• Clinical data 90%
  • Efficacy 80%
  • Security 70%
  • Toxicity 30%

Foeniculum vulgare
Fructus Foeniculi

Synonyms

Anethum foeniculum Clairv., A. foeniculum L., A. rupestre Salisb., Feniculum commune Bubani, Foeniculum azoricum Mill., F. capillaceum Gilib.,  F. dulce DC., F. foeniculum (L.) H. Karst., F. offi cinale All., F. panmorium DC., F. piperitum DC., F. sativum Bertol, Ligusticum divaricatum Hoffmannsegg et Link, L. foeniculum Crantz, Meum foeniculum (L.) Spreng., Ozodia foeniculacea Wight et Arn., Selinum foeniculum (L.) E.H.L. Krause. Apiaceae are also known as Umbelliferae.

General appearance

Cremocarp, oblong 3.5–10.0 mm long, 1–3 mm wide, externally greyish yellow-green to greyish yellow often with pedicel 2–10 mm long. Mericarps usually free, glabrous, each bearing fi ve prominent slightly crenated ridges.

Major chemical constituents

The major constituent is the essential oil (2–6%), which contains transanethole (50–82%), (+)-fenchone (6–27%), estragole (methylchavicol) (3–20%), limonene (2–13%), p-anisaldehyde (6–27%), α-pinene (1–5%) and α-phellandrene (0.1–19.8%) (9, 12, 14, 21, 22).

Medicinal uses of Foeniculum vulgare

Uses supported by clinical data
None.
Uses described in pharmacopoeias and well established documents
Foeniculum vulgare: symptomatic treatment of dyspepsia, bloating and fl atulence. As an expectorant for mild infl ammation of the upper respiratory tract. Treatment of pain in scrotal hernia, and dysmenorrhoea.
Uses described in traditional medicine
Treatment of blepharitis, bronchitis, constipation, conjunctivitis, diabetes, diarrhoea, dyspnoea, fever, gastritis, headache, pain, poor appetite and respiratory and urinary tract infections. As an aphrodisiac, anthelminthic,
emmenagogue, galactagogue and vermicide.

Pharmacology

Experimental pharmacology

Analgesic and antipyretic activities

Intragastric administration of 500 mg/kg body weight (bw) of a 95% ethanol extract of Fructus Foeniculi to mice reduced the perception of pain as measured in the hot-plate test, and decreased yeast-induced pyrexia. Intragastric administration of 500.0 mg/kg bw of a 95% ethanol extract of the fruits to rats had signifi cant (P < 0.05) analgesic activity in the hot-plate reaction test. In mice with yeast-induced pyrexia, treatment with 500.0 mg/kg bw of the same extract reduced rectal temperature from 36.5 ºC to 34.7 ºC 90 minutes after administration.

Antimicrobial activity

An essential oil from the fruits inhibited the growth of Alternaria species, Aspergillus fl avus, A. nidulans, A. niger, Cladosporium herbarum, Cunninghamella echinulata, Helminthosporium saccharii, Microsporum gypseum, Mucor mucedo, Penicillium digitatum, Rhizopus nigricans, Trichophyton roseum and T. rubrum in vitro. In another study, an essential oil was not active against Aspergillus species in vitro but a methanol extract of the fruits inhibited the growth of Helicobacter pylori (the bacterium associated with gastritis and peptic ulcer disease) in vitro, minimum inhibitory concentration 50.0 μg/ml. An essential oil from the fruits inhibited the growth of Candida albicans, Escherichia coli, Lentinus lepideus, Lenzites trabea, Polyporus versicolor, Pseudomonas aeruginosa and Staphylococcus aureus, and Kloeckera apiculata, Rhodotorula rubra and Torulopsis glabrata in vitro. An ethyl acetate extract of the seeds inhibited the growth of Shigella fl exneri, and an 80% ethanol extract of the seeds inhibited the growth of Bacillus subtilis and Salmonella typhi at concentrations of 250.0 μg/ml in vitro.

