Misconception about cancer

U.S. Senate, Environmental
POLLUTION,
PESTICIDES,
AND
CANCER:
Testimony, March 6, 1991
Risk Factors for Cancer
MISCONCEPTIONS
Bruce N. Ames and Lois S. Gold
Dr. Bruce N. Ames is a Professor of Biochanisq
md Molecular Biology md Director of the National Institute of
Enviro~~~~ntd Health Sciences Ccnlcr. Univmiry of California. Bdeley. CA 94720. He is a member of the National Academy
of Sciences and was on their Commission on Life Sciences. He was a manbe? of the National Clncer Advisory Board of the
Ntiond Cmcm IrrJtilu~ (1976.82). His many aw&s include: dxe Gcrrrrl Motors Cmccr R-ch
Fo&on
prire (1983).
the Tyler Prize for environmaul &,icvemcnt (1985x the Gold Medal Awmi of the An&can Jnstirulc of Cbemisls (1991). d,c
Glenn Foundation Award of the Gnontologicll
Society of America (1992). tbe Lnvclw Institutes Award for Excellence in
Fnvironmmti
Health Rewuch (1995). the Ho,& Found&x Rire for Ecotoxicobgy (1996) 4 the J,,xn F’riz (1997). His
380 publications
have resulted in his being tie 23rd most-cited
scientist
(in al1 fields)
(1973.84).
BNAmes@UCLinL4,Bcrkcley.~u
(510)642-5165
Dr. Lois Swirsky Gold is Dirw~~ of the Carcinogenic Potency Roj-xr at the Nationa.! Imtimtc of Envimnmmul HeaM
Sciences Center, University of California. Berkclcy. CA 94720 md a Senior Scientist Lt tke Berkeley National Laboratory.
Berkeley, CA 94720. She has published 80 papers on analyses of animal Ctests and implications for cancer pcvmtion.
interspecies extrapolation and regulatory policy. The cUCi”O~&C
Potexy Databae (CPDB). published ~6 L CRC -k.
analyses resulu of 5ooO chronic. ,0”8-term cmcer tests on 1300 cbemicrls. Dr. Gold h= served on the Panel of Expert
Reviewers for the National Toxicology Rogram the Boards of the Hward Center for Risk Analysis md the ANlnpolir Center.
pnd wss a memberof rhe Hward Risk Mvlngemmt Group. Loi@~trncy.Bakclcy.educy.Berkeley.edu
(510)486-7080
-.
Summary
1. The major causes of cancer are:
a) Smoking:
About a third of U.S. CPIICW (90% of lung ~UCW);
The quarter of the
b) Dietary
imbalances, e.g., lack of dietary fruits & vegetables:
population
eating the least fruits & vegetables bas double the cancer rate for most types of
cancer compared to the quarter eating the most;
c) Chronic infections:
mostly in developing countries;
d) Hormonal factors influenced by life style.
Cancer mortality
2. There is no epidemic of cancer, except for lung cancer due to smoking.
rates have declined 15% since 1950 (excluding
lung cancer and adjusted for the increased
lifespan of the population).
3.
Regulatory
policy focused on traces of synthetic
chemicals is based on misconceptions
about animal cancer tests. Recent research contradicts these ideas:
Half of all chemicals tested in standard high dose
a) Rodent carcinogens are not rare.
animal cancer tests, wbetber occurring naturally or produced synthetically,
are “carcinogens”;
b) There sre high-dose effects in these rodent cancer tests that are not relevant to Lowdo=
human exposures and which can explain the bigb proportion of carcinogens;
c) Though 99.9% of the chemicals humans ingest are natural, the focus of regulatory
policy is on synthetic chemicals.
l
Over 1000 chemicals have been described in coffee:
27 have been tested and 19 are
rodent carcinogens.
l
plants we eat contain thousands of natural pesticides, which protect plants from insects
and other predators:
64 have been tested and 35 are-rodent e&inogenk.
4. There is no convinciog evidence that synthetic chemical pollutants are important for human
cancer.
Regulations
that try to eliminate
minuscule
levels of synthetic
chemicals
are
The U.S. spends
enormously
expensive: EPA estimates its regulations
cost $140 billion/year.
100 times more to prevent one hypothetical,
highly uncertain, death from a synthetic chemical
Attempting
to reduce tiny hypothetical
than it spends to save a life by medical intervention.
risks also has costs, e.g., if reducing synthetic pesticides makes fruits and vegetables more
expensive, thereby decreasing consumption,
then cancer will be increased, particularly
for the
pCl0r.
5. Improved
health will come from knowledge due to biomedical research, and from lifestyle
changes by individuals.
Little money is spent on biomedical
research or on educating the
public about lifestyle hazards, compared to the costs of regulations.
Myths And Facts About Synthetic Chemicals and Human Canczr
Various misconceptions about the relationship between environmental pollution and human
disease, particularly cancer, drive regulatory policy. We highlight nine such misconceptions and
briefly present the scientific evidence that undermines each.
M&conception
II: Cancer rates are soaring. Cancer death rates overall in the U.S. (atIer
adjusting for age and excluding lung cancer due to smoking) have declined 15% since 1950 (1.2).
The types of cancer deaths that have been decreased since 1950 are primarily stomach, cervical,
uterine, and rectal. The types that have increased are primarily lung cancer (90% is due to
smoking, as are 35 W of all cancer deaths in the U.S.), melanoma (probably due to sunburns), and
non-Hodgkin’s lymphoma. (Cancer incidence rates are also of interest, although, they should not
be taken in isolation, because trends in the recorded incidence rates are biased by improvements in
registration and diagnosis (2,311.
Cancer is one of-the degenerative diseases of old age, increasing exponentially with age in
both rodents and humans. External factors, however, can markedly increase cancer rates (e.g.,
Life
cigarette smoking in humans) or decrease them (e.g., caloric restriction in rodents).
expectancy has continued to rise since 1950. Thus the increases in cancer deaths are due to the
delayed effect of increases in smoking and to increasing life expectancy (2,3X
. .
Misconception #Zz Envirhmental
synthetic chemicals an? an important cause of human
cancer. Neither epidemiology nor toxicology supports the idea that synthetic industrial chemicals
are important for human cancer. Epidemiological studies have identified the factors that are likely
to have a major effect on reducing rates of cancer: reduction of smoking, improving diet (e.g.,
increased consumption of fruits and vegetables), and control of infections (4). Although some
epidemiologic studies find an association between cancer and low levels of industrial pollutants, the
associations are usually weak, the results are usually conflicting, and the studies do not correct for
potentially large confounding factors like diet. Moreover, the exposure to synthetic pollutants are
tiny and rarely seem plausible as a causal factor when compared to the background of natural
chemicals that are rodent carcinogens (5). Even assuming that the EPA’s worst-case risk estimates
for synthetic pollutants are true risks, the proportion of cancer that EPA could prevent by regulation
would be tiny (6). Occupational exposure to carcinogens can cause cancer, though how much has
been a controversial issue: a few percent seems a reasonable estimate (4). The main conttibutor was
asbestos in smokers. Exposures to substances in the workplace can be high in comparison with other
chemical exposures in food, air, or water. Past occupational exposures have sometimes been high
and therefore comparatively little quantitative extrapolation may be required for risk assessment
from high-dose rodent tests to high-dose occupational exposures. Since occupational cancer is
concentrated among small groups exposed at high levels, there is an opportunity to control or
eliminate risks once they are identified. We (4) estimate that diet accounts for about one-third of
cancer risk in agreement with the earlier estimate of Doll and Pete(2). Other factors are lifestyle
influencing hormones, avoidance of intense sun exposure, increased physical activity, and reduced
consumption of alcohol.
