6-[2-(2-methyl-1H-imidazol-1-yl)ethyl]-1,3,5-triazine-2,4-diamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 May - 28 Oct 2017

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted Dec 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted May 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Landesleitstelle Bayern, Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Schwabach, Deutschland

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

6-[2-(2-methyl-1H-imidazol-1-yl)ethyl]-1,3,5-triazine-2,4-diamine

EC Number:

254-074-6

EC Name:

6-[2-(2-methyl-1H-imidazol-1-yl)ethyl]-1,3,5-triazine-2,4-diamine

Cas Number:

38668-46-1

Molecular formula:

C9H13N7

IUPAC Name:

6-[2-(2-methyl-1H-imidazol-1-yl)ethyl]-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: Charles River, 97633 Sulzfeld, Germany
- Females (nulliparous and non-pregnant): yes
- Age at study initiation: 8 -10 weeks
- Weight at study initiation: step 1, animals no. 1-3: 151-168 g, step 2, animals no 4-6: 173-286 g
- Fasting period before study: Yes, the animals were fasted for 16 - 19 h before dosing.
- Housing: Full barrier in an air conditioned room, animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet: Altromin 1324 maintenance diet, ad libitum
- Water: tap water, sulphur acidified to a pH of appriximately 2.8, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From:17 Aug 2017 To: 06 Sep 2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL
- Justification for choice of vehicle: This vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no. (if required): 612118 (sterile water, Delta Medical)


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 per step / 2 steps performed

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy of survivors performed: yes, the animals were sacrificed with an overdosage of pentobarbital. All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In the absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.
- Other examinations performed: clinical signs, body weight other: cageside observations included skin and flur, eyes and mucous membranes. Also respiratory, circulatroy, autonomic and central nervous systems and somatomotor acitivity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhea, lethargy, sleep and coma.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Body weight:

No effect on body weight was noted.

Gross pathology:

Necropsy revealed no substance-related findings.

Any other information on results incl. tables

Table 1: Mortality Data, LD₅₀Cut-Off

Starting Dose (mg/kg bw)	Number of Animals	Number of Intercurrent Deaths	LD50Cut-Off
2000	6	0	> 2000

bw = body weight

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

Conclusions:

Under the conditions of the present study, a single oral application of the test substance to rats at a dose of 2000 mg/kg body weight was not associated with signs of toxicity or mortality.
The median lethal dose of test substance after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): > 2000 mg / kg bw.

CLP: not classified