1,2-dichloro-3-nitrobenzene

Endpoint summary

Description of key information

The acute oral LD50 value in male rats is 1070 mg/kg (Löser 1980) and the dermal LD50 value in rats is greater than 2500 mg/kg bw (Löser 1981). No acute inhalation study is available.

However, the acute oral toxicity study in cats demonstrate a methemoglobin formation. Therefore the classification for acute toxicity is increased.

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:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles.

Principles of method if other than guideline:

Acute oral toxicity in rats

GLP compliance:

no

Test type:

standard acute method

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: 9 weeks
- Weight at study initiation: 177 g
- Housing: 5 animals per cage (Macrolon Type III)
- Diet (e.g. ad libitum): Altromin R 1324 (Altromin GmbH, Lage, Germany) ad libitum
- Water (e.g. ad libitum): tap-water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1.5
- Humidity (%): 60 +/- 5
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 20 ml/kg bw

Doses:

100, 500, 1000, 1500, 2000, 3100 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Animals were observed 1, 2, 4, 8 and 24 h post-application, and twice daily thereafter up to 14 days. Animals were weighed on the application day and at the end of the observation period (day 14).

Statistics:

LD50 with confidence interval for p<= 0.05 was calculated by Probit-analysis (Fink and Hund 1965. Arzneim.-Forsch. 15:624).

Sex:

male

Dose descriptor:

LD50

Effect level:

1 070 mg/kg bw

Based on:

test mat.

95% CL:

0.77 - 1.36

Remarks on result:

other: clinical signs: reduced body weights, increased diuresis, sedation, scrubby coat

Mortality:

refer to remarks on results

Clinical signs:

other: refer to remarks on results

Gross pathology:

not examined

Mortality

 

Dose level (mg/kg bw)	Mortality
100	0/10
500	1/10
1000	4/10
1500	8/10
2000	8/10
3100	10/10

 

Mortalities occurred at dose levels equal to and exceeding 500 mg/kg bw between day 2 and 9 following administration. Enhanced diuresis, loss of weight and scubby fur were observed in all animals dosed 500 - 3100 mg/kg bw. These symptoms were slight to moderate and started to appear 1 h (1000 - 3100 mg/kg bw) and on day 2 (500 mg/kg bw) after administration, continuing up to the end of the observation period. No clinical signs were observed in animals dosed with 100 mg/kg bw.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The calculated LD50 was 1070 mg/kg bw.

Executive summary:

Löser (1980) The acute oral toxicity of 1,2 -dichloro-3 -nitrobenzene was investigated in male Wistar rats. 6 Groups of 10 animals were dosed with 100, 500, 1000, 1500, 2000 and 3100 mg/kg bw 1,2 -dichloro-3 -nitrobenzene per gavage, and observed for 14 days following the exposure for mortality and clinical signs. Mortalities occurred at dose levels equal to and exceeding 500 mg/kg bw between day 2 and 9 following administration. Enhanced diuresis, loss of weight and scubby fur were observed in all animals dosed 500 - 3100 mg/kg bw. These symptoms were slight to moderate and started to appear 1 h (1000 - 3100 mg/kg bw) and on day 2 (500 mg/kg bw) after administration, continuing up to the end of the observation period. No clinical signs were observed in animals dosed with 100 mg/kg bw. The calculated LD50 was 1070 mg/kg bw, with a confidence interval for p < 0.05 = 0.77 - 1.36

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 070 mg/kg bw

Quality of whole database:

Acceptable, well-documented study report which meets basic scientific principles.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles.

Principles of method if other than guideline:

Acute dermal toxicity in rats

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

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: ca. 14 weeks
- Weight at study initiation: 179 g
- Housing: 5 animals per cage (Macrolon type III)
- Diet (e.g. ad libitum): Altromin R 1324 (Altromin GmbH, Lage, Germany) ad libitum
- Water (e.g. ad libitum): tap-water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1.5
- Humidity (%): 60 +/- 5
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

not specified

Vehicle:

polyethylene glycol

Duration of exposure:

not specified

Doses:

2500 mg/kg bw

No. of animals per sex per dose:

10 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs and mortality several times on the day of administration, and twice daily thereafter (once on weekends and holidays) up to the end of the observation period. Animals were weighed on the day of admisitration and at hte end of the 14-days observation period.
- Necropsy of survivors performed: no

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality, no clinical signs were observed

Mortality:

no effects

Clinical signs:

other: no effects

Gross pathology:

not examined

No signs of toxicity were observed in all male animals treated with 2500 mg/kg bw. No mortalities occurred.

Interpretation of results:

GHS criteria not met

Executive summary:

The test material was dissolved in Lutrol (polyethylene glycol) at 0.5 g/ml and applied to the skin of 10 male animals. No signs of toxicity were observed in all male animals treated with 2500 mg/kg bw. No mortalities occurred.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 500 mg/kg bw

Quality of whole database:

Acceptable, well-documented study report which meets basic scientific principles.

Additional information

Acute toxicity: oral
The acute oral toxicity of 1,2 -dichloro-3 -nitrobenzene was investigated in male Wistar rats. 6 Groups of 10 animals were dosed with 100, 500, 1000, 1500, 2000 and 3100 mg/kg bw 1,2 -dichloro-3 -nitrobenzene per gavage, and observed for 14 days following the exposure for mortality and clinical signs. Mortalities occurred at dose levels equal to and exceeding 500 mg/kg bw between day 2 and 9 following administration. Enhanced diuresis, loss of weight and scubby fur were observed in all animals dosed 500 - 3100 mg/kg bw. These symptoms were slight to moderate and started to appear 1 h (1000 - 3100 mg/kg bw) and on day 2 (500 mg/kg bw) after administration, continuing up to the end of the observation period. No clinical signs were observed in animals dosed with 100 mg/kg bw. The calculated LD50 was 1070 mg/kg bw (Löser 1980).

 

Acute toxicity: dermal

The acute dermal toxicity of the test substance 2,3-dichloronitrobenzene was evaluated with male Wistar rats in a limited documented study. The test material was dissolved in Lutrol (polyethylene glycol) at 0.5 g/ml and applied to the skin of 10 male animals. No signs of toxicity were observed in all male animals treated with 2500 mg/kg bw. No mortalities occurred. (Löser 1981).

Justification for classification or non-classification

The acute oral LD50 value in male rats is 1070 mg/kg (Löser 1980) and the dermal LD50 value in rats is greater than 2500 mg/kg bw (Löser 1981). No acute inhalation study is available.
According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Acute Tox. 4, H 302 (harmful if swallowed), is adequate.

 

Based on the the acute oral toxicity study in cats, which demonstrate a methemoglobin formation, the classification is tightened.

 

Therefore, 1,2-dichlore-3-nitrobenzene is classified as Acute Tox. 3 (H301: Toxic if swallowed), Acute Tox. 3 (H331: Toxic if inhaled), Acute Tox. 4 (H312: Harmful in contact with skin).