THE DETECTION, IDENTIFICATION AND QUANTITATIVE DETERMINATION OF METHYL FORMATE IN
THE TISSUES*
WITH REPORT OF A FATAL CASE
ALEXANDER O. GETTLER
From the Chemical Laboratories ofBellevue Hospital and Washington Square College,
New York University, New York
The sudden death of a hospital patient was reported to the
Chief Medical Examiner's Office of New York City on April 17th,
1938. The following history was obtained from the hospital
records:
Patient M. Q., white, female, aged 19 months, admitted March 30th. A
simple mastoidectomy (ether anesthesia) was performed without exposure of
dura or sinus. Recovery was uneventful and complete and the patient was to
be discharged, April 18th. About 6:30 P.M. of April 17th, the nurse, noticing
that the child was suffering from an itching scalp caused by vermin, poured one
ounce of a liquid insecticide upon a sponge placed upon the child's scalp, and
covered the sponge and the top of head with a tightly fitting bathing cap.
The application was left on for about 20 minutes. When it was removed the
child was in collapse, somewhat cyanotic and breathing infrequently Caffeine
benzoate, coramine, adrenalin and atropine, also O2—CO2 inhalation were
administered and the patient rallied somewhat. The pupils were small and
did not react to light; knee jerks were absent; body flaccid; Babinsky and
abdominal reflex were absent. The patient gradually became weaker, ceased
to breathe, and the heart stopped.
The autopsy, performed by Dr. Milton Helpern, Assistant Medical Examiner
in the Office of the Chief Medical Examiner of New York City, revealed pediculosis capitis, a healing mastoidectomy wound, and congestion of the brain,
lungs, liver, kidneys and spleen. Other incidental findings consisted of hyperplasia of the lymphoid tissue in the spleen, thymus and mesenteric lymph nodes
and a bicornuate uterus.
Microscopic examination by Dr. Helpern of sections from the various organs
did not reveal any characteristic changes, other than congestion. Sections
* Received for publication June 17, 1939.
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METHYL FORMATE POISONING
189
from various parts of the brain and meninges showed only congestion of the
blood vessels; the architecture was normal. In the lungs, many alveoli contained edema fluid, and some contained small numbers of desquamated pigmented macrophages. Small foci of hyperplastic lymphoid tissue were found
adjacent to the bronchioles. There was no evidence of any pneumonic process
in any of the sections. The heart was not unusual. The thymus was normal.
Sections of several small lymph nodes and of the spleen revealed hyperplasia
of the germinal centers of the follicles. No unusual changes were noted in the
liver and kidneys other than congestion.
The body of the child weighed 10 kilos (22 lbs.); the brain 1050 grams;
the liver 440 grams; and the stomach contents measured 26 ml.
Since no definite pathological changes which would account for the child's
death were found, the brain, liver and stomach contents were submitted for
chemical analysis.
Analytical procedures. Aliquot portions of the brain, liver and stomach
contents were analyzed routinely for various poisons. Methyl (wood) alcohol
was the only substance found and that in very small amount.
The micro isolation method1 was then applied to the distillate from 600
grams of brain. Slightly more than 0.15 ml. of a volatile liquid was isolated.
The boiling point2 of this liquid was 47.5°C. Since the boiling point of methyl
alcohol is 66°C, it was evident that another liquid with a much lower boiling
point was also present.
The 0.15 ml. of liquid was therefore distilled fractionally by means of
Gettler's distillation capillary3. Five successive fractions were obtained, with
the following boiling points: 32.0°, 33.0°, 37.5°, 44.5°, 63.5°, 64.0°.
To establish the identity of the first and second fractions boiling at 32.0°
and 33.0°C. respectively, a micromolecular weight determination4 was made.
The liquid had a molecular weight of 60.4. On consulting the tables of physical
constants it was found that methyl formate (boiling point 32.3° and molecular
weight 60) agreed fairly well with the boiling point and molecular weight of the
isolated liquid.
The last two fractions which boiled at 63.5° and 64.0°C. respectively had a
molecular weight of 32.3, coinciding in boiling point and molecular weight with
methyl alcohol. The 3rd and 4th fractions were evidently mixtures of methyl
formate and methyl alcohol. Since methyl formate hydrolyzes appreciably in
water, in bodyfluids,and during distillation, it was to be expected that some of
the methyl formate which the child had absorbed was present in the distillates
as free methyl alcohol and formic acid. The former was identified as described
above. The latter was identified by typical mercurous formate crystals, and
by the production of an orange color when treated with resorcin and sulfuric
acid6.
The stomach contents were analyzed in a similar manner, but only a trace
of methyl alcohol could be demonstrated. This, together with the short time
between onset of symptoms and death, seems to corroborate the history of the
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ALEXANDER O. GETTLER
case, that the methyl formate insecticide was absorbed through the skin or by
inhalation.
Having established that the toxic substances in the child's body were methyl
formate, methyl alcohol, and formic acid, the organ distillates were next quantitatively analysed.
In order to determine the total quantity of methyl formate that reached the
brain and the liver, aliquot portions of the distillates from each organ were made
alkaline and refluxed. This hydrolyzed the methyl formate present, liberating
all of the methyl alcohol. The latter was then determined quantitatively by
the methoxy method 6 . The total quantity of methyl formate (hydrolyzed and
unhydrolyzed) present in the organs was calculated from the methyl alcohol
content after hydrolysis. Ten hundred fifty grams of brain contained 246.5
mg., and 440 grams of liver contained 97.2 mg. of methyl formate.
SUMMARY
1. An acute fatal poisoning by absorption of methyl formate
is described.
2. Analytical procedures for the isolation of the methyl formate from the organs, and methods for the identification of
methyl formate are given.
3. The quantitative determination of the methyl formate in
the organs is described.
REFERENCES
(1) GETTLER, A. 0 . AND SIEGEL, H.: Isolation from Human Tissues of Easily
Volatile Organic Liquids and Their Identification. Arch. Path.,
19: 208, Feb. 1935.
(2) EMICH, F . : "Siedepunkbesrimmung" Lehrbuch der Mikrochemie, page 51,
J. F. Bergmann, Miinchen, 1926; described by Lanzar and Zechner,
Monatshefte fur Chemie, 38: 219, 1917.
(3) GETTLER, A. 0 . AND F I N E , J.: Ind. and Eng. Chem., Anal. Ed., 1 1 : 469,
1939.
(4) NIEDERL, J. B., TRATJTZ, 0 . R. AND PLENTL, A. A.: Microvaporimetric
Determination of Molecular Weight. Ind. and Eng. Chem., Anal.
Ed., 8: 252, 1936.
(5) ROSENTHALER, L.: "Mikroanalyse Toxikologische," Gebriider Borntraegei,
Berlin, 1935.
(6) NIEDERL, J. B. AND NIEDERL, V.: Micromethods of Quantitative Organic
Elementary Analysis, p. 187, John Wiley and Sons, Inc., New York,
1938.