2-amino-6-methyl-1,2,4-triazolo[1,5-a]pyrimidin-5(1H)-one

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 May 2016 to 09 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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Due to technical reason, temperature values (3 occasions, maximum of 25.5°C) outside the expected range of 17-23°C were recorded. This deviation is not considered to impact the results or integrity of this study as confirmed by the site veterinarian.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

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)

Sex:

male/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: Young adults (age range not given)
- Weight at study initiation: Between 221g and 254g (at dosing)
- Fasting period before study: Not reported
- 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): 21.0 – 25.5 °C
- Humidity (%): 30 – 68%
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12 hours light daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: The test item was administered as supplied in a single dose. Sufficient water was used to dampen the test material to ensure good contact with the skin.

Details on dermal exposure:

TEST SITE
- Area of exposure: back of animal
- % coverage: Approximately 10% area of the toal body surface
- Type of wrap if used: Semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, using water at body temperature
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

Five male and five female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, skin irritation, body weight
- Frequency of observations and weighing: Clinical observations at 1 and 5 hours after treatment and then daily. Body weights recorded on day ) (just before treatment) and on days 7 and 14.

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 occured during the study

Clinical signs:

No adverse clinical signs or any type of local effect was observed after treatment with the test item or during the 14 day observation period

Body weight:

There were no treatment related changes in body weight. The body weights were within the range commonly recorded for the strain and animal age.

Gross pathology:

No macroscopic changes were observed

Other findings:

- Other observations: No treatment related skin irritation was observed in any animal throughout the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

An acute dermal toxicity study was performed according to OECD Guideline 402. The median lethal dose (LD50) of the test substance after a single dermal administration was greater than 2000 mg/kg bw in male and female CRL:(WI) rats.

Executive summary:

An acute dermal toxicity study was performed according to OECD Guideline 402. Five male and five female CRL:(WI) rats were treated with a single, semi occlusive dermal application of the test substance at the limit dose of 2000 mg/kg body weight (bw). Test item was administered as supplied without dilution. The application period was 24 hours, followed by a 14-day observation period. Clinical observations along with a check of viability and mortality were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. All animals were euthanized and subjected to a gross macroscopic examination at the end of the 2 weeks observation period.

No mortality occurred during the study. No adverse clinical signs or any type of local effect was observed after treatment with the test item or during the 14 day observation period. There were no treatment related changes in body weight. The body weights were within the range commonly recorded for this strain and age. No macroscopic changes were seen.

The median lethal dose (LD50) of the test substance after a single dermal administration was greater than 2000 mg/kg bw in male and female CRL:(WI) rats.