Registration Dossier

Administrative data

acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
(2S,3S)-2,3-dihydroxysuccinic acid - 2-[(3R)-piperidin-3-yl]-1H-isoindole-1,3(2H)-dione (1:1)
EC Number:
Cas Number:
Molecular formula:
C13 H14 N2 O2 . C4 H6 O6
(2S,3S)-2,3-dihydroxysuccinic acid - 2-[(3R)-piperidin-3-yl]-1H-isoindole-1,3(2H)-dione (1:1)

Test animals

other: CrlGlxBrlHan:WI

Administration / exposure

Route of administration:
oral: gavage
other: 0.5% aqueous hydroxyethylcellulose (Natrosol® 250 HX)
200 and 2000 mg/kg

Results and discussion

Effect levels
Dose descriptor:
approximate LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Based on:
test mat.

Applicant's summary and conclusion

Interpretation of results:
other: Category 3 according CLP
Under the conditions of the present study, no mortality was seen in rats subsequent to single oral administration of 200 mg/kg CD 713 TD.
Subsequent to 2000 mg/kg, all three females had to be sacrificed.
Thus, the approximate lethal dose (ALD) in rats for CD 713 TD, an intermediate in the synthesis of BI 1356 BS, is between 200 mg/kg and 2000 mg/kg.
Executive summary:


Based on the legal requirements for Workers Safety according to current German law (Gefahrstoffverordnung [Ordinance on Dangerous Substances], 15 November 1999), this study was designed to evaluate in rats the acute toxicity of CD 713 TD subsequent to a single oral administration by gavage.

The study was performed following the revised version of OECD Guideline 423 (Acute Oral Toxicity - Acute Toxic Class Method, October 2000) and in accordance with the principles of Good Laboratory Practice, as described by the respective OECD Guidelines and current German law (Chemikaliengesetz [Chemicals Act] 2002).

Study design:

CD 713 TD was suspended in 0.5% aqueous hydroxyethylcellulose (Natrosol® 250 HX) and administered by oral gavage (10 mL/kg) at single doses of 200 mg/kg and 2000 mg/kg, respectively, to groups of three CrlGlxBrlHan:WI rats, which were approximately 8 weeks old. Their body weight ranged from 177 g to 195 g in males and from 131 g to 136 g in females.

The observation period post administration was 14 days. Clinical signs were evaluated frequently on the day of administration (Day 1), as well as once or twice daily thereafter. Body weight was recorded one day before administration (Day -1), and, during the observation period, on Day 1, 2, 8 and 15, respectively. At the end of the observation period, necropsy was performed on all animals, and all gross macroscopical changes were recorded.

Main results:

200 mg/kg

No mortality occurred in both male and female rats.

Clinical observations were recorded on Day 1 only and comprised piloerection (in both male and female rats from 0.25 h to 2.0 h post administration) as well as reduced motor activity (in males 0.5 h post administration only). All rats returned to normal on Day 1 (4.0 h post administration).

No influence on body weight development and no gross macroscopic changes at necropsy were observed.

2000 mg/kg

All three females had to be sacrificed on Day 1 (about 0.5 h post administration) due to poor general condition (characterized by convulsions and lateral position) for reasons of animal welfare. Piloerection (starting 0.25 h post administration) was the only clinical sign observed earlier.

Alterations in the liver (stasis) and the small intestine (discoloration, liquid luminal content) were observed at necropsy of all three females.