-------
-------
EPA/600/8-88/070
JULY 1988
SUMMARY REVIEW OF HEALTH
EFFECTS ASSOCIATED WITH
PROPYLENE
Health Issue Assessment
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL
ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
RESEARCH TRIANGLE PARK, NC 27711
-------
Disclaimer
This document has been reviewed in accordance with U.S.
Environmental Protection Agency policy and approved for publication.
Mention of trade names or commercial products does not constitute
endorsement or recommendation for use.
-------
Preface
The Office of Health and Environmental Assessment has
prepared this health issue assessment to serve as a source
document for EPA use. The health assessment was developed for
use by the Office of Air Quality Planning and Standards to support
decision making regarding possible regulation of propylene as a
hazardous air pollutant under the Clean Air Act, as amended in 1977.
In the development of the assessment document, the scientific
literature has been inventoried, key studies have been evaluated and
summary/conclusions have been prepared so that the chemical's
toxicity and related characteristics are qualitatively identified
Observed effect levels and other measures of dose-response
relationships are discussed, where appropriate, so that the nature of
the adverse health responses is placed in perspective with observed
environmental levels.
through"
ha8 been reviewed
Information regarding sources, emissions, atmospheric
transformation, ambient air concentrations, and human exposure is
summarized to provide a preliminary indication of the potential
presence of this substance in the ambient air. While the available
information is presented as accurately as possible it is
acknowledged to be limited and dependent in many instances on
assumption rather than specific data. This information is not
intended and, therefore, should not be used as an exposure
assessment by which to estimate risk to public health.
If a review of the health information indicates that the Aqencv
should consider regulatory action for this substance, a considerable
effort will be undertaken to obtain appropriate, more detailed
information regarding sources, emissions, and ambient air con-
centrations. Such data will provide additional information for drawina
regulatory conclusions regarding the extent and significance of public
exposure to this substance.
in
-------
-------
Table of Contents
Page
Figures and Tables vj
Authors, Contributors, and Reviewers '.'.'.'. vjj
1. Background Information '.'.'.'.'.'.'.'.'.'.'.' 1
1.1 Chemical Characterization and Measurement . '. '. '. . 1
1.2 Environmental Release, Transformation
and Exposure 2
1.3 Environmental Effects 11
2. Health Effects .'.'.'.'.'.'.'."" 13
2.1 Pharmacokinetics and Metabolism 13
2.2 Biochemical Effects 13
2.3 Acute Toxicity 14
2.4 Subchronic Toxicity 15
2.5 Chronic Toxicity 15
2.6 Mutagenicity '.'.'.'. -\Q
2.7 Carcinogenicity 18
2.8 Other Health Effects '...'.'.'.'.'.'/. 20
3. Summary 21
4. References 23
-------
Figures
Number
1-1 Daytime propylene reaction sequences in the
1-2
urban troposphere
Hydroxyl radical-initiated gas-phase oxidation
of propylene
Page
Tables
Number
Page
1 -1 Propylene concentrations in selected ambient
air samples 4
1-2 Reactants and products in the propylene-NOx-air
photooxidation system • • °
2-1 Incidence of epithelial changes in the nasal cavities
of rats exposed to propylene via inhalation 16
2-2 Incidence of tumors in mice exposed to propylene
via inhalation 19
VI
-------
Authors, Contributors, and Reviewers
The following personnel of Dynamac Corporation were involved
in the preparation of this document: Dr. Finis Cavender (Department
Director); Dr Nicolas P. Hajjar (Project Manager/Principal Author);
Dr. William McLellan, and Louis Borghi (Authors); Dr. Norbert Paqe
(Technical Reviewer); Anne Gardner (Technical Editor); and Gloria
Fine (Information Specialist). This document was prepared bv
Dynamac Corp., Rockville, MD under contract to the Environmental
Criteria and Assessment Office, Research Triangle Park NC (Dr
Dennis J. Kotchmar, Project Manager/Author).
Drafts of this document have also been reviewed for scientific
and technical merit by the following scientists: Dr. E. E. Sandmever
Transcontec, Inc., Pittsburgh, PA; Dr. Dennis Lynch, Experimental
Toxicology Branch, NIOSH, Cincinnati, OH; Dr. Michael Farrow
Experimental Pathology Laboratories, Inc., Herndon VA- Dr'
noT6!/!?6^- Valcovic' Reproductive Effects Assessment Group'
EPA, Washington, DC; Dr. Jerry N. Blancato, Exposure Assessment
Group, EPA Washmgton, DC; and Dr. Arthur Chiu, Carcinoqen
Assessment Group, EPA, Washington, DC.
.The information presented in this document is based on literature
searches of databases and updates, the most recent of which was
conducted during March 1988.
VII
-------
-------
1. BACKGROUND INFORMATION
This overview provides a brief summary of the data available on
the health effects of exposure to propylene. Emphasis is placed on
determining whether there is evidence to suggest that propylene
exerts effects on human health under conditions and at concen-
trations commonly experienced by the general public. Both acute and
chronic effects are addressed, including general toxicity, muta-
genicity, and carcinogenicity. To place the health effects discussion
in perspective, this report also summarizes air quality aspects of
propylene in the United States, including sources, distribution, fate,
and concentrations associated with certain point sources.
1.1 Chemical Characterization and Measurement
Propylene (CAS No. 115-07-1) has the chemical structure
CHaCH = CH2- It is a colorless gas with a molecular weight of 42.08
It is only slightly soluble in water (44.6 ml/100 ml at 20°C and 1 atm
or 82.1 mg/100 ml) and has a high vapor pressure (10 atm at
19.8°C) (TDB; Schoenberg et al., 1982).
Although infrared spectrophotometry can be used to detect
propylene in gaseous mixtures (International Agency for Research on
Cancer, 1979), gas chromatography (GC) is the analytical method
most commonly used to measure concentrations of the compound in
environmental media and combustion gases. For the qualitative and
quantitative determination, gas chromatography with flame ionization
detection (GC/FID) and mass spectroscopy (MS) have been used
extensively, e.g., Nelson and Quigley (1982) and Crow et al. (1982)
for ambient air concentrations; Hoff et al. (1982) for pyrolysis
products; and Yoshida et al. (1978) for polymer combustion gases.
Cryogenic collection and the use of solid adsorbents have been used
as sample preconcentration steps preceding GC analyses. The GC
method used by Westberg et al. (1974) for the separation of Ca-Ce
hydrocarbons in ambient air uses a special chemically bonded
stationary phase and has a detection limit of 0.5 ppb. Single run C2-
GIO HC analysis was accomplished using the open trap cryo-
focusing/GC-reinjection technique (Matuska -et al., 1986). An aver-
age retention time of 4.322 minutes was reported for propylene.
Rudolph et al. (1981) developed a GC/FID method for
determination of low levels of Ca-Cs hydrocarbons in grab samples
(0.5-2 cm3) of air. Hydrocarbons in the samples are first
concentrated on a packed pre-column with porous silica and
-------
Carbosieve B kept at -35°C and then separated on a column
packed with untreated porous silica (Spherosil XOB 075). The
detection limit for propylene using this method is 4 ppt. A similar
GC/FID method for determining C2-Cs hydrocarbons has recently
been described by Reineke and Bachmann (1985). This method
employs a three-detector setup and reproducibly quantifies
propylene at concentrations as low as 12 ppt.
A GC/FID method, with detection limits of 2 x 10-12 M for gas
and 5x10-8 ml for gas dissolved in 1 liter of sea water at standard
temperature and pressure, was used by Swinnerton and Linnenbom
(1967) to measure propylene concentrations in sea water samples.
Frisch et al. (1982) used a gas radio chromatographic liquid
scintillation spectrophotometric method to detect propylene in the
smoke of cigarettes made with a tobacco filler treated with a
radiolabeled insecticide.
1.2 Environmental Release, Transformation, and Exposure
Domestic production capacity of propylene, as of January 1,
1984, was estimated to be about 22.3 billion pounds annually,
involving 37 companies operating at 61 plant sites (SRI International,
1984). The compound is produced as a by-product of petroleum
refining and as a coproduct of ethylene manufacture. Propylene is
used in both chemical and refinery applications. Refinery-generated
propylene is the main source of the compound for nonchemical uses,
whereas the ethylene coproduct material is used mainly in chemical
applications. Chemical applications accounted for about 58 percent of
domestic consumption of the compound in 1979; refinery applications
accounted for the remaining 42 percent. Propylene is marketed in
three grades: refinery (50-70 percent pure), chemical (90-96
percent pure), and polymer (>99 percent pure) (Chemical
Economics Handbook, 1980; Schoenberg et al., 1982).
The current demand of 14.6 billion pounds of propylene annually
for chemical applications is expected to grow at an average rate of 5
percent per year through 1988, to a level of 17.7 billion pounds
annually (Chemical Marketing Reporter, 1984). Propylene is used
both in the chemical and the petroleum industries as a monomer in
the production of polypropylene (27 percent), and as a raw material
in the production of acrylonitrile (18 percent), propylene oxide (9.7
percent), and cumene (7.9 percent of the consumption). Production
of isopropyl alcohol, other alcohols, and numerous miscellaneous
chemicals (e.g., propylene oligomers, butyraldehydes, acrylic acid,
ally! chloride, and acrolein) account for the remainder of propylene
chemical consumption (Chemical Economics Handbook, 1980;
Schoenberg et al., 1982; Chemical Marketing Reporter, 1984).