Antispasmodic activity

An ethanol extract of the fruits, 2.5–10.0 ml/l, 1 part fruits:3.5 parts 31% ethanol, inhibited acetylcholine- and histamine-induced guinea-pig ileal contractions in vitro. An essential oil from the fruits reduced intestinal spasms in mouse intestine, and was 26% as active as papaverine. Intragastric administration of 2.0 3.0 g/kg bw of an infusion of the fruits to cats inhibited acetylcholine- and histamine-induced ileum spasms by 50%. An essential oil from the fruits, 25.0 μg/ml and 10.0 μg/ml, respectively, inhibited oxytocin- and prostaglandin E2-induced contractions of isolated rat uterus and reduced the frequency of the latter but not the former.

Cardiovascular effects

Intravenous administration of a 50% ethanol extract of the fruits (dose not specifi ed) reduced blood pressure in dogs. An aqueous extract of the fruits, 10% in the diet, reduced blood pressure in rats. The effect was abolished by pretreatment of the animals with atropine. An unspecifi ed extract of the seeds had diuretic effects in rabbits after intragastric administration. The effect was blocked by pretreatment of the animals with morphine.
Intragastric administration of 500.0 mg/kg bw of a 95% ethanol extract of the fruits to rats induced diuresis. The effect was comparable to that observed in animals treated with 960.0 mg/kg bw of urea, and was almost double that in controls.

Estrogenic and antiandrogenic activities

Intragastric administration of 2.5 mg/kg bw of an acetone extract of the seeds daily for 15 days to male rats decreased the protein concentration in the testes and vas deferens, and increased it in the seminal vesicles and prostate gland. The same dose of the same extract administered to female rats daily for 10 days increased the weight of the mammary glands, while higher doses induced vaginal cornifi cation, increased the weight of
the oviduct, endometrium, myometrium, cervix and vagina, and induced estrus. A follow-up study demonstrated that the acetone extract induced cellular growth and proliferation of the endometrium, and stimulated metabolic changes in the myometrium of rats. These changes appearedto favour the survival of spermatocytes and the implantation of the zygote in the uterus. Conversely, intragastric administration of 2.0 g/kg bw of an aqueous extract of the seeds per day for 25 days signifi cantly (P < 0.025) reduced female fertility in mice compared with controls. No effect was observed in male mice. Intragastric administration of 0.5 mg/kg bw or 2.5 mg/kg bw of an acetone extract of the fruits per day for 10 days to ovariectomized female rats had estrogenic effects. Intragastric administration (dose not specifi ed) of an essential oil from the fruits to goats increased the amount of milk produced and the fat content of the milk. Lactating mice fed the fruits in the diet (concentration not specifi ed) produced pups that ate a larger quantity of fennel-containing foods, suggesting that the constituents of the fruits may be passed in breast milk. Intragastric administration of 250.0 mg/kg bw of unspecifi ed extracts of the fruits induced estrus and increased the size of the mammary glands and oviducts in adult ovariectomized rats, and exerted an antiandrogenic effect in adult male mice. It also increased the weight of the cervix and vagina of ovariectomized rats, and increased the concentration of nucleic acids and protein in cervical and vaginal tissues. The hyperplasia and hypertrophy of the cervix and vagina were similar to changes seen during estrus in normal female rats. Subcutaneous administration of anethole (dose not specifi ed) to sexually immature female rats increased uterine weight and induced estrus. However, in ovariectomized mice the same treatment was not estrogenic. Intramuscular injection of 100.0 mg/kg bw or 500.0 mg/kg bw of anethole per day for 7 days to rats induced a signifi cant decrease in dorsolateral prostate weight (P < 0.05). Intragastric administration of 50.0 mg/kg bw, 70.0 mg/kg bw or 80.0 mg/kg bw of trans-anethole to rats had anti-implantation effects, with the maximum effect (100%) at the highest dose. The compound showed estrogenic effects, and did not demonstrate anti-estrogenic, progestational or androgenic effects.

Expectorant and secretolytic effects

Application of an infusion of Fructus Foeniculi, 9.14 mg/ml, to isolated ciliated frog oesophagus epithelium increased the transport velocity of fl uid by 12%, suggesting an expectorant effect. Administration of 1.0–9.0 mg/kg bw anethole and 1.0–27.0 mg/kg bw fenchone by inhalation to urethanized rabbits produced a decrease in the specific gravity of the respiratory fl uid and enhanced the volume output of respiratory tract fluid.

