3-ETHYL-5,5-DIMETHYL-GAMMA BUTYROLACTONE

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 10 and 25 June 2008.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 423 without any deviation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

Directive N° 2004/73/EC

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2007-01-11 / Signed on 2007-02-21

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(3S)-3-ethyl-5,5-dimethyloxolan-2-one

Molecular formula:

C8 H14 O2

IUPAC Name:

(3S)-3-ethyl-5,5-dimethyloxolan-2-one

Constituent 2

Reference substance name:

(3R)-3-ethyl-5,5-dimethyloxolan-2-one

Molecular formula:

C8 H14 O2

IUPAC Name:

(3R)-3-ethyl-5,5-dimethyloxolan-2-one

Test material form:

liquid

Details on test material:

- Physical state: colourless translucent liquid
- Storage condition of test material: Room temperature

Specific details on test material used for the study:

- Date received: 02 June 2008
- The test item was considered as 100% of the study

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle, France)
- Age at study initiation: 8 - 9 weeks.
- Weight at study initiation: 184 - 221 g
- Housing: housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff, ad libitum but food was removed at D-1 and then redistributed 4 hours after the test item administration.
- Water: tap-water from public distribution, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 41-70%
- Air changes: at least ten changes per hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: from 10 To 25 June, 2008.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.13 mL/kg bw

ADMINISTRATION OF TEST ITEM:
Animals received an effective dose of 2000 mg/kg bw of the test item, administered by gavage under a volume of 2.13 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min, 1, 3 and 4 hours after test item administration and thereafter once daily for 14 days. Animals were weighed pretest (Day 0) and on Day 2, 7 and 14.
- Necropsy of survivors performed: Yes; Animals were killed on Day 14 and subjected to macroscopic examination.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: It was noted the death of 1 treated rat, 6 hours after the test item administration.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Mortality:

It was noted the death of 1 treated rat, 6 hours after the test item administration.

Clinical signs:

other: A decrease of the spontaneous activity (6/6) associated with a myosis (3/6), a decrease of Preyer's reflex (6/6), muscle tone (3/6) and righting reflex (6/6) was registered in the treated animals, during the 1st day of the test. The animals recovered a no

Gross pathology:

The macroscopical examination of the animal which died during the study revealed a thinning of the forestomach.
The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the test conditions, the oral LD50 for test substance is higher than 2000 mg/kg bw and the LD50 cut-off is 2500 mg/kg bw in female rats. Therefore the test substance is not classified according to the criteria of the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and classified in category 5 (H303) according to the GHS.

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, 6 female Sprague Dawley rats were given a single oral (gavage) dose of test item at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

It was noted the death of 1 treated rat, 6 hours after the test item administration.A decrease of the spontaneous activity (6/6) associated with myosis (3/6), a decreased of Preyer’s reflex (6/6), muscle tone (3/6) and righting reflex (6/6) was registered in the treated animals, during the first day of the test. The animals recovered a normal activity the 2 nd day of the test.The body weight evolution of the animals remained normal throughout the study.The macroscopical examination of the animal which died during the study revealed a thinning of the corpus and the forestomach.The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes

Under the test conditions, the oral LD50 for test substance is higher than 2000 mg/kg bw and the LD50 cut-off is 2500 mg/kg bw in female rats. Therefore the test substance is not classified according to the criteria of the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and classified in category 5 (H303) according to the GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.