Data on the current demand for propylene in refinery applications
were not available. In refinery applications, propylene is used as a
feedstock for high-octane blending components of gasoline (e.g.,
-------
alkylate and polymer gasoline) and as a fuel (Chemical Economics
Handbook, 1980; Schoenberg et al., 1982).
Propylene is expected to be released to the environment mainly
in pyrolysis gases from the combustion processes and incidentally in
gaseous emissions from industrial manufacturing and use operations
However, quantitative estimates of such industrial releases were not
found. Sivertsen (1983) identified propylene as a constituent of the
fugitive hydrocarbon emissions of an ethylene cracking unit at a
petrochemical plant in Norway, but quantitative data were not
presented.
Propylene is also expected to be released to the environment in
the combustion gases of hydrocarbon fuels, wood, cigarettes and
synthetic polymers, refuse, etc. Jackson (1978) found that the
propylene content of the exhaust gases of automobiles burning
leaded and unleaded gasoline was lower in late-model cars
equipped with oxidative catalytic converters (2.9 percent as carbon)
than earlier models without converters (6.5 percent as carbon)
Sigsby et al. (1987) found similar results with propylene content
decreasing further to 1.9 percent as carbon in 1982 models
Propylene has also been detected in the exhaust gases of diesel-
fuel-powered automobiles, emitted at a rate of 0.0207 g/mile
(International Agency for Research on Cancer, 1979), and j'et engines
at maximum concentrations of about 130-143 ppm (Katzman and
Libby, 1975). The compound has been found in the combustion
gases and smoke from plant materials such as white pine wood
(OMara, 1974) and cigarette tobacco treated with radiolabeled
methoprene, an insect growth regulator (at 0.2 per cent of the total
radioactivity recovered in the smoke) (Frisch et al., 1982). Levels of
< 0.4-1.5 ppm propylene were found in the flue gases of a
municipal incinerator (Carotti and Kaiser, 1972).
Propylene can be released to the environment as emissions from
incinerators burning hazardous waste. Allen et al. (1986) monitored
stack emissions from an incinerator burning hazardous (infectious)
hospital waste (infectious and noninfectious) and calculated an
emission factor for propylene of < 0.0011 g/kg. Propylene was not
found above the detection limit (0.5 ppm) in any of 22 samples taken.
Thermal decomposition products of polymers such as
polyethylene (Hoff et al., 1982), polyamides (Yoshida et al 1978)
and polyacrylonitrile (Woolley, 1982) have been found to'contain
propylene. Woolley reported that propylene was present at a
concentration of about 10.7 ppm in the combustion gases following
the burning of 5 kg of polypropylene in a 27-m3 room (closed door)
In addition to these sources, propylene is produced as a natural
metabolite of trees and germinating beans, corn, cotton, and peas
(Vancura and Stotzky, 1976; Kusy and Kusy, 1982).
Propylene concentrations in ambient air samples have been
found to vary diurnally and with wind direction (Bos et al., 1977).
-------
Sexton and Westberg (1984) reported that ground-level
concentrations of propylene in urban air samples collected in seven
US cities ranged from 4 to 17 ppbC (geometric mean), whereas
concentrations in rural surface air samples from six domestic sites
ranged from <0.5 to 3.0 ppbC (geometric mean). Selected ambient
air monitoring data are presented in Table 1-1.
Table 1-1. Propylene Concentrations in Selected Ambient Air
Samples
Location Concentration Reference
Azusa, CA
Los-Angeles, CA
Philadelphia, PA3
Rural Southern Ontario
Atlantic Ocean (marine air)
Arctic air
(spring haze)
(summer)
Bombay, India3
Delft The Netherlands
Japan (industrial area near
petrochemical plant)
Julich, FRG (semirural)
Sydney, Australia
Lancaster, England
United Kingdom (rural)
4 ppb avg.
10.5 ppb avg.
7-32 ppb (vol.)
7-260 ppb
18-141 ppt
0.05 ppb
1180 ppt avg.
5 pptb
24 ppt
187 ppt
0.4-18.7 ppb
9.1 ppb (vol.) avg.
8 ppb max.
10-100 ppb
5 ppb
7.4 ppb (vol.) avg.
5.1 ppbc
Geometric mean
0.7 ppb avg.;
0.10-4.8 ppb
ranqe
Altshuller et al. (1971)
Altshuller et al. (1971)
Grosjean and Fung (1 984)
Giannovario et al. (1 976)
Anlauf etal. (1985)
Rudolph etal. (1981)
Schmidbauer and Oehme (1985)
Khalil and Rasmussen (1984)
Hovetal. (1984)
Hovetal. (1984)
Netravalkar and Mohan Rao (1984)
Mohan Rao and Pandit (1 988)
Bos etal. (1977)
International Agency for Research
on Cancer (1 979)
Rudolph etal. (1981)
Nelson and Quigley (1982)
Colbeck and Harrison (1985)
International Agency for Research
on Cancer (1979)
^Suburban location near industrial complexes.
^Difference in concentration in and out of haze layers.
Propylene concentrations have been shown to be higher inside
the home than outside. Lamb et al. (1985) detected propylene at
concentrations of 0.6, 7.1, and 2.2 yg/m.3 inside a home in August
1981, December 1981, and June 1982, respectively. The ambient air
concentrations outside the home were 0.9 and 0.5 ixg/m.3 jn
December 1981 and June 1982, respectively. The authors attributed
the increased levels of propylene (and other hydrocarbons) in the
home to sources such as gas heating, automobile exhaust, and
aerosol propellents.
Surface water samples taken from the Gulf of Mexico, Caribbean
Sea, Atlantic Ocean, and Pacific Ocean have been found to contain
-------
propylene at concentrations of 0.1-16 ng/l (Swinnerton and
Lamontagne, 1974).
Estimates of occupational exposures to propylene have been
reported in industrial hygiene surveys performed by the National
Institute for Occupational Safety and Health. According to the
National Occupational Hazard Survey (NOHS), 10,274 workers were
potentially exposed to propylene in domestic workplace environments
in 1970. Preliminary data for 1980 by the National Occupational
Exposure Survey (NOES) indicate that 4,548 workers, including 136
women, were exposed to the compound.
Atmospheric concentration limits in the workplace have not been
established for propylene by either the Occupational Safety and
Health Administration or the American Conference of Governmental
industrial Hygienists. However, a suggested maximum permissible
exposure limit of 4,000 ppm (6,984 mg/m3) (one-fifth the lower
flammable limit) has been suggested by Gerarde (1963).
Propylene'has odor thresholds of 5.7-28.6 ppm (10-50 ma/m3
detection) and about 57.3 ppm (100 mg/m3, recognition) an
organoleptic (taste) limit of 0.5 mg/l, and a light sensitivity to the eves
of approximately 6.3 ppm (11 mg/m3) (Verschueren, 1983-
Krasovitskaya and Malyarova, 1966).
Propylene released to the environment from point and nonpoint
sources is expected to partition into the atmosphere due to its hiqh
vapor pressure. However, its mobility may be limited because of the
relatively higher density of propylene (1.45) as compared to air (1 0)
Moreover, since propylene is also highly reactive, chemical reactions
and degradative processes will probably limit its transport and
decrease its residence time in the atmosphere.
The chemical properties of propylene are characterized by its
double bond and allylic hydrogen atoms. The carbon-carbon double
bond serves as a source of electrons and thus will easily undergo
electrophilic addition reactions that are characteristic of alkenes
Several types of reactions that occur at room temperature include the
addition of halogens and hydrogen halides, hydroxylation glycol
formation, and ozonolysis (Morrison and Boyd, 1973) Propylene
reacts vigorously with oxidizing materials such as NO2, N2O4 and
t2?; Fu1rthermore' ''Quid propylene will explode on contact with water
at 315-348 K (Schoenberg et al., 1982).
The atmospheric fate and photochemical reactions of propylene
such as the formation of photochemical oxidants and smog have
been studied by several investigators. Graedel et al (1976)
developed a mathematical model of photochemical processes to
study the fundamental atmospheric chemistry of the troposphere
The model included chemical kinetics, time-related appearances of
trace contaminated sources, solar flux variations, bulk airflow and a
geographical matrix of "reaction volumes." Data on the diurnal rates
-------
of several groups of reactions between atmospheric components and
propylene indicated that the principal reactant was the hydroxyl
radical (OH), which accounted for more than 75 percent of the total
propylene removed. The reactions of propylene with ozone occurred
predominantly in the evening. The reactions of propylene with atomic
oxygen or excited SOa were reported to be insignificant in the
environment because of their relatively low concentration. Eight
daylight photochemical reaction chains involved in the removal of
propylene from the atmosphere are shown in Figure 1-1. Pathways
1 2. and 3 produced two aldehyde molecules for each propylene
molecule, whereas pathways 4-7 produced one aldehyde molecule
and one free radical. The free radicals, in turn, produced additional
hydrogen radicals by other reactions. The authors concluded that
once the chain of propylene attack began, the production of
aldehydes, organic radicals, and organic nitrate products was self-
sustaining.
