Disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl]azo]-4-[[4-[(2-chloro-5-sulphonatophenyl)amino]-6-fluoro-1,3,5-triazin-2-yl]amino]benzenesulphonate

Endpoint summary

Description of key information

The acute oral median lethal dose (LD50) of test substance is >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:

experimental study

Adequacy of study:

key study

Study period:

27 May 1980 to 27 June 1980

Reliability:

1 (reliable without restriction)

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:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif: RAIf (SPF) strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-house
- Age at study initiation: 7-8 weeks old
- Fasting period before study: overnight
- Housing: During the treatment and observation period the animals were housed in groups of 5 in Macrolon cages (type 3), individually marked with picric acid
- Diet: NAFAG, Gossau SG rat food ad libitum
- Water: ad libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Photoperiod: 10 hours light cycle day

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
20 mL/kg bw

DOSAGE PREPARATION:
Test substance was suspended to achieve the corresponding dosage level. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
Volume (ml/kg body-weight): 10, 20

Doses:

3000, 4000 and 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily and weighing Days 1, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

LD50 Including 95 % confidence limits were calculated by the loglt model.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

One female at the dose of 5000 mg/kg bw was found dead 5 hours after the dosing.

Clinical signs:

other: Clinical signs observed included sedation, dyspnoea, exophthalmos, ruffled fur, diarrhoea and curved body position. These were seen at all the used dose levels. The animals recovered within 7 days.

Gross pathology:

No substance related gross organ changes were seen.

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50 ) in rats was determined to be greater than 5000 mg/kg bw.

Executive summary:

An acute oral toxicity study with FAT 40138/A was conducted according to the methodology that is equivalent to the OECD Guideline 401. Groups of 5 males and 5 females each, were administered the test substance by gavage. The doses administered were 3000, 4000 and 5000 mg/kg bw. Clinical signs, mortality check and body weight were recorded during an observation period of 14 days. Animals were submitted to a necropsy whenever they died, survivors at the end of the observation period.

 

No mortality was seen at the dose levels of 3000 and 4000 mg/kg bw. However, one female at the dose of 5000 mg/kg bw was found dead 5 hours after the dosing. Clinical signs observed included sedation, dyspnoea, exophthalmos, ruffled fur, diarrhoea and curved body position. These were seen at all the used dose levels.The animals recovered within 7 days. The test item administration did not affect body weight gains at any dose levels. Further, no substance related gross organ changes were seen with any of the treated animals. Hence, based on the above findings, the acute oral median lethal dose (LD50 ) in rats was determined to be greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Comparable to OECD 401 guideline.

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, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies)

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Three studies are available for the assessment of oral toxicity potential of the substance. An acute oral toxicity of FAT 40138/D was determined in a study conducted according to OECD Guideline 401 and EU Method B.1 under GLP conditions. No mortality occurred throughout the observation period. Piloerection, hunched posture and dyspnea were observed in all the treated animals. Additionally, reduced locomotor activity was observed in the females. The animals recovered within 4 days. The test item administration did not affect body weight gains at any dose levels. Further, no substance related gross organ changes were seen with any of the treated animals. Hence, based on the above findings, the acute oral median lethal dose (LD50) in rats was determined to be greater than 2000 mg/kg bw. In addition to the above key study, two supporting studies are available and in these studies the acute oral LD50 in rats was determined to be greater than 5000 mg/kg bw.

 

Acute inhalation toxicity:

Currently no study to assess acute inhalation toxicity of Reactive Yellow 143 is available. However, low vapour pressure owing to high melting point (>350 °C), the substance is considered to have low volatility. Synthesis and formulation of this chemical is performed in a closed process; the final product consists of liquid formulations only. 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 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 liquid formulation, the exposure via inhalation is unlikely. Further, Reactive Yellow 143 was found to be highly soluble in water (water solubility >89 g/L) and have low log partition coefficient (<-3.69), 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 (LD50 >2000 mg/kg bw) in the available acute oral toxicity study with no mortality or systemic toxicity, hence it does not need to be classified as STOT SE. Taking the above arguments into account, low toxicity potential is expected on acute exposure of Reactive Yellow 143 via inhalation route and hence, testing by the inhalation route was considered scientifically not necessary.

 

Acute dermal toxicity:

Currently no study to assess the acute dermal toxicity of Reactive Yellow 143 is available. However, the high molecular weight of the chemical is 742 g/mol, indicating it being too large for dermal absorption. It has water solubility of >89 g/L and n-octanol/water partition coefficient (log P) of <-3.69, indicating it being too hydrophilic to cross the lipid rich environment of the stratum corneum in the epidermis. Hence, the dermal uptake for the substance will be low. Synthesis and formulation of this chemical is performed in a closed process; the final product consists of liquid formulations only. In addition, the use of this substance will not result in aerosols, particles or droplets, so exposure to humans via the dermal route will be unlikely to occur. The chemical showed low toxicity potential in the available acute oral toxicity study, with no mortality or systemic toxicity (LD₅₀>2000 mg/kg bw), hence it does not need to be classified as STOT SE. Similarly, absence of local toxicity in eye and skin irritation studies as well as absence of systemic toxicity in sensitization studies, further supports the conclusion that low toxicity is expected for the chemical via the dermal route. Taking the above arguments into account, low toxicity potential is expected on acute exposure of Reactive Yellow 143 via dermal route and hence testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the observed LD₅₀of >2000 mg/kg bw in the acute oral toxicity study, the test substance does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.