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C10H20


150° and 300°


Burning oil distillate kerosene



From the residue left after distillation at 300°, liquid paraflSn,
vaseline, and solid paraflSn are prepared. These are essentially
paraffins that distil between 300° and 390°C.

LIQUID PETROLATUM

Liquid petrolatum may be obtained from petrolatum after
the fractions distilling under 330° have been removed. The re-
maining liquid, when distilled between 330° to 390°, gives liquid
petrolatum which is purified by treating with sulphuric acid, and
then by caustic soda, and by filtering while hot through some
decolorizing agent, like animal charcoal or Fuller's earth. It
is used in medicine as a cathartic and as a vehicle for other drugs.

Petrolatum, U. S. P. or petroleum jelly, is a soft paraffin or
vaseline obtained from the liquid paraffin distillate. . The part
solidifying at 38°-54° is called petrolatum or vaseUne.

Paraffin durum, or hard paraffin, is chemically similar to vase-
line, but has a higher melting point, 50°-57°, hence it will cry-
stalUze out of the distillate before vaseline. It is prepared in the
cakes of commerce by pressure, and on account of its inertness is
used in the laboratory around the stoppers of acid and alkali
bottles. It has been used by "beauty specialists" to remedy
minor deformities by injecting under the skin, a procedure which
is not recommended.

Light liquid petrolatum (petrolatum levis) is used as a vehicle



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PETROLEUM 15

especially for nasal and throat sprays. It is itself an emollient
and as such serves to soothe, and to protect inflamed mucous
membranes, and at the same -time mild antiseptics like menthol
or eucalyptol are incorporated with it. A popular nasal spray
or nebula consists of one per cent, each of menthol and eucalyptol
in light liquid petrolatum.

Liquid petrolatum (heavy-Petrolatum ponderosum or gravis)
is used as a cathartic and is very servicable where a cathartic
has to be given continuously as in chronic constipation and
certain diseases of the intestine. It acts mechanically. Any
non-absorbable fluid may act in the same way. It is valuable in
these cases, because it does not cause griping, and does not be-
come inert through continual use. The physical difference be-
tween light and heavy petrolatums is mainly a difference of
viscosity.

The following tables show how the boiling point changes as the
molecular weight increases.



Substance


Molecular


Boiling




formula


point


Methane


CH4


-164°


Ethane


C2H6


- 84°


Propane


CaHg


- 45°


Butane


C4H10 ^ ,


r


Pentane


C6H12


36°


Hexane


CeHu


70°


Eicosane


C20H42


330°


Penta tria contane


C36H72


331°


Dimyricyl


C60H122





OCCURRENCE IN NATURE

Methane, br marsh gas, CH4, the first of the series, is found
in marshes and coal mines in varying amounts, and wherever
decomposition of vegetable matter in lack of oxygen occurs.
Mixed with air, methafne is known as the fire damp of mines. It
is one of the gases of the intestine, and in smaller amounts may
be found in respired air. It may be prepared synthetically in a
number of ways. These methods have little direct interest in
pharmacology, but since they are fundamental and illustrate how



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16 CHEMICAL PHABMACOLOGY

paraffins may be formed from the elements they are briefly
indicated:

SYNTHESIS OF METHANE

I. Hydrogen sulphide and carbon bisulphide passed through
a red hot tube containing copper, yield CH4.

2H2S + CSa + 4Cu = 4CuS + CH4

II. By passing carbon monoxide and hydrogen over reduced
nickel at 200**C.

CO + 3Ha = CH4 + H2O

III. At 250**C., CO2 is also reduced in the presence of finely
divided nickel.

CO, + 4Ha = CH4 + 2H2O

IV. Methyl alcohol or wood spirit can be converted into
methane by changing to methyl iodide and then (a) the iodide
nascent hydrogen:

CH3OH + la + 2H = CH,I + H2O + HI or (6)
CH3I + 2H = 2CH4 + HI
These and many other methods are used for preparing methane.
Methane itself has no uses in medicine. The most important
derivatives of methane from a pharmacological point of view, are
methyl alcohol because of its toxicity and as a source of form-
aldehyde. The latter is used because of its antiseptic action.

