E. T. Contis et al. (Editors) Food Flavors: Formation, Analysis and Packaging Influences 1998 Elsevier Science B.V. 401

Some Toxic Culinary Herbs in North America

Arthur O. Tucker and Michael J. Maciarello

Department of Agriculture and Natural Resources, Delaware State University, Dover, DE 19901-2277

A b s t r a c t In recent years, new herbs, particularly from Asia and Latin America,

have appeared upon the North American markets. Some of these herbs have accumulated sufficient toxicological literature to question their safety, and caution is advised on their consumption: hoja santalyerba santa acuyo {Piper auritum Humb., Bonpl., & Kunth), California bay [Umbellularia californica (Hook. & Arnott) Nutt.], perilla/5/1/^0 [Perilla frutescens (L.) Britton], pink/red peppercorns (Schinus terebinthifolia Raddi and S. molle L.), and ^ p a z ^ r ^ / w o r m s e e d / c h e n o p o d i u m {Chenopodium ambrosioides L.). Examination of the essential oils by GC/MS revealed many dominant components which are documented to be toxic to mammalian systems.

1 . INTRODUCTION

In the United States, flavor ingredients are regulated by the Food and Drug Administration (FDA) under the Food Additives Amendment, section 409 of the Food and Drugs Act, passed by the 1958 Congress. The Flavor and Extract Manufacturers' Association (FEMA) provides an expert panel to determine those flavors and levels which are excepted from the coverage of section 409 and whose use in food is "generally recognized as safe" (GRAS); this is summarized in Chapter 21, Parts 182 and 184 of the Code of Federal Regulations (C.F.R.). In 1972 the National Academy of Sciences' Food Protection Committee reviewed GRAS chemicals, and since then the FEMA expert panel has reviewed flavor ingredients with periodic publications in Food Technology, In Europe, a classification of Nature-identical is similar to GRAS, and the European Community (EC) is preparing inventories of flavoring materials. Good introductions to food regulation are Hutt and Merrill [1], Stofberg [2],

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and Burdock [3]; some additional information is provided in Leung and Foster [4].

Fragrance ingredients in the U.S. are regulated by the in-house Research Institute for Fragrance Materials (RIFM) with findings published in Food and Chemical Toxicology, a cross reference list was published in 1992 [5]. On an international scale, the International Fragrance Association (IFRA) has published a Code of Practice with periodic updates from 1974 to the present date in a two-ring binder [6].

While these agencies have provided lists of safe flavors and fragrances, they have, in addition, provided advice and, sometimes, bans against certain products on the market. In recent years, new herbs, particularly from Asia and Latin America, have appeared upon the North American markets and have not been closely examined by these agencies. Some of these herbs have accumulated sufficient toxicological literature to question their safety.

2. MATERIALS AND METHODS

Vouchers of plants were deposited in the Claude E. Phillips Herbarium, Delaware State University (DOV). Oils were distilled with a neo-Clevenger of Moritz after Kaiser and Lang with the modification of Hefendehl [7, 8]. Mass spectra were recorded with a 5970 Hewlett-Packard Mass Selective detector coupled to a HP 5890 GC using a HP 50 m X 0.2 mm fused silica column coated with 0.33 jxm FFAP (crosslinked). The GC was operated under the following conditions: injector temp.: 250°C; oven temp, program: 60°C held for one min, then 2.5°C per min to 115°C, then 1.0°C per min to 210°C and held for 30 min; injection size: l|xL (~50% solution in spectroscopy grade n-pentane) split 1:100. The MSD EI was operated under the following conditions: electron impact source 70 eV, 250°C. Identifications were made by Kovats Indices and library searches of our volatile oil library supplemented with those of NBS, NIST, and Wiley.

3. RESULTS AND DISCUSSION

3. 1. SASSAFRAS AND HOJA SANTA/YERBA SANTA ACUYO

An extract or oil of the root of sassafras. Sassafras albidum (Nutt.) Nees, is hepatocarcinogenic in mice, rats, and dogs from the content of 74-85% safrole. Safrole is viewed as a precarcinogen which is

403

metabolized to the carcinogenic T-sulfooxysafrole via T-hydroxysafrole (in mouse liver). Separate from carcinogenicity, ingestion of 5 ml of sassafras oil by an adult or a few drops by a toddler will cause death or induce vomiting, tachycardia, and tremors. Consumption of 10 cups or more per day of sassafras tea will induce diaphoresis in an adult.

Sassafras root has been banned by the FDA since 1960 and the Council of Europe since 1974; the FDA ruling was comprehensively reviewed in 1976 and upheld.

