Clinical Toxicology

ISSN: 1556-3650 (Print) 1556-9519 (Online) Journal homepage: http://www.tandfonline.com/loi/ictx20

The toxicology of zinc chloride smoke producing

bombs and screens

Ayman El Idrissi, Lisanne van Berkel, Nadia E. Bonekamp, Diana J. Z.

Dalemans & Marcel A. G. van der Heyden

To cite this article: Ayman El Idrissi, Lisanne van Berkel, Nadia E. Bonekamp, Diana
J. Z. Dalemans & Marcel A. G. van der Heyden (2017) The toxicology of zinc chloride
smoke producing bombs and screens, Clinical Toxicology, 55:3, 167-174, DOI:
10.1080/15563650.2016.1271125

To link to this article: http://dx.doi.org/10.1080/15563650.2016.1271125

Published online: 11 Jan 2017.

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CLINICAL TOXICOLOGY, 2017
VOL. 55, NO. 3, 167–174
http://dx.doi.org/10.1080/15563650.2016.1271125

REVIEW

The toxicology of zinc chloride smoke producing bombs and screens

Ayman El Idrissia
, Lisanne van Berkela
, Nadia E. Bonekampa
, Diana J. Z. Dalemansa
and
Marcel A. G. van der Heydenb
a
Honours Program CRU2006 Bachelor, University Medical Center Utrecht, Utrecht, The Netherlands; bDepartment of Medical Physiology,
Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands

ABSTRACT ARTICLE HISTORY

Context: Zinc chloride (ZnCl2)-based smoke bombs and screens are in use since the Second World Received 2 May 2016
War (1939–1945). Many case descriptions on ZnCl2 smoke inhalation incidents appeared since 1945. Revised 29 November 2016
Objective: We provide a comprehensive overview of the clinical symptoms and underlying pathophysi- Accepted 5 December 2016
ology due to exposure to fumes from ZnCl2 smoke producing bombs. In addition, we give a historical Published online 10 January
2017
overview of treatment regimens and their outcomes.
Methodology: We performed a literature search on Medline, Scopus and Google Scholar databases KEYWORDS
using combinations of the following search terms “smoke bomb”, “smoke screen”, “ZnCl2”, Smoke bomb; smoke
“intoxication”, “poisoning”, “case report”, “HE smoke”, “hexachloroethane smoke”, “smoke inhalation” screen; ZnCl2; poisoning;
and “white smoke”. We retrieved additional reports based on the primary hits. We collected 30 case ARDS; hexachloroethane;
reports from the last seven decades encompassing 376 patients, 23 of whom died. Of all the patient metal fume fever
descriptions, 31 were of sufficient detail for prudent analysis.
Results and conclusions: Intoxication with clinical signs mainly took place in war situations and in
military and fire emergency training sessions in enclosed spaces. Symptoms follow a biphasic course
mainly characterised by dyspnoea, coughing and lacrimation, related to irritation of the airways in the
first six hours, followed by reappearance of early signs complemented with inflammation related signs
and tachycardia from 24 h onwards. Acute respiratory stress syndrome developed in severely affected
individuals. Chest radiographs did not always correspond with clinical symptoms. Common therapy
comprises corticosteroids, antibiotics and supplemental oxygen or positive pressure ventilation in 64%
of the cases. Of the 31 patients included, eight died, three had permanent lung damage and 15
showed complete recovery, whereas in five patients outcome was not reported. Early signs likely relate
to caustic reactions in the airway lining, whereas inhaled ZnCl2 particles may trigger an inflammatory
response and associated delayed fibrotic lung damage. Smoke bomb poisoning is a potentially lethal
condition that can occur in large cohorts of victims simultaneously.

