Other Additives
In addition to the aforementioned major
groups of additives, there are many others in-
cluding clarifying agents,
humectants,
glazes,
polishes,
anticaking
agents, firming agents,
propellants, melting agents, and enzymes.
These intentional additives present consider-
able scientific and technological problems as
well as
legal,
health, and public relations
challenges. Future introduction of new addi-
tives will probably become increasingly dif-
ficult, and some existing additives may be
disallowed as further toxicological studies
are carried out and the safety requirements
become more stringent.
INCIDENTAL ADDITIVES OR
CONTAMINANTS
Radionuclides
Natural radionuclides contaminate air,
food, and water. The annual per capita intake
of natural radionuclides has been estimated
to range from 2 Becquerels (Bq) for
232
Th
to
K.
The total
exposure of the U.S. population to natural
radiation has been estimated at about 3
mSv.
In addition, 0.6 mSv is caused by man-made
radiation (Sinclair 1988).
Radioactive
Fallout
Major concern about rapidly increasing
levels of radioactive fallout in the environ-
ment and in foods developed as a result of
the extensive testing of nuclear weapons by
the United States and the Soviet Union in the
1950s. Nuclear fission generates more than
200 radioisotopes of some 60 different ele-
ments. Many of these radioisotopes are harm-
ful to humans because they may be incor-
porated into body tissues. Several of these
radioactive isotopes are absorbed efficiently
by the organism because they are related
chemically to important nutrients; for exam-
ple,
strontium-90 is related to calcium and
cesium-137
to potassium. These radioactive
elements are produced by the following
nuclear reactions, in which the half-life is
given in
parentheses:
fission products are formed in the strato-
sphere and gradually come down to earth.
Every spring about one-half to two-thirds of
the fission products in the stratosphere come
down and are eventually deposited by precip-
itation. Figure
11-6
gives a schematic out-
line of the pathways through which the
fallout may reach us.
Previous page
Among the radioisotopes that can be taken
up in the food chain, the most significant as
internal radiation hazards are
barium-140,
cesium-137,
iodine-131,
iodine-133,
stron-
tium-89,
and
strontium-90.
131
I
is chemically similar to ordinary
iodine and, therefore, accumulates in the thy-
roid gland. It has a half-life of eight days and
is a beta-gamma emitter. Because milk is
produced year round and is consumed within
one half-life, the presence of this isotope in
longer life span, which is important because
radiation effects are cumulative.
In 1964, the rate of fallout of
90
Sr
was
about 40 pc/day/m
2
. Total intake of
90
Sr
dur-
ing that period was about 40 pc/day/person
in some Western countries. Because about
3,000 m
2
of arable land are required to pro-
duce food for one person, the total amount of
90
Sr
deposited on that surface was estimated
to be 120 nc per day. This means a reduction
of about 3000-fold, indicating a highly effec-
tive barrier mechanism. The amount of
radioactivity gradually diminished after the
United States and the Soviet Union ceased
their atmospheric test programs. Emergency
measures for decontaminating essential food
items such as milk have been developed.
Such procedures use ion-exchange methods
WATER
SOIL
PRECIPITATION
FALLOUT
NUCLEAR
TEST
AIR
EXHALATION
1967).
Because the fallout comes down with
precipitation, precipitation is a major factor.
In addition, uptake by plants is influenced by
soil type. Wiechen (1972) found that the
137
Cs
content of milk from a small herd of
cows averaged 26 pc per kg when the ani-
mals grazed on an area of sandy soil but
increased to 244
pc/kg
when they were trans-
ferred to moorland. The primary contamina-
tion level of the two soil types was 280 and
262 pc per kg, respectively. The higher trans-
fer rate of
137
Cs
in the moorland soil-grass-
milk chain was the result of the low potas-
sium content of this soil
in game
animals from the southeastern United States
resulted from their feeding on mushrooms
in wooded areas. Common gill mushrooms
(Agaricaceae)
from these areas had
137
Cs
levels as high as 29,000
pc/kg
wet weight,
with a mean of 15,741
pc/kg.
These elevated
levels occurred without similar concentration
of potassium-40. White-tailed deer in these
regions had
137
Cs
levels ranging from 250 to
152,940 pc/kg body weight.
