Tetrasodium 2-[[8-[[3-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]benzoyl]amino]-1-hydroxy-3,6-disulphonato-2-naphthyl]azo]naphthalene-1,5-disulphonate

Endpoint summary

Description of key information

Oral LD50 (rat, male/female) > 2000 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:

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

Adequacy of study:

key study

Study period:

From September 21 to October 12, 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

The read across approach is detailed into the document attached to the IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted March 22,1996

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd
- Age at study initiation: females 10 weeks old; males 8 weeks old.
- Weight at study initiation: females 177 - 184 g; males 205 - 213 g.
- Fasting period before study: fasting for approximately 16 to 16.5 hours. Food was provided again approximately 3 hours after dosing.
- Housing: groups of three in Makrolon type4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: pelleted standard Kliba 3433, batch no. 39/99, rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst), available ad libitum.
- Water: community tap water from Itingen, available ad libitum.
- Acclimation period: 6 days, under laboratory conditions, after health examination. Only animals without any visible signs of ilrness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Relative humidity: 40 - 70 %
- Air changes: 10-15 air changes per hour.
- Photoperiod: 12 hour light/dark cycle.
- Other: recorded music was played for approximately 8 hours during the light period.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- Application volume / kg body weight: 10 ml

TEST ARTICLE PREPARATION
The test article was placed into a glass beaker on a tared Mettler balance and the vehicle (bidistilled water) was added. A weight by volume dilution was prepared using a magnetic stirrer as homogenizer. Homogeneity of the test article in the vehicle was maintained during treatment.
The preparation was made shortly before each dosing.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females or 3 males

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: four times during test day 1 and once daily during days 2 - 15.
- Frequency of weighing: on test day 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: necropsies were performed by experienced prosectors. At the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN (Rhöne Merieux GmbH, D-88471 Laupheim). The animals were examined macroscopically and all abnormalities recorded. Thereafter, they were discarded.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No death occurred during the study.

Clinical signs:

No clinical signs were noted during the observation period.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

other: not classified, according to the CLP Regulation (EC) No 1272/2008

Conclusions:

LD50 (male and female) > 2000 mg/kg bw

Executive summary:

Two groups, each using three female or three male Hanlbm: WIST (SPF) rats, were treated withtest item at 2000 mg/kg by oral gavage. The test article was suspended in vehicle (bi-distilled water) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day I prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

No death occurred during the study. No clinical signs were noted during the observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.

Conclusion

LD50 (male and female) > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

ACUTE TOXICITY - ORAL ROUTE

A sheet of testing results, indicating an LD50 value for Reactive Red 147, is available. Unfortunately, the reliability of the data cannot be judged because of the lacking of details about test material, testing procedures and conditions and test results. The LD50 was indicated to be higher than 5000 mg/kg.

In order to deeper investigate the acute oral toxicity potential of Reactive Red 147, the available information on the structural analogous Similar Substance 01 has been taken into consideration; the read across approach can be considered as appropriate and suitable to assess the property under investigation (details about the approach are reported into the IUCLID section 13).

Two groups, each using three female or three male rats, were treated with Similar Substance 01 at 2000 mg/kg by oral gavage. No death occurred during the study and no clinical signs were noted during the observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. Therefore, the substance resulted to be not harmful/toxic if swallowed.

Justification for classification or non-classification

According to the CLP Regulation (EC) No 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 the 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 greater than 2000 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).