Sodium 1-amino-9,10-dihydro-9,10-dioxo-4-[[3-[(1-oxopropyl)amino]phenyl]amino]anthracene-2-sulphonate

Endpoint summary

Description of key information

The acute oral LD50 was found to be greater than 2500 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:

supporting study

Study period:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Code No.: FAT 20242/E
Batch No.: EN 1500.52
Contents of active ingredients: 100%
Validity: April 1991
Description: Solid/powder; Solubility in water: Approx. (10g/L at 20°C, pH 7.3)
Test article received: June 2, 1986.

Species:

rat

Strain:

other: Albino rats, Tif: RAIf(SPF), F3-hybrid of RII 1/Tif x RII 2/Tif

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 SIsseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 172 to 203 g
- Fasting period before study: Prior to dosing, the animals were fasted overnight
- Housing: The animals were kept under conventional laboratory conditions. They were caged in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding (Societe Parisienne des sciures, Pantin).
- Individual identification: By colour code using picric acid.
- Diet: Rat food, NAFAG N° 890, NAFAG AG, Gossau, SG Switzerland; ad libitum
- Water: Provided ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 55 ± 15%
- Air changes: Approx. 15 air changes/h
- Photoperiod: 12 hours light/day

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

(Siegfried AG, Zofingen/Switzerland

Details on oral exposure:

VEHICLE

- Volume (ml/kg body weight) applied: 20

Doses:

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:
*Mortality: Daily; a.m. and p.m. on working day, a.m. on weekend days.
*Signs and symptoms: Daily
*Body weight: On day 1, 7 and 14
- Necropsy of survivors performed: yes, the animals were submitted to a gross necropsy at the end of the observation period.

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Preliminary study:

None

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was seen.

Clinical signs:

other: Dyspnea, ruffled fur and curved body position, being comon symptoms in acute tests, were observed after the test item administration. The animals recovered within 12 days.

Gross pathology:

The animals were submitted to a gross necropsy at the end of the observation period.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for FAT 20242/E was claculated to be >5000 mg/kg bw.

Executive summary:

A study was performed to determine the acute oral toxicity of FAT 20242/E in rats via oral route in accordance with OECD Guideline 401. Following oral administration to 5 male and 5 female albino rats at 5000 mg/kg bw, the animals were observed for mortality, clinical signs and body weights during the 14 day post-treatment observation period. No mortality was seen. Dyspnea, ruffled fur and curved body position, being comon symptoms in acute tests, were observed after the test item administration. The animals recovered within 12 days. Expected weight gain in males and females seen. No deviations from normal morphology were found at post mortem examination. Hence based on these findings, the LD50 for FAT 20242/E was concluded to be >5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

High quality OECD guideline study

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

Oral:

The study considered to be key was performed to determine the acute oral toxicity of FAT 20242/E in rats via oral route in accordance with OECD Guideline 401. Following oral administration to 5 male and 5 female albino rats at 5000 mg/kg bw, the animals were observed for mortality, clinical signs and body weights during the 14 day post-treatment observation period. No mortality was seen.Dyspnea, ruffled fur and curved body position, being comon symptoms in acute tests, were observed after the test item administration. The animals recovered within 12 days. Expected weight gain in males and females seen. No deviations from normal morphology were found at post mortem examination. Hence based on these findings, the LD50 for FAT 20242/E was concluded to be >5000 mg/kg bw.

A supporting study was carried out for the determination of the acute oral LD50 of FAT 20242/A using 80 Tif. RAI rats by following OECD TG 401. Before administration by oral intubation, FAT 20242/A was suspended in polyethylene glycol (PEG 400).The test material was administered at1000,2500, 5000 and 7000 mg/kg bw respectively. At 1000 mg/kg bw, no mortality was seen. However, 15, 55 and 50 % mortality was seen at 2500, 5000 and 7000 mg/kg bw, respectively. Sedation, dyspnoea, exophthalmos, ruffled fur, diarrhoea, body position (ventral, lateral and curved) and convulsions were the clinical signs observed. The clinical signs reversed by day 8. At necropsy,no substance related gross organ changes were seen.In conclusion, the acute oral LD50 of FAT 20242/A in rats of both sexes observed over a period of 14 days is greater than 2500 mg/kg bw.

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of FAT 20242/I is available. However, the vapour pressure for the target chemical is low owing to the high melting point >300 °C, hence its 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. Further the chemical was found to have low acute toxicity when tested via oral route with no mortality and clinical signs when tested at 5000 mg/kg bw. Hence, considering all the above arguments, it is considered that FAT 20242/I 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 20242/I is available. However, the molecular weight of the chemical is 487.45 g/mol, indicating moderate potential for dermal absorption. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50 >2000 mg/kg bw). 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 chemical only show up upon dermal exposure and not after systemic application. Hence, low toxicity is expected on acute dermal exposure of FAT 20242/I and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

The acute oral LD50 of FAT 20242/A in rats of both sexes observed over a period of 14 days is greater than 2500 mg/kg bw. The test item does not meet the criteria for classification according to the Globally Harmonized Classification System.