The 1986 nuclear reactor accident at Cher-
nobyl in the Soviet Union distributed radio-
active fallout over most of Western Europe
and the rest of the world. In addition to short-
term problems with radionuclides of short
half-life, there are ongoing concerns in coun-
tries far removed from the source of the con-
tamination. In the United Kingdom there are
concerns over the contamination of sheep,
zenoid compounds (Exhibit
11-3)
(Mitchell
1966).
In addition to the pesticide com-
pounds, there may be residues of their metab-
olites,
which may be equally toxic. Two
important properties of the chlorinated hydro-
carbons are their stability, which leads to per-
sistence in the environment, and their
solubility in fat, which results in their depo-
sition and accumulation in fatty tissues. The
structure of some of the chlorinated hydro-
carbon insecticides is given in Figure
11—7.
Aldrin
is a technical compound containing
about 95 percent of the compound
Exhibit 11-3 Classes of Chlorinated Hydrocar-
bon Insecticides
Class
I—Oxygenated
Compounds
• Chlorobenzilate • Methoxychlor
• Dicofol • Neotran
• Dieldrin • Ovex
• Endosulfan • Sulfenone
• Endrin • Tetradifon
• Kepone
8
Cl
6
,
and contains 58 percent
chlorine. Residues of this compound in ani-
mal and plant tissues are converted into
dieldrin by epoxidation. The epoxide is the
stable form and, thus, it is usual to consider
these compounds together.
Dieldrin contains about 85 percent of the
compound 1, 2, 3, 4, 10, 10-hexachloro-6, 7-
epoxy-1,
4, 4a, 5, 6, 7, 8,
8a-octahydro-exo-l,
4-endo-exo-5,8-dimethano-naphthalene
(HEOD). It has a molecular weight of 381,
formula
C
12
H
8
Cl
6
O,
and contains 56 percent
chlorine. DDT is a technical compound that
contains about 70 percent of the active ingre-
dient pp'-DDT. In addition, there are other
isomers, including op'-DDT, as well as
H
5
Cl
7
.
It
has a molecular weight of 373.5 and contains
67 percent chlorine. In animal and plant tis-
sues,
it epoxidizes to heptachlor epoxide,
which is analogous in structure to HEOD
(dieldrin).
Although relatively stable, the organochlo-
rine pesticides undergo a variety of reactions
that may result in metabolites that are as
toxic or more toxic to mammals than the
original compound. An example is the effect
of ultraviolet light on DDT (Van Middelem
1966).
Under the influence of ultraviolet
light and air, 4,4'-dichlorobenzophenone is
formed. Without air,
2,3-dichloro-l,l,4,4-tet-
rakis-(p-chlorophenyl)-2-butene
is formed.
The latter may be oxidized to 4,4'-dichlo-
robenzophenone (Figure
11-8).
In mamma-
lian tissue, 2,2-bis
-DDE
pp
1
-DDT
ALDRIN
DIELDRIN
TDE
(RHOTHANE)
ENDOSULFAN
sis,
and demethylation (Figure
11-10).
Thio-
phosphates may be changed to sulfoxides
and sulfones in animals and
plants.
In animal products, chlorinated hydrocar-
bon residues are predominantly present in
the lipid portion, organophosphates in both
lipid and aqueous parts. In plant materials,
the residue of chlorinated hydrocarbons are
mostly surface bound or absorbed by waxy
materials,
but some can be translocated to
inner parts. Extensive research has demon-
strated that processing methods such as
washing,
blanching, heating, and canning
may remove large proportions of pesticide
residues (Liska and Stadelman 1969; Farrow
Air
Absent
UV
Light
air
DOT
ooe
DOA
Exhibit
11-4
Classification of Organophospho-
rous Insecticides
Aliphatic
Derivatives
• Butonate • Mevinphos
• Demeton • Mipefox
• Dichlorvos •
Naled
• Dimefox • Phorate
• Dimethoate • Phosphamidon
• Dithiodemeton • Schradan
• Ethion • Sulfotepp
• Malathion • Tepp
• Methyl demeton • Trichlorofon
Aromatic (Cyclic) Derivatives
• Azinphosmethyl • EPN
• Carbophenothion • Fenthion
• Diazinon • Methyl parathion
• Dicapthon • Parathion
• Endothion • Ronnel
abendazole residues in potatoes, and Elkins
Table
11-6
Water Solubilities of Some
Organophosphorus
Insecticides
Insecticide
(ppm)
Carbophenothion
2
Parathion
24
Azinphosmethyl
33
Diazinon
40
Methyl
parathion 50
Phorate
85
Malathion
145
Dichlorvos
1000
Dimethoate
7000
Mevinphos
°o
Source:
From L.E.
tions on the use of many chlorinated hydro-
carbon pesticides have been instituted in
many areas. As a result, the intake of these
chemicals should further decrease in future
years.
