Appendix A
Selected Substances in Food Subjected to Some Degree of Carcinogenicity Testing in Animals and for Which Some Positive Results Have Been Reported
|
Substance |
Nature of Supporting Evidence |
Extent of Natural Occurrence in Foods |
References |
|
From Higher Plants |
|
|
|
|
Allyl isothiocyanate |
Bladder papillomas in male rats; negative in mice and female rats; clastogenic, mutagenic |
Raw cabbage, 0.04-2.7 ppm; horseradish, 2,000 ppm; black mustard seed, 10,000 ppm |
NTP, 1982; Ishidate et al., 1988; McGregor et al., 1988 |
|
Anthraquinone, 1-hydroxy |
Cecum, colon, and liver tumors in male rats |
|
Mori et al., 1990 |
|
Asarone,à - and á- (oil of calamus) |
Malignant tumors in the duodenal region'' in male and female rats |
Asarum and acorns spp (sweet flag) ≈ 20,000 ppm |
Taylor et al., 1967 |
|
Substance |
Nature of Supporting Evidencea |
Extent of Natural Occurrence in Foodsb |
Referencesc |
|
Benzaldehyde |
Forestomach tumors in male and female mice |
Found in over 40 foods; fruits and vegetables, 0.2-1 ppm; white bread, 5.0-10 pm; wines, 0.01-1.0 ppm; cocoa, coffee, tea, 2.0 ppm; shellfish, 0.01 ppm |
NTP, 1990a |
|
Caffeine |
Increased multiplicity but not incidence of spontaneous mammary gland tumors in female mice |
Tea, coffee, maté, guaraná, cola nuts; 0.5 to 5.0% of the plant product |
Welsch et al., 1988 |
|
Capsaicin |
Duodenal adenocarcinoma in male and female mice (significant only when all treated groups combined); not mutagenic |
In pungent (hot) red peppers (q.v.); <0.1 to 1.0% of dry fruit |
Toth et al., 1984 (as reported by Watts, 1985) |
|
Capsicum annuum; (hot) peppers |
Liver tumors in rats |
Widely used spice, especially in warmer climates |
Hoch-Ligeti, 1950 |
|
Chrysazin |
Colon tumors in male rats |
|
Mori et al., 1985 |
|
Ecdysone, alpha |
Liver tumors in male and female Egyptian toads |
Insects and crustaceans, spinach, plants, relationship to food |
El-Mofty et al., 1987 |
|
Estragole |
Liver tumors in female mice; forms DNA adducts |
Apple, bilberry <0.03 ppm; basil and oregano ≈ 100 ppm; tarragon ≈ 1%; anise and star anise ≈ 5.0% |
Miller et al., 1983; Randerath et al., 1985 |
|
Ethyl acrylate |
Negative in 2 strains of male and female rats; forestomach tumors in male mice, male and female rats |
Dill ≈ 1.0 ppm; pineapple, 0.8 ppm; raspberry; durian |
Miller et al., 1985; NTP, 1986 |
|
Eugenol |
Data equivocal for liver tumors in female and male mice. |
Oranges, cherries and many fruits ≈ 0.02 ppm; tomato, carrot ≈ 0.2 ppm, wines, liquors ≈ 0.1 ppm; cottage cheese, fish ≈ 3.0 ppm; anise ≈ 0.2%; cloves ≈ 10% |
NTP, 1983 |
|
Substance |
Nature of Supporting Evidencea |
Extent of Natural Occurrence in Foodsb |
Referencesc |
|
Furfural |
In male rats 2/50 at high-dose only showed cholangio-carcinomas; none in females. In male mice, increased incidence of adenomas and carcinomas in high-dose group; in females, increased incidence of adenomas at high-dose |
Cocoa, coffee, 55-255 ppm; wine, tr-10 ppm; whiskies, cider, sherry, wines, 1-30+ ppm, sauerkraut, tomato, cinnamon, cloves, wheaten bread, 1-14 ppm; many fruits, tr.-1 ppm |
NTP, 1990 |
|
Gossypol |
Neck myxosarcomas in female mice |
Cottonseed meal, limit of .045% (U.S.) and .06% (P.A.G.) free gossypol |
Dhaliwal et al., 1987 |
|
D-Limonene |
Kidney tumors in male rats |
Citrus juices ≈ 200 ppm; citrus oils 50-90%; other fruits and vegetables 1-30 ppm; coffee, tea ≈ 1 ppm; spices, trace -5% |
NTP, 1990b |
|
Piper nigrum; (black and white) pepper |
