Chromate(2-), [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-2-hydroxy-5-nitrobenzenesulfonato(3-)]-, disodium

Endpoint summary

Description of key information

LD50 >5000 mg/kg bw (based on test material)
LD50 >2850 mg/kg bw (based on active ingredient)

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:

1974

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Name: FAT 20010/A
Purity: 57 %

Species:

rat

Strain:

other: CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 95 to 117g
- Fasting period before study:starved overnight

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 16.7 ml/kg bodyweight

MAXIMUM DOSE VOLUME APPLIED:5g/kg bodyweight

Doses:

5000 mg/kg bodyweight

No. of animals per sex per dose:

Ten rats (five males and five females)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,mortality

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 850 mg/kg bw

Based on:

act. ingr.

Mortality:

There were no mortalities occuring throughout the study period.

Clinical signs:

Signs of reaction to treatment, observed shortly after treatment, included lethargy, pilo-erection, diuresis and diarrhoea. The urine and faeces of all rats were stained orange.

Body weight:

Recovery of all animals, as judged by external appearance and behaviour, was apparently complete two days after treatment. This observation was substantiated by normal bodyweight increases compared with controls.

Gross pathology:

No abnormalities recorded.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal oral close (LD50) to rats of FAT 20010/A was found to be greater than 5000 mg/kg bodyweight.

Executive summary:

Acute oral toxicity test was performed on FAT 20010/A according to CIBA internal guidelines equivalent or similar to OECD TG 401. Ten rats (5 male and 5 female) weighing 95 to 117g were dosed at a 5g/kg bw and observed for 14 days. No mortality was observed at the end of the 14-day observation period. But signs of reaction to treatment included lethargy, pilo-erection, diuresis and diarrhoea. The urine and faeces of all rats were stained orange. All the animals recovered, showed normal bodyweight increase in comparison to controls and gross pathology was normal. The acute median lethal oral toxicity (LD50) to rats of FAT 20010/A was found to be greater than 5000 mg/kg bodyweight. The acute median lethal toxicity based on the active ingredient was calculated to be >2850 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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:

In an acute oral toxicity study 10 rats (5 males and 5 females) were administered 5000 mg/kg bw test substance FAT 20010/A by oral gavage and observed for 14 days. All animals survived until the end of the study period and no changes in the body weight and macroscopic findings were observed. The only clinical signs observed, were orange stained urine and faeces. Based on the observations, median lethal oral dose (LD50) to rats of FAT 20010/A was found to be greater than 5000 mg/kg bodyweight based on the test material and >2850 mg/kg bw based on the active ingredient.

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Acid Orange 154 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>280 °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 9.3 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 study (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 above arguments into account, low toxicity potential is expected on acute exposure of Acid Orange 154 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Dermal:

Currently no study to assess the acute dermal toxicity potential of Acid Orange 154 is available. However, the molecular weight of Acid Orange 154 is 849.7 g/mol, indicating it being large for dermal absorption. It has water solubility of 9.3 g/L and n-octanol/water partition coefficient (log P) of -0.008, 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 study (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 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 Orange 154 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 study, 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.