2-amino-5-(2-hydroxyethyl)-6-methyl-4(3H)-pyrimidinone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 November 2017 - 31 January 2018

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

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:

2-amino-5-(2-hydroxyethyl)-6-methyl-4(3H)-pyrimidinone

Cas Number:

6940-45-0

Molecular formula:

C7H11N3O2

IUPAC Name:

2-amino-5-(2-hydroxyethyl)-6-methyl-4(3H)-pyrimidinone

impurity 1

Reference substance name:

Sodium acetate

EC Number:

204-823-8

EC Name:

Sodium acetate

Cas Number:

127-09-3

Molecular formula:

C2H4O2.Na

IUPAC Name:

sodium acetate

additive 1

Reference substance name:

Silicon dioxide

EC Number:

231-545-4

EC Name:

Silicon dioxide

Cas Number:

7631-86-9

Molecular formula:

SiO2

IUPAC Name:

Silicon dioxide

Test material form:

solid: granular

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 103901

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dobrá Voda, Slovak Republic
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 160-190 g
- Fasting period before study: yes, overnight prior to dosing.

- Housing:
The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central airconditioning. Sanitation was performed according to the standard operation procedures.

- Diet (e.g. ad libitum):
The laboratory food ssniff (Spezialdiäten GmbH, Germany) was offered at recommended doses each day approximately at the same time. The certificate of analysis is included in the raw data.

- Water (e.g. ad libitum):
The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodical analysed and recorded; certificate of analysis is included in the raw data.

- Acclimation period:
The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment. The acclimation was according to the standard operation procedure.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.26 ± 0.16 °C
- Humidity (%): 53.33 ± 1.86 %
- Photoperiod (hrs dark / hrs light): 12-hour light /12-hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Olive oil is a standard vehicle according to OECD TG 423
- Lot/batch no. (if required): L63417:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kb-bw

DOSAGE PREPARATION (if unusual): mixing

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: ince no toxicity was expected, a limit dose was chosen to reduce animal use.

Doses:

2000 mg/kg-bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2, and 4 hours later following administration
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight. Observations included: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory,
autonomic and central nervous systems, somatomotor activity, and behavioural pattern. Particular
attention was given to potential neurologic endpoints such as tremors, convulsions, salivation,
diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: No mortality was observed during the study. During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.

Gross pathology:

All animals were necropsied. They were euthanized by anesthetic overdose (Isoflurane). During necropsy, no macroscopic findings were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item SP02 (trade name: 5OHMIC) is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test SP02 (trade name: 5OHMIC) is classified in Category 5/Unclassified with a LD50 cut off value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats.

Executive summary:

The test item SP02 (trade name: 5OHMIC) administered to 6 females at a limit dose of 2000 mg/kg body weight did not cause death. No signs of toxicity were observed during the first 4 hours in females or the 14-day observation period thereafter. The body weights of all animals were increasing during the study. No body weight losses were observed between the first and second week after administration of the test item. During necropsy, no macroscopic findings were observed.