Introduction PbO (1.0%) and chlorinated vapours (10.8%), including hydro-

gen chloride (HCl) [3,4]. Additionally, ethylene tetrachloride
Smoke screens are in use for many centuries as a tactical aid
(C2Cl4), carbon monoxide dichloride (COCl2) and carbon tetra-
in military operations. Pre-industrial applications depended
chloride (CCl4) vapours arise [3,4].
on the combustion of natural products, such as damp straw,
Although a 1943 publication suggested limited health
to generate an opaque cloud. New smoke generating techni-
risks [1], three separate reports published in 1945 illustrated
ques emerged during the First World War (1914–1918) [1].
the hazards of ZnCl2 smoke exposure [5–7]. Currently, the sci-
The French army developed the zinc chloride (ZnCl2)-based
entific literature contains nearly 30 reports on subsequent
smoke screen. Ignition of a mixture of zinc (Zn), carbon tetra-
incidents involving ZnCl2 exposure (Table 1). Most of these
chloride (CCl4), zinc oxide (ZnO) and diatomite generated a
cases involve the use of smoke bombs during military train-
ZnCl2 aerosol [2]. In the United States prior to the Second
ings. Only several cases report civilian casualties in a non-
World War (1939–1945), an improved mixture of Zn, ammo-
nium perchlorate (NH4ClO4), hexachloroethane (HC) and military setting. We summarize these reports and discuss
ammonium chloride (NH4Cl) allowed easier transportation their clinical courses, imaging results, treatments and out-
and storage. Further refinements to the mixture occurred comes. We conclude by reviewing the pathophysiological
later [2]. The final compounds are ZnO, HC and aluminium mechanisms involved in ZnCl2 exposure.
metal. In a thermochemical reaction these compounds pro-
Methods
duce heat and an aerosol, from here onwards described as
ZnCl2 smoke or fumes, that consists of ZnCl2 (62.5%), We screened Medline, Scopus and Google Scholar databases
ZnO (9.6%), iron oxides (10.7%), aluminium oxides (5.4%) using combinations of the following search terms “smoke

CONTACT Marcel A. G. van der Heyden m.a.g.vanderheyden@umcutrecht.nl Department of Medical Physiology, Division of Heart & Lungs, University
Medical Center Utrecht, Yalelaan 50, 3584 CM Utrecht, The Netherlands

These authors contributed equally.
ß 2017 Informa UK Limited, trading as Taylor & Francis Group
168 A. EL IDRISSI ET AL.

Table 1. Overview of ZnCl2 intoxication cases.

Year of exposure/ Cases
Case publication Origin Subjects Fatalities analysed Remarks Ref.
Sailor overcome by a smoke screen 1942/1945 United Kingdom 1 0 1 [5]
Explosion of smoke generators in 1943/1945 United Kingdom 7 3 1 Incident occurred in [6]
adjacent room Mediterranean
during WWII
Smoke generators ignited next to 1943/1945 United Kingdom 70 10 Incident occurred in [7]
air-raid shelter Malta during WWII
Smoke bomb ignited at night in unknown/1952 United States 47 0 [8]
fraternity house
Exposure to smoke during military 1952/1954 United Kingdom 1 0 1 [9]
training
Exposure to smoke during military 1955/1956 Sweden 3 0 1 [10]
training in bunker
Exposure to smoke during military 1955/1956 Sweden 12 0 1 [10]
training in tunnel
Exposure to smoke during military 1959/1961 United States 3 0 3 [11]
survival training
Smoke bomb thrown into truck 1961/1963 Netherlands 17 1 4 [12]
with soldiers
Smoke generator ignited in fire unknown/1963 Canada 2 1 1 [13]
prevention exercise
Exposure to smoke during military unknown/1964 United Kingdom 3 1 1 [14]
exercise
Soldier exposed to smoke at prac- 1967/1974 Germany 1 0 1 [15]
tice march
Smoke bomb thrown into house 1969/1974 Germany 1 0 1 [15]
at military training
Smoke blown into tunnel at 1970/1974 Germany 1 0 1 [15]
military training
Simulation of an airplane fire with 1979/1980 United States 135 0 [16]
smoke bombs
Soldier ignited smoke bomb during 1983/1987 Singapore 1 0 1 [17]
bee attack
Exposure to smoke grenade in unknown/1986 United States 1 0 1 [18]
closed civilian vehicle
Soldiers passing through smoke- 1985/1988, 1992 Denmark 5 2 2 [19,20]
filled pipeline
Soldiers exposed to smoke in an unknown/1989 France 12 0 [21]
enclosed room
Soldiers exposed to smoke in an unknown/1992 United Kingdom 7 0 1 [22]
enclosed room
Exposure to smoke in sewer during unknown/1996 Switzerland 1 0 1 [23]
military training
Soldier lay on the ground next to unknown/1999 United States 1 0 1 [24]
smoke canister
Exposure to smoke during military unknown/1999 Denmark 13 0 [25]
exercise
Smoke bomb thrown into small unknown/2000 Finland 6 2 2 [26]
cottage
Exposure to smoke during military unknown/2000 Finland 1 0 1 [26]
training
Accidental smoke bomb ignition 2003/2005, 2006, Taiwan 20 0 3 [27–32]
in combat exercise 2008, 2010
Smoke bomb used in fire drill at unknown/2008 Spain 1 1 1 [33]
school
Civilians hit by smoke bomb unknown/2015 Turkey 3 2 Victims received [34]
capsules in Syrian war treatment in a
Turkish hospital

