Methoxycarbonyloxycyclooct-4-ene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 18, 1985 - November 13, 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Remarks:

Study performed around/just before the time GLP was introduced in Europe, but internal QA statement.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methoxycarbonyloxycyclooct-4-ene

EC Number:

401-620-8

EC Name:

Methoxycarbonyloxycyclooct-4-ene

Cas Number:

87731-18-8

Molecular formula:

C10H16O3

IUPAC Name:

(1R,3aS,6aS)-octahydropentalen-1-yl methyl carbonate; (1S,3aS,6aS)-octahydropentalen-1-yl methyl carbonate; (3Z)-cyclooct-3-en-1-yl methyl carbonate; (4Z)-cyclooct-4-en-1-yl methyl carbonate; bicyclo[3.2.1]octan-8-yl methyl carbonate

Test material form:

liquid

Test animals

Species:

rat

Strain:

other: CD (Sprague-Dawley derived)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent, UK
- Age at study initiation: 4 to 6 weeks
- Weight at study initiation: 100 to 151 g
- Fasting period before study: Overnight prior to and approximately 4 hours after dosing
- Housing: Group housed per sex in metal cages with wire mesh floors
- Diet: A standard laboratory rodent diet (Labsure LAD 1) was provided ad libitum
- Water: Water was provided ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22
- Humidity (%): 53 (daily mean)
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4.72 mL/kg (relative density 1.0593)

Doses:

Preliminary study: 1000, 2500 and 5000 mg/kg bodyweight
Main study: 2000, 2500, 3200, 4000 and 5000 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed directly after dosing; then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed at least twice per day. Clinical signs were recorded at each observation.
- Necropsy of survivors performed: yes, all animals on the main study were killed on Day 15 by cervical dislocation and subjected to a macroscopic post mortem examination
- Body weights: Days 1, 8 and 15 and at death

Statistics:

Finney (1971) Probit Analysis (3rd Edition) Cambridge University Press

Results and discussion

Preliminary study:

The LD50 was between 2500 and 5000 mg/kg bodyweight

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

4 200 mg/kg bw

Based on:

test mat.

95% CL:

> 3 400 - < 5 500

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 400 mg/kg bw

Based on:

test mat.

95% CL:

> 1 900 - < 2 900

Mortality:

Deaths occurred amongst male rats dosed at 4000 mg/kg and above (2 at 4000 and 5 at 5000 mg/kg) and amongst female rats dosed at 2000 g/kg and above (2 at 2000, 3 at 2500, 4 at 3200, 4 at 4000 and 5 at 5000 mg/kg) within 22 and 47 hours of dosing.

Clinical signs:

other: Signs of reaction to treatment observed shortly after dosing in all rats were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, pallor of the extremities and increased salivation. The

Gross pathology:

No abnormalities were observed in surviving animals. In animals that died during the study pallor of the liver, kidneys and spleen were seen.

Applicant's summary and conclusion

Interpretation of results:

other: Not harmful according to EU CLP (1272/2008 and its amendments)

Conclusions:

The substance has a female LD50 of 2400 mg/kg bw and a male LD50 of 4200 mg/kg bw.

Executive summary:

The substance was tested in an acute oral toxicity study with male and female Sprague-Dawley rats (OECD TG 401). Based on the results of a preliminary study, the following doses were used in the main study: 2000, 2500, 3200, 4000 and 5000 mg/kg bw. Deaths occurred amongst male rats dosed at 4000 mg/kg and above and amongst female rats dosed at 2000 g/kg and above within 22 and 47 hours of dosing. Signs of reaction to treatment observed shortly after dosing in all rats were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, pallor of the extremities and increased salivation. These were accompanied by: ptosis in all male rats treated at 3200 mg/kg and in one male rat treated at 4000 mg/kg, a comatose-like condition amongst rats in all dose groups, increased lacrimation amongst rats dosed at 2500, 3200 and 4000 mg/kg. Recovery as judged by external appearance and behaviour was apparently complete by Day 5. Body weight losses were recorded for all but one of the rats that died and one surviving female at 2000 mg/kg. No abnormalities were observed in surviving animals. In animals that died during the study pallor of the liver, kidneys and spleen were seen. The female LD50 resulted in 24000 mg/kg bw (between 1900 and 2900 mg/kg bw) and the male LD50 resulted in 4200 mg/kg bw (between 3400 and 5500 mg/kg bw).