Since cancer is due, in part, to normal aging, to the extent that the major external risk factors
for cancer are diminished (smoking, unbalanced diet, chronic infection and hormonal factors)
cancer will occur at a later age, and the proportion of cancer caused by normal metabolic processes
will increase. Aging and its degenerative diseases appear to be due in good part to the accumulation
of &dative damage to DNA and other macromolecules (7). By-products of normal metabolism -superoxide, hydrogen peroxide, and hydroxyl radical -- are the same &dative mutagens produced
by radiation. Oxidative lesions in DNA accumulate with age, so that by the time a rat is old it has
about a million oxidative DNA lesions per cell (7). Mutations also accumulate with age. DNA is
oxidized in normal metabolism because antioxidant defenses, though numerous, are not perfect.
Antioxidant defenses against oxidative damage include vitamins C and E and caratenoids, most of
which come from dietary fruits and vegetables.
Smoking contributes to about 35% of U.S. cancer, about one-quarter of heart disease, and
about 400,ooO premature deaths per year in the United States (8). Tobacco is a known cause of cancer
of the lung, bladder, mouth, pharynx, pancreas, stomach, larynx, esophagus and possibly colon.
Tobacco causes even more deaths by diseases other than cancer. Smoke contains a wide variety $
Smoking is also a severe oridative stress and causes
mutagens and rodent carcinogens.
inflammation in the lung. The oxidants in cigarette smoke--mainly nitrogen oxides--deplete the
body’s antioxidants. ~-Thus, smokers must ingest two to three times more Vita-min C than nonsmokers to achieve the wme level in blood, but they rarely do. Inadequate concentration of Vitamin
C in plasma is more common among single males, the poor, and smokers (7). Men with inadequate
diets or who smoke may damage both their somatic DNA and the DNA of their sperm. When the
level of dietary Vitamin C is insufficient to keep seminal fluid Vitamin C at an adequate level, the
&dative
lesions in sperm DNA are increased 250% (9-11). Paternal smoking, therefore, may
plausibly increase the risk of birth defects and appears to increase childhood cancer in offspring
(9,10,12).
Chronic inflammation from chronic infection results in release of axidative mutagens from
phagocytic cells and is a major contributor to cancer (4.13). White cells and other phagocytic cells of
then immune system combat bacteria, parasites, and virus-infected cells by destroying them with
potent, mutagenic oxidizing agents. The oxidants protect humans from immediate death from
infection, but they &o-cause &dative damage to DNA mutation, and chronic cell killing with
compensatory cell division (14,15) and thus contribute to the carcinogenic process. Antioxidants
appear to inhibit some of the pathology of chronic inflammation.
We estimate that chronic
infections contribute to about one-third of the world’s cancer, mostly in developing countries.
Endogenous reproductive hormones play a large role in cancer, including breast, prostate,
ovary and endometrium (X,17), contributing to as much as 20% of all cancer. Many lifestyle factors
such as lack of exercise, obesity and reproductive history influence hormone levels and therefore
risk.
Genetic factors play a significant role in cancer and interact with lifestyle and other risk
factors. Biomedical research is uncovering important genetic variation in humans.
Misamception t3: Reducing pesticide residues is an effective way to prevent diet-related
cancer. On the contrary, fruits and vegetables are of major importance for reducing cancer: if they
become more expensive by reducing use of synthetic pesticides, cancer is likely to increase. People
with low incomes eat fewer fruits and vegetables and spend a higher percentage of their income on
food.
Dietary Fruits and Vegetables and Cancer Prevention.
Consumption of adequate fruits and
vegetables is associated with a lowered risk of degenerative diseases including cancer,
Over 200 studies in the
cardiovascular
disease, cataracts, and brain dysfunction
(7).
epidemiological literature have been reviewed that show, with great consistency, an association
between lack of adequate consumption of fruits and vegetables and cancer incidence (18-20) (Table
1). The quarter of the population with the lowest dietary intake of fruits and vegetables compared to
the quarter with the highest intake has roughly twice the cancer rate for most types of cancer flung,
larynx, oral cavity, esophagus, stomach, colon and rectum, bladder, pancreas, cervix, and ovary).
Only 22% of Americans met the intake recommended by the NC1 and the National Research Council
(21-23): 5 servings of fruits and vegetables per day. When the public is told about hundreds of minor
hypothetical risks, they lose perspective on what is important: half the public does not know that
fruits and vegetables protect against cancer (24).
Micronutrients
in fruits and vegetables are nnticohwgens.
Antioxidants in fruits and
vegetables may account for some of their beneficial effect as discussed in Misconception Y2.
However, the effects of dietary antioxidants are difficult to diwntangle by epidemiological &dies
from other important vitamins and ingredients in fruits and vegetables (19,20,22.25).
Folate deficiency, one of the most common vitamin deficiencies, causes extensive
chromosome breaks in human genes (26). Approximately 10% of the US population (27) is deficient
at the level causing chromosome breaks. In two small studies of low income (mainly AfricanAmerican) elderly (26) and adolescents (29) nearly half were folate deficient to this level. Th,e
mechanism is deficient methylation of uracil to thymine, and subsequent incorporation of urad
into human DNA (4 million/cell) (26). During repair of urecil in DNA. transient nicks *re
formed; two opposing nicks causes a chromosome break. Both high DNA uracil levels and
chromosome breaks in humans are reversed by folate administration (26). Chromosome breaks
could contribute to the increased risk of cancer and cognitive defects associated with folate
deficiency in humans (26). Folate deficiency also damages human sperm (30), cansos neural tube
defects in the fetus, and 10% of U.S. heart disease (26).
3
Other micronutrients are likely to play a significant role in the prevention and repair of
DNA damage, and thus are important to the maintenance of long term health. Deficiency of
vitamin B12 causes a functional folate deficiency, accumulation of homocysteine (a risk factor for
-‘~ heart disease) (31), and misincorporation of uracil into DNA (32). Strict vegetarians are at
increased risk of developing a Vitamin B12 deficiency (31). Niacin contributes to the repair of DNA
strand breaks by maintaining nicotinamide adenine dinucleotide levels for the poly ADP-ribose
protective response to DNA damage (33). As a result, dietary insuiliciencies of niacin (15% of some
populations are deficient (34)). folate. and antioxidants may act synergistically to adversely affect
DNA synthesis and repair. Diets deficient in fruits and vegetables are commonly low in folate,
antioxidants, (e.g., Vitamin C) and many other micronutrients, and result in significant amounts
of DNA damage and higher cancer rates (4,X$35).
Optimizing micronutrient intake can have a major impact on health. Increasing research
in this area and efforts to improve micronutrient intake and balanced diet should be a high priority
for public policy.
