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IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins. Lyon (FR): International Agency for Research on Cancer; 1993. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 56.)

Cover of Some Naturally Occurring Substances

Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins.

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CAFFEIC ACID

1. Exposure Data

1.1. Chemical and physical data

1.1.1. Synonyms, structural and molecular data

  • Chem. Abstr. Serv. Reg. No.: 331-39-5
  • Chem. Abstr. Name: 3-(3,4-Dihydroxyphenyl)-2-propenoic acid
  • Synonyms: Caffeic acid; 5(4)-(2-carboxyethenyl)-l,2-dihydroxybenzene; 4-(2′-carboxy-vinyl)-l,2-dihydroxybenzene; 3,4-dihydroxybenzeneacrylic acid; 3,4-dihydroxycinnamic acid; 3-(3,4-dihydroxyphenyl)propenoic acid; 3-(3,4-dihydroxyphenyl)-2-propenoic acid
Image 006a-3_001

1.1.2. Chemical and physical properties

  • (a) Description: Yellow prisms or plates from water (Lide, 1991)
  • (b) Melting-point: Decomposes at 225 °C (Lide, 1991)
  • (c) Solubility: Sparingly soluble in cold water; very soluble in hot water and cold ethanol (Budavari, 1989)
  • (d) Stability: Caffeic acid exists in cis and trans forms, trans being the predominant naturally occurring form (Janssen Chimica, 1991). Solutions of caffeic acid and its derivatives (e.g., chlorogenic and isochlorogenic acids) are unstable in sunlight and ultraviolet light. The trans form of caffeic acid is partially converted to the cis form, which in turn is partially converted to the lactone, aesculetin (Grodzinska-Zachwieja et al., 1973; Hartley & Jones, 1975; Borges & Pinto, 1989).
  • (e) Reactivity: Caffeic acid inhibited the formation of N-nitrosodimethylamine in vitro from simulated gastric juice and nitrite and in vivo in rats given aminopyrine and nitrite (Kuenzig et al., 1984). With lower concentrations of caffeic acid than of reactants, caffeic acid can, however, catalyse nitrosamine formation (Dikun et al., 1991).

1.1.3. Trade names, technical products and impurities

Caffeic acid is not known to be a significant commercial product. It is available as the trans isomer in research quantities at purities ranging from 97% to > 99%; the cis isomer of caffeic acid is not available commercially (Fluka Chemie AG, 1990; Riedel-de Haen, 1990; Janssen Chimica, 1991; Lancaster Synthesis, 1991; TCI America, 1991; Aldrich Chemical Co., 1992).

1.1.4. Analysis

Since ultraviolet light partially converts the trans isomers of several cinnamic acids, including caffeic acid, to their respective cis forms (Kahnt, 1967), it is important in any study of cinnamic acid derivatives in plant materials to have an accurate, rapid method for the determination of both the cis and trans isomers. Hartley and Jones (1975) separated cis from trans isomers of caffeic acid as their trimethylsilyl derivatives by gas chromatography with flame ionization detection. Conkerton and Chapital (1983) reported the separation of cis from trans isomers of caffeic acid by reverse-phase high-performance liquid chromatography (HPLC), using ultraviolet and electrochemical detection in series. Borges and Pinto (1989) reported the separation of cis- from trans-cafteic acids and aesculetin by isocratic HPLC with ultraviolet detection at 350 nm. Hydroxycinnamic acids, including caffeic acid, were separated from maize tissue samples on a reverse-phase HPLC column with ultraviolet detection at 254 nm (Hagermari & Nicholson, 1982).

An improved capillary gas chromatography procedure with flame ionization detection was developed for the analysis of nonvolatile organic acids and fatty acids in flue-cured tobacco hydrolysates. Two major nonvolatile organic acids, citric and malic acids, and two minor acids, quinic and caffeic acids, were readily quantified as their trimethylsilyl derivatives in an aqueous extract of tobacco (Court & Hendel, 1986).

Caffeic acid has been determined in grape juice, apple juice and pear juice using reverse-phase HPLC with diode array detection (Spanos & Wrolstad, 1990a,b; Spanos et al., 1990).

Ficarra et al. (1990) reported the use of HPLC with diffuse infrared reflectance spectroscopy for qualitative and quantitative analysis of naturally occurring phenolic compounds, including caffeic acid, in the medicinal plant Crataegus oxyacantha L.

