National Toxicology Program

6.0 ENVIRONMENTAL OCCURRENCE AND PERSISTENCE

Chlorogenic and caffeic acid are constituents of fruits, leaves, and other tissues of numerous dicotyledenous plant species from the families Caprifoliaceae, Compositae, Cruciferae, Cucurbitaceae, Labiatae, Leguminosae, Polygonaceae, Saxifragaceae, Solanaceae, Theaceae, Umbelliferae, and Valerianaceae (Herrmann, 1956; Litvinenko et al., 1975; both cited by IARC, 1993).

6.1 Medicinal Plants Containing Chlorogenic and Caffeic Acid

Medicinal plants containing chlorogenic acid include B. folium, O. folium, and S. herba (Schneider-Leukel et al., 1992).

Medicinal plants containing chlorogenic and caffeic acid include hawthorn (C. oxyacantha) berries, flowers, and leaves and Angelica roots (A. archangelica) (Budavari, 1996), lemon balm (M. officinalis) (Chlabicz and Galasinski, 1986; cited by IARC, 1993), timothy grass (Phleum pratense) (Mino and Harada, 1974; cited by IARC, 1993), burdock (A. lappa) roots (Leung, 1980; cited by IARC, 1993), and dandelions (T. officinale) (Williams et al., 1996).

Medicinal plants containing caffeic acid include Du Huo (A. pubescens) (Chen et al., 1995), a fern (D. mariesii) (Cui et al., 1990; cited by IARC, 1993), roots of a thorny evergreen shrub (C. spinarum) (Raina et al., 1971; cited by IARC, 1993), I. jamanica (Nair and Pannikkar, 1990; cited by IARC, 1993), Centaurium umbellatum (Hatjimanoli and Debelmas, 1977; cited by IARC, 1993), wormwood (Artemisia sp.) (Kimura et al., 1985a); coltsfoot (T. farfara) (Didry et al., 1980; cited by IARC, 1993), essential oil of Scotch broom (Cytisus scoparius) flowers (Kurihara and Kikuchi, 1980; cited by IARC, 1993), elephant creeper (A. speciosa) seeds (Agarwal and Rastogi, 1974; cited by IARC, 1993), essential oil of fennel (Foeniculum vulgare) (Trenkle, 1971; cited by IARC, 1993), and germander speedwell (Veronica chamaedrys) (Swiatek et al., 1971; cited by IARC, 1993).

6.2 Plants Used to Make Beverages that Contain Chlorogenic and Caffeic Acid

Chlorogenic and caffeic acid constitute about 6% of the chemical composition of green coffee beans (Coffea arabica) (Budavari, 1996). Another source stated that chlorogenic acid constitutes about 9% of the chemical composition of green C. robusta beans and about 7% of green C. arabica beans (Wasserman et al., 1993). The coffee plant is a native of tropical Africa but has been cultivated in many other tropical countries, including Java, West Indies, and Brazil (Budavari, 1996).

Chlorogenic acid is present in tea (Camillia sinensis) (concentration not provided), originally native to Southeast Asia, which is now cultivated in over 30 countries (Graham, 1992). Chlorogenic acid is a constituent of chicory (Cichorium intybus) roots (Clifford et al., 1987) and matÈ (the leaves of Ilex paraguensis), which is grown in some South American countries, including Brazil, Uruguay, Argentina, and Paraguay (Budavari, 1996).

6.3 Fruits, Vegetables, and Spices Containing Chlorogenic and Caffeic Acid

Vegetables that contain chlorogenic acid and/or caffeic acid include broad bush beans; red and sugar beetroots; Chinese, red, savoy, and white cabbages; carrots; cauliflower; celery; kale; kohlrabi; eggplant; lettuce; onions; peas; sweet peppers; potatoes; regular and black radishes; rhubarb; rutabagas; tomatoes; and zucchinis (Schmidtlein and Herrmann, 1975a,b,c; Stàhr and Herrmann, 1975a,b,c,d; all cited by IARC, 1993). Other vegetables containing chlorogenic acid and/or caffeic acid include artichokes (Leung, 1980; Hinou et al., 1989; both cited by IARC, 1993), red peppers (Kusnawidjaja et al., 1969; cited by IARC, 1993), sweet potatoes (Hayase and Kato, 1984; cited by IARC, 1993), soy beans (Pratt and Birac, 1979; cited by IARC, 1993), and spinach (Kusnawidjaja et al., 1969; cited by IARC, 1993).

The presence of chlorogenic acid in many species of the potato (Solanaceae) family has been extensively investigated. Chlorogenic acid constitutes up to 90% of the total phenolic content of potato tubers (Friedman, 1997) and its main function is presumably as a defense against phytopathogens (Deshpande et al., 1984; cited by Friedman, 1997). The average chlorogenic acid concentration per 100 g of potato sprout, leaf, or root material was 754 mg, 224 mg, and 26 mg, respectively (Friedman, 1997). The average chlorogenic acid concentration found in tubers was 17 mg chlorogenic acid/100 g tuber. About 50% of the phenolic compounds in potato tubers were located in the peel and adjoining tissues (Hasegawa et al., 1966; cited by Friedman, 1997). Temperature and organic content of the soil affect the chlorogenic acid content of potatoes (Kaldy and Lynch, 1983; cited by Friedman, 1997). Both chlorogenic and caffeic acid contents of potatoes increase from potato wounding or exposure to pathogens and viral infections (Dinkle, 1964; cited by Friedman, 1997). Chlorogenic acid content in potato tubers is greater when potatoes are stored for prolonged periods at low temperatures than when stored at higher temperatures (Mondy et al., 1966; cited by Friedman, 1997). Potatoes that have turned green due to exposure to light after harvest contain higher levels of chlorogenic acid (Dao and Friedman, 1994; Friedman, 1997). No correlation was found between the chlorogenic acid content of potatoes and the rate of browning during growth and after harvest (Mapson et al., 1963; cited by Friedman, 1997). However, chlorogenic acid may cause bluish-gray discoloration of boiled or steamed potatoes following exposure to air, known as "after-cooking blackening or darkening" (Friedman, 1997).