Mlsconcep&n&
Human~tocarcinogensandotherpotential
-arepearty
all to synthetic chemicals. On the contrary, 99.9% of the chemicals humans ingest are natural. The
amounts of synthetic pesticide residues in plant foods are insignificant compared to the amount of
natural pesticides produced by plants themselves (36,37). Of all dietary pesticides that humans eat,
99.99% are natural: they are chemicals produced by plants to defend themselves against fungi,
insects, and other animal predators (36,37). Each plant produces a different array of such chemicals
On average Americans ingest roughly 5,000 to 10,000 different natural pesticides and their
breakdown products. Americans eat about 1,500 mg of natural pesticides per person per day, which is
about 10,000 times more than they consume of synthetic pesticide residues.
Even though only a small proportion of natural pesticides has been tested for
carcinogenicity, half of those tested (35/64) are rodent carcinogens, and naturally occurring
pesticides that are rodent carcinogens are ubiquitous in fruits, vegetables, herbs, and spices (38)
(Table 2).
Cooking foods produces about 2,000 mg per person per day of burnt material that contains
many rodent carcinogens and many mutagens. By contrast, the residues of 200 synthetic chemicals
measured by FDA, including the synthetic pesticides thought to be of greatest importance, average
only about 0.09 mg per person per day (36,38). The known natural rodent carcinogens in a single
cup of coffee are about equal in weight to an entire year’s worth of carcinogenic synthetic pesticide
residues, even though only 3% of the natural chemicals in roasted coffee have been tested for
carcinogenicity (5) (Table 3). This does not mean that coffee is dangerous, but rather that
assumptions about high dose animal cancer tests for assessing human risk at low doses need
reexamination. No diet can be free of natural chemicals that are rodent carcinogens (38).
Misconception #5: Cancer risks to humane can be assessed by standard high-danimal
cancer tests. Approximately half of all chemicals -- whether natural or synthetic - that have been
tested in standard animal cancer tests are rodent carcinogens (39.40) (Table 4). What are the
explanations for the high positivity rate? In standard cancer tests rodents are given chronic, neartoxic doses, the maximum tolerated dose (MTD). Evidence is accumulating that it may be cell
division caused by the high dose itself, rather than the chemical per se, that is increasing the cancer
rate. High doses can cause chronic wounding of tissues, cell death, and consequent chronic cell
division of neighboring cells, which is a risk factor for cancer (39). Each time a cell divides it
increases the probability that a mutation will occur, thereby increasing the risk for cancer. At the
low levels to which humans are usually exposed, such increased cell division does not occur.
Therefore, the very low levels of chemicals to which humans are exposed through water pollution or
synthetic pesticide residues are likely to pose no or minimal cancer risks.
It seems likely that a high proportion of all chemicals, whether synthetic
or natural. might be
“carcinogens” if run through the standard rodent bioassay at the MTD, but this will be primarily
due to the effects of high doses for the non-mutagens, and a synergistic effect of cell division at high
doses with DNA damage far the mutagens (41-43). Without additional data on mechanism of
carcinogenesis for each chemical, the interpretation of B positive result in a rodent bioassay is
highly uncertain. The carcinogenic effects may be limited to the high does tested. The recent report
4
i
‘.
of the National Research Council, Science and Judgment in Risk Assessment (44) supports these
ideas. The EPA’s draft document Working Paper for Considering Draft Revisions to the U.S. EPA
..~ Guidelines for Cancer Risk Assessment (44) is a step toward improvement in the use of animal
cancer test results.
In regulatory policy, the “virtually
safe dose” (VSD), corresponding to a maximum,
hypothetical cancer risk of one in a million, is estimated from bioassay results using a linear
model. To +e extent that carcinogenicity in rodent bioassaya is due to the effecta of high doses for the
non-mutagens, and a synergistic effect of cell division at high doses with DNA damage for the
mutagens, then this model ie inappropriate.
Moreover, as currently calculated, the VSD can be
known without ever conducting a bioassay: for 96% of the NCILNTP rodent carcinogens, the VSD is
within a factor of 10 of the ratio MTD1740,000 (45). This is about as precise as the estimate obtained
from conducting near-replicate cancer tests of the same chemical (45).
Misconception t6: Spd.heti~
chemicals pose gmater carcinogenic hezardsthannatd
chemicals.
Gaining a broad perspective about the vast number of chemicals to which humans are
exposed can be helpful when setting research and regulatory priorities (5,3’7,46,47). Rodent
hioassays provide little information about mechanisms of carcinogenesis and low-dose risk. The
assumption that synthetic chemicals are hazardous has led to a bias in testing, such that synthetic
chemicals account for 77% of the 559 chemicals tested chronically in both rats and mice (Table 4).
The natural world of chemicals has never been tested systematically. One reasonable strategy is to
use a rough index to compare atid rank possible carcinogenic hazards from a wide variety of
chemical exposures at levels that humans typically receive, and then to focus on those that rank
highest (5,47,48). Ranking is a critical first step that can help to set priorities for selecting chemicals
for chronic bioassay or mechanistic studies, for epidemiological research, and for regulatory
policy. Although one cannot say whether the ranked chemical exposures are likely to h-e of major or
minor importance in human cancer, it is not prudent to focus attention on the possible hazards at the
bottom off a ranking if, using the same methodology to identify hazard, there are numerous common
human exposures with much greater possible hazards. Our analyses are based on the HERP index
(Human Exposure/Rodent Potency), which indicates what percentage of the rodent carcinogenic
potency (TD50 in mg/kg/day) a human receives from a given daily lifetime exposure (n&kg/day).
TD50 values in our Carcinogenic Potency Database span a lo-million-fold range across chemicals
(49). (Table 5).
Overall, our analyses have shown that HERP values for some historically high exposures in
the workplace and some pharmaceuticals rank high, and that there is an enormous background of
naturally occurring rodent carcinogens in typical portions of common foods that cast doubt on the
relative importance of low-dose exposures to residues of synthetic chemicals such as pesticides
(5,47,50). A committee of the National Research CounciLNational Academy of Sciences recently
reached similar conclusions about natural vs. synthetic chemicals in the diet, and called for further
research on natural chemicals (51).
The possible carcinogenic hazards from synthetic pesticides (at average exposurea) are
minimal compared to the background of nature’s pesticides, though neither may be a hazard at the
low doses consumed (Table 5). Table 5 also indicates that many ordinary foods would not pass the
regulatory criteria used for synthetic chemicals. For many natural chemicals the HERP dues
are
in the top half of the table, even though natural chemicals are markedly underrepresented beczu~e so
few have been tested in rodent hioassays. Caution is necessary in drawing conclusions from the
occurrence in the diet of natural chemicals that are rodent carcinogens. It is not argued here that
these dietary exposures are necessarily of much relevance to human cancer. Our results call for a
re-evaluation of the utility of animal cancer tests in protecting the public against minor hypothetical
risks.
-~
Misc0nception 17: Tbe tonic0logy of synthetic CbemicalE is different fmm that of natural
chemicals. It is often assumed that because natural chemicals are part of human evolutionary
history, whereas synthetic chemicals are recent, the mechanisms that have evolved in animals to
cope with the toxicity of natural chemicals will fail to protect against synthetic chemicals. This
assumption is flawed for several reasons (37.39).
