Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Endpoint summary

Description of key information

The acute oral LD50 of FAT 40068/A in rats of both sexes observed over a period of 14 days is approximately 7700 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:

1974

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:

no

Principles of method if other than guideline:

As per the internationally accepted guidelines

GLP compliance:

no

Remarks:

study pre-dates GLP

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Identified as: FAT 40068/A

Species:

rat

Strain:

other: Tif. RAI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeding unit, CIBA-GEIGY Limited, Basle, Switzerland
- Age at study initiation: 6 to 7 weeks
- Weight at study initiation: 160 to 180 g
- Fasting period before study: Overnight before the treatment
- Housing: males and females were segregated and housed in Macrolon cages (Type 3) in groups of 5
- Diet: food (NAFAG, Gossau SG, rat food) ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22 + 1 °C
- Humidity (%): 50

IN-LIFE DATES: 1974

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: suspended at 30% with polyethylene glycol (PEG 400)

DOSAGE PREPARATION: Before treatment the suspension was homogeneously dispersed with an Ultra- Turrax and during treatment it was kept stable with a magnetic stirrer.

Doses:

4640, 6000, 7000 and 7750 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: 2 h, 24 h, 48 h, 7 days and 14 days (mortality reported)
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

7 700 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed at the doses of 4640, 6000 and 7000 mg/kg bw. However 5 out of 10 animals died at the dose of 7750 mg/kg bw.

Clinical signs:

other: Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, 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.

Gross pathology:

No substance related gross organ changes were seen with dead and sacrificed animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of FAT 40068/A in rats of both sexes observed over a period of 14 days is approximately 7700 mg/kg bw.

Executive summary:

An acute oral toxicity study was conducted according to guideline equivalent or similar to OECD TG 401 to evaluate toxicity of REACTIVE BLUE 069. The test substance was suspended at 30 % with polyethylene glycol (PEG 400). Doses of 4640, 6000, 7000 and 7750 mg/kg bw were administered to rats divided in four groups each containing 5 males and 5 females. The treated animals were observed for 14 days for clinical signs and mortality. No mortality was observed at the doses of 4640, 6000 and 7000 mg/kg bw. However 5 out of 10 animals died at the dose of 7750 mg/kg bw. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, 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. No substance related gross organ changes were seen at post mortem examinations. Based on the findings of the study, the acute oral LD50 of FAT 40068/A in rats of both sexes observed over a period of 14 days is approximately 7700 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

7 700 mg/kg bw

Quality of whole database:

Good quality study conducted according to internationally accepted and sound scientific principles, well documented

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute study: oral

An acute oral toxicity study was conducted according to guideline equivalent or similar to OECD TG 401 to evaluate toxicity of Reactive Blue 069. The test substance was suspended at 30 % with polyethylene glycol (PEG 400). Doses of 4640, 6000, 7000 and 7750 mg/kg bw were administered to rats divided in four groups each containing 5 males and 5 females. The treated animals were observed for 14 days for clinical signs and mortality. No mortality was observed at the doses of 4640, 6000 and 7000 mg/kg bw. However 5 out of 10 animals died at the dose of 7750 mg/kg bw. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, 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. No substance related gross organ changes were seen with dead and sacrificed animals. Based on the findings of the study, the acute oral LD50 of FAT 40068/A in rats of both sexes observed over a period of 14 days is approximately 7700 mg/kg bw.

Acute toxicity: inhalation

Currently no study to assess the acute inhalation toxicity potential of Reactive Blue 069 is available. The calculated value for vapour pressure was found to be <2.6E-5 Pa at 25 °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 57.8 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: 7700 mg/kg bw), with no systemic toxicity being seen, hence it does not need to be classified STOT SE. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Reactive Blue 069 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Acute toxicity: dermal

Currently no study to assess the acute dermal toxicity potential of Reactive Blue 069 is available. However, the molecular weight of Reactive Blue 069 is 666.4 g/mol, indicating it being too large for dermal absorption. It has water solubility of 57.8 g/L and n-octanol/water partition coefficient (log P) of -3.33, 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 study (LD50: 7700 mg/kg bw), with no systemic toxicity observed, 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 into consideration the above arguments, low toxicity is expected on acute dermal exposure of Reactive Blue 069 and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the results of an acute oral toxicity study (LD50 = 7700 mg/kg bw), the test substance does not warrant classification under the CLP (Regulation [EC] 1272/2008) criteria.