CI” Concentration (umoles/L)

5888 |

4080 |

3020

2800

1880

@ 4. nN i. 4 4.
@ 1 2 3 4 a) a)

Absorbance Units

Figure Al. Standard curve: Chloride ion concentration
as a function of absorbance at 480 nm.
Regression equation: y=37.7 + 4329x + 5156.4x°;
correlation coefficient = 0.999.

18


1/(Td-3)

235

.38

625

.28

15

18

.@5

0.88 +
@ 18 28 30 40 58 68 78 88 9B 180

(HC1] Conen. - @.4)

Figure 6. Reciprocal response-time as a function of HCl concen-
tration. (N=42, time is in minutes, concentration is in parts per
thousand, regression correlation coefficient=0.92.)

12


In order to define the levels of HCl exposure necessary to produce
(i) physical incapacitation and (ii) death in the laboratory rat, we
conducted the following study. Rats were exposed to a selected range of
HC1 concentrations (2,000 to 100,000 ppm) while enclosed in an electrically
powered rotating cage assembly. The elapsed time from initiation of the
exposure until the animal could no longer perform the coordinated act of
walking in the rotating cage was recorded as the time-to-incapacitation (t,;).
Time-to-death (tg) was recorded (with cage rotation stopped at ty) when
visible signs of respiration ceased. An equation was then derived for each
endpoint that related response time to HCl concentration.

MATERIALS AND METHODS.

Animals. Male albino rats, Sprague-Dawley strain, were acquired from
Charles River Laboratories, Wilmington, MA. On receipt they were inspected
by a veterinarian and housed in isolated quarters for 10 days with food and
water available continuously. When ready for use, the animals were fasted
overnight, weighed, and placed in separate compartments of the rotating
cage.

Exposure chamber. The chamber used in this study has been described
in detail previously (4). Briefly, it is a polymethylmethacrylate (PMMA) box,
25.4 by 22 by 22 cm, equipped with an internal motor-driven PMMA cage rotating
at 6 rpm. This cylindrical cage, similar to an exercise wheel, is 20 cm in
diameter and 22 cm long and is covered with a polypropylene screen of
1/3-inch mesh. There are three compartments in the cage, designed to accommo-
date one animal each. Two interior fans ensure rapid and efficient mixing
of the chamber atmosphere with the incoming gas.

HCl gas handling and analysis. Anhydrous HCl gas (technical grade,
Matheson Gas Products, East Rutherford, NJ) was delivered through a corrosion-
resistant pressure regulator (Matheson model B16A-330) connected to an all-
glass rotameter; compressed air (breathing grade) was delivered at controlled
pressure through a second rotameter. The two flowing gases were mixed at a
glass Y-tube connected to an inlet port in a top corner of the chamber,
stirred into the chamber atmosphere by the two interior fans, and then exited
the chamber at a port diametrically opposite the inlet. A vinyl tube, 1.2 cm
in diameter, conducted the exhausted gas behind a water screen at the rear
of the stainless steel fume hood in which the entire apparatus was situated.

The chamber atmosphere was sampled at appropriate intervals during
exposures by withdrawing a 50-mL aliquot of the HCl-air mixture into a 60-mL
plastic syringe. The syringe tip was immediately placed beneath the surface
of a beaker of deionized water, and 10 mL of water was withdrawn. Absorption
of HCl into the water was ensured by shaking the capped syringe for 3 min.
The aqueous sample was expelled into a Technicon AutoAnalyzer sample cup
and covered to prevent evaporative loss while awaiting analysis.

The AutoAnalyzer procedure (Figure 1) was adapted from a Technicon
standard method (15) for chloride analysis. Hydrogen chloride concentration
was assumed to equate with chloride ion concentration; chamber air samples,


