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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 5 october 1999 to 26 october 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

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:

Substance identity: Javanol
Appereance: Liquid

Test animals

Species:

rat

Strain:

other: HanBrl: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd - Biotechnology & Animal Breeding Division CH-4414 Füllinsdorf / Switzerand
- Age at study initiation:
Males: 9 weeks
Females: 12 weeks
- Weight at study initiation:
Males: 235.2 to 242.5 g
Females: 201.3 to 221.4 g
- Fasting period before study: NA
- Housing: individually in Makrolon type-3 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: 7 days under laboratories 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

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 24 hours before treatment the backs of the animals were clipped with an eletric clipper
- % coverage: 10% of total body surface
- Type of wrap if used: semi-occlusive dressing and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Twenty-four hours after the application, the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels and the reaction sites were assessed.

TEST MATERIAL
- Amount applied (volume or weight with unit): 2000 mg/kg body weight

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

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. At the end of observation period all animals were sacrificed by intraperitoneal injection of Narcoren at a dose of at least 2.0 ml/kg body weight. 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

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic or local signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

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

Executive summary:

The acute dermal toxicity of the test material was assessed in five male and five female HanIbm: WIST (SPF) rats. The animals were dermally treated with undiluted Javanol at 2000 mg/kg bw. The test material was applied to the clipped skin (backs) of the rats and covered with semi-occlusive dressing for 24 hours. After the 24hr exposure period, the skin was flused with water and the site assessed for reactions and the animals were observed over a 14 -day period. The animals examined for clinical signs four times during day 1 and once daily during days 2 -15, along with mortality/viability

Body weights were recorded on day 1 prior to administration and on days 8 and 15. At termination, all animals were necropsied and examined macroscopically. No deaths occured during the study and no systemic or local signs of toxicity observed during the observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. The LD50 for this study was greater than 2000 mg/kg body weight.