General results of the investigations showing the effect of formaldehyde upon digestion and health online

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Issued Deceimber 21, 1908.



United States Department of Agriculture,

BUREAU OF CHEMISTRY Circular No. 42.
H. W. WILEY, Chief of Bureau.



GENERAL RESULTS OF THE INVESTIGATIONS SHOWING THE EFFECT
OF FORMALDEHYDE UPON DIGESTION AND HEALTHS

r

r

INTRODUCTION.

Formaldehyde is one of those preservatives the use of which in
foods has been almost universally condemned by experts, physicians,
and the general public. Nevertheless, as formaldehyde has hereto-
fore been used to quite an extent in certain foods, especially dairy
products, and is still advertised under its own and other names for
use in such products to a limited extent, it seemed wise to include
this substance in the plan of investigation.

.Formaldehyde is derived from the first member of the alcohol
group, namely, methyl or wood alcohol. Each of the alcohols has
an aldehyde corresponding thereto, as, for instance, formaldehyde
from methyl alcohol, acetaldehyde derived from ethyl alcohol, which
is the ordinary alcohol of commerce, and so on with the other alco-
hols. It has been very generally believed that the toxicity of alco-
hols, and they are more or less toxic, was greater as the series
ascended that is, if methyl or ethyl alcohol is considered as the basis
of comparison the toxicity of the higher alcohols (such as butyl,
propyl, and amyl) is greater than that of methyl or ethyl alcohol.
Following this plan of classification, the toxicity of methyl alcohol

a By reason of the restrictions placed by law upon the printing and distribution of
bulletins exceeding 100 pages, it is not possible to supply the demand for Bulletin 84,
Influence of Food Preservatives and Artificial Colors on Digestion and Health, from
the regular edition. In order to give as wide a circulation as possible to the results
of the experimental work, it has been deemed advisable, in the case of Part V, on
Formaldehyde, as in the case of Part I, on Boric Acid and Borates; Part II, on Sali-
cylic Acid and Salicylates; Part III, on Sulphurous Acid and Sulphites; and Part IV,
on Benzoic Acid and Benzoates (Circulars 15, 31, 37, and 39), to publish the results
in the form of a circular for general distribution.
61958 Cir. 4208



should be less than that of ethyl alcohol. There is a lack of exact
experimentation on this point, but the evidence which has lately
been secured leads to the conclusion that some modification of this
common belief is necessary. The degree of toxicity of methyl and
ethyl alcohol in small amounts is largely in favor of the methyl
alcohol, while if relatively larger quantities are employed the methyl
alcohol is far more toxic than the ethyl alcohol, and, as a corollary
from this, formaldehyde under the same conditions should be more
toxic than acetaldehyde. Attention should also be called to the fact
that formaldehyde represents the simplest form of aldehyde known
that is, its chemical constitution shows that it is made up of carbon
and water. By multiplying the simple molecule, for instance, by six
the ordinary formula for a sugar is obtained. In other words, if a
chemist could start with six molecules of formaldehyde and put
them together in a strictly natural way, he would produce sugar,
which is a highly nutritious food in respect of its power to furnish
heat, energy, and fatty tissue.

Physiological botanists suppose that formaldehyde is the first
product of chemical synthesis, tending to build up the cellulose or
woody tissue of plants, and forming by condensation the starch and
sugar which the plant contains. Its biological activity is supposed
by some physiologists to extend even further, so as to be a very
important aid in the building up of nitrogenous tissues. In this
connection it must be remembered that formaldehyde not only
possesses to a marked degree the property of combining with itself
to form new bodies, but, as has already been suggested, it unites in a
very intimate manner with the proteids. Therefore, when added
to milk, which contains a very large proportion of nitrogenous
materials, formaldehyde may enter into a chemical combination
with these substances. To determine whether any difference would
be observed in the activity of the preservative under these condi-
tions, the formaldehyde was administered immediately after it was
mixed with milk and also after allowing it to stand for forty-eight
hours in contact with the milk. This length of time gave ample
opportunity for the completion of any chemical reactions which the
formaldehyde might undergo in connection with the protein sub-
stances.

Another point which was carefully considered was that presum-
ably, in the case of formaldehyde, we are dealing with a substance
universally considered to be of a poisonous character, and for this
reason much more care was necessarily exercised in regulating the
quantity administered in order that no sudden or unexpected toxic
effects might be produced.