5
a) Humans have many natural defenses that make us well buffered against normal
exposures to toxins (3’0, end these we usually general, rather then tailored for each specific
chemical. Thus they work against both natural and synthetic chemicals. Examples of general
defenses include the continuous shedding of cells exposed to toxins -- the surface layers of the mouth,
esophagus, stomach, intestine, colon, skin, and lungs ere discarded every few days; DNA repair
enzymes, which repair DNA that was damaged from many different sources; and detoxification
enzymes~ of the liver and other organs which generally target classes of toxins rather then
individual taxins. That defenses are usually general, rather than specific for each chemical,
makes good evolutionary sense. The reason that predators of plants evolved general defenses is
presumably ta be prepared to counter a diverse and ever-changing array of plant toxins in an
evolving world; if e herbivore had defenses against only a set of specific toxins, it would be at a great
disadvantage in obtaining new food when favored fwds became scarce or evolved new toxins.
b) Various natural toxins, which have been present throughout vertebrate evolutionary
histoly, nevertheless ceuse cancer in vertebrates (37,40). Mold toxins, such as aflatoxin, have been
shown to cause cancerin rodents end other species including humans (Table 4). Many of the
common elements ere carcinogenic to humans et high doses (e.g., salts of cadmium, beryllium,
Furthermore,
nickel, chromium, end arsenic) despite their presence throughout evolution:
epidemiological studies from various parts of the world show that certain natural chemicals in food
may be carcinogenic risks to humans; for example, the chewing of betel nuts with tobacco has been
correlated with oral cancer world-wide.
c) Humans have not had time to evolve a “toxic harmony” with all of their dietary plant%
The human diet has changed dramatically in the last few thousand years. Indeed, very few of the
plants that humans eat today (e.g., coffee, cocoa, tea, potatoes, tomatoes, corn, avocados, mangoes,
olives, and kiwi fruit), would have been present in e hunter-gatherer’s diet. Natural selection
works far too slowly for humans to have evolved specific resistance to the food toxins in these newly
introduced plants.
d) DDT is oRen viewed es the typically dangerous synthetic pesticide because it concentrates
in the tissues and persists for years, being slowly released into the bloodstream. DDT, the first
synthetic pesticide, eradicated malaria from many parts of the world, including the U.S. It was
effective against many vectors of disease such as mosquitoes, tsetse flies, lice, ticks, and fleas.
DDT wes also lethal to many crop pests, and significantly increased the supply and lowered the cost
of food, making fresh nutritious foods more accessible to poor people. It wes also remarkably nontoxic to humans. A 1970 National Academy of Sciences report concluded: “In little more than two
decades DDT has prevented 500 million deaths due to malaria, that would other wise have been
inevitable (52).” There is no convincing epidemiological evidence, nor is there much toxicological
plausibility,
that the levels normally found in the environment ere likely to be a significant
contributor to cancer. DDT wes unusual with respect to bioconcentration, and because of its chlorine
substituents it takes longer to degrade in nature then most chemicals; however, these are properties
of relatively few synthetic chemicals. In addition. many thousands of chlorinated chemicals are
produced in nature and natural pesticides also can bioconcentrate if they ere fat soluble. Potatoes,
for exemple, naturelly contain the fat soluble neurotoxins solanine and chaconine, which can be
detected in the bloodstream of all potato eaters. High levels of these potato neurotoxins hsve been
shown to cause birth defects in rodents (37).
e) Since no plot of lend is immune to attack by insects, plants need chemical defenses -either natural or synthetic -- in order to survive pest attack. Thus, there is a trade-off between
naturally occurring pesticides end synthetic pesticides. One consequence of disproportionate
concern about synthetic pesticide residues is that some plant breeders develop plants ts be more
insect-resistant by making them higher in natural toxins. A recent case illustrates the potential
hazards of this appmach to pest control: When a major grower introduced a new variety of highly
insect-resistant celery into commerce, people who handled the celery developed rashes when they
were subsequently exposed to sunlight. Some detective work found that the pest-resistant celery
contained 6,200 parts per billion (ppb) of carcinogenic (end mutagenic) psoralens instead of the 800
pph present in common celery (37).
Misconception #FL-Pesticides and other eynthetlc r.hemicaIs are dim-up&g our hormonea
Synthetic hormone mimics ere likely to be the next big environmental issue, with accompanying
large expenditures. Hormonal factors are important in cancer (Misconception t2). A recent ho*
‘.
(531, holds that traces of synthetic chemicals, such as pesticides with weak hormonal activity, may
contribute to center end reduce sperm counts. The book ignores the fact that our normal diet
contains natural chemicals that have estrogenic activity millions of times higher then that due to
the traces of synthetic estrogenic chemicals (54,551 end that lifestyle factors can markedly change
the levels of endogenous hormones (Misconception X2). The low levels of exposure to residues of
industrial chemicals in humans are toxicologically implausible es a significant cause of cancer or
bf reproductive abnormalities, especially when compared to the natural background (N-56). In
addition, it has not been shown that sperm counts really are declining (577, and even if they were,
there ere many more likely causes, such es smoking and diet (Misconception Y 2).
Misconception x9: Regulation of low hypotheticd risks advances public health. There is no
risk-free world, end resources are limited; therefore, society must set priorities based on which
risks ere most important in order to seve the most lives. The EPA reports that its regulations cost
$140 billion per year. It has been argued that overall these regulations harm public health (58-611,
because “wealthier is not only healthier but highly risk reducing.” One estimate indicates “that for
every 1% increase in income, mortality is reduced by 0.05%” (59). In addition, the median toxin
control program costs 58 times more per life-year saved than the median injury prevention program
and 146 times more than the median medical program (62). It has been estimated that the U.S. could
prevent 60,000 deaths a year by redirecting resources to more cost effective programs (63). The
discrepancy is likely to be greater because cancer risk estimates used for toxin control programs are
worst-case, hypotheticel
estimates, end the true risks et low dose ere often likely to be zero
(5,38,61)(Misconception t5).
Regulatory efforts to reduce low-level human exposures to synthetic chemicals ere expensive
because they aim to eliminate minuscule concentrations that now can be measured with improved
techniques. These efforts we distractions from the major task of improving public health through
increasing knowledge, public understanding of how lifestyle influences health, end effectiveness
Basic biomedical research is the basis for
in incentives and spending to maximize health.
improved public health end longevity, yet its cost is less then 10% the cost to society of EPA
regulations.
Rules on air and water pollution ere necessary (e.g., it wes e public health advance to phese
lead out of gasoline) and clearly, cancer prevention is not the only reason for regulations. But worst
case scenarios, with their con~comitant large costs to the economy, are not in the interest of public
health and can be counterproductive.
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;lyv.y? Ifirk Ad.: IO:14
Gcqh. M. (w90) How much unEc* can &A &a
Amc~. B.N.. Sbigcnrg,. M.K., H,~.z,,. T.M. (,99J)Oxidmu,
.ndaxi&nu. .d tk dcpcnemive diruscs d&g.
Proc. Nd. Ad.
sci. USA; w:79,5-7922.
Pam R. Loocz. AD.. Borchm. J.. II,,,,,. M.. Ha&, C.. I,. (19%) Mw‘zIi~fra
Sm+i”g in Dw.loprd Cc”““iu
1950so-2co0.
oxf~d.‘En&nb:
tied
hi”e’“i;y
Pr&.
