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7
Propane1
Acute Exposure Guideline Levels
PREFACE
Under the authority of the Federal Advisory Committee Act (FACA) P.L.
92-463 of 1972, the National Advisory Committee for Acute Exposure Guide-
line Levels for Hazardous Substances (NAC/AEGL Committee) has been estab-
lished to identify, review, and interpret relevant toxicologic and other scientific
data and develop AEGLs for high-priority, acutely toxic chemicals.
AEGLs represent threshold exposure limits for the general public and are
applicable to emergency exposure periods ranging from 10 minutes (min) to 8
hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for
each of five exposure periods (10 and 30 min and 1, 4, and 8 h) and are distin-
guished by varying degrees of severity of toxic effects. The three AEGLs are
defined as follows:
AEGL-1 is the airborne concentration (expressed as parts per million or
milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is
predicted that the general population, including susceptible individuals, could
experience notable discomfort, irritation, or certain asymptomatic, nonsensory
1
This document was prepared by the AEGL Development Team composed of Peter
Bos (RIVM, The Dutch National Institute of Public Health and the Environment), Julie
M. Klotzbach (Syracuse Research Corporation), Chemical Managers Steven Barbee and
Larry Gephart (National Advisory Committee [NAC] on Acute Exposure Guideline Lev-
els for Hazardous Substances), and Ernest V. Falke (U.S. Environmental Protection
Agency). The NAC reviewed and revised the document and AEGLs as deemed neces-
sary. Both the document and the AEGL values were then reviewed by the National Re-
search Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC com-
mittee has concluded that the AEGLs developed in this document are scientifically valid
conclusions based on the data reviewed by the NRC and are consistent with the NRC
guidelines reports (NRC 1993, 2001).
288
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289
Propane
effects. However, the effects are not disabling and are transient and reversible
upon cessation of exposure.
AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a
substance above which it is predicted that the general population, including sus-
ceptible individuals, could experience irreversible or other serious, long-lasting
adverse health effects or an impaired ability to escape.
AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a
substance above which it is predicted that the general population, including sus-
ceptible individuals, could experience life-threatening health effects or death.
Airborne concentrations below the AEGL-1 represent exposure concentra-
tions that could produce mild and progressively increasing but transient and
nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsen-
sory effects. With increasing airborne concentrations above each AEGL, there is
a progressive increase in the likelihood of occurrence and the severity of effects
described for each corresponding AEGL. Although the AEGL values represent
threshold levels for the general public, including susceptible subpopulations,
such as infants, children, the elderly, persons with asthma, and those with other
illnesses, it is recognized that individuals, subject to idiosyncratic responses,
could experience the effects described at concentrations below the correspond-
ing AEGL.
SUMMARY
Propane is a colorless and odorless gas. It is poorly soluble in water. The
lower explosive limit is 2.3%. Propane is an important constituent of liquefied
petroleum gas and sometimes the main compound in liquefied petroleum gas
used as (bus) fuel. It is a byproduct from various refinery processes. Its main use
is in the synthesis of chemicals, such as ethylene and propylene. It is also used
as an aerosol propellant and as a refrigerant. Because it is easily accessible, pro-
pane is often used in inhalant abuse and in suicide attempts.
The toxicity of propane is low, so very high concentrations can be as-
sumed in propane abuse. The predominant effects observed in such cases are
effects on the upper and lower airways of the respiratory tract and on the brain.
Quantitative human data include an old study on the warning properties of pro-
pane and a study involving propane at low concentrations.
Toxicity and mortality data are sparse. Cardiac sensitization has been stud-
ied mainly in dogs and one study provides good quantitative data. Only an old
study with guinea pigs focused on CNS depression. Propane was negative in the
bacterial reverse mutation assay (Ames test). Carcinogenicity and reproductive
toxicity studies are lacking.
The AEGL-1 values are based on a study of the warning properties of pro-
pane (Patty and Yant 1929). No effects were noted during a 10-min exposure to
propane at 10,000 ppm, but distinct vertigo was reported by volunteers exposed
at 100,000 ppm for 2 min. An intraspecies uncertainty factor of 1 was consid-
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290 Acute Exposure Guideline Levels
ered adequate because the concentration-response curve for CNS effects appears
to be steep and, thus, interindividual variability will be relatively small. Further,
10,000 ppm appears to be a conservative starting point considering the effects
reported at 100,000 ppm. The anesthetic potency of propane is estimated to be
lower than that of butane (Drummond 1993). The AEGL-1 values for propane,
therefore, should not be lower than those for butane, which are based on the
same study by Patty and Yant (1929). For consistency, the AEGL-1 values for
propane are derived similarly to those for butane, including the approach for
time scaling. Data on butane suggest a relatively high value for n (Stoughton and
Lamson 1936), so time extrapolation was performed with n = 3. Data on butane
(Gill et al. 1991) and propane (Stewart et al. 1977) indicate that steady-state
plasma concentrations for propane are reached within 30 min. By analogy with
other substances that depress the CNS, the effects are assumed to be solely con-
centration dependent. Therefore, time extrapolation was performed from 10 min
to 30-min and 60-min exposures. The calculated values for AEGL-1 are pre-
sented in Table 7-1. These values are considered protective of the irregular
breathing observed in guinea pigs when exposed to propane at 20,000-29,000
ppm for up to 2 h (Nuckolls 1933). All of the AEGL-1 values are more than
10% of the lower explosive limit.