Figure 1-1. Daytime propylene reaction sequences in the uitoan troposphere.
Source: Graedel ef al. (1976).
CH262 + CH3CHO Q Oa CH3CH02 + HCHO
^CH^HCHaO*
03 ± °3
O
CH3CH = CHSOj.H-4 —"CH3CH
(8)
(3)
(7)
CH3C(OH)HCH2
CH2 + HO
INO
HCHO + CHgCHOH
CH3CHCH2OH
Formaldehyde
CH3CH2CHO
3 z
Propionaldehyde
CH2 = CHCHO + HO2
Acraleiin
CH3CHO + CH3O
Acetaldehyde
The OH-initiated gas-phase oxidation of several compounds,
including propylene, was studied by Edney et al. (1982). The
-------
mechanism of _ this oxidation reaction with propylene is shown in
Figure 1-2. Using the rate constant and average OH concentration
values, the atmospheric half-life of propylene was calculated to be
7.7 hours at approximately 23°C.
Figure 1-2. Hydroxyl radical-initiated gas-phase oxidation of propylene
Source: Edney et a/. (1982).
CH3CH = CH2 + OH*
O,
/* . \
CH3CHOH - CH2O2
NO 4- NO2
CH3CHOH - CH2O*
V
HCHO + CH3CHO n
CH3CHO2 - CH2OH
NO 4- NO2
CH3CHO*- CH2OH
°*/
y HO2
The atmospheric residence time (T) of propylene can be
estimated using the method of Lyman et al. (1982), which estimates
residence time as a function of reaction rates with hydroxyl radicals
and ozone but does not consider reactions with other substances or
photodissociation. Therefore, T must be considered a maximum
value. Using the rate constants for reactions of propylene with OH
(koH = 1-5 x 1010 liter-mo 1-1-sec-l) and O3 (kQa = 7.8 x 103
liter-moM-sec-1), and average concentrations for OH (global
annual average, 1.8 x 10-15 mo| / I) and O3 (urban annual average,
5.0 x 10-9 mof/ I), the estimated TQH is 10.3 hours and the TO, is
7.1 hours.
et al. (1979, 1980) studied the photo-oxidation of
in an evacuable photochemical smog chamber.
Akimoto
* ""* ' ™~ w — •—«««•'•'-' f-r>ivs«.v/vsll{^llllOCll Ol I lt_/U UlldlllUCr
Quantitative analysis of the products was made in situ by a long-
path Fourier transform infrared spectrometer. The products formed
under dry or humid conditions (relative humidity 40 percent) in the
photo-oxidation system containing propylene, NOX, and air are listed
in Table 1-2. Maximum ozone formation was obtained when the
initial concentration ratio of propylene to NOX was larger than 3 In
the presence of water vapor, maximum ozone formation was slightly
lower compared to the dry air system. There was no effect on the
yield of other chemicals. However, the addition of water vapor
markedly enhanced the yield of formic acid (from about 0.16 to 0 53
-------
ppm maximum yield), which was ascribed to the reaction of
propylene with formed ozone. The authors suggested that the
mechanism may involve the following reactions:
x°
CH2OO--> CH2 I -» HCOOH
•CH2OO- + H2O-> [CH2OO-H2O]-»HCOOH + H2O
Mutagenic, genotoxic, and cytotoxic effects of the photochemical
reaction products of propylene plus NOX have been reported. These
are briefly discussed in Section 3.6.
The effects of water vapor and carbon monoxide on the photo-
oxidation of propylene in the presence of NOX were also investigated
by Nguyen and Phillips (1979). Water vapor (<11,000 ppm) had no
effect on the photo-oxidation rate of propylene by NOX or on the
yield of NO2 and 03. The formation of formic acid was not
investigated by the authors. Carbon monoxide (<200 ppm), on the
other hand, increased the rate of propylene photo-oxidation and
product formation.
Table 1-2. Reactants and Products in the Propylene-NOx-Air
Photo-Oxidation System
Initial Concentration, ppm
Experiment
1
2
3
4
C3H6
3.05
3.04
3.06
3.01
NOX
1.500
1.403
1.583
1.516
NO
1.477
1.358
0.016
0.012
Maximum Yield,
Experiment
1
2
3
4
03
1.20
1.04
1.30
1.15
HCHO CH3CHO
1.75 1.30
1.82 1.32
1.92 1.18
1.82 1.32
PAN&
0.75
0.64
0.76
0.59
NO2
0.023
0.045
1.567
1.504
ppm
PGDN0
0.10
0.11
0.10
0.09
H2Oa
<1
1.7X104
<•<
1.7X104
N205 HNO3
0.03 0.23
0.05 NDd
0.06 0.19
0.04 NDd
aRH=40% at30°C.
bperoxyacetyl nitrate.
CT ,2-Propanediol dinitrate.
dNot determined due to H2O interference.
Source: Akomoto et al. (1980).
-------
Propylene glycol dinitrate was the major product in the gas-
phase reaction of N2Os with propylene in dry air in an evacuable
smog chamber (Hoshino et al., 1978). Other products were
acetaldehyde, propylene oxide, NC>2, and HNO3. The ratio of
propylene glycol dinitrate, acetaldehyde, and propylene oxide
appeared to be independent of the N2C>5 concentration. The authors
suggested that the formation of propylene glycol dinitrate in the
propylene-NOx-air photo-oxidation system resulted from the
reaction of propylene with generated N2O5 or N03 (nitric oxide)
radical (Hoshino et al., 1978; Akimoto et al., 1979, 1980).
The gas-phase reactions of nitrate radicals with a series of
organic compounds, including propylene, in air at room temperature
were recently reported by Atkinson et al. (1984). The reactions with
alkenes were, shown to proceed via initial NO3 radical addition to the
double bond:
ONO2
• N03 + CH3CH = CH2 -> CH3CHCH2 + CH3 CHCH2ONO2
Under atmospheric conditions, the two radicals formed are
expected to react with O2 rapidly to yield the nitroxyperoxyalkyl
nitrate and dinitrate as final products, although the exact reaction
pathway for dinitrate formation is not known. The rate constant for
the gas-phase reaction of propylene with nitrate radicals was
reported to be 4.2 ± 0.9 x 10-12 liter-moM-sec-i. Based on
the kinetic data generated in this study together with the observed
ambient atmospheric concentrations of the NO3 radicals that are
more prevalent during the nighttime, the authors suggested that the
reactions of the NO3 radicals with the more reactive alkenes and
hydroxy-substituted aromatic compounds may be an important
nighttime sink for the radicals and the reactive organic compounds.
Shepson et al. (1985) conducted smog chamber studies of
C3H6/N2Os reactions at low (ppm) reaction levels to determine the
various reaction mechanisms and yields for the production of organic
nitrates. The concentration of N2Os and propylene in the dark
reaction were 0.68 and 1.85 ppm respectively. Major products
positively identified were propylene glycol dinitrate, 2-hydroxypropyl
nitrate, and 2-(nitrooxy) propyl alcohol. Limited evidence was also
presented for the formation of a-(nitrooxy) acetone, which is
produced by a series of reactions summarized as follows:
02
C3H6 + NO3 -* CH3C(O)CH2ONO2 (unbalanced)
The authors reported that under their experimental conditions,
which more closely approximate atmospheric conditions, the yields of
propylene glycol dinitrate are not nearly or large as has been shown
experimentally at higher initial concentrations of N2Os/C3H6. This
was due to the competing reactions producing formaldehyde and
acetaldehyde, or a-(nitrooxy) acetone. The formation of a-(nitro-
-------
oxy) acetone was considered to be a significant finding, since it has
been shown to be mutagenic (Shepson et al., 1985; Kleindienst et
al.f 1985; see also the mutagenicity section).
Upon release to surface waters, a small amount of propylene
may dissolve in water, but most of the released material is expected
to volatilize to the atmosphere. Propylene has been detected in
marine and fresh waters, in trace amounts. Propylene surface levels
in the Gulf of Mexico have been determined at 9.3 x 10-'ml / I and
In the North Atlantic at 5.9 x 1Q-7ml / I water. Fresh water levels in
Russia have been determined at 0.5 mg propylene in 1965
(Sandmeyer, 1985). In water bodies, propylene is readily degraded
by microorganisms. Therefore, propylene is not expected to
bioaccumulate or bioconcentrate in organisms and food chains.
Under calm atmospheric conditions, it has been reported that
propylene will sink to the ground because it is denser than air
(OHMTADS). However, due to its high vapor pressure, it is expected
that releases of propylene to soil would be readily transported to air
or water.
Two studies were reported on the microbial oxidation and
metabolism of propylene (Cerniglia et al., 1976; Perry, 1980).
