4-hydroxycoumarin

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental start: March 5, 2021; experimental completion: April 2, 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-hydroxycoumarin

EC Number:

214-060-2

EC Name:

4-hydroxycoumarin

Cas Number:

1076-38-6

Molecular formula:

C9H6O3

IUPAC Name:

4-hydroxycoumarin

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Identification: 4-Hydroxycoumarin
CAS Number: 1076-38-6
Batch: HCN20002
Purity: 100.3%
Molecular Weight: 162.14
Physical state/Appearance: off white powder
Expiry Date: 26 September 2022
Storage Conditions: 15-25°C protected from light

Test animals

Species:

rat

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: commonly used laboratory strain will be obtained from an accredited supplier.
- Age at study initiation: 8-12 weeks
- Fasting : yes
- Housing: Cages conforming to the 'Code of Practice for the Housing and Care of Animals Bred, Supplied or Used for Scientific Purposes’ (Home Office, London, 2014).
- Diet (e.g. ad libitum): The animals will have access ad libitum to 5LF2 EU Rodent Diet, except for a period of fasting from the evening of the day prior to dosing (Day-1) until approximately 3 hours after dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 40 to 70%.
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark
- Air: A minimum of 15 air changes/hour.

Administration / exposure

Route of administration:

oral: gavage

Details on oral exposure:

The test article will be dispersed in a physiologically compatible vehicle, with preference given to purified water, 1% w/v aqueous methyl cellulose or corn oil.

Doses:

The first dose level is selected from four possible doses (5, 50, 300 or 2000 mg/kg) using available information from the Sponsor or from literature. If no information is available then a starting dose of 300 mg/kg will be selected.

No. of animals per sex per dose:

Dose-range finding study: 1
Definitive study: 5

Control animals:

no

Details on study design:

Groups of animals of a single sex are dosed in a stepwise procedure using fixed doses of the test article at 5, 50, 300 or 2000 mg/kg. The initial dose level, selected on the basis of results of a sighting study, is the dose expected to cause some signs
of toxicity without causing severe toxic effects or mortality. The selected dose levels will be recorded by the Study Director on a dispensary request form. Further groups of animals may be dosed at higher or lower fixed doses, depending
on the presence or absence of clinical signs or mortality (following the flow diagram presented in Section 9). This procedure continues until the dose causing evident toxicity or no more than one death is identified, or when no effects are seen at the
highest dose or when deaths occur at the lowest dose. Evident toxicity, as described in the Test Guideline, is a general term which describes clear signs of toxicity following administration of test article which are of
a severity such that administration at the next highest fixed dose level can be expected to cause either severe pain and enduring signs of severe distress, a moribund state or probable mortality in most animals.

Results and discussion

Preliminary study:

None of the animals died at the highest dose of 2000 mg/kg dose level.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Based on the results from the Acute Exposure Oral Toxicity in rats, the, definitive acute oral LD 50 for femaless for the test item was determined to be > 2000 mg/kg. Based on the LD50 and the criteria of the CLP Regulation, the test item is not classified for acute oral toxicity.