Food chemistry and chemophobia

Abstract

Chemophobia is the exaggerated fear of anything ‘chemical’ which is found quite widespread both in the Western world and in Asia. That food incontrovertibly is chemistry seems to require regulation of all sorts. As we will see below, that would truly necessitate gargantuan determination exceeding every regulatory effort to date. Worse, it will be futile. Our food is peppered with natural compounds such as organohalogens, dioxins, aflatoxins, and many others. These we will briefly discuss, including their natural whereabouts. Overall, the aim of this paper is to show that food is chemistry beyond our immediate control, including those synthetic chemicals that are deemed to be artificial and should not be found in ‘safe’ food. The latter is an overestimation of regulatory competence and an underestimation of nature to produce most unlikely chemicals in unlikely places, including our food.

Full text

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Food Security
The Science, Sociology and Economics
of Food Production and Access to Food
ISSN 1876-4517
Food Sec.
DOI 10.1007/s12571-013-0251-2
Food chemistry and chemophobia
Gordon W.Gribble

1 23
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ORIGINAL PAPER
Food chemistry and chemophobia
Gordon W. Gribble
Received: 23 August 2012 /Accepted: 6 February 2013
#Springer Science+Business Media Dordrecht and International Society for Plant Pathology 2013
Abstract Chemophobia is the exaggerated fear of anything
‘chemical’which is found quite widespread both in the
Western world and in Asia. That food incontrovertibly is
chemistry seems to require regulation of all sorts. As we will
see below, that would truly necessitate gargantuan determi-
nation exceeding every regulatory effort to date. Worse, it
will be futile. Our food is peppered with natural compounds
such as organohalogens, dioxins, aflatoxins, and many
others. These we will briefly discuss, including their natural
whereabouts. Overall, the aim of this paper is to show that
food is chemistry beyond our immediate control, including
those synthetic chemicals that are deemed to be artificial and
should not be found in ‘safe’food. The latter is an
overestimation of regulatory competence and an underesti-
mation of nature to produce most unlikely chemicals in
unlikely places, including our food.
Keywords Chemistry .Organohalogens .Chemophobia .
Food safety .Food security
Introduction
This paper is an extension of my presentation at the sympo-
sium ‘Food Safety versus Food Security’held on October 4,
2011, in Wageningen, The Netherlands. My particular focus
at the symposium was to compare natural and synthetic
chemicals in food with respect to toxicity and concentration,
and to address ‘chemophobia’, the irrational fear of chemicals
which is particularly pervasive in the Western world and in
Asia, if not worldwide (Gribble 1991;Kauffman1991;
Worman and Gribble 1992; Hagen and Worman 1995;
Billington et al. 2008). I shall also address a number of issues
in the context of food safety concerning those naturally oc-
curring compounds which are ubiquitous in our food, includ-
ing mycotoxins and other natural chemicals that can and do
cause illness and death in humans. A basic premise of this
paper is that the “dose makes the poison”–everything is toxic
at some level.
Phobia
Various dictionaries define ‘phobia’as ‘A fear or anxiety that
exceeds normal proportions or that has no basis in reality; an
obsessive or irrational dread,’or ‘An exaggerated, usually
inexplicable and illogical fear of a particular object or class
of objects,’or ‘A persistent, abnormal, or illogical fear of a
specific thing or situation.’What we, as scientists, are fighting
is the following: ‘The whole aim of practical politics is to keep
the populace alarmed (and hence clamorous to be led to
safety) by menacing it with an endless series of hobgoblins,
all of them imaginary.’(Mencken 1949).
Dianne Dumanoski (Boston Globe reporter and co-author
of ‘Our Stolen Future’) in 1990 told an environmental gath-
ering that ‘there is no such thing as objective reporting’
….‘I’ve become even more crafty about finding the voices
to say the things I think are true. That’smysubversivemis-
sion.’(Ray 1993).
Paul Watson (Greenpeace): ‘It doesn’t matter what is true,
it only matters what people believe is true.’(Watson 1993).
At a 1985 conference in Bavaria, Dr. Walter Simmler
provided this summary, ‘Chemophobia is —justified by
industry —formalized by government —nourished by the
media —tolerated, at least, by politicians —kindled by
whoever expects personal or collective gains of sorts’
(Crummett 2002).
G. W. Gribble (*)
Department of Chemistry, Dartmouth College, Hanover, NH
03755, USA
e-mail: Gordon.W.Gribble@Dartmouth.edu
Food Sec.
DOI 10.1007/s12571-013-0251-2
Author's personal copy

One might argue that the birth of chemophobia and the
related chemical fear of chlorine, ‘chlorophobia’, occurred
in 1962 with Rachel Carson’s‘Silent Spring’(Carson 1962).
Subsequent chemical accidents such as the dioxin exposure
in Times Beach, Missouri (1971) (Gough 1986), Love
Canal, New York (1976) (Mazur 1998), Seveso, Italy
(1976) (Fuller 1979), Bhopal, India (1984) (Eckerman
2005), and the publication of ‘Our Stolen Future’by Theo
Coburn et al. (1996) (Coburn et al. 1996) all conspired to
inflame the lay public against chemicals.