Dioxin
The term
dioxin
is used to represent two
related groups of chlorinated organic com-
pounds,
polychlorinated dibenzo-/?-dioxins
(PCDD) and polychlorinated
dibenzofurans
Figure
11-10
Oxidation, Hydrolysis, and Demethylation Reactions of Organophosphorous Insecti-
cides.
Source: From L.E. Mitchell, Pesticides: Properties and Prognosis, in Organic Pesticides in the
Environment,
R.F. Gould, ed., 1966, American Chemical Society.
DDT
Tomatoes
Green
beans
Spinach
Potatoes
CARBARYL
Tomatoes
Green
for PCDD and 135 for PCDF. These
compounds are lipophilic, have low volatil-
ity, and are extremely stable. They are also
very toxic, although the toxicity of each iso-
mer may vary widely. These compounds may
exhibit acute toxicity, carcinogenicity, and
teratogenicity (birth defects). They are ubiq-
uitous environmental contaminants and are
present in human tissues.
PCDD
PCDF
Figure
11-12
Chemical
Structure
of
Polychlorinated
Dibenzo-/?-dioxins
(PCDD)
and
Polychlorinated
Dibenzofurans (PCDF)
Current value accepted
1969
Meeting
Source:
From J.R.
Wessel,
Pesticide Residues in Foods, in
Environmental Contaminants
1
0.012
0.0005
0.02
0.005
0.002
Average
1965-1969
0.00008
0.0005
0.0008
0.00005
0.00003
0.0001
0.00001
0.00001
0.001
0.0002
0.0001
Range
(0.00006-0.00013)
(None-0.0021)
(0.0005-0.0010)
(0.00002-0.00007)
(0.00002-0.00005)
(0.0001-0.0004)
(0.000001-0.00001)
(0.000001-0.00002)
(0.0008-0.0016)
(0.00007-0.00025)
lead to environmental contamination but also
to incorporation of the dioxins in the paper
used for making coffee filters, tea bags, milk
cartons, and so forth. Dioxins can migrate
into milk from cartons, even if the cartons
have a polyethylene plastic coating. Un-
bleached coffee filters and cardboard con-
tainers have been produced to overcome this
problem, and there have also been improve-
ments in the production of wood pulp using
alternative bleaching agents. The FDA guide-
line for dioxin in fish is 25 parts per trillion
(Cordle 1981). Dioxin is considered a very
potent toxin, but information on harmful
effects on humans is controversial.
Polychlorinated Biphenyls (PCBs)
The PCBs are environmental contaminants
that are widely distributed and have been
found as residues in foods. PCBs are pre-
pared by chlorination of biphenyl, which
results in a mixture of isomers that have dif-
ferent chlorine contents. In North America,
the industrial compounds are known as Aro-
clor;
these are used industrially as dielectric
fluids in transformers, as plasticizers, as heat
transfer and hydraulic fluids, and so forth.
The widespread industrial use of these com-
pounds results in contamination of the envi-
ronment through leakages and spills and
ppm in poultry, and 0.3 ppm in eggs. The tol-
erance level for PCB in fish was reduced
from 5 to 2 ppm in 1984. Although there has
been a good deal of concern about the possi-
ble toxicity of PCBs, there is now evidence
that PCBs are much less toxic than initially
assumed (American Council on Science and
Health 1985).
Zabik and Zabik
(1996)
have reviewed the
effect of processing on the removal of PCBs
from several foods. In the processing of veg-
etable oil the PCB present in the crude oil
was completely removed; some was removed
by the hydrogenation catalyst, but most was
lost by deodorization. The PCB was recov-
ered in the deodorizer distillate.
Asbestos
Asbestos is widely distributed in the envi-
ronment as a result of industrial pollution.
Many water supplies contain asbestos fibers,
which may become components of foods
(especially beverages). An additional source
of asbestos fibers may be asbestos filtration
Figure 11-13 The Numbering System Used in PCBs and the Prevalent Substitution Pattern of Chlorine
Table
11-8
Information
on Aroclor Preparations
1.15
2.04
3.10
3.90
4.96
6.30
6.80
8.70
Average Molecular
Weight
192
221
261
288
327
372
389
453
pads;
such contamination has been suggested
to occur in the filtration of beer (Pontefract
1974).