Lung, liver, and skin tumors in male and female mice; liver tumors in male and female Egyptian toads |
Widely used spice |
Concon et al., 1979; El-Mofty et al., 1988; El-Mofty et al., 1991 |
|
Phytic acid |
Kidney tumors in male and female rats |
Oil seed, legumes, cereal grains |
Hiasa et al., 1992 |
|
Ptaquiloside |
Ileal, mammary, and bladder tumors in female rats |
Bracken fern ("fiddleheads") |
Hirono et al., 1984; Hirono et al., 1987 |
|
Quercetin |
Intestinal and bladder tumors in male and female "albino" rats; kidney tumors in male F344/N rats; liver tumors in female F344 rats; mutagenic |
Ubiquitous in food plants, esp. in rinds of plant fruits |
Pamukcu et al., 1980; Dunnick and Hailey, 1992; NTP, 1992 |
|
Safrole |
Liver tumors in 3 strains male and female mice; liver tumors in 2 strains male rats, 1 strain female rats; clastogenic, forms DNA adducts |
Cocoa, nutmeg, mace, black pepper, ≈ 0.2% |
Lipsky et al., 1981; Innes et al., 1969; Vesselinovitch et al., 1979; Wislocki et al., 1977; Borchert et al., 1973; Boberg et al., 1983; Miller et al., 1983; Ishidate et al., 1988; Randerath et al., 1985 |
|
Sesamol |
Forestomach tumors in male rats and male and female mice |
Sesame seeds and oil |
Hirose et al., 1990; Tamano et al., 1992 |
|
Shikimic acid |
Leukemia in male and female mice; glandular stomach tumors in male mice |
Important biosynthetic precursor in most plants |
Evans and Osman, 1974 |
|
Substance |
Nature of Supporting Evidencea |
Extent of Natural Occurrence in Foodsb |
Referencesc |
|
8-methoxypsoralen (Xanthotoxin) |
Kidney and Zymbal's gland tumors in male rats; mutagenic, clastogenic |
|
NTP, 1989 |
|
Xylitol |
Bladder tumors in mice; adrenal gland tumors in rats |
Carrots, lettuce, onions, raspberries, and spinach |
Anonymous, 1977 |
|
In addition to the list above, the committee is aware of other data on carcinogenic effects of benzene, cycasin, methoxyazoxymethylacetate, and styrene. See Appendix B. |
|||
|
From Edible Fungi |
|
|
|
|
Acetaldehyde methylformyl-hydrazone |
Lung, forestomach, clitoral tumors in female mice; preputial, lung tumors in male mice |
Several species of edible mushrooms, especially of the genus Gyromitra |
Toth et al., 1981 |
|
Glutamyl p-hydrazino-benzoic acid |
Subcutaneous tumors in male mice |
Edible mushrooms (Agaricus bisporus) and several Gyromitra species |
Toth, 1986 |
|
p-Hydrazino-benzoic acid |
Aorta and large artery tumors in male and female mice |
Several species of edible mushrooms, especially of the genus Gyromitra |
McManus et al., 1987 |
|
From Fungal Contaminants of Food |
|||
|
In addition to aflatoxin B1, the committee is aware of other data on carcinogenic effects for aflatoxin B2, aflatoxin G2, aflatoxin G2, Fusarium monliforme toxins, Penicillium islandicum toxins (e.g., islanditoxin), T-2 toxin, ochratoxins, and sterigmatocystin. See Chapter 2 and Appendix B. |
|||
|
Carcinogens Formed During Traditional Preparation and Processing |
|||
|
Benz[a]anthracene |
Benign liver and lung tumors in mice |
Coconut oil, 0.5-13.7 ng/g; broiled meat, 0.2-1.1 ng/g; broiled fish, 0.6-2.9 ng/g; smoked fish, 0.2-189 ng/g; ham, 1.3-12 ng/g; cereal, 0.4-6.8 ng/g; lettuce, 6.1-15.4 ng/g; tomatoes 0.3 ng/g; spinach, 16.1 ng/g; roasted coffee, 0.5-42.7 ng/g; tea, 2.9-36 ng/g; whisky, 0.04-0.08 ng/g |
Klein, 1963 |
|
Substance |
Nature of Supporting Evidencea |
Extent of Natural Occurrence in Foodsb |
Referencesc |
|
Benzo[a]pyrene |
