1,3,5-Triazine-2,4-diamine, N2-[(1R,2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-yl]-6-(1-fluoroethyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine

EC Number:

619-749-5

Cas Number:

730979-19-8

Molecular formula:

C16H20FN5

IUPAC Name:

N-[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/Winkelmann GmbH, 33178 Borchen, Germany
- Age at study initiation: 9-13 weeks
- Weight at study initiation: 168-188 g
- Fasting period before study: 16-24 hours before administration until 2-4 hours after administration
- Housing: 3/cage (groupwise) in polycarbonate cages on low dust wood granulate bedding
- Diet (e.g. ad libitum): standard diet Provimi Kliba 3883 PM S15 Maus/Ratte Haltung, Kaiseraugst Switzerland, ad libitum
- Water (e.g. ad libitum): tap water ad libitum from polycarbonate bottles
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: tap water with 2% Cremophor EL

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: AE 1170437 was formulated in tap water with the aid of 2% Cremophor EL. The applied formulations were well mixed before administration. The formulations for administration were prepared at room temperature.

CLASS METHOD
- Rationale for the selection of the starting dose: Starting dose level was that which was most likely to produce mortality in some of the dosed animals.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (3+3, Class method)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations several time on the day of administration and subsequently at least once daily, weight gain weekly until the end of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (nature, duration, intensity), body weight

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Mortality:

1/6 animals died during the observation period (day 4).

Clinical signs:

other: No clinical signs were observed during the observation period.

Gross pathology:

Necropsies performed at the end of the study revealed no particular findings. In the animal that died during the observation period no other changes than autolysis were detected.

Any other information on results incl. tables

Conclusion:

According to OECD guideline 423 the LD50 cut-off of the test material was determined to be 2500 mg/kg bw (Category 5, LD50 >2000-5000 mg/kg bw, according to the criteria of the Globally Harmonised Classification System). The test material does not have to be classified according to the criteria of the DSD and the CLP regulation.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008