Food and Chemical Toxicology 47 (2009) 2234

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Food and Chemical Toxicology

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Review

Safety assessment of coriander (Coriandrum sativum L.) essential oil as a food ingredient
George A. Burdock a,*, Ioana G. Carabin b
a b

Burdock Group, 801 N Orange Ave, Suite 710, Orlando, FL 32801, United States Women in Science, 3785 7th Lane, Vero Beach, FL 32968, United States

a r t i c l e

i n f o

a b s t r a c t
Coriander essential oil is used as a avor ingredient, but it also has a long history as a traditional medicine. It is obtained by steam distillation of the dried fully ripe fruits (seeds) of Coriandrum sativum L. The oil is a colorless or pale yellow liquid with a characteristic odor and mild, sweet, warm and aromatic avor; linalool is the major constituent ($70%). Based on the results of a 28 day oral gavage study in rats, a NOEL for coriander oil is approximately 160 mg/kg/day. In a developmental toxicity study, the maternal NOAEL of coriander oil was 250 mg/kg/day and the developmental NOAEL was 500 mg/kg/day. Coriander oil is not clastogenic, but results of mutagenicity studies for the spice and some extracts are mixed; linalool is non-mutagenic. Coriander oil has broad-spectrum, antimicrobial activity. Coriander oil is irritating to rabbits, but not humans; it is not a sensitizer, although the whole spice may be. Based on the history of consumption of coriander oil without reported adverse effects, lack of its toxicity in limited studies and lack of toxicity of its major constituent, linalool, the use of coriander oil as an added food ingredient is considered safe at present levels of use. 2008 Elsevier Ltd. All rights reserved.

Article history: Received 26 August 2008 Accepted 4 November 2008

Keywords: Coriander Toxicity Spice Essential oil GRAS

Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1. Historical perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1.1. Description, natural occurrence and sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1.2. Specifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1.3. Composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1.4. Contamination of coriander . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1.5. Commercial uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1.6. Regulatory history . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2. Consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.1. Estimation methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.2. Consumption summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Biological data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Absorption, metabolism and excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.1. Biochemical/pharmacological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Toxicological studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.1. Acute toxicity studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.2. Irritation studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.3. Short-term and subchronic toxicity studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 23 23 24 24 25 25 25 25 25 27 27 27 27 28 28 28 28

2.

Abbreviations: CAS, chemical abstracts service; CFR, code of federal regulations; CoE, council of Europe; DINFO, daily intake via natural food occurrence; FCC, food chemicals codex; FEMA, avor and extract manufacturers association; FDA, food and drug administration; GRAS, generally recognized as safe; IOFI, International Organisation of Flavor Industries; JECFA, joint FAO/WHO expert committee on food additives and contaminants; MSDI, maximum survery-derived daily intake; NACGM, National Association of Chewing Gum Manufacturers; NAS, National Academy of Sciences; NOEL, no-observed-effect-level; PADI, possible average daily intake; PMDI, possible maximum daily intake; PPM, parts per million; TAMDI, theoretical added maximal daily intake. * Corresponding author. Tel.: +1 407 802 1400. E-mail address: gburdock@burdockgroup.com (G.A. Burdock). 0278-6915/$ - see front matter 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.fct.2008.11.006

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3. 4.

2.2.4. Developmental and reproductive toxicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.5. Immunotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.6. Genotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.7. Cytotoxicity studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.8. Sensitization studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Observations in humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledegement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . .

28 29 29 29 30 31 31 31 31 31 31

1. Introduction Coriander essential oil (CAS No. 8008-52-4) (hereinafter referred to as coriander oil) is obtained by steam distillation of the dried fully ripe fruits (seeds) of Coriandrum sativum L. of the family Apiaceae (synonymous with Umbelliferae). The oil has a characteristic odor of linalool and a mild, sweet, warm, aromatic avor. In the food industry, coriander oil is used as a avoring agent and adjuvant. Coriander oil is approved for food uses by FDA, FEMA and the Council of Europe (CoE). This review evaluates the safety-in-use of coriander oil as a food ingredient. 1.1. Historical perspective Coriander has a long history of use. It is mentioned in Sanskrit literature as far back as 5000 B.C. and in the Greek Eber Papyrus as early as 1550 B.C. (Uhl, 2000). Coriander was used in traditional Greek medicine by Hippocrates (ca. 460377 B.C.). The seeds of coriander were found in the ancient Egyptian tomb of Ramses the Second. The Egyptians called this herb the spice of happiness, probably because it was considered to be an aphrodisiac. It was used for cooking and for childrens digestive upset and diarrhea. The Greeks and Romans also used coriander to avor wine and as a medicine (Grieve, 1971). Demand by the Romans for coriander was so great, it was imported from as far away as Egypt. Subsequently, it was introduced into Great Britain by the Romans (Livarda and van der Veen, 2008). The use of coriander to accelerate childbirth has been cited in manuscript illustrations (from the early 13th Century) on medieval midwifery (Reus, 1996). Thus, the seeds (dried) have been in use for almost 7000 years (Kiple and Ornelas, 2000). The oil has been used as a food and fragrance ingredient since the 1900s (Opdyke, 1973). Coriander is a native to the Mediterranean and Middle Eastern region. The etymology of coriander starts with the Greek word korannon, a combination of koris and annon (a fragrant anise) and referred to the ripe fruit (Uchibayashi, 2001). The Roman naturalist, Pliny the Elder, rst used the genus name Coriandrum, derived from koris (a stinking bug), in reference to the fetid smell of the leaves and unripe fruit (Blumenthal, 2000; Grieve, 2003). 1.1.1. Description, natural occurrence and sources Coriander oil, essential or volatile, is obtained by steam distillation of the dried, fully ripe fruits (seeds) of C. sativum L. The seeds are comminuted just before distilling the oil. The volatile oil yield ranges between 0.3% and 1.1%. Coriander extract from the fruits of C. sativum is very rich in fat and poor in essential oil (Salzer, 1977). The seeds contain on average 18% oil (fatty acids/triglycerides); however, the essential oil content of seeds is approximately 0.84%. The essential oil (steam distilled) is produced mainly in Eastern Europe, with Russia one of the leading producers (Floreno, 1997). The inclusion of unripe fruits or other parts of the plant

during distillation of the dried seeds imparts an obnoxious odor to the oil. General descriptive characteristics of coriander oil are summarized in Table 1. The oil is a colorless or pale yellow liquid with a characteristic odor and taste of coriander. The oil has a mild, sweet, warm and aromatic avor (Burdock, 2002a). The oral-balsamic undertone and peppery-woody, suave top note of the oil are characteristic features of this fragrance (Arctander, 1960). The aroma detection threshold value of coriander oil is reported as 37 ppm. Taste characteristics of coriander oil at 50 ppm are reported as sweet, fresh, herbal, spicy, terpy and cilantro-like. Nitz et al. (1992) reported no obvious sensory differences in avors of coriander extracts prepared by distillation or by supercritical carbon dioxide extraction. The organoleptic characteristics of the distilled oil tend to deteriorate during prolonged storage especially if left exposed to light and air. However, storage of the oil for one year in the dark, did not affect the organoleptic characteristics of the oil (Misharina, 2001). C. sativum is an annual, herbaceous plant originally from the Mediterranean and Middle Eastern regions. It grows 2560 cm (924 in.) in height. It has thin, spindle-shaped roots, erect stalk, alternate leaves and small, pinkish-white owers. The plant owers from June to July and yields round fruits consisting of two pericarps. The plant is cultivated for its aromatic leaves and seeds. The phylogenetic classication of C. sativum is provided in Table 2. There are two varieties of C. sativum: vulgare Alef. and microcarpum DC. These varieties differ in the fruit size and oil yield: vulgare has fruits of 35 mm diameter and yields 0.10.35% essential oil, while microcarpum fruits are 1.53 mm and yield 0.81.8% essential oil (Small, 1997). For the highest yield of quality essential oil, harvesting should be completed when the fruits have attained ripeness (Tsvetkov, 1970), as evidenced by a rust red color, then dried by placing in drying lofts. The seeds are ground and used as a spice, particularly in Eastern Europe. The essential oil distilled from the seeds is used in condiments and liqueurs. The leaves, referred to in the US as cilantro, are extensively used in Eastern cooking,