The AEGL-2 values are based on cardiac sensitization. In a well-
performed cardiac sensitization test, beagle dogs were exposed to propane at
50,000, 100,000, or 200,000 ppm (Reinhardt et al. 1971). No cardiac sensitiza-
tion occurred in six dogs exposed at 50,000 ppm, whereas it was observed in
two of 12 dogs at 100,000 ppm. These findings were supported by a second
study using the same protocol in which a median effective concentration (EC50)
of 180,000 ppm was reported (Clark and Tinston 1982). Cardiac sensitization in
beagle dogs is relevant to human exposures because humans exposed at high
concentrations to several substances might develop cardiac arrhythmia. The no-
effect concentration of 50,000 ppm was chosen as the basis for the AEGL-2
values. The cardiac sensitization model with the dog is considered an appropri-
ate model for humans and is highly sensitive because the response is optimized
by the exogenous administration of epinephrine (Brock et al. 2003; ECETOC
2009). This protocol is designed conservatively with built-in safety factors and,
thus, no additional safety factors are needed (ECETOC 2009). Accordingly, an
interspecies uncertainty factor of 1 was applied. The information available indi-
cates that cardiac sensitization is a concentration-related threshold effect and
concentrations that do not produce a positive response in a short-term test also
will not produce the effect when exposures are continued for longer durations.
Although these considerations are mainly based on experiments with halo-
carbons (e.g., HFC-134a) reaching a steady-state plasma concentration in a very
short timeframe, it also is considered to be true for a compound like propane
because a steady-state plasma concentration is nearly reached within 30 min.
Applying a total uncertainty factor of 3 to 50,000 ppm yields a (rounded) value
of 17,000 ppm, which was assigned to all AEGL-2 durations. This concentration
is greater than 50% of the lower explosive limit.
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Propane
The same study used to derive the AEGL-2 values also was used as start-
ing point for AEGL-3 values. Although a marked cardiac response occurred in
two of 12 beagle dogs exposed to propane at 100,000 ppm, no deaths were oc-
curred. One case of ventricular fibrillation and cardiac arrest occurred at
200,000 ppm. The concentration of 100,000 ppm was used as the basis for the
AEGL-3 values. After applying a total uncertainty factor of 3, a (rounded) value
of 33,000 ppm was assigned to all AEGL-3 time periods.
The AEGL values for propane are summarized below in Table 7-1.
1. INTRODUCTION
Propane is a byproduct of various refinery processes. It is often used to
produce liquefied petroleum gas. Liquefied petroleum gas is generally a mixture
of predominantly butane and propane in varying proportions, but sometimes
propane is the main component liquefied petroleum gas used as (bus) fuel. Pro-
pane is also used in the manufacture of ethylene and propylene, as a basic mate-
rial in chemical synthesis in a number of processes, as an aerosol propellant to
replace the chlorofluorocarbons, as a refrigerant in chemical refining and gas
processing operations, as a fuel in welding and cutting operations, and as a sol-
vent and extractant in deasphalting and degreasing of crude oils (Low et al.
1987). Propane also has been reported to be used in cosmetic products like shav-
ing creams (Moore 1982). Ethyl mercaptan is often added to propane to give it a
pungent odor. Additional chemical and physical properties of propane are pre-
sented in Table 7-2.
2. HUMAN TOXICITY DATA
2.1. Acute Lethality
2.1.1. Case Reports
Several fatalities from propane have been reported. Most case reports deal
with suicide attempts (Püschel 1979; Avis and Archibald 1994; Graefe et al.
1999; Fonseca et al. 2002) or inhalant abuse (Haq and Hameli 1980; Tsoukali et
al. 1998). Also some autoerotic fatalities, considered to be accidental deaths
involving inhalation or propane, have been reported (Püschel 1979; Rauschke
and Harzer 1983; Pragst et al. 1991; McLennan et al. 1998). One accidental
death from propane exposure in open space has been reported (Püschel 1979).
There were 39 deaths in Virginia between 1987and 1996 likely as a direct con-
sequence of exposure to an abused inhalant; five of the cases were associated
with propane (Bowen et al. 1999). These reports do not provide quantitative
dose-response data, so are not further described. In cases of propane abuse and
with autoerotic fatalities, repeated exposure and regular abuse of other volatile
organic solvents cannot be excluded. Data on intoxication by liquefied petro-
leum gas (mixture of predominantly propane and butane in varying proportions)
are not considered.