1.2. Production and use

1.2.1. Production

No information was available to the Working Group about the worldwide production, trade or consumption of caffeic acid.

1.2.2. Use

Several studies have been done to develop drugs based on caffeic acid for use in the treatment of asthma and allergies (Koshihara et al., 1984; Murota & Koshihara, 1985). The antibacterial effect of caffeic acid and of its oxidation products was studied in four bacteria, Staphylococcus aureus, Streptococcus faecalis, Salmonella typhimurium and Escherichia coli. Bactericidal activity appeared only after oxidation of caffeic acid and under alkaline conditions (Cuq & Jaussan, 1991).

1.3. Occurrence

1.3.1. Plants

Caffeic acid occurs naturally in a wide range of plants, free and in various combined forms (Conkerton & Chapitel, 1983). Caffeic acid and chlorogenic acids are constituents of numerous species, including Umbelliferae, Cruciferae, Cucurbitaceae, Polygonaceae Compositae, Labiatae, Solanaceae, Leguminosae, Saxifragaceae, Caprifoliaceae, Theaceae and Valenanaceae (Herrmann, 1956; Litvinenko et al., 1975).

Caffeic acid has been identified in plants used for medicinal purposes, including Davallia manesii Moore (Davalliaceae), a fern used in Korean folk medicine for the treatment of the common cold neuralgia and stomach cancer and in China as a traditional medicine for treatment of lumbago, rheumatism, toothache and tinnitus (Cui et al., 1990); the roots of Canssa spinarum L. (Apocynaceae), a thorny, evergreen shrub used medicinally in India as a purgative and for the treatment of rheumatism (Raina et al., 1971); the flowers of Ixora javanica, also used in Indian medicine, as an antitumour agent, gastric sedative, intestinal antiseptic and astringent (Nair & Panikkar, 1990); Centaurium umbellatum Gil. (Gentia-naceae), a medicinal plant used in numerous countries combined with other plants (Hatjimanoli & Debelmas, 1977); and Artemisia rubripes Nakai, a Chinese plant used medically (Koshihara et al., 1984).

Caffeic acid has been found in the flowers, leaves and buds of the medicinal plant Crataegus oxyacantha L. (a Rosaceae with cardiovascular effects) (Ficarra et al, 1990); in the flowers of Tussilago farfara L. (an antispasmodic) with caffeoyl tartric acid (Didry et al. 1980); in the essential oil of flowers of Cytisus scoparius L. (Kurihara & Kikuchi, 1980); in the leaves of Melissa officinalis L. (a Labiatae which inhibits viral development and tumour cell division) with chlorogenic acid (Chlabicz & Galasiński, 1986) and in timothy grass (Phleum pratense L.) with chlorogenic acid isomers (Mino & Harada, 1974); in the seeds of Argyreia speciosa Sweet (elephant creeper, a Convolvulaceae with hypotensive and spasmolytic activity (Agarwal & Rastogi, 1974); in the essential oil of Foeniculum vulgare (Umbelliferae) (Trenkle 1971); in the herb Veronica chamaedrys L. (Światek et al., 1971); and in the roots of Arctium lappa L. (burdock, a Compositae or Asteraceae used as a diuretic) with chlorogenic acid (Leung, 1980).

1.3.2. Fruits, vegetables and seasonings

Caffeic acid is present in a variety of fruits, vegetables and seasonings, predominantly in the form of ester conjugates, including chlorogenic acids (esters of caffeic acid and quinic acid) and related compounds. These conjugates may be hydrolysed upon ingestion, leading to variable uptakes of caffeic acid. Table 1 summarizes the levels of caffeic acid and its conjugates in various fruits and vegetables, as determined by thin-layer chromatography following enzymic, acid and/or alkaline hydrolysis.

Table 1. Occurrence of caffeic acid and its conjugates in various fruit and vegetables.

Table 1

Occurrence of caffeic acid and its conjugates in various fruit and vegetables.

Caffeic acid (free and conjugated) has been found at concentrations > 1000 ppm (mg/kg) in thyme, basil aniseed, caraway, rosemary, tarragon, marjoram, savory, sage, dill and absinthe (Ames et al., 1991). Other agricultural products that have been found to contain carteic acid and conjugates include sweet potatoes (Hayase & Kato, 1984), sunflower seeds and meal (Pomenta & Burns, 1971; Felice et al., 1976), soya beans (Pratt & Birac, 1979), tobacco (Andersen & Vaughn, 1970), spinach, red peppers, apricots, coconut and rolled oats (Kusnawidjaja et al., 1969; Ames et al., 1991).