Sassafras leaves and commercial file powders normally do not contain any safrole but may contain up to trace quantities (average 0.66% of oil). Sassafras leaves are permitted by FDA in foods if safrole-free.

Yet, while toxic to humans, safrole does have a market. Safrole is an important raw material for the synthesis of heliotropin for fragrances and piperonyl butoxide, a synergist for insecticides. The principal source of safrole has been the Brazilian sassafras, Ocotea pretiosa (Nees) Mez, but a moratorium on the cutting down of Brazilian sassafras trees in Brazilia is steering buyers to China in search of Cinnamomum species rich in safrole. Sassafras would have a similar market if available in sufficient quantities. Safrole has also been used as a precursor in underground production of methylenedioxymethamphetamine (MDMA, ecstasy, XTC, Adam) [9-14].

Recently, leaves of ''hoja santa" have been recommended for cooking [15-17], and, under the alternate name of ''yerba santa acuyo," these leaves have appeared in some herbal teas marketed in North America [18]. We have identified the hoja santalyerba santa acuyo sold in the U.S. as Piper auritum Humb., Bonpl., & Kunth (DOV13107), not P. sanctum (Miq.) Schlecht. ex Miq., despite the misleading common names.

Piper auritum is a common on moist forest edges and open sites from Mexico to Colombia and in some of the islands of the West Indies [19]. Alternate names applied to this species include momo (Tabasco), xmacolan (Yucatan, Maya), acoyo (Veracruz), hoja de la estrella (Costa Rica), santa maria, cordoncillo (Nicaragua), anisillo, monca blanca (Costa Rica), hoja de jute, and juniapra (Guatamela). In Veracruz, the leaves are used for seasoning tamales, while in Costa Rica, the fresh leaves are applied to relieve headaches [20]. Leaves of hinojo sabalero (P. auritum) have traditionally been used to feed, and thereby flavor fish in Panama [21]. Leaves of P. auritum contain 70-77% safrole and caphoradione A and B, two aporphine-type alkaloids of unknown physiological activity [22-25]. Our analysis of a commercial yerba santa acuyo sample reveals 68.89% safrole, while fresh leaves of P, auritum have 36.69±2.76% safrole (Table 1). The safrole of hoja santa is as toxic as safrole of sassafras, and no parts of P. auritum are GRAS.

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TABLE 1. THE ESSENTIAL OILS OF A COMMERCIAL DRIED YERBA SANTA ACUYO AND FRESH LEAVES OF PIPER AURITUM (DOV13107) Compound Commercial % Fresh Mean ± SD % (N = 3) & Oil Yield oil yield a-pinene camphene p-pinene sabinene myrcene a-phellandrene a-terpinene limonene p-phellandrene (^)-2-hexenal (Z)-p-ocimene y-terpinene p-cymene terpinolene allo-ocimene 2-nonanone a-copaene camphor linalool P-cubebene bornyl acetate terpinen-4-ol P-caryophyllene a-humulene germacrene D a-muurolene germacrene B bicyclogermacrene 5-cadinene safrole methyl eugenol (Z)-nerolidol (Z)-methyl isoeugenol eugenol

0.22 0.60 0.13 0.51 0.21 0.17 0 1.14 0.10 0.13 0.13 0 4.13 2.25 3.91 0 0 1.15 1.09 0 0.44 0.27 0.87 2.97 0.44 4.84 1.70 0 1.82 0.62

68.89 0 0 0.81 0

0.54±0.17 6.48±0.47 0.31±0.07 7.0610.39 0.3810.66 4.2310.10 0.0310.05 9.7310.20 1.0010.25 0.2910.29 0 1.4810.21

16.1310.44 0.4810.27

11.3510.55 0.4510.02 0.1910.04 0.0910.16 0 3.1410.12 0.3810.31 0 0 0.1010.05 0 0.3010.07 0.0810.02 0.1210.03 0 0.0210.03

36.6912.76 0.0110.02 0.0710.00 0 0.0110.02

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3.2. CALIFORNIA BAY

The leaves of California bay, Umbellularia californica (Hook. & Arnott) Nutt., have been marketed in either jars or wreaths by several companies based in California as a substitute of Greek bay, Lauras nobilis L. The leaves of California bay contain a mean of 36-47% umbellulone with little geographic variation but considerable variation during the season [26-29]; our analysis of a commercial California bay oil shows 5.43% umbellulone (Table 2).