ETHANE

This is the second member of the paraffin or methane series.
It occurs in small quantities in natural gas and crude petroleum.
Its derivatives only are important. It may be prepared synthe-
tically in a number of ways, which show that it is made up of two
methyl (CH3) groups, as the following reaction shows:
2CH3I + 2Na = CH3.CH3 + 2NaI
Ethane is also formed when ethylene is treated with nascent
hydrogen:

C2H4 -f" 2H = CaHe
or when ethyl iodide is treated with hydrogen
CaHfil + 2H = C2H6 + HI
while ethane is not used in medicine its derivatives are exceedingly
important.



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METHANE SEBIES



17



IMPORTANT DRUGS OF THE METHANE SERIES
m. ALCOHOLS

The drugs of the methane* series includes alcohols, ethers,
ketones, and many derivatives which are used as narcotics or
hypnotics.

Alcohols are hydroxyl derivatives of the marsh gas series (c/.
phenols). According to the number of hydroxyls in the molecule
they are classified as:

1. Monatomic or monhydric

2. Diatomic or dihydric, etc.

No gaseous alcohols are known. Up to C12H26OH with few
exceptions they are neutral, colorless liquids with a pleasant odor
and burning taste. The more important members of the mon-
hydric alcohols with their boiUng point and specific gravity are
as follows:



Substance



Chemical
fommla



B.P.



Spec.
Grav.



Relative

toxicity

(Baer)



Methyl alcohol. .
Ethylalcohol. . . .
Propyl alcohol. .'.

Butyl alcohol

Amyl alcohol



CHgOH
CaHfiOH
CHtOH
C4H9OH
CsHiiOH



66°

97°
117°
131°



0.812
0.806
0.817
0.823
0.825



0.8 (?)

1.

2.

3.

4.



Ethyl alcohol is the only one that is used in medicine to any
degree. Methyl and amyl alcohols are of importance because of
their toxicity. The relative toxicity given by Baer does not
hold good for all forms of life. It is only approximate at best.
For man, it is incorrect, methyl being more toxic than ethyl.
As. we ascend in the alcoholic series, the members soon become
more solid, and much lees soluble, hence less toxic. A drug that
is insoluble in the tissues or fluids of the body is inert. However,
many substances that are insoluble in water dissolve readily in
the body fluids. Next to water, alcohol is the solvent that will
dissolve the greatest number of substances.

Methyl alcohol, or wood spirit, is prepared on a large scale by
the dry distillation of wood. It is important in medicine chiefly
because many cases of poisoning have arisen from its use.. Its



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18 CHEMICAL PHARMACOLOGY

actions in general are the same as ethyl alcohol, and are exerted
mainly on the central nervous system. It seems to have a
selective action on the optic nerve, and blindness often follows
its use; even one dose of about 60 cc. has caused permanent
blindness. Many such cases have been reported recently.
In repeated doses it is much more toxic than, ethyl alcohol. It
has been used in patent medicines because it is cheaper than
ordinary alcohol. Its use, however, should be condemned
unhesitatingly.

The main differences in the intoxication of methyl and ethyl
alcohols are: The coma produced by methyl alcohol may last
for several days, as compared with a few hours in case of ethyl
alcohol. Methyl alcohol readily attacks the optic nerve and may
cause the blindness, which is absent in the action of ethyl alcohol.
The oxidation products of methyl alcohol, formaldehyde and
formic acid, are prone to irritate the kidneys and bladder, con-
sequently nephritis and cystitis are frequent after wood alcohol
poisoning.

Tests for Methyl Alcohol

1. It burns with a luminous flame. In this it resembles ethyl
alcohol. In the body however, it is not so readily oxidized.

2. It dissolves fats, oils, resins, etc. and is extensively used for
this purpose being a better solvent for these than ethyl alcohol.
This greater solvent power for lipoids may be the cause of its
greater toxicity.