bomb”, “smoke screen”, “ZnCl2”, “intoxication”, “poisoning”,
“case report”, “HE smoke”, “hexachloroethane smoke”, “smoke
inhalation” and “white smoke”. We retrieved publications
from 1945 through 2015. We excluded reports on non-ZnCl2-
based smoke producing devices, i.e., those using other chem-
ical compounds. We retrieved additional case reports on the
basis of references in the primary hits. Information on patient
cohorts described more than once were combined and cited
by the individual reports. Native readers from the
Department of Medical Physiology read reports written in
non-English languages (Dutch, French, German and Swedish)
and discussed these with us in detail.
We subsequently selected those reports on individual
patients of ZnCl2 smoke exposure that provided sufficiently
detailed information with respect to symptoms, diagnostics,
treatment regimens and/or outcomes (Table 1, column “cases
analysed”). We analysed each of these cases separately and
mapped the collected data to identify commonalities and
trends across cases. This approach excluded three cohorts
that failed to provide details for individual patients [7,8,16].

In the first cohort [7], ZnCl2 fumes in a tunnel intoxicated 70
subjects in 1943. Of these, 35 patients passed through first-
aid care facilities and experienced dyspnoea, chest pain/tight-
ness, retrosternal and epigastric pain, stridor and red and
running eyes. Ten patients died. In the early 1950s, a
thoughtless prank exposed 47 students to ZnCl2 smoke in a
fraternity house [8]. Of the 35 hospitalized cases, all experi-
enced cough, approximately two-thirds showed fever and
sore throat and one-third displayed vomiting, headache and
chest pain. No deaths occurred. In 1979 a detonated smoke
bomb exposed 135 individuals to ZnCl2 smoke in an airport
disaster drill [16]. Since exposure occurred in open air, only
10 to 20% of the patients experienced clinical signs (cough,
sore throat, abnormal taste) and no fatalities occurred.
Results
In total we obtained 30 reports on ZnCl2 smoke exposure,
containing 376 patients, for review (Table 1). Three papers
consisted of large patient groups (47, 70 and 135 individuals),
10 papers described patient groups between 12 and 20 indi-
viduals in size, whereas 10 papers described groups between
two and seven patients. Finally, seven papers only described
an individual case. At least two case reports represent every
decade since 1940. Case reports originated from Europe (17
papers), North America (six papers) and Asia (seven papers).
Two reports described one incident involving two Danish
soldiers [19,20]. Six reports covered the same set of 20
Taiwanese soldiers exposed in a military training exercise
[27–32].
The best studied cohort hitherto consists of the Taiwanese
soldiers [27–32]. They experienced ZnCl2 fume intoxication
during a three to ten minutes exposure to dense smoke in a
narrow tunnel during a combat exercise in 2003. All subjects
suffered from nausea, sore throat, cough, shortness of breath
and chest tightness. Five soldiers developed acute respiratory
distress syndrome (ARDS). One patient suffering from ARDS
improved upon prolonged treatment with high-dose cortico-
steroids, methylprednisolone and extracorporeal life support
[31]. The majority of patients presented a restrictive type of
functional lung impairment, and a combination of functional
tests and high-resolution CT scanning may predict its severity
[27]. Fumes from ZnCl2 smoke producing bombs caused hep-
atotoxicity in two patients [28]. A follow-up study among all
twenty soldiers and a large control group, indicated that
ZnCl2 smoke can induce acute, dose-dependent liver dysfunc-