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292 Acute Exposure Guideline Levels
TABLE 7-1 Summary of AEGL Values for Propane
End Point
Classification 10 min 30 min 1h 4h 8h (Reference)
10,000 ppma 6,900 ppma 5,500 ppma 5,500 ppma 5,500 ppma
AEGL-1 CNS
(nondisabling) (18,000 (12,000 (9,900 (9,900 (9,900 depression
mg/m3) mg/m3) mg/m3) mg/m3) mg/m3) (Patty and
Yant 1929)
See belowb See belowb See belowb See belowb See belowb
AEGL-2 Cardiac
(disabling) sensitization
(Reinhardt et
al. 1971)
See belowc See belowc See belowc See belowc See belowc
AEGL-3 Cardiac
(lethal) sensitization
(Reinhardt et
al. 1971)
a
The AEGL-1 value is greater than 10% of the lower explosive limit for propane in air of
23,000 ppm. Therefore, safety considerations against the hazard of explosion must be
taken into account.
b
The AEGL-2 values for all time periods is 17,000 ppm (31,000 mg/m3), which is greater
than 50% of the lower explosive limit for propane in air of 23,000 ppm. Therefore, ex-
treme safety considerations against the hazard of explosion must be taken into account.
c
The AEGL-3 values for all time periods is 33,000 ppm (59,000 mg/m3), which is greater
than the lower explosive limit for propane in air of 23,000 ppm. Therefore, extreme
safety considerations against the hazard of explosion must be taken into account.
TABLE 7-2 Chemical and Physical Properties of Propane
Parameter Value Reference
Synonyms Dimethylmethane, propylhydride Lewis 1999
CAS registry no. 74-98-6
Chemical formula C3H8
Molecular weight 44.11 Lide 1999
Physical state Gas Lewis 1999
Color Colorless Lewis 1999
Odorless when purea
Odor Lewis 1999
Melting point -187.6°C Lide 1999;
-189.7°C Low et al. 1987
Boiling point -42.1°C Lide 1999
Solubility 65 mg/L in water Low et al. 1987
Density
Vapor 1.56 (air = 1) Lewis 1999;
0.585 g/cm3 (-44.5°C) (water = 1)
Liquid Low et al. 1987
Vapor pressure 1.33 kPa (26.9°C) Low et al. 1987
Flammability Extremely flammable gas ECB 2000
Explosive Lower explosive limit = 2.3% Lewis 1999
1 mg/m3 = 0.555 ppm
Conversion factors Low et al. 1987
1 ppm = 1.80 mg/m3
a
Although propane is considered to be odorless and ethyl mercaptan is often added as a
warning agent, it has been reported that the odor of propane can be detected at 980-
19,650 ppm (1,800-36,000 mg/m3) (Ruth 1986).
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Propane
Most deaths were from asphyxia induced by a combination of plastic bag
suffocation and propane inhalation. Autopsy findings generally were very simi-
lar and included frothy material in the upper airways and oral cavity, petechial
hemorrhages in the epicardium and pleural spaces, and cerebral and pulmonary
congestion and edema. A few case reports of fatalities provide some quantitative
information (Pragst et al. 1991; Graefe et al. 1999) or qualitative information
(Haq and Hameli 1980) on propane concentrations in tissues. The highest con-
centrations of propane in tissues were reported by Graefe et al. (1999) as 1,100
μg/mL in the blood, 1,028 μg/g in the lungs, 820 μg/g in the brain, 572 μg/g in
the liver, and 256 μg/g in the kidneys. Pragst et al. (1991) reported a blood con-
centration of 720 μg/mL, a lung concentration of 230 μg/mL, and a brain con-
centration of 120 μg/mL.
2.2. Nonlethal Toxicity
2.2.1. Case Reports
No data were available.
2.2.2. Experimental Studies
Caucasian volunteers (4-8 per group, males and females, 20-22 years of age)
underwent single exposures to propane at 1,000 ppm for up to 10 min and at 250
or 500 ppm for up to 8 h (Stewart et al. 1977). In addition, some subjects were
repeatedly exposed to propane at 1,000 ppm for 8 h/day for 9 days over 2 weeks.
Exposure concentrations were continuously monitored. Clinical parameters (e.g.,
complete blood count, blood urea nitrogen, serum enzymes, urine analysis),
adrenocortical function, neurological and neurobehavioral tests (a battery of cogni-
tive tests, spontaneous electroencephalogram, and visual evoked response), pul-
monary function (spirometry measurements), and cardiac responses (including
electrocardiogram) were evaluated. No effects from propane on any of the pa-
rameters studied were found and no subjective responses were noted.
Patty and Yant (1929) studied the warning properties of several alkanes,
including propane. In a continuous exposure test, subjects were exposed to pro-
pane at slowly increasing concentrations up to 50,000 ppm for an unknown du-
ration (but at least 6 min). In an intermittent exposure test, subjects were ex-
posed at fixed concentrations (10,000, 20,000, 50,000, and 100,000 ppm) for a
few minutes. Exposure groups consisted of 3-6 people (males and females, 20-
30 years of age). Propane was not detected in the continuous exposure test at
concentrations up to 50,000 ppm, but was “readily perceptible” (mean score of
2) at 46,000 ppm in the intermittent exposure test. The odor-detection score was
below moderate intensity at 100,000 ppm, with no signs of irritation reported.