Propane-grown cells of Mycobacterium convolutum oxidized
propylene rapidly to acrylate. The rate of oxidation was 51 u' Oa/mg
cells/hour. However, microbial growth was not observed because the
acrylate inhibited fatty acid oxidation by these microorganisms. A
mixed culture of two microbial species capable of utilizing propylene
as the sole source of carbon and energy was also isolated by soil
enrichment (Cerniglia et al., 1976). One was a red-pigmented
organism designated YS-3R and identified as being similar to
Thermus aquaticus (a thermophilic heterotrophic organism), and the
other was a small, white, colony-forming organism designated YS-
3 (Perry, 1980). An axenic culture isolated from marine soil and
designated as strain PL-1 also metabolized propylene and utilized it
as the sole carbon source. The rate of oxidation was 81 ul O2/mg
cells/hour. Radiolabeled experiments with [1~14C] propylene and
14CO2 in the presence or absence of arsenite (an inhibitor of
pyruvate metabolism) indicated that propylene was not metabolized
into pyruvate, but rather was cleaved into two products, the first
containing one carbon atom and the second containing two. Isocitrate
lyase activity and fatty acid profile determination further indicated that
the mixed culture and strain PL-1 oxidized propylene at the double
bond, resulting in cleavage of the molecule.
In contrast, the ratio of propylene's 5-day biochemical oxygen
demand to its chemical oxygen demand (5-day BOD/COD), used as
an estimate of biodegradability, was zero, indicating that it was
relatively undegradable (Lyman et al., 1982). However, the
experimental conditions for BOD determination were not presented,
and a complete evaluation of this finding could not be made.
10
-------
1.3 Environmental Effects
The available literature on the ecological effects of propylene was
very limited. Data were found only on the in vivo and in vitro effects
of propylene on higher plants. No toxicity data were found on the
effects of propylene on aquatic plants, invertebrates, microorganisms,
or fish. Van Haut and Prinz (1979) reported that propylene's toxicity
to plants was essentially insignificant when compared to ethylene,
and they concluded that propylene emissions would have practically
no adverse effects on plant growth. In a short-term test, plants,
including the bushbean, radish, cress, petunia, and geranium,
showed characteristic damage following exposure to ethylene at
concentrations ranging from 0.1 to 1.44 mg/m3 for varied periods of
time; i.e., 0.5-14.0 days. Propylene concentrations ranging from 360
to 1500 times those of ethylene (actual concentrations not given)
were needed to achieve comparable growth inhibition, but such high
propylene concentrations are not expected to be found in the
ambient air.
In an in vitro study of the mechanism of action of ethylene as a
plant growth inhibitor, Smith et al. (1983) examined the effect of
ethylene and some of its analogs, including propylene, on the
oxidation of indole-3-acetic acid. Ethylene and its analogs inhibited
the oxidation of indole-3-acetic acid by peroxidase under
conditions where the Fep + + ±? Compound III (an oxy-ferrous
complex of peroxidase) shuttle was activated. Inhibition occurred only
in the presence of the superoxide anion radical (O2~). Spectral and
kinetic data indicated that ethylene and its analogs enhanced the rate
of reaction of C>2~ with peroxidase; i.e., the Fep+ + ±s Compound III
shuttle, resulting in the formation of Compound III. Propylene was a
less effective inhibitor than ethylene.
11
-------
-------
2. HEALTH EFFECTS
2.1 Pharmacokinetics and Metabolism
Limited information was available on the metabolism of
propylene. The kinetics of uptake and metabolism of propylene in
male CBA mice was studied by Svensson and Osterman-Golkar
(1984). Groups of 15 mice were placed in a closed recirculation 11-
liter chamber and exposed to propylene at eight concentrations
ranging from 95 to 1,715 ppm. The level of propylene in the air was
determined by gas chromatography and was followed for at least one
half-life during the exposure period. The rate of uptake at
equilibrium (between 100 and 150 minutes after onset of exposure)
was estimated from the slope of the concentration-time curve and
expressed in milligrams of propylene per kilogram of body weight per
hour. The metabolism of propylene followed Michaelis-Menton
kinetics. A double reciprocal plot of these rates versus chamber
concentration (which is a Lineweaver-Burk representation of
Michaelis-Menton kinetics) allowed determination of the Km and
Vmax- The Km (concentration in air at which uptake proceeds at
half-maximum velocity) was 800 ± 60 ppm, and the Vmax
(maximum rate of uptake) was 8 ± 0.5 mg/kg/hour. Since propylene
was expected to be oxidized to propylene oxide in a manner similar
to that previously demonstrated for ethylene in mice, the combined
uptake of both ethylene and propylene was studied. It was found that
the uptake of 14C-ethylene (0.01 ppm), in the presence of a high
concentration of propylene (1,260 ppm), was lower than in the
absence of propylene. This finding suggested a competitive
interaction of both compounds in their metabolic pathways and
indicated that propylene is converted in vivo to propylene oxide. The
authors reported that the metabolic pathway of propylene involved
oxidation to the corresponding oxide and subsequent alkylation of
nucleophilic sites in macromolecules. Alternatively, propyiene and/or
propylene oxide were metabolized by other pathways and excreted
(see also below).
2.2 Biochemical Effects
Svensson and Osterman-Golkar (1984) also studied the
alkylation of macromolecules in mice exposed to 14C-propylene to
demonstrate the transient appearance of propylene oxide in tissues.
In one experiment, the mice were exposed for 1 hour to an
atmosphere containing 2830 ppm of 14C-propylene and then
sacrificed 13 hours later. Hemoglobin from blood and DNA from, the
13
-------
liver, testes, spleen, lungs, and kidneys were isolated, and labeled
alkylation products in these macromolecules were identified. The
amount of radioactivity bound to the DNA of the liver and pooled
organs was below the level of detection. The hemoglobin was
hydrolyzed, and the resulting amino acids chromatographed by ion
exchange after adding carrier amino acids and 2-hydroxypropylated
derivatives of cysteine, histidine, and valine. The major part of the
radioactivity of hemoglobin (about 70 percent) eluted with serine,
glycine, and alanine, indicating extensive biodegradation of propylene
followed by biosynthetic incorporation of 1 and 2 I4c-carbon
fragments into amino acids. Hemoglobin hydrolysates also showed
radioactivity associated with S-(2-hydroxypropyl) cysteine, N-(2-
hydroxypropyl) valine, and N-(2-hydroxypropyl) histidine. The de-
gree of alkylation of cysteine and valine was 2 nmol/g of hemo-
globin, and that for histidine was 0.9 nmol/g of hemoglobin. In
another experiment, mice were exposed to 20,000 ppm of unlabeled
propylene for 4 hours/day for 8 days. Blood was collected
immediately after the last exposure and hemoglobin alkylation
assessed. The degree of alkylation was 2.2 nmol N-(2-hydroxy-
propyl) histidine/g of hemoglobin per hour. Two diastereoisomers of
the histidine derivative were isolated, which were similar to those
obtained from the reaction of DL-propylene oxide with histidine. The
authors suggested that these results indicate nonstereospecific
oxidation of propylene to propylene oxide. However, the data
presented do not necessarily support such a mechanism.
The role of the cytochrome P-450 system in the hepatotoxicity
of propylene was investigated by Osimitz and Conolly (1985). Male
Sprague-Dawley rats (200- 275 g) were pretreated with either
polychlorinated biphenyls (PCB, Aroclor 1254), phenobarbital (PB),
0-naphthoflavone (BNF), or BNF + PB to maximally induce the
appropriate isozymes of cytochrome P-450. Appropriate vehicle
control groups were also included. The animals (at least four rats per
group) were then exposed to CP-grade propylene (>99.5 percent
pure) at 0 or 50,000 ppm for 4 hours. All animals were sacrificed 20
hours postexposure, and measurements of serum sorbitol
dehydrogenase (SDH) and alanine leucine transaminase (ALT)
activities were taken as indicators of hepatotoxicity. Propylene was
not hepatotoxic in untreated, PB-, BNF-, or BNF + PB-treated
animals, but it was hepatotoxic in rats pretreated with PCB. The
authors concluded that an isozyme of cytochrome P-450 induced
by PCB is required to convert propylene to a hepatotoxic metabolite
in pretreated rats.
2.3 Acute Toxicity
No LDso values or lethal dose estimates were found in the
literature. Reports in the early literature indicate that propylene is not
very toxic. Exposure of white mice to a mixture of 50 percent
propylene and 50 percent air ^produced anesthesia in 8 minutes
(Riggs, 1925). Riggs (1925) performed a study in which white rats of
14
-------
a "pure strain and great uniformity" were exposed to a gas mixture
containing propylene (purity, 99 percent) at concentrations ranging
from 40 to 70 percent. Oxygen levels were maintained at 25 percent,
whereas the concentrations of nitrogen were varied. The sex and
number of animals exposed were not reported. At 40 percent,
propylene produced a light anesthesia within 15-20 minutes-
exposure up to 6 hours produced no visible signs of toxicity!