TABLE Al

RESPONSE TIMES AND HC1 CONCENTRATIONS*

ty Cetis HC1, tg Crtg, HCL,
min pptemin ppt min ppt-min ppt
5.5 516.8 94.0 6.2 595.1 96.0
6.5 416.3 64.0 7.5 497.9 66.4
7.7 514.6 66.8 8.5 582.7 68.5
8.1 801.1 98.9 9.3 924.7 99.4
9.5 403.2 42.4 10.2 685.1 67.2
9.5 521.7 54.9 10.4 701.9 67.5
9.5 521.7 54.9 10.5 412.8 39.3
9.7 643.7 66.4 12.0 517.1 43.1
9.7 643.7 66.4 14.0 585.5 41.8
10.7 450.4 42.1 14.2 596.1 42.0
13.3 549.2 41.3 15.5 579.1 37.4
13.5 559.5 41.4 18.5 619.0 33.5
14.5 535.3 36.9 19.0 913.6 48.1
16.0 519.8 32.5 21.0 325.9 15.5
17.7 834.5 47.1 21.5 418.5 19.5
19.0 289.6 15.2 22.0 294.6 13.4
20.5 395.2 19.3 25.0 406.1 16.2
21.2 288.0 13.6 27.5 592.9 21.6
23.0 367.2 16.0 28.5 586.7 20.6
26.0 528.8 20.3 30.5 480.1 15.7
26.5 567.5 21.4 33.0 490.7 14.9
29.5 459.2 15.6 34.0 513.0 15.1
32.0 472.0 14.7 34.5 371.7 10.8
32.5 486.7 15.0 36.5 549.8 15.1
33.5 356.3 10.6 37.0 343.0 9.3
35.5 531.1 15.0 39.5 365.7 9.3
36.0 332.4 9.2 42.0 442.1 10.5
37.0 376.0 10.2 47.0 521.5 11.1
37.0 275.2 7.4 50.0 612.2 12.2
38.0 685.4 18.0 51.5 980.7 19.0
38.0 348.4 9.2 58.0 456.3 7.9
39.0 400.9 10.3 62.0 348.1 5.6
51.5 272.7 5.3 63.0 385.6 6.1
54.0 745.5 13.8 65.5 922.0 14.1
56.0 439.4 7.8 84.0 740.7 8.8
57.0 447.5 7.9 95.0 269.6 2.8
59.0 326.7 5.5 99.0 684.6 6.9
61.0 364.0 6.0 107.0 909.6 8.5
89.0 586.5 6.6 109.0 1100.7 10.1
93.0 263.0 2.8 155.0 464.1 3.0
131.0 393.3 3.0 186.5 426.9 2.3
183.0 416.7 2.3 229.0 589.7 2.6
185.0 422.4 2.3

*Concentrations and C*t-products are in parts per thousand (ppt).

19


13.

14.

15.

16.

17.

18.

19,

Nogues C, Fouet C, Picart P, Jouany JM. Experimental intoxications
by PVC thermal degradation products: Study of the respiratory tract
lesions. J. Combustion Toxicol. 1981; 2:108-120.

Spurgeon JC, Speitel LC, Feher RE. Thermal decomposition products
of aircraft interior materials. Washington, DC: Federal Aviation
Administration Report No. FAA-RD-77-20, 1977.

Technicon AutoAnalyzer Methodology. Technicon Laboratory Method
File N-5b. Tarrytown, NY: Technicon Corporation, 1969.

Terrill JB, Montgomery RR, Reinhardt CF. Toxic gases from fires.
Science 1978; 200:1343-1347.

The International Technical Information Institute. The toxic and hazard-

ous industrial chemicals safety manual. Tokyo: International Tech-
nical Information Institute, 1978; 272-273.

Wohlslagel J, DiPasquale LC, Vernot EH. Toxicity of solid rocket
motor exhaust: Effects of HCl, HF, and alumina on rodents. J. Com-
bustion Toxicol. 1976; 3:61-70.

Zall DM, Fisher D, Garner MQ. Photometric determination of chlorides
in water. Anal. Chem. 1956; 28:1665-1668.

16


and coincided with urination/defecation; it obviously represents the rapid
absorption of HCl by these excretory products. The increased slope of the
concentration curve toward the end of the exposure was also a common
observation and usually coincided with gasping and hyperactivity in the
subjects due to an obviously severe decrease in pulmonary ventilation, often
borne out by the loss of pink coloration (cyanosis) in the extremities.

Times-to-incapacitation were measured for 43 animal exposures and
times-to-death for 42 animals. These response times, the corresponding
Ct-products, and the calculated average HCl concentrations are listed in
Table Al in the Appendix. The relationship between response time and HCl
concentration is shown in Figure 3 for the incapacitation endpoint and in
Figure 4 for lethality.

The choice of a rectangular hyperbola, y = a + k/(x-b), as the
mathematical form for the statistically derived regression equation seemed
an obvious one, because that mathematical relationship corresponds to the
physiological one between dose and the response to a toxic insult. The
translated axes, which now represent the asymptotic values for the two
variables, correspond to the theoretical threshold concentration for
the selected toxic endpoint and to the irreducible time to achieve that
effect by an overwhelming concentration of toxicant.

