1-[2-[[4-[(2-chloro-4-nitrophenyl)azo]phenyl]ethylamino]ethyl]pyridinium acetate

Endpoint summary

Description of key information

LD50(male/female) = 2122 mg/kg bw    

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:

From December 12, 1978 to January 10, 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)

GLP compliance:

no

Remarks:

Study conducted before 1981

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 to 8 weeks old
- Fasting period before study: overnight before treatment
- Housing: housed in groups of 5 in Macrolon cages
- Diet: NAFAG, Gossau SG ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1 °C
- Humidity (%): 55 ± 5 %
- Photoperiod (hrs dark / hrs light): 10 hours light cycle day

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Amount of vehicle : 10, 20 ml/kg
The test item was suspended. Before treatment the suspension was homogeneously suspended with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Doses:

Doses (mg/kg bw) : 1000, 2000, 3000, 5000
Volume (ml/kg bw): 10, 20

No. of animals per sex per dose:

5 per sex per dose

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: bodyweights were recorded immediately prior to dosing (control weights) and at 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 122 mg/kg bw

Based on:

test mat.

Remarks on result:

other: effect level in a range of 1656-2619 mg/kg bw

Mortality:

(1000 mg/kg bw) no deaths; (2000 mg/kg bw) 4 death; (3000 mg/kg bw) 9 death; (5000 mg/kg bw) all animals were found dead

Clinical signs:

Sedation, Dyspnoea, Exophtalmos, Ruffled fur, Body Position (Curved) in all the concentration tested.
Diarrhoea was observed at doses of 1000, 2000 and 3000 mg/kg bw.
Convultions were observed at the dose of 5000 mg/kg bw.

Interpretation of results:

other: CLP criteria not met

Conclusions:

LD50 (male/female) = 2122 mg/kg bw

Executive summary:

Method

The test substance was tested for Acute Oral Toxicity on rats according to a method similar to the OECD Guideline 401. Five animals per sex per dose were administered by gavage with the test item at four different concentrations ( 1000, 2000, 3000 and 5000 mg/kg bw).

Observations

During the treatment and observation period the animals were housed in groups of 5 in Macrolon cages. Animals fasted overnight were treated by oral intubation. Physical condition and rate of deaths were monitored throughout the whole observation period.

During the test Sedation, Dyspnoea, Exophtalmos, Ruffled fur, Body Position (Curved) in all the concentration tested. Diarrhoea was observed at doses of 1000, 2000 and 3000 mg/kg bw. Convultions were observed at the dose of 5000 mg/kg bw.

At 1000 mg/kg bw no deaths occurred and at the maximum dose (5000 mg/kg bw) all the animals were found dead, at the other concentrations the following number of animals were found dead: 4 animals at 2000 mg/kg bw and 9 animals at 3000 mg/kg bw.

Conclusion

LD50 (male/female) = 2122 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 122 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key study (Huntsman, 1978) was performed according to a method similar to OECD guideline 401, following oral administration of four doses to the rats (1000, 2000, 3000, 5000 mg/kg bw). At 1000 mg/kg bw no deaths occurred and at the maximum dose (5000 mg/kg bw) all the animals were found dead, at the other concentrations the following number of animals were found dead: 4 animals at 2000 mg/kg bw and 9 animals at 3000 mg/kg bw. The acute oral LD50 was determined to be 2122 mg/kg bw.

The supporting study (Huntsman, 1980) was performed according to a method similar to OECD guideline 401 and following administration administration of six doses to the rats (1000, 2200, 2500, 3000, 5000 mg/kg bw). At 1000 and 2000 mg/kg bw no deaths occurred and at the maximum doses (5000 and 3000 mg/kg bw) all the animals were found dead, at the other concentrations the following number of animals were found dead: 2 animals at 2200 mg/kg bw and 8 animals at 2500 mg/kg bw. The acute oral LD50 was determined to be 2343 mg/kg bw.

The values reported above are in line with the results obtained with further tests conducted with  Similar Substance 01, where the LD50 was found to be in a range of 2710 – 7080 mg/kg bw. More details are reported in the file attached below.

LD50 (male/female) = 2122 mg/kg bw

Justification for classification or non-classification

According to the CLP Regulation (EC n. 1272/2008), 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The oral LD50 value was established to be 2122 mg/kg body weight, therefore the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity Category 4: 300 < ATE ≤ 2000 mg/kg bw).