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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[(1-amino-9,10-dihydro-4-hydroxy-9,10-dioxo-2-anthryl)oxy]ethyl ethyl carbonate
EC Number:
254-959-7
EC Name:
2-[(1-amino-9,10-dihydro-4-hydroxy-9,10-dioxo-2-anthryl)oxy]ethyl ethyl carbonate
Cas Number:
40530-60-7
Molecular formula:
C19H17NO7
IUPAC Name:
2-[(1-amino-9,10-dihydro-4-hydroxy-9,10-dioxo-2-anthryl)oxy]ethyl ethyl carbonate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Identification: FAT 93503/A
Item N°: 0033275
Vers N°: 99 Labor Mischung 1
Purity: Approximately 96 %
Color/Physical state: Red powder
Expiry date: January 2005
Storage conditions: In the original container, at room temperature (range of 20 +/- 3 °C), away from direct sunlight.
Safety precautions: Routine hygienic procedure were used to ensure the health and safety of the personnel.

Test animals

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.

Administration / exposure

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.

Results and discussion

Effect levels
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:
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.
Body weight:
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.
Gross pathology:
No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

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.