The least squares regression equation for incapacitation is

= 3 + 336/(HC1-0.3),

where: ty is in minutes and
HCl concentration is in parts per thousand (ppt).

The constants, a=3 and b=0.3, in the physiological interpretation of the
equation, suggest that the threshold concentration of HCl that would just
produce incapacitation following an infinitely long exposure period would
be 300 ppm (0.3 ppt) and that the shortest ty that could be obtained from
an infinite exposure concentration would be 3 minutes. These values seem
to be reasonable projections (as limiting values) of the results of our
experiments, wherein an average HCl concentration of 94,000 ppm produced a
ty of 5.5 min and a 2,000-ppm exposure gave a ty of just over 3 hours

(185 min). Analogous comments are applicable to the resultant equation for
lethal endpoints:

tg = 3 + 411/(HC1-0.4).

This equation for a hyperbola, which was used to describe the experi-
mental results, can be linearized in two different ways, once the parameters,
a and b, have been assigned values. One approach is a log-log plot, which
for the incapacitation endpoint would be a plot of log (t4-3) versus
log(HC1-0.3); such a plot is depicted in Figure 5. A second linearizing
transformation is illustrated by Figure 6 for the lethality data, wherein
the reciprocal of (tg-3) is plotted against (HC1-0.4).

8


in the absence of added HC1, contained no detectable chloride ion. The
analytical principle is the spectrophotometric measurement, at 480
nanometers (nm), of ferric thiocyanate formed from the stoichiometric
displacement of thiocyanate, by chloride, from a solution of mercuric
thiocyanate in the presence of ferric ion (19).

Immediately before the analysis of each set of unknowns, a series
of chloride standards, in the concentration range of 50 to 4,500 micro-
moles/L, was analyzed, and the results were used to calculate a standard
response curve. These working standards were routinely prepared from
dilutions of a standardized sodium chloride solution. (Initially, the
sodium chloride solutions were compared with standard chloride solutions,
prepared from constant~boiling hydrochloric acid and from primary standard
grade potassium chloride, to verify that both the acidic and neutral
chloride solutions gave identical color responses--which they did.)

The spectrophotometric absorbance (Abs) of the ferric thiocyanate is
not a linear function of chloride concentration over the entire 50- to
4,500-micromole/L range; so the standard curve was calculated as a regression
equation, using the working standard results:

y=atbxt cx’,
where: y is chloride ion concentration, in micromoles/L,
x is the measured absorbance, and

a, b, and c are the least squares regression coefficients.

Chamber concentrations of HCl gas were expressed in ppm by volume (ppm, v/v)
at mean ambient temperature (25 °C) and atmospheric pressure (730 mm Hg).

A typical calculation for converting chloride concentration in the aqueous
sample to HCl concentration in chamber air would be:

1000 10 760 | 298.1 _

50 * 1000 * 22-4 * 739 * 273.1

[HCl] = [cl] x

= [C1] x 5.091,
where: [HC1] is chamber concentration in ppm (v/v),
[C1] is sample chloride concentration in micromoles/L,
22.4 is molar gas volume at STP, in L/mole, and
1000 10

50 * 1000

are dilution factors.

Exposure procedure. Airflow through the chamber, from the compressed,
breathing air supply, was maintained at 12 L/min for all experiments. Flow
rate from the HCl tank was selected to give the desired chamber concentration
when mixed with the airflow, based on preexposure trials. The steady-state
concentration that developed in the chamber, in the presence of animals, was
always less than the incoming concentration.



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APPENDIX

17



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(854)

Technical Report Documentation Page

To Report No. 2, Government Accession No. 3. Recipient's Catalog No.
FAA-AM-85-5

4, Title and Subtitle 5. Report Date

Inhalation Toxicology: IV. Times To Incapacitation MAY 1985

and Death for Rats Exposed Continuously to Atmospheric
Hydrogen Chloride Gas

&. Performing Organization Code

8. Performing Organization Report No.

7, Author! s)
Charfes R. Crane, Donald C. Sanders, Boyd R. Endecott ~AM-85-
and John k. Abbott > Boy meecort, FAA-AM-85-4

9. Performing Organization Name and Address 10. Work Unit No. (TRAIS)
FAA Civil Aeromedical Institute
P.O. Box 25082 TT. Contract or Grant No.

