FIRE AND MATERIALS, VOL.

10, 125-132 (1986)

Toxicity and Incapacitation due to

Hydrogen Chloride
Merritt M. Birky
Birky Associates, Inc., R t #3 Box 270, Boonsboro, Md 21713, USA

Hydrogen chloride is the principal product released during the combustion of poly(vinylch1oride). It is classified as a
sensory and pulmonary irritant. The toxicity of hydrogen chloride (HCI) has been the subject of numerous acute
toxicological studies on rodents to determine the effect of HCI exposure on humans during fires. The lethality studies
show that HCI destroys the upper respiratory tract and the eyes of rodents. A few of the rodent studies measured the
HCI concentration required to produce incapacitation within a given shortexposure period. These concentrations were
higher than the lethal concentrations due to the fact that most deaths occur postexposure. The findings from rodent
studies were basically confirmed by exposing non-human primates (baboons) to high HCI concentrations for 5 min and
measuring escape potential. I n the baboon study, no statistical significance could be found between the time-to-effect
parameters, failure modes and the HCI concentrations. The relevance of the baboon behavioral model and physiological
response to human escape-potential in a fire environment that contains HCI is questionable. In terms of the behavioral
model, the baboons were able to carry out the escape routine with their eyes closed during the exposure. Inability to see
was not considered incapacitating. Humans would have great difficulty escaping from a fire with their eyes closed.
Furthermore, the baboons escaped by one simple action; jumping out. Most humans could not escape from a fire by one
simple, instantaneous act. Based on the review of HCI toxicity and basic toxicological principles, elements required for
the development of an appropriate animal incapacitation model for irritants are proposed. Exposure of animals to
irritants, such as HCI, will only provide information on human escape impairment from fire when the animal models
address the direct result of irritant effects on vision and respiratory function. Most of the present studies measure the
delayed, secondary systemic effects that produce asphyxia. Clearly, the measurement of vision or the lack of vision
should be of primary importance in any irritant smoke incapacitation model.

such as carbon monoxide (CO) or hydrogen cyanide

INTRODUCTION
Various studies have demonstrated that approximately
802, of fire fatalities are due to smoke inhalati~n.'-~
Efforts to quantify the cause of death, that is, to pinpoint
the specific toxic products responsible for deaths, have
identified carlbon monoxide as being in the lethal range in
at least 50% of the victim^.^.^ While 50% of the victims
had lethal levels of carbon monoxide, it is not clear from
these studies whether other toxic products contributed to
the inability of the victims to escape the fire and what
other toxic products contributed to the deaths. Stated
another way, fatality studies cannot determine if in-
capacitating concentrations of other toxic products pre-
vented escape.
Since all fires produce irritant gases, a great deal of
speculation tias centered around the role of these gases in
leading to early incapacitation that prevents escape. One
hypothesis is that an individual is first incapacitated by
irritants, unable to escape and then exposed to lethal
concentrations of carbon monoxide. The irritant gases in
question include hydrogen chloride (HCl), hydrogen
fluoride (HF), acrolein and other aldehydes, and other
combustion products. The pathology resulting from the
inhalation of irritants is fairly well established in animal
studies and (accidentalhuman exposures. This, however,
does not address the incapacitating effects.
There is a tendency in the disciplineof fire toxicology to
treat irritants as lesser hazards than systemic toxicants
(HCN). Irritants are toxicants, and are lethal. Studies
show that irritants have a full range of potency just as
asphyxiants. The accidental release of methyl isocyanate
and exposure of humans in Bhopal, India, in 1985
tragically demonstrated both one extreme of the potency
range of an irritant and its toxic nature. Methyl isocyanate
is characterized as an irritant, but it is obviously lethal, as
about 2000 people perished in Bhopal. Both natural and
synthetic materials produce irritant products, such as
acrolein and other aldehydes, when exposed to thermal
overload as in a fire.
The irritant HCl has received a great deal of attention in
the last few years. The primary source of HCl in fire is
synthetic chlorinated materials such as poly(viny1-
chloride), or PVC. The role of PVC in incapacitation and
death during smoke exposure has remained unresolved
for some time due to the difficulty in measuring inhaled
chloride in fire victims against a large reservoir of
naturally occurring chloride in the human system. This
difficulty in determining the degree of exposure and
incapacitatingeffects of HCl is compounded by the lack of
an animal model that approximates the human re-
spiratory system and models human incapacitation. Most
of the information on the toxicity of HCl relies on rodent
lethality studies that neither approximate the human
respiratory tract physiology nor model human escape
capabilities or incapacitation. Admittedly, little inform-
ation exists on the nature of human incapacitation,so it is
difficult to sort out the factors that contribute to it and to

0308 0501/86/030125-08$05.00 Received 24 December 1985

0 1986 by John Wiley & Sons, Ltd. Accepted 14 April 1986
126 M. M. BIRKY
recognize when one has an appropriate model.
Recent studies on non-human primates were an effort
to correct the rodent deficiencies and incapacitation
factor^.^ It is instructive, however, to review the rodent
studies on HC1, HCl aerosols and smoke from burning
PVC before reviewing the effects of HCl gas on non-
human primate behavior.
RODENT STUDIES ON HYDROGEN CHLORIDE
In one study, rabbits and guinea pigs were exposed
simultaneously to HCl at various concentrations and
exposure periods ranging from 5 to 7200min.6 Post-
exposure observation period was for 50 days and above.
