FATAL POISONING DUE TO A CATIONIC DETERGENT OF THE
QUATERNARY AMMONIUM COMPOUND TYPE*
LESTER ADELSON, M.D., AND IRVING SUNSHINE, P H . D .
Laboratory of the Cuyahoga County Coroner's Office and the Institute of Pathology of Western
Reserve University School of Medicine, Cleveland, Ohio
The past decade has witnessed the introduction of large numbers of synthetic
detergents as antiseptics and cleaning and wetting agents in medicine and
industry. Many of these compounds are dissociable colloidal electrolytes and
are termed cationic or anionic according to the sign of the charge on the hydrophobic group conferring the surface activity. A few are nondissociable, and these
are termed nonionic.11 The cationic detergents are generally the hydrochlorides
of an amine or quaternary ammonium salts. Examples of this type are Zephiran
(alkyldimethylbenzyl ammonium chloride), Triton K 12 (cetyldimethylbenzyl
ammonium chloride), Triton K 60 (lauryldimethylbenzyl ammonium chloride),
Retarder LA (stearyltrimethyl ammonium bromide) and Emulsol 606 (lauryl
ester of glycine hydrochloride). The anionic detergents are in general the sodium
salts of fatty acids with a long alkyl and, or, aryl chain which has been sulfonated.
Examples of this variety include Duponol LS (sodium oleyl sulfate), Triton W
30 (sodium salt of alkylphenoxylethyl sulfonate), Drene (triethanolaminelauryl
sulfate) and cetyl sulfate (sodium cetyl sulfate). The quaternary ammonium
salts are powerful germicidal compounds and one of the most useful antibacterial
weapons that have come into use in those industries where sterilization is of
paramount importance. They are rapidly effective against microorganisms at
high dilutions and, at the same time, are relatively nontoxic, nonirritating and
inexpensive. Their marked surface-active properties increase their general utility.12
The synthetic detergents produce diverse effects on biologic materials and
systems, including the precipitation and denaturization of proteins, the inactivation of viruses, enzymes and toxins, and hemolysis and bacteriostasis. This wide
range of biologic activity should lead to serious toxic phenomena following their
introduction into, and absorption by, higher animals. Nonetheless no human
deaths resulting from the direct toxic effect of the synthetic detergents have been
recorded to this time. A possible explanation for this fact is that the detergents
are excellent bacteriocidal and bacteriostatic agents in such high dilutions that
the concentrations ordinarily used are relatively nontoxic to man in the amounts
likely to be ingested.
We have recently had the opportunity to study the case of a 45-year-old woman
who died rapidly following the accidental ingestion of an alcoholic solution of
Hyamine 2389, a cationic detergent of the quaternary ammonium compound
type. Although such cases have been unknown up to this time, they may become
more frequent as the use of synthetic detergents increases.
* Received for publication, March 3, 1952.
656
POISONING BY CATIONIC DETERGENT
657
COMPOSITION, CHEMISTRY AND USES OF HYAMINE 2 3 S 9 5
Hyamine 2389 is a 50 per cent aqueous solution of methyldodecylbenzyltrimethyl ammonium chloride. In common with many other synthetic detergents
it contains no phenol, iodine, heavy metal salts or compounds yielding available
chlorine. Physically this 'substance is an amber, slightly viscous, aqueous solution with a mild characteristic odor and a bitter astringent taste. The active
ingredient is nonvolatile, and the 50 per cent aqueous solution which is distributed by the manufacturer is readily diluted to 10 per cent, at which concentration it is sold commercially. Hyamine 2389 is miscible in all proportions with
methanol, ethanol, isopropanol, triethylene glycol and other water-miscible
solvents. It is incompatible with certain anion-active materials that react with
the hydrocarbon cation of the Hyamine 2389, yielding insoluble compounds that
reduce its general activity and effectiveness. The trade name of the 10 per cent
Hyamine 2389 solution in the present case is Syntho-San.
Syntho-San solutions have good wetting power, penetrating crevices and
killing a wide variety of gram-positive and gram-negative organisms. The phenol
coefficient by the FDA method is 20. For restaurant and tavern use it is recommended that 1 ounce of Syntho-San be diluted with 4 gallons of water, giving a
concentration of the active ingredient of 200 parts per million.
The label on the bottle in which the,detergentis sold warns against contaminating food with the cleansing argent.::
,•••••«.
REPORT OF CASE
While in a tavern, the decedent, a 45-year-old white woman, was served a
drink made up of f of an ounce of whiskey and 2\ ounces of supposed ginger ale.