Table 1 General description of coriander oil. Botanical source Botanical family Synonyms Coriandrum sativum L. Apiaceae (Umbelliferae) Coriander oil; coriander, oil (Coriandrum sativum L.); coriander fruit oil; oil of coriander; oils, coriander Flavor ingredient 8008-52-4 2334 2334 Store in full, tight containers protected from light. Avoid exposure to excessive heat

Functionality in food CAS No. NAS No. FEMA No. Packaging and storage

CAS = chemical abstracts service; FEMA = avor and extract manufacturers association; NAS = national academy of sciences.

24 Table 2 Classication of the coriander bol=COSA, site accessed 09.08.08). Kingdom Subkingdom Superdivision Division Class Subclass Order Family Genus Species

G.A. Burdock, I.G. Carabin / Food and Chemical Toxicology 47 (2009) 2234

plant

(http://plants.usda.gov/java/prole?sym-

Plantae (plants) Tracheobionta (vascular plants Spermatophyta (seed plants) Magnoliophyta (owering plants) Magnoliopsida (dicotyledons) Rosidae Apiales Apiaceae (the carrot family) Coriandrum L. Coriandrum sativum L.

Indian foods and in certain Mexican dishes. The roots are often used in Thai cooking. The fresh herbs and unripe fruit have a bug-like smell, while ripe fruits exhibit a pleasant tangy odor and taste (PDR, 1998). The seeds are used to prepare an infusion (3%), tincture and uid extract (Burdock, 2002a). Additionally, a brownish-yellow liquid oleoresin (a naturally occurring mixture of a resin and an essential oil) is produced from selected quality seed (Arctander, 1960). Subbulakshmi et al. (1991) reported that c-irradiation and storage for 3 months did not affect the sensory qualities of powdered coriander spice. In another study, c-irradiation of coriander to reduce the microbial content may result in decreased linalool content (Sjovall et al., 1990). 1.1.2. Specications Specications of coriander oil from the (Food Chemicals Codex) FCC (2003) are summarized in Table 3. 1.1.3. Composition The predominant constituent of essential oil of coriander is linalool (Fig. 1), which forms approximately two thirds of the oil (Salzer, 1977; Lawrence, 1980a,b; Budavari et al., 1999; Gil et al., 2002; Grosso et al., 2008). Typical compositional analysis of coriander oil is as follows: alcohols: linalool (6080%), geraniol (1.24.6%), terpinen-4-ol (trace-3%), a-terpineol (<0.5%); hydrocarbons: c-terpin-

Table 3 Coriander oil specications (FCC, 2003). Characteristics Angular rotation Appearance Heavy metals (as Pb) Identication Odor Solubility in alcohol Specic gravity Refractive index FCC = food chemicals codex. Metrics Between +8 and +15 Colorless or pale yellow liquid Passes test Infrared absorption spectrum Characteristic of coriander Passes test. One milliliter dissolves in 3 ml of 70% alcohol Between 0.863 and 0.875 Between 1.462 and 1.472 at 20 C

ene (18%), r-cymene (trace-3.5%), limonene (0.54%), a-pinene (0.28.5%), camphene (trace-1.4%), myrcene (0.22%); Ketones (79%): camphor (0.94.9%); esters: geranyl acetate (0.14.7%), linalyl acetate (02.7%); coumarins/furanocoumarins: umbelliferone, bergapten. Coriander oil was reported to contain approximately 30% terpene hydrocarbons and 70% oxygenated compounds (Karlsen et al., 1971). The BACIS (1999) reports the presence of 122 constituents in coriander seed (BACIS, 1999), although the nal number may be >200. The 18 main components constitute approximately 97% of the total oil. When reconstituted in the concentrations found in the natural sample, the reconstituted oil did not give the odor impression of coriander oil (Smalleld, 2003). Hence, a major sensory effect of the oil apparently comes from the remaining trace constituents that occur, on average, in concentrations of about 0.01% or less. Although, mono and polyunsaturated fatty acids are minor constituents of the oil, they contribute to the characteristic aroma of the oil (Bauer et al., 1997). Ishikawa et al. (2003) reported identication of 33 compounds from the water-soluble portion of the methanol extract of coriander fruit. Two photosensitizing furanocoumarins have been isolated and characterized from the plant, coriander (Ashwood-Smith et al., 1989). Gil et al. (2002) compared the essential oil composition of coriander fruits from plants growing in Argentina and Europe. The variation in the oil composition was related to the relative proportion of the constituents and not to the presence or absence of a particular component. Geographic location, fertilization and weediness (weed competition) also affected the chemical prole. The European samples showed more stable concentration of the major components compared to samples from Argentina. Better conditions for fruit production favored linalool and camphor production in samples from both places. In a study of 15 samples of coriander seeds for volatile contents, the oil distilled from the Polish variety of coriander (C. sativum var. microcarpum) met the requirements of the British Pharmacopoeia (Shellard, 1967). The composition of coriander fruits was shown to change according to the degree of maturity (Msaada et al., 2007). Coriander fruits were gathered from northeastern Tunisia over a two month period, at initial maturity (full green fruits), for middle stage maturity (greenbrown fruits) and, brown fruits representing the nal stage of maturity. During the initial stage, the quantitatively predominant substance was geranyl acetate, but which represented less than 1.0% of the total constituents at the mature stage. Linalool, the second most quantitatively predominant substance (10.96 of 66.29%), became the most predominant substance in the mature fruit, representing 87.54% of a 95.39% of volume identied (Table 4).

Table 4 Essential oil composition of coriander at various stages of maturity (adapted from Msaada et al., 2007). Constituents Percent of total identied for particular stage Initial Geranyl acetate Linalool p-Cymene-8-ol Nerol Neral Carvacrol cis-Dihydrocarvone Anethole Thymol Other substances (32) Total quantity identied 46.72 10.96 1.36 1.53 1.42 1.04 <1.0 <1.0 <1.0 <1.0 66.29 Mid-stage 2.85 76.33 Trace Trace <1.0 <1.0 3.21 1.41 <1.0 <1.0 86.91 Mature <1.0 87.54 Trace Trace <1.0 <1.0 2.36 <1.0 1.85 <1.0 95.39

Fig. 1. Chemical structure of linalool, an important constituent of coriander oil.

