Download FOOD ADDITIVES - Soegijapranata Catholic University

Lecture Material - Food Safety
Inneke Hantoro
FOOD ADDITIVES
Direct & Indirect Chemical Residues
Definition
• Any substance added to food during production,
processing, treatment, packaging, transportation or
storage.
• In legally term, it defined as “ any substance the
intended use of which results or may reasonably be
expected to result directly or indirectly in its
becoming component or otherwise affecting the
characteristics of any food” (FDA/IFIC, 1992).
• Direct additives are added to a food for a specific
purpose and are identified on the ingredient label of
the food.
• Indirect additives unintentionally become part of the
food in trace amount due to its handling, packaging,
etc.
• Excessive levels of an additive or inclusion of an
undeclared additive may be directly dangerous in
some instances.
Migration of Packaging
• Plastic consists of its polymer, plasticizers, antistatic
agents, stabilizers and antioxidants, etc.
• Some components are more likely to migrate into
foods than others, esp. residual plastic monomers
and plasticizers.
• The plastic monomers of most health concern are
vinyl chloride, and styrene.
1. Vinyl Chloride Monomer (VCM)
• The monomer of polyvinyl chloride (PVC).
• It leaches into both water and fats.
• Typical products that absorb VCM are bottled
mineral water and cooking oils.
• Mineral water (stored in PVC bottles) has been
shown to take up VCM. After 6 months, a
concentration of 170 mg/l was measured.
• This may lead to a daily intake of 120 ng per person
in countries where PVC bottled drinking water is
used.
• In cooking oils, higher concentrations have been
found, 14.8 mg/kg.
• It also the most available for migration from the
‘cling films’ that are used for all kinds of foods.
• Vinyl chloride has been identified as a liver
carcinogen in animal models as well as in humans.
• Acute intoxication causes depression of the central
nervous system and hepatic damage.
2. Styrene
• While paper and board materials may transmit taint
or odor to a food, plastics have a much greater
potential to do this.
• These taints may be residual monomer e.g. styrene.
This is probably the compound usually responsible
when consumers detect a 'plastic taste' in a food
• Styrene prefers to leach into fats.
• Typical sources of styrene: deli packaging (sausages,
ham, smoked beef/ bacon/ fish, etc) and yoghurt
cups.
• It is a potent mutagen.
• Styrene-induced toxic effects include renal and
hepatic damage, pulmonary edema, and cardiac
arrhythmia. The oral LD50 in rats is relatively low is 5
g/kg.
• Average concentrations of 27 ppb have been
measured in high-fat yogurt, 71 ppb in fruit yogurt,
20 to 70 ppb in other desserts, 18 to 180 ppb in meat
products and 5 ppb in packed fruit and vegetable
salads.
• For styrene, a provisional ADI of 40 ng/kg has been
calculated.
3. Plasticizers
• Important plasticizers in PVC plastics are the phthalic
acid esters di-(2- ethylhexyl) phthalate (DEHP) and din-butyl phthalate (DBP).
• The phthalic acid esters DEHP and DBP have low
acute toxicities.
• However, liver or lung damage by the leached
plasticizers has been suggested. DEHP and DBP
appear to be non-genotoxic carcinogens.
• Since they are widely distributed in materials
involved in transportation, construction, clothing,
medicine, and packaging, the concern about their
health effects has increased.
• Different plastics and forms are designed for specific
product containment situations.
• Use of this plastic packaging in a manner other than
that for which it was designed may cause significant
migration of plastic compounds into the food.
Situation that can promote contaminants
migration:
• Heating containers (by microwave oven) which are
designed solely for chilled foods.
• Overheating ‘heat resistant’ containers.
• Coming close to laminating leftovers covered with
cling wrap in the microwave.
Following the instruction on the label / packaging is
important!
Nitrates, Nitrites, and N-nitroso compounds
• Nitrates (NO3) and nitrites (NO2) are used to preserve
meat products, such as bacon, ham, hot dogs, and
cold cuts.
• The addition of nitrite can give desirable color to
meat products (pink) and flavor, retards fat oxidation,
and prevent bacterial growth (especially Clostridium
botulinum).
• Nitrites was intentionally added to meat in the 16th
or 17th century.
1. Nitrites
• Nitrite inhibits the bacterial production by inhibiting
certain enzymes within the microbe and on its cell
membrane.
• Nitrite weakens the bacterial spores, reducing the
like-hood of germination.
• Nitrite is very reactive and can be directly toxic or
form carcinogenic N-nitroso compounds.
• It can oxidize blood oxyhemoglobin (ferrous form) to
methemoglobin (ferric form).
• Oxyhemoglobin is a good transport for oxygen
throughout the body, while oxygen can’t bind to
methemoglobin  unavailable for respiration.
• Excessive nitrite intake can lead to cyanosis and
suffocation.
• The average lethal dose of nitrite is approx. 4 g as
sodium nitrite.
• The sub-lethal doses of nitrite may lead to
abnormalities in metabolism of the body.
• When nitrite is acidified to nitric oxide, it provides
antimicrobial activity.