Gastrointestinal effects

Intragastric administration of 24.0 mg/kg bw of the fruits increased spontaneous gastric motility in unanaesthetized rabbits; at a dose of 25.0 mg/kg bw the fruits reversed the reduction of gastric motility induced by pentobarbital.

Sedative effects

Intragastric administration of an essential oil from the fruits (dose not specifi ed) to mice reduced locomotor activity and induced sedation.
A single intraperitoneal administration of 200.0 mg/kg bw of an ether extract of the seeds enhanced barbiturate induced sleeping time in mice. However, intragastric administration of 200.0 mg/kg bw of the extract per day for 7 days decreased barbiturate-induced sleeping time.

Toxicology

Intragastric administration of 3.0 g/kg bw of a 95% ethanol extract of the fruits induced piloerection and reduced locomotor activity in mice. Acute (24-hour) and chronic (90-day) oral toxicity studies with an ethanol extract of the fruits were performed in rodents. Acute doses were 0.5 g/kg, 1.0 g/kg and 3.0 g/kg per day; the chronic dose was 100.0 mg/kg per day. No acute or chronic toxic effects were observed. The acute median lethal dose (LD50) of anethole in rats was 3.8 mg/kg bw after intragastric administration. Intragastric or subcutaneous administration of 10.0–16.0 g/kg bw of a 50% ethanol extract of the fruits to mice had no toxic effects. The oral LD50 of an essential oil from the fruits in mice was 1326.0 mg/kg bw. Chronic use of high doses of trans-anethole in rodent dietary studies has been shown to induce cytotoxicity, cell necrosis and cell proliferation. In rats, hepatotoxicity was observed when dietary intake exceeded 30.0 mg/kg bw per day. In female rats, chronic hepatotoxicity and a low incidence of liver tumours were reported with a dietary intake of trans-anethole of 550.0 mg/kg bw per day, a dose about 100 times higher than the normal human intake. In chronic feeding studies, administration of trans-anethole, 0.25%, 0.5% or 1% in the diet, for 117–121 weeks had no effect on mortality or haematology, but produced a slight increase in hepatic lesions in the treated groups compared with controls. Unscheduled DNA synthesis was not induced in vitro by anethole, but was induced by estragole, an effect that was positively correlated with rodent hepatocarcinogenicity. However, the dose of estragole used (dose not specifi ed) in the rodent studies was much higher than the dose normally administered to humans. Low doses of estragole are primarily metabolized by Odemethylation, whereas higher doses are metabolized primarily by 1′-hydroxylation, and the synthesis of 1′ hydroxyestragole, a carcinogenic metabolite of estragole.

Clinical pharmacology

No information available.

Adverse reactions

In rare cases, allergic reactions such as asthma, contact dermatitis and rhinoconjunctivitis have been reported in sensitive patients.

Contraindications

The fruits are contraindicated in cases of known sensitivity to plants in the Apiacaeae. Owing to the potential estrogenic effects of the essential oil from the seeds and anethole (44, 45, 50), its traditional use as an emmenagogue, and the lack of human studies demonstrating effi cacy, Fructus Foeniculi should not be used in pregnancy. Pure essential oils should not be given to infants and young children owing to the danger of laryngeal spasm, dyspnoea and central nervous system excitation.

Warnings

The pure essential oil from the fruits may cause infl ammation, and has an irritant action on the gastrointestinal tract.

