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Administrative data

Description of key information

P-chloronitrobenzene was found to be harmful if swallowed, in contact with skin and by inhalation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: no pathologic examination performed, no individual animal data, lack of details on test substance
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Germany
- Weight at study initiation: 160 - 180 g
- Housing: 5 in one cage
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
no data
Doses:
100, 200, 300, 350, 400, 500, 600 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Statistics:
LD50 was calculated by Probit-analysis (Fink and Hund 1965. Arzneim.-Forsch. 15:624).
Sex:
male
Dose descriptor:
LD50
Effect level:
294 mg/kg bw
Mortality:
200 mg/kg bw: 3/10 animals died 2d after application
300 mg/kg bw: 5/10 animals died 2-3d after application
350 mg/kg bw: 5/10 animals died 2-3d after application
400 mg/kg bw: 8/10 animals died 2-4d after application
500 mg/kg bw: 8/10 animals died 2-3d after application
600 mg/kg bw: 10/10 animals died 3h-4d after application
Clinical signs:
reduced general condition, cyanotic appearance, diarrhea, increased excretion of urine
Body weight:
no data
Gross pathology:
no data

Table 1:

Dose (mg/kg bw)

Time of death

Dead

Symptoms

Number of rats used

100

200

300

350

400

500

600

-

2d

2-3d

2-3d

2-4d

2-3d

3h-4d

0

3

5

5

8

8

10

0

10

10

10

10

10

10

10

10

10

10

10

10

10

Value: (232 - 349 mg/kg bw)


Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Classification:
GHS: Acute Oral Category 3
Executive summary:

Loeser (Bayer AG), 1979

The acute oral toxicity of 1 -chloro-4 -nitrobenzene was investigated in male Wistar II rats comparable to OECD guideline 401.

7 male groups of 10 animals were dosed with 100, 200, 300, 350, 400, 500 and 600 mg/kg bw 1-chloro-4 -nitrobenzene per gavage and observed for 14 days following exposure for mortality and clinical signs. Mortalities occurred at dose levels equal to and exceeding 200 mg/kg bw 2 days after administration. Reduced general condition, cyanotic appearance, diarrhea, increased excretion of urine were observed in all male animals dosed 200 - 600 mg/kg bw. Symptoms started to appear between 3 hours (600 mg/kg bw) and 4 days (400 and 600 mg/kg bw) after administration. No clinical signs were observed in animals dosed with 100 mg/kg bw in male rats. The calculated LD50 for male rats was 294 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
294 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: adopted according to OECD SIDS, peer reviewed data
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
number of animals which show effects is missing
Principles of method if other than guideline:
Method: other: head-only exp., atmosph. contained vapor and micro-
crystalline particles (particle size: 2.7 up to greater 90 µm, respirable fraction: 6.8 to 92.3 %), 16100 mg/m³ was the highest attainable concentration
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Crl:CD
Sex:
male
Route of administration:
inhalation
Type of inhalation exposure:
head only
Vehicle:
other: air
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
2.63, 2.84, 3.27, 3.35, 3.73, 6.12, 9.47, 16.1 mg/l (approx. 2630, 2840, 3270, 3350, 3730,6120, 9470, 16100 mg/m³)
No. of animals per sex per dose:
10
Control animals:
not specified
Sex:
male
Dose descriptor:
LCLo
Effect level:
ca. 16 100 mg/m³ air
Exp. duration:
4 h
Mortality:
at 16100 mg/m3: 1/10 3 days post exposure
Clinical signs:
other: during and immediately following exposure: cyanosis, corneal opacity, abnormal arched-back posture, lethargy, reddish-brown nasal and frothy mouth discharges,tachypnea, semi-prostration   -  from 1 - 14 days post-exposure: pallor, lacrimation, alopecia, c
Body weight:
weight loss: 6-13 % within the first 24 hours with normal gain thereafter
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LCLo (inhalation) = 16100 mg/m3 air
Classification:
GHS: Acute Inhalation Category 4
Executive summary:

Dupont, 1981

The acute inhalative toxicity of 1-chloro-4-nitrobenzene was investigated in study comparable to OECD guideline 403 with acceptable restrictions. Rats were exposed head-only to an atmosphere containing vapour and microcrystalline particles up to 16100 mg/m³ air for 4 hours. Clinical signs of toxicity were related to dose. During and immediately after exposure cyanosis, corneal opacity, abnormal arched-back posture, lethargy, reddish-brown nasal and frothy mouth discharges, tachypnea, semi-prostration were observed. From 1 - 14 days post exposure, pallor, lacrimation, alopecia, corneal opacity, stained perineal area, dermal irritations were observed. Also weight loss of 6 - 13 % was detected within the first 24 hours but weight gain normalized therafter. Three days post exposure death occurred at 16100 mg/m³ in 1 of 10 animals. Therefore the LCLo was 16100 mg/m³ air.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
16 100 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
: only males were tested, no pathologic examination was performed, lack of details on test substance
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation: 180-200 g
- Fasting period before study: no data
- Housing: 5 per cage
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
Dermal application according to the method of Noakes and Sanderson, Brit. J. Industr. Med. 26, 1969, 59
Observation time: 14 days
Duration of exposure:
24 hours
Doses:
500, 600, 700, 900, 1000, 1200 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Sex:
male
Dose descriptor:
LD50
Effect level:
750 mg/kg bw
Mortality:
600 mg/kg: 2 of 10 3 days after application
700 mg/kg: 5 of 10 3-4 days after application
900 mg/kg: 8 of 10 3-4 days after application
1000 mg/kg: 8 of 10 3-4 days after application
1200 mg/kg: 10 of 10 3h-3 days after application
Clinical signs:
sedation, cyanotic appearance, unkempt fur, palmospasm, low body temperature
Body weight:
not examined
Gross pathology:
not examined

