NNAATTUURRAALLLLYY OOCCCCUURRRRIINNGG MMUUTTAAGGEENNSSaanndd CCAARRCCIINNOOGGEENNSS FFOOUUNNDDiinn FFOOOODDSS aanndd BBEEVVEERRAAGGEESS

(continued from page 3)

ETHYL ACRYLATE (pineapple)—rodent carcinogen

ETHYL BENZENE (coffee)—rodent carcinogen

ETHYL CARBAMATE (bread, rolls, red wine)—mutagen androdent carcinogen

FURAN AND FURAN DERIVATIVES (bread, onions, celery,mushrooms, sweet potatoes, rolls, cranberry sauce, coffee)—many are mutagens

FURFURAL (bread, coffee, nuts, rolls, sweet potatoes)—furanderivative and rodent carcinogen

HETEROCYCLIC AMINES (roast beef, turkey)—mutagens androdent carcinogens

HYDRAZINES (mushrooms)—mutagens and rodent carcinogens

HYDROGEN PEROXIDE (coffee, tomatoes)—mutagen and rodentcarcinogen

HYDROQUINONE (coffee)—rodent carcinogen

D-LIMONENE (black pepper, mangos)—rodent carcinogen

4-METHYLCATECHOL (coffee)—rodent carcinogen

METHYL EUGENOL (basil, cinnamon, and nutmeg in apple andpumpkin pies)—rodent carcinogen

PSORALENS (celery, parsley)—mutagens; rodent and human car-cinogens

QUERCETIN GLYCOSIDES (apples, onions, tea, tomatoes)—mutagens and rodent carcinogens

SAFROLE (nutmeg in apple and pumpkin pies, black pepper)—rodent carcinogen

The holiday season is agood time to remem-ber that the American

food supply is by far thebest in the world—and thebest it has been in the histo-ry of this country. It is thebest not only in terms of itsabundance and variety, butalso in terms of its safety.Our diet—like diets aroundthe world—is made up ofwater, macronutrients (car-bohydrates, proteins, andfats), micronutrients (vita-mins and minerals), and tensof thousands of other natu-rally occurring chemicals. Afew of these latter chemicalseither have been shown tocause cancer in laboratoryrodents in research studiesor have been shown to be“mutagens” when testedwith bacteria. Mutagens,because they can damageDNA—genetic material—are often thought of as “pos-sible animal carcinogens.”Mutagen tests such as theAmes test are often used asquick indicators to predicthow likely a chemical is tocause cancer.

Back in 1958, when theUnited States Congresspassed legislation (the so-called Delaney amendmentto the 1938 Food, Drug, andCosmetics Act) to keep

“carcinogens” out of ourprocessed food supply, itwas assumed that carcino-gens (a) were rarely foundin foods and (b) were putthere by humans, either pur-posely, through food addi-tives, or inadvertently, in theform of pesticide residues.The Delaney amendmentbanned from American foodany artificial substance thatcould be shown to causecancer in lab animals—nomatter how small theamount of the substance in afood or how high the dosegiven to test animals. Someprogress has been madesince 1958, however: In1996 the Food QualityProtection Act removed thescientifically untenable“zero-risk” requirementfrom the approval processfor pesticides. This nar-rowed the scope of the irra-tionally restrictive Delaneyclause.1

In the 40+ years sinceDelaney was passed, it hasbecome clear that many nat-urally occurring chemi-cals—chemicals that areplentiful in our food sup-ply—cause cancer inrodents when fed in highdoses over a lifetime.Furthermore, scientistsBruce N. Ames and Lois

Swirsky Gold have analyzedhuman exposure to chemicals,both natural and man-made(synthetic), that have been clas-sified as “rodent carcinogens.”The researchers have concludedthat when ranked on an index(the HERP Index) that compareshuman exposure to the dose thatincreases tumors in rodents, thepossible cancer hazard to

humans from the background ofdietary intake of nature’s ownrodent carcinogens ranks high incomparison to the possible haz-ard from residues of syntheticpesticides or additives.