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1.1.4. Contamination of coriander Several investigators reported contamination of coriander and its products with mycotoxins, pesticides and other materials. Aziz and Youssef (1991) reported detection of aatoxin B1 (8 lg/kg) and G1 (2 lg/kg) in two samples of coriander. In another study, El-Kady et al. (1995) reported detection of aatoxins B1 and G1 in one sample of coriander seeds. In a screening of nine samples of coriander spice, Saxena and Mehrotra (1989) reported presence of mycotoxins in six samples (5, aatoxin; 1, ochratoxin; 2, zearalenone; and 1, citrinin). In a screening of 126 spice samples for the presence mycotoxin, 20 out of 50 coriander samples showed the presence of 1051 lg/kg ochratoxin A (Thirumala-Devi et al., 2001). Several other reports attempting to investigate the contamination of coriander could not detect presence of aatoxin (Llewellyn et al., 1992; Jaffar et al., 1993; MacDonald and Castle, 1996). In a microbiological survey of four selected spices, including coriander, aerobic bacteria plate count values for coriander ranged from 103 to 105 colony forming units (CFU)/g of spice (Satchell et al., 1989). Kaphalia et al. (1990) reported detection of hexachlorohexane (0.4 ppm) and DDT (0.36 ppm) in four samples of coriander spice. Briggs and McLaughlin (1975) reported a low-temperature, thinlayer chromatography method for the detection of polybutene contamination in volatile oils. Chaigneau and Muraz (1993) reported that the use of ethylene oxide as a disinfectant prior to storage of coriander resulted in detection of 2-chloroethanol (10 ppm) even 6 months after treatment. Dent (1977) reported a rapid method, utilizing a cold isopropanol defatting system, for the extraction of lth from coriander. 1.1.5. Commercial uses 1.1.5.1. Uses as a food ingredient. In avor compositions, coriander oil blends well with cardamom, anise, bergamot, clary, nutmeg, clove and sage. The oil is extensively used as a avoring agent in all types of food products, including alcoholic beverages, tobacco, candy, pickles, meat sauce and seasonings. The average use levels range from 0.1 to 100 ppm. Coriander oil is reported to possess antimicrobial properties against selected pathogenic and saprophytic microorganisms, indicating that it may be useful as a disinfectant (Deans and Ritchie, 1987; Meena and Sethi, 1994; Elgayyar et al., 2001). Coriander is recognized as one of the most important spices in the world and is of great signicance in international trade (Small, 1997). It has been estimated that the annual world production of coriander oil has a value of about 50 million dollars, making it the worlds second most important essential oil after orange oil (Lawrence, 1993). A large amount of coriander seeds are used in certain classic spice blends particularly those of Indian Curry. This spice blend has not been replaced by a liquid essential oil mixture. The seeds are widely used to season curries, puddings, breads, sausages, liqueurs, cakes, gin essences and spicy sauces (Facciola, 1990). Coriander oil may have future use as a free radical scavenger, preventing oxidative deterioration in foods. In a report by Ramadan and Moersel (2006), coriander oil was shown to have greater activity against the radical generating activity of 1,1-diphenyl-2picrylhydrazyl in several oils. The order of effectiveness among various oils in inhibiting free radicals was coriander> blackcumin> cottonseed> peanut> sunower> walnut> hemp seed> linseed> olive> niger seed. 1.1.5.2. Non-food uses. In perfumery, the warm and sweet notes of coriander oil blend well with bergamot and sage colognes, with oral notes in jasmine, lilac, honeysuckle and apple-blossom. In perfumes of an Oriental type, coriander oil produces interesting effects with Ceylon cinnamon and olibanum (olibanum is also known as frankincense, an aromatic resin obtained from trees of

the genus Boswellia, particularly Boswellia sacra (syn. B. carteri, B. thurifera)). Coriander oil is also used in consumer products such as soap, creams, lotions and perfumes (Opdyke, 1973). The reported use levels in these consumer products are summarized in Table 5. The fruits and oil of coriander are used to cover the taste or correct the nauseating or griping qualities of other medicines. Coriander is also used in aromatherapy (Cooksley, 2003). Corianders popularity comes not only from its use for oil, but also from its use for decoration (e.g., for pastries) and as a domestic spice. The oil is mainly used as a avoring agent in pharmaceutical preparations (Leung and Foster, 1996), however, because coriander oil has bactericidal and fungicidal properties, it is used as a stomachic, spasmolytic and carminative. It is also used for sub-acid gastritis, diarrhea and dyspepsia of various origins as well as for its digestive stimulation, stomachic and antibilious properties (Platel and Srinivasan, 2004). In folk medicine, coriander nds use against intestinal parasites and as a component of embrocations for rheumatism and joint pain (Wichtl, 1994). Coriander has been reported to possess strong lipolytic activity (Leung and Foster, 1996), and, as a member of carrot family, its use has been suggested with caution, because of potential allergic reactions from furanocoumarins (Brinker, 1998; NMCD, 2003). 1.1.6. Regulatory history Coriander oil has been approved for use in food by FDA, FEMA and the Council of Europe (Table 6). FDA has approved coriander oil as generally recognized as safe (GRAS) with no limitations cited for the use of coriander oil as a avoring agent and adjuvant. The Flavor and Extract Manufacturers Association has approved coriander oil (FEMA No. 2334) as GRAS for use in foods as a avoring ingredient (Hall and Oser, 1965). The CoE (1970) included coriander oil in its recommendation of substances, spices and seasonings whose use is deemed admissible with a possible limitation of the active principle in the nal products (Opdyke, 1973). The Council of Europe is currently evaluating 600 natural avoring source materials and has published its rst report, which does not include coriander oil. The International Organisation of Flavor Industries (IOFI) has categorized coriander oil as nature identical. Coriander is also reported in the Herbs of Commerce (Foster, 1992). Use of coriander is approved by Commission E for dyspeptic complaints and loss of appetite (Blumenthal, 1998). Coriander oil is included in the chemical inventory of the EPA Toxic Substances Control Act. Coriander oil is included in the FDA report of inactive ingredients for currently marketed drug products for oral solution and elixir (FDA, 1996). The American Herbal Products Association (McGufn et al., 1997) has categorized coriander fruit as Class 1 (herbs that can be safely consumed when used appropriately). The minimum and maximum use levels of coriander oil approved by FEMA (Burdock, 2002a) and the (National Association of Chewing Gum Manufacturers) NACGM (1977) for various food categories are presented in Table 7. 1.2. Consumption 1.2.1. Estimation methods Several methods can be applied to estimate the consumption of a substance in the diet. First, the per capita estimate of intake, also
Table 5 Use levels of coriander oil in fragrance products (Opdyke, 1973). Product Soap Creams, lotion Perfumes Usual level (%) 0.02 0.02 0.04 Maximum level (%) 0.05 0.06 0.6

26 Table 6 Regulatory status of coriander oil. Agency FDA Citation/comments

G.A. Burdock, I.G. Carabin / Food and Chemical Toxicology 47 (2009) 2234

Food category No restrictions

Permitted functionality (12) Flavoring agents and adjuvants

Use limits cGMP

FEMA CoE IOFI

21 CFR 182.2 substances generally recognized as safe essential oil, oleoresin (solvent-free), and natural extractives (including distillates) 2334, GRAS III Natural and articial avoring substances. partial agreement in the social and public health eld

Flavor ingredient Deemed admissible with a possible limitation of the active principle in the nal product Nature Identical

cGMP = current good manufacturing practices; CFR = code of federal regulations; CoE = council of Europe; FDA = US food and drug administration; FEMA = avor and extract manufacturers association; GRAS = generally recognized as safe; IOFI = international organisation of avor industries.