Fnga. C.G.. Ma.&+
PA.. Shigclug,. MIC. HclkxA, HJ.. ,.=A. RA.. Amu. B-N. (1991) I\lsabic add F-s
.gainst
cndogsrmr oxidarivc damage in hmnm ‘psm. Pra. Nd. Acd. Sci. USA, 88:1 lWA-llo3a
Ames BN. MM
PA. Fr.g.. C.G.. sligmng~ M.K.. Hqm. TM (1994) AmJo*r
prrvcnsol cfbhh defcpl mdcmacr.
In: h&is&
D.R O&n, A. cds. Mok.MaGzted DcrrIapvwl
TotiiW NW Ydr: plenum FXbJithipg Cmpn$m. 243-25.9.
Fng.. CG.:M&.
PA.. &mb&
A,., RmpsL DA,.. Ames. RN. (19%) smating md law tiudnt
MI
m-se
mwd.dn
d.m.gc m +-em DNA. Mu. Ru.; 36,:,9%20X
Ji B.-T. Shq K-0.. line MS., zhmg. W..Wxbold.q
S. Ga. Y.-T.. Ybtp. D.-M.. Tim.F. (1997) PumaI ciga~~e nnW
ad the
risk of cbildhd ca,c.zr mm-.~goffrpring d n.m.16~
m&en. I. cfNod. CF. I+; ss:Ug-y.
Cxistm. S.. H,gcm, TM.. Shigcnng,. M.K. tics. B.h. (1997) Chrmic idcdm d dlmm~on
lud m nytiy
and u”cer. In:
Puloulcr. J. Htig,
S., Cdr. “icrobu nm,dMnii s.aq: ,n,<crim 01 o 6yu o,Cawr.
‘++d: Oxford Uruvsn~,’ Rnl. 0 )x”‘.
Sh.cm E hiim,
EJ., Covey. JM.. Kcim. K fv ., Pmsr, M (1988) AmvUcd =.a+
mdu? plmged DNA dmmgc m
ncighbdrin; cds [pbbrbsd cm,,,,,, ,pr~
in Gtiogcsris
1989 M.~IM):6281.
Camwgrrurr.
9:2297-2301.
YundGm. K.. Mikr. B.E.. Hcancr. G.H. (1986) Macrophagc-mcdiucd ao,
d drag-ruirun, variti
h n mouic munm~ry
ulmor u.0 Enc. cami Rzr.: 4632346.2431.
HcndcB.E., Roar. R.K.. pi~c, MC. (1991) Townrd the primly prrvcntim d unccr. SC~KI: 254:1131-1138.
Fcigclron. KS., Hmdsrwn. B.S. (19%) Ermgau md bru,, -I.
C.rc*og.ncri:
17:2279-2284..
Blak. 0.. Pamnon, B.. Suhr. A. (1992) Fmi~ vegctabla .nd c.nmr prw&m:
A review ofthe =@cmiologic midcncc. NW. ord
c2nc: 1&l-29.
c,ance, covrrs COnwO~~2:325-357.
Slcinmuq K.A.,Pcocr. ,.D. (1991) “egcubkr, fmi< ad U~CLI. I. Epidemic4
Hi& MJ., Giacor~ A.. C&U
CPJ. (,w) Epidunidogy o/D&r md GKU. 74 ut Su~ru. En nd: Elks Honuccd Ii&d.
Htmkr. DJ.. WiMf WC. (1993) Dia. Wy six. md bran mm. Epidmd. hr.; 15:110-l B2.
7
21.
28.
29.
30.
31.
32.
33.
3%
39.
40.
41.
42
43.
M.
45.
46.
47.
48.
49.
50.
51.
52
53.
54.
55.
2:
59.
60.
61.
62
63.
64
BLxk. G. (19.~2) ~hlhcd.u NTPO” , dc for .ntioxidmu in reducing cana, rirk. No. Revirw~M:207-213.
Pmmrwn, B.H., Bkd, G., Rolcnkrgcr, W.F., Pm. D.. Kahk, LL (19%) Fti md vcsebk. m the htiun
die,: D.u fm the
NHANE.5 n mrvq. Am. J. Pvblk “#‘ah: 80:,443-,449.
A Natimd Onssr hrulirti Grqhic. (19%) why UI five7 1. Nd. 6rc. Id.: M:1314.
srinmcu. EA., Pcucr, I.D. (19-s) vsgcIxt4u. hiI. an.3 ODccr prm.ntieo: * mc,w. 1. Am Did Auoc.: 96:1027-,039.
Blount. B.C., M.&M.M,Wchr
C. ~.cGls~or !J.. Hirq R, Wmp. G.. Wid;nmum~c.S.N..
E”mm.R.B.. Ama. B.N. (1997)
Impliohnr
for cancer d nsvmd
Fohtc &h&r+
CYIkc, ud
llL,,’ mrrmdon mm hDNA d dumwromc hukqc
dunqc. Prm. Nod Acad SC;.LISA. W:i prca.
Scnti. FR, Pikh. S.M. (1985) hdysis d fdlts dul fm Lc -d
NuiaYl Hulrh d N~titim Eumhutian SUWCYWANES
Ig. 1. NUT.; 115:139&402
B&y. LB., W+,,er, EA.. ~&in&s
GJ., A+,
P.E.. i\ppkdmt H.. titi.
C.C.. tir~qnni
I.. Dimhtg. IS. (1979) Fehio ud
baurboldr. Am I. C,ba. N&T.:
k-m ~talu( and kmudagiul
‘mmng,‘in p-y
bid c.lddy psnm‘ h
urbo lowillanx
32:2346-2353.
B.&y, LB., W.g~r, P.A., ~l,ri.t&in. GJ.. Dwis, C.G.. Appkhf.
H.. A”+.
PE. Dx=y. E.. D+=+. J.S. (1982) Fob.% .od irm
dducmu
fm w&l la-mconc hauubol.,,. Am. 1. C,k. NW.;
.uuu md ban.loiogiul
finding‘ in k&k ad Spnirh-Amaiun
35:1023-,032.
Wdlok
L. Wmdrv A.. Lmb. R. Amer. B. (19947)Nuti6m.l d @ve
drica d ~-km- 1d.w 10 fcnitiry in&.-a in
n-m&i
mm. FAkiJ.
(Abihic,); in hi.
;$a,
Y. (19%) “iumi, B-12.h: nqkr. E.E. Fikr.LJ.. ds. PrueuXwLdgr
in Nuairin.Wuhingtm.
D.C.:JlSIPmr,
191
p&u
miring
vndl into
G&nm.sin.k.
S.N.. Fidl. s. (1994, Bmc marroly ecus fmml viumin 812. d fdus&ciau
DNA. Blch-&3:1656h
Zhng. I.Z. H&g.
SM.. Svadtid,
ME (1993) Pdy(ADPtissucl d ti.i,,~m~
mu 1. NM,,.: 123~1349-55.
,,ccba,. E.L (1993) N&in d&&q
.d MOC, in wanm.,. An. Cdl. NW; u:412-6.
in rbc US pqxhim.
Am.,. Ch. NW.; 50338-16.
Suhr.A.F..Blod;.G..,unc~.L.D.(,989)Fd~~~udfoodArm,. BN..Pmfcl, M., cd& Lx (19w) Diary pcl.iddc‘ (99.99% dl+?=l,.
Pra. Nd. .k‘d. sci. US& 11’1:777-7781.
A,,,+ ~2-4.. pm& &A.,~,
is. (,9-x,) NC,,,~, c,mnkd .I,., .)ntkm obcmiul,: Cmpndvc
totigyy.
