Myristica fragrans, ext.

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No guideline followed, no GLP, but acceptable basic data.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2009

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The LD50 was calculated using the method described by Lorke (1983). Nutmeg oil at a dose of 10, 100 and 1000 ul/kg was administered intraperitoneal (i.p.) to groups of three mice each. Based on the results of mortality in each group after 24 h., four more mice were administered different doses of nutmeg oil in order to obtain the least and most toxic values and the LD50 was calculated by the geometric mean of these values (Lorke D. 1983. A new approach to practical acute toxicity testing, Arch Toxicol 54: 275-287).

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Myristica fragrans, ext.

EC Number:

282-013-3

EC Name:

Myristica fragrans, ext.

Cas Number:

84082-68-8

Molecular formula:

Unspecified (UVCB)

IUPAC Name:

Nutmeg Oil (Myristica fragrans, ext.)

Details on test material:

- Name of test material (as cited in study report): Nutmeg Oil
- Physical state: liquid
- Composition of test material, percentage of components:
Chemical analysis of the sample of volatile oil of nutmeg (nutmeg oil) that was used for this study indicates the presence of 37 constituents representing 99.3% of the total of nutmeg oil. The percentage of major and most important constituents were terpinen-4-ol (31.3%), γ-terpinene (7.8%), myristicin (7.1%), p-cymene (6.5%), α-terpineol (5.2%), α-pinene (4.9%), β-pinene (4.6%), elemicin (4.8%), α-terpinene (3.5%), limonene (3.2%), methyleugenol (0.8%), eugenol (0.2%), trans-methylisoeugenol (0.1%), and linalool (0.4%).
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

polyethylene glycol

Remarks:

diluted in water at a ratio of 30:70

Doses:

10, 100 and 1000 ul/kg was administered intraperitoneal (i.p.) to groups of three mice each. Based on the results of mortality in each group after 24 h., four more mice were administered different doses of nutmeg oil in order to obtain the least and most toxic values.

No. of animals per sex per dose:

3/dose and 4/dose

Control animals:

not specified

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 2 150 other: uL/kg/24h.

Remarks on result:

other: mouse, i.p.

Any other information on results incl. tables

All the animals lost their righting reflex followed by clonic seizures before death. This clonus was accompanied by periods of running (running-bouncing clonus).

Applicant's summary and conclusion

Conclusions:

The LD50 i.p. of nutmeg oil for mice was 2150 uL/kg/24 h. All the animals lost their righting reflex followed by clonic seizures before death. This clonus was accompanied by periods of running (running-bouncing clonus). Based on these results, the test substance does not need to be classified for acute toxicity according to the EU criteria outlined in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC.

Executive summary:

The acute intraperitoneal (i.p.) toxicity of nutmeg oil to mice was investigated. Chemical analysis of the sample of volatile oil of nutmeg (nutmeg oil) that was used for this study indicates the presence of 37 constituents representing 99.3% of the total of nutmeg oil. The percentage of major and most important constituents were terpinen-4-ol (31.3%),γ-terpinene (7.8%), myristicin (7.1%), p-cymene (6.5%),α-terpineol (5.2%),α-pinene (4.9%),β-pinene (4.6%), elemicin (4.8%),α-terpinene (3.5%), limonene (3.2%), methyleugenol (0.8%), eugenol (0.2%), trans-methylisoeugenol (0.1%), and linalool (0.4%). Briefly, nutmeg oil at a dose of 10, 100 and 1000 ul/kg was administered intraperitoneal (i.p.) to groups of three mice each. Based on the results of mortality in each group after 24 h., four more mice were administered different doses of nutmeg oil in order to obtain the least and most toxic values and the LD50 was calculated by the geometric mean of these values (Lorke D. A new approach to practical acute toxicity testing, Arch Toxicol 54: 275-287). This method requires a few animals to give median values and has been proved valid for its accuracy (van Noordwijk AJ, van Noordwijk J. 1988. An accurate method for estimating an approximate lethal dose with few animals, tested with a Monte Carlo procedure. Arch Toxicol 61: 333-343). The LD50 i.p. of nutmeg oil for mice was 2150 uL/kg/24 h. All the animals lost their righting reflex followed by clonic seizures before death. This clonus was accompanied by periods of running (running-bouncing clonus). Based on these results, the test substance does not need to be classified for acute toxicity according to the EU criteria outlined in Annex I of 1272/2008/EC and Annex VI of 67/548/EEC.