TABLE 2. A COMMERCIAL CALIFORNIA BAY OIL. Compound % a-pinene P-pinene sabinene myrcene 1,8-cineole y-terpinene isopentyl butyrate /j-cymene terpinolene trans-s&hinQne, hydrate CJ5-sabinene hydrate terpinen-4-ol umbellulone methyl chavicol a-terpineol a-terpinyl acetate (£)-a-bisabolene geranyl acetate methyl eugenol elemol (£)-cinnamyl acetate (Z)-isoeugenol thymol chavicol

2.43 1.12

15.31 0.13

28.16 4.17 0.25 1.53 1.47 7.47 0.27 1.42 5.42 0.11

11.42 2.23 0.29 0.51 1.70 0.64 0.33 2.22 1.44 0.40

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Umbellulone is toxic to the central nervous system when ingested and causes convulsive sneezing, headaches, and sinus irritation when inhaled deeply [30]. Contact with the oil or its vapors has resulted in severe headache, skin irritation, and in some cases unconsciousness. Umbellulone can be hemolytic but apparently acts by blocking pulmonary circulation [31]. Leaves of U. californica also contain the alkaloids domesticine, n(9r-domesticine, and isoboldine of unknown toxicity [32]. Hence, no parts of California bay are GRAS.

3.3. PERILLA/S///SO

TABLE 3. THE ESSENTIAL OIL OF FRESH TOPS (TERMINAL 0.5 m) OF PERILLA FRUTESCENS TIA TO'(DOVI3009). Compound & Oil Yield Mean ± SD % (N = 3) oil yield a-pinene P-pinene sabinene myrcene a-terpinene limonene 1,8-cineole terpinolene l-octen-3-ol a-copaene linalool P-caryophyllene a-humulene a-terpineol germacrene D (Z,£)-a-farnesene 5-cadinene perillaldehyde trans-shisool perillyl alcohol

0.12±0.04 1.27±0.29 1.15±0.31 0.33±0.09 0.63±0.19 0.11±0.19

30.63+7.01 0.31±0.11 0.18±0.06 0.71+0.27 0.27±0.04 1.52±0.16 6.0510.06 0.6410.06 0.3110.06 2.8910.22 4.9810.48 0.2010.05

43.5016.54 2.5310.84 0.6510.31

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Perilla or shiso, Perilla frutescens (L.) Britton, has recently captivated chefs [33] but is very variable in morphology and chemistry [34, 35]. Leaves of perilla may contain 0-94% perilla ketone [36-44], which is a potent lung toxin [45, 46]. Perilla and/or perilla ketone may cause acute pulmonary edema in cattle and sheep, atypical interstitial pneumonia or emphysema in cattle, and restrictive lung disease in horses [47-53] Perilla can also cause "intestinal propulsion" in mice [54]. Many forms of perilla are documented to produce contact dermatitis on prolonged handling [55, 56] In the field, perilla is also allelopathic [57]

Recently the Vietnamese cultivar Tia To' has become popular on the fresh herb market in North America. This seed line, which has green upper leaf surfaces and purple under leaf surfaces [58], has no perilla ketone but is dominated by 43.50±6.52% perillaldehyde (Table 3), providing a cumin-like odor. Forms of P. frutescens high in perillaldehyde are popular in Japan as aojiso for suppressing the sardine odor of niboshi soup stock [59]. Perillaldehyde has sedative, antidermatophytic, and allelopathic properties [57, 60-64] and although it was given GRAS status by FEMA in 1978, its full safety still remains to be resolved. No parts of perilla are GRAS [65].

3.4. PINK/RED PEPPERCORNS {BAIES ROSE DE BOURBON)

Pink or red peppercorns are primarily the fruits of Schinus terebinthifolia Raddi, Brazilian pepper tree, but the fruits of S. molle L., the Peruvian or California pepper tree, are also harvested. Both species are in the Anacardiaceae, the poison ivy family, and both species are documented to cause contact dermatitis. Both species are also documented to cause ashthma-like attacks (with as little as one peppercorn, depending upon the individual) when ingested, with accompanying violent headache, swollen eyelids, shortness of breath, chest pains, sore throat, hoarseness, upset stomach, and diarrhea.

While the plant parts of these species of Schinus are toxic, the oils of both species contain no unusual constituents and are not toxic. The fruits of both species contain triterpenoids (not isolated in the essential oil), two of which have been characterized as active site-directed specific competitive inhibitors of phospholidase A2. No whole parts of these two species of Schinus are GRAS, and the FDA issued a warning in 1982; only the oil of S. molle is GRAS [66-74].

