Trisodium bis[3-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-2-hydroxy-5-nitrobenzenesulphonato(3-)]chromate(3-)

Endpoint summary

Description of key information

LD50 > 5000 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:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

September 10, 1975

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

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
- Age at study initiation:6 weeks
- Weight at study initiation:average body weight of 170 g (male) and 145 g (female)
- Fasting period before study:
- Housing:Rats were caged singly and kept in a room
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Photoperiod (hrs dark / hrs light):12 hours artificial light and 12 hours darkness in each 24 hour period

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

tap water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 % w/v

MAXIMUM DOSE VOLUME APPLIED:20 ml/kg (equivalent to 5 g/kg of compound)

Doses:

20 ml/kg (equivalent to 5000 mg/kg bw)

No. of animals per sex per dose:

Ten rats (5 males and 5 females)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, mortality

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the 14 day observation period.

Clinical signs:

No clinical symptoms were recorded during the 14 day observation period.

Gross pathology:

At autopsy no changes in organs or tissues caused by the administration of the test compound were seen.

Interpretation of results:

other: CLP criteria not met

Conclusions:

LD50 > 5000 mg/kg bw

Executive summary:

Method

The compound was tested on 10 healthy Sprague-Dawley rats (5 males/ 5 females), aged 6 weeks having average body weight of 170g (male) and 145 g (female). Rats were caged singly and kept in a room maintained at a temperature of 21 °C with 12 hour light/dark period.

A 25 % w/v suspension of the compound in tap-water was administered as a single dose by gavage to rats which had been fasted for 18 hours, at a dose rate of 20 ml/kg (equivalent to 5000 mg/kg bw).

Observation

After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period, surviving animals were killed by exsanguination under ether anaesthesia and an autopsy performed. No clinical symptoms were recorded and no deaths occurred during the 14 day observation period. At autopsy no changes in organs or tissues caused by the administration of the test compound were seen.

Conclusion

The acute oral LD50 in rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg bw. The compound has therefore is not considered to cause acute toxicity to the rat by this route of administration.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 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

Quality of whole database:

No studies on the "Acute Oral Toxicity" are available for the substance in itself nevertheless, two studies were conducted with an analogue molecule (Similar Substance 01). Further information are reported in the Read Across justification attached to section 13.

Additional information

No studies on the "Acute Oral Toxicity" are available for the substance in itself nevertheless, two studies were conducted with an analogue molecule (Similar Substance 01). Further information are reported in the Read Across justification attached to section 13.

The key study was performed in 1975 to assess the toxicity of the test substance according to in-house methods before the implementation of OECD guidelines. The methods are considered to be equivalent to modern methods as per guidelines. The compound was tested on 10 healthy Sprague-Dawley rats (5 males/ 5 females), aged 6 weeks having average body weight of 170 g (male) and 145 g (female) as a single dose by gavage to rats which had been fasted for 18 hours, at a dose rate of 20 ml/kg (equivalent to 5000 mg/kg of compound). No clinical symptoms were recorded and no deaths occurred during the 14 day observation period. At autopsy no changes in organs or tissues caused by the administration of the test compound were seen. Therefore, the acute oral LD50 in rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg. The compound has therefore is not considered to cause acute toxicity to the rat by this route of administration.

 

In the supporting study the compound was tested on 40 Tif. RAI rats (20 males/ 20 females), aged 6 to 7 weeks old and weighed 160 to 180 g. The animals were treated at a concentration 4640, 6000, 6800, 7750 mg/kg bw. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The surviving animals had recovered within 7 to 8 days. They were killed and autopsied after an observation period of 14 days. On autopsy no substance related gross organ changes were seen. The LD50 was calculated by probit analysis method. The acute oral LD50 of in rats of both sexes observed over a period of 14 days is 6519 (6143-6918) mg/kg bw based on the test material and 2933 mg/kg bw based on the active ingredient .The compound has therefore is not considered to cause acute toxicity to the rat by this route of administration.

 

Taking both results into consideration, the test substance is judged to cause no acute oral toxicity up to 2000 mg/kg bw. It is most likely that even higher doses of the purified chemical are not of acute toxicity as demonstated by the key study selected. Why the test sample fomulation of the second study demonstrated higher toxicity while having a lower test substance concentration remains elusive.

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 greater than 2000 mg/kg bw in both tests, therefore the substance is not classified for acute toxicity, according to the CLP Regulation (EC n. 1272/2008).