Prop-2-yn-1-yl 1H-imidazole-1-carboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

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: 17th December 2001

Deviations:

not applicable

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Guidance Document on Acute Oral Toxicity Testing, OECD Series on Testing and Assessment No 24, 2001

Version / remarks:

No 24, 2001

Deviations:

not specified

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Guidance Document on the Recognition, Assessment and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation. Environmental Health and Safety Publications Series on Testing and Assessment No 19, 2000

Version / remarks:

No 19, 2000

Deviations:

not specified

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:

prop-2-yn-1-yl 1H-imidazole-1-carboxylate

EC Number:

695-595-2

Cas Number:

83395-38-4

Molecular formula:

C7H6N2O2

IUPAC Name:

prop-2-yn-1-yl 1H-imidazole-1-carboxylate

Test material form:

solid

Specific details on test material used for the study:

Name: 2-propyn-1-yl 1H-imidazole-1-carboxylate
Batch no.: 0802-2#
CAS no.: 83395-38-4
Storage: Room temperature (20±5°C)
Expiry date: November 4, 2021
Appearance: white solid
Purity: 99.1 %
Homogeneity: homogeneous
Production date: 13. Oct. 2020
EC no.: 695-595-2
Molecular formula: C7H6N2O2
Molecular weight: 150.13 g/mol

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Institute of Experimental Pharmacology and Toxicology, Center of Experimental Medicine of the Slovak Academy of Sciences, Dobrá Voda, Slovak Republic
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Fasting period before study: yes. Animals were fasted prior to dosing (food but not water was withheld over-night)
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage, in a room equipped with central air-conditioning. The room temperature was maintained within the range of 22±2 °C. The relative humidity will be 55±10 %. The light regime was set to a 12-hour light / 12-hour dark cycle. The sanitation was performed according to standard operation procedures.
- Diet (e.g. ad libitum): A standard laboratory food KKZ-P/M (UEFT CEM SAS) was available ad libitum.
- Water (e.g. ad libitum): The animals received tap water for human consumption. Supply of drinking water was unlimited. The quality of drinking water is periodical monitored (including microbiological control) and recorded
- Acclimation period: The animals were acclimated to the condition identical to the condition during the experiment at least 5 days prior to the start of treatment. The acclimation was according to standard operation procedures.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2 °C
- Relative humidity (%): 55±10 %
- Air changes (per hr): central air-conditioning
- Photoperiod (hrs dark / hrs light): 12-hour light / 12-hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Aqua Pro Injectione Bieffe

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage): Appropriate vehicle
- Justification for choice of vehicle: Ultra pure water such as API is a common vehicle for water soluble items in toxicity studies like OECD TG 423
- Lot/batch no. (if required): 19L1001

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A limit dose of 2000 mg/kg body weight was used as a starting dose. Available information indicated that the test item is likely to be non-toxic regarding acute toxicity, therefore, a limit dose of 2000 mg/kg body weight was used as a starting dose.

Doses:

2000 mg/kg body weight, 300 mg/kg body weight and 50 mg/kg body weight

No. of animals per sex per dose:

3 animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed individually immediately after the administration of the test item and then 0.5, 1, 2 and 4 hours later. Each animal was inspected daily for the next 14 days.
Individual weights of animals were determined shortly before the test item administration and weekly thereafter. Weight changes after first and second week after administration were calculated and recorded.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behavioural patterns. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

Mortality of 3/3 females at limit dose of 2000 mg/kg body weight and 3/3 females at the dose of 300 mg/kg body weight was observed.
All six female animals survived after administration at the dose of 50 mg/kg body weight.

Clinical signs:

other: The test item 2-propyn-1-y1 1H-imidazole-1-carboxylate administered to 3 females Wistar rats at a limit dose of 2000 mg/kg caused slight immediate reaction (piloerection) and after two hours some somatomotor and coordination problems in two animals were r

Gross pathology:

No visible pathological findings other than hyperemia of liver were observed in Animals No. 1 - 3 dosed with 2000 mg/kg body weight and Animals No. 3 - 6 dosed with 300 mg/kg body weight.
No pathological findings in Animals No. 7 - 12 dosed with 50 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LD50 of the test item 2-propyn-1-y1 1H-imidazole-1-carboxylate is greater than 50 mg/kg and lower than 300 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 item 2-propyn-1-y1 1H-imidazole-1-carboxylate is classified GHS Category 3 with a LD50 cut off value 200 mg/kg body weight, after single oral administration to Wistar rats.

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item “2-propyn-1-y1 1H-imidazole-1-carboxylate” when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used.

A limit dose of 2000 mg/kg body weight was used as a starting dose. Available information indicated that the test item is likely to be non-toxic regarding acute toxicity, therefore, a limit dose of 2000 mg/kg body weight was used as a starting dose.

In the first step, one group of 3 females was dosed. The test item in limit dose caused mortality of all animals within 24 hours after administration. In a second step, 3 females were treated with dose of 300 mg/kg body weight. The test item in the dose of 300 mg/kg caused mortality of all animals within 48 hours after administration. In a third step, 3 females were treated with dose of 50 mg/kg body weight. The test item in dose 50 mg/kg did not cause death of animals and therefore another 3 females were treated 48 hours later at the same dose level. All animals survived at this dose level.

The test item 2-propyn-1-y1 1H-imidazole-1-carboxylate administered to 3 females Wistar rats at a limit dose of 2000 mg/kg caused reaction 1 hour after administration of test item (sleep behavior, somatomor discoordination). Within two hours Animal 1 died and after 4 hours died Animal 2. Animal 3 died within 24 hours. During necropsy we did not see any obvious pathological changes in gastrointestinal tract or other organs other than liver hyperemia.

Dose of 300 mg/kg of body weight caused slight reaction (piloerection). After 24 hours Animal 5 died and blood in the urine in Animal 4 was observed. Within 48 hours Animals 4 and 6 died. Autolytic processes were observed during necropsy of all animals at this dose level.

Dose of 50 mg/kg did not induce signs of intoxication, change of health, nor any other adverse reactions during 14-days observation period. During necropsy we did not observe any macroscopic findings in all Animals at this dose level.

The LD50 of the test item 2-propyn-1-y1 1H-imidazole-1-carboxylate is greater than 50 mg/kg and lower than 300 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 item 2-propyn-1-y1 1H-imidazole-1-carboxylate is classified GHS Category 3 with a LD50 cut off value 200 mg/kg body weight, after single oral administration to Wistar rats.