(1α,2α,5α)-2,2,6-trimethylbicyclo[3.1.1]heptan-2-ol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-03-12 to 1979-05-31

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

See "Principles of method other than guideline"

Principles of method if other than guideline:

- Principle of test: Acute oral toxicity test in rats
- Short description of test conditions: Wistar rats were treated with different doses of the test item (5 males and 5 females per dose). Animals were observed for signs of toxicity for 14 days and then subjected to gross pathology. No detailed description of environmental conditions and clinical signs is available. Body weights were recorded at the beginning and after the 14-day observation period.
- Parameters analysed / observed: Mortality, gross pathology

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(1α,2α,5α)-2,2,6-trimethylbicyclo[3.1.1]heptan-2-ol

EC Number:

225-591-4

EC Name:

(1α,2α,5α)-2,2,6-trimethylbicyclo[3.1.1]heptan-2-ol

Cas Number:

4948-28-1

Molecular formula:

C10H18O

IUPAC Name:

(1R,2S,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Rationale for use of males: Both males and females were used
- Age at study initiation: Approx. 6-8 weeks
- Weight at study initiation: 184 - 278 g
- Fasting period before study: 18 hours
- Housing: In galvanized cages with indirect bedding
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 2 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature-controlled room
- Humidity (%): Not specified
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From day 0 to day 15

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

The test article was used in 25% gravimetric suspension, warmed to liquification for dosing

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25%

Doses:

1260, 2000, 2520 and 3140 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter. Body weights were recorded at the beginning of the study and after the 14-day observation period.
- Necropsy of survivors performed: Yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 050 mg/kg bw

Based on:

test mat.

95% CL:

> 1 630 - < 2 580

Mortality:

1260 mg/kg bw: 0/5 males and 2/5 females died
2000 mg/kg bw: 2/5 males and 3/5 females died
2520 mg/kg bw: 2/5 males and 4/5 females died
3140 mg/kg bw: 4/5 males and 3/5 females died

Clinical signs:

other: Clinical signs consisted of slight and severe depression,

Gross pathology:

The superficial examination appeared normal. In one male animals of the 1260 mg/kg bw group, a lesion on the left lobe of the lung was observed and one female animal of the 1260 mg/kg bw group showed a distended, gas filled stomach. In one male animal of the 2520 mg/kg bw group, fibrous tissue encasing heart and lungs was observed.

Applicant's summary and conclusion

Conclusions:

In an acute oral toxicity study in male and female rats, the LD50 was found to be 2050 mg/kg bw in male and females.

Executive summary:

In a GLP compliant acute oral toxicity study in Wistar rats, the test item was applied at doses of 1260, 2000, 2520 and 3140 mg/kg bw to 5 males and 5 females per dose by oral administration. Animals were observed for pharmacologic activity and drug toxicity 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. Animals were weighted before start of the treatment and at day 14. Non-survivors and and animals surviving the 14-day observation period were subjected to gross necropsy. From a dose of 1260 mg/kg bw (females) and 2000 mg/kg bw (males), slight to severe depression was observed in all animals in the first 24 hours. Body weight gain decreased with increasing doses. At 1260 mg/kg bw, 0/5 males and 2/5 females, at 2000 mg/kg bw, 2/5 males and 3/5 females, at 2520 mg/kg bw, 2/5 males and 4/5 females and at 3140 mg/kg bw, 4/5 males and 3/5 females died. Thus, the LD50 was found to be 2050 mg/kg bw for males and females.