
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

 

Executive summary:

Hofmann (Hoechst AG, 1986)

 

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.

 

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:

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: 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

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:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

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.

Timeendpoint 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

 

Executive summary:

Hofmann T (1986)

 

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.

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. 4-nitrotoluene was applied undiluted to clipped intact areas of the skin which had been pre-softened with Polyethylenglycol 400, using a method equivalent to OECD guideline 404 (semi-occlusive coverage, 4h exposure duration, GLP).

 

Treatment with 4-nitrotoluene: the test substance produced no erythema or edema at any time point of measurement (24/48/72h).

Mean individual erythema scores (24/48/72 h): 0.0 / 0.0 / 0.0 

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

 

 

Eye irritation:

A key study is identified. The skin irritation of 2-nitrotoluene has been investigated in a GLP compliant study according to OECD guideline 405 / EU B.5 with no deviations.

 

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

-         Cornea score: 0.0 / 0.0 / 0.0;

-         Conjunctiva score: 0.3 / 0.7 / 0.3 (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.