Oklahoma City, Oklahoma 73125

13. Type of Report and Period Covered

12. Sponsoring Agency Name and Address OAM Report
Office of Aviation Medicine
Federal Aviation Administration
800 Independence Avenue, SW. 14, Sponsoring Agency Code
Washington, DC 20591

15. Supplementary Notes
This work was performed under task AM-B-82-TOX-43.

16, Abstract

Laboratory rats were exposed continuously to measured atmospheric concentrations of
hydrogen chloride (HC1) gas until they expired. The exposure time required to
produce lethality was measured, as was the time at which physical incapacitation
occurred. Incapacitation was defined operationally as loss of the ability to

walk in a motor-driven wheel. These two endpoints, time-to-incapacitation and
time-to-death, were equated to atmospheric HCl concentration by statistically
derived regression equations. The possible relationship between the effective toxic
doses of HCl gas for rats and those reported for humans is discussed.

a Joe nl
‘ %
f pf
fle
17, Key Words 18, Distribution Statement
Combustion toxicology; Smoke, Irritant Document is available to the public
gas; Time-to-incapacitation; Time-to— through the National Technical Information
death; Aircraft cabin fire. Service, Springfield, Virginia 22161.
19, Security Classif. (of this report) 20. Security Clossif. (of this page) Zi No. of Pages | 22. Price
Unclassified Unclassified 19

Form DOT F 1700.7 (8-72) Reproduction of completed page authorized



Time (min)

Survival

248
220 |
220 |
188 f
160
140 Ff
120 f+
18@
80
68
40
28

i. ieee of
@ 16 20 30 4@ 5@ 68 70 88 98 100

HCl Concentration (ppt)

Figure 4. Survival time as a function of HCl concentration.
(N=42, time is in minutes, concentration is in parts per thousand,
exposure was continuous at the indicated concentration until the
animal expired; regression parameters: correlation coefficient=0.92,
standard error of estimate=22.0, 95% confidence interval for the
constant, 411, is 364 to 474.)

10


Incapacitation Time (min)

Ue oe

g +. nN rw 4. n 4
@ 1@ 28 3@ 48 58 60 78 88 96 180
HCl Concentration (ppt)

Figure 3. Incapacitation time as a function of HCl concentra-
tion. (N=43, time is in mimutes, concentration is in parts per
thousand; regression parameters: correlation coefficient=0.96,
standard error of estimate=11.2, 95% confidence interval for the
constant, 336, is 314 to 358.)



With the fasted, weighed rats in their respective segments of the
rotating cage, the chamber was sealed and cage rotation was begun. The
mixing fans were turned on; the flowing HCl-air mixture, previously cali-
brated, was diverted into the chamber inlet; and the timer was started

(to).

Samples of chamber atmosphere (50 mL) were taken manually at
0.5, 1.5, 3, 5, and 8 min, and at 4-min intervals thereafter throughout
the exposure. The elapsed time (ty) was noted at which the animals could
no longer walk in a coordinated fashion in the cage, and at this point
rotation was stopped. Observation continued until visible signs of
respiration ceased, at which time tg was recorded for each animal.

"Dose" response calculations. Using the calculated values from the
AutoAnalyzer assays, a plot of HCl concentration versus exposure time was
constructed. The integrated areas under this curve from t = tp to t = ty
and from t = tg to t = tg were calculated for each animal, and these
(concentration x time) products were designated Cty and Ctg respectively.
(This Ct-product can be viewed as a quantity that is related to the
inhalation dose received by each animal, depending in part on how constant
the animal's minute respiratory volume (MRV) is during the exposure.)

An "average" exposure concentration was calculated as the quotient of
the Ct-product divided by the time to the particular response; i.e., ty or tq.
An equation relating response time to exposure concentration was generated
by the Marquardt procedure (12) for least squares estimation of nonlinear
parameters.

RESULTS AND DISCUSSION.

The precision of the HCl assay procedure, documented by assaying six
replicate samples each of 14 concentrations (50 to 4,500 micromoles/L) ,
is quite good; the standard deviation for the 14 sets of six measurements
averaged 0.002 Abs and the coefficient of variation averaged less than
3 percent. A plot of Abs versus concentration for these 84 chloride standards,
as well as the least squares regression curve, can be found in the Appendix
as Figure Al.

