methyl 2-hydroxybut-3-enoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-09-20 to 2021-11-08

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Short report

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:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008-05-30

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998-08

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

2017-10-09

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

methyl 2-hydroxybut-3-enoate

EC Number:

831-109-9

Cas Number:

5837-73-0

Molecular formula:

C5H8O3

IUPAC Name:

methyl 2-hydroxybut-3-enoate

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Han:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. Cserkesz u. 90., 1103 Budapest, Hungary
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult rats, min. 8-10 weeks
- Weight at study initiation: 200-300 g
- Fasting period before study: No
- Housing: Max. 3 animals/cage during acclimatisation and individually during exposure in type III polypropylene/polycarbonate cages with certified laboratory bedding
- Diet: Ad libitum (ssniff® SM R/M-Z+H complete diet)
- Water: Ad libitum (tap water)
- Acclimation period: At least 5 days
- Microbiological status: SPF at arrival and kept in a good conventional environment during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): More than 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From day 0 to day 14

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10 % area of the total body surface
- % coverage: 10 % area of the total body surface
- Type of wrap: Sterile gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal will then be wrapped with semi-occlusive plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test item was removed, using water at body temperature.
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

200, 1000 and 2000 mg/kg bw

No. of animals per sex per dose:

One female animal per dose (200, 1000 and 2000 mg/kg bw) was treated with the test item in the range-finding test and one female animal was treated with a single dose (200 mg/kg bw) in the main test.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighted directly before treatment and at day 7 and 15 or at preliminary sacrifice
- Necropsy of survivors performed: Yes

Statistics:

Not required

Results and discussion

Preliminary study:

A range-finding study was performed to determine the starting dose for the main test. The starting dose of the range-finding study was 200 mg/kg bw. The animal did not die in this first step, therefore one further rat was treated with 1000 mg/kg body weight in range-finding study. This animal did not die in second step, therefore one further rat was treated with 2000 mg/kg body weight in range-finding study. This animal died on Day 1. The animal treated with 1000 mg/kg bw was however humanely killed on Day 5 as the test item caused with some delay corrosive local signs.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Remarks on result:

not determinable

Remarks:

Not determinable as the substance induced delayed local corrosive effects and the study was stopped for animal welfare reasons.

Mortality:

Yes, the animal treated with 2000 mg/kg bw died on day 1. Animals treated with 1000 and 200 (main test) mg/kg bw were humanely killed before the end of the 14-day observation period as the test item caused with some delay corrosive local signs.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

The body weight was only measured for the rat dosed with 200 mg/kg bw in the range-finding test as all other animals had to be humanely killed before further weighting was possible. The rat dosed with 200 mg/kg bw showed a stable body weight gain.

Gross pathology:

Not performed

Other findings:

The test item induced local corrosive symptoms like erythema, oedema, crust, (bloody) wounds, scabs and necrosis

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

In an acute dermal toxicity study according to OECD guideline 402 and GLP, the test item could not be classified into any toxicity category as delayed local corrosive effects occured.

Executive summary:

In an acute dermal toxicity study according to OECD guideline 402 and GLP, the toxicity of test item was assessed when administered in a single dermal dose to rats at one or more defined dose levels. At first, the range-finding study was performed in one female Han:WIST rat. The starting dose was 200 mg/kg bw. The test item was applied in original form and left in contact with the skin for a 24 hours period in all animals. The animal did not die in this first step, therefore one further rat was treated with 1000 mg/kg body weight in range-finding study. This animal did not die in second step, therefore one further rat was treated with 2000 mg/kg body weight in range-finding study. This animal died on Day 1. The animal treated with 1000 mg/kg bw was however humanely killed on Day 5 as the test item caused with some delay corrosive local signs. Based on this finding one further animal was treated 200 mg/kg bw in main study. This animal was however also humanely killed on Day 4 because of massive skin corrosion developing with time. The study was terminated for animal welfare reasons, because the test item caused massive skin damage up to clear and massive skin corrosion over time at 1000 mg/kg bw, and even at 200 mg/kg bw in the second test animal. This massive skin damage was not to be expected based on the in vitro skin irritation/corrosivity tests classifying the test item as irritant but clearly not as corrosive.