tion [29]. Huang et al. linked systemic inflammation to ZnCl2
exposure in this cohort, in which tumour necrosis factor a
concentrations increased and all patients had leucocytosis
[30]. Furthermore, temporarily decreased haemoglobin levels,
haematocrit and red blood cell counts associated also with
ZnCl2 fume exposure in this cohort [32].
Modes of exposure
Exposures resulted mainly from incidents during war situa-
tions (four reports, 81 patients) [5–7,34], military trainings (19
reports, 85 patients) [9–11,14,15,19–32] and fire trainings
CLINICAL TOXICOLOGY 169
(three reports, 138 patients) [13,16,33]. In general, exposure
of the victims to ZnCl2 smoke occurred in confined spaces
only, like air-raid shelters, bunkers, tunnels, pipelines, rooms
and vehicles. In the case described by Evans, for example,
ignition of 79 smoke generators directly exposed 70 of the
116 individuals present in a tunnel to ZnCl2 smoke fumes [7].
Loh et al. also described two cases of ZnCl2 smoke exposure
in a tunnel [28].
Several cases of ZnCl2 smoke exposure in confined spaces
resulted from negligence or mischievous behaviour. Hoekstra
described a case in which a smoke bomb was jokingly
thrown in the back of a truck with 17 people in it. Of these
individuals, nine were briefly observed at the infirmary whilst
four others were hospitalised. One individual eventually suc-
cumbed to his injuries [12]. In a similar case reported by
Pettil€a et al., a group of youngsters threw a smoke bomb
into a small cottage with six people in it. Two individuals
developed severe symptoms and were hospitalised. Both
later died as a result of the exposure [26]. In cases of open
air exposure, victims were directly next to the source
[11,16,24]. In one case, a soldier ignited a smoke grenade
under a poncho to escape from a bee attack [17]. The result-
ing symptoms in this case were most likely due to ZnCl2
intoxication rather than phosgene [35].
Clinical course
Because the majority of reported exposures occurred in mili-
tary, police, or fire rescue training, most of the exposed indi-
viduals were young men. In fact, all case reports that
contained sufficient information for analysis included only
males (20 reports, 31 patients) [5,6,9–15,17–20,22–24,
26,28,31,33]. The ages of four patients were not reported
[12]. The remaining 27 cases had a mean age of 24.1 years.
Clinical effects following exposure to ZnCl2 typically had a
biphasic pattern. Symptoms occurring immediately after
exposure included mucosal irritation, lacrimation, dyspnoea,
cough, sore throat, retrosternal pain, nausea and vomiting.
Some patients developed fever. These symptoms often sub-
sided within several hours to one day.
Extensively exposed patients developed a second wave of
symptoms of respiratory inflammation over the following
days. Typical symptoms included dyspnoea, cough, fever, and
malaise. It could take up to several weeks for the pyrexia and
dyspnoea to abate. In most cases of ZnCl2 exposure, patients
fully recovered.
Three papers reported transaminase elevations suggestive
for hepatic effects of fume inhalation from ZnCl2 producing
bombs [26,28,29]. Alanine aminotransferase (ALT) concentra-
tions peaked between three and five weeks after the expos-
ure, and returned to normal between six and eight weeks
following exposure [29]. The median ALT concentration in
the group of 20 exposed soldiers from Taiwan was approxi-
mately tenfold higher in comparison to a reference group of
64 non-exposed soldiers. The 10 individuals closest to the
ZnCl2 source presented significantly higher ALT concentra-
tions than the other 10 patients [29]. The authors reported
170 A. EL IDRISSI ET AL.