Cynara scolymus L. (Compositae or Asteraceae, artichoke) contains up to 2% O-diphe-nohc derivatives such as caffeic acid. 1,3-Dicaffeoylquinic acid and 3-caffeoylquinic acid (chlorogenic acid) are believed to be among the active constituents (Leung, 1980; Hinou et al., 1989),

The content of caffeic acid in the peel of potato tubers changes with the physical state of the tuber: It is highest during profound dormancy, drops during emergence from dormancy and remains low during sprouting of the tubers. During dormancy, the largest amount is contained in the eyes of the tubers (18.7 µg/g crude weight), a smaller amount in the peel (12.5 µg/g crude weight) and the smallest amount in the pulp (2.3 µg/g crude weight) At the end of dormancy, the peel contains the largest amount of caffeic acid (3.7 µg/g crude weight) the eyes a smaller amount (2.8 µg/g crude weight) and the pulp the least (0.7 µg/g crude weight) (Morozova et al., 1975). Increased biosynthesis of caffeic acid and chlorogenic acid was reported in Irish potato tubers and of caffeic acid, chlorogenic acid and isochlorogenic acid m sweet potato roots after infection or stress (Kuc, 1972).

Chlorogenic acid, which is metabolized to caffeic acid, is present in apricots, cherries plums and peaches at concentrations ranging approximately from 50 to 500 ppm (mg/kg) (Ames et al., 1991). It is also present in coffee beans, potatoes, apples and tobacco leaves in significant quantities: 34–140 mg/kg fresh weight in several varieties of potato 120–310 mg/1 juice produced from apples, 890 mg/kg fresh, mature apples and 5590–6740mg/kg dry tea shoots (Iwahashi et al., 1990). Neochlorogenic acid, which is also metabolized to caffeic acid, is present at concentrations ranging from approximately 50 to 500 ppm (mg/kg) in apples, pears, peaches, apricots, plums, cherries, Brussels sprouts, kale, cabbage and broccoli (Ames et al., 1991).

Relatively small changes occurred in the caffeic and quinic acid contents of sunflower kernels during storage; however, the chlorogenic acid content decreased during storage at 5 °C, 15 °C and 40 °C for 120 days (Pomenta & Burns, 1971).

The occurrence of caffeic acid conjugates in coffee beans has been reviewed (IARC, 1991). The conjugates of caffeic acid are present in green and roasted beans, the total percentage of chlorogenic acids in commercial roasted coffee samples ranging from 0.2 to 3.8% (Trugo, 1984; Maier, 1987).

1.3.3. Beverages

Caffeic acid is present in free and conjugated forms in beverages made from agricultural plants of which it is a constituent. Assuming that one cup of coffee contains 10 g of ground coffee, a level of 15–325 mg chlorogenic acids per cup can be calculated on the basis of the percentage range given above (Viani, 1988). Actual data from the USA give an average of 190 mg total chlorogenic acids per cup of brewed coffee (Clinton, 1985).

Caffeic acid is also found in fruit juices and wine. Apple juice has been reported to contain caffeic acid at 0–10 mg/1 (Kusnawidjaja et al., 1969) and chlorogenic acid at 20-60 mg/1, but the levels may be much higher (~200 mg/1), especially in fermented juice (Kusnawidjaja et al., 1969; Brause & Raterman, 1982; Cilliers et al., 1990).

In 50 samples of commercial white wines, the average concentration of caffeic acid was 2.5 mg/1. German Riesling wines contained the highest concentration (4.1 mg/1), followed by Japanese koshu wine (3.1 mg/1), Chardonnay wine (1.7 mg/1) and Sémillon wine (0.9 mg/1) (Okamura & Watanabe, 1981). Italian wines and a sherry were also found to contain caffeic acid (Cartoni et al., 1991).

The influence of variety, maturity, processing and storage on the phenolic composition of pear, grape and apple juice has been investigated (Spanos & Wrolstad, 1990a,b; Spanos et al., 1990). The concentration of chlorogenic acid increases by about six fold when apple juices are processed by diffusion extraction at different temperatures over that found by conventional pressing. In grape juices, the addition of sulfur dioxide during processing resulted in higher levels of caffeic acid.

