FOOD SAFETY other contaminants, pages 340 344, c k winter

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Osterholm MT and Norgan AP (2004) The role of irradiation in
food safety. New England Journal of Medicine 350:
1898–1901.
Perales I and Garcia MI (1990) The influence of pH and temperature on the behaviour of S. enteritidis phage type 4 in homemade mayonnaise. Letters in Applied Microbiology 10: 19–22.
Roberts JA, Cumberland P, Sockett PN et al. (2002) The study of
infectious intestinal disease in England: Socioeconomic
impact. Epidemiology and Infection 129: 1–11.
Takkinen J, Ammon A, Robstad O, Breuer T, and the Campylobacter Working Group (2003) European Survey of Campylobacter surveillance and diagnosis 2001. Eurosurveillance 8:
207–213.
Tuttle J, Gomez T, Doyle MP et al. (1999) Lessons for a large
outbreak of E. coli O157:H7infections: Insights into the infectious dose and method of widespread contamination of hamburger patties. Epidemiology and Infection 122: 185–192.
Zaidi AKM, Awasthi S, and deSilva HJ (2004) Burden of infectious
diseases in South Asia. British Medical Journal 328: 811–815.

Other Contaminants
C K Winter, University of California at Davis, Davis,
CA, USA
ª 2005 Elsevier Ltd. All rights reserved.

Food may be contaminated with many chemicals
that pose the potential for toxicological consequences in humans consuming the contaminated
food items. In addition to the presence of contaminants such as mycotoxins, pesticide residues, and
heavy metals, food may contain numerous organic
contaminants that enter the food supply from environmental sources or as a result of chemical reactions
that occur during food processing. This article
focuses on three types of food contaminants: dioxins
(including dibenzofurans and polychlorinated biphenyls), acrylamide, and perchlorate. Each of these
classes has been subject to considerable regulatory
scrutiny, scientific study, and popular media coverage. It is likely that concerns regarding the presence
of these contaminants in the food supply will continue throughout the next decade or longer, and that

significant efforts will be made to reduce human
exposure to these substances from food. This article
discusses how these types of food contaminants
enter the food supply, the types of food items in
which they are most likely to occur, and the potential toxicological consequences resulting from exposure to these contaminants.

speaking, the dioxins of potential toxicological concern
are polychlorinated dibenzo-p-dioxins (PCDDs). They
are related, both structurally and toxicologically, to
polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs). Structures of generic
PCDDs, PCDFs, and PCBs are shown in Figure 1.
Due to their structural and toxicological similarity
and to avoid confusion, all three related groups of
chemicals are considered to represent ‘‘dioxins’’ for
the purposes of this article. Specific chemicals belonging to this family are referred to as congeners. Collectively, there are more than 200 dioxin-related
congeners, and each possesses unique toxicological
and chemical properties.
Occurrence in the Environment and in Food

PCDDs and PCDFs are primarily introduced into
the environment as by-products of combustion processes. These by-products have been identified in the
exhaust gases from sources such as cigarette smoke;
industrial and municipal waste incinerators; power
plants burning coal, oil, or wood; and automobiles.
In addition to these human sources, PCDDs and
PCDFs are also produced naturally by combustion
in forest fires and from volcanic eruptions.
Historically, PCDDs and PCDFs have also been
produced as impurities during organic chemical synthesis. The most notable and most toxic dioxin congener,
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has

been shown to be produced in the synthesis of the
herbicide 2,4,5-T, one of the herbicide components
of Agent Orange, notoriously used in the Vietnam
War. Although 2,4,5-T is now banned for use in
the United States because of TCDD and other
dioxin impurities, health concerns over the exposure of military veterans to Agent Orange and to
TCDD continue to be raised. PCDDs and PCDFs
can also be produced through the use of chlorine
O
PCDD
O
Cl

Cl

PCDF
O
Cl

Cl

PCB

Dioxins
Dioxins are organic chemicals that comprise a family of
ubiquitous environmental contaminants. Technically

Cl

Cl

Figure 1 Chemical structures of generic PCDDs, PCDFs,
and PCBs.