The word ‘chemical’became a dirty word —despite the
fact that everything we see, smell, and touch is chemical!
While chemical scares invariably appear on the front page,
the follow-up stories that often refute the initial scares never
do. Four notable case reports are these: (Lieberman and
Kwon 2004) (1) The Love Canal Final Report: ‘Victims’
were found to possess somewhat better health and showed
lower incidences of all forms of cancer than the general
population of the rest of the state of New York; (2) A
second, larger study to examine a possible connection
between breast cancer risk and exposure to DDT and
PCBs has found no strong evidence to support such a
link (Krieger et al. 1994); (3) The EPA official who
ordered the evaluation of Times Beach, Missouri, later
admitted that this was a mistake and was unnecessary;
and (4) The retraction of the ‘endocrine disruptor syner-
gistic effect’paper (McLachlan 1997).
Of molecules, concentrations and toxicity
To avoid the word ‘chemical’, euphemisms abound in the
media: wine ‘aroma’,flower‘bouquet’, perfume ‘fra-
grance’, restaurant ‘odor’, bakery ‘smell’, garbage ‘stench’,
and skunk ‘scent’. Of course, these descriptors are volatile
chemicals that we are breathing! And, our chemical vita-
mins are called ‘nutrients’!Nomatterhowwedescribe
chemistry, the basic tenet of pharmacology is that ‘The
Dose Makes the Poison’(Frank and Ottoboni 2011).
Molecules are really small! Indeed, one can easily calcu-
late that in a single drop of water there are 6×10
20
individ-
ual molecules of H
2
O (600 billion billion). This incredibly
large number is made strikingly relevant when one realizes
that this figure is roughly equivalent to the number of grains
of sand on all the beaches on earth!
An example of how infinitesimal molecules are is to ima-
gine dioxin in a glass of milk (100 mL). At concentrations
down to a part-per-trillion (ppt) this corresponds to 180 billion
molecules, an amount detectable by today’s analytical
methods. However, at lower levels such as a part-per-
quintillion this amount of dioxin cannot be detected analyti-
cally, despite the presence of 180,000 molecules of dioxin in
the glass of milk! Indeed, it is suggested by an EPA scientist
that ‘one would expect to find every known compound at a
concentration of 1 part per quadrillion or higher in a sample of
drinking water’(Donaldson 1977; Crummett 2002).
Any chemical can be toxic —depending on the dose.
Several cases of fatal water consumption —not involving
drowning —have occurred in recent years. At Chico State
University in California in 2005, the fraternity Chi Tau’s
‘Hell Week’involved water hazing. Pledges were forced to
drink up to five gallons of water. The ‘winning’pledge
drank six gallons in less than 4 h and died. Two other
pledges became comatose but survived. In 2008, also in
California, a radio station contest was to see who could
drink the most water without urinating. The ‘winner’was
a young woman who drank only two gallons of water very
quickly and subsequently died. The body becomes water
logged as the sodium ion concentration plummets and cells
swell and burst. The brain enlarges and becomes ‘water
logged’(Frank and Ottoboni 2011).
Cases of sodium chloride fatalities are also well known.
Although essential for life, a fatal dose in children can be as
little as two tablespoons (LD
50
3,000 mg/kg). A famous
case in a Boston hospital involved a nurse who inadvertently
substituted salt for sugar in an infant’s formula, which killed
the baby (Frank and Ottoboni 2011).
Numerous cases of fatal caffeine consumption have oc-
curred (Dimaio and Garriott 1974; Sullivan 1977). While
moderate caffeine consumption appears beneficial, a lethal
dose is not much higher than the typical ‘two cups’of
coffee. A five-year-old girl ingested 53 ‘Tri-Aqua’tablets,
which is a caffeine-containing over-the-counter diuretic, and
died6hlater.Thisamountofcaffeine (amount 3 g) is
equivalent to 30 cups of coffee. Other fatal caffeine episodes
include a 35-year-old woman accidentally given 3.23 g
intravenously, a 15-month-old child mistakenly given
90 ml of a 20 % caffeine solution, instead of a 2 % solution,
a 45-year-old woman given 50 g of caffeine instead of 50 g
of glucose, and a 27-year-old woman who committed sui-
cide by taking 10 g of caffeine.
Other common chemicals that we ingest, such as sodium
fluoride, aspirin, vitamin D, potatoes (solanine), spinach and
rhubarb (oxalic acid), probably pose more of a health threat
than the minute synthetic pesticide residues that may be in
our food. Indeed, a common misconception is that ‘natural’
(‘organic’) food is inherently safer than food made using
synthetic pesticides. Winter and Katz have examined “die-
tary exposure of consumers to pesticides found in twelve
commodities implicated as having the greatest potential for
pesticide residue contamination by a United States-based
environmental advocacy group.”They conclude that “(1)
exposures to the most commonly detected pesticides on the
twelve commodities pose negligible risks to consumers, (2)
substitution of organic forms of the twelve commodities for
conventional forms does not result in any appreciable
G.W. Gribble
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reduction of consumer risks, and (3) the methodology used
by the environmental advocacy group to rank commodities
with respect to pesticide risks lacks scientific credibility.”