She swallowed a mouthful (approximately 1 ounce) and immediately complained
of feeling ill. She spat out what little remained in her mouth and then went to
the woman's washroom, where she vomited. Returning to the bar she said to
her escort, "Taste this drink. It tastes funny-." He did so carefully and instantly
ejected the liquid, stating that it burned his mouth. The bartender also tasted,
the drink and agreed that something was wrong. It was then discovered that
the supposed ginger ale was in reality undiluted Syntho-San, which had been
poured into a ginger ale bottle to be taken to another store. The woman continued to complain of feeling ill and was helped across the street to an industrial
clinic, where she was seen at once by a physician. At the time of admission she
appeared apprehensive, restless and intoxicated. Her pulse was rapid and of
good quality. She attempted to vomit again but was unsuccessful. Six milligrams of apomorphine was given intramuscularly, and she promptly vomited
clear mucoid material. No lavage was carried out. The patient rapidly became
incoherent and disoriented. Her respirations were labored and soon developed
into typical Cheyne-Stokes breathing, accompanied by deep cyanosis and dilation
of the pupils. Intranasal oxygen was given, with improvement in the patient's
color. Cardiac action remained good until the end. Terminally, generalized
twitching developed. Coramine was injected intravenously without producing
658
ADELSON AND SUNSHINE
any noticeable results, and she died 15 minutes after admission to the clinic and
approximately 25 minutes after ingesting the drink.
Autopsy. Complete autopsy conducted 1 6 | hours post mortem disclosed only
severe bilateral pulmonary congestion and edema and visceral congestion. The
right lung weighed 890 grams; the left lung, 775 grams. There was no corrosion
of any portion of the gastrointestinal tract. Incidental findings included bilateral
chronic salpingitis and follicular adenomas of the thyroid.
Microscopic examination confirmed the gross findings and added nothing of
note.
Toxicologic analysis. The blood alcohol level was 0.01 per cent by weight. Acid
ether extraction of the liver yielded a crystalline material, not freely soluble in
TABLE 1
T H E E F F E C T O F A Q U E O U S AND ALCOHOLIC SOLUTIONS OF S Y N T H O - S A N ON A L B I N O R A T S
NUMBER OF ANIMALS
DOSE
(.ML. PER 100 GM.)
Total
Survived
Died
A. Syntho-San, 3 parts
Water, 1 part
1.0
0.5
0.25
4
5
2
0
5
2
4
0
0
B. Syntho-San, 3 parts
40 per cent alcohol, 1 part
1.0
0.5
0.25
6
4
2
0
2
2
6
2
0
C. Syntho-San, 3 parts
Whiskey, 1 part
1.0
0.5
0.25
2
3
1
0
2
1
2
1
0
D. Water, 3 parts
Absolute alcohol, 2 parts
1.0 '
0.5
0.25
1
2
1
2
0
0
-
-
-
chloroform, which gave a positive reaction for the presence of quaternary ammonium compounds. Assay of the gastric content (volume 300 ml.) by Auerbach's
method 2 disclosed 0.5 mg. of quaternary ammonium compounds per 100 ml.
Complete toxicologic analysis of the blood and organs eliminated the presence of
commonly occurring heavy metal salts (mercury, arsenic, bismuth and antimony), barbiturates and salicylates, commonly occurring organic volatile substances (phenols, chlorinated hydrocarbons, aldehydes and cyanides) and alkaloids.
Experimental procedure. To - evaluate the toxicity of Syntho-San, experiments
were carried out with 32 adult albino rats wherein the animals were fed, by
stomach tube, solutions of the detergent mixed with (A) water, (B) pure ethyl
alcohol of the same strength as the whiskey and (C) whiskey. In all the solutions
the proportions of detergent and the diluent were the same as that ingested by
the decedent, namely approximately 3 : 1 . Control animals fed pure ethyl alco-
POISONING BY CATIONIC DETERGENT
659
hol and water in 40 per cent strength (80 proof) were also studied (D). The
amount of detergent present in the mixtures was approximately 75 mg. per ml.
All the animals that died showed a uniform pattern of behavior. For approximately 2 or 3 minutes following the feeding of the mixture they remained quiet
They then developed severe and violent generalized convulsions, which lasted for
several minutes, terminating in death within 5 minutes after the feeding. Gross
and microscopic autopsy findings in the rats were limited to nonspecific pulmonary edema and visceral congestion.
Toxicity studies of the apomorphine given to the patient were carried out on
white mice. The results indicated no undue effects as compared with apomorphine
from a second hospital pharmacy.
Analysis of experimental results. The minimal lethal dose of the alcoholic solution of the detergents, 0.5 ml. per 100 Gm., is equivalent to a dosage of 370
mg. of Syntho-San per kilogram of body weight. The data indicate that alcohol
potentiates the lethal effect.