Human dietary intake ofnature’s pesticides is about10,000 times higher than humanintake of synthetic pesticidesthat are rodent carcinogens. In

““NNaattuurraall”” FFooooddss aarree nnoottCCaarrcciinnooggeenn--FFrreeee

The presumption that natural chemi-cals are not hazardous but syntheticones are has no scientific support.

Substances should be evaluated accordingto their human carcinogenic potential, notaccording to their origin—and to do sorequires more biological information thancan be provided by a rodent cancer test.

Naturally occurring rodent carcino-gens are present in far greater amounts inour food supply than are pesticide and other

chemical residues (the much-publicizedrodent carcinogens). As we enjoy our holi-day dinner, we should remember the bene-fits that scientific research has brought toAmerican agriculture and food technology.Science has made our food safer, morenutritious, more attractive, more abundant,more widely available, and more enjoy-able—and has done so at relatively lowcost. The American food supply is truly theenvy of the world!

1 slice white bread contains 167 µg (micrograms) furfural.Rodent carcinogenic dose of furfural =

197 mg (milligrams)/kg (kilogram) body wt/day,which is the same as 197,000 µg/kg/day.

Equivalent human dose (for a 70 kg person, about 155 pounds) = 197,000 x 70 = 82,600 slices of bread/day.

167

NNaattuurraall VVeerrssuuss SSyynntthheettiicc

When looking at this example,remember the conditions of the animalstudies: Doses are fed every day of therodent’s life (usually two years). To get anequivalent carcinogenic dose, a humanwould have to consume those 82,600 slicesof bread every day for years.

The primary risk factor in holidaymeals—other than the risk of food poison-ing from the improper handling or prepara-tion of food—is getting too much of a goodthing. A hungry holiday eater can easilyconsume 2,000-plus calories at one sitting.A consistent intake of excessive caloriescontributes to obesity, with its attendanthigher risk of heart disease. Interestingly,excessive caloric intake has been called the“most striking” carcinogen in rodent car-cinogenicity studies. Body weight is a goodpredictor of a rat’s risk of cancer as shownin comparisons of rats on calorie-restricted

diets and rats permitted to eat all they want.In our quest to reduce our cancer risk

by manipulating our diet, we should focus ondietary imbalances in what we eat, not ontrace chemicals. Numerous epidemiologicalstudies have indicated that people who con-sume a diet high in fruits and vegetables havea lower risk for various types of cancer. Thisis true in spite of the fact that natural chemi-cals that are also rodent carcinogens occurabundantly in many of these same fruits andvegetables. Note that the populations studiedlowered their risks even though their foodpresumably contained synthetic pesticideresidues. High fruit and vegetable consump-tion was still protective against cancer.

The foods on our Holiday Menu arehealthful and wholesome despite the pres-ence in them of some of Mother Nature’sown chemicals that have been shown to becarcinogenic in high-dose rodent tests.

AARREE TTHHEERREE ““PPOOIISSOONNSS”” iinnOOUURR FFOOOODD SSUUPPPPLLYY??

The focus of the ACSH holiday menu is on “carcinogens,”defined here as chemicals, either natural or synthetic, thatcause cancer in rodents when consumed in large amounts.

A related topic, however, is that of “poisons,” technically knownas toxicants. Just as it is scientifically unwarranted to believethat the food supply is free of natural rodent carcinogens andmutagens, it is equally unrealistic to equate “natural” with safe.Foods abound in natural chemicals that are toxic or potentiallytoxic—because all chemicals will be toxic at some dose.

Toxicologists have confirmed that food naturally containsa myriad of chemicals traditionally thought of as “poisons.”Potatoes contain solanine, arsenic, and chaconine. Lima beanscontain hydrogen cyanide, a classic suicide substance. Carrotscontain carototoxin, a nerve poison. And nutmeg, black pepper,and carrots all contain the hallucinogenic compound myristicin.