1.3.4. Other sources

Caffeic acid has also been identified in wood smoke condensates (Ohshima et al., 1989) and in the bee product, propolis, presumably from resin gathered from caffeic acid-containing plants (Čižmárik & Matel, 1970).

1.4. Regulations and guidelines

No information was available to the Working Group concerning the regulatory status of caffeic acid.

2. Studies of Cancer in Humans

No data were available to the Working Group.

3. Studies of Cancer in Experimental Animals

3.1. Oral administration

3.1.1. Mouse

Groups of 30 male and 30 female B6C3F1 (C57B1/6N × C3H/HeN F1) mice, six weeks of age, were fed a diet containing 0 or 2% [20 g/kg of diet] caffeic acid (purity, ≥ 98%) for 96 weeks (intakes, 2120 mg/kg bw per day for males and 3126 mg/kg bw per day for females). Squamous-cell papillomas and carcinomas occurred in the forestomachs of treated mice (4/30 papillomas and 3/30 carcinomas in males and 0/29 papillomas and 1/29 carcinomas in females), but not in controls. The incidences of epithelial hyperplasia of the forestomach were increased significantly (p < 0.01) in both treated males and females. Renal-cell adenomas were found in 8/29 (p < 0.01) females and in 0/29 controls; one renal adenocarcinoma was seen in a treated male. Significant increases in the incidence of renal tubular-cell hyperplasia were seen in both treated males and treated females. An increased incidence of alveolar type II-cell tumours (adenomas plus carcinomas) of the lung (8/30; p < 0.05) was reported in males but not in females. Spontaneous incidences of alveolar-cell tumours in male B6C3F1 mice have been reported to be 2.2–13.9% (Hagiwara et al., 1991).

3.1.2. Rat

Groups of 30 male and 30 female Fischer 344 rats, six weeks of age, were fed a diet containing 0 or 2% [20 g/kg of diet] caffeic acid (purity, ≥ 98%) for 104 weeks (intakes, 678 mg/kg bw per day for males and 814 mg/kg bw per day for females). Squamous-cell papillomas and carcinomas occurred in the forestomach in 23/30 (papillomas) and 17/30 (carcinomas) males and in 24/30 (papillomas) and 15/30 (carcinomas) females. No neoplastic change was noted in the forestomachs of an untreated group of 30 males and 30 females. The frequency of forestomach hyperplasia was also increased significantly in animals of each sex as compared to the control level (p < 0.01). Renal tubular-cell adenomas., were seen in four treated males but in no untreated male or in females.Significant increases in the incidence of renal tubular-cell hyperplasia were seen in both treated males and treated females (Hagiwara et al., 1991).

3.2. Administration with known carcinogens

3.2.1. Sequential exposure

(a) Mouse

Three groups of 30 female CD-1 mice, seven weeks of age, were treated topically with 200 nmol [51 mg] 7,12-dimethylbenz[a]anthracene (DMBA) in 200 µl acetone. After one week, the mice were treated topically with 5 nmol [3 mg] 12-O-tetradecanoylphorbol 13-acetate (TEA) with or without simultaneous caffeic acid [purity unspecified] at 10 or 20 µmol [1.8 or 3.6 mg] twice a week for 19 weeks. The mean number of skin tumours per mouse treated with TPA and the high dose of caffeic acid was significantly lower than that in the group treated with TPA alone: 1.12, 4.43 and 6.18 tumours/mouse in the groups treated with TPA plus 20 µmol caffeic acid, TPA plus 10 µmol caffeic acid and TPA alone, respectively (Huang et al., 1988).

(b) Rat

Two groups of 20 female Sprague-Dawley rats, 50 days of age, received 25 mg/kg bw DMBA in 0.5 ml sesame oil by gavage. One week later, the animals were fed a diet containing 0.5% [5 g/kg of diet] caffeic acid (purity, > 99%) for 51 weeks. The mammary glands, ear ducts, stomach, liver and kidneys were examined. The incidence of papillomas of the forestomach was significantly increased (6/19) in animals treated with DMBA plus caffeic acid as compared to rats treated with DMBA alone (0/19; p < 0.01) No other significant increase in tumour incidence was found (Hirose et al., 1988).