The most common form of this con-
taminant is
chrysotile
asbestos, which occurs
as minute fibers of about 24 nm in size. The
amount of asbestos in water supplies is
extremely low, in the
nanogram
11-9
Asbestos Fibers in Beverages and
Water
Sample
No.
ofFibers/Lx 1CP
Beer
4.3
Sherry
4.1
Soft
drink 12.2
Tap
water, Ottawa 2.0
Tap
water, Toronto 4.4
Source:
From
H.M.
Cunningham and
R.D.
Ponte-
fract,
Asbestos Fibers in Beverages and Drinking
Water,
Nature,
Vol. 232, pp. 332-333,
1971.
may be produced in a food during process-
ing, or may occur incidentally through the
•
Chlortetracycline
and oxytetracy-
cline
• Streptomycin and
dihydrostrepto-
mycin
•
Neomycin,
oleandomycin,
spiramy-
cin
• Chloramphenicol
• Framycetin, bacitracin, and
poly-
myxins
• Tylosin
1
and
nisin
1
• Nystatin
1
NoI
used in human therapeutics
ria.
The action is bacteriostatic and not bac-
tericidal. The tetracyclines have been used to
delay spoilage in poultry and fish. Their
effectiveness seems to decrease quite rapidly,
and lake bottoms into highly toxic methyl
mercury compounds. This conversion scheme
is shown in Figure
11—14.
Formation of the
more volatile dimethyl mercury is favored at
alkaline pH. The less volatile monomethyl
form is favored at acid pH. Because much of
the mercury pollution ends up in rivers and
lakes where it is converted into methyl mer-
cury, contamination of fish with mercury has
been a great concern. In many animal tissues,
methyl mercury may comprise as much as 99
percent of the total mercury present. The
present interest in mercury and its effect on
humans and wildlife originated with the dis-
covery of mercury as the causative agent in
the Minamata disease in Japan. Near the
town of Minamata, a chemical industry used
mercury compounds as catalysts for the con-
version of acetylene into acetaldehyde and
vinyl chloride. Organic mercury compounds
Figure 11-14 Conversion of Inorganic Mercury and Some Mercury-Containing Compounds to Methyl
Mercury. Source: From N. Nelson, Hazards of Mercury, Environmental
Res.,
Vol. 4, pp. 41-50, 1971,
Academic Press.
were released into the waters of Minamata
Bay and contaminated fish and shellfish.
Many cases of mercury poisoning occurred,
Apples New Zealand
11 -135
Pears Australia 40-260
Tomatoes United Kingdom
12-110
Potatoes United Kingdom 5-32
Wheat Sweden 8-12
Rice Japan 227-1000
Rice United Kingdom 5-15
(imports)
Carrots United States 20
White bread United States 4-8
Whole milk United States 3-10
Beer United States 4
Source:
From N. Nelson, Hazards of Mercury,
Envi-
ronmental
Res.,
Vol. 4, pp. 41-50,
1971,
Academic
Press.
Table
11-11
Mercury Levels in Atlantic Coast
Fish
Species Hg
Level Range
(ppm)
result of environmental contamination,
pickup of the metal from equipment, or the
solder of tin cans. It has been estimated that
nearly 90 percent of the ingested lead is
derived from food (Somers and Smith 1971).
However, only 5 percent of this is absorbed.
In the early 1970s, the average North Ameri-
can car was reported to emit 2.5 kg of lead
per year (Somers and Smith 1971), and
Zuber and colleagues (1970) reported that
crops grown near busy highways had a high
lead content (in some cases, exceeding 100
ppm of lead in the dry
matter).
The removal
of lead from gasoline has eliminated this
source of contamination. Lead can also be
picked up by acid foods such as fruit juices
that are kept in glazed pottery made with
lead-containing glazes. Both lead and tin
may be taken up by foods from the tin of
cans and from the solder used in their manu-
facture. The amounts of lead and tin taken up
depend on the type of tin plate and solder
used and on the composition and properties
of the canned foods. In a study on the
detinning of cans by spinach, Lambeth et
al.
(1969)
found that detinning was significantly
materials that are now known to occur in the
environment. The structural formulas of the
major members of this group are presented in
Figure
11-15.