Moreover, all chemicals, whether natural or synthetic, arepotential toxicants at high doses but are perfectly safe whenconsumed in low doses. Take common table salt, for example:This everyday chemical, when consumed in excess, can causeelevations in blood pressure in sensitive individuals; a couple oftablespoonsful can kill a small child. Selenium, a mineral essen-tial in the human diet, can cause nausea and nerve changeswhen chronically consumed in excess. The familiar stimulantcaffeine is also a toxicant if consumed in high doses (say, 50 to100 cups of coffee per day). Supplements of the essential min-eral iron all too often cause poisoning in children.

When it comes to toxicants in the diet—natural or syn-thetic—the dose makes the poison.

If national regulatory policies lead toa reduction in the number of agriculturalchemicals available to farmers, food pro-duction could drop—and food pricesincrease. Such a situation could actuallyincrease cancer rates if people faced withhigher food costs were to choose to eatfewer fruits and vegetables.

Epidemiological evidence now con-firms that a generous intake of fruits andvegetables reduces the risk of cancer. Itwould be ironic, indeed, if misplaced fer-vor about removing supposed carcino-gens—synthetic chemicals—from ourfood supply were to result in decreasedconsumption of the very foods thought tobe protective against cancer.

other words, consumers whochoose to worry about eatingchemicals shown to cause cancerin rodents (and ACSH does notrecommend that you worry aboutthis hypothetical risk) shouldunderstand that the human diet isfull of naturally occurring rodentcarcinogens.

Present scientific knowledgesuggests that residues of syntheticrodent carcinogens in our diet areunlikely to pose a risk of cancer inthe quantities we consume on adaily, monthly, or yearly basis. Thedata are inadequate to allow us toevaluate human risk at low doses,and the uncertainties are enormous.

We hear much about “carcino-gens” in our food. But the mediause the designation “carcinogen”most frequently in conjunctionwith man-made rodent carcino-gens—substances such as Alar (afruit-ripening chemical), saccharin(a synthetic, noncaloric sweetener),and BHA (butylated hydrox-yanisole, a synthetic antioxidant).What ACSH will demonstrate inthis menu is that chemicals that arerodent carcinogens, or that are sus-pected of being such, abound innature.

Many of these naturally occur-ring rodent carcinogens are naturalpesticides—chemicals that plantsproduce to repel or kill predators.Of the approximately 10,000 suchnatural pesticides occurring in thediet, only about 60 have been test-ed in rodent experiments.2 Thesechemicals are found in a wide vari-ety of our food plants: Brusselssprouts, cantaloupe, cauliflower,

cherries, chili peppers, cocoa, gar-lic, grapes, kale, lentils, lettuce,and radishes—to name just a fewthat are not in our Holiday Menu.2

The consumption of smalldoses of rodent carcinogens,whether of natural or syntheticorigin, is quite unlikely to pose acancer hazard to humans. Whenyou understand that carcinogensand mutagens are everywhere inMother Nature’s own food supply,you can see the absurdity of pan-icking over tiny levels in the foodsupply of synthetic chemicals(such as pesticide residues) thatare “carcinogens” when fed inlarge doses over a lifetime torodents. If you chose to believethat every rodent carcinogen wasalso a potential human carcino-gen, and if you then chose toextrapolate directly from rodent tohuman, the background of natural-ly occurring chemicals that peopleconsume at levels close to therodent-carcinogenic dose wouldstill cast doubt on the importancefor human cancer of syntheticchemical residues.

Note, for example, on theHoliday Menu that the bread in thestuffing contains furfural, a rodentcarcinogen. But when you takeinto account the difference in bodyweight between a human and arodent, you will see that, based onthe carcinogenicity data availablefrom the laboratory, a personwould have to eat 82,600 slices ofbread to consume an amount offurfural equal to the amount thatincreased the risk of cancer inrodents.