[Cir. 42]



Another fact worthy of consideration is that inasmuch as milk is
the most prone of all ordinary foods to deterioration and requires the
most careful treatment the temptation to use such an efficient pre-
servative as formaldehyde is proportionately greater, especially dur-
ing the summer months. The arguments which have been advanced
in favor of other preservatives in small quantities should theoretic-
ally carry more weight in the case of milk than of other common
foods, and if these arguments are valid in any case they would be
especially so when applied to dairy products. It is generally admitted
that there is no known preservative so effective, so readily employed,
and in some respects so likely to escape detection as minute quanti-
ties of formaldehyde, and therefore all the conditions which relate
to its use deserve the greater care and consideration. It should not
be forgotten, however, that a supposititious commercial necessity can
not be cited as an excuse for the addition to foods of substances
which are injurious.

In this connection it seems not out of place to call attention to the
fact that apart from the injurious effects of formaldehyde itself its
use as a preservative would be especially inadvisable in milk or cream,
because its addition in dilute solution prevents the growth of acid-
forming bacteria, but has no effect in retarding the action of many
harmful organisms; in other words, the milk is prevented from becom-
ing sour, and thus indicating its age, and the danger signal is thus
removed while the other -organisms which are capable of producing
disease continue to multiply in the milk with practically the same
degree of rapidity as if the formaldehyde were not present.

Attention is again called to the proper and legitimate signification
of the term " injurious to health," when used in this connection.
This phrase does not signify that a food which has an injurious sub-
stance added to it must in every instance produce notably injurious
effects upon the consumer immediately. The question can only
be logically and fairly studied by considering the continued or cumu-
lative effects, nor are these necessarily of such a character as to result
in objective symptoms. Insidious effects which are produced on
the cells of the organs or on their histological structure are no less
important; in fact, they are more important. These are the injuries
which at first escape detection and may go to irremediable lengths
before any outward symptoms of their existence are manifested.

All of these points have been kept in view iri the consideration of
this question, but none of them has had any influence on the obser-
vation and recording of the data. As in all other cases, this part of
the work has been conducted absolutely without reference to any pre-
conceived theory. The sole endeavor has been to control the quan-

[Cir. 42]



tity and quality of the food, the nutritive value of the ration, and
the course of life of the subject, and to record the effect observed on
the health and the metabolic processes in general. This work has
been distributed among a large number of observers, each having
control of a particular part of the investigation and working inde-
pendently. In this case, as in all of the others, it was not until the
figures were collated, tabulated, and studied that the tendencies
induced by the preservative were known, and not until then could
any attempt be made to determine the general effects or to draw
conclusions from the data.

While it is not to be expected that the mass of compiled figures
presented are absolutely free from error, the general effects which
were produced are unmistakable, and it is believed the conclusions
drawn therefrom are deduced on sound principles of reasoning and
are based on reliable data, the marked uniformity of the analytical
results and the absence of contradiction in the individual data being
especially marked in this experiment.

ORGANIZATION AND CONTROL OF THE EXPERIMENT.

The twelve men who became members of the table for testing the
effects of formaldehyde on health and digestion were carefully exam-
ined before the beginning of the experiment, as in previous cases.
The medical history of each man was ascertained, no one being
admitted who was not free from organic disease or who had suffered
from serious illness of any kind within a year or two, who was pre-
disposed to any hereditary malady, or who exhibited any feebleness
of constitution which would make him an easy victim to disease.
The usual daily examinations were made of each man, the temper-
ature, pulse, and body weight being recorded. When any variation
from the normal was noticed, the observation was checked by an
attendant, who was always present and supervised the securing of
the data for the clinical and medical history; and any symptoms
reported were carefully considered, to determine how far such dis-
orders might be attributed to the use of the preservative.

ADMINISTRATION OF THE PRESERVATIVE.
SCHEDULE OF ADMINISTRATION.

This series of investigations was begun on the 12th of November,
1904, and concluded on the 17th of December, 1904. The fore
period covers ten days of observation, the preservative period fifteen
days, and the after period ten days. The dates of the several sub-
periods are given in Table I.

[Cir. 42]



TABLE I. Dates of periods and subperiods, Series IX.



Period and subperiod.


Date of
begin-
ning.


Date of

ending.


Foreperiod


1904.
Nov. 12


1904.
Nov. 21


First subperiod


do...