Table 7 Approved food uses of coriander oil by FEMA Burdock (2002a) and NACGM (1977). Food category Use level (ppm) Usual Alcoholic beverage Baked goods Chewing gum Chewing guma Confection frosting Frozen dairy 105.70 53.60 0.09 0.06 8.90 39.15 Max 121.20 62.06 6.62 0.08 13.80 47.35 Gelatin, pudding Hard candy Hard candya Meat products Nonalcoholic beverages Soft candy Food category Use level (ppm) Usual 26.18 7.51 160.25 43.00 2.77 42.14 Max 32.86 7.51 181.11 68.47 8.94 46.91

FEMA = avor and extract manufacturers association. a NACGM = national association of chewing gum manufacturers; ppm = parts per million.

called Maximum Survey-derived Daily Intake (MSDI), is based on disappearance data of the amounts added to food as an ingredient. The second, Daily Intake via Natural Food Occurrence (DINFO), is intake as the result of the presence of a substance as an intrinsic or natural part of food (Burdock, 2002b). In contrast to these methods, which are based on the actual intake of the food ingredient, the Theoretical Added Maximal Daily Intake (TAMDI) values such as FEMA Possible Average Daily Intake (PADI) and Possible Maximum Daily Intake (PMDI) are calculated based on theoretical consumption of food to which the ingredient has been added. DINFO is calculated based on the concentration of substance in food and the consumption of the food(s). A brief description of each of these methods is provided below along with the calculated values. 1.2.1.1. Per capita consumption. Per capita estimate of intake, MSDI, is based on disappearance data from periodic surveys of ingredient manufacturers of the volume of ingredients produced during the survey year. The method is easy to use because it divides the total annual production by the population in the survey year and the number of days per year. The assumption is that there is a nite amount of substance available and the general population ingests it as an added food ingredient regardless of source at the retail level. The primary sources of data for per capita estimates are the surveys conducted by the National Academy of Sciences (NAS) under contract to FDA and published by Clydesdale (1997). The last survey, conducted in 1987, was based on voluntary reporting by manufacturers. Because the NAS has not conducted a survey since 1987, Lucas et al. (1999) conducted the FEMA 1995 Poundage and Technical Effects Update Survey. Lucas et al. (1999) claimed a response rate of 87% of total annual sales volume of FEMA-afliated avor manufacturers and users with regard to the total annual sales volume. Some considerations are necessary in the use of these survey data: (1) because not all producers participate, it is generally held that the amount reported is a fraction of the actual volume and; (2) because not all persons eat all foods each day in each category in which the substance may be added and conversely, some consum-

ers may seek out the substance, therefore, distribution of consumption may be uneven. In order to compensate for these variables, FDA assumes (1) only 60% of the actual value was reported and (2) only 10% of the US population (243.9 million in 1987) consumes 100% of the calculated amount (Clydesdale, 1997). Based on these variables and the annual poundage disappearance reported by the producers to NAS of 34,800 lb for the years 1987 (NAS, 1989), the calculated individual consumption of coriander oil is 2.95 mg/day or 0.0487 mg/kg/day (for an average individual weighing 60 kg). For consumption estimates based on the Lucas et al. (1999) reported disappearance value, the following assumptions are made: (1) 10% of the population consumes the entire avoring, (2) a correction factor of 80% is used and (3) a 1995 US population of 261.1 million. Based on these factors and the Lucas et al. (1999) reported disappearance value of 6090 lb, the calculated individual consumption of coriander oil is 0.362 mg/day or 0.00604 mg/kg/ day. Several reports suggest that coriander is mainly consumed as a avor ingredient and the annual consumption of coriander alone in US during the year 1987 was 901,000 lbs, while the annual consumption of coriander oil during the same year was 34,800 lbs. As coriander contains approximately 1% oil, the oil consumption from coriander will be 901 lbs. Thus the consumption ratio of coriander oil is 0.023, indicating negative food predominance. Based on disappearance data of the coriander of 1501666.67 lb for the years 1987 (Clydesdale, 1997), the calculated individual consumption of coriander oil from the intake of coriander seeds as a spice is estimated to be 0.0127 mg/kg/day. 1.2.1.2. Theoretical added maximum daily intake (TAMDI). The TAMDI is calculated based on upper use levels and the estimated daily intakes of foods. For example, FEMA GRAS is for two levels of use, the average usual and average maximum (Burdock, 2002a). The TAMDI is determined using the average maximum level times the estimated daily intake of the food to which the substance is added. The estimated daily intake would presumably be maximized as well, using the 90th percentile consumption.

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27

The FEMA PADI is similar to the TAMDI concept, using usual use level values and mean consumption estimates of designated food categories (based on Market Research Corporation of America mean frequency of eating and USDA mean portion size of 34 general food categories) (MRCA, 1965). Therefore, the FEMA PADI of 16.6413 mg/day or 0.2774 mg/kg/day is the mean consumption of coriander oil that is based on an approved usual level of use by FEMA. The conservatism of the PADI method assumes that the usual amount of substance is added to the entire food category, not just the substance within that category. For example, the consumption of a substance added only to marshmallow cream cookies (a relatively rarely eaten food) would account for very little consumption, but the FEMA assumption is that the substance is added to all baked goods, not just the small portion of baked goods represented by an exotic cookie. The PMDI can be calculated using the mean consumption of food as above and the maximum levels approved by FEMA (Table 7). The PMDI calculated theoretical value for coriander oil was 21.8813 mg/day or 0.3647 mg/kg/day. 1.2.2. Consumption summary The total lower-intake consumption value for coriander oil was estimated by the FEMA disappearance per capita consumption, and equal to 0.3624 mg/day 0.00604 mg/kg/day. The total higher-intake consumption value for coriander oil was estimated by the NAS disappearance per capita consumption and equal to or 2.9476 mg/day or 0.0487 mg/kg/day (Table 8). As coriander seeds, which contains approximately 1% oil, is commonly consumed as a spice, intake of the oil from consumption of coriander seeds is estimated as 0.0127 mg/kg/day. Thus, the total consumption of coriander oil from its presence in coriander seed (0.0127) and its consumption as an oil (0.0487; NAS determination) is estimated as 0.0714 mg/kg/day. 2. Biological data As coriander oil has been used for a long time without any reported serious toxic effects, very few studies on the toxicity of the oil have appeared in the published literature. Some studies have appeared on coriander seed, powder and extract and, these studies are included in the following section to gain a better perspective on the possible toxicity, if any, of the oil. It is also important to distinguish studies between the essential oil and the fatty acid oil of coriander. Fatty acid oil is different (contains oleic, petroselinic and linolenic fatty acids and not linalool) and therefore should not be confused with essential oil of coriander. Some of the studies in the published literature on the fatty acid oil of coriander mistakenly designate it as coriander oil. The single greatest constituent of coriander oil, linalool ($70% of the oil), has been investigated for its safety. The available data on coriander oil, along with relevant summary information on the biological effects and toxicity of linalool is described below. Other substances are present at fairly low levels, at or below their use in food (Burdock, 2002a) and would therefore not make a substantive contribution to the potential effect(s) of coriander oil.