Figure 2 is a plot, for a representative experiment, of the assayed
HCl concentration as a function of exposure time, with ty and tg indicated.
In this experiment, ty was 32 min and tq was 33 min. The integrated area
under the curve from t = 0 to t = 32, which would be C-ty, is indicated as
the hatched area and is numerically equal to 471,993 ppm-min. The average
HCl concentration, calculated as the quotient, C+t;/ty, is 14,750 ppm.

Variations in HCl concentration in the chamber atmosphere are evident
in Figure 2 and were typically observed in all exposures, despite a flow
rate of one chamber volume per minute. The increase in concentration that
begins at about 12 min could reflect saturation of the fur and moist
surfaces of the animal with HCl and thus a decreased rate of removal from
the atmosphere. A significant drop in concentration, such as occurred
during the 20- to 24-min interval, was a typical feature of all experiments




More recently, research interest has focused on the short-term response
from brief exposures to HCl-containing combustion products (smoke). The
current widespread use of chlorine-containing synthetic materials has
prompted toxicological research in such diverse areas as synthetic fuels
(5,18), construction and insulation materials (7,13,16), electrical insula-
tion (3), and our primary interest, aircraft construction and furnishing
materials (8,9).

In the mid-1970's, Federal Aviation Administration (FAA) scientists
evaluated 75 in-use aircraft cabin interior materials, including several
containing chlorinated polymers, for toxic gas emissions (14) and the
resulting inhalation toxicity to rats (4). All the chlorine-containing
materials released HCl when burned.

The extreme solubility of HCl gas in water has presented a serious
problem to scientists who have attempted to maintain constant atmospheric
concentrations for animal exposure experiments. Machle (11) reported it
was impossible to prevent a rapid fall in HCl concentration when the rela~
tive humidity was above 25 percent, due to HCl dissolving in the condensate
on the walls. Other scientists, including ourselves, have found it necessary
to utilize dynamic flow systems with relatively high flow rates in order to
maintain reasonably stable concentrations (5,8,10,18). Even under these
conditions, whole-body exposures using multiple animals result in marked
variations in the "equilibrium" concentrations attained, dependent in part
on the number of animals in the exposure chamber. Absorption/solution of
HCl in fur, exhaled moisture, and expelled urine necessitates frequent
analysis of the chamber atmosphere if an accurate measure of exposure con-
centration versus time is desired.

The toxicity of inhaled HCl, as an individual agent, is not well defined.
One problem is with the definition of a lethal "dose." Two experimental
techniques have been used to obtain such values, and the lethal inhalation
doses so obtained differ both in value and in applicability. In one approach,
an animal is exposed continuously to a defined concentration of HCl until
death occurs; in the other, the animal is removed from the HCl atmosphere
after a defined exposure interval and dies a few days (to several months)
later. The HCl doses in the two cases obviously are going to differ, but
valid arguments may be made for the significance of each approach depending
on the ultimate application of the data.

A second problem of definition arises if one is interested, not in
lethal doses, but in exposures that produce incapacitation sufficient to
prevent one's escape from a fire. For studies with laboratory animals, loss
of the ability to carry out a defined function, or sequence of functions,
can be evaluated. With human subjects, endpoints are more apt to be based
on performance decrements, discomfort, irritation, pain, or intolerance.
However, the exposure to an irritant gas considered to be "intolerable"
by a human volunteer who is free to terminate his or her exposure might
impede, but not necessarily prevent, the same individual from escaping a
burning aircraft cabin when the likely alternative is considered. So, with
animal subjects one cannot measure the more subjective contributions
to incapacitation; with human subjects one dares not continue exposure
to the point of actual collapse.


There is obviously some scatter in the measured values of time-to-response,
which increases in absolute value--as one would predict--with decreasing
HC1 concentration. This is most readily observed in Figures 3 and 4; the
seemingly large variation in tg that occurs at higher HCl concentrations
in Figure 6 is an artifactual exaggeration that has been introduced by
the use of reciprocal response time as a plotting variable. The regression
curves are, from visual inspection of the figures, reasonable and useful
reflections of the relationship between concentration and response time. The
statistical measures of the "goodness of fit" are listed in the legends of
the individual figures for the pertinent regression parameters.

The magnitude of the HCl concentration required to produce incapacita-
tion (and/or death) was significantly greater than the authors had expected
based on statements found in the scientific literature. Machle et al. (11)
had reported lethal Ct-products of 72,000 ppmemin for rabbits and guinea
pigs; Barrow et al. (1) have stated that 3,090 ppm-min would be incapaci-
tating for humans while other sources (6,9) suggest limits below 10,000
ppmemin, while in the present study the Ct-product averaged about 500,000
ppm-min.