Nov. 16




Nov. 17


Nov. 21


Preservative period


Nov. 22


Dec. 6


First subperiod


do


Nov. 26


Second subperiod . .


Nov. 27


Dec. 1


Third subperiod


Dec. 2


Dec. 6


After period


aDec. 8


Dec. 17


First subperiod


Dec. 8


Dec. 12


Second subperiod


Dec. 13


Dec. 17









a In tabulating the results the data for December 7 are omitted owing to the fact that the preservative
was administered only on the morning of that day, and it was then deemed advisable, on account of the
condition of the subjects, to begin the after period.

Table II shows the administration of the formaldehyde during the
preservative period. The quantity given daily during the first pre-
servative subperiod is 100 milligrams, during the second preservative
subperiod 200 milligrams, and during the third preservative sub-
period 200 milligrams, making a total of 2.5 grams administered
during the entire preservative period.

TABLE II. Schedule of administration of preservative, Series IX.



Period and date (1904).


Formaldehyde added to milk imme-
diately before taking.


Formaldehyde added to milk
two days before tajdng.o


No. 1.

Gms.
0.1
.1
.1
.1
. 1


No. 2.


No. 3.


No. 4.


No. 5.


No. 6.

Gms.
0.1
.1
.1
.1
.1


No. 7.


No. 8.

Gms.
0.1
.1
.1
.1
.1


No. 10

Gms.
0.1
.1
.1

;>


No. 11


No. 12


First subperiod:
Nov. 22


Gms.
0.1
.1
.1
.1
.1


Gms.
0.1
.1
.1
.'1
.1


Gms.
0.1
.1
.1
.1
.1


Gms.
0.1
.1
.1
.1
.1


Gms.
0.1
.1
.1
.1
.1


Gms.
0.1
.1
.1
.1
.1


Gms.
0.1
.1
.1
.1
.1


23..


24


25...


26..


Total


.5


.5

.2
.2
.2
.2
.2


.5

.2
.2
.2
.2
.2


.2
.2
.2
.2
.2


.5

.2
.2
.2

.2
.2


.5

.2
.2
.2
.2
.2


.5

.2
.2
.2
.2
.2


.5 .5


.5


tOtOtOtOtO II Or


Second subperiod:
Nov. 27


2
'.2
.2
.2

1.0


to to to to to


tototototo


to to to to to


28...


29


30


Dec. 1..


Total


1.0


1.0

.2
.2
.2
.2
.2


1.0

.2
.2
.2
.2
.2


I f

tototototo || o


1.0

.2
.2
.2
.1
.0


1.0

.2

.2
.2
.2
.2


1.0

.1
.0
.0
.0
.0


1.0

.2
.2
.2
.1
-0


1.0

.2
.2
.2
.2
.2


1.0


Third subperiod:
Dec. 2


to to to to to


to to to to to


to to to to to


3


4..


5


6..::::::::::::::....::.:


Total b


1.0


1.0


1.0


1.0


1.0


.7


1.0


.1


.7


1.0


1.0





a No. 9. left the city before the entire observation was completed and therefore his data are omitted.

b On Dec. 7 those subjects who were still receiving the preservative were given 0.1 gram, but it
was deemed inadvisable to continue the preservative period for another five days, and the after period
was accordingly begun on Dec. 8, the data for Dec. 7 being disregarded in the tabulations.

[Cir. 42]



It will be noted that only Nos. 6, 8, and 10 failed to take the
scheduled amount oij preservative. No. 8 received the smallest
amount, taking only 0.1 gram on the first day of the last subperiod
and none thereafter, while Nos. 6 and 10 took only O'.l gram on the
next to the last day of the preservative period and none on the last
day, making a total for the subperiod of 0.7 gram.

METHOD OF ADMINISTRATION.

An aqueous solution of formaldehyde was administered in milk.
The strength of a stock solution was determined from time to time
and the proper volume to secure the amount required by the schedule
was added to the milk taken by the subjects. On account of the
liquid nature of this substance it was not possible to administer it in
any better way. The quantity added in the first subperiod was not
sufficient to impart any taste to the milk, but in the larger quantities
a slightly disagreeable taste was noticeable. In the case of half of
the men (Nos. 1 to 6) the preservative was added to the milk imme-
diately before it was drunk; and in order that ample time might be
given for any chemical union which might take place between the
formaldehyde and the protein constituents of the milk, that admin-
istered to Nos. 7 to 12 was added to the milk two days before con-
sumption.

