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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Some limitations in the reporting of the experimental design and results.
Justification for type of information:
An assessment of acute toxicity is required to fulfil REACH Annex VII information requirements. An acute oral toxicity study identified in the literature search (Klimisch 2) was considered sufficient to fulfil the endpoint.

Data source

Reference
Reference Type:
publication
Title:
Clastogenicity of Beta-Caryophyllene in Mouse
Author:
Molina-Jasso D, Álvarez-González I, Madrigal-Bujaidar E
Year:
2009
Bibliographic source:
Biol. Pharm. Bull. 32(3), 520-522

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: The acute toxicity was determined according to Lorke (1983) A new approach to practical acute toxicity testing. Archives of Toxicology 54 (4): 275-287.
- Short description of test conditions: The compound was dissolved in corn oil and administered orally to mice. In the first step, animals received doses of 10, 100 and 1000 mg/kg. In the second step, doses up to 5000 mg/kg were administered.
- Parameters analysed / observed: Mortality and signs of toxicity
GLP compliance:
not specified
Remarks:
Study was performed in a university research laboratory.
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Caryophyllene
EC Number:
201-746-1
EC Name:
Caryophyllene
Cas Number:
87-44-5
Molecular formula:
C15H24
IUPAC Name:
(1R,4E,9S)-4,11,11-trimethyl-8-methylidenebicyclo[7.2.0]undec-4-ene
Specific details on test material used for the study:
- Source: β-Caryophyllene (97% purity) was obtained from Sigma Chemicals (St Louis, MO, USA)

Test animals

Species:
mouse
Strain:
other: NIH
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6 weeks
- Weight at study initiation: 25 g
- Housing: Polypropylene cages
- Diet: Rodent Laboratory chow 5001, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 23°C
- Photoperiod (hrs dark / hrs light): 12 h dark-light schedule

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: Not reported
Doses:
First step: 10, 100 and 1000 mg/kg
Second step: doses up to 5000 mg/kg
No. of animals per sex per dose:
Not reported
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days in the first step, observation period for second step not reported
Statistics:
None reported for mortality.

Results and discussion

Preliminary study:
No mortality or other signs of toxicity were observed 7 days post-administration at doses of 10, 100 and 1000 mg/kg.
Effect levels
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality was detected at any dose level up to 7-days post administration
Clinical signs:
other: No signs of toxicity were observed at doses up to 5000 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study considered reliable with restriction (Klimisch 2), the LD50 (cut-off) was determined to be ≥ 5,000 mg/kg bw. No mortality or clinical signs of toxicity were observed.
Executive summary:

The acute oral toxicity of beta-caryophyllene was determined in 6 -week old male mice (2009). In the first step, animals received doses of 10, 100 and 1000 mg/kg of the test item dissolved in corn oil. No mortality or signs of toxicity wer observed 7 days post-administration. In the second step, doses up to 5000 mg/kg were administered. No mortality or signs of toxicity were observed up to 5000 mg/kg. This study was considered to be reliable with restriction (Klimisch 2), despite minor limitations in reporting. Since the substance has an acute LD50 in excess of 5000 mg/kg by the oral route of administration, the substance is not classifiable for acute toxicity by this route of exposure.

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