Acute dermal toxicity of p-nitrochlorobenzene in rats

Dose (mg/kg bw)

Time of death

Dead

Symptoms

Number of rats used

500

600

700

900

1000

1200

-

3d

3-4d

3-4d

3-4d

3h-2d

0

2

5

8

8

10

10

10

10

10

10

10

10

10

10

10

10

10

Value: (670 - 830 mg/kg bw)

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Classification:
DSD: Xn, R21 Harmful in contact with skin
GHS: Acute Dermal Category 3 H311
Executive summary:

Loeser, Bayer AG, 1979

The study was performed comparable to guideline study 402 with acceptable restrictions (no pathologic examination was performed, lack of details on test substance). The acute dermal toxicity of 1-chloro-4-nitrobenzene was investigated in 10 male rats per dose according to the method of Noakes and Sanderson, 1969. The animals were dosed with 500, 600, 700, 900, 1000, 1200 mg/kg body weight. Sedation, cyanotic appearance, unkempt fur, palmospasm, low body temperature were observed at dose levels equal to and exceeding 600 mg/kg body weight. The LD50 was 750 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
750 mg/kg bw

Additional information

p-chloronitrobenzene is toxic by oral administration, dermal contact and by inhalation.

The acute oral toxicity of 1 -chloro-4 -nitrobenzene was investigated in male Wistar II rats in a study comparable to OECD

guideline 401 with acceptable restrictions. 7 male groups of 10 animals were dosed with 100, 200, 300, 350, 400, 500 and 600 mg/kg bw 1-chloro-4-nitrobenzene per gavage and observed for 14 days following exposure for mortality and clinical signs. Mortalities occurred at dose levels equal to and exceeding 200 mg/kg bw 2 days after administration. Reduced general condition, cyanotic appearance, diarrhea, increased excretion of urine were observed in all male animals dosed 200 - 600 mg/kg bw. Symptoms started to appear between 3 hours (600 mg/kg bw) and 4 days (400 and 600 mg/kg bw) after administration. No clinical signs were observed in animals dosed with 100 mg/kg bw in male rats. The calculated LD50 for male rats was 294 mg/kg bw.

The dermal LD50 ranges for rats are between 750 - 1722 mg/kg body weight and the ranges in rabbit studies are between 2000 - 3160 mg/kg bw.

In a study performed comparable to guideline study 402 with acceptable restrictions the acute dermal toxicity of 1 -chloro-4 -nitrobenzene was investigated in male rats. The LD50 was 750 mg/kg body weight (Loeser, Bayer AG, 1979).

The acute inhalative toxicity of 1 -chloro-4 -nitrobenzene was investigated in study comparable to OECD guideline 403 with acceptable restrictions. Rats were exposed head-only to an atmosphere containing vapour and microcrystalline particles up to 16,100 mg/m³ air for 4 hours. Clinical signs of toxicity were related to dose. During and immediately after exposure cyanosis, corneal opacity, abnormal arched-back posture, lethargy, reddish-brown nasal and frothy mouth discharges, tachypnea, semi-prostration were observed. From 1 - 14 days post exposure pallor, lacrimation, alopecia, corneal opacity, stained perineal area, dermal irritations were observed. Aslo weight loss of 6 - 13 % was detected within the first 24 hours but weight gain normailzed therafter. Three days post exposure death occured at 16100 mg/m³ in 1 of 10 animals. Therefore the LCLo was 16100 mg/m³air (Dupont, 1981).

Justification for classification or non-classification

Based on the available study results, the following classification is derived; this deviates from the present legal classification (see Section 2):

LD50(oral) = 294 mg/kg bw

Classification:

DSD: Xn, R22 Harmful if swallowed

GHS: Acute Oral Category 3 H301

LD50(dermal) = 750 mg/kg bw

Classification:

DSD: Xn, R21 Harmful in contact with skin

GHS: Acute Dermal Category 3 H311

LCLo (inhalation) = 16100 mg/m3 air

Classification:

DSD: Xn, R20 Harmful by inhalation

GHS: Acute Inhalation Category 3 H331