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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 May 2016 to 14 June 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-amino-6-methyl-1,2,4-triazolo[1,5-a]pyrimidin-5(1H)-one
EC Number:
248-387-7
EC Name:
2-amino-6-methyl-1,2,4-triazolo[1,5-a]pyrimidin-5(1H)-one
Cas Number:
27287-73-6
Molecular formula:
C6H7N5O
IUPAC Name:
2-amino-6-methyl-1,2,4-triazolo[1,5-a]pyrimidin-5(1H)-one
Test material form:
solid: particulate/powder
Details on test material:
-Storage conditions: room temperature in the dark
-Colour: beige

Test animals

Species:
rat
Strain:
other: Crl:WI Wistar rats
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 - 10 weeks old
- Weight at study initiation: 201 - 218g
- Fasting period before study: Overnight prior to dosing
- Housing: Animals were housed individually in Type II polypropylene/polycarbonate cages. Animals were housed with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet (e.g. ad libitum): Yes
- Water (e.g. ad libitum): Yes
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 - 25.0°C
- Humidity (%): 32 - 70%
- Air changes (per hr): 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light from 6:00am to 6:00pm

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 17.5 mg/L, 55 mg/L and 200 mg/L for 175, 500 and 2000 mg/kg bw doses respectively.
- Amount of vehicle (if gavage): 1% Carboxymethyl cellulose (CMC)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:
175, 550 and 2000 mg/kg body weight
No. of animals per sex per dose:
175 mg/kg bw = 1 animal
550 mg/kg bw = 1 animal
2000 mg/kg bw = 3 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs 30 minutes after dosing, then at approximately 1, 2, 3, 4 and 6 hours after dosing and once each day for 14 days thereafter. Body weights were recorded on days -1, 0 (before treatment), 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: All animals were necropsied and subject to gross macroscopic examination.
Statistics:
The LD50 was calculated using the AOT425StatPgm program. This program was prepared for the US Environmental Protection Agency by Westat, May 2001 and updated by the US EPA June 2003. This programme was constructed using the most appropriate method to estimate the LD50.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
There was no mortality during the study
Clinical signs:
At dose level 175 mg/kg bw, hunched back was observed only on the day of treatment in 1/1 animals.
At dose level 550 mg/kg bw, hunched back and decreased activity were observed only on the day of treatment in 1/1 animals.
At dose level 2000 mg/kg bw, hunched back in 3/3 animals, decreased activity in 2/3 animals, incoordination in 1/3 animals and piloerection in 1/3 animals on the day of treatment.
There were no further clinical signs after Day 0 at any dose level.
Body weight:
There were no treatment related effects on body weight or body weight gain
Gross pathology:
At necropsy there were no observations to be reported at any dose level

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
An acute oral toxicity study was conducted with 5 female Crl:WI rats according to the OECD guideline 425. Under the conditions of this study, the estimated acute oral median lethal dose (LD50) of the test item was found to be greater than 2000 mg/kg bw in female Crl:WI rats.
Executive summary:

An acute oral toxicity (up and down procedure) study was conducted with 5 female Crl:WI rats according to the OECD guideline 425.  

Animals were treated with a single oral (gavage) dose of the test substance at dose levels of 175, 550 or 2000 mg/kg body weight (bw) followed by a 14-day observation period. The animals were fasted overnight prior to treatment and food was returned 3 hours after dosing. Animals were observed individually after dosing at 30 minutes, then 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days thereafter. Body weight was measured on Day -1, just before dosing and weekly thereafter. All animals were examined macroscopically at the end of the observation period.

There was no mortality during the study. At dose level 175 mg/kg bw, hunched back was observed only on the day of treatment in 1/1 animals. At dose level 550 mg/kg bw, hunched back and decreased activity were observed only on the day of treatment in 1/1 animals. At dose level 2000 mg/kg bw, hunched back in 3/3 animals, decreased activity in 2/3 animals, incoordination in 1/3 animals and piloerection in 1/3 animals on the day of treatment.

There were no further clinical signs after Day 0 at any dose level. There were no treatment related effects on body weight or body weight gain. Body weights were within the range commonly recorded for this strain and age. At necropsy, there were no observations to be reported at a dose level of 175, 550 or 2000 mg/kg bw.

Under the conditions of this study, the estimated acute oral median lethal dose (LD50) of the test item was found to be greater than 2000 mg/kg bw in female Crl:WI rats.