3. It is miscible with water in all proportions, the same as
ethyl alcohol.

4. Methyl alcohol may be converted into methyl salicylate
(oil of Wintergreen) as follows :

To some sodium salicylate in a test tube, add an equal volume
of methyl alcohol and concentrated sulphuric acid. Heat gently.
The odor is that of methyl salicylate; which is an important anti-
rheumatic remedy.

,0H .OH ^

CeH/ + CH3OH = CgH/ + NaOH .

^COONa ^COOCHs

Sodiumsalicylate methylalcohol methylsalicylate.
Oleum betulse (oil of birch) is also methyl salicylate.



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ALCOHOL 19

5. Methyl alcohol readily yields formaldehyde on oxidation.
Heat a small copper spiral to redness and drop it quickly into
a test tube containing two or three drops of methyl alcohol.
Note the odor of formalin. This same reaction takes place in
the body when methyl alcohol is taken.

H H

H— C— H-> H— C— 0H-> H— Cf

I ^ I ^H .

H H

Methane Methyl alcohol Formaldehyde

An oxidation of the hydrocarbons has not been observed in
the body.

ETHYL ALCOHOL

Ethyl alcohol, C2H6OH, grain alcohol, or alcohol, is the next
higher homologue in the methyl series, and is the result of fer-
mentation of the sugars, of fruits and certain plants. Sugar
and consequently alcohol may be prepared from any plant that
contains starch. The U. S. P. (IX) requires that the ordinary
commercial alcohol contain not less than 92.3 per cent, by weight
and 94.9 per cent, by volume of C2H5OH. When a specific
kind of alcohol is not mentioned, ethyl alcohol is always
understood.

Alcohol dilutum contains alcohol, one-half, and distilled water
one-half by volume.

Alcohol dehydratum or absolute alcohol is obtained by treating
96 per cent, alcohol with quicklime, and distilling. The lime
holds all but the last traces of water which are taken out with
anhydrous copper sulphate. When rectified again, it contains
0.5 per cent, water in which form it is used commercially, but the
pure absolute alcohol can be obtained by treating the latter with
barium oxide and re-distillation. Absolute alcohol is so hygro-
scopic that as a rule it is not found on the ordinary market.
It contains 0.5 to 1 per cent, water. To prove the presence of
water in alcohol, drop a small piece of anhydrous copper sul-
phate into 5 cc. of alcohol. Shake and let it stand. If the



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20 CHEMICAL PHARMACOLOGY

slightest trace of water be present, a light blue color develops.
Also if a few drops of liquid paraflSn be added to the same
amount of alcohol and shaken, a cloudiness due to the formation
of an emulsion by the water, indicates the presence of water.

Whiskey, is prepared from fermented grain, potatoes, or any-
thing containing starch. The starch is hydrolyzed to glucose and
this on fermentation yields alcohol. Whiskey contains about
45 to 56 per cent, alcohol.

Gin, containing about 40 per cent, alcohol, is also made from
grain and in its final distillation, juniper berries, anise seed, etc.,
are added.

Rum, prepared from fermented molasses, contains from 45 to
55 per cent, alcohol.

Brandy, prepared from fermented juices of such fruits as
grapes, apples, peaches, etc. contains about 45 to 55 per cent, of
alcohol.

Wine, champagne, and beer, are obtained by direct fermenta-
tion and are not distilled. Wine and champagne contain about
8 to 10 per cent, alcohol.

Beer is produced by fermenting malted grain with the addition
of hops, for the taste. It contains from 3 to 5 per cent, alcohol.

Alcohol is important because of:

1. Its local irritant action.

2. Its action on the central nervous system.

3. Its destructive action on the tissues.

4. Its supposed food value.

A study of these properties places alcohol among drugs and
poisons rather than among foods.

