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Table 1. Review of epidemiological studies on cancer showing protection by consumption of fruits and vegetables.
Cancer site Fraction of studies showing significant cancer protection Relative Risk (median) Low vs. High Quartile of consumption
Epithelial    
Lung 24/25 2.2
Oral 9/9 2.0
Larynx 4/4 2.3
Esophagus 15/16 2.0
Stomach 17/19 2.5
Pancreas 9/11 2.8
Cervix 7/8 2.0
Bladder 3/5 2.1
Colorectal 20/35 1.9
Miscellaneous 6/8                         
Hormone-dependent    
Breast 8/14 1.3
Ovary/endometrium 3/4 1.8
Prostate 4/4 1.3
     
Total 129/172




Table 2. Carcinogenicity of natural plant pesticides tested
in rodents (Fungal toxins are not included) (49).

Carcinogens: N=35 Acetaldehyde methylformylhydrazone, allyl isothiocyanate, arecoline.HCl, benzaldehyde, benzyl acetate, caffeic acid, catechol, clivorine, coumarin, crotonaldehyde, cycasin and methylazoxymethanol acetate, 3,4-dihydrocou-marin, estragole, ethyl acrylate, N2-y-glutamyl-p-hydrazino- benzoic acid, hexanal methylformylhydrazine, p-hydrazinobenzoic acid. HCl, hydroquinone, 1-hydroxyanthraquinone, lasiocarpine, d-limonene, 8-methoxypsoralen, N-methyl-N-formylhydrazine, a-methylbenzyl alcohol, 3-methylbutanal methyl formylhydrazone, methylhydrazine, monocrotaline, pentanal methyl- formylhydrazone, petasitenine, quercetin, reserpine, safrole, senkirkine, sesamol, symphytine.         
Noncarcinogens: N=28 Atropine, benzyl alcohol, biphenyl, d-carvone, deserpidine, disodium glycyr- rhizinate, emetine.2HCl, ephedrine sulphate, eucalyptol, eugenol, gallic acid, geranyl acetate, p-N-[y-l(+)-glutamyl]-4-hydroxy-methylphenylhydrazine, glycyrrhetinic acid"p-hydrazinobenzoic acid, isosafrole, kaempferol, d-menthol, nicotine, norharman, pilocarpine, piperidine, protocatechuic acid, rotenone, rutin sulfate, sodium benzoate, turmeric oleoresin, vinblastine         
These rodent carcinogens occur in: absinthe, allspice, anise, apple, apricot, banana, basil, beet" broccoli, Brussels sprouts, cabbage, cantaloupe, caraway, cardamom, carrot, cauliflower, celery, cherries, chili pepper, chocolate milk, cinnamon, cloves, cocoa, coffee, collard greens, comfrey herb tea, corn, coriander, currants, dill, eggplant, endive, fennel, garlic, grapefruit, grapes, guava, honey, honeydew melon"horseradish, kale, lemon, lentils, lettuce, licorice, lime, mace, mango, marjoram, mint, mushrooms, mustard, nutmeg, onion, orange, paprika, parsley, parsnip, peach, pear, peas, black pepper, pineapple, plum, potato, radish, raspberries, rhubarb, rosemary, rutabaga, sage, savory, sesame seeds, soybean, star anise, tarragon, tea, thyme, tomato, turmeric, and turnip.




Table 3. Carcinogenicity in rodents of natural
chemicals in roasted coffee.

Positive: N=19 Acetaldehyde, benzaldehyde, benzene, benzofuran, benzo(a)pyrene, caffeic acid, catechol, 1,2,5,6-dibenzanthracene, ethanol, ethylbenzene, formaldehyde, furan, furfural, hydrogen peroxide, hydroquinone, limonene, styrene, toluene, xylene         
Not positive: N=8 Acrolein, biphenyl, choline, eugenol, nicotinamide, nicotinic acid, phenol, piperidine
Uncertain: Caffeine
Yet to test: ~1000 chemicals



Table 4. Proportion of chemicals evaluated as carcinogenic.
Chemicals tested in both rats and mice(a) 330/559 (59%)
Naturally-occurring chemicals 73/127 (57%)
Synthetic chemicals 257/432 (59%)


Chemicals tested in rats and/or mice(a)    
Chemicals in Carcinogenic Potency Database 668/1275 35/64
Natural pesticides 14/23 19/28
Mold toxins (52%) (55%)
Chemicals in roasted coffee (61%) (68%)


Innes negative chemicals retested (a, b) 16/34 (47%)
Physician's Desk Reference (PDR): drugs with reported cancer tests (c) 117/241 (49%)
FDA database of drug submissions (d) 125/282 (44%)


NOTES;

(a): From the Carcinogenic Potency Database (51).
(b): The 1969 study by Innes et al. is frequently cited as evidence that the proportion of carcinogens is low, as only 9% of 119 chemicals tested (primarily pesticides) were positive. However, these tests, which were only in mice with few animals per grouy, lacked the power of modern tests. Of the 34 Innes negative chemicals that have been retested using modern protocols: 16 were positive.
(c): Davies and Monro (85).
(d): Contrera et al. (86). 140 drugs are in both the FDA and PDR databases.



