Ethyl 3-hydroxypropanoate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-09-08 ~ 2022-01-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

1. Animal information
- Species and strain : Specific pathogen-free (SPF) rabbits, New Zealand White
- Breeder / Supplier : SAMTACO BIOKOREA (105 Seorang-ro, Osan-si, Gyeonggi-do, Republic of Korea)
- Justification of selection : New Zealand White rabbits have been widely used in eye irritation/corrosion tests. Abundant relevant data exist and are available for the interpretation and evaluation of the results for this type of study.
- Sex : Male
- Number of animals : At receipt 4, At first dose 3
- Body weight ranges : At receipt 1.949 – 2.116 kg, At first dose 2.204 – 2.322 kg

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL/eye

Duration of treatment / exposure:

1. Initial test
An initial test using one animal was performed. Test article was administered once to observe eye reaction. Irritation was observed after administration and then both eyes were washed with about 50 mL of physiological saline injection solution 20 to 30 seconds. Corrosion or strong irritation was not observed in the initial test. After administration of the test article, the eye reaction was observed after about 1, 24, 48, and 72 hours, and additional observations were made until 21 days postdose including the day of administration.

2. Confirmatory test
Corrosive or severe irritant effect was not observed in the initial test so a confirmatory test was performed using two additional animals. The confirmatory test was conducted in sequential order of animal ID in one animal at a time. After administration of the test article, eye reaction was observed after about 1, 24, 48, and 72 hours, and additional observations were made until 21 days
postdose including the day of administration.

Observation period (in vivo):

Clinical signs were observed at least once daily throughout the experimental period.

Duration of post- treatment incubation (in vitro):

The day of administration was designated as Day 0 and animals were observed for 21 days.

Number of animals or in vitro replicates:

Initial test : 1 ea
Confirmatory test : 2 ea

Details on study design:

1. Environmental conditions and monitoring
This study was performed in barriered animal Room No. 11 on the 1st floor of Research Bldg. #1 in the Nonclinical Research Institute, Chemon Inc. Environmental controls were set to maintain following conditions: temperature range of 19 ± 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 the room were measured hourly by computer-based automatic sensors and environmental conditions such as ventilation frequency and luminous intensity were monitored on a regular basis. According to the results of environmental monitoring during the housing period, mean daily temperature of was 18.4-20.6 °C and mean daily relative humidity was 49.9-62.6 %, and there were no environmental deviations that could affect this study.

2. Diet, water, and contaminants
Animals were provided pellet food for rabbits (Cargill Agri Purina, Inc.) purchased from Biopia (207, Sinsan Building, 508, Beonyeong-ro, Gunpo-si, Gyeonggi-do, Republic of Korea) ad libitum. According to the certificates on diet components and contaminants supplied by the diet provider, there was no factor that could affect this study. Groundwater was disinfected by ultraviolet sterilizer and ultrafiltration and made available via water bottle ad libitum. Water was analyzed by the authorized Gyeonggido Institute of Health & Environment (62 Chilbo-ro 1 Beon-gil, Gwonseon-gu, Suwon-si, Gyeonggi-do, Republic of Korea) and quality satisfied the standards for drinking water.

3. Cages and housing
Animals were individually housed in stainless steel cages (W 550 × L 680 × H 405 mm) during the whole housing period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 - <= 1.7

Max. score:

1.7

Reversibility:

fully reversible within:

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0.7 - <= 2

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 - <= 0.3

Max. score:

0.3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

other: conjunctival redness

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The average scores of conjunctival redness at 24, 48, and 72 hours were 1 in all animals.
The average scores of corneal opacity were 2, 0.7, and 1; the average scores of iris were 0, 0.3, and 0; and the average scores of conjunctivae chemosis were 0, 0.3, and 1.7, respectively, in sequential order of animal ID.

Other effects:

In the initial test, hyperemic conjunctiva and corneal opacity were observed from Day 0 to Day 6.
In the confirmatory test in animal (#2) hyperemic conjunctiva and corneal opacity were observed from Day 0 to Day 2, chemosis was observed on Day 1, and iris congestion was observed on Day 2.
Moreover, in animal (#3) in the confirmatory test, hyperemic conjunctiva, corneal opacity, and chemosis were observed from Day 0 to Day 6.

Applicant's summary and conclusion

Interpretation of results:

Category 2B (mildly irritating to eyes) based on GHS criteria

Conclusions:

The average scores of conjunctival redness at 24, 48, and 72 hours were 1 in all animals.
The average scores of corneal opacity were 2, 0.7, and 1; the average scores of iris were 0, 0.3, and 0; and the average scores of conjunctivae chemosis were 0, 0.3, and 1.7, respectively, in sequential order of animal ID.

Based on the overall results, under present experimental conditions, the test article, Ethyl
3-hydroxypropanoate, was categorized as GHS Category 2B (reversible effects on the eye).

Executive summary:

This study was performed to evaluate acute eye irritation/corrosion potential of Ethyl 3-hydroxypropanoate in male New Zealand White rabbits. The test article was applied to the ocular mucous membranes of the left eyes and, for comparison, the right eyes remained untreated.

There were no test article-related changes in body weight.
In the initial test and confirmatory test, hyperemic conjunctiva, corneal opacity, chemosis, and iris congestion were observed and they were attributed to the test article.
The average scores of conjunctival redness at 24, 48, and 72 hours were 1 in all animals.
The average scores of corneal opacity were 2, 0.7, and 1; the  average scores of iris were 0, 0.3, and 0; and the average scores of conjunctivae chemosis were 0, 0.3, and 1.7, respectively, in  sequential order of animal ID.
Based on the overall results, under present experimental  conditions, the test article, Ethyl 3-hydroxypropanoate, was categorized as GHS Category 2B (reversible effects on the eye).