2.1. Absorption, metabolism and excretion No studies on absorption, metabolism and excretion of coriander oil were found in the published literature, but several investigators have studied the absorption, metabolism and excretion of linalool in both in vivo and in vitro experiments (Hildebrandt, 1901; Parke et al., 1974; Chadha and Madhyastha, 1984; Boutin et al., 1985; Scheline, 1991). These studies suggest that glucuronic acid conjugation and excretion are the primary routes of metabolism of linalool, while repeated administration results in allylic oxidation. The majority of linalool and its metabolites are excreted in the urine and, smaller amounts excreted in expired air and feces. In addition to conjugation with glucuronide, linalool is hydroxylated and sulfated. These studies, therefore, also suggest that the primary constituent of coriander oil, linalool, is rapidly absorbed, metabolized and excreted from the body. 2.1.1. Biochemical/pharmacological effects The effects of coriander oil on pentobarbital-induced sleeping time in mice were investigated by Marcus and Lichtenstein (1982). Groups of six SpragueDawley male white mice (although, no such strain has been reported) were injected intraperitoneally with 50 mg/kg pentobarbital plus 50 mg/kg of coriander oil. Simultaneous administration of coriander oil and pentobarbital to mice did not signicantly increase pentobarbital-induced sleeping time. However, administration of coriander oil 30 min prior to the administration of pentobarbital resulted in a prolongation of pentobarbital-induced sleeping time (146% of control) (Marcus and Lichtenstein, 1982). Coriander has been advocated as an anti-diabetic remedy. Recent experimental studies have suggested antihyperglycemic effects of coriander seeds in streptozotocin-diabetic mice (SwanstonFlatt et al., 1990; Gray and Flatt, 1999). Gray and Flatt (1999) reported that incorporation of coriander into the diet (62.5 g/kg) or in drinking water (2.5 g/L, prepared by 15 min decoction) reduced hyperglycemia of streptozotocin-diabetic mice. Medhin et al. (1986a) demonstrated that aqueous extracts of coriander seeds inhibit the electrically-evoked contractions of spiral strips and tubular segments of isolated central ear artery from rabbit. In another study, Medhin et al. (1986b) reported that the water extract of coriander seed had hypotensive effects in rats. Chithra and Leelamma (1997) investigated changes in lipid metabolism in SpragueDawley female rats (n = 6) fed a high fat diet containing coriander seed powder (10%) for 75 days. The levels of total cholesterol and triglycerides were decreased signicantly in serum, liver and heart. The serum levels of very low and lowdensity lipoprotein cholesterol were decreased, while high-density lipoprotein cholesterol increased. The investigators concluded that coriander seeds had hypolipidemic effects. In another study, Chithra and Leelamma (1999) studied the changes in levels of lipid peroxides and activity of antioxidant enzymes in SpragueDawley female rats (n = 6) maintained on a high fat diet containing 10% coriander seed powder for 90 days. Feeding a diet containing coriander seed powder resulted in a signicant decrease in the levels of lipid peroxides as determined by malondialdehyde, hydroperoxides and conjugated dienes in liver and heart. The levels of free fatty acids in serum, liver and heart of the treated animals were signicantly decreased. Antioxidant-related enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glucose 6-phosphate dehydrogenase and glutathione reductase were signicantly increased in the liver and heart of the treated animals. The results of this study suggest that coriander seed may protect various tissues by preventing the formation of free radicals. In yet another study, Chithra and Leelamma (2000) reported that feeding coriander seed (10%) protected

Table 8 Consumption of coriander oil. FEMA per capita Low-intake value (mg/day) Added ingredient 0.3624 (mg/kg/day) 0.00604 NAS per capita High-intake value (mg/day) 2.9476 (mg/kg/day) 0.0487

FEMA = avor and extract manufacturers association; NAS = national academy of sciences.

28

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against the 1,2-dimethylhydrazine-induced colon and intestine tumors in male SpragueDawley rats. As a major constituent of a spice mix added to a diet (2%), coriander, at a level of 40% in the mix (80 ppm), when fed to female Wistar rats for 8 weeks, favorably enhanced the activities of pancreatic lipase, chymotrypsin and amylase. Additionally, feeding the diet containing the spice mix signicantly stimulated the bile ow and bile acid secretion (Platel et al., 2002). In a series of experiments on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes, Reddy and Lokesh, 1992 reported that linalool, the principle component of coriander oil, at concentrations up to 600 lM had no signicant effects on ascorbate/Fe2+-induced lipid peroxidation of rat liver microsomes. In a series of studies, Weber and colleagues studied the effects of fatty acids (oil) from the seeds of coriander on lipid metabolism (Weber et al., 1995, 1999, 2003; Richter et al., 1996). Feeding of coriander oil containing high proportions (72%) of a positional isomer of oleic acid, i.e. petroselinic (cis-6-octadecenoic) acid to rats (12% in diet) for 10 weeks resulted in a signicant decrease in proportions of arachidonic acid in the cellular lipids of rats. A marked- to severe-fat inltration, as well as fatty cysts in livers of rats fed coriander oil were noted. It should be indicated that in all these studies the coriander oil used was not the essential oil. 2.2. Toxicological studies 2.2.1. Acute toxicity studies The acute oral toxicity (LD50) of coriander oil in rats was reported as 4.13 g/kg (2.486.14 g/kg). The acute dermal toxicity (LD50) of coriander oil in rabbits was reported as >5 g/kg of body weight (Hart, 1971). Details of both of these acute toxicity studies were not available. The acute oral LD50 of the major constituent of coriander oil, linalool, in OsborneMendel rats was reported to be greater than 2.79 g/kg. The authors noted ataxia soon after treatment and, time of death to be 418 h (Jenner et al., 1964). Although, the study was performed before the institution of good laboratory practices, the study meets the FDA Redbook core standards (FDA, 1982). Collectively, these studies indicate that coriander oil and its major constituent, linalool (6080%), are of slight acute toxic potential (Hodge and Sterner, 1949; Derelanko and Hollinger, 1995). As coriander oil contains approximately 70% linalool, the oral LD50 studies suggest that the lethality caused by the oil is from its constituent, linalool. 2.2.2. Irritation studies Application of full strength coriander oil to intact or abraded rabbit skin for 24 h under occlusion was irritating (Hart, 1971). In another report, coriander oil was classied as very mildly irritating to the skin (Tisserand and Balacs, 1995). In a 48 h closed-patch test, coriander oil at a concentration of 6% in petrolatum, produced no irritation in 25 human subjects (Kligman, 1971). Kligman (1970) reported that a 20% solution of linalool (major component of coriander oil) in petrolatum was non-irritating in a 48 h patch test in humans. In another study of linalool, Fuji et al. (1972) reported that in a closed-patch test, linalool did not produce primary irritation in 28 normal human subjects at 20% in Vaseline or ointment, in 30 subjects when applied at 2%, or in 84 subjects with dermatoses, when tested at 0.4% in ethanol or cream base. 2.2.3. Short-term and subchronic toxicity studies In an unpublished study submitted to the Research Institute for Fragrance Materials (RIFM) (proprietary data, published as summary report in peer-reviewed journal), coriander oil was tested in a 28 day study in rats (RIFM, 1990; Letizia et al., 2003).