Exposure to propylene at 55, 65, 70 percent produced a deep
anesthesia within 3-6, 2-5, 1-3 minutes, respectively. Animals
exposed to 55 percent propylene for 7.5 hours recovered within 2
minutes postexposure and exhibited no signs of overt toxicity.
However, propylene concentrations of 65 or 70 percent led to
respiratory failure and death after 2 hours or 20-25 minutes
respectively.
Brown (1924) reported similar effects in cats. Anesthesia was
induced and maintained at propylene concentrations between 37 and
50 percent. At propylene concentrations of 65 and 70 percent, a fall
in blood pressure was reported. In dogs, propylene has been shown
to be a cardiac sensitizer (Krantz et al., 1948). Two mongrel dogs
were administered intravenous injections of epinephrine hydrochloride
at 0.01 mg/kg and then allowed to breathe a propylene/air mixture
(propylene concentration not specified) for 10 minutes. Propylene
caused a sensitization of the myocardium to the epinephrine in both
dogs, resulting in multifocal ventricular tachycardia that progressed to
ventricular fibrillation and caused death.
No further information was found on cardiac sensitization to
epinephrine following propylene exposure.
2.4 Subchronic Toxicity
No compound-related toxic effects were observed in male and
female F344/N rats and B6C3F! mice following repeated exposure to
propylene for 14 days (5 animals/sex/dose) or 14 weeks (10
animals/sex/dose) at concentrations of 0, 625, 1,250, 2,500, 5,000,
and 10,000 ppm for 6 hours/day, 5 days/week (National Toxicology
Program, 1985). In an early study (Reynolds, 1926), six white mice of
unspecified strain and sex were exposed to impure propylene at a
concentration of 35 percent for five exposures of 90 minutes each
over a 10-day period. No toxic effects were noted except for the
liver of one animal, which showed moderate fatty degeneration.
Subchronic exposure of single mice for 60 minutes (11 exposures in
33 days, 14 exposures in 41 days, and 20 exposures in 58 days) did
not cause any obvious toxic effects except for slight fatty
degeneration of the livers of the mice receiving 14 and 20 exposures.
2.5 Chronic Toxicity
Quest et al. (I984) recently reported the results of an NTP
carciriogenicity/chronic toxicity bioassay with propylene in F344/N
rats arid B6C3F! mice. Groups of 50 rats and mice of each sex were
15
-------
exposed to air containing propylene at concentrations of 5,000 or
10,000 ppm for 6 hours/day, 5 days/week for 103 weeks. Control
groups were exposed in the same manner but to clean, filtered air.
For safety reasons, the highest dose level used was based on a
concentration that was one-half the lower flammability limit of
propylene, and may have been below the maximum tolerated dose.
Propylene had no effect on weight gain or mortality when compared
to controls in either species or sex.
Histopathologic findings indicated a positive trend in the
incidence of C-cel! hyperplasia in the thyroid glands of propylene-
exposed rats. In addition, increased incidences of nonneoplastic
lesions developed in the nasal cavities of the exposed rats (Table 2-
1). These lesions included epithelial hyperplasia in the anterior part of
the nasal cavity in females exposed at 10,000 ppm; squamous
metaplasia in males and females exposed at 5,000 ppm and in
females exposed at 10,000 ppm; and inflammatory changes,
characterized by an influx of lymphocytes, macrophages, and
granulocytes, in the nasal lumen of males exposed at both
concentration levels.
Table 2-1. Incidence of Epithelial Changes in the Nasal Cavities of Rats
Exposed to Propylene via Inhalation
Exposure level
Observation
Epithelial hyperplasia
Male
Female
Squamous metaplasia
Male
Female
Inflammation
Male
Female
0
2/50 (4%)
0/49 (0%)
2/50 (4%)
0/49 (0%)
11/50(22%)
8/49 (16%)
5,000 ppm
2/50 (4%)
4/50 (8%)
19/50 (38%)a
15/50 (30%)a
21/50 (42%)a
10/50 (20%)
10,000 ppm
5/50 (10%)
9/50(18%)a
7/50 (14%)
6/50 (12%)a
19/50 (38%)
13/50 (26%)
^Significantly (p<0.05) higher than control values.
Source: Quest et al. (1984).
There were no corresponding lesions of the nasal cavities in
mice exposed to propylene. However, there was an increased
incidence of chronic, focal, renal inflammation in males (0 of 50, 17
of 49, and 9 of 49) and in females (1 of 50, 7 of 49, and 6 of 49)
exposed to propylene at 0, 5,000, and 10,000 ppm, respectively.
2.6 Mutagenicity
Two studies have evaluated the mutagenic potential of propylene.
The compound was nonmutagenic in an £. coli survival assay and
the Sa/mone//a/microsomal reverse mutation assay. Landry and
Fuerst (1968) reported that propylene was not mutagenic to E. coli B.
The pure gas was bubbled through a 10-ml suspension of the cells
for 10 minutes and the cells subsequently maintained under the
16
-------
gaseous atmosphere for 24 hours. Mutation rates were determined
by counting the survival cells, which, formed colonies after treatment
with penicillin and neutralization with penicillinase.
Propylene was also evaluated for mutagenicity in the Ames
reversion assay and found to be nonmutagenic in Salmonella
typhtmurium tester strains TA97, TA98, and TA100 (Hughes et al
1984). The compound, diluted in ethanol, was tested at dose levels
ranging from 6.3 to 626.0 pg/plate, in triplicate, with and without
metabolic activation. Metabolic activation consisted of two liver S9
systems (rat and hamster) induced with Aroclor 1254.
Recently, two reports have described the mutagenic, genotoxic
and cytotoxic effects of the photochemical reaction products of
propylene and NOX. The photooxidation products of CsHfi/NOv
showed increased mutagenic activity when compared to the
reactants in the Ames assay using Salmonella typhimurium tester
strain TA100 (Kleindienst et al., 1985). The tester strain was exposed
for 20 hours to the irradiated products of the reactants CaHe NO
and NOX-NO at initial concentrations of 826, 505, and 20o' ppb'
respectively. Metabolic activation (S9 from livers of male CD-1 rats
induced with Aroclor 1254) had no significant effect on mutagenic
activity; however, the number of revertants did increase as a function
of exposure time (-160 excess revertants/plate after 2.7 hours and
-625 revertants/plate after 7.5 hours of exposure). An attempt was
made to account for the excess revertants by summing the
contributions of the individual major and minor reaction products (the
major reaction products of this system are described in Section 1 2)
Of the major and minor reaction products, only HCHO and PAN had
mutagenic activities above the detection limit, contributing 19 and 27
revertants/plate, respectively, after 7.5 hours of exposure When the
number of revertants contributed by minor products such as
peroxide, was added to those contributed by PAN and HCHO, only
20 percent of the observed mutagenic response could be accounted
for. Another possible product of the photochemical reaction of
propylene and N2Os suggested by Shepson et al. (1985) is a-
(nitrooxy) acetone which has been shown to be mutagenic.
S. typhimurium strain TA100 was also exposed to the products
of the C3H6/N2O5 dark reaction to determine to what extent
CaHe/NOs reactions contributed to the mutagenic response. A small
mutagenic response was observed for this mixture (180 excess
revertants/plate above controls), with S9 activation having no
significant effect on mutagenic activity. The contribution to the total
response for reaction products a-nitratoacetone, HCHO and PAN
was estimated to be 22, 2, and 8 revertants/plate, respectively
However, the contribution of all known reaction products accounted
for only a small fraction of the total observed response (-19
percent). A number of possible explanations for the observed
mutagenic effect were suggested by the authors, including the
presence of an unknown potent mutagen not detected in the analysis
17
-------
of reaction products, the production of a mutagen from a reaction
that occurred in the test medium, and the combined effect of two or
more reaction products acting synergistically (Klemdienst et al.,
1985).
The photochemical reaction products of propylene and
increased the frequency of sister-chromatid exchanges (SCE's) and
the rate of growth inhibition in cultured Chinese hamster V79 cells
(Shiraishi and Bandow, 1985). Cultured cells were exposed for 2
hours to the photochemical reaction products produced in a smog
chamber using four initial concentration ratios of reactants
(propylene: NOa): 0.5:0.25, 1.0:0.5, 2.0:1.0, and 3.0:1.5 ppm. At the
lowest concentration of reaction products, the mean SCE frequency
was significantly higher when compared to control cells (14.18 per
cell versus 6.84 per cell, p < 0.001). At higher concentrations, a
greater frequency of SCE was observed, approximately two to four
times greater than control cells (significantly different at p < 0.001).
The photochemical reaction products inhibited cell growth in a
dose-dependent manner, with a mean inhibition rate of 7, 22, 44,
and 59 percent, respectively, for the four levels of concentrations
tested. In contrast, propylene and NOa alone failed to induce SCE s
in V79 cultures.
Cell cultures were also exposed for 2 hours to NOa and 03
concentrations ranging from 0.5 to 8.0 and 0.13 to 1.0 ppm,
respectively. Both compounds significantly increased the frequency
of SCE's in V79 cells, but their effects were weaker than those
induced by the photochemical reaction products of propylene and
NO2- The authors concluded that the strong induction of SCE's in
V79 cells by the photochemical reaction products was due to a
multiple effect resulting from an interaction between reaction
products (Shiraishi and Bandow, 1985).