Statistical analysis of the mortality data was not done.
Deaths were tabulated according to probable cause and
time. Exposure of rabbits and guinea pigs to 4416 ppm for
30 min resulted in 100%mortality. Most of the deaths that
occurred during or shortly after the exposure were
attributed to respiratory tract damage. The deaths of some
of the animals of both species were attributed to liver
damage. Acute toxic changes in the liver and lungs were
tabulated as a single category, so the percentage of the
lethalities due to respiratory tract damage cannot be
obtained from the data. The finding of embolic and
thrombotic lesions with infarctions in the heart, liver,
kidney and spleen suggested vascular damage. Fatty
metamorphosis of the liver was present in both species.
High concentrations of HCl produced necrosis of the
tracheal, bronchial and alveolar epithelium.
In another study, rats and mice were exposed to HC1
and HCl with water aerosols (mist) for 5 and 30 rnin
periods.' The post-exposure observation period was 7
days. In the exposures with HCl/water aerosols, 64% of
the water droplets were 1pm or less in diameter.
In this study the LC,, values for 5 rnin exposures of rats
and mice to HCl gas were 40 989 ppm and 13 745 ppm,
respectively. The 5 rnin exposures to the HCl/water
aerosol decreased the LC,, slightly for the 5 rnin expo-
sures to 31008 ppm for rats and 11238 ppm for mice. For
rats this is a slight increase in toxicity due to the moisture,
although the 95% confidence limits for the two types of
exposure data overlap. Exposure of rats and mice for
30min to HCl resulted in an LC50 of 4701ppm and
2644 ppm, respectively. The water mist/HCl exposures for
30min produced an LC,, of 5666ppm for rats and
2142 ppm for mice. In the 30-min exposures, the toxicity of
HCl and HCl aerosol are nearly identical.
Gross pathological examination of the rats and mice in
this study showed severe irritation of the upper re-
spiratory tract and moderate-to-severe alveolar emphy-
sema and edema of the lungs. The death pattern was
about the same for the animals exposed to HCl and HCl
aerosol. Rats were considerably more tolerant of HC1
than were mice and the rabbits and guinea pigs of the
previous study. Corneal erosion and clouding were noted
in both species for both dry HCl and HCl aerosol.
Respiratory tract pathology was similar to that reported
in the earlier study. The pathology (hepatic lesions) of
other organs reported earlier was not confirmed.
In a third study, rats and mice were exposed for 5 rnin to
HCl gas with and without pre-exposure to carbon
monoxide.* Pre-exposure to carbon monoxide was
limited to a carboxyhemoglobin (COHb) saturation of
25%. The post-exposure observation period was 7 days.
For rats the LC,, concentration for HCl alone was
40989ppm and 39010ppm with 25% COHb. For mice
the LC50 concentration for HC1 alone was 13 745 ppm
and 10663 ppm with 25% COHb. The authors concluded
that carbon monoxide concentrations that are not hazar-
dous to life do not enhance the toxicity of HCl. However,
as noted by the authors, the CO exposure superimposed
on the individual contaminant exposures (HCl) might
have resulted in more rapid deaths.
In an effort to study the effects of inert particulates on
HCl toxicity, rats and mice were exposed to HCl alone and
in combination with inert aluminum oxide particles (1.4~)
for 60mir1.~Lethality data were determined for a post-
exposure period of 14 days. The LC,, for rats and mice
exposed to HCl alone were 3124ppm and 1108ppm.
respectively. The addition of the alumina dust to HCl
exposures was reported to have no net effect on the
mortality as compared with the HCl alone for either the
rats or mice, although no statistical analysis of the data
was presented.
Rats and guinea pigs were exposed to the combined
effectsof HCl and CO in smoke from burning PVC and
wood." In these experiments, HCl and CO were
generated from the combustion of a vinyl-covered hard-
board in a fire room. Gaseous HCl was added to the tire
products to attain the desired level of this gas. The
exposures were for 30 rnin with the time of delayed deaths
reported. Initially,the protocol was to expose the animals
for 30min and determine the death rate over 7 days.
However, due to gross damage to eyes, noses, mouths and
hairless parts of the feet, surviving animals were killed
prior to 7 days for humanitarian reasons. Exposure of rats
for 30min to 3298ppm to HCl and 3925ppm of CO
produced 100% mortality in 24 h. The same experimental
conditions produced an 80% mortality rate in guinea pigs.
In a second set of experimental conditions 4555 ppm of
HCl alone produced 100%mortality in rats and guinea
pigs in 24h. Similarly, exposure to 2380ppm HCl for
30 rnin produced a 67% mortality rate in rats in 5 h and an
87% mortality rate in guinea pigs in the same time. In the
combustion studies, carboxyhemoglobinvalues were pro-
vided on fatalities at the end of the 30 rnin exposures. No
statistical analysis of the data, such as calculation of LCs,,
values, was reported in this study. The mortality rate was
simply listed as a function of concentration.
The authors of this combustion study concluded that for
rats and guinea pigs HCl enhances the toxicity of carbon
monoxide. The enhancement occurred mainly at con-
centrations of HCl which could be lethal when present
alone. This enhancement was attributed by the authors to
excitement and overbreathing, and was most significant
for the guinea pigs. (Note: High levels of carbon dioxide
were also present which will increase the respiratory rate.)
