Decan-4-olide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

From 2002-07-02 to 2002-09-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Test was conducted in accordance with Japanese guideline for medicine (yakushin yaku No.88, 1993-08-10) which is similar to OECD test guideline No. 420 but not under GLP conditions. γ-caprolactone, as a aliphatic γ-lactone, is considered adequate for read-across purpose (see §"Toxicokinetics").

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Japanese guideline for medicine (yakushin yaku No.88, 1993-08-10)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

yes

Remarks:

housing of animals not reported

Principles of method if other than guideline:

not applicable

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Hexan-4-olide

EC Number:

211-778-8

EC Name:

Hexan-4-olide

Cas Number:

695-06-7

IUPAC Name:

5-ethyldihydrofuran-2(3H)-one

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): gamma-caprolactone
- Physical state: transparent liquid without color
- Storage condition of test material: room temperature in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles Liver Japan
- Age at study initiation: purchased at age of week 4
- Weight at study initiation: male: 87-96g, female: 70-82g when reveived
- Fasting period before study: 17-18 hr
- Housing: no data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23+/-3
- Humidity (%): 50+/-20
- Air changes (per hr): 10-15/hr
- Photoperiod (hrs dark / hrs light): 12 hr/12 hr

IN-LIFE DATES: From: 2002-07-03 To: 2002-07-24

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 20 mL/kg
- Justification for choice of vehicle: test substance is dissolved in water at 10% and stable in water
- Lot/batch no. (if required): 1XA1 (Japanese pharmacopoeia)

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: administered at 2000 mg/kg due to low toxicity expected

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs, mortality, behavior: after administration to 1, 2, and 4 hourr, 1 to 14 day (every day); bodyweight: day 0, 1, 3, 5, 7, 10 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs was performed:

Statistics:

not performed

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred at the dose levels of 2000 mg/kg bw during the observation period.

Clinical signs:

other: No clinical signs were observed in the animals treated at the dose level of 2000 mg/kg bw.

Gross pathology:

No macroscopic lesions were observed at 2000 mg/kg bw.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Oral LD50Combined > 2000 mg/kg bw

Executive summary:

In a limit acute oral toxicity study performed according to Japanese guideline for medicines (which is similar to the OECD test guideline No. 420) but not in compliance with GLP, 5 Sprague-Dawley rats/sex were administered a single oral dose of 2000 mg/kg bw of the γ-caprolactone (97.4 % pure). The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

No animal died. No clinical signs or effects on body weight were observed at 2000 mg/kg bw. Gross pathological examinations at 14 days (terminal necropsy) revealed no test substance-related findings.

Oral LD₅₀Combined > 2000 mg/kg bw

 

Under the test conditions, γ-caprolactone is not classified according to the Regulation EC No. 1272/2008 (CLP) and the Directive 67/548/EEC. This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

γ-caprolactone, as aliphatic γ-lactone, is considered adequate for read-across purpose (see §"Toxicokinetics").