THE MECHANISM OF THE TOXIC ACTION OF

CYANOGEN CHLORIDE

C. I. REED
University of Kansas

Received for publication April 10, 1920

The question has been raised as to the hydrolysis of cyanogen

chloride in the body and the mechanism of its toxic action, and
it has been suggested that the toxic action may not be, primarily,
a cyanide action. It is the purpose of this paper to present
pharmacological evidence on this point.
Heyman and Masoin (1) have shown that with cyanide com-
pounds, sodium thiosulphate forms, in the body, sodium sulpho-
cyanide which is non-toxic. Hunt (2) has found that an in-
jection of sodium thiosulphate a short time before exposure,
protected animals against one to eight times the lethal dose
of hydrocyanic acid. Pierret and Duhot (3) and Lang (4) have
also called attention to the protective action of this substance
against the action of cyanides. Heymans and Masoin also
found that if this compound was administered after the onset
of symptoms of cyanide poisoning, it served only to lessen the
severity of the symptoms and did not act as a complete anti-
dote. They found further, that when administered before
exposure to hydrocyanic acid in doses too small to offer complete
protection, it still served to lessen the severity of the symptoms
in proportion to the size of the dose.
Teichmann and Nagel (5) have recently reported a series of
investigations in which it was found that mice exposed to 0.1
per cent hydrocyanic acid vapor died in from 2 to 6 minutes.
Intraperitoneal injections of 3 mgm. of sodium thiosuiphate per
gram of body weight 3 to 5 minutes after gassing resulted in
saving 7 out of 12 animals while 9 of 14 untreated controls
died. They concluded that sodium thiosulphate is less effective
301
302 C. I. REED

in saving mice that have been gassed than those that have been
injected with hydrocyanic acid, though Lang reported favorable
results under the latter conditions.
These authors found further that treatment with thiosuiphate
was more effective in treating animals that have been gassed
with sub-lethal concentrations of hydrocyanic acid. They sug-
gest the use of thiosulphate as a proper treatment for cyanide
poisoning in industrial work.
These results have been verified many times and the evidence
presented is sufficient to establish the action of sodium thiosul-
phate in protecting against the toxic effects of hydrocyanic acid.
An effort is here made to show that a similar protective reaction
occurs with relation to cyanogen chloride, as evidence that this
latter compound acts as a cyanide.
In one series of experiments, mice were injected with 0.25 cc.
of a 10 per cent solution of sodium thiosulphate an hour before
exposure for 7 minutes to concentrations of 0.78 mgm. of cya-
nogen chloride per liter of air. These animals survived without
symptoms while untreated controls died in 30 minutes after
exposure.
In a second series, dogs received 20 cc. of a 10 per cent solu-
tion of sodium thiosulphate by stomach 30 minutes before ex-
posure. Other dogs received 50 cc. of the solution in 0.9 per
cent NaC1, subcutaneously about the same time. These ani-
mals died in from 10 to 11 minutes while controls died in 3
minutes after exposure to a concentration of 1.98 mgm. for 3
minutes. The concentration of the antidote solution was evi-
dently too low though it was sufficient to exercise some alleviative
influence.
In a third series dogs received intravenously, 20 cc. of the 50
per cent solution of thiosuiphate by stomach, and 50 cc. by
mouth, 15 minutes before exposure to 0.8 mgm. per liter of
cyanogen chloride for 7 minutes. Control animals were all
dead in 6 minutes after exposure, with typical symptoms of
cyanide poisoning, while the treated animals survived without
symptoms at any time except sneezing and lachrymation during
exposure.
 TOXIC ACTION OF CYANOGEN CHLORIDE 303

Of two goats next subjected to this experiment and exposed

to a concentration of 2.5 mgm. per liter for 3 minutes, the con-
trol died in 70 hours, showing some convulsion, respiratory
paralysis at times, and pulmonary edema with exudate. The
other had received subcutaneously, 80 cc. of the 50 per cent
solution of sodium thiosuiphate, 40 minutes before exposure and
survived without symptoms.
On account of certain difficulties with this method, further
experiments were carried out by injecting subcutane9usly, a
freshly prepared 2 per cent solution of cyanogen chloride in
0.9 per cent NaC1. Of 14 control dogs receiving injections of
this solution in amounts varying from 5 to 40 mgm. per kilo
of body weight, 9 died within an hour, the others surviving a
10-day period of observation.
Of 9 dogs receiving a standard dose of the thiosulphate solu-
tion 15 minutes before injection of doses of cyanogen chloride
varying from 15 to 40 mgm. per kilo of body weight, one only
died in an hour, the others surviving without any marked symp-
toms. The minimum proportion of thiosuiphate that will pro-
tect against a given dosage of cyanogen chloride has not been
determined but it was evidently too low in this one case, indicating
a wide range of individual susceptibility.

SUMMARY AND CONCLUSIONS

It has been definitely established that sodium thiosuiphate

will protect against the toxic action of hydrocyanic acid by the
formation of non-toxic sodium sulpho-cyanide and since these
experiments show similar protective reactions against the toxic
effects of cyanogen chloride, it is probable that death immedi-
ately following the administration of the latter by any means,
is due to cyanide action entirely, though there may be other
factors in cases of delayed death. Further evidence on this
point may be found in the fact that ‘the symptoms immediately
following posioning with cyanogen chloride are typical in every
way of those following poisoning by hydrocyanic acid, though de-
layed deaths among thiosuiphate treated animals that have
304 C. I. REED

been exposed to lethal concentrations of cyanogen chloride are

probably due to the action of chlorine.

REFERENCES

(1) HEYMANS AND MAS0IN: Arch. Internat. de Pharmacod., iii, 359, 1896-1897.
(2) HUNT: Arch. Internat. de Pharmacod., xii, 447, 1903-1904.
(3) PIERRET ET DUHOT: L’Echo Medicale du Nord, xvii, 221, 1913.
(4) LANG: Arch. f. exp. Path. u. Pharm., xxxiv, 247.
(5) TEICHMANN AND NAGEL: Biochem. Zschr., xviii, 312, 1919.