dec-9-en-2-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 09 and 29 January, 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:

dec-9-en-2-one

EC Number:

685-618-4

Cas Number:

35194-30-0

Molecular formula:

C10 H18 O

IUPAC Name:

dec-9-en-2-one

Test material form:

liquid

Details on test material:

- Physical state: colorless liquid
- Storage condition of test material: Room temperature, darkness.

Specific details on test material used for the study:

- Test item was considered at 100% for the study
- Date received: 17 December 2007

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 weeks
- Weight at study initiation: 180-198 g
- Fasting period before study: Food was removed at Day 1 and then redistributed 4 h after the test item administration.
- Housing: Animals were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff, ad libitum
- Water: Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20-23 °C
- Humidity: 32-60 %
- Air changes: na data
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: from 09 to 29 January, 2008.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

TEST SUBSTANCE ADMINISTRATION
- Test substance was administered by gavage under a volume of 2.38 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.

MAXIMUM DOSE VOLUME APPLIED: 2.38 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females/dose

Control animals:

yes

Remarks:

control animals received distilled water at 2 mL/kg bw

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 14 days after administration of the test item. Observations and a mortality report were then carried out every day for 14 days. Animals were weighed on Day 0 (just before administering the test item) then on Days 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels, then animals were subjected to macroscopic observations.

Statistics:

None

Results and discussion

Preliminary study:

None

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: One mortality was observed.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: One mortality and clinical signs were observed at 2000 mg/kg bw.

Mortality:

It was noted the death of 1 treated rat, 4 days after the test item administration.

Clinical signs:

other: A decrease of the spontaneous activity (6/6) associated with mydriasis (3/6), dyspnea (1/6), hypothermia (1/6), a piloerection (1/6), a decrease of muscle tone (1/6), an absence of Preyer’s reflex (1/6) and a decrease or an absence of righting reflex (2/6

Gross pathology:

The macroscopical examination of the animal which died during the study revealed a thinning of the corpus and the forestomach, and the presence of black foci at the level of the corpus.
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 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 substance at 2000 mg/kg bw. Control animals (6 females) received distilled water at 2 mL/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, 4 days after the test item administration. A decrease of the spontaneous activity (6/6) associated with mydriasis (3/6), dyspnea (1/6), hypothermia (1/6), a piloerection (1/6), a decrease of muscle tone (1/6), an absence of Preyer’s reflex (1/6) and a decrease or an absence of righting reflex (2/6) was registered in the treated animals, from thirty minutes after the test item administration. The animals recovered a normal activity the 3rd 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, and the presence of black foci at the level of the corpus.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.