When alcohol over 60 per cent, is applied to the skin it tends
to unite with the living protoplasm and the reaction produces
redness, itching and a sense of heat. On mucous membranes
and especially on abrasions the irritant action is much greater.
If applied to blood or protein solution, alcohol over 60 per cent,
will cause precipitation on standing. This union with protein
confers astringent properties on alcohol. Alcohol, however,
even in strong solutions (90 per cent.) may be slowly injected
into the blood stream without causing precipitation, since the
circulation causes it to be rapidly diluted. On the cerebrum



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ALCOHOL 21

alcohol depresses progressively the psychic, sensory and motor
functions. It attacks the brain functions in the reverse order of
their evolution. The sense of judgment, attention, perception,
reflection, and logical sequence are first to be depressed. The
apparent stimulation being due to depression of the controlling
function. There is no stimulation of the intellectual faculties,
as shown by psychological tests of accuracy, rapidity, or mental
exercise. There is no stimulation of the motor areas of the brain
as shown by response to electrical stimulation of the areas.
There is no stimulation of the medulla as judged by effect on
blood pressure, heart and respiration. There is no stimulation
of the cord as judged from the condition of the reflexes. The
peripheral nerves and nerve endings are depressed and neuritis
may be produced by continued use of alcohol. Bacterial toxins
and heavy metals such as lead and arsenic may cause a similar
neuritis.

The destructive action on the tissues is shown by :

The antiseptic action. The growth of microorganisms is
retarded by all concentrations over 10 per cent. The greatest
effect being manifested by about 70 per cent. This is apparently
due to the fact that stronger solutions cause a precipitation film
on the surface of the organism which retards absorption.

The gastro-intestihal tract especially of the stomach of alco-
holics frequently shows a chronic inflammatory condition.
Nephritis and hepatitis are very common^ and neuritis due to
alcohol is relatively frequent.

Alcohol as a food — sl great deal can be oxidized in the body and
to that extent it is a food. A dog weighing 25 lbs. is known to
have oxidized 95 per cent, of 16 grams absolute alcohol in 53^
hours. It can also replace fat' and carbohydrates to a certain
degree and spare protein waste, but it cannot build up tissue.
Since it is easily oxidized and can supply energy, and prevent
tissue destruction, it may be used as a medicinal food. Its
destructive action on the tissues and its proneness to result in
the formation of a vicious habit, prevent its being classified with
foods.

Offer gives the following experiment on a healthy man to show
the effects of alcohol, as a food:



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22



CHEMICAL PHABHACOLOGY





Oram


Nitrogen




Period 1.


Diet alone


Loss, 0.3441


Body nearly in nitro-
genous equilibrium


Period 2.


Diet 100 grams of


Loss, 1.1689


Toxic action on tis-


*


alcohol




sues


Period 3.


Diet 100 grams of


Gain, 0.2335


Tolerance beginning




alcohol




to be established,
and alcohol acting as
a protein-spaiing
foodstuff


Period 4.


Diet alone


Loss, O.OUO




Period 5.


Diet with added fat
equivalent to 100
grms. of alcohol


Gain, 1.5654





The Fate of Alcohol in the Body. — Alcohol is readily absorbed.
Even from the stomach from which absorption is usually slight,
about 20 per cent, of ingested alcohol is absorbed. After ab-
sorption the greatest amounts are found in the blood and central
nervous system. When the blood contains 0.12 per cent, there
is stupor, but as much as 0.72 per cent, has been found in a case of
fatal intoxication. More than six parts per one-thousand in the
blood invariably proves fatal. It is said that if stupor or un-
consciousness after a drinking bout last over 10-12 hours re-
covery rarely takes place. Traces remain in the blood for
twenty-four hours, but over 95 per cent, of the amoimt ingested
is oxidized. Whether the blood normally contains traces of
alcohol is a disputed question. Traces have been found in normal
blood but there is a question whether or not this was formed
by an abnormal fermentation of carbohydrates in the intestine,
rather than as a normal product of digestion.

B. Fischer reports the following analysis of the alcoholic con-
tent of the organs of a man who died from alcoholic intoxication :

Weight Organ Alcohol

2720 grams Stomach and intestines 30 . 6 grams

2070 grams Blood— *heart and lungs 10 . 85 grams

1820 grams Kidneys and liver 7 . 8 grams

1365 grams Brain 4.8 grams

Ethyl alcohol is recognized by its odor and by chemical tests.



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ALCOHOL TESTS 23

Since it distils easily from water solution, if it is in dilute solutions,
as beer, or in colored solutions, as wines, it should be distilled
before testing. The first part of the distillate should bje used for
the test.