Forestomach tumors in mice; mammary tumors in female rats |
Margarine, 0.9-36 ng/g; coconut oil, 0.3-8.2 ng/g; broiled meat, 0.17-50 ng/g; broiled fish, 0.2-0.9 ng/g; smoked fish, 1-78 ng/g; ham, <0.5-14.6 ng/g; bacon, 0.16-0.25 ng/g; cereal, 0.19-4.13 ng/g; potatoes, 0.09 ng/g; flour, 0.73; bread, 0.23; toasted bread, 0.39-0.56; lettuce, 2.8-12.8; tomatoes, 0.2-0.22; spinach, 7.4; fruits, 0.5-30; roasted coffee, 0.3-15.8; tea, 3.9-21.3; whisky, 0.04 |
Neal and Rigdon, 1967; McCormick, 1981 |
|
Catechol |
Glandular stomach tumors in male and female rats |
|
Hirose et al., 1990 |
|
Dibenz[a,h]-anthracene |
Forestomach and lung tumors in mice |
|
Larinow and Soboleva, 1938; Lorenz and Stewart, 1948; Snell and Stewart, 1962, 1963 |
|
In addition to the list above, the committee is aware of other data on carcinogenic effects of 7H-Dibenzo[c,g]-carbazole, Dibenzo[a,h]-pyrene, Dibenzo[a,i]-pyrene, Me-A-alpha-C(2-Amino-3-methyl-9H-pyrido-[2,3-b]indole), and 5-methylchyrysene. N-Nitroso-N-demethylamine is discussed in Chapter 2, and the committee also is aware of other data on carcinogenic effects on N-Nitroso-N-dibutylamine, N-Nitroso-diethylamine, N-Nitroso-methylethylamine, N-Nitroso-nornicotine, N-Nitroso-piperidine, and N-Nitroso-pyrrolidine. See Appendix B. |
|||
|
IQ(2-Amino-3-methylimidazo[4,5-f]quinoline) |
Lung, liver, and forestomach tumors in male and female mice; mammary gland, Zymbal gland, and liver tumors in female rats; liver, Zymbal gland, colon, and small intestine tumors in male and female rats; liver tumors in male and female monkeys |
Fried ground beef, 0.5-20 ng/g; broiled beef, 0.19 ng/g; sun-dried, broiled sardines, 20 ng/g; broiled salmon, 0.3-1.8 ng/g; fried fish, 0.16 ng/g; fried egg, 0.1 ng/g |
Ohagaki et al., 1984, 1986; Tanaka et al., 1985; Takayama et al., 1984; Adamson et al., 1990, 1991 |
|
MeIQ |
Liver tumors in female mice; forestomach tumors in male and female mice; Zymbal gland, oral cavity, and colon tumors in male and female rats; mammary gland tumors in female rats; skin tumors in male rats |
Fried fish, 0.03 ng/g; grilled, sun-dried sardines, 20-72 ng/g; broiled sardines, 16.6 ng/g |
Ohgaki et al., 1986; Kato et al., 1989 |
|
Substance |
Nature of Supporting Evidencea |
Extent of Natural Occurrence in Foodsb |
Referencesc |
|
MeIQx |
Liver tumors in male and female mice; lung tumors in female mice; lymphoma and leukemia in male mice; liver and Zymbal gland tumors in male and female rats; clitoral gland tumors in female rats; skin tumors in male rats. |
Fried ground beef, 0.45-12.3 ng/g; broiled beef, 2.11 ng/g; fried fish, 6.44 ng/g; broiled mutton, 1.01 ng/g; broiled salmon, 1.4-5 ng/g; dried, smoked mackerel, 0.8 ng/g; broiled chicken, 2.33 ng/g; canned roasted eel, 1.1 ng/g |
Ohgaki et al., 1987, Kato et al., 1988 |
|
PhIP2-Amino-1-methyl-6-phenylimidazo[4,5-]pyridine |
Lymphoma in male and female mice, colon tumors in male rats, mammary gland tumors in female rats, and colon tumors in female rats |
Broiled chicken 38.1 ng/g, broiled 42.5 ng/g, fried fish 69.2 ng/g, fried ground beef 15 ng/g |
Felton et al 1986, Esumi et al 1989, Ito et al 1991, Wakabayashi et al 1992 |
|
In addition to PhIP, the committee is aware of other data on carcinogenic effects of A-alpha-C (2-Amino-9H-pyrido[2,3-b]indole), Glu-P-1 (2-Amino-6-methyldipyrido[1,2-a:3',2'-d]-imidazole, Glu-P-2 (2-Aminodipyrido[1,2-a:3',2'-d]-imidazole, Trp-P-1 (Tryptophan-P-1), and Trp-P-2 (Tryptophan-P-2). |
|||
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