No symptoms were reported after 10 min of exposure at 10,000 ppm, but dis-
tinct vertigo was reported when volunteers were exposed at 100,000 ppm for 2
min. The subjects were fully capable of leaving the test chamber.
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294 Acute Exposure Guideline Levels
2.2.3. Human Experience
The data on human exposure to propane are very limited. Most data, espe-
cially the animal data, indicate that cardiac sensitization as an important effect.
However, as with other alkanes, CNS depressing effects are also to be expected.
The available data are not sufficient to determine which of the two effects occur
at lower concentrations.
2.3. Summary
Fatal cases of propane intoxication (abuse, suicide attempts, autoerotic
cases) have been reported. Death occurred as a result of asphyxia. Organs that
were most often seriously affected in these cases were the brain and heart. These
case reports do not provide adequate data for a quantitative evaluation of pro-
pane toxicity.
A single or repeated daily 8-h exposure to propane at up to 1,000 ppm had
no effect on a number of clinical parameters, heart function, brain function, lung
function, neurobehavioral parameters, or adrenocortical function (Stewart et al.
1977). No symptoms were noted following a 10-min exposure at 10,000 ppm,
but “distinct vertigo” was reported after 2 min of exposure at 100,000 ppm. The
exposed subjects were capable of leaving the exposure chamber unassisted. No
complaints of irritation were reported at 100,000 ppm. Propane was “readily
perceptible” at 46,000 ppm (Patty and Yant 1929).
3. ANIMAL TOXICITY DATA
3.1. Acute Lethality
3.1.1. Rats
Clark and Tinston (1982) exposed groups of six male or female Alderley
Park rats to various concentrations of propane for 15 min. The 15-min LC50 (le-
thal concentration, 50% lethality) for propane was more than 800,000 ppm. At
these high concentrations, oxygen was added to maintain an oxygen content of
20%. No further details were given.
3.2. Nonlethal Toxicity
3.2.1. Monkeys
Cardiac sensitization of propane was studied in groups of three anesthe-
tized Rhesus monkeys in an open-chest preparation. Monkeys were artificially
ventilated via an endotracheal cannula and several parameters of cardiac func-
tion (pulmonary arterial pressure, atrial pressure, aortic blood pressure, heart
rate, and myocardial force) were studied. Monkeys were exposed to propane at
100,000 or 200,000 ppm propane for 5 min (Belej et al. 1974). No effects were
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Propane
found on any parameter studied. In a similar series of experiments, exposure to
propane at 200,000 ppm caused a decrease in respiratory volume, but the de-
crease was not statistically significant (Aviado and Smith 1975).
3.2.2. Dogs
Krantz et al. (1948) reported cardiac sensitization by propane (unspecified
concentration) in unanesthetized dogs. Dogs were administered epinephrine hy-
drochloride (0.01 mg/kg) intravenously and were subsequently exposed to pro-
pane at concentrations between 150,000 to 900,000 ppm; an epinephrine chal-
lenge was injected after approximately 10 min of exposure.
Reinhardt et al. (1971) studied cardiac sensitization in unanesthetized,
healthy, male, beagle dogs (13-26 months of age). Target propane exposure con-
centrations were 50,000 ppm (6 dogs), 100,000 ppm (12 dogs), and 200,000
ppm (12 dogs). Actual concentrations were measured, but were not reported.
Marked responses to injected epinephrine (0.008 mg/kg), either defined as ar-
rhythmias posing a serious threat to life (e.g., multiple consecutive ventricular
beats) or which ended in cardiac arrest (e.g., ventricular fibrillation), were
judged to represent significant cardiac sensitization. The incidences of marked
responses were 0/6, 2/12, and 7/12 (one case of ventricular fibrillation and car-
diac arrest) for the 50,000, 100,000, and 200,000 ppm exposure groups, respec-
tively. No marked responses were observed in 13 unexposed dogs and chal-
lenged with epinephrine following the same procedure.
Clark and Tinston (1982; see Beck et al. [1973] for methodologic details)
studied cardiac sensitization in unanesthetized beagle dogs exposed to propane
for 5 min followed by an intravenous epinephrine injection. The procedure was
similar to that of Reinhardt et al. (1971). Cardiac sensitization was judged to
have occurred when ventricular tachycardia or ventricular fibrillation resulted
from the challenge injection of epinephrine. An EC50 of 18% (180,000 ppm) was
reported, with a 95% confidence interval of 12-26%.
Hemodynamic effects of propane were studied in groups of seven anesthe-
tized adult mongrel dogs. Dogs were artificially ventilated via an endotracheal
cannula and several parameters of cardiac function (pulmonary arterial pressure,
atrial pressure, ventricular pressure, heart rate, and stroke volume) were studied
(Zakhari 1977). Each dog was exposed to nominal concentrations of propane at
2.5, 5.0, 10.0, 15.0, and 20.0% (25,000, 50,000, 100,000, 150,000, and 200,000
ppm, respectively) via respirator for 5 min; each exposure immediately followed
the preceding one. No further details were given on actual exposure concentra-
tions. Myocardial contractility (the rate of rise in left ventricular pressure)
showed a concentration-related decrease starting at 25,000 ppm. Other effects
reported at higher concentrations included decrease in aortic pressure and stroke
work, decrease in cardiac output, and increase in vascular resistance. The indi-
vidual contribution of propane (as opposed to anesthesia) to produce these ef-
fects is unclear.
