Caryophylli-Aetheroleum-Summary-Report-Committee-Veterinary-Medicinal-Products En.Pdf

The European Agency for the Evaluation of Medicinal Products Veterinary Medicines Evaluation Unit

EMEA/MRL/406/98-FINAL May 1998

COMMITTEE FOR VETERINARY MEDICINAL PRODUCTS

CARYOPHYLLI AETHEROLEUM

SUMMARY REPORT

1. Caryophylli aetheroleum is the volatile oil of the flower buds of Syzygium aromaticum (L.) Merr. & Perry (synonym: cloves), which contain 15 to 18% of the oil. The oil contains: eugenol (80 to 90%), eugenyl acetate (2 to 27%), ß-caryophyllene (5 to 12%), methyl salicylate, methyl eugenol, benzaldehyde, methyl amyl keton and a-ylangene.

2. Caryophylli aetheroleum is contained in two veterinary medicinal combination products containing 9 and 6 other active ingredients, respectively. The concentration of Caryophylli aetheroleum in the first product is 0.008%. It is administered as a nose-spray to newborn of all food producing species as a respiratory stimulant. The dose ranges from 0.1 g to 0.3 g, depending on body weight. The maximum single dose of Caryophylli aetheroleum is 0.024 mg. The treatment may be repeated after 10 to 15 seconds. In the other product, Caryophylli aetheroleum is contained in a concentration of 0.5%. The oinment is used for disinfection of the udder and to prevent transmission of diseases of the udder of cattle, horses, goats, sheep, and pigs. The ointment is used as frequently as is required. Caryophylli aetheroleum is traditionally used orally in human medicine as a carminative, and occasionally for the treatment of flatulent colic, and topically for symptomatic relief of toothache. The doses used are 0.05 to 0.2 ml. Cloves, which contain Caryophylli aetheroleum, are used as a spice and for flavouring of food.

3. Caryophylli aetheroleum has mild antiseptic properties. This activity is attributed to eugenol. The oil has antihistaminic, and antispamodic properties. Eugenol is a powerful inhibitor of platelet. Eugenol, eugenol acetate and methyl acetate are reported to exhibit trypsin-potentiating activity.

4. No information on pharmacokinetics was provided.

5. The oral LD50 for rats is reported to be 2.65 g/kg bw. 6. There is no information on long-term toxicity, effect on reproduction and teratogenicity, mutagenicity, carcinogenicity or immunotoxicity of Caryophylli aetheroleum.

7. Caryophylli aetheroleum is stated to be a dermal and mucous membrane irritant. Contact dermatitis, cheilitis and stomatitis have been reported. Because of these irritant properties it is stated in the summary information provided that concentrated clove oil is not suitable for internal use in large doses. The irritant nature is attributed to eugenol, which is also said to have sensitising properties.

8. The spice clove is listed by the Council of Europe as a natural source of food flavouring (category N2, indicating that clove can be added to foodstuffs in small quantities, with a possible limitation of an active principle). The substance is listed as “Generally Recognised As Safe” in the USA. In the summary information provided it is stated that in humans the accepted ADI of eugenol is 2.5 mg/kg bw but no reference has been provided.

7 Westferry Circus, Canary Wharf, London E14 4HB, UK Switchboard: (+44-171) 418 8400 Fax: (+44-171) 418 8447 E_Mail: [email protected] http://www.eudra.org/emea.html ãEMEA 1998 Reproduction and/or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged 9. The use Caryophylli aetheroleum in the doses recommended is unlikely to result in residues in edible tissues posing a risk to the health of the consumer

Conclusions and recommendation Having considered the criteria laid down by the Committee for the inclusion of substances in Annex II of Council Regulation (EEC) No. 2377/90 and in particular that: · the ADI of the major constituent is very high when compared to the administered doses, · After recommended therapeutic use the amount of residues in edible tissue will not pose any risk for the consumer, · animals are unlikely to be sent for slaughter immediately after treatment; the Committee concludes that there is no need to establish an MRL Caryophylli aetheroleum and recommends its inclusion in Annex II of Council Regulation (EEC) No. 2377/90 according to the following table:

Pharmacologically active Animal species Other provisions substance(s) Caryophylli aetheroleum All food producing species

2/2 ãEMEA 1998