Table 2. Frequency of symptoms present after ZnCl2 smoke exposure. be related to the pattern of ZnCl2 particle diffusion through-
Time after exposure out the lungs. It took a relatively long time, i.e., from seven
Number of
0–6 h 6–24 h >24 h different cases weeks up to 12 months, for the radiographs to return
General symptoms to normal.
Fever (>38  C) 5 5 12 20 Radiographic results did not correlate with the severity of
Malaise 2 2 0 4
Cyanosis 4 2 5 9 symptoms. This was especially apparent in the first few hours
Tachycardia 0 2 5 6 after exposure when patients experienced early symptoms,
Shock 1 0 3 4 such as coughing and dyspnoea. Radiographs taken at this
Respiratory symptoms
Dyspnoea 12 5 11 20 stage generally showed no signs of lung infiltrate.
Tachypnoea 4 3 10 14 Conversely, radiographs may show bilateral consolidations a
Cough 17 1 10 20
Sore throat 10 1 1 11
few days after exposure, at a time when patients begin to
Frothy sputum 4 1 0 4 recuperate and feel better.
Purulent sputum 0 0 2 2 ZnCl2 smoke exposure and spirometry parameters
ARDS 1 0 3 4
Gastrointestinal symptoms appeared to exhibit an inverse relationship. The amount of
Nausea 5 0 1 6 smoke a victim was exposed to depended on whether the
Vomiting 7 0 0 7 exposure was in open air as opposed to a confined space,
Abnormal taste 1 0 0 1
Other symptoms whether the individual was wearing a gas mask and the dur-
Burning/tearing eyes 4 1 0 5 ation of the exposure. Schenker et al. provided the most
Chest pain/tightness 10 1 6 15
Abdominal pain 2 0 2 3
extensive account on spirometry results following ZnCl2
Subcutaneous crepitus 0 1 3 4 smoke exposure in open air [16]. This report described spir-
Pneumothorax 0 0 2 2 ometry results for 63 individuals and found no significant
Generalised seizures 0 0 1 1
Limited exercise tolerance 1 0 4 4 effect of exposure in open air on either FEV1 or FVC.
Liver injury n.d. n.d. 13 13 However, in cases in which victims were located in an
enclosed space and wore ill-fitting gas masks [19,20] or when
exposure was less than two minutes [21,23,30], spirometry
parameters were aberrant (i.e., restrictive ventilation impair-
no occurrences of jaundice, bilirubin elevations or any other ment with mostly reduced TLC, VC and FEV1 values) but nor-
signs indicative for liver impairment.
malized within two to seven weeks.
Table 2 provides an overview of the main symptoms pre-
Individuals exposed for longer than two minutes showed
sented in the individual case reports. It specifically shows the
a remarkably slower pace of normalization (several months)
number of cases reporting a symptom at a particular point in
or incomplete recovery of lung function [18,22,25–27,30,31].
time after exposure. As illustrated by Table 2, many symp-
Reports on vital parameters show that virtually all patients
toms existed for a brief period immediately after exposure,
exhibited signs of inflammation, such as fever, tachypnoea and
only to reappear again after one to several days. Extra-pul-
tachycardia [6,7,11–14,18–20,22,23,26,27,30,31,33]. Leukocyte
monary symptoms, such as subcutaneous crepitus and gener-
counts were elevated in most cases, with higher levels in
alized seizures were uncommon and reported in few cases
severely exposed patients [8,12,15,28,30]. The most common
more than one day after exposure [29]. The clinical outcome
acid-base disorder found at acute presentation was respiratory
depended highly on the dose and length of exposure.
Unfortunately, absolute numbers of smoke density and alkalosis, as a consequence of hyperventilation [19,22,26,31].
exposure time were lacking. Extensive exposure could lead to Unfortunately, the individual case reports lacked functional
a severe disease course culminating in ARDS and death assessment outcome.
[19,20,25,26]. In addition, a high exposure dose associated
with lasting damage to the respiratory system. For example, Post-mortem findings
victims exposed to a dense cloud of ZnCl2 smoke in a con-
fined space developed subglottic stenosis and restricted pul- Seven reports discussed post-mortem findings of patients
monary dysfunction [6,26]. who died as a result of ZnCl2 smoke exposure
[7,12–14,19,20,33]. The eight patients from these reports had
a median survival of 10 days after exposure (range
Imaging and functional tests 4 hours–32 days). Macroscopically, the mucous membranes of
A total of 23 reports include data from chest radiograph the tracheobronchial and upper respiratory tracts were
examinations of patients following exposure to ZnCl2 smoke severely damaged [7,12–14,33]. More specifically, mucosae
[5,6,8,11–16,18–23,25–28,30–33]. These radiographs showed had a red and very oedematous aspect [7]. Additionally,
an interesting pattern when ordered chronologically. In the there was necrosis, roughening and a yellow-grey colouring
acute setting, immediately after hospital admission, radio- of the mucosae [7,12–14]. The lungs showed a solid homoge-
graphs remained unremarkable or exhibited signs of pulmon- neous aspect with oedema, areas of haemorrhage and infarc-
ary oedema located around the hilar regions of the lungs. tion and widespread fibrosis [7,12–14,19,20,33]. A dry and
Only radiographs taken more than 48 h after exposure red surface with prominent vascular septa arose when the
showed more diffuse bilateral infiltrative processes. This may lungs were sliced [14]. Two reports described necrosis,

