Sodium bis[2-chloro-4-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-5-hydroxybenzenesulphonamidato(2-)]chromate(1-)

Endpoint summary

Description of key information

The acute oral median lethal dose (LD50) of Acid Red 211 in rats of both sex is greater than 5,000 mg/kg.

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:

Nov 1976

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)

Deviations:

not specified

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5 to 6 weeks
- Weight at study initiation: 162 (M) to 136 g (F).
- Diet: ad libitum (Dakes special Diet with added Vit. E)
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2 °C
- Photoperiod (hrs dark / hrs light): 12 hours darkness and 12 hours artificial light in each 24 hour period.
- Rats were cages singly.

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Tap water

Details on oral exposure:

DOSAGE PREPARATION :
A 25 % w/v solution of the compound in tap water was administered as a single dose by gavage to rats which had been fasted for 18 h, at a rate of 20 ml/kg. (equivalent to 5 g/kg. of compound).

Doses:

- 5000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the 14 day observation period.

Clinical signs:

other: 24 h after administration the faeces were stained by the compound.

Gross pathology:

Autopsy: No changes in organs or tissues caused by the administration of the test substance were seen.

Other findings:

24 h after administration the faeces were stained by the compound.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of FAT 20028/B in rats of both sex is greater than 5,000 mg/kg.

Executive summary:

An acute oral toxicity study was carried out with FAT 20028/B in rats. Five rats per sex were used for this experiment. FAT 20028/B was used at 5000 mg/kg dose levels. All animals were observed over a period of 14 days. Mortality, body weights and clinical signs were recoded. At the end of the observation period, all animals were killed to be autopsied and gross pathology was carried out. No deaths occurred during the 14 day observation period. At autopsy, no substance related gross organ changes were seen. In conclusion, acute oral median lethal dose (LD₅₀) of FAT 20028/B in rats of both sex is greater than 5,000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute Oral Toxicity:

In a key study, an acute oral toxicity study was carried out with FAT 20028/C in rats comparable to OECD 401 guideline. In total, 30 rats were used for this experiment (5 /sex/dose). FAT 20028/C was used at 3000, 4000 and 5000 mg/kg dose levels. The test item was suspended in CMC 2 % and administered by oral intubation. All animals were observed over a period of 14 days. Mortality, body weights and clinical signs were recoded. At the end of the observation period, all animals were killed to be autopsied and gross pathology was carried out. No deaths occurred during the 14 day observation period. Sedation, dyspnoea, exophthalmos, ruffled fur, diarrhoea, curved body position like signs and symptom were observed (slight to moderate) in all dose group animals. The animals recovered within 8 days. At autopsy, no substance related gross organ changes were seen. In conclusion, acute oral median lethal dose (LD₅₀) of FAT 20028/C in rats of both sex is greater than 5,000 mg/kg. In another two supporting studies, oral LD₅₀ was greater than 5000 and 10000mg/kg in rats, respectively.

Acute Inhalation Toxicity:

Currently no study to assess the acute inhalation toxicity potential of Acid Red 211 is available. However, the vapour pressure for the substance can be considered low (1.42 × 10 ^-4 Pa) and owing to the high melting point (>350 °C). Hence, the substance is considered to have low volatility. Synthesis and spray drying of this chemical is performed in a closed process; the final product consists of non-dusty granules. Hence, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. Based on column 2, ‘Specific rules for adaptation from column 1’ of the table given in REACH Annex VII, the study on acute inhalation toxicity only needs to be conducted if an exposure via inhalation is to be expected, based on vapour pressure and/or the likelihood of an exposure to aerosols, particles or droplets. Referring to the expected low volatility of the substance, the fact that the substance is imported into the EU in a formulated form as a dust-free powder or as a granulate, the exposure via inhalation is considered to be unlikely. Further, the chemical is found to have water solubility of 1.6 g/L, hence in the case of dust of the substance entering the respiratory tract, it will be trapped in the mucus and cleared, thereby further limiting the absorption. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD₅₀>5000 mg/kg bw) with no mortality or systemic toxicity being seen upto 5000 mg/kg bw, hence it does not need to be classified STOT SE. Taking the above arguments into account, low toxicity potential is expected on acute exposure of Acid Red 211 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Acute Dermal Toxicity:

Currently no study to assess the repeated dose dermal toxicity of Acid Red 211 is available. However, the molecular weight of the chemical is 885.6 g/mol, indicating it being too large for dermal absorption. It has water solubility of 1.8 g/L and n-octanol/water partition coefficient (log P) of 1.33, indicating it being too hydrophilic to cross the lipid rich environment of the stratum corneum. Hence, the dermal uptake for the substance will be low. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD₅₀>5000 mg/kg bw), with no mortality or systemic toxicity being seen up to 5000 mg/kg bw, hence it does not need to be classified STOT SE. Similarly, absence of local toxicity in skin irritation as well as sensitization studies, further supports the conclusion that low toxicity is expected for the chemical via the dermal route. Further, experience with similar chemical substances has demonstrated that it is very unlikely that toxicity related to the intrinsic properties of the chemical only show up upon dermal application and not after systemic exposure. Taking these arguments into account, low toxicity potential is expected on acute dermal exposure of Acid Red 211 and hence testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the observed LD₅₀of >5000 mg/kg bw in the acute oral toxicity study, Acid Red 211 does not considered to be classified according to according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.