Three groups of 15 male Fischer 344 rats, six weeks of age, were administered 150 mg/kg bw N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in dimethyl sulfoxide by gavage. One week later, animals were fed a diet containing 0.5% [5 g/kg of diet] caffeic acid (purity, > 98%) or caffeic acid plus other phenolic antioxidants (0.2% catechol plus 0.5% butylated hydroxyanisole plus 0.25% 2-tert-butyl-4-methylphenol) for 35 weeks or the basal diet. The oesophagus, stomach, intestines, liver and kidneys were examined. Squamous-cell carcinomas of the forestomach occurred in 1/15 animals in the group treated with MNNG alone, in 4/15 in the group receiving MNNG plus caffeic acid (no significant difference from controls given MNNG alone) and in 12/15 in the group receiving MNNG plus caffeic acid together with phenolic antioxidants (p < 0.01). No other increase in tumour incidence was found (Hirose et al., 1991).

3.2.2. Prior or concomitant exposure Mouse

Female ICR/Ha mice, nine weeks of age, were fed a diet containing 0.06 mmol/g [10 g/kg of diet] caffeic acid (purity, 99%). From experimental day 8, the mice were also given 1 mg benzo[a]pyrene by gavage twice a week for four weeks. The diet containing caffeic acid was removed three days after the last benzo[a]pyrene treatment. Mice were killed at 211 days of age. In the 17 effective mice, the number of forestomach tumours (≥ 1 mm)/mouse [histology unspecified] was significantly decreased by caffeic acid (p < 0.05) (3.1 versus 5.0 tumours/mouse among 38 mice treated with benzo[a]pyrene alone) (Wattenberg et al., 1980). [The Working Group noted the limited reporting.]

4. Other Relevant Data

4.1. Absorption, distribution, metabolism and excretion

In rats, chlorogenic acid is hydrolysed in the stomach and intestine to caffeic and quinic acids (Czog et al., 1974). A number of metabolites have been identified (Fig. 1). Glucuronides of meta-coumaric acid and meta-hydroxyhippuric acid appear to be the main metabolites in humans. After oral administration of caffeic acid to human volunteers, O-methyl-ated derivatives (ferulic, dihydroferulic and vanillic acids) were excreted rapidly in the urine while the meta-hydroxyphenyl derivatives appeared later. The dehydroxylation reactions were ascribed to the action of intestinal bacteria (Arnaud, 1988).

Fig. 1

Fig. 1

Proposed metabolic pathways of caffeic acid

4.2. Toxic effects

4.2.1. Humans

No data were available to the Working Group.

4.2.2. Experimental data

Five male Fischer 344 rats, six weeks of age, were given 20 g/kg of diet caffeic acid (purity, > 98%) in basal diet for four weeks. The forestomachs of all treated animals showed epithelial hyperplasia. No hyperplasia was detected in the five untreated controls (Hirose et al., 1987).

A group of 15 male Syrian golden hamsters, seven weeks of age, was fed a diet containing 1% [10 g/kg diet] caffeic acid (purity, > 98%) for 20 weeks. The dose level of 1% was selected as one-fourth the LD50 in rats. The stomachs and urinary bladders were processed for histopathological and autoradiographic examinations. Mild epithelial hyperplasia of the forestomach was noted in 14/15 treated animals (severe in one) and in 7/15 untreated animals (p < 0.001). Assessment of 3H-thymidine incorporation revealed an increase in the number of labelled cells in the forestomach and pyloric region of the glandular stomach as compared with untreated rats, but this was not statistically significant (Hirose et al., 1986).

