1,4:5,8-Dimethanonaphthalene, 2-ethylidene-1,2,3,4,4a,5,8,8a-octahydro-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 June 1989 - 27 June 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD test guidelines, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(3R,6S,9E)-9-ethylidenetetracyclo[6.2.1.1³,⁶.0²,⁷]dodec-4-ene; (3S,6R,9E)-9-ethylidenetetracyclo[6.2.1.1³,⁶.0²,⁷]dodec-4-ene

EC Number:

700-518-3

Cas Number:

38233-76-0

Molecular formula:

C14H18

IUPAC Name:

(3R,6S,9E)-9-ethylidenetetracyclo[6.2.1.1³,⁶.0²,⁷]dodec-4-ene; (3S,6R,9E)-9-ethylidenetetracyclo[6.2.1.1³,⁶.0²,⁷]dodec-4-ene

Details on test material:

- Name of test material (as cited in study report): ED-TCD
- Chemical name cited in report: 2-ethylidene-1,2,3,4,4a,5,8,8a-octahydro-1,4:5,8-dimethano-naphthalene
- Physical state: Clear liquid
- Analytical purity: 99.3%
- Storage condition of test material: Refrigerated (c. 4°C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 Weeks (5 weeks at receipt, then 2 weeks' acclimatization)
- Weight at study initiation: Males: 147 - 208 g; Females: 124 to 154 g
- Housing: Stainless steel cages with wire-screen bottom and front
- Diet (e.g. ad libitum): free access to cereal-based, open formula basal diet for rats
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: (Main study) From: 06 June 1989 To: 20 June 1989

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 33.7 - 256.2 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bodyweight
- Justification for choice of vehicle: Determined during a preliminary study (results of which were not presented)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

337, 506, 759, 1139, 1709, 2562 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: Bodyweights recorded on days 0, 3, 7, and 14. The rats were observed regularly for signs of intoxication, during the first 4 hours after treatment and thereafter, at least once daily through an observation period of 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology.

Statistics:

LD50 calculated by Finney method (Finney, D.J., Probit Analysis, Cambridge University Press, 3rd Edition, 1971).

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

849 mg/kg bw

95% CL:

658 - 1 068

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

666 mg/kg bw

95% CL:

488 - 895

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

1 089 mg/kg bw

95% CL:

804 - 1 471

Mortality:

Males: all animals died in the 1139, 1709, and 2562 mg/kg dose levels; 2 out of 5 animals died in the 507 and 759 mg/kg dose levels. No animals died in the 337 mg/kg level.
Females: All rats died at 2562 mg/kg, and 4 out of 5 rats died at the 1709 mg/kg dose level. Two out of five rats died at the 759 and 1139 mg/kg dose levels, and no rats died at the 507 mg/kg level.

At all dose levels, deaths occurred within 2 days of treatment with the test material.

Clinical signs:

other: Sluggishness, piloerection and diarrhoea were all seen within one hour of treatment in the highest dose level. Later in the observation period, symptoms such as tremor, soiled furs, coma and pallour were noted.

Gross pathology:

Macroscopic examination of the animals that died and of the animals which survived did not reveal treatment-related changes in any of the dose levels.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of ED-TCD by oral administation in rats was determined to be 666 mg/kg in males (95% confidence limit 488-895), 1089 mg/kg in females (95% confidence limit 804 - 1471), and 849 mg/kg (95% confidence limit 658 - 1068) overall (ignoring the sex difference).