1-chloro-4-nitrobenzene

Endpoint summary

Description of key information

p-Chloronitrobenzene is considered not irritating to the skin and to the eyes.

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:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Non-GLP study performed according to a method similar to OECD Guideline 404. Limited details on test item provided.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

lack of details on test substance

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: W. Ostrop, Meerbusch, Germany
- Weight at study initiation: 2.9 kg
- Diet (e.g. ad libitum): Mümmel Z, Ssniff, Soest, Germany
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18 °C
- Humidity (%): 40 %
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg

Duration of treatment / exposure:

24 hour(s)

Observation period:

8 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: a 2.5 x2.5 cm area
- Gauze pads were loaded with 500mg 1-chloro-4 -nitrobenzene suspended with 1 or 2 drops of water
- Type of wrap if used: The test areas were covered occlusive with a layer of PVC-film (5 x 5 cm) and adhesive tape (Leukoflex)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- after 24 hours

OBSERVATION TIME POINTS
- reading times: 24,48 72 hours and day 8 post application, control-reading 48 hours and day 8 post appl. was not included in the evaluation

SCORING SYSTEM
According to: Code of Federal Regulations, Title 16, Section 1500.41

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

other: after 72 hours score 1

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

other: after 72 hours score 1

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 8 days (score 1)

Irritation parameter:

edema score

Basis:

animal #3

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #4

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #5

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

after 8 days score 3

Irritation parameter:

edema score

Basis:

animal #6

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

A 48-h reading was not performed. This deficiency was overcome by assuming that the 48-h score is identical to the 24-h score. Thus, the average score per endpoint was calculated as follows (intact skin only):
reading: erythema: 0.0 (0 in all animals at all times) reading: oedema:   1.8

Based on the 24-72 h readings, no classification is necessary.

Erythema		Skin irritation / Animal No.						Total	Mean
	Time	1	2	3	4	5	6
Intact skin	24h 72h	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
	8d	0	0	0	0	0	0
Scarified skin	24h 72h	0 0	0 0	0 0	0 0	1 0	0 0	1 0	0.17 0
	8d	0	0	0	0	0	0

Oedema		Skin irritation / Animal No.						Total	Mean
	Time	1	2	3	4	5	6
Intact skin	24h 72h	2 0	2 1	2 2	2 0	2 2	3 1	13 6	2.17 1.0
	8d	1	1	2	1	3	1
Scarified skin	24h 72h	2 0	2 1	2 2	0 0	2 2	2 1	10 6	1.67 1.0
	8d	1	2	1	1	3	2

Interpretation of results:

GHS criteria not met

Conclusions:

Classification:
DSD: not classified
EU-GHS: not classified

Executive summary:

Schreiber (Bayer AG), 1980

The skin irritation potential of 1 -chloro-4 -nitrobenzene was investigated in 6 New Zealand White rabbits conducted comparable to OECD-guideline 404.

A 2.5 x 2.5 cm area of intact shaved animal skin and scarified skin was used to apply the test substance. Gauze pads were loaded with 500 mg 1-chloro-4-nitrobenzene suspended with 1 or 2 drops of water. The test areas were covered occlusive with a layer of PVC-film (5 x 5 cm) and adhesive tape (Leukoflex). The exposure duration was 24 hours. The reading times were 24, 72 hours and 8 days after application. Day 8 post application was not included in the evaluation. The mean erythema scores at 24, 72 hours and 8 days were 0.0 in all animals in intact skin. The mean oedema score at the 24 hour reading point was 2.17 and at 72 hours 1.0. The criteria for classification are not fulfilled.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

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:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Non-GLP study performed according to a method similar to OECD Guideline 405. No individual animal data and no detailed doucmentation available.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no individual animal data

Principles of method if other than guideline:

Method according to: Code of Federal Regulations, Title 16, Section 1500.42

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1,5 - 2,0 kg
- Housing: single
- Diet: ad libitum, Erka 8300, Robert Koch oHG, Hamm, Germany
- Water: ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 100 mg (undissolved)

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 24 hours of application

SCORING SYSTEM:
Draize according to Code of Federal Regulations, Title 16, Section 1500.42

TOOL USED TO ASSESS SCORE:
fluorescein

Irritation parameter:

other: irritation index

Basis:

mean

Time point:

other: 1h

Score:

6

Max. score:

110

Reversibility:

not specified

Remarks on result:

other: highest irritation index after 1 hour

Irritant / corrosive response data:

Irritation index 6, maximum 110

Interpretation of results:

GHS criteria not met

Conclusions:

After 1 hour the test substance induced the highest irritation index of 6. Therefore no classification according to FDA guideline is required.

