Contact dermatitis was reported in a cake factory worker after external exposure to a 5% concentration of Aetheroleum Anisi (47). Occasional allergic reactions to the oil affecting the skin, respiratory tract and gastro- intestinal tract are reported (15). Inhalation of powdered Fructus Anisi induced an allergic effect in one subject with asthma. Skin-prick tests showed a positive reaction to the fruits and the patient had high specific anti-aniseed immunoglobulin E antibodies in his blood (48). Anethole toxicity in infants has been reported, and presents clinically with symp- toms of hypertonia, continued crying, atypical ocular movements, twitch- ing, cyanosis, vomiting and lack of appetite (7, 49). Ingestion of 1.0–5.0 ml of the oil can result in nausea, vomiting, seizures and pulmonary oedema (50). In cases of overdose (> 50 mg/kg), the ingestion of milk and alcohol is contraindicated owing to increased resorption.
Contraindications
Aetheroleum Anisi is contraindicated in cases of known allergy to aniseed and anethole (48). Owing to the traditional use of the oil as an emmenagogue and to induce labour, its experimental estrogenic and potential mutagenic ef- fects, and reports of anethole toxicity in infants (7, 49), use of the oil in preg- nancy and nursing, and in children under the age of 12 years is contraindi- cated.
Warnings
Applications of Aetheroleum Anisi should be limited to inhalation thera- py (51).
Precautions
Carcinogenesis, mutagenesis, impairment of fertility
Inconsistent results have been reported concerning the mutagenicity of trans-anethole in the Salmonella/microsome assay. One group showed that anethole was mutagenic (52), another that it was very weakly muta- genic in S. typhimurium strains TA1535, TA100 and TA98 (53). In a fur- ther study, trans-anethole (concentrations not specified) did not increase the mutant frequency in the Salmonella/microsome assay, but did increase mutant frequency in the L5178Y mouse-lymphoma TK+/- assay in a dose-dependent manner, with metabolic activation (49). Trans-anethole did not induce chromosome aberrations in vitro in the Chinese hamster ovary cell assay (49). Trans-anethole was weakly hepatocarcinogenic in female rats when administered at a dose of 1% in the diet for 121 weeks;
however, this effect is not mediated by a genotoxic event (54). Trans-an- ethole was investigated for its antifertility activity in rats, after intragastric administration of doses of 50.0 mg/kg bw, 70.0 mg/kg bw and 80.0 mg/kg bw (55). Anti-implantation activity of 100% was observed in animals treated with the highest dose. The compound has been reported to show estrogenic, antiprogestational, androgenic and antiandrogenic activities (55).
Pregnancy: non-teratogenic effects
See Contraindications. Nursing mothers See Contraindications. Paediatric use See Contraindications. Other precautions
No information available on general precautions or on precautions con- cerning drug interactions; drug and laboratory test interactions; and tera- togenic effects in pregnancy.
Dosage forms
Essential oil. Preparations containing 5–10% essential oil for inhalation are also available. Store in a well-filled, tightly sealed container, protected from light and heat (5).
Posology
(Unless otherwise indicated)
Average daily dose for internal use: essential oil 0.3 g; equivalent for other preparations (15).
References
1. Egyptian pharmacopoeia, 3rd ed. Cairo, General Organization for Govern- ment Printing, 1972.
2. Hungarian pharmacopoeia, 7th ed. Budapest, Medicina Könyvhiadó, 1986. 3. Thai pharmacopoeia. Vol. 1. Bangkok, Department of Medical Sciences,
Ministry of Public Health, 1987.
4. Farmakope Indonesia, 4th ed. Jakarta, Departmen Kesehatan, 1995. 5. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1996. 6. African pharmacopoeia. Vol. 1. Lagos, Organization of African Unity, Scien-
WHO monographs on selected medicinal plants
7. Hänsel R et al., eds. Hagers Handbuch der pharmazeutischen Praxis. Bd 6,
Drogen P–Z, 5th ed. [Hager’s handbook of pharmaceutical practice. Vol. 6,
Drugs P–Z, 5th ed.] Berlin, Springer, 1994.
8. de Guzman CC, Siemonsma JS, eds. Plant resources of South-East Asia,
No. 13. Spices. Bogor, PROSEA, 1999.