(Winter and Katz 2011). Nature is not benign!
Natural toxins
Probably all plants, trees, and vegetables produce their own
complement of natural pesticides. It is estimated that we ingest
10,000 times more natural than synthetic pesticides, up to
1.5 g per day (Ames and Gold 1989). Notable examples of
natural pesticides (insecticides, fungicides, etc.) are nicotine,
caffeine, cocaine, and pyrethrin, all of which have powerful
insecticidal properties. Recent examples of natural pesticides
have been identified in mint (1R,2R)-2-methyl-5-(propan-2-
ylidene) cyclohexanol, (1), asparagus, N,N-dimethyl-1,2-
dithiolan-4-amine; also known as nereistoxin (2), and 1,2-
dithiolane- 4-carboxylic acid, (3), tomato, tridecan-2-one (4),
and marigold, 2,2′:5′,2″-terthiophene, (5).
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Some of these ‘natural’pesticides are highly toxic to humans.
For example, the edible Asian mushroom Russula subnigricans
contains cycloprop-2-ene carboxylic acid (6) that has caused
several cases of fatal rhabdomyolysis. Eating only two or three
pieces of this mushroom can be fatal. The concentration of this
natural toxic chemical in the mushroom is 720 ppm (Matsuura
et al. 2009). A diet regime of herbs containing natural
aristolochic acid during a slimming regimen has led to fatal
kidney disease and urothelial cancer in hundreds of women.
This ‘Chinese Herbs Nephropathy’was first observed in
Belgium in 1991 (Greensfelder 2000; Nortier et al. 2000;
Stiborová et al. 2002;Arltetal.2002,2004; Cosyns 2003).
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Aflatoxins (7–8) are mold metabolites formed on peanuts
and corn and are known to cause liver cancer (Goldblatt 1969;
Wild and Gong 2010). Qidong city has the highest incidence
of liver cancer in China, 72.1 and 19.1 per 100,000 for males
and females, respectively, during the years 1988–1992 (Parkin
et al. 1997) and 65 % of the population showed signs of
aflatoxin exposure (Pool 1992). Peanuts grown by African
farmers are very susceptible to fungal growth and subsequent
aflatoxin contamination, which is favored and promoted by
hot, humid conditions. Ochratoxin (9) is another ubiquitous
mycotoxin produced by the fungi Aspergillus ochraceus and
Penicillium verrucosum that contaminates cereals, spices,
grapes, coffee, and can be found in beer, wine, and meat
products (van der Merwe et al. 1965a,b;Pitt2000). This
fungal metabolite is possibly carcinogenic.
The following foods contain natural pesticides that cause
cancer in rats or mice and are present at levels ranging from
a few ppb to 4 million ppb: apples, bananas, basil, broccoli,
cabbage, carrots, cauliflower, celery, cinnamon, cloves, co-
coa, comfrey tea, honeydew melon, kale, mushrooms, mus-
tard, nutmeg, parsley, peaches, black pepper, pineapples,
radishes, raspberries, tarragon, and turnips (Ames et al.
1990; Ames 1991). Apple juice contains 137 natural volatile
chemicals, of which only five have been tested for carcino-
genicity; of these, three have been found to be carcinogenic.
Black pepper extracts cause tumors in mice at a level of
4 mg per day for 3 months (160 mg/kg [ppm]); average
human intake is 140 mg/day. The false morel mushroom
contains 11 hydrazines, 3 of which are known carcinogens.
One of these is present at a concentration of 50 mg/100 g of
mushroom (500 ppm) and causes tumors in mice at the level
of 0.02 mg per mouse per day. Some of the natural rodent
carcinogens are listed in Table 1(Ames and Gold 1989;
Ames et al. 1990;Ames1991).
Several natural pesticides are identical or nearly so to
man-made pesticides. Methyl bromide (bromomethane), a
commercial fumigant and pesticide, which is now banned in
California, is actually produced from natural soil bromide
by several plants such as broccoli, cabbage, radish, turnip,
rapeseed and mustard. ‘Given the ubiquitous distribution of
bromide in soil, methyl bromide production by terrestrial
higher plants is likely to be a large source for atmospheric
methyl bromide’(Gan et al. 1998). Given the rates of
production that were measured in the laboratory, the esti-
mated annual global production of methyl bromide from
rapeseed is 6,600 t. Ironically, this research was done in
California.
Other natural mycotoxins are known to be toxic to humans.
Tomatoes infected with fungi (Penicillium tularense,
Stemphylium eturmiumum,Stemphylium lycopersici)become
contaminated with several mycotoxins (janthitrems, paspalinine,
paxilline, stemphols, infectopyrone, and macrosporin)
(Andersen and Frisvad 2004). Their thin skin makes tomatoes
very susceptible to mold and decay.