News and Journals

References
1. Asian crude drugs, their preparations and specifi cations. Asian pharmacopoeia.
Manila, Federation of Asian Pharmaceutical Associations, 1978.
2. African pharmacopoeia. Vol. 1. Lagos, Nigeria, Organization of African Unity,
Scientifi c, Technical and Research Commission, 1985.
3. Standard of ASEAN herbal medicine. Vol. 1. Jakarta, ASEAN Countries,
1993.
4. The Japanese pharmacopoeia, 13th ed. (English version). Tokyo, Ministry of
Health and Welfare, Japan, 1996.
5. Pharmacopoeia of the Republic of Korea, 7th ed. Seoul, Taechan yakjon,
1998.
6. The Ayurvedic pharmacopoeia of India. Part I. Vol. I. New Delhi, Ministry
of Health and Family Welfare, Department of Indian System of Medicine
and Homeopathy, 1999.
7. European pharmacopoeia, 3rd ed. Suppl. 2001. Strasbourg, Council of
Europe, 2000.
8. Pharmacopoeia of the People’s Republic of China. Vol. I (English ed.).
Beijing, China, Chemical Industry Press, 2000.
9. Hänsel R et al., eds. Hagers Handbuch der pharmazeutischen Praxis. Bd 5,
Drogen E–O, 5th ed. [Hager’s handbook of pharmaceutical practice. Vol. 5,
Drugs E–O, 5th ed.] Berlin, Springer, 1993.
10. Tanaka T. ed. Nippon Yakuso Zensho. [Encyclopedia of Japanese Medicinal
Plants.] Tokyo, Shin-Nihon Shuppan, 1995 [in Japanese].
11. Bensky D, Gamble A, Kaptchuk T, eds. Chinese herbal medicine, materia
medica, rev. ed. Seattle, WA, Eastland Press, 1993.
12. Bisset NG. Herbal drugs and phytopharmaceuticals. Boca Raton, FL, CRC
Press, 1994.
13. Holmes P. The energetics of western herbs. Vol. 1, rev. 3rd ed. Boulder, CO, Snow Lotus, 1997.
14. Farnsworth NR, ed. NAPRALERT database. Chicago, IL, University of
Illinois at Chicago, 9 February 2001 production (an online database available
directly through the University of Illinois at Chicago or through the Scientifi
c and Technical Network (STN) of Chemical Abstracts Services).
15. Medicinal plants in China. Manila, World Health Organization Regional Offi
ce for the Western Pacifi c, 1989 (WHO Regional Publications, Western Pacifi
c Series, No. 2).
16. Youngken HW. Textbook of pharmacognosy, 6th ed. Philadelphia, PA, Blakiston,
1950.
17. Quality control methods for medicinal plant materials. Geneva, World Health
Organization, 1998.
18. British herbal pharmacopoeia. Exeter, British Herbal Medicine Association,
1996.
19. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1996.
20. 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).
21. Bruneton J. Pharmacognosy, phytochemistry, medicinal plants. Paris, Lavoisier
Publishing, 1995.
22. The Japanese pharmacopoeia 13th edition commentary. Tokyo, Hirokawa
Shoten, 1996 [in Japanese].
23. Forster HB, Niklas H, Lutz S. Antispasmodic effects of some medicinal
plants. Planta Medica, 1980, 40:309–319.
24. Weiss RF. Lehrbuch der Phytotherapie, 7th ed. [Textbook of phytotherapy,
7th ed.] Stuttgart, Hippokrates, 1991.
25. Blumenthal M et al., eds. The complete German Commission E monographs.
Austin, TX, American Botanical Council, 1998.
26. Reynolds JEF, ed. Fennel, fennel oil. In: Martindale – the extra pharmacopoeia,
30th ed. London, The Pharmaceutical Press, 1993.
27. Hare HA, Caspari C, Rusby HH. The national standard dispensatory. Philadelphia,
PA, Lea and Febiger, 1916.
28. Albert-Puleo M. Fennel and anise as estrogenic agents. Journal of Ethnopharmacology,
1980, 2:337–344.
29. Mascolo N et al. Biological screening of Italian medicinal plants for antiinfl
ammatory activity. Phytotherapy Research, 1987 1:28–31.
30. Tanira MOM et al. Pharmacological and toxicological investigations on Foeniculum
vulgare dried fruit extract in experimental animals. Phytotherapy
Research, 1996, 10:33–36.
31. Sharma SK, Singh VP. The antifungal activity of some essential oils. Indian
Drugs and Pharmaceuticals Industry, 1979, 14:3–6.
32. Dikshit A, Husain A. Antifungal action of some essential oils against animal