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296 Acute Exposure Guideline Levels
3.2.3. Guinea Pigs
Nuckolls (1933) exposed groups of three guinea pigs to propane at 22,000-
29,000 ppm or 47,000-55,000 ppm for 5, 30, 60, or 120 min. The animals were
observed during exposure and for 10 days after exposure. The concentrations
were analyzed periodically and adjustments made to maintain the predetermined
concentrations. Animals exposed at 22,000-29,000 ppm showed occasional
chewing movements and irregular breathing, but these effects did not worsen as
the exposure duration increased. Animals recovered quickly and appeared nor-
mal after exposure ended. Guinea pigs exposed at 47,000-55,000 ppm for 5 min
showed occasional tremors and chewing movements. Continuation of exposure
resulted in irregular breathing, occasional retching, and chewing movements,
and the animals became somewhat stupid (as reported by study authors) but
were able to walk. They sat huddled with their eyes partly shut. The description
of the effects suggests that the effects did not increase in severity with continua-
tion of exposure. One guinea pig exposed for 2 h at 47,000-55,000 ppm was
examined histopathologically 7 days after exposure; no effects were found.
3.2.4. Rats
The 10-min EC50 for CNS depression (ataxia and loss of righting reflex)
by propane was 28% (280,000 ppm; 95% confidence interval of 22-35%) (Clark
and Tinston 1982). Oxygen was added at propane concentrations greater than
250,000 ppm to maintain an oxygen concentration of 20%. Groups of six male
or female Alderley Park rats were exposed to various concentrations of propane.
No further details were given.
3.2.5. Mice
Cardiac sensitization by propane was studied in groups of anesthetized
Swiss male mice. Mice were exposed to propane at 10% (n = 3) or 20% (n = 5)
for 6 min (Aviado and Belej 1974). At 20%, propane was balanced with oxygen
in order to prevent asphyxia. Mice were exposed with and without a challenge
dose of epinephrine hydrochloride (intravenous injection of 6 μg/kg) 2 min after
the start of exposure. Electroencephalogram was continuously recorded during
exposure. No effects were observed in unchallenged mice, but propane at both
concentrations sensitized the heart to epinephrine.
3.3. Neurotoxicity
In an experimental study with humans, Patty and Yant (1929) reported no
symptoms after 10 min of exposure to propane at 10,000 ppm, but distinct ver-
tigo occurred after exposure for 2 min at 100,000 ppm. In rats, a 10-min EC50
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Propane
for CNS depression (ataxia and loss of righting reflex) of 28% (280,000 ppm)
was reported for propane, with a 95% confidence interval of 22-35% (Clark and
Tinston 1982). No other data were available.
3.4. Developmental and Reproductive Toxicity
No data were available.
3.5. Genotoxicity
Propane was negative for reverse mutations in the Ames test, with and
without metabolic activation (citation of an unpublished report in Moore
[1982]).
3.6. Carcinogenicity
No data were available.
3.7. Summary
Exposure to a mixture of propane at 800,000 ppm and oxygen at 20% for
15 min was not lethal to rats. Hemodynamic properties of propane and the po-
tential for cardiac sensitization were studied in monkeys, dogs, and mice. Pro-
pane caused cardiac sensitization in these species. However, in most studies, the
animals were tested under anesthesia, which make these studies unsuitable for a
quantitative evaluation of the potency of propane for cardiac sensitization. The
individual contribution of propane (as opposed to anesthesia) to produce the
effects is unclear. In a well-performed study, cardiac sensitization was found in
2/12 unanesthetized dogs exposed to propane at 100,000 ppm and in 7/12 dogs
at 200,000 ppm, of which one showed ventricular fibrillation and cardiac arrest
(Reinhardt et al. 1971). Exposure to propane lasted for 10 min with a challenge
injection of epinephrine after 5 min of exposure. No effects were observed at
50,000 ppm. These findings were supported by a second study using the same
protocol in which an EC50 of 180,000 ppm was reported (Clark and Tinston
1982).
Slight effects on the respiratory rate were reported in guinea pigs exposed
to propane at 22,000-29,000 ppm for up to 2 h. Guinea pigs exposed at 47,000-
55,000 ppm for 2 h became somewhat stupid (as reported by study authors) but
were able to walk. A 10-min EC50 for CNS depression of 280,000 ppm was re-
ported; oxygen was added at propane concentrations greater than 250,000 ppm
to maintain the oxygen concentration at 20%.
Propane was negative in the bacterial reverse mutation (Ames) test with
and without metabolic activation.