FOOD SAFETY/Other Contaminants

to bleach wood pulp, although most bleaching
processes now use nonchlorine agents such as
hydrogen peroxide.
PCBs have been produced synthetically since the
1930s and have been widely used for industrial
applications, such as dielectric fluids in transformers
(due to their inflammability) and capacitors in electrical machinery. Like their PCDD and PCDF counterparts, PCBs are extremely persistent in the
environment and are of toxicological concern. As a
result, the synthesis and industrial use of PCBs were
significantly curtailed in the 1970s, although environmental residues of PCBs are still commonly
detected today.
Although dioxin release into the environment has
been known to occur for several decades, data are
still limited with respect to the degree to which
dioxins contaminate the food supply. Dioxin analysis in the laboratory is extremely expensive because
methods must identify hundreds of different congeners, detection limits are required in the sub-part per
trillion range, and significant precautions must be
taken to minimize exposure of laboratory personnel
to the analytical standards used for dioxin
congeners.
Dioxins are highly fat soluble and have been
shown to accumulate in the fat of birds, fish, and
food animals. The US Environmental Protection

Agency (EPA) has estimated that more than 95%
of human exposure to dioxins results from dietary
intake of animal fats. The major food sources for
dioxin exposure include fish, poultry, meats, milk,
and milk products. Dioxins are excreted in human
breast milk and result in exposures to nursing
infants.
Historically, it has been shown that human dioxin
exposures, as determined by analyzing human tissues and environmental samples, have decreased significantly since 1987 due to engineering controls to
limit dioxin emissions during combustion processes
and to increased regulatory control over other
sources of dioxin exposure. Dietary dioxin exposures to UK consumers were reduced by nearly
two-thirds from 1982 to 1992, and subsequent
studies showed even lower exposures in 1997.
Nevertheless, dioxins are still ubiquitous in the
environment and human exposure still occurs.
Toxicological Considerations

Dioxin exposure at significant dose levels has been
linked to a large number of adverse health effects.
Large acute exposures, resulting from chemical accidents and/or occupational exposure to dioxins, have
caused a severe skin condition known as chloracne.

341

A variety of other skin effects, such as rashes and
discoloration, have also been attributed to acute
dioxin exposures, as has liver damage.
Concerns from chronic exposure to dioxins
include cancer, reproductive effects, and developmental effects. The most toxic dioxin congener,

TCDD, was classified by the International Agency
for Research on Cancer as a human carcinogen.
From a biochemical standpoint, PCDDs, PCDFs,
and PCBs appear to cause their toxic effects through
chemical binding to a specific cellular receptor
known as the Ah receptor. Specific dioxin congeners
vary dramatically with respect to their abilities to
bind with the Ah receptor; TCDD binds extremely
effectively, whereas other congeners are more limited in their binding capabilities. The degree to
which various dioxin congeners bind with the Ah
receptor seems to be directly related to the number
and location of chlorine atoms on the congeners.
Assessing the potential human health risks from
exposure to dioxins presents significant challenges.
Dioxin levels in specific food items can be quite
variable, and, as discussed previously, data concerning dioxin levels on foods are frequently not
available.
Another difficulty encountered in assessing dioxin
risks is to appropriately account for exposures to the
various congeners and to account for the toxicological differences among congeners. This is most
appropriately achieved through a toxic equivalency
factor (TEF) approach that assigns a potency factor
to each of the congeners relative to that of the most
toxic dioxin TCDD. For example, the TEF for
TCDD is 1 and the TEF for 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (with chlorines added to the
1 and 2 positions and otherwise similar to TCDD) is
0.1 based on findings that 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin is 10 times less capable of binding to
the Ah receptor than is TCDD. To calculate a total
dioxin exposure, the dietary contributions of each of
the dioxin congeners are multiplied by their corresponding TEFs and summed to determine a TCDD

equivalent exposure.
According to the World Health Organization
(WHO), a tolerable daily intake (TDI) for TCDD
was established at 10 pg TCDD per kilogram bodyweight per day in 1990, although revisions by WHO
reduced the TDI range to 1–4 pg/kg/day in 1999. A
1997 UK survey of dioxin consumer exposure provided an upper bound of 1.8 pg TCDD equivalent/
kg/day. Surveys from other countries, using slightly
different TEF approaches, yielded exposures of
0.7 pg/kg/day in Italy, 1.4 pg/kg/day in Norway,
2.4–3.5 pg/kg/day in Spain, and 0.2 pg/kg/day in
New Zealand.