The fumonisins, such as fumonisin B1 (15), are myco-
toxins produced by the Fusarium molds, Fusarium
verticillioides and F. moniliforme that infect corn, wheat,
and other cereals (Wild and Gong 2010). The less processed
the corn is, the more fumonisin will be present. Refined corn
products, corn flakes, corn starch, and high fructose sugar,
have lower amounts or no fumonisin present. These toxins
are heptatoxic and nephrotoxic to horses, cattle, and swine,
and may have caused fatal birth defects in babies whose
mothers consumed corn tortillas contaminated with
Tab l e 1 Natural food compounds that are carcinogens in rodents
(Ames and Gold 1989; Ames et al. 1990; Ames 1991)
Carcinogen Source ppm
5- (10) and 8-
methoxypsoralen (11)
parsley 14
parsnips 32
Sinigrin (allyl
isothiocyanate (12))
cabbage 35–590
cauliflower 12–66
brussel sprouts 110–1560
Limonene (13) orange juice 31
Caffeic acid (14) apples, carrots, celery 50–200
cherries, eggplant, grapes,
lettuce, pears, plums
potatoes, coffee 1800
Neochlorogenic acid
(caffeic acid)
apples, apricots, broccoli 50–500
brussel sprouts, cabbage
cherries, kale, peaches
pears, plums
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fumonisin during their pregnancy in Texas in 1991 (Marasas
et al. 2004). Fumonisin has been linked to esophageal can-
cer in humans (Bezuidenhout et al. 1988; Stockmann-
Juvalla and Savolainen 2008). Aflatoxin fungus was present
on corn used in U.S. pet food that led to the deaths of 23
dogs and cats in 2005. In 1998 more than 80 % of the Texas
corn crop was contaminated by Aspergillus flavus
(Josephson 2001; Klich 2007).
Vomitoxin (16) is a mycotoxin that contaminates grains
(wheat, barley, oat, rye, corn) and less often rice, This Type
B trichothecene is also known as deoxynivalenol (DON)
and is produced primarily by Fusarium graminearum
(Gilberella zeae) and F. culmorum which cause head blight
in wheat and ear rot in maize (Gautam and Dill-Macky
2011).
The toxic potato glycoalkaloids α-chaconine and α-
solanine present a potential threat to humans as a billion
people worldwide eat potato, and this food contains 90–
175 mg/kg fresh weight of total glycoalkaloids (Mensinga
et al. 2005).
The simplest organochlorine compound methyl chloride
(chloromethane) has multiple natural sources (fungi, marine
algae, forest fires, plants, volcanoes, potatoes) that dwarf
anthropogenic emissions by about 200 fold. It is estimated
that with each breath we inhale 10
12
–10
13
molecules of
methyl chloride without ill effect (Winterton 1996). Some
other natural organochlorine compounds are shown below
(17–20).
Chloroform -
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A spectacular example of natural pesticides in action is
seen with the edible Japanese Lily Lilium maximowiczii.
When this plant is attacked by the pathogenic fungus
Fusarium oxysporum the lily biosynthesizes seven
Food chemistry and chemophobia
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fungicidal chlorinated phenols (21–27) at the site of infec-
tion (Monde et al. 1988). Interestingly, these novel com-
pounds are structurally similar to man-made chlorinated
fungicides but were previously unknown to science.
An example of both a synthetic and natural compound,
desirable in low concentrations but toxic in high amounts, is
diacetyl (28). This natural compound is the familiar odor of
butter and some white wines (Chardonnay, Sauvignon
Blanc, white Burgundy). It is also added to microwave
popcorn, but plant workers who are often exposed to high
concentrations of diacetyl (1.3–98 ppm) in the ‘mixing
room’experience high rates of chronic cough and lung-
function abnormalities (‘bronchiolitis’) (Kreiss et al. 2002).
Nature’s complexity and synthetic versatility is illustrated
with the favorite edible seaweed Asparagopsis taxiformis,
‘limu kohu’, of native Hawaiians. This alga produces more
than 100 halogenated compounds that contribute to the
aroma of this delicacy (Scheme 1) (Moore 1977).
Although present in very small quantities and probably
degraded during steaming, these compounds may be impli-
cated in the relative high incidence of stomach cancer in this
population. As good alkylation reaction substrates, like tear
gases and nerve agents, several of these organohalogens are
expected to be very reactive towards DNA and proteins.
One can speculate that these natural compounds serve the
alga as repellents, feeding deterrents, antibacterials, or anti-
fouling agents.
Dioxins
A food contaminant of great concern is ‘dioxin’, a descriptor
that represents a large number of polychlorinated dibenzo-p-
dioxins that arise as a result of industrial processes and
Scheme 1 Organohalogens
from Hawaiian Red Alga
(Asparagopsis taxiformis)
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combustion products (Gribble 1974;Crummett2002;
Baccarelli et al. 2005). What is generally unknown is
that dioxins have several natural sources, as do the
related polychlorinated dibenzofurans. Major reposito-
ries of natural dioxins are ancient ball clays in deep
sediments in the U.S., Germany, Spain, Australia, and
Japan deposited in the Tertiary Era (72 Ma) (Horii et
al. 2008).