The mechanism of action for HCl toxicity in rats, based on observations
during this study, seems to be primarily one of mechanical suffocation. This
suffocation seems to be the result of mechanical blockage of the upper airways
(nasopharyngeal) caused by the extreme inflammatory and corrosive action
of this strong mineral acid on these tissues. Postmortem examination (gross
pathology, performed by forensic pathologist W. R. Kirkham, M.D., Ph.D.)
indicated surprisingly little damage to airways below the trachea, but
almost total destruction from pharynx to nares.

The major significance of this study is that, for the first time, we
have data that relate animal response times to HCl concentrations as a
continuous function over significant time and concentration spans. Until
this study, which was conducted in 1980, no information was available that
measured incapacitation as a function of concentration; and lethality
data were available only as LCs5g values, and then only for specified exposure
times; e.g., a 30-min LCs5g, a 2-h LCs, a 6-h LC5q, etc. (If one has values
for 30-min and 6-h LC59'ss how does one find the 3-h LC59?)

Our concern about the difference between the results of this study and
literature suggestions for the incapacitating/lethal doses of HC1 for
humans prompted the FAA to sponsor research to ascertain the effects of HCl
exposure for a nonhuman primate species. The published results of that
study (10), at Southwest Research Institute, indicate that the HCl exposure
necessary to incapacitate baboons was at least 10 times greater than
literature values suggested for humans.

The significance of that support, from experimental data using primates,
for the rodent data reported in this study is that it strengthens the
suspicion that literature values for humans are possibly just overly conserva-
tive estimates--estimates that may have been based on (dis)comfort indices
as endpoints, rather than actual incapacitation. Therefore, HCl in smoke
from natural fires may contribute less to incapacitation, and thus to
failure to escape the fire, then had been previously assumed.

13



10.

Il.

12.

REFERENCES

Barrow CS, Alarie Y, Warrick JC, Stock MF. Comparison of the sensory
irritation response in mice to chlorine and hydrogen chloride. Arch.
Environ. Health 1977; 32:68-76.

Cralley LV. The effect of irritant gases upon the rate of ciliary
activity. J. Ind. Hyg. Toxicol. 1942; 24:193-198.

Crane CR, Endecott BR, Sanders DC, Abbott JK. Electrical insulation
fire characteristics. Vol. II. Toxicity. Washington, DC: Urban
Mass Transportation Administration Report No. UMTA-MA-06-0025-79-2,
II, 1979.

Crane CR, Sanders DC, Endecott BR, Abbott JK, Smith PW. Inhalation
toxicology: 1. Design of a small-animal test system. II. Determina-
tion of the relative toxic hazards of 75 aircraft cabin materials.
Washington, DC: Federal Aviation Administration Office of Aviation
Medicine Report No. FAA~AM-77-9, 1977.

Darmer KI Jr., Kinkead ER, DiPasquale LC. Acute toxicity in rats
and mice exposed to hydrogen chloride gas and aerosols. Am. Ind.
Hyg. Assoc. J. 1974; 35:623-631.

Dyer RF, Esch VH. Polyvinyl chloride toxicity in fires. J. Am.
Med. Assoc. 1976; 235:393-397.

Einhorn IN. Physiological and toxicological aspects of smoke produced
during the combustion of polymeric materials. Environ. Health
Perspect. 1975; 11:163-189.

Higgins EA, Fiorica V, Thomas AA, Davis HV. The acute toxicity of
brief exposures to HF, HCl, NO,, and HCN singly and in combination
with CO. Washington, DC: Federal Aviation Administration Office
of Aviation Medicine Report No. FAA-AM-71-41, 1971.

Jacobs MB. The analytical chemistry of industrial poisons, hazards,
and solvents, 2nd ed. New York: Interscience Publishers, Inc.,
1949; 379.

Kaplan HL, Grand AF, Rogers WR, Switzer WG, Hartzell GE. A research
study of the assessment of escape impairment by irritant combustion
gases in postcrash aircraft fires. Washington, DC: Department of
Transportation/Federal Aviation Administration Report No. DOT/FAA/
CT-84/16, 1984.