Caffeic acid effectively inhibits lipoxygenase and thereby inhibits the biosynthesis of leukotnenes, which are involved in immunoregulation and in a variety of diseases, including asthma, inflammation and allergic conditions. It blocks platelet aggregation by inhibiting the production of thromboxane A2, which can cause bronchoconstriction (Koshihara et al., 1984; Murota & Koshihara, 1985). Caffeic acid has been widely used as a pharmacological inhibitor in a variety of organ and cell systems, and Sugiura et al. (1989) have shown that caffeic acid and several of its derivatives (at IC50 of 10−8–10−7M) specifically inhibit the 5-lipoxy-genase. Caffeic acid (at l0−4M [0.2 g]) inhibited the proliferation of malignant human haematopoietic cell lines, as measured by 3H-thymidine incorporation (Snyder et al., 1989); at a concentration of 17.5 µM [3.2 mg], it modified the differentiation of HL-60 cells to mature granulocytes (Miller et al., 1990) by affecting leukotriene formation. The cloning efficiency of T-lymphocyte progenitor cells is also inhibited in vitro by caffeic acid and restored by leukotriene B4, indicating a regulatory role for arachidonic acid metabolites(Miller et al., 1989). Several investigators have demonstrated that caffeic acid at 10−4M inhibits lipid peroxidation induced by superoxide anion and formation of hydroxyl radicals in vitro (Iwahashi et al., 1990; Toda et al, 1991; Zhou & Zheng, 1991).

4.3. Reproduction and developmental toxicity

No data were available to the Working Group.

4.4. Genetic and related effects

4.4.1. Humans

No data were available to the Working Group.

4.4.2. Experimental systems (see also Table 2)

Table 2. Genetic and related effects of caffeic acid.

Table 2

Genetic and related effects of caffeic acid.

When tested alone, caffeic acid was not mutagenic to Salmonella typhimurium and did not induce gene conversion in Saccharomyces cerevisiae D7. Forward mutations were induced in cultured mouse lymphoma L5178Y cells, and chromosomal aberrations were induced in cultured Chinese hamster ovary cells. The clastogenic effect could not be ascribed to the hydrogen peroxide that was present at low concentrations in freshly prepared caffeic acid solutions (Hanham et al., 1983). Caffeic acid did not induce micronuclei in bone-marrow or intestinal cells of mice treated in vivo.

The effects of simultaneous exposure of cells to some transition elements and caffeic acid have also been studied. In the presence of manganese (MnCl2) chelated with glycine, caffeic acid induced mutations in S. typhimurium, gene conversion in S. cerevisiae D7 and chromosomal aberrations in Chinese hamster ovary cells (Stich et al., 1981a,b).

The phenethyl ester of caffeic acid inhibited adenovirus-induced transformation in rat embryo fibroblasts (Su et al., 1991).

Caffeic acid decreased MNNG-induced mutation in S. typhimurium (Francis et al., 1989). Treatment of Chinese hamster ovary K-1 cells with caffeic acid increased the incidence of sister chromatid exchange induced by mitomycin C and ultraviolet radiation. In contrast, the number of x ray-induced sister chromatid exchanges was reduced by post-treatment with caffeic acid during the G1 phase of the cell cycle (Sasaki et al., 1989).

5. Summary of Data Reported and Evaluation

5.1. Exposure data

Caffeic acid is found in many fruits, vegetables, seasonings and beverages consumed by humans, principally in conjugated forms such as chlorogenic acid.

5.2. Human carcinogenicity data

No data were available to the Working Group.

5.3. Animal carcinogenicity data

Caffeic acid was tested for carcinogenicity by oral administration in the diet in one study in mice and one study in rats. In mice, it produced renal-cell adenomas in females and a high incidence of renal tubular-cell hyperplasia in animals of each sex. An increase in the combined incidence of squamous-cell papillomas and carcinomas of the forestomach was seen in male mice, and a high incidence of hyperplasia of the forestomach was seen in both males and females. In rats, it produced squamous-cell papillomas and carcinomas of the forestomach in animals of each sex and a few renal-cell adenomas in males.

Oral administration of caffeic acid in combination with known carcinogens resulted in enhancing or inhibiting effects depending upon the carcinogen and the time of administration.

5.4. Other relevant data

Humans and experimental animals metabolize caffeic acid to the same metabolites and hydrolyse chlorogenic acid to caffeic acid.

Caffeic acid did not induce micronuclei in mice treated in vivo. It produced gene mutation and chromosomal aberrations in cultured rodent cells. It did not induce gene mutation in bacteria.

5.5. Evaluation1

No data were available on the carcinogenicity of caffeic acid to humans.

There is sufficient evidence in experimental animals for the carcinogenicity of caffeic acid.

Overall evaluation

Caffeic acid is possibly carcinogenic to humans (Group 2B).

6. References

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Footnotes

1

For definition of the italicized terms, see Preamble, pp. 26–29.

©International Agency for Research on Cancer, 1993.
Bookshelf ID: NBK513593
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