While deaths were generally associated with high levels 01
carboxyhemoglobin,the mortality rate would have been
similar without the CO.
The most extensive toxicological research on fire
products was based on the change in respiratory function,
respiratory rate and tidal volume of mice.'' In these
studies a furnace was connected to a whole body ple-
thysmograph. The plethysmograph is a small chamber in
which the body of a mouse is placed with the head
 TOXICITY AND INCAPACITATION DUE TO HYDROGEN CHLORIDE 127

protruding through a perforated latex dam/which provides destruction of upper respiratory tract from pharynx to
an airtight seal between the body and the head. A pressure nares and little damage to airways below the trachea.
transducer measures the change in air pressure surround- Table 1 summarizes the HCI toxicological findings by
ing the body due to respiration. During exposure to various investigators on different animal species and
irritants the frequency and depth of respiration changes. exposure times. Dose (concentration x exposure time) is
This is reflected as changes in air pressure surrounding the calculated and listed in the table in an effort to compare
body of the rodent and recorded. Based on the change in the results of various studies. However, due to the fact that
respiratory function, a 50% decrease in respiratory rate some investigators observed the animals for different
was defined as the RD,, (respiratory decrease of 50%). periods of time post-exposure, the comparisons must be
Based on this methodology, the RD,, was reported for made with caution. It is interesting to note that the LC,,
irritants including chlorine, HCI and PVC smoke.lZFor for 5-min exposures for rats and mice as reported by
HCI the RD,, was determined to be 309ppm or Darmer et a/.’ and Higgins et ~ 1are. identical.
~ It must be
0.454mg1.-’ The RD,, for a plasticized PVC was deter- concluded that these are not independent measurements.
mined to be 0.19mg1-’. Smoke from PVC was some-
what more toxic than the equivalent HCI concentration.
This R D , , value obtained in mice was interpreted as being NON-HUMAN PRIMATE STUDY
incapacitating to man in a few minute^.'^
In order to determine the effect of nasal filtration in mice
the acute toxicities of HCl and thermal decomposition Objective and protocol
products from PVC were compared between mice with
and without tracheal ~annu1ation.l~ Severe pulmonary Non-human primates (juvenile African savannah
damage was noted in the cannulated animals. The LC,, baboons) and rats were exposed to various toxicants
for HCI of the cannulated animals was 1095ppm and including acrolein, HCI and CO.’ The primary objective
10 137ppm for the uncannulated ones. Extensive destruc- of this study was to determine the ability of irritant gases
tion of the eyes and nasal passages with no involvement of to impair human escape from an aircraft-fire environ-
the lower respiiratory tract was noted in the uncannulated ment. A secondary objective was to evaluate the relevance
animals. and validity of the rodent laboratory toxicity test results
In a recent study, time to incapacitation and time to to predict effects on humans. Both objectives were to be
death of rats were determined for anhydrous HCl gas.” accomplished by measuring performance-decrement dur-
Hydrogen chloride concentrations ranged from 2000 ppm ing exposure of non-human primates to selected irritant
to lOoOOOpp~n.Time to incapacitation (ti) was defined gases.
when the animals could no longer walk in a driven Both non-human primate and rodent measurements
rotating cage. Time to death ( t d )was defined when visible were proposed using the same experimental protocol in
signs of respiration ceased. Based on this experimental order to correlate rodent incapacitation model results
protocol, incapacitation occurred in 5.5 min when the with primate results. Since previous studies on irritants
HCl concentration was 94000 ppm. The shortest time to had been limited to rodents, the program was designed to
death was slightly more than 6min from exposure to evaluate the adequacy of these rodent models in predict-
96 OOO ppm. Basically, the incapacitating concentration ing human toxicity and the impairment of human escape
was equivalent to lethal concentrations. Gross post- capabilities in the fire environment. Carbon monoxide,
mortem pathological examination showed almost total a non-irritant product, was evaluated in the study
since extensive data using rats and various behavioral/
incapacitation models have been used to study fire
toxicity and develop animal models.
Table 1. Summary of HCI toxicity on rodents
The experimental protocol proposed for this study was
Species i‘(rnin) LC,. LC x T Ref. Comments to train non-human primates and rats to escape from an
Rabbits 30 4 452 1 33 500 6 Est. LC,, exposure chamber by pressing one of two levers. The
50 days post correct lever that allowed escape from the toxic gas was
Guinea pigs 30 4 452 1 33 500 6 Est. LC,, identified by a colored light which was turned on simulta-
50 days post neously with a tone. After a 5 min exposure to selected
Rats 5 40 989 204 945 8 toxic gases, the start of a trial was identified with an audio
Mice 5 13 745 68 725 8
7 7 days post
tone (cue) with simultaneous lighting above the levers.
Rats 5 40 989 204 945
Mice 5 13 745 68 725 7 7 days post
Ten seconds after the cue the bars of the cage were
Rats 30 4 701 141 030 7 7 days post electrified. ‘Avoidance’ was defined as a correct response
Mice 30 2 644 79 320 7 7 days post and exit from the chamber within 10s after the cue.
Rats 5 31 008 155 040 7 +Aerosol ‘Escape’ was defined as a correct response and exiting the
Mice 5 11 238 56 190 7 +Aerosol chamber after 10 s, that is, after a shock but within 30 s.