SUMMAEY OF RESULTS.
MEDICAL, AND CLINICAL DATA.

The formaldehyde in the quantities administered did not produce
any marked symptoms until the third preservative subperiod, a lapse
of ten days; then headache and pain in the stomach and intestines
became general, in many cases producing cramps, and in a few cases
attended by nausea and vomiting. Only two exceptions are noted.
A burning sensation in the throat was reported in the majority of
cases. In four cases out of eleven a well marked itching rash appeared
on the chest and thighs, causing great discomfort, slight symptoms of
this nature being reported in a fifth case. The general symptoms,
therefore, are headache and abdominal pains, while a slight tendency
to lower the temperature may be noted as a minor symptom, and the
development of the rash, though marked, occurs in only about half
of the cases.

It is important to observe that in the case of healthy young men it
requires some time for this drug to produce an effect noticeable in a
symptomatic way, as above described. That no effect is produced,

[Cir. 42]



however, until after ten days would not be a logical conclusion. It is
evident that the system is able for some time to control the develop-
ment of conditions which later become pronounced, but that no ill
effects are produced prior to that time is not probable. After ten
days, however, ten cases out of twelve develop marked symptoms of
malaise, intestinal trouble, and distress, and in many cases positive
symptoms of a local character, such as the rash which has been men-
tioned. The apparent tendency to lower the temperature is men-
tioned as one of the symptoms, but inasmuch as no special investiga-
tion was made in this respect it is advisable that further studies be
prosecuted before positive statements are made, yet it is not without
signification that this unexpected condition of affairs was noticed,
and also that there was a tendency to its continuation in some
instances into the after period. (See figs. 1 and 2.)

BODY WEIGHT.

There is a slight tendency shown in the case of those subjects
receiving the formaldehyde directly in milk to a loss of body weight
under the administration of the preservative amounting to 0.2 kilo-
gram per day for each man, while in the case of the subjects receiving
milk preserved for forty-eight hours there does not appear to be any
noteworthy decrease in the body weight until the after period, when
an average loss of 0.5 kilogram is recorded. (See figs. 3 and 4.)

The ratio of food weight to the body weight is practically constant
throughout the experiment. These changes in weight are of interest
as correlated with the corresponding increase in volume of the urine
and in the moisture in the feces, and as contrasted with the tendency
to decrease the excretion of the principal food elements studied.

WEIGHT AND WATER CONTENT OF THE FECES.

These data show, in the case of the subjects receiving formaldehyde
directly, an increase in moisture amounting to 2 per cent and a slight
decrease (1 gram per day) in the amount of dry feces excreted. In
the case of the subjects receiving the preservative forty-eight hours
after it had been added to the milk there is a decrease both in the
moisture content and in the weight of dry matter excreted, amount-
ing to 1.6 per cent and 3 grams daily, respectively, this decrease being
further augmented in the after period. There is thus shown a slight
derangement of the normal processes, which is unfavorable and
probably has some bearing on the loss of body weight.

[Cir. 42]



8

URINE.
VOLUME, SPECIFIC GRAVITY, AND TOTAL SOLIDS.

The data in the case of the direct administration ofthe preservative
(Nos. 1 to 6) show an increase in the volume of the urine excreted,
accompanied by a slight decrease in its specific gravity and practically
no change in the amount of solids excreted. The same condition
prevails in the case of the indirect administration, though it is less
marked during the preservative period and more so in the after
period.

There is in general, therefore, a tendency to slight diuresis and a
decrease in specific gravity under the administration of the preserva-
tive, while practically no effect is produced on the excretion of total
solids. It is interesting to note the connection between these increases
in volume of urine excreted and the losses in body weights. The
increase in volume for Nos. 1 to 6 and the decrease in weight occur
during the preservative period, while for Nos. 7, 10, 11, and 12 these
conditions are both more marked in the after period.

ALBUMIN AND REACTION.

From the somewhat limited data at hand no definite conclusions
can be drawn regarding the presence of albumin in the urine or the
acidity of the urine. There is, however, in a few instances an apparent
tendency to produce albumin, and in general during the administra-
tion of the formaldehyde there is a tendency to decrease the normal
acidity. Considering the action of formaldehyde in general on
secretions, especially the digestive secretions, this observation is in
accordance with that of others who have shown that changes in the
gastric juice are accompanied by corresponding changes in the acidity
of the urine, an increased secretion of acid producing a decrease
in the acidity of the urine. These two conditions have an important
physiological bearing on the normal functions of the body, and such
a derangement must be regarded as harmful or at least as leading
to harmful results.