342 FOOD SAFETY/Other Contaminants

The US Food and Drug Administration (FDA) has
been monitoring finfish, shellfish, and dairy products for dioxins since 1995 and initiated dioxin
analysis of foods analyzed in its Total Diet Study
in 1999. Specific findings from the FDA’s annual
Total Diet Study can be obtained from the FDA,
although human exposure estimates, in terms of
the amount of TCDD equivalent exposure per kilogram of body weight per day, have not been published by the FDA.
The EPA recommends that consumers follow the
existing Federal Dietary Guidelines to reduce fat
consumption and, subsequently, dioxin exposure.
Such guidelines suggest that consumers choose fish,
lean meat, poultry, and low- or fat-free dairy products while increasing consumption of fruits, vegetables, and grains. Dioxin exposure can be further
minimized by trimming visible fat from meats,
removing the skin of fish and poultry, reducing the
amount of butter or lard used in cooking, and replacing cooking methods such as frying with methods

such as boiling or oven broiling.

Acrylamide
Acrylamide is a widely used and versatile industrial
chemical. Its most common use is as a coagulant in
water treatment and purification. It is also used as a
soil conditioner, in the sizing of paper and textiles,
in ore processing, and as a construction aid for the
building of tunnels and dam foundations.
Acrylamide is considered by the International
Agency for Research on Cancer to be ‘‘probably
carcinogenic to humans’’ based on the results of
several animal carcinogenicity studies. As a result,
there has been widespread concern about the potential risks from exposure to acrylamide among industrial, manufacturing, and laboratory workers.
Consumer exposure to acrylamide in treated drinking water has posed a much lower concern since
drinking water is subject to special treatment techniques that control the amount of acrylamide in
drinking water.
Swedish researchers developed laboratory techniques that allowed for the detection of biological
reaction products (hemoglobin adducts) of acrylamide in human blood samples; results from their
studies allowed correlations to be made between
occupational activities and acrylamide exposures.
The findings that acrylamide occurred in tobacco
smoke and that smokers had increased levels of
hemoglobin adducts relative to nonsmokers provided a suggestion that acrylamide may be formed
during incomplete combustion of organic matter or
during heating. Interestingly, the researchers found

significant levels of hemoglobin adducts in blood
samples of nonsmoking humans not exposed occupationally to acrylamide. This led to speculation that
the human diet could contain significant quantities of

acrylamide. In April 2002, Swedish researchers published results of research that demonstrated the presence of acrylamide in several common foodstuffs,
with the highest levels found in fried and baked
foods. These findings stimulated worldwide interest
in identifying the potential mechanisms for acrylamide formation in foods, in assaying a wide variety
of foods for acrylamide levels, and in developing risk
assessment and risk mitigation procedures.
Occurrence in Food

The findings from the initial Swedish study indicated
that the highest levels (150–4000 mg/kg) of acrylamide were detected in carbohydrate-rich foods such
as potatoes and in heated commercial potato products (potato chips) and crispbread. Moderate levels
(5–50 mg/kg) were measured in protein-rich foods
that were heated, whereas unheated or boiled
foods showed no detectable acrylamide (<5 mg/kg).
The governments of several countries throughout
the world performed similar analyses of acrylamide
in foods and findings were fairly consistent with
those reported in the Swedish study. The FDA analyzed dozens of foods for acrylamide levels and concluded that the highest levels were observed in
french fries (29 samples; range, 117–1030 mg/kg)
and in potato chips (40 samples; range,
117–2762 mg/kg). Multiple samples from different
lots of the same commercial food products showed
significant variability, with the highest levels often
several times greater than the lowest levels. Commercial potato products that could be prepared by
baking or by other methods showed much higher
levels of acrylamide in the baked products. Acrylamide levels in baby food ranged from below the
detection level (<10 mg/kg) to 130 mg/kg. All infant
formula samples had levels below 10 mg/kg, and
acrylamide levels in dairy products were also low.
The widespread findings of acrylamide in foodstuffs throughout the world provided the basis for

numerous studies designed to elucidate the mechanisms for acrylamide formation in foods. It has been
demonstrated that acrylamide can be formed from
classical Maillard reactions as well as from reaction
of the fatty acid oxidation product acrolein with
ammonia and subsequent oxidation steps. The
most plausible explanation for the relatively high
acrylamide levels in fried potato products derives
from a mechanism involving the reaction of the
amino group of the amino acid asparagine with the