9. Halmai J, Novak I. Farmakognózia. [Pharmacognosy] Budapest, Medicina Könyvhiadó, 1963.
10. Farnsworth NR, ed. NAPRALERT database. Chicago, IL, University of Illinois at Chicago, 10 January 2001 production (an online database available directly through the University of Illinois at Chicago or through the Scien- tific and Technical Network (STN) of Chemical Abstracts Services).
11. Youngken HW. Textbook of pharmacognosy, 6th ed. Philadelphia, PA, Blakiston, 1950.
12. Quality control methods for medicinal plant materials. Geneva, World Health Organization, 1998.
13. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World Health Organization, 1997 (WHO/FSF/FOS/97.7; available from Food Safety, World Health Organization, 1211 Geneva 27, Switzerland). 14. British herbal pharmacopoeia. Exeter, British Herbal Medicine Association,
1996.
15. Blumenthal M et al., eds. The complete German Commission E monographs. Austin, TX, American Botanical Council, 1998.
16. Shukla HS, Tripathi SC. Antifungal substance in the essential oil of anise (Pimpinella anisum L.). Agricultural and Biological Chemistry, 1987, 51:1991–1993.
17. Gangrade SK et al. In vitro antifungal effect of the essential oils. Indian
Perfumer, 1991, 35:46–48.
18. Müller-Riebau F, Berger B, Yegen O. Chemical composition and fungitoxic properties to phytopathogenic fungi of essential oils of selected aromatic plants growing wild in Turkey. Journal of Agricultural and Food Chemistry, 1995, 43:2262–2266.
19. El-Keltawi NEM, Megalla SE, Ross SA. Antimicrobial activity of some Egyptian aromatic plants. Herba polonica, 1980, 26:245–250.
20. Janssen AM et al. Screening for antimicrobial activity of some essential oils by the agar overlay technique. Pharmazeutisch Weekblad (Scientific Edition), 1986, 8:289–292.
21. Pepeljnjak S et al. Antimycotic activities of Pimpinella anisum L. fruit and essential oil. In: Ethnopharmacology 2000: challenges for the new millenni-
um, Zurich, Switzerland, 4–7 September, 2000. Zurich, 2000:75 (P2A).
22. Pourgholami MH et al. The fruit essential oil of Pimpinella anisum exerts anticonvulsant effects in mice. Journal of Ethnopharmacology, 1999, 66:211– 215.
23. Elisabetsky E et al. Sedative properties of linalool. Fitoterapia, 1995, 66:407– 414.
24. Elisabetsky E, Silva Brum LF, Souza DO. Anticonvulsant properties of linalool in glutamate-related seizure models. Phytomedicine, 1999, 6:107–113. 25. Silva Brum LF, Elisabetsky E, Souza DO. Effects of linalool on [3H] MK801
and [3H] muscimol binding in mouse cortical membranes. Phytotherapy
Research, 2001, 15:422–425.
26. Silva Brum LF et al. Effects of linalool on glutamate release and uptake in mouse cortical synaptosomes. Neurochemical Research, 2001, 26:191–194. 27. Chainy GBN et al. Anethole blocks both early and late cellular responses
transduced by tumor necrosis factor: effect on NF-B, AP-1, JNK, MAPKK and apoptosis. Oncogene, 2000, 19:2943–2950.
28. Reiter M, Brandt W. Relaxant effects on tracheal and ileal smooth muscles of the guinea pig. Arzneimittelforschung, 1985, 35:408–414.
29. Gunn JWC. The carminative action of volatile oils. Journal of Pharmacology
and Experimental Therapeutics, 1920, 16:39–47.
30. Albuquerque AA, Sorenson AL, Leal-Cardoso JH. Effects of essential oil of
Croton zehntneri, and of anethole and estragole on skeletal muscles. Journal of Ethnopharmacology, 1995, 49:41–49.
31. Boskabady MH, Ramazani-Assari M. Relaxant effect of Pimpinella anisum on isolated guinea pig tracheal chains and its possible mechanism(s). Journal
of Ethnopharmacology, 2001, 74:83–88.