Table 5. Ranking Possible Carcinogenic Hazards
from Average U.S. Exposures

(Chemicals that occur naturally in foods are in bold.)

J Daily human exposure: The calculations assume an average daily dose for a lifetime.
Possible hazard: The human exposure to a rodent carcinogen is divided by 70 kg to give a mg/kg/day of human exposure, and this dose is given as the percentage of the TD50 in the rodent (mg/kg/day) to calculate the Human Exposure/Rodent Potency index (HERP), i.e., 100% means that the human exposure in mg/kg/day is equal to the dose estimated to give 50% of the rodents tumors. TD50 values used in the HERP calculation are averages calculated by taking the harmonic mean of the TD50s of the positive tests in that species from the Carcinogenic Potency Database. Average TD50 values, have been calculated separately for rats and mice, and the more potent value is used for calculating possible hazard. The less potent value is in parentheses.


Possible hazard:
HERP (%)
        Average daily       
U.S. exposure
    Human dose    
of Rodent carcinogen
Potency TD50
(mg/kg/day)a
RATS             MICE
140
EDB: workers (high exposure) (before 1977) Ethylene dibromide, 150 mg
1.52
(7.45)
17
Clofibrate Clorfibrate, 2g
169
 
14
Phenobarbital, 1 sleeping pill Phenobarbital, 60 mg
(+)
6.09
6.8
1,3-Butadiene: rubber workers (1978- 86) 1,3-Butadiene, 66.0 mg
(261)
13.9
6.1
Tetrachloroethylene: dry cleaners with dry-topdry units (1980-90)b Tetrachloroethylene, 433 mg
101
(126)
4.0
Formaldehyde: workers Formaldehyde, 6.1 mg
2.19
43.9
2.1
Beer, 257 g Ethyl alcohol, 13.1
9110
(–)
1.4
Mobile home air (14 hours/day) Formaldehyde, 2.2 mg
2.19
(43.9)
0.9
Methylene chloride: workers (1940s- 80s) Methylene chloride, 471 mg
724
(918)
0.5
Wine, 28.0 g Ethyl alcohol, 3.36 ml
9119
(–)
0.4
Conventional home air (14 hours/day) Formaldehyde, 598 mg
2.19
(43.9)
0.1
Coffee, 13.3g Caffeic acid, 23.9 mg
297
(4900)
0.04
Lettuce, 14.9 g Caffeic acid, 7.90 mg
297
(4900)
0.03
Safrole in spices Safrole, 1.2 mg
(441)
51.3
0.03
Orange juice, 138 g d-Limonene, 4.28 mg
204
(–)
0.03
Pepper, black, 446 mg d-Limonene, 3.57 mg
204
(–)
0.02
Mushroom (Agnricos bisporus 2.55 g) Mixture of hydrazines, etc. (whole mushroom)
(–)
20,300
0.02
Apple, 32.0 g Caffeic acid, 3.40 mg
297
(4900)
0.02
Coffee, 13.3 g Catechol, 1.33 mg
118
(244)
0.02
Coffee, 13.3 g Furfural, 2.09 mg
(683)
197
0.009
BHA: daily US avg (1975) BHA, 4.6 mg
745
(5530)
0.008
Beer (before 1979), 257 g Dimethylnitrosamine, 726 ng
       0.124       
    (0.189)    
0.008
Aflatoxin: daily US avg (1984- 89) Aflatoxin, 18 ng
   0.0032   
(+)
0.007
Cinnamon, 21.9 mg Coumarin, 65.0 mg
13.9
(103)
0.006
Coffee, 13.3 g Hydroquinone, 333 mg
82.8
(225)
0.005
Saccharin: daily US avg (1977) Saccharin, 7 mg
2140
(–)
0.005
Carrot, 12.1 g Aniline, 624 mg
194c
(–)
0.004
Potato, 54.9 g Caffeic acid, 867 mg
297
(4900)
0.004
Celery, 7.95 g Caffeic acid, 858 mg
297
 (4900)
0.004
White bread, 676 g Furfural, 500 mg
(683)
197
0.003
Nutmeg, 27.4 mg d-Limonene, 466 mg
204
(–)
0.003
Conventional home air (14 hour/day) Benzene, 155 mg
(169)
77.5
0.002
Carrot, 12.1 g Caffeic acid, 374 mg
297
(4900)
0.002
Ethylene thiourea: daily US avg (1990) Ethylene thiourea, 9.51 mg
7.9
(23.5)
0.002
[DDT: daily US avg (before 1972 ban)] [DDT, 13.8 mg]
(84.7)
12.3
0.001
Plum, 2.00 g Caffeic acid, 276 mg
297
(4900)
0.001
BHA: daily US avg (1987) BHA, 700 mg
745
(5530)
0.001
Pear, 3.29 g Caffeic acid, 240 mg
297
(4900)
0.001
[UDMH: daily US avg (1988)] [UDMH, 2.S2 mg (from Alar)]
( – )
3.96
0.0009
Brown mustard, 68.4 mg Allyl isothiocyanate, 62.9 mg
96
( – )
0.0008
[DDE: daily US avg (before 1972 ban)] [DDE, 6.91 mg]
( – )
12.5
0.0007
TCDD: daily US avg (1994) TCDD, 12,0 pg
0.0000235
(0.000156)
0.0007
Bacon, 11.5 g Diethylnitrosaminc, 11.5 ng
0.0237
(+)
0.0006
Mushroom (Aguricus bisporus 2.55 g) Glutamyl-p-hydrazino- benzoate
107 mg
277
0.0004
Bacon, 11.5 g N-Nitrosopyrrolidine, 196 ng
(0.799)
0.679
0.0004
Bacon, 11.5 g Dimethylnitrosamine, 34.5 ng
0.124
 (0.189)
0.0004
[EDB: Daily US avg (before 1984 ban)] [EDB, 420 ng]
1.52
(72,5)
0.0004
Tap water, l liter (1987-92) Bromodichloromthane, 13 mg
(72.5)
47.7
0.0003
Mango, 1.22 g d-Limonene, 48.8 mg
204
(–)
0.0003
Beer, 257 g Furfural, 39.9 mg
(683)
197
0.0003
Tap water, l liter (1987-92) Chloroform, 17 mg
(262)
90.3
0.0003
Carbaryl: daily US avg (1990) Carbaryl, 2.6 mg
14.1
(–)
0.0002
Celery, 7.95 g 8-Methoxypsoralen, 4.86 mg<(B>
32.4
(–)
0.0002
Toxaphene: daily US avg (1990) Toxaphene, 595 ng
(–)
5.57
0.00009
Mushroom (Agaricus bisporas, 2.55 g) p-Hydraziaobenzoate, 28 mg
454c
 