The oil at a dose level of 160, 400 and 1000 mg/kg/day in 1% methylcellulose was administered by gavage to SpragueDawley rats (10/sex/group). Control animals received vehicle alone. No treatment related effects on survival, clinical observations, body weights or food consumption were noted. In the high-dose (1000 mg/kg/day) males and females and, in the mid-dose (400 mg/kg/day) males, increases in absolute and relative kidney weights were noted. Both absolute and relative liver weights were increased in the mid- and high-dose males and females. Although a signicant increase in absolute liver weight was noted in low-dose (160 mg/kg/day) females, the corresponding relative liver weight was not signicant. Increases in total protein and serum albumin were observed in the mid- and high-dose males and the high-dose females. Serum calcium was also increased in male rats receiving the high-dose of coriander oil. Histological observations revealed a high incidence of degenerative lesions in the renal cortex of the high-dose males, a low incidence of lesions in the non-glandular region of the stomach in the mid- and high-dose females and a high incidence of slight peritoneal hepatocellular cytoplasmic vacuolization in the liver of high-dose females. Similar hepatic lesions with lower incidence were also noted in the low- and mid-dose females. No macroscopic or microscopic changes in reproductive organs were noted. Based on the results of this study, a no-observedeffect-level (NOEL) was determined as 160 mg/kg/day for male rats, while for females the NOEL was less than 160 mg/kg/day (Letizia et al., 2003). The details of the study were not available for independent evaluation. No subchronic studies on coriander oil were found in the published literature. In an unpublished report cited in JECFA (2003) and Oser (1968) evaluated the subchronic toxicity of linalool in male and female rats. The details of the study were not reported, but the no-observed-effect-level (NOEL) of linalool was reported as 50 mg/kg/day (Oser, 1968). 2.2.4. Developmental and reproductive toxicity In an in vivo reproductive and developmental toxicity screening test, virgin Crl CD rats (10/group) were administered (by gavage) 0, 250, 500 or 1000 mg coriander oil/kg body weight daily, 7 days prior to cohabitation, through cohabitation (maximum of 7 days), gestation, delivery and a 4 day post-parturition period. The total duration of the exposure to coriander oil was 39 days. In this study, the maternal indices studied were twice daily observation, measurement of body weights, food consumption, duration of gestation and fertility parameters (mating and fertility index, gestation index, number of offspring per litter). Offspring were observed daily for clinical signs, examination for gross external malformations and measurement of body weight. An increase in body weight and food consumption was noted at 250 mg/kg/day of coriander oil treatment. A non-statistically signicant decrease in body weight and food consumption and decreased gestation index and decreased length of gestation were noted at 500 mg/kg/day. At the highest dose (1000 mg/kg/day) a statistically signicant decrease in body weight and food consumption, decrease in gestation index, length of gestation and litter size were noted. The only effect on offspring was a decrease in viability of pups at 1000 mg/kg/day. The investigators concluded that there were no effects observed in the dams at the low-dose of 250 mg/kg/day or in the offspring at the 250 and 500 mg/kg/day levels. The maternal no-observed-adverse-effect-level (NOAEL) was determined as 250 mg/kg/day and the developmental NOAEL was established as 500 mg/kg/day (RIFM, 1989; Vollmuth et al., 1990; FFHPVC, 2002). Al-Said et al. (1987) studied the effect of the aqueous extract of fresh coriander seeds on fertility in Wistar female rats. The extract was prepared by boiling coriander seeds in water and lyophilizing the ltrate (1 kg seeds yielded about 6 g of the dried extract). Rats were treated orally (not further dened, but presumably via

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gavage) with 0, 250 and 500 mg/kg coriander extract and were monitored for effects on estrus cycle, implantation, fetal loss, abortion, teratogenicity and serum progesterone levels on days 5, 12 and 20 of pregnancy. At both dose levels (250 and 500 mg/kg), coriander extract produced a dose-dependent, signicant anti-implantation effect, but failed to produce complete infertility. No signicant changes in the weight and length of the fetuses and no abnormalities in the organs of the offspring were noted. On day 5 of the extract treatment, a signicant decrease in the serum progesterone level was noted. The investigators suggested that decrease in progesterone may be responsible for the anti-implantation effects of the extract. In another study, Matsui et al. (1967) evaluated the effects of 112 natural products on fertility in mice. The investigators concluded that aqueous extract of coriander did not affect fertility in the female mouse. As both these studies were conducted with an aqueous extract of the coriander, the observed effects may not be relevant to the effects of coriander essential oil. 2.2.5. Immunotoxicity Gaworski et al. (1994) investigated the immunotoxicity of several food avoring ingredients, including coriander oil, in mice. Female CD1 mice (68 weeks of age; n = 30) were administered (gavage) coriander oil at concentrations of 313, 625 or 1250 mg/ kg/day for 5 days. Based on acute toxicity studies, the highest dose was expected to produce minimal toxicity. Immunotoxicity was evaluated using the plaque-forming cell (PFC) and host-resistance assays. Coriander oil did not show any effect on immune function in this study. Similarly, in a screening test in female B6C3F1 mice for humoral and cell-mediated immune responses, no adverse effects of linalool were reported (Gaworski et al., 1994). 2.2.6. Genotoxicity Higashimoto et al. (1993) studied the mutagenicity of coriander extracts (hot water, methanol and hexane) in Salmonella typhimurium strains TA98 and TA100 by the Ames assay. The extracts were not mutagenic in either of the strains, with and without S9 metabolic activation. Similarly, Bersani et al. (1981) and Chughtai et al. (1998) reported that coriander spice was negative in Ames Salmonella microsome test. Contrary to these observations, coriander fruit extract has been reported to be mutagenic in the Ames assay with S. typhimurium strains TA98 and TA100 (Mahmoud et al., 1992). In this study, the extract was prepared from ne powder with 95% ethanol and concentrating the extract under vacuum. The test was performed by adding 10 mg of the extract. In another study on the screening of streptomycin-dependent strains of S. typhimurium TA98 for in vitro detection of spice-induced mutagenicity, the alcoholic extract of coriander spice was mutagenic to the streptomycin-dependent TA98 strain. With a streptomycinindependent TA98 strain, the spice extract was not mutagenic in the absence of S9, but was somewhat (statistical analysis not reported by authors) mutagenic in the presence of S9 (Shashikanth and Hosono, 1987). Heibatullah et al. (2008), examined the genotoxicity in cultured rat embryo broblast cells in the comet assay, of coriander drop (not further dened) and an alcoholic extract of coriander at concentrations of up to 1019 and 1020 mg, respectively. The freshly prepared broblasts were incubated with test substances for 20 min at 37 C according to the laboratorys modied McKelveyMartin procedure. Hydrogen peroxide was used as a positive control. The authors concluded that neither coriander preparation was genotoxic in this assay. Ishidate et al. (1984) investigated the primary mutagenicity screening of food additives, including coriander fruit oil, in the chromosomal aberration test in vitro using a Chinese hamster broblast cell line CHL. The cells were exposed to three different doses of coriander oil (maximum dose, 0.125 mg/ml) for 24 and

