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

Endpoint summary

Description of key information

The acute toxicity of substance FAT 20043 was determined according to in-house methods before the implementation of OECD guidelines. The methods are considered to be equivalent to current OECD guidelines. The acute oral LD50 of FAT 20043 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.

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:

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)

Principles of method if other than guideline:

To identify LD50 of FAT 20043/E

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. (males) and 145 g. (females)
- Fasting period before study: 18 h
- Housing: Rats were caged singly and kept in a room
- Diet: ad libitum (Oakes Special Diet with added l/it. E)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- 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 5 g/kg of compound)

No. of animals per sex per dose:

5

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

Statistics:

Not specified

Preliminary study:

None

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.

Body weight:

None

Gross pathology:

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

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of FAT 20043/B in rats is greater than 5000 mg/kg. body weight.

Executive summary:

The compound FAT 20043/B 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 of compound). 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. The acute oral LD50 of FAT 20043/B 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.

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:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral:

A study was performed in 1975 to assess the toxicity of the test substance FAT 20043/B according to in-house methods before the implementation of OECD guidelines. The methods are considered to be equivalent to todays OECD guidelines. The compound FAT 20043/B was tested on 10 healthy Sprague-Dawley rats (5 males/ 5 females), aged 6 weeks having average body weights of 170 g (males) and 145 g (females), respectively. The dose was applied 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 of FAT 20043/B 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 another similar study the compound FAT 20043/A 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. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, 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 secrified 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 FAT 20043/A in rats of both sexes observed over a period of 14 days is 6519 (6143-6918) mg/kg 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.

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Acid Red 183 is available. However, the vapour pressure for the substance can be considered low 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 chemical 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 41.2 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, hence it does not need to be classified STOT SE and low toxicity is expected for this chemical via the inhalation route. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Acid Red 183 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

 

Dermal: 

The molecular weight of Acid Red 183 is 582.8 g/mol, indicating it being large for dermal absorption. It has water solubility of 41.2 g/L and n-octanol/water partition coefficient (log P) of -2.35, 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 upto 5000 mg/kg bw, hence it does not need to be classified as STOT SE. Similarly, absence of systemic toxicity in skin irritation and sensitisation studies, further supports the conclusion that no adverse effects are 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 exposure and not after systemic application. Taking above arguments into account, low toxicity is expected on acute dermal exposure of Acid Red 183 and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the observed LD50 of >5000 mg/kg bw in acute oral studies, the test substance does not need to be classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.