Ethanone, 1-(3-methyl-2-benzofuranyl)-

Endpoint summary

Description of key information

Acute oral toxicity

The acute oral toxicity of the test item was tested according to OECD guideline 401. The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 200 mg/kg but less than 2000 mg/kg bodyweight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24 February 1987)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CD (Crl : CD ® BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for use of males: Both males and females were used to compare both sexes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 203 to 221 g (males) and 211 to 228 g (females)
- Fasting period before study: Overnight
- Housing: In groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet: Ad libitum (except fastig period before dosing and 3-4 hours after dosing)
- Water: Ad libitum (except fastig period before dosing and 3-4 hours after dosing)
- Acclimation period: At least five days
- Method of randomisation in assigning animals to test and control groups: Animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 48-55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From day 0 to day 14

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2.5, 20 and 200 mg/mL (dose-range finding test) and 20 mg/mL (main study)
- Amount of vehicle: 10 mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL

DOSAGE PREPARATION: The test material was warmed in a warming bath to produce a liquid and then freshly prepared, as required, as a solution at the appropriate concentration in arachis oil BP.

Doses:

25, 200 and 2000 mg/kg bw (dose range finding study) and 200 mg/kg bw (main study)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing on day 0 and on days 7 and 14.
- Necropsy of survivors performed: Yes

Statistics:

Not specified

Preliminary study:

A range-finding study was performed to establish a dosing regime. One male and one female animal were exposed to 25, 200 and 2000 mg/kg bw. Animals treated with 2000 mg/kg were found dead one day after dosing. Clinical signs of toxicity noted were hunched posture, Iethargy, ataxia, decreased respiratory rate, ptosis and pilo-erection. Based an this information, a dose level of 200 mg/kg bodyweight was selected for the main study.

Key result

Sex:

male/female

Dose descriptor:

LD100

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

200 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths at 200 mg/kg bw (main study). At 2000 mg/kg bw (range finding test), all animals died.

Clinical signs:

other: Common signs of systemic toxicity noted were lethargy and/or hunched posture during the day of dosing. All animals recovered one day after dosing (main study at 200 mg/kg bw). Animals dose with 2000 mg/kg bw showed hunched posture, Iethargy, ataxia, decre

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Similar to ECHA "Guidance on the Application of the CLP Criteria" version 5.0, July 2017 in chapter 3.1.5.1.3 Example 3: Since at a dose of 200 mg/kg bw. no mortality and only slight transient symptoms without necropsy findings were observed, at the next dose 2000 mg/kg bw in the range finder study 1 male and 1 female died (all animals) , based on expert judgement it can be assumed that the likely LD50 is > 300 mg/kg bw.

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 200 mg/kg but less than 2000 mg/kg bodyweight.

Executive summary:

In an acute, GLP compliant oral toxicity study according to OECD guideline 401, 5 male and 5 female Sprague-Dawley CD rats were treated with a single oral gavage dose of 200 mg/kg bw. This dose was chosen based on a previous dose range finding test with 25, 200 and 2000 mg/kg bw (1 male and 1 female per dose) where all animals at 2000 mg/kg bw died. Rats at 200 mg/kg bw showed lethargy and/or hunched posture during the day of dosing. All animals recovered one day after dosing. Animals dosed with 2000 mg/kg bw showed hunched posture, Iethargy, ataxia, decreased respiratory rate, ptosis and pilo-erection. Based on the data, the acute oral median lethal dose (LD50) of the test material in the rat was found to be greater than 200 mg/kg but less than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 200 - < 2 000 mg/kg bw

Quality of whole database:

Reliable without restrictions

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity, rat, RL1

In an acute, GLP compliant oral toxicity study according to OECD guideline 401, 5 male and 5 female Sprague-Dawley CD rats were treated with a single oral gavage dose of 200 mg/kg bw. This dose was chosen based on a previous dose range finding test with 25, 200 and 2000 mg/kg bw (1 male and 1 female per dose) where all animals at 2000 mg/kg bw died. Rats at 200 mg/kg bw showed lethargy and/or hunched posture during the day of dosing. All animals recovered one day after dosing. Animals dosed with 2000 mg/kg bw showed hunched posture, Iethargy, ataxia, decreased respiratory rate, ptosis and pilo-erection. Based on the data, the acute oral median lethal dose (LD50) of the test material in the rat was found to be greater than 200 mg/kg but less than 2000 mg/kg bodyweight.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Thus, the test item is concluded to be classified for acute oral toxicity (category 4) under Regulation (EC) No 1272/2008, as amended for fifteenth time in Regulation (EU) No 2020/1182.