Several hypotheses have been advanced for the origin
of these dioxins, including ancient forest fire deposits,
volcanic emissions, chloroperoxidase oxidative dimeriza-
tion of natural chlorophenols, and mineral-promoted
synthesis. Lightning-induced forest fires and peroxidase-
catalyzed dimerization of natural chlorophenols (e.g., in com-
post) are now well-documented (Winterton 2000;
Crummett 2002). Six New Brunswick peat bogs have
yielded several dioxins along with chloroform and
chlorophenols (Silk et al. 1997). The dioxins observed
in this study are not normally present in anthropogenic
dioxin mixtures, and radiolabeled chloride experiments
support an in vivo biosynthesis origin via chlorophenols
and chloroperoxidase. Several marine sponges contain
unprecedented polybrominated dioxins 29–31 (Utkina
et al. 2001,2002).
A remarkable development in dioxin research is that
the mammalian enzyme in our white blood cells,
myeloperoxidase (MPO), can effect oxidative dimeriza-
tion of chlorophenols to dioxins (Scheme 2)(Wittsiepe
et al. 1999,2000). Thus, a human biosynthesis of dioxins is
possible.
Natural product chemists have also discovered naturally
occurring polychlorinated dibenzofurans. The slime mold
Dictyostelium purpureum and the lichen Lecanona sp. produce
the dibenzofurans 32 and 33 (Sawada et al. 2000; Tanahashi et
al. 2001; Takenaka et al. 2005), and numerous simple furans
such as 34–36 occur naturally in food (Keay et al. 2008).
Food and health supporting chemicals
Many of nature’s chemicals found in food are not pesticides;
quite a few of these chemicals are highly beneficial for our
health. Indeed, some 8,000 polyphenols called flavonoids
are present in myriad fruits, vegetables, tea, wine and other
foods (Benavente-García and Castillo 2008; Hounsome et
al. 2008). These phytochemicals are known to have
antioxidant and anticancer properties (Chen and Blumberg
2008).
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Three commonexamples are myricetin (37), robinetin (38),
and quercetin (39). For example, some of these and other
flavonoids prevent formation of carcinogenic polycyclic aro-
matic diol epoxides, and can deactivate them if present
(Huang et al. 1983).
The related flavanones (40) and flavones (41) are also
important anticancer phytochemicals. They act as suppressing
agents to prevent new cancers, blocking agents to prevent
carcinogens from reaching initiation sites, and transforming
agents to facilitate metabolism of carcinogens into less toxic,
excretable compounds (Benavente-García and Castillo 2008).
Scheme 2 Myeloperoxidase
induced dioxin formation from
chlorophenols
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A new example is 42 found in chocolate, grapes, and red
wine. Chocolate is a powerful antioxidant, a cholesterol
lowering agent (LDL and triglycerides), and an atheroscle-
rosis inhibitor (Vinson et al. 2006).
Discussion and conclusion
Food is chemistry, and with the current focus on chemical food
safety –pesticides, antibiotics, dioxins - the subsequent contra-
dictory perspective generates hard questions that beg for an-
swers. Food safety and food security do get in each other’sway
if a dichotomy is maintained between natural and artificial
(man-made) chemistry. We have seen in this contribution that
such a dichotomy is untenable and, I propose, counterproduc-
tive in a world where increasing amounts of foods are required
to feed an ever-increasing world population. Regulating so-
called artificial chemicals such as organohalogens can only be
achieved by blinding oneself to the natural presence of such
along with many other compounds.
In order to maintain food production of high standard,
food safety should be focused on those aspects that measur-
ably affect human health, simply because chemical exposure
is inherent in food consumption. Therein we simultaneously
consume the good and the bad, and by diversifying diet –
the nutritional advice par excellence- we, in effect, minimize
exposure to those deleterious compounds. The dose makes
the poison.
What do measurably affect food quality and human
health are pathogens, bacteria and fungi. Food-borne infec-
tions in the U.S. annually account for 5,000 deaths and
325,000 hospitalizations, of some 76 million cases (Taubes
2008). Recent cases include E. coli (0157:H7) in spinach,
lettuce, and beef, and Listeria in celery, hot dogs, cheese,
and cantaloupe. The potency of E. coli (0157:H7) is seen by
the fact that only 15 cells per gram of hamburger were
present in one case, and only 10 cells sufficed to cause
illness.
In conclusion, it is of vital importance for the welfare of
the current world’s population –and the unborn billions to
come –that a safe and abundant food supply is available.
Our food regulators must be fully educated about what
constitutes safe food so that precise and scientifically guided
recommendations will be made. There can be no excuse; the
science is there to be adopted.
References
Ames, B. N. (1991). Natural carcinogens and dioxin. Science of the
Total Environment, 104, 159–166.
Ames, B. N., & Gold, L. S. (1989). Pesticides, risk, and applesauce.
Science, 244, 755–757.
Ames, B. N., Profet, M., & Gold, L. S. (1990). Dietary pesticides
(99.99 % all natural). Proceedings of the National Academy of
Sciences USA, 87, 7777–7781.
Andersen, B., & Frisvad, J. C. (2004). Natural occurrence of fungi and
fungal metabolites in moldy tomatoes. Journal of Agriculture and
Food Chemistry, 52, 7507–7513.
Arlt, V. M., Stilborova, M., & Schmeiser, H. H. (2002). Aristolochic
acid as a probable human cancer hazard in herbal remedies: a
review. Mutagenesis, 17(4), 265–277.