Several of these, especially
benzo(a)pyrene (3,4-benzopyrene), have been
found to be carcinogenic. Usually, the poly-
cyclic hydrocarbons occur together in foods,
especially in smoked foods, because the aro-
matic hydrocarbons are constituents of wood
smoke. Trace quantities of PAHs have been
found in a variety of foods, and this may be
the result of environmental
contamination.
The PAHs may be carcinogenic and mu-
tagenic. The level of carcinogenicity may
vary widely between different members of
this group. Minor constituents of PAH mix-
tures may make large contributions to the
carcinogenic activity of the mixture. Certain
methylchrysenes, particularly the 5-isomer,
which is one of the most carcinogenic com-
pounds known, may dominate the carcino-
genic activity of a mixture
(Bartle
1991).
Rhee and Bratzler (1968) analyzed hydro-
carbons in smoke, and the amounts found in
smoke and in the vapor phase (smoke filtered
other common products.
Bartle
(1991) has
stated that cereals are likely to be a greater
hazard, especially in the form of flour, than
smoked or barbecued foods. Although cereal
has a much lower PAH content than smoked
or roasted foods do, cereal is consumed in
much greater
amounts.
Bacterial and Fungal Toxins
Microbial toxins are some of the most
potent toxins known to humans. They may
be the result of microbial growth in foods or,
as in the case of fungal toxins, growth of
molds during the production of many agri-
cultural crops.
Bacterial toxins are produced mainly from
species of the genera
Staphylococcus
and
Clostridium. The Staphylococcus poison usu-
ally results from improperly handled food in
food service establishments and in the home,
but rarely from food processing plants.
Although the toxin seldom causes human
death, it is highly toxic. In contrast, botuli-
num toxin has a high fatality rate. The neuro-
Figure 11-15
Chemical Structure of Some Polycyclic Aromatic Hydrocarbons
,2-Benzan-
thracene
Chrysene
3,4-Benzopyrene
1 ,2-Benzopyrene
Whole Smoke
51.5
3.8
5.5
5.7
7.0
2.6
1.2
0.9
Vapor Phase
28.4
1.9
4.1
4.2
4.3
0.3
0.4
Trace
Source:
From K.S.
Rhee
and LJ. Bratzler, Polycy-
clic Hydrocarbon Composition of Wood Smoke, J.
Food
ScL,
Polycyclic Aromatic Hydrocarbons Found in Smoked Food Products (ppb)
Source:
From J.W. Howard and T. Fazio, A Review of Polycyclic Aromatic Hydrocarbons in
Foods,
Agr.
Food
Chem.,
Vol. 17, pp.
527-531,1969,
American Chemical Society.
Food
Product
Beef,
chipped
Cheese, Gouda
Fish
Herring
Herring (dried)
Salmon
Sturgeon
White
Ham
Frankfurters
Pork roll
Benzo
(a)-
anthracene
0.4
1.7
0.5
Pyrene
0.5
2.6
2.2
1.8
2.0
4.4
4.0
11.2
3.8
2.5
4-Methyl-
pyrene
2.0
Table
11-14 Polycyclic
Aromatic Hydrocarbons
In
Unsmoked Food Products
Fluoran- Pyrene
Food
Product
thene (ppb) (ppb)
Cheese, cheddar 0.8 0.7
Fish,
haddock 1.6 0.8
Fish,
herring (salted) 0.8 1.0
Fish,
salmon 1.8 1.4
, B
2
,
G
1
,
and
G
2
.
The
names result from the blue and green fluores-
cence of these compounds when viewed
under ultraviolet light.
Aflatoxin
B
1
is a very
powerful liver carcinogen; a level of 15 ppb
in the diet of rats resulted in tumors in 100
percent of cases after 68 weeks (Scott 1969).
Ducklings are used as test animals because
they are especially sensitive to aflatoxins.
The aflatoxins, for which the formulas are
shown in Figure
11-16,
can occur in many
foods but are particularly common in pea-
nuts.
Roasting of peanuts reduces the level of
Perylene 0.6 —
11,12-Benzfluoranthene
1.8 —
Anthanthrene 0.9 —
1,12-Benzperylene
2.2 —
3,4-Benzfluoranthene
1.2
—
Coronene 0.9 —
lndenopyrene 0.7 —
Source:
From W. Fritz, Formation of Carcinogenic
Hydrocarbons During Thermal Treatment of Foods,
Nahrung,
Vol.