Chemical Tests for Ethyl Alcohol

1. To a small portion of the distillate add a crystal of potassium
bichromate and a few drops of H2SO4 and warm. The alcohol
is oxidized to the aldehyde and acetic acid with the characteris-
tic odor, and the chromate is reduced giving a green color. Do
not use too much bichromate.

1. K2Cr207,+ H2SO4 = K2SO4 + H2Cr207 (H2O + 2Cr03)

2. 3C2H5OH + 2Cr03 + 3H2SO4 = 3CH3CHO + Cr2-

(804)3 + 6H2O

2. Lieben's Iodoform Test. — To a few drops of dilute alcohol
in a test tube add a crystal of iodine. Warm gently and add
drop by drop KOH until the red color just disappears. Note
the odor. When the sediment has settled examine under the
microscope.

CzHbOH + 4I2 + 6K0H = CHI3 + HCOOK + 5KI + 6H2O.

Bromoform can be prepared in the same way by using bro-
mine instead of iodine. Acetone also gives this test but differs
from alcohol in that it will give it when NH4OH is used instead
ofKOHorNaOH.

3. Ethyl Acetate Test. — Mix equal volumes of alcohol or the
liquid to be tested and concentrated sulphuric acid : About 2 cc.
each. To this add about 0.1 gram dry sodium acetate and heat.
Ethyl acetate is formed if alcohol is present and is- recognized by
its odor :

O ,OC2H5

1. C2H6 OH + H2SO4 JS{ + H2O

O^ ^OH

2. CH3C00Na + C2H6.O.SO2OH = CH3COOC2H6 +

NaHS04

There is no evidence that any substance formed in making
these tests is ever formed from alcohol in the body.



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24



CHEMICAL PHARMACOLOGY



To Determine the Amount of Ethyl Alcohol in Liquors

Place 100 cc. of tfie liquid in a flask of about 300 cc. capacity.
Add 50 cc. of water. Connect with a condenser and distil over
100 cc. This contains all the alcohol in a water solution. De-
termine the specific gravity of the distillate by means of a pyc-
nometer, Westphal balance, or a delicate hydrometer. Read
the per cent, of alcohol from tables prepared for this purpose.
See U. S. P. IX, page 633. These tables were prepared as fol-
lows: Water has a specific gravity of 1.0000. Absolute alcohol
has a specific gravity of 0.79365, consequently between per
cent, alcohol and 100 per cent, we have a range of sp. gr. of
0.20635. By mixing known amounts of water and alcohol and
carefully measuring the sp. gr. of such mixtures, the tables
were prepared.

Propyl and Butyl Alcohols

Propyl and butyl alcohols are not used in medicine and are of
interest only as impurities in preparations of ethyl alcohol.
Propyl is more powerful in its action than ethyl and butyl still
stronger than propyl. The toxic action increases with increas-
ing molecular weight. This is known as the Rule of Richardson.
There are two propyl alcohols — the normal and the isopropyl.

There are Four Butyl Alcohols. C4H»0H






B. P.


Specific gravity at 20°


CHr-CH2— CHs— CHjOH


117°


.810


Normal butyl alcohol (primary carbinol)






(CHa)2CH— CHjOH


117°


.806


Isobutyl alcohol (primary isopropyl carbinol)






^^' ^^^CHOH .


100°


.808


Normal secondary butyl alcohol (methyl ethyl






carbinol)






(CH,),COH


83°


.786


Tertiary butyl alcohol (trimethyl carbinol)







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BUTYL ALCOHOLS 25

The normal alcohol when oxidized gives propionic aldehyde and
acid, while oxidation of isopropyl alcohol gives acetone.