• 4 • • 5 • • 6 • • 7 • • 8 • • 9 •

AACCSSHH’’ss RReevviieeww ooff tthhee LL iitteerraattuurree oonn NNaattuurraallllyyOOccccuurrrriinngg CCaarrcciinnooggeennss LLeeaaddss UUss ttoo

TThhrreeee GGeenneerraall CCoonncclluuss iioonnss

First, it would be unrealistic toattempt to remove from our foodsupply every known trace of every

natural chemical that tests positive in ahigh-dose rodent test. Even human car-cinogens may be neither toxic nor carcino-genic at very low doses. Imagine, forexample, the unrealistic expectation of“zero exposure” to sunlight—a skin car-cinogen. Even though we know sunlightcan, in high doses, cause human cancers,would we want to dispense with the skin’sproduction of vitamin D under sunlight? Itis important to emphasize that with naturalcarcinogens, as with synthetic compounds,the “dose makes the poison.”

Second, scientists are just scratchingthe surface in their quest to identifynature’s own rodent carcinogens. It isalready evident that we should reject thepresumptions—one might almost callthem superstitions—that the label “natu-ral” means “safe and free of rodent car-cinogens” and that “synthetic” substancesare the only rodent carcinogens. No scien-tific evidence supports these beliefs.

Indeed, a recent review of rodent car-cinogen studies demonstrated that of chemi-cals tested for their cancer-causing potential,

57% of the naturally occurring ones and59% of the synthetic ones were evaluated aspositive: virtually identical percentages4!

It is also important to realize thatbecause of our initial regulatory biasagainst synthetic chemicals, we haveexamined many more of them in rodentcarcinogen tests than we have naturallyoccurring chemicals—even though99.99% of the chemicals humans areexposed to are natural.

Third, the increasing body of evi-dence documenting the carcinogenicity (atleast under laboratory conditions) of com-mon, everyday substances found in naturehighlights the contradiction we Americanshave created up to now in our regulatoryapproach to carcinogens. This contradic-tion can be seen most clearly in the hugediscrepancy that exists between the weightwe have placed on synthetic carcino-gens—we’ve been trying to purge thecountry of them—and, at the same time,the relative lack of attention we havegiven to natural carcinogens. We havelargely ignored natural carcinogens, andhave similarly ignored the fact that thecarcinogenicity rate in rodent experimentsis virtually the same for both naturally

Here’s a calculation relating the rodents’ risk to yours3:

AMERICAN COUNCIL ON SCIENCE AND HEALTHDr. Elizabeth M. Whelan, President

“No human diet can be free ofnaturally occurring chemicals

that are rodent carcinogens.Of the chemicals that people eat,

99.99% are natural.”

—Dr. Bruce Ames andDr. Lois Swirsky Gold,

University of California,Berkeley

NNAATTUURRAALLLLYY OOCCCCUURRRRIINNGG MMUUTTAAGGEENNSSaanndd CCAARRCCIINNOOGGEENNSS FFOOUUNNDDiinn FFOOOODDSS aanndd BBEEVVEERRAAGGEESS

ACETALDEHYDE (apples, bread, coffee, meat,tomatoes)—mutagen and potent rodent carcinogen

ACRYLAMIDE (bread, rolls)—rodent and humanneurotoxin; rodent carcinogen

AFLATOXIN (nuts)—mutagen and potent rodentcarcinogen; also a human carcinogen

ALLYL ISOTHIOCYANATE (arugula, broccoli,mustard)—mutagen and rodent carcinogen

ANILINE (carrots)—rodent carcinogen

BENZALDEHYDE (apples, coffee, tomatoes)—rodentcarcinogen

BENZENE (butter, coffee, roast beef)—rodent carcinogen

BENZO(A)PYRENE (bread, coffee, pumpkin pie, rolls,tea)—mutagen and rodent carcinogen