12,
pp. 799-804,
1968.
ingestion of moldy feed by animals, aflatox-
ins may end up as contaminants in milk and
meat. Aflatoxins found in milk may be Ml
or M2, where M stands for metabolic; these
are also toxic. The development of aflatoxins
depends very much on temperature and
moisture conditions. With peanuts, contami-
nation occurs mostly during the drying
period. Improper drying and storage are
responsible for most of the contamination.
This has been found to apply for rice. Opti-
especially corn. Molds of the species
Fusarium produce several mycotoxins in
countries with moderate climates (Andrews
et
al.
1981).
Two of these are zearalenone
and deoxynivalenol (Figure
11-17).
Zearale-
none, of F-2 toxin, is produced by Fusarium
molds that grow on corn (Marasas et al.
1979) that is immature or high in moisture at
harvest. Deoxynivalenol, also known as
vomitoxin, has been found in wheat and bar-
ley (Trenholm et al. 1981; Scott et al. 1983).
During the wet summer of 1980, wheat
grown in Ontario showed sprouting of ker-
nels and pink discoloration. Experiments on
milling showed that the vomitoxin was dis-
tributed throughout the milled products and
was not destroyed by the bread-making pro-
cess.
Patulin is another Aspergillus metabo-
lite and has been indicated as a food con-
taminant, especially in fruits, as a result of
storage rot. It has been found as a constituent
of apple juice (Harwig et al. 1973).
Natural Toxicants
In spite of the prevalent perception that
2,
pp. 173-177, 1969.
B,
G,
B
2
G
2
trial and error. This process is effective in
eliminating foods that cause acute symptoms
of toxicity but is less effective in dealing
with the long-term effects. Coon
(1973)
has
stated that past experience has provided
more knowledge on the safety margins of
natural foods than animal experimentation.
Many natural food components, such as caf-
feine, goitrogens, and cyanogenic
glyco-
sides,
would not be approved for human
consumption if examined with the tech-
niques now required for intentional addi-
tives.
Because our foods contain so many
potentially toxic substances, the best defense
is to consume a varied diet.
Some natural toxins such as seafood toxins
or fungal toxins may occur at abnormally high
PATULIN
STERIGMATOCYSTIN
OCHRATOXIN
A
individuals (Coon 1973). The latter case is
probably the most difficult to deal with in reg-
ulatory aspects. Banning of foods that are
considered safe for most people is unthink-
able,
and protection of diseased or allergic
individuals becomes a problem. Some exam-
ples of natural toxins in foods are given below.
Sulfur Compounds
Many cruciferous plants contain goitro-
gens,
which are known as glucosinolates.
They are harmful if ingested in excessive
amounts. Plants of the genus
Allium,
includ-
ing onions, chives, and garlic, contain pre-
cursors of sulfur-containing compounds that
can be liberated by enzymic action.
Salunkhe and Wu (1977) have described
the enzymic breakdown of the glucosinolate
to isothiocyanate and goitrin (Figure
11-18).
In addition to being goitrogens, the isothio-
cyanates produced from glucosinolates in
rapeseed (canola) oil have been found to
problem more difficult to control. In 1987,
mussels cultivated in Eastern Canada were
found to be poisonous, and the cause was
established as the toxin domoic acid. Para-
lytic shellfish poisoning has been observed in
many of the world's fishing areas. Although
some of these toxins have been identified,
many remain
uncharacterized (Shantz
1973).
The poison saxitoxin, from California mus-
sels and Alaska butter clams, is a dibasic salt
and is highly soluble in water.
Caffeine
Caffeine is a naturally occurring chemi-
cal,
1,3,7-trimethylxanthine
(Figure
11-19),
which is found in the leaves, seeds, and fruits
of more than 63 species of plants growing all
over the world. It occurs as a constituent of
coffee, tea, cocoa, and chocolate, and is an
additive in soft drinks and other foods. Be-
cause humans have used it for thousands of
years,
caffeine has GRAS status in the
United States. Roberts and Barone (1983)
have estimated that daily caffeine consump-
tion in the United States is 206
9, pp. 265-324, 1977.
GOITRIN
(S-
5-
VINYLOXAZOLIDINE-2-THIONE)
THIOCYANATE
ISOTHIOCYANATE
CYCLIZATION
NITRILE
S
SULFUR
UNSTABLEAGLUCON
GLUCOSE
BISULFATE
PROGO(TRIN
THIOGLUCOSIOE
GLUCOHYDROLASE
E.C.
3.2.3.1
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