Cyclopropanemethanol, 1-methyl-2-[(1,2,2-trimethylbicyclo[3.1.0]hex-3-yl)methyl]-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 23 September to 14 October 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1S,2S)-, rel-

Molecular formula:

C15H26O

IUPAC Name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1S,2S)-, rel-

Constituent 2

Reference substance name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1R,2R)-, rel-

Molecular formula:

C15H26O

IUPAC Name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1R,2R)-, rel-

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Javanol
- Physical state: Pale yellow viscous liquid

Test animals

Species:

rat

Strain:

other: Hanlbm: WIST (SPF) rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd
Wölferstrasse 4, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation:
Males: 8 weeks
Females: 10 weeks
- Weight at study initiation:
Males: 201 - 211 g
Females: 174 - 187 g
- Fasting period before study: overnight prior to intubation
- Housing: Makrolon type-4 cages
- Diet (e.g. ad libitum): Pelleted standard Kliba 3433, ad libitum
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum
- Acclimation period: one week under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

The animals received a single dose of the test article on a mg/kg body weight/day basis by oral gavage following fasting for approximately 17 hours, but with free access to water. Food was provided again approximately 3 hours after dosing.
Dose / kg body weight/day : 2000 mg
Application volume / kg body weight/day : 10ml
Rationale: Oral administration was used as this one possible route of human exposure during manufacture, handling and use of the test article.

Doses:

2000 mg/ kg bw/d

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Mortality/Viability:four times during test day 1 and once daily for surviving animals during days 2-15.
Body weights: on test day 1 (pre-administration), 8 and 15 for surviving animals.
Clinical signs: each animal was examined for changes in appearance and behaviour four times during day 1, and once daily for surviving animals during days 2-15.

Necropsy: Necropsies were performed by experienced prosectors. The animals were examined macroscopically and all abnormalities recorded. Thereafter, they were discarded.

Statistics:

No statistical analysis was used as no deaths occured.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic findings were observed at the necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of Javanol after single oral administration to rats of both sexes, observed over a period of 14 days is :
LD50 : greater than 2000 mg/kg

Executive summary:

The study was performed to assess the acute oral toxicity of Javanol in Wistar (SPF) rats, in accorance with the GLP principles and following OECD 401 test guidelines (adopted 1987) and Method B1 Acute Toxicity-Oral (Acute Toxic Class Method) of the EC Directive No. 92/69/EEC. In the study, a group of five male and five female HanIbm: WIST (SPF) rats was treated with Javanol at 2000 mg/kg by oral gavage. The test article was suspended in vehicle polyethylene glycol (PEG400) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. The animals were examined for clinical signs four times during day 1 once daily during days 2 -15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

No deaths occured during the study and no clinical signs of toxicity were observed during the observation period.

The body weight of the animals was within the range of physiological variability known for rats of this strain and age and no macroscopic findings were observed at necropsy.

The LD50 for the study was greater than 2000 mg/kg bw. Therefore, it is not classified according to the Regulation (EC) No. 1272 -2008 and according to the GHS. No signal word or hazard statement is required.