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298 Acute Exposure Guideline Levels
4. SPECIAL CONSIDERATIONS
4.1. Metabolism and Disposition
Volunteers (Caucasian students, 20-22 years of age) underwent single ex-
posures to propane at 250 ppm or 500 ppm for 1 h (1 male; 1 female), 2 h
(1 male; 1 female), or 8 h (2 males, 2 females) (see Section 2.2.2 for more de-
tails) (Stewart et al. 1977). Post-exposure alveolar breath concentrations of pro-
pane decreased rapidly. Fifteen minutes after exposure, propane concentrations
were less than 2 ppm and 10 ppm in subjects exposed at 250 and 500 ppm, re-
spectively, for 2 h. Propane also was analyzed in blood sampled 15 min before
the end of a 1-, 2-, and 8-h exposure at 250 or 500 ppm, and of an 8-h exposure
at 1,000 ppm. The blood concentration of propane ranged from 0.04 to 0.09
μg/mL, and was somewhat greater in the 500-ppm group. Concentrations did not
differ significantly for the different exposure durations. These results indicate
that an equilibrium between propane in alveolar breath and in blood is rapidly
reached. The propane concentration in blood at the end of an 8-h exposure was
similar for subjects exposed at 500 and 1,000 ppm.
Tsukamoto et al. (1985) exposed male ICR mice (number of animals not
specified) for 1 h to a mixture of propane, air, and oxygen (in the proportion of
2:1:1); animals were killed immediately after exposure. Besides propane, ace-
tone and isopropanol were detected in blood and tissues as metabolites. Tissue
concentrations of acetone ranged from 19 to 29 μg/g, with the highest concentra-
tions found in the liver, followed by the blood, brain, and kidneys. Endogenous
concentrations of acetone in unexposed mice were negligible. The isopropanol
concentration in tissues ranged from 25 to 35 μg/g, with the highest concentra-
tions in the blood.
4.2. Species Variability
No data were available.
5. DATA ANALYSIS FOR AEGL-1
5.1. Summary of Human Data Relevant to AEGL-1
No effects from a single or repeated daily 8-h exposure to propane at up to
1,000 ppm on a number of clinical parameters, heart function, brain function,
lung function, neurobehavioral parameters, and adrenocortical function were
found in 2 male and 2 female volunteers (Stewart et al. 1977). No symptoms
were noted following a 10-min exposure to propane at 10,000 ppm, but “distinct
vertigo” was reported after 2 min of exposure at 100,000 ppm. Exposure groups
consisted of 3-6 volunteers (male and female). No complaints of irritation were
reported at 100,000 ppm. Propane was “readily perceptible” (mean score of 2) at
46,000 ppm (Patty and Yant 1929).
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306 Acute Exposure Guideline Levels
Chemical Substances and Physical Agents and Biological Exposure Indices.
American Conference of Government Industrial Hygienists: Cincinnati, OH.
Aviado, D.M., and M.A. Belej. 1974. Toxicity of aerosol propellants in the respiratory
and circulatory systems. I. Cardiac arrhythmia in the mouse. Toxicology 2(1):31-
42.
Aviado, D.M. and D.G. Smith. 1975. Toxicity of aerosol propellants in the respiratory
and circulatory systems. VIII. Respiration and circulation in primates. Toxicology
3(2):241-252.
Avis, A.P., and J.T. Archibald. 1994. Asphyxial suicide by propane inhalation and plastic
bag suffocation. J. Forensic Sci. 39(1):253-256.
Beck, P.S., D.G. Clark, and T.J. Tinston. 1973. The pharmacological actions of bromo-
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Propane
APPENDIX A
DERIVATION OF AEGL VALUES FOR PROPANE
Derivation of AEGL-1 Values
Key study: Patty, F.A., and W.P. Yant. 1929. Odor Intensity
and Symptoms Produced by Commercial Propane,
Butane, Pentane, Hexane, and Heptane Vapor.
U.S. Bureau of Mines Report of Investigation
No. 2979. Washington, DC: U.S. Department of
Commerce, Bureau of Mines.
Toxicity end point: 10-min exposure to 10,000 ppm is no-observed-
adverse-effect level CNS depression
C3 × t = k for extrapolation to 30 and 60 min,
Time scaling:
flatlining assumed for 60 min to 4- and 8-h
exposure (based on 60-min steady-state
concentration).
k = (10,000 ppm)3 × 10 min = 1013 ppm3-min
Uncertainty factors: 1 for interspecies variability
1 for interindividual variability
Combined uncertainty factor of 1
Calculations:
10,000 ppma (18,000 mg/m3)
10-min AEGL-1:
C3 × 30 min = 1013 ppm3-min
30-min AEGL-1:
C = 6,900 ppma (rounded) (12,000 mg/m3)
C3 × 60 min = 1013 ppm3-min
1-h AEGL-1:
C = 5,500 ppma (rounded) (9,900 mg/m3)
Set equivalent to 1-h AEGL-1 of 5,500 ppma
4-h AEGL-1:
(9,900 mg/m3)
Set equivalent to 1-h AEGL-1 of 5,500 ppma
8-h AEGL-1:
(9,900 mg/m3)
a
The AEGL-1 value is greater than 10% of the lower explosive limit for propane in air of
23,000 ppm. Therefore, safety considerations against the hazard of explosion must be
taken into account.
