Trisodium [μ-[3-[[4'-[[6-benzamido-1-hydroxy-3-sulpho-2-naphthyl]azo]-3,3'-dihydroxy[1,1'-biphenyl]-4-yl]azo]-4,5-dihydroxynaphthalene-2,7-disulphonato(7-)]]dicuprate(3-)

Endpoint summary

Description of key information

The oral LD50 for Direct Blue 094 was found to be >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:

From 09 November, 1978 to 6 December, 1978

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:

Groups of 5 male and 5 female rats each were administered test dose of 4000, 5000, 6000 and 7000 mg/kg bw respectively. Mortality and clinical signs were observed for each group for a period of 14 days.

GLP compliance:

no

Remarks:

Study predates GLP

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Batch No.: EN 80524/76
Physical appearance: Solid
Test material received: October 17, 1978

Species:

rat

Strain:

other: Tif. RAI rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Inbred rats (male and females) : CIBA-GEIGY Limited, Basel, Switzerland.
- Strain : Tif: RAIf (SPF)
- Age at study initiation: 7 to 8 weeks.
- Weight at study initiation: Average weight of 205 gm.
- Housing : Macrolon cages (Type 3)
- Diet : Rats received ad libitum rat food - NAFAG, Gossau SG.
- Water : ad libitum.
- Acclimation period: 4 days.

ENVIRONMENTAL CONDITIONS
- Temperature : 22 +/- 1 °C
- Humidity : 55 +/- 5 %
- Photoperiod : 10 hours light cycle day.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

Test material and formulation:
FAT 11127/B was suspended in PEG 400. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer. Animals fasted overnight were treated by oral intubation.
Volume fed: 20 ml/kg bw.

Doses:

4000, 5000, 6000 and 7000 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: 1, 2, 4, 6 and 24 hours after dosing on Day 1 and daily thereafter till Day 14
- Weighing: Day 1, 7 and 14
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 000 mg/kg bw

Based on:

test mat.

Mortality:

2 female rats of 5000 mg/kg group were found dead within 24 hours of dosing. No mortality was observed with any other groups.

Clinical signs:

other: Sedation and diarrhoea were observed in all test groups in first 24 hours. Dyspnoea persisted till Day 8 in all test groups. Exophthalmos was seen till Day 6. Ruffled fur was observed in till day 8, while curved body position lasted in all test groups til

Gross pathology:

No substance related gross organ changes were seen.

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of FAT 11127/B in rats of both sexes observed over a period of 14 days is greater than 7000 mg/kg bw.

Executive summary:

FAT 11127/B was tested for acute oral toxicity potential (LD50) using methodology similar to OECD Guideline 401. 5 rats per sex per group were tested with doses of 4000, 5000, 6000 and 7000 mg/kg bw. The test substance was administered using oral gavage. Animals were observed for 14 days for mortality, clinical signs and changes in bodyweights. They were submitted at random to a necropsy whenever they died, survivors at the end of the observation period.

2 animals were found dead at the dose of 5000 mg/kg bw within 24 hours of observation. No other mortality was seen at any of the tested doses. Clinical signs observed included sedation, diarrhoea, dyspnoea, exopthalmos, ruffled fur and curved body position. The surviving animals recovered within 8 days. No significant changes in body weights was observed. No gross pathological changes were observed. Hence, based on the above findings, the oral LD50 for FAT 11127/B was determined to be >7000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

7 700 mg/kg bw

Quality of whole database:

Good quality study

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:

other justification

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral:

Acute toxicity potential of Direct Blue 094 was evaluated in two studies conducted with a methodology similar to OECD Guideline 401.

In the study designated as key (1978), groups of rats containing 5 males and 5 females each, were administered FAT 11127/B via gavage at the doses of 4000, 5000, 6000 and 7000 mg/kg bw and observed over a period of 14 days. Sedation, dyspnoea, exopthalmos, ruffled fur and body position (curved) were observed. 2 animals were found dead at the dose of 5000 mg/kg bw within 24 hours of observation. Based on these findings, the LD50 for FAT 11127/B was determined to be >7000 mg/kg bw.

In a study designated as supporting and conducted with method similar to OECD Guideline 401 (1974), groups of rats each containing 5 males and 5 females each were administered FAT 11127/A at the doses of 3590, 4640 and 7750 mg/kg bw respectively and observed over a period of 7 days. Sedation, Dyspnoea, Exopthalmos, Ruffled fur and body position (curved) was observed. No gross pathological changes and no mortality was observed. Hence, the LD50 was determined to be >7700 mg/kg bw.

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Direct Blue 094 is available. However, the vapour pressure for the target chemical is considered to be low owing to the high melting point of 254 °C, hence its considered to have low volatility. The median particle size of Direct Blue 094 was 73.152 µm, which indicates that the chemical may not be able to reach the alveolar region of respiratory tract. 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. Further, the chemical was found to have low acute toxicity when tested via oral route with LD50 >5000 mg/kg bw. Hence, considering all the above arguments, it is considered that Direct Blue 094 has a low toxicity potential via inhalation route and thus the study on acute inhalation toxicity is considered scientifically not necessary. 

Dermal:

Currently no study to assess acute dermal toxicity of Direct Blue 094 is available. However, the molecular weight of the chemical is 1088 g/mol, indicating it being too large for dermal absorption. Hence, the dermal uptake for the chemical is expected to be low. The partition coefficient (n-octanol/water) of Direct Blue 094 was determined to be -2.16, this indicates poor lipophilicity that will limit the crossing of chemical into the stratum corneum, supporting the hypothesis that dermal absorption for the chemical will be low. The chemical showed low toxicity potential in the available acute oral toxicity study (LD50 >5000 mg/kg bw). Similarly, absence of systemic toxicity when applied epidermally in skin irritation as well as sensitization studies, further supports the conclusion that no adverse effects are expected 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. Hence, low toxicity is expected on acute dermal exposure of Direct Blue 094 and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

No toxicity was seen in the acute oral toxicity studies with Direct Blue 094, hence the substance does not warrant classification for acute toxicity as per the criteria of Regulation (EC) No. 1272/2008.