tetrasodium 4-{4-[(9,10-dioxo-4-{[4-(2-sulfophenoxy)phenyl]amino}-9,10-dihydroanthracen-1-yl)amino]phenoxy}benzene-1-sulfonate 4-{4-[(9,10-dioxo-4-{[4-(4-sulfophenoxy)phenyl]amino}-9,10-dihydroanthracen-1-yl)amino]phenoxy}benzene-1-sulfonate

Endpoint summary

Description of key information

The acute oral LD50 was found to be greater than 5000 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:

1979

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)

GLP compliance:

no

Remarks:

Study predates GLP

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

FAT 21030/C

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Healthy random bred rats of the Tif: RAIf (SPF) strain (7 to 8 weeks old) raised on the premises were used for the experiment. They were kept at a room temperature of 22±2 °C, at a relative humidity of 55±10 % and on a 10 hours light cycle day. They received ad libitum rat food - NAFAG, Gossau SG - and water. Prior to treatment the animals were adapted to our laboratories for a minimum of 4 days.

During the treatment and observation period the animals were housed in groups of 5 in Macrolon cages (type 3), individually marked with picric acid.

Route of administration:

other: Oral intubation

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

- Volume: 10 and 20 ml/kg.
- DOSAGE PREPARATION: FAT 21030/C was suspended in polyethylene glycol (PEG 400). Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Doses:

1000, 3000, 4000 and 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

After administration of the compound, the animals were observed for 14 days. Physical condition and rate of deaths were monitored throughout the whole obseravtion period. At the end of the observation period, surviving animals were killed and an autopsy performed.

Statistics:

LD50 including 95% confidence limits were calculated by the logit model.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured during the 14 day observation period.

Clinical signs:

other: Sedation, dyspnoea, exophtalmos, ruffled fur, diarrhoea and curved body position were observed with all dose groups. The animals recovered within 7 days.

Gross pathology:

No substance related gross organ changes were observed in dead and killed animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of FAT 21030/C in rats was considered to be >5000 mg/kg bw.

Executive summary:

The LD50 of FAT 21030/C was evaluated in a study conducted using methodology similar to OECD Guideline 401. Groups of rats (each containing 5 males and 5 females) were administered FAT 21030/C at 1000, 3000, 4000 and 5000 mg/kg bw. The test item was suspended in polyethylene glycol (PEG 400) and administered by oral intubation.

No deaths occurred in animals that received doses of 1000, 3000 and 5000 mg/kg bw, however one female was found dead at 4000 mg/kg bw during the 14 day observation period. Sedation, dyspnoea, exophtalmos, ruffled fur, diarrhoea and curved body position were observed with all dose groups. The animals recovered within 7 days. At autopsy, no substance related gross organ changes were seen.

Based on the above findings, the acute oral LD50 of FAT 21030/C observed over a period of 14 days was considered to be >5000 mg/kg bw.

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:

Additional information

Oral:

Two acute oral studies were performed with FAT 21030. In both studies, the LD50 oral was found to be greater than 5000 mg/kg bw.

In the study (1979) designated to be key, the LD50 of FAT 21030/C was evaluated using methodology similar to OECD Guideline 401. Groups of rats (each containing 5 males and 5 females) were administered FAT 21030/C at 1000, 3000, 4000 and 5000 mg/kg bw. No deaths occurred in animals that received doses of 1000, 3000 and 5000 mg/kg bw, however one female was found dead at 4000 mg/kg bw during the 14 day observation period. Sedation, dyspnoea, exophtalmos, ruffled fur, diarrhoea and curved body position were observed with all dose groups. The animals recovered within 7 days. At autopsy, no substance related gross organ changes were seen. Based on the above findings, the acute oral LD50 of FAT 21030/C observed over a period of 14 days was considered to be >5000 mg/kg bw.

In the supporting study (1975), no deaths occurred and no symptoms were seen in a group of rats administered FAT 21030/A at 5000 mg/kg bw. Hence the acute oral LD50 was considered to be >5000 mg/kg bw.

Inhalation:

Currently no study is available to assess the acute inhalation toxicity potential of Acid Green 40:1. However, the vapor pressure of the chemical investigated is calculated to be very low owing to the high melting point of 241 °C, hence its considered to have low volatility. Water solubility of 7.7 g/L indicates the substance being hydrophilic that may cause retention of dust in the mucus if the substance enters the 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 Acid Green 40:1 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 FAT 21030 is available. However, the molecular weight of the chemical is 778.8 g/mol, indicating substance being too large for dermal absorption. The Log Pow was reported to be - 2.61 and water solubility to be 7.7 g/L, indicating substance being too hydrophilic to cross the lipid rich environment of the stratum corneum. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50 >2000 mg/kg bw) and was not classified for acute toxicity or STOT SE. Similarly, absence of systemic toxicity 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 substance only show up upon dermal exposure and not after systemic application. Hence, low toxicity is expected on acute dermal exposure of FAT 21030 and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

The available acute oral toxicity studies demonstrate that FAT 21030 is of low acute toxicity. Therefore, FAT 21030 should not be classified for acute oral toxicity according to CLP regulation criteria.