• If it reacts with amines under acidic conditions,
carcinogenic nitrosamines may be formed.
• The residual amounts of nitrites in various meat
products should not exceeded 100 mg/kg, or 50
mg/kg for dried meat products, and 175 mg/kg for
cured bacon.
• ADI for nitrites expressed as sodium nitrites is 0.1
mg/kg body weight.
2. Nitrates
• Commonly found in water and vegetables, especially
those grown with high-nitrate fertilizer.
• It has low reactivity  not toxic.
• However, nitrate becomes a hazard when it is
reduced to nitrite! Dietary nitrates can be converted
to nitrites during digestion.
• Cases of life-threatening methemoglobinemia when
the patient’s diet contained too many nitrate sources
(e.g. drinking water and spinach) within a short time
span.
• 5% of ingested nitrates in saliva is reduced to nitrite
by bacteria.
3. N-nitroso compounds
• There are 2 types: nitrosamines & nitrosamides.
• They are formed when a nitroso group replaces a
hydrogen attached to a nitrogen  nitrosation.
• The formation of these compounds is encouraged at
high temperature and can be catalyzed directly by
stomach acid or bacteria.
• Nitrosamines are generally stable and can be quickly
distributed through the body, although need
metabolic activation for mutagenic and carcinogenic
activity.
• Nitrosamines are found in cured meat products and
malt products (beer).
• Another case: nitrosamine in rubber baby bottle
nipples!
• Nirosamides are direct mutagen.
• They can be decomposed at mild alkaline condition
or destroyed by cooking.
• The mutagenic/carcinogenic potential of nitroso
compounds in animal models is well documented,
but the toxicity to humans is not proven.
• Exposure to nitroso compound can be minimized as
contaminants by using ascorbic and erythorbic acids
in curing solutions, which have synergistic effect on
nitrite.
• The level of sodium ascorbate is 550 ppm together
with sodium nitrite (100-200 ppm) in bacon product
(USFDA).
• If sugar and LAB are also added, the amount of
nitrite used is about 40 ppm.
• The max limit of nitrosamine allowed in fried bacon
is 10 ppb (USFDA).
• Nitrite in smoked fish should be monitored as well 
at least 100 ppm in vacuum packed smoked fish to
prevent botulism, but should also be less than 200
ppm to prevent nitrite poisoning.
Sulfites
• Sulfites (SO3) are used as antioxidants to prevent
enzymatic browning, inhibit bacterial growth (in
wine), bleaching agent, dough conditioner, to
prevent melanosis on shrimp, and in the production
of some food packaging.
• They are present in the form of sulfur dioxide,
sodium sulfite, sodium metabisulfite, sodium
bisulfite.
• Individuals with asthma problem are sensitive to
sulfites.
• GRAS (Generally Recognized As Safe) since 1959, but
then they are banned by FDA (1986) after reported
causing some health problems when they used to
maintain the color and crispness of the salad greens.
• Sulfites sprayed onto foods produce the most rapid
allergic reactions.
• Sulfites can destroy thiamin  banned by FDA to be
used in important sources of the vitamin (e.g.
enriched flour).
• FDA requires that product labels declare sulfites in
excess of 10 ppm (detected level).
• Sulfites are not permitted to be used in meats.
• Their limit in shrimp is 100 ppm.
• The major food groups contributing to dietary intake
of sulphites consist of a wide variety of foods and
soft drinks (dried fruit 600–2000 mg/kg; lime and
lemon juice, ‘barley water’ 350 mg/kg; concentrated
grape juice 2000 mg/kg; beer and cider 20–200
mg/kg; wines 200–260 mg/kg).
• The ADI for sulphites (expressed as sulphur dioxide)
is 0.7 mg/kg body weight.
• Unpackaged food in bulk form should have a sign
stating that sulfites were used.
• Case sulfite poisoning in US (1997), canned tuna
contained sulfites (not declared on the label) 
sulfites were identified from one of the ingredients –
the hydrolyzed vegetable protein (used as flavor
enhancer).
Phenolic Antioxidants
• They are used to protect fats against oxidation.
• Butylated hydroxytoluene (BHT) and butylated
hydroxyanisole (BHA) are radical scavenger.
• They interfere propagation step during lipid
peroxidation.
• Curiously, these antioxidants can exhibit both
antitumorigenic and tumorigenic effects, and they
are known to alter enzyme activity affecting
detoxification of xenobiotics.
• BHA and BHT have low acute toxicity.
• They are categorized as GRAS in FDA.
• In 1980’s BHA was suspected to have carcinogenic
potential in animals and to be nongenotoxic 
should have a threshold dose.
• BHT metabolism is more complex and slower than
BHA. It is reported to have toxic effects on organ
systems.
• However, BHA and BHT are still permitted to be used
in food  0.02% (200 ppm) of the fat oil content of
the food product or 50 ppm (combined BHA and
BHT) if they are used dry low-fat product.
Salts
• An important food additive for prevention of bacterial
growth, for necessary technical reason, or for flavor.