Proc. Nd. Acd Sci.
USA: rw782-7786.
d p&k
c.rhqtis
hunir in fd. Tn: Tmrmt, D.. .A. Fee-4 Ckmid
Gold. LS.. She, T.H.. Am,. BH. (199’0 Prioritiut*n
Rid AmlyrL. Lmdm: Gy.m
L Ha,, Ud. in ~CII.
~mmc,.B.N.. G.,M, LS., Sh+mga, h4.1~ (~5~6P Cmmpcvauian.
,dcz~t high&
-ruxts
d risk usarmenl RLtti..:
,6:613x517.
Gold. Id.. She. T.H., her. B.N. (1997) Ovewicw md t+lc
.rx.l YI d dx a+mic
7ri.rr
PolmL-$ Md GLMIOXiCR LLb.
Boer Rum. l$.%~~~z~~4
Lsy
_D__,-., F .A,~
-...- “&k - . . .. “fca,&0~bc
. . -- .~~.~~
~uttcruonh, B. cmcuy. R., hhgm,. K. (1995) ,i ,rnlcgy fcie,~iJiahing mode d aaim d chemiul aknopen~ .I. guide for
qruchu
m ,iik ~,ss,mm,. Cant. ,a,.: 93:129-146.
AIRS. B.N.. Sbigmq,. M.K.,, Gold. LS. (1993) DNA krims. iduibk
DNA n+r. -6 cell ditiim: lbrcc key fsams in
mvlngmcrir and urcinogmsrra. Environ. HLd,h Pmprct.; 101(supp15J:35~.
her, B.N., Gold, Ls. (19%) olaniul
cxchogencsh: Tm many rodm ordnaemr. Pnx. N&l. AC& Sci. USA, 87:7772-7Th5.
Nsdonnl Ruurc,, Cam&.,. cd. (1994) Scirncr and hdgnuti in Rirt A.mrssmum. (Caomioss cm Ri,k Anesmncnt of Huudour Air
PO”“unU. wuhingcn. D.C.),
Gaylm. D.W.. Gold. 1s. (1995) Quick caim.u d Ihc quhtory rLavlly ds dac bud m lhc muimum lnknlcd doe fa mdent
bilwruys Rqd. Toxxico,. Pkmulcd.: 22:57-6.X
Gob, LS. Slce T.H. Stem B.R M.&y. N.B.. Am,. BN. (1993) PC”& clrdnogmic hazards fm n.tw.l .“d I+.+
ci,m;n;iul.:*s~
c.&,k,.
i: C.&m CR.. d. Cm,aivr
,hi,avn.wl
RL~hwa..-d.
Boer Ram, FL: Lewis hb4hhen.
203-235.
- .. ..
_ ^
. ^ I.^_~ . .~. --~~:L*- ..A---~c-&,
scklce;&$.7,.2~,
Anus.
an..hug.w.
IL. b.n~.
I..>. (,x4,
luNun
n: rrynu famed by cdling fmd. cmprirm
0, bknsuy
Gold. LS.. Slar. T.H.,,M&y,
N.B., Amer. B.N.%%ie=?
rcwks with dlcr *mud*
in *e Cutiqenic
PoImcy Iklabau. c hnc. hr.: 83~21.29.
- .. . .
.
.
_
^
r
1
^..
n-LI-.L
.
Cold. LS.. sla nc. ~I.“.. MMley,n.d.. CI.mlxe,. “_T)_,IK.7M~.
q c4a.b.~ lm Gold.
L, Amer. BX. (195T c%rcinxmic
LS.. Zcigcr. E...~d,. “~~t
ofcarc~geic
PO~my f.+ $h‘mxici‘y
D‘uabalu. Bca R-m, a, r c Plcrr, 1=x5.
Gold. L.C. G.lfti;e~ G.B.. she. T.H. (ww) salmg prm”~.zcr MO ng pdbls spdnogmic ham* m the wmkpkce. In: “h*
Caret ApplLnriar. IimhU~w. ad
CM. Chis,i.,,i. DC.. Kelwy, LT., cd,. CkmbdRirt
Auurnud 0-* *rcup.ridNedIk.
.I,
-~ UrcolWwu
ran
1 m.LI:.L:-_
c _,._ a,
.-YWC
rrorpcr,.
ns‘-L,:
‘“V‘u,un~
Y’“,W
7.-JXI,
Nuicd Rcwnh Ccmcil. (199.5) Clrcinogrm and Aryi.mcvur~~
in ha HD&I: d Cqwhn
JNmrally
Occwin# Md
5 uknk Subruncc,. Whinpm
DC.: N&d
Au&my Prcrr.
x. a~.,., Aodrmy of Mcnar (U.S.). Cmmime m Rexarch in Ihc lift Sckncu. cd. (1970) Tk Lifr ScirKu: Recrnr Pqnss
md A.w,icc&m 10 “au,,,,, Atmti,. ,k Wdd c,‘Bidwla,_
Rurorcl. R~qvirmwntfo, rk F”lw~. (X,&m., Audemy d Sdslccr.
Wuhinglal). 526 p.
Cdhn, T.. Lhmmski, D.. Mycn. JP. (1’9%) Our Sdrn Furwe: Arc w Tktitig
ow Ferlilily. IruUi~mce. ad Swid?:
A
S&d,% Ddrcrivr Sm-,. NW Yak: hnm.
mk in hum.n die.r
Ehrm. Sn.
Sdc. S.H. (199.4, Disuw and cnvimnm at,,, crcmgcnr md awi~vogmr .,A their pa&k
PoNbion h!&.; 1129.33. ’
Sdc. S.H. (1995) Fntimmvl
and diary uvogsl, .nd hum.,, hulih: L the a problem? Em. Health Pap.: 103~346451.
Rhdi, IL, B,&, G. (,m) phyloc,,rc.p omvn, dfdr
--A cmpdivm
d lim-mm vduu. Nxr. Cmc.: 26:19%.
Koku G. (15%) Muwing ma up. .pana by ,pcm. nhs New Yqt Tbw. fiy 4:W.
Ed&). (=‘-I).
Vim.;. W.K. (1992) F&i Trdeo~.
Clxfod. C,&nd: orford “m.hty
hsr.
Sh.n.hm. I.D., TX-,
A.,,. (19%) How to t.,k .kzcu tisk: How vc&hlmtioned rcgtimr
un UI: ‘Ip13. WutigM.
D.C.
Hait. c Fauld.d.m.
Hah.bW.
cd (1%) RLk Cm.v, mdtivea Sad: Guing Burrr Rc.dfsfraRq&icm
Hex Y&z oxfad Univentiy Press.
Gnhm. J. ‘Wimcr. J., CA. (i995) Rid wrsau RLk Tmdeofls Lt Proucr+ Hdli
ad Ik EmvironnwnI. htidge.
tiauchu~:
H.n.rd UAkity
Pru,.
KC. Gdmn, I.D. (195) Fivchundd
life-utig
Tmgr.T.0.. A&am, MB, Plirkin,J.S.. S&an. D.G.. Siegel. I.E.. WM.
ikwcruionr
d tkir scdfenivcncrs.
Rtik AMI ‘.: 15:369-389.
In: Hh, R. cd. Rirb, Cmlr.
d
hvcmnenu b Mewing.