CHa— CH2— CH2OH -> CH3— CH(OH)— CH3

Primary propyl alcohol (normal) Secondary propyl alcohol (iso-
propyl alcohol)

Normal butyl occurs in traces in fusel oil. It is also produced
by Bacillus butylicus when grown on glycerine and various
sugars, but it has little biological importance. The toxicity of
these and other alcohols on fish has been studied by Picaud who
gives the relative toxicity as follows:

Methyl .66

Ethyl 1.00

Propyl 2.00

Butyl 3.00

Amyl 10.00

On the isolated mammalian heart Hemmedter foimd that the
pumping power as measured by the amoimt expelled in 30 sec-
onds was reduced by the various alcohols as follows:



Methyl


19 cc.


Ethyl


17 cc.


Propyl


79 cc.


Butyl


161 cc.


Amyl


323 cc.



Isopropyl is more toxic than normal, but normal butyl is
more toxic than isobutyl. Alcohols with branched chains are
less toxic than those with straight chains.

Amyl alcohols :

Only primary isobutyl carbinol and secondary butyl car-
binol, are important in pharmacology. Ordinary amyl alcohol
is a mixture of these. Both occur in fusel oil, and are
formed through the life processes of the yeast cell and are
derived from proteins. Consequently where a fermentation
mash contains proteins, as when grain and potatoes are used,
more amyl alcohol is produced, than in the preparation of rum
or brandy where the mash contains less protein. Yeast may



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26



CHEMICAL PHARMACOLOGY

Amyl Alcohol or Pentyl Alcohol

(Amylum-starch)
There are Eight Amtl Alcohols









Specific






B. P.


gravity tJm
20°


1. Normal primary (butyl carbi-








nol


CHr-CHr- CHr-CHs— CHiOH
CH,v


138"


.817


2. Isobutyl carbinol (primary)






>CH— CHr-CHiOH


130°


.810




ch/






3. Secondary butyl carbinol (pri-


CHiv.

)>CH— CHiOH
CH«— ch/






mary) (active amyl alcohol). .


128»


.816








4. Tertiary butyl carbinol (pri-


CH,\

CH.^C— CHjOH
CH,/






mary)


113"








6. Methyl propyl carbinol (secon-


CHr,^

^CHOH
CHr-CHs— Ch/






dary)


119*










6; Methyl isopropyl carbinol (sec-


CH,v
CHiv ^CHOH

CH«^






ondary)


112«»


.819


7. Diethyl carbinol


CHr-CHtv

yCHOH
CHr- ch/








117"










8. Dimethyl ethyl carbinol (ter-


CH,\

CHs^C— OH
CHr-CH/






tiary)


102"









produce amyl alcohol from its own protein consequently, all
yeast alcohols may contain amyl alcohol. The specific constit-
uent of the protein from which* amyl alcohol is prepared appears
to be leucine and isoleucine. Ehrlich, using a pure culture of
yeast, found that when this acted on a sugar solution contain-
ing leucine it readily yielded isoamyl alcohol and isoleucine
yielded amyl alcohol. The reactions are represented as follows:

(1) (CH3)2.CH.CH2CH(NH2).COOH+ H2O = (CH3)2.CH.

CH2CH2.OH + CO2 + NH3
Leucine Isoamyl alcohol

(2) CH3.CH(C2H5).CH.(NH2).COOH + H2O = CH3.CH(C2H6.

CH2OH + CO2 + NH3
Isoleucine ' d-amyl alcohol

The amyl alcohols are colorless oily liquids insoluble in water,



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AMYL ALCOHOL 27

with a disagreeable characteristic odor and acrid taste. Their
action in general resembles ethyl alcohol but they are about four
times as toxic. They are more locally irritant, and some authori-
ties state that the effect of chronic use is more deleterious than
in the case of pure ethyl alcohol.

Fusel oil is to some extent used in the preparation of essences
and perfumes, and exerts an influence on other perfumes. The
essential oils and aromatic substances develop their finest odors
in alcohol from a special source. In some cases such alcohols are
treated with charcoal which removes most of the fusel oil, the
remaining traces act with other aromatic bodies to produce a
harmony which cannot be reached by any other alcohol. Ehr-
lich points out ^hat *Hhe great variety of the bouquets of wine
and aromas of brandy, cognac, arrak, rum, etc. may be very
simply referred to the manifold variety of the proteins of the raw
materials (grapes, corn, rice, sugar cane, etc.) from which they



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