CHANGES IN THE RELATIVE EXCRETION OF SULPHUR COMPOUNDS.

In the case of the direct administration of the preservative there is
a slight tendency manifested to derange the normal relations of the
compounds of sulphur excreted during the preservative period.
There is a decrease in the neutral sulphur amounting to a little over
1 per cent of the total sulphur eliminated and a slight increase in the

[Cir. 42]



inorganic sulphates, while the ethereal sulphates remain practically
the same throughout. For those subjects who received the preserva-
tive after it had stood in milk for two days there is seen an increase in
the quantity of neutral sulphur excreted amounting to about 1.4 per
cent, accompanied by a slight decrease in the inorganic sulphates,
while again the ethereal sulphates remain constant.

These data alone show evidence of an increased sulphur metabolism
in the case of Nos. 1 to 6 and a retardation in the case of Nos. 7 to 12,
though the excretion of total sulphur shows practically no change.

NITROGEN METABOLISM.

A remarkably uniform tendency is manifested, in regard to the
metabolism of the nitrogen of the food, to increase slightly its assimi-
lation and to retard the breaking-down processes in the cells. The
stimulating of assimilation is in accordance with the observations of
numerous authors who ascribe to formaldehyde the power of exciting
digestive secretions, its influence on the pancreatic and biliary secre-
tions being very marked. On the other hand, formaldehyde has a
retarding effect on the digestive enzyms, which in this case appears
not to have been so marked as the stimulating effects exerted on the
digestive juices themselves. The decrease in the metabolized nitrogen
excreted in connection with the loss of weight contraindicates any
increase in the anabolic processes. Apparently the same effect is
produced by the formaldehyde on the nitrogen metabolism when it
is added directly to the milk and when it has stood in contact with
it for two days, though in the latter case it is somewhat more marked.

PHOSPHORIC ACID METABOLISM.

There is an unmistakable tendency shown to derange the metabol-
ism of phosphoric acid, which again is manifested to practically the
same extent under the two conditions of the experiment. There is a
slightly increased absorption of the phosphorus compounds from the
alimentary canal, accompanied by a marked increase in the excretion
of metabolized phosphoric acid, amounting to over 4 per cent. There
is only one exception to this increased excretion in the individual
data, namely, No. 7, in which case an abnormal excretion of phos-
phoric acid was recorded in the fore period.

The balances are decreased in all cases except No. 7 a condition
which is quite abnormal in the case of phosphoric acid and can not be
regarded as other than an unfavorable effect, which would ultimately
produce harmful results.

[Cir. 42]



10



SULPHUR METABOLISM.

In the sulphur metabolism the same conditions are shown to exist
as were found in the case of nitrogen, namely, a tendency to increase
the absorption of the sulphur constituents of the food and retard the
normal katabolic activities. The decrease in nonmetabolized sulphur
is a little over 1 per cent in both cases, while the decrease in metabo-
lized sulphur excreted amounts to 4.6 per cent for Nos. 1 to 6 and 2.7
per cent for Nos. 7 to 12. There is almost as close an individual
agreement shown in this case as in the previous balances, and there is
no marked difference between the summaries for those taking the
formaldehyde directly and those to whom it was given in milk pre-
served for two days.

TABLE III. Comparative summary of principal determinations made Series IX.
[Averages are per man per day.]



Data.


Formaldehyde (Nos. 1-6).


Formaldehyde (Nos. 7-12).a


Fore
period.


Preserv-
ative
period.


After
period.


Fore
period.


Preserv-
ative
period.


After
period.


Temperature (F.)- -


98.3
63.50

101.00
77.35
23.00

970.00


98.0
63.27

108. 00
79.45
22.00

1,085.00


98.1
63.27

103.00
77.87
23.00

1,062.00


98.4
63.01

116.00
78.34
25.00

1,170.00
63.6

.246
2.035
.143
2.424

9.94
85.02

33.24
60.46

12.54
79.34


98.3

62.93

96.34
76.78
22.00

1,191.00
70.00

.279
2.001
.143
2.423

8.81

82.62

29.12

64.88

10.96
76.61


98.1
62.43

91.00
76.46
21.00

1,309.00

72.7

.217
2.089