1,4:5,8-Dimethanonaphthalene, 1,2,3,4,4a,5,8,8a-octahydro-, (1R,4S,4aR,5S,8R,8aS)-rel-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 September 2009 to 29 October 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(1R,2R,3S,6R,7S,8S)-tetracyclo[6.2.1.1³,⁶.0²,⁷]dodec-4-ene

EC Number:

700-678-4

Cas Number:

1076-12-6

Molecular formula:

C12H16

IUPAC Name:

(1R,2R,3S,6R,7S,8S)-tetracyclo[6.2.1.1³,⁶.0²,⁷]dodec-4-ene

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report):

- Physical state: clear colorless liquid (non-GLP)
- Analytical purity: 99.5% (non-GLP)

- Lot/batch No.: 20080625003
- Expiration date of the lot/batch: 22 June 2009
-
- Storage condition of test material: refrigerator in the cold
- Other:

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan Inc.
- Age at study initiation: 9 weeks
- Weight at study initiation: Experiment 1 = 195-205g; Experiment 2 = 185-189g
- Fasting period before study: 16-17 hours
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24
- Humidity (%): 55
- Air changes (per hr): 10-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 18 September to 02 October 2009

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/L and 200 mg/L
- Amount of vehicle (if gavage): 10 mL/kg bodyweight

- Lot/batch no. (if required): V8A6289


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bodyweight

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: guideline recommendations

Doses:

300 mg/kg bodyweight in Experiments 1 and 2; 2000 mg/kg in Experiment 3

No. of animals per sex per dose:

3 per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other)
- Frequency of observations and weighing: observations before dosing, at 30 minutes and 1, 2, 3 and 4 hours on day of administration and daily from days 2 to 15. Bodyeight determinaiton on day of dosing and on days 1, 3, 7 and 14 days thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: all organs and tissues examined macroscopically

Statistics:

Mean and standard deviations of bodyweights calculated; no conducted statistical analysis

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

Experiment 1: 1/3 animals died on day 3
Experiment 2: 1/3 animals died on day 2
Experiment 3: 3/3 animals died between 1 to 4 hours after dosing

Clinical signs:

other: Mucous stools in 2/3 and 3/3 animals in experiments 1 and 2 respectively at 1 to 3 hours after dosing or on the following day of administration. Mucous stools 2/3 animals in experiment 3 at 1 and 2 hours after dosing. Soiled periproctal region in 1/3 and

Gross pathology:

No abnormalities observed at necropsy including the dead animals.

Other findings:

Death was considered to be caused by actions on the central nerve system or emaciation due to deterioration of general conditions.

Any other information on results incl. tables

In surviving animals in experiments 1 and 2, mucous stool or soiled periproctal region all disappeared by 2 days after administration. Although the decreased body weight or suppressed body weight gain was noted on the following day of administration, favorable increased gain was observed on 3 days after administration or later in experiments 1 and 2.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 cut off value of TCD was estimated to be 500 mg/kg under the conditions of this study.