• The chemical name for salt, sodium chloride, reveals
that sodium is in fact a component of salt. By weight,
salt is composed of 40% sodium and 60% chloride. One
teaspoon of salt weighs 5 grams and contains about
2,300 mg of sodium.
• Both sodium and chloride ions are important in
physiological processes, but excess sodium directly
cause hypertension (high blood pressure), a major risk
factor for heart disease, stroke and kidney disease.
• The typical modern consumption of sodium is 10-20
times the amount needed for physiological balance.
• Potassium containing table salt substitutes can cause
hyperkalemia in high dose.
• FDA limit sodium to 2400 mg daily for a 2000- calorie
diet.
• The best way to reduce salt intake: read labels and
make educated choices!
Sodium labelling defined by FDA:
• Sodium free or salt free: Less than 5 mg per serving
• Very low sodium: 35 mg or less of sodium per serving
• Low sodium: 140 mg or less of sodium per serving
• Low sodium meal: 140 mg or less of sodium per 3 ½
oz
• Reduced or less sodium: At least 25% less sodium
than the regular version
• Light in sodium: 50% less sodium than the regular
version
• Unsalted or no salt added: No salt added to the
product during processing
Nonnutritive sweeteners
• Low calorie sweeteners, such as saccharin,
aspartame, acesulfame.
Saccharin
• It is 300 times sweeter than sugar.
• It is not metabolized  no calories.
• It comes in the forms of pure saccharin, ammonium
saccharin, calcium saccharin, and sodium saccharin.
• Saccharin has low direct toxicity  has a threshold.
• It was allowed to be used in beverage additive at not
more than 12 mg/fluid ounce, not more than 30 mg
per serving as processed food additive.
• ADI for saccharin is 2.5 mg/kg body weight.
• But it has been implicated as a potential human
carcinogenic (since 1981), then it was de-listed as a
safe food additive.
• In April 2000, saccharin was de-listed as a possible
human carcinogen due to the lack of data in humans
suggesting a carcinogenic hazard.
• This decision caused a controversy. Another source
stated that saccharin correlated bladder cancer.
• Saccharin-containing products are still required to
have warning statement on their labels.
Aspartame
• Approved in 1981 as artificial sweetener.
• It is 200 times sweeter than sugar and has the same
number of calories per teaspoonful.
• Aspartame is a dipeptide consisting of L-aspartic acid
and the methyl ester of L-phenylalanine.
• It can be hydrolyzed into aspartic acid, phenylalanine
and methanol during digestion.
• Chronic methanol exposure can cause visual
impairment.
• Phenylalanine can interfere with amino acid
transport and lead to nervous system disturbances
 only a problem in people with the rare genetic
disease phenylketonuria (PKU) – unable to
metabolize phenylalanine properly.
• When aspartame containing product are heated or
stored for a long period, aspartame can be
decomposed into diketopiperazine (DKP), a tumor
agent.
• ADI for DKP is 30 mg/kg bw.
• ADI for aspartame is 50 mg/kg bw.
• In ready to bake product aspartame is limited to
0.5% by weight.
Stevioside
• A natural sweetener from Stevia rebuadiana plant.
• It is 200-300 times sweeter than sugar and have no
calories.
• It was used as a common sweetener in Japan (herbal
teas) during 1980’s.
• It was banned in 1991 because of the lack of formal
toxicological evaluation proving its safety.
• It is not allowed in Canada and some EU.
• Some current studies indicate that steviol, a
metabolite of stevioside may have toxic effect (EC).
• Ironically, stevia is allowed as a nutritional
supplement (FDA Import Allert 45-06, 1996).
Color additives
• FD&C color  safe for foods, drugs and cosmetics.
• Certified color belong to four classes: azo dyes,
triphenylmethane dyes, xanthene dyes and
sulfonated indigo dyes.
• They should be used at less than 300 ppm, according
to GMP it is still too high considering the
tolerances of other chemical residues!
• Some colorants have been de-listed due to their
carcinogenic potential, such as:
- FD&C Red No.1  hepatocarcinogenic
- FD&C Red No.2  still used in developing countries
(insufficient toxicological evidence to human health)
- FD&C Red No. 4  originally margarine/butter
colorant, delisted in 1976 due to its toxicity.
- FD&C Red No. 40  allowed in US but not in some
European countries.
- Citrus Red No. 2  only allowed for coloring orange
skins, implicated as animal carcinogen.
- FD&C Yellow No.3 and No. 4  originally used as
margarine colorants, delisted in 1959 due to
hepatotoxicity.
- Yellows No. 5 (tartrazine) and 6 (sunset yellow) are
associated with allergic reactions and specifically
required to be declared on ingredient labels.
- Orange B is permanently listed, but is restricted to be
used on the surfaces of sausage casings at level of no
more than 150 ppm.
Reference
• Schmidt, R. H. & G. E. Rodrick. (2003). Food
Safety Handbook. John Wiley & Sons Inc. New
Jersey.
• Wood R., L. Foster, A. Damant & P. Key. (2004).
Analytical Methods for Food Additives. CRC
Press. Boca Raton.