BENZOFURAN (coffee)—rodent carcinogen

BENZYL ACETATE (jasmine tea)—rodent carcinogen

CAFFEIC ACID (apples, carrots, celery, cherrytomatoes, coffee, pears, grapes, lettuce, mangos, potatoes)—rodent carcinogen

CATECHOL (coffee)—rodent carcinogen

COUMARIN (cinnamon in pies)—rodent carcinogen

1,2,5,6-DIBENZ(A)ANTHRACENE (coffee)—rodentcarcinogen

ESTRAGOLE (apples, basil)—rodent carcinogen

ETHYL ALCOHOL (bread, red wine, white wine, rolls,tomatoes)—rodent and human carcinogen

(continued on page 6)

occurring and synthetic carcinogens. Ofthe thousands of natural pesticides identi-fied, fewer than 100 have been investigat-ed adequately in rodent tests.2

All of our efforts to reduce risks ofcancer should:

• focus first and foremost on substancesand conditions of exposure that havebeen shown in human epidemiologicalstudies to cause cancer. The use oftobacco (particularly cigarettes), over-exposure to sunlight, and dietary imbal-ances are examples of “cancer risk fac-tors” well studied in humans, not just inlaboratory rodents.5

• emphasize dietary patterns, such asincreasing consumption of fruits andvegetables, that have been shown inhuman epidemiological studies todecrease cancer risk.

• reject “carcinogen-of-the-week”scares—those hyped indictments of arti-ficial sweeteners, pesticides, food color-ings, and other synthetic ingredients thatat high doses cause cancer in rodents.

• demand that our government’s regula-tory efforts to reduce cancer risk bebased on sound science, not on emotionor on the sort of neo-Luddite ideologiesthat reject our technological, industrialway of life.

1 The Food Quality Protection Act of 1996 actually moved regulation of pesticide residues onprocessed foods from section 409 of the Food, Drug, and Cosmetic Act, where the Delaney clauseis placed, to section 408. The effect of this change is that the provisions of the Delaney clause nolonger apply to pesticide residues, although they do still apply to food additives.

2 Gold LS, Slone TH, Ames BN. Prioritization of possible carcinogenic hazards in food. In: TennantDR, ed. Food Chemical Risk Analysis. London: Chapman & Hall; 1997:269–295.

3 Data for calculations obtained from: Gold LS, Slone TH, Stern BR, Manley NB, Ames BN.Possible carcinogenic hazards from natural and synthetic chemicals: setting priorities. In: CothernCR, ed. Comparative Environmental Risk Assessment. Boca Raton, FL: Lewis Publishers;1993:209–235.

4 Gold LS, Slone TH, Ames BN. What do animal cancer tests tell us about human cancer risk?:Overview of analyses of the carcinogenic potency database. Drug Metab Rev.1998;30(2):359–404.

5 ACSH does not here reject the use of animal testing for the prediction of human cancer risk, butrather calls for common sense in assessing the results of such tests (for details, see the ACSH book-let Of Mice and Mandates). Further research is needed to establish the mechanisms by which differ-ent chemicals, whether natural or synthetic, cause cancer. Without such work we have no sound sci-entific basis for extrapolating from high-dose rodent tests to the much lower doses typically seen inhuman exposures. ACSH specifically rejects extrapolating from high-dose rodent cancer tests topredict cancer risk in humans. ACSH notes, however, that a chemical, whether natural or synthetic,that causes cancer in many animal species (not just in rodents) at many levels of exposure and inmany experiments should be given regulatory attention. ACSH notes further that considerationshould be given to setting human tolerance levels to such an animal carcinogen. This rational andreasonable approach is now followed by government agencies in the case of one natural (and usual-ly unavoidable) carcinogen, aflatoxin, a substance produced by a fungus that grows naturally onpeanuts, corn, and other products. The Food and Drug Administration, noting the potency of thishuman carcinogen, has set reasonable and workable limits for human exposure to it.