Fruits containing chlorogenic acid and/or caffeic acid include blueberries; black, red, and white currants; green, yellow, and red gooseberries; grapefruits; lemons; oranges; strawberries; sweet melons; and watermelons (Schmidtlein and Herrmann, 1975a,b,c; Stàhr and Herrmann, 1975a,b,c,d; all cited by IARC, 1993). Others include apples (Iwahashi et al., 1990; cited by IARC, 1993), apricots (Kusnawidjaja et al., 1969; cited by IARC, 1993), coconuts (Kusnawidjaja et al., 1969; cited by IARC, 1993), and grapes (Shahrzad and Bitsch, 1996).

Herbs and spices containing chlorogenic and/or caffeic acid include aniseed, caraway, cloves, coriander, star anise (Dirks and Herrmann, 1984), chives, fennel, garlic, horseradish, and parsley (Schmidtlein and Herrmann, 1975a,b,c; Stàhr and Herrmann, 1975a,b,c,d; all cited by IARC, 1993).

6.4 Other Agricultural Products Containing Chlorogenic and Caffeic Acid

Other agricultural products containing chlorogenic and/or caffeic acid include rolled oats (Kusnawidjaja et al., 1969; cited by IARC, 1993), sunflower seeds and meal (Pomenta and Burns, 1971; Felice et al., 1976; both cited by IARC, 1993), tobacco leaves (Anderson and Vaughn, 1970; cited by IARC, 1993), and castor beans (Freedman et al., 1962).

6.5 Presence of Chlorogenic Acid in Wastes

Chlorogenic acid and caffeic acid may be expected in the wastes generated by industries making coffee and processed potatoes. Anaerobic treatment has been found to reduce the chlorogenic acid content of waste from the instant coffee-making process to 60% of its original level (Azhar and Stuckey, 1994).

7.0 HUMAN EXPOSURE

Human exposure occurs from the ingestion of medicinal or dietary plants containing chlorogenic or caffeic acid, some of which are listed in Section 6 of this report.

Both acids are present in a wide variety of common dietary vegetables, fruits, and spices. While uncooked potatoes contain an average of 17 mg chlorogenic acid/100 g (170 ppm) tuber, oven-baked potatoes, French fried potatoes, mashed potato flakes, and prepared potato skins were found to contain no chlorogenic acid (Lyon and Barker, 1984; Dao and Friedman, 1996; both cited by Friedman, 1997). Boiling and microwaving reduced the amount of chlorogenic acid to 35% and 55% of the original level, respectively. Stewed potatoes contained the same quantity of chlorogenic acid as raw potatoes (Friedman, 1997). Potato flour was found to contain 341 ppm chlorogenic acid (34.1 mg chlorogenic acid/100 g flour) and 59 ppm caffeic acid (5.9 mg caffeic acid/100 g flour) (Sosulski et al., 1982).

Additionally, beverages are prepared from some chlorogenic acid- and/or caffeic acid-containing plants. For coffee, 15 to 325 mg of chlorogenic acids are consumed from one cup prepared using 10 g of ground coffee beans (Viani, 1988; cited by IARC, 1993). In the United States, the average cup of brewed coffee contains 190 mg total chlorogenic acids (Clinton, 1985; cited by IARC, 1993). The per capita consumption of coffee in 1993 was 26 gallons (SRI Int., 1998). Thus, the average person ingests 79.04 g chlorogenic acids/year from drinking coffee. Brewed coffee has a higher chlorogenic acid content than instant coffee (Wasserman et al., 1993). Regular (Graham, 1992), chicory, and dandelion tea (Clifford et al., 1987), fruit juices, and wine are other sources of oral exposure (IARC, 1993). Cherry juice was found to contain 85 mg chlorogenic acid/L and 3.7 mg caffeic acid/L (Shahrzad and Bitsch, 1996). The amount of caffeic acid in black and green grape juice was 1.05 and 0.37 mg/L, respectively. In South America, exposure to chlorogenic and caffeic acid occurs from drinking matÈ (a type of tea).

Caffeic acid has been identified in the smoke condensates used to smoke fish and meat (Ohshima et al., 1989), and may be ingested from eating these products.

Heat processing of dehulled, defatted sunflower flour, which is done to remove or inactivate toxic compounds (e.g., trypsin inhibitors, hemagglutinins), also reduces the content of chlorogenic acid and, to a lesser extent, caffeic acid (Sastry and Subramanian, 1985).

Inhalation exposure to chlorogenic and caffeic acids occurs from tobacco smoking.

8.0 REGULATORY STATUS

A search of CFR titles 7, 21, 29, 40, and 49 was performed, but no regulations pertaining to chlorogenic acid or caffeic acid were found.