pathogens. Fitoterapia, 1984, 55:171–176.
33. Mahady GB et al. In vitro susceptibility of Helicobacter pylori to botanicals
used traditionally for the treatment of gastrointestinal disorders. Phytomedicine,
2000, 7(Suppl. II): 95.
34. Janssen AM et al. Screening for antimicrobial activity of some essential oils
by the agar overlay technique. Pharmazeutisch Weekblad (Scientifi c Edition),
1986, 8:289–292.
35. Conner DE, Beuchat LR. Effects of essential oils from plants on growth of
food spoilage yeast. Journal of Food Science, 1984, 49:429–434.
36. Jimenez Misas CA, Rojas Hernandez NM, Lopez Abraham AM. Contribución
a la evaluación biológica de plantas cubanas. III. [The biological assessment
of Cuban plants. III.] Revista Cubana de Medicina Tropicale, 1979,
31:21–27.
37. Izzo AA et al. Biological screening of Italian medicinal plants for antibacterial
activity. Phytotherapy Research, 1995, 9:281–286.
38. Haginiwa J, Harada M, Morishita I. [Pharmacological studies on crude drugs
VII. Properties of essential oil components of aromatics and their pharmacological
effects on mouse intestine.] Yakugaku Zasshi, 1963, 83:624–628 [in
Japanese].
39. Schuster KP. Wirkungstärke und Wirkungsverluste spasmolytische wirksamer
Arzneidrogen, galenischer Zubereitungen und Arzneifertigwaren, geprüft
am isolierten Darm des Meerschweinchens und am Darm der Katze in situ.
[Intensity and loss of the in situ effect of spasmolytically active drugs,
galenic preparations (crude drugs) and galenic drugs in fi nished dosage form,
on isolated gut of guinea-pig and cat.] Dissertation, University of Munich,
1971.
40. Ostad SN et al. The effect of fennel essential oil on uterine contraction as a
model for dysmenorrhea, pharmacology and toxicology study. Journal of
Ethnopharmacology, 2001, 76:299–304.
41. Mokkhasmit M et al. Pharmacological evaluation of Thai medicinal plants.
Journal of the Medical Association of Thailand, 1971, 54:490–504.
42. Haranath PSRK, Akther MH, Sharif SI. Acetylcholine and choline in common
spices. Phytotherapy Research, 1987, 1:91–92.
43. Skovronskii VA. [The effect of caraway, anise, and of sweet fennel on urine
elimination.] Sbornik nauchnikh trudov l'vovskogo veterinarnozootekhnicheskogo
instituta, 1953, 6:275–282 [in Russian].
44. Malini T et al. Effect of Foeniculum vulgare Mill seed extract on the genital
organs of male and female rats. Indian Journal of Physiology and Pharmacology,
1985, 29:21–26.
45. Annusuya S et al. Effect of Foeniculum vulgare seed extracts on cervix and
vagina of ovariectomised rats. Indian Journal of Medical Research, 1988,
87:364–367.
46. Alkofahi A, Al-Hamood MH, Elbetieha AM. Archives of Sexually Transmitted
Diseases and Human Immunodefi ciency Virus Research, 1996, 10:189–
196.
47. Mills S, Bone K. Principles and practice of phytotherapy. Edinburgh, Churchill
Livingstone, 2000.
48. Shukla HS, Upadhyay PD, Tripathi SC. Insect repellent properties of essential
oils of Foeniculum vulgare, Pimpinella anisum and anethole. Pesticides,
1989, 23:33–35.
49. Zondek B, Bergmann E. Phenol methyl esters as oestrogenic agents. Biochemical
Journal, 1938, 32:641–643.
50. Farook T et al. Effect of anethole on accessory sex tissue of albino rats. Journal
of Research in Ayurvedic Science, 1989, 15:167–170.
51. Dhar SK. Anti-fertility activity and hormonal profi le of trans-anethole in
rats. Indian Journal of Physiology and Pharmacology, 1995, 39:63–67.
52. Müller-Limmroth W, Fröhlich HH. Wirkungsnachweis einiger phytotherapeutischer
Expektorantien auf den mukoziliaren Transport. [Effect of various
phytotherapeutic expectorants on mucociliary transport.] Fortschrift für
Medizin, 1980, 98:95–101.
53. Boyd EM, Sheppard EP. An autumn-enhanced mucotropic action of inhaled
terpenes and related volatile agents. Pharmacology, 1971, 6:65–80.
54. Niiho Y, Takayanagi I, Takagi K. Effects of a combined stomachic and its
