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

Endpoint summary

Description of key information

Oral: Acute oral toxicity was assessed in a study similar to OECD Test Guideline 401 (OECD 401, Rel.1, Acute Oral Toxicity adopted February 24, 1987), resulting in a LD50 of greater than 2000 mg/kg body weight. No adverse effects noted in either males or females.

Inhalation: No data

Dermal: Acute dermal toxicity was assessed in a study similar to OECD Test Guideline 402 (OECD 402, Rel.1, Acute Dermal Toxicity adopted February 24, 1987),

resulting in a LD50 of greater than 2000 mg/kg body weight. No adverse effects noted in either males or females.

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:

From 23 September to 14 October 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Substance identity: Javanol
Appereance: Liquid

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral:

A key study was identified (RCC 1997, rel. 1).

The acute oral toxicity of Javanol was assessed in a group of 5 male and 5 female HanIbm Wistar (SPF) rats, in accorance with the GLP principles and following OECD 401 test guidelines (adopted 1987) and Method B1 Acute Toxicity-Oral of the EC Directive No. 92/69/EEC. In the study, rats were administered a single dose via gavage of 2000 mg/kg bw javanol suspended in polyethylene glycol (PEG-400). There were no deaths, no macroscopic findings and no clinical signs of toxicity. Under the conditions of this study, the oral LD50 for Javanol is greather 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.

Dermal:

A key study was identified (RCC, 1999, Rel.1)

The acute dermal toxicity of Javanol was assessed in a group of 5 male and 5 female HanIbm Wistar (SPF) rats in accorance with the GLP principles and following OECD 402 test guidelines (adopted 1987) and Method B3 Acute Toxicity-Dermal of the EC Directive No. 92/69/EEC. In the study, rats were treated with Javanol at 2000 mg/kg body weight by dermal application.

The test article was applied undiluted 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. There were no local signs of toxicity, no deaths, no macroscopic findings, no clinical signs of toxicity and body weights were within normal range for the strain and age. Under the conditions of this study, the dermal LD50 for Javanol is greather than 2000 mg/kg bw.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity (Oral):

Under the test conditions, the oral LD50 of the test substance is > 2000 mg/kg bw in rats. Therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the GHS. No signal word or hazard statement is required. 

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required. The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw≥C > 1000 mg/kg bw). No classification is required. The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute dermal toxicity study.

Specific target organ toxicity: single exposure (Inhalation):

No information was available. Since acute oral and dermal toxicity data are available, this study is not required.

Aspiration hazard:

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met