FOOD SAFETY/Other Contaminants

HO

O

OH
O

H2N

OH
O

+

HO

NH2

HO

OH

glucose

asparagine

heat,
several steps
O
NH2
acrylamide
Figure 2 Proposed mechanism for acrylamide formation in
foods.

carbonyl group of a reducing sugar such as glucose
during baking and frying. This mechanism is shown
in Figure 2. Potatoes are high in asparagine and in
reducing sugars, and they are commonly prepared
for consumption by frying or baking; all of these
factors help explain the relatively high levels of
acrylamide in heated potato products.
Toxicological Considerations

Laboratory toxicology studies have indicated that
acrylamide is carcinogenic and also has been
associated with the development of reproductive
toxicity, genotoxicity, and neurotoxicity. Epidemiological and analytical studies of people exposed to

acrylamide in the workplace have indicated that
acrylamide does indeed enter the bloodstream of
workers and can be detected and quantified as
hemoglobin adducts, thus indicating both exposure
and absorption of acrylamide. Such studies have not,
however, indicated increases in cancer rates among
those exposed occupationally to acrylamide. To
date, the only documented toxicological effect
observed in epidemiological studies of workers
exposed to acrylamide is neurotoxicity. This effect
is primarily an acute effect caused by large exposures to acrylamide for relatively short periods of
time, leading to nervous system damage, weakness,
and incoordination of limbs.
From a biochemical standpoint, it is likely that the
health effects caused by high levels of exposure in
humans and in laboratory animals may result from a
Michael-type nucleophilic addition reaction of
amino acids (both amino and sulfhydryl groups),
peptides, and proteins to acrylamide because of the
presence of the ,-unsaturated conjugated structure
in acrylamide. This is a common toxicological pathway for many reactive compounds. It is likely that
high doses of acrylamide may overwhelm the defensive mechanisms of the body such as glutathione

343

conjugation and may cause reaction with biologically significant nucleophiles, leading to mutations
and possible carcinogenicity.
Although it is clear that humans have been consuming significant amounts of acrylamide in their
diets for a long time, the relatively new discovery
of acrylamide as a food contaminant has raised

several questions. Significant efforts are currently
being made to better understand the levels of acrylamide throughout the food chain and to estimate
dietary exposure to acrylamide. In addition, there is
much emphasis on developing food processing
approaches that can reduce acrylamide formation.
Regulatory limits for acrylamide in food have yet
to be established since dietary acrylamide risk
assessments are still being developed. In the meantime, the FDA recommends that consumers eat a
balanced diet that includes a wide variety of foods
low in trans fat and saturated fat and rich in highfiber grains, fruits, and vegetables.

Perchlorate
Perchlorate exists as an anion (ClOÀ
4 ) with a central
chlorine atom surrounded by four oxygen atoms
arranged in a tetrahedron. Perchlorate is manufactured in the United States and is used as the primary
ingredient of solid rocket propellant. Perchlorate
wastes from the manufacture and/or improper disposal of perchlorate-containing chemicals are frequently detected in the soil and water. Levels of
perchlorate have been detected in 58 California public water systems and in water samples from 18
states.
The widespread water contamination by perchlorate and its potential to cause health effects in those
consuming contaminated drinking water have led
four US agencies—the EPA, Department of Defense,
Department of Energy, and National Aeronautics
and Space Administration—to request that the
US National Academy of Sciences convene a study
on ‘‘Toxicological Assessment of Perchlorate
Ingestion.’’
Occurrence in Food

Although the primary concerns from perchlorate
contamination result from drinking water consumption, recent evidence has indicated that
perchlorate may contaminate food items as well.
A small survey of 22 lettuce samples purchased in
northern California showed perchlorate contamination in 4 samples. A subsequent study of
California lettuce showed detectable perchlorate
levels in all 18 samples tested. The toxicological


344 FOOD SAFETY/Heavy Metals

significance of such findings has not been established, but the studies clearly indicate that perchlorate can enter lettuce, presumably from growing
conditions in which perchlorate has contaminated
water or soil.
Milk has also been shown to be subject to perchlorate contamination. A small survey of seven
milk samples purchased in Lubbock, Texas, indicated that perchlorate was present in all of the samples at levels ranging from 1.12 to 6.30 mg/l. To put
such findings in perspective, the State of California
has adopted an action level of 4 mg/l for perchlorate
in drinking water, whereas the EPA has yet to establish a specific drinking water limit.
Toxicological Considerations