Arlt, V. M., Alunni-Perret, V., Quatrehomme, G., Ohayon, P., Albano,
L., Gaïd, H., et al. (2004). Aristolochic acid (AA)-DNA adduct as
marker of AA exposure and risk factor for AA nephropathy-
associated cancer. International Journal of Cancer, 111, 977–
980.
Baccarelli, A., Pesatori, A. C., Consonni, D., Mocarelli, P., Patterson,
D. G., Jr., Caporaso, N. E., et al. (2005). Health status and plasma
dioxin levels in chloracne cases 20 years after the Seveso, Italy
accident. British Journal of Dermatology, 152, 459–465.
Benavente-García, O., & Castillo, J. (2008). Update on uses and
properties of citrus flavonoids: new findings in anticancer, car-
diovascular, and anti-inflammatory activity. Journal of
Agriculture and Food Chemistry, 56, 6185–6205.
Bezuidenhout, S. C., Gelderblom, W. C. A., Gorst-Allman, C. P.,
Horak, R. M., Marasas, W. F. O., Spiteller, G., & Vleggaar, R.
(1988). Structure elucidation of the fumonisins, mycotoxins from
Fusarium moniliforme.Journal of the Chemical Society,
Chemical Communications, 743–745.
Billington, S., Smith, R. B., Karousos, N. G., Cowham, E., & Davis, J.
(2008). Covert approaches to countering adult chemophobia.
Journal of Chemical Education, 85(3), 379–380.
Carson, R. (1962). Silent spring. Greenwich: Fawcett.
Chen, C.-Y. O., & Blumberg, J. B. (2008). In vitro activity of almond
skin polyphenols for scavenging free radicals and inducing qui-
none reductase. Journal of Agriculture and Food Chemistry, 56,
4427–4434.
Coburn, T., Dumanoski, D., & Myers, J. P. (1996). Our stolen future.
New York: Dutton.
Cosyns, J.-P. (2003). Aristolochic acid and ‘Chinese herbs nephropa-
thy’, a review of the evidence to date. Drug Safety, 26(1), 33–
48.
Crummett, W. B. (2002). Decades of dioxin. Bloomington: Xlibris.
Dimaio, V. J. M., & Garriott, J. C. (1974). Lethal caffeine poisoning in
a child. Forensic Science, 3, 275–278.
Donaldson, W. T. (1977). Trace organics inn water. Environmental
Science and Technology, 11(4), 348–351.
Eckerman, I. (2005). The Bhopal saga —causes and consequences of
the world’s largest industrial disaster. India: Universities Press.
Food chemistry and chemophobia
Author's personal copy

Frank, P., & Ottoboni, M. A. (2011). The dose makes the poison (3rd
ed.). Hoboken: John Wiley.
Fuller, J. G. (1979). Poison that fell from the sky. New York: Berkeley
Books.
Gan, J., Yates, S. R., Ohr, H. D., & Sims, J. J. (1998). Production of
methyl bromide by terrestrial higher plants. Geophysical Research
Letters, 25, 3595–3598.
Gautam, P., & Dill-Macky, R. (2011). Type I host resistance and
trichothecene accumulation in Fusarium-infected wheat heads.
American Journal of Agriculture and Animal Science, 6(2),
231–241.
Goldblatt, L. A. (1969). Aflatoxin: Scientific background, control, and
implications. New York: Academic.
Gough, M. (1986). Dioxin, agent orange: the facts.NewYork:
Plenum.
Greensfelder, L. (2000). Herbal product linked to cancer. Science, 288,
1946.
Gribble, G. W. (1974). TCDD —a deadly molecule. Chemistry, 47,15–18.
Gribble, G. (1991). The chemophobia conundrum. Chemistry &
Industry, 591.
Hagen, E. W., & Worman, J. J. (1995). An endless series of hobgoblins.
Kearney: Morris.
Horii, Y., van Bavel, B., Kannan, K., Petrick, G., Nachtigall, K., &
Yamashita, N. (2008). Novel evidence for natural formation of
dioxins in ball clay. Chemosphere, 70, 1280–1289.
Hounsome, N., Hounsome, B., Tomos, D., & Edwards-Jones, G.
(2008). Plant metabolites and nutritional quality of vegetables.
Journal of Food Science, 73, R48–R65.
Huang, M.-T., Wood, A. W., Newmark, H. L., Sayer, J. M., Yagi,
H., Jerina, D. M., et al. (1983). Inhibition of the mutagenicity
of bay-region diol-epoxides of polycyclic aromatic hydrocar-
bons by phenolic plant flavonoids. Carcinogenesis, 4, 1631–
1637.
Josephson, J. (2001). Mold in maize. Environmental Health
Perspectives, 109, A132–A133.
Kauffman, G. B. (1991). Chemophobia. Chemistry in Britain, June, 512–
516.
Keay, B. A., Hopkins, J. M., & Dibble, P. W. (2008). Five-membered
rings with one heteroatom together with their benzo and other
carbocyclic-fused derivatives. In A. R. Katritzky, C. A. Ramsden,
E. F. V. Scriven, & R. J. K. Taylor (Eds.), 3.08 —Furans and
their benzo derivatives: applications, comprehensive heterocyclic
chemistry III (Vol. 3) (pp. 571–623). Amsterdam: Elsevier.