Rats 30 5 660 1 69 800 7 +Aerosol Changes in response times were to be determined as a
Mice 30 2142 64 260 7 +Aerosol function of toxic gas concentration. Performance or
Rats 60 3124 187 440 9 14 days post impairment was to be determined as changes in time to
Mice 60 1108 66 480 9 14 days post ‘avoid‘ and ‘escape’ as a result of the toxic effects of the
Rats 5 39010 195 050 8 + 25% COHb
gases. Correlation of the results from the two animal
6 days post
Mice 5 10 663 53 305 8 + 25% COHb species would serve to determine the relevance of rodent
7 days post toxicity data to primates which, in principle, should more
closely approximate human effects and response.
128 M. M.BIRKY
The complex avoidance/escape paradigm was modified
for the rats due to the inability to train them. First, the
same color light was used above both levers and pressing
of either lever opened the cage. Second, even with this
change, the rats could not be trained at a satisfactory level
of ‘avoidance’. Consequently, only the ‘escape’ paradigm
(electric shock) was used. The rats were exposed only to
CO and HCl. Primates were exposed to all three toxi-
cants. All toxicant exposures were done singly, that is, no
combination of toxic products was studied.
Carbon monoxide results
Dose-response data were determined for rats and
primates exposed to carbon monoxide. Using the modi-
fied paradigm, the rat data showed that the percentage of
animals failing to escape increased with increasing CO
concentrations. Statistical analysis of this data shows that
half of the rats will fail to escape if exposed to about
6660 ppm for 5 min. Statistical analysis of the escape time
data show that escape time increased as the average CO
concentration increased. The slope of this relationship
was 0.001 min ppm-’.
For the primates, no statistically significant relation-
ship was observed between the average CO exposure
concentration and escape time. However, decrease in time
to incapacitation (incapacitation is defined as inability to
escape, i.e. failure as defined above) did correlate with
average increase in CO concentration. About one-half of
the primates failed to escape at 6850 ppm as a result of the
5 min exposure. Of those baboons that failed to escape,
became unconscious and in which blood samples were
obtained, the carboxyhemoglobin saturation ranged from
60% to 71%. No carboxyhemoglobin data were reported
for those baboons that escaped under the same test
conditions. However, it was noted that there was con-
siderable variability among animals in their sensitivity to
carbon monoxide.
HCI exposure results
Rats were exposed for 5 min to HCl concentrations from
11 800 ppm to 87 660 ppm. At all concentrations except
the 87660 ppm, the animals were able to perform the
escape task. No statistical correlation between time to
escape and HC1 concentrations was noted. Delayed
mortality occurred in all but the lowest two concentra-
tions. A statistical analysis of the mortality data showed
a correlation between the time of post-exposure deaths
with HCl concentration.
The non-human primates were exposed to HC1 con-
centrations from 190ppm to 17290ppm for 5min. No
statistical significance could be found between escape
time and HCl concentration. Furthermore, no statisti-
cally significantdose related effects on performance could
be found. The two highest HCl concentrations
(16 570 ppm and 17 290 ppm) resulted in the death of the
animals.
Acrolein results
As noted earlier, rats were not exposed to acrolein. The
primates were exposed to acrolein concentrations of 12 to
2780 ppm for 5 min. Statistical analysis of the data showed
that there was no correlation between escape time and
acrolein concentration. No statistically significant correl-
ation could be obtained between acrolein concentrations
and the other performance parameters. In these expo-
sures, two of the animals died. One died approximately 1
day post-exposure to 1025ppm and one died about 1 h
post-exposure to 2780 ppm.
DISCUSSION
The above review of rodent and primate studies on
irritants demonstrates the difficulties with developing
short exposure dose response effects that are amenable to
statistical analysis. Part of the difficulty in obtaining valid
statistics on acute-short time exposures to irritants is due
to the fact that the predominate tissue effects that lead to
death are delayed. This is especially true since most of the
injury pathology has been limited to the observations on
the respiratory tract. As a consequence, a number of the
investigators simply reported approximate dose required
to kill or reported time of deaths after exposure. In one
study, the animals were killed for humanitarian reasons
before the post-exposure period was completed.
In the rodent studies and on the limited primate
exposures post-exposure deaths occur at much lower
concentrations than the concentrations that produce
incapacitation within the exposure period. This occurs
since incapacitation is measured only during exposure.
The post-exposure effect is vividly demonstrated in the
rats exposed to high concentrations of HC1 where the
post-mortem pathological observation noted ‘surpris-
ingly little damage to the airways below the trachea but
almost total destruction from pharynx to nares’.15 This
phenomenon is most likely to be more acute in rodents
because of the complex upper respiratory tract physiology
where much of the HCl is trapped. This is clearly
demonstrated by the results on cannulated animal^.'^ In
the case of humans and non-human primates, severe lung
damage will most likely occur prior to total destruction of
the upper respiratory tract.
The relationship or translation/extrapolation of the
effects of pure HCl gas on rodents and on non-human
primates to the fire environment and to human escape-
potential from a fire must be carried out with extreme
caution with full knowledge of the limitations. There are
two very important questions that must be considered
before this extrapolation can be made with confidence:
(1) What is the relationship of rodent and non-human
primate HC1 results to smoke from PVC; and
(2) What is the relationship of the animal incapacitation
models to human escape potential?