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310 Acute Exposure Guideline Levels
Derivation of AEGL-2 Values
Key study: Reinhardt, C.F., A. Azar, M.E. Maxfield,
P.E. Smith, Jr., and L.S. Mullin. 1971. Cardiac
arrhythmias and aerosol “sniffing”. Arch
Environ. Health 22(2):265-279.
Toxicity end point: Short-term exposure (10 min with epinephrine
injection after 5 min) induced cardiac sensitization
in dogs; no-observed-adverse-effect level was
50,000 ppm.
Time scaling: Flatlining assumed for 10 and 30 min and for
1, 4, and 8 h.
Uncertainty factors: 1 for interspecies variability
3 for interindividual variability
Combined uncertainty factor of 3
Calculations:
50,000 ppm ÷ 3 = 17,000 ppmb (rounded)
10-min AEGL-2:
31,000 mg/m3)
30-min AEGL-2: Set equivalent to 10-min AEGL-2 of
17,000 ppmb (31,000 mg/m3)
1-h AEGL-2: Set equivalent to 10-min AEGL-2 of
17,000 ppmb (31,000 mg/m3)
4-h AEGL-2: Set equivalent to 10-min AEGL-2 of
17,000 ppmb (31,000 mg/m3)
8-h AEGL-2: Set equivalent to 10-min AEGL-2 of
17,000 ppmb (31,000 mg/m3)
b
The AEGL-2 value is greater than 50% of the lower explosive limit for propane in air of
23,000 ppm. Therefore, extreme safety considerations against the hazard of explosion
must be taken into account.
Derivation of AEGL-3 Values
Key study: Reinhardt, C.F., A. Azar, A., M.E, Maxfield,
P.E. Smith Jr., and L.S. Mullin. 1971. Cardiac
arrhythmias and aerosol “sniffing”. Arch
Environ. Health 22(2):265-279.
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311
Propane
Toxicity end point: Short-term exposure (10 min with epinephrine
injection after 5 min) induced cardiac sensitization
in dogs; no deaths occurred at 100,000 ppm.
Time scaling: Flatlining assumed for 10 and 30 min and for
1, 4, and 8 h.
Uncertainty factors: 1 for interspecies variability
3 for interindividual variability
Combined uncertainty factor of 3
Calculations:
100,000 ppm ÷ 3 = 33,000 ppmc (rounded)
10-min AEGL-3:
(59,000 mg/m3)
Set equal to 10-min AEGL-3 of 33,000 ppmc
30-min AEGL-3:
(59,000 mg/m3)
Set equal to 10-min AEGL-3 of 33,000 ppmc
1-h AEGL-3:
(59,000 mg/m3)
Set equal to 10-min AEGL-3 of 33,000 ppmc
4-h AEGL-3:
(59,000 mg/m3)
Set equal to 10-min AEGL-3 of 33,000 ppmc
8-h AEGL-3:
(59,000 mg/m3)
c
The AEGL-3 value is greater than the lower explosive limit for propane in air of 23,000
ppm). Therefore, extreme safety considerations against the hazard of explosion must be
taken into account.
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312 Acute Exposure Guideline Levels
APPENDIX B
CATEGORY GRAPH FOR PROPANE
Propane Toxicity
1000000
100000
AEGL - 3
AEGL - 2
Human - No effect
10000 Human Discomfort
AEGL - 1
Human - Disabling
Animal - No effect
Animal - Discomfort
ppm
1000
Animal Disabling
Animal - Some Lethality
Animal - Lethal
AEGL
100
10
1
0 60 120 180 240 300 360 420 480
Minutes
FIGURE B-1 Category graph of toxicity data and AEGLs values for propane.
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Propane
APPENDIX C
ACUTE EXPOSURE GUIDELINE LEVELS FOR PROPANE
Derivation Summary for Propane
AEGL-1 VALUES
10 min 30 min 1h 4h 8h
10,000 ppma 6,900 ppma 5,500 ppma 5,500 ppma 5,500 ppma
(18,000 mg/m3) (12,000 mg/m3) (9,900 mg/m3) (9,900 mg/m3) (9,900 mg/m3)
Key reference: Patty, F.A., W.P. and Yant. 1929. Odor Intensity and Symptoms
Produced by Commercial Propane, Butane, Pentane, Hexane, and Heptane Vapor.
U.S. Bureau of Mines Report of Investigation. No. 2979. Washington, DC:
U.S. Department of Commerce, Bureau of Mines.
Test species/Strain/Number: Groups of 3-6 human subjects (males and females,
20-30 years of age). The study was focused on the warning properties of several
alkanes.
Exposure route/Concentrations/Durations: Subjects were exposed to slowly
increasing concentrations up to 50,000 ppm (continuous exposure test, total
exposure was at least 6 min), followed by exposure to fixed concentrations for a
few minutes on the same day (intermittent exposure test). The fixed exposure
concentrations were approximately 10,000, 20,000, 50,000, and 100,000 ppm.
Effects: No odor detection or irritation was reported during the continuous
exposure test. No symptoms were reported after 10 min of exposure at 10,000 ppm,
but distinct vertigo was reported when volunteers were exposed at 100,000 ppm for
2 min. No irritation was noticed at 100,000 ppm for 10 min. The subjects were
capable of leaving the test chamber unassisted.