One study reports the mutagenic effects of the reaction products
of Oa and propylene on E. coli K 12 343/113. Nover and Botzenhart
(1985) showed induction of gal*, arg+ and MTR-mutations in
qrowing cells after treatment with ozonized propylene. The treatment
with ozone was carried out under UV irradiation (3000-4000
angstroms) to increase the concentration of the reaction products
which were hydrocarbon radicals, peroxides, aldehydes and ketones.
Similar reaction products of propylene with Os are shown in Figure
1-1 Nover and Botzenhart (1985) relate the mutagenic effects to
the "photochemical smog" reaction products but not to propylene or
other hydrocarbons studied.
2.7 Carcinogenicity
Two studies have been reported on the carcinogenic potential of
propylene in rats and mice. In one, Maltoni et al. (1982) presented
the results of carcinogenicity studies with several chemicals,
including propylene, conducted in an attempt to identify potential
brain carcinogens. In the study with propylene, groups of 120
18
-------
Sprague-Dawley rats were exposed to propylene in air at 200
1,000 or 5,000 ppm for 7 hours/day, 5 days/week for 104 weeks'
One female rat exposed at 1,000 ppm had a meningioma. However'
since 2 of the total 325 female controls in the study also had
menmgiomas, the authors concluded that propylene did not cause
brain tumors in rats. No data were presented for any other
parameters of the study.
The more definitive study was the NTP carcinogenicity/chronic
toxicity bioassay with propylene in F344/N rats and B6C3Fi mice
reported by Quest et al. (1984). There was no increase noted in the
incidence of any neoplasm in the propylene-exposed rats when
compared with the controls. In fact, a negative (p <0.05) trend was
observed in the incidence of total thyroid tumors in female rats with
the incidence of C-cell adenomas of the thyroid in the 10000-pDm
group significantly (p <0.05) lower than in controls. However as
indicated above, there was a positive trend in the incidence of C-
cell hyperplasia in female rats.
In the exposed mice, both increases and decreases were noted
in the incidences of certain tumors (Table 2-2). In female mice
sigmf.cant (p <0.05) positive trends in the incidences of hemanqio-
sarcomas, combined hemangiomas and hemangiosarcomas and
uterine endometrial stromal polyps were observed in the high' dose
group but the ^ncidences were not significantly different from
controls. Similarly, in exposed males, significant (p <0.05) decreases
onmh6 in.cidences of hepatocellular adenomas, lung adenomas, and
combined lung adenomas and carcinomas were observed in the low
dose group although this was not seen in the high dose group There
was, however, a significant (p <0.05) negative trend in the incidence
of lung adenomas and carcinomas in males, but the biological
meaning of this is questionable, since the matched control rate was
considerably higher than the historical control rate.
Exposed *° p«>pylene via
Exposure level, ppm
Females
Hemangiosarcomas
Hemangiomas and hemangiosarcomas
Uterine endometrial stromal polyps
Mates
Hepatocellular adenomas
Lung adenomas
Luna adenomas and carcinomas
0
0/50
0/50
0/47
5/50
9/50
16/50
5,000
0/49
1/49
0/47
0/49
1/49
4/49
10,000
3/50
4/50
3/48
3/49
4/50
7/50b
aOnly neoplasms with incidences apparently different from controls
^Significant (p < 0.05) negative trend.
Source: Quest et al. (1984).
19
-------
Under the conditions of the study and at the concentrations
tested, it was concluded that propylene is not carcinogenic in F344/N
rats and B6C3Fi mice.
In addition to these two studies, Quest et al. (1984) reported that
in a preliminary report by Maltoni, no carcinogenic response was
found in Swiss mice exposed by inhalation for 18 months, to
propylene at concentrations of 200, 1000, or 5000 ppm for 7
hours/day, 5 days/week.
A weight of evidence characterization for propylene using EPA's
Guidelines for Carcinogen Risk Assessment involves taking account
of several types of information:
• The NTP bioassays in rats and mice provide some indication of
carcinogenic activity, such as positive trends in the incidence of
hemangiosarcomas and combined hemangiomas and
hemangiosarcomas in female mice and a hint of bladder
hyperplasia in female rats.
• Propylene is metabolized to propylene oxide (the strength of this
data base requires further scrutiny). Propylene oxide and
ethylene oxide are alkylating agents, and there is sufficient animal
evidence for their carcinogenicity.
• The similarity of endpoints in the mouse between propylene
(trend of hemangiomas) and propylene oxide (incidence of
hemangiomas) provides additional indication of potential
carcinogenic activity.
Since no epidemiological data are available, the human data base is
inadequate. The available direct animal bioassay data for propylene
can be viewed as inadequate but bordering on limited. The animal
evidence is elevated to the limited category by considering the
supporting information on metabolites to include the carcinogenicity
of metabolites and the commonality of site of action between the
metabolites and parent compound propylene. Thus the overall
weight-of-evidence becomes Group C, possibly a human carcin-
ogen.
A quantitative cancer unit risk derivation is not warranted at this
time qiven that there is not a statistically significant animal dose-
response study available, and thus the quantitative analysis cannot
be developed.
2.8 Other Health Effects
No studies were found on teratogenicity, reproductive effects,
neurotoxicity, or other types of health effects on hurnans.
20
-------
3. SUMMARY
Propylene is an olefinic hydrocarbon with the chemical structure
3CH = CH2. It is highly soluble in water and has a high vapor
pressure. Current domestic production capacity has been estimated
to be about 22 billion pounds. Propylene is a product obtained from
crude oil by distillation and used in several chemical and refinery
processes. In the chemical industry, propylene is used as a starting
material in the manufacture of polypropylene, acrylonitrile, propylene
oxide, and as a component in fuel. In refinery applications, it is used
as a feedstock or additive to gasoline and fuels.
Propylene may be released to the environment in gaseous
emissions from industrial production, chemical utilization, and various
combustion processes. Ambient concentrations in urban areas of the
United States have generally been found to range from about 1 to 10
ppb, whereas concentrations in rural air samples are approximately
an order of magnitude lower.
Gas chromatography with flame ionization detection and mass
spectrqscopy has been used extensively to measure concentrations
of propylene in environmental media.
Propylene released to the environment from point and nonpoint
sources is expected to partition into the atmosphere due to its high
vapor pressure. However, propylene has a relatively higher density
and is also highly reactive; therefore, its transport will be limited.
Propylene is one of several "volatile organic compounds" that
are precursors of photochemical oxidants and other smog
components. In ambient air, propylene is susceptible to attack by
nydroxyl radicals and ozone, although the former accounts for more
than 75 percent of the total propylene removed. The reactions of
propylene with hydroxyl radicals occur mainly during the daytime-
with ozone, during the evening; and with NO3 radicals, at night The
end products of these reactions are several aldehydes (e.g acrolein
formaldehyde, and acetaldehyde), acids, ketones, and nitrates, but
other products have also been identified. The atmospheric half-life
of propylene has been estimated to be 7.7 hours.
Trace levels of propylene have been detected in marine and
fresh waters. In water, propylene would probably be subjected to
chemical and degradative processes. Propylene is not expected to
bioconcentrate or bioaccumulate in organisms and food chains and
has been reported to be metabolized by some microorganisms
Available environmental effects data are limited to studies with higher
21
-------
plants. Some toxic effects were reported at very high concentrations;
however, these concentrations are not expected to be found in the
environment, except for cases associated with industrial leaks or
spills.
One study on the uptake and metabolism of propylene in mice
following inhalation exposure indicates that propylene is readily
metabolized, having Km and Vmax values of 800 ± 60 ppm and 8 ±
05 mg/kg/hour, respectively. Propylene is apparently oxidized to
propylene oxide and also metabolized into 1 and 2 carbon fragments,
which are readily incorporated into certain amino acids. Propylene
and/or propylene oxide also alkylates blood hemoglobin in mice via
conjugation with cysteine, valine, or histidine to form the
corresponding S- and N-(2-hydroxypropyl) derivatives.
Limited data from acute toxicity studies indicate that propylene is
not very toxic to rats (strain and sex not reported); only light
anesthesia was noted following exposure to a 40 percent
concentration of prppylene for 6 hours. Similarly, no compound-
related toxic effects were found in subchronic studies with F344/N
rats and B6C3F-J mice exposed to propylene at concentrations up to
10,000 ppm for 6 hours/day, 5 days/week for 14 days or 14 weeks.
Propylene was also not carcinogenic in F344/N rats and B6C3Fi
mice following exposure at concentrations up to 10,000 ppm for 6
hours/day, 5 days/week for 103 weeks. However, nonneoplastic
lesions such as inflammation, epithelial hyperplasia, and squamous
metaplasia developed in the nasal cavities of exposed rats, and renal
inflammation was noted in exposed mice.