Machle W, Kitzmiller KV, Scott EW, Treon JF. The effect of the
inhalation of hydrogen chloride. J. Ind. Hyg. Toxicol. 1942;
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Marquardt D. An algorithm for least squares estimation of nonlinear
parameters. J. Soc. Indust. Appl. Math. 1963; 11(2):431-441

15



INHALATION TOXICOLOGY: IV. TIMES TO INCAPACITATION AND DEATH FOR
RATS EXPOSED CONTINUOUSLY TO ATMOSPHERIC HYDROGEN CHLORIDE GAS

INTRODUCTION.

The recognition that toxic components of smoke are principal factors
contributing to lethality in aircraft fires is well established. To date,
however, research in this area has been concerned primarily with the
contribution made by only two of these components; namely, carbon
monoxide (CO) and hydrogen cyanide (HCN). These two gases have been
classified by toxicologists as examples of "systemic" toxicants, a rather
imprecise but commonly used term. An additional class of toxicants found
in smoke is referred to simply as "irritant" gases.

Hydrogen chloride (HC1) is the most commonly recognized member of the
irritant gas family. It is the major decomposition product of many halogen-
ated polymers used in aircraft today--polymers such as polyvinyl chloride
(PVC) and polychloroprene, used in electrical wiring insulation, cabin
wall and ceiling panels, seats, fabrics, etc.

Hydrogen chloride gas is extremely soluble in water, forming hydro-
chloric acid. It is very reactive chemically, highly irritating and
inflammatory to all biological tissue, and quite corrosive to most metals.
It has an Occupational Safety and Health Administration (OSHA) industrial
exposure ceiling (never exceed) of five parts per million (ppm) (17). A
l-hour exposure to 100 ppm has been said to be the tolerance limit for
humans (6,9); more severe exposures may result in laryngeal spasms or
pulmonary edema, according to Dyer and Esch (9). The same authors docu-
mented the delayed complications (dyspnea, chemical pneumonitis, and death)
from HCl exposure in a study of 175 firefighters who were exposed to smoke
from PVC fires.

Historically, HCl gas has been recognized as a hazard to industrial
personnel, particularly during its manufacture and its use in the etching
and electroplating industries (9). In 1942, Nachle et al. (11)
exposed rabbits and guinea pigs to HCl concentrations from 30 ppm to
12,300 ppm for time periods of 5 minutes to 120 hours. They noted that a
30-min exposure to 3,900 ppm HCl produced 100-percent mortality within
2 months postexposure, as did exposure to 660 ppm for 2 or more hours.

They concluded that the upper limit of safety for long exposures was

about 30 ppm. This concentration (30 ppm) was shown by Cralley (2) to inhibit
ciliary activity in excised rabbit trachea following a 10-min exposure.
Barrow and coworkers (1) explained the mechanism of HCl sensory irritation

as a reaction with functional chemical groups in the membrane of trigeminal
nerve endings lining the nasal passages.




LOG(Ti-3)

2.5F

2.8

1.5

1.8

8.5

2.0 : . . -
@@ @5 1.0 1.5 2@ 2.5

LOG(HC1-@.3)

Figure 5. Log-log plot of (tj-3) versus (HC1-0.3), a linearized
form of the equation relating response time to concentration. (N=43,
time is in minutes, concentration is in parts per thousand, regression
correlation coefficient=0.96.)

11



SUMMARY AND CONCLUSIONS.

Rats were exposed in the Civil Aeromedical Institute (CAMI) inhalation
toxicity assay system to selected atmospheric concentrations of HCl gas in
air; these concentrations ranged from 2,000 to 100,000 ppm. The CAMI system
utilizes an enclosed rotating wheel that allows the measurement of a physical
incapacitation endpoint as well as the traditional one of lethality. These
two endpoints were measured time-to-incapacitation (tj) and time-to-death (tq);
observed response times ranged from 5.5 to 229 minutes. Results were plotted
as scatter plots (response time versus HCl concentration), and then regres-
sion equations were fit to each data set using a nonlinear least squares
technique.

The resulting response equations are:

ti 3 + 336/(HC1-0.3) for incapacitation and

tq 3 + 411/(HC1-0.4) for lethality,
where response times are in minutes and HCl concentrations are in parts per
thousand.

These results suggest that HCl, in smoke from natural fires, would
not be nearly so incapacitating as had been previously thought, with concen-
trations necessary to produce incapacitation in 10 minutes possibly being
as much as 10 times greater than those suggested by the scientific
literature.

14