32. Sharaf G, Goma N. Phytoestrogens and their antagonism to progesterone and testosterone. Journal of Endocrinology, 1965, 31:289–290.
33. Albert-Puleo M. Fennel and anise as estrogenic agents. Journal of Ethno-
pharmacology, 1980, 2:337–344.
34. Boyd EM, Pearson GL. On the expectorant action of volatile oils. American
Journal of the Medical Sciences, 1946, 211:602–610.
35. Van Dongen K, Leusink H. The action of opium-alkaloids and expectorants on the ciliary movements in the air passages. Archives of International
Pharmacodynamics, 1953, 93:261–276.
36. Boyd EM, Sheppard EP. Effect of steam inhalation of volatile oils on the output and composition of respiratory tract fluid. Journal of Pharmacology
and Experimental Therapeutics, 1968, 163:250–256.
37. Boyd EM. A review of studies on the pharmacology of the expectorants and inhalants. International Journal of Clinical Pharmacology, 1970, 3:55–60. 38. Boyd EM, Sheppard EP. Inhaled anisaldehyde and respiratory tract fluid.
Pharmacology, 1970, 3:345–352.
39. Gershbein LL. Regeneration of rat liver in the presence of essential oils and their components. Food and Cosmetics Toxicology, 1977, 15:173–181.
40. Jenner P et al. Food flavourings and compounds of related structure. I. Acute oral toxicity. Food and Cosmetics Toxicology, 1964, 2:327–343.
41. Newberne P et al. The FEMA GRAS assessment of trans-anethole used as a flavouring substance. Food and Chemical Toxicology, 1999, 37:789–811. 42. Rompelberg CJ, Verhagen H, Van Bladeren PJ. Effects of the naturally oc-
curring alkenylbenzenes eugenol and trans-anethole on drug-metabolizing enzymes in the rat liver. Food and Chemical Toxicology, 1993, 31:637–645.
WHO monographs on selected medicinal plants
43. Truhaut R et al. Chronic toxicity/carcinogenicity study of trans-anethole in rats. Food and Chemical Toxicology, 1989, 27:11–20.
44. Sangster SA, Caldwell J, Hutt AJ et al. The metabolic dispostion of [methoxy14C]-labelled trans-anethole, estragole, and p-propylanisole in hu-
man volunteers. Xenobiotica, 1987, 17:1223–1232.
45. Caldwell J, Sutton JD. Influence of dose size on the disposition of trans-[me- thoxy-14C] anethole in human volunteers. Food and Chemical Toxicology, 1988, 26:87–91.
46. Sangster SA, Caldwell J, Smith RL. Metabolism of anethole. II. Influence of dose size on the route of metabolism of trans-anethole in the rat and mouse.
Food and Chemical Toxicology, 1984, 22:707–713.
47. Garcia-Bravo B et al. Occupational contact dermatitis from anethole in food handlers. Contact Dermatitis, 1997, 37:38–39.
48. Fraj J et al. Occupational asthma induced by aniseed. Allergy, 1996, 51:337– 339.
49. Gorelick NJ. Genotoxicity of trans-anethole in vitro. Mutation Research, 1995, 326:199–209.
50. Chandler RF, Hawkes D. Aniseed – a spice, a flavor, a drug. Canadian Phar-
maceutical Journal, 1984, 117:28–29.
51. Bisset NG. Herbal drugs and phytopharmaceuticals. Boca Raton, FL, CRC Press, 1994.
52. Sekizawa J, Shibamoto T. Genotoxicity of safrole-related chemicals in micro- bial test systems. Mutation Research, 1982, 101:127–140.
53. Swanson AB et al. The mutagenicities of safrole, estragole, eugenol, trans- anethole, and some of their known or possible metabolites for Salmonella
typhimurium mutants. Mutation Research, 1979, 60:143–153.
54. Marshall AD, Caldwell J. Lack of influence of modulators of epoxide me- tabolism on the genotoxicity of trans-anethole in freshly isolated rat hepato- cytes assessed with the unscheduled DNA synthesis assay. Food and Chemi-
cal Toxicology, 1996, 34:337–345.
55. Dhar SK. Anti-fertility activity and hormonal profile of trans-anethole in rats. Indian Journal of Physiology and Pharmacology, 1995, 39:63–67.