ingredients on rabbit stomach motility in situ. Japanese Journal of Pharmacology,
1977, 27:177–179.
55. Shipochliev T. [Pharmacological research into a group of essential oils. II.
Effect on the motor activity and general state of white mice in separate applications
or after iproniazid phosphate.] Veterinarno-Meditsinski Nauki.
1968, 5:87–92 [in Bulgarian].
56. Han YB, Shin KH, Woo WS. Effect of spices on hepatic microsomal enzyme
function in mice. Archives of Pharmacal Research, 1984, 7:53–56.
57. Shah AH, Qureshi S, Ageel AM. Toxicity studies in mice of ethanol extracts
of Foeniculum vulgare fruit and Ruta chalepensis aerial parts. Journal of
Ethno-pharmacology, 1991, 34:167–172.
58. Opdyke DLJ. Monographs on fragrance raw materials: fennel oil. Food and
Cosmetics Toxicology, 1974, 12:879–880.
59. Opdyke DLJ. Monographs on fragrance raw materials: fennel oil, bitter.
Food and Cosmetics Toxicology, 1976, 14:309.
60. Mokkhasmit M et al. Study on the toxicity of Thai medicinal plants. Bulletin
of the Department of Medical Science, 1971, 12:36–65.
61. Ostad SN, Khakinegad B, Sabzevari O. The study of teratogenic effect of
fennel essential oil in vitro. Toxicology Letters, 2000, 116:89 [abstract].
62. Newberne P et al. The FEMA GRAS assessment of trans-anethole used as a
fl avouring substance. Food and Chemical Toxicology, 1999, 37:789–811.
63. Truhaut R et al. Chronic toxicity/carcinogenicity study of trans-anethole in
rats. Food and Chemical Toxicology, 1989, 27:11–20.
64. Howes AJ, Chan VS, Caldwell J. Structure-specifi city of the genotoxicity of
some naturally occurring alkenylbenzenes determined by the unscheduled
DNA synthesis assay in rat hepatocytes. Food and Chemical Toxicology,
1990, 28:537–542.
65. Fennel TR et al. Major role of hepatic sulfotransferase activity in the metabolic
activation, DNA adduct formation, and carcinogenicity of 1’-hydroxy-
2’,3’-dehydroestragole in infant male C57BL/J66 × C3H/HeJ F1 mice.
Cancer Research, 1985, 45:5310–5320.
66. Anthony A et al. Metabolism of estragole in rat and mouse and infl uence of
dose size on excretion of the proximate carcinogen 1’-hydroxyestragole.
Food and Chemical Toxicology, 1987, 25:799–806.
67. Jensen-Jarolim E et al. Characterization of allergens in Apiaceae spices: anise,
fennel, coriander and cumin. Clinical and Experimental Allergy, 1997,
27:1299–1306.
68. Schwartz HJ et al. Occupational allergic rhinoconjunctivitis and asthma due
to fennel seed. Annals of Allergy, Asthma and Immunology, 1997, 78:37–40.
69. Wüthrich B, Hoffer T. Nahrungsmittelallergie: das Sellerie-Beifuss-
Gerwürz-Syndrom. Assoziation mit einer Mangofrucht-Allergie? [Food
allergy: the celery-mugwort-spice syndrome. Association with mango
allergy?] Deutsche medizinische Wochenschrift, 1984, 109:981–986.
70. Stäger J, Wuthrich B, Johansson SG. Spice allergy in celery-sensitive patients.
Allergy, 1991, 46:475–478.
71. Morimoto I et al. Mutagenicity screening of crude drugs with Bacillus subtilis
rec-assay and Salmonella/microsome reversion assay. Mutation Research,
1982, 97:81–102.
72. Yamamoto H, Mizutani T, Nomura H. [Studies on the mutagenicity of crude
drug extracts. I.] Yakugaku Zasshi, 1982, 102:596–601 [in Japanese].
73. Mahmoud I et al. Mutagenic and toxic activities of several spices and some
Jordanian medicinal plants. International Journal of Pharmacognosy, 1991,
30:81–85.
74. Marcus C, Lichtenstein EP. Interactions of naturally occurring food plant
components with insecticides and pentobarbital in rats and mice. Journal of
Agricultural and Food Chemistry, 1982, 30:563–568.
75. Sekizawa J, Shibamoto T. Genotoxicity of safrole-related chemicals in microbial
test systems. Mutation Research, 1982, 101:127–140.
76. Ishidate M et al. Primary mutagenicity screening of food additives currently
used in Japan. Food and Chemical Toxicology, 1984, 22:623–636.