Ethyl 3-hydroxypropanoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-09-14 ~ 2022-01-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

OECD Guideline for Testing of Chemicals, TG 420 (17 Dec 2001) ‘Acute Oral Toxicity – Fixed Dose Procedure’

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

ethyl 3-hydroxypropanoate

Cas Number:

623-72-3

Molecular formula:

C5H10O3

IUPAC Name:

ethyl 3-hydroxypropanoate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

1. Environmental conditions and monitoring
This study was performed in the barriered animal Room No. 17 on the 2nd floor of Research Bldg. #1 in the Nonclinical Research Institute, Chemon Inc. Environmental controls were set to maintain following conditions: temperature range of 22 ± 3 °C, relative humidity range of 55 ± 15 %, ventilation of 10–20 air changes/hr, 150-300 Lux of luminous intensity, and a 12-hr light/12-hr dark cycle. Throughout the study period, temperature and humidity of animal room were measured hourly by computer-based automatic sensors and environmental conditions such as ventilation frequency and luminous intensity will be monitored on a regular basis. According to the results of environmental monitoring, the room was maintained at a mean daily temperature of 20.4-22.4 °C and a mean daily relative humidity of 53.5-58.2 %, and there were no deviations that could affect this study.

2. Animal information
- Species and strain : Specific pathogen-free (SPF) rats, Sprague-Dawley [Crl:CD(SD)]
- Breeder / Supplier : Orient Bio Inc. (322, Galmachi-ro, Jungwon-gu, Seongnam-si, Gyeonggi-do, Republic of Korea)
- Justification of selection : Rats are considered suitable for toxicity testing and therefore
have been widely used. Abundant relevant data exist and are available for use in interpretation and evaluation of the results for this type of study. According to OECD Guideline TG 420, only
female rats were used in this study.
- Sex : Female
- Number of animals At receipt 12, At dosing 6
- Age of animals At receipt 7 weeks, At dosing 8 weeks
- Body weight at receipt 182.30-206.03 g
- Body weight at dose 204.84-230.26 g
- Disposition of remaining animals : Remaining animals were euthanized.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Name: Sterile Distilled water for Injection Lot No.: 44W6F21 Storage conditions: Room temperature (refrigeration after preparation) Supplier: Dai Han Pharm. Co., Ltd. Justification of selection: This vehicle is suitable for the preparation of the test art

Details on oral exposure:

# Administration
- Route and justification : Oral administration was chosen as per sponsor’s request.
- Frequency and duration : Once a day, single dose.
- Dose volume : Dose volumes for each animal were calculated based on individual fasted body weight measured on each day of administration.
- Method : After overnight fasting (about 16-20 hours), the dorsal skin of animals was held firmly and prepared test article was directly administered into the stomach using a syringe tube with a feeding needle. Food was offered about 3-4 hours postdose.

Doses:

2000 mg/kg

No. of animals per sex per dose:

No. of animal 4 Female

Control animals:

yes

Details on study design:

1. Clinical signs
All animals were observed for clinical signs once daily. On each day of administration, animals were observed continuously during the first 30 minutes postdose and subsequently hourly until 4 hours postdose. The day of dosing was designated as Day 1 and clinical signs were observed until Day 15. Sequential dosing was continued until adequate results were available to determine the GHS category.
2. Body weight
Animals were weighed on Day 1 (predose), 2, 4, 8, and 15.
3. Necropsy
On Day 15, all survivors were anesthetized by inhalation of CO2 gas and terminated by exsanguination from the posterior vena cava and abdominal aorta. All vital organs in the cranial, thoracic, and abdominal cavities were macroscopically observed. There were no abnormal indings, so preservation of organs and histopathological examinations were not performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

discriminating dose

Effect level:

ca. 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortalities : There were no mortalities.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

There were no test article-related effects.

Gross pathology:

There were no test article-related effects.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Based on the above results, when Ethyl 3-hydroxypropanoate was administered to Sprague-Dawley rats by acute oral fixed dose procedure, the GHS category of the test article was determined to be ‘5/unclassified.’

Conclusions:

The present study was performed to evaluate toxicity of Ethyl 3-hydroxypropanoate in Sprague-Dawley rats following an acute oral administration using a fixed dose procedure.
In this study, there were no mortalities and no test article-related effects in body weight changes and necropsy findings.
Clinical signs observed in G3 (2000 mg/kg) were considered to be test article-related because they were observed in high dose group and observed right after administration.
Based on the above results, when Ethyl 3-hydroxypropanoate was administered to Sprague-Dawley rats by acute oral fixed dose procedure, the GHS category of the test article was determined to be ‘5/unclassified.’