0.00008
PCBs: daily US avg (1984-86) PCBs, 98 ng
1.74
(9.58)
0.00008
DDE/DDT: daily US avg (1990) DDE, 659 ng
(–)
12.5
0.00007
Parsnip, 54.0 mg 8-Methoxypeoralen, 1.57 mg
32.4
(–)
0.00007
Toast, 67.6 g Urethane, 811 ng
(41.3)
16.9
0.00006
Hamburger, pan fried, 85 g PhIP, 176 ng
4.29c
(28.6)c
0.00005
Estragole in spices Estragole, 1.99 mg
(–)
51.8
0.00005
Parsley, fresh, 324 mg 8-Methoxypsoralea, 1.17 mg
32.4
(–)
0.00003
Hamburger, pan fried, 85 g MelQx, 38.1 ng
1.99
(24.3)
0.00002
Dicofol: daily US avg (1990) Dicofol, 544 ng
(–)
32.9
0.00001
Cocoa, 3.34 g a-Methylhenzyl alcohol, 4.3 mg
458
(–)
0.00001
Beer, 257 g Urethane, 115 ng
(41.3)
16.9
0.000005
Hamburger, pan fried, 85 g IQ, 6.38 ng
1.89c
(19.6)
0.000001
Lindane: daily US avg (1990) Lindane, 32 ng
(–)
30.7
0.0000004
PCNB: daily US avg (1990) PCNB (Quintozene), 19.2 ng
(–)
71.1
0.0000001
Chlorobenzilate: daily US avg (1989) Chlorobenzilate, 6.4 ng
(–)
93.9
<0.00000001
Chlorothalonil; daily US avg (1990) Chlorothalonil, <6.4 ng
828d
(–)
0.000000008
Folpet: daily US avg (1990) Folpet, 12.8 ng
2280d
 
    0.000000006     
Captan: daily US avg (1990) Captan, l 1.5 ng
2690d
(2730)d


Notes:
a: no data in CPDB; ( – ) = negative in cancer test; (+) = positive cancer test(s) not suitable for calculating a TD50.
b: This is not an average, but a reasonably large sample (1027 workers).
c: TD50 harmonic mean was estimated for the base chemical from the hydrochloride salt.
d: Additional data from EPA that is not in the CPDB were used to calculate these TD50 harmonic means.


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