3-Oxabicyclo[3.1.0]hexan-2-one, 4-(1,1-dichloro-2,2,2-trifluoroethyl)-6,6-dimethyl-, (1R,4R,5S)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(1R,4R,5S)- 4-(1,1-Dichloro-2,2,2-trifluoroethyl)-6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one

EC Number:

606-114-2

Cas Number:

187592-70-7

Molecular formula:

C9H9Cl2F3O2

IUPAC Name:

(1R,4R,5S)- 4-(1,1-Dichloro-2,2,2-trifluoroethyl)-6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: Males: 252-270g, females: 204-222g
- Fasting period before study: overnight + 3-4 hours after dosing
- Housing: solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): 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 Services Limited, Witham, Essex, UK) was allowed throughout the study.
- Water (e.g. ad libitum): See above
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 49-70
- Air changes (per hr):15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

One dose by gavage, using a metal cannula attached to a graduated syringe

Doses:

Using all available information, 200 mg/kg bodywitht was selected as the starting dose. A group of three fasted females was treated with the starting dose. Based on the result from this dose level further groups of fasted animals were treated t a dose level of 200 mg/kg bodyweight.

No. of animals per sex per dose:

3 Females: 2000 mg/kg
3 Females + 3 males: 200 mg/kg

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: ½, 1, 2, 4 hours after dosing and then once daily for 14 days.
- Frequency of weighing: At day 0 (Day of dosing) + on day 7 +14.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs: Signs of systemic toxicity noted were hunched posture, lethargy, pilo-erection, decreased respiratory rate, laboured respiration and ataxia, developing on the day of dosing and lasting up to one day after dosing.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

500 - 1 000 mg/kg bw

Based on:

test mat.

Mortality:

Two animals treated with 2000 mg/kg were found dead.

Clinical signs:

other: Signs of systemic toxicity noted in animals treated with 200 mg/kg were hunched posture, lethargy, pilo-erection, decreased respiratory rate, laboured respiration, clonic convulsions, tonic convulsions, prostration, increased salivation, splayed gait and

Gross pathology:

Abnormalties noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, pale spleen and dark kidneys. Nor abnormalities were noted at necropsy of animals killed at the end of the study.

Applicant's summary and conclusion

Conclusions:

The acute oral LD50 of the test material, Fluorlacton, in the Sprague-Dawley CD strain rat was estimated as being in the range of 500 to 1000 mg/kg.

Executive summary:

Mortalities were noted at 2000 mg/kg bodyweight (2/3). No mortalities were noted at 200 mg/kg bodyweight.