Disodium 4,4'-bis(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-ylazo)-1,1'-biphenyl-2,6'-disulphonate

Endpoint summary

Description of key information

Acute Oral Toxicity

LD50 = 2387 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:

October 24, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River France (76410 Saint Aubin les Elbeuf, France)
- Weight at study initiation: between 119 and 184 g for males and between 110 and 155 g for females
- Fasting period before study: yes
- Housing: animals were kept in pre-sterilized polycarbonate cages (five animals per cage) with a size of 42.0 x 27.0 x 15.0 cm covered with a stainless steel wire mesh lid containing food and a water bottle.
- Diet: certified pelleted Rat and Mouse diet Ref A 04C N.A.R. Villemoisson sur Orge, France). Food was given ad libitum during all the study with the exception of the period prior to treatment
- Water: free access to tap water filtered with Millipore filters (0.22 micron) in water bottles.
- Acclimation period: for a minimal period of seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 °C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): light/dark cycle was 12 hours per day

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 and 20 ml/kg
- Lot/batch no.: batch n o 1178

MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg, in a volume of 20 ml/kg

Doses:

3000, 2000, 1500, 1000, 750 and 500 mg/kg bw

No. of animals per sex per dose:

5 per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed frequently the day of treatment and twice a day during the observation period to note any change in behaviour
or health condition. The mortality was checked daily during the observation period. Bodyweights were recorded on D 1, D 5, D 8, and D 15.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of the organs was performed on all animals found dead during the study and those killed by CO2 asphyxiation at the end of the observation period.

Preliminary study:

Fifteen minutes after dosing at 5000 mg/kg, clonic convulsions were observed in 7 animals, dyspnea and pilo-erection in 3 animals. On Day 2, pilo-erection was observed in the survivor (male 04).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 387 mg/kg bw

Based on:

test mat.

95% CL:

> 1 905.94 - < 3 164.91

Mortality:

see tables attached

Clinical signs:

other: see tables attached

Gross pathology:

see tables attached

Chronic convulsions were observed 15 mins after gavage at 3000 mg/kg in 8 animals, and at 2000 mg/kg in 3 animals.

On Day 2, no clinical sign was observed. At the dose levels of 1500, 1000, 750 and 500 mg/kg, no clinical sign was recorded.

PATHOLOGICAL EXAMINATIONS

No macroscopic abnormalities were observed at necropsy of the animals found dead during the study or those sacrificed at the end of the observation period. Consequently, no sampling of tissues and no histological investigations were performed.

Interpretation of results:

other: CLP criteria not met

Conclusions:

LD50 = 2387 mg/kg bw

Executive summary:

Method

The study was conducted according to the recommendations of the OECD Guideline N° 401.

Results

The first study was performed at the dose level of 5000 mg/kg bw in distilled water; 7 animals out of 10 died in the first 15 minutes and 2 animals on Day 2.

The second study, therefore, was performed with the following doses in distilled water: 3000, 2000, 1500, 1000, 750 and 500 mg/kg bw. The main clinical sign was chronic convulsions at the dose levels of 5000, 3000 and 2000 mg/kg bw. No clinical sign was observed at the other doses. The bodyweight gain of the survivors was not influenced by the treatment. Macroscopic investigations revealed no lesions in the animals found dead during e study or those sacrificed at the end of the observation period.

Conclusion

LD50 = 2387 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 387 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 study was conducted according to the recommendations of the OECD Guideline 401.

The first study was performed at the dose level of 5000 mg/kg bw in distilled water; 7 animals out of 10 died in the first 15 minutes and 2 animals on Day 2.

The second study, therefore, was performed with the following doses in distilled water: 3000, 2000, 1500, 1000, 750 and 500 mg/kg bw. The main clinical sign was clonic convulsions at the dose levels of 5000, 3000 and 2000 mg/kg. No clinical sign was observed at the other doses. The bodyweight gain of the survivors was not influenced by the treatment. Macroscopic investigations revealed no lesions in the animals found dead during e study or those sacrificed at the end of the observation period.

The LD50 value calculated in this study was 2387 mg/kg bw.

This result is in line with the one obtained in the supporting study where the LC50 value was greater than 5000 mg/kg bw. Only a short abstract is available for this test.

Justification for classification or non-classification

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

In the case of oral exposure route, the acute toxicity hazard categories and acute toxicity estimates (ATE) defining the respective categories are:

- Category 1: ATE ≤ 5 mg/kg bw

- Category 2: 5 < ATE ≤ 50 mg/kg bw

- Category 3: 50 < ATE ≤ 300 mg/kg bw

- Category 4: 300 < ATE ≤ 2000 mg/kg bw

The acute oral LD50 in rats was established to be greather than 2000 mg/kg bw (2387 mg/kg bw), therefore, the substance is not classified for acute toxicity, according to the CLP Regulation (EC n. 1272/2008).