Menu analysis prepared by ACSH staff, directors, and scientific advisors, with technical assistance fromDr. Ruth Kava, Director of Nutrition, and Dr. Leonard Flynn, scientific consultant.Art Director, Yelena Ponirovskaya. reprint 2004—5000 © ACSH

VegetablesBBrrooccccoollii SSppeeaarrssallyl isothiocyanate

BBaakkeedd PPoottaattooethyl alcohol, caffeic acid

SSwweeeett PPoottaattooethyl alcohol, furfural

Rolls with Butteracetaldehyde, acrylamide, benzene, ethyl alcohol, benzo(a)pyrene,

ethyl carbamate, furan derivatives, furfural

DessertsPPuummppkk iinn PPiiee

benzo(a)pyrene, coumarin, methyl eugenol, safrole

AAppppllee PPiieeacetaldehyde, caffeic acid, coumarin, estragole, ethyl alcohol,

methyl eugenol, quercetin glycoside, safrole

Fruit TrayFFrreesshh AApppplleess ,, GGrraappeess ,, MMaannggooss,, PPeeaarrss,, PPiinneeaappppllee

acetaldehyde, benzaldehyde,caffeic acid, d-limonene, estragole, ethyl acrylate,

quercetin glycosides

BeveragesRReedd WWiinnee,, wwhhiittee wwiinnee

ethyl alcohol, ethyl carbamate

CCooffffeeeebenzo(a)pyrene, benzaldehyde, benzene, benzofuran, caffeic acid, catechol,

1,2,5,6-dibenz(a)anthracene, ethyl benzene, furan, furfural,hydrogen peroxide, hydroquinone, d-limonene, 4-methylcatechol

TTeeaabenzo(a)pyrene, quercetin glycosides

JJaassmmiinnee TTeeaabenzyl acetate

AppetizersCCrreeaamm ooff MMuusshhrroooomm SSoouupp

hydrazines

Fresh Relish TrayCCaarrrroottss

aniline, caffeic acid

CChheerrrryy TToommaattooeessbenzaldehyde, caffeic acid, hydrogen peroxide, quercetin glycosides

CCeelleerryycaffeic acid, furan derivatives, psoralens

Assorted NutsMMiixxeedd RRooaasstteedd NNuuttss

aflatoxin, furfural

Green SaladTToosssseedd LLeettttuuccee aanndd AArruugguullaa wwiitthh BBaassiill --MMuussttaarrdd VViinnaaiiggrreettttee

allyl isothiocyanate, caffeic acid, estragole, methyl eugenol

EntreesRRooaasstt TTuurrkkeeyy

heterocyclic amines

BBrreeaadd SSttuuffff iinngg(with onions, celery, black pepper & mushrooms)

acrylamide, ethyl alcohol, benzo(a)pyrene, ethyl carbamate,furan derivatives, furfural, dihydrazines, d-limonene, psoralens,

quercetin glycosides, safrole

CCrraannbbeerrrryy SSaauucceefuran derivatives

or

PPrriimmee RRiibb ooff BBeeeeff wwiitthh PPaarrsslleeyy SSaauucceebenzene, heterocyclic amines, psoralens

• 3 •• 10 •

The American Council on Science and Health(ACSH) is an independent,non-profit consumer education organization concerned with issues related to food, nutrition,chemicals, pharmaceuticals, lifestyle, the environment, and health. ACSH combats the hype, scares, and exaggerations in health reports by putting risks in perspective, with the help of some four hundred scientific and medical experts.

Reach us with questions or donations at:

AMERICAN COUNCIL ON SCIENCEAND HEALTH

1995 Broadway, 2nd floorNew York, NY 10023-5860

Tel. 212-362-7044Toll Free: 866-905-2694

Fax. 212-362-4919ACSH@acsh.org

ACSH.orgHealthFactsAndFears.com

Riskometer.orgTheScooponSmoking.org