Relationship of pure gas study to the fire environment
Rodent results summarized above on the effects of pure
HCI gas and HCl gas in combination with moisture,
carbon monoxide, inert particulates and actual smoke
from the combustion of PVC suggest that the results of
pure HCl exposures provide reasonable approximations
to the combined effects of HCl and some of the factors
 TOXICITY AND INCAPACITATION DUE TO HYDROGEN CHLORIDE
present in a fire environment. That is, the addition of
moisture to HCl and actually burning PVC does not
appear to produce a significantly different gross toxicity
than that of pure HCl. With the present information, this
judgment must be limited to the effects on rodents.
Furthermore, conclusions from these limited studies must
be stated with the followingcaution. First, the rodent and
non-human primate studies do not address the issue of
time-to-effectand the more complex task of escape from a
building fire. Second, while the respiratory system is
obviously affected and is the most extensively studied
organ system, visual impairment may be a serious uniden-
tified phenomenon, especially in relationship to escape,
and may be the limitation on human escape. This will be
discussed later. However, none of the studies addressed
this issue. Third, studies on other irritants suggest a much
more complex phenomenon with regard to the effects of
moisture and particulates. These effects were shown to be
concentration and particle size dependent.
As an example, studies on sulfur dioxide show that
aerosols potentiate the effects of the irritant.I6 The
potentiation was dependent on the concentration of the
'inert' aerosol and particle size. The submicron particles
were more effective than the larger ones. Furthermore, the
post-exposure potentiation was dependent on aerosol
dose and was relatively slow to d e ~ e l o p . ' ~ Formalde-
.'~
hyde toxicity was also dependent on the concentration
and particle size of the inert aerosol.16 Relative humidity
(RH) was found to be important in the sulfur dioxide
toxicity with a tenfold potentiation occurring at 80%
RH as compared with 50% RH." At high humidity the
potentiation occurred rapidly.
The studies with sulfur dioxide suggest that the potenti-
ation due to moisture is partly due to the conversion of
sulfur dioxide to sulfuric acid. This does not happen in the
case of HCl. The primate experimental protocol involved
dry HCl in order to maintain a fixed concentration for the
exposure periods. When the relative humidity was above
500/,,, droplets appeared on the chamber walls, so one
infers from this that the RH was maintained below 50%.
Whether or not the primate will respond differently when
aerosols and other toxic products from PVC smoke are
present is unanswered by this study.
The potentiation effect of irritant gases by inert aerosols
noted above is consistent with the fact that small aerosols
will pass through the upper respiratory tract and reach the
alveoli of the lungs, where the aerosol is retained. The
irritant adsorbed on the particulate is then released in
the lungs. It is well known that when PVC is involved in a
fire HCl is adsorbed on the surfaces of the smoke or
particulates. It has been reported that particulates from
burning PVC contain up to 1 to 2% by weight HCl.I9 It
has been shown in limited rodent studies that the toxicity
of smoke from PVC is slightly higher than the equivalent
HC1 concentration. This may be due to the effect of inert
particdates and to other chemicals that are produced.
As noted above, one reported study has actually burned
PVC and wood in an effort to determine the combined
effects of HC1 and CO.'O This study involved an exposure
to products other than just HCl and CO. In these
experiments the HCl and CO were generated from the
combustion of a vinyl-covered hardboard. Gaseous HCl
was added to the fire products to attain the desired level of
this gas. The conclusion of this study using rats and guinea
129
pigs is that the HCl enhances the toxicity of carbon
monoxide, although the effect appears to be minimal,
It is instructive to note the cautions put forward by the
authors who have exposed rodents to PVC fire products.
They note that while deaths were generally associated
with high levels of carboxyhemoglobin, 'it is probable,
however, that the most important effects of the presence of
hydrogen chloride will accompany sub-lethal exposures,
firstly because the highly irritant nature of the gas may
result in more people being prevented from using escape
routes in the early stages of fires in buildings by con-
centrations of fire gases and smoke which may be
otherwise relatively harmless at the time and, secondly,
because survivors may suffer long term, even permanent,
injury from high concentrations of this gas'.'O
To understand the significance of this statement, one
must be aware that when PVC is burned or involved first
or early in a fire HCl is given off before lethal levels of
carbon monoxide are produced. This is due to the fact that
HCl is released at a relatively low temperature (180"C)
compared with the combustion temperatures of common
materials. Carbon monoxide is generally produced in
high concentrations because of the oxygen depletion by
the fire.
Relationship of non-human primate results to
human escape
'The primary objective of the non-human primate study
was to assess the potential of representative combustion
atmosphere irritant gases to impair human escape from a
postcrash aircraft fire environment.The secondary objec-
tive was to evaluate the relevance and validity of presently
used rodent laboratory test methods in predicting the
potential of combustion gases to impair human escape
~apability.'~ The logic for attaining the secondary objec-
tive goes as follows. If the non-human primate results are
shown to be relevant to human escape potential, then
these results can be used to validate the rodent animal
model. If the primate behavioral model is not relevant to
human escape potential, then it cannot be used to validate
the rodent models.
