Ethyl 3-hydroxypropanoate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion, other

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

Remarks:

OECD Guideline for Testing of Chemicals, TG 404 (28 Jul 2015) ‘Acute Dermal Irritation/Corrosion’

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 404 (Acute Dermal 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

In vitro test system

Test system:

isolated skin discs

Remarks:

New Zealand White rabbits have been widely used in skin irritation/corrosion tests.

Source species:

rabbit

Cell type:

non-transformed keratinocytes

Cell source:

foreskin from a single donor

Source strain:

New Zealand White

Details on animal used as source of test system:

# 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 skin
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 5, At first dose 3
- Body weight ranges : At receipt 1.967 – 2.081 kg, At first dose 2.296 – 2.352 kg

Justification for test system used:

The mean scores of erythema and edema were calculated from the grades and the category of the test article was assigned with reference to the GHS guidelines below:

Details on test system:

1. Initial test
An initial test using one animal was performed. The test article was sequentially applied to the animal 3 times as follows: The first patch was applied to the first site and removed after about 3 minutes. The second patch was applied to a different site and removed after about 1 hour. The third patch was applied to a different site and removed after about 4 hours and the skin reaction was observed. An untreated skin area, a control site, was set in the same animal. There was no erythema, edema, or corrosion. After removing the third patch, the skin reaction was observed about 24, 48, and 72 hours after removal and additional observations were made for 14 days including the day of administration.

2. Confirmatory test
A confirmatory test was done using two animals since no skin reaction or corrosion was observed in the initial test. One patch was applied per animal and removed after 4 hours. A patch of gauze without test article was applied to the control site of each animal and removed after 4 hours. After removing the patches, the skin reaction was observed about 1, 24, 48, and 72 hours after removal and additional observations were made for 14 days including the day of administration.

Control samples:

yes, concurrent no treatment

Amount/concentration applied:

0.5 mL/site

Duration of treatment / exposure:

About twenty-four hours before the test article administration, the dorsal skin was shaved by electric hair clipper without damaging the skin. On the day of administration, a 0.5 mL aliquot of test article was soaked onto patches of 2.5 cm × 2.5 cm gauze and the gauze which was put on the skin of the test article site. The gauze was secured with non-permeable and non-irritating adhesive dressing to prevent evaporation of the test article.

A confirmatory test was done using two animals since no skin reaction or corrosion was observed in the initial test. One patch was applied per animal and removed after 4 hours. A patch of gauze without test article was applied to the control site of each animal and removed after 4 hours. After removing the patches, the skin reaction was observed about 1, 24, 48, and 72 hours after removal and additional observations were made for 14 days including the day of administration.

Number of replicates:

Initial test of number : 1 ea
Confirmatory test of number : 2 ea

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

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 18.4-20.5 °C and mean daily relative humidity was 57.0-62.6 %, 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.

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL/site

Duration of treatment / exposure:

1. Initial test
An initial test using one animal was performed. The test article was sequentially applied to the animal 3 times as follows: The first patch was applied to the first site and removed after about 3 minutes. The second patch was applied to a different site and removed after about 1 hour. The third patch was applied to a different site and removed after about 4 hours and the skin reaction was observed. An untreated skin area, a control site, was set in the same animal.

2. Confirmatory test
A confirmatory test was done using two animals since no skin reaction or corrosion was observed in the initial test. One patch was applied per animal and removed after 4 hours. A patch of gauze without test article was applied to the control site of each animal and removed after 4 hours.

Observation period:

In the initial test, skin reactions were graded after removing the patch at about 3 minutes, 1 hour, and 4 hours after application of the test article. In the case of the confirmatory test, patches were removed after about 4 hours and the skin was washed gently with sterile Distilled water for Injection to remove any remaining test article.

1. Initial test
Erythema & Eschar formations : 0.05, 1, 4, 24, 48, 72 hrs
Edema : 0.05, 1, 4, 24, 48, 72 hrs

2. Confirmatory test
Erythema & Eschar formations : 1, 24, 48, 72
Edema : 1, 24, 48, 72

Number of animals:

Initial test of number : 1 ea
Confirmatory test of number : 2 ea

Details on study design:

In the initial test, skin reactions were graded after removing the patch at about 3 minutes, 1 hour, and 4 hours after application of the test article. In the case of the confirmatory test, patches were removed after about 4 hours and the skin was washed gently with sterile Distilled water for Injection to remove any remaining test article. Macroscopic grading of erythema, edema, bleeding, and eschar formation were performed at about 1, 24, 48, and 72 hours after removal of the patches. Edema was evaluated by a combination of observation by naked eye and palpation. Grading of skin reactions were performed according to the table below. For the initial test in one animal, the test site was examined immediately after the patch had been removed.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

There were no test article-related changes when skin irritation/corrosion was evaluated in both the initial and confirmatory tests.

Other effects:

There were no test article-related clinical signs and body weight changes.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the overall results, under present experimental conditions, the test article, Ethyl 3-hydroxypropanoate, did not match any GHS category.

Executive summary:

This study was performed to evaluate acute skin irritation/corrosion potential of Ethyl 3-hydroxypropanoate in male New Zealand White rabbits. The test article was applied to intact skin of the rabbits.
There were no test article-related clinical signs and body weight changes.
There were no test article-related changes when skin irritation/corrosion was evaluated in both the initial and confirmatory tests.
Based on the overall results, under present experimental conditions, the test article, Ethyl 3-hydroxypropanoate, did not match any GHS category.