Tmgs. T.O.. Gnhm. I.D. (,$%I The oppommity cat, d h.+u?d
md tiwr.kwd:
Ge”ing &t,.r R.rdrrfrm
R&L. &,. New Yak NY: C&d “nircni~y Pms. 165.173.
bnu.I.RM..
lJlh.4. B.M.. “dcrio.M.G.,F ‘~~.,ccu.
L. Han ER.. Rlioo. A,.. Baa, R-R.. Fti. H-L, Gan. JJ.. Klein.
..’ L. A,hkh
&dmlhl for lumtigmi~y
in micr.: A pldimmlly nce 3.
M.. MilchdL L. FWmx. I. (1969) Bims.y d pcsicjdcr and il!d”,lh
Nnd.C.nc.h.:
42:1101-,114.
8
Table 1. Review of epidemiological studies on cancer showing proteaion
-.~ vegetables
Fracnon of studies
showing significant
Cancer site
cancer protection
Epitbelial
Lung
24t25
Oral
9i9
Larynx
Esophagus
Stomach
Pancreas
Cervix
Bladder
Colorectal
Miscellaneous
Hormone-dependent
Breast
Ovarylendometrinm
Prosrate
Total
Source: Block et al. (18)
by consumption of fruits and
Relabve nsk (medmn)
Low vs. High Quartile)
of consumption
2.2
2.0
1.3
1.8
1.3
Table 2. Carcinoeenicitv
_
- of natural .Dlant .Desticides tested in rodents (Fungal toxins are not
included.)
acetaldehvde metbylfonnylhydrazone, ally1 Isothlocyanate, arecohne.HCl,
Carcmogens:
N=35
benzaldehyde, beniyl a&tat& caffeic acid, catechoi, clivorine, coumarin,
crotonaldehyde. cycasin and methylazoxymethanol acetate, 3,4-dihydrocoumarin.
estragole, ethyl acrylate. NZ-g-glutamyl-p-hydrazinobenzoic
acid, hexanal
methylformylhydrazine,
p-hydrazinobenzoic acid.HCl, hydroquinone. lhydroxyanthraquinone, lasiocarpine. d-limonene. 8-methoxypsoralen. N-methyl3-methylbutanal
a-methylbenzyl
alcohol,
N-formylhydrazine,
methylfonnylhydrazone, methylhydrazine. monocrotahne. pentanal methylformylhydrazone, petasitenine. quercetin, reserpine. &role, senkirkine, sesamol,
symphytine
Noncarcinogens:
N=29
atmpine, benzyl alcohol, biphenyl. d-carvone, deserpidine, disodium glycyrrhizinate, emetine.2HCl. ephedrine sulphate. eucalyptol. eugenol. gallic acid,
geranyl acetate, b-N-[g-l(+)-glutamyl]-4-hydroxy-methylphenylhydrazine.
acid,
glycyrrhetinic acid, glycyrrhizinate. disodium, p-hydrazinobenzoic
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.
chilli pepper, chocolate milk, cinnamon, cloves, cocoa, coffee. collard greens, comfrey berh tea,
corriander, currants, dill, eggplant, endive, fennel, garlic, grapefruit. grapes, guava, honey,
honeydew melon, horseradish, kale, lemon, lentils, lettuce. licorice, lime, mace, mango,
majoram. mushrooms, mustard, nutmeg, onion, orange, paprika, parsley, parsnip, peach, pear,
peas. black pepper, pineapple, plum, potato, radish, raspberries. rhubarb, rosemary, rutabaga,
sage. savory. sesameseeds, soybean, star anise, tarragon, tea, thyme, tomato. turmeric. and
t&p.
Source: Gold et al. (38)
9
Table 3. Carcinogenicity in rodents of natural chemicals in roasted coffee.
TJos1uve:
knzofuran. benzo(o)pyrene. caffetc acid,
al&h d be aid h d be
N=19
$e!chol ‘1 >5 6?ibe~&~race~?bsnol
ethylbenzene, formaldehyde, furan,
fmfural,‘hyh~gen peroxide, hydro&none. iirnonene. styrene, toluene, xylene
Not positive:
N=8
acrolein, biphenyl. choline, eugenol. nicotinamide. nicotinic acid, phenol,
piperidine
Uncertain:
caffeine
Yet to test:
- loo0 chemicals
Source: Gold et al. ~(40):
Table 4. Proportion of chemicals evaluated as carcinogenic.
Chenucals tested m both rats and once
330/559
(59%)
Naturally-occuning chemicals
131127
(57%)
Synthetic chemicals
2571432
(59%)
Natural pesticides
35Ki4
(55%)
Mold toxins
14/23
(61%)
Chemicals in roasted coffee
19/28
(68%)
Innes negative chemicals retesteda
16134
(47%)
Drugs in the Physician’s Desk Reference
117l241
(49%)
Chemicals tested in rats and/or mice
* The 1969 study by Innes et al (6.4) is frequently cited as evidence that the proponion of carcinogens
is low. as only 9% of 119 chemicals tested (primarily pesticides) were positive in cancer tests on mice.
However, these tests lacked the power of modern tests (40). We have found 34 of the hmes negative
chemicals that have been retestedusing modem protocols: 16 were positive (a), again about half.
Source: Gold er al. (40).
10
[Chemicals
Table 5. Rankincc Possible Carcinoneoic Hazards from Average U.S. Exposures.
that occur naturally in foods are in boih.] Daily human crposurct Reasonable daily intakes arc used to
facilitate comparisons. The calculations assume a daily dose for a lifetime. Possible harnrd: The human dose of
rodent carcinogen is divided by 70 kg to give a m&Q/day of human exposure, and this dose is given as Ihe
percentage of the l-D% in the rodent (m&/day)
to calculate the Human &posurelR&nt
Potency index (HERP).
i.e.. 100% means that the human exposure in mg/lg&ay is equal lo the dose c&mated m give 50% of the rcdents
tumors. ITI50 values used in the HERI’ calculation are averages calculated by Iaking the harmonic mean of the
TD5@s of the positive te.s~~in that species from the Carcinogenic Potency D&base. Average TDm values, have
pcssible hazard.
t&~&uhted
separately for r&s and mice, and the more potent value is u%d fOr d~ulating
Pnrrihle
PMencv
. “-“.“.HWllLUldcseof
TDSO bvvkd~y~
hazard:
rodent carcinoaen
Rats
Mice
HERP (90)
Average daily US exposure
1.52
(7.45)
140
EDB: wc+ers (high exposure) (before Ed~ylene ditromick:, 1% mg
1977)
Clotibrate. 2 g
17
Clofibke
14
Phenobarbital, 60 mg
Phenobarbital, 1 sleeping pill
13.9
1,3-Butadiene, 66.0 mg
6.8
13.Bufadiene: rubber workers (197886)
Te&achloroetbylene. 433 mg
101
6.1
Tebachlomlhy1ene: dry cleaners with
urn
dry-to-dry units (198wo)b
4.0
Fomxildehyde. 6.1 mg
2.19
Formaldehyde: worlrers
Ethyl alcohol, 13.1 ml
9110
2.1
Beer, 25; g
Mobile borne air (14 hoursiday)
Formaldehyde. 2.2 mg
2.19
1.4
Methylene chloride, 471 mg
724
Methylene chloride: woken (194oS0.9
8W
Ethyl alcohol, 3.36 ml
9110
0.5
Wine, 28.0 g
C-1
Formaldehyde, 598 mg
2.19
(43.9)
0.4
Conventimal home air (14 hoursldav)
Caffeic acid, 23.9 mg
297
0.1
Coffee, 13.3 g
(4900)
Caffeic acid, 7.90 mg
297
0.04
Lettuce, 14.9 g
(4900)
Safrole, 1.2 mg
51.3
0.03
Safrole in spices
ii”
d-Limonene,
4.28 mg
0.03
Orange juice, 138 g
;I;
d-Limonene,
3.57 mg
0.03
204
Pepper, black, 446 mg
Mixture
of hydrazises,
0.02
Mushroom
(Agoricus bisporus
2woo
etc. (whole mushroom)
2.55 g)
Csffeic acid, 3.40 mg
0.02
297
Apple, 32.0 g
(49w
118
Catechol, 1.33 mg
0.02
Coffee, 13.3 g
Furfural,
2.09 mg
I??