In the light of the primary objectives of the non-human
primate study to measure impairment of human escape
potential the second question raised earlier has two parts;
the relevance of the non-human primate physiology and
whether the escape/behavioralmodel used in the primate
study is representative of or a measure of the ability of
humans to escape from a fire involving PVC. From a
respiratory physiologicalperspective,the baboon is prob-
ably as close to a human as one can get. However, the
clinical observations made in the study raise some
interesting questions. As in any toxicological experi-
mental protocol, careful observations are invaluable and,
in the case of the primate study, the clinical observations
provide some information regarding this q u e s t i ~ n .Ac-
~
cording to these observations the baboons blinked,
coughed and salivated copiously. Copious salivation will
significantlyreduce HCl intake if respiration is occurring
through the mouth. Do humans salivate copiously when
exposed to HCl and, just as importantly, does it happen
on exposure to smoke from burning PVC? This raises the
question of just how representative the baboon is to
130 M. M. BIRKY
human response and whether baboons would respond in
the same way to smoke from PVC.
It is interesting to note that the non-human primate
study does not report evidence of bronchoconstriction,
laryngeal spasms and eye damage during exposure to the
strong irritants, even at high concentrations. The clinical
observations of the baboon exposed to 2780 ppm of HCl
indicate that the animal began to cough and choke
immediately, but apparently the animal recovered from
this. Laryngeal spasms are reported to occur in human
exposures to strong irritants such as HCl. The cause of
death in animals that succumbed rapidly during exposure
to sulfuric acid is reported to be bronchoconstriction and
laryngeal spasm.20g2’Is this response typical of humans,
or was it simply not observed in the baboon study because
of the limited number of animals?
Eye damage was reported in various rodent s t ~ d i e s . ’ ~
Did it occur in the non-human primate study or did it not
occur because the animals kept their eyes closed? What is
the relevance of this phenomenon to human escape?
This leads directly into the second part of the question,
i.e. what is the relevance of the non-human primate
escape paradigm to human escape potential? Based on
the clinical observations of the non-human primates and
recognizing that information processing and sustained
actions are required to escape from a burning structure, it
should be clear that the primate behavioral model has
limited relevance to human ability to escape from the
environment of a fire. This is best demonstrated by the
baboons’ apparent ability to perform the escape task with
their eyes closed during the acrolein tests. At 25 ppm it is
noted that the animal kept its eyes closed during most of
the exposure and at 250ppm it was recorded that the
animal’s eyes were closed during the exposure. This
obviously will reduce pain and protect the eyes for future
vision. However, this response is inappropriate for escap-
ing from a fire. In spite of the observation that the animals
kept their eyes closed and successfully performed the
escape task, the authors of the study conclude that while
the statement that ‘20ppm of acrolein is at once insuffer-
able, may be accurate, such a statement should not be
interpreted as meaning that these exposures would in-
capacitate humans or prevent their e~cape’.~ On the
contrary, inability to see is clearly incapacitating when
trying to escape from a fire.
In the HCl exposures, eye irritation was first reported
at 2780ppm. At 17000ppm the baboon had its eyes
closed most of the time but was able to escape. It would
appear that in this behavioral model sight, or the absence
of it, does not constitute incapacitation. Apparently,in the
baboon study, vision was not a requirement for escape. In
contrast, most humans would have great difficulty trying
to escape from a structure and aircraft fire with their eyes
closed.
For practical reasons, there are many inherent limi-
tations to any animal behavioral model. For example,
pulling a lever on cue after extensive training does not
model either the complex decision-making requirements
or the sustained short-term exertion required for human
escape from a burning building or aircraft. However,
ability to see or keep one’s eyes open should be required in
any behavioral model used for escape.
It was noted earlier that most of the rats developed
clouded corneas when exposured to high concentrations
of HCl. None of the studies report what minimum
exposure and time were required to produce this phe-
nomenon or a dose-response for this effect. The clinical
information on the baboons does not report whether they
developed clouded corneas. This raises the question of
whether ability to see or keep one’s eyes open would be a
more realistic measure of escape potential.
From the above discussion the relevance of the non-
human primate performance model to human effects and
performance is questionable. In addition, in neither of the
two irritant gases could statistically valid dose -
response/performance relationships be obtained for in-
capacitation or for lethality in either animal species. In
spite of this lack of statistical validity, the authors
conclude that ‘laboratory tests with rodents may be used
to predict escape impairment of humans exposed to
HCl’.5 This conclusion is apparently based on the observ-
ations that for a 5min exposure the ‘threshold con-
centrations which caused severe post exposure respir-
atory effects and lethality appears to be fairly close in the
two specie^'^ (referring to rodents and baboons). How-
ever, the other part of the equation that must be addressed
before this conclusion is valid is the relevance of the
measured parameters to approximate human incapaci-
tation in a fire behavior. The inability to obtain a
statistical correlation between exposure concentration
and performance of various animal species is due to the
inappropriateness of the performance model for the
nature of the toxic response. The measured response is
due to delayed effects. Furthermore, no amount of
repetition or efforts to obtain statistical validity will
resolve this issue.
It appears that the difficulty with most behavioral
(incapacitation) paradigms used in fire toxicity studies is
that the incapacitation models have been based on and
validated with carbon monoxide. For example, it was
concluded, based on the primate work and calculations
on humans, that ‘these human data (referring to CO
toxicity) provide support for the validity of the rat [and
the baboon] as a model for predicting human escape
impairment by CO. This conclusion may be correct, but
the problem in the fire environment is not just CO;
otherwise the non-human primate work would not be
necessary.
PRINCIPLES FOR AN INCAPACITATION
MODEL
Based on the above review of HCl toxicity, it is instructive
to go back to some basic principles to toxicology22in
order to construct a more appropriate behavioral model.