End point/Concentration/Rationale: No AEGL-1 effects at 10 min exposure to
10,000 ppm; consistent with butane.
Uncertainty factors/Rationale:
Total uncertainty factor: 1
Interspecies: 1, test subjects were humans
Intraspecies: 1, the concentration-response curve appears to be very steep indicating
small interindividual variability; no irritation at 100,000 ppm for 10 min; a higher
factor would result in unrealistically low values compared with occupational
standards.
Modifying factor: Not applicable
Animal-to-human dosimetric adjustment: Not applicable
Time scaling: n = 3 for time scaling from 10 min to 60 min (animal data for
cyclopropane and butane suggest high value of n); because steady state is reached
within 30 min, the values for 4- and 8-h exposures are similar to the 60-min value.
Data adequacy: Database is poor.
a
The AEGL-1 value is greater than 10% of the lower explosive limit for propane in air of
23,000 ppm. Therefore, safety considerations against the hazard of explosion must be
taken into account.
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314 Acute Exposure Guideline Levels
AEGL-2 VALUES
10 min 30 min 1h 4h 8h
See belowa See belowa See belowa See belowa See belowa
Key reference: Reinhardt, C.F., A. Azar, M.E. Maxfield, P.E. Smith Jr., and L.S.
Mullin. 1971. Cardiac arrhythmias and aerosol “sniffing”. Arch Environ. Health
22(2):265-279.
Test species/Strain/Number: Male beagles, number of dogs exposed was 6
(low exposure group) or 12 (mid- and high-exposure group).
Exposure route/Concentrations/Durations: Inhalation exposure for 10 min at
50,000, 100,000, or 200,000 ppm.
Effects:
0 ppm No effects
50,000 ppm No effects
100,000 ppm Marked response in 2/12 dogs
200,000 ppm Marked response in 7/12 dogs, one of which had cardiac arrest
End point/Concentration/Rationale: No cardiac sensitization at 50,000 ppm
Uncertainty factors/Rationale:
Total uncertainty factor: 3
Interspecies: 1, canine cardiac sensitization assay appears to be a good model for the
human heart.
Intraspecies: 3, the test is a conservative test for sensitive individuals because an
excess of epinephrine is used.
Modifying factor: Not applicable
Animal-to-human dosimetric adjustment: Not applicable
Time scaling: Cardiac sensitization is a concentration-related threshold effect and
concentrations that do not produce a positive response in short-term tests will also
not produce the effect when exposures are continued for longer periods.
Data adequacy: Database is poor. Data on cardiac sensitization are sufficient but
quantitative data are lacking on possible CNS effects so that a comparison of CNS
effects and cardiotoxicity cannot be made.
a
The AEGL-2 values for all time periods is 17,000 ppm (31,000 mg/m3). The AEGL-2
value is greater than 50% of the lower explosive limit for propane in air of 23,000 ppm.
Therefore, extreme safety considerations against the hazard of explosion must be taken
into account.
AEGL-3 VALUES
10 min 30 min 1h 4h 8h
See belowa See belowa See belowa See belowa See belowa
Key reference: Reinhardt, C.F., A. Azar, M.E. Maxfield, P.E. Smith Jr., and
L.S. Mullin. 1971. Cardiac arrhythmias and aerosol “sniffing”. Arch Environ.
Health 22(2):265-279.
Test species/Strain/Number: Male beagles, number of dogs exposed was 6
(low-exposure group) or 12 (mid- and high-exposure group).
(Continued)
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Propane
AEGL-3 VALUES Continued
10 min 30 min 1h 4h 8h
See belowa See belowa See belowa See belowa See belowa
Exposure route/Concentrations/Durations: Inhalation exposure for 10 min at 50,000,
100,000, or 200,000 ppm.
Effects:
0 ppm No effects
50,000 ppm No effects
100,000 ppm Marked response in 2/12 dogs
200,000 ppm Marked response in 7/12 dogs, one of which had cardiac arrest
End point/Concentration/Rationale: No deaths from cardiac sensitization at 100,000
ppm.
Uncertainty factors/Rationale:
Total uncertainty factor: 3
Interspecies: 1, the canine cardiac sensitization assay appears to be a good model for
the human heart.
Intraspecies: 3, the test is a conservative test for sensitive individuals because an
excess of epinephrine is used.
Modifying factor: Not applicable
Animal-to-human dosimetric adjustment: Not applicable
Time scaling: Cardiac sensitization is a concentration-related threshold effect and
concentrations that do not produce a positive response in short-term tests will also
not produce the effect when exposures are continued for longer periods.
Data adequacy: Database is poor. Data on cardiac sensitization are sufficient but
quantitative data are lacking on possible CNS effects so that a comparison on the
potency for CNS effects and cardiotoxicity cannot be made.
a
The AEGL-3 values for all time periods is 33,000 ppm (59,000 mg/m3).The AEGL-3
value is greater than the lower explosive limit for propane in air of 23,000 ppm. There-
fore, extreme safety considerations against the hazard of explosion must be taken into
account.
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