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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September to 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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Javanol
- Physical state: Pale yellow viscous liquid
- Analytical purity: 88.4% (GC, sum of two peaks)
- Lot/batch No.: 008825
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
- Analytical purity: 88.4% (GC, sum of two peaks)
- Lot/batch No.: 008825

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
5 males and 5 females
Identification by unique cage number and corresponding color-coded spots on the tail.
Aclimatization one week under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
Husbandry conditions: Standard Laboratory Conditions Air conditioned with 10-15 air changes per hour continuously monitored environment with a target range for room temperature of 22 +/- 3°C, and for relative humidity between 40-70% (values above 70% during cleaning process possible). The animals were provided with a 12-hour light, 12-hour dark cycle. Music was played during the light period.
Husbandry accomodation: Groups of five in Makrolon type-4 cages with standard softwood bedding
Husbandry diet: Pelleted standard Kliba 3433, batch no. 90/97 rat maintenance diet available ad libitum. Results of analyses for contaminants are archived at RCC.
Husbandry water: Community tap water from Itingen, available ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC.

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 males and 5 females
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:
No clinical signs of toxicity were observed during the study period.
Body weight:
The body weight of the animals was within the range of physiological variability known for rats of this strain and age.
Other findings:
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 single oral administration to rats of both sexes, observed over a period of 14 days, could not be estimated as no death occured.
LD50 : greater than 2000 mg/kg
Executive summary:

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.

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.

No macroscopic findings were observed at necropsy.