Toxicants are categorized by type and general locus of
action, such as immediate versus delayed, reversible
versus irreversible and local versus systemic. Local effects
are those that occur at the site of first contact between the
biological system and the toxicant. Irritants fall in this
category. The counterpart to local effects is systemic
effects, which require adsorption and distribution of the
toxicant to a site distant from the entry point. Most
systemic toxicants do not produce a similar degree of
toxicity in all organs but usually produce the major
toxicity in one or two organs. These are referred to as
target organs. Thus an exposure to a systemic toxicant
 TOXICITY AND INCAPACITATION DUE TO HYDROGEN CHLORIDE
does not have a demonstrable effect until the toxicant
reaches the target organ and causes a response. The
central nervous system is the target organ most frequently
involved in systemic toxicity.
This process of reaching the target organ requires two
steps. The first is exposure and the second is distribution
in the body to the target organ. Exposure via inhalation is
quite rapid, and depends on concentration of toxicant,
respiratory rate and volume. The time required for the
second step, distribution, will depend on the chemical
properties of the toxicant and circulatory system. The
time to observe an effect will depend on the response time
of the reaction to the chemical and what effect is being
measured. Some effects are immediately observable and
some, such as carcinogenic effects, require years to
develop.
With this background it is instructive to review the CO
and HCl rodent and non-human primate models and
results. There are two interesting points to be made about
the CO exposures and results. Carbon monoxide is a
systemic toxicant and the target organ is the central
nervous system (brain). O n inhalation, C O is rapidly
adsorbed in the blood, bound to the hemoglobin mole-
cules and rapidly distributed throughout the circulatory
system. This results in rapid brain (target organ) hypoxia
and, depending on concentration, the consequence of this
effect is immediately observable (measurable) by a num-
ber of performance parameters that have been used in
smoke toxicity. The result is ‘immediate’,even relative to a
short exposure time of 5 mins. The same is basically true
for exposure to hydrogen cyanide, since it is a systemic
toxicant and results in brain hypoxia, although via a
different mechanism.
Now, consider exposure to HCl. It is very clear from the
extensive rodent inhalation studies reviewed above that
HCl first produces a local effect when it contacts the
mucosa of the respiratory tract. It also affects the eyes and
may impair vision first. Apparently, no one has studied
this as a model of incapacitation. Destruction of these
tissues requires some time to develop. The time required
is, of course, concentration dependent, but for the grossly
observable respiratory tract effects it is generally longer
than Smin and will take as long as a few hours to a few
days to reach its maximum effect unless a massive
exposure occurs. While the initial effect is irritation of the
mucoba, what is being measured in most of the animal
performance and lethality studies above is not the irritant
effectbut a secondary, systemic effect of brain hypoxia due
to respiratory tract tissue destruction. As a consequence,
the rodent ‘performs’,as does the primate, until some vital
capacity is compromised, such as oxygen delivery to the
brain. If this is the cause of human incapacitation in fire
then the model may be appropriate, but this seems very
unlikely given the irritant nature of HCl and the fact that
the animals must close their eyes. It simply means that the
traditionally measured performance parameters used for
C O toxicity are inappropriate measures of incapacitation
from irritants such as HCl.
An analogy with carcinogens may be instructive. One
would not expect to measure within exposure change in
animal performance from a 3 0 min exposure to a carcino-
gen that has a latency period of years. This is obviously an
overstatement, but illustrates the inappropriateness of the
performance models used in the rat and primate studies to
131
determine HCl toxicity. Validating a behavioral model
based on a systemic toxicant such as carbon monoxide
does not necessarily validate the model for other combus-
tion toxicants. Neither does simply changing the animal
species, since the behavioral model is in question.
With this background it is clear why there is a large
discrepancy between the toxicity of HCl as determined
from respiratory rate measurements on mice (RD,, of
309 ppm) and the lethality and performance results on
rodents and primates (1 5 OOO to 94 000 ppm). The change in
respiratory function is a direct measure of the effect of HCl
on the site of first contact. These functions include
increased pulmonary flow resistance, increased tidal
volume and decreased respiratory frequency. The
performance changes as measured in most of the studies
are the secondary or indirect result of damage to the
respiratory system.
How toxicity numbers are translated or extrapolated to
human escape ability is still open to question and is not
answered by this analysis. That is, how any toxicity or
performance number is translated to humans is still open
to debate. It should be clear, however, that the model must
measure the correct parameter before the translation is
made. In addition, it should be clear by this time that
producing brain hypoxia with an irritant takes some time.
Furthermore, while escape from a fire environment is the
first prerequisite, it is not a sufficient criterion. Post-
exposure survival is also critical, as is the quality of
survival. Most of the numbers generated above do not
provide for survival.
SUMMARY AND CONCLUSIONS
The experimental results on the effects of the irritants, HCl
and acrolein, on performance are interesting and certainly
further our knowledge of the effects of irritants on
primates. It is the first step in developing information on
toxicity of smoke from burning materials such as PVC.
Extrapolation of these data to human toxicity and human
escape potential from a burning building or aircraft could
be very misleading, if not dangerous. The relevance of
these results to escape potential when humans are
exposed to irritants in a fire environment is open to
question. The studies fail to answer some basic questions
about the effects of HCl on vision and resulting eye-
damage. Part of the difficulty with the results of these
rodent and non-human primate studies is the lack of
definition of human incapacitation in fires. Is it lack of
mobility due to systemic toxic effects or is it lack of ability
to see due to irritant smoke, etc.?