numerous cysts and yellowish areas interpreted as foci of
pneumonitis [13,33].
The macroscopic observations were congruent with the
microscopic findings. Lungs were mostly airless because of
intra-alveolar and interstitial oedema and haemorrhage. In
addition, intra-alveolar fibrosis with varying degrees of alveo-
lar condensation contributed to this airlessness [7,12–14,19,
20,33]. Widespread occlusion of micro vessels developed as a
result of endothelial cell proliferation and clots [19,33].
Arterial injection of barium-gelatin sulphate, from which ves-
sels appear white on an arteriogram when properly filled,
confirmed the reduced filling of small arteries [19].
Besides the findings in the respiratory system, ZnCl2
exposure associated also with congestion and oedema of
liver, kidney, spleen and brain [7,19,33]. One report empha-
sized the absence of microscopic abnormalities in liver and
kidneys of two patients [7], whereas another reported tubular
necrosis in one patient [19]. Five patients showed cardiac
involvement (right sided dilatation in four, a large right ven-
tricular thrombus and thrombi in epicardic blood vessels in
one patient) [7,19,33], whereas the heart of a sixth patient
was normal [7].
Treatment
Of the 31 reviewed cases, all but one described treatment
regimens [5]. The most frequently applied treatments were
supplemental oxygen and positive pressure ventilation, anti-
biotics, corticosteroids and various combinations of these.
Five or fewer patients received other forms of pharmacother-
apy, e.g., terpinhydrate, codein, promethazine, aminophylline
and calcium. Several cases also mentioned non-pharmaco-
logical therapies, such as bed rest, tracheotomy, physical
therapy and steam inhalation. Only eight or fewer cases
received non pharmacological therapies. In general, treat-
ment regimens followed the prevailing developments in clin-
ical care during the last seven decades.
The first report on the use of corticosteroids in the treat-
ment of ZnCl2 smoke intoxication appeared in 1961 [11]. In
subsequent years, different types of corticosteroids became
available. The use of corticosteroid therapy as the main treat-
ment for ZnCl2 smoke intoxication, either alone or in combin-
ation with antibiotics and supplemental oxygen/positive
pressure ventilation, increased during the seven decades cov-
ered in this analysis. In the first four decades (1945–1984),
physicians used corticosteroids in 44% (7 out of 16) of cases.
This number increased to 86% (12 out of 14) in the last three
decades (1985–2015).
None of the analysed case reports published prior to 1956
mentioned supplemental oxygen or artificial ventilation. In
fact, positive pressure ventilation became widely applied
since the 1950s only [36,37]. However, patients in the series
reported by Evans received supplemental oxygen through a
partial rebreathing mask [7].
The treatment regimen for ZnCl2 smoke-induced injury
frequently included antibiotics in order to prevent bacterial
infection of damaged lung tissue. In the time period preced-
ing 1985, patients underwent courses of sulfapyridine [6],
CLINICAL TOXICOLOGY 171
sulfathiazole [6], penicillin [9,10,12,13], streptomycin [10,12],
erythromycin [10], tetracycline [10,11,15], benzylpenicillin [10]
and chloramphenicol [15]. After 1985, patients received
erythromycin [18], oxacillin [26], gentamicin [26], ceftriaxone
[26], ceftazidime [28,31] and levofloxacin [33]. These cases
illustrate the wide use of antibiotics in the treatment of
ZnCl2 smoke intoxication. Even though the prescribed
courses followed the development of antibiotics through his-
tory, the courses of antibiotics tended to differ greatly across
all cases. This is most likely due to differing antibiotic proto-
cols across countries and hospitals. Generally, physicians pre-
scribed antibiotics as a prophylactic treatment rather than to
cure existing bacterial infections. This practice is analogous
to the case of aspiration pneumonitis in children with hydro-
carbon exposures. It is known for decades that antibiotics
and steroids are not useful in hydrocarbon aspiration pneu-
monitis [38,39], however, they are still prescribed in these
children. Similarly, antibiotics are part of the common ther-
apy for ZnCl2 smoke intoxication, however, evidence that
they are part of the optimal treatment is absent.
Outcome
Figure 1 provides information on disease outcome for all
31 patients included in this review [5,6,9–15,17–20,
22–24,26,28,31,33]. Primary outcome was complete recovery
or permanent damage measured by chest radiograph or spir-
ometry. In five patients, no data about complete recovery or
permanent damage were given [6,26,28,31]. In two patients,
spirometry was performed, however, no data were presented
when the patient had fully recovered [26,31]. In three
patients, no spirometry or chest radiograph was performed
to assess recovery [6,28]. Approximately, 25% of the patients
died due to ZnCl2 smoke-induced injury and 50% made a
complete recovery.
Recovery times varied greatly from several days to 12
months after exposure. Recovery assessment by chest radio-
graphy had a median of 69 days (mean 163 days, range
48–366 days). Recovery time based on chest radiograph
results was not reported for one patient. In two patients that
underwent spirometry only, clinical recovery time was 28
days. For seven patients that both underwent chest radio-
graph and spirometry assessment, recovery time based on
radiograph results varied between 10 and 100 days, with a