Klich, M. A. (2007). Aspergillus flavus: the major producer of aflatox-
in. Molecular Plant Pathology, 8(6), 713–722.
Kreiss, K., Gomaa, A., Kullman, G., Fedan, K., Simoes, E. J., &
Enright, P. L. (2002). Clinical bronchiolitis obliterans in workers
at a microwave-popcorn plant. The New England Journal of
Medicine, 347(5), 330–338.
Krieger,N.,Wolff,M.S.,Hiatt,R.A.,Rivera,M.,Vogelman,J.,
& Orentreich, N. (1994). Breast cancer and serum organo-
chlorines: a prospective study among white, black, and Asian
women. Journal of the National Cancer Institute, 86,589–
599.
Lieberman, A. J., & Kwon, S. C. (2004). Facts versus fears: a review
of the greatest unfounded health scares of recent times.New
York: American Council on Science and Health.
Marasas, W. F. O., Riley, R. T., Hendricks, K. A., Stevens, V. L.,
Sadler, T. W., Gelineau-van Waes, J., et al. (2004). Fumonisins
disrupt sphingolipid metabolism, folate transport, and neural tube
development in embryo culture and in vivo: a potential risk factor
for human neural tube defects among populations consuming
fumonisin-contaminated maize. Journal of Nutrition, 134,711–
716.
Matsuura, M., Saikawa, Y., Inui, K., Nakae, K., Igarashi, M.,
Hashimoto, K., et al. (2009). Identification of the toxic trigger
in mushroom poisoning. Nature Chemical Biology, 5, 465–
467.
Mazur, A. (1998). A hazardous inquiry: the Rashomon effect at Love
Canal. Cambridge: Harvard University Press.
McLachlan, J. A. (1997). Synergistic effect of environmental estro-
gens: report withdrawn. Science, 277, 462–463.
Mencken, H. L. (1949). A Mencken chrestomathy. New York: Knopf.
Mensinga, T. T., Sips, A. J. A. M., Rompelberg, C. J. M., van Twillert,
K., Meulenbelt, J., van den Top, H. J., et al. (2005). Potato
glycoalkaloids and adverse effects in humans: an ascending
dose study. Regulatory Toxicology and Pharmacology, 41,66–
72.
Monde, K., Satoh, H., Nakamura, M., Tamura, M., & Takasugi, M.
(1988). Organochlorine compounds from a terrestrial higher
plant: structures and origin of chlorinated orcinol derivatives from
diseased bulbs of Lilium maximowiczii.Journal of Natural
Products, 61, 913–921.
Moore, R. E. (1977). Volatile compounds from marine algae. Accounts
of Chemical Research, 10,40–47.
Nortier, J. L., Martinez, M.-C. M., Schmeiser, H. H., Arlt, V. M.,
Bieler, C. A., Petein, M., et al. (2000). Urothelial carcinoma
associated with the use of a Chinese herb (Aristolochia
fangchi). The New England Journal of Medicine, 342,1686–
1692.
Parkin, D. M., Whelan, S. L., Ferlay, J., et al. (1997). Cancer incidence
in five continents vol VII. IARC Sci Pub No 143, Lyon: IARC,
322–5.
Pitt, J. I. (2000). Toxigenic fungi: which are important? Medical
Mycology, 38,17–22.
Pool, R. (1992). Wresting anticancer secrets from garlic and soy sauce.
Science, 257, 1349.
Ray, D. L. (1993). Environmental overkill: whatever happened to
common sense? (p. 171). Washington: Regnery Gateway.
Sawada, T., Aono, M., Asakawa, S., Ito, A., & Awano, K. (2000).
Structure determination and total synthesis of a novel antibacterial
substance, AB0022A, produced by a cellular slime mold. Journal
of Antibiotics, 53, 959–966.
Silk, P. J., Lonergan, G. C., Arsenault, T. L., & Boyle, C. D. (1997).
Evidence of natural organochlorine formation in peat bogs.
Chemosphere, 35, 2865–2880.
Stiborová, M., Frie, E., Sopko, B., Wiessler, M., & Schmeiser, H. H.
(2002). Carcinogenic aristolochic acids upon activation by DT-
diaphorase form adducts found in DNA of patients with Chinese
herbs nephropathy. Carcinogenesis, 23, 617–625.
Stockmann-Juvalla, H., & Savolainen, K. (2008). A review of the toxic
effects and mechanisms of action of fumonisin B1. Human &
Experimental Toxicology, 27, 799–809.
Sullivan, J. L. (1977). Caffeine poisoning in an infant. Journal of
Pediatrics, 90, 1022–1023.
Takenaka, Y., Hamada, N., & Tanahashi, T. (2005). Monomeric and
dimeric dibenzofurans from cultured mycobionts of Lecanora
iseana.Phytochemistry, 66, 665–668.
Tanahashi, T., Takenaka, Y., Nagakura, N., & Hamada, N. (2001).