Propylene was not mutagenic in an Escherichia coli assay when
bubbled through the cells for 10 minutes, nor in Salmonella
typhimurium strains TA97, TA98, and TA100 at dose levels up to 626
ug in ethanol per plate. Mutagenic and cytotoxic effects of
photochemical reaction products of propylene and NOX have recently
been reported in S. typhimurium strain TA100 and cultured Chinese
hamster V79 cells without activation; mutagenic effects of the
reaction products of 03 and propylene on E. coli K12 343/113 have
also been reported; no other mutagenicity studies were available. No
teratogenicity, reproductive effects, or neurotoxicity studies of
propylene with laboratory animals were found in the available
literature. Similarly, there were no epidemiologic or case studies
available to assess its effects on humans.
According to EPA's carcinogen risk assessment guidelines, the
animal evidence for the carcinogenicity of propylene is judged to be
only limited. This equates to a Group C classification, given that
there is no epidemiologic data and the animal evidence is limited.
22
-------
4. REFERENCES
Akimoto, H.; Sakamaki, F.; Hoshino, M.; Inoue, G.; Okuda, M (1979)
Photochemical ozone formation in propylene-nitrbgen oxide-dry
air system. Environ. Sci. Technol. 13: 53-58.
H;!, Bandow' K: Sakamaki, F.; Inoue, G.; Hoshino, M.;
Okuda, M. (1980) Photooxidation of the propylene-NOx-air
system studied by long-path Fourier transform infrared
spectrometry. Environ. Sci. Technol. 14: 172-179.
Allen, R. J.; Brenniman, G. R.; Darling, C. (1986) Air pollution
emissions from the incineration of hospital waste. J Air Pollut
Control Assoc. 36: 829-831. • u ui.
' A- P.; Lonneman, W. A.; Sutterfield, F. D.; Kopczynski, S.
L. (1971) Hydrocarbon composition of the atmosphere of the Los
Angeles Basm-1967. Environ. Sci. Technol. 5: 1009-1016.
Anlauf K. G.; Bottenheim, J. W.; Brice, K. A.; Fellin, P.; Wiebe H
A; Schiff, H. I.; Mackay, G. I.; Braman, R. S.; Gilbert, R. (1985)
Measurement of atmospheric aerosols and photochemical
products at a rural site in SW Ontario. Atmos. Environ. 19: 1859-
1 o/ 0.
Atkinson, R.; Plum, C. N.; Carter, W. P. L.; Winer, A. M.; Pitts, J. N
Jr. (1984) Rate constants for the gas-phase reactions of 'nitrate
radicals with a series of organics in air at 298 + 1 K J Phvs
Chem. 88: 1210-1215. ' '
Bos, R.; Guicherit, R.; Hoogeveen, A. (1977) Distribution of some
hydrocarbons in ambient air near Delft and the influence on the
formation of secondary air pollutants. Sci. Total Environ. 7: 269-
281.
•
Brown, W. E. (1924) Experiments with anesthetic gases propylene
methane, dimethyl-ether. J. Pharmacol. Exp. Ther. 23: 485-496.'
Carotti, A. A.; Kaiser, E. R. (1972) Concentrations of twenty gaseous
chemical species in the flue gas of a municipal incinerator J Air
Pollut. Control Assoc. 22: 248-253.
Cerniglia, C. E.; Blevins, W. T.; Perry, J. J. (1976) Microbial oxidation
and assimilation of propylene. Appl. Environ. Microbiol. 32: 764-
768.
Chemical Economics Handbook. (1980) Menlo Park CA- SRI
International. Sections 300.5400A-.54070.
23
-------
Chemical Marketing Reporter. (1984) Propylene prices are dropping
as producers reduce inventory. November 5: 15 (col. 1).
Colbeck, I.; Harrison, R. M. (1985) The concentrations of specific
C2-Ce hydrocarbons in the air of NW England. Atmos. Environ.
19: 1899-1904.
Crow, W. L; Hall, R. C.; Cox, H. G.; Ogle, L. D.; Gise, J. P. (1982)
Continuous and unattended monitoring of hydrocarbons in ambient
air Presented at: 75th annual meeting of the Air Pollution Control
Association; June; New Orleans, LA. Pittsburgh, PA: Air Pollution
Control Association; paper no. 82-31.5.
Edney, E.; Mitchell, S.; Bufalini, J. J. (1982) Atmospheric chemistry
of several toxic compounds. Research Triangle Park, NC: U. S.
Environmental Protection Agency, Environmental Sciences
Research Laboratory; EPA report no. EPA-600/3-82-092.
Available from: NTIS, Springfield, VA; PB83-146340.
Frisch, A. R; Francis, B. W.; Chavis, M. K.; Jenkins, R. W., Jr.
(1982) Cigarette smoke formation studies: VII. the fate of (5-
l4C)-methoprene in cigarette smoke. Beitr. Tabakforsch. Int. 11:
203-208.
Gerarde, H. W. (1963) Propylene, CH3CH = CH2 (Propene,
Methylethylene) In: Patty, F. A., ed. Industrial hygiene and
toxicology: 2nd rev. ed. New York, NY: Interscience Publishers; p.
1204. (Fasset, D. W.; Irish, D. D., eds. Toxicology: v. II).
Giannovario, J. A.; Grob, R. L.; Rulon, P. W. (1976) Analysis of trace
pollutants in the air by means of cryogenic gas chromatography. J.
Chromatogr. 121: 285-294.
Graedel, T. E.; Farrow, L. A.; Weber, T. A. (1976) Kinetic studies of
the photochemistry of the urban troposphere. Atmos. Environ. 10:
1095-1116.
Grosjean, D.; Fung, K. (1984) Hydrocarbons and carbonyls in Los
Angeles air. J. Air Pollut. Control Assoc. 34: 537-543.
Hoff, A.; Jacobsson, S.; Pfaffli, P.; Zitting, A.; Frostling, H. (1982)
Degradation products of plastics: polyethylene and styrene-
containing thermoplastics - analytical, occupational and
toxicologic aspects. Scand. J. Work Environ. Health 8(suppl. 2):
1-60.
Hoshino M.; Ogata, T.; Akimoto, H.; Inoue, G.; Sakamaki, F.; Okuda,
M. (1978) Gas phase reaction of N2Os with propylene. Chem.
Lett. 12: 1367-1370.
Hov, O.; Penkett, S. A.; Isaksen, I. S. A.; Semb, A. (1984) Organic
gases in the Norwegian Arctic. Geophys. Res. Lett. 11: 425-428.
Hughes, T. J.; Sparacino, C.; Frazier, S. (1984) Validation of
chemical and biological techniques for evaluation of vapors in
24
-------
ambient air/mutagehicity testing of twelve (12) vapor-phase
compounds. Research Triangle Park, NC: U.S. Environmental
Protection Agency, Health Effects Research Laboratory EPA
report no. EPA-600/1-84-005. Available from: NTIS
Springfield, VA; PB84-164219.
International Agency for Research on Cancer. (1979) Propylene and
polypropylene. In: IARC monographs on the evaluation of the
carcinogenic risk of chemicals to humans: v. 19. Lyon, France-
World Health Organization; pp. 213-230.
Jackson, M. W. (1978) Effect of catalytic emission control on exhaust
hydrocarbon composition and reactivity. Presented at: Passenger
Car Meeting; June; Troy, Ml. Warrendale, PA: Society of
Automotive Engineers, Inc.; SAE technical paper no. 780624.
Katzman, H.; Libby, W. F. (1975) Hydrocarbon emissions from jet
engines operated at simulated high-altitude supersonic flight
conditions. Atmos. Environ. 9: 839-842.
Khalil, M. A. «.; Rasmussen, R. A. (1984) Statistical analysis of trace
gases in arctic haze. Geophys. Res. Lett. 11: 437-440.
Kleindienst, T. E:; Shepson, P. B.; Edney, E. O.; Cupitt, L. T.;
Claxton, L. D. (1985) The mutagenic activity of the products of
propylene photooxidation. Environ. Sci. Technol. 19: 620-627.
Krantz, J. C., Jr.; Carr, C. J.; Vitcha, J. F. (1948) Anesthesia: XXXI. a
study of cyclic and noncyclic hydrocarbons on cardiac
automatiaty. J. Pharmacol. Exp. Ther. 94: 315-318.
Krasovitskaya, M. L.; Malyarova, L. K. (1966) Small concentrations of
hydrocarbons in the air of naphtha-chemical plants. Biol. Deistvie
Gig. Znach. Atmos. Zagryaz. (9): 74-100 [Cited from: Chem
Abstr. 65: 14324c, 1966].
Kusy, V.; Kusy, J. (1982) Gas chromatographic analysis of
metabolites of trees damaged by exhalations. Collect Czech
Chem. Commun. 47: 1807-1817.
Lamb, B.; Westberg, H.; Bryant, P.; Dean, J.; Mullins, S. (1985) Air
infiltration rates in pre- and post-weatherized houses J Air
Pollut. Control Assoc. 35: 545-551.
Landry, M. M.; Fuerst, R. (1968) Gas ecology of bacteria Dev Ind
Microbiol. 9: 370-380.
Lyman, W. J.; Reehl, W. F.; Rosenblatt, D. H. (1982) Handbook of
chemical property estimation methods: environmental behavior of
organic compounds. New York, NY: McGraw-Hill Book Company.