mean of 31 days and a median of 16 days. Based on spiro-
metry results of four patients, recovery times varied from 10
to 275 days, with a mean of 76 days and a median of 10
days. Spirometry based recovery times were not provided for
the other three patients.
Outcome related to treatment
Treatment of ZnCl2-induced smoke injury consisted of mono-
therapy using supplemental oxygen or positive pressure ven-
tilation, antibiotics or corticosteroids, or co-therapy using
combinations of these. The groups are small, except for the
patients treated with supplemental oxygen/positive pressure
ventilation, corticosteroids and antibiotics. Therefore, we
172 A. EL IDRISSI ET AL.
8 died 3 permanent damage
7 1 1 2
Median 18 after established
days (9-54) unknown by chest
amount of radiograph
r spirometry
days
Figure 1. Clinical outcomes classified as died, “permanent damage” or “complete recovery” of 31 patients with ZnCl2 smoke poisoning. Patient numbers are indi-
cated in bold font. Extent of permanent damage was established by imaging (chest radiograph) or functional (spirometry) techniques, or by a combination of both
investigations.
cannot make statements on the optimal treatment regimen.
Even in the group that received what is now considered as
common care (supplemental oxygen/positive pressure venti-
lation, corticosteroids and antibiotics), the mortality rate is
considerable (6 out of 14 patients died). It is plausible that
those who received more treatment were sicker and there-
fore had a higher mortality rate than those requiring less
treatment.
Human pathogenesis and animal studies
The pathophysiological mechanism of ZnCl2 smoke-induced
injury was the subject of much speculation in early case
reports. Initially, authors attributed the typical biphasic
course of symptoms to direct damage to the airways and
subsequent lung tissue damage. In fact, Whitaker theorised
that early symptoms arose by direct irritation of the airways.
This irritation may partially result from hydrochloric acid
formed in the explosion. He thought that late symptoms
resulted from damage to the alveolar epithelium caused by
retained smoke particles in the lungs [5]. Another theory
postulated by Evans suggested that both the precipitation of
heated smoke particles in the lungs and the hygroscopic and
astringent properties of ZnCl2 caused the lung damage [7].
Indeed, initial symptoms, such as coughing and chest
tightness, appear to result directly from irritation of tissue
structures within the throat, trachea and bronchi [20].
Systemic factors are, however, likely involved in the develop-
ment of later symptoms. For example, a rapid increase in the
pro-inflammatory cytokine TNF-a, haematological changes
(i.e., temporary reduction of haemoglobin, red blood cell
count and haematocrit) and transaminase elevations associ-
ated with fume exposure from ZnCl2 smoke producing
bombs [26,28,30,32]. These findings as well as the associated
temperature rise in many cases, suggest the involvement of
systemic inflammation. ZnCl2 smoke inhalation may in fact
induce a form of metal fume fever. In metal fume fever, tis-
sue damage by a heavy metal leads to the discharge of
31 patients 5 unknown
15 complete recovery
6 2 7
established established established established
by by chest by by chest
radiograph spirometry radiograph +
spirometry
cytokines causing signs of systemic inflammation [20]. The
involvement of inflammatory cells may also explain cases in
which lung fibrosis developed, as these cells can activate
fibroblasts in the lung parenchyma [40].
Animal studies provided useful insights into the patho-
physiological mechanisms involved in ZnCl2 smoke induced
injury. In particular, several animal studies confirm the posi-
tive correlation between exposure dose and severity of symp-
toms [41–44]. For example, Karlsson et al. found that
rats exposed to a relatively high dose of ZnCl2 smoke
(200 mg/m3) for five minutes had a 50% mortality rate [41].
In comparison, the US National Institute for Occupational
Safety and Health declared a dosage of 50 mg/m3 immedi-
ately dangerous to life and health [45]. Rats exposed to a
dose of 50 mg/m3 showed minor symptoms, e.g., wet noses
and swollen eyelids. These symptoms disappeared gradually
and the animals appeared normal 24–48 h after exposure.
Rats exposed to higher doses developed severe symptoms in
the hours after exposure [41].
In animal studies, diffuse bronchopneumonia and intersti-
tial pneumonitis in the first three days after exposure domi-
nated the histological findings. In the first and second week
after exposure, inflammatory infiltrates in the lungs and dis-
seminated confluent atelectasis were found. These findings
are consistent with the biphasic course of the disease as
observed in the reviewed cases. Interestingly, rats sacrificed
three months after exposure still showed residual inflamma-
tory infiltrate and band-like atelectasis [41]. This is also con-
gruent with the extended recovery times observed in
multiple cases. In addition, ZnCl2 smoke exposure induced
acute inflammation and necrosis of the larynx and bronchi in
rats and rabbits [42].
Radiological findings in dogs showed pulmonary oedema
with an increased lung volume as soon as two hours after
exposure [46]. This is striking, as chest radiographs appeared
unremarkable in the acute setting in patients. A possible
explanation for these inconsistent findings may be differen-
ces in the exposure doses. That is, the dog study may have
exposed the subjects to relatively higher concentrations of