Dibenzofurans from the cultured lichen mycobionts of Lecanora
cinereocarnea.Phytochemistry, 58,85–1134.
Taubes, G. (2008). The bacteria fight back. Science, 321,356–
361.
Utkina, N. K., Denisenko, V. A., Scholokova, O. V., Virovaya, M. V.,
Gerasimenko, A. V., Popov, D. Y., et al. (2001). Spongiadioxins A
and B, two new polybrominated dibenzo-p-dioxins from an
Australian marine sponge Dysidea dendyi.Journal of Natural
Products, 64, 151–153.
Utkina, N. K., Denisenko, V. A., Virovaya, M. V., Scholokova, O. V.,
& Prokof’eva, N. G. (2002). Two new minor polybrominated
dibenzo-p-dioxins from the marine sponge Dysidea dendyi.
Journal of Natural Products, 65, 1213–1215.
G.W. Gribble
Author's personal copy

van der Merwe, K. J., Steyn, P. S., Fourie, L., Scott, D. B., & Theron, J.
J. (1965a). Ochratoxin A, a toxic metabolite produced by
Aspergillus ochraceus Wilh. Nature, 205,1112–1113.
van der Merwe, K. J., Steyn, P. S., & Fourie, L. (1965b). Mycotoxins.
Part II. The constitution of ochratoxins A, B, and C, metabolites
of Aspergillus ochraceus Wilh. Journal of the Chemical Society,
7083–7088.
Vinson, J. A., Proch, J., Bose, P., Muchler, S., Taffera, P., Shuta, D., et
al. (2006). Chocolate is a powerful ex vivo and in vivo antioxi-
dant, an antiatherosclerotic agent in an animal model, and a signif-
icant contributor to antioxidants in the European and American
diets. Journal of Agriculture and Food Chemistry, 54, 8071–
8076.
Watson, P. (1993). Earthforce! An Earth warrior’s guide to strategy.La
Canada: Chaco Press.
Wild, C. P., & Gong, Y. Y. (2010). Mycotoxins and human disease:
a largely ignored global health issue. Carcinogeneis, 31,71–
82.
Winter, C. K. & Katz, J. M. (2011), Dietary exposure to pesticide
residues from commodities alleged to contain the highest contam-
ination levels. Journal of Toxicology, Article ID 589674, 7 pages.
doi:10.1155/2011/589674
Winterton, N. (1996). A role for methyl chlorine in evolution? Mutation
Research, 372,147–148.
Winterton, N. (2000). Chlorine: the only green element —towards a wider
acceptance of its role in natural cycles. Green Chemistry, 2,173–
225.
Wittsiepe, J., Kullmann, Y., Schrey, P., Selenka, F., & Wilhelm, M.
(1999). Peroxidase-catalyzed in vitro formation of polychlorinated
dibenzo-p-dioxins and dibenzofurans from chlorophenols.
Toxicology Letters, 106,191–200.
Wittsiepe, J., Kullmann, Y., Schrey, P., Selenka, F., & Wilhelm, M.
(2000). Myeloperoxidase-catalyzed formation of PCDD/F from
chlorophenols. Chemosphere, 40, 963–968.
Worman, J. J., & Gribble, G. W. (1992). Herbicides and chemophobia.
Journal of Arboriculture, 18,10–14.
Professor Gribble received his
B.S. degree in Chemistry in
1963 from the University of Cal-
ifornia, Berkeley, and his Ph.D.
in Organic Chemistry in 1967
from the University of Oregon.
After spending a year at UCLA
as a National Cancer Institute
Postdoctoral Fellow, he joined
the faculty of Dartmouth College
in 1968. Dr. Gribble has been a
National Institutes of Health Re-
search Career Development
Awardee (1971–76), a National
Science Foundation Professional
Development Awardee (1977–78), and an American Cyanamid Aca-
demic Achievement Awardee (1988). In 2005 he was named to the
endowed Chair “The Dartmouth Professor of Chemistry.”He is the co-
editor of “Progress in Heterocyclic Chemistry”and the co-author of
“Palladium in Heterocyclic Chemistry.”
Professor Gribble’s research programs involve several areas of organic
chemistry, most of which involve synthesis: biologically active natural
products, novel indole chemistry, anticancer triterpenoid synthesis, new
synthetic methodology, and novel radical and cycloaddition chemistry of
heterocycles. Of prime interest is the synthesis of plant indole alkaloids
that are potent anticancer or antibiotic agents. Current work in this area is
focused on ellipticine, vobasine, marine alkaloids, indolocarbazoles, and
the zwitterionic alkaloids such as sempervirine.Thus, for example, several
years ago Dr. Gribble developed a highly efficient synthesis of ellipticine,
a derivative of which is currently used to treat several forms of human
cancer. In the area of new synthetic methodology, Dr. Gribble and his
students have been investigating the chemistry of nitroindoles. A newer
area of research is the synthesis and biological activity of triterpenoids in
the chemoprevention of cancer and diseases related to inflammation. One
of these synthetic triterpenoids is in Phase III clinical trials for chronic
kidney disease in stage 4 diabetes patients.
Food chemistry and chemophobia
Author's personal copy