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3.5. EPAZOrjS/WORMSEED/CHENOPODIUM

Epazote (alias Mexican tea) has been promoted in a number of English books and articles on Mexican cooking as adding an unusual flavor to foods and preventing flatulence from bean dishes [16, 17, 75-77]; it is also known as paico in Peru [78]. Epazote, which is derived from the Nahutal epazotl, is Chenopodium ambrosioides L., alias Teloxys ambrosioides (L.) W. A. Weber [79-81]; this is the same species known as wormseed and yields wormseed oil (alias chenopodium oil). Wormseed oil is antifungal and anthelmintic (purgative to intestinal worms and amoebae), but the therapeutic dose is close to the minimum toxic level [82-85]. The active ingredient of C. ambrosioides is 6-100% ascaridole [66, 86-92]. The scant literature indicates that epazote is C. ambrosioides var. ambrosioides and relatively low in ascaridole; C. ambrosioides var. anthelminticum (L.) Gray, which is supposedly higher in ascaridole and thus called wormseed, is differentiated by leaves being more strongly toothed than the typical variety, the lower sometimes almost laciniate-pinattifid with mostly leafless spikes [93]. Our analysis by GC/MS of an epazote from Texas reveals 1.98±0.70% ascaridole, while two commercial wormseed/chenopodium oils have 16.20% and 43.10% ascaridole (Table 4). Chenopodium ambrosioides also contains isoascaridole and ascaridole 3,4-epoxide, which have unknown toxicity [94].

Wormseed oil causes skin and mucous-membrane irritation, headache, vertigo, nausea, vomiting, constipation, tinnitus, temporary deafness, diplopia and blindness, transient stimulation followed by depression of the central nervous system leading to delirium and coma, occasional convulsions, circulatory collapse due to vasomotor paralysis and sometimes pulmonary edema. Wormseed oil is also toxic to the kidneys and liver and haematuria, alburinuria and jaundice have been observed. Wormseed oil is irritating to the skin and not recommended for skin applications by IFRA. Only 1 tsp of wormseed oil has been reported to be fatal to a 14-month old baby, while a two-year old child died after being given 16 minims (0.947 cc) of oil over a period of 3 weeks [6, 73]. Leaves of C. ambrosioides have been reported to be carcinogenic in rats [95].

We note that C. ambrosoides is included in almost every book on poisonous plants [96, 97]. No parts of C. ambrosioides are GRAS; in 1974 the Council of Europe included chenopodium oil in the list of natural flavoring substances not permitted [6, 73].

Chenopodium ambrosioides does have two chemical forms which may be nontoxic. These chemovarieties may have either 26-43% trans-pinocarveol or 62-65% pinocarvone, giving them a fragrance reminiscent

409

of typical balm-of-Gilead [Cedronella canariensis (L.) P. Webb & Berthel.] [98, 99]. Future exploration of this species as a culinary herb should investigate these selections.

TABLE 4. THE ESSENTIAL OIL OF 0.5 m FRESH FLOWERING TOPS OF AN EPAZOTE FROM TEXAS (DOVI9551) AND TWO COMMERCIAL WORMSEED/ CHENOPODIUM OILS. Compound & Oil Yield oil yield dimethyl sulfide tricyclene a-pinene a-fenchene camphene p-pinene sabinene 5-3-carene myrcene a-phellandrene a-terpinene limonene P-phellandrene 1,8-cineole y-terpinene ;7-cymene terpinolene trans-limonenQ oxide benzaldehyde fra/J5-dihydrocarvone carvone fran^-carveol CJ5-carveol ascaridole eugenol thymol carvacrol

Epazote Mean± SD % (N = 3)

0.39+0.06 0.01+0.01 0.22+0.18 0.82±0.72 0.02±0.03 0.14±0.06 0.18±0.05 0.01+0.01 0.0310.06 0.01±20.02 0.01±0.02

17.54±2.16 42.3219.31

0.0910.02 0 0.5810.10 8.0910.56 0 0.091010 0 0.0910.15 2.2810.72 1.0610.58 0.2510.43 1.9810.70 0 0.0210.04 0.0410.07

Wormseei Oil

0 0 3.18 0 0 0 0 0 0 0

12.71 11.56 0 6.32 0.09

18.22 0.37 0 0.39 0 0.44 0 0

16.20 0 0.23 0.47

d Chenopdium OU

0 0 0 0 0 0 0 0 0 0

12.24 5.73 0 0 1.16

12.78 0 0 0 0 0.38 0 0

43.10 0.15 0.17 0.34

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4. ACKNOWLEDGMENTS

Analytical research was supported by the State of Delaware and the Cooperative State Research, Education, and Extension Service (#801-15-010). Thanks are also extended to the Professional Development Committee and the Department of Agriculture & Natural Resources, Delaware State University for support of travel.

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