48 h and the incidence of polyploid cells, as well as of cells with structural aberrations, such as chromatid or chromosome gaps, breaks, exchanges, ring formations, fragmentations, etc., was measured. Treatment with coriander oil resulted in a 2% formation of polyploid cells; the incidence of cells with structural aberrations was 0%. These results suggest that coriander oil was not clastogenic. In an antimutagenic/anticarcinogenic activity testing of 62 Egyptian food and medicinal preparations, Badria (1994) reported that coriander seed extract did not show antimutagenicity activity against 2-aminoanthracene-induced mutagenesis in S. typhimurium strain TA98 in the presence of metabolic activation (S9). Kanazawa (1995) reported that a 90% methanol extract from 50 mg of coriander suppressed Trp-P-2 [3-amino-1-methyl-5H-pyrido(4,3-b)indole]-induced mutagenicity in an S. typhimurium TA98 strain in the presence of S9. Similarly, in another report, Natake et al. (1989) also reported that coriander herb extract markedly suppressed the mutagenic action of Trp-P-2 in the Ames assay. Several investigators have studied the genotoxicity of linalool in different assays (Rockwell and Raw, 1979; Florin et al., 1980; Ishidate et al., 1984; Heck et al., 1989). Linalool was negative in S. typhimurium strains TA92, TA94, TA98, TA100, TA1535, TA1537 and TA1538 in the presence or absence of S9 metabolic activation. Similarly, in the Chinese hamster broblast cell assay, at a maximum concentration of 0.25 mg/ml, linalool did not induce chromosomal aberrations (Ishidate et al., 1984). When tested in rat hepatocytes at concentrations up to 50 nl/ml, linalool did not induce unscheduled DNA synthesis (UDS) (Heck et al., 1989). Incubation of linalool (1251000 mg/plate) with Escherichia coli WP2 uvrA did not induce mutations (Yoo, 1986). Similarly, incubation of linalool at a concentration 17 pg with Bacillus subtilis H17 (ret+) and M45 (ret) was negative (Oda et al., 1979). However, in another study, linalool was found to be mutagenic at 10 ll/disk (Yoo, 1986). The positive responses are contradicted by the results of the same assay by other investigators (Oda et al., 1979). In a mouse lymphoma assay in L5 178Y TK cells with S9 metabolic activation, linalool (at a concentration of 200 nl/ml) was negative, but was weakly positive (details of statistical signicance not available; report in abstract form) without S9 activation at 150 nl/ml (Heck et al., 1989). In an in vivo study employing the standard mouse micronucleus assay, there was no evidence of an increased incidence of micronucleated polychromatic erythrocytes at any of the dose levels of linalool studied (Putman, 1987). In summary, results of a chromosomal aberration test using Chinese hamster broblasts demonstrate that coriander oil was not clastogenic. No genotoxicity studies with coriander oil were found in the published literature, however, studies on the mutagenicity of coriander spice or extracts ranged from equivocal to positive in the S. typhimurium Ames assay. Linalool, the major constituent of coriander oil, was found to be non-mutagenic in several different genotoxicity assays. 2.2.7. Cytotoxicity studies Coriander oil has been reported to inhibit a broad-spectrum of microorganisms (Dwivedi and Dwivedi, 1972; Deans and Ritchie, 1987; Baratta et al., 1998; Cantore et al., 2004). Basilico and Basilico (1999) investigated the inhibitory effects of coriander essential oil on the mycelial growth and ochratoxin A production by Aspergillus ochraceus NRRL 3174. Treatment of the fungus with coriander oil at concentrations of 0, 500, 750 and 1000 ppm for 7, 14 or 21 days at 25 C was not effective in inhibiting the growth or production of ochratoxin A. In another study, coriander oil, at a concentration of 0.2% and greater, completely inhibited the growth of Aspergillus parasiticus NRRL 2999 (Tantaoui-Elaraki and Beraoud, 1994). In, contrast, the essential oil of coriander was found not to

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inhibit the growth of A. parasiticus CFR 223 or aatoxin production on palm kernel broth inoculated at 106 spores/ml, in contrast to the essential oil of sweet basil (Ocimum basilicum) (Atanda et al., 2007). The coriander essential oil was tested for its antibacterial activity against eight human pathogenic gram-positive and gram-negative bacteria by the lter paper disc agar method. Except for the Corynebacterium diphtheriae, coriander oil was effective against Staphylococcus aureus, Streptococcus haemolyticus, B. subtilis (gram-positive), Pseudomonas aeruginosa, E. coli, Klebsiella species and Proteus vulgaris (gram-negative) (Singh et al., 2002). Lis-Balchin et al. (1998) compared the antimicrobial activity of coriander oil with Pelargonium spp. essential oils at concentrations of 500 ppm against Saccharomyces ludwigii, Zygosaccharomyces bailii, Salmonella enteriditis and Listeria innocua. Coriander oil, at concentrations of 500 ppm, was effective against all four bacterial species. Delaquis et al. (2002) determined the minimum inhibitory concentration (MIC) of coriander oil against gram-positive bacteria, gram-negative bacteria and Saccharomyces cerevisiae. The MIC for coriander oil were as follows: E. coli O157:H7, 0.23%; Listeria monocytogenes, 0.47%; S. aureus, 0.4% and; S. cerevisiae 0.13%. These results demonstrate that coriander oil was effective at concentrations less than 0.5% (vol/vol). 2.2.8. Sensitization studies In an attempt to induce sensitization in a maximization test, coriander oil was tested on 25 volunteers at a concentration of 4% in petrolatum. The oil did not produce a sensitization reaction in any of the subjects tested (Kligman, 1966, 1971). Several studies have shown that commonly used spices produce allergic symptoms in a small percentage of individuals with atopic dermatitis. In these individuals, symptoms may vary from itching and stinging of the lips and mouth, to anaphylatic shock. Skin testing has been recommended to identify individuals who may be allergic to spices. In a study of 50 patients with known allergies to spices with 2+ or stronger skin prick test reactions, 42 were skin prick tested with an extract of coriander spice (5%). The reactions were graded from 1+ to 4+ according to the recommendations of the Northern Society of Allergology. Of the 42 tested, 29 showed reaction to coriander. The distributions of graded reactions were as follows: seven showed 4+; 13 showed 3+; eight showed 2+ and one showed 1+ reaction (Ono et al., 1998). In another study by the same group of investigators, from a group of 46 patients with positive prick test reaction to spices, 20 were (containing protein; molecular weight >1 kD), 3, 5 and 12 showed positive reactions, tested with 1%, 5% and 10% coriander extract. Of the 20 tested at 1%, 5% and 10% coriander spice extract, respectively (Niinimaki et al., 1995). In a study of 71 patients with a skin test positive to curry, 59% showed positive reaction to coriander in a scratch method test (Niinimaki and Hannuksela, 1981). In a scratch test with powdered coriander spice in 70 patients with positive skin test to birch and/or mugwort pollens and celery, 26 showed positive reactions to coriander (Stager et al., 1991). Bock (1993) reported a case of a 14-year-old girl with a severe allergic reaction (anaphylaxis) after consuming a food containing coriander. A skin prick test with coriander produced a positive reaction. A double-blind, placebo-controlled, food challenge test was performed with coriander in this subject. The challenge elicited mild symptoms, but a reaction sufcient to suggest that coriander was responsible for the symptoms seen in this patient. In another report, Moneret-Vautrin et al. (2002) presented a case of a 26-year-old woman with multiple systemic reactions (urticaria and laryngeal angioedema) after consumption of food containing different spices. Skin prick tests conrmed polysensitization to pollens from artemisia, sunower, grass and paritory (Anacyclus pyrethrum). Tests with food allergens were highly positive to