Executive summary:

Hoechst AG, 1977

The eye irritation potential of 1 -chloro-4 -nitrobenzene was investigated in 6 Himalyan rabbits according to the FDA guideline (federal register, Vol 38, No. 187, 1973). 100 mg undissolved test substance was applied into the conjunctival sac of one eye of each animal. The other untreated eye served as control. The eyes were rinsed 24 hours after application of the test substance.

The eye irritation reactions were examined and scored using the Draize method 1, 7 and 24, 48 and 72 hours after application.

After 1 hour the test substance induced the highest irritation index of 6. Therefore no classification according to FDA guideline is required.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

study performed according to a method similar to OECD Guideline 405. No detailed documentation available

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

lack of details on test substance

Principles of method if other than guideline:

Method according to: Code of Federal Regulations, Title 16, Section 1500.42

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: W. Ostrop, Meerbusch, Germany
- Weight at study initiation: 2,9 kg
- Diet (e.g. ad libitum): Mümmel Z, Ssniff, Soest, Germany
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18 °C
- Humidity (%): 40 %
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Vehicle:

not specified

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 ml bulk volume

Duration of treatment / exposure:

8 days

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

6

Irritation parameter:

conjunctivae score

Basis:

other: 6/6

Time point:

24 h

Score:

2

Max. score:

110

Reversibility:

fully reversible

Remarks:

after 8d

Irritation parameter:

conjunctivae score

Basis:

other: 4/6

Time point:

48 h

Score:

2

Max. score:

110

Reversibility:

fully reversible

Remarks:

after 8d

Irritation parameter:

conjunctivae score

Basis:

other: 2/6

Time point:

72 h

Score:

2

Max. score:

110

Reversibility:

fully reversible

Remarks:

after 8d

Irritant / corrosive response data:

reading: summary of the effects (cornea, iris, conjunctiva, only conjunctiva affected): 
24 hs: score 2/110 in 6/6 rabbits; 
48 hs: score 2/110 in 4/6 rabbits;
72 hs: score 2/110 in 2/6 rabbits; 
8d: score 0/110 in 6/6 rabbits (not included for calculation of irritation index)
primary eye irritation index: 1.3

Interpretation of results:

GHS criteria not met

Reference 3

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The skin irritation potential of 1 -chloro-4 -nitrobenzene was investigated in 6 New Zealand White rabbits. An 2.5 x 2.5 cm area of intact shaved animal skin and scarrified skin was used to applicate the test substance. Gauze pads were loaded with 500mg 1 -chloro-4-nitrobenzene suspended with 1 or 2 drops of water. The test areas were covered occlusive with a layer of PVC-film (5 x 5 cm) and adhesive tape (Leukoflex). The exposure duration was 24 hours. The reading times were 24, 48, 72 hours and 8 days after application. Day 8 post application was not included in the evaluation. The mean erythema scores at 24, 72 hours and 8 days were 0.0 in all animals in intact skin. The mean oedema score at the 24 hour reading point was 2.17 and at 72 hours 1.0. The mean scores do not justify classification as skin irritant (Schreiber, Bayer AG, 1980).

The eye irritation potential of 1-chloro-4 -nitrobenzene was investigated in 6 Himalayan rabbits according to the FDA guideline (federal register, Vol 38, No. 187, 1973). 100 mg undissolved test substance was applied into the conjunctival sac of one eye of each animal. The other untreated eye served as control. The eyes were rinsed 24 hours after application of the test substance.

The eye irritation reactions were examined and scored using the Draize method 1, 7 and 24, 48 and 72 hours after application.

After 1 hour the test substance induced the highest irritation index of 6. Therefore no classification according to FDA guideline is required (Hoechst AG, 1977). Although the study does not meet all requirement of the currently applicable guidelines, the non-irritating results from the supporting studies confirm the report.

Justification for classification or non-classification

No classification required.