2-[(1-amino-9,10-dihydro-4-hydroxy-9,10-dioxo-2-anthryl)oxy]ethyl ethyl carbonate

Endpoint summary

Description of key information

Acute toxicity: oral

Acute oral toxicity of FAT 93503/A was evaluated when administered by single oral gavage to Wistar rats, followed by an observation period of 14 days. This study was performed according to the OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method). Two groups, each using three male or three female Hanlbm: WIST (SPF) rats were treated with FAT 93503/A at 2000 mg/kg by oral gavage, in a stepwise manner. No deaths occurred during the study. No clinical signs were observed in all males during the observation period. One female animal was observed with ruffled fur, hunched posture and tremor from 1 to 5 hours after the administration. Two female animals showed a marked loss of body weight (24.5 % and 23 %) one week after treatment. The body weight of the other animals was within the range commonly recorded for animals of this strain and age. No macroscopic findings were observed at necropsy. Based on the findings of the study, the median lethal dose of FAT 93503/A after single oral administration to rats of both sexes, observed over a period of 14 days was found to be >2000 mg/kg bw.

Acute toxicity: inhalation

Currently no study to assess the acute inhalation toxicity potential of Disperse Red 302 is available. However, the vapour pressure for the substance can be considered low (1.46 x 10^-9 Pa). 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 substance is imported into the EU in a formulated form as liquid formulation, the exposure via inhalation is considered to be unlikely. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD₅₀>2000 mg/kg bw) with no mortality or systemic toxicity, hence it does not need to be classified STOT SE. Taking the above arguments into account, low toxicity potential is expected on acute exposure of Disperse Red 302 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 of Disperse Red 302 is available. However, the substance has very low solubility in water (0.224 µg/L), hence dermal uptake is likely to be low as the substance is considered as not sufficiently soluble in water to partition from the Stratum corneum into the epidermis, indicating limited dermal absorption.Synthesis and spray drying of this chemical is performed in a closed process;without isolation of reaction products. Isolated products consist of either liquid formulations or dust free granules (non-dusty solid). In addition, the use of this substance will not result in aerosols, particles or droplets, so exposure to humans via the dermal route will be unlikely to occur. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD₅₀>2000 mg/kg bw) with no mortality or systemic toxicity, hence it does not need to be classified STOT SE. Similarly, absence of local toxicity in skin and eye irritation as well as sensitization studies further supports the conclusion that low toxicity is expected for the chemical via the dermal route. Taking above arguments into account, low toxicity potential is expected on acute exposure of Disperse Red 302 via dermal route and hence acute toxicity testing by the dermal route was considered scientifically not necessary.

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:

31 January, 2000 to 01 March, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd., Biotechnology & Animal Breeding Division, Wölferstrasse 4, CH-4414 Füllinsdorf / Switzerland.
- Age at study initiation: Male and female: 8-10 weeks.
- Weight at study initiation: Males: 218.4 - 229.6 g and females: 157.4-161.7 g
- Diet: ad libitum
- Water: Community tap water from Füllinsdorf available ad libitum.
- Acclimation period: One week under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 32-45 %
- Air changes: Air-conditioned with 10-15 changes per hour.
- Photoperiod: 12-hour artificial fluorescent light, 12-hour dark cycle. Music was played during the light period.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

The animals received a single dose of the test article on a 2000 mg/kg bw basis by oral gavage following fasting for approximately 18 h, but with free access to water. Food was provided again approximately 3 h after dosing.

Dose: 2000 mg/kg bw
Application volume: 10 ml/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
OBSERVATIONS:
- Mortality / Viability: One, two, three and five hours after the administration during test day 1 and once daily during days 2-15.
- Body weights: On test days 1 (pre-administration), 8 and 15.
- Clinical signs: Each animal was examined for changes in appearance and behaviour four times during day 1, and once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: Yes. Necropsies were performed at the end of the observation period and all animals were sacrificed by intraperitoneal injection of NARCOREN at a dose of at least 2.0 ml/kg body weight (equivalent to at least 320 mg sodium pentobarbitone/kg kg bw).
- Other examinations performed: Macroscopic findings

Statistics:

No statistic analysis was used as no deaths occurred.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed in all males during the observation period. One female animal was observed with ruffled fur, hunched posture and tremor from 1 to 5 h after the administration.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose (LD50) of FAT 93503/A after single oral administration to rats of both sexes, observed over a period of 14 days is >2000 mg/kg bw.

Executive summary:

The purpose of this study was to assess the acute oral toxicity of FAT 93503/A when administered by single oral gavage to Wistar rats, followed by an observation period of 14 days. The study was performed according to the OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method). Two groups, each using three males or three females Hanlbm: WIST (SPF) rats were treated with FAT 93503/A at 2000 mg/kg bw by oral gavage. The test article was suspended in vehicle (PEG 300) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg bw. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15. Mortality / viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs were observed in all males during the observation period. One female animal was observed with ruffled fur, hunched posture and tremor from 1 to 5 h after the administration. Two female animals showed a marked loss of body weight (24.5 % and 23 %) one week after treatment. The body weight of the other animals was within the range commonly recorded for animals of this strain and age. No macroscopic findings were observed at necropsy. In conclusion, the median lethal dose (LD₅₀) of FAT 93503/A after single oral administration to rats of both sexes, observed over a period of 14 days is >2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

High quality GLP 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 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

Justification for classification or non-classification

Based on the observed LD₅₀of >2000 mg/kg bw in the acute oral toxicity study, Disperse Red 302 does not considered to be classified according to according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.