Maltoni, C.; Ciliberti, A.; Carretti, D. (1982) Experimental contributions
in identifying brain potential carcinogens in the petrochemical
industry. Ann. N.Y. Acad. Sci. 381: 216-249.
25
-------
Matuska, P.; Koval, M.; Seller, W. (1986) A high resolution gc
analysis method for determination of C2-C10 hydrocarbons in air
samples. HRC CC J. High Resolut. Chromatogr. Chrornatogr.
Commun. 9: 577-583.
Mohan Rao, A.M.; Pandit, G.G. (1988) Concentrations of C2-C5
hydrocarbons in atmospheric Air at Deonar, Bombay, in relation to
possible sources. Atmos. Environ. 22; 395-401.
Morrison, R. T.; Boyd, R. N. (1973) Alkenes II. Reactions of the
carbon-carbon double bond: electrophilic and free-radical
addition. In: Organic chemistry. 3rd ed. Boston, MA: Allyn and
Bacon, Inc.; pp. 177-224.
National Toxicology Program. (1985) Technical report on the
toxicology and carcinogenesis studies of propylene (CAS No.
115-07-1) in F344/N rats and B6C3F-| mice (inhalation studies).
Research Triangle Park, NC: U.S. Department of Health and
Human Services, Public Health Service, National Institutes of
Health NTP TR 272; NIH publ. no. 85-2528; NTP-83-025.
Available from: NTIS, Springfield, VA; PB86-145521/AS.
Nelson, P. F.; Quigley, S. M. (1982) Non-methane hydrocarbons in
the atmosphere of Sydney, Australia. Environ. Sci. Technol. 16:
650-655.
Netravalkar, A. J.; Mohan Rao, A. M. (1984) Seasonal variations in
the concentrations of ethylene, acetylene and propylene at
Trombay, Bombay. Sci. Total Environ. 35: 33-40.
Nguyen, Y. V.; Phillips, C. R. (1979) The roles of water vapor and
carbon monoxide in the photooxidation of propylene. Water Air Soil
Pollut. 11: 323-337.
NOES National Occupational Exposure Survey [data base], (n.d.)
Cincinnati, OH: National Institute for Occupational Safety and
Health, U. S. Department of Health and Human Services.
NOHS National Occupational Hazard Survey [data base], (n.d.)
Cincinnati, OH: National Institute for Occupational Safety and
Health, U. S. Department of Health and Human Services.
Nover, H.; Botzenhart, K. (1985) Bactericidal effects of
photochemical smog constituents produced by a flow reactor. III.
Communication: Determination of mutagenic effects of
photochemical smog on Escherichia coli K 12 343/113. Zentralbr.
Bakteriol. Mikrobiol. Hyg. Abt. 1 Orig. B 181: 71-80.
O'Mara M M. (1974) The combustion products from synthetic and
natural products - part 1: wood. J. Fire Flammability 5: 34-53.
OHMTADS, Oil and Hazardous Materials Technical Assistance Data
System [data base], (n.d.) Falls Church, VA: NIH/EPA Chenmcal
Information System; OHMTADS accession no. 7216875.
26
-------
Osimitz, T. G.; Conolly, R. B. (1985) Mixed-function oxidase system
induction and propylene hepatotoxicity. J. Toxicol. Environ. Health
15i 39-49.
Perry, J. J. (1980) The role to co-oxidation and commensalism in
the biodegradation of recalcitrant molecules. Research Triangle
Park, NC: U. S. Army Research Office; report no. DAAG-29-
In'o^159- Available fr°m: NTIS, Springfield, VA; AD-
A080845.
Quest, J. A.; Tomaszewski, J. E.; Haseman, J. K.; Boorman G A-
Douglas, J. F.; Clarke, W. J. (1984) Two-year inhalation toxicity
study of propylene in F344/N rats and B6C3F^ mice. Toxicol ADD!
Pharmacol. 76: 288-295. '
Reineke, F. J.; Baechmann, K. (1985) Gas chromatographic
determination of C2-Cs hydrocarbons and halocarbons in ambient
air by simultaneous use of three detectors. J. Chromatogr. 323:
323 "329.
Reynolds, C. (1926) Comparative studies of propylene, ethylene
nitrous oxide and ether. J. Pharmacol. Exp. Ther. 27: 93-99.
Riggs, L. K. (1925) Anesthetic properties of the olefine hydrocarbons
ethylene, propylene, butylene and amylene. J. Am. Pharm. Assoc.'
1 4l 380-387.
Rudolph, J.; Ehhalt, D. H.; Khedim, A.; Jebsen, C. (1981)
Determination of C2-C5 hydrocarbons in the atmosphere at low
parts per 109 to high parts per 1Q12 levels. J. Chromatogr. 217:
o0 1 "3 1 0 .
Sahdmeyer, E. E. (1985) [General and specific comments on the
preliminary draft summary health assessment document for
propylene]. Pittsburgh, PA: Transcontec, Inc.
Schmidbauer N; Oehme, M. (1985) Analysis of light hydrocarbons
(L-2-L-6) at PPT levels by high resolution gas chromatography. J
High Resolut. Chromatogr. Commun. 8: 404-406.
Schoenberg, M. R.; Blieszner, J. W.; Papadopoulos, C. G (1982)
Propylene In: Kirk, R. E.; Othmer, D. F., eds. Kirk-Othmer
encyclopedia of chemical technology: volume 19, powder coatinqs
to recycling. 3rd ed. New York, NY: John Wiley & Sons; pp. 228-
Sexton, K.; Westberg, H. (1984) Nonmethane hydrocarbon
composition of urban and rural atmospheres. Atmos. Environ. 18:
~i I 32 .
Shepson, P B ; Edney, E. O.; Kleindienst, T. E.; Pittman, J. H.;
Namie, G. R.; Cupitt, L. T. (1985) The production of organic
nitrates from hydroxyl and nitrate radical reaction with propylene
Environ. Sci. Technol. 19: 849-854. pywiw.
27
-------
Shiraishi, F.; Bandow, H. (1985) The genetic effects of the
photochemical reaction products of propylene plus NC-2 on
cultured Chinese hamster cells exposed in vitro. J. Toxicol.
Environ. Health 15: 531-538.
Sigsby, J. E., Jr.; Tejada, S.; Ray, W.; Lang, J. M.; Duncan, J. W.
(1987) Volatile organic compound emissions from 46 m-use
passenger cars. Environ. Sci. Technol. 21: 466-475.
Sivertsen B. (1983) Estimation of diffuse hydrocarbon leakages from
petrochemical factories. J. Air Pollut. Control Assoc. 33: 323-327.
Smith A. M.; Morrison, W. L; Milham, P. J. (1983) Ethylene
enhances reactivity of superoxide with peroxidase to form the
oxy-ferrous complex. Biochemistry 22: 1645-1650.
SRI International. (1984) 1984 Directory of chemical producers,
United States. Menlo Park, CA: SRI International; pp. 837-839.
Svensson, K.; Osterman-Golkar, S. (1984) Kinetics of metabolism
of propene and covalent binding to macromolecules in the mouse.
Toxicol. Appl. Pharmacol. 73: 363-372.
Swinnerton, J. W.; Lamontagne, R. A. (1974) Oceanic distribution of
low-molecular-weight hydrocarbons: baseline measurements.
Environ. Sci. Technol. 8: 657-663.
Swinnerton, J. W.; Linnenbom, V. J. (1967) Determination of the C1
to C4 hydrocarbons in sea water by gas chromatography. J. Gas
Chromatogr. 5: 570-573.
TDB, Toxicology Data Bank [data base], (n.d.) Bethesda, MD:
National Library of Medicine, U. S. Department of Health and
Human Services; TDB no. 0175.
van Haul, H.; Prinz, B. (1979) Beurteilung der relativen
Pflanzenschaedlichkeit organischer Luftverunreinigungen im L/6-
Kurzzeittest [Analysis of the relative damage to plants by organic
air pollutants using the /JS-short-term test]. Staub Remhalt. Luft
39: 408-414.
Vancura, V.; Stotzky, G. (1976) Gaseous and volatile exudates from
germinating seeds and seedlings. Can. J. Bot. 54: 518-532.
Verschueren, K. (1983) Handbook of environmental data oh organic
chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co.;
pp. 1027-1028.
Westberg, H. H.; Rasmussen, R. A.; Holdren, M. (1974) Gas
chromatographic analysis of ambient air for light hydrocarbons
using a chemically bonded stationary phase. Anal. Chem. 46:
1852-1854.
Woolley, W. D. (1982) Smoke and toxic gas production from burning
polymers. J. Macromol. Sci. Chem. A17: 1-33.
28
-------
Yoshida, Y.; Kono, K.; Harada, A. (1978) Toxicity of pyrolysis
products of thermal-resistant plastics including polyamide and
polyester. Nippon Eiseigaku Zasshi 33: 450-458.
0 U.S.GOVEHNMENTPniNTINQOmCEM988 - 548-158/87007
29
-------
------- |