ZnCl2 smoke, causing more severe symptoms in these sub-
jects. This difference may, however, also result from variation
between species.
Extra-pulmonary symptoms of ZnCl2 producing bomb fume
inhalation are uncommon, except for hepatotoxicity. A num-
ber of reports described raised serum ALT concentrations
[26,28,29]. ALT concentrations increased from week one to two
after exposure and reached a peak in week three to five. A pos-
sible cause of the transaminase elevations is the treatment
regimen for pulmonary symptoms. Both steroids and antibiot-
ics are potentially hepatotoxic. A more likely cause, however,
are chlorinated compounds present in the smoke, such as CCl4
[44]. These chlorinated compounds are hepatotoxic [47,48]. In
the metabolism of CCl4 a trichloromethylperoxyl radical is
formed. This compound may attribute to liver injury [47].
There is not much convincing evidence supported by
studies in men. Cullumbine exposed volunteers to increasing
concentrations of ZnCl2 smoke, 80 mg/m3 and 120 mg/m3
respectively, for two minutes [49]. Subjects exposed to the
lower dose showed only minor symptoms, such as slight nau-
sea and an occasional cough. Those exposed to a concentra-
tion of 120 mg/m3 clearly had more severe symptoms; all
volunteers complained of irritation of the nose, throat and
chest. Moreover, all the subjects experienced nausea and had
a cough. Cullumbine’s study supports our findings that peo-
ple who are exposed to a higher concentration of ZnCl2
smoke (e.g., those who were closer to the source of the
smoke or who were exposed in a confined space), showed
more severe symptoms.
Based on animal studies, Cullumbine estimated a human
lethal dose of 50,000 mg min/m3. In a confined room this
dosage can be reached within two to three minutes [49].
Limitations
Publication bias likely favours reporting of more severe cases
and likely underreports milder exposures.
Information on ZnCl2 exposure dose was in many cases
not available or incomparable due to a lack of standardisa-
tion. In order to allow for cross-group comparisons, we used
the exposure time and space in which the exposure took
place, i.e., confined space or open air, as proxies for the
exposure dose. We assumed that exposure doses were higher
for those that were exposed for a prolonged time period
and/or in a confined space.
Several case reports provide no information on the exact
constituents of the ZnCl2 smoke producing devices.
Therefore, there is a possibility that chemical agents other
than ZnCl2 may be responsible for the systemic effects, for
instance hepatotoxicity, described. The available published
cases primarily included healthy young men in military ser-
vice. The health effects may differ among women, children,
older patients, or patients with other chronic illness (espe-
cially pulmonary disease).
Conclusions and recommendations
Smoke screens and smoke bombs containing ZnCl2 may cause
serious harm in exposed individuals. Exposures most often
CLINICAL TOXICOLOGY 173
occur in military training activities or combat. The primary
determinants of health effects are the intensity and duration
of exposure. Even brief exposures, especially occurring in
confined spaces, result in mucosal irritation of the respiratory
tract, eyes, and upper digestive tract with dyspnoea, cough,
and lacrimation being the most common symptoms. Airway
inflammation resembling metal fume fever often follows one
to two days after an intense exposure. Severe cases may pro-
gress to ARDS. Chest radiographs may appear normal or
mildly abnormal early in the course of disease despite severe
symptoms and may remain abnormal while symptoms are
resolving. Maintaining adequate oxygen delivery is likely the
most important treatment goal. No clear and convincing evi-
dence supports the use of corticosteroids or antibiotics.
Acknowledgements
We thank Malin Jonsson-Boezelman (Genome Institute of Singapore),
Jane Synnergren (University of Sko €vde, Sweden), Hugues Abriel (Bern
University, Switzerland), Yuan Ji and Alexandre Bossu (both University
Medical Hospital Utrecht, The Netherlands) for their help in retrieving
and/or translating non-English case reports.
Disclosure statement
The authors report no declarations of interest.
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