Methyl [1α,2β(Z)]-(±)-3-oxo-2-(pent-2-enyl)cyclopentaneacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 14 September 1999 and 06 October 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl [1α,2β(Z)]-(±)-3-oxo-2-(pent-2-enyl)cyclopentaneacetate

EC Number:

243-497-1

EC Name:

Methyl [1α,2β(Z)]-(±)-3-oxo-2-(pent-2-enyl)cyclopentaneacetate

Cas Number:

20073-13-6

Molecular formula:

C13H20O3

IUPAC Name:

methyl 2-[(1S,2S)-3-oxo-2-[(2Z)-pent-2-en-1-yl]cyclopentyl]acetate

Specific details on test material used for the study:

Sponsor's identification: JASMONEIGE (LOT NO. 75028)
Lot number: 75028
Date recieved: 24 August 1999
Description: colourless liquid.
Storage conditions: approximately 4 °C in the dark under nitrogen.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Sprague-Dawley CD (Crl: CD (SD) IGS BR) strain rats supplied by Charles Rivers (UK) Ltd., Margate, Kent, UK. were used. At the start of the main study the males weighed 229 to 245 g, and the females 220 to 232 g, and were eight to twelve weeks of age. After an acclimatisation period of at least five days the 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.

The animals were housed in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diets Servies Limited, Witham, Essex, UK) was allowed throughout the study.

The temperature and relative humidity were controlled to remain with target ranges of 19 to 25 °C and 30 to 70 % respectively. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

All animals were dosed once only by gavage using metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

Doses:

Range finding study: 2000 mg/kg
Main study: 2000 mg/kg

No. of animals per sex per dose:

Range finding: 1 male and 1 female
Main study: 5 males and 5 females.

Control animals:

no

Details on study design:

Range finding study
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently onces daily for five days.
Individual bodyweigths were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropises were performed.

Main study
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently onces daily for five days.
Individual bodyweigths were recorded prior to dosing on Day 0 and on Days 7 and 14
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Preliminary study:

There were no deaths. Clinical signs of toxicity noted were hunched posture, lethargy, pilo-erection and decreased respiratory rate. Animals recovered one day after dosing.
Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main study.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths

Clinical signs:

other: Hunched posture was commonly noted with incidents of lethargy, ataxia, decreased respiratory rate, laboured respiration and ptosis. Animals recovered one day after dosing.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material, Jasmoneige (LOT NO. 75028), in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that in the OECD guidelines of testing of chemicals No. 401 "Acute Oral toxicity" (adopted 24 February 1987) and method B1 of Commission Directive 92/68/EEC.

Following a range finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of undiluted test material at a dose level of 2000 mg/kg bodyweight. The animals were observed for fouteen days after the day of dosing and were killed and subjected to gross pathological examination.

There were no deaths. Hunched posture was commonly noted with isolated incidents of lethargy, ataxia, decreased respiratory rate, laboured respiration and ptosis. Animals recovered one day after dosing.

Animals showed expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

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