DISCUSSION
It has been amply demonstrated experimentally that the synthetic detergents
inhibit several vital metabolic enzymatic processes. Zephiran, a typical cationic
detergent, inhibits cholinesterase,8 and at a dilution of 1:35,000 destroys completely the ability of yeast cells to consume oxygen by interfering with the
cytochrome c-cytochrome oxidase system.13 At this concentration the aerobic
and anaerobic oxidation of glucose is markedly diminished. The lactic acid oxidase present in E. coli, an enzyme that ordinarily reacts directly with oxygen, is
inhibited by cationic detergents. 9 This reaction also takes place in a cell-free
system. Catalase yields an inactive precipitate with cationic detergents.11 Destruction of detergent-sensitive enzymes readily accounts for metabolic cessation, cell death and increased permeability in bacteria exposed to lethal concentrations of these materials. In this respect the mechanism of poisoning is different
from that produced by such substances as mercury, which combines reversibly
with the sulfhydryl groups of the proteins and enzymes.4
The reaction between detergent and enzyme is materially influenced by the
hydrogen-ion concentration. Baker, Harrison and Miller3 have shown that the
cationic detergents are most effective in inhibiting bacterial respiration and glycolysis in neutral or slightly alkaline solutions. They point out that optimal
bactericidal activity is dependent on the length of the alkyl chain in the molecule
and that the introduction of a benzyl group enhances the antibacterial properties.
In view of the above data indicating that inhibition of essential enzymatic
reactions concerned with nervous function and intracellular oxidation is a group
characteristic of the cationic detergents, it is a reasonable inference that such
was the mechanism causing death in the present case. Several of the clinical
features presented by the decedent are similar to those observed in individuals
poisoned by organic phosphorus insecticides. 6,7 These substances destroy cholinesterase and thus permit accumulation of acetylcholine, leading to the syndrome
660
ADELSON A N D S U N S H I N E
of pathologic hyperstimulation of the. parasympathetic nervous' system along
with stimulation of the central nervous system and the peripheral motor nerves.
The postmortem findings in our case are identical with those described by
Merrill10 in a 39-year-old man who died 50 minutes after the intramuscular injection of 0.5 milligram of neostigmine methylsulfate, a specific anticholinesterase, again pointing to uncontrolled acetylcholine activity 1 as an important feature
of the toxic effect of the detergent. This aspect of the present case indicates the
advisability of the immediate institution of atropine therapy in doses of 2 milligrams per hour in individuals poisoned by the cationic detergents, the treatment
suggested by Grob in poisoning by the organic phosphorus insecticides.
Several other possible therapeutic measures suggest themselves, including
immediate emesis, gastric lavage and oxygen inhalations. However, present
experience would indicate that the detergent is absorbed so rapidly and acts so
quickly that these actions are not likely to be instituted sufficiently promptly to
prove efficacious. Nonetheless these procedures should be carried out as quickly
and expeditiously as possible. Inasmuch as the cationic detergents are known to
combine readily and avidly with protein, the feeding of egg white or milk may
be useful in removing from solution the quaternary ammonium salts responsible
for the fatal outcome.
It is of interest that the experimental data demonstrate that alcohol increases
the lethal effects of Syntho-San. A possible explanation is that the alcohol, by
producing vasodilatation of the gastric and duodenal mucosal blood vessels,
hastens the absorption of the detergent and thus results in a rapid rise of the
blood level with prompt distribution of the compound throughout the entire
organism. The synergism between detergent and alcohol indicates the necessity
of exercising extreme care in the use and dilution of the detergents in bars and
taverns where alcoholic liquors are dispensed.
SUMMARY
The first fatal human poisoning due to the ingestion of cationic detergent is
reported. The toxic agent responsible for the fatality was less than 1 ounce of
an alcoholic solution of Syntho-San, a 10 per cent aqueous solution of methyldodecylbenzyltrimethyl ammonium chloride. The lethal effect is probably the
result of a combined inhibition of cholinesterase and intracellular oxidative
enzymes. Experimental investigation with albino rats demonstrates that alcohol
(whiskey) increases the toxic effect of the detei'gent.
Acknowledgment. T h e authors wish to express their thanks to D r s . Stanley Levey a n d
Lawrence Peters of Western Reserve University School of Medicine for their assistance.with
t h e experimental portion of this paper. T h e y also wish t o thank W. E . Botwright of t h e
Rohm and H a a s Company for his cooperation.
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POISONING BY CATIONIC DETERGENT
601
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