Compositae (sunower our) and Apiaceae (coriander). The double-blind, placebo-controlled, oral challenge to coriander was positive at 265 mg, resulting in sneezing and rhinorrhea. At 1.5 h after the challenge, the quantitative score for nasal dysfunction increased from 0/15 to 10/15. The results of the study suggest that the patient was allergic to sunower our and coriander spice with associated sensitization to pollens from mugwort, birch, Gramineaceae and Parientaria. These investigators also reported results of skin prick tests in 15 children (<15 years) and 50 adults with food allergies. Of the 15 children tested, four developed positive prick tests to coriander, while 9 of the 50 adults showed a positive reaction (Moneret-Vautrin et al., 2002). Garcia-Gonzalez et al. (2002) reported a case of a 43-year-old woman (baker, confectioner) with work related rhinoconjunctivitis. On skin prick testing, the woman showed an immediate positive response with coriander protein extract. Enzyme immunoassay inhibition studies with the patients serum revealed cross-reactivity among the IgE components from coriander, aniseed, caraway, fennel and dill extract. Suhonen et al. (1979) reported a case of a 51-year-old woman, who after 3 years of occupational exposure to coriander (spice) developed respiratory symptoms of immediate hypersensitivity. Skin prick tests, nasal and bronchial challenge tests and the RAST assay were positive to coriander. Additional studies on the spice were performed by subjecting the spice to column chromatography, enzymatic digestion of the fractions and skin testing. These studies suggested that the allergen was a protein. A 27-year-old male butcher with symptoms of rhinitis and asthma, showed a positive reaction when tested with coriander extract by skin prick test; ELISA results conrmed the presence of IgE-mediated hypersensitivity (Sastre et al., 1994, 1996). In a study on the characterization of allergens in Apiaceae spices, including coriander, Jensen-Jarolim et al. (1997) tested sera of 15 patients who experienced adverse reactions to spiced foods and characterized their IgE binding patterns on coriander extracts through immunoblot and inhibition experiments. Of the 15 patients tested, ve showed a positive IgE immunoblot to coriander protein extract. The investigators concluded that Bet v 1 (main allergen of birch pollen, a 17 kDa glycoprotein) and proling-related allergens may, besides higher molecular weight allergenic molecules, be responsible for Type I allergy to coriander, a member of the Apiaceae family. Kanny et al. (1995) reported a 38-year-old woman pharmacist with severe anaphylactic reaction to mustard masked in chicken dips. Although coriander was not reported to be present in the chicken dip, on skin prick test, the woman developed a positive reaction with mustard, curry and coriander. In a spice allergy evaluation study, 55 patients with localized and generalized suspected contact dermatitis were patch tested with several spice preparations, including coriander, at concentrations of 10% and 25% in white petrolatum. Using the Finn chamber, the spice preparations were applied to the upper back. The sample was applied for 48 h and the application site was scored at 48 and 96 h. No patient showed any reaction at a concentration of 10%, however two patients showed positive reaction at 25% spice preparation (Futrell and Rietschel, 1993). In summary, the above-described studies show that spices, including coriander, produce allergic symptoms in a small percentage of individuals. The symptoms of allergy to coriander may vary from itching and stinging of the lips and mouth to anaphylactic shock. Some investigators have reported positive skin prick tests and specic IgE production to coriander. In a few individuals, following consumption of coriander, severe allergic reactions have been reported. The majority of these reports are from the use of coriander as a spice and not as an essential oil. In one study, the allergen has been shown to be heat-resistant and probably a protein with a specic IgE in the serum. The essential oil is unlikely

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to contain the protein component that has been suggested to be responsible for the allergic reaction. Considering the high consumption of coriander, the reported incidence of anaphylaxis is very low. 2.3. Observations in humans In a case-control study in Tunisia of nasopharyngeal carcinoma (n = 80), Jeannel et al. (1990) reported that after adjustment for empirical living condition score, the spices included in the basic stewing preparation (mixture of red and black pepper, garlic oil, caraway, and coriander) in home-cooked foods was one of the food factors associated with an increased incidence of nasopharyngeal cancer. As other factors were also associated with the nasopharyngeal carcinoma and coriander was a constituent of one of the preparations, it is unlikely that coriander was associated with nasopharyngeal carcinoma. Other studies of coriander, including genotoxicity studies, suggest that coriander oil may not be carcinogenic. 3. Discussion Coriander oil is used in the food industry as a avor ingredient. It is obtained by steam distillation of the dried fully ripe fruits (seeds) of C. sativum L. The oil is a colorless or pale yellow liquid with a characteristic odor and mild, sweet, warm and aromatic avor. Coriander oil has been recognized as GRAS for use in food by FDA and FEMA and is approved for use by the Council of Europe. The oil is used as a avor ingredient in the majority of the food categories, including alcoholic beverages, candy, pickles, meat sauce and seasonings. The average use levels range from 0.1 to 100 ppm. The oil is also used in consumer products such as soap, creams, lotion and perfumes. The major constituent of the volatile oil is the monoterpene alcohol, linalool ($70%). Coriander has a long history of use as a traditional medicine and avoring agent; however, few studies evaluating its toxic effects were found in the scientic literature. The main constituent of coriander oil, linalool, has been studied to some extent for its safety. No studies on the biological fate of coriander oil per se in the human body have appeared, but in animal studies one of the major constituents of the oil, linalool, is rapidly absorbed, metabolized and excreted from the body. Coriander oil and its major constituent, linalool, have low acute oral and dermal toxicity in laboratory animals. The acute lethality studies suggest that the toxicity of the oil is from its constituent, linalool. Based on the results of a 28 day oral gavage study in rats, a NOEL for coriander oil was determined as 160 mg/kg/day for male rats, while in females the NOEL for coriander oil was less than 160 mg/kg/day. The details of the study were not available for independent review as the original data are proprietary. In animal skin testing, coriander oil was irritating to rabbits. However, in human skin testing, both coriander oil and its major constituent, linalool, produced no irritation. In a sensitization study in humans, coriander oil did not produce sensitization reaction. Published studies in the literature have shown that spices, including coriander, produce allergic symptoms in a small percentage of individuals. In these individuals, symptoms may vary from itching and stinging of the lips and mouth, to anaphylactic shock. Skin testing has been recommended to identify individuals who may be allergic to spices. Some investigators have reported positive skin prick tests and specic IgE to coriander. Severe allergic reactions have been reported in few individuals following consumption of coriander. The allergen in coriander has been shown to be heat-resistant and probably a protein with a specic IgE antibody in the serum. The essential oil is unlikely to contain the protein component, which is suggested to be responsible for the

allergic reaction. Considering the high consumption of coriander, the reported incidence of anaphylaxis is rare. No subchronic studies on coriander oil were found in the published literature, but its major constituent, linalool, was evaluated in a subchronic toxicity in male and female rats. The details of the study were not available, however, the NOEL of linalool was reported as 50 mg/kg/day. In a developmental toxicity study, the maternal NOAEL of coriander oil was determined as 250 mg/kg/ day and the developmental NOAEL was established as 500 mg/ kg/day. In a chromosomal aberration test using Chinese hamster broblasts, coriander oil was found to be non-clastogenic. Some studies have appeared on the mutagenicity of coriander spice or extracts. These studies reported equivocal to positive results in the S. typhimurium Ames assay. The major constituent of coriander oil, linalool, has been studied for mutagenicity in several different assays and was found to be non-mutagenic. Coriander oil has been reported to possess broad-spectrum, antimicrobial activity. 4. Conclusion The data available on the toxicity of coriander oil are limited. However, coriander and its oil have a long history of dietary use, with no record of harm caused by consumption of these ingredients. Moreover, coriander oil has been in commercial use in the fragrance industry for at least 100 years, without any record of having caused adverse effects. In summary, based on the history of consumption of coriander oil without reported adverse effects, lack of its toxicity in limited studies and lack of toxicity of its major constituent, linalool, the use of coriander oil as an added food ingredient is considered safe at present levels of use. Conict of interest statement The authors declare that there are no conicts of interest. Acknowledgement The descriptions, compilations, analysis and reviews of research contained in this article were funded by Philip Morris USA Inc. References
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