3a,4,5,6,7,7a-hexahydro-5-methoxy-4,7-methano-1H-indene

Endpoint summary

Description of key information

Acute Oral Toxicity, Edwards (1985)

Under the conditions of the study the acute oral LD50 of the test material was between 2.0 and 5.0 mL/kg bodyweight (equivalent to between 2020 and 5050 mg/kg when taking the density of the test material as 1.01 as detailed in the study report).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 April 1985 to 30 April 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of mice were orally intubated at 3 dose levels using graded volumes of the test material. Animals were observed for up to 7 days after intubation. All animals dying were autopsied. All survivors were killed and examined post mortem after 7 days.
The study was conducted in accordance with S.O.P. No 195.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

not specified

Remarks:

White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4-5 weeks old
- Weight at study initiation: 21 - 27 g
- Fasting period before study: 4 hours prior to dosing
- Housing: the animals were housed individually
- Diet: ad libitum commercial pelleted diet after treatment
- Water: ad libitum after treatment

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10.0 mL/kg

DOSAGE PREPARATION: the test material was dosed undiluted

DOSES
- The most relevant dose-level for the class of the test material was selected (5.0 mL/kg), and three male and three female animals are dosed at this level. Two groups of one male and one female were dosed above (10.0 mL/kg) and below (2.0 mL/kg) this level.

Doses:

2.0, 5.0 and 10.0 mL/kg

No. of animals per sex per dose:

2.0 and 10.0 mL/kg: 1 animal per sex
5.0 mL/kg: 3 animals per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days (any animal dying during this period was autopsied)
- Necropsy of survivors performed: yes
- Other examinations performed: yes, surviving animals were weighed before termination

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 - < 5 mL/kg bw

Based on:

test mat.

Mortality:

The mice dosed at 10.0 and 5.0 mL/kg were found dead after 18 hours.

Clinical signs:

- The mice dosed at 10.0 mL/kg were somnolent and showing signs of stress and laboured breathing within 30 minutes after treatment. The mice became semi-comatose after 1 hour, comatose after 2 hours and were found dead after 18 hours.
- The mice dosed at 5.0 mL/kg showed similar symptoms and were found dead after 18 hours.
- The female mouse dosed at 2.0 mL/kg was showing signs of stress and was ataxic after 2 hours, but recovered within 18 hours. The male mouse dosed at this level appeared unaffected by treatment.

Gross pathology:

- Autopsy of the mice that died revealed slight irritation of the small intestines and pale liver and kidneys.
- The surviving mice gained weight during the 7-day observation period and presented a normal appearance at autopsy.

Conclusions:

Under the conditions of this study the acute oral LD50 of the test material was between 2.0 and 5.0 mL/kg bodyweight.

Executive summary:

The acute oral toxicity of the test material was investigated with male and female mice.

During the study groups of mice were orally intubated at 3 dose levels using graded volumes of the test material. Animals were observed for up to 7 days after intubation. All animals dying were autopsied. All survivors were killed and examined post mortem after 7 days.

The most relevant dose-level for the class of the test material was selected (5.0 mL/kg), and three male and three female animals are dosed at this level. Two groups of one male and one female were dosed above (10.0 mL/kg) and below (2.0 mL/kg) this level.

The mice dosed at 10.0 mL/kg were somnolent and showing signs of stress and laboured breathing within 30 minutes after treatment. The mice became semi-comatose after 1 hour, comatose after 2 hours and were found dead after 18 hours. The mice dosed at 5.0 mL/kg showed similar symptoms and were found dead after 18 hours. The female mouse dosed at 2.0 mL/kg was showing signs of stress and was ataxic after 2 hours, but recovered within 18 hours. The male mouse dosed at this level appeared unaffected by treatment.

Autopsy of the mice that died revealed slight irritation of the small intestines and pale liver and kidneys. The surviving mice gained weight during the 7-day observation period and presented a normal appearance at autopsy.

Under the conditions of this study the acute oral LD50 of the test material was between 2.0 and 5.0 mL/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

Acute Oral Toxicity, Edwards (1985)

The acute oral toxicity of the test material was investigated with male and female mice. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study Groups of mice were orally intubated at 3 dose levels using graded volumes of the test material. Animals were observed for up to 7 days after intubation. All animals dying were autopsied. All survivors were killed and examined post mortem after 7 days.

The most relevant dose-level for the class of the test material was selected (5.0 mL/kg), and three male and three female animals are dosed at this level. Two groups of one male and one female were dosed above (10.0 mL/kg) and below (2.0 mL/kg) this level.

The mice dosed at 10.0 mL/kg were somnolent and showing signs of stress and laboured breathing within 30 minutes after treatment. The mice became semi-comatose after 1 hour, comatose after 2 hours and were found dead after 18 hours. The mice dosed at 5.0 mL/kg showed similar symptoms and were found dead after 18 hours. The female mouse dosed at 2.0 mL/kg was showing signs of stress and was ataxic after 2 hours, but recovered within 18 hours. The male mouse dosed at this level appeared unaffected by treatment.

Autopsy of the mice that died revealed slight irritation of the small intestines and pale liver and kidneys. The surviving mice gained weight during the 7-day observation period and presented a normal appearance at autopsy.

Under the conditions of the study the acute oral LD50 of the test material was between 2.0 and 5.0 mL/kg bodyweight (equivalent to between 2020 and 5050 mg/kg when taking the density of the test material as 1.01 as detailed in the study report).

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to acute oral toxicity.