With our present limited knowledge it appears to make
little scientific sense to study irritants using animal-
performance models developed for CO systemic in-
capacitation. In the case of irritants such as HCl, it appears
to be more appropriate to explore visual or respiratory
decrement. If a task performance model is to be used, it
should be one based on visual acuity and not one that can
be performed without sight or simply momentary sight.
Furthermore, it should be some task that requires a
performance that cannot be completed by a single,
instantaneous action. Does this suggest that a maze
rodent performance model be used to study HCl toxicity?
Perhaps, but before this can be answered definitively, it
132 M. M.BIRKY
must be decided how much of the rodent escape-
navigation is dependent on olfactory sensing. Can a
rodent run through a maze with its eyes closed? Before
results from such a model could be interpreted it would be
necessary to know the relationship between olfactory
sensing and directionalityin rodents, the effects of HCl on
REFERENCES
1. B. A. Zikria, G. C. Weston, M. Chodoff and J. M. Ferrer, J. of
Trauma 12, 641-5 (1972)
2. W. G. Berl and B. M. Halpin, Human Fatalities from Unwanted
Fires, Applied Physics LaboratoryIJohns Hopkins University
(1978).
3. M. M. Birky, B. M. Halpin, Y. H. Caplan, R. S. Fisher, J. M.
McAllister and A. M. Dixon, Fire and Materials 3, 211-18
(1979).
4. R. A. Anderson, A. A. Watson and W. D. Harland, Med. Sci. Law
21,288-94 (1981).
5. H. L. Kaplan, A. F. Grand, W. R. Rogers, W. G. Switzer and G. E.
Hartzell, A research study of the assessment of escape impair-
ment by irritant combustion gases in postcrash aircraft fires.
DOTIFAAICT-84I16, September (1984).
6. W. Mackle, K. V. Kitzmiller, E. W. Scott and J. F. Treon, J. of Ind.
Hyg. and Tox. 24,222-5 (1942).
7. K. 1. Darmer, E. R. Kinkead and L. C. DiPasquale, Am. Ind. Hyg.
Assoc. J. 35, 623 (1974).
8. E. A. Higgins, V. Fiorica, A. A. Thomas and H. V. Davis. The
acute toxicity of brief exposures to HF, HCI, NO, and HCN
singly and in combination with CO. Washington, DC, Federal
Aviation Administration Off ice of Aviation Medicine, Report No.
FAA-AM-71-47 (1971).
9. J. Wohlslagel, L. C. DiPasquale and E. H. Vernot, Toxicity of
solid rocket motor exhaust-effects of HCI, HF and alumina on
rodents. AMRL-TR-75- 125 (1975).
10. P. C. Bowes, J. A. G. Edgington and R. D. Lynch, The inhalation
toxicity of poly-vinyl chloride pyrolysis products. Fire Research
Note No. 7048, Fire Research Station (1976).
11. C. S. Barrow, Y. Alarie, J. C. Warrock and M. F. Stock, Arch.
Environ. Health 32, 68-76 (1977).
this sensing and the relationship of this change to visual
sensing in humans. These problems with a rodent maze
appear insurmountable. It would be considerably more
direct to measure the change in corneal opacity or some
other measure of eye irritation as it relates to ability to
escape.
12. C. S. Barrow, Y. Alarie and M. F. Stock, Fire and Materials 1,
147-53 (1976).
13. L. E. Kane, C. S.Barrow and Y. Alarie, Amer. lnd. Hyg. Assoc. J.
40,207-29 (1979).
14. R. C. Anderson and Y. Alarie, Acute lethal effects of polyvinvl-
chloride thermal decomposition products in normal and cannu-
lated mice (Abstract), Society of Toxicology, 19th Annual
Meeting, Washington, DC, 9-1 3 March (1980).
15. C. R. Crane, D. C. Sanders, B. R. Endecott and J. K. Abbott.
Inhalation toxicology: IV. Times to incapacitation and death for
rats exposed continuously to atmospheric hydrogen chloride
gas. Civil Aeromedical Institute, Federal Aviation Administr-
ation, May (1985).
16. M. 0. Amdur, The effect of aerosols on the response to irritants
gases. In Inhaled Particlesand Vapours, edited by C. N. Davies,
Pergamon Press, Oxford (1961), pp. 281-92.
17. M. 0. Amdur and D. W. Underhill, Arch. Environ. Health 16,
460-68 (1968).
18. C. McJilton, N. R. Frank and R. E. Charlson, Science 182,
503-4 (1973).
19. J. P. Stone, R. N. Hazlett, J. E. Johnson and H. Carhart, J of
Fire and Flammability 4, 42-50 (1973).
20. M. 0. Amdur, R. 2. Schultz and P. Drinker, Arch. Ind. Hyg.
Occup. Med. 5, 318-29 (1952).
21. R. E. Pattle, F. Burgess and H. Cullumbine, J. Pathol. Bacterrol
72, 219-32 (1956).
22. J. Casarett and C. D. Doull, Toxicology, the Basic Science of
Poisons, 2nd edn, Macmillan Publishing Co., New York (1980,
Ch. 2, p. 16.
Received 24 December 1985; accepted 14 April 1986.