Perchlorate is thought to exert its toxic effects at
high doses by interfering with iodide uptake into
the thyroid gland. This inhibition of iodide uptake
can lead to reductions in the secretion of thyroid
hormones that are responsible for the control of
growth, development, and metabolism. Disruption
of the pituitary–hypothalamic–thyroid axis by perchlorate may lead to serious effects, such as carcinogenicity, neurodevelopmental and developmental
changes, reproductive toxicity, and immunotoxicity. Specific concerns relate to the exposures of
infants, children, and pregnant women because

the thyroid plays a major role in fetal and child
development.
The ability of perchlorate to interfere with iodide
uptake is due to its structural similarity with iodide.
In recognition of this property, perchlorate has been
used as a drug in the treatment of hyperthyroidism
and for the diagnosis of thyroid or iodine metabolism disorders.
Ammonium perchlorate was found to be nongenotoxic in a number of tests, which is consistent
with the fact that perchlorate is relatively inert
under physiological conditions and is not metabolized to active metabolites in humans or in test
animals.
Workers exposed to airborne levels of perchlorate
absorbed between 0.004 and 167 mg perchlorate per
day. These workers showed no evidence of thyroid
abnormality, and a No Observed Adverse Effect
Level was established at 34 mg absorbed perchlorate/day. Perchlorate does not accumulate in the
human body, and 85–90% of perchlorate given to
humans is excreted in the urine within 24 h.
See also: Cancer: Epidemiology and Associations
Between Diet and Cancer. Fish. Food Intolerance.
Food Safety: Mycotoxins; Pesticides; Bacterial
Contamination; Heavy Metals.

Further Reading
Becher G (1998) Dietary exposure and human body burden of
dioxins and dioxin-like PCBs in Norway. Organohalogen
Compounds 38: 79–82.
Buckland SJ (1998) Concentrations of PCDDs, PCDFs and PCBs
in New Zealand retain foods and assessment of dietary exposure. Organohalogen Compounds 38: 71–74.
Environmental Protection Agency (2001) Dioxin: Scientific

Highlights from Draft Reassessment. Washington, DC: US
Environmental Protection Agency, Office of Research and
Development.
Food and Drug Administration (2002) Exploratory Data on Acrylamide in Foods. Washington, DC: US Food and Drug Administration, Center for Food Safety and Applied Nutrition.
Friedman M (2003) Chemistry, biochemistry, and safety of acrylamide. A review. Journal of Agricultural and Food Chemistry
51: 4504–4526.
Jimenez B (1996) Estimated intake of PCDDs, PCDFs and
co-planar PCBs in individuals from Madrid (Spain) eating an
average diet. Chemosphere 33: 1465–1474.
Kirk AB, Smith EE, Tian K, Anderson TA, and Dasgupta PK
(2003) Perchlorate in milk. Environmental Science and Technology 37: 4979–4981.
Sharp R and Walker B (2003) Rocket Science: Perchlorate and the
Toxic Legacy of the Cold War Washington, DC: Environmental Working Group.
Tareke E, Rydberg P, Karlsson P, Eriksson S, and Tornqvist M
(2002) Analysis of acrylamide, a carcinogen formed in heated
foodstuffs. Journal of Agricultural and Food Chemistry 50:
4998–5006.
Urbansky ET (2002) Perchlorate as an environmental contaminant.
Environmental Science and Pollution Research 9: 187–192.
Zanotto E (1999) PCDD/Fs in Venetian foods and a quantitative
assessment of dietary intake. Organohalogen Compounds
44: 13–17.

Heavy Metals
G L Klein, University of Texas Medical Branch at
Galveston, Galveston TX, USA
ª 2005 Elsevier Ltd. All rights reserved.

Food that we are culturally habituated to consume is
usually thought to be safe. However, some foods are

naturally contaminated with substances, the effects
of which are unknown. Crops are sprayed with
pesticides while they are being cultivated; some animals are injected with hormones while being raised.
Meanwhile, other foods are mechanically processed
in ways that could risk contamination. This article
discusses food contamination with heavy metals, the
heavy metals involved, their toxicities, and their
sources in the environment. A brief consideration
of medical management is also included. Five metals
are considered in this category: lead, mercury, cadmium, nickel, and bismuth.