0.02
Coffee, 13.3 g
(633)
BHA. 4.6 mg
0.009
745
BHA: daily US avg (1975)
ww
Dimethylnitrosamine,
(0.189)
0.124
0.008
Beer (before 1979), 257 g
726 ng
18 ag
0.0032
0.008
Aflatoxia:
daily US avg (1984. Aflatoxio,
(+)
891
Coumarin,
65.0 mg
13.9
0.007
Cinnamon, 21.9 mg
Hydroquinoae,
333 mg
82.8
0.006
Coffee, 13.3 g
E2
2140
Saccharin. 7 mg
0.005
Saccharin: daily us avg (1977)
C-1
c
Aniline,
624 mg
0.005
Carrot, 12.1 g
(F-1
Cnffeic acid, 867 mg
:Lz
0.004
Potato, 54.9 g
gz;
Caffeic acid, 858 mg
297
0.004
Celery, 7.95 g
197
Furlural,
500
“g
0.004
White bread, 67.6 g
(683)
.__
0.003
d-Limonene,
4Bb mg
Nutmeg, 27.4 mg
(-)
77.5
0.003
Conventional home air (14 hour/day)
Benzene, 155 mg
f%
297
Caffeic acid, 374 mg
0.002
carrot, 12.1 *
(49w
7.9
0.002
Elhylene thiourea: daily US avg (1990) Ethylene tiourea. 9.51 mg
G&Z
DDT: daily us avg @fore 1972 ban)1 [DDT, 13.8 mgl
0.002
(84.7)
297
Caffeic acid, 276 mg
0.001
Plum, 2.00 g
$2;
745
BHA. 700 mg
BHA: daily US avg (1987)
0.001
297
Caffeic
acid,
240
mg
0.001
(4900)
Pear, 3.29 g
6.09
Table 5 conki.
0.001
O.WO9
@JDMH: daily US avg (1988))
Brown mustard, 68.4 mg
O.ooO8
[DDE: daily US avg &fore
o.ocQ7
o.ooo7
O.CQ36
0.@305
O.CON
TCDD: dailv US PYP(1994)
Bacon. 11.5-g
- ’
Mushroom (Agaricus
bisporur
2.55 g)
Jasmine tea, 2.19 g
Bacon, 11.5 g
O.@Nl
Bacon,
O.CiO4
[EDB: D@y US avg (before 1984
1972
tdl
11.5 g
t&l
O.KO4
o.coo3
o.coo3
o.cno3
o.oco3
o.ooo2
Tao water. 1 litex (1987-92)
M&a,
-1.22 g.
Beer, 257 g
Trm water. 1 liter (1987-92)
ca;baryl: daily vi avg (19%)
Celery, 7.95 g
O.C-302
o.OOco9
O.oooO8
O.oooO8
O.oooO7
Toxaphene: daily US avg (1990)
Mushroom
(Agaricus
bisporus, 2.55 g)
FCBs: daily US avg (1984-86)
DDE/DDT: daily US avg (1990)
Parsnip, 54.0 rag
o.oooo7
OJXXO6
O.COOO5
O.MOO5
Toast, 67.6 g
Hamburger, pan fried, 85 g
Estragole in spices
Parsley, fresh, 324 mg
o.lxiw3
o.coxI2
O.cwol
Hamburger, pan fried, 85 g
Dicofol: daily US avg (1990)
Cocoa, 3.34 g
O.CKOl
0.000005
0.000001
0.m
o.ixcoOO1
KJDMH. 2.82 mn (frcm Alar)1
Ally1 isothiocykate,
6i.9 mg
-pDE, 6.91 mgl
(-4
96
3.96
(-)
1-j
12.5
TCDD. 12.0 pi
Dieihylniuos2mine, 11.5 ng
Clutamyl-p-hydrarinobeazoate, 107 mg
Benzyl acetate, 504 mg
N-Nitrosopyrrolidine,
196 sg
Dimethylnitrosamine,
34.5 ng
IEDB. 420 wl
o.lxoO2.35
0.0237
(O.oool%)
Bmmodichl-,
13 mg
d-Limooene,
48.8 mg
Furfural,
39.9 mg
Chlomfcrm. 17 mg
Carbaryl, 2.6 mg
8.Metboxypsoralen,
4.86 tug
Toxaphene. 595 ng
p-Hydrazioobenzoate,
28
i-s
(-1
(0.799)
0.124
(0.189)
1.52
(7.45)
47.7
LEa
gE;
14.1
32.4
I;;$
90.3
;I;
c-1
5.57
454c
1.74
f-1
32.4
;g;;;,
(41.3)
4.29c
16.9
mg
FCBs, 98 “g
DDE, 659 ng
I-Metboxypsoralen,
1.57
mg
-Urethane, 811 ng
PLIP. 176 ng
Estragole, 1.59 mg
8.Methoxypsoralen,
1.17
mg
MeIQx, 38.1 og
Dicofol. 544 ng
a-Metbylbenzyl
alcohol,
4.3 mg
Urethane, 115 ag
IQ, 6.38 ng
Lindane. 32 ng
F’CNB (Quhtmne), 19.2 “g
Chloroknzilate. 6.4 ng
Beer, 257 g
Hamburger, pan fried, 85 g
Lir!dane: daily us avg (1990)
FCNB: daily us avg (1990)
Chlorotenzilate: daily US avg
(1989)
Chlomtbalonil: daily US avg (1990) Chlomtionil.
~6.4 ag
<O.oGoxQOl
Folpet. 12.8 “g
0.000000008 Folpet: daily US avg (1990)
Captan, 11.5 ng
0.000000006 Captan: daily US avg (1990)
aI.= = m &m h (-JJDB; (-) = negadve in cancer test (+) = positive canca t&s)
32.4
1.99
kii
WJ
c-4
(-)
EiP
(-4
(24.3)
32.9
6)
16.9
g3
;I;
71.1
93.9
a.sd
(-) .
zzw
i59cd
(md,
not suitable fOr calculating a
bIhir is no[ an average. but a reasonably large sample (1027 workers).
CTD~ hammnic man was estimated for the bare chemical born tix hydmhloride salt
dAdditional data from EPA that is not in Ihe CF’DB were used IO calculate tkx TD50 harmonic nxms.
Source:
Gold er al. (40).
12